SignatureFinder enables sequence mining to identify cobalamin-dependent photoreceptor proteins.

Photoreceptors control cellular processes in response to light. Most photoreceptors sense blue or red light, but the recent discovery of the cobalamin-dependent photoreceptor, CarH, has expanded the wavelength range of photoreception to other regions of the electromagnetic spectrum to include the green light region. Further identification of cobalamin-dependent green light-sensitive photoreceptors has been hampered owing to poor annotation of the light responsiveness of cobalamin-binding domains (CBDs) in public databases.

Airway total bacterial density, microbiota community composition and relationship with clinical parameters in bronchiectasis.

Background And Objective: This study explored the relationship between total bacterial density, airway microbiota composition and clinical parameters in bronchiectasis. We determined changes with time during clinical stability and following antibiotic treatment of a pulmonary exacerbation.

Methods: We conducted a multicentre longitudinal cohort study of UK participants with CT confirmed bronchiectasis.

Solubilisation & purification of membrane proteins using benzylamine-modified SMA polymers.

Extraction of proteins from the membrane using styrene maleic acid co-polymers (SMA), forming SMA lipid particles (SMALPs), has allowed for the first time the purification of membrane proteins with their lipid bilayer environment. To date, SMA2000 has been the most effective polymer used for this purpose, with a 2:1 ratio of styrene:maleic acid, and styrene and maleic acid moieties spread statistically throughout the chain. However, SMA2000 is a highly polydisperse polymer that contains an array of different polymer lengths and sequences.

Rationalizing the Influence of Small-Molecule Dopants on Guanine Crystal Morphology.

Many spectacular optical phenomena in animals are produced by reflective assemblies of guanine crystals. The crystals comprise planar H-bonded layers of π-stacked molecules with a high in-plane refractive index. By preferentially expressing the highly reflective π-stacked (100) crystal face and controlling its cross-sectional shape, organisms generate a diverse array of photonic superstructures.

Research Priorities for Atrial Fibrillation in Australia: A Statement From the Australian Cardiovascular Alliance Clinical Arrhythmia Theme.

Atrial fibrillation (AF) is highly prevalent in the Australian community, ranking amongst the highest globally. The consequences of AF are significant. Stroke, dementia and heart failure risk are increased substantially, hospitalisations are amongst the highest for all cardiovascular causes, and Australians living with AF suffer from substantial symptoms that impact quality of life.

Mechanistic Insights and Knowledge Gaps in the Effects of Radiation Therapy on Cardiac Arrhythmias.

Stereotactic body radiation therapy (SBRT) is an innovative modality for the treatment of refractory ventricular arrhythmias (VAs). Phase 1/2 clinical trials have demonstrated the remarkable efficacy of SBRT at reducing VA burden (by >85%) in patients with good short-term safety. SBRT as an option for VA treatment delivered in an ambulatory nonsedated patient in a single fraction during an outpatient session of 15 to 30 minutes, without added risks of anesthetic or surgery, is clinically relevant.

Reduced connexin-43 expression, slow conduction and repolarisation dispersion in a model of hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is an inherited heart muscle disease that is characterised by left ventricular wall thickening, cardiomyocyte disarray and fibrosis, and is associated with arrhythmias, heart failure and sudden death. However, it is unclear to what extent the electrophysiological disturbances that lead to sudden death occur secondary to structural changes in the myocardium or as a result of HCM cardiomyocyte electrophysiology. In this study, we used an induced pluripotent stem cell model of the R403Q variant in myosin heavy chain 7 (MYH7) to study the electrophysiology of HCM cardiomyocytes in electrically coupled syncytia, revealing significant conduction slowing and increased spatial dispersion of repolarisation - both well-established substrates for arrhythmia.

COVID-19, lockdowns, and the mental wellbeing of LGBTQ people in Australia.

LGBTQ communities around the world entered the COVID-19 pandemic with generally high rates of poor mental health and faced additional challenges including stigma, discrimination, and barriers to care. This study sample was drawn from a survey of 3135 LGBTQ adults residing in Australia during the pandemic. Regression analysis was used to explore individual differences in psychological distress and perceived change in mental wellbeing since the onset of the pandemic as well as the impact of lockdowns, by taking advantage of a natural experiment comparing the states that experienced more extensive lockdowns (Victoria and New South Wales) to the rest of Australia.

Development of a pharmaceutical database as an aid to the nonclinical detection of drug-induced cardiac toxicity.

The Health and Environmental Sciences Institute (HESI) Cardiac Safety Committee designed and created a publicly accessible database with an initial set of 128 pharmacologically defined pharmaceutical agents, many with known cardiotoxic properties. The database includes specific information about each compound that could be useful in evaluating hypotheses around mechanisms of drug-induced cardiac toxicity or for development of novel cardiovascular safety assays. Data on each of the compounds was obtained from published literature and online sources (e.

