Proteins Implicated in the Reduced Virulence of and Mutants in Osteomyelitis.

Using a murine osteomyelitis model, we recently demonstrated that and mutants generated in the USA300 strain LAC are attenuated to a greater extent than an isogenic mutant and that this can be attributed to a significant extent to the increased production of extracellular proteases in both mutants. Based on this, we used a mass-based proteomics approach to compare the proteomes of LAC, its isogenic , , and mutants, and isogenic derivatives of all four of these strains unable to produce the extracellular proteases aureolysin, SspA, SspB, ScpA, or SplA-F. This allowed us to identify proteins that were present in reduced amounts in , and / mutants owing to the increased production of extracellular proteases.

A Comprehensive Review of the Diagnostics for Pediatric Tuberculosis Based on Assay Time, Ease of Operation, and Performance.

Pediatric tuberculosis (TB) is still challenged by several diagnostic bottlenecks, imposing a high TB burden in low- and middle-income countries (LMICs). Diagnostic turnaround time (TAT) and ease of operation to suit resource-limited settings are critical aspects that determine early treatment and influence morbidity and mortality. Based on TAT and ease of operation, this article reviews the evolving landscape of TB diagnostics, from traditional methods like microscopy and culture to cutting-edge molecular techniques and biomarker-based approaches.

Fecal Microbiome and Metabolomic Profiles of Mixed-Fed Infants Are More Similar to Formula-Fed than Breastfed Infants.

Many infants consume both human milk and infant formula (mixed-fed); however, few studies have investigated how mixed feeding affects the gut microbiome composition and metabolic profiles compared to exclusive breastfeeding or formula feeding. Herein, how delivery mode and early nutrition affect the microbiome and metabolome of 6-week-old infants in the STRONG Kids2 cohort was investigated. Fecal samples were collected from exclusively breastfed (BF; n = 25), formula-fed (FF; n = 25) or mixed-fed (MF; n = 25) participants.

Gelatin Nanoemulsion-Based Co-Delivery of Terbinafine and Essential Oils for Treatment of Biofilms.

Fungal infections represent a significant global health challenge. is a particularly widespread pathogen, with both molecular and biofilm-based mechanisms making it resistant to or tolerant of available antifungal drugs. This study reports a combination therapy, active against , utilizing terbinafine and essential oils incorporated into a gelatin-based nanoemulsion system (T-GNE).

Comprehensive Analysis of the Proteome of Wild-Type and 5Δ Cells in Response to Bisphenol A (BPA) Exposure.

Bisphenol A, an endocrine-disrupting compound, is widely used in the industrial production of plastic products. Despite increasing concerns about its harmful effects on human health, animals, and the environment, the use of BPA has been banned only in infant products, and its effects on cellular processes are not fully understood. To investigate the impact of BPA on eukaryotic cells, we analyzed the proteome changes of wild-type and -deleted strains exposed to different doses of BPA using sample multiplexing-based proteomics.

The Structural, Biophysical, and Antigenic Characterization of the Goose Parvovirus Capsid.

Goose parvovirus (GPV) is an etiological agent of Derzsy's disease, afflicting geese and Muscovy ducks worldwide. Its high mortality rate among goslings and ducklings causes large losses to the waterfowl industry. Toward molecular and structural characterization, virus-like particles (VLPs) of GPV were produced, and the capsid structure was determined by cryogenic electron microscopy (cryo-EM) at a resolution of 2.

Alcohol Use Disorder and the Gut-Brain Axis: A Narrative Review of the Role of Gut Microbiota and Implications for Treatment.

Alcohol use disorder (AUD) affects millions of people worldwide and can lead to deleterious physical and social consequences. Recent research has highlighted not only the effect of alcohol on the gut microbiome, but also the role of the gut microbiome and the gut-brain axis in the development and maintenance of alcohol use disorder. This review provides an overview of the reciprocal relationship between alcohol consumption and the gut microbiome, including the effects of alcohol on gut microbial composition, changes in gut microbial metabolites in response to alcohol consumption, and how gut microbial metabolites may modulate alcohol use behavior.

Spore-Derived Isolates from a Single Basidiocarp of Bioluminescent Reveal Multifaceted Phenotypic and Physiological Variations.

The fungal genus is noted for its bioluminescence and the production of biologically active secondary metabolites. We isolated 47 fungal strains of germinated from spores of a single mushroom. We first noted a high degree of variation in the outward appearances in radial growth and pigmentation among the cultures.

The Effect of Mono- and Di-Saccharides on the Microbiome of Dairy Cow Manure and Its Odor.

