105 research outputs found
Electrophysiology of Concatameric Pannexin 1 Channels Reveals the Stoichiometry of C-Terminal Autoinhibition
Codi d'Art PĂșblic: 8008-1 (La RepĂșblica); Reportatge realitzat als dies 4 i 18-7-1990Pericas, Enric (arquitecte); Viaplana, Albert (arquitecte i estructura); Viladomat Massanas, Josep (escultura);Joan Pie (MedallĂł); Piñón, Helio (Estr
Past and future decline of tropical pelagic biodiversity
Author's accepted version (postprint).This is an Accepted Manuscript of an article published by the National Academy of Sciences in PNAS on 26/05/2020.Available online: https://www.pnas.org/content/pnas/117/23/12891.full.pdfA major research question concerning global pelagic biodiversity remains unanswered: when did the apparent tropical biodiversity depression (i.e., bimodality of latitudinal diversity gradient [LDG]) begin? The bimodal LDG may be a consequence of recent ocean warming or of deep-time evolutionary speciation and extinction processes. Using rich fossil datasets of planktonic foraminifers, we show here that a unimodal (or only weakly bimodal) diversity gradient, with a plateau in the tropics, occurred during the last ice age and has since then developed into a bimodal gradient through species distribution shifts driven by postglacial ocean warming. The bimodal LDG likely emerged before the Anthropocene and industrialization, and perhaps âŒ15,000 y ago, indicating a strong environmental control of tropical diversity even before the start of anthropogenic warming. However, our model projections suggest that future anthropogenic warming further diminishes tropical pelagic diversity to a level not seen in millions of years.acceptedVersio
Resistance to antiangiogenic therapy is directed by vascular phenotype, vessel stabilization, and maturation in malignant melanoma
Angiogenesis is not only dependent on endothelial cell invasion and proliferation, it also requires pericyte coverage of vascular sprouts for stabilization of vascular walls. Clinical efficacy of angiogenesis inhibitors targeting the vascular endothelial growth factor (VEGF) signaling pathway is still limited to date. We hypothesized that the level of vessel maturation is critically involved in the response to antiangiogenic therapies. To test this hypothesis, we evaluated the vascular network in spontaneously developing melanomas of MT/ret transgenic mice after using PTK787/ZK222584 for anti-VEGF therapy but also analyzed human melanoma metastases taken at clinical relapse in patients undergoing adjuvant treatment using bevacizumab. Both experimental settings showed that tumor vessels, which are resistant to anti-VEGF therapy, are characterized by enhanced vessel diameter and normalization of the vascular bed by coverage of mature pericytes and immunoreactivity for desmin, NG-2, platelet-derived growth factor receptor ÎČ, and the late-stage maturity marker α smooth muscle actin. Our findings emphasize that the level of mural cell differentiation and stabilization of the vascular wall significantly contribute to the response toward antiangiogenic therapy in melanoma. This study may be useful in paving the way toward a more rational development of second generation antiangiogenic combination therapies and in providing, for the first time, a murine model to study this
How many human proteoforms are there?
Despite decades of accumulated knowledge about proteins and their post-translational modifications (PTMs), numerous questions remain regarding their molecular composition and biological function. One of the most fundamental queries is the extent to which the combinations of DNA-, RNA- and PTM-level variations explode the complexity of the human proteome. Here, we outline what we know from current databases and measurement strategies including mass spectrometry-based proteomics. In doing so, we examine prevailing notions about the number of modifications displayed on human proteins and how they combine to generate the protein diversity underlying health and disease. We frame central issues regarding determination of protein-level variation and PTMs, including some paradoxes present in the field today. We use this framework to assess existing data and to ask the question, "How many distinct primary structures of proteins (proteoforms) are created from the 20,300 human genes?" We also explore prospects for improving measurements to better regularize protein-level biology and efficiently associate PTMs to function and phenotype
Expression of Genes Encoding Multi-Transmembrane Proteins in Specific Primate Taste Cell Populations
BACKGROUND: Using fungiform (FG) and circumvallate (CV) taste buds isolated by laser capture microdissection and analyzed using gene arrays, we previously constructed a comprehensive database of gene expression in primates, which revealed over 2,300 taste bud-associated genes. Bioinformatics analyses identified hundreds of genes predicted to encode multi-transmembrane domain proteins with no previous association with taste function. A first step in elucidating the roles these gene products play in gustation is to identify the specific taste cell types in which they are expressed. METHODOLOGY/PRINCIPAL FINDINGS: Using double label in situ hybridization analyses, we identified seven new genes expressed in specific taste cell types, including sweet, bitter, and umami cells (TRPM5-positive), sour cells (PKD2L1-positive), as well as other taste cell populations. Transmembrane protein 44 (TMEM44), a protein with seven predicted transmembrane domains with no homology to GPCRs, is expressed in a TRPM5-negative and PKD2L1-negative population that is