Beals

Intermediate filaments (IFs) are integral components of the cytoskeleton. They provide cells with tissue-specific mechanical properties and are involved in numerous cellular processes. Due to their intricate architecture, a 3D structure of IFs has remained elusive. Here we use cryo-focused ion-beam milling, cryo-electron microscopy and tomography to obtain a 3D structure of vimentin IFs (VIFs). VIFs assemble into a modular, intertwined and flexible helical structure of 40 α-helices in cross-section, organized into five protofibrils...

BACKGROUND: Because of controversial results from clinical studies comparing different dental local anesthesia methods in children, the primary objective of this randomized, split-mouth, crossover, controlled trial was to compare pain intensity during local anaesthesia (LA) performed with a computer-controlled LA delivery system (C-CLADS) versus a conventional syringe (CONV). Secondary objectives included comparisons during dental treatment. METHODS: Participants (4-8 years) with tooth pair requiring similar treatment were recruited from five French hospitals...

Connecting genes to phenotypic traits in bacteria is often challenging because of a lack of environmental context in laboratory settings. Laboratory-based model ecosystems offer a means to better account for environmental conditions compared to standard planktonic cultures, and can help link genotypes and phenotypes. Here, we present a simple, cost-effective, laboratory-based model ecosystem to study aerobic methane-oxidizing bacteria (methanotrophs) within the methane-oxygen counter gradient typically found in the natural environment of these organisms...

Circadian (∼24 h) rhythms are a fundamental feature of life, and their disruption increases the risk of infectious diseases, metabolic disorders, and cancer 1-6 . Circadian rhythms couple to the cell cycle across eukaryotes 7,8 but the underlying mechanism is unknown. We previously identified an evolutionarily conserved circadian oscillation in intracellular potassium concentration, [K + ] i 9,10 . As critical events in the cell cycle are regulated by intracellular potassium 11,12 , an enticing hypothesis is that circadian rhythms in [K + ] i form the basis of this coupling...

The blood-brain barrier (BBB) serves as a highly intricate and dynamic interface connecting the brain and the bloodstream, playing a vital role in maintaining brain homeostasis. BBB dysfunction has been associated with multiple neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS); however, the role of the BBB in neurodegeneration is understudied. We developed an ALS patient-derived model of the BBB by using cells derived from 5 patient donors carrying C9ORF72 mutations. Brain microvascular endothelial-like cells (BMEC-like cells) derived from C9ORF72-ALS patients showed altered gene expression, compromised barrier integrity, and increased P-glycoprotein transporter activity...

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Adenosine Deaminases Acting on RNA (ADARs) catalyze the deamination of adenosine to inosine in double-stranded RNA (dsRNA). ADARs' ability to recognize and edit dsRNA is dependent on local sequence context surrounding the edited adenosine and the length of the duplex. A deeper understanding of how editing efficiency is affected by mismatches, loops, and bulges around the editing site would aid in the development of therapeutic gRNAs for ADAR-mediated site-directed RNA editing (SDRE). Here, a SELEX (systematic evolution of ligands by exponential enrichment) approach was employed to identify dsRNA substrates that bind to the deaminase domain of human ADAR2 (hADAR2d) with high affinity...

Neural oscillations reflect fluctuations in the relative excitation/inhibition of neural systems1 , 2 , 3 , 4 , 5 and are theorized to play a critical role in canonical neural computations6 , 7 , 8 , 9 and cognitive processes.10 , 11 , 12 , 13 , 14 These theories have been supported by findings that detection of visual stimuli fluctuates with the phase of oscillations prior to stimulus onset.15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 However, null results have emerged in studies seeking to demonstrate these effects in visual discrimination tasks,24 , 25 , 26 , 27 raising questions about the generalizability of these phenomena to wider neural processes...

Nearly 3 million people in the UK have a neurological condition; stroke, traumatic brain injury, Parkinson's disease, multiple sclerosis, brain tumour, motor neurone disease, among others - all affecting the person for the rest of their life. The NHS provides treatment at the onset of a condition but after that, there is a huge need for ongoing support. Research shows that those who are supported and know more about their condition are less likely to have to call on further in-hospital and GP care. There is enormous scope for improving the quality of life for those with neurological conditions...

BACKGROUND: Migrants in the United Kingdom (UK) may be at higher risk of SARS-CoV-2 exposure; however, little is known about their risk of COVID-19-related hospitalisation during waves 1-3 of the pandemic. METHODS: We analysed secondary care data linked to Virus Watch study data for adults and estimated COVID-19-related hospitalisation incidence rates by migration status. To estimate the total effect of migration status on COVID-19 hospitalisation rates, we ran mixed-effect Poisson regression for wave 1 (01/03/2020-31/08/2020; wildtype), and mixed-effect negative binomial regressions for waves 2 (01/09/2020-31/05/2021; Alpha) and 3 (01/06/2020-31/11/2021; Delta)...

