UROPOT: study protocol for a randomized, double-blind phase I/II trial for metabolism-based potentiation of antimicrobial prophylaxis in the urological tract.

Background: Urinary tract catheters, including Double-J or ureteral stents, are prone to bacterial colonization forming biofilms and leading to asymptomatic bacteriuria. In the context of asymptomatic bacteriuria, endourological procedures causing mucosa-inducing lesions can lead to severe infections. Antibiotic prophylaxis is warranted, yet its efficacy is limited by biofilm formation on stents.

Interactors and neighbors of ULK1 complex members.

The ULK1 kinase complex plays a crucial role in autophagosome biogenesis. To identify interactors or regulators of ULK1 complex assembly influencing autophagosome biogenesis, we performed an interaction proteomics screen. Employing both affinity purification and proximity labeling of - and -terminal tagged fusion proteins coupled to quantitative mass spectrometry, we identified 317 high-confidence interactors or neighbors of the four ULK1 complex members, including both member-specific and common interactors.

Cdk8 and Hira mutations trigger X chromosome elimination in naive female hybrid mouse embryonic stem cells.

Mouse embryonic stem cells (ESCs) possess a pluripotent developmental potential and a stable karyotype. An exception is the frequent loss of one X chromosome in female ESCs derived from inbred mice. In contrast, female ESCs from crosses between different Mus musculus subspecies often maintain two X chromosomes and can model X chromosome inactivation.

Light-Activated Agonist-Potentiator of GABA Receptors for Reversible Neuroinhibition in Wildtype Mice.

Gamma aminobutyric acid type A receptors (GABARs) play a key role in the mammalian central nervous system (CNS) as drivers of neuroinhibitory circuits, which are commonly targeted for therapeutic purposes with potentiator drugs. However, due to their widespread expression and strong inhibitory action, systemic pharmaceutical potentiation of GABARs inevitably causes adverse effects regardless of the drug selectivity. Therefore, therapeutic guidelines must often limit or exclude clinically available GABAR potentiators, despite their high efficacy, good biodistribution, and favorable molecular properties.

Large ischemic core defined by visually assessed ASPECTS predicts functional outcomes comparably accurate to automated CT perfusion in the 6-24 h window.

Introduction: Automated CT perfusion (aCTP) is commonly used to select patients with anterior circulation large vessel occlusion (aLVO) for endovascular treatment (EVT). The equivalence of visually assessed Non-contrast CT Alberta Stroke Program Early CT Scores (ASPECTS) and aCTP based selection in predicting favorable functional outcomes remains uncertain.

Patients And Methods: Retrospective multicenter study of adult aLVO patients from the Swiss Stroke Registry (2014-2021) treated with EVT or best medical treatment 6-24 h after stroke onset.

From the Ground Up: Stakeholder Perspectives on Housing Interventions to Reduce Environmentally Mediated Infections.

Background: Housing conditions are intrinsically linked to human health, with inadequate housing potentially increasing exposure to environmentally mediated pathogens. Housing interventions that aim to improve housing and reduce environmentally mediated infections, such as finished floors and housing upgrades for vector-borne diseases, remain relatively under-explored as health interventions. This study explored facilitators of and barriers to funding, implementing, and scaling up housing improvements as health interventions to reduce environmentally mediated infectious diseases.

Applying kitchen compost promoted soil chrysene degradation by optimizing microbial community structure.

Chrysene, as a high molecular weight polycyclic aromatic hydrocarbon (PAH), has become an important factor in degrading soil quality and constraining the safe production of food crops. Compost has been widely used to amend contaminated soil. However, to date, the main components of kitchen compost that enhance the biodegradation of chrysene in the soil remain unidentified.

Vapor flux induced by temperature gradient is responsible for providing liquid water to hypoliths.

Commonly comprised of cyanobacteria, algae, bacteria and fungi, hypolithic communities inhabit the underside of cobblestones and pebbles in diverse desert biomes. Notwithstanding their abundance and widespread geographic distribution and their growth in the driest regions on Earth, the source of water supporting these communities remains puzzling. Adding to the puzzle is the presence of cyanobacteria that require liquid water for net photosynthesis.

A comparative study of the developability of full-length antibodies, fragments, and bispecific formats reveals higher stability risks for engineered constructs.

