Community-based physical and social activity for older adults with mild frailty: a rapid qualitative study of a collaborative intervention pilot.

Background: Intervening to modify frailty trajectories may be critical to maintain health and independence in later life. The Active Ageing Programme (AAP) is a 16-week community-based intervention for older people with mild frailty that combines physical activity and social interaction. The programme aims to positively impact resilience and wellbeing, changing the physical, mental and social factors that impact on frailty trajectories.

Ligand identification in CryoEM and X-ray maps using deep learning.

Motivation: Accurately identifying ligands plays a crucial role in the process of structure-guided drug design. Based on density maps from X-ray diffraction or cryogenic-sample electron microscopy (cryoEM), scientists verify whether small-molecule ligands bind to active sites of interest. However, the interpretation of density maps is challenging, and cognitive bias can sometimes mislead investigators into modeling fictitious compounds.

Don't Forget the Humble Text Message: 25 Years of Text Messaging in Health.

Since the early studies exploring the use of SMS text messaging for health intervention, text messaging has played a pivotal role in the advancement of mobile health. As an intervention modality, text messaging has provided vital learnings for the design and delivery of interventions, particularly in low-resource settings. Despite the advances in technology over the last 25 years, text messaging is still being used in largely the same way to deliver health information, behavior change interventions, and support.

Tackling anxiety through innovation: Development and pilot study of an in-the-moment messaging intervention for young adults.

Objective: Anxiety disorders are highly prevalent around the world and are associated with significant disability, comorbidity and costs to society. Digital tools have the potential to deliver equitable, convenient and sustainable interventions for anxiety. We aimed to co-design and pilot-test an in-the-moment intervention to help young people manage anxiety.

Ligand Identification in CryoEM and X-ray Maps Using Deep Learning.

Motivation: Accurately identifying ligands plays a crucial role in the process of structure-guided drug design. Based on density maps from X-ray diffraction or cryogenic-sample electron microscopy (cryoEM), scientists verify whether small-molecule ligands bind to active sites of interest. However, the interpretation of density maps is challenging, and cognitive bias can sometimes mislead investigators into modeling fictitious compounds.

Structure and topography of the synaptic V-ATPase-synaptophysin complex.

Synaptic vesicles are organelles with a precisely defined protein and lipid composition, yet the molecular mechanisms for the biogenesis of synaptic vesicles are mainly unknown. Here we discovered a well-defined interface between the synaptic vesicle V-ATPase and synaptophysin by in situ cryo-electron tomography and single-particle cryo-electron microscopy of functional synaptic vesicles isolated from mouse brains. The synaptic vesicle V-ATPase is an ATP-dependent proton pump that establishes the proton gradient across the synaptic vesicle, which in turn drives the uptake of neurotransmitters.

The SkillsCenter: Creating scalable research opportunities for STEM students.

Undergraduate students generally need laboratory skills and experience to be accepted into a position within an academic lab or a company. However, those settings are traditionally where students would develop that necessary expertise. We developed a laboratory course paradigm to equip students with the skills they need to access future opportunities.

Digital interventions for self-management of prediabetes: A scoping review.

Background: Rates of prediabetes, which can lead to type 2 diabetes, are increasing worldwide. Interventions for prediabetes mainly focus on lifestyle changes to diet and exercise. While these interventions are effective, they are often delivered face-to-face, which may pose a barrier to those with limited access to healthcare.

Post-Translational Modifications Control Phase Transitions of Tau.

The self-assembly of Tau(297-391) into filaments, which mirror the structures observed in Alzheimer's disease (AD) brains, raises questions about the role of AD-specific post-translational modifications (PTMs) in the formation of paired helical filaments (PHFs). To investigate this, we developed a synthetic approach to produce Tau(291-391) featuring N-acetyllysine, phosphoserine, phosphotyrosine, and N-glycosylation at positions commonly modified in post-mortem AD brains, thus facilitating the study of their roles in Tau pathology. Using transmission electron microscopy (TEM), cryo-electron microscopy (cryo-EM), and a range of optical microscopy techniques, we discovered that these modifications generally hinder the assembly of Tau into PHFs.

Use of Consumer Wearables in Health Research: Issues and Considerations.

As wearable devices, which allow individuals to track and self-manage their health, become more ubiquitous, the opportunities are growing for researchers to use these sensors within interventions and for data collection. They offer access to data that are captured continuously, passively, and pragmatically with minimal user burden, providing huge advantages for health research. However, the growth in their use must be coupled with consideration of their potential limitations, in particular, digital inclusion, data availability, privacy, ethics of third-party involvement, data quality, and potential for adverse consequences.

Unrepresented, unheard and discriminated against: A qualitative exploration of relatives' and professionals' views of palliative care experiences of people of African and Caribbean descent during the COVID-19 pandemic.

Background: People of African and Caribbean descent experienced disproportionately high mortality from COVID-19 and have poor access to palliative care.

Aim: To explore palliative care experiences of people of African and Caribbean descent during and immediately prior to the pandemic.

Design: Qualitative interview study with thematic analysis.

Promoting sexual health in older adults: Findings from two rapid reviews.

Background: Sexual health throughout the life course is increasingly recognised as important to maintaining one's overall health, wellbeing, and relationships. We aimed to provide an overview of the evidence on sexual health needs and sexual health promotion in later life.

Methods: We undertook two rapid reviews, drawing on systematic review evidence.

A simple flash and freeze system for cryogenic time-resolved electron microscopy.

