-
Horowitz Helms opublikował 5 miesięcy, 1 tydzień temu
Human populations, especially European, are polymorphic in the RHD gene. A significant fraction of their members carry no copy of the coding section of RHD gene, which results in their Rh-negative blood type. Theoretically, this polymorphism should be unstable. Carriers of the less frequent allele are penalized by reduced fertility because of the immunization of RhD-negative mothers by their RhD-positive babies, which results in hemolytic disease of the fetus and newborn in their subsequent progeny. For about 90 years, some form of balancing selection has been suspected to sustain this polymorphism. Several recent studies showed that the RhD-positive heterozygotes express higher viability than both types of homozygotes. However, the genotype of subjects in these studies was estimated only by indirect methods. Here we compared the physical and mental health of 178 women and 86 men who were directly tested for their RHD genotype. The results showed that RhD-positive homozygotic women had worse and RhD-positive homozygotic men better physical health than RhD-negative homozygotes; the difference between RhD-negative homozygotes and heterozygotes was not significant. Our results confirmed that health of RhD-positive heterozygotes and homozygotes differ. Therefore, any result of the comparison of subjects with RhD-positive and RhD-negative phenotype depends on the heterozygote-to-homozygote ratio in the RhD-positive sample. It is, therefore, crucial to analyze the effects of RHD-genotypes, not phenotypes in future studies.Satellite-tracking of adult bumphead sunfish, Mola alexandrini, revealed long-distance latitudinal migration patterns covering thousands of kilometers. Horizontal and vertical movements of four bumphead sunfish off Taiwan were recorded with pop-up satellite archival tags in 2019-2020. Two individuals moved northward and traveled to Okinawa Island and Kyushu, Japan and two moved southwards; crossing the equator, to Papua New Guinea and New Caledonia. During daytime, bumphead sunfish descended below the thermocline and ascended to mixed layer depths (MLD) during nighttime. The N-S migrants, however, demonstrated different habitat utilization patterns. Instead of using prevailing currents, the northward movements of sunfish cohorts exhibited extensive use of mesoscale eddies. Fish in anticyclonic eddies usually occupied deeper habitats whereas those in cyclonic eddies used near-surface habitats. On northward excursions, fish spent most of their time in regions with high dissolved oxygen concentrations. Southward movement patterns were associated with major currents and thermal stratification of the water column. In highly stratified regions, fish stayed below the thermocline and frequently ascended to MLD during daytime either to warm muscles or repay oxygen debts. These results for bumphead sunfish present important insights into different habitat use patterns and the ability to undergo long-distance migrations over varying spatial-temporal scales and features.There is no consistent conclusion on which adiposity measure is best to predict cardiovascular risk factors in youth. The present study aims to assess the performance of body mass index (BMI), waist circumference (WC), and waist-to-height ratio (WHtR) in predicting abnormal left ventricular structure in Chinese hypertensive youth. A total of 1180 youth aged 6-17 years with hypertension from the China Child and Adolescent Cardiovascular Health Study were included in this study. Logistic regression model, receiver operator characteristic (ROC) curve analysis and net reclassification improvement (NRI) method were used to assess performance of BMI, WC, and WHtR in predicting left ventricular hypertrophy (LVH) and left ventricular geometry (LVG). A 1-standard deviation increment in any of three indexes in predicting LVH and LVG were similar, e.g., with the odds ratios and 95% confidence intervals of 1.34 (1.16-1.55), 1.25 (1.08-1.45) and 1.40 (1.20-1.62), respectively. In addition, ROC analysis and NRI method confirmed the similar performance of three adiposity indexes in predicting LVH and LVG. In conclusion, BMI, WC and WHtR had similar performance in predicting abnormal left ventricular structure in Chinese hypertensive youth, but all three indexes had limited value in prediction. WHtR is a simple and convenient adiposity index for screening youth at high risk of target organ damage.Over the next decade, more than a million eukaryotic species are expected to be fully sequenced. This has the potential to improve our understanding of genotype and phenotype crosstalk, gene function and interactions, and answer evolutionary questions. Here, we develop a machine-learning approach for utilizing phylogenetic profiles across 1154 eukaryotic species. This method integrates co-evolution across eukaryotic clades to predict functional interactions between human genes and the context for these interactions. We benchmark our approach showing a 14% performance increase (auROC) compared to previous methods. Using this approach, we predict functional annotations for less studied genes. We focus on DNA repair and verify that 9 of the top 50 predicted genes have been identified elsewhere, with others previously prioritized by high-throughput screens. Overall, our approach enables better annotation of function and functional interactions and facilitates the understanding of evolutionary processes underlying co-evolution. The manuscript is accompanied by a webserver available at https//mlpp.cs.huji.ac.il .With the rapid advancement of sequencing technologies, next generation sequencing (NGS) analysis has been widely applied in cancer genomics research. More recently, NGS has been adopted in clinical oncology to advance personalized medicine. Clinical applications of precision oncology require accurate tests that can distinguish tumor-specific mutations from artifacts introduced during NGS processes or data analysis. Therefore, there is an urgent need to develop best practices in