Ca1.3 channel clusters characterized by live-cell and isolated plasma membrane nanoscopy.

A key player of excitable cells in the heart and brain is the L-type calcium channel Ca1.3. In the heart, it is required for voltage-dependent Ca-signaling, i.

SBRT for Cardiac Ablation in Patients With Refractory Ventricular Tachycardia.

Background: This case details a 44-year-old man with end-stage ischemic cardiomyopathy with refractory ventricular tachycardia (VT). The patient has a single-chamber implantable cardioverter-defibrillator, has had 2 VT ablations, and uses medication to manage his VT. Despite these interventions, he continued to have episodes of VT.

Overlap chronic GVHD is associated with adverse survival outcomes compared to classic chronic GVHD.

Chronic graft-versus-host-disease (cGVHD) is divided into two subtypes: classic (absence of acute GVHD features) and overlap cGVHD ('ocGVHD'), in which both chronic and acute GVHD clinical features are present simultaneously. While worse outcomes with ocGVHD have been reported, there are few recent analyses. We performed a secondary analysis of data from the ABA2 trial (N = 185), in which detailed GVHD data were collected prospectively and systematically adjudicated.

Higher abatacept exposure after transplant decreases acute GVHD risk without increasing adverse events.

In the ABA2 study, the T-cell costimulation blockade agent, abatacept, was safe and effective in preventing acute graft-versus-host disease (aGVHD) after unrelated-donor hematopoietic cell transplant (HCT), leading to US Food and Drug Administration approval. Here, we performed a determination of abatacept pharmacokinetics (PK), which enabled an examination of how abatacept exposure-response relationships affected clinical outcomes. We performed a population PK analysis of IV abatacept using nonlinear mixed-effect modeling and assessed the association between abatacept exposure and key transplant outcomes.

Narrowing yield gaps does not guarantee a living income from smallholder farming-an empirical study from western Kenya.

Crop yields in sub-Saharan Africa need to increase to keep pace with food demands from the burgeoning population. Smallholder farmers play an important role in national food self-sufficiency, yet many live in poverty. Investing in inputs to increase yields is therefore often not viable for them.

Anle138b interaction in α-synuclein aggregates by dynamic nuclear polarization NMR.

Small molecules that bind to oligomeric protein species such as membrane proteins and fibrils are of clinical interest for development of therapeutics and diagnostics. Definition of the binding site at atomic resolution via NMR is often challenging due to low binding stoichiometry of the small molecule. For fibrils and aggregation intermediates grown in the presence of lipids, we report atomic-resolution contacts to the small molecule at sub nm distance via solid-state NMR using dynamic nuclear polarization (DNP) and orthogonally labelled samples of the protein and the small molecule.

Evaluating combined effects of pesticide and crop nutrition (with N, P, K and Si) on weevil damage in East African Highland Bananas.

Banana weevil (Cosmopolites sordidus, Germar) is a major pest in East African Highland Banana. The influence of crop nutritional status on weevil damage is poorly understood. Nutrient availability affects the nutritional quality of plants for weevils and may affect weevil damage.

A function-based typology for Earth's ecosystems.

As the United Nations develops a post-2020 global biodiversity framework for the Convention on Biological Diversity, attention is focusing on how new goals and targets for ecosystem conservation might serve its vision of 'living in harmony with nature'. Advancing dual imperatives to conserve biodiversity and sustain ecosystem services requires reliable and resilient generalizations and predictions about ecosystem responses to environmental change and management. Ecosystems vary in their biota, service provision and relative exposure to risks, yet there is no globally consistent classification of ecosystems that reflects functional responses to change and management.

The major urinary protein gene cluster knockout mouse as a novel model for translational metabolism research.

Scientific evidence suggests that not only murine scent communication is regulated by major urinary proteins, but that their expression may also vary in response to metabolism via a yet unknown mechanism. Major urinary proteins are expressed mainly in the liver, showing a sexually dimorphic pattern with substantially higher expression in males. Here, we investigate the metabolic implications of a major urinary protein knockout in twelve-week-old male and female C57BL/6N mice during ad libitum feeding.

