Epistasis at the cell surface: what is the role of Erg3 loss-of-function in acquired echinocandin resistance?

Echinocandins, which target the fungal β-1,3-glucan synthase (Fks), are essential for treating invasive fungal infections, yet resistance is increasingly reported. While resistance typically arises through mutations in Fks hotspots, emerging evidence suggests a contributing role of changes in membrane sterol composition due to mutations. Here, we present a clinical case of () in which combined mutations in and , but not alone, appear to confer echinocandin resistance.

The Human Mycobiome: Composition, Immune Interactions, and Impact on Disease.

The fungal component of microbiota, known as the mycobiome, inhabits different body niches such as the skin and the gastrointestinal, respiratory, and genitourinary tracts. Much information has been gained on the bacterial component of the human microbiota, but the mycobiome has remained somewhat elusive due to its sparsity, variability, susceptibility to environmental factors (e.g.

Wall incorporation of the β-1,3-glucan cross-linking protein Pir1 in the human pathogen Candida albicans is facilitated by the presence of two or more Pir repeat units.

The Pir1 protein in the prevalent pathogenic yeast Candidaalbicans has been hypothesized to be important for cellular integrity by crosslinking cell wall β-1,3-glucans. However, recent studies with deletion mutants have reported contrasting results concerning its actual importance for wall integrity. Here, we present functional characterization of the two members of the Pir family (Pir1 and Pir32) as well as protein structure modeling and mutagenesis studies to elucidate how Pir1, the most important family member, is incorporated into the cell wall.

Large reductions in tropical bird abundance attributable to heat extreme intensification.

Although species exhibit widespread sensitivity to environmental conditions, the extent to which human-driven climate change may have already altered their abundance remains unclear. Here we quantify the impact of climate change on bird populations from across the world by combining models of their response to environmental conditions with a climate attribution framework. We identify a dominant role of intensified heat extremes compared to changes in average temperature and precipitation.

Hierarchical network of thermal plumes and their dynamics in turbulent Rayleigh-Bénard convection.

The link between characteristic coherent structures and their statistical properties in turbulent flows remains largely unclear and is thus a central bottleneck for a better understanding of turbulent flows. Here, we demonstrate this link for the important problem of thermal convection. We show how the hierarchical plume network in the near-wall region of the flow, which becomes increasingly sparse with increasing distance away from the wall, is connected to the marginal stability of the thermal boundary layer and the resulting global heat transport.

Origin of Transitions Inversion in Rare-Earth Vanadates.

In correlated transition-metal oxides, orbital-ordering appears to always precede magnetic ordering (T_{N} View Article and Find Full Text PDF

Explaining and predicting the Southern Hemisphere eddy-driven jet.

The summertime eddy-driven jet (EDJ) in the Southern Hemisphere is a critical mediator between regional climate and large-scale phenomena, guiding synoptic systems that shape weather patterns. Uncertainties in global climate models (GCMs)-particularly in projecting changes in remote drivers like tropical warming, stratospheric polar vortex strengthening, and asymmetric tropical Pacific warming-hinder predictions of EDJ trends and associated regional outcomes. In this study, we develop a causal framework that combines observations, reanalysis datasets, and storylines estimated from the Coupled Model Intercomparison Project (CMIP) projections to attribute past EDJ changes and predict plausible future trajectories.

The interplay between homeostatic synaptic scaling and homeostatic structural plasticity maintains the robust firing rate of neural networks.

Critical network states and neural plasticity enable adaptive behavior in dynamic environments, supporting efficient information processing and experience-dependent learning. Synaptic-weight-based Hebbian plasticity and homeostatic synaptic scaling are key mechanisms that enable memory while stabilizing network dynamics. However, the role of structural plasticity as a homeostatic mechanism remains less consistently reported, particularly under activity inhibition, leading to an incomplete understanding of its functional impact.

Synergistic risks of ambient air particulate matter and ozone exposure on low birth weight: An 11-year longitudinal Chinese maternity cohort study.

Observational epidemiological studies have demonstrated that maternal exposure to air pollution increases the risk of adverse pregnancy outcomes. However, interactions among multiple environmental exposures remain underexplored. In this study, we performed an epidemiological analysis on 147,979 pregnant women recruited from nine provinces in southeastern China between 2013 and 2023, focusing on the risk of low birth weight (LBW).

Newly Developed Structure-Based Methods Do Not Outperform Standard Sequence-Based Methods for Large-Scale Phylogenomics.

Recent developments in protein structure prediction have allowed the use of this previously limited source of information at genome-wide scales. It has been proposed that the use of structural information may offer advantages over sequences in phylogenetic reconstruction, due to their slower rate of evolution and direct correlation to function. Here, we examined how recently developed methods for structure-based homology search and tree reconstruction compare with current state-of-the-art sequence-based methods in reconstructing genome-wide collections of gene phylogenies (i.

Baboons at a Crossroads: Hybridisation Events and Genomic Links of Central Mozambique's Baboons With Papio Neighbors.

Objectives: Hybridisation plays a critical role in species evolution and is widespread among primates, particularly in the genus Papio. Several baboon hybridisation zones have been identified in Africa, with Gorongosa National Park in Mozambique being notable for chacma baboons exhibiting phenotypic and genomic traits of both chacma and yellow baboons. This study builds on earlier research by leveraging new genomic data to refine our understanding of the relationships between Central Mozambique baboons and other baboon populations, focusing on chacma, yellow, and kinda baboons.

The Effects of Forecasts on the Accuracy and Precision of Expectations.

Quantitative forecasts have become increasingly prominent as tools for aiding public understanding of sociopolitical trends. But how much, and what, do people learn from quantitative forecasts? In this note, we show through a preregistered survey experiment that real forecasts of the 2022 French presidential election significantly affect expectations of the election result. The direction of that effect hinges on how the forecast is presented.

