Understanding the Link Between Childhood Family Structure Histories and Adult Health

A wide body of literature has documented the deleterious consequences of various family structures and instability in the lives of children, adolescents, and young adults. To date, however, most of this research has focused on cognitive and behavioral outcomes. Socioeconomic disparities and stress associated with family structures and instability, however, point to potential links between families and health. This study sought to address this relationship by using data from the National Longitudinal Study of Adolescent to Adult Health to construct a novel measure of childhood family structure histories through the application of clustered sequence analysis. This method revealed four clusters of family structure histories: children who spend the majority of their youth in families with two biological parents, those who grow up primarily in single-parent homes, those who transition into one or more stepparent families, and those who spend their childhoods in homes without either parent, instead living primarily with other adult family members or in foster homes. These four clusters were used to examine relationships with several health-related measures in early middle adulthood, including health lifestyles, as well as a variety of health outcomes derived from self-reported survey and biomarker data. Results show that, compared to children raised primarily in families with two biological parents, those who grow up in other family structure history clusters are more likely to engage in unhealthy behaviors and experience poor health outcomes in early middle adulthood

Appendices to Fomby, Paula, Joshua A. Goode, Kim-Phuong Truong-Vu, and Stefanie Mollborn (2019). “Adolescent Technology, Sleep, and Physical Activity Time in Two U.S. Cohorts.” Youth & Society.

This document includes three tables and one figure provided as appendices to Fomby, Paula, Joshua A. Goode, Kim-Phuong Truong-Vu, and Stefanie Mollborn (2019). “Adolescent Technology, Sleep, and Physical Activity Time in Two U.S. Cohorts.” Youth & Society.The advent of Internet-enabled mobile digital devices has transformed U.S. adolescent technology use over the last decade, yet little is known about how these changes map onto other health-related behaviors. We provide a national profile of how contemporary technology use fits into adolescents’ daily health lifestyles compared with the previous generation, with particular attention to whether and for whom technology use displaces time spent in sleep or physical activity. Time diaries were collected from 11- to 17-year-olds in 2002-2003 (N = 1,139) and 2014-2016 (N = 527) through the U.S. Panel Study of Income Dynamics Child Development Supplement. Contemporary adolescents spent 40 minutes more per week in technology-focused activities, but their composition was more varied compared with the earlier cohort. Contemporary technology use was predictive of less time in physical activity, and adolescents who engaged in frequent video game play spent less time in physical activity compared with peers with other technology use profiles.National Science Foundation (NSF) grant SES 1729463; Eunice Kennedy Shriver National Institute of Child Health and Human Development (P2C HD066613)Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/150195/1/fomby et al 2019 youth and society appendices.pdf137Description of fomby et al 2019 youth and society appendices.pdf : Main document (appendix to published article

Silibinin-mediated metabolic reprogramming attenuates pancreatic cancer-induced cachexia and tumor growth.

Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer-related deaths in the US. Cancer-associated cachexia is present in up to 80% of PDAC patients and is associated with aggressive disease and poor prognosis. In the present studies we evaluated an anti-cancer natural product silibinin for its effectiveness in targeting pancreatic cancer aggressiveness and the cachectic properties of pancreatic cancer cells and tumors. Our results demonstrate that silibinin inhibits pancreatic cancer cell growth in a dose-dependent manner and reduces glycolytic activity of cancer cells. Our LC-MS/MS based metabolomics data demonstrates that silibinin treatment induces global metabolic reprogramming in pancreatic cancer cells. Silibinin treatment diminishes c-MYC expression, a key regulator of cancer metabolism. Furthermore, we observed reduced STAT3 signaling in silibinin-treated cancer cells. Overexpression of constitutively active STAT3 was sufficient to substantially revert the silibinin-induced downregulation of c-MYC and the metabolic phenotype. Our in vivo investigations demonstrate that silibinin reduces tumor growth and proliferation in an orthotopic mouse model of pancreatic cancer and prevents the loss of body weight and muscle. It also improves physical activity including grip strength and latency to fall in tumor-bearing mice. In conclusion, silibinin-induced metabolic reprogramming diminishes cell growth and cachectic properties of pancreatic cancer cells and animal models

Pandemic Politics in Eurasia:Roadmap for a New Research Subfield

© 2020 Taylor & Francis Group, LLC. The sudden onset of COVID-19 has challenged many social scientists to proceed without a robust theoretical and empirical foundation upon which to build. Addressing this challenge, particularly as it pertains to Eurasia, our multinational group of scholars draws on past and ongoing research to suggest a roadmap for a new pandemic politics research subfield. Key research questions include not only how states are responding to the new coronavirus, but also reciprocal interactions between the pandemic and society, political economy, regime type, center-periphery relations, and international security. The Foucauldian concept of “biopolitics” holds out particular promise as a theoretical framework

Pandemic Politics in Eurasia:Roadmap for a New Research Subfield

The sudden onset of the coronavirus pandemic has challenged many scholars of the social sciences to proceed in the absence of a robust theoretical research foundation upon which to build. This article seeks to help scholars meet this challenge, particularly as it pertains to Eurasia, through bringing together a multinational group of scholars in order to develop the roadmap for a new pandemic politics research subfield. It begins with a discussion of how states are responding to COVID-19 before moving into an exploration of reciprocal interactions between the pandemic and society, political economy, regime type, center-periphery relations, and international security. Finally, it discusses the potential novel contributions of a theoretical foundation rooted in the Foucauldian concept of “biopolitics.” Ultimately, we hope to spark an ongoing conversation regarding how political science and the social sciences more broadly can be used to understand the impacts of the pandemic and inform policymaking amidst the current and potential future pandemics

