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1.
Effect of postnatal development on calcium currents and slow charge movement in mammalian skeletal muscle 总被引:16,自引:3,他引:13
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Single- (whole-cell patch) and two-electrode voltage-clamp techniques were used to measure transient (Ifast) and sustained (Islow) calcium currents, linear capacitance, and slow, voltage-dependent charge movements in freshly dissociated fibers of the flexor digitorum brevis (FDB) muscle of rats of various postnatal ages. Peak Ifast was largest in FDB fibers of neonatal (1-5 d) rats, having a magnitude in 10 mM external Ca of 1.4 +/- 0.9 pA/pF (mean +/- SD; current normalized by linear fiber capacitance). Peak Ifast was smaller in FDB fibers of older animals, and by approximately 3 wk postnatal, it was so small as to be unmeasurable. By contrast, the magnitudes of Islow and charge movement increased substantially during postnatal development. Peak Islow was 3.6 +/- 2.5 pA/pF in FDB fibers of 1-5-d rats and increased to 16.4 +/- 6.5 pA/pF in 45-50-d-old rats; for these same two age groups, Qmax, the total mobile charge measurable as charge movement, was 6.0 +/- 1.7 and 23.8 +/- 4.0 nC/microF, respectively. As both Islow and charge movement are thought to arise in the transverse-tubular system, linear capacitance normalized by the area of fiber surface was determined as an indirect measure of the membrane area of the t-system relative to that of the fiber surface. This parameter increased from 1.5 +/- 0.2 microF/cm2 in 2-d fibers to 2.9 +/- 0.4 microF/cm2 in 44-d fibers. The increases in peak Islow, Qmax, and normalized linear capacitance all had similar time courses. Although the function of Islow is unknown, the substantial postnatal increase in its magnitude suggests that it plays an important role in the physiology of skeletal muscle. 相似文献
2.
Molecular evolution of voltage-sensitive ion channel genes: on the origins of electrical excitability 总被引:14,自引:0,他引:14
We have analyzed nucleic acid and amino acid sequence alignments of a
variety of voltage-sensitive ion channels, using several methods for
phylogenetic tree reconstruction. Ancient duplications within this family
gave rise to three distantly related groups, one consisting of the Na+ and
Ca++ channels, another the K+ channels, and a third including the cyclic
nucleotide-binding channels. A series of gene duplications produced at
least seven mammalian homologues of the Drosophila Shaker K+ channel;
clones of only three of these genes are available from all three mammalian
species examined (mouse, rat, and human), pointing to specific genes that
have yet to be recovered in one or another of these species. The
Shaw-related K+ channels and the Na+ channel family have also undergone
considerable expansion in mammals, relative to flies. These expansions
presumably reflect the needs of the high degree of physiological and
neuronal complexity of mammals. Analysis of the separate domains of the
four-domain channels (Ca++ and Na+) supports their having evolved by two
sequential gene duplications and implies the historical existence of a
functional two-domain channel.
相似文献
3.
Prashant G. Bhat Ajay M. V. Kumar Balaji Naik Srinath Satyanarayana Deepak KG Sreenivas A. Nair Suryakanth MD Einar Heldal Donald A. Enarson Anthony J. Reid 《PloS one》2013,8(12)
Background
Severe acute malnutrition (SAM) is the most serious form of malnutrition affecting children under-five and is associated with many infectious diseases including Tuberculosis (TB). In India, nutritional rehabilitation centres (NRCs) have been recently established for the management of SAM including TB. The National TB Programme (NTP) in India has introduced a revised algorithm for diagnosing paediatric TB. We aimed to examine whether NRCs adhered to these guidelines in diagnosing TB among SAM children.Methods
A cross-sectional study involving review of records of all SAM children identified by health workers during 2012 in six tehsils (sub-districts) with NRCs (population: 1.8 million) of Karnataka, India.Results
Of 1927 identified SAM children, 1632 (85%) reached NRCs. Of them, 1173 (72%) were evaluated for TB and 19(2%) were diagnosed as TB. Of 1173, diagnostic algorithm was followed in 460 (37%). Among remaining 763 not evaluated as per algorithm, tuberculin skin test alone was conducted in 307 (41%), chest radiography alone in 99 (13%) and no investigations in 337 (45%). The yield of TB was higher among children evaluated as per algorithm (4%) as compared to those who were not (0.3%) (OR: 15.3 [95%CI: 3.5-66.3]). Several operational challenges including non-availability of a full-time paediatrician, non-functioning X-ray machine due to frequent power cuts, use of tuberculin with suboptimal strength and difficulties in adhering to a complex diagnostic algorithm were observed.Conclusion
This study showed that TB screening in NRCs was sub-optimal in Karnataka. Some children did not reach the NRC, while many of those who did were either not or sub-optimally evaluated for TB. This study pointed to a number of operational issues that need to be addressed if this collaborative strategy is to identify more TB cases amongst malnourished children in India. 相似文献4.
