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排序方式: 共有604条查询结果,搜索用时 109 毫秒
291.
Vidhya Jagannathan Jeanette Bannoehr Philippe Plattet Regula Hauswirth Cord Dr?gemüller Michaela Dr?gemüller Dominique J. Wiener Marcus Doherr Marta Owczarek-Lipska Arnaud Galichet Monika M. Welle Katarina Tengvall Kerstin Bergvall Hannes Lohi Silvia Rüfenacht Monika Linek Manon Paradis Eliane J. Müller Petra Roosje Tosso Leeb 《PLoS genetics》2013,9(10)
Hereditary nasal parakeratosis (HNPK), an inherited monogenic autosomal recessive skin disorder, leads to crusts and fissures on the nasal planum of Labrador Retrievers. We performed a genome-wide association study (GWAS) using 13 HNPK cases and 23 controls. We obtained a single strong association signal on chromosome 2 (praw = 4.4×10−14). The analysis of shared haplotypes among the 13 cases defined a critical interval of 1.6 Mb with 25 predicted genes. We re-sequenced the genome of one case at 38× coverage and detected 3 non-synonymous variants in the critical interval with respect to the reference genome assembly. We genotyped these variants in larger cohorts of dogs and only one was perfectly associated with the HNPK phenotype in a cohort of more than 500 dogs. This candidate causative variant is a missense variant in the SUV39H2 gene encoding a histone 3 lysine 9 (H3K9) methyltransferase, which mediates chromatin silencing. The variant c.972T>G is predicted to change an evolutionary conserved asparagine into a lysine in the catalytically active domain of the enzyme (p.N324K). We further studied the histopathological alterations in the epidermis in vivo. Our data suggest that the HNPK phenotype is not caused by hyperproliferation, but rather delayed terminal differentiation of keratinocytes. Thus, our data provide evidence that SUV39H2 is involved in the epigenetic regulation of keratinocyte differentiation ensuring proper stratification and tight sealing of the mammalian epidermis. 相似文献
292.
Mutants of Saccharomyces cerevisiae were isolated which supported three mutations: two unlinked chromosomic mutations conferring thermosensitivity and cold sensitivity respectively, and a mitochondrial mutation conferring paromomycin sensitivity. When studied on isolated mitochondria, these mutants exhibited low phosphorylation efficiency and great proton permeability of their inner mitochondrial membrane. Experiments were carried out on whole cells: determination of growth rates, cellular yields and cellular respiration, either in the presence of triethyltin, an ATP synthase inhibitor, or in the presence of uncoupler, demonstrating that the proton leakage is actually a physiological phenomenon linked to the cold-sensitive phenotype. Experiments performed on isolated mitochondria confirmed the existence of such a proton leakage. 相似文献
293.
294.
Cartron PF Bellot G Oliver L Grandier-Vazeille X Manon S Vallette FM 《FEBS letters》2008,582(20):3045-3051
Bax insertion into the mitochondrial outer membrane is essential for the implementation of apoptosis. However, little is known about the first stage of Bax integration into the mitochondrial outer membrane. We have recently shown that TOM22, a mitochondrial outer membrane receptor, is important for insertion, although other reports have suggested that only mitochondrial lipids are involved in this process. Here, we show that monomers, but not dimers, of Bax require the presence of TOM22 and TOM40 to integrate into mitochondria. In addition we show that once inserted into the membrane, Bax can act as a receptor for cytosolic Bax. 相似文献
295.
Improvement of the Thermostability and Activity of a Pectate Lyase by Single Amino Acid Substitutions, Using a Strategy Based on Melting-Temperature-Guided Sequence Alignment 总被引:1,自引:0,他引:1
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Zhizhuang Xiao Hlne Bergeron Stephan Grosse Manon Beauchemin Marie-Line Garron David Shaya Traian Sulea Miroslaw Cygler Peter C. K. Lau 《Applied microbiology》2008,74(4):1183-1189
In the vast number of random mutagenesis experiments that have targeted protein thermostability, single amino acid substitutions that increase the apparent melting temperature (Tm) of the enzyme more than 1 to 2°C are rare and often require the creation of a large library of mutated genes. Here we present a case where a single beneficial mutation (R236F) of a hemp fiber-processing pectate lyase of Xanthomonas campestris origin (PLXc) produced a 6°C increase in Tm and a 23-fold increase in the half-life at 45°C without compromising the enzyme's catalytic efficiency. This success was based on a variation of sequence alignment strategy where a mesophilic amino acid sequence is matched with the sequences of its thermophilic counterparts that have established Tm values. Altogether, two-thirds of the nine targeted single amino acid substitutions were found to have effects either on the thermostability or on the catalytic activity of the enzyme, evidence of a high success rate of mutation without the creation of a large gene library and subsequent screening of clones. Combination of R236F with another beneficial mutation (A31G) resulted in at least a twofold increase in specific activity while preserving the improved Tm value. To understand the structural basis for the increased thermal stability or activity, the variant R236F and A31G R236F proteins and wild-type PLXc were purified and crystallized. By structure analysis and computational methods, hydrophobic desolvation was found to be the driving force for the increased stability with R236F. 相似文献
296.
