排序方式: 共有72条查询结果,搜索用时 31 毫秒
61.
Since organisms develop and thrive in the face of constant perturbations due to environmental and genetic variation, species may evolve resilient genetic architectures. We sought evidence for this process, known as canalization, through a comparison of the prevalence of phenotypes as a function of the polygenic score (PGS) across environments in the UK Biobank cohort study. Contrasting seven diseases and three categorical phenotypes with respect to 151 exposures in 408,925 people, the deviation between the prevalence–risk curves was observed to increase monotonically with the PGS percentile in one-fifth of the comparisons, suggesting extensive PGS-by-Environment (PGS×E) interaction. After adjustment for the dependency of allelic effect sizes on increased prevalence in the perturbing environment, cases where polygenic influences are greater or lesser than expected are seen to be particularly pervasive for educational attainment, obesity, and metabolic condition type-2 diabetes. Inflammatory bowel disease analysis shows fewer interactions but confirms that smoking and some aspects of diet influence risk. Notably, body mass index has more evidence for decanalization (increased genetic influence at the extremes of polygenic risk), whereas the waist-to-hip ratio shows canalization, reflecting different evolutionary pressures on the architectures of these weight-related traits. An additional 10 % of comparisons showed evidence for an additive shift of prevalence independent of PGS between exposures. These results provide the first widespread evidence for canalization protecting against disease in humans and have implications for personalized medicine as well as understanding the evolution of complex traits. The findings can be explored through an R shiny app at https://canalization-gibsonlab.shinyapps.io/rshiny/. 相似文献
62.
Ankit K Pathak Gyan Prakash Mishra Bharathram Uppili Safal Walia Saman Fatihi Tahseen Abbas Sofia Banu Arup Ghosh Amol Kanampalliwar Atimukta Jha Sana Fatma Shifu Aggarwal Mahesh Shanker Dhar Robin Marwal Venkatraman Srinivasan Radhakrishnan Kalaiarasan Ponnusamy Sandhya Kabra Partha Rakshit Rahul C Bhoyar Abhinav Jain Mohit Kumar Divakar Mohamed Imran Mohammed Faruq Divya Tej Sowpati Lipi Thukral Sunil
K Raghav Mitali Mukerji 《Nucleic acids research》2022,50(3):1551
During the course of the COVID-19 pandemic, large-scale genome sequencing of SARS-CoV-2 has been useful in tracking its spread and in identifying variants of concern (VOC). Viral and host factors could contribute to variability within a host that can be captured in next-generation sequencing reads as intra-host single nucleotide variations (iSNVs). Analysing 1347 samples collected till June 2020, we recorded 16 410 iSNV sites throughout the SARS-CoV-2 genome. We found ∼42% of the iSNV sites to be reported as SNVs by 30 September 2020 in consensus sequences submitted to GISAID, which increased to ∼80% by 30th June 2021. Following this, analysis of another set of 1774 samples sequenced in India between November 2020 and May 2021 revealed that majority of the Delta (B.1.617.2) and Kappa (B.1.617.1) lineage-defining variations appeared as iSNVs before getting fixed in the population. Besides, mutations in RdRp as well as RNA-editing by APOBEC and ADAR deaminases seem to contribute to the differential prevalence of iSNVs in hosts. We also observe hyper-variability at functionally critical residues in Spike protein that could alter the antigenicity and may contribute to immune escape. Thus, tracking and functional annotation of iSNVs in ongoing genome surveillance programs could be important for early identification of potential variants of concern and actionable interventions. 相似文献
63.
Gunjan Goel Ashwani Kumar Vikas Beniwal Mamta Raghav Anil K. Puniya Kishan Singh 《International biodeterioration & biodegradation》2011,65(7):1061-1065
Tannins, present in various foods, feeds and forages, have anti-nutritional activity; however, presence of tannase in microorganisms inhabiting rumen and gastrointestinal tract of animals results in detoxification of these tannins. The present investigation was carried out to study the degradation profile of tannins by Enterococcus faecalis and to purify tannase. E. faecalis was observed to degrade tannic acid (1.0% in minimal media) to gallic acid, pyrogallol and resorcinol. Tannase from E. faecalis was purified up to 18.7 folds, with a recovery of 41.7%, using ammonium sulphate precipitation, followed by DEAE-cellulose and Sephadex G-150. The 45 kDa protein had an optimum activity at 40 °C and pH 6.0 at substrate concentration of 0.25 mM methyl gallate. 相似文献
64.
