Human ACE2 transgenic pigs are susceptible to SARS-CoV-2 and develop COVID-19-like disease.

Animal models that accurately reflect COVID-19 are vital for understanding mechanisms of disease and advancing development of improved vaccines and therapeutics. Pigs are increasingly recognized as valuable models for human disease due to their genetic, anatomical, physiological, and immunological similarities to humans, and they present a more ethically viable alternative to non-human primates. However, pigs are not susceptible to SARS-CoV-2 infection which limits their utility as a model.

Interferon-α promotes HLA-B-restricted presentation of conventional and alternative antigens in human pancreatic β-cells.

Interferon (IFN)-α is the earliest cytokine signature observed in individuals at risk for type 1 diabetes (T1D), but the effect of IFN-α on the antigen repertoire of HLA Class I (HLA-I) in pancreatic β-cells is unknown. Here we characterize the HLA-I antigen presentation in resting and IFN-α-exposed β-cells and find that IFN-α increases HLA-I expression and expands peptide repertoire to those derived from alternative mRNA splicing, protein cis-splicing and post-translational modifications. While the resting β-cell immunopeptidome is dominated by HLA-A-restricted peptides, IFN-α largely favors HLA-B and only marginally upregulates HLA-A, translating into increased HLA-B-restricted peptide presentation and activation of HLA-B-restricted CD8 T cells.

Frequency-specific changes in prefrontal activity associated with maladaptive belief updating in volatile environments in euthymic bipolar disorder.

Bipolar disorder (BD) involves altered reward processing and decision-making, with inconsistencies across studies. Here, we integrated hierarchical Bayesian modelling with magnetoencephalography (MEG) to characterise maladaptive belief updating in this condition. First, we determined if previously reported increased learning rates in BD stem from a heightened expectation of environmental changes.

Post-colonoscopy cancer rates in Scotland from 2012 to 2018: A population-based cohort study.

Aim: The aim of this work was to quantify post-colonoscopy colorectal cancer (PCCRC) rates in National Health Service (NHS) Scotland using World Endoscopy Association guidelines, compare incidence between health boards and referral streams and explore comparisons in results with published data from other healthcare systems.

Method: This is a population-based cohort study using NHS Scotland data between 2012 and 2018. All people undergoing colonoscopy between 2012 and 2018 and subsequently diagnosed as having bowel cancer up to 3 years after their investigation were included.

Range shifts as drivers of niche breadth and dispersal ability in wild populations.

Research Highlight: Edwards, O. M., Zhai, L.

A Global Relationship Between Genome Size and Encoded Carbon Metabolic Strategies of Soil Bacteria.

Microbial traits are critical for carbon sequestration and degradation in terrestrial ecosystems. Yet, our understanding of the relationship between carbon metabolic strategies and genomic traits like genome size remains limited. To address this knowledge gap, we conducted a global-scale meta-analysis of 2650 genomes, integrated whole-genome sequencing data, and performed a continental-scale metagenomic field study.

Understanding the Mechanism of Electrochemical CO Capture by Supercapacitive Swing Adsorption.

Carbon dioxide capture underpins an important range of technologies that can help to mitigate climate change. Improved carbon capture technologies that are driven by electrochemistry are under active development, and it was recently found that supercapacitor energy storage devices can reversibly capture and release carbon dioxide. So-called supercapacitive swing adsorption (SSA) has several advantages over traditional carbon dioxide capture technologies such as lower energy consumption and the use of nontoxic materials.

Effect of Exact Exchange on the Energy Landscape in Self-Consistent Field Theory.

Density functional approximations can reduce the spin symmetry breaking observed for self-consistent field (SCF) solutions compared to Hartree-Fock theory, but the amount of exact Hartree-Fock (HF) exchange appears to be a key determinant in broken symmetry. To elucidate the precise role of exact exchange, we investigate the energy landscape of unrestricted Hartree-Fock and Kohn-Sham density functional theory for benzene and square cyclobutadiene, which provide paradigmatic examples of closed-shell and open-shell electronic structures, respectively. We find that increasing the amount of exact exchange leads to more local SCF minima, which can be characterized as combinatorial arrangements of unpaired electrons in the carbon π system.

