Broad substrate scope C-C oxidation in cyclodipeptides catalysed by a flavin-dependent filament.

Cyclic dipeptides are produced by organisms across all domains of life, with many exhibiting anticancer and antimicrobial properties. Oxidations are often key to their biological activities, particularly C-C bond oxidation catalysed by tailoring enzymes including cyclodipeptide oxidases. These flavin-dependent enzymes are underexplored due to their intricate three-dimensional arrangement involving multiple copies of two distinct small subunits, and mechanistic details underlying substrate selection and catalysis are lacking.

Daily rhythm in DNA methylation and the effect of total sleep deprivation.

Numerous hormones and genes exhibit diurnal 24-hr rhythms that can also be affected by sleep deprivation. Here we studied diurnal rhythms in DNA methylation under a 24-hr sleep/wake cycle and a subsequent 29 hr of continual wakefulness (1 night of sleep deprivation). Fifteen healthy men (19-35 years) spent 3 days/nights in a sleep laboratory: (1) adaptation; (2) baseline; (3) total sleep deprivation day/night.

The fattening speed: Understanding the impact of internet speed on obesity, and the mediating role of sedentary behaviour.

We examine the impact of access to high-speed internet on obesity. Using 14 waves of longitudinal data from the Household, Income and Labour Dynamics in Australia (HILDA) survey and a newly constructed dataset on the rollout and adoption rate of the National Broadband Network (NBN) across Australian postcodes, we find that access to high-speed internet has a positive effect on obesity. Specifically, our preferred instrumental variable estimates, which predict the variation in timing and location of internet access upgrades, suggest that a 1 % increase in the proportion of a postcode that has access to NBN is associated with a 1.

Association between volume and cost in low-resection volume regions: a population-level study on pancreatoduodenectomy for pancreatic cancer patients.

Background: Pancreatoduodenectomy (PD) is a highly complex, invasive, and costly surgical procedure. Limited evidence on the PD volume-cost relationship in countries with a low population density exists. This study aimed to investigate this issue in Australia.

Hospital readmission after surviving sepsis: A systematic review of readmission reasons and meta-analysis of readmission rates.

Purpose: To review the evidence regarding hospital readmission diagnoses and analyse related readmission rates following a sepsis admission.

Methods: Five databases, grey literature, and selected article reference lists were searched in May and June 2024. Included studies investigated sepsis survivor readmissions and reported readmission diagnoses and rates.

Pulsed EPR Methods in the Angstrom to Nanometre Scale Shed Light on the Conformational Flexibility of a Fluoride Riboswitch.

Riboswitches control gene regulation upon external stimuli such as environmental factors or ligand binding. The fluoride sensing riboswitch from Thermotoga petrophila is a complex regulatory RNA proposed to be involved in resistance to F cytotoxicity. The details of structure and dynamics underpinning the regulatory mechanism are currently debated.

Internet and Gambling: Insights from Australia's NBN Rollout.

Gambling is a well-known leisure activity that leads to significant consequences when consumed excessively. We provide an analysis of the impact of access to faster and more reliable internet connection on gambling. We rely on variations in the rollout of Australia's largest infrastructure project, National Broadband Network (NBN) installation, to measure internet speed at the postcode level.

EPR spectroscopic characterisation of native Cu-binding sites in human serum albumin.

Human serum albumin (HSA) is the most abundant plasma protein, which functions to transport a large range of ligands within the circulation. These interactions have important implications for human health and disease. The primary binding site for Cu ions on HSA is known to be the so-called amino-terminal Cu and Ni binding (ATCUN) motif.

Risk factors for smoking in adolescence: evidence from a cross-sectional survey in Switzerland.

Background: Cigarette smoking during adolescence is a major public health concern with far-reaching health implications. Adolescents who smoke are at an increased risk of developing long-term health problems and are more likely to continue smoking into adulthood. Therefore, it is vital to identify and understand the risk factors that contribute to adolescent smoking - which in turn facilitate the development of targeted prevention and intervention programs.

