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41.
The role of complement in Alzheimer's disease pathology 总被引:12,自引:0,他引:12
Complement proteins are integral components of amyloid plaques and cerebral vascular amyloid in Alzheimer brains. They can be found at the earliest stages of amyloid deposition and their activation coincides with the clinical expression of Alzheimer's dementia. This review will examine the origins of complement in the brain and the role of beta-amyloid peptide (Abeta) in complement activation in Alzheimer's disease, an event that might serve as a nidus of chronic inflammation. Pharmacology therapies that may serve to inhibit Abeta-mediated complement activation will also be discussed. 相似文献
42.
Randolph AG Lange C Silverman EK Lazarus R Silverman ES Raby B Brown A Ozonoff A Richter B Weiss ST 《American journal of human genetics》2004,75(4):709-715
The IL12B gene on chromosome 5q31-33 encodes the p40 subunit of interleukin 12, an immunomodulatory cytokine. To test the hypothesis that the IL12B gene contains polymorphisms associated with asthma, we genotyped six haplotype-tagging polymorphisms in the IL12B gene, both in 708 children enrolled in the Childhood Asthma Management Program (CAMP) and in their parents. Using the family-based association test (FBAT) program and its haplotype (HBAT) and phenotype (PBAT) options, we tested each polymorphism and haplotype for association with asthma and asthma-related phenotypes. We tested positive associations for replication in a case-control study comparing 177 adult moderate-to-severe asthmatics with 177 nonasthmatic controls. In whites in the CAMP cohort, the A allele of the IL12B G4237A polymorphism was undertransmitted to asthmatic children (P=.0008, recessive model), the global test for haplotypes for affection status was positive (P=.009, multiallelic chi (2)), and two polymorphisms were associated with different atopy phenotypes. In addition, we found a strong association between the IL12B_4237 and IL12B_6402 polymorphisms and an asthma-severity phenotype in whites, which we also found in the independent population of white adult asthmatics. IL12B may be an important asthma gene. 相似文献
43.
Ruth H. Thurstan Julie P. Hawkins Lee Raby Callum M. Roberts 《Journal for Nature Conservation》2013,21(5):253-261
Marine inshore communities, including biogenic habitats have undergone dramatic changes as a result of exploitation, pollution, land-use changes and introduced species. The Firth of Forth on the east coast of Scotland was once home to the most important oyster (Ostrea edulis Linnaeus, 1758) beds in Scotland. 19th and early 20th century fisheries scientists documented the degradation and loss of these beds, yet transformation of the wider benthic community has been little studied. We undertook archival searches, ecological surveys and shell community analysis using radioisotope dated sediment cores to investigate the history of decline of Forth oyster beds over the last 200 years and the changes to its wider biological communities. Quadrat analysis of the present day benthos reveal that soft-sediment communities dominate the Firth of Forth, with little remaining evidence of past oyster beds in places where abundant shell remains were picked up by a survey undertaken in 1895. Queen scallops (Aequipecten opercularis Linnaeus, 1758) and horse mussels (Modiolus modiolus Linnaeus, 1758) were once common within the Forth but have also markedly decreased compared to the earlier survey. Ouranalyses of shell remains suggest that overall mollusc biomass and species richness declined throughout the 19th century and early 20th century, suggesting broader-scale community change as human impacts increased and as habitats degraded. Inshore communities in the Firth of Forth today are less productive and less diverse compared to past states, with evidence suggesting that most of the damage was done by early bottom trawling and dredging activities. Given the pervasive nature of intensive trawling over the past 150 years, the kind of degradation we document for the Firth of Forth is likely to be commonplace within UK inshore communities. 相似文献
44.
Graham D. Raby Timothy D. Clark Anthony P. Farrell David A. Patterson Nolan N. Bett Samantha M. Wilson William G. Willmore Cory D. Suski Scott G. Hinch Steven J. Cooke 《PloS one》2015,10(4)
An improved understanding of bycatch mortality can be achieved by complementing field studies with laboratory experiments that use physiological assessments. This study examined the effects of water temperature and the duration of net entanglement on physiological disturbance and recovery in coho salmon (Oncorhynchus kisutch) after release from a simulated beach seine capture. Heart rate was monitored using implanted electrocardiogram biologgers that allowed fish to swim freely before and after release. A subset of fish was recovered in respirometers to monitor metabolic recovery, and separate groups of fish were sacrificed at different times to assess blood and white muscle biochemistry. One hour after release, fish had elevated lactate in muscle and blood plasma, depleted tissue energy stores, and altered osmoregulatory status, particularly in warmer (15 vs. 10°C) and longer (15 vs. 2 min) capture treatments. A significant effect of entanglement duration on blood and muscle metabolites remained after 4 h. Oxygen consumption rate recovered to baseline within 7–10 h. However, recovery of heart rate to routine levels was longer and more variable, with most fish taking over 10 h, and 33% of fish failing to recover within 24 h. There were no significant treatment effects on either oxygen consumption or heart rate recovery. Our results indicate that fishers should minimize handling time for bycatch and maximize oxygen supply during crowding, especially when temperatures are elevated. Physiological data, such as those presented here, can be used to understand mechanisms that underlie bycatch impairment and mortality, and thus inform best practices that ensure the welfare and conservation of affected species. 相似文献
45.