Properties of Cosmic Lithium Isotopes Measured by the Alpha Magnetic Spectrometer.

We present the first measurement of cosmic-ray fluxes of ^{6} Li and ^{7} Li isotopes in the rigidity range from 1.9 to 25 GV. The measurements are based on 9.

Arbor-TVB: A Novel Multi-Scale Co-Simulation Framework with a Case Study on Neural-Level Seizure Generation and Whole-Brain Propagation.

Computational neuroscience has traditionally focused on isolated scales, limiting understanding of brain function across multiple levels. While microscopic models capture biophysical details of neurons, macroscopic models describe large-scale network dynamics. Integrating these scales, however, remains a significant challenge.

Multi-Omics Analysis of Experimentally Evolved Candida auris Isolates Reveals Modulation of Sterols, Sphingolipids, and Oxidative Stress in Acquired Amphotericin B Resistance.

Clinical isolates of Candida auris show a high prevalence of resistance to Amphotericin B (AmB)-an uncommon trait in most Candida species. Alterations in ergosterol biosynthesis can contribute to acquired AmB resistance in C. auris laboratory strains but are rarely seen in clinical isolates.

Simplified two-compartment neuron with calcium dynamics capturing brain-state specific apical-amplification, -isolation and -drive.

Mounting experimental evidence suggests the hypothesis that brain-state-specific neural mechanisms, supported by the connectome shaped by evolution, could play a crucial role in integrating past and contextual knowledge with the current, incoming flow of evidence (e.g., from sensory systems).

Agent-based modeling for realistic reproduction of human mobility and contact behavior to evaluate test and isolation strategies in epidemic infectious disease spread.

Agent-based models have proven to be useful tools in supporting decision-making processes in different application domains. The advent of modern computers and supercomputers has enabled these bottom-up approaches to realistically model human mobility and contact behavior. The COVID-19 pandemic showcased the urgent need for detailed and informative models that can answer research questions on transmission dynamics.

Formation of spatial vegetation patterns in heterogeneous environments.

Functioning of many resource-limited ecosystems is facilitated through spatial patterns. Patterns can indicate ecosystems productivity and resilience, but the interpretation of a pattern requires good understanding of its structure and underlying biophysical processes. Regular patterns are understood to form autogenously through self-organization, for which exogenous heterogeneities are negligible.

Outcomes and Predictors of Mortality in Patients with Severe COVID-19 and COPD admitted to ICU: A multicenter study.

Background: High mortality rates among patients with chronic obstructive pulmonary disease (COPD) admitted to intensive care units (ICUs) during the COVID-19 pandemic highlight the need for tailored clinical management strategies.

Study Design And Methods: Epidemiological, clinical, and laboratory data were collected in REDCap for 6,512 patients hospitalized with COVID-19 across 55 Spanish ICUs. Patients were stratified into three groups: those with COPD, those with other chronic respiratory diseases (CRD), and those without respiratory comorbidities (No CRD).

MACE-OFF: Short-Range Transferable Machine Learning Force Fields for Organic Molecules.

Classical empirical force fields have dominated biomolecular simulations for over 50 years. Although widely used in drug discovery, crystal structure prediction, and biomolecular dynamics, they generally lack the accuracy and transferability required for first-principles predictive modeling. In this paper, we introduce MACE-OFF, a series of short-range transferable force fields for organic molecules created using state-of-the-art machine learning technology and first-principles reference data computed with a high level of quantum mechanical theory.

Simple large-scale quantitative phenotyping and antimicrobial susceptibility testing with Q-PHAST.

The characterization of antimicrobial susceptibility and other relevant phenotypes in large collections of microbial isolates is a common need across research and clinical microbiology laboratories. Robotization provides unprecedented throughput but involves costs that are prohibitive for the average laboratory. Here, using affordable materials and open-source software, we developed Q-PHAST (Quantitative PHenotyping and Antimicrobial Susceptibility Testing), a unique solution for cost-effective, large-scale phenotyping in a standard microbiology laboratory.

Genetic Variants and Clinical Phenotyping in 39 Pediatric Patients with Neuropathic Pain.

Pathogenic variants in voltage-gated sodium channels (VGSCs) may cause disturbed sensory function, including small fiber neuropathy (SFN) in adults, but little is known about their role in children and adolescents.A total of 39 prospectively enrolled children (age 12.03 ± 4.

Towards developing an operational Indian ocean dipole warning system for Southeast Asia.

Two strong positive Indian Ocean Dipole (IOD) events in 2019 and 2023 led to multiple disasters over Southeast Asia, highlighting the need for warnings of IOD events. This paper presents a stock-take of the current criteria for IOD monitoring and prediction and describes the development of an IOD warning system for Southeast Asia. We examined how subjective choices such as observational datasets, baseline periods, and time averaging affect IOD event identification.

Refining Boolean models with the partial most permissive scheme.

Motivation: In systems biology, modeling strategies aim to decode how molecular components interact to generate dynamical behavior. Boolean modeling is more and more used, but the description of the dynamics generated by discrete variables with only two values may be too limited to capture certain dynamical properties. Multivalued logical models can overcome this limitation by allowing more than two levels for each component.

Adaptive-precision potentials for large-scale atomistic simulations.

Large-scale atomistic simulations rely on interatomic potentials, providing an efficient representation of atomic energies and forces. Modern machine-learning (ML) potentials provide the most precise representation compared to electronic structure calculations, while traditional potentials provide a less precise but computationally much faster representation and, thus, allow simulations of larger systems. We present a method to combine a traditional and a ML potential into a multi-resolution description, leading to an adaptive-precision potential with an optimum of performance and precision in large, complex atomistic systems.