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42674471 | 10.1007/s00013-016-0932-0 | In this paper we study the biharmonic operator perturbed by an inverse
fourth-order potential. In particular, we consider the operator
$A=\Delta^2-V=\Delta^2-c|x|^{-4}$ where $c$ is any constant such that
$c<\left(\frac{N(N-4)}{4}\right)^2$. The semigroup generated by $-A$ in
$L^2(\mathbb{R}^N)$, $N\geq5$, extrapolates to a bounded holomorphic
$C_0$-semigroup on $L^p(\mathbb{R}^N)$ for $p\in [p^{'}_0,p_0]$ where
$p_0=\frac{2N}{N-4}$ and $p_0^{'}$ is its dual exponent. Furthermore, we study
the boundedness of the Riesz transform $\Delta A^{-1/2}$ on $L^p(\mathbb{R}^N)$
for all $p\in(p_0^{'},2]$ | Fourth-order Schr\"odinger type operator with singular potentials | fourth-order schr\"odinger type operator with singular potentials | biharmonic perturbed fourth potential. delta delta frac semigroup mathbb extrapolates holomorphic semigroup mathbb frac exponent. boundedness riesz transform delta mathbb | non_dup | [] |
42693862 | 10.1007/s00013-016-0933-z | Let $X$ be a compact Riemann surface of genus $g\geq 2$, and let $Aut(X)$ be
its group of automorphims. We show that the exponent of $Aut(X)$ is bounded by
$42(g-1)$. We also determine explicitly the infinitely many values of $g$ for
which this bound is reached and the corresponding groups. Finally we discuss
related questions for subgroups $G$ of $Aut(X)$ that are subject to additional
conditions, for example being solvable.Comment: final version, 13 pages, several improvements thanks to the refere | On the exponent of the automorphism group of a compact Riemann surface | on the exponent of the automorphism group of a compact riemann surface | riemann genus automorphims. exponent explicitly infinitely reached groups. subgroups pages improvements thanks refere | non_dup | [] |
29549647 | 10.1007/s00013-016-1008-x | We prove a general divisibility theorem that implies, e.g., that, in any
group, the number of generating pairs (as well as triples, etc.) is a multiple
of the order of the commutator subgroup. Another corollary says that, in any
associative ring, the number of Pythagorean triples (as well as four-tuples,
etc.) of invertible elements is a multiple of the order of the multiplicative
group.Comment: 7 pages. A Russian version of this paper is at
http://halgebra.math.msu.su/staff/klyachko/papers.htm . V.2: misprints
corrected, some applications generalised. V.3: minor additions and
corrections. V.4: Some corrections and generalisations (see Theorem on
Monomorphisms and Subgroups). V.5: A reference is adde | Strange divisibility in groups and rings | strange divisibility in groups and rings | divisibility e.g. generating triples etc. commutator subgroup. corollary says associative pythagorean triples tuples etc. invertible multiplicative pages. russian halgebra.math.msu.su staff klyachko papers.htm misprints corrected generalised. minor additions corrections. generalisations monomorphisms subgroups adde | non_dup | [] |
42713831 | 10.1007/s00013-016-1009-9 | Let R be a unital commutative ring and let $M$ be an $R$-module that is
generated by $k$ elements but not less. Let $E_n(R)$ be the subgroup of
$GL_n(R)$ generated by the elementary matrices. In this paper we study the
action of $E_n(R)$ by matrix multiplication on the set $Um_n(M)$ of unimodular
rows of $M$ of length $n \ge k$. Assuming $R$ is moreover Noetherian and
quasi-Euclidean, e.g., $R$ is a direct sum of finitely many Euclidean rings, we
show that this action is transitive if $n > k$. We also prove that $Um_k(M)
/E_k(R)$ is equipotent with the unit group of $R/(a_1)$ where $(a_1)$ is the
first invariant factor of $M$. These results encompass the well-known
classification of Nielsen non-equivalent generating tuples in finitely
generated Abelian groups.Comment: 7 pages, no figure. Results and proofs are unchanged. The
modifications are the following: - one new reference - correction of a very
confusing typo in Corollary C (the author thanks W. van der Kallen) -
correction of two typos on page 6 (the author thanks D. Oancea | Finitely generated modules over quasi-Euclidean rings | finitely generated modules over quasi-euclidean rings | unital commutative module less. subgroup elementary matrices. multiplication unimodular rows noetherian quasi euclidean e.g. finitely euclidean rings transitive equipotent encompass nielsen generating tuples finitely abelian pages figure. proofs unchanged. modifications confusing typo corollary thanks kallen typos thanks oancea | non_dup | [] |
78511706 | 10.1007/s00013-016-1011-2 | We show that a Born-Infeld soliton can be realised either as a spacelike
minimal graph or timelike minimal graph over a timelike plane or a combination
of both away from singular points. We also obtain some exact solutions of the
Born-Infeld equation from already known solutions to the maximal surface
equation. Further we present a method to construct a one-parameter family of
complex solitons from a given one parameter family of maximal surfaces.
Finally, using Ramanujan's Identities and the Weierstrass-Enneper
representation of maximal surfaces, we derive further non-trivial identities.Comment: 12 pages, published online in Archiv der Mathemati | Born-Infeld solitons, Maximal surfaces and Ramanujan's identities | born-infeld solitons, maximal surfaces and ramanujan's identities | born infeld soliton realised spacelike timelike timelike away singular points. born infeld maximal equation. solitons maximal surfaces. ramanujan identities weierstrass enneper maximal derive trivial pages archiv mathemati | non_dup | [] |
42686882 | 10.1007/s00013-017-1076-6 | Let $(\mathcal{M},g)$ be a compact Riemannian manifold of dimension $N\geq
2$. We prove the existence of a family $(\Omega_\varepsilon)_{\varepsilon\in
(0,\varepsilon_0)}$ of self-Cheeger sets in $(\mathcal{M},g)$ . The domains
$\Omega_\varepsilon\subset\mathcal{M}$ are perturbations of geodesic balls of
radius $\varepsilon$ centered at $p \in \mathcal{M}$, and in particular, if
$p_0$ is a non-degenerate critical point of the scalar curvature of $g$, then
the family $(\partial \Omega_\varepsilon)_{\varepsilon \in (0,\varepsilon_0)}$
constitutes a smooth foliation of a neighborhood of $p_0$.Comment: Revised argument on section 2, Results unchanged. Published in Archiv
der Mathemati | Existence of Self-Cheeger sets on Riemannian manifolds | existence of self-cheeger sets on riemannian manifolds | mathcal riemannian manifold omega varepsilon varepsilon varepsilon cheeger mathcal omega varepsilon mathcal perturbations geodesic balls varepsilon centered mathcal degenerate curvature omega varepsilon varepsilon varepsilon constitutes foliation neighborhood .comment revised argument unchanged. archiv mathemati | non_dup | [] |
73987841 | 10.1007/s00013-017-1114-4 | We prove the pointwise decay of solutions to three linear equations: (i) the
transport equation in phase space generalizing the classical Vlasov equation,
(ii) the linear Schrodinger equation, (iii) the Airy (linear KdV) equation. The
usual proofs use explicit representation formulae, and either obtain
$L^1$---$L^\infty$ decay through directly estimating the fundamental solution
in physical space, or by studying oscillatory integrals coming from the
representation in Fourier space. Our proof instead combines "vector field"
commutators that capture the inherent symmetries of the relevant equations with
conservation laws for mass and energy to get space-time weighted energy
estimates. Combined with a simple version of Sobolev's inequality this gives
pointwise decay as desired. In the case of the Vlasov and Schrodinger equations
we can recover sharp pointwise decay; in the Schrodinger case we also show how
to obtain local energy decay as well as Strichartz-type estimates. For the Airy
equation we obtain a local energy decay that is almost sharp from the scaling
point of view, but nonetheless misses the classical estimates by a gap. This
work is inspired by the work of Klainerman on $L^2$---$L^\infty$ decay of wave
equations, as well as the recent work of Fajman, Joudioux, and Smulevici on
decay of mass distributions for the relativistic Vlasov equation.Comment: 16 pages; expository with some (hopefully) new material. v2: fixed
typos in the Strichartz exponent, sharpened interpolation to remove epsilon
loss, updated reference list. v4: added Remark 23 showing how to recover
standard L^1-L^\infty decay estimates from the weighted L^2-L^\infty argument
for Schrodinge | A commuting-vector-field approach to some dispersive estimates | a commuting-vector-field approach to some dispersive estimates | pointwise generalizing vlasov schrodinger airy equation. usual proofs formulae infty estimating studying oscillatory integrals coming fourier space. combines commutators capture inherent symmetries conservation laws weighted estimates. sobolev inequality pointwise desired. vlasov schrodinger recover sharp pointwise schrodinger strichartz estimates. airy sharp nonetheless misses gap. inspired klainerman infty fajman joudioux smulevici relativistic vlasov pages expository hopefully material. typos strichartz exponent sharpened interpolation remove epsilon updated list. remark recover infty weighted infty argument schrodinge | non_dup | [] |
83836198 | 10.1007/s00013-018-1162-4 | To a smooth and symmetric function $f$ defined on a symmetric open set
$\Gamma\subset\mathbb{R}^{n}$ and a real $n$-dimensional vector space $V$ we
assign an associated operator function $F$ defined on an open subset
$\Omega\subset\mathcal{L}(V)$ of linear transformations of $V$, such that for
each inner product $g$ on $V$, on the subspace
$\Sigma_{g}(V)\subset\mathcal{L}(V)$ of $g$-selfadjoint operators,
$F_{g}=F_{|\Sigma_{g}(V)}$ is the isotropic function associated to $f$, which
means that $F_{g}(A)=f(\mathrm{EV}(A))$, where $\mathrm{EV}(A)$ denotes the
ordered $n$-tuple of real eigenvalues of $A$. We extend some well known
relations between the derivatives of $f$ and each $F_{g}$ to relations between
$f$ and $F$. By means of an example we show that well known regularity
properties of $F_{g}$ do not carry over to $F$.Comment: 13 pages. Added an example to show that loss of regularity is
possible. Extended the bibliography. Comments are welcom | Isotropic functions revisited | isotropic functions revisited | gamma mathbb assign omega mathcal transformations subspace sigma mathcal selfadjoint sigma isotropic mathrm mathrm ordered tuple eigenvalues extend derivatives regularity carry .comment pages. regularity possible. bibliography. comments welcom | non_dup | [] |
93950979 | 10.1007/s00013-018-1183-z | We describe a method for solving linear systems over the localization of a
commutative ring $R$ at a multiplicatively closed subset $S$ that works under
the following hypotheses: the ring $R$ is coherent, i.e., we can compute finite
generating sets of row syzygies of matrices over $R$, and there is an algorithm
that decides for any given finitely generated ideal $I \subseteq R$ the
existence of an element $r$ in $S \cap I$ and in the affirmative case computes
$r$ as a concrete linear combination of the generators of $I$.Comment: Improvement of the metho | Linear systems over localizations of rings | linear systems over localizations of rings | solving localization commutative multiplicatively hypotheses coherent i.e. generating syzygies decides finitely ideal subseteq affirmative computes concrete generators .comment metho | non_dup | [] |
129362809 | 10.1007/s00013-018-1185-x | In this note we study the control problem for the heat equation on
$\mathbb{R}^d$, $d\geq 1$, with control set $\omega\subset\mathbb{R}^d$. We
provide a necessary and sufficient condition (called $(\gamma,
a)$-\emph{thickness}) on $\omega$ such that the heat equation is
null-controllable in any positive time. We give an estimate of the control cost
with explicit dependency on the characteristic geometric parameters of the
control set. Finally, we derive a control cost estimate for the heat equation
on cubes with periodic, Dirichlet, or Neumann boundary conditions, where the
control sets are again assumed to be thick. We show that the control cost
estimate is consistent with the $\mathbb{R}^d$ case.Comment: To appear in Archiv der Mathematik with DOI
:10.1007/s00013-018-1185-x. A section added with discussion of approximation
of the control problem on cubes by the control problem on whole Euclidean
spac | Sharp geometric condition for null-controllability of the heat equation
on $\mathbb{R}^d$ and consistent estimates on the control cost | sharp geometric condition for null-controllability of the heat equation on $\mathbb{r}^d$ and consistent estimates on the control cost | mathbb omega mathbb gamma emph omega controllable time. dependency geometric set. derive cubes dirichlet neumann thick. mathbb archiv mathematik cubes euclidean spac | non_dup | [] |
129351514 | 10.1007/s00013-018-1259-9 | In this paper we connect algebraic properties of the pair-of-pants product in
local Floer homology and Hamiltonian dynamics. We show that for an isolated
periodic orbit the product is non-uniformly nilpotent and use this fact to give
a simple proof of the Conley conjecture for closed manifolds with aspherical
symplectic form. More precisely, we prove that on a closed symplectic manifold
the mean action spectrum of a Hamiltonian diffeomorphism with isolated periodic
orbits is infinite.Comment: 9 pages, revised version, main results unchanged, Archiv der
Mathematik, 201 | Conley conjecture and local Floer homology | conley conjecture and local floer homology | connect algebraic pants floer homology dynamics. orbit uniformly nilpotent conley conjecture manifolds aspherical symplectic form. precisely symplectic manifold diffeomorphism orbits pages revised unchanged archiv mathematik | non_dup | [] |
84327683 | 10.1007/s00013-018-1292-8 | In this note we study a two-particle bound system (molecule) moving on the
positive half-line under the influence of randomly distributed singular
two-particle interactions generated by a Poisson process. We give a rigorous
definition of the underlying Hamiltonian and study its spectral properties. As
a main result we prove that, with finite probability, the random interactions
destroy the discrete part of the spectrum which is present in the free system.
Most interestingly, this phenomenon is somewhat contrary to the role attributed
to random interactions in the context of Anderson localisation where disorder
is generally associated with a suppression of transport | A remark on the effect of random singular two-particle interactions | a remark on the effect of random singular two-particle interactions | molecule moving randomly singular poisson process. rigorous properties. destroy system. interestingly phenomenon somewhat contrary attributed anderson localisation disorder suppression | non_dup | [] |
2564736 | 10.1007/s00014-003-0780-y | We give an example of two JSJ decompositions of a group that are not related
by conjugation, conjugation of edge-inclusions, and slide moves. This answers
the question of Rips and Sela stated in "Cyclic splittings of finitely
presented groups and the canonical JSJ decomposition," Ann. of Math. 146
(1997), 53-109.
On the other hand we observe that any two JSJ decompositions of a group are
related by an elementary deformation, and that strongly slide-free JSJ
decompositions are genuinely unique. These results hold for the decompositions
of Rips and Sela, Dunwoody and Sageev, and Fujiwara and Papasoglu, and also for
accessible decompositions.Comment: 11 pages; shortened and reorganized; mathematical content unchange | On uniqueness of JSJ decompositions of finitely generated groups | on uniqueness of jsj decompositions of finitely generated groups | decompositions conjugation conjugation inclusions slide moves. answers rips sela stated cyclic splittings finitely canonical decomposition ann. math. decompositions elementary deformation slide decompositions genuinely unique. hold decompositions rips sela dunwoody sageev fujiwara papasoglu accessible pages shortened reorganized mathematical unchange | non_dup | [] |
18245385 | 10.1007/s00015-007-1205-5 | Paleomagnetic analyses were carried out on samples from 19 localities within two different mega-tectonic units in Northern Romania: Tisza-Dacia (11 localities) and ALCAPA (8 localities). The samples cover a range of different lithologies: (1) Late Cretaceous red-coloured marl to marly limestone, (2) Eo- Oligocene flysch sediments, and (3) mid-Miocene (Langhian) tuffite (Dej tuff and related sediments). The Late Cretaceous and mid-Miocene specimens carry secondary paleomagnetic signals exhibiting a counter clockwise deflection of the paleo-declinations by some 30°, while the Eo-Oligocene localities indicate an overall clockwise deflected (between some 45° and <90°) paleodeclination with respect to present-day north. Clockwise rotation postdates the age of sedimentation (Lower Oligocene), as well as (at least partially) thrusting of the Pienides onto the Tisza-Dacia mega-tectonic unit, which occurred between 20.5 and 18.5 Ma. Clockwise rotation predates post-12 Ma counter clockwise rotations inferred for the mid-Miocene localities. Surprisingly, the clockwise rotations of the first rotational stage not only affected the (par-) autochthonous sedimentary cover of the Tisza-Dacia megatectonic unit, but also the allochthonous flysch nappes of the Pienides, i.e. the eastern tip of the ALCAPA mega-tectonic unit. Well-documented opposed rotation of the remainder of ALCAPA necessitates a detachment of this eastern tip of ALCAPA after 18.5 Ma. The most likely location for this detachment zone is along the margins of the Transcarpathian depression. During a second (post-12 Ma) stage, counter clockwise rotations of up to 30° affected the entire working area. Regarding timing and magnitude, these second stage rotations are similar to rotations documented for the East Slovak basin, but different from those reported from the South Apuseni Mountains and the Central and Inner West Carpathians located west of the East Slovak basin | The contact zone between the Alcapa and Tisza-Dacia mega-tectonic units of northern Romania in the light of new paleomagnetic data | the contact zone between the alcapa and tisza-dacia mega-tectonic units of northern romania in the light of new paleomagnetic data | paleomagnetic localities mega tectonic northern romania tisza dacia localities alcapa localities cover lithologies cretaceous coloured marl marly limestone oligocene flysch sediments miocene langhian tuffite tuff sediments cretaceous miocene specimens carry paleomagnetic exhibiting counter clockwise deflection paleo declinations oligocene localities clockwise deflected paleodeclination north. clockwise postdates sedimentation oligocene partially thrusting pienides tisza dacia mega tectonic occurred clockwise predates counter clockwise rotations inferred miocene localities. surprisingly clockwise rotations rotational autochthonous sedimentary cover tisza dacia megatectonic allochthonous flysch nappes pienides i.e. eastern alcapa mega tectonic unit. documented opposed remainder alcapa necessitates detachment eastern alcapa detachment margins transcarpathian depression. counter clockwise rotations area. timing rotations rotations documented east slovak basin apuseni mountains west carpathians west east slovak basin | non_dup | [] |
18245388 | 10.1007/s00015-007-1226-0 | The southernmost Upper Rhine Graben and adjacent Jura experienced basement- rooted shortening that occurred after the deposition of the Pliocene fluvial “Sundgau gravels”. Folds affecting the base of these gravels systematically trend NE to ENE. Combined evidence from reflection seismic lines and contour maps of the base-Tertiary and base-Pliocene levels indicates that these folds probably formed by thick-skinned reactivation of both NNE-SSW and WSW-ENE-striking faults. This thick-skinned shortening is NW-SE oriented, i.e. parallel to the maximum horizontal stresses inferred from seismotectonics. NNE-SSW-striking faults (paralleling the Upper Rhine Graben) have been reactivated in sinistral strike-slip mode. However, dextrally transpressive reactivation of the WSW-ENE-trending faults that belong to the Rhine-Bresse Transfer Zone is interpreted to predominate. Deflections of recent river courses around the crests of en-échelon-aligned surface anticlines suggest that the deformation is ongoing at present. Retro-deformation of the folds affecting the base of the Sundgau gravels indicates horizontal displacement rates of about 0.05 mm/a. This corresponds to a minimum strain rate in the order of 2·10-16 s-1, given the maximum time span of 2.9 Ma for this deformation, i.e. the biostratigraphically determined minimum age of the gravels. A change from thin-skinned tectonics, that prevailed during the main phase of Jura folding, to very probably still ongoing thick-skinned tectonics is inferred to have occurred in the Late Pliocene. We speculate that this change might be linked to the incipient inversion of Permo-Carboniferous troughs within the Alpine foreland in general. This inversion in dextrally transpressive or purely compressive mode along a WNW-ESE-trending basement fault, that is part of the Rhine-Bresse Transfer Zone, which in turn was prestructured during the formation of the Permo-Carboniferous troughs, could have triggered the 1356 Basel earthquake | Latest Pliocene to recent thick-skinned tectonics at the Upper RhineGraben – Jura Mountains junction | latest pliocene to recent thick-skinned tectonics at the upper rhinegraben – jura mountains junction | southernmost rhine graben adjacent jura experienced basement rooted shortening occurred deposition pliocene fluvial “sundgau gravels”. folds affecting gravels systematically ene. reflection seismic contour tertiary pliocene folds probably thick skinned reactivation striking faults. thick skinned shortening oriented i.e. stresses inferred seismotectonics. striking faults paralleling rhine graben reactivated sinistral strike slip mode. dextrally transpressive reactivation trending faults belong rhine bresse interpreted predominate. deflections river courses crests échelon aligned anticlines deformation ongoing present. retro deformation folds affecting sundgau gravels displacement span deformation i.e. biostratigraphically gravels. skinned tectonics prevailed jura folding probably ongoing thick skinned tectonics inferred occurred pliocene. speculate incipient inversion permo carboniferous troughs alpine foreland general. inversion dextrally transpressive purely compressive trending basement fault rhine bresse prestructured permo carboniferous troughs triggered basel earthquake | non_dup | [] |
18246208 | 10.1007/s00015-008-1247-3 | A correlation of tectonic units of the Alpine-Carpathian-Dinaridic system of orogens, including the substrate of the Pannonian and Transylvanian basins, is presented in the form of a map. Combined with a series of crustal-scale cross sections this correlation of tectonic units yields a clearer picture of the threedimensional architecture of this system of orogens that owes its considerable complexity to multiple overprinting of earlier by younger deformations. The synthesis advanced here indicates that none of the branches of the Alpine Tethys and Neotethys extended eastward into the Dobrogea Orogen. Instead, the main branch of the Alpine Tethys linked up with the Meliata- Maliac-Vardar branch of the Neotethys into the area of the present-day Inner Dinarides. More easterly and subsidiary branches of the Alpine Tethys separated Tisza completely, and Dacia partially, from the European continent. Remnants of the Triassic parts of Neotethys (Meliata-Maliac) are preserved only as ophiolitic mélanges present below obducted Jurassic Neotethyan (Vardar) ophiolites. The opening of the Alpine Tethys was largely contemporaneous with the Latest Jurassic to Early Cretaceous obduction of parts of the Jurassic Vardar ophiolites. Closure of the Meliata-Maliac Ocean in the Alps and West Carpathians led to Cretaceous-age orogeny associated with an eclogitic overprint of the adjacent continental margin. The Triassic Meliata- Maliac and Jurassic Western and Eastern Vardar ophiolites were derived from one single branch of Neotethys: the Meliata-Maliac-Vardar Ocean. Complex geometries resulting from out-of-sequence thrusting during Cretaceous and Cenozoic orogenic phases underlay a variety of multi-ocean hypotheses, that were advanced in the literature and that we regard as incompatible with the field evidence. The present-day configuration of tectonic units suggests that a former connection between ophiolitic units in West Carpathians and Dinarides was disrupted by substantial Miocene-age dislocations along the Mid-Hungarian Fault Zone, hiding a former lateral change in subduction polarity between West Carpathians and Dinarides. The SW-facing Dinaridic Orogen, mainly structured in Cretaceous and Palaeogene times, was juxtaposed with the Tisza and Dacia Mega-Units along a NW-dipping suture (Sava Zone) in latest Cretaceous to Palaeogene times. The Dacia Mega-Unit (East and South Carpathian Orogen, including the Carpatho-Balkan Orogen and the Biharia nappe system of the Apuseni Mountains), was essentially consolidated by E-facing nappe stacking during an Early Cretaceous orogeny, while the adjacent Tisza Mega-Unit formed by NW-directed thrusting (in present-day coordinates) in Late Cretaceous times. The polyphase and multi-directional Cretaceous to Neogene deformation history of the Dinarides was preceded by the obduction of Vardar ophiolites onto to the Adriatic margin (Western Vardar Ophiolitic Unit) and parts of the European margin (Eastern Vardar Ophiolitic Unit) during Late Jurassic to Early Cretaceous times | The Alpine-Carpathian-Dinaridic orogenic system : correlation and evolution of tectonic units | the alpine-carpathian-dinaridic orogenic system : correlation and evolution of tectonic units | tectonic alpine carpathian dinaridic orogens pannonian transylvanian basins map. crustal tectonic clearer picture threedimensional architecture orogens owes considerable overprinting younger deformations. advanced none branches alpine tethys neotethys eastward dobrogea orogen. branch alpine tethys meliata maliac vardar branch neotethys dinarides. easterly subsidiary branches alpine tethys separated tisza dacia partially continent. remnants triassic neotethys meliata maliac preserved ophiolitic mélanges obducted jurassic neotethyan vardar ophiolites. opening alpine tethys largely contemporaneous latest jurassic cretaceous obduction jurassic vardar ophiolites. closure meliata maliac ocean alps west carpathians cretaceous orogeny eclogitic overprint adjacent continental margin. triassic meliata maliac jurassic eastern vardar ophiolites branch neotethys meliata maliac vardar ocean. geometries thrusting cretaceous cenozoic orogenic underlay ocean hypotheses advanced regard incompatible evidence. tectonic former connection ophiolitic west carpathians dinarides disrupted substantial miocene dislocations hungarian fault hiding former lateral subduction polarity west carpathians dinarides. facing dinaridic orogen structured cretaceous palaeogene juxtaposed tisza dacia mega dipping suture sava latest cretaceous palaeogene times. dacia mega east carpathian orogen carpatho balkan orogen biharia nappe apuseni mountains essentially consolidated facing nappe stacking cretaceous orogeny adjacent tisza mega directed thrusting cretaceous times. polyphase directional cretaceous neogene deformation dinarides preceded obduction vardar ophiolites adriatic margin vardar ophiolitic margin eastern vardar ophiolitic jurassic cretaceous | non_dup | [] |
