The mammalian Ire1 inhibitor, 4µ8C, exhibits broad anti- activity and in a treatment model of fungal keratitis.

Objective: The fungal unfolded protein response consists of a two-component relay in which the ER-bound sensor, IreA, splices and activates the mRNA of the transcription factor, HacA. Previously, we demonstrated that is essential for virulence in a murine model of fungal keratitis (FK), suggesting the pathway could serve as a therapeutic target. Here we investigate the antifungal properties of known inhibitors of the mammalian Ire1 protein both and in a treatment model of FK.

The mammalian Ire1 inhibitor, 4μ8C, exhibits broad anti- activity and in a treatment model of fungal keratitis.

Objective: The fungal unfolded protein response consists of a two-component relay in which the ER-bound sensor, IreA, splices and activates the mRNA of the transcription factor, HacA. Previously, we demonstrated that is essential for virulence in a murine model of fungal keratitis (FK), suggesting the pathway could serve as a therapeutic target. Here we investigate the antifungal properties of known inhibitors of the mammalian Ire1 protein both and in a treatment model of FK.

Recycling and 3D-Printing Biodegradable Membranes for Gas Separation-toward a Membrane Circular Economy.

Polymer membranes employed in gas separation play a pivotal role in advancing environmental sustainability, energy production, and gas purification technologies. Despite their significance, the current design and manufacturing of these membranes lack cradle-to-cradle approaches, contributing to plastic waste pollution. This study explores emerging solutions, including the use of biodegradable biopolymers such as polyhydroxybutyrate (PHB) and membrane recycling, with a focus on the specific impact of mechanical recycling on the performance of biodegradable gas separation membranes.

Kin-recognition and predation shape collective behaviors in the cannibalistic nematode Pristionchus pacificus.

Kin-recognition is observed across diverse species forming an important behavioral adaptation influencing organismal interactions. In many species, the molecular mechanisms involved are difficult to characterize, but in the nematode Pristionchus pacificus molecular components regulating its kin-recognition system have been identified. These determine its predatory behaviors towards other con-specifics which prevents the killing and cannibalization of kin.

The Aspergillus fumigatus UPR is variably activated across nutrient and host environments and is critical for the establishment of corneal infection.

The Aspergillus fumigatus unfolded protein response (UPR) is a two-component relay consisting of the ER-bound IreA protein, which splices and activates the mRNA of the transcription factor HacA. Spliced hacA accumulates under conditions of acute ER stress in vitro, and UPR null mutants are hypovirulent in a murine model of invasive pulmonary infection. In this report, we demonstrate that a hacA deletion mutant (ΔhacA) is furthermore avirulent in a model of fungal keratitis, a corneal infection, and an important cause of ocular morbidity and unilateral blindness worldwide.

Divergent combinations of cis-regulatory elements control the evolution of phenotypic plasticity.

The widespread occurrence of phenotypic plasticity across all domains of life demonstrates its evolutionary significance. However, how plasticity itself evolves and how it contributes to evolution is poorly understood. Here, we investigate the predatory nematode Pristionchus pacificus with its feeding structure plasticity using recombinant-inbred-line and quantitative-trait-locus (QTL) analyses between natural isolates.

Rapid Transition from a High-Fat, High-Fructose to a Low-Fat, Low-Fructose Diet Reverses Gains in Bone Mass and Strength.

Purpose: Obesity is thought to negatively impact bone quality and strength despite improving bone mineral density. We hypothesized that 1) continuous consumption of a high-fat, high-sugar (HFS) diet would impair bone quality and strength, and 2) a change from an HFS diet to a low-fat, low-sugar (LFS) would reverse HFS-induced impairments to bone quality and strength.

Methods: Six-week-old male C57Bl/6 mice ( n = 10/group) with access to a running wheel were randomized to an LFS diet or an HFS diet with simulated sugar-sweetened beverages (20% fructose in place of regular drinking water) for 13 wk.

Asymmetric membranes for gas separation: interfacial insights and manufacturing.

State-of-the-art gas separation membrane technologies combine the properties of polymers and other materials, such as metal-organic frameworks to yield mixed matrix membranes (MMM). Although, these membranes display an enhanced gas separation performance, when compared to pure polymer membranes; major challenges remain in their structure including, surface defects, uneven filler dispersion and incompatibility of constituting materials. Therefore, to avoid these structural issues posed by today's membrane manufacturing methodologies, we employed electrohydrodynamic emission and solution casting as a hybrid membrane manufacturing method, to produce ZIF-67/cellulose acetate asymmetric membranes with improved gas permeability and selectivity for CO/N, CO/CH, and O/N.

Neuroscience: Hedonic worms gorge on high-energy foods.

Cannabinoids can enhance the preference for calorific foods through hedonic feeding behaviors. A new study identifies and characterizes these indulgent behaviors in the nematode Caenorhabditis elegans, providing insights into the mechanisms of their regulation.

A host defense peptide mimetic, brilacidin, potentiates caspofungin antifungal activity against human pathogenic fungi.

Fungal infections cause more than 1.5 million deaths a year. Due to emerging antifungal drug resistance, novel strategies are urgently needed to combat life-threatening fungal diseases.

Sibling Resemblance in Physical Activity Levels: The Peruvian Sibling Study on Growth and Health.

Physical activity is associated with a host of positive health outcomes and is shaped by both genetic and environmental factors. We aim to: (1) estimate sibling resemblance in two physical activity phenotypes [total number of steps∙day and minutes for moderate steps per day (min∙day)]; and (2) investigate the joint associations of individual characteristics and shared natural environment with intra-pair sibling similarities in each phenotype. We sampled 247 biological siblings from 110 nuclear families, aged 6-17 years, from three Peruvian regions.