Monitoring the conformational ensemble and lipid environment of a mechanosensitive channel under cyclodextrin-induced membrane tension.

Membrane forces shift the equilibria of mechanosensitive channels enabling them to convert mechanical cues into electrical signals. Molecular tools to stabilize and methods to capture their highly dynamic states are lacking. Cyclodextrins can mimic tension through the sequestering of lipids from membranes.

CRISPR antiphage defence mediated by the cyclic nucleotide-binding membrane protein Csx23.

CRISPR-Cas provides adaptive immunity in prokaryotes. Type III CRISPR systems detect invading RNA and activate the catalytic Cas10 subunit, which generates a range of nucleotide second messengers to signal infection. These molecules bind and activate a diverse range of effector proteins that provide immunity by degrading viral components and/or by disturbing key aspects of cellular metabolism to slow down viral replication.

Spectroscopically Orthogonal Labelling to Disentangle Site-Specific Nitroxide Label Distributions.

Unlabelled: Biomolecular applications of pulse dipolar electron paramagnetic resonance spectroscopy (PDS) are becoming increasingly valuable in structural biology. Site-directed spin labelling of proteins is routinely performed using nitroxides, with paramagnetic metal ions and other organic radicals gaining popularity as alternative spin centres. Spectroscopically orthogonal spin labelling using different types of labels potentially increases the information content available from a single sample.

Pulse Dipolar Electron Paramagnetic Resonance Spectroscopy Distance Measurements at Low Nanomolar Concentrations: The Cu-Trityl Case.

Recent sensitivity enhancements in pulse dipolar electron paramagnetic resonance spectroscopy (PDS) have afforded distance measurements at submicromolar spin concentrations. This development opens the path for new science as more biomolecular systems can be investigated at their respective physiological concentrations. Here, we demonstrate that the combination of orthogonal spin-labeling using Cu ions and trityl yields a >3-fold increase in sensitivity compared to that of the established Cu-nitroxide labeling strategy.

Usability of Clinical Decision Support for Adult Sepsis Detection.

This review summarized current literature investigating the usability of computerized clinical decision support (CCDS) systems for the early detection of sepsis in adult inpatients. Ten databases were systematically searched, identifying nine studies. Overall, the lack of good usability testing and the critical need for setting-specific testing were highlighted, as each different CCDS and unique hospital environment brings a diverse range of usability concerns that must be managed for CCDS systems to effectively improve patient care.

START NOW: a cognitive behavioral skills training for adolescent girls with conduct or oppositional defiant disorder - a randomized clinical trial.

Background: Conduct disorder (CD) and oppositional defiant disorder (ODD) both convey a high risk for maladjustment later in life and are understudied in girls. Here, we aimed at confirming the efficacy of START NOW, a cognitive-behavioral, dialectical behavior therapy-oriented skills training program aiming to enhance emotion regulation skills, interpersonal and psychosocial adjustment, adapted for female adolescents with CD or ODD.

Methods: A total of 127 girls were included in this prospective, cluster randomized, multi-center, parallel group, quasi-randomized, controlled phase III trial, which tested the efficacy of START NOW (n = 72) compared with standard care (treatment as usual, TAU, n = 55).

Activation of Csm6 ribonuclease by cyclic nucleotide binding: in an emergency, twist to open.

Type III CRISPR systems synthesize cyclic oligoadenylate (cOA) second messengers as part of a multi-faceted immune response against invading mobile genetic elements (MGEs). cOA activates non-specific CRISPR ancillary defence nucleases to create a hostile environment for MGE replication. Csm6 ribonucleases bind cOA using a CARF (CRISPR-associated Rossmann Fold) domain, resulting in activation of a fused HEPN (Higher Eukaryotes and Prokaryotes Nucleotide binding) ribonuclease domain.

