Thrombopoietin (TPO) is a plasma glycoprotein that binds its receptor on megakaryocytes (MKs) and MK progenitors, resulting in enhanced platelet production. The mechanism by which TPO is secreted from hepatocytes remains poorly understood. Lectin mannose-binding 1 (LMAN1) and multiple coagulation factor deficiency 2 (MCFD2) form a complex at the endoplasmic reticulum membrane, recruiting cargo proteins into COPII vesicles for secretion.
View Article and Find Full Text PDFBackground: Perinatal depression is estimated to affect ~ 12% of pregnancies and is linked to numerous negative outcomes. There is currently no model to predict perinatal depression at multiple time-points during and after pregnancy using variables ascertained early into pregnancy.
Methods: A prospective cohort design where 858 participants filled in a baseline self-reported survey at week 4-10 of pregnancy (that included social economics, health history, various psychiatric measures), with follow-up until 3 months after delivery.
Congenital dyserythropoietic anemia type II (CDAII) results from loss-of-function mutations in . In contrast to humans, SEC23B-deficient mice deletion do not exhibit CDAII but die perinatally with pancreatic degeneration. Here, we demonstrate that expression of the full SEC23A protein (the SEC23B paralog) from the endogenous regulatory elements of completely rescues the SEC23B-deficient mouse phenotype.
View Article and Find Full Text PDFBackground: Collecting longitudinal data during and shortly after pregnancy is difficult, as pregnant women often avoid studies with repeated surveys. In contrast, pregnant women interact with certain websites at multiple stages throughout pregnancy and the postpartum period. This digital connection presents the opportunity to use a website as a way to recruit and enroll pregnant women into a panel study and collect valuable longitudinal data for research.
View Article and Find Full Text PDFErythropoietin (EPO) stimulates erythroid differentiation and maturation. Though the transcriptional regulation of EPO has been well studied, the molecular determinants of EPO secretion remain unknown. Here, we generated a HEK293T reporter cell line that provides a quantifiable and selectable readout of intracellular EPO levels and performed a genome-scale CRISPR screen that identified SURF4 as an important mediator of EPO secretion.
View Article and Find Full Text PDFDepressive symptoms during and after pregnancy confer risks for adverse outcomes in both the mother and child. Postpartum depression is traditionally diagnosed after birth of the child. Perinatal depression is a serious, prevalent heterogeneous syndrome that can occur during the period from conception through several months after childbirth.
View Article and Find Full Text PDFApproximately one-third of the mammalian proteome is transported from the endoplasmic reticulum-to-Golgi via COPII-coated vesicles. SEC23, a core component of coat protein-complex II (COPII), is encoded by two paralogous genes in vertebrates ( and ). In humans, SEC23B deficiency results in congenital dyserythropoietic anemia type-II (CDAII), while SEC23A deficiency results in a skeletal phenotype (with normal red blood cells).
View Article and Find Full Text PDFThe authors of the article have informed the Journal that an author, Dr. Sacoby Wilson of the University of Maryland School of Public Health, was inadvertently omitted from the published version of their manuscript due to a miscommunication regarding authorship criteria.
View Article and Find Full Text PDFThe metalloprotease ADAMTS13 cleaves von Willebrand factor (VWF) in circulating blood, limiting the size of VWF multimers and regulating VWF activity. Abnormal regulation of VWF contributes to bleeding and to thrombotic disorders. ADAMTS13 levels in plasma are highly variable among healthy individuals, although the heritability and the genetic determinants of this variation are unclear.
View Article and Find Full Text PDFThe original publication of this paper contains an error. The correct image of figure 5 is shown in this paper.
View Article and Find Full Text PDFEstuarine sediments in regions with prolonged histories of industrial activity are often laden to significant depths with complex contaminant mixtures, including trace metals and persistent organic pollutants. Given the complexity of assessing risks from multi-contaminant exposures, the direct measurement of impacts to biological receptors is central to characterizing contaminated sediment sites. Though biological consequences are less commonly assessed at depth, laboratory-based toxicity testing of subsurface sediments can be used to delineate the scope of contamination at impacted sites.
View Article and Find Full Text PDFObjective: The development of the Biophilic Design Matrix (BDM) was to aid designers or other specialists in identifying and quantifying biophilic features through a visual inventory of interior spaces.
Background: With mounting evidence to support the healing attributes of biophilic environments, we propose a method to identify biophilic content within interior spaces. Such a strategy offers much promise to the advancement of restorative environments.