Phase diagrams of the Langmuir monolayer of dicyclopropyl alpha mycolic acid (α-MA), cyclopropyl methoxy mycolic acid (MeO-MA), and cyclopropyl ketomycolic acids (Keto-MA) from Mycobacterium tuberculosis were obtained by thermodynamic analysis of the surface pressure (π) vs. average molecular area (A) isotherms at temperatures in the range of 10-46 °C. The Langmuir monolayers of MAs were shown to exhibit various phases depending on the temperature (T) and the π values. In the Langmuir monolayer of Keto-MA, the carbonyl group in the meromycolate chain apparently touches the water surface to give the molecule a W-shape in all the temperatures and surface pressures studied. Keto-MA formed a rigid solid condensed film, with four hydrocarbon chains packing together, not observed in the others. In contrast, the monolayer films of α-and MeO-MAs having no such highly hydrophilic intra-chain groups in the meromycolate chain were mostly in liquid condensed phase. This novel insight into the packing of mycolic acids opens up new avenues for the study of the role of mycolic acids in the mycobacterial cell envelopes and pathogenic processes. 相似文献
297.
298.
Effect of individual or paired housing during post-weaning on feed intake, growth rate and behaviour of lambs 总被引:1,自引:0,他引:1
The aim of this study was to compare the behaviour and weight gain of weaned lambs penned either in pairs or alone, with visual and tactile contacts between pens. A 2 × 2 factorial experiment was conducted over seven weeks. Forty-eight Dorset lambs (twenty-five females and twenty-three males) were randomly distributed among pens. All pairs were non-twin lambs of the same sex. They were fed haylage (48.9% of DM) and a commercial pelleted feed both provided ad libitum. Weight of lambs was recorded at d0 and then weekly until d49. Consumption of dry matter and average daily gain (ADG) were also recorded. Lamb postures, activities and total bleats were directly observed in the morning and in the afternoon on six different days (d1, d2, d5, d12, d19, d26). On d1, observations were done only in the afternoon. For paired lambs, data were averaged by pen. Lambs penned alone were less active, slept more (P < 0.03) and walked less (P < 0.001) than paired lambs. Total bleats were not affected by housing treatment or sex, but were significantly higher for the first two days (P < 0.0001). Lamb growth performance was unaffected by the type of housing (P > 0.05). There was a significant difference in ADG (P < 0.001), total gain (P < 0.001), kg concentrate kg−1 gain (P < 0.05) and final body weight (P < 0.05) in favor of males as compared to females. Our results suggest that a housing system in which individually raised lambs are allowed visual, tactile, and auditive contact with each other, compared to lambs housed in pairs, does not impact negatively on their growth and behaviour. 相似文献
299.
Drew R. Ekman Quincy Teng Daniel L. Villeneuve Michael D. Kahl Kathleen M. Jensen Elizabeth J. Durhan Gerald T. Ankley Timothy W. Collette 《Metabolomics : Official journal of the Metabolomic Society》2009,5(1):22-32
Alterations in hepatic lipid profiles of fathead minnows (FHM) exposed to the synthetic estrogen 17α-ethynylestradiol (EE2)
were determined using 1H-NMR spectroscopy-based metabolite profiling. The exposures were conducted using either 10 ng/l or 100 ng/l EE2 via a continuous
flow water delivery system. Livers were collected at 1, 4, and 8 days of the exposure and 8 days after the chemical was removed
from the water (i.e. an 8 day depuration). The exposure resulted in a number of sex-specific changes in lipid profiles that
were also highly time dependent. Those metabolites most affected by exposure included phosphatidylcholine, diglycerides, triglycerides
and cholesterol. In addition, changes in the length and degree of unsaturation of hepatic fatty acids were observed. Lipid
profiles in plasma for fish collected on the 4th day of exposure were also analyzed in order to provide further insights into
changes observed in hepatic metabolite changes. Using validated partial least-squares discriminant analysis (PLS-DA), the
response trajectories of the male liver lipid profiles at both exposure concentrations were compared. This analysis indicated
that the males exposed to the low concentration of EE2 (10 ng/l) were largely able to recover from the exposure once the chemical
was removed from the water. Conversely, the males exposed to the high concentration (100 ng/l) did not appear to recover from
the exposure despite the 8 day depuration. 相似文献
300.
Manon Rosselin Jaime Santo‐Domingo Flavien Bermont Marta Giacomello Nicolas Demaurex 《EMBO reports》2017,18(3):451-463
Mitochondrial flashes mediated by optic atrophy 1 (OPA1) fusion protein are bioenergetic responses to stochastic drops in mitochondrial membrane potential (Δψm) whose origin is unclear. Using structurally distinct genetically encoded pH‐sensitive probes, we confirm that flashes are matrix alkalinization transients, thereby establishing the pH nature of these events, which we renamed “mitopHlashes”. Probes located in cristae or intermembrane space as verified by electron microscopy do not report pH changes during Δψm drops or respiratory chain inhibition. Opa1 ablation does not alter Δψm fluctuations but drastically decreases the efficiency of mitopHlash/Δψm coupling, which is restored by re‐expressing fusion‐deficient OPA1K301A and preserved in cells lacking the outer‐membrane fusion proteins MFN1/2 or the OPA1 proteases OMA1 and YME1L, indicating that mitochondrial membrane fusion and OPA1 proteolytic processing are dispensable. pH/Δψm uncoupling occurs early during staurosporine‐induced apoptosis and is mitigated by OPA1 overexpression, suggesting that OPA1 maintains mitopHlash competence during stress conditions. We propose that OPA1 stabilizes respiratory chain supercomplexes in a conformation that enables respiring mitochondria to compensate a drop in Δψm by an explosive matrix pH flash. 相似文献