排序方式: 共有65条查询结果,搜索用时 15 毫秒
41.
Sarah V Holdridge Stacey A Armstrong Anna MW Taylor Catherine M Cahill 《Molecular pain》2007,3(1):1-8
The molecular identity and pharmacological properties of mechanically gated ion channels in sensory neurons are poorly understood. We show that FM1-43, a styryl dye used to fluorescently label cell membranes, permeates mechanosensitive ion channels in cultured dorsal root ganglion neurons, resulting in blockade of three previously defined subtypes of mechanically activated currents. Blockade and dye uptake is voltage dependent and regulated by external Ca2+. The structurally related larger dye FM3-25 inhibited mechanically activated currents to a lesser degree and did not permeate the channels. In vivo, FMI-43 decreases pain sensitivity in the Randall-Selitto test and increases the withdrawal threshold from von Frey hairs, together suggesting that the channels expressed at the cell body in culture mediate mechanosensation in the intact animal. These data give further insight into the mechanosensitive ion channels expressed by somatosensory neurons and suggest FM dyes are an interesting tool for studying them. 相似文献
42.
Biased mutations and microsatellite variation 总被引:4,自引:6,他引:4
Mutation bias is one of the forces that may constrain the variation at
microsatellite loci. Here, we study the dynamics of population statistics
and the genetic distance between two populations under multiple stepwise
mutations with linear bias and random drift. Expressions are derived for
these statistics as functions of time, as well as at mutation-drift
equilibrium. Applying these expressions to published data on humans and
chimpanzees, the regression coefficient of mutation bias on allele size was
estimated to be at least between - 0.0064 and -0.013. The assumption of
mutational bias produces larger estimates of divergence times than are
obtained in its absence; in particular, the time of split between African
and non-African human populations is estimated to be between 183,000 and
222,000 years, assuming one-step mutations and no selection. With multistep
mutations, the divergence time is estimated to be lower.
相似文献
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45.
Luijendijk P Boekholdt SM Blom NA Groenink M Backx AP Bouma BJ Mulder BJ De Winter RJ 《Netherlands heart journal》2011,19(10):436-439
Aortic coarctation is a common congenital cardiac defect, which can be diagnosed over a wide range of ages and with varying degrees of severity. We present two cases of patients diagnosed with aortic coarctation in adulthood. Both patients were treated by an endovascular approach. These cases demonstrate the variety of indications in which percutaneous treatment is an excellent alternative for surgical treatment in adult native coarctation patients. 相似文献
46.
Johan M. Lorenzen Jan Menne Bernhard MW. Schmidt Mascha Schmidt Filippo Martino Robert Dietrich Senguel Samiri Hans Worthmann Meike Heeren Karin Weissenborn Hermann Haller Mario Schiffer Jan T. Kielstein Thomas Thum 《PloS one》2012,7(10)
Background
In early May 2011, an outbreak of hemorrhagic colitis associated with hemolytic–uremic syndrome (HUS) first developed in Northern Germany and spread to 15 other countries in Europe. The outbreak-strain O104:H4, which combined virulence factors of typical enteroaggregative and Shiga-Toxin–producing E. coli was associated with an unusual high rate of hemolytic uremic syndrome. Also an unexpected high rate of coma and seizures leading to mechanical ventilation and ICU treatment was observed. MicroRNAs are small ribonucleotides orchestrating gene expression. We tested whether circulating microRNAs in serum of HUS patients during the 2011 epidemics are altered in this patient cohort and related to clinical manifestations.Methodology/Principal Findings
We profiled microRNAs using RNA isolated from serum of patients and healthy age-matched controls. The results were validated in 38 patients at baseline, 29 patients during follow-up and 21 age-matched healthy controls by miRNA-specific quantitative RT-PCR. Circulating levels of miR-24, miR-126 were increased in HUS patients versus controls. There was no association between these microRNAs and renal function or the need for renal replacement therapy. In contrast, levels of miR-126 were associated with neurological symptoms at baseline and during follow-up. In addition, miR-126 (on admission) and miR-24 (on admission and during follow-up) were associated with platelet count.Conclusions/Significance
Circulating microRNAs are strongly altered in this patient cohort and associated with neurological symptoms as well as platelet count. 相似文献47.
