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排序方式: 共有210条查询结果,搜索用时 15 毫秒
101.
Jian Jing Jagath R. Junutula Christine Wu Jemima Burden Hugo Matern Andrew A. Peden Rytis Prekeris 《Molecular biology of the cell》2010,21(17):3041-3053
Many proteins are retrieved to the trans-Golgi Network (TGN) from the endosomal system through several retrograde transport pathways to maintain the composition and function of the TGN. However, the molecular mechanisms involved in these distinct retrograde pathways remain to be fully understood. Here we have used fluorescence and electron microscopy as well as various functional transport assays to show that Rab11a/b and its binding protein FIP1/RCP are both required for the retrograde delivery of TGN38 and Shiga toxin from early/recycling endosomes to the TGN, but not for the retrieval of mannose-6-phosphate receptor from late endosomes. Furthermore, by proteomic analysis we identified Golgin-97 as a FIP1/RCP-binding protein. The FIP1/RCP-binding domain maps to the C-terminus of Golgin-97, adjacent to its GRIP domain. Binding of FIP1/RCP to Golgin-97 does not affect Golgin-97 recruitment to the TGN, but appears to regulate the targeting of retrograde transport vesicles to the TGN. Thus, we propose that FIP1/RCP binding to Golgin-97 is required for tethering and fusion of recycling endosome-derived retrograde transport vesicles to the TGN. 相似文献
102.
Genome-wide mapping of susceptibility to coronary artery disease identifies a novel replicated locus on chromosome 17
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Farrall M Green FR Peden JF Olsson PG Clarke R Hellenius ML Rust S Lagercrantz J Franzosi MG Schulte H Carey A Olsson G Assmann G Tognoni G Collins R Hamsten A Watkins H 《PLoS genetics》2006,2(5):e72
Coronary artery disease (CAD) is a leading cause of death world-wide, and most cases have a complex, multifactorial aetiology that includes a substantial heritable component. Identification of new genes involved in CAD may inform pathogenesis and provide new therapeutic targets. The PROCARDIS study recruited 2,658 affected sibling pairs (ASPs) with onset of CAD before age 66 y from four European countries to map susceptibility loci for CAD. ASPs were defined as having CAD phenotype if both had CAD, or myocardial infarction (MI) phenotype if both had a MI. In a first study, involving a genome-wide linkage screen, tentative loci were mapped to Chromosomes 3 and 11 with the CAD phenotype (1,464 ASPs), and to Chromosome 17 with the MI phenotype (739 ASPs). In a second study, these loci were examined with a dense panel of grid-tightening markers in an independent set of families (1,194 CAD and 344 MI ASPs). This replication study showed a significant result on Chromosome 17 (MI phenotype; p = 0.009 after adjustment for three independent replication tests). An exclusion analysis suggests that further genes of effect size λsib > 1.24 are unlikely to exist in these populations of European ancestry. To our knowledge, this is the first genome-wide linkage analysis to map, and replicate, a CAD locus. The region on Chromosome 17 provides a compelling target within which to identify novel genes underlying CAD. Understanding the genetic aetiology of CAD may lead to novel preventative and/or therapeutic strategies. 相似文献
103.
DNA methylation is an epigenetic mechanism that has the potential to affect plant phenotypes and that is responsive to environmental and genomic stresses such as hybridization and polyploidization. We explored de novo methylation variation that arises during the formation of triploid asexual dandelions from diploid sexual mother plants using methylation‐sensitive amplified fragment length polymorphism (MS‐AFLP) analysis. In dandelions, triploid apomictic asexuals are produced from diploid sexual mothers that are fertilized by polyploid pollen donors. We asked whether the ploidy level change that accompanies the formation of new asexual lineages triggers methylation changes that contribute to heritable epigenetic variation within novel asexual lineages. Comparison of MS‐AFLP and AFLP fragment inheritance in a diploid × triploid cross revealed de novo methylation variation between triploid F1 individuals. Genetically identical offspring of asexual F1 plants showed modest levels of methylation variation, comparable to background levels as observed among sibs in a long‐established asexual lineage. Thus, the cross between ploidy levels triggered de novo methylation variation between asexual lineages, whereas it did not seem to contribute directly to variation within new asexual lineages. The observed background level of methylation variation suggests that considerable autonomous methylation variation could build up within asexual lineages under natural conditions. 相似文献
104.
