Respiratory processes of early-evolved hyperthermophiles in sulfidic and low-oxygen geothermal microbial communities.

Thermophilic microbial communities growing in low-oxygen environments often contain early-evolved archaea and bacteria, which hold clues regarding mechanisms of cellular respiration relevant to early life. Here, we conducted replicate metagenomic, metatranscriptomic, microscopic, and geochemical analyses on two hyperthermophilic (82-84 °C) filamentous microbial communities (Conch and Octopus Springs, Yellowstone National Park, WY) to understand the role of oxygen, sulfur, and arsenic in energy conservation and community composition. We report that hyperthermophiles within the Aquificota (Thermocrinis), Pyropristinus (Caldipriscus), and Thermoproteota (Pyrobaculum) are abundant in both communities; however, higher oxygen results in a greater diversity of aerobic heterotrophs.

Research Priorities for Autonomous Sensory Meridian Response: An Interdisciplinary Delphi Study.

Autonomous Sensory Meridian Response (ASMR) is a multisensory experience most often associated with feelings of relaxation and altered consciousness, elicited by stimuli which include whispering, repetitive movements, and close personal attention. Since 2015, ASMR research has grown rapidly, spanning disciplines from neuroscience to media studies but lacking a collaborative or interdisciplinary approach. To build a cohesive and connected structure for ASMR research moving forwards, a modified Delphi study was conducted with ASMR experts, practitioners, community members, and researchers from various disciplines.

Teaching Family? Care/Work Policy in Selected Family Courses in Canada's Research-Intensive Universities.

To what degree is explicit care/work policy taught in family courses in Canada's leading research-intensive universities? We analyze family courses in sociology departments and in political studies and women's/gender studies programs in Canada's 15 R1 universities to make a contribution to the scholarship of teaching and learning. This national scan marks a methodological innovation from curriculum studies that generally adopt a single-program or single-site focus. From a Canadian universe of 74 family courses, we identify 15 whose formal course calendar description explicitly addresses care/work family policy (measures to reconcile caring for young children with employment, through early learning and childcare, parental leaves, and child benefits).

Rare disease 101: an online resource teaching on over 7000 rare diseases in one short course.

Background: An estimated 3.5 million people in the UK live with a rare disease however due to the rarity of each individual condition this is not currently reflected in mainstream medical education. As a result, common features of living with a rare condition include diagnostic delay, poor coordination of health and social care and lack of access to specialist care and treatment.

Cytochrome oxidase requirements in Bordetella reveal insights into evolution towards life in the mammalian respiratory tract.

Little is known about oxygen utilization during infection by bacterial respiratory pathogens. The classical Bordetella species, including B. pertussis, the causal agent of human whooping cough, and B.

'Follow the science': Popular trust in scientific experts during the coronavirus pandemic.

The coronavirus pandemic increased the role played by scientific advisers in counselling governments and citizens on issues around public health. This raises questions about how citizens evaluate scientists, and in particular the grounds on which they trust them. Previous studies have identified various factors associated with trust in scientists, although few have systematically explored a range of judgements and their relative effects.

Risk and Resilience Variants in the Retinoic Acid Metabolic and Developmental Pathways Associated with Risk of FASD Outcomes.

Fetal Alcohol Spectrum Disorder (FASD) is a common neurodevelopmental disorder that affects an estimated 2-5% of North Americans. FASD is induced by prenatal alcohol exposure (PAE) during pregnancy and while there is a clear genetic contribution, few genetic factors are currently identified or understood. In this study, using a candidate gene approach, we performed a genetic variant analysis of retinoic acid (RA) metabolic and developmental signaling pathway genes on whole exome sequencing data of 23 FASD-diagnosed individuals.

Sex Differences in Dystonia.

Background: Prior studies have indicated that female individuals outnumber male individuals for certain types of dystonia. Few studies have addressed factors impacting these sex differences or their potential biological mechanisms.

Objectives: To evaluate factors underlying sex differences in the dystonias and explore potential mechanisms for these differences.

A quantitative and qualitative analysis of patient group narratives suggests common biopsychosocial red flags of undiagnosed rare disease.