11252348 | 10.1007/s00015-008-1251-7 | This study documents ammonoids with a precise stratigraphic control at the middle/late Anisian (Pelsonian/Illyrian) boundary from a new locality in eastern Lombardy-Giudicarie (Monte Guglielmo) and from classical sections in Giudicarie. These ammonoid faunas allow revising the taxonomic interpretation of Ceratites cimeganus Mojsisovics 1882 and of the genus Paraceratites Hyatt 1900. Ceratites cimeganus is here assigned to the North American genus Rieppelites Monnet & Bucher 2005. In eastern Lombardy-Giudicarie, R. cimeganus is diagnostic of a distinct biochronological unit (cimeganus Zone) bracketed between the older Bulogites zoldianus Zone and the younger Judicarites euryomphalus–Paraceratites trinodosus zones. The recognition of this cimeganus Zone significantly improves worldwide correlation since it is recognized in several other Tethyan basins (Dolomites, Northern Calcareous Alps) as well as in North America (Nevada). These new data allow a redefinition of the middle/late Anisian boundary in the western Tethys, which is here intercalated between the zoldianus and cimeganus zones. This limit is marked by a clear ammonoid turnover (e.g. disappearance of Acrochordiceras and Balatonites, appearance of Rieppelites). Finally, the presence of sections including the cimeganus Zone in eastern Lombardy-Giudicarie allow the establishment of local gaps in sedimentation, which may reflect the regional and important transgression of the pelagic Prezzo Limestone over the shallow water platform carbonates of a “Camorelli-Dosso dei Morti barrier”, as also underlined by the spatial distribution of brachiopod lumachellas | Ammonoids of the Middle/Late Anisian boundary (Middle Triassic) and the transgression of the Prezzo Limestone in eastern Lombardy-Giudicarie (Italy) | ammonoids of the middle/late anisian boundary (middle triassic) and the transgression of the prezzo limestone in eastern lombardy-giudicarie (italy) | documents ammonoids precise stratigraphic anisian pelsonian illyrian locality eastern lombardy giudicarie monte guglielmo giudicarie. ammonoid faunas revising taxonomic ceratites cimeganus mojsisovics genus paraceratites hyatt ceratites cimeganus assigned genus rieppelites monnet bucher eastern lombardy giudicarie cimeganus diagnostic biochronological cimeganus bracketed older bulogites zoldianus younger judicarites euryomphalus–paraceratites trinodosus zones. recognition cimeganus improves worldwide recognized tethyan basins dolomites northern calcareous alps america nevada redefinition anisian tethys intercalated zoldianus cimeganus zones. marked ammonoid turnover e.g. disappearance acrochordiceras balatonites appearance rieppelites cimeganus eastern lombardy giudicarie establishment gaps sedimentation reflect transgression pelagic prezzo limestone shallow platform carbonates “camorelli dosso morti barrier” underlined brachiopod lumachellas | non_dup | [] |
18246207 | 10.1007/s00015-008-1259-z | This excursion guide results form a field trip to the Glarus nappe complex organized by the Swiss Tectonic Studies Group in 2006. The aim of the excursion was to discuss old and recent concepts related to the evolution of the Glarus thrust. The major aspects were (i) the interplay between deformation, fluid flow and geochemical alteration, (ii) episodic versus continuous deformation and fluid flow, and (iii) the link between large-scale structures, microstructures, and geochemical aspects. Despite 150 years of research in the Glarus nappe complex and the new results discussed during the excursion, there exist controversies that still are unsolved | The Glarus thrust : excursion guide and report of a field trip of the Swiss Tectonic Studies Group (Swiss Geological Society, 14.16. 09. 2006) | the glarus thrust : excursion guide and report of a field trip of the swiss tectonic studies group (swiss geological society, 14.16. 09. 2006) | excursion guide trip glarus nappe organized swiss tectonic excursion concepts glarus thrust. interplay deformation geochemical alteration episodic deformation microstructures geochemical aspects. glarus nappe excursion controversies unsolved | non_dup | [] |
18246525 | 10.1007/s00015-008-1288-7 | A map-view palinspastic restoration of tectonic units in the Alps, Carpathians and Dinarides reveals the plate tectonic configuration before the onset of Miocene to recent deformations. Estimates of shortening and extension from the entire orogenic system allow for a semi-quantitative restoration of translations and rotations of tectonic units during the last 20 Ma. Our restoration yielded the following results: (1) The Balaton Fault and its eastern extension along the northern margin of the Mid-Hungarian Fault Zone align with the Periadriatic Fault, a geometry that allows for the eastward lateral extrusion of the Alpine-Carpathian-Pannonian (ALCAPA) Mega-Unit. The Mid-Hungarian Fault Zone accommodated simultaneous strike-perpendicular shortening and strike-slip movements, concomitant with strike-parallel extension. (2) The Mid-Hungarian Fault Zone is also the locus of a former plate boundary transforming opposed subduction polarities between Alps (including Western Carpathians) and Dinarides. (3) The ALCAPA Mega-Unit was affected by 290 km extension and fits into an area W of present-day Budapest in its restored position, while the Tisza-Dacia Mega-Unit was affected by up to 180 km extension during its emplacement into the Carpathian embayment. (4) The external Dinarides experienced Neogene shortening of over 200 km in the south, contemporaneous with dextral wrench movements in the internal Dinarides and the easterly adjacent Carpatho-Balkan orogen. (5) NS convergence between the European and Adriatic plates amounts to some 200 km at a longitude of 14° E, in line with post-20 Ma subduction of Adriatic lithosphere underneath the Eastern Alps, corroborating the discussion of results based on high-resolution teleseismic tomography. The displacement of the Adriatic Plate indenter led to a change in subduction polarity along a transect through the easternmost Alps and to substantial Neogene shortening in the eastern Southern Alps and external Dinarides. While we confirm that slab-pull and rollback of oceanic lithosphere subducted beneath the Carpathians triggered back-arc extension in the Pannonian Basin and much of the concomitant folding and thrusting in the Carpathians, we propose that the rotational displacement of this indenter provided a second important driving force for the severe Neogene modifications of the Alpine-Carpathian-Dinaridic orogenic system | A map-view restoration of the Alpine-Carpathian-Dinaridic system for early miocene | a map-view restoration of the alpine-carpathian-dinaridic system for early miocene | palinspastic restoration tectonic alps carpathians dinarides reveals plate tectonic onset miocene deformations. shortening orogenic restoration translations rotations tectonic restoration yielded balaton fault eastern northern margin hungarian fault align periadriatic fault eastward lateral extrusion alpine carpathian pannonian alcapa mega unit. hungarian fault accommodated simultaneous strike perpendicular shortening strike slip movements concomitant strike extension. hungarian fault locus former plate transforming opposed subduction polarities alps carpathians dinarides. alcapa mega fits budapest restored tisza dacia mega emplacement carpathian embayment. dinarides experienced neogene shortening contemporaneous dextral wrench movements dinarides easterly adjacent carpatho balkan orogen. adriatic plates amounts longitude subduction adriatic lithosphere underneath eastern alps corroborating teleseismic tomography. displacement adriatic plate indenter subduction polarity transect easternmost alps substantial neogene shortening eastern southern alps dinarides. confirm slab pull rollback oceanic lithosphere subducted beneath carpathians triggered pannonian basin concomitant folding thrusting carpathians propose rotational displacement indenter driving neogene modifications alpine carpathian dinaridic orogenic | non_dup | [] |
18246526 | 10.1007/s00015-008-1289-6 | The Cenozoic-age metamorphic structure of the Alps consists of a throughgoing pressure-dominated belt (blueschists and eclogites) that strikes parallel to the orogen and was later truncated by two thermal domes characterised by Barrow-type metamorphism (Lepontine dome and Tauern window). This study documents for the first time that relics of Fe-Mg carpholite occur also within meta-sedimentary units that are part of the north-eastern Lepontine structural and metamorphic dome, where so far exclusively Barrovian assemblages were found. They occur in meta-sediments of both Valais Oceanderived Lower Penninic Bündnerschiefer and structurally lower Europe-derived Sub-Penninic cover nappes and slices. These high-pressure units were subsequently overprinted by a thermal event, as is documented by the growth of new minerals typical for Barrovian metamorphism. We present evidence for a two-stage metamorphic evolution in the northern part of the Lepontine dome: (1) Early subduction-related syn-D1 (Safienphase) HP/LT metamorphism under blueschist facies conditions (350–400 °C and 1.2–1.4 GPa) was immediately followed by “cold” isothermal (or cooling) decompression during D2 nappe-stacking (Ferrera phase). (2) Collisionrelated Barrovian overprint (500–570 °C and 0.5–0.8 GPa) postdates the D3 nappe-refolding event (Domleschg phase) and represents a late heating pulse, separated by D2 and D3 from the D1 high-pressure event. It occurred before and/or during the initial stages of D4 (Chièra phase) representing a second nappe-refolding event. In discussing possible heat sources for the late Barrow-type heating pulse it is argued that heat release from radioactive decay of accreted material may play an important role in contributing much to heat production. Based on the field evidence, we conclude that heat transfer was essentially conductive during these latest stages of the thermal evolution | From subduction to collision : thermal overprint of HP/LT meta-sediments in the north-eastern Leopontine Dome (Swiss Alps) and consequences regarding the tectono-metamorphic evolution of the Alpine orogenic wedge | from subduction to collision : thermal overprint of hp/lt meta-sediments in the north-eastern leopontine dome (swiss alps) and consequences regarding the tectono-metamorphic evolution of the alpine orogenic wedge | cenozoic metamorphic alps throughgoing dominated belt blueschists eclogites strikes orogen truncated domes characterised barrow metamorphism lepontine dome tauern window documents relics carpholite meta sedimentary eastern lepontine metamorphic dome exclusively barrovian assemblages found. meta sediments valais oceanderived penninic bündnerschiefer structurally europe penninic cover nappes slices. subsequently overprinted documented minerals barrovian metamorphism. metamorphic northern lepontine dome subduction safienphase metamorphism blueschist facies immediately “cold” isothermal cooling decompression nappe stacking ferrera collisionrelated barrovian overprint postdates nappe refolding domleschg heating separated event. occurred chièra representing nappe refolding event. discussing barrow heating argued radioactive accreted contributing production. essentially conductive latest | non_dup | [] |
18245391 | 10.1007/s00015-008-1300-2 | Seismic source characterization is performed as part of the PEGASOS project for the assessment of the seismic hazard at the 4 sites of the Swiss Nuclear Power Plants. The analysis is performed according to the Level 4 procedures for expert elicitation defined in the guidelines of the US Nuclear Regulatory Committee whereby the quantification of uncertainties plays a crucial role. According to our analysis, which is one amongst four that were performed in the frame of PEGASOS, the most important epistemic uncertainty is related to the question as to weather basement-rooted faults at the margins of pre-existing Permo-Carboniferous troughs are prone for compressive or transpressive reactivation under the present-day stress field or not. The question after the present-day style of deformation in the Alpine foreland (thick-skinned versus thin-skinned) is closely related to this key question. Together with the consideration of uncertainties regarding the mapping of seismogenic zones and/or line sources alternative zonations are presented in form of a logic tree with 21 branches. Area sources play a predominant role in the working area located at the margin of a diffuse plate boundary. Earthquake recurrence relationships are discussed by taking into account a series of uncertainties. These concern the evaluation of b-values and the evaluation of a-values once the b-values were fixed. Both parameters in the Gutenberg-Richter law are based on non-perfect and incomplete catalogue data that were carefully analysed beforehand. Since PEGASOS demanded an analysis of annual probabilities down to one event in 107 years, the question after the value of the maximum possible earthquake magnitude Mmax and related error in Mmax estimates plays a crucial role. We estimate Mmax by using geological as well as statistical methods. Mmax = 6.9 cannot be excluded in most areas, in the Basel area Mmax = 7.3 is possible. Uncertainties in a, b and Mmax are again discussed in form of a logic tree, this time with 18 branches. Hence the final logic tree has 378 branches and represents the seismic source characterization input into PSHA that takes account of all uncertainties we are aware of. Betr. u.a. Erdbebengefährdung in der Region Base | Seismic source characterization of the Alpine foreland in the context of a probabilistic seismic hazard analysis by PEGSOS Expert Group 1 (EG1a) | seismic source characterization of the alpine foreland in the context of a probabilistic seismic hazard analysis by pegsos expert group 1 (eg1a) | seismic pegasos seismic hazard swiss plants. expert elicitation guidelines regulatory committee whereby quantification plays crucial role. amongst pegasos epistemic weather basement rooted faults margins permo carboniferous troughs prone compressive transpressive reactivation not. style deformation alpine foreland thick skinned skinned closely question. consideration seismogenic zones zonations logic branches. predominant margin diffuse plate boundary. earthquake recurrence uncertainties. concern fixed. gutenberg richter perfect incomplete catalogue carefully analysed beforehand. pegasos demanded probabilities earthquake mmax mmax plays crucial role. mmax geological methods. mmax excluded basel mmax possible. mmax logic branches. logic branches seismic psha aware betr. u.a. erdbebengefährdung | non_dup | [] |
60250 | 10.1007/s00015-008-1301-1 | The seismic hazard model used in the PEGASOS project for assessing earth-quake hazard at four NPP sites was a composite of four sub-models, each produced by a team of three experts. In this paper, one of these models is described in detail by the authors. A criticism sometimes levelled at probabilistic seismic hazard studies is that the process by which seismic source zones are arrived at is obscure, subjective and inconsistent. Here, we attempt to recount the stages by which the model evolved, and the decisions made along the way. In particular, a macro-to-micro approach was used, in which three main stages can be described. The first was the characterisation of the overall kinematic model, the “big picture” of regional seismogenesis. Secondly, this was refined to a more detailed seismotectonic model. Lastly, this was used as the basis of individual sources, for which parameters can be assessed. Some basic questions had also to be answered about aspects of the approach to modelling to be used: for instance, is spatial smoothing an appropriate tool to apply? Should individual fault sources be modelled in an intraplate environment? Also, the extent to which alternative modelling decisions should be expressed in a logic tree structure has to be considered. \u | Preparing a seismic hazard model for Switzerland : the view from PEGASOS expert group 3 (EG1c) | preparing a seismic hazard model for switzerland : the view from pegasos expert group 3 (eg1c) | seismic hazard pegasos assessing earth quake hazard composite team experts. authors. criticism sometimes levelled probabilistic seismic hazard seismic zones arrived obscure subjective inconsistent. attempt recount evolved decisions way. macro micro described. characterisation kinematic “big picture” seismogenesis. secondly refined seismotectonic model. lastly assessed. answered smoothing fault modelled intraplate decisions logic considered. | non_dup | [] |
19725360 | 10.1007/s00015-009-1317-1 | The Bathonian Global Stratotype Section and Point (GSSP) is proposed at\ud
the base of limestone bed RB071 (bed 23 in Sturani 1967) in the Ravin du\ud
Bès Section (43º 57' 38" N, 6º 18' 55" E), Bas-Auran area, “Alpes de Haute\ud
Provence” French department. The Ravin du Bès Section, as formal candidate\ud
GSSP for the base of the Bathonian Stage, satisfies most of the requirements\ud
recommended by the International Commission on Stratigraphy: 1) The exposure\ud
extends over 13 m in thickness. At the Bajocian-Bathonian transition,\ud
no vertical (bio-, ichno- or tapho-) facies changes, condensation, stratigraphic\ud
gaps or hiatuses have been recorded. Structural complexity, synsedimentary\ud
and tectonic disturbances, or important alterations by metamorphism are not\ud
relevant constraints. 2) There is a well-preserved, abundant and diverse fossil\ud
record across the boundary interval, with key markers (ammonites and\ud
nannofossils) for worldwide correlation. The base of the Bathonian Stage\ud
and Zigzag Zone in Bas-Auran corresponds to the first occurrence level of\ud
Gonolkites convergens Buckman, which coincides with the first occurrence of\ud
Morphoceras parvum Wetzel. Calcareous nannofossils, as secondary global\ud
marker, are present in all beds and allow characterizing the Bajocian-Bathonian\ud
transition. 3) Regional analyses of sequence stratigraphy and manganese\ud
chemostratigraphy are available. Spectral gamma-ray data corroborate an\ud
Early Bathonian deepening half-cycle of second order. 4) The criteria of accessibility,\ud
conservation and protection are assured by the “Réserve Naturelle\ud
Géologique de Haute Provence”. The Cabo Mondego Section (Portugal) is\ud
suggested as the Bathonian auxiliary section and point (ASSP) within this\ud
GSSP proposal | Formal proposal for the Bathonian GSSP (Middle Jurassic) in the\ud
Ravin du Bès Section (Bas-Auran, SE France) | formal proposal for the bathonian gssp (middle jurassic) in the\ud ravin du bès section (bas-auran, se france) | bathonian stratotype gssp limestone sturani ravin auran “alpes haute provence” french department. ravin formal candidate gssp bathonian satisfies recommended commission stratigraphy extends thickness. bajocian bathonian ichno tapho facies condensation stratigraphic gaps hiatuses recorded. synsedimentary tectonic disturbances alterations metamorphism constraints. preserved abundant diverse fossil record markers ammonites nannofossils worldwide correlation. bathonian zigzag auran occurrence gonolkites convergens buckman coincides occurrence morphoceras parvum wetzel. calcareous nannofossils marker beds characterizing bajocian bathonian transition. stratigraphy manganese chemostratigraphy available. gamma corroborate bathonian deepening order. accessibility conservation protection assured “réserve naturelle géologique haute provence”. cabo mondego portugal bathonian auxiliary assp gssp proposal | non_dup | [] |
16209005 | 10.1007/s00015-012-0098-0 | Thrusting fault zone in foreland basins are characterized by highly foliated zones generally enriched in phyllosilicates which can play a major role on the mechanical behaviour of the fault. In this context, investigations of synkinematic clay minerals permit to determine the origin of the fluid from which they precipitated as well as the mechanisms of deformation. Our study is focused on clay mineral assemblages (illite and chlorite) in a major thrust fault located in the Monte Perdido massif (southern Pyrenees), a shallow thrust that affects upper cretaceouspaleocene platform carbonates and lower Eocene marls and turbidites | Microtextural investigation (SEM and TEM study) of phyllosilicates in a major thrust fault zone (Monte Perdido, southern Pyrenees): impact on fault reactivation | microtextural investigation (sem and tem study) of phyllosilicates in a major thrust fault zone (monte perdido, southern pyrenees): impact on fault reactivation | thrusting fault foreland basins foliated zones enriched phyllosilicates fault. investigations synkinematic clay minerals permit precipitated deformation. focused clay mineral assemblages illite chlorite thrust fault monte perdido massif southern pyrenees shallow thrust affects cretaceouspaleocene platform carbonates eocene marls turbidites | non_dup | [] |
80685961 | 10.1007/s00015-016-0238-z | CB acknowledges financial support from Optimus (Aberdeen) ltd. Petroceltic International plc are thanked for providing access to the subsurface data used in this study and for permission to publish images used here. Schlumberger are thanked for providing use of Petrel software under their academic agreement with the University of Aberdeen. RWHB thanks the organisers of the 12th Emile Argand Conference on Alpine Geological Studies for the invitation and financial support to participate in the Montgenevre workshop. Reviewers Enrico Tavarnelli, Thierry Dumont and editors Christian Sue and Stefan Schmid are all thanked for their comments that have significantly improved this contribution.Peer reviewedPublisher PD | Platform-basin transitions and their role in Alpine-style collision systems : a comparative approach | platform-basin transitions and their role in alpine-style collision systems : a comparative approach | acknowledges optimus aberdeen ltd. petroceltic thanked subsurface permission publish here. schlumberger thanked petrel academic aberdeen. rwhb thanks organisers emile argand alpine geological invitation participate montgenevre workshop. reviewers enrico tavarnelli thierry dumont editors christian stefan schmid thanked comments contribution.peer reviewedpublisher | non_dup | [] |
185269721 | 10.1007/s00015-018-0327-2 | We have investigated successive episodes of ocean-continent and continent–continent convergence in Western Serbia\ud
(Drina-Ivanjica thrust sheet). The coupled application of structural and petrological analyses with Illite Crystallinity measurements and K/Ar dating has revealed the timing and structural characteristics of multiple regional deformation phases, and allowed us to revise the origin of the different Triassic units outcropping in the study area. D1 tectonic burial was characterized by anchizonal metamorphism, dominantly WNW-verging isoclinal folding (F1), and related axial planar cleavage (S1) formation in the Paleozoic basement and the stratigraphic cover of the Drina-Ivanjica thrust sheet exposed along the northern rim of this thrust sheet. The timing of D1 deformation is constrained by K/Ar ages suggesting 135–150 Ma tectonic burial for the Drina-Ivanjica thrust sheet. D1 deformation and metamorphism is correlated with the closure of the Vardar ocean by top-W to NW ophiolite obduction and the underthrusting of the Adriatic distal passive margin below the oceanic upper plate. Since D1 structures are lacking in the southern occurrences of Triassic rocks within the study area it is proposed that this Triassic is may not be the original sedimentary cover of the Drina-Ivanjica Paleozoic\ud
basement. We propose that this southern Triassic originated from a more external Dinaridic thrust sheet and was transported to its present-day position by a top-NE backthrust presumably during late Early Cretaceous–Paleogene times. Mapscale, NW–SE striking D2 thrust faults and abundant NW–SE trending F2 folds observed in all units correspond to the general trend of the Dinaridic orogen and are attributed to the latest Cretaceous–Paleogene collision between Adria and Europe. Regional Latest Cretaceous–Paleogene shortening was followed by strike-slip tectonics (N–S shortening and perpendicular extension) and subsequent Miocene normal faulting in both orogen-parallel and orogen-perpendicular directions driven by slab rollback processes of the Carpathian-Dinaridic realm | Structural and geochronological constraints from the Drina-Ivanjica thrust sheet (Western Serbia): implications for the Cretaceous–Paleogene tectonics of the Internal Dinarides | structural and geochronological constraints from the drina-ivanjica thrust sheet (western serbia): implications for the cretaceous–paleogene tectonics of the internal dinarides | successive episodes ocean continent continent–continent serbia drina ivanjica thrust sheet petrological illite crystallinity dating timing deformation revise triassic outcropping area. tectonic burial anchizonal metamorphism dominantly verging isoclinal folding axial planar cleavage paleozoic basement stratigraphic cover drina ivanjica thrust sheet exposed northern thrust sheet. timing deformation constrained ages tectonic burial drina ivanjica thrust sheet. deformation metamorphism closure vardar ocean ophiolite obduction underthrusting adriatic distal passive margin oceanic plate. lacking southern occurrences triassic rocks triassic sedimentary cover drina ivanjica paleozoic basement. propose southern triassic originated dinaridic thrust sheet transported backthrust presumably cretaceous–paleogene times. mapscale nw–se striking thrust faults abundant nw–se trending folds dinaridic orogen attributed latest cretaceous–paleogene collision adria europe. latest cretaceous–paleogene shortening strike slip tectonics shortening perpendicular miocene faulting orogen orogen perpendicular directions slab rollback carpathian dinaridic realm | non_dup | [] |
2642458 | 10.1007/s00016-007-0326-6 | Julian Schwinger's influence on twentieth century science is profound and
pervasive. Of course, he is most famous for his renormalization theory of
quantum electrodynamics, for which he shared the Nobel Prize with Richard
Feynman and Sin-itiro Tomonaga. But although this triumph was undoubtedly his
most heroic work, his legacy lives on chiefly through subtle and elegant work
in classical electrodynamics, quantum variational principles, proper-time
methods, quantum anomalies, dynamical mass generation, partial symmetry, and
more. Starting as just a boy, he rapidly became the pre-eminent nuclear
physicist in the late 1930s, led the theoretical development of radar
technology at MIT during World War II, and then, soon after the war, conquered
quantum electrodynamics, and became the leading quantum field theorist for two
decades, before taking a more iconoclastic route during his last quarter
century.Comment: 54 pages, no figure | Julian Schwinger: Nuclear Physics, the Radiation Laboratory,
Renormalized QED, Source Theory, and Beyond | julian schwinger: nuclear physics, the radiation laboratory, renormalized qed, source theory, and beyond | julian schwinger twentieth century profound pervasive. famous renormalization electrodynamics shared nobel prize richard feynman itiro tomonaga. triumph undoubtedly heroic legacy lives chiefly subtle elegant electrodynamics variational principles proper anomalies more. rapidly became eminent physicist radar soon conquered electrodynamics became theorist decades iconoclastic route quarter pages | non_dup | [] |
1942006 | 10.1007/s00016-008-0395-1 | One of the less known facets of Ludwig Boltzmann was that of an advocate of
Aviation, one of the most challenging technological problems of his times.
