Selection During Larval Recruitment in a Blue Mussel Hybrid Zone

The processes of recruitment in marine bivalves and their larvae can be caused by process that occur before, during, or after these organisms settle. The mussel species Mytilus edulis and M. galloprovincialis form a hybrid zone located in southwest England. Individuals with hybrid genotypes settle in the M. galloprovincialis parental populations, but the hybrid zone does not appear to be expanding. Comparisons of allele and genotype frequencies of recently settled mussels from different age classes in the M. galloprovincialis population show a marked decrease in M. edulis-specific alleles and hybrid genotypes. These data demonstrate that there is likely selection acting against individuals with M. edulis alleles that settle in the M. galloprovincialis population

Qualitative Data Analysis: Comparison Between Traditional and Computerized Text Analysis

Most often quantitative data is used in the social sciences. Sometimes, however, researchers must use qualitative data for exploration. In a study on communication effectiveness we used both quantitative and qualitative data. After analyzing the quantitative data we used both a traditional text analysis and a computerized text analysis. Our aim in this paper is to discuss variance, or lack thereof, between outcomes utilizing traditional and computerized text analysis

A Comprehensive Overview of Mobility and Aging in the Year 2020 (and beyond)

Mobility can be defined as the ability to move effectively and purposefully though the environment in order to accomplish goals. Mobility can be conceptualized and measured in four broad ways. First, the speed, success, and quality of specific movements can be measured, such as gait and balance. Second, one can assess a person’s ability to complete activities of daily living (ADLs) and instrumental activities of daily living (IADLs) that involve movement. Third, the occurrence of adverse events, such as falls and motor vehicle crashes, can be measured. Finally, the range of a person’s movement inside and outside the home can be assessed. Regardless of how it is conceptualized, mobility is one of the most important determinants of quality of life and independence in adulthood. Unfortunately, the prevalence of mobility limitations increases with age. This book chapter will provide a comprehensive overview of mobility among older adults

Rapid, Low-Cost Detection of Zika Virus Using Programmable Biomolecular Components

The recent Zika virus outbreak highlights the need for low-cost diagnostics that can be rapidly developed for distribution and use in pandemic regions. Here, we report a pipeline for the rapid design, assembly, and validation of cell-free, paper-based sensors for the detection of the Zika virus RNA genome. By linking isothermal RNA amplification to toehold switch RNA sensors, we detect clinically relevant concentrations of Zika virus sequences and demonstrate specificity against closely related Dengue virus sequences. When coupled with a novel CRISPR/Cas9-based module, our sensors can discriminate between viral strains with single-base resolution. We successfully demonstrate a simple, field-ready sample-processing workflow and detect Zika virus from the plasma of a viremic macaque. Our freeze-dried biomolecular platform resolves important practical limitations to the deployment of molecular diagnostics in the field and demonstrates how synthetic biology can be used to develop diagnostic tools for confronting global health crises.Defense Threat Reduction Agency (DTRA) (HDTRA1-14-1-0006)United States. National Institutes of Health (NIH AI100190

Translating Preclinical Models of Alcohol Seeking and Consumption into the Human Laboratory using Intravenous Alcohol Self-Administration Paradigms

Preclinical models of Alcohol Use Disorder (AUD) have advanced theoretical, mechanistic, and pharmacological study of the human condition. “Liking” and “wanting” behaviors reflect core processes underlying several models of AUD. However, the development and application of translational models of these preclinical approaches are at an incipient stage. The goal of this study was to examine how intravenous free-access and progressive-ratio, operant-response human alcohol self-administration paradigms can be used as translational human model parallel of preclinical “liking” and “wanting”. Participants were 40 adults (Mean age=23.7, SD=2.0; 45% Female) of European descent who reported 12.6 drinking days (SD=5.2) out of the previous 30 (average= 4.1 drinks/drinking day (SD=1.7)). Individuals diverged in their alcohol self-administration behavior, such that free-access and progressive-ratio paradigm outcomes were not significantly correlated (p=.44). Free-access alcohol seeking was related to enjoying alcohol (p.70) to preferred level of breath alcohol concentration (BrAC) in the free-access session, a measure of liking alcohol. Family history of alcoholism, disinhibition traits, and recent drinking history were significantly related (p’s<.05) to alcohol seeking in the progressive-ratio paradigm, a measure of wanting alcohol. We conclude that intravenous alcohol self-administration paradigms show promise in modeling behaviors that characterize and parallel alcohol “liking” and “wanting” in preclinical models. These paradigms provide a translational link between preclinical methods and clinical trials