enriched in the bottom portion of taste buds and may represent developmentally immature taste cells. Calcium homeostasis modulator 1 (CALHM1), a component of a novel calcium channel, along with family members CALHM2 and CALHM3; multiple C2 domains; transmembrane 1 (MCTP1), a calcium-binding transmembrane protein; and anoctamin 7 (ANO7), a member of the recently identified calcium-gated chloride channel family, are all expressed in TRPM5 cells. These proteins may modulate and effect calcium signalling stemming from sweet, bitter, and umami receptor activation. Synaptic vesicle glycoprotein 2B (SV2B), a regulator of synaptic vesicle exocytosis, is expressed in PKD2L1 cells, suggesting that this taste cell population transmits tastant information to gustatory afferent nerve fibers via exocytic neurotransmitter release. CONCLUSIONS/SIGNIFICANCE: Identification of genes encoding multi-transmembrane domain proteins expressed in primate taste buds provides new insights into the processes of taste cell development, signal transduction, and information coding. Discrete taste cell populations exhibit highly specific gene expression patterns, supporting a model whereby each mature taste receptor cell is responsible for sensing, transmitting, and coding a specific taste quality
The Habitable Exoplanet Observatory (HabEx) Mission Concept Study Final Report
The Habitable Exoplanet Observatory, or HabEx, has been designed to be the Great Observatory of the 2030s. For the first time in human history, technologies have matured sufficiently to enable an affordable space-based telescope mission capable of discovering and characterizing Earthlike planets orbiting nearby bright sunlike stars in order to search for signs of habitability and biosignatures. Such a mission can also be equipped with instrumentation that will enable broad and exciting general astrophysics and planetary science not possible from current or planned facilities. HabEx is a space telescope with unique imaging and multi-object spectroscopic capabilities at wavelengths ranging from ultraviolet (UV) to near-IR. These capabilities allow for a broad suite of compelling science that cuts across the entire NASA astrophysics portfolio. HabEx has three primary science goals: (1) Seek out nearby worlds and explore their habitability; (2) Map out nearby planetary systems and understand the diversity of the worlds they contain; (3) Enable new explorations of astrophysical systems from our own solar system to external galaxies by extending our reach in the UV through near-IR. This Great Observatory science will be selected through a competed GO program, and will account for about 50% of the HabEx primary mission. The preferred HabEx architecture is a 4m, monolithic, off-axis telescope that is diffraction-limited at 0.4 microns and is in an L2 orbit. HabEx employs two starlight suppression systems: a coronagraph and a starshade, each with their own dedicated instrument
The Habitable Exoplanet Observatory (HabEx) Mission Concept Study Final Report
The Habitable Exoplanet Observatory, or HabEx, has been designed to be the
Great Observatory of the 2030s. For the first time in human history,
technologies have matured sufficiently to enable an affordable space-based
telescope mission capable of discovering and characterizing Earthlike planets
orbiting nearby bright sunlike stars in order to search for signs of
habitability and biosignatures. Such a mission can also be equipped with
instrumentation that will enable broad and exciting general astrophysics and
planetary science not possible from current or planned facilities. HabEx is a
space telescope with unique imaging and multi-object spectroscopic capabilities
at wavelengths ranging from ultraviolet (UV) to near-IR. These capabilities
allow for a broad suite of compelling science that cuts across the entire NASA
astrophysics portfolio. HabEx has three primary science goals: (1) Seek out
nearby worlds and explore their habitability; (2) Map out nearby planetary
systems and understand the diversity of the worlds they contain; (3) Enable new
explorations of astrophysical systems from our own solar system to external
galaxies by extending our reach in the UV through near-IR. This Great
Observatory science will be selected through a competed GO program, and will
account for about 50% of the HabEx primary mission. The preferred HabEx
architecture is a 4m, monolithic, off-axis telescope that is
diffraction-limited at 0.4 microns and is in an L2 orbit. HabEx employs two
starlight suppression systems: a coronagraph and a starshade, each with their
own dedicated instrument.Comment: Full report: 498 pages. Executive Summary: 14 pages. More information
about HabEx can be found here: https://www.jpl.nasa.gov/habex
Oceans and Coastal Ecosystems and Their Services
Ocean and coastal ecosystems support life on Earth and many
aspects of human well-being. Covering two-thirds of the planet,
the ocean hosts vast biodiversity and modulates the global climate
system by regulating cycles of heat, water and elements, including
carbon. Marine systems are central to many cultures, and they also
provide food, minerals, energy and employment to people. Since
previous assessments1
, new laboratory studies, field observations
and process studies, a wider range of model simulations, Indigenous
knowledge, and local knowledge have provided increasing evidence
on the impacts of climate change on ocean and coastal systems, how
human communities are experiencing these impacts, and the potential
solutions for ecological and human adaptation.Peer reviewe
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