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981.
Ca2+-calmodulin-dependent protein kinase II (CaMKII) is a key regulator of glutamatergic synapses and plays an essential role
in many forms of synaptic plasticity. It has recently been observed that stimulating dendrites locally with a single glutamate/glycine
puff induces a local translocation of CaMKII into spines that subsequently spreads in a wave-like manner towards the distal
dendritic arbor. Here we present a mathematical model of the diffusion, activation and translocation of dendritic CaMKII.
We show how the nonlinear dynamics of CaMKII diffusion-activation generates a propagating translocation wave, provided that
the rate of activation is sufficiently fast. We also derive an explicit formula for the wave speed as a function of physiological
parameters such as the diffusivity of CaMKII and the density of spines. Our model provides a quantitative framework for understanding
the spread of CaMKII translocation and its possible role in heterosynaptic plasticity. 相似文献
982.
Water resource management encompasses a variety of regulations and mandates relevant to water protection and restoration. Awareness of the value-added biological monitoring and assessment to water resource management
is increasing worldwide, but especially in countries that have implemented proactive water law and regulatory frameworks for
protection of surface waters. Biological communities provide an integrated response to pollutants and human disturbance within
watersheds through their continuous exposure to the magnitude, duration, and frequency of stressors, and, thus, are important
for assessing ecosystem health. The selection of proper bioindicators can provide additional benefits through their use in
causal analysis of impaired waters and measurement of ecosystem recovery after restoration. A process for implementing biological
indicators in a monitoring and assessment framework is outlined for managers and practitioners of water resource protection
and restoration. 相似文献
983.
984.
Gravitt PE Paul P Katki HA Vendantham H Ramakrishna G Sudula M Kalpana B Ronnett BM Vijayaraghavan K Shah KV;CATCH Study Team 《PloS one》2010,5(10):e13711
Background
While many studies have compared the efficacy of Pap cytology, visual inspection with acetic acid (VIA) and human papillomavirus (HPV) DNA assays for the detection cervical intraepithelial neoplasia and cancer, few have evaluated the program effectiveness.Methods and Findings
A population-based sample of 5603 women from Medchal Mandal in Andhra Pradesh, India were invited to participate in a study comparing Pap cytology, VIA, and HPV DNA screening for the detection of CIN3+. Participation in primary screening and all subsequent follow-up visits was rigorously tracked. A 20% random sample of all women screened, in addition to all women with a positive screening test result underwent colposcopy with directed biopsy for final diagnosis. Sensitivity, specificity, positive and negative predictive values were adjusted for verification bias. HPV testing had a higher sensitivity (100%) and specificity (90.6%) compared to Pap cytology (sensitivity = 78.2%; specificity = 86.0%) and VIA (sensitivity = 31.6%; specificity = 87.5%). Since 58% of the sample refused involvement and another 28% refused colposcopy or biopsy, we estimated that potentially 87.6% of the total underlying cases of CIN3 and cancer may have been missed due to program failures.Conclusions
We conclude that despite our use of available resources, infrastructure, and guidelines for cervical cancer screening implementation in resource limited areas, community participation and non-compliance remain the major obstacles to successful reduction in cervical cancer mortality in this Indian population. HPV DNA testing was both more sensitive and specific than Pap cytology and VIA. The use of a less invasive and more user-friendly primary screening strategy (such as self-collected swabs for HPV DNA testing) may be required to achieve the coverage necessary for effective reduction in cervical cancer mortality. 相似文献985.
986.
Abramian AM Comenencia-Ortiz E Vithlani M Tretter EV Sieghart W Davies PA Moss SJ 《The Journal of biological chemistry》2010,285(53):41795-41805
Tonic inhibition in the brain is mediated largely by specialized populations of extrasynaptic receptors, γ-aminobutyric acid receptors (GABA(A)Rs). In the dentate gyrus region of the hippocampus, tonic inhibition is mediated primarily by GABA(A)R subtypes assembled from α4β2/3 with or without the δ subunit. Although the gating of these receptors is subject to dynamic modulation by agents such as anesthetics, barbiturates, and neurosteroids, the cellular mechanisms neurons use to regulate their accumulation on the neuronal plasma membrane remain to be determined. Using immunoprecipitation coupled with metabolic labeling, we demonstrate that the α4 subunit is phosphorylated at Ser(443) by protein kinase C (PKC) in expression systems and hippocampal slices. In addition, the β3 subunit is phosphorylated on serine residues 408/409 by PKC activity, whereas the δ subunit did not appear to be a PKC substrate. We further demonstrate that the PKC-dependent increase of the cell surface expression of α4 subunit-containing GABA(A)Rs is dependent on Ser(443). Mechanistically, phosphorylation of Ser(443) acts to increase the stability of the α4 subunit within the endoplasmic reticulum, thereby increasing the rate of receptor insertion into the plasma membrane. Finally, we show that phosphorylation of Ser(443) increases the activity of α4 subunit-containing GABA(A)Rs by preventing current run-down. These results suggest that PKC-dependent phosphorylation of the α4 subunit plays a significant role in enhancing the cell surface stability and activity of GABA(A)R subtypes that mediate tonic inhibition. 相似文献
987.