Laura Bix Raghav Prashant Sundar Nora M. Bello Chad Peltier Lorraine J. Weatherspoon Mark W. Becker 《PloS one》2015,10(10)
Background
Front of pack (FOP) nutrition labels are concise labels located on the front of food packages that provide truncated nutrition information. These labels are rapidly gaining prominence worldwide, presumably because they attract attention and their simplified formats enable rapid comparisons of nutritional value.Methods
Eye tracking was conducted as US consumers interacted with actual packages with and without FOP labels to (1) assess if the presence of an FOP label increases attention to nutrition information when viewers are not specifically tasked with nutrition-related goals; and (2) study the effect of FOP presence on consumer use of more comprehensive, traditional nutrition information presented in the Nutritional Facts Panel (NFP), a mandatory label for most packaged foods in the US.Results
Our results indicate that colored FOP labels enhanced the probability that any nutrition information was attended, and resulted in faster detection and longer viewing of nutrition information. However, for cereal packages, these benefits were at the expense of attention to the more comprehensive NFP. Our results are consistent with a potential short cut effect of FOP labels, such that if an FOP was present, participants spent less time attending the more comprehensive NFP. For crackers, FOP labels increased time spent attending to nutrition information, but we found no evidence that their presence reduced the time spent on the nutrition information in the NFP.Conclusions
The finding that FOP labels increased attention to overall nutrition information by people who did not have an explicit nutritional goal suggests that these labels may have an advantage in conveying nutrition information to a wide segment of the population. However, for some food types this benefit may come with a short-cut effect; that is, decreased attention to more comprehensive nutrition information. These results have implications for policy and warrant further research into the mechanisms by which FOP labels impact use of nutrition information by consumers for different foods. 相似文献65.
Aortic valve (AV) disease is often characterized by the formation of calcific nodules within AV leaflets that alter functional biomechanics. In vitro, formation of these nodules is associated with osteogenic differentiation and/or increased contraction and apoptosis of AV interstitial cells (AVICs), leading to growth of calcium phosphate crystal structures. In several other cell types, increased intracellular Ca(2+) has been shown to be an important part in activation of osteogenic differentiability. However, elevated intracellular Ca(2+) is known to mediate cell contraction, and has also been shown to lead to apoptosis in many cell types. Therefore, a rise in intracellular Ca(2+) may precede cellular changes that lead to calcification, and fibroblasts similar to AVICs have been shown to exhibit increases in intracellular Ca(2+) in response to mechanical strain. In this study, we hypothesized that strain induces intracellular Ca(2+) accumulation through stretch-activated calcium channels. We were also interested in assessing possible correlations between intracellular Ca(2+) increases and apoptosis in AVICs. To test our hypothesis, cultured porcine AVICs were used to assess correlates between strain, intracellular Ca(2+), and apoptosis. Ca(2+) sensitive fluorescent dyes were utilized to measure real-time intracellular Ca(2+) changes in strained AVICs. Ca(2+) changes were then correlated with AVIC apoptosis using flow cytometric Annexin V apoptosis assays. These data indicate that strain-dependent accumulation of intracellular Ca(2+) is correlated with apoptosis in AVICs. We believe that these findings indicate early mechanotransductive events that may initiate AV calcification pathways. 相似文献
66.
67.