The role of gene splicing, gene amplification and regulation in mosquito insecticide resistance 总被引:5,自引:0,他引:5
Hemingway J Hawkes N Prapanthadara L Jayawardenal KG Ranson H 《Philosophical transactions of the Royal Society of London. Series B, Biological sciences》1998,353(1376):1695-1699
The primary routes of insecticide resistance in all insects are alterations in the insecticide target sites or changes in the rate at which the insecticide is detoxified. Three enzyme systems, glutathione S-transferases, esterases and monooxygenases, are involved in the detoxification of the four major insecticide classes. These enzymes act by rapidly metabolizing the insecticide to non-toxic products, or by rapidly binding and very slowly turning over the insecticide (sequestration). In Culex mosquitoes, the most common organophosphate insecticide resistance mechanism is caused by co-amplification of two esterases. The amplified esterases are differentially regulated, with three times more Est beta 2(1) being produced than Est alpha 2(1). Cis-acting regulatory sequences associated with these esterases are under investigation. All the amplified esterases in different Culex species act through sequestration. The rates at which they bind with insecticides are more rapid than those for their non-amplified counterparts in the insecticide-susceptible insects. In contrast, esterase-based organophosphate resistance in Anopheles is invariably based on changes in substrate specificities and increased turnover rates of a small subset of insecticides. The up-regulation of both glutathione S-transferases and monooxygenases in resistant mosquitoes is due to the effects of a single major gene in each case. The products of these major genes up-regulate a broad range of enzymes. The diversity of glutathione S-transferases produced by Anopheles mosquitoes is increased by the splicing of different 5' ends of genes, with a single 3' end, within one class of this enzyme family. The trans-acting regulatory factors responsible for the up-regulation of both the monooxygenase and glutathione S-transferases still need to be identified, but the recent development of molecular tools for positional cloning in Anopheles gambiae now makes this possible. 相似文献
5.
6.
Pamela Orjuela-Sánchez Nadira D Karunaweera Mônica da Silva-Nunes Natal S da Silva Kézia KG Scopel Raquel M Gonçalves Chanaki Amaratunga Juliana M Sá Duong Socheat Rick M Fairhust Sharmini Gunawardena Thuraisamy Thavakodirasah Gawrie LN Galapaththy Rabindra Abeysinghe Fumihiko Kawamoto Dyann F Wirth Marcelo U Ferreira 《BMC genetics》2010,11(1):65
Background
The ideal malaria parasite populations for initial mapping of genomic regions contributing to phenotypes such as drug resistance and virulence, through genome-wide association studies, are those with high genetic diversity, allowing for numerous informative markers, and rare meiotic recombination, allowing for strong linkage disequilibrium (LD) between markers and phenotype-determining loci. However, levels of genetic diversity and LD in field populations of the major human malaria parasite P. vivax remain little characterized.Results
We examined single-nucleotide polymorphisms (SNPs) and LD patterns across a 100-kb chromosome segment of P. vivax in 238 field isolates from areas of low to moderate malaria endemicity in South America and Asia, where LD tends to be more extensive than in holoendemic populations, and in two monkey-adapted strains (Salvador-I, from El Salvador, and Belem, from Brazil). We found varying levels of SNP diversity and LD across populations, with the highest diversity and strongest LD in the area of lowest malaria transmission. We found several clusters of contiguous markers with rare meiotic recombination and characterized a relatively conserved haplotype structure among populations, suggesting the existence of recombination hotspots in the genome region analyzed. Both silent and nonsynonymous SNPs revealed substantial between-population differentiation, which accounted for ~40% of the overall genetic diversity observed. Although parasites clustered according to their continental origin, we found evidence for substructure within the Brazilian population of P. vivax. We also explored between-population differentiation patterns revealed by loci putatively affected by natural selection and found marked geographic variation in frequencies of nucleotide substitutions at the pvmdr-1 locus, putatively associated with drug resistance.Conclusion
These findings support the feasibility of genome-wide association studies in carefully selected populations of P. vivax, using relatively low densities of markers, but underscore the risk of false positives caused by population structure at both local and regional levels.See commentary: http://www.biomedcentral.com/1741-7007/8/907.
