A graph theoretical approach to experimental prioritization in genome-scale investigations.

The goal of systems biology is to gain a network level understanding of how gene interactions influence biological states, and ultimately inform upon human disease. Given the scale and scope of systems biology studies, resource constraints often limit researchers when validating genome-wide phenomena and potentially lead to an incomplete understanding of the underlying mechanisms. Further, prioritization strategies are often biased towards known entities (e.

KNeXT: a NetworkX-based topologically relevant KEGG parser.

Automating the recreation of gene and mixed gene-compound networks from Kyoto Encyclopedia of Genes and Genomes (KEGG) Markup Language (KGML) files is challenging because the data structure does not preserve the independent or loosely connected neighborhoods in which they were originally derived, referred to here as its topological environment. Identical accession numbers may overlap, causing neighborhoods to artificially collapse based on duplicated identifiers. This causes current parsers to create misleading or erroneous graphical representations when mixed gene networks are converted to gene-only networks.

A Systematic Approach to Evidence-Based Design for Measurable Health and Wellness Outcomes: Curating and Translating Evidence to Practice.

Objectives: Evaluating evidence from peer-review literature for use in evidence-based design is often challenging for the design disciplines, requiring access to the peer-reviewed literature, expertise in evaluating methods and findings, and translating the results into actionable design and operational recommendations.

Purpose: The purpose of this methods paper is to elucidate the process for systematic evaluation of research to translate evidence into practical application to improve design for occupant health and wellness.

Background: Researchers have found strong connections in environmental design influence on health and wellness that have proven to be substantiative in the effort to improve health and well-being.

Aon: a service to augment Alliance Genome Resource data with additional species.

Objective: Cross-species comparative genomics requires access to accurate homology data across the entire range of annotated genes. The Alliance of Genome Resources (AGR) provides an open-source and comprehensive database of homology data calculated using a wide array of algorithms at differing stringencies to elucidate orthologous relationships. However, the current AGR application program interface (API) is limited to five homology endpoints for nine species.

Long-term drinking stability in the open-access self-administration monkey model.

The Non-Human Primate (NHP) model for the study of Alcohol Use Disorders (AUD) as developed in our laboratories is critical to our understanding of the pathophysiology of voluntary, chronic, ethanol consumption. Previous work in this model established categories of ethanol consumption that parallel reported categories of human consumption across a spectrum spanning low drinking, binge drinking, heavy drinking, and very heavy drinking, albeit at generally higher daily intakes across categories than documented in people. Original categories assigned to ethanol consumption patterns were established using a limited cohort of rhesus macaques.

Age-Dependent Relationships Between Disease Risk and Testosterone Levels: Relevance to COVID-19 Disease.

Testosterone levels in men appear to be prognostic of a number of disease outcomes, including severe COVID-19 disease. Testosterone levels naturally decline with age and are lower in individuals with a number of comorbidities and chronic conditions. Low testosterone may therefore be both a cause and a consequence of illness, including COVID-19 disease.

Exploring links between pathogen avoidance motivation, COVID-19 case counts, and immune function.

Objectives: The selection pressures exerted by pathogens have played important roles in shaping the biology and behavior of animals, including humans. Immune systems recognize and respond to cues of infection or damage by coordinating cellular, humoral, and metabolic shifts that promote recovery. Moreover, animals also possess a repertoire of behavioral tools to help combat the threat of pathogens, often referred to as the behavioral immune system.

Waco COVID Survey: A Community-Based SARS-CoV-2 Serological Surveillance Study in Central Texas.

In early-2020, the epidemiology of the SARS-CoV-2 virus was still in discovery and initial reports about the role of asymptomatic individuals were developing. The Waco COVID Survey was implemented in mid-2020 with targeted serological surveillance to assess relationships among risk factors and asymptomatic transmission in McLennan County, Texas, USA. Because large-scale random sampling of the population was not feasible, a targeted and repeated sampling of specific clustered groups of asymptomatic individuals was employed.

Ethanol alters the relationship between IGF-1 and bone turnover in male macaques.

Insulin-like growth factor 1 (IGF-1) influences bone turnover. Transient decreases in IGF-I levels and/or bioavailability may contribute to the detrimental effects of alcohol on bone. The goals of this non-human primate study were to i) evaluate the 20-h response of bone turnover markers to ethanol consumption and ii) assess how ethanol consumption influences the relationship between IGF-1 and these markers.

