Public Health.

Background: The Impact of Intensive Treatment of Systolic Blood Pressure on Brain Perfusion, Amyloid and Tau in Older Adults (IPAT) is an ongoing randomized control trial (RCT) for prevention of Alzheimer's disease (AD) (NCT05331144). The primary outcome of the trial is to assess the impact of intensive lowering of high systolic blood pressure (SBP) on the accumulation of brain amyloid in older adults for a study duration of 2 years. Study recruitment started on October 25 of 2022 and will end in September of 2025.

A modular system for programming multistep activation of endogenous genes in stem cells.

Unlabelled: Although genomes encode instructions for mammalian cell differentiation with rich syntactic relationships, existing methods for genetically programming cells have modest capabilities for stepwise regulation of genes. Here, we developed a sequential genetic system that enables transcriptional activation of endogenous genes in a preprogrammed, stepwise manner. The system relies on the removal of an RNA polymerase III termination signal to induce both the transcriptional activation and the DNA endonuclease activities of a Cas9-VPR protein to effect stepwise progression through cascades of gene activation events.

Understanding Support for Municipal Political Parties: Evidence from Canada.

The province of Ontario, Canada, has a longstanding history of non-partisanship in municipal elections. In this distinctive context, we report results on citizen attitudes toward municipal partisanship using a survey of eligible voters in Canada's most populous province. Using a mixed-methods approach, we focus on three interrelated research questions.

Excessive firing of dyskinesia-associated striatal direct pathway neurons is gated by dopamine and excitatory synaptic input.

The striatum integrates dopaminergic and glutamatergic inputs to select preferred versus alternative actions. However, the precise mechanisms underlying this process remain unclear. One way to study action selection is to understand how it breaks down in pathological states.

The human health effects of unconventional oil and gas (UOG) chemical exposures: a scoping review of the toxicological literature.

Many chemicals associated with unconventional oil and natural gas (UOG) are known toxicants, leading to health concerns about the effects of UOG. Our objective was to conduct a scoping review of the toxicological literature to assess the effects of UOG chemical exposures in models relevant to human health. We searched databases for primary research studies published in English or French between January 2000 and June 2023 on UOG-related toxicology studies.

More than sport: A social-identity intervention to support transitions out of elite sport.

Elite athletes often make large personal sacrifices to pursue excellence, but there is insufficient support for them when they leave elite sport. Identity loss is central to athletes' transition trajectories and hence the management of identity change is a crucial area for support. The More Than Sport (MTS) program is a novel digital intervention that aims to provide this support-helping athletes manage identity change in the process of leaving elite sport.

Increased Muc5AC and Decreased Ciliated Cells in Severe Asthma Partially Restored by Inhibition of IL-4Rα Receptor.

The role of IL-13 on the airway epithelium in severe asthma leading to airway remodeling remains poorly understood. To study IL-13-induced airway remodeling on goblet cells and cilia in the airway epithelium in severe asthma and the impact of an anti-IL4Rα antibody, dupilumab, . Quantitative computed tomography of the lungs and endobronchial biopsies and brushings were obtained in 51 participants (22 with severe asthma, 11 with nonsevere asthma, and 18 healthy participants) in SARPIII (Severe Asthma Research Program III) and measured for mucin and cilia-related proteins.

Topping-Off a Long Thoracic Stabilization With Semi-Rigid Constructs May Have Favorable Biomechanical Effects to Prevent Proximal Junctional Kyphosis: A Biomechanical Comparison.

Study Design: In-vitro cadaveric biomechanical study.

Objectives: Long posterior spinal fusion is a standard treatment for adult spinal deformity. However, these rigid constructs are known to alter motion and stress to the adjacent non-instrumented vertebrae, increasing the risk of proximal junctional kyphosis (PJK).

Premeiotic 24-nt phasiRNAs are present in the genus and unique in biogenesis mechanism and molecular function.

Reproductive phasiRNAs (phased, small interfering RNAs) are broadly present in angiosperms and play crucial roles in sustaining male fertility. While the premeiotic 21-nt (nucleotides) phasiRNAs and meiotic 24-nt phasiRNA pathways have been extensively studied in maize () and rice (), a third putative category of reproductive phasiRNAs-named premeiotic 24-nt phasiRNAs-have recently been reported in barley () and wheat (). To determine whether premeiotic 24-nt phasiRNAs are also present in maize and related species and begin to characterize their biogenesis and function, we performed a comparative transcriptome and degradome analysis of premeiotic and meiotic anthers from five maize inbred lines and three teosinte species/subspecies.

Premeiotic 24-nt phasiRNAs are present in the genus and unique in biogenesis mechanism and molecular function.

Reproductive phasiRNAs are broadly present in angiosperms and play crucial roles in sustaining male fertility. While the premeiotic 21-nt phasiRNAs and meiotic 24-nt phasiRNA pathways have been extensively studied in maize () and rice (), a third putative category of reproductive phasiRNAs-named premeiotic 24-nt phasiRNAs-have recently been reported in barley () and wheat (). To determine whether premeiotic 24-nt phasiRNAs are also present in maize and related species and begin to characterize their biogenesis and function, we performed a comparative transcriptome and degradome analysis of premeiotic and meiotic anthers from five maize inbred lines and three teosinte species/subspecies.