Boltzmann followed closely the studies of pioneers like Otto Lilienthal in
Berlin, and during a lecture on a prestigious conference he vehemently defended
further investments in the area. In this article I discuss his involvement with
Aviation, his role in its development and his correspondence with two flight
pioneers, Otto Lilienthal e Wilhelm Kress.Comment: 15 pages, no figure | Boltzmann and the art of flying | boltzmann and the art of flying | facets ludwig boltzmann advocate aviation challenging technological times. boltzmann closely pioneers otto lilienthal berlin lecture prestigious vehemently defended investments area. involvement aviation correspondence flight pioneers otto lilienthal wilhelm pages | non_dup | [] |
78519488 | 10.1007/s00016-013-0122-4 | We provide a tour of Barcelona, Catalonia, Spain, following four routes through the city and one elsewhere in the city and beyond, focusing on sites of importance in physics. Route 1 covers the Old Town, its Gothic Quarter, Plaça del Rei, Plaça de Sant Jaume, and Jewish Quarter. Route 2 identifies sites on and close to La Rambla, the main promenade in the city. Route 3 goes from the medieval shipyards to the Board of Commerce to Citadel Park. Route 4 concentrates on the Extension (Eixample) and covers the restored University, the Industrial University, and the new campus of the University of Barcelona. Elsewhere in the city and beyond are the Fabra Observatory; the Plaça de les Glòries with its large steel sculpture depicting the meridian arc from Dunkirk to Barcelona; Montjuïc, the site of the National Art Museum of Catalonia; and the National Museum of Science and Technology in Terrassa | Physical Science in Barcelona | physical science in barcelona | tour barcelona catalonia spain routes city elsewhere city focusing physics. route covers town gothic quarter plaça plaça sant jaume jewish quarter. route identifies rambla promenade city. route goes medieval shipyards board commerce citadel park. route concentrates eixample covers restored industrial campus barcelona. elsewhere city fabra observatory plaça glòries steel sculpture depicting meridian dunkirk barcelona montjuïc museum catalonia museum terrassa | non_dup | [] |
42735184 | 10.1007/s00016-016-0185-0 | The modern picture of the neutrino as a multiple mass highly mixed neutral
particle has emerged over 40 years of study. Best known of the issues leading
to this picture was the apparent loss of neutrinos coming from the sun. This
article describes another piece of evidence that supports the picture; the
substantial reduction of high energy muon type neutrinos observed in nature.
For much of the 40 year period, before the modern picture emerged this
observation was known as the "atmospheric neutrino anomaly", since as will be
seen, these neutrinos originate in the Earth's atmosphere.
This paper describes the discovery of the atmospheric neutrino anomaly. We
explore the scientific context and motivations in the late 1970's from which
this work emerged. The gradual awareness that the observations of atmospheric
neutrinos were not as expected took place in the 1983-1986 period.Comment: 46 pages, 24 figures. To be published in Physics in Perspective
Version 2 has a table of contents, a table of figures and the DOI added The
final publication is available at Springer via
http://dx.doi.org/10.1007/s00016-016-0185- | History of "Anomalous" Atmospheric Neutrino Events: A First Person
Account | history of "anomalous" atmospheric neutrino events: a first person account | modern picture neutral emerged study. picture apparent neutrinos coming sun. describes piece supports picture substantial muon neutrinos nature. modern picture emerged anomaly neutrinos originate earth atmosphere. describes discovery anomaly. explore motivations emerged. gradual awareness neutrinos took pages figures. perspective contents publication springer | non_dup | [] |
83837111 | 10.1007/s00016-017-0195-6 | We aim to carry out an assessment of the scientific value of Oppenheimer's
research on black holes in order to determine and weigh possible factors to
explain its neglect by the scientific community, and even by Oppenheimer
himself. Dealing primarily with the science and looking closely at the
scientific culture and the scientific conceptual belief system of the 1930s,
the present article seeks to supplement the existent literature on the subject
by enriching the explanations and possibly complicating the guiding questions.
We suggest a rereading of Oppenheimer as a more intriguing, ahead-of-his-time
figure.Comment: 19 pages, Phys. Perspect. (2017 | The Early Scientific Contributions of J. Robert Oppenheimer: Why Did the
Scientific Community Miss the Black Hole Opportunity? | the early scientific contributions of j. robert oppenheimer: why did the scientific community miss the black hole opportunity? | carry oppenheimer holes weigh neglect oppenheimer himself. dealing primarily looking closely conceptual belief seeks supplement existent enriching explanations possibly complicating guiding questions. rereading oppenheimer intriguing ahead pages phys. perspect. | non_dup | [] |
11246876 | 10.1007/s00018-002-8453-3 | Viral infections are serious battles between pathogens and hosts. They can result in cell death, elimination of the virus or latent infection keeping both cells and pathogens alive. The outcome of an infection is often determined by cell signalling. Viruses deliver genomes and proteins with signalling potential into target cells and thereby alter the metabolism of the host. Virus interactions with cell surface receptors can elicit two types of signals, conformational changes of viral particles, and intracellular signals triggering specific cellular reactions. Responses by cells include stimulation of innate and adaptive immunity, growth, proliferation, survival and apoptosis. In addition, virus-activated cell signalling boosts viral entry and gene delivery, as recently shon for adenoviruses and adeno-associated viruses. This review illustrates that multiple activation of host cells during viral entry profoundly impacts the elaborate relationship between hosts and viral pathogens | Signalling in viral entry. | signalling in viral entry. | viral infections serious battles pathogens hosts. elimination latent keeping pathogens alive. signalling. viruses deliver genomes signalling thereby alter metabolism host. receptors elicit conformational viral intracellular triggering reactions. stimulation innate adaptive immunity proliferation apoptosis. signalling boosts viral entry delivery shon adenoviruses adeno viruses. illustrates viral entry profoundly impacts elaborate hosts viral pathogens | non_dup | [] |
11246759 | 10.1007/s00018-002-8509-4 | Clustering of neurotransmitter receptors in the postsynaptic membrane is critical for efficient synaptic transmission. During neuromuscular synaptogenesis, clustering of acetylcholine receptors (AChRs) is an early sign of postsynaptic differentiation. Recent studies have revealed that the earliest AChR clusters can form in the muscle independent of motorneurons. Neurally released agrin, acting through the muscle-specific kinase MuSK and rapsyn, then causes further clustering and localization of clusters underneath the nerve terminal. AChRs themselves are required for agrin-induced clustering of several postsynaptic proteins, most notably rapsyn. Once formed, AChR clusters are stabilized by several tyrosine kinases and by components of the dystrophin/utrophin glycoprotein complex, some of which also direct postnatal synaptic maturation such as formation of postjunctional folds. This review summarizes these recent results about AChR clustering, which indicate that early clustering can occur in the absence of nerves, that AChRs play an active role in the clustering process and that partly different mechanisms direct formation versus stabilization of AChR clusters | Neuromuscular synaptogenesis: clustering of acetylcholine receptors revisited. | neuromuscular synaptogenesis: clustering of acetylcholine receptors revisited. | clustering neurotransmitter receptors postsynaptic synaptic transmission. neuromuscular synaptogenesis clustering acetylcholine receptors achrs postsynaptic differentiation. earliest achr motorneurons. neurally released agrin acting musk rapsyn clustering localization underneath nerve terminal. achrs agrin clustering postsynaptic notably rapsyn. achr stabilized tyrosine kinases dystrophin utrophin glycoprotein postnatal synaptic maturation postjunctional folds. summarizes achr clustering clustering nerves achrs clustering partly stabilization achr | non_dup | [] |
38275525 | 10.1007/s00018-005-5260-7 | To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldVernix caseosa is a white cream-like substance that covers the skin of the foetus and the newborn baby. Recently, we discovered antimicrobial peptides/proteins such as LL-37 in vernix, suggesting host defence functions of vernix. In a proteomic approach, we have continued to characterize proteins in vernix and have identified 20 proteins, plus additional variant forms. The novel proteins identified, considered to be involved in host defence, are cystatin A, UGRP-1, and calgranulin A, B and C. These proteins add protective functions to vernix such as antifungal activity, opsonizing capacity, protease inhibition and parasite inactivation. The composition of the lipids in vernix has also been characterized and among these compounds the free fatty acids were found to exhibit antimicrobial activity. Interestingly, the vernix lipids enhance the antimicrobial activity of LL-37 in vitro, indicating interactions between lipids and antimicrobial peptides in vernix. In conclusion, vernix is a balanced cream of compounds involved in host defence, protecting the foetus and newborn against infection | Vernix caseosa as a multi-component defence system based on polypeptides, lipids and their interactions | vernix caseosa as a multi-component defence system based on polypeptides, lipids and their interactions | publisher article. please click hyperlink links fieldvernix caseosa cream substance covers foetus newborn baby. discovered antimicrobial peptides vernix defence vernix. proteomic continued characterize vernix variant forms. defence cystatin ugrp calgranulin protective vernix antifungal opsonizing protease parasite inactivation. lipids vernix fatty exhibit antimicrobial activity. interestingly vernix lipids enhance antimicrobial lipids antimicrobial peptides vernix. vernix balanced cream defence protecting foetus newborn | non_dup | [] |
53974248 | 10.1007/s00018-006-6039-1 | The use of anti-5-methylcytosine antibodies in affinity columns allowed the identification of methylated sequences in the genome of Drosophila melanogaster adults. In view of the presence of transposable elements amongst the identified sequences, it has been suggested that DNA methylation is involved in transposon control in the fly genome. On the contrary, a re-analysis of these data can furnish several intriguing elements that could open new questions about the role that DNA methylation plays in the fly genome. The aim of the present paper is to discuss some features that emerge from the analysis of the identified methylated sequences | DNA methylation of fly genes and transposons | dna methylation of fly genes and transposons | methylcytosine antibodies affinity columns methylated drosophila melanogaster adults. transposable amongst methylation transposon genome. contrary furnish intriguing methylation plays genome. emerge methylated | non_dup | [] |
11249045 | 10.1007/s00018-006-6081-z | Nicotinic acetylcholine receptors (nAChRs) exist in many subtypes and are found in the peripheral and central nervous system where they mediate or modulate synaptic transmission. We review how tyrosine phosphorylation and kinases regulate muscle and neuronal nAChRs. Interestingly, although some of the same kinase players interact with the various receptor subtypes, the functional consequences are different. While concerted action of MuSK, Abl- and Src-family kinases (SFKs) regulates the synaptic distribution of nAChRs at the neuromuscular junction, SFKs activate heteromeric neuronal nAChRs in adrenal chromaffin cells, thereby enhancing catecholamine secretion. In contrast, the activity of homomeric neuronal nAChRs, as found in the hippocampus, is negatively regulated by tyrosine phosphorylation and SFKs. It appears that tyrosine kinases provide the means to regulate all nAChRs; but the functional consequences, even those caused by the same kinase family, are specific for each receptor subtype and location | Regulation of nicotinic acetylcholine receptors by tyrosine kinases in the peripheral and central nervous system: same players, different roles | regulation of nicotinic acetylcholine receptors by tyrosine kinases in the peripheral and central nervous system: same players, different roles | nicotinic acetylcholine receptors nachrs subtypes peripheral nervous mediate modulate synaptic transmission. tyrosine phosphorylation kinases regulate neuronal nachrs. interestingly players interact subtypes consequences different. concerted musk kinases sfks regulates synaptic nachrs neuromuscular junction sfks activate heteromeric neuronal nachrs adrenal chromaffin thereby enhancing catecholamine secretion. homomeric neuronal nachrs hippocampus negatively regulated tyrosine phosphorylation sfks. tyrosine kinases regulate nachrs consequences subtype | non_dup | [] |
36025292 | 10.1007/s00018-006-6249-6 | El pdf del artículo es la versión de autor.Betaine homocysteine methyltransferase (BHMT), a Zn2+-dependent thiolmethyltransferase, contributes to the regulation of homocysteine levels, whose increases are considered a risk factor for cardiovascular diseases. Most plasma homocysteine is generated through the liver methionine cycle, in which BHMT metabolizes approximately 25% of this non-protein amino acid. This process allows recovery of one of the three methylation equivalents used in phosphatidylcholine synthesis through transmethylation, a major homocysteine producing pathway. Although BHMT has been known for over 40 years the difficulties encountered in its isolation precluded detailed studies until very recently. Thus, the last 10 years, since the sequence became available, have yielded extensive structural and functional data. Moreover, recent findings offer clues for potential new functions for BHMT. The purpose of this review is to provide an integrated view of the knowledge available on BHMT, and to analyze its putative roles in other processes through interactions undercover to date.Ministerio de Educación y Ciencia (PM 97/0064, BMC 2002-0243 and BFU 2005-00050 to M.A.P. and SAF 2003-03713 to D.P-S.) and Fondo de Investigación Sanitaria (FIS 01/1077 and RCMN C03/08 to M.A.P.Peer reviewe | Betaine homocysteine S-methyltransferase: just a regulator of homocysteine metabolism? | betaine homocysteine s-methyltransferase: just a regulator of homocysteine metabolism? | artículo versión autor.betaine homocysteine methyltransferase bhmt thiolmethyltransferase contributes homocysteine cardiovascular diseases. homocysteine methionine bhmt metabolizes acid. recovery methylation equivalents phosphatidylcholine transmethylation homocysteine producing pathway. bhmt difficulties encountered isolation precluded recently. became yielded extensive data. offer clues bhmt. bhmt analyze putative roles undercover date.ministerio educación ciencia m.a.p. fondo investigación sanitaria rcmn m.a.p.peer reviewe | non_dup | [] |
70290067 | 10.1007/s00018-007-6554-8 | Monothiol glutaredoxins with the CGFS sequence at the active site are widespread among prokaryotes and eukaryotes. Two subclasses exist, those with a single glutaredoxin domain and those with a thioredoxin-like region followed by one or
more glutaredoxin domains. Studies in Saccharomyces cerevisiae have demonstrated the role of the Grx5 protein in the biogenesis of iron-sulphur clusters. Grx5 homologues in other eukaryotes could carry out similar functions. Two S. cerevisiae monothiol glutaredoxins with the thioredoxin-like extension, Grx3 and Grx4, are modulators of the transcriptional activator Aft1, which regulates iron uptake in yeast. The human PICOT protein is a Grx3/Grx4 homologue with the same hybrid primary structure, which regulates protein kinase C activity and may participate in physiological processes such as control of cardiac function. Therefore, monothiol glutaredoxins share a common basic structural motif and biochemical mechanism of action, while participating in a diversity of cellular functions as protein redox regulators | Monothiol glutaredoxins: a common domain for multiple functions | monothiol glutaredoxins: a common domain for multiple functions | monothiol glutaredoxins cgfs widespread prokaryotes eukaryotes. subclasses glutaredoxin thioredoxin glutaredoxin domains. saccharomyces cerevisiae biogenesis iron sulphur clusters. homologues eukaryotes carry functions. cerevisiae monothiol glutaredoxins thioredoxin modulators transcriptional activator regulates iron uptake yeast. picot homologue hybrid regulates participate physiological function. monothiol glutaredoxins share motif biochemical participating diversity redox regulators | non_dup | [] |
18153864 | 10.1007/s00018-007-7006-1 | Glycogen synthase 2 (Gys-2) is the ratelimiting enzyme in the storage of glycogen in liver and adipose tissue, yet little is known about regulation of Gys-2 transcription. The peroxisome proliferator-activated receptors (PPARs) are transcription factors involved in the regulation of lipid and glucose metabolism and might be hypothesized to govern glycogen synthesis as well. Here, we show that Gys-2 is a direct target gene of PPARalpha, PPARbeta/delta and PPARgamma. Expression of Gys-2 is significantly reduced in adipose tissue of PPARalpha-/-, PPARbeta/delta-/- and PPARgamma+/- mice. Furthermore, synthetic PPARbeta/delta, and gamma agonists markedly up-regulate Gys-2 mRNA and protein expression in mouse 3T3-L1 adipocytes. In liver, PPARalpha deletion leads to decreased glycogen levels in the refed state, which is paralleled by decreased expression of Gys-2 in fasted and refed state. Two putative PPAR response elements (PPREs) were identified in the mouse Gys-2 gene: one in the upstream promoter (DR-1prom) and one in intron 1 (DR-1int). It is shown that DR-1int is the response element for PPARs, while DR-1prom is the response element for Hepatic Nuclear Factor 4 alpha (HNF4alpha). In adipose tissue, which does not express HNF4alpha, DR-1prom is occupied by PPARbeta/delta and PPARgamma, yet binding does not translate into transcriptional activation of Gys-2. Overall, we conclude that mouse Gys-2 is a novel PPAR target gene and that transactivation by PPARs and HNF4alpha is mediated by two distinct response elements | Glycogen synthase 2 is a novel target gene of peroxisome proliferator-activated receptors. | glycogen synthase 2 is a novel target gene of peroxisome proliferator-activated receptors. | glycogen synthase ratelimiting enzyme storage glycogen adipose transcription. peroxisome proliferator receptors ppars glucose metabolism hypothesized govern glycogen well. pparalpha pparbeta delta ppargamma. adipose pparalpha pparbeta delta ppargamma mice. synthetic pparbeta delta gamma agonists markedly regulate adipocytes. pparalpha deletion glycogen refed paralleled fasted refed state. putative ppar ppres upstream promoter prom intron ppars prom hepatic alpha alpha adipose express alpha prom occupied pparbeta delta ppargamma translate transcriptional ppar transactivation ppars alpha | non_dup | [] |
53974236 | 10.1007/s00018-007-7231-7 | DNA methylation is generally limited to CpG doublets located at gene promoter with an involvement in gene silencing. Surprisingly, two recent papers showed an extensive methylation affecting coding portions of transcriptionally active genes in human and plants prompting a rethink of DNA methylation in eukaryotes. Actually, gene body methylation is not surprising since it was repeatedly reported in invertebrates, where it interferes with transcriptional elongation preventing aberrant transcription initiations. As a whole, data published suggest that the most ancestral function of DNA methylation is the control of genes that are susceptible to transcriptional interference and not to gene silencing. The recruitment of DNA methylation for silencing represents a successive tinkered use. In view of this additional function, invertebrate-vertebrates transition has been accompanied by new constrains on DNA methylation that resulted in the strong conservation of the DNA methylation machinery in vertebrates and in the non-viability of mutants lacking DNA methylation | A new synthesis in epigenetics: towards an unified function of DNA methylation from invertebrates to vertebrates | a new synthesis in epigenetics: towards an unified function of dna methylation from invertebrates to vertebrates | methylation doublets promoter involvement silencing. surprisingly papers extensive methylation affecting coding portions transcriptionally prompting rethink methylation eukaryotes. methylation surprising repeatedly invertebrates interferes transcriptional elongation preventing aberrant initiations. ancestral methylation susceptible transcriptional interference silencing. recruitment methylation silencing successive tinkered use. invertebrate vertebrates accompanied constrains methylation resulted conservation methylation machinery vertebrates viability mutants lacking methylation | non_dup | [] |