Longitudinal changes in COVID-19 concern and stress: Pandemic fatigue overrides individual differences in caution.

Background: Pandemic fatigue describes a phenomenon whereby individuals experience a decrease in COVID-19 concern over time, despite their risk for infection remaining stable, or even increasing. Individual differences in the experience of pandemic fatigue may have important implications for people's adherence to public health recommendations.

Design And Methods: Using data collected from a large community cohort in McLennan County, TX, longitudinal changes in COVID-19-related concern, stress, and affect across three appointments separated by approximately 4 weeks (July-November 2020) were examined.

Establishment, Persistence, and Reactivation of Latent HIV-1 Infection in Renal Epithelial Cells.

HIV-1 persistence in different cell types presents the main obstacle to an HIV-1 cure. We have previously shown that the renal epithelium is a site of HIV-1 infection and that the kidney represents a separate viral compartment from blood. Whether renal cells can harbor latent virus that can be reactivated upon treatment with latency reversing agents (LRAs) is unknown.

Pairing food and drink: A physiological model of blood ethanol levels for a variety of drinking behaviors.

We present a blood ethanol concentration compartment model which utilizes an animal's ethanol intake, food intake, and weight to predict the animal's blood ethanol concentration at any given time. By incorporating the food digestion process into the model we can predict blood ethanol concentration levels over time for a variety of drinking and eating scenarios. The model is calibrated and validated using data from cohorts of male monkeys, and is able to capture blood ethanol concentration kinetics of the monkeys from a variety of drinking behavior classifications.

Dose-response effects of alcohol on biochemical markers of bone turnover in non-human primates: Effects of species, sex and age of onset of drinking.

Purpose: Alcohol consumption suppressed bone turnover in male non-human primates; however, it is unclear the extent to which this effect depends upon biological variables. Using archived plasma samples, we investigated whether sex, age of onset of alcohol intake, and species influence the effects of graded increases in alcohol consumption on bone turnover markers.

Methods: 91 male and female macaques (rhesus and cynomolgus), ranging in age from 4 years (adolescent) to 10 years (adult) were required to increase their consumption of ethanol in 30-day increments: 0 g/kg/day, followed by 0.

Using hierarchical similarity to examine the genetics of Behçet's disease.

Objective: Behçet's disease (BD) is a multisystem inflammatory disease that affects patients along the historic silk road. Thus far, the pathogenesis of the disease has proved elusive due to the complex genetic interactions of the disease. In this paper, we seek to clarify the genetic factors of the disease while also uncovering other diseases of interest that present with a similar genotype as BD.

Unrealistic Optimism and Risk for COVID-19 Disease.

Risk perception and consequently engagement in behaviors to avoid illness often do not match actual risk of infection, morbidity, and mortality. Unrealistic optimism occurs when individuals falsely believe that their personal outcomes will be more favorable than others' in the same risk category. Natural selection could favor overconfidence if its benefits, such as psychological resilience, outweigh its costs.

Integration of evidence across human and model organism studies: A meeting report.

The National Institute on Drug Abuse and Joint Institute for Biological Sciences at the Oak Ridge National Laboratory hosted a meeting attended by a diverse group of scientists with expertise in substance use disorders (SUDs), computational biology, and FAIR (Findability, Accessibility, Interoperability, and Reusability) data sharing. The meeting's objective was to discuss and evaluate better strategies to integrate genetic, epigenetic, and 'omics data across human and model organisms to achieve deeper mechanistic insight into SUDs. Specific topics were to (a) evaluate the current state of substance use genetics and genomics research and fundamental gaps, (b) identify opportunities and challenges of integration and sharing across species and data types, (c) identify current tools and resources for integration of genetic, epigenetic, and phenotypic data, (d) discuss steps and impediment related to data integration, and (e) outline future steps to support more effective collaboration-particularly between animal model research communities and human genetics and clinical research teams.

Immunogenicity, safety, and efficacy of sequential immunizations with an SIV-based IDLV expressing CH505 Envs.

A preventative HIV-1 vaccine is an essential intervention needed to halt the HIV-1 pandemic. Neutralizing antibodies protect against HIV-1 infection in animal models, and thus an approach toward a protective HIV-1 vaccine is to induce broadly cross-reactive neutralizing antibodies (bnAbs). One strategy to achieve this goal is to define envelope (Env) evolution that drives bnAb development in infection and to recreate those events by vaccination.