Sebastiaan J. van Hal Hong Foo Christopher C. Blyth Kenneth McPhie Paul Armstrong Vitali Sintchenko Dominic E. Dwyer 《PloS one》2009,4(9)
Background
Influenza causes annual epidemics and often results in extensive outbreaks in closed communities. To minimize transmission, a range of interventions have been suggested. For these to be effective, an accurate and timely diagnosis of influenza is required. This is confirmed by a positive laboratory test result in an individual whose symptoms are consistent with a predefined clinical case definition. However, the utility of these clinical case definitions and laboratory testing in mass gathering outbreaks remains unknown.Methods and Results
An influenza outbreak was identified during World Youth Day 2008 in Sydney. From the data collected on pilgrims presenting to a single clinic, a Markov model was developed and validated against the actual epidemic curve. Simulations were performed to examine the utility of different clinical case definitions and laboratory testing strategies for containment of influenza outbreaks. Clinical case definitions were found to have the greatest impact on averting further cases with no added benefit when combined with any laboratory test. Although nucleic acid testing (NAT) demonstrated higher utility than indirect immunofluorescence antigen or on-site point-of-care testing, this effect was lost when laboratory NAT turnaround times was included. The main benefit of laboratory confirmation was limited to identification of true influenza cases amenable to interventions such as antiviral therapy.Conclusions
Continuous re-evaluation of case definitions and laboratory testing strategies are essential for effective management of influenza outbreaks during mass gatherings. 相似文献988.
989.
Mascha Toepoel Regine P. M. Steegers‐Theunissen N. Joop Ouborg Barbara Franke Angela M. González‐Zuloeta Ladd Paul H. L. J. Joosten Everardus J. J. van Zoelen 《Birth defects research. Part A, Clinical and molecular teratology》2009,85(7):629-636
BACKGROUND: Neural tube defects are multifactorial malformations involving both environmental exposures, such as maternal nutrition, and genetic factors. Aberrant expression of the platelet‐derived growth factor alpha‐receptor (PDGFRA) gene has been implicated in neural‐tube‐defect etiology in both mice and humans. METHODS: We investigated possible interactions between the PDGFRA promoter haplotype of mother and child, as well as maternal glucose, myo‐inositol, and zinc levels, in relation to spina bifida offspring. Distributions were determined of the PDGFRA promoter haplotypes H1 and H2 in a Dutch cohort, consisting of 88 spina bifida children with 56 of their mothers, and 74 control children with 72 of their mothers, as well as maternal plasma glucose, myo‐inositol, and red blood cell zinc concentrations. RESULTS: A significantly higher frequency of H1 was observed in children with spina bifida than in controls (30.1 vs. 20.3%; OR = 1.69, 95% CI 1.02–2.83). High maternal body mass index (BMI) and glucose were significant risk factors for both H1 and H2 children, whereas low myo‐inositol and zinc were risk factors for H2 but not for H1 children. Stepwise multiple logistic regression analysis showed that high maternal glucose and low myo‐inositol are the main risk factors for H2 spina bifida children, whereas for H1 spina bifida children, maternal BMI was the main risk factor. Interestingly, H1 mothers (median 165.5 cm) showed a significantly lower body height than H2 mothers (median 169.1 cm; p = 0.003). CONCLUSIONS: These data suggest that the child's PDGFRA promoter haplotype is differentially sensitive for periconceptional exposure to glucose, myo‐inositol, and zinc in the risk of spina bifida. Birth Defects Research (Part A), 2009. © 2009 Wiley‐Liss, Inc. 相似文献
990.
Chung-Hin Chui Raymond Siu-Ming Wong Roberto Gambari Gregory Yin-Ming Cheng Marcus Chun-Wah Yuen Kit-Wah Chan See-Wai Tong Fung-Yi Lau Paul Bo-San Lai Kim-Hung Lam Cheuk-Lam Ho Chi-Wai Kan Kelvin Sze-Yin Leung Wai-Yeung Wong 《Bioorganic & medicinal chemistry》2009,17(23):7872-7877
A list of diethynylfluorenes and their gold(I) derivatives have been studied for their antitumor activity as a function of their structure–activity relationships. End-capping the fluoren-9-one unit with gold(I) moieties could significantly strengthen the cytotoxic activity in vitro on three human cancer cell lines with induction of reactive oxygen species generation on Hep3B hepatocellular carcinoma cells and exhibit attractive antitumor activity from in vivo nude mice Hep3B xenograft model with limited adverse effects on vital organs including liver and kidney. 相似文献