272 research outputs found

    Common and Distinct Roles of Juvenile Hormone Signaling Genes in Metamorphosis of Holometabolous and Hemimetabolous Insects

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    Insect larvae metamorphose to winged and reproductive adults either directly (hemimetaboly) or through an intermediary pupal stage (holometaboly). In either case juvenile hormone (JH) prevents metamorphosis until a larva has attained an appropriate phase of development. In holometabolous insects, JH acts through its putative receptor Methoprene-tolerant (Met) to regulate Krüppel-homolog 1 (Kr-h1) and Broad-Complex (BR-C) genes. While Met and Kr-h1 prevent precocious metamorphosis in pre-final larval instars, BR-C specifies the pupal stage. How JH signaling operates in hemimetabolous insects is poorly understood. Here, we compare the function of Met, Kr-h1 and BR-C genes in the two types of insects. Using systemic RNAi in the hemimetabolous true bug, Pyrrhocoris apterus, we show that Met conveys the JH signal to prevent premature metamorphosis by maintaining high expression of Kr-h1. Knockdown of either Met or Kr-h1 (but not of BR-C) in penultimate-instar Pyrrhocoris larvae causes precocious development of adult color pattern, wings and genitalia. A natural fall of Kr-h1 expression in the last larval instar normally permits adult development, and treatment with an exogenous JH mimic methoprene at this time requires both Met and Kr-h1 to block the adult program and induce an extra larval instar. Met and Kr-h1 therefore serve as JH-dependent repressors of deleterious precocious metamorphic changes in both hemimetabolous and holometabolous juveniles, whereas BR-C has been recruited for a new role in specifying the holometabolous pupa. These results show that despite considerable evolutionary distance, insects with diverse developmental strategies employ a common-core JH signaling pathway to commit to adult morphogenesis

    Characterization of the Endothelial Cell Cytoskeleton following HLA Class I Ligation

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    Vascular endothelial cells (ECs) are a target of antibody-mediated allograft rejection. In vitro, when the HLA class I molecules on the surface of ECs are ligated by anti-HLA class I antibodies, cell proliferation and survival pathways are activated and this is thought to contribute to the development of antibody-mediated rejection. Crosslinking of HLA class I molecules by anti-HLA antibodies also triggers reorganization of the cytoskeleton, which induces the formation of F-actin stress fibers. HLA class I induced stress fiber formation is not well understood.The present study examines the protein composition of the cytoskeleton fraction of ECs treated with HLA class I antibodies and compares it to other agonists known to induce alterations of the cytoskeleton in endothelial cells. Analysis by tandem mass spectrometry revealed unique cytoskeleton proteomes for each treatment group. Using annotation tools a candidate list was created that revealed 12 proteins, which were unique to the HLA class I stimulated group. Eleven of the candidate proteins were phosphoproteins and exploration of their predicted kinases provided clues as to how these proteins may contribute to the understanding of HLA class I induced antibody-mediated rejection. Three of the candidates, eukaryotic initiation factor 4A1 (eIF4A1), Tropomyosin alpha 4-chain (TPM4) and DDX3X, were further characterized by Western blot and found to be associated with the cytoskeleton. Confocal microscopy analysis showed that class I ligation stimulated increased eIF4A1 co-localization with F-actin and paxillin.Colocalization of eIF4A1 with F-actin and paxillin following HLA class I ligation suggests that this candidate protein could be a target for understanding the mechanism(s) of class I mediated antibody-mediated rejection. This proteomic approach for analyzing the cytoskeleton of ECs can be applied to other agonists and various cells types as a method for uncovering novel regulators of cytoskeleton changes

    Characterization of a Lamellocyte Transcriptional Enhancer Located within the misshapen Gene of Drosophila melanogaster

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    Drosophila has emerged as an excellent model system in which to study cellular and genetic aspects of hematopoiesis. Under normal developmental conditions and in wild-type genetic backgrounds, Drosophila possesses two types of blood cells, crystal cells and plasmatocytes. Upon infestation by a parasitic wasp or in certain altered genetic backgrounds, a third hemocyte class called the lamellocyte becomes apparent. Herein we describe the characterization of a novel transcriptional regulatory module, a lamellocyte-active enhancer of the misshapen gene. This transcriptional control sequence appears to be inactive in all cell types of the wild-type larva, including crystal cells and plasmatocytes. However, in lamellocytes induced by wasp infestation or by particular genetic conditions, the enhancer is activated and it directs reporter GFP or DsRed expression exclusively in lamellocytes. The lamellocyte control region was delimited to a 140-bp intronic sequence that contains an essential DNA recognition element for the AP-1 transcription factor. Additionally, mutation of the kayak gene encoding the dFos subunit of AP-1 led to a strong suppression of lamellocyte production in tumorous larvae. As misshapen encodes a protein kinase within the Jun N-terminal kinase signaling pathway that functions to form an active AP-1 complex, the lamellocyte-active enhancer likely serves as a transcriptional target within a genetic auto-regulatory circuit that promotes the production of lamellocytes in immune-challenged or genetically- compromised animals

    Fcγ Receptors in Solid Organ Transplantation.

