Structural basis of Spliced Leader RNA recognition by the Trypanosoma brucei cap-binding complex.

Kinetoplastids are a clade of eukaryotic protozoans that include human parasitic pathogens like trypanosomes and Leishmania species. In these organisms, protein-coding genes are transcribed as polycistronic pre-mRNAs, which need to be processed by the coupled action of trans-splicing and polyadenylation to yield monogenic mature mRNAs. During trans-splicing, a universal RNA sequence, the spliced leader RNA (SL RNA) mini-exon, is added to the 5'-end of each mRNA.

Ethosuximide: Subunit- and Gβγ-dependent blocker and reporter of allosteric changes in GIRK channels.

Background And Purpose: The antiepileptic drug ethosuximide (ETX) suppresses epileptiform activity in a mouse model of GNB1 syndrome, caused by mutations in Gβ protein, likely through the inhibition of G-protein gated K (GIRK) channels. Here, we investigated the mechanism of ETX inhibition (block) of different GIRKs.

Experimental Approach: We studied ETX inhibition of GIRK channels expressed in Xenopus oocytes with or without their physiological activator, the G protein subunit dimer Gβγ.

Rhythmic categories in horse gait kinematics.

Anecdotally, horses' gaits sound rhythmic. Are they really? In this study, we quantified the motor rhythmicity of horses across three different gaits (walk, trot, and canter). For the first time, we adopted quantitative tools from bioacoustics and music cognition to quantify locomotor rhythmicity.

Association between patient perception of disease status and different components of the Minimal Disease Activity (MDA) criteria in psoriatic arthritis.

Objective: The aim of this analysis was to evaluate the relationship between the criteria met of the Minimal Disease Activity (MDA) score for psoriatic arthritis (PsA) and patient-perceived disease status.

Methods: We analysed data from the ReFlaP study (NCT03119805), a cross-sectional international study of adult patients with PsA. Patients self-reported if they felt their PsA was in remission (REM), low disease activity (LDA) or neither.

Empirical antibiotic therapy improves outcomes in mechanically ventilated patients with COVID-19: An emulated targeted trial within a prospective, multicentre cohort study.

Background: Bacterial pulmonary superinfections develop in a substantial proportion of mechanically ventilated COVID-19 patients and are associated with prolonged mechanical ventilation requirements and an increased mortality. Albeit recommended, evidence supporting the use of empirical antibiotics at intubation is weak and of low quality. The aim of this study was to elucidate the effect of empirical antibiotics, administered within 24hours of endotracheal intubation, on superinfections, duration of mechanical ventilation, and mortality in mechanically ventilated patients with COVID-19.

The impact of neoadjuvant therapy in patients with left-sided resectable pancreatic cancer: an international multicenter study.

Purpose: To assess the association between neoadjuvant therapy and overall survival (OS) in patients with left-sided resectable pancreatic cancer (RPC) compared to upfront surgery.

Background: Left-sided pancreatic cancer is associated with worse OS compared to right-sided pancreatic cancer. Although neoadjuvant therapy is currently seen as not effective in patients with RPC, current randomized trials included mostly patients with right-sided RPC.

Antigenic determinants underlying IgE-mediated anaphylaxis to peanut.

Background: Studies of human IgE and its targeted epitopes on allergens have been very limited. We have an established method to immortalize IgE encoding B cells from allergic individuals.

Objective: To develop an unbiased and comprehensive panel of peanut-specific human IgE mAbs to characterize key immunodominant antigenic regions and epitopes on peanut allergens to map the molecular interactions responsible for inducing anaphylaxis.

Restimulation by macrophages exhausts T cells.

Inhibiting T cell exhaustion is an attractive cancer immunotherapy strategy. In this issue of Immunity, Waibl Polania et al. examine the microenvironmental signals regulating terminal T cell exhaustion and find that antigen presentation by tumor-associated macrophages, not tumor cells, drives terminal T cell exhaustion in glioblastoma.

Enormous Out-of-Plane Charge Rectification and Conductance through Two-Dimensional Monolayers.