There is an urgent need for global food systems transformation to realize a future where planetary health reaches its full potential. Paramount to this vision is the ability of stakeholders across sectors to understand how foods and dietary patterns impact food systems inclusive of all domains of sustainability-environmental, nutrition/health, economic and social. This article is a synopsis of presentations by 3 food systems experts to share the latest science in a session entitled "How do you measure sustainability? Opportunities for consistent and holistic metrics to support food systems transformation" at the American Society for Nutrition's 2023 annual conference...

Pacific Island Countries (PICs) collectively have the lowest rates of access to safely managed or basic drinking water and sanitation globally. They are also the least urbanised, have dynamic socioeconomic and increasing climate-linked challenges. Community-based water managers need to respond to variability in water availability and quality caused by a range of hazards. Water Safety Planning (WSP), a widely adopted approach to assessing water supply, offers a risk-based approach to mitigating both existing and future hazards...

This fiber population study has assessed the prevalence of the color and type of trace fibers present on upholstered seats in a specific setting to identify the most common and rare colors and to determine their evidentiary value. Nearly 22,000 fibers were collected via tape lifts from 25 fabric covered chair seats in a lobby area on Beale Air Force Base and examined microscopically to determine their apparent colors. Overall, blue and white/colorless were the most and nearly equally common colors (32.0 % and 31...

Empathy is a multifaceted concept that is vital to effective social functioning; yet, it is impaired in high schizotypy groups. Furthermore, empathy has been found to be a mediator in the relationship between schizotypy and social functioning, highlighting the importance of empathy as a driver in social outcomes. Despite this, the four-factor structure of a widely-used measure of empathy-the Interpersonal Reactivity Index (IRI)-has been found to be psychometrically weak in high schizotypy samples. As such, this study aimed to assess differences in the item-level network of the IRI between high ( n = 427) and low schizotypy groups ( n = 470)...

Inosine (I), resulting from the deamination of adenosine (A), is a prominent modification in the human transcriptome. The enzymes responsible for the conversion of adenosine to inosine in human mRNAs are the ADARs (adenosine deaminases acting on RNA). Inosine modification introduces a layer of complexity to mRNA processing and function, as it can impact various aspects of RNA biology, including mRNA stability, splicing, translation, and protein binding. The relevance of this process is emphasized in the growing number of human disorders associated with dysregulated A-to-I editing pathways...

The aim of this study was to assess the effects of serum vitamin D levels and its relationship to early dental implant failures. A total of 174 implants in 109 patients were placed and serum vitamin D levels of those patients were noted the day of implant placement. Implants were followed up until restoration, approximately 3-6 months later, and any implant failure was noted based on 50% or more bone loss or implant mobility. Eight individuals had an implant fail early and their vitamin D levels had a mean of 42...

Since its launch in a 1984 Special Issue of Child Development, significant contributions and insights have followed that have expanded our understanding of psychopathology and normal human growth and development. Despite these efforts, there are persistent and under-analyzed skewed patterns of vulnerability across and within groups. The persistence of a motivated forgetfulness to acknowledge citizens' uneven access to resources and supports, or as stated elsewhere, "inequality presence denial," is, at minimum, a policy, social and health practice problem...

The broader adoption of urine-diverting technologies (UDTs) and related products has been proposed as a strategy for moving towards a more circular economy. While some studies have explored the performance of UDTs, the interconnected factors involving supply, demand, and economic feasibility of UDTs remain under-researched. Our systematic review addresses this gap. Our search identified only 64 relevant, peer-reviewed studies, 71 % of which addressed the supply side (primarily the technical aspect of UDTs) and 58 % of which addressed the demand side (focusing on consumers' perceptions)...

BACKGROUND: SARS-CoV-2 variant Omicron rapidly evolved over 2022, causing three waves of infection due to sub-variants BA.1, BA.2 and BA.4/5. We sought to characterise symptoms and viral loads over the course of COVID-19 infection with these sub-variants in otherwise-healthy, vaccinated, non-hospitalised adults, and compared data to infections with the preceding Delta variant of concern (VOC). METHODS: In a prospective, observational cohort study, healthy vaccinated UK adults who reported a positive polymerase chain reaction (PCR) or lateral flow test, self-swabbed on alternate weekdays until day 10...

BACKGROUND: Adrenoleukodystrophy (ALD) is a multifaceted, X-linked, neurodegenerative disorder that comprises several clinical phenotypes. ALD affects patients through a variety of physical, emotional, social, and other disease-specific factors that collectively contribute to disease burden. To facilitate clinical care and research, it is important to identify which symptoms are most common and relevant to individuals with any subtype of ALD. METHODS: We conducted semi-structured qualitative interviews and an international cross-sectional study to determine the most prevalent and important symptoms of ALD...