Background: The 'diagnostic odyssey' is a common challenge faced by patients living with rare diseases and poses a significant burden for patients, their families and carers, and the healthcare system. The diagnosis of rare diseases in clinical settings is challenging, with patients typically experiencing a multitude of unnecessary tests and procedures. To improve diagnosis of rare disease, clinicians require evidence-based guidance on when their patient may be presenting with a rare disease.

Design and characterization of protective pan-ebolavirus and pan-filovirus bispecific antibodies.

Monoclonal antibodies (mAbs) are an important class of antiviral therapeutics. MAbs are highly selective, well tolerated, and have long in vivo half-life as well as the capacity to induce immune-mediated virus clearance. Their activities can be further enhanced by integration of their variable fragments (Fvs) into bispecific antibodies (bsAbs), affording simultaneous targeting of multiple epitopes to improve potency and breadth and/or to mitigate against viral escape by a single mutation.

Liver-derived plasminogen mediates muscle stem cell expansion during caloric restriction through the plasminogen receptor Plg-R.

An intriguing effect of short-term caloric restriction (CR) is the expansion of certain stem cell populations, including muscle stem cells (satellite cells), which facilitate an accelerated regenerative program after injury. Here, we utilized the MetRS (MetRS) transgenic mouse to identify liver-secreted plasminogen as a candidate for regulating satellite cell expansion during short-term CR. Knockdown of circulating plasminogen prevents satellite cell expansion during short-term CR.

Stroke Alters the Function of Enteric Neurons to Impair Smooth Muscle Relaxation and Dysregulates Gut Transit.

Background: Gut dysmotility is common after ischemic stroke, but the mechanism underlying this response is unknown. Under homeostasis, gut motility is regulated by the neurons of the enteric nervous system that control contractile/relaxation activity of muscle cells in the gut wall. More recently, studies of gut inflammation revealed interactions of macrophages with enteric neurons are also involved in modulating gut motility.

Monovalent SARS-COV-2 mRNA vaccine using optimal UTRs and LNPs is highly immunogenic and broadly protective against Omicron variants.

The emergence of highly transmissible severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) that are resistant to the current COVID-19 vaccines highlights the need for continued development of broadly protective vaccines for the future. Here, we developed two messenger RNA (mRNA)-lipid nanoparticle (LNP) vaccines, TU88mCSA and ALCmCSA, using the ancestral SARS-CoV-2 spike sequence, optimized 5' and 3' untranslated regions (UTRs), and LNP combinations. Our data showed that these nanocomplexes effectively activate CD4 and CD8 T cell responses and humoral immune response and provide complete protection against WA1/2020, Omicron BA.

Flavonoids Regulate Redox-Responsive Transcription Factors in Glioblastoma and Microglia.

The tumor microenvironment (TME) has emerged as a valuable therapeutic target in glioblastoma (GBM), as it promotes tumorigenesis via an increased production of reactive oxygen species (ROS). Immune cells such as microglia accumulate near the tumor and its hypoxic core, fostering tumor proliferation and angiogenesis. In this study, we explored the therapeutic potential of natural polyphenols with antioxidant and anti-inflammatory properties.

Sympathetic-Mediated Intestinal Cell Death Contributes to Gut Barrier Impairment After Stroke.

Tissue injury induced by stroke is traditionally thought to be localised to the brain. However, there is an accumulating body of evidence to demonstrate that stroke promotes pathophysiological consequences in peripheral tissues including the gastrointestinal system. In this study, we investigated the mechanisms underlying gut permeability after stroke.

Anticoagulation for the treatment of septic cerebral venous sinus thrombosis in the setting of pediatric sinogenic and otogenic intracranial infections.

Objective: Septic cerebral venous sinus thrombosis (CVST) is a recognized complication of pediatric sinogenic and otogenic intracranial infections. The optimal treatment paradigm remains controversial. Proponents of anticoagulation highlight its role in preventing thrombus propagation and promoting recanalization, while others cite the risk of hemorrhagic complications, especially after a neurosurgical procedure for an epidural abscess or subdural empyema.

Multi-omic rejuvenation and life span extension on exposure to youthful circulation.

Heterochronic parabiosis (HPB) is known for its functional rejuvenation effects across several mouse tissues. However, its impact on biological age and long-term health is unknown. Here we performed extended (3-month) HPB, followed by a 2-month detachment period of anastomosed pairs.