Heterogeneous integration of emerging two-dimensional (2D) materials with mature three-dimensional (3D) silicon-based semiconductor technology presents a promising approach for the future development of energy-efficient, function-rich nanoelectronic devices. In this study, we designed a mixed-dimensional junction structure in which a 2D monolayer (e.g.

Targeting TRPC channels for control of arthritis-induced bone erosion.

Arthritis leads to bone erosion due to an imbalance between osteoclast and osteoblast function. Our prior investigations revealed that the Ca-selective ion channel, Orai1, is critical for osteoclast maturation. Here, we show that the small-molecule ELP-004 preferentially inhibits transient receptor potential canonical (TRPC) channels.

Epithelial OPA1 links mitochondrial fusion to inflammatory bowel disease.

Dysregulation at the intestinal epithelial barrier is a driver of inflammatory bowel disease (IBD). However, the molecular mechanisms of barrier failure are not well understood. Here, we demonstrate dysregulated mitochondrial fusion in intestinal epithelial cells (IECs) of patients with IBD and show that impaired fusion is sufficient to drive chronic intestinal inflammation.

Multi-tissue characterization of the constitutive heterochromatin proteome in Drosophila identifies a link between satellite DNA organization and transposon repression.

Noncoding satellite DNA repeats are abundant at the pericentromeric heterochromatin of eukaryotic chromosomes. During interphase, sequence-specific DNA-binding proteins cluster these repeats from multiple chromosomes into nuclear foci known as chromocenters. Despite the pivotal role of chromocenters in cellular processes like genome encapsulation and gene repression, the associated proteins remain incompletely characterized.

Maternal characteristics and their relation to early mother-child interaction and cognitive development in toddlers.

Early mother-infant interaction is believed to have a significant impact on the social, cognitive, and emotional development of children. These interactions are not only influenced by child and contextual factors but also by the mother's personality traits and strain. In this study, we investigated the relation between maternal factors such as personality, depressive symptoms, or experiencing of emotions, and (i) children's early cognitive development and (ii) interaction patterns in a sample of 116 mother-child dyads (mean child age = 18.

Short-term impact of low air pressure on plants' functional traits.

Lower atmospheric pressure affects biologically relevant physical parameters such as gas partial pressure and concentration, leading to increased water vapor diffusivity and greater soil water content loss through evapotranspiration. This might impact plant photosynthetic activity, resource allocation, water relations, and growth. However, the direct impact of low air pressure on plant physiology is largely unknown.

Effectiveness and Safety of Adalimumab in Patients With Very Early-Onset Inflammatory Bowel Disease: A Retrospective Study on Behalf of the Porto Inflammatory Bowel Disease Working Group of European Society for Pediatric Gastroenterology Hepatology and Nutrition.

Background And Aims: Patients with very early-onset inflammatory bowel disease (VEO-IBD), with an age of onset < 6 years, can present with severe manifestations and may require biologic therapy. Infliximab and adalimumab are approved for induction and maintenance in pediatric IBD patients but are licensed only above the age of 6 years. Effectiveness and safety data on adalimumab in this patient population are lacking.

Outcomes of mechanical thrombectomy for medium vessel occlusion in acute ischemic stroke patients with ASPECTS 4-5 vs. 6-7: a retrospective, multicenter, and multinational study.

Introduction: Mechanical thrombectomy (MT) efficacy in medium vessel occlusion (MeVO) stroke, particularly in patients with low Alberta Stroke Program Early Computed Tomography Score (ASPECTS), remains less explored.

Methods: This retrospective study analyzed data from 443 AIS patients treated with MT for MeVO and low ASPECTS (4-7) at 37 centers across North America, Asia, and Europe, from September 2017 to July 2021. Patients were categorized into ASPECTS of 4-5 and 6-7.

Impact of fluorination on membrane-protein stabilization and extraction by lactobionamide detergents.

We report the synthesis of a series of detergents with a lactobionamide polar head group and a tail containing four to seven perfluorinated carbon atoms. Critical micellar concentrations (CMCs) were determined using isothermal titration calorimetry (ITC) and surface tension (SFT) measurements, showing a progressive decrease from 27 mM to about 0.2 mM across the series.