Gennady V. Pogorelko Parijat S. Juvale William B. Rutter Marion Hütten Thomas R. Maier Tarek Hewezi Judith Paulus Renier AL van der Hoorn Florian MW Grundler Shahid Siddique Vincenzo Lionetti Olga A. Zabotina Thomas J. Baum 《The Plant journal : for cell and molecular biology》2019,98(6):1000-1014
Plants mount defense responses during pathogen attacks, and robust host defense suppression by pathogen effector proteins is essential for infection success. 4E02 is an effector of the sugar beet cyst nematode Heterodera schachtii. Arabidopsis thaliana lines expressing the effector‐coding sequence showed altered expression levels of defense response genes, as well as higher susceptibility to both the biotroph H. schachtii and the necrotroph Botrytis cinerea, indicating a potential suppression of defenses by 4E02. Yeast two‐hybrid analyses showed that 4E02 targets A. thaliana vacuolar papain‐like cysteine protease (PLCP) ‘Responsive to Dehydration 21A’ (RD21A), which has been shown to function in the plant defense response. Activity‐based protein profiling analyses documented that the in planta presence of 4E02 does not impede enzymatic activity of RD21A. Instead, 4E02 mediates a re‐localization of this protease from the vacuole to the nucleus and cytoplasm, which is likely to prevent the protease from performing its defense function and at the same time, brings it in contact with novel substrates. Yeast two‐hybrid analyses showed that RD21A interacts with multiple host proteins including enzymes involved in defense responses as well as carbohydrate metabolism. In support of a role in carbohydrate metabolism of RD21A after its effector‐mediated re‐localization, we observed cell wall compositional changes in 4E02 expressing A. thaliana lines. Collectively, our study shows that 4E02 removes RD21A from its defense‐inducing pathway and repurposes this enzyme by targeting the active protease to different cell compartments. 相似文献
48.
Y chromosome variation of mice and men 总被引:7,自引:5,他引:2
DNA sequences from the nonrecombining portion of the Y chromosome were
compared with autosomal and X-linked sequences from mice and humans to test
the neutral prediction that ratios of polymorphism to divergence are the
same for different genes. Intraspecific variation within Mus domesticus was
compared with divergence between M. domesticus and Mus caroli for Sry, a
region 5' to Sry, and four X-linked genes, Hprt, Plp, Amg, and Glra2. None
of these comparisons revealed significantly reduced variation on the Y
chromosome. Intraspecific variation within humans was compared with
divergence between humans and chimpanzees for three Y-linked loci (Zfy, the
YAP region, and the Sry region), seven X- linked loci (Il2rg, Plp, Hprt,
Gk, Ids, Pdhal, and Dmd), and the beta- globin locus on chromosome 11. In
these comparisons, the observed level of variation on the human Y
chromosome was slightly lower than expected, but was significantly lower in
only one case (Sry region vs. Dmd). These results suggest that the levels
of variability on the Y chromosome in mice and humans are close to expected
values given the effective population size and mutation rates for these
loci. There is at most only a modest reduction in variability that may be
attributed to natural selection (either genetic hitchhiking or background
selection).
相似文献
49.
Sifringer M Uhlenberg B Lammel S Hanke R Neumann B von Moers A Koch I Speer A 《Human genetics》2004,114(2):149-156
Myosin VIIA is an unconventional myosin that has been implicated in Usher syndrome type 1B, atypical Usher syndrome, non-syndromic autosomal recessive hearing impairment (DFNB2) and autosomal dominant hearing impairment (DFNA11). Here, we present a family with non-syndromic autosomal dominant hearing impairment that clinically resembles the previously published DFNA11 family. The affected family members show a flat audiogram at young ages and only modest progression, most clearly at the high frequencies. In addition, they suffer from minor vestibular symptoms. Linkage analysis yielded a maximum two-point lodscore of 3.43 for marker D11S937 located within 1 cM of the myosin VIIA gene. The myosin VIIA gene was sequenced and 11 nucleotide variations were found. Ten nucleotide changes represent benign intronic variants, silent exon mutations or non-pathologic amino acid substitutions. One variant, a c.1373AT transversion that is heterozygously present in all affected family members and absent in 300 healthy individuals, is predicted to result in an Asn458Ile amino acid substitution. Asn458 is located in a region of the myosin VIIA motor domain that is highly conserved in different classes of myosins and in myosins of different species. To evaluate whether the Asn458Ile mutation was indeed responsible for the hearing impairment, a molecular model of myosin VIIA was built based on the known structure of the myosin II heavy chain from Dictyostelium discoideum. In this model, conformational changes in the protein caused by the amino acid substitution Asn458Ile are predicted to disrupt ATP/ADP binding and impair the myosin power-stroke, which would have a severe effect on the function of the myosin VIIA protein. 相似文献
50.
Manon JM van Oosten Radboud JEM Dolhain Jan W Koper Elisabeth FC van Rossum Marieke Emonts Khik H Han Jacques MGW Wouters Johanne MW Hazes Steven WJ Lamberts Richard A Feelders 《Arthritis research & therapy》2010,12(4):R159