432 research outputs found
Tissue fusion over non-adhering surfaces
Tissue fusion eliminates physical voids in a tissue to form a continuous
structure and is central to many processes in development and repair. Fusion
events in vivo, particularly in embryonic development, often involve the
purse-string contraction of a pluricellular actomyosin cable at the free edge.
However in vitro, adhesion of the cells to their substrate favors a closure
mechanism mediated by lamellipodial protrusions, which has prevented a
systematic study of the purse-string mechanism. Here, we show that monolayers
can cover well-controlled mesoscopic non-adherent areas much larger than a cell
size by purse-string closure and that active epithelial fluctuations are
required for this process. We have formulated a simple stochastic model that
includes purse-string contractility, tissue fluctuations and effective friction
to qualitatively and quantitatively account for the dynamics of closure. Our
data suggest that, in vivo, tissue fusion adapts to the local environment by
coordinating lamellipodial protrusions and purse-string contractions
Universal quantum computation with the Orbital Angular Momentum of a single photon
We prove that a single photon with quantum data encoded in its orbital
angular momentum can be manipulated with simple optical elements to provide any
desired quantum computation. We will show how to build any quantum unitary
operator using beamsplitters, phase shifters, holograms and an extraction gate
based on quantum interrogation. The advantages and challenges of these approach
are then discussed, in particular the problem of the readout of the results.Comment: First version. Comments welcom
Ciliary Neurotrophic Factor Protects Striatal Neurons against Excitotoxicity by Enhancing Glial Glutamate Uptake
Ciliary neurotrophic factor (CNTF) is a potent neuroprotective cytokine in different animal models of glutamate-induced excitotoxicity, although its action mechanisms are still poorly characterized. We tested the hypothesis that an increased function of glial glutamate transporters (GTs) could underlie CNTF-mediated neuroprotection. We show that neuronal loss induced by in vivo striatal injection of the excitotoxin quinolinic acid (QA) was significantly reduced (by âŒ75%) in CNTF-treated animals. In striatal slices, acute QA application dramatically inhibited corticostriatal field potentials (FPs), whose recovery was significantly higher in CNTF rats compared to controls (âŒ40% vs. âŒ7%), confirming an enhanced resistance to excitotoxicity. The GT inhibitor dl-threo-ÎČ-benzyloxyaspartate greatly reduced FP recovery in CNTF rats, supporting the role of GT in CNTF-mediated neuroprotection. Whole-cell patch-clamp recordings from striatal medium spiny neurons showed no alteration of basic properties of striatal glutamatergic transmission in CNTF animals, but the increased effect of a low-affinity competitive glutamate receptor antagonist (Îł-d-glutamylglycine) also suggested an enhanced GT function. These data strongly support our hypothesis that CNTF is neuroprotective via an increased function of glial GTs, and further confirms the therapeutic potential of CNTF for the clinical treatment of progressive neurodegenerative diseases involving glutamate overflow
Colloquium: Mechanical formalisms for tissue dynamics
The understanding of morphogenesis in living organisms has been renewed by
tremendous progressin experimental techniques that provide access to
cell-scale, quantitative information both on theshapes of cells within tissues
and on the genes being expressed. This information suggests that
ourunderstanding of the respective contributions of gene expression and
mechanics, and of their crucialentanglement, will soon leap forward.
Biomechanics increasingly benefits from models, which assistthe design and
interpretation of experiments, point out the main ingredients and assumptions,
andultimately lead to predictions. The newly accessible local information thus
calls for a reflectionon how to select suitable classes of mechanical models.