Reconciling Variability in Multiple Stressor Effects Using Environmental Performance Curves.

Understanding the effects of multiple stressors has become a major focus in ecology and evolution. While many studies have investigated the combined effects of stressors, revealing massive variability, a mechanistic understanding that reconciles the diversity of multiple stressor outcomes is lacking. Here, we show how performance curves can fill this gap by revealing mechanisms that shape multiple stressor outcomes.

Soil Nitrogen Supply Exerts Largest Influence on Leaf Nitrogen in Environments with the Greatest Leaf Nitrogen Demand.

Accurately representing the relationships between nitrogen supply and photosynthesis is crucial for reliably predicting carbon-nitrogen cycle coupling in Earth System Models (ESMs). Most ESMs assume positive correlations amongst soil nitrogen supply, leaf nitrogen content, and photosynthetic capacity. However, leaf photosynthetic nitrogen demand may influence the leaf nitrogen response to soil nitrogen supply; thus, responses to nitrogen supply are expected to be the largest in environments where demand is the greatest.

Approximate Hamiltonians from a Linear Vibronic Coupling Model for Solution-Phase Spin Dynamics.

The linear vibronic coupling (LVC) model is an approach for approximating how a molecular Hamiltonian changes in response to small changes in molecular geometry. The LVC framework thus has the ability to approximate molecular Hamiltonians at low computational expense but with quality approaching multiconfigurational calculations, when the change in geometry compared to the reference calculation used to parametrize it is small. Here, we show how the LVC approach can be used to project approximate spin Hamiltonians of a solvated lanthanide complex along a room-temperature molecular dynamics trajectory.

Clinical characteristics affecting weight loss in an East Asian population receiving semaglutide: A STEP 6 subgroup analysis.

Objective: To explore the effects of semaglutide versus placebo on body weight (BW) by subgroups of baseline characteristics.

Methods: In STEP 6, Japanese and Korean adults with overweight or obesity were randomized to subcutaneous semaglutide 2.4 mg, semaglutide 1.

Sex and Cardiac Operations: Are We Being Fair to Our Female Patients?

Background: Research suggests that although men have a higher cardiovascular disease (CVD) rate, women with CVD are more likely to experience a poorer prognosis, possibly owing to incorrect diagnosis and poorer treatment. A question not yet addressed is whether some of this inequality could be due to sex bias when selecting patients for operation.

Method: The participants were from the Scottish Heart Health Extended Cohort who had been admitted to hospital with a cardiovascular diagnosis over the study period.

Identifying people at risk of rheumatoid arthritis in primary care: qualitative study.

Background: Identification of rheumatoid arthritis (RA) in primary care is challenging and often delayed. Anti-cyclic citrullinated peptide (anti-CCP) antibody testing of people presenting to primary care with new-onset musculoskeletal symptoms without synovitis could help address this; those testing positive are at increased risk of developing RA.

Aim: To explore how primary care clinicians currently identify and refer patients with suspected RA, and the behaviours required to implement a prediction model for guiding targeted anti-CCP testing for non-specific musculoskeletal symptoms in primary care.

Symptom appraisal and help-seeking before a cancer diagnosis during pregnancy: a qualitative study.

Background Estimated incidence of cancer diagnosis during or shortly after pregnancy is 1 in 1,000 women. Pregnancy can impact symptom appraisal and help-seeking for symptoms subsequently diagnosed as cancer. Little is known about the pathway to cancer diagnosis in pregnancy or delays that women can encounter.

Antidepressants and risk of postural hypotension: a self-controlled case series study.

Background Antidepressants are associated with postural hypotension (PH), but it is not typically recognised as a common adverse effect. PH is linked with serious complications in older adults (e.g.