A litmus test for classifying recognition mechanisms of transiently binding proteins.

Partner recognition in protein binding is critical for all biological functions, and yet, delineating its mechanism is challenging, especially when recognition happens within microseconds. We present a theoretical and experimental framework based on straight-forward nuclear magnetic resonance relaxation dispersion measurements to investigate protein binding mechanisms on sub-millisecond timescales, which are beyond the reach of standard rapid-mixing experiments. This framework predicts that conformational selection prevails on ubiquitin's paradigmatic interaction with an SH3 (Src-homology 3) domain.

Mapping spatial distribution and geographic shifts of East African highland banana (Musa spp.) in Uganda.

East African highland banana (Musa acuminata genome group AAA-EA; hereafter referred to as banana) is critical for Uganda's food supply, hence our aim to map current distribution and to understand changes in banana production areas over the past five decades. We collected banana presence/absence data through an online survey based on high-resolution satellite images and coupled this data with independent covariates as inputs for ensemble machine learning prediction of current banana distribution. We assessed geographic shifts of production areas using spatially explicit differences between the 1958 and 2016 banana distribution maps.

Structure and Gating Behavior of the Human Integral Membrane Protein VDAC1 in a Lipid Bilayer.

The voltage-dependent anion channel (VDAC), the most abundant protein in the outer mitochondrial membrane, is responsible for the transport of all ions and metabolites into and out of mitochondria. Larger than any of the β-barrel structures determined to date by magic-angle spinning (MAS) NMR, but smaller than the size limit of cryo-electron microscopy (cryo-EM), VDAC1's 31 kDa size has long been a bottleneck in determining its structure in a near-native lipid bilayer environment. Using a single two-dimensional (2D) crystalline sample of human VDAC1 in lipids, we applied proton-detected fast magic-angle spinning NMR spectroscopy to determine the arrangement of β strands.

The calcium-free form of atorvastatin inhibits amyloid-β(1-42) aggregation in vitro.

Alzheimer's disease is characterized by the presence of extraneuronal amyloid plaques composed of amyloid-beta (Aβ) fibrillar aggregates in the brains of patients. In mouse models, it has previously been shown that atorvastatin (Ator), a cholesterol-lowering drug, has some reducing effect on the production of cerebral Aβ. A meta-analysis on humans showed moderate effects in the short term but no improvement in the Alzheimer's Disease Assessment Scale-Cognitive Subscale behavioral test.

Amantadine has potential for the treatment of COVID-19 because it inhibits known and novel ion channels encoded by SARS-CoV-2.

The dire need for COVID-19 treatments has inspired strategies of repurposing approved drugs. Amantadine has been suggested as a candidate, and cellular as well as clinical studies have indicated beneficial effects of this drug. We demonstrate that amantadine and hexamethylene-amiloride (HMA), but not rimantadine, block the ion channel activity of Protein E from SARS-CoV-2, a conserved viroporin among coronaviruses.

Moderate Differences in Plasma Leptin in Mares Have no Effect on Either the Amino Acid or the Fatty Acid Composition of the Uterine Fluid.

Female mammalian reproductive functions are closely linked to body condition and metabolic status. Energy homeostasis is regulated by endocrine hormones such as insulin, IGF-I, leptin, and adiponectin via the hypothalamic-pituitary-adrenal axis. These metabolic hormones and their receptors are also expressed in reproductive tissues and the embryo.

High risk of relapsed disease in patients with NK/T-cell chronic active Epstein-Barr virus disease outside of Asia.

Chronic active Epstein-Barr virus (EBV) disease (CAEBV) is characterized by high levels of EBV predominantly in T and/or natural killer cells with lymphoproliferation, organ failure due to infiltration of tissues with virus-infected cells, hemophagocytic lymphohistiocytosis, and/or lymphoma. The disease is more common in Asia than in the United States and Europe. Although allogeneic hematopoietic stem cell transplantation (HSCT) is considered the only curative therapy for CAEBV, its efficacy and the best treatment modality to reduce disease severity prior to HSCT is unknown.

