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排序方式: 共有367条查询结果,搜索用时 15 毫秒
21.
Mirjam?S. de?Pagter Markus?J. van?Roosmalen Annette?F. Baas Ivo Renkens Karen?J. Duran Ellen van?Binsbergen Masoumeh Tavakoli-Yaraki Ron Hochstenbach Lars?T. van?der?Veken Edwin Cuppen Wigard?P. Kloosterman 《American journal of human genetics》2015,96(4):651-656
Chromothripsis represents an extreme class of complex chromosome rearrangements (CCRs) with major effects on chromosomal architecture. Although recent studies have associated chromothripsis with congenital abnormalities, the incidence and pathogenic effects of this phenomenon require further investigation. Here, we analyzed the genomes of three families in which chromothripsis rearrangements were transmitted from a mother to her child. The chromothripsis in the mothers resulted in completely balanced rearrangements involving 8–23 breakpoint junctions across three to five chromosomes. Two mothers did not show any phenotypic abnormalities, although 3–13 protein-coding genes were affected by breakpoints. Unbalanced but stable transmission of a subset of the derivative chromosomes caused apparently de novo complex copy-number changes in two children. This resulted in gene-dosage changes, which are probably responsible for the severe congenital phenotypes of these two children. In contrast, the third child, who has a severe congenital disease, harbored all three chromothripsis chromosomes from his healthy mother, but one of the chromosomes acquired de novo rearrangements leading to copy-number changes. These results show that the human genome can tolerate extreme reshuffling of chromosomal architecture, including breakage of multiple protein-coding genes, without noticeable phenotypic effects. The presence of chromothripsis in healthy individuals affects reproduction and is expected to substantially increase the risk of miscarriages, abortions, and severe congenital disease. 相似文献
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Fabrizio Chiodo Marco Marradi Boris Tefsen Harm Snippe Irma van Die Soledad Penadés 《PloS one》2013,8(8)
Improved detection of anti-carbohydrate antibodies is a need in clinical identification of biomarkers for cancer cells or pathogens. Here, we report a new ELISA approach for the detection of specific immunoglobulins (IgGs) against carbohydrates. Two nanometer gold glyconanoparticles bearing oligosaccharide epitopes of HIV or Streptococcus pneumoniae were used as antigens to coat ELISA-plates. A ~3,000-fold improved detection of specific IgGs in mice immunized against S. pneumoniae respect to the well known BSA-glycoconjugate ELISA was achieved. Moreover, these multivalent glyconanoparticles have been employed in solid phase assays to detect the carbohydrate-dependent binding of human dendritic cells and the lectin DC-SIGN. Multivalent glyconanoparticles in ELISA provide a versatile, easy and highly sensitive method to detect and quantify the binding of glycan to proteins and to facilitate the identification of biomarkers. 相似文献
24.
Michel J. Vos Serena Carra Floris Bosveld Karin Klauke Harm H. Kampinga 《Aging cell》2016,15(2):217-226
During aging, oxidized, misfolded, and aggregated proteins accumulate in cells, while the capacity to deal with protein damage declines severely. To cope with the toxicity of damaged proteins, cells rely on protein quality control networks, in particular proteins belonging to the family of heat‐shock proteins (HSPs). As safeguards of the cellular proteome, HSPs assist in protein folding and prevent accumulation of damaged, misfolded proteins. Here, we compared the capacity of all Drosophila melanogaster small HSP family members for their ability to assist in refolding stress‐denatured substrates and/or to prevent aggregation of disease‐associated misfolded proteins. We identified CG14207 as a novel and potent small HSP member that exclusively assisted in HSP70‐dependent refolding of stress‐denatured proteins. Furthermore, we report that HSP67BC, which has no role in protein refolding, was the most effective small HSP preventing toxic protein aggregation in an HSP70‐independent manner. Importantly, overexpression of both CG14207 and HSP67BC in Drosophila leads to a mild increase in lifespan, demonstrating that increased levels of functionally diverse small HSPs can promote longevity in vivo. 相似文献
25.
