1,064 research outputs found
Intracellular uptake of macromolecules by brain lymphatic endothelial cells during zebrafish embryonic development
The lymphatic system controls fluid homeostasis and the clearance of macromolecules from interstitial compartments. In mammals brain lymphatics were only recently discovered, with significant implications for physiology and disease. We examined zebrafish for the presence of brain lymphatics and found loosely connected endothelial cells with lymphatic molecular signature covering parts of the brain without forming endothelial tubular structures. These brain lymphatic endothelial cells (BLECs) derive from venous endothelium, are distinct from macrophages, and are sensitive to loss of Vegfc. BLECs endocytose macromolecules in a selective manner, which can be blocked by injection of mannose receptor ligands. This first report on brain lymphatic endothelial cells in a vertebrate embryo identifies cells with unique features, including the uptake of macromolecules at a single cell level. Future studies will address whether this represents an uptake mechanism that is conserved in mammals and how these cells affect functions of the embryonic and adult brain
Structural and functional conservation of non-lumenized lymphatic endothelial cells in the mammalian leptomeninges
The vertebrate CNS is surrounded by the meninges, a protective barrier comprised of the outer dura mater and the inner leptomeninges, which includes the arachnoid and pial layers. While the dura mater contains lymphatic vessels, no conventional lymphatics have been found within the brain or leptomeninges. However, non-lumenized cells called Brain/Mural Lymphatic Endothelial Cells or Fluorescent Granule Perithelial cells (muLECs/BLECs/FGPs) that share a developmental program and gene expression with peripheral lymphatic vessels have been described in the meninges of zebrafish. Here we identify a structurally and functionally similar cell type in the mammalian leptomeninges that we name Leptomeningeal Lymphatic Endothelial Cells (LLEC). As in zebrafish, LLECs express multiple lymphatic markers, containing very large, spherical inclusions, and develop independently from the meningeal macrophage lineage. Mouse LLECs also internalize macromolecules from the cerebrospinal fluid, including Amyloid-β, the toxic driver of Alzheimer's disease progression. Finally, we identify morphologically similar cells co-expressing LLEC markers in human post-mortem leptomeninges. Given that LLECs share molecular, morphological, and functional characteristics with both lymphatics and macrophages, we propose they represent a novel, evolutionary conserved cell type with potential roles in homeostasis and immune organization of the meninges
Gravitational Waves from Gravitational Collapse
Gravitational wave emission from the gravitational collapse of massive stars
has been studied for more than three decades. Current state of the art
numerical investigations of collapse include those that use progenitors with
realistic angular momentum profiles, properly treat microphysics issues,
account for general relativity, and examine non--axisymmetric effects in three
dimensions. Such simulations predict that gravitational waves from various
phenomena associated with gravitational collapse could be detectable with
advanced ground--based and future space--based interferometric observatories.Comment: 68 pages including 13 figures; revised version accepted for
publication in Living Reviews in Relativity (http://www.livingreviews.org
Chitin Modulates Innate Immune Responses of Keratinocytes
Chitin, after cellulose the second most abundant polysaccharide in nature, is an essential component of exoskeletons of crabs, shrimps and insects and protects these organisms from harsh conditions in their environment. Unexpectedly, chitin has been found to activate innate immune cells and to elicit murine airway inflammation. The skin represents the outer barrier of the human host defense and is in frequent contact with chitin-bearing organisms, such as house-dust mites or flies. The effects of chitin on keratinocytes, however, are poorly understood.
We hypothesized that chitin stimulates keratinocytes and thereby modulates the innate immune response of the skin. Here we show that chitin is bioactive on primary and immortalized keratinocytes by triggering production of pro-inflammatory cytokines and chemokines. Chitin stimulation further induced the expression of the Toll-like receptor (TLR) TLR4 on keratinocytes at mRNA and protein level. Chitin-induced effects were mainly abrogated when TLR2 was blocked, suggesting that TLR2 senses chitin on keratinocytes.
We speculate that chitin-bearing organisms modulate the innate immune response towards pathogens by upregulating secretion of cytokines and chemokines and expression of MyD88-associated TLRs, two major components of innate immunity. The clinical relevance of this mechanism remains to be defined
Membranes by the Numbers
Many of the most important processes in cells take place on and across
membranes. With the rise of an impressive array of powerful quantitative
methods for characterizing these membranes, it is an opportune time to reflect
on the structure and function of membranes from the point of view of biological
numeracy. To that end, in this article, I review the quantitative parameters
that characterize the mechanical, electrical and transport properties of
membranes and carry out a number of corresponding order of magnitude estimates
that help us understand the values of those parameters.Comment: 27 pages, 12 figure
Magnetic Coupling in the Quiet Solar Atmosphere
Three kinds of magnetic couplings in the quiet solar atmosphere are
highlighted and discussed, all fundamentally connected to the Lorentz force.
