Many students work during college to offset rising costs, but significant time on the job affects postsecondary outcomes. Analyzing the High School Longitudinal Study (N = 4,418), this article ...estimates the effects of hours worked on grades, credits earned, persistence, stopping out (i.e., unenrolling for 5 months before reenrolling), and dropping out. The polynomial regression analysis shows that after adjusting for background characteristics, prior academic achievement, institution types, and family obligations, “traditional” undergraduate students begin seeing deleterious effects at 20 hours, which becomes even more severe for those working 28+ hours (and the worst for Pell Grant recipients working long hours). While some work was good for students, on average, financial and family circumstances help explain the curvilinear relationships.
Schizophrenia is a heritable brain illness with unknown pathogenic mechanisms. Schizophrenia's strongest genetic association at a population level involves variation in the major histocompatibility ...complex (MHC) locus, but the genes and molecular mechanisms accounting for this have been challenging to identify. Here we show that this association arises in part from many structurally diverse alleles of the complement component 4 (C4) genes. We found that these alleles generated widely varying levels of C4A and C4B expression in the brain, with each common C4 allele associating with schizophrenia in proportion to its tendency to generate greater expression of C4A. Human C4 protein localized to neuronal synapses, dendrites, axons, and cell bodies. In mice, C4 mediated synapse elimination during postnatal development. These results implicate excessive complement activity in the development of schizophrenia and may help explain the reduced numbers of synapses in the brains of individuals with schizophrenia.
Abstract
The discovery that experimental delivery of dsRNA can induce gene silencing at target genes revolutionized genetics research, by both uncovering essential biological processes and creating ...new tools for developmental geneticists. However, the efficacy of exogenous RNA interference (RNAi) varies dramatically within the Caenorhabditis elegans natural population, raising questions about our understanding of RNAi in the lab relative to its activity and significance in nature. Here, we investigate why some wild strains fail to mount a robust RNAi response to germline targets. We observe diversity in mechanism: in some strains, the response is stochastic, either on or off among individuals, while in others, the response is consistent but delayed. Increased activity of the Argonaute PPW-1, which is required for germline RNAi in the laboratory strain N2, rescues the response in some strains but dampens it further in others. Among wild strains, genes known to mediate RNAi exhibited very high expression variation relative to other genes in the genome as well as allelic divergence and strain-specific instances of pseudogenization at the sequence level. Our results demonstrate functional diversification in the small RNA pathways in C. elegans and suggest that RNAi processes are evolving rapidly and dynamically in nature.
Recently published single-cell sequencing data from individual human sperm (
=41,189; 969-3377 cells from each of 25 donors) offer an opportunity to investigate questions of inheritance with improved ...statistical power, but require new methods tailored to these extremely low-coverage data (∼0.01× per cell). To this end, we developed a method, named rhapsodi, that leverages sparse gamete genotype data to phase the diploid genomes of the donor individuals, impute missing gamete genotypes, and discover meiotic recombination breakpoints, benchmarking its performance across a wide range of study designs. We then applied rhapsodi to the sperm sequencing data to investigate adherence to Mendel's Law of Segregation, which states that the offspring of a diploid, heterozygous parent will inherit either allele with equal probability. While the vast majority of loci adhere to this rule, research in model and non-model organisms has uncovered numerous exceptions whereby 'selfish' alleles are disproportionately transmitted to the next generation. Evidence of such 'transmission distortion' (TD) in humans remains equivocal in part because scans of human pedigrees have been under-powered to detect small effects. After applying rhapsodi to the sperm data and scanning for evidence of TD, our results exhibited close concordance with binomial expectations under balanced transmission. Together, our work demonstrates that rhapsodi can facilitate novel uses of inferred genotype data and meiotic recombination events, while offering a powerful quantitative framework for testing for TD in other cohorts and study systems.