11252034 | 10.1007/s00018-008-8065-7 | The high-affinity Na+-dependent carnitine transporter OCTN2 (SLC22A5) has a high renal expression and reabsorbs most filtered carnitine. To gain more insight into substrate specificity of OCTN2, we overexpressed hOCTN2 in L6 cells and characterized the structural requirements of substances acting as human OCTN2 (hOCTN2) inhibitors. A 1905-bp fragment containing the hOCTN2 complete coding sequence was introduced into the pWpiresGFP vector, and L6 cells were stably transduced using a lentiviral system. The transduced L6 cells revealed increased expression of hOCTN2 on the mRNA, protein and functional levels. Structural requirements for hOCTN2 inhibition were predicted in silico and investigated in vitro. Essential structural requirements for OCTN2 inhibition include a constantly positively charged nitrogen atom and a carboxyl, nitrile or ester group connected by a 2-4-atom linker. Our cell system is suitable for studying in vitro interactions with OCTN2, which can subsequently be investigated in vivo | Pharmacological manipulation of L-carnitine transport into L6 cells with stable overexpression of human OCTN2 | pharmacological manipulation of l-carnitine transport into l6 cells with stable overexpression of human octn2 | affinity carnitine transporter octn reabsorbs filtered carnitine. insight specificity octn overexpressed hoctn substances acting octn hoctn inhibitors. fragment hoctn coding pwpiresgfp stably transduced lentiviral system. transduced hoctn levels. hoctn silico vitro. octn constantly positively nitrogen atom carboxyl nitrile ester atom linker. studying octn subsequently | non_dup | [] |
41996749 | 10.1007/s00018-008-8119-x | This is the author's final draft of the paper published as Cellular and Molecular Life Sciences, 2008, 65 (20), pp. 3126-3133. The original publication is available at www.springerlink.com. Doi: 10.1007/s00018-008-8119-xThe epidermis, the outer layer of the skin composed of keratinocytes, is a stratified epithelium that functions as a barrier to protect the organism from dehydration and external insults. The epidermis develops following the action of the transcription factor p63, amember of the p53 family of transcription factors. The Trp63 gene contains two promoters driving the production of distinct proteins, one with an N-terminal transactivation domain (TAp63) and one without (ΔNp63), although their relative contribution to epidermal development is not clearly established. Trp63 mutations are involved in the pathogenesis of several human diseases, phenotypically characterized by ectodermal dysplasia. In this review, we summarize the current advances that have been made in understanding the role of p63 in epidermal morphogenesis | p63 in epithelial development. | p63 in epithelial development. | draft publication xthe epidermis outer composed keratinocytes stratified epithelium barrier protect organism dehydration insults. epidermis develops amember factors. promoters driving transactivation epidermal established. pathogenesis phenotypically ectodermal dysplasia. summarize advances epidermal morphogenesis | non_dup | [] |
33312350 | 10.1007/s00018-008-8184-1 | Olfactory ensheathing cells (OECs) have been shown previously to express Toll-like receptors and to respond to bacteria by translocating nuclear factor-kB from the cytoplasm to the nucleus. In this study,we show that OECs extended significantly more pseudopodia when they were exposed to Escherichia coli than in the absence of bacteria (p=0.019). Coimmunoprecipitation showed that E. coli binding to OECs was mediated by Toll-like receptor 4. Lyso-\ud
Tracker, a fluorescent probe that accumulates selectively\ud
in lysosomes, and staining for type 1 lysosomeassociated\ud
membrane proteins demonstrated that endocytosed FITC-conjugated E. coli were translocated to lysosomes. They appeared to be subsequently broken down, as shown by transmission electron microscopy. No obvious adherence to the membrane and less phagocytosis was observed when\ud
OECs were incubated with inert fluorescent microspheres.\ud
The ability of OECs to endocytose bacteria supports the notion that OECs play an innate immune function by protecting olfactory tissues from bacterial infection | Olfactory ensheathing cells are attracted to, and can endocytose, bacteria | olfactory ensheathing cells are attracted to, and can endocytose, bacteria | olfactory ensheathing oecs express toll receptors respond bacteria translocating cytoplasm nucleus. oecs pseudopodia exposed escherichia coli bacteria coimmunoprecipitation coli oecs toll lyso tracker fluorescent accumulates selectively lysosomes staining lysosomeassociated endocytosed fitc conjugated coli translocated lysosomes. appeared subsequently broken microscopy. obvious adherence phagocytosis oecs incubated inert fluorescent microspheres. oecs endocytose bacteria supports notion oecs innate immune protecting olfactory tissues bacterial | non_dup | [] |
36025295 | 10.1007/s00018-008-8201-4 | El pdf del artículo es la versión de autor.Wilson’s disease is characterized by long-term hepatic accumulation of copper leading to liver disease with reduction of S-adenosylmethionine synthesis. However, the initial changes in this pathway remain unknown and constitute the objective of the present study. Using the Long Evans Cinnamon rat model early alterations in the mRNA and protein levels, as well as in the activities of several enzymes of the methionine cycle were detected. Noteworthy, the main change was a redox mediated 80% decrease in the mRNA levels of the methionine adenosyltransferase regulatory subunit as compared to the control group. Moreover, changes in S-adenosylmethionine, S-adenosylhomocysteine, methionine and glutathione levels were also observed. In addition, in vitro experiments show that copper affects the activity and folding of methionine adenosyltransferase catalytic subunits. Taken together, these observations indicate that early copper accumulation alters methionine metabolism with a pattern distinct from that described previously for other liver diseases.Ministerio de Educación y Ciencia (BMC2002-00243 and BFU2005-00050 to M.A.P. and SAF2006-03489 to D.P-S.) and the Fondo de Investigación Sanitaria del Instituto de Salud Carlos III (RCMN C03/08 to M.A.P.). M. D. was supported by fellowships of the RCMN C03/08 and PI05/0563 grants of the Fondo de Investigación Sanitaria del Instituto de Salud Carlos III.Peer reviewe | Early effects of copper accumulation on methionine metabolism | early effects of copper accumulation on methionine metabolism | artículo versión autor.wilson’s hepatic accumulation copper adenosylmethionine synthesis. unknown constitute study. evans cinnamon alterations enzymes methionine detected. noteworthy redox methionine adenosyltransferase regulatory subunit group. adenosylmethionine adenosylhomocysteine methionine glutathione observed. copper affects folding methionine adenosyltransferase catalytic subunits. copper accumulation alters methionine metabolism diseases.ministerio educación ciencia m.a.p. fondo investigación sanitaria instituto salud carlos rcmn m.a.p. fellowships rcmn grants fondo investigación sanitaria instituto salud carlos iii.peer reviewe | non_dup | [] |
36025303 | 10.1007/s00018-008-8516-1 | El pdf del artículo es la versión post-print.Methionine adenosyltransferases (MAT) are the family of enzymes that synthesize the main biological methyl donor, S-adenosylmethionine. The high sequence conservation among catalytic subunits from bacteria and Eukarya preserves key residues that control activity and oligomerization, which is reflected in the protein structure. However, structural differences among complexes with substrates and products have led to proposals of several reaction mechanisms. In parallel, folding studies are starting to explain how the three intertwined domains of the catalytic subunit are produced, and the importance of certain intermediates in attaining the active final conformation. This review analyzes the available structural data and proposes a consensus interpretation that facilitates an understanding of the pathological problems derived from impairment of MAT function. In addition, new research opportunities directed toward clarification of aspects that remain obscure are also identified.Ministerio de Educación y Ciencia (BMC2002-00243 and BFU2005-00050 to M.A.P.), the Fondo de Investigación Sanitaria del Instituto de Salud Carlos III (RCMN C03/08 to M.A.P.), the National Institutes of Health (GM31186 to G.D.M. and CA06927 to FCCC) and an appropriation from the Commonwealth of Pennsylvania.Peer reviewe | Structure-function relationships in methionine adenosyltransferases | structure-function relationships in methionine adenosyltransferases | artículo versión print.methionine adenosyltransferases enzymes synthesize methyl donor adenosylmethionine. conservation catalytic subunits bacteria eukarya preserves oligomerization reflected structure. complexes substrates proposals mechanisms. folding intertwined catalytic subunit intermediates attaining conformation. analyzes proposes consensus facilitates pathological impairment function. opportunities directed toward clarification obscure identified.ministerio educación ciencia m.a.p. fondo investigación sanitaria instituto salud carlos rcmn m.a.p. institutes g.d.m. fccc appropriation commonwealth pennsylvania.peer reviewe | non_dup | [] |
36051530 | 10.1007/s00018-008-8547-7 | 23 páginas, 8 figuras, 2 tablas.Coenzyme Q is a lipid molecule required for respiration and antioxidant protection. Q biosynthesis in Saccharomyces cerevisiae requires nine proteins (Coq1p–Coq9p). We demonstrate in this study that Q levels are modulated during growth by its conversion from demethoxy-Q (DMQ), a late intermediate. Similar conversion was produced when cells were subjected to oxidative stress conditions. Changes in Q6/DMQ6 ratio were accompanied by changes in COQ7 gene mRNA levels encoding the protein responsible for the DMQ hydroxylation, the penultimate step in Q biosynthesis pathway. Yeast coq null mutant failed to accumulate any Q late biosynthetic intermediate. However, in coq7 mutants the addition of exogenous Q produces the DMQ synthesis. Similar effect was produced by over-expressing ABC1/COQ8. These results support the existence of a biosynthetic complex that allows the DMQ6 accumulation and suggest that Coq7p is a control point for the Q biosynthesis regulation in yeast.The work was supported by the Spanish Ministerio de Ciencia y Tecnología, Grant BFU2005–03017/BMC, and by NIH GM45952 to CFC.Peer reviewe | Hydroxylation of demethoxy-Q6 constitutes a control point in yeast coenzyme Q6 biosynthesis | hydroxylation of demethoxy-q6 constitutes a control point in yeast coenzyme q6 biosynthesis | páginas figuras tablas.coenzyme molecule respiration antioxidant protection. biosynthesis saccharomyces cerevisiae nine p–coq modulated conversion demethoxy intermediate. conversion subjected oxidative conditions. accompanied encoding hydroxylation penultimate biosynthesis pathway. yeast failed accumulate biosynthetic intermediate. mutants exogenous produces synthesis. expressing biosynthetic accumulation biosynthesis yeast.the spanish ministerio ciencia tecnología cfc.peer reviewe | non_dup | [] |
36043607 | 10.1007/s00018-009-0040-4 | El pdf del artículo es la versión post-print.-- et al.Pancreatitis-associated protein 1 (PAP1) belongs to the Reg family of secretory proteins. Several important biological roles have been attributed to PAP1 but the signaling pathways activated by this protein remain only partially understood. Here, we describe the intracellular pathways triggered by PAP1 in a pancreatic acinar cell line. Taking advantage of the fact that PAP1 induces its own transcription, we performed ChIP assays to analyze the recruitment of transcriptional factors on its promoter. Our results show that PAP1 increased the transactivation activity of pap1 and the binding on its promoter of the nuclear factors C/EBPβ, P-CREB, P-ELK1, EGR1, STAT3, and ETS2, which are downstream targets of MAPK signaling. p44/42, p38, and JNK MAPKs activity increased after PAP1 treatment. In addition, pharmacological inhibition of these kinases markedly inhibited the induction of pap1 mRNA. Taken together, these results indicated that the mechanism of PAP1 action involves the activation of the MAPK superfamily.This work was supported by the FIS PI050599 and FIS PI081608 projects to E. Folch-Puy, Acción Integrada HF2006-0092 and CIBERehd to D. Closa and Spanish Ministry of Science and Technology BFU2007-63120 and CSD2006-49 to G. López-Rodas. CIBERehd is funded by the Instituto de Salud Carlos III. E. Folch-Puy is the recipient of a Ramón y Cajal contract from the Spanish Ministry of Education and Science. M. Ferrés-Masó is the recipient of a FIS-Instituto de Salud Carlos III contract PI050599.Peer reviewe | PAP1 signaling involves MAPK signal transduction | pap1 signaling involves mapk signal transduction | artículo versión print. al.pancreatitis belongs secretory proteins. roles attributed pathways partially understood. intracellular pathways triggered pancreatic acinar line. advantage induces chip assays analyze recruitment transcriptional promoter. transactivation promoter ebpβ creb stat downstream targets mapk signaling. mapks treatment. pharmacological kinases markedly inhibited mrna. involves mapk superfamily.this projects folch acción integrada ciberehd closa spanish ministry lópez rodas. ciberehd funded instituto salud carlos iii. folch recipient ramón cajal contract spanish ministry science. ferrés masó recipient instituto salud carlos contract .peer reviewe | non_dup | [] |
195924 | 10.1007/s00018-009-0093-4 | This is the author's final draft of the paper published as Cellular and Molecular Life Sciences, 2009, 66 (20), pp. 3337-3352. The original publication is available at www.springerlink.com. Doi: 10.1007/s00018-009-0093-4The G protein-coupled receptors (GPCRs) are a superfamily of transmembrane receptors that have a broad distribution and can collectively recognise a diverse array of ligands. Activation or inhibition of GPCR signalling can affect many (patho)physiological processes, and consequently they are a major target for existing and emerging drug therapies. A common observation has been that the pharmacological, signalling and regulatory properties of GPCRs can differ in a cell- and tissue-specific manner. Such “phenotypic” diversity might be attributable to post-translational modifications and/or association of GPCRs with accessory proteins, however, post-transcriptional mechanisms are also likely to contribute. Although approximately 50% of GPCR genes are intronless, those that possess introns can undergo alternative splicing, generating GPCR subtype isoforms that may differ in their pharmacological, signalling and regulatory properties. In this review we shall highlight recent research into GPCR splice variation and discuss the potential consequences this might have for GPCR function in health and disease | Alternative splicing of G protein-coupled receptors: physiology and pathophysiology | alternative splicing of g protein-coupled receptors: physiology and pathophysiology | draft publication receptors gpcrs superfamily transmembrane receptors broad collectively recognise diverse array ligands. gpcr signalling patho physiological emerging therapies. pharmacological signalling regulatory gpcrs manner. “phenotypic” diversity attributable translational modifications gpcrs accessory transcriptional contribute. gpcr intronless possess introns undergo splicing generating gpcr subtype isoforms pharmacological signalling regulatory properties. highlight gpcr splice consequences gpcr | non_dup | [] |
11262786 | 10.1007/s00018-009-0141-0 | The mammalian brain is extremely sensitive to alterations in cellular homeostasis as a result of environmental or physiological insults. In particular, hypoxic/ischemic challenges (i.e. reduced oxygen and/or glucose delivery) cause severe and detrimental alterations in brain function and can trigger neuronal cell death within minutes. Unfortunately, as we age, oxygen delivery to cells and tissues is impaired, thereby increasing the susceptibility of neurons to damage. Thus, hypoxic (neuronal) adaptation is significantly compromised during aging. Many neurological diseases, such as stroke, Alzheimer's disease (AD), Parkinson's disease and diabetes, are characterized by hypoxia, a state that is believed to only exacerbate disease progression. However, the contribution of hypoxia and hypoxia-mediated pathways to neurodegeneration remains unclear. This review discusses current evidence on the contribution of oxygen deprivation to AD, with an emphasis on hypoxia inducible transcription factor-1 (HIF-1)-mediated pathways and the association of AD with the cytoskeleton regulator cyclin-dependent kinase 5. (Part of a multi-author review.) | Contribution of hypoxia to Alzheimer's disease: is HIF-1alpha a mediator of neurodegeneration? | contribution of hypoxia to alzheimer's disease: is hif-1alpha a mediator of neurodegeneration? | mammalian extremely alterations homeostasis physiological insults. hypoxic ischemic challenges i.e. glucose delivery detrimental alterations trigger neuronal minutes. unfortunately delivery tissues impaired thereby susceptibility damage. hypoxic neuronal adaptation compromised aging. neurological stroke alzheimer parkinson hypoxia believed exacerbate progression. hypoxia hypoxia pathways neurodegeneration unclear. discusses deprivation emphasis hypoxia inducible pathways cytoskeleton regulator cyclin review. | non_dup | [] |
11264002 | 10.1007/s00018-009-0145-9 | Acute mountain sickness (AMS) is a neurological disorder that typically affects mountaineers who ascend to high altitude. The symptoms have traditionally been ascribed to intracranial hypertension caused by extracellular vasogenic edematous brain swelling subsequent to mechanical disruption of the blood-brain barrier in hypoxia. However, recent diffusion-weighted magnetic resonance imaging studies have identified mild astrocytic swelling caused by a net redistribution of fluid from the "hypoxia-primed" extracellular space to the intracellular space without any evidence for further barrier disruption or additional increment in brain edema, swelling or pressure. These findings and the observation of minor vasogenic edema present in individuals with and without AMS suggest that the symptoms are not explained by cerebral edema. This has led to a re-evaluation of the relevant pathogenic events with a specific focus on free radicals and their interaction with the trigeminovascular system. (Part of a multi-author review.) | Emerging concepts in acute mountain sickness and high-altitude cerebral edema: from the molecular to the morphological | emerging concepts in acute mountain sickness and high-altitude cerebral edema: from the molecular to the morphological | mountain sickness neurological disorder affects mountaineers ascend altitude. traditionally ascribed intracranial hypertension extracellular vasogenic edematous swelling disruption barrier hypoxia. weighted mild astrocytic swelling redistribution hypoxia primed extracellular intracellular barrier disruption increment edema swelling pressure. minor vasogenic edema cerebral edema. pathogenic radicals trigeminovascular system. review. | non_dup | [] |
77000187 | 10.1007/s00018-009-0180-6 | Next-generation sequencing technologies are now being exploited not only to analyse static genomes, but also dynamic transcriptomes in an approach termed RNA-seq. Although these powerful and rapidly evolving technologies have only been available for a couple of years, they are already making substantial contributions to our understanding of genome expression and regulation. Here, we briefly describe technical issues accompanying RNA-seq data generation and analysis, highlighting differences to array-based approaches. We then review recent biological insight gained from applying RNA-seq and related approaches to deeply sample transcriptomes in different cell types or physiological conditions. These approaches are providing fascinating information about transcriptional and post-transcriptional gene regulation, and they are also giving unique insight into the richness of transcript structures and processing on a global scale and at unprecedented resolution | RNA-seq: from technology to biology. | rna-seq: from technology to biology. | sequencing technologies exploited analyse genomes transcriptomes termed seq. powerful rapidly evolving technologies couple substantial regulation. briefly accompanying highlighting array approaches. insight gained deeply transcriptomes physiological conditions. fascinating transcriptional transcriptional giving insight richness transcript unprecedented | non_dup | [] |
18522865 | 10.1007/s00018-009-0184-2 | Fatigue accounts for an important part of the burden experienced by patients with neuromuscular disorders. Substantial high prevalence rates of fatigue are reported in a wide range of neuromuscular disorders, such as Guillain-Barré syndrome and Pompe disease. Fatigue can be subdivided into experienced fatigue and physiological fatigue. Physiological fatigue in turn can be of central or peripheral origin. Peripheral fatigue is an important contributor to fatigue in neuromuscular disorders, but in reaction to neuromuscular disease fatigue of central origin can be an important protective mechanism to restrict further damage. In most cases, severity of fatigue seems to be related with disease severity, possibly with the exception of fatigue occurring in a monophasic disorder like Guillain-Barré syndrome. Treatment of fatigue in neuromuscular disease starts with symptomatic treatment of the underlying disease. When symptoms of fatigue persist, non-pharmacological interventions, such as exercise and cognitive behavioral therapy, can be initiated | Fatigue in neuromuscular disorders: Focus on Guillain-Barré syndrome and Pompe disease | fatigue in neuromuscular disorders: focus on guillain-barré syndrome and pompe disease | fatigue accounts burden experienced neuromuscular disorders. substantial prevalence fatigue neuromuscular disorders guillain barré syndrome pompe disease. fatigue subdivided experienced fatigue physiological fatigue. physiological fatigue peripheral origin. peripheral fatigue contributor fatigue neuromuscular disorders neuromuscular fatigue protective restrict damage. severity fatigue severity possibly exception fatigue occurring monophasic disorder guillain barré syndrome. fatigue neuromuscular starts symptomatic disease. fatigue persist pharmacological interventions exercise behavioral initiated | non_dup | [] |
30810088 | 10.1007/s00018-009-0235-8 | Catestatin, an endogenous peptide derived from