"I'm more than my sport": Exploring the dynamic processes of identity change in athletic retirement.

Retirement is one of the most impactful career transitions athletes face. Researchers recognise the role that athletic identity plays in this, but analysis of identity content and change processes is limited. Addressing this gap, we conducted a qualitative study exploring the experience of identity change in 21 competitive and successful elite athletes who had retired from sport.

Insular cortex subregions have distinct roles in cued heroin seeking after extinction learning and prolonged withdrawal in rats.

Evidence indicates that the anterior (aIC), but not posterior (pIC), insular cortex promotes cued reinstatement of cocaine seeking after extinction in rats. It is unknown whether these subregions also regulate heroin seeking and whether such involvement depends on prior extinction learning. To address these questions, we used baclofen and muscimol (BM) to inactivate the aIC or pIC bilaterally during a seeking test after extinction or prolonged withdrawal from heroin.

The human health effects of unconventional oil and gas development (UOGD): A scoping review of epidemiologic studies.

Objective: Unconventional oil and gas development (UOGD, sometimes termed "fracking" or "hydraulic fracturing") is an industrial process to extract methane gas and/or oil deposits. Many chemicals used in UOGD have known adverse human health effects. Canada is a major producer of UOGD-derived gas with wells frequently located in and around rural and Indigenous communities.

CRISPR-Cas9 screen of E3 ubiquitin ligases identifies TRAF2 and UHRF1 as regulators of HIV latency in primary human T cells.

Unlabelled: During HIV infection of CD4+ T cells, ubiquitin pathways are essential to viral replication and host innate immune response; however, the role of specific E3 ubiquitin ligases is not well understood. Proteomics analyses identified 116 single-subunit E3 ubiquitin ligases expressed in activated primary human CD4+ T cells. Using a CRISPR-based arrayed spreading infectivity assay, we systematically knocked out 116 E3s from activated primary CD4+ T cells and infected them with NL4-3 GFP reporter HIV-1.

Comprehensive Characterization of Commercial Reverse Osmosis Membranes through High-Temperature Cross-Flow Filtration.

Developing thermally stable reverse osmosis membranes is a potential game-changer in high-temperature water treatment. In this work, the performance of three commercial reverse osmosis membranes was evaluated with a series of high-temperature filtrations. The membranes were tested with different filtration methodologies: long-term operation, cyclic tests, controlled stepwise temperature increment, and permeability tests.

Use of Quantitative CT Imaging to Identify Bronchial Thermoplasty Responders.

Background: Bronchial thermoplasty (BT) is a treatment for patients with poorly controlled, severe asthma. However, predictors of treatment response to BT are defined poorly.

Research Question: Do baseline radiographic and clinical characteristics exist that predict response to BT?

Study Design And Methods: We conducted a longitudinal prospective cohort study of participants with severe asthma receiving BT across eight academic medical centers.

Glacial vicariance and secondary contact shape demographic histories in a freshwater mussel species complex.

Characterizing the mechanisms influencing the distribution of genetic variation in aquatic species can be difficult due to the dynamic nature of hydrological landscapes. In North America's Central Highlands, a complex history of glacial dynamics, long-term isolation, and secondary contact have shaped genetic variation in aquatic species. Although the effects of glacial history have been demonstrated in many taxa, responses are often lineage- or species-specific and driven by organismal ecology.

Intranasal parainfluenza virus type 5 (PIV5)-vectored RSV vaccine is safe and immunogenic in healthy adults in a phase 1 clinical study.

Respiratory syncytial virus (RSV) can lead to serious disease in infants, and no approved RSV vaccine is available for infants. This first in-human clinical trial evaluated a single dose of BLB201, a PIV5-vectored RSV vaccine administrated via intranasal route, for safety and immunogenicity in RSV-seropositive healthy adults (33 to 75 years old). No severe adverse events (SAEs) were reported.

The multi-lineage transcription factor ISL1 controls cardiomyocyte cell fate through interaction with NKX2.5.

Congenital heart disease often arises from perturbations of transcription factors (TFs) that guide cardiac development. ISLET1 (ISL1) is a TF that influences early cardiac cell fate, as well as differentiation of other cell types including motor neuron progenitors (MNPs) and pancreatic islet cells. While lineage specificity of ISL1 function is likely achieved through combinatorial interactions, its essential cardiac interacting partners are unknown.

Proteomic and genetic analyses of influenza A viruses identify pan-viral host targets.

Influenza A Virus (IAV) is a recurring respiratory virus with limited availability of antiviral therapies. Understanding host proteins essential for IAV infection can identify targets for alternative host-directed therapies (HDTs). Using affinity purification-mass spectrometry and global phosphoproteomic and protein abundance analyses using three IAV strains (pH1N1, H3N2, H5N1) in three human cell types (A549, NHBE, THP-1), we map 332 IAV-human protein-protein interactions and identify 13 IAV-modulated kinases.