As the resolution revolution in CryoEM expands to encompass all manner of macromolecular complexes, an important new frontier is the implementation of cryogenic time resolved EM (cryoTREM). Biological macromolecular complexes are dynamic systems that undergo conformational changes on timescales from microseconds to minutes. Understanding the dynamic nature of biological changes is critical to understanding function.

Progress and gaps of extracellular vesicle-mediated intercellular cargo transfer in the central nervous system.

A fundamentally novel function proposed for extracellular vesicles (EVs) is to transfer bioactive molecules in intercellular signaling. In this minireview, we discuss recent progress on EV-mediated cargo transfer in the central nervous system (CNS) and major gaps in previous studies. We also suggest a set of experiments necessary for bridging the gaps and establishing the physiological roles of EV-mediated cargo transfer.

Partial RAG deficiency in humans induces dysregulated peripheral lymphocyte development and humoral tolerance defect with accumulation of T-bet B cells.

The recombination-activating genes (RAG) 1 and 2 are indispensable for diversifying the primary B cell receptor repertoire and pruning self-reactive clones via receptor editing in the bone marrow; however, the impact of RAG1/RAG2 on peripheral tolerance is unknown. Partial RAG deficiency (pRD) manifesting with late-onset immune dysregulation represents an 'experiment of nature' to explore this conundrum. By studying B cell development and subset-specific repertoires in pRD, we demonstrate that reduced RAG activity impinges on peripheral tolerance through the generation of a restricted primary B cell repertoire, persistent antigenic stimulation and an inflammatory milieu with elevated B cell-activating factor.

Electron Tomographic Methods for Studying Organelles of the Murine Chemical Synapse.

Electron tomography of the chemical synapse provides important architectural information regarding the organization of synaptic organelles including synaptic vesicles, Nissl bodies, and early endosomes. Here, we describe methods for the preparation of select murine brain regions for high-pressure freezing, freeze substitution, and EM tomographic analysis of synaptic structures. The method uses fresh brain slices prepared using a vibratome and biopsy punches to collect specific brain regions of interest suitable for subsequent preservation and EM tomographic imaging.

Exploring Family Planning Perspectives Among Men Receiving Medications for Opioid Use Disorder: Implications for Service Development.

Objective: Studies have consistently found high rates of unintended pregnancy among women with substance use disorder. While research efforts have begun to focus on understanding needs and providing family planning services for women in treatment, few studies have included men. This has resulted in a gap in the literature regarding men's reproductive health experiences and family planning desires.

Multiomic Analysis Reveals Disruption of Cholesterol Homeostasis by Cannabidiol in Human Cell Lines.

The nonpsychoactive cannabinoid, cannabidiol (CBD), is Food and Dug Administration approved for treatment of two drug-resistant epileptic disorders and is seeing increased use among the general public, yet the mechanisms that underlie its therapeutic effects and side-effect profiles remain unclear. Here, we report a systems-level analysis of CBD action in human cell lines using temporal multiomic profiling. FRET-based biosensor screening revealed that CBD elicits a sharp rise in cytosolic calcium, and activation of AMP-activated protein kinase in human keratinocyte and neuroblastoma cell lines.

Rapid measurement of total lipids in zooplankton using the sulfo-phospho-vanillin reaction.

Zooplankton provide a vital source of nutrition to a variety of fish and marine predators. Measuring the total lipid content of zooplankton provides important information about diet quality available to predators, revealing details about trophic dynamics and ecosystem status. We analyze the performance of a microplate assay, utilizing the sulfo-phospho-vanillin (SPV) reaction, to quantify the total lipid content of various large crustacean zooplankton in a rapid and high throughput manner.

Synergistic activation of the insulin receptor via two distinct sites.

Insulin receptor (IR) signaling controls multiple facets of animal physiology. Maximally four insulins bind to IR at two distinct sites, termed site-1 and site-2. However, the precise functional roles of each binding event during IR activation remain unresolved.

Structural mechanism of muscle nicotinic receptor desensitization and block by curare.

Binding of the neurotransmitter acetylcholine to its receptors on muscle fibers depolarizes the membrane and thereby triggers muscle contraction. We sought to understand at the level of three-dimensional structure how agonists and antagonists alter nicotinic acetylcholine receptor conformation. We used the muscle-type receptor from the Torpedo ray to first define the structure of the receptor in a resting, activatable state.

Homotypic fibrillization of TMEM106B across diverse neurodegenerative diseases.

Misfolding and aggregation of disease-specific proteins, resulting in the formation of filamentous cellular inclusions, is a hallmark of neurodegenerative disease with characteristic filament structures, or conformers, defining each proteinopathy. Here we show that a previously unsolved amyloid fibril composed of a 135 amino acid C-terminal fragment of TMEM106B is a common finding in distinct human neurodegenerative diseases, including cases characterized by abnormal aggregation of TDP-43, tau, or α-synuclein protein. A combination of cryoelectron microscopy and mass spectrometry was used to solve the structures of TMEM106B fibrils at a resolution of 2.

Naloxone Co-Dispensing with Opioids: a Cluster Randomized Pragmatic Trial.

Background: Although naloxone prevents opioid overdose deaths, few patients prescribed opioids receive naloxone, limiting its effectiveness in real-world settings. Barriers to naloxone prescribing include concerns that naloxone could increase risk behavior and limited time to provide necessary patient education.

Objective: To determine whether pharmacy-based naloxone co-dispensing affected opioid risk behavior.