Introductions of non‐native predators often reduce biodiversity and affect natural predator–prey relationships and may increase the abundance of potential disease vectors (e.g., mosquitoes) ...indirectly through competition or predation cascades. The Santa Monica Mountains (California, U.S.A.), situated in a global biodiversity hotspot, is an area of conservation concern due to climate change, urbanization, and the introduction of non‐native species. We examined the effect of non‐native crayfish (Procambarus clarkii) on an existing native predator, dragonfly nymphs (Aeshna sp.), and their mosquito larvae (Anopheles sp.) prey. We used laboratory experiments to compare the predation efficiency of both predators, separately and together, and field data on counts of dragonfly nymphs and mosquito larvae sampled from 13 local streams. We predicted a lower predation efficiency of crayfish compared with native dragonfly nymphs and a reduced predation efficiency of dragonfly nymphs in the presence of crayfish. Dragonfly nymphs were an order of magnitude more efficient predators than crayfish, and dragonfly nymph predation efficiency was reduced in the presence of crayfish. Field count data showed that populations of dragonfly nymphs and mosquito larvae were strongly correlated with crayfish presence in streams, such that sites with crayfish tended to have fewer dragonfly nymphs and more mosquito larvae. Under natural conditions, it is likely that crayfish reduce the abundance of dragonfly nymphs and their predation efficiency and thereby, directly and indirectly, lead to higher mosquito populations and a loss of ecosystem services related to disease vector control.
Evaluación de los Efectos de un Cangrejo de Río Introducido sobre la Supervivencia de Mosquitos
Resumen
La introducción de depredadores no nativos con frecuencia reduce la biodiversidad y afecta a las relaciones naturales entre presa y depredador, e incluso puede incrementar indirectamente la abundancia de vectores potenciales de enfermedades (p. ej.: mosquitos) por medio de la competencia o las cascadas de depredación. Las montañas de Santa Mónica (California, E.U.A.), situadas en un punto caliente de biodiversidad global, son un área de importancia para la conservación debido al cambio climático, la urbanización y la introducción de especies no nativas. Examinamos el efecto que tiene un cangrejo de río no nativo (Procambarus clarkii) sobre un depredador en existencia, las ninfas de libélula (Aeshna sp.), y sobre su presa: las larvas de mosquito (Anopheles sp.). Usamos experimentos de laboratorio para comparar la eficiencia de depredación de ambos depredadores, de manera separada y conjunta, y datos de campo sobre los conteos de ninfas de libélula y larvas de mosquito muestreadas en 13 riachuelos locales. Predijimos una eficiencia de depredación más baja de los cangrejos de río en comparación con las ninfas de libélula y una eficiencia de depredación reducida de las ninfas de libélula en presencia de los cangrejos de río. Las ninfas de libélula fueron depredadores un orden de magnitud más eficientes que los cangrejos de río, y la eficiencia de depredación de las ninfas de libélula estuvo reducida en la presencia de cangrejos de río. Los datos de conteo de campo mostraron que las poblaciones de ninfas de libélula y de larvas de mosquito tuvieron una fuerte correlación con la presencia de cangrejos de río en los riachuelos, de tal manera que los sitios con cangrejos de río tendieron a tener menos ninfas de libélula y más larvas de mosquito. Bajo condiciones naturales, es probable que los cangrejos de río reduzcan la abundancia de ninfas de libélula y su eficiencia de depredación, lo que resulta directa e indirectamente en poblaciones mayores de mosquitos y una pérdida de los servicios ambientales relacionados con el control de los vectores de enfermedades.
