FILTER MEDIA TEST UNIT

Dow Chemicalhttp://deepblue.lib.umich.edu/bitstream/2027.42/96203/1/me450f12project10_report.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/96203/2/me450f12project10_photo.jp

Lysophospholipid (LPA) receptors (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database

Lysophosphatidic acid (LPA) receptors (nomenclature as agreed by the NC-IUPHAR Subcommittee on Lysophospholipid Receptors [50, 18]) are activated by the endogenous phospholipid LPA. The first receptor, LPA1, was identified as ventricular zone gene-1 (vzg-1) [38], leading to deorphanisation of members of the endothelial differentiation gene (edg) family as other LPA receptors along with sphingosine 1-phosphate (S1P) receptors. Additional LPA receptor GPCRs were later identified. Gene names have been codified as LPAR1, etc. to reflect the receptor function of proteins. The crystal structure of LPA1 was solved and demonstrates extracellular LPA access to the binding pocket, consistent with proposed delivery via autotaxin [12]. These studies have also implicated cross-talk with endocannabinoids via phosphorylated intermediates that can also activate these receptors. The identified receptors can account for most, although not all, LPA-induced phenomena in the literature, indicating that a majority of LPA-dependent phenomena are receptor-mediated. Binding affinities of unlabeled, natural LPA and AEAp to LPA1 were measured using backscattering interferometry (pKd = 9) [73]. Binding affinities were 77-fold lower than than values obtained using radioactivity [111]. Targeted deletion of LPA receptors has clarified signalling pathways and identified physiological and pathophysiological roles. Independent validation by multiple groups has been reported in the peer-reviewed literature for all six LPA receptors described in the tables, including further validation using a distinct read-out via a novel TGFα "shedding" assay [45]. LPA has also been described as an agonist for the transient receptor potential (Trp) ion channel TRPV1 [76] and TRPA1 [53]. LPA was originally proposed to be a ligand for GPCR35, but data show that in fact it is a receptor for CXCL17 [68]. All of these proposed non-GPCR receptor identities require confirmation and are not currently recognized as bona fide LPA receptors

High-resolution survey for planetary companions to young stars in the Taurus molecular cloud

Direct imaging in the infrared at the diffraction limit of large telescopes is a unique probe of the properties of young planetary systems. We survey 55 single class I and class II stars in Taurus in the L’ filter using natural and laser guide star adaptive optics and the near-infrared camera (NIRC2) of the Keck II telescope, in order to search for planetary-mass companions. We use both reference star differential imaging and kernel phase techniques, achieving typical 5σ contrasts of ∼6 mag at separations of 0.2 arcsec and ∼8 mag beyond 0.5 arcsec. Although, we do not detect any new faint companions, we constrain the frequency of wide separation massive planets, such as HR 8799 analogues. We find that, assuming hot-start models and a planet distribution with power-law mass and semimajor axis indices of −0.5 and −1, respectively, less than 20 per cent of our target stars host planets with masses >2 MJ at separations >10 au.The observatory was made possible by the generous financial support of the W. M. Keck Foundation. ALW would like to thank the Australian Government for their support through the Australian Postgraduate Award Scholarship and the Research School of Astronomy and Astrophysics at the Australian National University for the ANU Supplementary PhD Scholarship

Identification of Three Molecular and Functional Subtypes in Canine Hemangiosarcoma through Gene Expression Profiling and Progenitor Cell Characterization

Canine hemangiosarcomas have been ascribed to an endothelial origin based on histologic appearance; however, recent findings suggest that these tumors may arise instead from hematopoietic progenitor cells. To clarify this ontogenetic dilemma, we used genome-wide expression profiling of primary hemangiosarcomas and identified three distinct tumor subtypes associated with angiogenesis (group 1), inflammation (group 2), and adipogenesis (group 3). Based on these findings, we hypothesized that a common progenitor may differentiate into the three tumor subtypes observed in our gene profiling experiment. To investigate this possibility, we cultured hemangiosarcoma cell lines under normal and sphere-forming culture conditions to enrich for tumor cell progenitors. Cells from sphere-forming cultures displayed a robust self-renewal capacity and exhibited genotypic, phenotypic, and functional properties consistent with each of the three molecular subtypes seen in primary tumors, including expression of endothelial progenitor cell (CD133 and CD34) and endothelial cell (CD105, CD146, and αvβ3 integrin) markers, expression of early hematopoietic (CD133, CD117, and CD34) and myeloid (CD115 and CD14) differentiation markers in parallel with increased phagocytic capacity, and acquisition of adipogenic potential. Collectively, these results suggest that canine hemangiosarcomas arise from multipotent progenitors that differentiate into distinct subtypes. Improved understanding of the mechanisms that determine the molecular and phenotypic differentiation of tumor cells in vivo could change paradigms regarding the origin and progression of endothelial sarcomas

Quark-gluon vertex in general kinematics

The original publication can be found at www.springerlink.com Submitted to Cornell University’s online archive www.arXiv.org in 2007 by Jon-Ivar Skullerud. Post-print sourced from www.arxiv.org.We compute the quark–gluon vertex in quenched lattice QCD in the Landau gauge, using an off-shell mean-field O(a)-improved fermion action. The Dirac-vector part of the vertex is computed for arbitrary kinematics. We find a substantial infrared enhancement of the interaction strength regardless of the kinematics.Ayse Kizilersu, Derek B. Leinweber, Jon-Ivar Skullerud and Anthony G. William

