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11.
Iris Postmus Stella Trompet Anton J. M. de Craen Brendan M. Buckley Ian Ford David J. Stott Naveed Sattar P. Eline Slagboom Rudi G. J. Westendorp J. Wouter Jukema 《Journal of lipid research》2013,54(2):561-566
Proprotein convertase subtilisin-like/kexin type 9 (PCSK9) is a protein involved in LDL-cholesterol metabolism. The single-nucleotide polymorphism (SNP) rs11591147 has been associated with lower LDL-cholesterol and a lower risk of coronary heart disease. Because PCSK9 has high affinity to the LDL receptor, inhibiting PCSK9 is a testable therapeutic target for lipid-lowering therapy. Currently, several approaches to inhibit PCSK9 are under development, but it is unknown what the effects of those inhibitors will be on cognition or noncardiovascular clinical events. In this study, we assessed the association between rs11591147 and cognitive performance, activities of daily living (ADL), and noncardiovascular clinical events within 5,777 participants of the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER). Rs11591147 was associated with 10% to 16% lower LDL cholesterol levels (P = 3.62 × 10−12), but was not associated with cognitive performance, ADL, or noncardiovascular clinical events in the PROSPER study. Our findings suggest that lower cholesterol levels due to genetic variation in the PCSK9 gene are not associated with cognitive performance, functional status, or noncardiovascular clinical events. 相似文献
12.
Calcrete aquifers from the Yilgarn region of arid central Western Australia contain an assemblage of obligate groundwater invertebrate species that are each endemic to single aquifers. Fine-scale phylogeographic and population genetic analyses of three sympatric and independently derived species of amphipod (Chiltoniidae) were carried out to determine whether there were common patterns of population genetic structure or evidence for past geographic isolation of populations within a single calcrete aquifer. Genetic diversity in amphipod mitochondrial DNA (cytochrome c oxidase subunit I gene) and allozymes were examined across a 3.5 km2 region of the Sturt Meadows calcrete, which contains a grid of 115 bore holes (=wells). Stygobiont amphipods were found to have high levels of mitochondrial haplotype diversity coupled with low nucleotide diversity. Mitochondrial phylogeographic structuring was found between haplogroups for one of the chiltoniid species, which also showed population structuring for nuclear markers. Signatures of population expansion in two of the three species, match previous findings for diving beetles at the same site, indicating that the system is dynamic. We propose isolation of populations in refugia within the calcrete, followed by expansion events, as the most likely source of intraspecific genetic diversity, due to changes in water level influencing gene flow across the calcrete. 相似文献
13.
Jonathan D. Blount Emma I. K. Vitikainen Iain Stott Michael A. Cant 《Biological reviews of the Cambridge Philosophical Society》2016,91(2):483-497
Life‐history theory assumes that reproduction and lifespan are constrained by trade‐offs which prevent their simultaneous increase. Recently, there has been considerable interest in the possibility that this cost of reproduction is mediated by oxidative stress. However, empirical tests of this theory have yielded equivocal support. We carried out a meta‐analysis to examine associations between reproduction and oxidative damage across markers and tissues. We show that oxidative damage is positively associated with reproductive effort across females of various species. Yet paradoxically, categorical comparisons of breeders versus non‐breeders reveal that transition to the reproductive state is associated with a step‐change reduction in oxidative damage in certain tissues and markers. Developing offspring may be particularly sensitive to harm caused by oxidative damage in mothers. Therefore, such reductions could potentially function to shield reproducing mothers, gametes and developing offspring from oxidative insults that inevitably increase as a consequence of reproductive effort. According to this perspective, we hypothesise that the cost of reproduction is mediated by dual impacts of maternally‐derived oxidative damage on mothers and offspring, and that mothers may be selected to diminish such damage. Such oxidative shielding may explain why many existing studies have concluded that reproduction has little or no oxidative cost. Future advance in life‐history theory therefore needs to take account of potential transgenerational impacts of the mechanisms underlying life‐history trade‐offs. 相似文献
14.
Jackson Oyindamola Quilliam Richard S. Stott Andy Grant Helen Subke Jens-Arne 《Plant and Soil》2019,437(1-2):473-485
Plant and Soil - Root exudation is an important carbon (C) and energy source for soil microorganisms but quantifying its spatial distribution is challenging. We tested whether 14C imaging (analogue... 相似文献
15.
Phylogenetic relationships were determined for 76 partial P-element
sequences from 14 species of the melanogaster species group within the
Drosophila subgenus Sophophora. These results are examined in the context
of the phylogeny of the species from which the sequences were isolated.
Sequences from the P-element family fall into distinct subfamilies, or
clades, which are often characteristic for particular species subgroups.