We review both mechanical ingredientssuggested by the current knowledge of
tissue behaviour, and modelling methods that can helpgenerate a rheological
diagram or a constitutive equation. We distinguish cell scale ("intra-cell")and
tissue scale ("inter-cell") contributions. We recall the mathematical framework
developpedfor continuum materials and explain how to transform a constitutive
equation into a set of partialdifferential equations amenable to numerical
resolution. We show that when plastic behaviour isrelevant, the dissipation
function formalism appears appropriate to generate constitutive equations;its
variational nature facilitates numerical implementation, and we discuss
adaptations needed in thecase of large deformations. The present article
gathers theoretical methods that can readily enhancethe significance of the
data to be extracted from recent or future high throughput
biomechanicalexperiments.Comment: 33 pages, 20 figures. This version (26 Sept. 2015) contains a few
corrections to the published version, all in Appendix D.2 devoted to large
deformation
Ezrin enhances line tension along transcellular tunnel edges via NMIIa driven actomyosin cable formation
Transendothelial cell macroaperture (TEM) tunnels control endothelium barrier function and are triggered by several toxins from pathogenic bacteria that provoke vascular leakage. Cellular dewetting theory predicted that a line tension of uncharacterized origin works at TEM boundaries to limit their widening. Here, by conducting high-resolution microscopy approaches we unveil the presence of an actomyosin cable encircling TEMs. We develop a theoretical cellular dewetting framework to interpret TEM physical parameters that are quantitatively determined by laser ablation experiments. This establishes the critical role of ezrin and non-muscle myosin II (NMII) in the progressive implementation of line tension. Mechanistically, fluorescence-recovery-after-photobleaching experiments point for the upstream role of ezrin in stabilizing actin filaments at the edges of TEMs, thereby favouring their crosslinking by NMIIa. Collectively, our findings ascribe to ezrin and NMIIa a critical function of enhancing line tension at the cell boundary surrounding the TEMs by promoting the formation of an actomyosin ring.Peer reviewe
The JAK/STAT3 Pathway Is a Common Inducer of Astrocyte Reactivity in Alzheimer's and Huntington's Diseases.
Astrocyte reactivity is a hallmark of neurodegenerative diseases (ND), but its effects on disease outcomes remain highly debated. Elucidation of the signaling cascades inducing reactivity in astrocytes during ND would help characterize the function of these cells and identify novel molecular targets to modulate disease progression. The Janus kinase/signal transducer and activator of transcription 3 (JAK/STAT3) pathway is associated with reactive astrocytes in models of acute injury, but it is unknown whether this pathway is directly responsible for astrocyte reactivity in progressive pathological conditions such as ND. In this study, we examined whether the JAK/STAT3 pathway promotes astrocyte reactivity in several animal models of ND. The JAK/STAT3 pathway was activated in reactive astrocytes in two transgenic mouse models of Alzheimer's disease and in a mouse and a nonhuman primate lentiviral vector-based model of Huntington's disease (HD). To determine whether this cascade was instrumental for astrocyte reactivity, we used a lentiviral vector that specifically targets astrocytes in vivo to overexpress the endogenous inhibitor of the JAK/STAT3 pathway [suppressor of cytokine signaling 3 (SOCS3)]. SOCS3 significantly inhibited this pathway in astrocytes, prevented astrocyte reactivity, and decreased microglial activation in models of both diseases. Inhibition of the JAK/STAT3 pathway within reactive astrocytes also increased the number of huntingtin aggregates, a neuropathological hallmark of HD, but did not influence neuronal death. Our data demonstrate that the JAK/STAT3 pathway is a common mediator of astrocyte reactivity that is highly conserved between disease states, species, and brain regions. This universal signaling cascade represents a potent target to study the role of reactive astrocytes in ND
Evidence of a recent magma dike intrusion at the slow spreading Lucky Strike segment, Mid-Atlantic Ridge
Author Posting. © American Geophysical Union, 2004. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Journal of Geophysical Research 109 (2004): B12102, doi:10.1029/2004JB003141.Mid-ocean ridge volcanic activity is the fundamental process for creation of ocean crust, yet the dynamics of magma emplacement along the slow spreading Mid-Atlantic Ridge (MAR) are largely unknown. We present acoustical, seismological, and biological evidence of a magmatic dike intrusion at the Lucky Strike segment, the first detected from the deeper sections (>1500 m) of the MAR. The dike caused the largest teleseismic earthquake swarm recorded at Lucky Strike in >20 years of seismic monitoring, and one of the largest ever recorded on the northern MAR. Hydrophone records indicate that the rate of earthquake activity decays in a nontectonic manner and that the onset of the swarm was accompanied by 30 min of broadband (>3 Hz) intrusion tremor, suggesting a volcanic origin. Two submersible investigations of high-temperature vents located at the summit of Lucky Strike Seamount 3 months and 1 year after the swarm showed a significant increase in microbial activity and diffuse venting. This magmatic episode may represent one form of volcanism along the MAR, where highly focused pockets of magma are intruded sporadically into the shallow ocean crust beneath long-lived, discrete volcanic structures recharging preexisting seafloor hydrothermal vents and ecosystems.This study was made possible through the support
of the U.S. National Science Foundation (grants OCE-9811575, OCE-
0137164, and OCE-0201692) and the NOAA Vents Program
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