Anti-SARS-CoV-2 Activity of Adamantanes In Vitro and in Animal Models of Infection.

Coronavirus disease 2019 (COVID-19) has had devastating effects worldwide, with particularly high morbidity and mortality in outbreaks on residential care facilities. Amantadine, originally licensed as an antiviral agent for therapy and prophylaxis against influenza A virus, has beneficial effects on patients with Parkinson's disease and is used for treatment of Parkinson's disease, multiple sclerosis, acquired brain injury, and various other neurological disorders. Recent observational data suggest an inverse relationship between the use of amantadine and COVID-19.

Identifying primary and secondary MLH1 epimutation carriers displaying low-level constitutional MLH1 methylation using droplet digital PCR and genome-wide DNA methylation profiling of colorectal cancers.

Background: MLH1 epimutation is characterised by constitutional monoallelic MLH1 promoter hypermethylation, which can cause colorectal cancer (CRC). Tumour molecular profiles of MLH1 epimutation CRCs were used to classify germline MLH1 promoter variants of uncertain significance and MLH1 methylated early-onset CRCs (EOCRCs). Genome-wide DNA methylation and somatic mutational profiles of tumours from two germline MLH1: c.

Mechanistic impacts of bacterial diet on dopaminergic neurodegeneration in a α-synuclein model of Parkinson's disease.

Failure of inherently protective cellular processes and misfolded protein-associated stress contribute to the progressive loss of dopamine (DA) neurons characteristic of Parkinson's disease (PD). A disease-modifying role for the microbiome has recently emerged in PD, representing an impetus to employ the soil-dwelling nematode, as a preclinical model to correlate changes in gene expression with neurodegeneration in transgenic animals grown on distinct bacterial food sources. Even under tightly controlled conditions, hundreds of differentially expressed genes and a robust neuroprotective response were discerned between clonal strains overexpressing human alpha-synuclein in the DA neurons fed either one of only two subspecies of .

Paired Indoor and Outdoor Nitrogen Dioxide Associated With Childhood Asthma Outcomes in a Mixed Rural-Urban Setting: A Feasibility Study.

Introduction: Nitrogen dioxide (NO) is known to be a trigger for asthma exacerbation. However, little is known about the role of seasonal variation in indoor and outdoor NO levels in childhood asthma in a mixed rural-urban setting of North America.

Methods: This prospective cohort study, as a feasibility study, included 62 families with children (5-17 years) that had diagnosed persistent asthma residing in Olmsted County, Minnesota.

Attenuation of Dopaminergic Neurodegeneration in a Parkinson's Model through Regulation of Xanthine Dehydrogenase (XDH-1) Expression by the RNA Editase, ADR-2.

Differential RNA editing by adenosine deaminases that act on RNA (ADARs) has been implicated in several neurological disorders, including Parkinson's disease (PD). Here, we report results of a RNAi screen of genes differentially regulated in mutants, normally encoding the only catalytically active ADAR in , ADR-2. Subsequent analysis of candidate genes that alter the misfolding of human α-synuclein (α-syn) and dopaminergic neurodegeneration, two PD pathologies, reveal that reduced expression of , the ortholog of human xanthine dehydrogenase (XDH), is protective against α-synuclein-induced dopaminergic neurodegeneration.

Trust and vaccine hesitancy during the COVID-19 pandemic: A cross-national analysis.

Previous studies of vaccine hesitancy in the context of COVID-19 have reported mixed results in terms of the role played by political and institutional trust. This study addresses this ambiguity with a global analysis of the relationship between trust and vaccine hesitancy, disentangling the effects of generalized trust orientations, trust in specific institutions and conspiracy mentality. It first draws upon a cross-national survey of 113 countries to demonstrate that trust in government is a predictor of vaccine hesitancy across global regions.

Educational needs in diagnosing rare diseases: A multinational, multispecialty clinician survey.

Purpose: Recognizing rare diseases (RDs) and initiating appropriate investigation and referral is critical for timely diagnosis. Unfortunately, patients with RDs experience significant diagnostic delays, potentially leading to inappropriate or harmful testing or treatment and disease progression.

Methods: A 14-question survey assessing clinician knowledge, experience, and educational needs in RDs was emailed to US and European Union Medscape member clinicians.