cancer mutation detection using NGS and the need for standard reference data sets for systematically measuring accuracy and reproducibility across platforms and methods. Within the SEQC2 consortium context, we established paired tumor-normal reference samples and generated whole-genome (WGS) and whole-exome sequencing (WES) data using sixteen library protocols, seven sequencing platforms at six different centers. We systematically interrogated somatic mutations in the reference samples to identify factors affecting detection reproducibility and accuracy in cancer genomes. These large cross-platform/site WGS and WES datasets using well-characterized reference samples will represent a powerful resource for benchmarking NGS technologies, bioinformatics pipelines, and for the cancer genomics studies.Enhancing crop productivity and their nutritional quality are the key components and primary focus of crop improvement strategy for fulfilling future food demand and improving human health. Grain filling and endosperm development are the key determinants of grain yield and nutritional quality. GRAIN WIDTH and WEIGHT2 (GW2) gene encodes a RING-type E3 ubiquitin ligase and determines the grain weight in cereal crops. Here we report GW2 knockout (KO) mutants in Indica (var. MTU1010) through CRISPR/Cas9 genome editing. The endosperm of GW2-KO mutant seed displays a thick aleurone layer with enhanced grain protein content. Further the loss of function of OsGW2 results in improved accumulation of essential dietary minerals (Fe, Zn, K, P, Ca) in the endosperm of rice grain. Additionally, the mutants displayed an early growth vigour phenotype with an improved root and shoot architecture. The hull morphology of GW2-KO lines also showed improved, grain filling thereby promoting larger grain architecture. Together, our findings indicate that GW2 may serve as a key regulator of improved grain architecture, grain nutritional quality and an important modulator of plant morphology. The study offers a strategy for the development of improved rice cultivars with enriched nutritional quality and its possible implementation in other cereals as well.To study the effects of foliar application of putrescine (distilled water (0), 0.75, 1.5, and 2.25 mM) and water deficit stress (20%, 40%, 60%, and 80% available soil water depletion (ASWD)) on the physiological, biochemical, and molecular attributes of Salvia officinalis L., a factorial experiment was performed in a completely randomized design with three replications in the growth chamber. The results of Real-Time quantitative polymerase chain reaction (qRT-PCR) analysis showed that putrescine concentration, irrigation regime, and the two-way interaction between irrigation regime and putrescine concentration significantly influenced cineole synthase (CS), sabinene synthase (SS), and bornyl diphosphate synthase (BPPS) relative expression. The highest concentration of 1,8-cineole, camphor, α-thujone, β-thujone, CS, SS, and BPPS were obtained in the irrigation regime of 80% ASWD with the application of 0.75 mM putrescine. There was high correlation between expression levels of the main monoterpenes synthase and the concentration of main monoterpenes. The observed correlation between the two enzyme activities of ascorbate peroxidase (APX) and catalase (CAT) strongly suggests they have coordinated action. On the other hand, the highest peroxidase (PO) and superoxide dismutase (SOD) concentrations were obtained with the application of 0.75 mM putrescine under the irrigation regime of 40% ASWD. Putrescine showed a significant increase in LAI and RWC under water deficit stress. There was an increasing trend in endogenous putrescine when putrescine concentration was increased in all irrigation regimes. Overall, the results suggest that putrescine may act directly as a stress-protecting compound and reduced H2O2 to moderate the capacity of the antioxidative system, maintain the membrane stability, and increase secondary metabolites under water deficit stress.Upon perception of pathogens, plants can rapidly close their stomata to restrict pathogen entry into internal tissue, leading to stomatal immunity as one aspect of innate immune responses. The actin cytoskeleton is required for plant defense against microbial invaders. However, the precise functions of host actin during plant immunity remain largely unknown. Here, we report that Arabidopsis villin3 (VLN3) is critical for plant resistance to bacteria by regulating stomatal immunity. Our in vitro and in vivo phosphorylation assays show that VLN3 is a physiological substrate of two pathogen-responsive mitogen-activated protein kinases, MPK3/6. Quantitative analyses of actin dynamics and genetic studies reveal that VLN3 phosphorylation by MPK3/6 modulates actin remodeling to activate stomatal defense in Arabidopsis.Biological hotspots are places with outstanding biodiversity features, and their delineation is essential to the design of marine protected areas (MPAs). For the Central Coast of Canada’s Northern Shelf Bioregion, where an MPA network is being developed, we identified hotspots for structural corals and large-bodied sponges, which are foundation species vulnerable to bottom contact fisheries, and for Sebastidae, a fish family which includes species that are long-lived (> 100 years), overexploited, evolutionary distinctive, and at high trophic levels. Using 11 years of survey data that spanned from inland fjords to oceanic waters, we derived hotspot indices that accounted for species characteristics and abundances and examined hotspot distribution across depths and oceanographic subregions. The results highlight previously undocumented hotspot distributions, thereby informing the placement of MPAs for which high levels of protection are warranted. Given the vulnerability of the taxa that we examined to cumulative fishery impacts, prospective MPAs derived from our data should be considered for interim protection measures during the protracted period between final network design and the enactment of MPA legislations.