Targeted inhibition of miRNA maturation with morpholinos reveals a role for miR-375 in pancreatic islet development 总被引:5,自引:0,他引:5 下载免费PDF全文
Several vertebrate microRNAs (miRNAs) have been implicated in cellular processes such as muscle differentiation, synapse function, and insulin secretion. In addition, analysis of Dicer null mutants has shown that miRNAs play a role in tissue morphogenesis. Nonetheless, only a few loss-of-function phenotypes for individual miRNAs have been described to date. Here, we introduce a quick and versatile method to interfere with miRNA function during zebrafish embryonic development. Morpholino oligonucleotides targeting the mature miRNA or the miRNA precursor specifically and temporally knock down miRNAs. Morpholinos can block processing of the primary miRNA (pri-miRNA) or the pre-miRNA, and they can inhibit the activity of the mature miRNA. We used this strategy to knock down 13 miRNAs conserved between zebrafish and mammals. For most miRNAs, this does not result in visible defects, but knockdown of miR-375 causes defects in the morphology of the pancreatic islet. Although the islet is still intact at 24 hours postfertilization, in later stages the islet cells become scattered. This phenotype can be recapitulated by independent control morpholinos targeting other sequences in the miR-375 precursor, excluding off-target effects as cause of the phenotype. The aberrant formation of the endocrine pancreas, caused by miR-375 knockdown, is one of the first loss-of-function phenotypes for an individual miRNA in vertebrate development. The miRNA knockdown strategy presented here will be widely used to unravel miRNA function in zebrafish. 相似文献
26.
Crystal structure of quinone‐dependent alcohol dehydrogenase from Pseudogluconobacter saccharoketogenes. A versatile dehydrogenase oxidizing alcohols and carbohydrates 下载免费PDF全文
Henriëtte J. Rozeboom Shukun Yu Rene Mikkelsen Igor Nikolaev Harm J. Mulder Bauke W. Dijkstra 《Protein science : a publication of the Protein Society》2015,24(12):2044-2054
The quinone‐dependent alcohol dehydrogenase (PQQ‐ADH, E.C. 1.1.5.2) from the Gram‐negative bacterium Pseudogluconobacter saccharoketogenes IFO 14464 oxidizes primary alcohols (e.g. ethanol, butanol), secondary alcohols (monosaccharides), as well as aldehydes, polysaccharides, and cyclodextrins. The recombinant protein, expressed in Pichia pastoris, was crystallized, and three‐dimensional (3D) structures of the native form, with PQQ and a Ca2+ ion, and of the enzyme in complex with a Zn2+ ion and a bound substrate mimic were determined at 1.72 Å and 1.84 Å resolution, respectively. PQQ‐ADH displays an eight‐bladed β‐propeller fold, characteristic of Type I quinone‐dependent methanol dehydrogenases. However, three of the four ligands of the Ca2+ ion differ from those of related dehydrogenases and they come from different parts of the polypeptide chain. These differences result in a more open, easily accessible active site, which explains why PQQ‐ADH can oxidize a broad range of substrates. The bound substrate mimic suggests Asp333 as the catalytic base. Remarkably, no vicinal disulfide bridge is present near the PQQ, which in other PQQ‐dependent alcohol dehydrogenases has been proposed to be necessary for electron transfer. Instead an associated cytochrome c can approach the PQQ for direct electron transfer. 相似文献
27.