bovine chromogranin A, and its active domain cateslytin
display powerful antimicrobial activities. We have tested
the activities of catestatin and other related peptides on the
growth of Plasmodium falciparum in vitro. Catestatin
inhibits growth of the chloroquine-sensitive strain of
P. falciparum 3D7, exhibiting 88% inhibition at 20 lM.
A similar partial inhibition of parasite growth was observed
for the chloroquine-resistant strain, 7G8 (64%,) and the
multidrug-resistant strain, W2 (62%). In the presence of
parasite-specific lactate dehydrogenase, a specific protein–
protein interaction between catestatin and plasmepsin II
precursor was demonstrated. In addition, catestatin partially
inhibited the parasite-specific proteases plasmepsin in
vitro. A specific interaction between catestatin and
plasmepsins II and IV from P. falciparum and plasmepsin
IV from the three remaining species of Plasmodium known
to infect man was observed, suggesting a catestatininduced
reduction in availability of nutrients for protein
synthesis in the parasite | Catestatin, an endogenous Chromogranin A-derived peptide, inhibits in vitro growth of Plasmodium falciparum | catestatin, an endogenous chromogranin a-derived peptide, inhibits in vitro growth of plasmodium falciparum | catestatin endogenous bovine chromogranin cateslytin display powerful antimicrobial activities. catestatin peptides plasmodium falciparum vitro. catestatin inhibits chloroquine falciparum exhibiting parasite chloroquine resistant multidrug resistant parasite lactate dehydrogenase protein– catestatin plasmepsin precursor demonstrated. catestatin partially inhibited parasite proteases plasmepsin vitro. catestatin plasmepsins falciparum plasmepsin plasmodium infect catestatininduced availability nutrients parasite | non_dup | [] |
6117271 | 10.1007/s00018-010-0257-2 | Nuclear envelope complexity is expanding with respect to identification of protein components. Here we test the validity of proteomics results that identified 67 novel predicted nuclear envelope transmembrane proteins (NETs) from liver by directly comparing 30 as tagged fusions using targeting assays. This confirmed 21 as NETs, but 4 only targeted in certain cell types, underscoring the complexity of interactions that tether NETs to the nuclear envelope. Four NETs accumulated at the nuclear rim in normal fibroblasts but not in fibroblasts lacking lamin A, suggesting involvement of lamin A in tethering them in the nucleus. However, intriguingly, for the NETs tested alternative mechanisms for nuclear envelope retention could be found in Jurkat cells that normally lack lamin A. This study expands by a factor of three the number of liver NETs analyzed, bringing the total confirmed to 31, and shows that several have multiple mechanisms for nuclear envelope retention | Cell-specific and lamin-dependent targeting of novel transmembrane proteins in the nuclear envelope. | cell-specific and lamin-dependent targeting of novel transmembrane proteins in the nuclear envelope. | envelope expanding components. validity proteomics envelope transmembrane nets tagged fusions targeting assays. confirmed nets targeted underscoring tether nets envelope. nets accumulated fibroblasts fibroblasts lacking lamin involvement lamin tethering nucleus. intriguingly nets envelope retention jurkat normally lamin expands nets bringing confirmed envelope retention | non_dup | [] |
53264540 | 10.1007/s00018-010-0297-7 | In this paper we demonstrate the existence of a cytoplasmic processing step, never before described, involving both the pre-ribosomal subunits in the sea urchin Paracentrotus lividus. Northern-blot hybridization, primer extension, S1 mapping experiments and in situ hybridizations allowed us to demonstrate that cytoplasmic processed particles are successively re-imported into the nucleus where maturation of their RNAs is completed prior to being exported to the cytoplasm. Our findings lead to the proposal of a new model of ribosome maturation and shuttling | Evidence for a novel cytoplasmic processing event in ribosome maturation in the sea urchin Paracentrotus lividus. | evidence for a novel cytoplasmic processing event in ribosome maturation in the sea urchin paracentrotus lividus. | cytoplasmic never involving ribosomal subunits urchin paracentrotus lividus. northern blot hybridization primer situ hybridizations cytoplasmic processed successively imported nucleus maturation rnas completed exported cytoplasm. proposal ribosome maturation shuttling | non_dup | [] |
54025547 | 10.1007/s00018-010-0373-z | International audienceHepatitis C virus (HCV) release is linked to the formation of lipid droplet (LD) clusters in the perinuclear area of infected cells, induced by the core protein. We used electron microscopy (EM) to monitor and compare the number and size of LD in cells producing the mature and immature forms of the HCV core protein, and 3D EM to reconstruct whole cells producing the mature core protein. Only the mature protein coated the LD and induced their clustering and emergence from endoplasmic reticulum membranes enriched in this protein. We found no particular association between LD clusters and the centrosome in reconstructed cells. The LD clustering induced by the mature core protein was associated with an increase in LD synthesis potentially due, at least in part, to the ability of this protein to coat the LD. These observations provide useful information for further studies of the mechanisms involved in HCV-induced steatosis | Ultrastructural and quantitative analysis of the lipid droplet clustering induced by hepatitis C virus core protein.
:
HCV-induced lipid droplet clustering | ultrastructural and quantitative analysis of the lipid droplet clustering induced by hepatitis c virus core protein. : hcv-induced lipid droplet clustering | audiencehepatitis droplet perinuclear protein. microscopy monitor producing mature immature reconstruct producing mature protein. mature coated clustering emergence endoplasmic reticulum membranes enriched protein. centrosome reconstructed cells. clustering mature potentially coat steatosis | non_dup | [] |
37522426 | 10.1007/s00018-010-0380-0 | The IL-10 family of cytokines is comprised of IL-10, IL-19, IL-20, IL-22, IL-24, IL-26, and IFN-λs (IL-28A, IL-28B, and IL-29). The IL-10 family members bind to shared class II cytokine receptor chains that associate in various combinations in heterodimeric complexes. Upon interleukin/receptor complex formation, these proteins switch on the Jak/STAT pathway and elicit pleiotropic biological responses whose variety sharply contrasts with their structural similarities. IL-10 family members are involved in several human diseases and health conditions and hence their structural analyses may provide valuable information to design specific therapeutic strategies. In this review, we describe the human interleukin-10 family of cytokines, focusing on their structures and functions, with particular attention given to IL-22 and IL-10. We report on the recently published structures of IL-10 cytokine family members and their complexes with cognate transmembrane and soluble receptors as well as on interleukin physiology and physiopathology | Structure and function of interleukin-22 and other members of the interleukin-10 family | structure and function of interleukin-22 and other members of the interleukin-10 family | cytokines comprised bind shared cytokine chains associate combinations heterodimeric complexes. interleukin switch stat elicit pleiotropic sharply contrasts similarities. valuable therapeutic strategies. interleukin cytokines focusing cytokine complexes cognate transmembrane soluble receptors interleukin physiology physiopathology | non_dup | [] |
52693871 | 10.1007/s00018-010-0477-5 | International audienceThe cellular prion glycoprotein (PrP(C)) is ubiquitously expressed but its physiologic functions remain enigmatic, particularly in the immune system. Here, we demonstrate in vitro and in vivo that PrP(C) is involved in T lymphocytes response to oxidative stress. By monitoring the intracellular level of reduced glutathione, we show that PrP(-/-) thymocytes display a higher susceptibility to H(2)O(2) exposure than PrP(+/+) cells. Furthermore, we find that in mice fed with a restricted diet, a regimen known to increase the intracellular level of ROS, PrP(-/-) thymocytes are more sensitive to oxidative stress. PrP(C) function appears to be specific for oxidative stress, since no significant differences are observed between PrP(-/-) and PrP(+/+) mice exposed to other kinds of stress. We also show a marked evolution of the redox status of T cells throughout differentiation in the thymus. Taken together, our results clearly ascribe to PrP(C) a protective function in thymocytes against oxidative stress | Enhanced susceptibility of T lymphocytes to oxidative stress in the absence of the cellular prion protein.
:
PrPC and oxidative stress in T lymphocytes | enhanced susceptibility of t lymphocytes to oxidative stress in the absence of the cellular prion protein. : prpc and oxidative stress in t lymphocytes | audiencethe prion glycoprotein ubiquitously physiologic enigmatic immune system. lymphocytes oxidative stress. intracellular glutathione thymocytes display susceptibility cells. restricted diet regimen intracellular thymocytes oxidative stress. oxidative exposed kinds stress. marked redox thymus. ascribe protective thymocytes oxidative | non_dup | [] |
11287512 | 10.1007/s00018-010-0533-1 | Oxidative DNA damage to cells activates poly(ADP-ribose)polymerase-1 (PARP-1) and the poly(ADP-ribose) formed is rapidly degraded to ADP-ribose by poly(ADP-ribose)glycohydrolase (PARG). Here we show that PARP-1 and PARG control extracellular Ca(2+) fluxes through melastatin-like transient receptor potential 2 channels (TRPM2) in a cell death signaling pathway. TRPM2 activation accounts for essentially the entire Ca(2+) influx into the cytosol, activating caspases and causing the translocation of apoptosis inducing factor (AIF) from the inner mitochondrial membrane to the nucleus followed by cell death. Abrogation of PARP-1 or PARG function disrupts these signals and reduces cell death. ADP-ribose-loading of cells induces Ca(2+) fluxes in the absence of oxidative damage, suggesting that ADP-ribose is the key metabolite of the PARP-1/PARG system regulating TRPM2. We conclude that PARP-1/PARG control a cell death signal pathway that operates between five different cell compartments and communicates via three types of chemical messengers: a nucleotide, a cation, and proteins | Poly(ADP-ribose)glycohydrolase is an upstream regulator of Ca2+ fluxes in oxidative cell death | poly(adp-ribose)glycohydrolase is an upstream regulator of ca2+ fluxes in oxidative cell death | oxidative activates poly ribose polymerase parp poly ribose rapidly degraded ribose poly ribose glycohydrolase parg parp parg extracellular fluxes melastatin transient trpm pathway. trpm accounts essentially influx cytosol activating caspases causing translocation apoptosis inducing mitochondrial nucleus death. abrogation parp parg disrupts reduces death. ribose loading induces fluxes oxidative ribose metabolite parp parg regulating trpm parp parg operates compartments communicates messengers nucleotide cation | non_dup | [] |
19639669 | 10.1007/s00018-010-0541-1 | The protein kinase C (PKC) family of serine/threonine kinases consists of ten different isoforms grouped into three subfamilies, denoted classical, novel and atypical PKCs (aPKCs). The aPKCs, PKC?/? and PKC? serve important roles during development and in processes subverted in cancer such as cell and tissue polarity, cell proliferation, differentiation and apoptosis. In an effort to identify novel interaction partners for aPKCs, we performed a yeast two-hybrid screen with the regulatory domain of PKC?/? as bait and identified the Krüppel-like factors family protein TIEG1 as a putative interaction partner for PKC?/?. We confirmed the interaction of both aPKCs with TIEG1 in vitro and in cells, and found that both aPKCs phosphorylate the DNA-binding domain of TIEG1 on two critical residues. Interestingly, the aPKC-mediated phosphorylation of TIEG1 affected its DNA-binding activity, subnuclear localization and transactivation potential.Transforming growth factor-ß-inducible early response gene 1 is a novel substrate for atypical protein kinase C | Transforming growth factor-ß-inducible early response gene 1 is a novel substrate for atypical protein kinase Cs | transforming growth factor-ß-inducible early response gene 1 is a novel substrate for atypical protein kinase cs | serine threonine kinases isoforms grouped subfamilies denoted atypical pkcs apkcs apkcs serve roles subverted polarity proliferation apoptosis. effort partners apkcs yeast hybrid screen regulatory bait krüppel tieg putative partner confirmed apkcs tieg apkcs phosphorylate tieg residues. interestingly apkc phosphorylation tieg subnuclear localization transactivation potential.transforming inducible atypical | non_dup | [] |
30897206 | 10.1007/s00018-010-0547-8 | Oriented cellulose deposition is critical to plant patterning and models suggest microtubules constrain cellulose synthase movements through the plasma membrane. Though widespread in plants, urochordates are the only animals that synthesize cellulose. We characterized the distinctive cellulose microfibril scaffold of the larvacean house and its interaction with house structural proteins (oikosins). Targeted disruption of cytoskeletal elements, secretory pathways, and plasma membrane organization, suggested a working model for templating extracellular cellulose microfibrils from animal cells that shows both convergence and differences to plant models. Specialized cortical F-actin arrays template microfibril orientation and glycosylphosphatidylinositol-anchored proteins in lipid rafts may act as scaffolding proteins in microfibril elongation. Microtubules deliver and maintain cellulose synthase complexes to specific cell membrane sites rather than orienting their movement through the membrane. Oikosins are incorporated into house compartments directly above their corresponding cellular field of expression and interact with the cellulose scaffold to a variable extent | Cytoskeleton-mediated templating of complex cellulose-scaffolded extracellular structure and its association with oikosins in the urochordate Oikopleura | cytoskeleton-mediated templating of complex cellulose-scaffolded extracellular structure and its association with oikosins in the urochordate oikopleura | oriented cellulose deposition patterning microtubules constrain cellulose synthase movements membrane. widespread urochordates synthesize cellulose. distinctive cellulose microfibril scaffold larvacean house house oikosins targeted disruption cytoskeletal secretory pathways templating extracellular cellulose microfibrils models. specialized cortical actin arrays template microfibril glycosylphosphatidylinositol anchored rafts scaffolding microfibril elongation. microtubules deliver maintain cellulose synthase complexes orienting movement membrane. oikosins incorporated house compartments interact cellulose scaffold | non_dup | [] |
28937662 | 10.1007/s00018-010-0571-8 | The D-enantiomers of amino acids have been thought to have relatively minor functions in biological processes. While L-amino acids clearly predominate in nature, D-amino acids are sometimes found in proteins that are not synthesized by ribosomes, and D-Ala and D-Glu are routinely found in the peptidoglycan cell wall of bacteria. Here, we review recent findings showing that D-amino acids have previously unappreciated regulatory roles in the bacterial kingdom. Many diverse bacterial phyla synthesize and release D-amino acids, including D-Met and D-Leu, which were not previously known to be made. These noncanonical D-amino acids regulate cell wall remodeling in stationary phase and cause biofilm dispersal in aging bacterial communities. Elucidating the mechanisms by which D-amino acids govern cell wall remodeling and biofilm disassembly will undoubtedly reveal new paradigms for understanding how extracytoplasmic processes are regulated as well as lead to development of novel therapeutics | Emerging Knowledge of Regulatory Roles of D-Amino Acids in Bacteria | emerging knowledge of regulatory roles of d-amino acids in bacteria | enantiomers thought minor processes. predominate sometimes synthesized ribosomes routinely peptidoglycan bacteria. unappreciated regulatory roles bacterial kingdom. diverse bacterial phyla synthesize made. noncanonical regulate remodeling stationary biofilm dispersal aging bacterial communities. elucidating govern remodeling biofilm disassembly undoubtedly reveal paradigms extracytoplasmic regulated therapeutics | non_dup | [] |
36058986 | 10.1007/s00018-010-0586-1 | 11 páginas, 5 figuras, 1 tabla.-- et al.-- El pdf del artículo es la versión post-print.[Introduction]: Tff3 peptide exerts important functions in\ud
cytoprotection and restitution of the gastrointestinal (GI)\ud
tract epithelia. Moreover, its presence in the rodent inner\ud
ear and involvement in the hearing process was demonstrated\ud
recently. However, its role in the auditory system\ud
still remains elusive. Our previous results showed a deterioration\ud
of hearing with age in Tff3-deficient animals.\ud
[Results]: Present detailed analysis of auditory brain stem\ud
response (ABR) measurements and immunohistochemical\ud
study of selected functional proteins indicated a normal\ud
function and phenotype of the cochlea in Tff3 mutants.\ud
However, a microarray-based screening of tissue derived\ud
from the auditory central nervous system revealed an\ud
alteration of securin (Pttg1) and serpina3n expression\ud
between wild-type and Tff3 knock-out animals. This\ud
was confirmed by qRT-PCR, immunostaining and western\ud
blots.This work was supported by Ciberned, MiCINN\ud
and Red de Terapia Célular de Castilla y León.Peer reviewe | Altered expression of securin (Pttg1) and serpina3n in the auditory system of hearing-impaired Tff3-deficient mice | altered expression of securin (pttg1) and serpina3n in the auditory system of hearing-impaired tff3-deficient mice | páginas figuras tabla. artículo versión print. exerts cytoprotection restitution gastrointestinal tract epithelia. rodent involvement hearing recently. auditory elusive. deterioration hearing deficient animals. auditory immunohistochemical phenotype cochlea mutants. microarray screening auditory nervous alteration securin pttg serpina knock animals. confirmed immunostaining blots.this ciberned micinn terapia célular castilla león.peer reviewe | non_dup | [] |
36062518 | 10.1007/s00018-010-0596-z | El pdf del artículo es la versión pre-print.Chs5p is a component of the exomer, a coat complex required to transport the chitin synthase Chs3p from the trans-Golgi network to the plasma membrane. The Chs5p N-terminal region exhibits fibronectin type III (FN3) and BRCT domains. FN3 domains are present in proteins that mediate adhesion processes, whereas BRCT domains are involved in DNA repair. Several fungi-including Schizosaccharomyces pombe, which has no detectable amounts of chitin-have proteins similar to Chs5p. Here we show that the FN3 and BRCT motifs in Chs5p behave as a module that is necessary and sufficient for Chs5p localization and for cargo delivery. The N-terminal regions of S. cerevisiae Chs5p and S. pombe Cfr1p are interchangeable in terms of Golgi localization, but not in terms of exomer assembly, showing that the conserved function of this module is protein retention in this organelle and that the interaction between the exomer components is organism-specific. © 2010 Springer Basel AG.This work has been supported by grants BFU2007- 61866 from the CICYT and GR231 from the Junta de Castilla y León, Spain. NdL was supported by a fellowship from the Spanish Ministry of Science. RMG and PBS were supported by postgraduate I3P fellowships from the Spanish council of research (CSIC).Peer Reviewe | The FN3 and BRCT motifs in the exomer component Chs5p define a conserved module that is necessary and sufficient for its function | the fn3 and brct motifs in the exomer component chs5p define a conserved module that is necessary and sufficient for its function | artículo versión exomer coat chitin synthase golgi membrane. exhibits fibronectin brct domains. mediate adhesion brct repair. fungi schizosaccharomyces pombe detectable amounts chitin brct motifs behave module localization cargo delivery. cerevisiae pombe interchangeable golgi localization exomer assembly conserved module retention organelle exomer organism specific. springer basel ag.this grants cicyt junta castilla león spain. fellowship spanish ministry science. postgraduate fellowships spanish council csic .peer reviewe | non_dup | [] |
143885265 | 10.1007/s00018-011-0630-9 | Axons of primary olfactory neurons are intimately associated with olfactory ensheathing cells (OECs) from the olfactory epithelium until the final targeting of axons within the olfactory bulb. However, little is understood about the nature and role of interactions between OECs and axons during development of the olfactory nerve pathway. We have used high resolution time-lapse microscopy to examine the growth and interactions of olfactory axons and OECs in vitro. Transgenic mice expressing fluorescent reporters in primary olfactory axons (OMP-ZsGreen) and ensheathing cells (S100߭DsRed) enabled us to selectively analyse these cell types in explants of olfactory epithelium. We reveal here that rather than providing only a permissive substrate for axon growth, OECs play an active role in modulating the growth of pioneer olfactory axons. We show that the interactions between OECs and axons were dependent on lamellipodial waves on the shaft of OEC processes. The motility of OECs was mediated by GDNF, which stimulated cell migration and increased the apparent motility of the axons, whereas loss of OECs via laser ablation of the cells inhibited olfactory axon outgrowth. These results demonstrate that the migration of OECs strongly regulates the motility of axons and that stimulation of OEC motility enhances axon extension and growth cone activity.Griffith Sciences, Griffith Institute for Drug DiscoveryFull Tex | Stimulation of olfactory ensheathing cell motility enhances olfactory axon growth | stimulation of olfactory ensheathing cell motility enhances olfactory axon growth | axons olfactory intimately olfactory ensheathing oecs olfactory epithelium targeting axons olfactory bulb. understood oecs axons olfactory nerve pathway. lapse microscopy examine olfactory axons oecs vitro. transgenic expressing fluorescent reporters olfactory axons zsgreen ensheathing ߭dsred enabled selectively analyse explants olfactory epithelium. reveal permissive axon oecs modulating pioneer olfactory axons. oecs axons lamellipodial shaft processes. motility oecs gdnf stimulated migration apparent motility axons oecs ablation inhibited olfactory axon outgrowth. migration oecs regulates motility axons stimulation motility enhances axon cone activity.griffith griffith discoveryfull | non_dup | [] |
11450964 | 10.1007/s00018-011-0693-7 | Tbx3, a T-box transcription factor, regulates key steps in development of the heart and other organ systems. Here, we identify Sox4 as an interacting partner of Tbx3. Pull-down and nuclear retention assays verify this interaction and in situ hybridization reveals Tbx3 and Sox4 to co-localize extensively in the embryo including the atrioventricular and outflow tract cushion mesenchyme and a small area of interventricular myocardium. Tbx3, SOX4, and SOX2 ChIP data, identify a region in intron 1 of Gja1 bound by all tree proteins and subsequent ChIP experiments verify that this sequence is bound, in vivo, in the developing heart. In a luciferase reporter assay, this element displays a synergistic antagonistic response to co-transfection of Tbx3 and Sox4 and in vivo, in zebrafish, drives expression of a reporter in the heart, confirming its function as a cardiac enhancer. Mechanistically, we postulate that Sox4 is a mediator of Tbx3 transcriptional activity. [KEYWORDS: Amino Acid Sequence; Animals; COS Cells; Cercopithecus aethiops; Connexin 43/ genetics; Gene Expression Regulation; Humans; Male; Mice; Molecular Sequence Data; SOXC Transcription Factors/chemistry/ metabolism; T-Box Domain Proteins/ metabolism; Transcription, Genetic; Zebrafish] | Sox4 mediates Tbx3 transcriptional regulation of the gap junction protein Cx43 | sox4 mediates tbx3 transcriptional regulation of the gap junction protein cx43 | regulates organ systems. interacting partner pull retention assays verify situ hybridization reveals localize extensively embryo atrioventricular outflow tract cushion mesenchyme interventricular myocardium. chip intron chip verify heart. luciferase reporter displays synergistic antagonistic transfection zebrafish drives reporter confirming enhancer. mechanistically postulate mediator transcriptional activity. keywords cercopithecus aethiops connexin genetics humans soxc metabolism metabolism zebrafish | non_dup | [] |
36059157 | 10.1007/s00018-011-0729-z | 6 páginas con ilustraciones.Hepatitis C virus (HCV) translation is mediated by an internal ribosome entry site (IRES) located at the 5’\ud
end of the genomic RNA. The 3’ untranslatable region (3’UTR) stimulates translation by the recruitment\ud
of protein factors that simultaneously bind to the 5’ end of the viral genome. This leads to the formation\ud
of a macromolecular complex with a closed loop conformation, similar to that described for the captranslated\ud
mRNAs. We previously demonstrated the existence of a long range RNA-RNA interaction\ud
involving subdomain IIId of the IRES region and the stem-loop 5BSL3.2 of the CRE element at the 3’\ud
end of the viral genome. The present study provides evidences that the enhancement of HCV IRESdependent\ud
translation mediated by the 3’UTR is negatively controlled by the CRE region in the human\ud
hepatoma cell lines Huh-7 and Hep-G2 in a time-dependent manner. Domain 5BSL3.2 is the major\ud
partner in this process. Mutations in this motif lead to an increase in IRES activity by up to 8-fold. These\ud
data support the existence of a functional high order structure in the HCV genome that involves two\ud
evolutionarily conserved RNA elements, domain IIId in the IRES and stem-loop 5BSL3.2 in the CRE\ud
region. This interaction could have a role in the circularisation of the viral genome.This work was supported by Grants BFU2009-08137 from\ud
the Spanish Ministerio de Innovacio´n y Ciencia, CTS-5077 from the\ud
Junta de Andalucı´a and FEDER funds from the EU to A.B–H. C.R-LPeer reviewe | The functional RNA domain 5BSL3.2 within the NS5B coding sequence influences hepatitis C virus IRESmediated translation. | the functional rna domain 5bsl3.2 within the ns5b coding sequence influences hepatitis c virus iresmediated translation. | páginas ilustraciones.hepatitis translation ribosome entry ires genomic rna. untranslatable ’utr stimulates translation recruitment simultaneously bind viral genome. macromolecular conformation captranslated mrnas. involving subdomain iiid ires viral genome. evidences enhancement iresdependent translation ’utr negatively hepatoma manner. partner process. motif ires fold. involves evolutionarily conserved iiid ires region. circularisation viral genome.this grants spanish ministerio innovacio´n ciencia junta andalucı´a feder funds a.b–h. lpeer reviewe | non_dup | [] |