Susana Fuentes Els van Nood Sebastian Tims Ineke Heikamp-de Jong Cajo JF ter Braak Josbert J Keller Erwin G Zoetendal Willem M de Vos 《The ISME journal》2014,8(8):1621-1633
Recurrent Clostridium difficile infection (CDI) can be effectively treated by infusion of a healthy donor faeces suspension. However, it is unclear what factors determine treatment efficacy. By using a phylogenetic microarray platform, we assessed composition, diversity and dynamics of faecal microbiota before, after and during follow-up of the transplantation from a healthy donor to different patients, to elucidate the mechanism of action of faecal infusion. Global composition and network analysis of the microbiota was performed in faecal samples from nine patients with recurrent CDI. Analyses were performed before and after duodenal donor faeces infusion, and during a follow-up of 10 weeks. The microbiota data were compared with that of the healthy donors. All patients successfully recovered. Their intestinal microbiota changed from a low-diversity diseased state, dominated by Proteobacteria and Bacilli, to a more diverse ecosystem resembling that of healthy donors, dominated by Bacteroidetes and Clostridium groups, including butyrate-producing bacteria. We identified specific multi-species networks and signature microbial groups that were either depleted or restored as a result of the treatment. The changes persisted over time. Comprehensive and deep analyses of the microbiota of patients before and after treatment exposed a therapeutic reset from a diseased state towards a healthy profile. The identification of microbial groups that constitute a niche for C. difficile overgrowth, as well as those driving the reinstallation of a healthy intestinal microbiota, could contribute to the development of biomarkers predicting recurrence and treatment outcome, identifying an optimal microbiota composition that could lead to targeted treatment strategies. 相似文献
105.
Phylogeny of some Fusarium species, as determined by large-subunit rRNA sequence comparison 总被引:16,自引:0,他引:16
Fifty-two strains from eight species of Fusarium were analyzed by rapid
rRNA sequencing. Two highly variable stretches (138 and 214 nucleotides) of
the 5' end of the 28S-like rRNA molecule were sequenced. Such stretches
permit evaluation of the divergence between closely related species and
even between varieties within a species. The phylogenetic tree computed
from the number of nucleotide differences shows seven Fusarium species to
be more closely related to one another than the eighth species, F. nivale,
is to them. On the basis of these data, we discuss both the phylogenetic
value of taxonomical criteria and the impact of our findings on the
demarcation of the genus Fusarium. We conclude that this method is suitable
for establishing a precise phylogeny between closely related species within
a genus.
相似文献
106.
Water analyses from 80 small prairie ponds, 0.17 to 89.8 hectares, in Manitoba and Saskatchewan between 1967 to 1972 exhibited two basic ionic dominance patterns HCO3 > SO4 > Cl and SO4 > HCO3 > Cl. The order of SO4 and Cl were reversed in 40 percent of the bicarbonate ponds below 500 µmhos/cm. At salinities above 12,000 µmhos/cm, Cl exceeds SO4 in several wetlands. Temporary wetlands were characterised by Ca > K > Mg > Na / HCO3 > Cl > SO4, semi-permanent ponds Mg > Ca > Na > K / SO4 > HCO3 > Cl while the permanent pond structure was Ca > Mg > Na > K / HCO3 > SO4 > Cl.Conductivities of the wetlands studied ranged from 47 to 23,000 µmhos / cm.Seasonal changes in salinity varied within and between pond types as well as from year to year. The average salinity increase within season in temporary ponds was 67 percent, 63 percent in semi-permanent ponds and 20 percent for permanent ponds. These changes were affected by evaporation, transpiration, see-page and precipitation patterns. Ionic dominance patterns did not change within a season although Mg, K and HCO3 increased at higher rates than Ca, Na, CI and SO4.Temporary wetlands are slightly acidic, averaging pH 6.8 while semi-permanent and permanent ponds were alkaline, pH range 7.1 to 9.2. No stratification of pH with depth and minimal diurnal variation was recorded.At two study areas, Bradwell and St. Denis fhe following ranges (micrograms/litre) were recorded: 3 to 630 PO4-P, 10 to 650 NO3-N, 5 to 630 TDFe, 1 to 13 TDCu and 1 to 27 TDZn. Colour was 5 to 190 Hazen units at St. Denis and 10 to 110 for Bradwell.Two herbicides, 2,4-D and 2,4,5-T were detected at levels of 4 to 111 and 1.4 to 13.5 micrograms/litre, respectively, from 15 ponds at St. Denis. 相似文献
107.
108.
Nelson JF da Silveira Helen A Arcuri Carlos E Bonalumi Fátima P de Souza Isabel MVGC Mello Paula Rahal Jo?o RR Pinho Walter F de Azevedo 《BMC structural biology》2005,5(1):1
Background
Hepatitis C virus (HCV) currently infects approximately three percent of the world population. In view of the lack of vaccines against HCV, there is an urgent need for an efficient treatment of the disease by an effective antiviral drug. Rational drug design has not been the primary way for discovering major therapeutics. Nevertheless, there are reports of success in the development of inhibitor using a structure-based approach. One of the possible targets for drug development against HCV is the NS3 protease variants. Based on the three-dimensional structure of these variants we expect to identify new NS3 protease inhibitors. In order to speed up the modeling process all NS3 protease variant models were generated in a Beowulf cluster. The potential of the structural bioinformatics for development of new antiviral drugs is discussed. 相似文献109.