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    In the current era, one of the major factors limiting graft survival is chronic antibody-mediated rejection (ABMR), whilst patient survival is impacted by the effects of immunosuppression on susceptibility to infection, malignancy and atherosclerosis. IgG antibodies play a role in all of these processes, and many of their cellular effects are mediated by Fc gamma receptors (FcγRs). These surface receptors are expressed by most immune cells, including B cells, natural killer cells, dendritic cells and macrophages. Genetic variation in FCGR genes is likely to affect susceptibility to ABMR and to modulate the physiological functions of IgG. In this review, we discuss the potential role played by FcγRs in determining outcomes in solid organ transplantation, and how genetic polymorphisms in these receptors may contribute to variations in transplant outcome.MRC is supported by the NIHR Cambridge BRC, the NIHR Blood and Transplant Research Unit (Cambridge) and by a Medical Research Council New Investigator Grant (MR/N024907/1).This is the final version of the article. It first appeared from Springer via https://doi.org/10.1007/s40472-016-0116-

    Star Formation Laws and Efficiencies across 80 Nearby Galaxies

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    We measure empirical relationships between the local star formation rate (SFR) and properties of the star-forming molecular gas on 1.5 kpc scales across 80 nearby galaxies. These relationships, commonly referred to as "star formation laws," aim at predicting the local SFR surface density from various combinations of molecular gas surface density, galactic orbital time, molecular cloud free-fall time, and the interstellar medium dynamical equilibrium pressure. Leveraging a multiwavelength database built for the PHANGS survey, we measure these quantities consistently across all galaxies and quantify systematic uncertainties stemming from choices of SFR calibrations and the CO-to-H2_2 conversion factors. The star formation laws we examine show 0.3-0.4 dex of intrinsic scatter, among which the molecular Kennicutt-Schmidt relation shows a ∼\sim10% larger scatter than the other three. The slope of this relation ranges β≈0.9−1.2\beta\approx0.9{-}1.2, implying that the molecular gas depletion time remains roughly constant across the environments probed in our sample. The other relations have shallower slopes (β≈0.6−1.0\beta\approx0.6{-}1.0), suggesting that the star formation efficiency (SFE) per orbital time, the SFE per free-fall time, and the pressure-to-SFR surface density ratio (i.e., the feedback yield) may vary systematically with local molecular gas and SFR surface densities. Last but not least, the shapes of the star formation laws depend sensitively on methodological choices. Different choices of SFR calibrations can introduce systematic uncertainties of at least 10-15% in the star formation law slopes and 0.15-0.25 dex in their normalization, while the CO-to-H2_2 conversion factors can additionally produce uncertainties of 20-25% for the slope and 0.10-0.20 dex for the normalization.Comment: 10 pages main text + 2 appendices. ApJL in press. Data products available at https://www.canfar.net/storage/list/phangs/RELEASES/Sun_etal_2023 . Slides summarizing key results can be found at https://www.dropbox.com/s/5gsegexeo9n0t05/Sun_et_PHANGS_2023.pptx?dl=

    Cardiovascular and hormonal responses to static handgrip in young and older healthy men

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    The purpose of this study was to investigate the effect of age on cardiovascular changes and plasma concentrations of adrenomedullin (ADM), catecholamines, endothelin-1 (ET-1) and plasma renin activity (PRA) in healthy men. A total of 15 young (21 ± 0.3 years) and 15 older (64 ± 0.7 years) healthy men performed two 3-min bouts of static handgrip at 30% of maximal voluntary contraction, alternately with each hand without any break between the bouts. During exercise heart rate (HR), blood pressure (BP), stroke volume (SV) and pre-ejection period (PEP) and left ventricle ejection time (LVET) were measured. Blood samples were taken before exercise, at the end of both exercise bouts and in the fifth minute of the recovery period. The handgrip-induced increases in HR and cardiac output were significantly smaller in older than in young men (p < 0.01). SV decreased only in older men (p < 0.001). There were no differences between groups in BP increases. The baseline plasma ADM and catecholamines were higher in older man compared to young subjects. Handgrip caused increases in plasma ADM, ET-1 and PRA only in older men (p < 0.05). The increases in plasma ADM correlated positively with those of noradrenaline (NA), PRA, ET-1 and LVET and negatively with changes in total peripheral resistance (TPR), SV, PEP and PEP/LVET ratio. The increases in plasma ET-1 correlated positively with those of NA, PRA, TPR, mean BP and SV. These results revealed that ADM, ET-1 and angiotensin II can contribute to maintain vascular tone during static exercise in older but not in younger men

    Value of the Electrocardiogram in Localizing the Occlusion Site in the Left Anterior Descending Coronary Artery in Acute Anterior Myocardial Infarction

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    OBJECTIVES The study assessed the value of the electrocardiogram (ECG) as predictor of the left anterior descending coronary artery (LAD) occlusion site in relation to the first septal perforator (S1) and/or the first diagonal branch (D1) in patients with acute anterior myocardial infarction (AMI). BACKGROUND In anterior AMI, determination of the exact site of LAD occlusion is important because the more proximal the occlusion the less favorable the prognosis
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