The whole-cell patch-clamp technique was used to study the properties of inward ionic currents found in primary cultures of rat and mouse skeletal myotubes and in freshly dissociated fibers of the flexor digitorum brevis muscle of rats. In each of these cell types, test depolarizations from the holding potential (-80 or -90 mV) elicited three distinct inward currents: a sodium current (INa) and two calcium currents. INa was the dominant inward current: under physiological conditions, the maximum inward INa was estimated to be at least 30-fold larger than either of the calcium currents. The two calcium currents have been termed Ifast and Islow, corresponding to their relative rates of activation. Ifast was activated by test depolarizations to around -40 mV and above, peaked in 10-20 ms, and decayed to baseline in 50-100 ms. Islow was activated by depolarizations to approximately 0 mV and above, peaked in 50-150 ms, and decayed little during a 200-ms test pulse. Ifast was inactivated by brief, moderate depolarizations; for a 1-s change in holding potential, half-inactivation occurred at -55 to -45 mV and complete inactivation occurred at -40 to -30 mV. Similar changes in holding potential had no effect on Islow. Islow was, however, inactivated by brief, strong depolarizations (e.g., 0 mV for 2 s) or maintained, moderate depolarizations (e.g., -40 mV for 60 s). Substitution of barium for calcium had little effect on the magnitude or time course of either Ifast or Islow. The same substitution shifted the activation curve for Islow approximately 10 mV in the hyperpolarizing direction without affecting the activation of Ifast. At low concentrations (50 microM), cadmium preferentially blocked Islow compared with Ifast, while at high concentrations (1 mM), it blocked both Ifast and Islow completely. The dihydropyridine calcium channel antagonist (+)-PN 200-110 (1 microM) caused a nearly complete block of Islow without affecting Ifast. At a holding potential of -80 mV, the half-maximal blocking concentration (K0.5) for the block of Islow by (+)-PN 200-110 was 182 nM. At depolarized holding potentials that inactivated Islow by 35-65%, K0.5 decreased to 5.5 nM. 相似文献
8.
9.
Partial 18S rRNA sequences of five chelicerate arthropods plus a
crustacean, myriapod, insect, chordate, echinoderm, annelid, and
platyhelminth were compared. The sequence data were used to infer phylogeny
by using a maximum-parsimony method, an evolutionary-distance method, and
the evolutionary-parsimony method. The phylogenetic inferences generated by
maximum-parsimony and distance methods support both monophyly of the
Arthropoda and monophyly of the Chelicerata within the Arthropoda. These
results are congruent with phylogenies based on rigorous cladistic analyses
of morphological characters. Results support the inclusion of the
Arthropoda within a spiralian or protostome coelomate clade that is the
sister group of a deuterostome clade, refuting the hypothesis that the
arthropods represent the "primitive" sister group of a protostome coelomate
clade. Bootstrap analyses and consideration of all trees within 1% of the
length of the most parsimonious tree suggest that relationships between the
nonchelicerate arthropods and relationships within the chelicerate clade
cannot be reliably inferred with the partial 18S rRNA sequence data. With
the evolutionary-parsimony method, support for monophyly of the Arthropoda
is found in the majority of the combinations analyzed if the coelomates are
used as "outgroups." Monophyly of the Chelicerata is supported in most
combinations assessed. Our analyses also indicate that the
evolutionary-parsimony method, like distance and parsimony, may be biased
by taxa with long branches. We suggest that a previous study's inference of
the Arthropoda as paraphyletic may be the result of (a) having two few
arthropod taxa available for analysis and (b) including long-branched taxa.
相似文献
10.
We investigated the protective effect of vitamin D against liver damage caused by carbon tetrachloride (CCl4). Twenty-four male rats were divided into four equal groups: G1, untreated controls; G2, administered CCl4; G3, administered both CCl4 and vitamin D for 10 weeks; G4, administered CCl4 for 10 weeks and vitamin D for 12 weeks. At the end of experiment, intracardiac blood samples were taken and liver samples were removed. Hepatic damage due to CCl4 was assessed using biochemistry and histopathology. Glutathione (GSH) levels decreased, while malondialdehyde (MDA) levels increased in liver tissues of G2. Alanine transaminase (ALT), alkaline phosphatase (ALP), and gamma-glutamyl-transaminase (GGT) levels increased, while albumin (ALB) levels decreased. Hepatocyte degeneration, lobular disorder, sinusoid dilation, focal necrotic areas, hyperemia, and glycogen loss were observed. Hepatic fibrosis was observed around portal areas and central veins. Bridging fibrous septa were formed between portal veins. By immunohistochemistry, both matrix metalloproteinase-9 (MMP-9) and desmin reactivity were increased. All aspects of liver damage were at least partially prevented in rats treated with vitamin D. Vitamin D appears to act as an antioxidant and anti-fibrotic to protect the rat liver against damage. 相似文献