37830938 | 10.1007/s00018-011-0775-6 | MicroRNAs are short endogenous RNA molecules that are able to regulate (mainly inhibiting) gene expression at the post-transcriptional level. The MicroRNA expression profile is cell-specific, but it is sensitive to perturbations produced by stresses and diseases. Endothelial cells subjected to metabolic stresses, such as calorie restriction, nutrients excess (glucose, cholesterol, lipids) and hypoxia may alter their functionality. This is predictive for the development of pathologies like atherosclerosis, diabetes, and hypertension. Moreover, cancer cells can activate a resting endothelium by secreting pro-angiogenic factors, in order to promote neoangiogenesis, which is essential for tumor growth. Endothelial altered phenotype is mirrored by altered mRNA, microRNA, and protein expression, with a microRNA being able to control pathways by regulating the expression of multiple mRNAs. In this review we will consider the involvement of microRNAs in modulating the response of endothelial cells to metabolic stresses and their role in promoting or halting angiogenesis | MicroRNAs mediate metabolic stresses and angiogenesis | micrornas mediate metabolic stresses and angiogenesis | micrornas endogenous regulate inhibiting transcriptional level. microrna perturbations stresses diseases. endothelial subjected metabolic stresses calorie restriction nutrients excess glucose cholesterol lipids hypoxia alter functionality. predictive pathologies atherosclerosis hypertension. activate resting endothelium secreting angiogenic promote neoangiogenesis growth. endothelial altered phenotype mirrored altered microrna microrna pathways regulating mrnas. involvement micrornas modulating endothelial metabolic stresses promoting halting angiogenesis | non_dup | [] |
16210671 | 10.1007/s00018-011-0893-1 | Newly generated olfactory receptor axons grow from the peripheral to the central nervous system aided by olfactory ensheathing cells (OECs). Thus, OEC transplantation has emerged as a promising therapy for spinal cord injuries and for other neural diseases. However, these cells do not present a uniform population, but, instead, a functionally heterogeneous population that exhibits a variety of responses including adhesion, repulsion and crossover during cell-cell and cell-matrix interactions. Some studies report that the migratory properties of OECs are compromised by inhibitory molecules and potentiated by chemical gradients. Here, we demonstrated that rodent OECs express all the components of the Nogo Receptor complex and that their migration is blocked by Myelin. Next, we used cell tracking and traction force microscopy to analyze OEC migration and its mechanical properties over Myelin. Our data relate the absence of traction force of OEC with lower migratory capacity, which correlates with changes in the F-Actin cytoskeleton and focal adhesion distribution. Lastly, OEC traction force and migratory capacity is enhanced after cell incubation with the Nogo Receptor inhibitor NEP1-40 | Myelin-associated proteins block the migration of olfactory ensheathing cells: an in vitro study using single cell tracking and traction force microscopy | myelin-associated proteins block the migration of olfactory ensheathing cells: an in vitro study using single cell tracking and traction force microscopy | newly olfactory axons grow peripheral nervous aided olfactory ensheathing oecs transplantation emerged promising spinal cord injuries diseases. functionally heterogeneous exhibits adhesion repulsion crossover interactions. migratory oecs compromised inhibitory potentiated gradients. rodent oecs express nogo migration blocked myelin. tracking traction microscopy analyze migration myelin. relate traction migratory correlates actin cytoskeleton focal adhesion distribution. lastly traction migratory incubation nogo inhibitor | non_dup | [] |
11300232 | 10.1007/s00018-012-0926-4 | Knowledge of the functional organization of the GABAergic system, the main inhibitory neurotransmitter system, in the CNS has increased remarkably in recent years. In particular, substantial progress has been made in elucidating the molecular mechanisms underlying the formation and plasticity of GABAergic synapses. Evidence available ascribes a key role to the cytoplasmic protein gephyrin to form a postsynaptic scaffold anchoring GABA(A) receptors along with other transmembrane proteins and signaling molecules in the postsynaptic density. However, the mechanisms of gephyrin scaffolding remain elusive, notably because gephyrin can auto-aggregate spontaneously and lacks PDZ protein interaction domains found in a majority of scaffolding proteins. In addition, the structural diversity of GABA(A) receptors, which are pentameric channels encoded by a large family of subunits, has been largely overlooked in these studies. Finally, the role of the dystrophin-glycoprotein complex, present in a subset of GABAergic synapses in cortical structures, remains ill-defined. In this review, we discuss recent results derived mainly from the analysis of mutant mice lacking a specific GABA(A) receptor subtype or a core protein of the GABAergic postsynaptic density (neuroligin-2, collybistin), highlighting the molecular diversity of GABAergic synapses and its relevance for brain plasticity and function. In addition, we discuss the contribution of the dystrophin-glycoprotein complex to the molecular and functional heterogeneity of GABAergic synapses | Molecular and functional heterogeneity of GABAergic synapses | molecular and functional heterogeneity of gabaergic synapses | gabaergic inhibitory neurotransmitter remarkably years. substantial progress elucidating plasticity gabaergic synapses. ascribes cytoplasmic gephyrin postsynaptic scaffold anchoring gaba receptors transmembrane postsynaptic density. gephyrin scaffolding elusive notably gephyrin auto aggregate spontaneously lacks majority scaffolding proteins. diversity gaba receptors pentameric encoded subunits largely overlooked studies. dystrophin glycoprotein gabaergic synapses cortical defined. lacking gaba subtype gabaergic postsynaptic neuroligin collybistin highlighting diversity gabaergic synapses relevance plasticity function. dystrophin glycoprotein heterogeneity gabaergic synapses | non_dup | [] |
10635039 | 10.1007/s00018-012-0927-3 | The myosin isoform composition of the heart is\ud
dynamic in health and disease and has been shown to affect\ud
contractile velocity and force generation. While different\ud
mammalian species express different proportions of a and\ud
b myosin heavy chain, healthy human heart ventricles\ud
express these isoforms in a ratio of about 1:9 (a:b) while\ud
failing human ventricles express no detectable a-myosin.\ud
We report here fast-kinetic analysis of recombinant human\ud
a and b myosin heavy chain motor domains. This represents the first such analysis of any human muscle myosin\ud
motor and the first of a-myosin from any species. Our\ud
findings reveal substantial isoform differences in individual\ud
kinetic parameters, overall contractile character, and predicted cycle times. For these parameters, a-subfragment 1\ud
(S1) is far more similar to adult fast skeletal muscle myosin\ud
isoforms than to the slow b isoform despite 91% sequence\ud
identity between the motor domains of a- and b-myosin.\ud
Among the features that differentiate a- from b-S1: the\ud
ATP hydrolysis step of a-S1 is *ten-fold faster than b-S1,\ud
a-S1 exhibits *five-fold weaker actin affinity than b-S1,\ud
and actin a-S1 exhibits rapid ADP release, which is > tenfold faster than ADP release for b-S1. Overall, the cycle\ud
times are ten-fold faster for a-S1 but the portion of time\ud
each myosin spends tightly bound to actin (the duty ratio)\ud
is similar. Sequence analysis points to regions that might\ud
underlie the basis for this finding | Identification of functional differences between recombinant human α and β cardiac myosin motors | identification of functional differences between recombinant human α and β cardiac myosin motors | myosin isoform contractile generation. mammalian express proportions myosin healthy ventricles express isoforms failing ventricles express detectable myosin. recombinant myosin motor domains. myosin motor myosin species. findings reveal substantial isoform contractile character times. subfragment skeletal myosin isoforms slow isoform motor myosin. differentiate hydrolysis faster exhibits weaker actin affinity actin exhibits tenfold faster faster portion myosin spends tightly actin duty similar. underlie finding | non_dup | [] |
11300906 | 10.1007/s00018-012-0937-1 | The generation of neuronal cells from stem cells obtained from adult bone marrow is of significant clinical interest in order to design new cell therapy protocols for several neurological disorders. The recent identification in adult bone marrow of stem cells derived from the neural crest stem cells (NCSC) might explain the neuronal phenotypic plasticity shown by bone marrow cells. However, little information is available about the nature of these cells compared to mesenchymal stem cells (MSC), including their similarities and differences. In this paper, using transcriptomic as well as proteomic technologies, we compared NCSC to MSC and stromal nestin-positive cells, all of them isolated from adult bone marrow. We demonstrated that the nestin-positive cell population, which was the first to be described as able to differentiate into functional neurons, was a mixed population of NCSC and MSC. More interestingly, we demonstrated that MSC shared with NCSC the same ability to truly differentiate into Tuj1-positive cells when co-cultivated with paraformaldehyde-fixed cerebellar granule neurons. Altogether, those results suggest that both NCSC and MSC can be considered as important tools for cellular therapies in order to replace neurons in various neurological diseases | Mesenchymal stem cells and neural crest stem cells from adult bone marrow: characterization of their surprising similarities and differences | mesenchymal stem cells and neural crest stem cells from adult bone marrow: characterization of their surprising similarities and differences | neuronal marrow protocols neurological disorders. marrow crest ncsc neuronal phenotypic plasticity marrow cells. mesenchymal similarities differences. transcriptomic proteomic technologies ncsc stromal nestin marrow. nestin differentiate ncsc msc. interestingly shared ncsc truly differentiate cultivated paraformaldehyde cerebellar granule neurons. altogether ncsc therapies replace neurological | non_dup | [] |
41997242 | 10.1007/s00018-012-0948-y | Cell adhesion molecule 1 (CADM1), expressed\ud
by human lung mast cells (HLMCs), mediates their adhesion\ud
to airway smooth muscle (ASM), and contributes\ud
to ASM-dependent HLMC proliferation and survival.\ud
CADM1 is expressed in alternatively spliced isoforms, but\ud
those present in HLMCs and their function are not known.\ud
We cloned three functional and one cryptic non-functional\ud
isoform with alternative splicing between exons 7/11 and\ud
1/2, respectively, from HLMCs and human MC lines\ud
(HMC-1 and LAD2). Differentiated HLMCs and LAD2\ud
cells expressed the functional isoform SP4 containing\ud
exons 7/8/11 (*80% of clones), as well as SP1 (exons 7/8/\ud
9/11) and a novel SP6 (exons 7/8/9/10/11). In contrast,\ud
immature HMC-1 cells expressed only functional SP4. SP4\ud
overexpression in HMC-1 cells and HLMCs augmented\ud
homotypic adhesion to a greater extent than SP1 in various\ud
conditions. In contrast, CADM1 downregulation abolished\ud
homotypic adhesion, indicating that CADM1 is the sole\ud
receptor mediating mast cell aggregation. CADM1-mediated\ud
adhesion was enhanced by the presence of cell\ud
survival factors. SP1 overexpression in HMC-1 cells\ud
compromised survival compared to SP4 overexpression or\ud
control. CADM1 downregulation resulted in reduced\ud
viability and decreased expression of the pro-survival\ud
protein Mcl-1L, but not Blc-2 or Bcl-XL, and increased\ud
caspase-3/7 activity in both HMC-1 cells and HLMCs. This\ud
coincided with decreased basal Kit levels in HLMCs. In\ud
summary, human MCs express multiple CADM1 isoforms\ud
which exhibit differential regulation of survival and\ud
homotypic adhesion. The most highly expressed SP4 isoform\ud
is likely to contribute to MC aggregation and\ud
longevity in mastocytosis, and augment the pathophysiology\ud
of allergic diseases.Peer-reviewedPublisher Versio | CADM1 isoforms differentially regulate human mast cell survival and homotypic adhesion | cadm1 isoforms differentially regulate human mast cell survival and homotypic adhesion | adhesion molecule cadm mast hlmcs mediates adhesion airway contributes hlmc proliferation survival. cadm alternatively spliced isoforms hlmcs known. cloned cryptic isoform splicing exons hlmcs differentiated hlmcs isoform exons clones exons exons immature overexpression hlmcs augmented homotypic adhesion conditions. cadm downregulation abolished homotypic adhesion cadm sole mediating mast aggregation. cadm adhesion factors. overexpression compromised overexpression control. cadm downregulation resulted viability caspase hlmcs. coincided basal hlmcs. express cadm isoforms exhibit homotypic adhesion. isoform aggregation longevity mastocytosis augment pathophysiology allergic diseases.peer reviewedpublisher versio | non_dup | [] |
30698067 | 10.1007/s00018-012-0980-y | Primary cilia are singular, cytoskeletal organelles present in the majority of mammalian cell types where they function as coordinating centres for mechanotransduction, Wnt and hedgehog signalling. The length of the primary cilium is proposed to modulate cilia function, governed in part by the activity of intraflagellar transport (IFT). In articular cartilage, primary cilia length is increased and hedgehog signaling activated in osteoarthritis (OA). Here, we examine primary cilia length with exposure to the quintessential inflammatory cytokine interleukin-1 (IL-1), which is up-regulated in OA. We then test the hypothesis that the cilium is involved in mediating the downstream inflammatory response. Primary chondrocytes treated with IL-1 exhibited a 50% increase in cilia length after 3 h exposure. IL-1-induced cilia elongation was also observed in human fibroblasts. In chondrocytes, this elongation occurred via a protein kinase A (PKA)-dependent mechanism. G-protein coupled adenylate cyclase also regulated the length of chondrocyte primary cilia but not downstream of IL-1. Chondrocytes treated with IL-1 exhibit a characteristic increase in the release of the inflammatory chemokines, nitric oxide and prostaglandin E2. However, in cells with a mutation in IFT88 whereby the cilia structure is lost, this response to IL-1 was significantly attenuated and, in the case of nitric oxide, completely abolished. Inhibition of IL-1-induced cilia elongation by PKA inhibition also attenuated the chemokine response. These results suggest that cilia assembly regulates the response to inflammatory cytokines. Therefore, the cilia proteome may provide a novel therapeutic target for the treatment of inflammatory pathologies, including OA | Primary cilia elongation in response to interleukin-1 mediates the inflammatory response. | primary cilia elongation in response to interleukin-1 mediates the inflammatory response. | cilia singular cytoskeletal organelles majority mammalian coordinating centres mechanotransduction hedgehog signalling. cilium modulate cilia governed intraflagellar articular cartilage cilia hedgehog osteoarthritis examine cilia quintessential inflammatory cytokine interleukin regulated cilium mediating downstream inflammatory response. chondrocytes exhibited cilia exposure. cilia elongation fibroblasts. chondrocytes elongation occurred mechanism. adenylate cyclase regulated chondrocyte cilia downstream chondrocytes exhibit inflammatory chemokines nitric oxide prostaglandin mutation whereby cilia lost attenuated nitric oxide abolished. cilia elongation attenuated chemokine response. cilia assembly regulates inflammatory cytokines. cilia proteome therapeutic inflammatory pathologies | non_dup | [] |
39287611 | 10.1007/s00018-012-0995-4 | Human pluripotent stem cells [PSCs; including human embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs)] can infinitely proliferate in vitro and are easily accessible for gene manipulation. Megakaryocytes (MKs) and platelets can be created from human ESCs and iPSCs in vitro and represent a potential source of blood cells for transfusion and a promising tool for studying the human thrombopoiesis. Moreover, disease-specific iPSCs are a powerful tool for elucidating the pathogenesis of hematological diseases and for drug screening. In that context, we and other groups have developed in vitro MK and platelet differentiation systems from human pluripotent stem cells (PSCs). Combining this co-culture system with a drug-inducible gene expression system enabled us to clarify the novel role played by c-MYC during human thrombopoiesis. In the next decade, technical advances (e.g., high-throughput genomic sequencing) will likely enable the identification of numerous gene mutations associated with abnormal thrombopoiesis. Combined with such technology, an in vitro system for differentiating human PSCs into MKs and platelets could provide a novel platform for studying human gene function associated with thrombopoiesis | Pluripotent stem cells reveal the developmental biology of human megakaryocytes and provide a source of platelets for clinical application. | pluripotent stem cells reveal the developmental biology of human megakaryocytes and provide a source of platelets for clinical application. | pluripotent pscs embryonic escs pluripotent ipscs infinitely proliferate accessible manipulation. megakaryocytes platelets created escs ipscs transfusion promising studying thrombopoiesis. ipscs powerful elucidating pathogenesis hematological screening. platelet pluripotent pscs combining inducible enabled clarify played thrombopoiesis. decade advances e.g. throughput genomic sequencing enable numerous abnormal thrombopoiesis. differentiating pscs platelets platform studying thrombopoiesis | non_dup | [] |
39294272 | 10.1007/s00018-012-1036-z | Human natural killer-1 (HNK-1) carbohydrate, comprising a unique trisaccharide HSO(3)-3GlcAβ1-3Galβ1-4GlcNAc, shows well-regulated expression and unique functions in the nervous system. Recent studies have revealed sophisticated and complicated expression mechanisms for HNK-1 glycan. Activities of biosynthetic enzymes are controlled through the formation of enzyme-complexes and regulation of subcellular localization. Functional aspects of HNK-1 carbohydrate were examined by overexpression, knockdown, and knockout studies of these enzymes. HNK-1 is involved in several neural functions such as synaptic plasticity, learning and memory, and the underlying molecular mechanisms have been illustrated upon identification of the target carrier glycoproteins of HNK-1 such as the glutamate receptor subunit GluA2 or tenascin-R. In this review, we describe recent findings about HNK-1 carbohydrate that provide further insights into the mechanism of its expression and function in the nervous system | Regulated expression and neural functions of human natural killer-1 (HNK-1) carbohydrate. | regulated expression and neural functions of human natural killer-1 (hnk-1) carbohydrate. | killer carbohydrate comprising trisaccharide glcaβ galβ glcnac regulated nervous system. sophisticated complicated glycan. biosynthetic enzymes enzyme complexes subcellular localization. carbohydrate overexpression knockdown knockout enzymes. synaptic plasticity illustrated carrier glycoproteins glutamate subunit glua tenascin carbohydrate insights nervous | non_dup | [] |
53848658 | 10.1007/s00018-012-1074-6 | Estrogen (E(2)) regulates spermatogenesis, yet its direct target genes have not been identified in the testis. Here, we cloned the proximal 5' flanking region of the mouse fatty acid amide hydrolase (faah) gene upstream of the luciferase reporter gene, and demonstrated its promoter activity and E(2) inducibility in primary mouse Sertoli cells. Specific mutations in the E(2) response elements (ERE) of the faah gene showed that two proximal ERE sequences (ERE2/3) are essential for E(2)-induced transcription, and chromatin immunoprecipitation experiments showed that E(2) induced estrogen receptor β binding at ERE2/3 sites in the faah promoter in vivo. Moreover, the histone demethylase LSD1 was found to be associated with ERE2/3 sites and to play a role in mediating E(2) induction of FAAH expression. E(2) induced epigenetic modifications at the faah proximal promoter compatible with transcriptional activation by remarkably decreasing methylation of both DNA at CpG site and histone H3 at lysine 9. Finally, FAAH silencing abolished E(2) protection against apoptosis induced by the FAAH substrate anandamide. Taken together, our results identify FAAH as the first direct target of E(2) | The faah gene is the first direct target of estrogen in the testis: role of histone demethylase LSD1 | the faah gene is the first direct target of estrogen in the testis: role of histone demethylase lsd1 | estrogen regulates spermatogenesis testis. cloned proximal flanking fatty amide hydrolase faah upstream luciferase reporter promoter inducibility sertoli cells. faah proximal chromatin immunoprecipitation estrogen faah promoter vivo. histone demethylase mediating faah expression. epigenetic modifications faah proximal promoter compatible transcriptional remarkably decreasing methylation histone lysine faah silencing abolished protection apoptosis faah anandamide. faah | non_dup | [] |
34541660 | 10.1007/s00018-012-1108-0 | KIF1Bβ is a kinesin-like, microtubule-based molecular motor protein involved in anterograde axonal vesicular transport in vertebrate and invertebrate neurons. Certain KIF1Bβ isoforms have been implicated in different forms of human neurodegenerative disease, with characterization of their functional integration and regulation in the context of synaptic signaling still ongoing. Here, we characterize human KIF1Bβ (isoform NM015074), whose expression we show to be developmentally regulated and elevated in cortical areas of the CNS (including the motor cortex), in the hippocampus, and in spinal motor neurons. KIF1Bβ localizes to the cell body, axon, and dendrites, overlapping with synaptic-vesicle and postsynaptic-density structures. Correspondingly, in purified cortical synaptoneurosomes, KIF1Bβ is enriched in both pre- and postsynaptic structures, forming detergent-resistant complexes. Interestingly, KIF1Bβ forms RNA-protein complexes, containing the dendritically localized Arc and Calmodulin mRNAs, proteins previously shown to be part of RNA transport granules such as Purα, FMRP and FXR2P, and motor protein KIF3A, as well as Calmodulin. The interaction between KIF1Bβ and Calmodulin is Ca(+2)-dependent and takes place through a domain mapped at the carboxy-terminal tail of the motor. Live imaging of cortical neurons reveals active movement by KIF1Bβ at dendritic processes, suggesting that it mediates the transport of dendritically localized mRNAs. Finally, we show that synaptic recruitment of KIF1Bβ is activity-dependent and increased by stimulation of metabotropic or ionotropic glutamate receptors. The activity-dependent synaptic recruitment of KIF1Bβ, its interaction with Ca(2+) sensor Calmodulin, and its new role as a dendritic motor of ribonucleoprotein complexes provide a novel basis for understanding the concerted co-ordination of motor protein mobilization and synaptic signaling pathways.status: publishe | KIF1Bβ transports dendritically localized mRNPs in neurons and is recruited to synapses in an activity-dependent manner | kif1bβ transports dendritically localized mrnps in neurons and is recruited to synapses in an activity-dependent manner | kinesin microtubule motor anterograde axonal vesicular vertebrate invertebrate neurons. isoforms implicated neurodegenerative synaptic ongoing. characterize isoform developmentally regulated elevated cortical motor cortex hippocampus spinal motor neurons. localizes axon dendrites overlapping synaptic vesicle postsynaptic structures. correspondingly purified cortical synaptoneurosomes enriched postsynaptic forming detergent resistant complexes. interestingly complexes dendritically localized calmodulin mrnas granules purα fmrp motor calmodulin. calmodulin mapped carboxy tail motor. live cortical reveals movement dendritic mediates dendritically localized mrnas. synaptic recruitment stimulation metabotropic ionotropic glutamate receptors. synaptic recruitment sensor calmodulin dendritic motor ribonucleoprotein complexes concerted ordination motor mobilization synaptic pathways.status publishe | non_dup | [] |
78053018 | 10.1007/s00018-012-1115-1 | Tumor cell migration is essential for invasion and dissemination from primary solid tumors and for the establishment of lethal secondary metastases at distant organs. In vivo and in vitro models enabled identification of different factors in the tumor microenvironment that regulate tumor progression and metastasis. However, the mechanisms by which tumor cells integrate these chemical and mechanical signals from multiple sources to navigate the complex microenvironment remain poorly understood. In this review, we discuss the factors that influence tumor cell migration with a focus on the migration of transformed carcinoma cells. We provide an overview of the experimental and computational methods that allow the investigation of tumor cell migration, and we highlight the benefits and shortcomings of the various assays. We emphasize that the chemical and mechanical stimulus paradigms are not independent and that crosstalk between them motivates the development of new assays capable of applying multiple, simultaneous stimuli and imaging the cellular migratory response in real-time. These next-generation assays will more closely mimic the in vivo microenvironment to provide new insights into tumor progression, inform techniques to control tumor cell migration, and render cancer more treatable.National Science Foundation (U.S.) (Graduate Research Fellowship)Charles Stark Draper Laboratory (Research and Development Program (N.DL-H-550151))National Cancer Institute (U.S.) (R21CA140096 | Tumor cell migration in complex microenvironments | tumor cell migration in complex microenvironments | migration invasion dissemination tumors establishment lethal metastases distant organs. enabled microenvironment regulate progression metastasis. integrate navigate microenvironment poorly understood. migration migration transformed carcinoma cells. overview migration highlight benefits shortcomings assays. emphasize stimulus paradigms crosstalk motivates assays capable simultaneous stimuli migratory time. assays closely mimic microenvironment insights progression inform migration render treatable.national foundation u.s. graduate fellowship charles stark draper n.dl u.s. | non_dup | [] |
54024041 | 10.1007/s00018-012-1213-0 | International audienceLike most positive-strand RNA viruses, hepatitis C virus (HCV) forms a membrane-associated replication complex consisting of replicating RNA, viral and host proteins anchored to altered cell membranes. We used a combination of qualitative and quantitative electron microscopy (EM), immuno-EM, and the 3D reconstruction of serial EM sections to analyze the host cell membrane alterations induced by HCV. Three different types of membrane alteration were observed: vesicles in clusters (ViCs), contiguous vesicles (CVs), and double-membrane vesicles (DMVs). The main ultrastructural change observed early in infection was the formation of a network of CVs surrounding the lipid droplets. Later stages in the infectious cycle were characterized by a large increase in the number of DMVs, which may be derived from the CVs. These DMVs are thought to constitute the membranous structures harboring the viral replication complexes in which viral replication is firmly and permanently established and to protect the virus against double-stranded RNA-triggered host antiviral responses | Sequential biogenesis of host cell membrane rearrangements induced by hepatitis C virus infection.
