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21.
Glucagon-like peptide-1 receptor signaling modulates beta cell apoptosis 总被引:30,自引:0,他引:30
Li Y Hansotia T Yusta B Ris F Halban PA Drucker DJ 《The Journal of biological chemistry》2003,278(1):471-478
Glucagon-like peptide-1 (GLP-1) stimulates insulin secretion and augments beta cell mass via activation of beta cell proliferation and islet neogenesis. We examined whether GLP-1 receptor signaling modifies the cellular susceptibility to apoptosis. Mice administered streptozotocin (STZ), an agent known to induce beta cell apoptosis, exhibit sustained improvement in glycemic control and increased levels of plasma insulin with concomitant administration of the GLP-1 agonist exendin-4 (Ex-4). Blood glucose remained significantly lower for weeks after cessation of exendin-4. STZ induced beta cell apoptosis, which was significantly reduced by co-administration of Ex-4. Conversely, mice with a targeted disruption of the GLP-1 receptor gene exhibited increased beta cell apoptosis after STZ administration. Exendin-4 directly reduced cytokine-induced apoptosis in purified rat beta cells exposed to interleukin 1beta, tumor necrosis fator alpha, and interferon gamma in vitro. Furthermore, Ex-4-treated BHK-GLP-1R cells exhibited significantly increased cell viability, reduced caspase activity, and decreased cleavage of beta-catenin after treatment with cycloheximide in vitro. These findings demonstrate that GLP-1 receptor signaling directly modifies the susceptibility to apoptotic injury, and provides a new potential mechanism linking GLP-1 receptor activation to preservation or enhancement of beta cell mass in vivo. 相似文献
22.
Chromatin remodeling is crucial for gene regulation. Remodeling is often mediated through chemical modifications of the DNA template, DNA-associated proteins, and RNA-mediated processes. Y-linked regulatory variation (YRV) refers to the quantitative effects that polymorphic tracts of Y-linked chromatin exert on gene expression of X-linked and autosomal genes. Here we show that naturally occurring polymorphisms in the Drosophila melanogaster Y chromosome contribute disproportionally to gene expression variation in the testis. The variation is dependent on wild-type expression levels of mod(mdg4) as well as Su(var)205; the latter gene codes for heterochromatin protein 1 (HP1) in Drosophila. Testis-specific YRV is abolished in genotypes with heterozygous loss-of-function mutations for mod(mdg4) and Su(var)205 but not in similar experiments with JIL-1. Furthermore, the Y chromosome differentially regulates several ubiquitously expressed genes. The results highlight the requirement for wild-type dosage of Su(var)205 and mod(mdg4) in enabling naturally occurring Y-linked regulatory variation in the testis. The phenotypes that emerge in the context of wild-type levels of the HP1 and Mod(mdg4) proteins might be part of an adaptive response to the environment. 相似文献
23.
The roles of voltage-sensitive sodium (Na) and calcium (Ca) channels located on dendrites and spines in regulating synaptic signals are largely unknown. Here we use 2-photon glutamate uncaging to stimulate individual spines while monitoring uncaging-evoked excitatory postsynaptic potentials (uEPSPs) and Ca transients. We find that, in CA1 pyramidal neurons in acute mouse hippocampal slices, CaV(2.3) voltage-sensitive Ca channels (VSCCs) are found selectively on spines and act locally to dampen uncaging-evoked Ca transients and somatic potentials. These effects are mediated by a regulatory loop that requires opening of CaV(2.3) channels, voltage-gated Na channels, small conductance Ca-activated potassium (SK) channels, and NMDA receptors. Ca influx through CaV(2.3) VSCCs selectively activates SK channels, revealing the presence of functional Ca microdomains within the spine. Our results suggest that synaptic strength can be modulated by mechanisms that regulate voltage-gated conductances within the spine but do not alter the properties or numbers of synaptic glutamate receptors. 相似文献
24.
25.
Mirella Romero Bastidas Liliana Saucedo Picazo Bernardo Murillo Amador Alejandra Nieto Garibay Hever Latisnere Barragan Luis G. Hernandez Montiel 《Journal of Phytopathology》2016,164(2):122-124
In Baja California Sur, Mexico, a foliar disease occurred on sweet basil which seriously affected its quality and yield. The most common symptoms were yellowing and necrosis on leaves, caused by a downy mycelium growth on the lower leaf surface. Symptomatic leaves from two sampling sites were collected for morphological studies and molecular analysis of pathogen DNA. Based on morphological characteristics (sporangiophore size of 240–530 × 7–11 μm, branches of 5–8 order and a sporangia size of 27–31 × 21–25 μm) and molecular analysis (the GenBank blast of the PCR assays showed unique rDNA sequence data with 99% similarity to P. belbahrii), the pathogen was identified as Peronospora belbahrii, the causal agent of basil downy mildew. This is the first report of P. belbahrii affecting sweet basil in Mexico. 相似文献
26.
27.
Goldstein-Daruech N Cope EK Zhao KQ Vukovic K Kofonow JM Doghramji L González B Chiu AG Kennedy DW Palmer JN Leid JG Kreindler JL Cohen NA 《PloS one》2011,6(1):e15700
Cigarette smokers and those exposed to second hand smoke are more susceptible to life threatening infection than non-smokers. While much is known about the devastating effect tobacco exposure has on the human body, less is known about the effect of tobacco smoke on the commensal and commonly found pathogenic bacteria of the human respiratory tract, or human respiratory tract microbiome. Chronic rhinosinusitis (CRS) is a common medical complaint, affecting 16% of the US population with an estimated aggregated cost of $6 billion annually. Epidemiologic studies demonstrate a correlation between tobacco smoke exposure and rhinosinusitis. Although a common cause of CRS has not been defined, bacterial presence within the nasal and paranasal sinuses is assumed to be contributory. Here we demonstrate that repetitive tobacco smoke exposure induces biofilm formation in a diverse set of bacteria isolated from the sinonasal cavities of patients with CRS. Additionally, bacteria isolated from patients with tobacco smoke exposure demonstrate robust in vitro biofilm formation when challenged with tobacco smoke compared to those isolated from smoke naïve patients. Lastly, bacteria from smoke exposed patients can revert to a non-biofilm phenotype when grown in the absence of tobacco smoke. These observations support the hypothesis that tobacco exposure induces sinonasal biofilm formation, thereby contributing to the conversion of a transient and medically treatable infection to a persistent and therapeutically recalcitrant condition. 相似文献
28.