Plasminogen is the precursor of the serine protease plasmin, a central enzyme of the fibrinolytic system. Plasma levels of plasminogen vary by almost 2-fold among healthy individuals, yet little is known about its heritability or genetic determinants in the general population. In order to identify genetic factors affecting the natural variation of plasminogen levels, we performed a genome-wide association study and linkage analysis in a sample of 3456 young healthy individuals who participated in the Genes and Blood Clotting Study (GABC) or the Trinity Student Study (TSS).
View Article and Find Full Text PDFPlasma factor VIII (FVIII) and von Willebrand factor (VWF) circulate together as a complex. We identify VWF fragments sufficient for FVIII stabilization in vivo and show that hepatic expression of the VWF D'D3 domains (S764-P1247), either as a monomer or a dimer, is sufficient to raise FVIII levels in Vwf(-/-) mice from a baseline of ∼5% to 10%, to ∼50% to 100%. These results demonstrate that a fragment containing only ∼20% of the VWF sequence is sufficient to support FVIII stability in vivo.
View Article and Find Full Text PDFGlycans on mucosal surfaces have an important role in host-microbe interactions. The locus encoding the blood-group-related glycosyltransferase β-1,4-N-acetylgalactosaminyltransferase 2 (B4galnt2) is subject to strong selective forces in natural house-mouse populations that contain a common allelic variant that confers loss of B4galnt2 gene expression in the gastrointestinal (GI) tract. We reasoned that altered glycan-dependent intestinal host-microbe interactions may underlie these signatures of selection.
View Article and Find Full Text PDFAnimal feeding operations in the United States produce more than 500 million tons of manure annually. Disposal of poultry waste via application as fertilizer results in substantial runoff of poultry litter-associated contaminants (PLAC). Of particular concern are sex steroids, 17β-estradiol, estrone and testosterone, responsible for sex differentiation and development of reproductive structures.
View Article and Find Full Text PDFThe RIIIS/J inbred mouse strain is a model for type 1 von Willebrand disease (VWD), a common human bleeding disorder. Low von Willebrand factor (VWF) levels in RIIIS/J are due to a regulatory mutation, Mvwf1, which directs a tissue-specific switch in expression of a glycosyltransferase, B4GALNT2, from intestine to blood vessel. We recently found that Mvwf1 lies on a founder allele common among laboratory mouse strains.
View Article and Find Full Text PDFThe Sediment Quality Triad (SQT) consists of complementary measures of sediment chemistry, benthic community structure, and sediment toxicity. We applied the SQT at 20 stations in the tidal portion of the Anacostia River from Bladensburg, MD to Washington, DC to establish a baseline of conditions to evaluate the effects of management actions. Sediment toxicity was assessed using 10-day survival and growth tests with the freshwater amphipod, Hyalella azteca and the midge, Chironomus dilutus.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
August 2007
The zebrafish is a powerful model for studying vascular development, demonstrating remarkable conservation of this process with mammals. Here, we identify a zebrafish mutant, redhead (rhd(mi149)), that exhibits embryonic CNS hemorrhage with intact gross development of the vasculature and normal hemostatic function. We show that the rhd phenotype is caused by a hypomorphic mutation in p21-activated kinase 2a (pak2a).
View Article and Find Full Text PDFMutations in LMAN1 (ERGIC-53) or MCFD2 cause combined deficiency of factor V and factor VIII (F5F8D). LMAN1 and MCFD2 form a protein complex that functions as a cargo receptor ferrying FV and FVIII from the endoplasmic reticulum to the Golgi. In this study, we analyzed 10 previously reported and 10 new F5F8D families.
View Article and Find Full Text PDFA 28-d partial life-cycle test with the estuarine amphipod Leptocheirus plumulosus was developed in response to the need for an assay to mimic chronic exposure to sediment-associated contaminants. To ensure that toxicity tests have environmental relevance, it is essential to evaluate the relationship between laboratory responses and field measures of contamination. Consequently, one objective of the study was to compare the results of the chronic sediment toxicity test with L.
View Article and Find Full Text PDFIn Chesapeake Bay, Maryland, USA, some of the most contaminated sediments are found in the highly industrialized Baltimore Harbor-Patapsco River area. As part of a comprehensive assessment of sediment quality in this system, sediment toxicity was assessed in 10-d acute tests with the estuarine amphipod Leptocheirus plumulosus. Mean amphipod survival was significantly reduced in 7 of the 25 samples tested despite the occurrence of minor experimental artifacts.
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