Enhanced sensitivity for pulse dipolar EPR spectroscopy using variable-time RIDME.

Pulse dipolar EPR spectroscopy (PDS) measurements are an important complementary tool in structural biology and are increasingly applied to macromolecular assemblies implicated in human health and disease at physiological concentrations. This requires ever higher sensitivity, and recent advances have driven PDS measurements into the mid-nanomolar concentration regime, though optimization and acquisition of such measurements remains experimentally demanding and time expensive. One important consideration is that constant-time acquisition represents a hard limit for measurement sensitivity, depending on the maximum measured distance.

Diagnosis and Treatment of Invasive Aspergillosis Caused by Non- spp.

With increasing frequency, clinical and laboratory-based mycologists are consulted on invasive fungal diseases caused by rare fungal species. This review aims to give an overview of the management of invasive aspergillosis (IA) caused by non- spp.-namely , , and -including diagnostic and therapeutic differences and similarities to .

Machine learning estimation of human body time using metabolomic profiling.

Circadian rhythms influence physiology, metabolism, and molecular processes in the human body. Estimation of individual body time (circadian phase) is therefore highly relevant for individual optimization of behavior (sleep, meals, sports), diagnostic sampling, medical treatment, and for treatment of circadian rhythm disorders. Here, we provide a partial least squares regression (PLSR) machine learning approach that uses plasma-derived metabolomics data in one or more samples to estimate dim light melatonin onset (DLMO) as a proxy for circadian phase of the human body.

Combining C-reactive protein and quick sequential organ failure assessment (qSOFA) to improve prognostic accuracy for sepsis and mortality in adult inpatients: A systematic review.

Background And Aims: Infections are common in hospitals, and if mismanaged can develop into sepsis, a leading cause of death and disability worldwide. This study aimed to examine whether combining C-reactive protein (CRP) with the quick sequential organ failure assessment (qSOFA) improves its accuracy for predicting mortality and sepsis in adult inpatients.

Methods: PubMed, MEDLINE, EMBASE, Scopus, Web of Science, Science Direct, CINAHL, Open Grey, Grey Literature Report, and the Clinical Trials registry were searched using CRP and qSOFA search terms.

[Patient satisfaction with psychiatric day-care and inpatient treatment: Effects on physical and mental health].

Introduction: Quality assessment from the patient's point of view makes it possible to identify negative quality developments at an early stage. The focus is not on the medical result, but on what the patient wants. Correlations between patient satisfaction and physical and psychological treatment outcome were already shown in the 1990s.

Investigating Native Metal Ion Binding Sites in Mammalian Histidine-Rich Glycoprotein.

Mammalian histidine-rich glycoprotein (HRG) is a highly versatile and abundant blood plasma glycoprotein with a diverse range of ligands that is involved in regulating many essential biological processes, including coagulation, cell adhesion, and angiogenesis. Despite its biomedical importance, structural information on the multi-domain protein is sparse, not least due to intrinsically disordered regions that elude high-resolution structural characterization. Binding of divalent metal ions, particularly Zn, to multiple sites within the HRG protein is of critical functional importance and exerts a regulatory role.

When information security depends on font size: how the saliency of warnings affects protection behavior.

Prior research on how to improve the effectiveness of information security warnings has predominantly focused on either the informational content of warnings or their visual saliency. In an online experiment ( = 1'486), we disentangle the effect of both manipulations and demonstrate that both factors simultaneously influence decision making. Our data indicate that the proportion of people who engage in protection behavior can be increased by roughly 65% by making a particular warning message more visually salient (i.

Emotion processing in maltreated boys and girls: Evidence for latent vulnerability.

Evidence of alterations in emotion processing in maltreated youth has been hypothesized to reflect latent vulnerability for psychopathology. However, previous studies have not systematically examined the influence of psychopathology on the results. Here, we examined emotion recognition and learning in youth who differed in terms of presence vs.