Interpretation of psychiatric genome-wide association studies with multispecies heterogeneous functional genomic data integration.

Genome-wide association studies and other discovery genetics methods provide a means to identify previously unknown biological mechanisms underlying behavioral disorders that may point to new therapeutic avenues, augment diagnostic tools, and yield a deeper understanding of the biology of psychiatric conditions. Recent advances in psychiatric genetics have been made possible through large-scale collaborative efforts. These studies have begun to unearth many novel genetic variants associated with psychiatric disorders and behavioral traits in human populations.

Therapeutic vaccination with IDLV-SIV-Gag results in durable viremia control in chronically SHIV-infected macaques.

Despite incredible scientific efforts, there is no cure for HIV infection. While antiretroviral treatment (ART) can help control the virus and prevent transmission, it cannot eradicate HIV from viral reservoirs established before the initiation of therapy. Further, HIV-infected individuals reliably exhibit viral rebound when ART is interrupted, suggesting that the host immune response fails to control viral replication in persistent reservoirs.

Cisplatin-resistant triple-negative breast cancer subtypes: multiple mechanisms of resistance.

Background: Understanding mechanisms underlying specific chemotherapeutic responses in subtypes of cancer may improve identification of treatment strategies most likely to benefit particular patients. For example, triple-negative breast cancer (TNBC) patients have variable response to the chemotherapeutic agent cisplatin. Understanding the basis of treatment response in cancer subtypes will lead to more informed decisions about selection of treatment strategies.

On Finding and Enumerating Maximal and Maximum -Partite Cliques in -Partite Graphs.

Let denote an integer greater than 2, let denote a -partite graph, and let denote the set of all maximal -partite cliques in . Several open questions concerning the computation of are resolved. A straightforward and highly-scalable modification to the classic recursive backtracking approach of Bron and Kerbosch is first described and shown to run in (3 ) time.

Time for a Drink? A Mathematical Model of Non-human Primate Alcohol Consumption.

We simulate a non-human primate's alcohol drinking pattern in order to better understand temporal patterning of alcoholic drinks that can lead to the excessive intakes associated with alcohol use disorder. A stochastic mathematical model of alcohol consumption pattern is developed, where model parameters are calibrated to an individual monkey's drinking history. The model predicts a time series that simulates a monkey's alcohol intake in time, and we analyze this drinking pattern to understand the variations in day and night drinking, the lengths of drinks (intake in 5 or more consecutive secs), and lengths of bouts (1 or more drinks per 5 min occasion).

Integration of heterogeneous functional genomics data in gerontology research to find genes and pathway underlying aging across species.

Understanding the biological mechanisms behind aging, lifespan and healthspan is becoming increasingly important as the proportion of the world's population over the age of 65 grows, along with the cost and complexity of their care. BigData oriented approaches and analysis methods enable current and future bio-gerontologists to synthesize, distill and interpret vast, heterogeneous data from functional genomics studies of aging. GeneWeaver is an analysis system for integration of data that allows investigators to store, search, and analyze immense amounts of data including user-submitted experimental data, data from primary publications, and data in other databases.

Curating gene sets: challenges and opportunities for integrative analysis.

Genomic data interpretation often requires analyses that move from a gene-by-gene focus to a focus on sets of genes that are associated with biological phenomena such as molecular processes, phenotypes, diseases, drug interactions or environmental conditions. Unique challenges exist in the curation of gene sets beyond the challenges in curation of individual genes. Here we highlight a literature curation workflow whereby gene sets are curated from peer-reviewed published data into GeneWeaver (GW), a data repository and analysis platform.

Chronic ethanol drinking increases during the luteal menstrual cycle phase in rhesus monkeys: implication of progesterone and related neurosteroids.

Rationale: Sporadic reports of alcohol consumption being linked to menstrual cycle phase highlight the need to consider hormonally characterized menstrual cycle phase in understanding the sex-specific effects of risk for alcohol drinking in women.

Objectives: We investigated the association between menstrual cycle phase, characterized by circulating progesterone and menses, with accurate daily alcohol intakes in rhesus monkeys, and the contribution of progesterone derived neuroactive steroids to cycle-related alcohol drinking.

Methods: Menses (daily) and progesterone (2-3×/week) were obtained in female monkeys (n = 8, 5 ethanol, 3 control) for 12-18 months.