Bronchiectasis and asthma: Data from the European Bronchiectasis Registry (EMBARC).

Background: Asthma is commonly reported in patients with a diagnosis of bronchiectasis.

Objective: The aim of this study was to evaluate whether patients with bronchiectasis and asthma (BE+A) had a different clinical phenotype and different outcomes compared with patients with bronchiectasis without concomitant asthma.

Methods: A prospective observational pan-European registry (European Multicentre Bronchiectasis Audit and Research Collaboration) enrolled patients across 28 countries.

Pneumococcal serotypes and risk factors in adult community-acquired pneumonia 2018-20; a multicentre UK cohort study.

Background: Higher-valency pneumococcal vaccines are anticipated. We aimed to describe serotype distribution and risk factors for vaccine-serotype community-acquired pneumonia (CAP) in the two years pre-SARS-CoV-2 pandemic.

Methods: We conducted a prospective cohort study of adults hospitalised with CAP at three UK sites between 2018 and 2020.

Functional coupling between Piezo1 and TRPM4 influences the electrical activity of HL-1 atrial myocytes.

The transient receptor potential melastatin 4 (TRPM4) channel contributes extensively to cardiac electrical activity, especially cardiomyocyte action potential formation. Mechanical stretch can induce changes in heart rate and rhythm, and the mechanosensitive channel Piezo1 is expressed in many cell types within the myocardium. Our previous study showed that TRPM4 and Piezo1 are closely co-localized in the t-tubules of ventricular cardiomyocytes and contribute to the Ca-dependent signalling cascade that underlies hypertrophy in response to mechanical pressure overload.

Factors Associated With Experiences of Harassment or Abuse Among Lesbian, Gay, Bisexual, Trans, Queer, and Asexual Young People With Disability in Australia.

Lesbian, gay, bisexual, trans, queer, and asexual (LGBTQA+) young people with disability are known to experience higher rates of harassment or abuse than LGBTQA+ young people without disability. This study focused on participants in Australia and identified factors associated with harassment or abuse among LGBTQA+ adolescents and young adults who reported a disability as well as associations with mental health outcomes. Analyses were conducted from a national survey that included 2,500 LGBTQA+ people who reported a disability and were aged 14 to 21 years.

Empirical Quantification of Predictive Uncertainty Due to Model Discrepancy by Training with an Ensemble of Experimental Designs: An Application to Ion Channel Kinetics.

When using mathematical models to make quantitative predictions for clinical or industrial use, it is important that predictions come with a reliable estimate of their accuracy (uncertainty quantification). Because models of complex biological systems are always large simplifications, model discrepancy arises-models fail to perfectly recapitulate the true data generating process. This presents a particular challenge for making accurate predictions, and especially for accurately quantifying uncertainty in these predictions.

Implementation of a Children's Hospital Acute Care Behavior Response Team.

Background: Pediatric patients with behavioral needs are frequently admitted to the hospital for medical care; when behavioral crises occur, patients and staff are at risk for injury. Our aim was to implement a behavior response team (BRT) to increase the days between employee injury due to aggressive patient interactions on the inpatient medical units from 99 to 150 over 1 year.

Methods: A multidisciplinary team used quality improvement methods to design and implement the BRT system that includes 2 options: huddle to proactively plan for patients exhibiting early signs of escalation and STAT for immediate help for patients with imminent risk of harm to self or others.

Cervical screening among LGBTQ people: how affirming services may aid in achieving cervical cancer elimination targets.

To reach cervical cancer elimination targets it is necessary to increase screening rates among underserved populations such as LGBTQ communities. This paper examines rates of attendance and associated factors of cervical screening in LGBTQ communities. Data from 2,424 people aged 25 to 74 years and assigned female at birth were drawn from an online national Australian survey of LGBTQ adults.

Development of new adeno-associated virus capsid variants for targeted gene delivery to human cardiomyocytes.

Recombinant adeno-associated viruses (rAAVs) have emerged as one of the most promising gene therapy vectors that have been successfully used in pre-clinical models of heart disease. However, this has not translated well to humans due to species differences in rAAV transduction efficiency. As a result, the search for human cardiotropic capsids is a major contemporary challenge.

Polymorphic Solid Solutions in Molecular Crystals: Tips, Tricks, and Switches.

Crystal polymorphism has been a topic of much interest for the past 20 years or so, especially since its scientific (and legal) importance to the pharmaceutical industry was realized. By contrast, the formation of solid solutions in molecular crystals has been overlooked despite its long-standing prevalence in the analogous field of inorganic crystals. Wilfully forgotten, crystalline molecular solid solutions may be very common in our world since molecular compounds are rarely produced with 100% purity, and impurities able to form solid solutions are difficult to reject via recrystallization.