B Kornmatitsuk E Dahl E Ropstad JF Beckers H Gustafsson H Kindahl 《Acta veterinaria Scandinavica》2004,45(1):47
The high incidence of stillbirth in Swedish Holstein heifers has increased continuously during the last 15 years to an average
of 11% today. The pathological reasons behind the increased incidence of stillbirth are unknown. The present experiment was
undertaken to investigate possible causes of stillbirth and to study possible physiological markers for predicting stillbirth.
Twenty Swedish Holstein dairy heifers sired by bulls with breeding values for a high risk of stillbirth (n = 12) (experimental
group) and a low risk of stillbirth (n = 8) (control group, group B) were selected based on information in the Swedish AI-data
base. The experimental group consisted of 2 subgroups of heifers (groups A1 and A2) inseminated with 2 different bulls with
3.5% and 9% higher stillbirth rates than the average, and the control group consisted of heifers pregnant with 5 different
bulls with 0%–6% lower stillbirth rates than the average. The bull used for group A1 had also calving difficulties due to
large calves as compared to the bull in group A2 showing no calving difficulties. The heifers were supervised from 6–7 months
of pregnancy up to birth, and the pregnancies and parturitions were compared between groups regarding hormonal levels, haematology,
placental characteristics and calf viability. In group A1, 1 stillborn, 1 weak and 4 normal calves were recorded. In group
A2, 2 stillborn and 4 normal calves were registered. All animals in the control group gave birth to a normal living calf without
any assistance. The weak calf showed deviating profiles of body temperature, saturated oxygen and heart rates, compared with
the normal living calves. No differences of the placentome thickness, measured in vivo by ultrasonography were seen between the groups. The number of leukocytes and differential cell counts in groups A1 and A2
followed the profiles found in the control group. In group A1, a slight decrease of oestrone sulphate (E1SO4) levels was found
in the animal delivering a stillborn calf from the first 24-h blood sampling at 6 weeks to the second at 3 weeks prior to
delivery, while the levels of E1SO4 at both periods in the animal delivering a weak calf followed the profile in animals delivering
a normal living calf. During late pregnancy and at the time of parturition, the levels of E1SO4 and PAGs in animals delivering
a stillborn or weak calf (from group A1) followed the normal profiles found in animals delivering a normal living calf. In
group A2, low levels of E1SO4 and pregnancy associated glycoproteins (PAGs) over 24 h at both 3 and 6 weeks prior to parturition
(<1.5 nmol/L) were recorded in animals delivering a stillborn calf. During late pregnancy and parturition, the levels of E1SO4
and PAGs were slightly lower during 30–50 days prior to delivery and increased with a lower magnitude at the time of parturition.
In conclusion, our results indicate that the aetiology behind stillbirth varies depending on the AI-bulls used and is associated
with dystocia or low viability of the calves. Deviating profiles of oestrone sulphate (E1SO4) and pregnancy associated glycoproteins
(PAGs) in animals delivering a stillborn calf not caused by dystocia were observed, suggesting placental dysfunction as a
possible factor. The finding suggests that the analyses of E1SO4 and PAGs could be used for monitoring foetal well-being in
animals with a high risk of stillbirth at term. 相似文献
110.
In our studies of the health effects of internalized depleted uranium, we developed a simple and rapid light microscopic method to stain specifically intracellular uranium deposits. Using J774 cells, a mouse macrophage line, treated with uranyl nitrate and the pyridylazo dye 2-(5-bromo-2- pyridylazo)-5-diethylaminophenol, uranium uptake by the cells was followed. Specificity of the stain for uranium was accomplished by using masking agents to prevent the interaction of the stain with other metals. Prestaining wash consisting of a mixture of sodium citrate and ethylenediaminetetraacetic acid eliminated staining of metals other than uranium. The staining solution consisted of the pyridylazo dye in borate buffer along with a quaternary ammonium salt, ethylhexadecyldimethylammonium bromide, and the aforementioned sodium citrate/ethylene-diaminetetraacetic acid mixture. The buffer was essential for maintaining the pH within the optimum range of 8 to 12, and the quaternary ammonium salt prevented precipitation of the dye. Staining was conducted at room temperature and was complete in 30 min. Staining intensity correlated with both uranyl nitrate concentration and incubation time. Our method provides a simple procedure for detecting intracellular uranium deposits in macrophages. 相似文献