Cryosurgery is increasingly being used to treat prostate cancer; however, a major limitation is local recurrence of disease within the previously frozen tissue. We have recently demonstrated that tumor necrosis factor alpha (TNF-α), given 4h prior to cryosurgery can yield complete destruction of prostate cancer within a cryosurgical iceball. The present work continues the investigation of the cellular and molecular mechanisms and dynamics of TNF-α enhancement on cryosurgery. In vivo prostate tumor (LNCaP Pro 5) was grown in a dorsal skin fold chamber (DSFC) on a male nude mouse. Intravital imaging, thermography, and post-sacrifice histology and immunohistochemistry were used to assess iceball location and the ensuing biological effects after cryosurgery with and without TNF-α pre-treatment. Destruction was specifically measured by vascular stasis and by the size of histologic zones of injury (i.e., inflammatory infiltrate and necrosis). TNF-α induced vascular pre-conditioning events that peaked at 4h and diminished over several days. Early events (4-24 h) include upregulation of inflammatory markers (nuclear factor-κB (NFκB) and vascular cell adhesion molecule-1 (VCAM)) and caspase activity in the tumor prior to cryosurgery. TNF-α pre-conditioning resulted in recruitment of an augmented inflammatory infiltrate at day 3 post treatment vs. cryosurgery alone. Finally, pre-conditioning yielded enhanced cryosurgical destruction up to the iceball edge at days 1 and 3 vs. cryosurgery alone. Thus, TNF-α pre-conditioning enhances cryosurgical lesions by vascular mechanisms that lead to tumor cell injury via promotion of inflammation and leukocyte (esp. neutrophil) recruitment. 相似文献
68.
Raghav SK Gupta B Agrawal C Saroha A Das RH Chaturvedi VP Das HR 《Glycoconjugate journal》2006,23(3-4):167-173
Altered glycosylation of plasma proteins has been directly implicated in the pathogenesis of rheumatoid arthritis (RA). The
present study investigated the changes in the Concanavalin-A (Con-A)-bound plasma proteins in the RA patients in comparison to that of the healthy controls. Two proteins (MW ∼32 kDa
and ∼62 kDa) showed an alteration in expression while an altered monosaccharide profile (high mannose) was observed in the
∼62 kDa protein in the samples collected from RA patients. The 2-dimensional polyacrylamide gel electrophoresis analysis of
the Con-A-bound plasma samples showed a large number of protein spots, a few of which were differentially expressed in the
RA patients. Some unidentified proteins were detected in the RA patients which were absent in the control samples. The present
study, therefore, enunciates the role of carbohydrates as well as that of the acute phase response in the disease pathogenesis. 相似文献
69.
Kevin G. Soucy David O. Attarzadeh Raghav Ramachandran Patricia A. Soucy Lewis H. Romer Artin A. Shoukas Dan E. Berkowitz 《Radiation and environmental biophysics》2010,49(3):397-404
Radiation exposure can increase the risk for many non-malignant physiological complications, including cardiovascular disease.
We have previously demonstrated that ionizing radiation can induce endothelial dysfunction, which contributes to increased
vascular stiffness. In this study, we demonstrate that gamma radiation exposure reduced endothelial cell viability or proliferative
capacity using an in vitro aortic angiogenesis assay. Segments of mouse aorta were embedded in a Matrigel-media matrix 1 day
after mice received whole-body gamma irradiation between 0 and 20 Gy. Using three-dimensional phase contrast microscopy, we
quantified cellular outgrowth from the aorta. Through fluorescent imaging of embedded aortas from Tie2GFP transgenic mice,
we determined that the cellular outgrowth is primarily of endothelial cell origin. Significantly less endothelial cell outgrowth
was observed in aortas of mice receiving radiation of 5, 10, and 20 Gy radiation, suggesting radiation-induced endothelial
injury. Following 0.5 and 1 Gy doses of whole-body irradiation, reduced outgrowth was still detected. Furthermore, outgrowth
was not affected by the location of the aortic segments excised along the descending aorta. In conclusion, a single exposure
to gamma radiation significantly reduces endothelial cell outgrowth in a dose-dependent manner. Consequently, radiation exposure
may inhibit re-endothelialization or angiogenesis after a vascular injury, which would impede vascular recovery. 相似文献
70.