Knocking out genes to reveal drivers of natural selection on phenotypic traits: a study of the fitness consequences of albinism.

Conclusions about the adaptive significance of phenotypic traits typically rely on correlations between the trait and fitness, but pleiotropic effects of a single trait on fitness and covariation among traits can confound such comparisons. For example, a trait may have several benefits or costs which may be affected by its correlation to some other trait. We overcame this barrier by using CRISPR-Cas9 in captive cane toads () to create gene-knockout albinos.

Examining epidemiologic disparity across SARS-CoV-2 variant-dominant periods in Oklahoma County, Oklahoma (March 12, 2020-February 28, 2022).

Context: While it is well-known that age and race/ethnicity have been associated with poor COVID-19-related outcomes, it is less clear if vulnerable populations consistently experienced higher rates of poor outcomes over time.

Objective: Considering this, our study compared COVID-19-related outcomes by age group and racial/ethnic group across variant-dominant periods to assess how poor outcomes were experienced over time in Oklahoma County.

Design And Methods: In this retrospective observational study, we used health department surveillance data to compare COVID-19-related average daily case, hospitalization, and case fatality rates across three time periods-each dominated by different SARS-CoV-2 variants in Oklahoma County, Oklahoma, US.

Isoform-level profiling of mA epitranscriptomic signatures in human brain.

The RNA modification N6-methyladenosine (mA) is highly abundant in human brain and implicated in neurological disorders. Profiling mA within RNA isoforms is a critical step toward understanding the complex mechanisms that underpin brain function and disease; however, we lack an isoform-level atlas of mA sites in the brain. We applied Oxford Nanopore direct RNA sequencing (DRS) to three postmortem human brain regions-prefrontal cortex, caudate nucleus, and cerebellum-to simultaneously investigate the transcriptome and epitranscriptome at the isoform level.

Flow-sensitive HEG1 controls eNOS activity to prevent endothelial dysfunction, hypertension, and atherosclerosis.

Hypertension (HTN), the chronic elevation of blood pressure, accounts for more atherosclerotic cardiovascular disease deaths than any other modifiable risk factor. In the arteries, stable blood flow (s-flow) drives healthy, atheroprotective endothelial cell (EC) functions including nitric oxide (NO) production, barrier function, and anti-inflammatory programs via the action of flow-sensitive proteins. We showed that s-flow stimulates Heart-of-Glass 1 (HEG1) protein expression, localization to cell-cell junctions, and secretion from ECs.

Promoting environmentally sustainable food purchases in online grocery shopping: insights from a pilot randomised controlled field trial.

Objective: It remains unclear which interventions are effective in promoting more environmentally sustainable food choices within online grocery shopping environments. We set out to (1) use a plug-in (browser extension) to implement a pilot randomised controlled trial of eco-labels providing information on the environmental impact of specific food products, and (2) collect data to inform a larger trial investigating the effectiveness of eco-labels and other interventions promoting environmentally sustainable online food purchases. The plug-in was custom-built and active on a large UK supermarket website, accessed using the Google Chrome browser on a desktop or laptop.

Beyond Colonization: An Atypical Presentation of Maternal Group B Streptococcus Infection.

Group B Streptococcus (GBS), a commensal species that colonizes the genitourinary and GI tracts of many women, is well-studied as a leading cause of neonatal infection in the United States. Maternal colonization is the primary risk factor for neonatal sepsis, with vertical transmission from mother to fetus occurring during delivery. To reduce this risk, universal screening and intrapartum antibiotic prophylaxis have been implemented.

The cost-effectiveness of specialist hospital discharge and intermediate care services for patients who are homeless.

Background: Recognising the diverse healthcare needs of the population, there is a growing emphasis on tailoring hospital discharge processes to address the unique challenges faced by individuals who are homeless, aiming to enhance the efficiency and effectiveness of post-hospitalisation care for this vulnerable demographic. This study aimed to evaluate the costs and consequences of specialist hospital discharge and intermediate care (support after discharge) services for people who are homeless in England.

Methods: We estimated the comparative costs and consequences of different types of specialist care provided by 17 homeless hospital discharge and intermediate care services.

A suite of enhancer AAVs and transgenic mouse lines for genetic access to cortical cell types.

The mammalian cortex is comprised of cells classified into types according to shared properties. Defining the contribution of each cell type to the processes guided by the cortex is essential for understanding its function in health and disease. We use transcriptomic and epigenomic cortical cell-type taxonomies from mouse and human to define marker genes and putative enhancers and create a large toolkit of transgenic lines and enhancer adeno-associated viruses (AAVs) for selective targeting of cortical cell populations.

Enhancer AAVs for targeting spinal motor neurons and descending motor pathways in rodents and macaque.

Experimental access to cell types within the mammalian spinal cord is severely limited by the availability of genetic tools. To enable access to spinal motor neurons (SMNs) and SMN subtypes, we generated single-cell multiome datasets from mouse and macaque spinal cords and discovered putative enhancers for each neuronal population. We cloned these enhancers into adeno-associated viral vectors driving a reporter fluorophore and functionally screened them in the mouse.

Enhancer AAV toolbox for accessing and perturbing striatal cell types and circuits.

We present an enhancer-AAV toolbox for accessing and perturbing striatal cell types and circuits. Best-in-class vectors were curated for accessing major striatal neuron populations including medium spiny neurons (MSNs), direct- and indirect-pathway MSNs, Sst-Chodl, Pvalb-Pthlh, and cholinergic interneurons. Specificity was evaluated by multiple modes of molecular validation, by three different routes of virus delivery, and with diverse transgene cargos.