Engineered antibody formats, such as antibody fragments and bispecifics, have the potential to offer improved therapeutic efficacy compared to traditional full-length monoclonal antibodies (mAbs). However, the translation of these non-natural molecules into successful therapeutics can be hampered by developability challenges. Here, we systematically analyzed 64 different antibody constructs targeting Tumor Necrosis Factor (TNF) which cover 8 distinct molecular format families, encompassing full-length antibodies, various types of single chain variable fragments, and bispecifics.

Ultra-uniform perovskite crystals formed in the presence of tetrabutylammonium bistriflimide afford efficient and stable perovskite solar cells.

Compositional engineering of organic-inorganic metal halide perovskite allows for improved optoelectrical properties, however, phase segregation occurs during crystal nucleation and limits perovskite solar cell device performance. Herein, we show that by applying tetrabutylammonium bistriflimide as an additive in the perovskite precursor solution, ultra-uniform perovskite crystals are obtained, which effectively increases device performance. As a result, power conversion efficiencies (PCEs) of 24.

The pace of life for forest trees.

Tree growth and longevity trade-offs fundamentally shape the terrestrial carbon balance. Yet, we lack a unified understanding of how such trade-offs vary across the world's forests. By mapping life history traits for a wide range of species across the Americas, we reveal considerable variation in life expectancies from 10 centimeters in diameter (ranging from 1.

Large-Scale Mechanistic Models of Brain Circuits with Biophysically and Morphologically Detailed Neurons.

Understanding the brain requires studying its multiscale interactions from molecules to networks. The increasing availability of large-scale datasets detailing brain circuit composition, connectivity, and activity is transforming neuroscience. However, integrating and interpreting this data remains challenging.

Consequences of Local Conspecific Density Effects for Plant Diversity and Community Dynamics.

Conspecific density dependence (CDD) in plant populations is widespread, most likely caused by local-scale biotic interactions, and has potentially important implications for biodiversity, community composition, and ecosystem processes. However, progress in this important area of ecology has been hindered by differing viewpoints on CDD across subfields in ecology, lack of synthesis across CDD-related frameworks, and misunderstandings about how empirical measurements of local CDD fit within the context of broader ecological theories on community assembly and diversity maintenance. Here, we propose a conceptual synthesis of local-scale CDD and its causes, including species-specific antagonistic and mutualistic interactions.

Stable Isotope Labelling Reveals Water and Carbon Fluxes in Temperate Tree Saplings Before Budbreak.

Despite considerable experimental effort, the physiological mechanisms governing temperate tree species' water and carbon dynamics before the onset of the growing period remain poorly understood. We applied H-enriched water during winter dormancy to the soil of four potted European tree species. After 8 weeks of chilling, hydrogen isotopes in stem, twig and bud water were measured six times during 2 consecutive weeks of forcing conditions (Experiment 1).

TMX5/TXNDC15, a natural trapping mutant of the PDI family is a client of the proteostatic factor ERp44.

The ER is the organelle of nucleated cells that produces lipids, sugars, and proteins. More than 20 ER-resident members of the protein disulfide isomerase (PDI) family regulate formation, isomerization, and disassembly of covalent bonds in newly synthesized polypeptides. The PDI family includes few membrane-bound members.

Long-term impact of maternal prenatal smoking on EEG brain activity and internalizing/externalizing problem symptoms in young adults.

Objective: The objective of this study was to investigate the impact of smoking during pregnancy on the development of the child. While previous research has established its detrimental effects during early childhood, understanding potential long-term consequences into adulthood remains limited. This study specifically aimed to explore the influence of prenatal smoking exposure on brain activity and whether internalizing and externalizing symptoms are influenced by prenatal smoking exposure in a cohort of young adults.

Meditating on psychedelics. A randomized placebo-controlled study of DMT and harmine in a mindfulness retreat.

Background: In recent years, both meditation and psychedelics have attracted rapidly increasing scientific interest. While the current state of evidence suggests the promising potential of psychedelics, such as psilocybin, to enhance meditative training, it remains equivocal whether these effects are specifically bound to psilocybin or if other classical psychedelics might show synergistic effects with meditation practice. One particularly promising candidate is -dimethyltryptamine (DMT), an active ingredient of ayahuasca.

Diagnostic Benefit of Molecular Imaging in Patients Undergoing Heart Valve Surgery for Infective Endocarditis.

(1) Background: The successful treatment of infective endocarditis (IE) relies on detecting causative pathogens to administer targeted antibiotic therapy. In addition to standard microbiological cultivation of pathogens from tissue obtained during heart valve surgery, the potential of molecular biological methods was evaluated. (2) Methods: A retrospective study was performed on heart valve tissue from 207 patients who underwent heart valve surgery for IE.