Multiplex Immunoassay of Lower Genital Tract Mucosal Fluid from Women Attending an Urban STD Clinic Shows Broadly Increased IL1ß and Lactoferrin

BACKGROUND: More than one million new cases of sexually transmitted diseases (STDs) occur each day. The immune responses and inflammation induced by STDs and other frequent non-STD microbial colonizations (i.e. Candida and bacterial vaginosis) can have serious pathologic consequences in women including adverse pregnancy outcomes, infertility and increased susceptibility to infection by other pathogens. Understanding the types of immune mediators that are elicited in the lower genital tract by these infections/colonizations can give important insights into the innate and adaptive immune pathways that are activated and lead to strategies for preventing pathologic effects. METHODOLOGY/PRINCIPAL FINDINGS: 32 immune mediators were measured by multiplexed immunoassays to assess the immune environment of the lower genital tract mucosa in 84 women attending an urban STD clinic. IL-3, IL-1ß, VEGF, angiogenin, IL-8, ß2Defensin and ß3Defensin were detected in all subjects, Interferon-α was detected in none, while the remaining mediators were detected in 40% to 93% of subjects. Angiogenin, VEGF, FGF, IL-9, IL-7, lymphotoxin-α and IL-3 had not been previously reported in genital mucosal fluid from women. Strong correlations were observed between levels of TNF-α, IL-1ß and IL-6, between chemokines IP-10 and MIG and between myeloperoxidase, IL-8 and G-CSF. Samples from women with any STD/colonization had significantly higher levels of IL-8, IL-3, IL-7, IL-1ß, lactoferrin and myeloperoxidase. IL-1ß and lactoferrin were significantly increased in gonorrhea, Chlamydia, cervicitis, bacterial vaginosis and trichomoniasis. CONCLUSIONS/SIGNIFICANCE: These studies show that mucosal fluid in general appears to be an environment that is rich in immune mediators. Importantly, IL-1ß and lactoferrin are biomarkers for STDs/colonizations providing insights into immune responses and pathogenesis at this mucosal site

Hyperoxemia and excess oxygen use in early acute respiratory distress syndrome : Insights from the LUNG SAFE study

Publisher Copyright: © 2020 The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Background: Concerns exist regarding the prevalence and impact of unnecessary oxygen use in patients with acute respiratory distress syndrome (ARDS). We examined this issue in patients with ARDS enrolled in the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) study. Methods: In this secondary analysis of the LUNG SAFE study, we wished to determine the prevalence and the outcomes associated with hyperoxemia on day 1, sustained hyperoxemia, and excessive oxygen use in patients with early ARDS. Patients who fulfilled criteria of ARDS on day 1 and day 2 of acute hypoxemic respiratory failure were categorized based on the presence of hyperoxemia (PaO2 > 100 mmHg) on day 1, sustained (i.e., present on day 1 and day 2) hyperoxemia, or excessive oxygen use (FIO2 ≥ 0.60 during hyperoxemia). Results: Of 2005 patients that met the inclusion criteria, 131 (6.5%) were hypoxemic (PaO2 < 55 mmHg), 607 (30%) had hyperoxemia on day 1, and 250 (12%) had sustained hyperoxemia. Excess FIO2 use occurred in 400 (66%) out of 607 patients with hyperoxemia. Excess FIO2 use decreased from day 1 to day 2 of ARDS, with most hyperoxemic patients on day 2 receiving relatively low FIO2. Multivariate analyses found no independent relationship between day 1 hyperoxemia, sustained hyperoxemia, or excess FIO2 use and adverse clinical outcomes. Mortality was 42% in patients with excess FIO2 use, compared to 39% in a propensity-matched sample of normoxemic (PaO2 55-100 mmHg) patients (P = 0.47). Conclusions: Hyperoxemia and excess oxygen use are both prevalent in early ARDS but are most often non-sustained. No relationship was found between hyperoxemia or excessive oxygen use and patient outcome in this cohort. Trial registration: LUNG-SAFE is registered with ClinicalTrials.gov, NCT02010073publishersversionPeer reviewe

Introduction to Short Papers

The short paper presentations at the conference reflected the wide range of innovative research programs on adolescent vulnerabilities. Both human and nonhuman studies addressed topics ranging from the molecular basis of adolescent brain function to the long‐term neurobehavioral consequences of adolescent substance use. Although all of the short papers were extremely informative, the following describe those studies noted especially for their significant impact across the nascent field of research on adolescence

Layer 4 Gates Plasticity in Visual Cortex Independent of a Canonical Microcircuit.

Disrupting binocular vision during a developmental critical period can yield enduring changes to ocular dominance (OD) in primary visual cortex (V1). Here we investigated how this experience-dependent plasticity is coordinated within the laminar circuitry of V1 by deleting separately in each cortical layer (L) a gene required to close the critical period, nogo-66 receptor (ngr1). Deleting ngr1 in excitatory neurons in L4, but not in L2/3, L5, or L6, prevented closure of the critical period, and adult mice remained sensitive to brief monocular deprivation. Intracortical disinhibition, but not thalamocortical disinhibition, accompanied this OD plasticity. Both juvenile wild-type mice and adult mice lacking ngr1 in L4 displayed OD plasticity that advanced more rapidly L4 than L2/3 or L5. Interestingly, blocking OD plasticity in L2/3 with the drug AM-251 did not impair OD plasticity in L5. We propose that L4 restricts disinhibition and gates OD plasticity independent of a canonical cortical microcircuit