Lack of TYK2 signaling enhances host resistance to Candida albicans skin infection.

Candida albicans is the most common human fungal pathogen, causing diseases ranging from local to life-threating systemic infections. Tyrosine kinase 2 (TYK2), a crucial mediator in several cytokine signaling pathways, has been associated with protective functions in various microbial infections. However, its specific contribution in the immune response to fungal infections has remained elusive.

HDAC1 fine-tunes Th17 polarization in vivo to restrain tissue damage in fungal infections.

Histone deacetylases (HDACs) contribute to shaping many aspects of T cell lineage functions in anti-infective surveillance; however, their role in fungus-specific immune responses remains poorly understood. Using a T cell-specific deletion of HDAC1, we uncover its critical role in limiting polarization toward Th17 by restricting expression of the cytokine receptors gp130 and transforming growth factor β receptor 2 (TGF-βRII) in a fungus-specific manner, thus limiting Stat3 and Smad2/3 signaling. Controlled release of interleukin-17A (IL-17A) and granulocyte-macrophage colony-stimulating factor (GM-CSF) is vital to minimize apoptotic processes in renal tubular epithelial cells in vitro and in vivo.

Integrated multi-omics identifies pathways governing interspecies interaction between A. fumigatus and K. pneumoniae.

Polymicrobial co- and superinfections involving bacterial and fungal pathogens pose serious challenges for diagnosis and therapy, and are associated with elevated morbidity and mortality. However, the metabolic dynamics of bacterial-fungal interactions (BFI) and the resulting impact on disease outcome remain largely unknown. The fungus Aspergillus fumigatus and the bacterium Klebsiella pneumoniae are clinically important pathogens sharing common niches in the human body, especially in the lower respiratory tract.

The Hog1 MAP kinase is essential for the colonization of murine skin and intradermal persistence.

Unlabelled: , a multidrug-resistant human fungal pathogen, was first identified in 2009 in Japan. Since then, systemic infections have now been reported in more than 50 countries, with mortality rates of 30%-60%. A major contributing factor to its high inter- and intrahospital clonal transmission is that unlike most species, displays unique skin tropism and can stay on human skin for a prolonged period.

Do morphogenetic switching and intraspecies variation enhance virulence of Candida auris?

Intraspecies variations that affect pathogenicity and antifungal resistance traits pose a serious obstacle to efficient therapy of Candida auris infections. Recent reports indicate that mutations determine drug susceptibility and virulence. However, mutations alone cannot fully explain a bewildering variety of phenotypes in clinical isolates from known C.

Use of the Novel Site-Directed Enzyme Enhancement Therapy (SEE-Tx) Drug Discovery Platform to Identify Pharmacological Chaperones for Glutaric Acidemia Type 1.

Allosteric regulators acting as pharmacological chaperones hold promise for innovative therapeutics since they target noncatalytic sites and stabilize the folded protein without competing with the natural substrate, resulting in a net gain of function. Exogenous allosteric regulators are typically more selective than active site inhibitors and can be more potent than competitive inhibitors when the natural substrate levels are high. To identify novel structure-targeted allosteric regulators (STARs) that bind to and stabilize the mitochondrial enzyme glutaryl-CoA dehydrogenase (GCDH), the computational site-directed enzyme enhancement therapy (SEE-Tx) technology was applied.

A Tutorial for Enhancing Clarity and Transparency in Speech-Language-Hearing Sciences Intervention Research With the TIDieR.

Purpose: The speech-language-hearing sciences (SLHS) field relies on rigorous research to inform clinical practice and improve outcomes for individuals with communication, swallowing, and hearing needs. However, a significant challenge in our field is the lack of accessibility, transparency, and reproducibility of this research. Such insufficiencies limit the generalizability and impact of study findings, particularly intervention research, as it becomes difficult to replicate and use the interventions in both clinical practice and research.

The Hog1 MAP kinase is essential for the colonization of murine skin and intradermal persistence.

Unlabelled: , a multidrug-resistant human fungal pathogen, was first identified in 2009 in Japan. Since then, systemic infections have now been reported in more than 50 countries, with mortality rates of 30-60%. A major contributing factor to its high inter- and intrahospital clonal transmission is that unlike most species, displays unique skin tropism and can stay on human skin for a prolonged period.

Proline catabolism is a key factor facilitating Candida albicans pathogenicity.

Candida albicans, the primary etiology of human mycoses, is well-adapted to catabolize proline to obtain energy to initiate morphological switching (yeast to hyphal) and for growth. We report that put1-/- and put2-/- strains, carrying defective Proline UTilization genes, display remarkable proline sensitivity with put2-/- mutants being hypersensitive due to the accumulation of the toxic intermediate pyrroline-5-carboxylate (P5C), which inhibits mitochondrial respiration. The put1-/- and put2-/- mutations attenuate virulence in Drosophila and murine candidemia models and decrease survival in human neutrophils and whole blood.

Native human and mouse skin infection models to study Candida auris-host interactions.