In a previous experiment, we showed that the odor of manure slurries could be improved by anaerobic incubation with the sugars glucose, lactose, and sucrose. This improvement was due to reductions in the concentrations of malodorants, including dimethyl disulfide, -cresol, -ethylphenol, indole, and skatole, and a shift to the production of fruity esters, including ethyl butyrate and propyl propanoate. Due to large concentrations of lactic acid produced by the sugar-amended manure slurries, we inferred that lactic acid bacteria were involved in improving the manure slurry odor.

Enhanced Detection of Viable O157:H7 in Romaine Lettuce Wash Water Using On-Filter Propidium Monoazide-Quantitative PCR.

Accurate detection of viable O157:H7 in fresh produce wash water is critical for ensuring food safety and mitigating foodborne illnesses. This study evaluated an optimized on-filter propidium monoazide (PMA)-quantitative PCR (qPCR) method for detecting viable O157:H7 in romaine lettuce wash water, involving PMA pretreatment on a filter to block DNA amplification from dead cells. The method consistently detected viable cells across chemical oxygen demand (COD) levels of 1000 and 200 mg O/L, with no significant differences ( > 0.

Feeding Expressed Breast Milk Alters the Microbial Network of Breast Milk and Increases Breast Milk Microbiome Diversity over Time.

Breastfeeding supplies nutrition, immunity, and hormonal cues to infants. Feeding expressed breast milk may result in de-phased milk production and feeding times, which distort the real-time circadian cues carried by breast milk. We hypothesized that providing expressed breast milk alters the microbiotas of both breast milk and the infant's gut.

Further Development of SAMPDI-3D: A Machine Learning Method for Predicting Binding Free Energy Changes Caused by Mutations in Either Protein or DNA.

Background/objectives: Predicting the effects of protein and DNA mutations on the binding free energy of protein-DNA complexes is crucial for understanding how DNA variants impact wild-type cellular function. As many cellular interactions involve protein-DNA binding, accurately predicting changes in binding free energy (ΔΔG) is valuable for distinguishing pathogenic mutations from benign ones.

Methods: This study describes the development and optimization of the SAMPDI-3Dv2 machine learning method, which is trained on an expanded database of experimentally measured ΔΔGs.

Casein Kinase I Protein Hrr25 Is Required for Pin4 Phosphorylation and Mediates Cell Wall Integrity Signaling in .

Background: Casein kinase I protein Hrr25 plays important roles in many cellular processes, including autophagy, vesicular trafficking, ribosome biogenesis, mitochondrial biogenesis, and the DNA damage response in . Pin4 is a multi-phosphorylated protein that has been reported to be involved in the cell wall integrity (CWI) pathway and DNA damage response. Pin4 was reported to interact with Hrr25 in yeast two-hybrid and large-scale pulldown assays.

Integrative Analysis of Radiation-Induced Senescence-Associated Secretory Phenotype Factors in Kidney Cancer Progression.

Background: Ionizing radiation (IR) is a well-known inducer of cellular senescence and the senescence-associated secretory phenotype (SASP). SASP factors play dual roles in cancer, either promoting or inhibiting its development. This study investigates IR-induced SASP factors specifically secreted by renal cortical epithelial (RCE) cells and their role in promoting renal cell carcinoma (RCC) progression.

Missing Regulation Between Genetic Association and Transcriptional Abundance for Hypercholesterolemia Genes.

Low-density lipoprotein cholesterol (LDL-C) is a well-established risk factor for cardiovascular disease, and it plays a causal role in the development of atherosclerosis. Genome-wide association studies (GWASs) have successfully identified hundreds of genetic variants associated with LDL-C. Most of these risk loci fall in non-coding regions of the genome, and it is unclear how these non-coding variants affect circulating lipid levels.

Chromosome 4 Duplication Associated with Strabismus Leads to Gene Expression Changes in iPSC-Derived Cortical Neurons.

Background/objectives: Strabismus is the most common ocular disorder of childhood. Three rare, recurrent genetic duplications have been associated with both esotropia and exotropia, but the mechanisms by which they contribute to strabismus are unknown. This work aims to investigate the mechanisms of the smallest of the three, a 23 kb duplication on chromosome 4 (hg38|4:25,554,985-25,578,843).

The X-Linked Tumor Suppressor TSPX Regulates Genes Involved in the EGFR Signaling Pathway and Cell Viability to Suppress Lung Adenocarcinoma.