To Infuse or Ingest in Human Laboratory Alcohol Research

Human alcohol laboratory studies use two routes of alcohol administration: ingestion and infusion. The goal of this paper is to compare and contrast these alcohol administration methods. The work summarized in this report was the basis of a 2019 Research Society on Alcoholism Roundtable, “To Ingest or Infuse: A Comparison of Oral and Intravenous Alcohol Administration Methods for Human Alcohol Laboratory Designs.” We review the methodological approaches of each and highlight strengths and weaknesses pertaining to different research questions. We summarize methodological considerations to aid researchers in choosing the most appropriate method for their inquiry, considering exposure variability, alcohol expectancy effects, safety, bandwidth, technical skills, documentation of alcohol exposure, experimental variety, ecological validity, and cost. Ingestion of alcohol remains a common, and often a preferable, methodological practice in alcohol research. Nonetheless, the main problem with ingestion is that even the most careful calculation of dose and control of dosing procedures yields substantial and uncontrollable variability in the participants’ brain exposures to alcohol. Infusion methodologies provide precise exposure control but are technically complex and may be limited in ecological validity. We suggest that alcohol ingestion research may not be the same thing as alcohol exposure research; investigators should be aware of the advantages and disadvantages that the choice between ingestion and infusion of alcohol invokes

PIK3CA-associated developmental disorders exhibit distinct classes of mutations with variable expression and tissue distribution

Mosaicism is increasingly recognized as a cause of developmental disorders with the advent of next-generation sequencing (NGS). Mosaic mutations of PIK3CA have been associated with the widest spectrum of phenotypes associated with overgrowth and vascular malformations. We performed targeted NGS using 2 independent deep-coverage methods that utilize molecular inversion probes and amplicon sequencing in a cohort of 241 samples from 181 individuals with brain and/or body overgrowth. We identified PIK3CA mutations in 60 individuals. Several other individuals (n = 12) were identified separately to have mutations in PIK3CA by clinical targetedpanel testing (n = 6), whole-exome sequencing (n = 5), or Sanger sequencing (n = 1). Based on the clinical and molecular features, this cohort segregated into three distinct groups: (a) severe focal overgrowth due to low-level but highly activating (hotspot) mutations, (b) predominantly brain overgrowth and less severe somatic overgrowth due to less-activating mutations, and (c) intermediate phenotypes (capillary malformations with overgrowth) with intermediately activating mutations. Sixteen of 29 PIK3CA mutations were novel. We also identified constitutional PIK3CA mutations in 10 patients. Our molecular data, combined with review of the literature, show that PIK3CA-related overgrowth disorders comprise a discontinuous spectrum of disorders that correlate with the severity and distribution of mutations

