RESUMO
Interlocus sexual conflict is predicted to result in sexually antagonistic coevolution between male competitive traits, which are also female-detrimental, and mate harm resistance (MHR) in females. Little is known about the connection between life-history evolution and sexually antagonistic coevolution. Here, we investigated the evolution of MHR in a set of experimentally evolved populations, where mate-harming ability has been shown to have substantially reduced in males as a correlated response to the selection for faster development and early reproduction. We measured mortality and fecundity of females of these populations and those of their matched controls, under different male exposure conditions. We observed that the evolved females were more susceptible to mate harm - suffering from significantly higher mortality under continuous exposure to control males within the twenty-day assay period. Though these evolved females are known to have shorter lifespan, substantially higher mortality was not observed under virgin and single-mating conditions. We used fecundity data to show that this higher mortality in the experimentally evolved females was not due to the cost of egg production, and hence can only be attributed to reduced MHR. Further analysis indicated that this decreased MHR is unlikely to be due purely to the smaller size of these females. Instead, it is more likely to be an indirect experimentally evolved response attributable to the changed breeding ecology, and/or male trait evolution. Our results underline the implications of changes in life history traits, including lifespan, to the evolution of MHR in females.
RESUMO
Ligand-independent activation of VEGFRs is a hallmark of diabetes and several cancers. Like EGFR, VEGFR2 is activated spontaneously at high receptor concentrations. VEGFR1, on the other hand, remains constitutively inactive in the unligated state, making it an exception among VEGFRs. Ligand stimulation transiently phosphorylates VEGFR1 and induces weak kinase activation in endothelial cells. Recent studies, however, suggest that VEGFR1 signaling is indispensable in regulating various physiological or pathological events. The reason why VEGFR1 is regulated differently from other VEGFRs remains unknown. Here, we elucidate a mechanism of juxtamembrane inhibition that shifts the equilibrium of VEGFR1 towards the inactive state, rendering it an inefficient kinase. The juxtamembrane inhibition of VEGFR1 suppresses its basal phosphorylation even at high receptor concentrations and transiently stabilizes tyrosine phosphorylation after ligand stimulation. We conclude that a subtle imbalance in phosphatase activation or removing juxtamembrane inhibition is sufficient to induce ligand-independent activation of VEGFR1 and sustain tyrosine phosphorylation.
Assuntos
Células Endoteliais , Receptor 1 de Fatores de Crescimento do Endotélio Vascular , Células Endoteliais/metabolismo , Ligantes , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/genética , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/genética , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Transdução de Sinais/fisiologia , Membrana Celular/metabolismo , Tirosina/metabolismoRESUMO
BACKGROUND: The cytological examination of serous body effusions to diagnose and stage malignancy is well accepted in clinical medicine. Conventional smear (CS) and cell block (CB) study has to be complemented with immunohistochemistry (IHC) for a definitive diagnosis of malignancy and also to differentiate it from reactive mesothelial cells. Cytology microarray (CMA) is a modification of tissue microarray which involves core needle biopsy of multiple cell blocks and embedding it in a single block. AIM: The aim of this study was to assess the effectiveness of IHC technique in CMA for rapid diagnosis of malignancy and to reduce the cost of testing. MATERIALS AND METHODS: In this study, 82 pleural fluids were collected and subjected to CS and CB study followed by IHC in CMA blocks. Six commonly used antibodies were applied to confirm malignancy and diagnose the primary. RESULTS: Nineteen cases were diagnosed as malignancy by CB method. MOC-31 confirmed adenocarcinoma deposit in 67% cases of which 44% were proved to be of lung primary by TTF1. CONCLUSIONS: IHC on CMA blocks of effusion fluids is a very effective technique that can significantly reduce the cost of testing by >70%.
RESUMO
Cerebrotendinous xanthomatosis is a rare autosomal recessive lipid storage disease characterized by widespread tissue deposition of two neutral sterols, cholestenol and cholesterol, resulting in tendinous xanthomas, juvenile cataracts, progressive neurological defects, and premature death from arteriosclerosis. Because it is a treatable cause of cerebellar ataxia and dementia, its early diagnosis is desirable. Here, we have reported the case of an 11-year-old boy with this disorder who was diagnosed based on the cytological findings of fine needle aspiration and clinical features.