Mental health social care: scoping and developing new and necessary health and care research system.

Mental health social care is an emerging and evolving field of practice and research within mental health care in the UK. It recognises the significant role played by social determinants in the development of mental illness and distress, and in recovery and well-being. By considering mental health social care as a distinct health and care research system, this paper outlines key priorities for research, funding and capacity building.

Fitting a square peg in a round hole? A mixed-methods study on research ethics and collaborative health and social care research involving 'vulnerable' groups.

Background: Current research ethics frameworks that oversee health and social care research, in the United Kingdom and internationally, originated in biomedical research, having positivist underpinnings and an orientation towards experimental research. Limitations of these frameworks have been extensively documented including with regard to health and social care research that adopts collaborative approaches. This article contributes to debates about how the research ethics system deals with collaborative research with groups labelled or potentially perceived as vulnerable, and identifies practical recommendations to ensure a better fit between principles and practices of research ethics and those of collaborative research.

Inactivation of Salmonella and avian pathogens on hatchery eggs using gas phase hydroxyl-radical process vs formaldehyde fumigation: Efficacy, hatching performance and grow-out of Chickens.

Hatcheries have been identified as a significant source of Salmonella within poultry production. Consequently, there is a need for effective egg disinfection methods that can reduce the pathogen burden while preserving the egg integrity and embryo. The metrics for a successful egg disinfection method are typically a reduction in Total Aerobic Count (TAC) while retaining hatching rates.

Disturbed Flow Induces Reprogramming of Endothelial Cells to Immune-like and Foam Cells under Hypercholesterolemia during Atherogenesis.

Background: Atherosclerosis occurs preferentially in the arteries exposed to disturbed flow (d-flow), while the stable flow (s-flow) regions are protected even under hypercholesterolemic conditions. We recently showed that d-flow alone initiates flow-induced reprogramming of endothelial cells (FIRE), including the novel concept of partial endothelial-to-immune-cell-like transition (partial EndIT), but was not validated using a genetic lineage-tracing model. Here, we tested and validated the two-hit hypothesis that d-flow is an initial instigator of partial FIRE but requires hypercholesterolemia to induce a full-blown FIRE and atherosclerotic plaque development.

Disturbed Flow Induces Reprogramming of Endothelial Cells to Immune-like and Foam Cells under Hypercholesterolemia during Atherogenesis.

Background: Atherosclerosis occurs preferentially in the arteries exposed to disturbed flow (d-flow), while the stable flow (s-flow) regions are protected even under hypercholesterolemic conditions. We recently showed that d-flow alone initiates flow-induced reprogramming of endothelial cells (FIRE), including the novel concept of partial endothelial-to-immune-cell-like transition (partial EndIT), but was not validated using a genetic lineage-tracing model. Here, we tested and validated the two-hit hypothesis that d-flow is an initial instigator of partial FIRE but requires hypercholesterolemia to induce a full-blown FIRE and atherosclerotic plaque development.

Therapeutic Drug Monitoring for Dose Optimization of Infliximab in Patients With Inflammatory Bowel Disease: An Analysis of Canadian Real-World Data.

Although it is generally believed that infliximab dose optimization in patients with inflammatory bowel disease with low serum infliximab concentration at trough results in increased treatment persistence, empirical data to support this notion are lacking. This study evaluated the association of infliximab therapeutic drug monitoring (TDM) and TDM-associated dose optimization with persistence in real-world practice. Data from adults with Crohn's disease (CD) or ulcerative colitis (UC) who participated in a national patient support program (PSP) in Canada were analyzed.

Continuous cell type diversification throughout the embryonic and postnatal mouse visual cortex development.

The mammalian cortex is composed of a highly diverse set of cell types and develops through a series of temporally regulated events that build out the cell type and circuit foundation for cortical function. The mechanisms underlying the development of different cell types remain elusive. Single-cell transcriptomics provides the capacity to systematically study cell types across the entire temporal range of cortical development.

Testing the effect of ecolabels on the environmental impact of food purchases in worksite cafeterias: a randomised controlled trial.

Background: Reducing the environmental impact of foods consumed is important for meeting climate goals. We aimed to conduct a randomised controlled trial to test whether ecolabels reduce the environmental impact of food selected in worksite cafeterias, alone or in combination with increased availability of more sustainable meal options.

Methods: Worksite cafeterias (n = 96) were randomised to one of three study groups, with 54 included for final analysis.

Unearthing the secrets of Australia's most enigmatic and cryptic mammal, the marsupial mole.

The marsupial moles are arguably Australia's most enigmatic marsupials. Almost indistinguishable from placental (eutherian) moles, they provide a striking example of convergent evolution. Exploring the genome of the southern marsupial mole, we provide insights into its unusual biology.

Integrated multimodal cell atlas of Alzheimer's disease.

Alzheimer's disease (AD) is the leading cause of dementia in older adults. Although AD progression is characterized by stereotyped accumulation of proteinopathies, the affected cellular populations remain understudied. Here we use multiomics, spatial genomics and reference atlases from the BRAIN Initiative to study middle temporal gyrus cell types in 84 donors with varying AD pathologies.

Enhancer AAV toolbox for accessing and perturbing striatal cell types and circuits.

We present an enhancer AAV toolbox for accessing and perturbing striatal cell types and circuits. Best-in-class vectors were curated for accessing major striatal neuron populations including medium spiny neurons (MSNs), direct and indirect pathway MSNs, as well as Sst-Chodl, Pvalb-Pthlh, and cholinergic interneurons. Specificity was evaluated by multiple modes of molecular validation, three different routes of virus delivery, and with diverse transgene cargos.