Evolution and Diversity of TGF-β Pathways are Linked with Novel Developmental and Behavioral Traits.

Transforming growth factor-β (TGF-β) signaling is essential for numerous biologic functions. It is a highly conserved pathway found in all metazoans including the nematode Caenorhabditis elegans, which has also been pivotal in identifying many components. Utilizing a comparative evolutionary approach, we explored TGF-β signaling in nine nematode species and revealed striking variability in TGF-β gene frequency across the lineage.

Genomic and Phenotypic Trait Variation of the Opportunistic Human Pathogen Aspergillus flavus and Its Close Relatives.

Fungal diseases affect millions of humans annually, yet fungal pathogens remain understudied. The mold Aspergillus flavus can cause both aspergillosis and fungal keratitis infections, but closely related species are not considered clinically relevant. To study the evolution of A.

Reduced Wheel Running via a High-Fat Diet Is Reversed by a Chow Diet with No Added Benefit from Fecal Microbial Transplants.

Purpose: Chronic overfeeding via a high-fat/high-sugar (HFHS) diet decreases wheel running and substantially alters the gut metabolome of C57BL/6J mice. In this study, we tested the hypothesis that fecal microbial transplants can modulate the effect of diet on wheel running.

Methods: Singly housed, 6-wk-old male C57BL/6J mice were fed either a grain-based diet (CHOW) or HFHS diet and provided a running wheel for 13 wk.

Physical Activity Impacts of an Activity-Friendly Community: A Natural Experiment Study Protocol.

Background: Stakeholders from multiple sectors are increasingly aware of the critical need for identifying sustainable interventions that promote healthy lifestyle behaviors. Activity-friendly communities (AFCs) have been known to provide opportunities for engaging in physical activity (PA) across the life course, which is a key to healthy living and healthy aging.

Purpose: Our purpose is to describe the study protocol developed for a research project that examines: (a) the short- and long-term changes in total levels and spatial and temporal patterns of PA after individuals move from non-AFCs to an AFC; and (b) what built and natural environmental factors lead to changes in PA resulting from such a move, either directly or indirectly (e.

Genomic integration of transgenes using UV irradiation in .

Transgenes are widely used throughout molecular biology for numerous applications. In stable transgenes are usually generated by microinjection into the germline establishing extrachromosomal arrays. Furthermore, numerous technologies exist to integrate transgenes into the genome.

Sibling Resemblances in Physical Fitness in Three Distinct Regions in Peru: The Peruvian Sibling Study on Growth and Health.

We estimated sibling resemblance in health-related physical fitness (PF) and examined how individual characteristics and shared natural environment accounted for sibling similarities. The sample comprised 656 sibling pairs and 102 triplets (6-15 years of age), from three geographical areas of Peru. PF components included morphological (waist circumference, sum of skinfolds), muscular (handgrip strength, standing long jump), and motor (shuttle-run).

Sex or cannibalism: Polyphenism and kin recognition control social action strategies in nematodes.

Resource polyphenisms, where single genotypes produce alternative feeding strategies in response to changing environments, are thought to be facilitators of evolutionary novelty. However, understanding the interplay between environment, morphology, and behavior and its significance is complex. We explore a radiation of nematodes with discrete polyphenic mouth forms and associated microbivorous versus cannibalistic traits.

Systems Exercise Genetics Research Design Standards.

It is clear, based on a deep scientific literature base, that genetic and genomic factors play significant roles in determining a wide range of sport and exercise characteristics including exercise endurance capacity, strength, daily physical activity levels, and trainability of both endurance and strength. Although the research field of exercise systems genetics has rapidly expanded over the past two decades, many researchers publishing in this field are not extensively trained in molecular biology or genomics techniques, sometimes creating gaps in generating high-quality and cutting-edge research for publication. As current or former Associate Editors for Medicine and Science in Sports and Exercise that have handled the majority of exercise genetics articles for Medicine and Science in Sports and Exercise in the past 15 yr, we have observed a large number of scientific manuscripts submitted for publication review that have exhibited significant flaws preventing their publication; flaws that often directly stem from a lack of knowledge regarding the "state-of-the-art" methods and accepted literature base that is rapidly changing as the field evolves.

Correction: Protein fractional synthesis rates within tissues of high- and low-active mice.

[This corrects the article DOI: 10.1371/journal.pone.

Protein fractional synthesis rates within tissues of high- and low-active mice.

With the rise in physical inactivity and its related diseases, it is necessary to understand the mechanisms involved in physical activity regulation. Biological factors regulating physical activity are studied to establish a possible target for improving the physical activity level. However, little is known about the role metabolism plays in physical activity regulation.

Mitochondrial DNA lesions and copy number are strain dependent in endurance-trained mice.

In this pilot work, we selected two inbred strains that respond well to endurance training (ET) (FVB/NJ, and SJL/J strains), and two strains that respond poorly (BALB/cByJ and NZW/LacJ), to determine the effect of a standardized ET treadmill program on mitochondrial and nuclear DNA (nucDNA) integrity, and mitochondrial DNA (mtDNA) copy number. DNA was isolated from plantaris muscles (n = 37) and a gene-specific quantitative PCR-based assay was used to measure DNA lesions and mtDNA copy number. Mean mtDNA lesions were not different within strains in the sedentary or exercise-trained states.