:
HCV-induced membrane rearrangements | sequential biogenesis of host cell membrane rearrangements induced by hepatitis c virus infection. : hcv-induced membrane rearrangements | audiencelike strand viruses hepatitis replication consisting replicating viral anchored altered membranes. qualitative microscopy immuno reconstruction serial analyze alterations hcv. alteration vesicles vics contiguous vesicles vesicles dmvs ultrastructural surrounding droplets. infectious dmvs cvs. dmvs thought constitute membranous harboring viral replication complexes viral replication firmly permanently protect stranded triggered antiviral | non_dup | [] |
11301492 | 10.1007/s00018-012-1246-4 | Crohn's disease (CD) is one of main disease entities under the umbrella term chronic inflammatory bowel disease. The etiology of CD involves alterations in genetic, microbiological, and immunological factors. This review is devoted to the role of the bacterial wall compound muramyl dipeptide (MDP) for the activation of inflammatory pathways involved in the pathogenesis of CD. The importance of this molecule is underscored by the fact that (1) MDP, which is found in most Gram-negative and -positive bacteria, is able to trigger several immunological responses in the intestinal system, and (2) that alterations in several mediators of the MDP response including-but not restricted to-nucleotide oligomerization domain 2 (NOD2) are associated with CD. The normalization of MDP signaling is one of several important factors that influence the intestinal inflammatory response, a fact which emphasizes the pathogenic importance of MDP signaling for the pathogenesis of CD. The important aspects of NOD2 and non-NOD2 mediated effects of MDP for the development of CD are highlighted, as well as how alterations in these pathways might translate into the development of new therapeutic strategies | Muramyl dipeptide responsive pathways in Crohn's disease: from NOD2 and beyond | muramyl dipeptide responsive pathways in crohn's disease: from nod2 and beyond | crohn entities umbrella inflammatory bowel disease. etiology involves alterations microbiological immunological factors. devoted bacterial compound muramyl dipeptide inflammatory pathways pathogenesis molecule underscored gram bacteria trigger immunological intestinal alterations mediators restricted nucleotide oligomerization normalization intestinal inflammatory emphasizes pathogenic pathogenesis highlighted alterations pathways translate therapeutic | non_dup | [] |
48202982 | 10.1007/s00018-013-1270-z | International audienceING1 (Inhibitor of Growth 1) was identified and characterized as a "candidate" tumor suppressor gene in 1996. Subsequently four more genes, also characterized as "candidate" tumor suppressor genes, were identified by homology search: ING2, ING3, ING4 and ING5. The ING proteins are characterized by a high homology in their C-terminal domain which contains a Nuclear Localization Sequence (NLS) and a Plant HomeoDomain (PHD) which has a high affinity to Histone 3 tri-methylated on lysine 4 (H3K4Me3). The ING proteins have been involved in the control of cell growth, senescence, apoptosis, chromatin remodelling and DNA repair. Within the ING family, ING1 and ING2 form a subgroup since they are evolutionarily and functionally close. In Yeast, only one gene, Pho23, is related to ING1 and ING2 and possesses also a PHD. Recently, the ING1 and ING2 tumor suppressor status has been fully established since several studies have described the loss of ING1 and ING2 protein expression in human tumors and both ING1 and ING2 knockout mice were reported to have spontaneously developed tumors, B-cell lymphomas and soft tissue sarcomas respectively. In this review we will describe for the first time what is known about ING1 and ING2 genes, proteins, their regulations in both human and mice, and their status in human tumors. Furthermore, we explore the current knowledge about identified functions involving ING1 and ING2 in tumor suppression pathways especially in the control of cell cycle and in genome stability | ING1 and ING2: Multi-Faceted Tumor Suppressor Genes | ing1 and ing2: multi-faceted tumor suppressor genes | audienceing inhibitor candidate suppressor subsequently candidate suppressor homology homology localization homeodomain affinity histone methylated lysine senescence apoptosis chromatin remodelling repair. subgroup evolutionarily functionally close. yeast possesses phd. suppressor tumors knockout spontaneously tumors lymphomas sarcomas respectively. regulations tumors. explore involving suppression pathways | non_dup | [] |
61575808 | 10.1007/s00018-013-1327-z | Fas, also known as CD95 or APO-1, is a member of the tumor necrosis factor/nerve growth factor superfamily. Although best characterized in terms of its apoptotic function, recent studies have identified several other cellular responses emanating from Fas. These responses include migration, invasion, inflammation, and proliferation. In this review, we focus on the diverse cellular outcomes of Fas signaling and the molecular switches identified to date that regulate its pro- and anti-apoptotic functions. Such switches occur at different levels of signal transduction, ranging from the receptor through to cross-talk with other signaling pathways. Factors identified to date including other extracellular signals, proteins recruited to the death-inducing signaling complex, and the availability of different intracellular components of signal transduction pathways. The success of therapeutically targeting Fas will require a better understanding of these pathways, as well as the regulatory mechanisms that determine cellular outcome following receptor activation | Life in the Fas lane: differential outcomes of Fas signalling | life in the fas lane: differential outcomes of fas signalling | member necrosis nerve superfamily. apoptotic emanating fas. migration invasion inflammation proliferation. diverse switches regulate apoptotic functions. switches transduction ranging talk pathways. extracellular recruited inducing availability intracellular transduction pathways. success therapeutically targeting pathways regulatory | non_dup | [] |
33072576 | 10.1007/s00018-013-1374-5 | Cardiomyocytes grow during heart maturation or disease-related cardiac remodeling. We present evidence that the intercalated disc (ID) is integral to both longitudinal and lateral growth: increases in width are accommodated by lateral extension of the plicate tread regions and increases in length by sarcomere insertion within the ID. At the margin between myofibril and the folded membrane of the ID lies a transitional junction through which the thin filaments from the last sarcomere run to the ID membrane and it has been suggested that this junction acts as a proto Z-disc for sarcomere addition. In support of this hypothesis, we have investigated the ultrastructure of the ID in mouse hearts from control and dilated cardiomyopathy (DCM) models, the MLP-null and a cardiac-specific β-catenin mutant, cΔex3, as well as in human left ventricle from normal and DCM samples. We find that the ID amplitude can vary tenfold from 0.2 μm up to a maximum of ~2 μm allowing gradual expansion during heart growth. At the greatest amplitude, equivalent to a sarcomere length, A-bands and thick filaments are found within the ID membrane loops together with a Z-disc, which develops at the transitional junction position. Here, also, the tops of the membrane folds, which are rich in αII spectrin, become enlarged and associated with junctional sarcoplasmic reticulum. Systematically larger ID amplitudes are found in DCM samples. Other morphological differences between mouse DCM and normal hearts suggest that sarcomere inclusion is compromised in the diseased hearts | Cardiomyocyte growth and sarcomerogenesis at the intercalated disc | cardiomyocyte growth and sarcomerogenesis at the intercalated disc | cardiomyocytes grow maturation remodeling. intercalated disc longitudinal lateral accommodated lateral plicate tread sarcomere insertion margin myofibril folded lies transitional junction filaments sarcomere junction acts proto disc sarcomere addition. ultrastructure hearts dilated cardiomyopathy catenin cδex ventricle samples. vary tenfold allowing gradual growth. greatest sarcomere thick filaments loops disc develops transitional junction position. tops folds spectrin enlarged junctional sarcoplasmic reticulum. systematically amplitudes samples. morphological hearts sarcomere inclusion compromised diseased hearts | non_dup | [] |
70340840 | 10.1007/s00018-013-1422-1 | Fatty acids constitute a major part of the energy that we obtain from the diet and are
also the principal source for mammals to store energy. To use the incoming or stored
fatty acids as energy, the fatty acids needs to be metabolized of which the majority of
fatty acids will be degraded by the mitochondrial β-oxidation system that in the end
generates energy to the cell in the form of ATP. However, this organelle is not able to
handle all kinds of fatty acids of which very long chain fatty acids, long chain methylbranched
fatty acids and dicarboxylic acids are such cumbersome fatty acids. Therefore
a second organelle, the peroxisome, is required for metabolism of these particular fatty
acids. Also peroxisomes contain a β-oxidation system and similar to the mitochondrial
system is the initial substrate a CoA-esterified fatty acid, so-called acyl-CoA.
This thesis will focus on some enzymes that are active on these acyl-CoA esters, but
that are not directly involved in the β-oxidation per se. Instead they contribute to the
regulation of both acyl-CoA and free coenzyme A levels in different cellular
compartments. This thesis will also include how these fatty acid degrading systems can
be regulated at gene level by affecting different transcription factors by dietary ligands
and by fasting.
The peroxisomal Nudix hydrolase 7α (NUD7α), previously believed to be a CoASH
degrading enzyme, was demonstrated to be a medium chain diphosphatase, most active
on medium chain acyl-CoA esters, to produce 3’,5’-ADP and the corresponding 4’-
acylphosphopantetheine thereof. NUDT7α expression and activity was down regulated
by PPARα activation, which would prevent CoASH degradation and support a high
rate of the β-oxidation in peroxisomes during these conditions.
Peroxisomes are not only needed for the degradation of complex lipids, but are also
essential for many other metabolic pathways such as bile acid and etherphospholipid
synthesis and the degradation of D-amino acids and glyoxylate. The expression of gene
transcripts that code for the proteins involved in these peroxisomal pathways was
investigated almost throughout the whole mouse body with the aim to map the tissue
expression of these pathways. The peroxisomal β-oxidation system is present in all
examined tissues, however with differences in magnitude. More specifically expressed
pathways are e.g. glyoxylate and D-amino acid degradation pathways. Auxiliary
enzymes to the peroxisomal β-oxidation showed tissue specific expression, suggesting
a high degree of tissue specific metabolite patterns, also being dependent on the
metabolic state. The study also shows that PPARα is of major importance for the
regulation in liver of the peroxisomal “transcriptome” during fasting.
Mitochondria degrade both fatty acids and amino acids and the mitochondrial acyl-
CoA thioesterase 9 (ACOT9) was shown to hydrolyze both long chain acyl-CoAs as
well as short chain acyl-CoA intermediates and products of branched-chain amino acid
metabolism. Kinetic characterization of the enzyme suggests a thigh regulation of the
activity during different metabolic conditions in the mitochondria.
Dietary ω-3 PUFAs from fish oil (FO) and krill oil (KO) cause different changes in
lipid profiles and gene regulation when supplemented to mice. FO lowered most
plasma lipids whereas KO only significantly lowered non-esterified fatty acids in
plasma. FO showed a classical PPARα activation response by up regulating genes for
fatty acid utilization and oxidation whereas KO down regulates genes for cholesterol
and fatty acid synthesis | Peroxisomal and mitochondrial enzymes involved in lipid metabolism : studies on function and regulation | peroxisomal and mitochondrial enzymes involved in lipid metabolism : studies on function and regulation | fatty constitute diet principal mammals store energy. incoming stored fatty fatty metabolized majority fatty degraded mitochondrial oxidation generates atp. organelle handle kinds fatty fatty methylbranched fatty dicarboxylic cumbersome fatty acids. organelle peroxisome metabolism fatty acids. peroxisomes oxidation mitochondrial esterified fatty acyl coa. thesis enzymes acyl esters oxidation acyl coenzyme compartments. thesis fatty degrading regulated affecting dietary ligands fasting. peroxisomal nudix hydrolase believed coash degrading enzyme diphosphatase acyl esters acylphosphopantetheine thereof. nudt regulated pparα prevent coash degradation oxidation peroxisomes conditions. peroxisomes degradation lipids metabolic pathways bile etherphospholipid degradation glyoxylate. transcripts peroxisomal pathways pathways. peroxisomal oxidation tissues magnitude. pathways e.g. glyoxylate degradation pathways. auxiliary enzymes peroxisomal oxidation metabolite metabolic state. pparα peroxisomal “transcriptome” fasting. mitochondria degrade fatty mitochondrial acyl thioesterase acot hydrolyze acyl coas acyl intermediates branched metabolism. enzyme thigh metabolic mitochondria. dietary pufas fish krill supplemented mice. lowered lipids lowered esterified fatty plasma. pparα regulating fatty utilization oxidation regulates cholesterol fatty | non_dup | [] |
70343871 | 10.1007/s00018-013-1442-x | The pancreatic β cell relies on appropriate Ca2+ entry through voltage-gated calcium (CaV)
channels to accomplish its unique function insulin secretion and to guarantee its viability.
Well-regulated β cell CaV channels are critical to ensure adequate functional β cell mass,
thereby maintaining adequate insulin release and glucose homeostasis in the body. When β
cell CaV channels mediate insufficient or excessive Ca2+ influx due to either inherited or
acquired defects, β cell becomes malfunctioning and even dies. Type 1 diabetic (T1D)
serum hyperactivates β cell CaV1 channels driving Ca2+-dependent β cell apoptosis via
previously unappreciated mechanisms. The present PhD work has mechanistically dissected
T1D serum-induced hyperactivation of CaV1 channels in the β cell by combining patchclamp
techniques, confocal microscopy, as well as molecular and cellular approaches. It
reveals the following findings:
Functional CaV1.3 channels reside in 20 % of mouse islet CaV1.2-/- β cells. They
characteristically show a large unitary Ba2+ conductance with long-lasting openings in
plasma membrane patches of islet cells endowed with undetectable voltage-gated Na+
currents, larger cell capacitance (> 7 pF) and insulin mRNA. These observations pinpoint β
cell-specific CaV1.2-/- mice as a convenient small animal model for investigation of human
β cell CaV1.3 channel-related disorders such as T1D serum-induced hyperactivation of β
cell CaV1.3 channels.
T1D serum hyperactivates both CaV1.2 and CaV1.3 channels by elevating their
conductivity and number in the β cell plasma membrane. This finding emphasizes that both
CaV1.2 and CaV1.3 channels are potential druggable targets for prevention of Ca2+
overload-induced β cell death.
Apolipoprotein CIII (ApoCIII) in T1D serum is electrophysiologically validated to be
the actual factor enhancing CaV channel currents in the β cell. This validation opens up the
possibility to deplete or neutralize ApoCIII in T1D serum for medical intervention of CaV
channel hyperactivation-driven β cell destruction.
ApoCIII activates both PKA and Src kinase in a scavenger receptor class B type I/β1
integrin-dependent fashion to selectively hyperactivate β cell CaV1 channels without
altering β cell CaV1 channel expression. ApoCIII-induced hyperactivation of β cell CaV1
channels results from the enriched density and increased activity of functional CaV1
channels in the β cell plasma membrane. This newly-identified signaling pathway shows
great potential as a set of novel druggable targets for prevention of Ca2+-dependent β cell death in association with diabetes.
The key endocytic protein syndapin I/PACSIN 1 (PCS1) is richly expressed in β cells to
govern endocytic activity. PCS1-mediated endocytosis acts as a homeostatic control system
to fine-tune the CaV1 channel density in the β cell plasma membrane. These findings add a
new layer of complexity to the mechanisms of β cell CaV1 channel regulation.
ApoCIII impairs both constitutive and regulated β cell endocytosis with no influence on
PCS1 expression. Consequently, ApoCIII abrogates PCS1-dependent endocytic trafficking,
thereby accumulating excessive CaV1 channels in the β cell plasma membrane. These
results delineate a novel mechanism of Ca2+-dependent β cell destruction in diabetes
development and reveal a promising and attractive option to counteract the critical
diabetogenic process of Ca2+-dependent β cell death.