摘要
引入外来捕食者常常会导致生物多样性丧失, 影响自然界捕食者‐猎物关系, 还可能通过竞争或营养级联效应间接增加潜在疾病传播媒介 (如蚊子) 的数量。圣莫尼卡山脉 (美国加利福尼亚州) 位于全球生物多样性热点地区, 因气候变化、城市化和外来物种的引入受到了保护关注。我们在这里分析了外来的小龙虾 (克氏原螯虾 Procambarus clarkii) 对原有本地捕食者蜻蜓若虫 (Aeshna sp.) 及其猎物蚊子幼虫 (Anopheles sp.) 的影响。我们通过实验室实验比较了这两种捕食者分别捕食和一起捕食的效率, 以及当地 13 条溪流中蜻蜓若虫和蚊子幼虫的数量。我们预测小龙虾的捕食效率低于本地的蜻蜓若虫, 而在有小龙虾存在的情况下, 蜻蜓若虫的捕食效率会下降。结果表明蜻蜓若虫的捕食效率比小龙虾高一个数量级, 且小龙虾存在时蜻蜓若虫的捕食效率的确会下降。野外统计的数据显示, 蜻蜓若虫和蚊子幼虫的种群数量与溪流中小龙虾的存在有很强的相关性, 有小龙虾的位点一般蜻蜓若虫较少、蚊子幼虫较多。在自然条件下, 小龙虾可能会引起蜻蜓若虫丰度下降, 捕食效率降低, 从而直接和间接地导致蚊子种群数量增加, 还导致与控制疾病传播媒介相关的生态系统服务功能丧失。【翻译: 胡怡思; 审校: 聂永刚】
Article impact statement: The efficiency of native predators to control potential disease vectors is diminished in the presence of non‐native predators.
Purpose
This pilot study sought to (1) validate the use of a novel technology for single-sperm-cell genome sequencing (Sperm-seq) in infertile men who may not have optimal quantity or quality of ...sperm for genomic analysis and (2) compare these results to fertile donors.
Methods
Infertile men undergoing IVF with female partners with a previous history of failed fertilization with ICSI (FF) or poor blastulation of embryos (PB) were recruited from a large IVF center. Sperm-seq was used to analyze thousands of individual sperm and was carried out at an affiliated university research institute. Global aneuploidy rate, crossover locations, and crossover frequencies were assessed in the infertile population, and compared with a control group of 20 fertile donors, which were analyzed previously at the same laboratory.
Results
Eight patients were initially included, but 3 samples did not yield high-quality genomic data for analysis. A total of 10,042 sperm were analyzed from 5 patients, 2 in the FF group, and 3 in the PB group. The global aneuploidy rate among the samples was 2–4%, similar to the control group. Likewise, crossover locations and frequencies were similar.
Conclusion
Sperm-seq provides a robust analysis but may not be applicable to all male infertility cases due to technical limitations. This group of male infertility patients did not have higher rates of aneuploidy or abnormal crossover patterns compared to a fertile donor population. Our data may suggest that FF and PB phenotypes may not be related to sperm aneuploidy or meiotic errors but rather to other intrinsic nuclear anomalies.
Background
Active surveillance (AS) is the reference standard treatment for the management of low risk prostate cancer (PCa). Accurate assessment of tumor aggressiveness guides recruitment to AS ...programs to avoid conservative treatment of intermediate and higher risk patients. Nevertheless, underestimating the disease risk may occur in some patients recruited, with biopsy upgrading and the concomitant potential for delayed treatment.
Aim
To evaluate the accuracy of mpMRI and GPS for the prediction of biopsy upgrading during active surveillance (AS) management of prostate cancer (PCa).
Method
A retrospective analysis was performed on 144 patients recruited to AS from October 2013 to December 2020. Median follow was 4.8 (IQR 3.6, 6.3) years. Upgrading was defined as upgrading to biopsy grade group ≥2 on follow up biopsies. Cox proportional hazard regression was used to investigate the effect of PSA density (PSAD), baseline Prostate Imaging‐Reporting and Data System (PI‐RADS) v2.1 score and GPS on upgrading. Time‐to‐event outcome, defined as upgrading, was estimated using the Kaplan–Meier method with log‐rank test.