Background
Graphical models (e.g., Bayesian networks) have been used frequently to describe complex interaction patterns and dependent structures among genes and other phenotypes. Estimation of such networks has been a challenging problem when the genes considered greatly outnumber the samples, and the situation is exacerbated when one wishes to consider the impact of polymorphisms (SNPs) in genes. 相似文献46.
47.
Qifei Li Michal Dibus Alicia Casey Christina S. K. Yee Sara O. Vargas Shiyu Luo Samantha M. Rosen Jill A. Madden Casie A. Genetti Jan Brabek Catherine A. Brownstein Shideh Kazerounian Benjamin A. Raby Klaus Schmitz-Abe John C. Kennedy Martha P. Fishman Mary P. Mullen Joan M. Taylor Daniel Rosel Pankaj B. Agrawal 《PLoS genetics》2021,17(7)
ARHGAP42 encodes Rho GTPase activating protein 42 that belongs to a member of the GTPase Regulator Associated with Focal Adhesion Kinase (GRAF) family. ARHGAP42 is involved in blood pressure control by regulating vascular tone. Despite these findings, disorders of human variants in the coding part of ARHGAP42 have not been reported. Here, we describe an 8-year-old girl with childhood interstitial lung disease (chILD), systemic hypertension, and immunological findings who carries a homozygous stop-gain variant (c.469G>T, p.(Glu157Ter)) in the ARHGAP42 gene. The family history is notable for both parents with hypertension. Histopathological examination of the proband lung biopsy showed increased mural smooth muscle in small airways and alveolar septa, and concentric medial hypertrophy in pulmonary arteries. ARHGAP42 stop-gain variant in the proband leads to exon 5 skipping, and reduced ARHGAP42 levels, which was associated with enhanced RhoA and Cdc42 expression. This is the first report linking a homozygous stop-gain variant in ARHGAP42 with a chILD disorder, systemic hypertension, and immunological findings in human patient. Evidence of smooth muscle hypertrophy on lung biopsy and an increase in RhoA/ROCK signaling in patient cells suggests the potential mechanistic link between ARHGAP42 deficiency and the development of chILD disorder. 相似文献
48.
Expression QTL mapping by integrating genome-wide gene expression and genotype data is a promising approach to identifying functional genetic variation, but is hampered by the large number of multiple comparisons inherent in such studies. A novel approach to addressing multiple testing problems in genome-wide family-based association studies is screening candidate markers using heritability or conditional power. We apply these methods in settings in which microarray gene expression data are used as phenotypes, screening for SNPs near the expressed genes. We perform association analyses for phenotypes using a univariate approach. We also perform simulations on trios with large numbers of causal SNPs to determine the optimal number of markers to use in a screen. We demonstrate that our family-based screening approach performs well in the analysis of integrative genomic datasets and that screening using either heritability or conditional power produces similar, though not identical, results. 相似文献
49.
In‐person academic conferences are important to disseminate research and provide networking opportunities. Whether academics attend in‐person conferences is based on the cost, accessibility, and safety of the event. Therefore, in‐person conferences are less accessible to academics and stakeholders that are unable to overcome some of these factors, which then act as a barrier to equal and inclusive participation. Additionally, the carbon footprint of conference travel is increasingly becoming a factor in deciding on whether to attend a conference. Online conferences may provide opportunities to mitigate these challenges. Here, we illustrate how a learned society can move their conference online. Then, comparing data acquired from the virtual conference and previous in‐person conferences, we explore the aids and barriers influencing the decision of delegates to attend the meetings. Ultimately, moving meetings online aids delegate participation by removing concerns about travel, cost, and carbon emissions, but there remains a barrier to participation as online meetings are perceived as less effective for networking and social opportunities. 相似文献