KREH2 helicase represses ND7 mRNA editing in procyclic-stage Trypanosoma brucei by opposite modulation of canonical and ‘moonlighting’ gRNA utilization creating a proposed mRNA structure

Unknown factors regulate mitochondrial U-insertion/deletion (U-indel) RNA editing in procyclic-form (PCF) and bloodstream-form (BSF) T. brucei. This editing, directed by anti-sense gRNAs, creates canonical protein-encoding mRNAs and may developmentally control respiration. Canonical editing by gRNAs that specify protein-encoding mRNA sequences occurs amid massive non-canonical editing of unclear sources and biological significance. We found PCF-specific repression at a major early checkpoint in mRNA ND7, involving helicase KREH2-dependent opposite modulation of canonical and non-canonical ‘terminator’ gRNA utilization. Terminator-programmed editing derails canonical editing and installs proposed repressive structure in 30% of the ND7 transcriptome. BSF-to-PCF differentiation in vitro recreated this negative control. Remarkably, KREH2-RNAi knockdown relieved repression and increased editing progression by reverting canonical/terminator gRNA utilization. ND7 transcripts lacking early terminator-directed editing in PCF exhibited similar negative editing control along the mRNA sequence, suggesting global modulation of gRNA utilization fidelity. The terminator is a ‘moonlighting’ gRNA also associated with mRNA COX3 canonical editing, so the gRNA transcriptome seems multifunctional. Thus, KREH2 is the first identified repressor in developmental editing control. This and our prior work support a model whereby KREH2 activates or represses editing in a stage and substrate-specific manner. KREH2’s novel dual role tunes mitochondrial gene expression in either direction during development

CCNE1 and survival of patients with tubo-ovarian high-grade serous carcinoma: An Ovarian Tumor Tissue Analysis consortium study

BACKGROUND: Cyclin E1 (CCNE1) is a potential predictive marker and therapeutic target in tubo-ovarian high-grade serous carcinoma (HGSC). Smaller studies have revealed unfavorable associations for CCNE1 amplification and CCNE1 overexpression with survival, but to date no large-scale, histotype-specific validation has been performed. The hypothesis was that high-level amplification of CCNE1 and CCNE1 overexpression, as well as a combination of the two, are linked to shorter overall survival in HGSC. METHODS: Within the Ovarian Tumor Tissue Analysis consortium, amplification status and protein level in 3029 HGSC cases and mRNA expression in 2419 samples were investigated. RESULTS: High-level amplification (>8 copies by chromogenic in situ hybridization) was found in 8.6% of HGSC and overexpression (>60% with at least 5% demonstrating strong intensity by immunohistochemistry) was found in 22.4%. CCNE1 high-level amplification and overexpression both were linked to shorter overall survival in multivariate survival analysis adjusted for age and stage, with hazard stratification by study (hazard ratio [HR], 1.26; 95% CI, 1.08-1.47, p = .034, and HR, 1.18; 95% CI, 1.05-1.32, p = .015, respectively). This was also true for cases with combined high-level amplification/overexpression (HR, 1.26; 95% CI, 1.09-1.47, p = .033). CCNE1 mRNA expression was not associated with overall survival (HR, 1.00 per 1-SD increase; 95% CI, 0.94-1.06; p = .58). CCNE1 high-level amplification is mutually exclusive with the presence of germline BRCA1/2 pathogenic variants and shows an inverse association to RB1 loss. CONCLUSION: This study provides large-scale validation that CCNE1 high-level amplification is associated with shorter survival, supporting its utility as a prognostic biomarker in HGSC

Multiple Loci Are Associated with White Blood Cell Phenotypes

White blood cell (WBC) count is a common clinical measure from complete blood count assays, and it varies widely among healthy individuals. Total WBC count and its constituent subtypes have been shown to be moderately heritable, with the heritability estimates varying across cell types. We studied 19,509 subjects from seven cohorts in a discovery analysis, and 11,823 subjects from ten cohorts for replication analyses, to determine genetic factors influencing variability within the normal hematological range for total WBC count and five WBC subtype measures. Cohort specific data was supplied by the CHARGE, HeamGen, and INGI consortia, as well as independent collaborative studies. We identified and replicated ten associations with total WBC count and five WBC subtypes at seven different genomic loci (total WBC count—6p21 in the HLA region, 17q21 near ORMDL3, and CSF3; neutrophil count—17q21; basophil count- 3p21 near RPN1 and C3orf27; lymphocyte count—6p21, 19p13 at EPS15L1; monocyte count—2q31 at ITGA4, 3q21, 8q24 an intergenic region, 9q31 near EDG2), including three previously reported associations and seven novel associations. To investigate functional relationships among variants contributing to variability in the six WBC traits, we utilized gene expression- and pathways-based analyses. We implemented gene-clustering algorithms to evaluate functional connectivity among implicated loci and showed functional relationships across cell types. Gene expression data from whole blood was utilized to show that significant biological consequences can be extracted from our genome-wide analyses, with effect estimates for significant loci from the meta-analyses being highly corellated with the proximal gene expression. In addition, collaborative efforts between the groups contributing to this study and related studies conducted by the COGENT and RIKEN groups allowed for the examination of effect homogeneity for genome-wide significant associations across populations of diverse ancestral backgrounds

Supplemental materials for paper: Peer Network Processes in Adolescents' Health Lifestyles

These appendices provide additional details for our paper, including operationalization and modeling choices, full model results, and goodness of fit tests for the primary models