First the coupling of the convecting and overshooting fluid in the surface
layers of the Sun with the magnetic field. Here, the plasma motion provides the
dominant force, which shapes the magnetic field and drives the surface dynamo.
Progress in the understanding of the horizontal magnetic field is summarized
and discussed. Second, the coupling between acoustic waves and the magnetic
field, in particular the phenomenon of wave conversion and wave refraction. It
is described how measurements of wave travel times in the atmosphere can
provide information about the topography of the wave conversion zone, i.e., the
surface of equal Alfv\'en and sound speed. In quiet regions, this surface
separates a highly dynamic magnetic field with fast moving magnetosonic waves
and shocks around and above it from the more slowly evolving field of high-beta
plasma below it. Third, the magnetic field also couples to the radiation field,
which leads to radiative flux channeling and increased anisotropy in the
radiation field. It is shown how faculae can be understood in terms of this
effect. The article starts with an introduction to the magnetic field of the
quiet Sun in the light of new results from the Hinode space observatory and
with a brief survey of measurements of the turbulent magnetic field with the
help of the Hanle effect.Comment: To appear in "Magnetic Coupling between the Interior and the
Atmosphere of the Sun", eds. S.S. Hasan and R.J. Rutten, Astrophysics and
Space Science Proceedings, Springer-Verlag, Heidelberg, Berlin, 200
Further Experimental Studies of Two-Body Radiative \Upsilon Decays
Continuing our studies of radiative Upsilon(1S) decays, we report on a search
for Upsilon to gamma eta and Upsilon to gamma f_{J}(2220) in 61.3 pb^{-1} of
e^{+}e^{-} data taken with the CLEO II detector at the Cornell Electron Storage
Ring. For the gamma eta search the three decays of the eta meson to
pi^{+}pi^{-}pi^{0}, pi^{0}pi^{0}pi^{0}, and gamma gamma were investigated. We
found no candidate events in the two (3\pi)^{0} modes and no significant excess
over expected backgrounds in the gamma gamma mode to set a limit on the
branching fraction of B(Upsilon to gamma eta) < 2.1 x 10^{-5} at 90% C.L. The
three charged two-body final states h h-bar (h = pi^{+}, K^{+}, p) were
investigated for f_{J}(2220) production, with one, one, and two events found,
respectively. Limits at 90% C.L. of B(\Upsilon to gamma f_{J}) x B(f_{J} to h
h-bar) ~ 1.5 x 10^{-5} have been set for each of these modes. We compare our
results to measurements of other radiative Upsilon decays, to measurements of
radiative J/psi decays, and to theoretical predictions.Comment: 19 pages postscript, also available through
http://w4.lns.cornell.edu/public/CLNS, submitted to Physical Review
Double hadron leptoproduction in the nuclear medium
First measurement of double-hadron production in deep-inelastic scattering
has been measured with the HERMES spectrometer at HERA using a 27.6 GeV
positron beam with deuterium, nitrogen, krypton and xenon targets. The
influence of the nuclear medium on the ratio of double-hadron to single-hadron
yields has been investigated. Nuclear effects are clearly observed but with
substantially smaller magnitude and reduced -dependence compared to
previously measured single-hadron multiplicity ratios. The data are in fair
agreement with models based on partonic or pre-hadronic energy loss, while they
seem to rule out a pure absorptive treatment of the final state interactions.
Thus, the double-hadron ratio provides an additional tool for studying
modifications of hadronization in nuclear matter
The co-evolution of the genome and epigenome in colorectal cancer.
Colorectal malignancies are a leading cause of cancer-related death1 and have undergone extensive genomic study2,3. However, DNA mutations alone do not fully explain malignant transformation4-7. Here we investigate the co-evolution of the genome and epigenome of colorectal tumours at single-clone resolution using spatial multi-omic profiling of individual glands. We collected 1,370 samples from 30 primary cancers and 8 concomitant adenomas and generated 1,207 chromatin accessibility profiles, 527 whole genomes and 297 whole transcriptomes. We found positive selection for DNA mutations in chromatin modifier genes and recurrent somatic chromatin accessibility alterations, including in regulatory regions of cancer driver genes that were otherwise devoid of genetic mutations. Genome-wide alterations in accessibility for transcription factor binding involved CTCF, downregulation of interferon and increased accessibility for SOX and HOX transcription factor families, suggesting the involvement of developmental genes during tumourigenesis. Somatic chromatin accessibility alterations were heritable and distinguished adenomas from cancers. Mutational signature analysis showed that the epigenome in turn influences the accumulation of DNA mutations. This study provides a map of genetic and epigenetic tumour heterogeneity, with fundamental implications for understanding colorectal cancer biology
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