Systematic reviews of animal studies – Report of an international symposium

Objective: The Symposium on Animal Systematic Reviews held 24 May 2022, sought to bring organisations working on animal literature searching and systematic reviews together into the same virtual space for introductions and discussion.Background: Groups working on animal research synthesis are often siloed into preclinical, veterinary, and One Health settings. This symposium sought to define commonalities and differences in methodologies, resources, and philosophies and to discuss future needs.Methods: The 3-hour virtual symposium for veterinarians, researchers, and information specialists began with introductions by panelists from organisations involved in searching the literature for animal studies and conducting systematic reviews. This was followed by a panel discussion and question and answer period.Results: Panelists identified a need to ensure planning and accurate description of primary animal studies as a precursor to quality systematic reviews. They acknowledged and discussed differences in evidence synthesis expectations and tools based on the type of review, the types of studies available on the topic, and the focus on preclinical, veterinary, or One Health topics.Conclusion: The need to increase the speed and quality of evidence reviews, and to automate updates, requires investing in the development of both skilled teams and platforms. The symposium provided a chance to identify existing resources, define challenges, and note gaps unique to systematic reviews of animal studies.Application: This symposium acts as a baseline for ongoing discussions centred on improving the culture and pipeline for evidence syntheses of animal studies that inform decision-making

Anthrax Lethal Toxin-Induced Gene Expression Changes in Mouse Lung

A major virulence factor of Bacillus anthracis is the anthrax Lethal Toxin (LeTx), a bipartite toxin composed of Protective Antigen and Lethal Factor. Systemic administration of LeTx to laboratory animals leads to death associated with vascular leakage and pulmonary edema. In this study, we investigated whether systemic exposure of mice to LeTx would induce gene expression changes associated with vascular/capillary leakage in lung tissue. We observed enhanced susceptibility of A/J mice to death by systemic LeTx administration compared to the C57BL/6 strain. LeTx-induced groups of both up- and down-regulated genes were observed in mouse lungs 6 h after systemic administration of wild type toxin compared to lungs of mice exposed to an inactive mutant form of the toxin. Lungs of the less susceptible C57BL/6 strain showed 80% fewer differentially expressed genes compared to lungs of the more sensitive A/J strain. Expression of genes known to regulate vascular permeability was modulated by LeTx in the lungs of the more susceptible A/J strain. Unexpectedly, the largest set of genes with altered expression was immune specific, characterized by the up-regulation of lymphoid genes and the down-regulation of myeloid genes. Transcripts encoding neutrophil chemoattractants, modulators of tumor regulation and angiogenesis were also differentially expressed in both mouse strains. These studies provide new directions for the investigation of vascular leakage and pulmonary edema induced by anthrax LeTx

Frequency of breast cancer subtypes among African American women in the AMBER consortium

Abstract Background Breast cancer subtype can be classified using standard clinical markers (estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2)), supplemented with additional markers. However, automated biomarker scoring and classification schemes have not been standardized. The aim of this study was to optimize tumor classification using automated methods in order to describe subtype frequency in the African American Breast Cancer Epidemiology and Risk (AMBER) consortium. Methods Using immunohistochemistry (IHC), we quantified the expression of ER, PR, HER2, the proliferation marker Ki67, and two basal-like biomarkers, epidermal growth factor receptor (EGFR) and cytokeratin (CK)5/6, in 1381 invasive breast tumors from African American women. RNA-based (prediction analysis of microarray 50 (PAM50)) subtype, available for 574 (42%) cases, was used to optimize classification. Subtype frequency was calculated, and associations between subtype and tumor characteristics were estimated using logistic regression. Results Relative to ER, PR and HER2 from medical records, central IHC staining and the addition of Ki67 or combined tumor grade improved accuracy for classifying PAM50-based luminal subtypes. Few triple negative cases (< 2%) lacked EGFR and CK5/6 expression, thereby providing little improvement in accuracy for identifying basal-like tumors. Relative to luminal A subtype, all other subtypes had higher combined grade and were larger, and ER-/HER2+ tumors were more often lymph node positive and late stage tumors. The frequency of basal-like tumors was 31%, exceeded only slightly by luminal A tumors (37%). Conclusions Our findings indicate that automated IHC-based classification produces tumor subtype frequencies approximating those from PAM50-based classification and highlight high frequency of basal-like and low frequency of luminal A breast cancer in a large study of African American women