Proton Detected Solid-State NMR of Membrane Proteins at 28 Tesla (1.2 GHz) and 100 kHz Magic-Angle Spinning.

The available magnetic field strength for high resolution NMR in persistent superconducting magnets has recently improved from 23.5 to 28 Tesla, increasing the proton resonance frequency from 1 to 1.2 GHz.

Affective Dysregulation in Children Is Associated With Difficulties in Response Control in Emotional Ambiguous Situations.

Background: Affective dysregulation (AD), or synonymously "irritability," is a transdiagnostic construct that serves as a diagnostic criterion in various childhood mental disorders. It is characterized by severe or persistent outbursts of anger and aggression. Emotional self-regulation is highly dependent on the ability to process relevant and ignore conflicting emotional information.

Latitude dictates plant diversity effects on instream decomposition.

Running waters contribute substantially to global carbon fluxes through decomposition of terrestrial plant litter by aquatic microorganisms and detritivores. Diversity of this litter may influence instream decomposition globally in ways that are not yet understood. We investigated latitudinal differences in decomposition of litter mixtures of low and high functional diversity in 40 streams on 6 continents and spanning 113° of latitude.

Phylogeographic distribution of rhizobia nodulating common bean (Phaseolus vulgaris L.) in Ethiopia.

Rhizobia are soilborne bacteria that form symbiotic relations with legumes and fix atmospheric nitrogen. The nitrogen fixation potential depends on several factors such as the type of host and symbionts and on environmental factors that affect the distribution of rhizobia. We isolated bacteria nodulating common bean in Southern Ethiopia to evaluate their genetic diversity and phylogeography at nucleotide, locus (gene/haplotype) and species levels of genetic hierarchy.

Phase II Trial of Costimulation Blockade With Abatacept for Prevention of Acute GVHD.

Purpose: Severe (grade 3-4) acute graft-versus-host disease (AGVHD) is a major cause of death after unrelated-donor (URD) hematopoietic cell transplant (HCT), resulting in particularly high mortality after HLA-mismatched transplantation. There are no approved agents for AGVHD prevention, underscoring the critical unmet need for novel therapeutics. ABA2 was a phase II trial to rigorously assess safety, efficacy, and immunologic effects of adding T-cell costimulation blockade with abatacept to calcineurin inhibitor (CNI)/methotrexate (MTX)-based GVHD prophylaxis, to test whether abatacept could decrease AGVHD.

The effects of management practices on soil organic carbon stocks of oil palm plantations in Sumatra, Indonesia.

The rapid increase in global production of and demand for palm oil has resulted in large-scale expansion of oil palm monoculture in the world's tropical regions, particularly in Indonesia. This expansion has led to the conversion of carbon-rich land-use types to oil palm plantations with a range of negative environmental impacts, including loss of carbon from aboveground biomass and soil. Sequestration of soil organic carbon (SOC) in existing oil palm plantations is an important strategy to limit carbon losses.

Evidence for a causal role of superior frontal cortex theta oscillations during the processing of joint subliminal and conscious conflicts.

Consciously and subliminally processed information can both lead to conflicts that hinder goal-directed behaviour. Conflict monitoring processes are required to cope with situations where one or multiple conflicts occur. It has been suggested, that medial-frontal theta oscillations are associated with the implementation of cognitive control and that conflicts increase theta band activity.

Pregnancy as a model for aging.

The process of aging can be defined as the sum accumulation of damages and changes in metabolism during the life of an organism, due to both genetic predisposition and stochastic damage. During the gestational period and following parturition, similar damage can be seen due to the strenuous effect on the maternal body, exhibited on both the physiological and cellular level. In this review, we will focus on the similar physiological and cellular characteristics exhibited during pregnancy and aging, including induction of and response to oxidative stress, inflammation, and degradation of telomeres.