Fabrication of nanoparticles with precisely controllable plasmonic properties as tools for biomedical applications.

Metal nanoparticles are established tools for biomedical applications due to their unique optical properties, primarily attributed to localized surface plasmon resonances. They show distinct optical characteristics, such as high extinction cross-sections and resonances at specific wavelengths, which are tunable across the wavelength spectrum by modifying the nanoparticle geometry. These attributes make metal nanoparticles highly valuable for sensing and imaging in biology and medicine.

Enhanced sampling of robust molecular datasets with uncertainty-based collective variables.

Generating a dataset that is representative of the accessible configuration space of a molecular system is crucial for the robustness of machine-learned interatomic potentials. However, the complexity of molecular systems, characterized by intricate potential energy surfaces, with numerous local minima and energy barriers, presents a significant challenge. Traditional methods of data generation, such as random sampling or exhaustive exploration, are either intractable or may not capture rare, but highly informative configurations.

A Genome-Wide Association Screen for Genes Affecting Leaf Trichome Development and Epidermal Metal Accumulation in Arabidopsis.

To identify novel genes engaged in plant epidermal development, we characterized the phenotypic variability of rosette leaf epidermis of 310 sequenced Arabidopsis thaliana accessions, focusing on trichome shape and distribution, compositional characteristics of the trichome cell wall, and histologically detectable metal ion distribution. Some of these traits correlated with cLimate parameters of our accession's locations of origin, suggesting environmental selection. A novel metal deposition pattern in stomatal guard cells was observed in some accessions.

Association of aortic valve size with the degree of aortic valve calcification in severe high-gradient aortic stenosis.

Aims: Less pronounced calcification of the aortic valve (AVC) was observed in women with aortic stenosis (AS) as compared to men. Since women have smaller aortic valves (AV), this could explain a lower calcium load. We aimed to analyze the association of AV size with AVC independent from sex.

A comprehensive summary of the ASEV-CzeSEV joint meeting on extracellular vesicles.

This report summarizes the ASEV-CzeSEV Joint Meeting on Extracellular Vesicles (EVs), held at the Medical University of Vienna in September 2024. The conference focused on introducing and expanding EV research and infrastructure within the Czech Republic and Austria, highlighting areas for collaboration. Key sessions featured research on EV-based diagnostics, tissue regeneration, interspecies communication and therapeutic applications, with an emphasis on shared resources and cross-border partnerships.

Utilizing deep learning to predict Alzheimer's disease and mild cognitive impairment with optical coherence tomography.

Introduction: Diagnostic performance of optical coherence tomography (OCT) to detect Alzheimer's disease (AD) and mild cognitive impairment (MCI) remains limited. We aimed to develop a deep-learning algorithm using OCT to detect AD and MCI.

Methods: We performed a cross-sectional study involving 228 Asian participants (173 cases/55 controls) for model development and testing on 68 Asian (52 cases/16 controls) and 85 White (39 cases/46 controls) participants.

Frontal plane mechanical leg alignment estimation from knee x-rays using deep learning.

Objective: Lower limb malalignment can complicate symptoms and accelerate knee osteoarthritis (OA), necessitating consideration in study population selection. In this study, we develop and validate a deep learning model that classifies leg alignment as "normal" or "malaligned" from knee antero-posterior (AP)/postero-anterior (PA) radiographs alone, using an adjustable hip-knee-ankle (HKA) angle threshold.

Material And Methods: We utilized 8878 digital radiographs, including 6181 AP/PA full-leg x-rays (LLRs) and 2697 AP/PA knee x-rays (2292 with positioning frame, 405 without).

A comprehensive voice dataset for Hindko digit recognition.

Hindko is a language primarily spoken in Northwestern areas of Pakistan. Approximately eight million people speak the Hindko language. According to its native speakers, it is 7 largest language of Pakistan and 2 largest language of Khyber Pakhtunkhwa.