Overall, the aforementioned findings depict a mechanistic picture of how ApoCIII
renders CaV1 channels highly enriched and excessively activated in the β cell plasma
membrane, thereby resulting in pathologically exaggerated Ca2+ influx and Ca2+-dependent
β death. These findings lay the foundation for novel treatment strategies for diabetes | Mechanisms of type 1 diabetic serum-induced hyperactivation of CaV1 channels in the pancreatic β cell | mechanisms of type 1 diabetic serum-induced hyperactivation of cav1 channels in the pancreatic β cell | pancreatic relies entry gated calcium accomplish insulin secretion guarantee viability. regulated ensure adequate thereby maintaining adequate insulin glucose homeostasis body. mediate insufficient excessive influx inherited acquired defects malfunctioning dies. diabetic hyperactivates driving apoptosis unappreciated mechanisms. mechanistically dissected hyperactivation combining patchclamp confocal microscopy approaches. reveals reside islet cells. characteristically unitary conductance lasting openings patches islet endowed undetectable gated currents capacitance insulin mrna. pinpoint convenient disorders hyperactivation channels. hyperactivates elevating conductivity membrane. emphasizes druggable targets prevention overload death. apolipoprotein ciii apociii electrophysiologically validated enhancing currents cell. validation opens deplete neutralize apociii hyperactivation destruction. apociii activates scavenger integrin fashion selectively hyperactivate altering expression. apociii hyperactivation enriched membrane. newly great druggable targets prevention diabetes. endocytic syndapin pacsin richly govern endocytic activity. endocytosis acts homeostatic fine tune membrane. regulation. apociii impairs constitutive regulated endocytosis expression. apociii abrogates endocytic trafficking thereby accumulating excessive membrane. delineate destruction reveal promising attractive option counteract diabetogenic death. aforementioned depict mechanistic picture apociii renders enriched excessively thereby pathologically exaggerated influx death. foundation | non_dup | [] |
34996394 | 10.1007/s00018-013-1450-x | Focal adhesions are cellular structures through which both mechanical forces and regulatory signals are transmitted. Two focal adhesion-associated proteins, Crk-associated substrate (CAS) and vinculin, were both independently shown to be crucial for the ability of cells to transmit mechanical forces and to regulate cytoskeletal tension. Here, we identify a novel, direct binding interaction between CAS and vinculin. This interaction is mediated by the CAS SRC homology 3 domain and a proline-rich sequence in the hinge region of vinculin. We show that CAS localization in focal adhesions is partially dependent on vinculin, and that CAS–vinculin coupling is required for stretch-induced activation of CAS at the Y410 phosphorylation site. Moreover, CAS–vinculin binding significantly affects the dynamics of CAS and vinculin within focal adhesions as well as the size of focal adhesions. Finally, disruption of CAS binding to vinculin reduces cell stiffness and traction force generation. Taken together, these findings strongly implicate a crucial role of CAS–vinculin interaction in mechanosensing and focal adhesion dynamic | CAS directly interacts with vinculin to control mechanosensing and focal adhesion dynamics | cas directly interacts with vinculin to control mechanosensing and focal adhesion dynamics | focal adhesions forces regulatory transmitted. focal adhesion vinculin independently crucial transmit forces regulate cytoskeletal tension. vinculin. homology proline hinge vinculin. localization focal adhesions partially vinculin cas–vinculin stretch phosphorylation site. cas–vinculin affects vinculin focal adhesions focal adhesions. disruption vinculin reduces stiffness traction generation. implicate crucial cas–vinculin mechanosensing focal adhesion | non_dup | [] |
73939126 | 10.1007/s00018-013-1480-4. | Amyotrophic lateral sclerosis (ALS) is a lethal disease involving the loss of motor neurons. Although the mechanisms responsible for motor neuron degeneration in ALS remain elusive, the development of stem cell‐based therapies for the treatment of ALS has gained widespread support. Here, we review the types of stem cells being considered for therapeutic applications in ALS, and emphasize recent preclinical advances that provide supportive rationale for clinical translation. We also discuss early trials from around the world translating cellular therapies to ALS patients, and offer important considerations for future clinical trial design. Although clinical translation is still in its infancy, and additional insight into the mechanisms underlying therapeutic efficacy and the establishment of long‐term safety are required, these studies represent an important first step toward the development of effective cellular therapies for the treatment of ALS. S tem C ells 2014;32:1099–110 | Concise Review: Stem Cell Therapies for Amyotrophic Lateral Sclerosis: Recent Advances and Prospects for the Future | concise review: stem cell therapies for amyotrophic lateral sclerosis: recent advances and prospects for the future | amyotrophic lateral sclerosis lethal involving motor neurons. motor neuron degeneration elusive cell‐based therapies gained widespread support. therapeutic emphasize preclinical advances supportive rationale translation. translating therapies offer considerations design. translation infancy insight therapeutic efficacy establishment long‐term toward therapies als. ells | non_dup | [] |
19533194 | 10.1007/s00018-013-1549-0 | The head is innervated by 12 cranial nerves (I–XII) that regulate its sensory and motor functions. Cranial nerves are composed of sensory, motor, or mixed neuronal populations. Sensory neurons perceive generally somatic sensations such as pressure, pain, and temperature. These neurons are also involved in smell, vision, taste, and hearing. Motor neurons ensure the motility of all muscles and glands. Innervation plays an essential role in the development of the various orofacial structures during embryogenesis. Hypoplastic cranial nerves often lead to abnormal development of their target organs and tissues. For example, Möbius syndrome is a congenital disease characterized by defective innervation (i.e., abducens (VI) and facial (VII) nerves), deafness, tooth anomalies, and cleft palate. Hence, it is obvious that the peripheral nervous system is needed for both development and function of orofacial structures. Nerves have a limited capacity to regenerate. However, neural stem cells, which could be used as sources for neural tissue maintenance and repair, have been found in adult neuronal tissues. Similarly, various adult stem cell populations have been isolated from almost all organs of the human body. Stem cells are tightly regulated by their microenvironment, the stem cell niche. Deregulation of adult stem cell behavior results in the development of pathologies such as tumor formation or early tissue senescence. It is thus essential to understand the factors that regulate the functions and maintenance of stem cells. Yet, the potential importance of innervation in the regulation of stem cells and/or their niches in most organs and tissues is largely unexplored. This review focuses on the potential role of innervation in the development and homeostasis of orofacial structures and discusses its possible association with stem cell populations during tissue repair | Roles of innervation in developing and regenerating orofacial tissues | roles of innervation in developing and regenerating orofacial tissues | innervated cranial nerves i–xii regulate sensory motor functions. cranial nerves composed sensory motor neuronal populations. sensory perceive somatic sensations temperature. smell vision taste hearing. motor ensure motility muscles glands. innervation plays orofacial embryogenesis. hypoplastic cranial nerves abnormal organs tissues. möbius syndrome congenital defective innervation i.e. abducens facial nerves deafness tooth anomalies cleft palate. obvious peripheral nervous orofacial structures. nerves regenerate. maintenance repair neuronal tissues. organs body. tightly regulated microenvironment niche. deregulation pathologies senescence. regulate maintenance cells. innervation niches organs tissues largely unexplored. focuses innervation homeostasis orofacial discusses repair | non_dup | [] |
19964191 | 10.1007/s00018-013-1553-4 | Schizophrenia is a genetically complex disease considered to have a neurodevelopmental pathogenesis and defined by a broad spectrum of positive and negative symptoms as well as cognitive deficits. Recently, large genome-wide association studies have identified common alleles slightly increasing the risk for schizophrenia. Among the few schizophrenia-risk genes that have been consistently replicated is the basic Helix-Loop-Helix (bHLH) transcription factor 4 (TCF4). Haploinsufficiency of the TCF4 (formatting follows IUPAC nomenclature: TCF4 protein/protein function, Tcf4 rodent gene cDNA mRNA, TCF4 human gene cDNA mRNA) gene causes the Pitt-Hopkins syndrome-a neurodevelopmental disease characterized by severe mental retardation. Accordingly, Tcf4 null-mutant mice display developmental brain defects. TCF4-associated risk alleles are located in putative coding and non-coding regions of the gene. Hence, subtle changes at the level of gene expression might be relevant for the etiopathology of schizophrenia. Behavioural phenotypes obtained with a mouse model of slightly increased gene dosage and electrophysiological investigations with human risk-allele carriers revealed an overlapping spectrum of schizophrenia-relevant endophenotypes. Most prominently, early information processing and higher cognitive functions appear to be associated with TCF4 risk genotypes. Moreover, a recent human study unravelled gene × environment interactions between TCF4 risk alleles and smoking behaviour that were specifically associated with disrupted early information processing. Taken together, TCF4 is considered as an integrator ('hub') of several bHLH networks controlling critical steps of various developmental, and, possibly, plasticity-related transcriptional programs in the CNS and changes of TCF4 expression also appear to affect brain networks important for information processing. Consequently, these findings support the neurodevelopmental hypothesis of schizophrenia and provide a basis for identifying the underlying molecular mechanisms | Transcription factor 4 (TCF4) and schizophrenia: integrating the animal and the human perspective | transcription factor 4 (tcf4) and schizophrenia: integrating the animal and the human perspective | schizophrenia genetically neurodevelopmental pathogenesis broad deficits. alleles schizophrenia. schizophrenia consistently replicated helix helix bhlh haploinsufficiency formatting iupac nomenclature rodent cdna cdna pitt hopkins syndrome neurodevelopmental retardation. accordingly display developmental defects. alleles putative coding coding gene. subtle etiopathology schizophrenia. behavioural phenotypes dosage electrophysiological investigations allele carriers overlapping schizophrenia endophenotypes. prominently genotypes. unravelled alleles smoking disrupted processing. integrator bhlh controlling developmental possibly plasticity transcriptional programs processing. neurodevelopmental schizophrenia identifying | non_dup | [] |
42932802 | 10.1007/s00018-014-1618-z | Under physiological and pathological conditions, extracellular vesicles (EVs) are present in the extracellular compartment simultaneously with soluble mediators. We hypothesized that cytokine effects may be modulated by EVs, the recently recognized conveyors of intercellular messages. In order to test this hypothesis, human monocyte cells were incubated with CCRF acute lymphoblastic leukemia cell line-derived EVs with or without the addition of recombinant human TNF, and global gene expression changes were analyzed. EVs alone regulated the expression of numerous genes related to inflammation and signaling. In combination, the effects of EVs and TNF were additive, antagonistic, or independent. The differential effects of EVs and TNF or their simultaneous presence were also validated by Taqman assays and ELISA, and by testing different populations of purified EVs. In the case of the paramount chemokine IL-8, we were able to demonstrate a synergistic upregulation by purified EVs and TNF. Our data suggest that neglecting the modulating role of EVs on the effects of soluble mediators may skew experimental results. On the other hand, considering the combined effects of cytokines and EVs may prove therapeutically useful by targeting both compartments at the same time | Critical role of extracellular vesicles in modulating the cellular effects of cytokines | critical role of extracellular vesicles in modulating the cellular effects of cytokines | physiological pathological extracellular vesicles extracellular compartment simultaneously soluble mediators. hypothesized cytokine modulated recognized conveyors intercellular messages. monocyte incubated ccrf lymphoblastic leukemia recombinant analyzed. regulated numerous inflammation signaling. additive antagonistic independent. simultaneous validated taqman assays elisa purified evs. paramount chemokine synergistic upregulation purified tnf. neglecting modulating soluble mediators skew results. cytokines therapeutically targeting compartments | non_dup | [] |
77156232 | 10.1007/s00018-014-1627-y | By virtue of their general ability to bind (hold) translocating or unfolding polypeptides otherwise doomed to aggregate, molecular chaperones are commonly dubbed "holdases". Yet, chaperones also carry physiological functions that do not necessitate prevention of aggregation, such as altering the native states of proteins, as in the disassembly of SNARE complexes and clathrin coats. To carry such physiological functions, major members of the Hsp70, Hsp110, Hsp100, and Hsp60/CCT chaperone families act as catalytic unfolding enzymes or unfoldases that drive iterative cycles of protein binding, unfolding/pulling, and release. One unfoldase chaperone may thus successively convert many misfolded or alternatively folded polypeptide substrates into transiently unfolded intermediates, which, once released, can spontaneously refold into low-affinity native products. Whereas during stress, a large excess of non-catalytic chaperones in holding mode may optimally prevent protein aggregation, after the stress, catalytic disaggregases and unfoldases may act as nanomachines that use the energy of ATP hydrolysis to repair proteins with compromised conformations. Thus, holding and catalytic unfolding chaperones can act as primary cellular defenses against the formation of early misfolded and aggregated proteotoxic conformers in order to avert or retard the onset of degenerative protein conformational diseases | Molecular chaperones are nanomachines that catalytically unfold misfolded and alternatively folded proteins. | molecular chaperones are nanomachines that catalytically unfold misfolded and alternatively folded proteins. | virtue bind hold translocating unfolding polypeptides doomed aggregate chaperones commonly dubbed holdases chaperones carry physiological necessitate prevention aggregation altering native disassembly snare complexes clathrin coats. carry physiological chaperone families catalytic unfolding enzymes unfoldases drive iterative cycles unfolding pulling release. unfoldase chaperone successively convert misfolded alternatively folded polypeptide substrates transiently unfolded intermediates released spontaneously refold affinity native products. excess catalytic chaperones holding optimally prevent aggregation catalytic disaggregases unfoldases nanomachines hydrolysis repair compromised conformations. holding catalytic unfolding chaperones defenses misfolded aggregated proteotoxic conformers avert retard onset degenerative conformational | non_dup | [] |
50566660 | 10.1007/s00018-014-1682-4 | A growing body of experimental evidence supports the diagnostic relevance of circulating microRNAs in various diseases including cancer. The biological relevance of circulating microRNAs is, however, largely unknown, particularly in healthy individuals. Here, we propose a hypothesis based on the relative abundance of microRNAs with predominant tumor suppressor activity in the blood of healthy individuals. According to our hypothesis, certain sets of circulating microRNAs might function as a tumor surveillance mechanism exerting continuous inhibition on tumor formation. The microRNA-mediated tumor surveillance might complement cancer immune surveillance | Tumor surveillance by circulating microRNAs: a hypothesis | tumor surveillance by circulating micrornas: a hypothesis | growing supports diagnostic relevance circulating micrornas cancer. relevance circulating micrornas largely unknown healthy individuals. propose abundance micrornas predominant suppressor healthy individuals. circulating micrornas surveillance exerting formation. microrna surveillance complement immune surveillance | non_dup | [] |
55709426 | 10.1007/s00018-014-1697-x | The adipocyte-derived cytokine leptin acts as a metabolic switch, connecting the body's metabolism to high-energy consuming processes such as reproduction and immune responses. We here provide genetic and biochemical evidence that the metabolic and immune functions of leptin can be uncoupled at the receptor level. First, homozygous mutant fatt/fatt mice carry a spontaneous splice mutation causing deletion of the leptin receptor (LR) immunoglobulin-like domain (IGD) in all LR isoforms. These mice are hyperphagic and morbidly obese, but display only minimal changes in size and cellularity of the thymus, and cellular immune responses are unaffected. These animals also displayed liver damage in response to concavalin A comparable to wild-type and heterozygous littermates. Second, treatment of healthy mice with a neutralizing nanobody targeting IGD induced weight gain and hyperinsulinaemia, but completely failed to block development of experimentally induced autoimmune diseases. These data indicate that leptin receptor deficiency or antagonism profoundly affects metabolism, with little concomitant effects on immune functions | Leptin's metabolic and immune functions can be uncoupled at the ligand/receptor interaction level | leptin's metabolic and immune functions can be uncoupled at the ligand/receptor interaction level | adipocyte cytokine leptin acts metabolic switch connecting metabolism consuming reproduction immune responses. biochemical metabolic immune leptin uncoupled level. homozygous fatt fatt carry spontaneous splice mutation causing deletion leptin immunoglobulin isoforms. hyperphagic morbidly obese display cellularity thymus immune unaffected. displayed concavalin comparable heterozygous littermates. healthy neutralizing nanobody targeting hyperinsulinaemia failed experimentally autoimmune diseases. leptin deficiency antagonism profoundly affects metabolism concomitant immune | non_dup | [] |
156625917 | 10.1007/s00018-014-1754-5 | Small heat-shock proteins (sHsps) are a diverse family of intra-cellular molecular chaperone proteins that play a critical role in mitigating and preventing protein aggregation under stress conditions such as elevated temperature, oxidation and infection. In doing so, they assist in the maintenance of protein homeostasis (proteostasis) thereby avoiding the deleterious effects that result from loss of protein function and/or protein aggregation. The chaperone properties of sHsps are therefore employed extensively in many tissues to prevent the development of diseases associated with protein aggregation. Significant progress has been made of late in understanding the structure and chaperone mechanism of sHsps. In this review, we discuss some of these advances, with a focus on mammalian sHsp hetero-oligomerisation, the mechanism by which sHsps act as molecular chaperones to prevent both amorphous and fibrillar protein aggregation, and the role of post-translational modifications in sHsp chaperone function, particularly in the context of disease.SM was supported by a Royal Society
Dorothy Hodgkin Fellowship, HE is supported by an Australian
Research Council Future Fellowship (FT110100586) and JC is supported
by a National Health and Medical Research Council Project
Grant (#1068087) | Small heat-shock proteins: important players in regulating cellular proteostasis | small heat-shock proteins: important players in regulating cellular proteostasis | shock shsps diverse intra chaperone mitigating preventing aggregation elevated oxidation infection. assist maintenance homeostasis proteostasis thereby avoiding deleterious aggregation. chaperone shsps extensively tissues prevent aggregation. progress chaperone shsps. advances mammalian shsp hetero oligomerisation shsps chaperones prevent amorphous fibrillar aggregation translational modifications shsp chaperone royal dorothy hodgkin fellowship australian council fellowship council | non_dup | [] |
52193462 | 10.1007/s00018-014-1768-z | International audienceThe neuromuscular junction (NMJ) is the synaptic connection between motor neurons and muscle fibers. It is involved in crucial processes such as body movements and breathing. Its proper development requires the guidance of motor axons toward their specific targets, the development of multi-innervated myofibers, and a selective synapse stabilization. It first consists of the removal of excessive motor axons on myofibers, going from multi-innervation to a single innervation of each myofiber. Whereas guidance cues of motor axons toward their specific muscular targets are well characterized, only few molecular and cellular cues have been reported as clues for selecting and stabilizing specific neuromuscular junctions. We will first provide a brief summary on NMJ development. We will then review molecular cues that are involved in NMJ stabilization, in both pre- and post-synaptic compartments, considering motor neurons and Schwann cells on the one hand, and muscle on the other hand. We will provide links with pathologies and highlight advances that can be brought both by basic research on NMJ development and clinical data resulting from the analyses of neurodegeneration of synaptic connections to obtain a better understanding of this process. The goal of this review is to highlight the findings toward understanding the roles of poly- or single-innervations and the underlying mechanisms of NMJ stabilization | Mechanisms controlling neuromuscular junction stability. | mechanisms controlling neuromuscular junction stability. | audiencethe neuromuscular junction synaptic connection motor fibers. crucial movements breathing. proper guidance motor axons toward targets innervated myofibers selective synapse stabilization. removal excessive motor axons myofibers going innervation innervation myofiber. guidance cues motor axons toward muscular targets cues clues selecting stabilizing neuromuscular junctions. brief development. cues stabilization synaptic compartments motor schwann hand. links pathologies highlight advances brought neurodegeneration synaptic connections process. goal highlight toward roles poly innervations stabilization | non_dup | [] |
42939085 | 10.1007/s00018-014-1803-0 | In textbooks of biochemistry, nucleoside diphosphate conversion to a triphosphate by nucleoside diphosphate 'kinases' (NDPKs, also named NME or NM23 proteins) merits a few lines of text. Yet this essential metabolic function, mediated by a multimeric phosphotransferase protein, has effects that lie beyond a simple housekeeping role. NDPKs attracted more attention when NM23-H1 was identified as the first metastasis suppressor gene. In this review, we examine these NDPK enzymes from a developmental perspective because of the tractable phenotypes found in simple animal models that point to common themes. The data suggest that NDPK enzymes control the availability of surface receptors to regulate cell-sensing cues during cell migration. NDPKs regulate different forms of membrane enclosure that engulf dying cells during development. We suggest that NDPK enzymes have been essential for the regulated uptake of objects such as bacteria or micronutrients, and this evolutionarily conserved endocytic function contributes to their activity towards the regulation of metastasis | Nucleoside diphosphate kinases (NDPKs) in animal development | nucleoside diphosphate kinases (ndpks) in animal development | textbooks biochemistry nucleoside diphosphate conversion triphosphate nucleoside diphosphate kinases ndpks named merits text. metabolic multimeric phosphotransferase housekeeping role. ndpks attracted metastasis suppressor gene. examine ndpk enzymes developmental perspective tractable phenotypes themes. ndpk enzymes availability receptors regulate sensing cues migration. ndpks regulate enclosure engulf dying development. ndpk enzymes regulated uptake bacteria micronutrients evolutionarily conserved endocytic contributes metastasis | non_dup | [] |
29408822 | 10.1007/s00018-014-1804-z | Open Access This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited. Acknowledgments From the Berlin Laboratory, we thank Ingo Voigt for performing the injections of the two constructs into the oocytes, Bettina Seelhorst for her extensive technical assistance, Anna Thoma for taking specific care of the animals, and John Horn, Charite Core Facility for electron microscopy for performing expert analyses in ultra-cryosections with immunogold technique. Expert comments on the manuscript from Silke Frahm-Barske (Berlin) are also acknowledged. Special thanks to Bob Switzer at NeuroScience Associates Inc. for embedding, sectioning and staining mouse brains. This work was funded by TauRx Therapeutics, Singapore. C.R.H. and C.M.W. declare that they are officers in TauRx Therapeutics Ltd.Peer reviewedPublisher PD | Different pathways of molecular pathophysiology underlie cognitive and motor tauopathy phenotypes in transgenic models for Alzheimer’s disease and frontotemporal lobar degeneration | different pathways of molecular pathophysiology underlie cognitive and motor tauopathy phenotypes in transgenic models for alzheimer’s disease and frontotemporal lobar degeneration | acknowledgments berlin ingo voigt performing injections constructs oocytes bettina seelhorst extensive assistance anna thoma john horn charite facility microscopy performing expert ultra cryosections immunogold technique. expert comments silke frahm barske berlin acknowledged. thanks switzer neuroscience associates inc. embedding sectioning staining brains. funded taurx therapeutics singapore. c.r.h. c.m.w. declare officers taurx therapeutics ltd.peer reviewedpublisher | non_dup | [] |
52434684 | 10.1007/s00018-015-1873-7 | International audienceThe CD28 costimulatory receptor has a pivotal role in T cell biology as this molecule amplifies T cell receptor (TCR) signals to provide an efficient immune T cell response. There is a large debate about how CD28 mediates these signals. Here, we designed a CD28 gene targeted knock-in mouse strain lacking the cytoplasmic tail of CD28. As is the case in CD28-deficient (CD28 knockout) mice, regulatory T cell homeostasis and T cell activation are altered in these CD28 knock-in mice. Unexpectedly, the presence of a CD28 molecule deprived of its cytoplasmic tail could partially induce some early activation events in T cells such as signaling events or expression of early activation markers. These results unravel a new mechanism of T cell costimulation by CD28, independent of its cytoplasmic tail | In the absence of its cytosolic domain, the CD28 molecule still contributes to T cell activation | in the absence of its cytosolic domain, the cd28 molecule still contributes to t cell activation | audiencethe costimulatory pivotal molecule amplifies immune response. debate mediates signals. targeted knock lacking cytoplasmic tail deficient knockout regulatory homeostasis altered knock mice. unexpectedly molecule deprived cytoplasmic tail partially induce markers. unravel costimulation cytoplasmic tail | non_dup | [] |
42338877 | 10.1007/s00018-015-1915-1 | DiC14-amidine is a cationic lipid that was originally designed as a lipid nanocarrier for nucleic acid transport, and turned out to be a Toll-like receptor 4 (TLR4) agonist as well. We found that while E.coli lipopolysaccharide (LPS) is a TLR4 agonist in all species, diC14-amidine nanoliposomes are full agonists for human, mouse and cat receptors but weak horse agonists. Taking advantage of this unusual species-specificity, we used chimeric constructs based on the human and horse sequences and identified two regions in the human TLR4 that modulate the agonist activity of diC14-amidine. Interestingly, these regions lie outside the known LPS binding domain. Competition experiments also support our hypothesis that diC14-amidine interacts primarily with TLR4 hydrophobic crevices located at the edges of the TLR4/TLR4* dimerization interface. We have characterized potential binding modes using molecular docking analysis. Our data suggest that diC14-amidine nanoliposomes activate TLR4 by facilitating its dimerization in a process that is myeloid differentiation 2 (MD-2)-dependent and cluster of differentiation 14 (CD14)-independent. Our data suggest that TLR4 may be activated through binding at different anchoring points, expanding the repertoire of TLR4 ligands to non-MD-2-binding lipids.C.L. is a IEF Marie Curie Action Research Fellow (TLR4-CAT PIEF-GA-2012-326481) and would like to thank the Wiener-Anspach Foundation for financial support. K.L.I. was supported by a HBLB Veterinary Research Training scholarship. This work was supported by program grant support from the Wellcome Trust and the MRC to N.J.G and C.E.B.This is the final version of the article. It first appeared from Springer via http://dx.doi.org/10.1007/s00018-015-1915- | Critical residues involved in Toll-like receptor 4 activation by cationic lipid nanocarriers are not located at the lipopolysaccharide-binding interface | critical residues involved in toll-like receptor 4 activation by cationic lipid nanocarriers are not located at the lipopolysaccharide-binding interface | amidine cationic originally nanocarrier nucleic turned toll agonist well. e.coli lipopolysaccharide agonist amidine nanoliposomes agonists receptors horse agonists. advantage unusual specificity chimeric constructs horse modulate agonist amidine. interestingly domain. competition amidine interacts primarily hydrophobic crevices dimerization interface. docking analysis. amidine nanoliposomes activate facilitating dimerization myeloid independent. anchoring expanding repertoire ligands lipids.c.l. marie curie fellow pief wiener anspach foundation support. k.l.i. hblb veterinary scholarship. wellcome trust n.j.g c.e.b.this article. appeared springer | non_dup | [] |