Results
Overall rate of upgrading was 31.9% (n = 46). PSAD was higher in the patients who were upgraded (0.12 vs. 0.08 ng/ml2, p = .005), while no significant difference was present for median GPS in the overall cohort (overall median GPS 21; 22 upgrading vs. 20 no upgrading, p = .2044). On univariable cox proportional hazard regression analysis, the factors associated with increased risk of biopsy upgrading were PSA (HR = 1.30, CI 1.16–1.47, p = <.0001), PSAD (HR = 1.08, CI 1.05–1.12, p = <.0001) and higher PI‐RADS score (HR = 3.51, CI 1.56–7.91, p = .0024). On multivariable cox proportional hazard regression analysis, only PSAD (HR = 1.10, CI 1.06–1.14, p = <.001) and high PI‐RADS score (HR = 4.11, CI 1.79–9.44, p = .0009) were associated with upgrading. A cox regression model combining these three clinical features (PSAD ≥0.15 ng/ml2 at baseline, PI‐RADS Score and GPS) yielded a concordance index of 0.71 for the prediction of upgrading.
Conclusion
In this study PSAD has higher accuracy over baseline PI‐RADS score and GPS score for the prediction of PCa upgrading during AS. However, combined use of PSAD, GPS and PI‐RADS Score yielded the highest predictive ability with a concordance index of 0.71.
Meiosis, although essential for reproduction, is also variable and error-prone: rates of chromosome crossover vary among gametes, between the sexes, and among humans of the same sex, and chromosome ...missegregation leads to abnormal chromosome numbers (aneuploidy)
. To study diverse meiotic outcomes and how they covary across chromosomes, gametes and humans, we developed Sperm-seq, a way of simultaneously analysing the genomes of thousands of individual sperm. Here we analyse the genomes of 31,228 human gametes from 20 sperm donors, identifying 813,122 crossovers and 787 aneuploid chromosomes. Sperm donors had aneuploidy rates ranging from 0.01 to 0.05 aneuploidies per gamete; crossovers partially protected chromosomes from nondisjunction at the meiosis I cell division. Some chromosomes and donors underwent more-frequent nondisjunction during meiosis I, and others showed more meiosis II segregation failures. Sperm genomes also manifested many genomic anomalies that could not be explained by simple nondisjunction. Diverse recombination phenotypes-from crossover rates to crossover location and separation, a measure of crossover interference-covaried strongly across individuals and cells. Our results can be incorporated with earlier observations into a unified model in which a core mechanism, the variable physical compaction of meiotic chromosomes, generates interindividual and cell-to-cell variation in diverse meiotic phenotypes.
Bladder cancer has been successfully treated with immunotherapy, whereas prostate cancer is a cold tumor with inadequate immune-related treatment response. A greater understanding of the tumor ...microenvironment and methods for harnessing the immune system to address tumor growth will be needed to improve immunotherapies for both prostate and bladder cancer. Here, we provide an overview of prostate and bladder cancer, including fundamental aspects of the disease and treatment, the elaborate cellular makeup of the tumor microenvironment, and methods for exploiting relevant pathways to develop more effective treatments.
Variation in gene expression is a feature of all living systems and has recently been characterized extensively among wild strains of the model organism Caenorhabditis elegans. To enable researchers ...to query gene expression and gene expression variation at any gene of interest, we have created a user-friendly web application that shares RNA-seq transcription data for 208 wild C. elegans strains generated by the Caenorhabditis Natural Diversity Resource (CaeNDR). Here, we describe the features of the web application and the details of the data and data processing underlying it. We hope that this website, wildworm.biosci.gatech.edu/cendrexp/ , will help C. elegans researchers better understand their favorite genes and strains.Variation in gene expression is a feature of all living systems and has recently been characterized extensively among wild strains of the model organism Caenorhabditis elegans. To enable researchers to query gene expression and gene expression variation at any gene of interest, we have created a user-friendly web application that shares RNA-seq transcription data for 208 wild C. elegans strains generated by the Caenorhabditis Natural Diversity Resource (CaeNDR). Here, we describe the features of the web application and the details of the data and data processing underlying it. We hope that this website, wildworm.biosci.gatech.edu/cendrexp/ , will help C. elegans researchers better understand their favorite genes and strains.
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