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511.
Dmitri Samovski Bella Kalderon Einav Yehuda-Shnaidman Jacob Bar-Tana 《The Journal of biological chemistry》2010,285(10):6879-6890
The role played by long chain fatty acids (LCFA) in promoting energy expenditure is confounded by their dual function as substrates for oxidation and as putative classic uncouplers of mitochondrial oxidative phosphorylation. LCFA analogs of the MEDICA (MEthyl-substituted DICarboxylic Acids) series are neither esterified into lipids nor β-oxidized and may thus simulate the uncoupling activity of natural LCFA in vivo, independently of their substrate role. Treatment of rats or cell lines with MEDICA analogs results in low conductance gating of the mitochondrial permeability transition pore (PTP), with 10–40% decrease in the inner mitochondrial membrane potential. PTP gating by MEDICA analogs is accounted for by inhibition of Raf1 expression and kinase activity, resulting in suppression of the MAPK/RSK1 and the adenylate cyclase/PKA transduction pathways. Suppression of RSK1 and PKA results in a decrease in phosphorylation of their respective downstream targets, Bad(Ser-112) and Bad(Ser-155). Decrease in Bad(Ser-112, Ser-155) phosphorylation results in increased binding of Bad to mitochondrial Bcl2 with concomitant displacement of Bax, followed by PTP gating induced by free mitochondrial Bax. Low conductance PTP gating by LCFA/MEDICA may account for their thyromimetic calorigenic activity in vivo. 相似文献
512.
《Endocrinología y nutrición》2014,61(9):486-492
Urea has been recently proposed for the management of hyponatremia linked to the syndrome of inappropriate secretion of ADH (SIADH). The objective of the study was to review the levels of evidence for treatment of hyponatremia associated with SIADH with urea. We performed a: systematic review of experimental trials and grading according to SIGN. No clinical trials were found. The 6 studies analysed had methodological limitations and were prone to biases. In conclusion, there is no evidence to support the efficacy of urea for the treatment of hyponatremia following SIADH. 相似文献
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514.
Spike glycoprotein of SARS-CoV-2 mediates viral entry into host cells by facilitating virus attachment and membrane fusion. ACE2 is the main receptor of SARS-CoV-2 and its interaction with spike has shaped the virus’ emergence from an animal reservoir and subsequent evolution in the human host. Many structural studies on the spike:ACE2 interaction have provided insights into mechanisms driving viral evolution during the on-going pandemic. This review describes the molecular basis of spike binding to ACE2, outlines mechanisms that have optimised this interaction during viral evolution, and suggests directions for future research. 相似文献
515.
《Biochemical and biophysical research communications》2020,521(3):603-611
BackgroundVoltage-gated sodium channels Nav1.x mediate the rising phase of action potential in excitable cells. Variations in gene SCN5A, which encodes the hNav1.5 channel, are associated with arrhythmias and other heart diseases. About 1,400 SCN5A variants are listed in public databases, but for more than 30% of these the clinical significance is unknown and can currently only be derived by bioinformatics approaches.Methods and resultsWe used the ClinVar, SwissVar, Humsavar, gnomAD, and Ensembl databases to assemble a dataset of 1392 hNav1.5 variants (370 pathogenic variants, 602 benign variants and 420 variants of uncertain significance) as well as a dataset of 1766 damaging variants in 20 human sodium and calcium channel paralogs. Twelve in silico tools were tested for their ability to predict damaging mutations in hNav1.5. The best performing tool, MutPred, correctly predicted 93% of damaging variants in our hNav1.5 dataset. Among the 86 hNav1.5 variants for which electrophysiological data are also available, MutPred correctly predicted 82% of damaging variants. In the subset of 420 uncharacterized hNav1.5 variants MutPred predicted 196 new pathogenic variants. Among these, 74 variants are also annotated as damaging in at least one hNav1.5 paralog.ConclusionsUsing a combination of sequence-based bioinformatics techniques and paralogous annotation we have substantially expanded the knowledge on disease variants in the cardiac sodium channel and assigned a pathogenic status to a number of mutations that so far have been described as variants of uncertain significance. A list of reclassified hNav1.5 variants and their properties is provided. 相似文献
516.
Elizabeth W. Davidson Jennifer Snyder Donald Lightner Gregory Ruthig Julie Lucas Joel Gilley 《Biocontrol Science and Technology》2010,20(3):297-310
The introduced crayfish, Orconectes virilis (Cambarinae; Hagen 1870), has become a serious invasive species in Arizona (USA), altering stream ecosystems and contributing to the decline of native species. But because it is native to the eastern US, and related crayfish including endangered species inhabit nearby states, introduction of a biological control agent presents a unique challenge. This represents a feasibility study, in which we explored bacteria, nematodes, and a virus as potential biological control agents for O. virilis while avoiding harm to native species. White Spot Syndrome Virus (WSSV) from shrimp was found to be highly pathogenic and readily passed by cannibalistic behavior but not by water transmission. Potential activity of WSSV against representative non-target arthropods that may be found in the same ecosystems was also explored. 相似文献
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518.
James J. McKenna 《Human nature (Hawthorne, N.Y.)》1990,1(2):145-177
This paper and its subsequent parts (Part II and Part III) build on an earlier publication (McKenna 1986). They suggest that
important clinical data on the relationship between infantile constitutional deficits and microenvironmental factors relevant
to SIDS can be acquired by examining the physiological regulatory effects (well documented among nonhuman primates) that parents
assert on their infants when they sleep together.
I attempt to show why access to parental sensory cues (movement, touch, smell, sound) that induce arousals in infants while
they sleep could possibly help one of many different subclasses of infants either to override certain kinds of sleep-induced
breathing control errors suspected to be involved in SIDS or to avoid them altogether. I do not suggest that solitary nocturnal
sleep “causes” SIDS, that all parents should sleep with their infants, or that traditional SIDS research strategies should
be abandoned. However, using evolutionary data, I do suggest that an adaptive fit exists between parent-infant sleep contact
and the natural physiological vulnerabilities of the neurologically immature human infant, whose breathing system is more
complex than that of other mammals owing to its speech-breathing abilities. This “fit” is best understood, it is argued, in
terms of the 4–5 million years of human evolution in which parent-infant contact was almost certainly continuous during at
least the first year of an infant’s life. Thus, to dismiss the idea that solitary sleep has no physiological consequences
for infants does not accord with scientific facts.
James J. McKenna is Associate Professor of Anthropology and Chair of the Department of Sociology and Anthropology at Pomona
College. He also has an appointment as an Adjunct Clinical Assistant Professor in the Departments of Pediatrics, Child Psychiatry,
and Human Behavior at the University of California, Irvine, School of Medicine. His primary research interests and many of
his publications concern aspects of primate parenting and infant development among both human and nonhuman primates. For the
past seven years he has been investigating from an anthropological perspective possible environmental correlates of the sudden
infant death syndrome (SIDS) and has just finished a preliminary study on the physiological correlates of human parent-infant
co-sleeping. His earlier monograph on the subject (cited in this paper) has received much international attention. He and
his colleagues (Mosko and Dungy) are the first to have used standard polysomnographic techniques to document simultaneously
human parent-infant co-sleeping. He has won three awards for distinguished teaching at Pomona College. 相似文献