TSPX is an X-linked tumor suppressor that was initially identified in non-small cell lung cancer (NSCLC) cell lines. However, its expression patterns and downstream mechanisms in NSCLC remain unclear. This study aims to investigate the functions of TSPX in NSCLC by identifying its potential downstream targets and their correlation with clinical outcomes.

Quantitative Trait Loci for Phenology, Yield, and Phosphorus Use Efficiency in Cowpea.

Background/objectives: Cowpea is an important legume crop in sub-Saharan Africa (SSA) and beyond. However, access to phosphorus (P), a critical element for plant growth and development, is a significant constraint in SSA. Thus, it is essential to have high P-use efficiency varieties to achieve increased yields in environments where little-to- no phosphate fertilizers are applied.

The Plethora of RNA-Protein Interactions Model a Basis for RNA Therapies.

The notion of RNA-based therapeutics has gained wide attractions in both academic and commercial institutions. RNA is a polymer of nucleic acids that has been proven to be impressively versatile, dating to its hypothesized RNA World origins, evidenced by its enzymatic roles in facilitating DNA replication, mRNA decay, and protein synthesis. This is underscored through the activities of riboswitches, spliceosomes, ribosomes, and telomerases.

Production of Amyloid-β in the Aβ-Protein-Precursor Proteolytic Pathway Is Discontinued or Severely Suppressed in Alzheimer's Disease-Affected Neurons: Contesting the 'Obvious'.

A notion of the continuous production of amyloid-β (Aβ) via the proteolysis of Aβ-protein-precursor (AβPP) in Alzheimer's disease (AD)-affected neurons constitutes both a cornerstone and an article of faith in the Alzheimer's research field. The present Perspective challenges this assumption. It analyses the relevant empirical data and reaches an unexpected conclusion, namely that in AD-afflicted neurons, the production of AβPP-derived Aβ is either discontinued or severely suppressed, a concept that, if proven, would fundamentally change our understanding of the disease.

Prevalence of IMPG1 and IMPG2 Mutations Leading to Retinitis Pigmentosa or Vitelliform Macular Dystrophy in a Cohort of Patients with Inherited Retinal Dystrophies.

Background/objectives: The interphotoreceptor matrix proteoglycans 1 and 2 (IMPG1 and IMPG2) are two interdependent proteoglycans of the interphotoreceptor matrix (IPM). Mutations in IMPG1 or IMPG2 are linked to retinal diseases such as retinitis pigmentosa (RP) and vitelliform macular dystrophy (VMD), yet the specific mutations responsible for each condition remain undefined. This study identifies mutations in IMPG1 and IMPG2 linked to either RP or VMD.

Screening Methods to Discover the FDA-Approved Cancer Drug Encorafenib as Optimally Selective for Metallothionein Gene Loss Ovarian Cancer.

Background/objectives: All 11 metallothionein protein-coding genes are located on human chromosome 16q13. It is unique among human genetics to have an entire pathway's genes clustered in a short chromosomal region. Since solid tumors, particularly high-grade serous ovarian cancer (HGSC), exhibit high rates of monoallelic aneuploidy, this region is commonly lost.

Expanding the Mutation Spectrum for Inherited Retinal Diseases.

Background/objectives: Inherited retinal diseases (IRDs) represent a diverse group of genetic disorders characterized by degeneration of the retina, leading to visual impairment and blindness. IRDs are heterogeneous, sharing common clinical features that can be difficult to diagnose without knowing the genetic basis of the disease. To improve diagnostic accuracy and advance understanding of disease mechanisms, genetic testing was performed for 103 unrelated patients with an IRD at a single clinical site between 30 August 2022 and 5 February 2024.

Sleep Genetics and Cognitive Changes over Time: The Moderating Effect of Age and the Role of Brain.

Background: Sleep plays a crucial role in cognitive performance and cognitive changes in aging. In the current study, we investigated the role of sleep duration genetics in cognitive changes over time and the moderating effect of age.

Methods: Participants were drawn from the Reference Abilities Neural Network and the Cognitive Reserve studies of Columbia University.

Cell Type Specific Suppression of Hyper-Recombination by Human RAD18 Is Linked to Proliferating Cell Nuclear Antigen K164 Ubiquitination.

RAD18 is a conserved eukaryotic E3 ubiquitin ligase that promotes genome stability through multiple pathways. One of these is gap-filling DNA synthesis at active replication forks and in post-replicative DNA. RAD18 also regulates homologous recombination (HR) repair of DNA breaks; however, the current literature describing the contribution of RAD18 to HR in mammalian systems has not reached a consensus.