The World Health Organization (WHO) declared certain fungal pathogens as global health threats for the next decade. Candida auris (C. auris) is a newly emerging skin-tropic multidrug-resistant fungal pathogen that can cause life-threatening infections of high mortality in hospitals and healthcare settings.

Verbs Matter: A Tutorial for Determining Verb Difficulty.

Purpose: Research indicates that when teaching grammatical forms to children, the verbs used to model specific grammatical inflections matter. When learning grammatical forms, children have higher performance when they hear many unique verb forms that vary in their frequency and phonological complexity. In this tutorial, we demonstrate a method for identifying and characterizing a large number of verbs based on their frequency and complexity.

Five Additional Evidence-Based Principles to Facilitate Grammar Development for Children With Developmental Language Disorder.

Purpose: Because the development of grammatical forms is difficult for many children with developmental language disorder (DLD), language interventions often focus on supporting children's use of grammatical language. This article proposes five additional principles to those suggested by Fey et al. (2003) to facilitate the development of grammatical forms by children with DLD.

FOXO3A acts as immune response modulator in human virus-negative inflammatory cardiomyopathy.

Objective: Inflammatory cardiomyopathy is characterised by inflammatory infiltrates leading to cardiac injury, left ventricular (LV) dilatation and reduced LV ejection fraction (LVEF). Several viral pathogens and autoimmune phenomena may cause cardiac inflammation.The effects of the gain of function single-nucleotide polymorphism (SNP) rs12212067 on inflammation and outcome were studied in a cohort of patients with inflammatory dilated cardiomyopathy (DCMi) in relation to cardiac viral presence.

A Proteomic Approach for the Quantification of Posttranslational Protein Lysine Acetylation in Candida albicans.

Candida albicans is a normal component of the human microflora that colonizes mucosal/epithelial surfaces and the gastrointestinal tract as a commensal organism. However, in an immunocompromised host, it can cause life-threatening infections of high mortality and morbidity. Virulence as well as antifungal drug resistance of C.

Transcriptomics and Phenotyping Define Genetic Signatures Associated with Echinocandin Resistance in Candida auris.

Candida auris emerged as a human fungal pathogen only during the past decade. Remarkably, C. auris displays high degrees of genomic diversity and phenotypic plasticity, with four major clades causing hospital outbreaks with high mortality and morbidity rates.

Caregiver-Implemented Communication Interventions for Children Identified as Having Language Impairment 0 Through 48 Months of Age: A Scoping Review.

Purpose: Caregiver-implemented interventions are frequently used to support the early communication of young children with language impairment. Although there are numerous studies and meta-analyses supporting their use, there is a need to better understand the intervention approaches and identify potential gaps in the research base. With that premise, we conducted a scoping review to synthesize existing data with an end goal of informing future research directions.

Comparative Transcriptomics Reveal Possible Mechanisms of Amphotericin B Resistance in Candida auris.

Candida auris is an emerging multidrug-resistant human fungal pathogen often refractory to treatment by all classes of antifungal drugs. Amphotericin B (AmB) is a fungicidal drug that, despite its toxic side effects, remains a drug of choice for the treatment of drug-resistant fungal infections, including those caused by C. auris.

The Multifaceted Roles of Mast Cells in Immune Homeostasis, Infections and Cancers.

Mast cells (MCs) play important roles in normal immune responses and pathological states. The location of MCs on the boundaries between tissues and the external environment, including gut mucosal surfaces, lungs, skin, and around blood vessels, suggests a multitude of immunological functions. Thus, MCs are pivotal for host defense against different antigens, including allergens and microbial pathogens.

Multiplexed complexome profiling using tandem mass tags.

Complexome profiling is a rapidly spreading, powerful technique to gain insight into the nature of protein complexes. It identifies and quantifies protein complexes separated into multiple fractions of increasing molecular mass using mass spectrometry-based, label-free bottom-up proteomics. Complexome profiling enables a sophisticated and thorough characterization of the composition, molecular mass, assembly, and interactions of protein complexes.

Multidrug Resistance in Mammals and Fungi-From MDR to PDR: A Rocky Road from Atomic Structures to Transport Mechanisms.

Multidrug resistance (MDR) can be a serious complication for the treatment of cancer as well as for microbial and parasitic infections. Dysregulated overexpression of several members of the ATP-binding cassette transporter families have been intimately linked to MDR phenomena. Three paradigm ABC transporter members, ABCB1 (P-gp), ABCC1 (MRP1) and ABCG2 (BCRP) appear to act as brothers in arms in promoting or causing MDR in a variety of therapeutic cancer settings.

Quantification of zinc intoxication of after phagocytosis by primary macrophages.

Zinc (Zn) is a trace element, playing pivotal roles during host-pathogen interactions. Macrophages can sequester Zn and restrict bioavailability or increase phagolysosomal Zn to kill pathogens. This method quantifies Zn-mediated clearance of the human fungal pathogen after phagocytosis by innate immune cells.