Ilaria Guerini Nicola J Geisler Hengyao Niu Mareike Herzog Israel Salguero Bernardo Ochoa‐Montaño Emmanuelle Viré Patrick Sung David J Adams Thomas M Keane Stephen P Jackson 《The EMBO journal》2015,34(11):1509-1522
DNA double-strand break (DSB) repair by homologous recombination (HR) requires 3′ single-stranded DNA (ssDNA) generation by 5′ DNA-end resection. During meiosis, yeast Sae2 cooperates with the nuclease Mre11 to remove covalently bound Spo11 from DSB termini, allowing resection and HR to ensue. Mitotic roles of Sae2 and Mre11 nuclease have remained enigmatic, however, since cells lacking these display modest resection defects but marked DNA damage hypersensitivities. By combining classic genetic suppressor screening with high-throughput DNA sequencing, we identify Mre11 mutations that strongly suppress DNA damage sensitivities of sae2Δ cells. By assessing the impacts of these mutations at the cellular, biochemical and structural levels, we propose that, in addition to promoting resection, a crucial role for Sae2 and Mre11 nuclease activity in mitotic DSB repair is to facilitate the removal of Mre11 from ssDNA associated with DSB ends. Thus, without Sae2 or Mre11 nuclease activity, Mre11 bound to partly processed DSBs impairs strand invasion and HR. 相似文献
29.
Parental contribution and coefficient of coancestry among maize inbreds: pedigree, RFLP, and SSR data 总被引:3,自引:0,他引:3
R. Bernardo J. Romero-Severson J. Ziegle J. Hauser L. Joe G. Hookstra R. W. Doerge 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》2000,100(3-4):552-556
The genetic relationship between inbreds i and j can be estimated from pedigree or from molecular marker data. The objectives of this study were to: (1) determine whether
pedigree, restriction fragment length polymorphism (RFLP), and simple sequence repeat (SSR) data give similar estimates of
parental contribution and coefficient of coancestry (f
ij
) among a set of maize (Zea mays L.) inbreds, and (2) compare the usefulness of RFLP and SSR markers for estimating genetic relationship. We studied 13 maize
inbreds with known pedigrees. The inbreds were genotyped using 124 RFLP and 195 SSR markers. For each type of marker, parental
contributions were estimated from marker similarity among an inbred and both of its parents, and were subsequently used to
estimate f
ij
. Estimates of parental contribution differed significantly (α<0.05) between pedigree data and either type of marker, but
not between the marker systems. The RFLP estimates of parental contribution failed to sum to 1.0, reflecting a higher frequency
of non-parental bands with RFLP than with SSR markers. The f
ij
estimated from pedigree, RFLP, and SSR data were highly correlated (r=0.87–0.97), although significant differences were found among the three sets of f
ij
estimates. We concluded that pedigree and marker data often lead to different estimates of parental contribution and f
ij
, and that SSR markers are superior to RFLP markers for estimating genetic relationship. A relevant question is whether or
not the inbreds previously genotyped with an older marker system (e.g., RFLP) need to be re-analyzed with a newer marker system
(e.g., SSR) for the purpose of estimating genetic relationship. Such re-analysis seems unnecessary if data for the same type
of marker are available for a given inbred and both of its parents.
Received: 2 June 1999 / Accepted: 30 July 1999 相似文献
30.
Cifuentes M García MA Arrabal PM Martínez F Yañez MJ Jara N Weil B Domínguez D Medina RA Nualart F 《Journal of cellular physiology》2011,226(6):1425-1432
Osteosarcoma is the most common type of malignant bone cancer, accounting for 35% of primary bone malignancies. Because cancer cells utilize glucose as their primary energy substrate, the expression and regulation of glucose transporters (GLUT) may be important in tumor development and progression. GLUT expression has not been studied previously in human osteosarcoma cell lines. Furthermore, although insulin and insulin-like growth factor (IGF-I) play an important role in cell proliferation and tumor progression, the role of these hormones on GLUT expression and glucose uptake, and their possible relation to osteosarcoma, have also not been studied. We determined the effect of insulin and IGF-I on GLUT expression and glucose transport in three well-characterized human osteosarcoma cell lines (MG-63, SaOs-2, and U2-Os) using immunocytochemical, RT-PCR and functional kinetic analyses. Furthermore we also studied GLUT isoform expression in osteosarcoma primary tumors and metastases by in situ hybridization and immunohistochemical analyses. RT-PCR and immunostaining show that GLUT1 is the main isoform expressed in the cell lines and tissues studied, respectively. Immunocytochemical analysis shows that although insulin does not affect levels of GLUT1 expression it does induce a translocation of the transporter to the plasma membrane. This translocation is associated with increased transport of glucose into the cell. GLUT1 is the main glucose transporter expressed in osteosarcoma, furthermore, this transporter is regulated by insulin in human MG-63 cells. One possible mechanism through which insulin is involved in cancer progression is by increasing the amount of glucose available to the cancer cell. 相似文献