When examined locally among closely related species, the evolution of P
elements is characterized by vertical transmission, whereby the P-element
phylogeny traces the species phylogeny. On a broader scale, however, the
P-element phylogeny is not congruent with the species phylogeny. One
feature of P-element evolution in the melanogaster group is the presence of
more than one P-element subfamily, differing by as much as 36%, in the
genomes of some species. Thus, P elements from several individual species
are not monophyletic, and a likely explanation for the incongruence between
P-element and species phylogenies is provided by the comparison of
paralogous sequences. In certain instances, horizontal transfer seems to be
a valid alternative explanation for lack of congruence between species and
P-element phylogenies. The canonical P-element subfamily, which represents
the active, autonomous transposable element, is restricted to D.
melanogaster. Thus, its origin clearly lies outside of the melanogaster
species group, consistent with the earlier conclusion of recent horizontal
transfer.
相似文献
16.
Somatic hypermutation and selection of B cells in thymic germinal centers responding to acetylcholine receptor in myasthenia gravis 总被引:8,自引:0,他引:8
Sims GP Shiono H Willcox N Stott DI 《Journal of immunology (Baltimore, Md. : 1950)》2001,167(4):1935-1944
The muscle weakness in myasthenia gravis (MG) is mediated by autoantibodies against the nicotinic acetylcholine receptor (AChR) at the neuromuscular junction. Production of these pathogenic autoantibodies is believed to be associated with germinal centers (GC) and anti-AChR-secreting plasma cells in the hyperplastic thymus of patients with early onset MG (EOMG). Here, we describe the repertoire of rearranged heavy chain V genes and their clonal origins in GC from a typical EOMG patient. Three hundred fifteen rearranged Ig V(H) genes were amplified, cloned, and sequenced from sections of four thymic GC containing AChR-specific B cells. We found that thymic GC contain a remarkably heterogeneous population of B cells. Both naive and circulating memory B cells undergo Ag-driven clonal proliferation, somatic hypermutation, and selection. Numerous B cell clones were present, with no individual clone dominating the response. Comparisons of B cell clonal sequences from different GC and known anti-AChR Abs from other patients showed convergent mutations in the complementarity determining regions. These results are consistent with AChR driving an ongoing GC response in the thymus of EOMG patients. This is the first detailed analysis of B cell clones in human GC responding to a defined protein Ag, and the response we observed may reflect the effects of chronic stimulation by autoantigen. 相似文献
17.
18.
Isolation of novel bacteria, including a candidate division, from geothermal soils in New Zealand 总被引:4,自引:0,他引:4
Stott MB Crowe MA Mountain BW Smirnova AV Hou S Alam M Dunfield PF 《Environmental microbiology》2008,10(8):2030-2041
We examined bacterial diversity of three geothermal soils in the Taupo Volcanic Zone of New Zealand. Phylogenetic analysis of 16S rRNA genes recovered directly from soils indicated that the bacterial communities differed in composition and richness, and were dominated by previously uncultured species of the phyla Actinobacteria , Acidobacteria , Chloroflexi , Proteobacteria and candidate division OP10. Aerobic, thermophilic, organotrophic bacteria were isolated using cultivation protocols that involved extended incubation times, low-pH media and gellan as a replacement gelling agent to agar. Isolates represented previously uncultured species, genera, classes, and even a new phylum of bacteria. They included members of the commonly cultivated phyla Proteobacteria , Firmicutes , Thermus/Deinococcus , Actinobacteria and Bacteroidetes , as well as more-difficult-to-cultivate groups. Isolates possessing < 85% 16S rRNA gene sequence identity to any cultivated species were obtained from the phyla Acidobacteria , Chloroflexi and the previously uncultured candidate division OP10. Several isolates were prevalent in 16S rRNA gene clone libraries constructed directly from the soils. A key factor facilitating isolation was the use of gellan-solidified plates, where the gellan itself served as an energy source for certain bacteria. The results indicate that geothermal soils are a rich potential source of novel bacteria, and that relatively simple cultivation techniques are practical for isolating bacteria from these habitats. 相似文献
19.
A PBX1 transcriptional network controls dopaminergic neuron development and is impaired in Parkinson's disease 下载免费PDF全文
J Carlos Villaescusa Bingsi Li Enrique M Toledo Pia Rivetti di Val Cervo Shanzheng Yang Simon RW Stott Karol Kaiser Saiful Islam Daniel Gyllborg Rocio Laguna‐Goya Michael Landreh Peter Lönnerberg Anna Falk Tomas Bergman Roger A Barker Sten Linnarsson Licia Selleri Ernest Arenas 《The EMBO journal》2016,35(18):1963-1978
20.