Ewa G. Klaver-Król Nizare R. Henriquez Sebe J. Oosterloo Peter Klaver Harm Kuipers Machiel J. Zwarts 《Journal of electromyography and kinesiology》2010,20(6):1107-1114
In surface electromyography (sEMG), the distribution of motor unit potential (MUP) velocities has been shown to reflect the proportion of faster and slower propagating MUPs. This study investigated whether the distribution of MUP velocities could distinguish between sprinters and endurance athletes in not-specifically trained muscle (biceps brachii). sEMG results were acquired from 15 sprinters and 18 endurance athletes during short static contractions (3.8 s) at three force levels: unloaded, 10% and 20% of maximum voluntary contraction. The features extracted from the sEMG were: the mean muscle conduction velocity (CV) – estimated using the inter-peak latency and the cross-correlation methods, the within-subject skewness of MUP velocities (expressing the relative proportions of faster and slower propagating MUPs), and the within-subject standard deviation of MUP velocities. Sprinters had a higher CV than endurance athletes using both methods. Sprinters also demonstrated a greater proportion of fast propagating MUPs, as indicated by the skewness. Thus, the distribution of MUP velocities was able to demonstrate physiological differences between sprinters and endurance athletes during short contractions at low forces. The findings can be extrapolated to the motor unit level. Since the investigated muscle was not involved in specific training, the differences seem to reflect inherited properties. 相似文献
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Lagaud G Karicheti V Knot HJ Christ GJ Laher I 《American journal of physiology. Heart and circulatory physiology》2002,283(6):H2177-H2186
The effects of two structurally distinct inhibitors of gap junction communication were studied by using three different forms of vasoconstriction in pressurized rat middle cerebral arteries. The sensitivity of myogenic tone (at 60 mmHg), vasopressin-induced tone (10 nM, at 20 mmHg), and depolarizing solution-induced tone (80 mM K(+), at 20 mmHg) to inhibition by heptanol (1.0 microM to 3.0 mM) or 18alpha-glycyrrhetinic acid (18alpha-GA, 1.0 to 50 microM) were determined. Pressure-induced myogenic tone was inhibited by heptanol (IC(50) = 0.75 +/- 0.09 mM) and 18alpha-GA ( approximately 30 microM). Vasopressin-induced vasoconstriction was also inhibited by heptanol (IC(50) = 0.4 +/- 0.3 mM) and 18alpha-GA (>1 microM). Depolarizing solution-induced vasoconstriction was less sensitive to inhibition by heptanol compared to vasopressin (P < 0.01) or pressure-induced constriction (P < 0.05). However, 18alpha-GA did not inhibit depolarization-induced constriction. Sharp microelectrode experiments on isolated arteries revealed stable membrane potentials, with no detectable effect of heptanol (1 mM) or 18alpha-GA (20-30 microM) on the average membrane potential at 20 mmHg. However, approximately 20% of impaled cells (5 of 28) exhibited uncharacteristic oscillations in membrane potential after pharmacological uncoupling. At 60 mmHg a approximately 7- to 9-mV hyperpolarization and corresponding vasodilation (approximately 50%) was observed, and the frequency of membrane potential oscillations doubled (9 of 23 cells). These data indicate that gap junctions play an important role in the maintenance and modulation of membrane potential and tone in cerebral resistance arteries. 相似文献
30.
The response of a nematode community to a decreasing organic matter loading was studied. Monthly observations were made at three stations at an intertidal brackish-water mudflat in the Ems estuary in 1980 (highly polluted), 1987 (moderately polluted) and 1993 (no significant pollution). Nematodes were identified and counted in the upper 1 cm of the sediment.The decrease of organic pollution was followed by an increase in species diversity, whereas numerical densities decreased. Diatom eating nematodes, being dominant under eutrophic conditions in 1980, decreased strongly, partly as a consequence of decreasing diatom standing stock. Eudiplogaster pararmatus, an indicator of organic enrichment, decreased strongly to disappear completely in 1993. Bonger's maturity index was used to describe the response of the nematode community. At 2 most polluted stations a strong response was observed from 1980 to 1987: a decrease of colonizer species. After 1987, although persister species increased, no further development towards a more natural succession type community occurred, probably due to the natural stress of the habitat (high mudflat, low salinities). 相似文献