Phospho-regulation of ASCL1-mediated chromatin opening during cellular reprogramming.

The proneural transcription factor ASCL1 regulates neurogenesis and drives somatic cell reprogramming into neurons. However, not all cell types can be reprogrammed by ASCL1, raising the questions of what provides competence and how we can overcome barriers to enable directed differentiation. Here, we investigate how levels of ASCL1 and its phosphorylation modulate its activity over progressive lineage restriction of mouse embryonic stem cells.

The role of lipids in regulating macrophage antifungal immunity.

Macrophages are critical components of the antifungal immune response. Disturbance in the number or function of these innate immune cells can significantly increase susceptibility to invasive fungal infections. Pathogenic fungi cause billions of infections every year and have an unmet clinical need, with many infections associated with unacceptably high mortality rates that primarily affect vulnerable patients with underlying immune defects.

Glucagon-like peptide-1 receptor agonist use in pregnancy: a review.

Glucagon-like peptide-1 receptor agonists are peptide analogues that are used to treat type 2 diabetes mellitus and obesity. The first medication in this class, exenatide, was approved in 2005, and these medications, specifically semaglutide, have become more popular in recent years due to their pronounced effects on glycemic control, weight reduction, and cardiovascular health. Due to successful weight loss from these medications, many women previously diagnosed with oligomenorrhea and unable to conceive have experienced unplanned pregnancies while taking the medications.

Fear of cancer recurrence experienced by pediatric survivors of childhood cancer: a scoping review.

Purpose: In contrast to the extensive literature on fear of cancer recurrence (FCR) experienced by adults, literature evaluating pediatric FCR has just begun to emerge. Given the rapidly expanding body of work assessing FCR in childhood and adolescence, a scoping review was conducted to synthesize existing findings. We aimed to assess (1) the characteristics and methods of this literature, (2) how pediatric FCR has been measured, and (3) the extant knowledge of FCR experienced by pediatric survivors of cancer.

Percutaneous Vocal Fold Lateralization in children - a case series of a Brazilian tertiary pediatric hospital (pediatric vocal fold lateralization cases in a Brazilian hospital).

Objectives: Percutaneous Vocal Fold Lateralization (PVFL) consists of external fixation with non-absorbable percutaneous suture of the vocal fold in a lateral position, under direct glottic visualization. The objective of this study is to determine the effectiveness of PVFL in a university pediatric hospital, as well as to describe the potential risks and complications of the surgery.

Methods: Retrospective cohort study, with data collected from electronic medical records.

and genes regulate release, germination and growth of gemma in .

Strigolactones (SLs), a class of carotenoid-derived hormones, play a crucial role in flowering plants by regulating underground communication with symbiotic arbuscular mycorrhizal fungi (AM) and controlling shoot and root architecture. While the functions of core SL genes have been characterized in many plants, their roles in non-tracheophyte plants like liverworts require further investigation. In this study, we employed the model liverwort species , which lacks detectable SL production and orthologs of key SL biosynthetic genes, including () and ().

Tracking SARS-CoV-2 variants of concern in wastewater: an assessment of nine computational tools using simulated genomic data.

Wastewater-based surveillance (WBS) is an important epidemiological and public health tool for tracking pathogens across the scale of a building, neighbourhood, city, or region. WBS gained widespread adoption globally during the SARS-CoV-2 pandemic for estimating community infection levels by qPCR. Sequencing pathogen genes or genomes from wastewater adds information about pathogen genetic diversity, which can be used to identify viral lineages (including variants of concern) that are circulating in a local population.

How selective antagonists and genetic modification have helped characterise the expression and functions of vascular P2Y receptors.

Vascular P2Y receptors mediate many effects, but the role of individual subtypes is often unclear. Here we discuss how subtype-selective antagonists and receptor knockout/knockdown have helped identify these roles in numerous species and vessels. P2Y receptor-mediated vasoconstriction and endothelium-dependent vasodilation have been characterised using the selective antagonists, MRS2179 and MRS2216, whilst AR-C118925XX, a P2Y receptor antagonist, reduced endothelium-dependent relaxation, and signalling evoked by UTP or fluid shear stress.

One in, one out: Commensal fungus protects against infection.

Gut-resident fungi have a broad influence over health and disease. In this issue of JEM, Sekeresova Kralova et al. (https://doi.

Detection of oxaliplatin- and cisplatin-DNA lesions requires different global genome repair mechanisms that affect their clinical efficacy.

The therapeutic efficacy of cisplatin and oxaliplatin depends on the balance between the DNA damage induction and the DNA damage response of tumor cells. Based on clinical evidence, oxaliplatin is administered to cisplatin-unresponsive cancers, but the underlying molecular causes for this tumor specificity are not clear. Hence, stratification of patients based on DNA repair profiling is not sufficiently utilized for treatment selection.

Relating mutational signature exposures to clinical data in cancers via signeR 2.0.

Background: Cancer is a collection of diseases caused by the deregulation of cell processes, which is triggered by somatic mutations. The search for patterns in somatic mutations, known as mutational signatures, is a growing field of study that has already become a useful tool in oncology. Several algorithms have been proposed to perform one or both the following two tasks: (1) de novo estimation of signatures and their exposures, (2) estimation of the exposures of each one of a set of pre-defined signatures.

How metals fuel fungal virulence, yet promote anti-fungal immunity.

Invasive fungal infections represent a significant global health problem, and present several clinical challenges, including limited treatment options, increasing rates of antifungal drug resistance and compounding comorbidities in affected patients. Metals, such as copper, iron and zinc, are critical for various biological and cellular processes across phyla. In mammals, these metals are important determinants of immune responses, but pathogenic microbes, including fungi, also require access to these metals to fuel their own growth and drive expression of major virulence traits.

Varying the expression pattern of the strigolactone receptor gene results in phenotypes distinct from both wild type and knockout mutants.

The action of the petunia strigolactone (SL) hormone receptor DAD2 is dependent not only on its interaction with the PhMAX2A and PhD53A proteins, but also on its expression patterns within the plant. Previously, in a yeast-2-hybrid system, we showed that a series of a single and double amino acid mutants of DAD2 had altered interactions with these binding partners. In this study, we tested the mutants in two plant systems, and petunia.

Immune-related neurodegeneration in the midbrain causes pulmonary dysfunction in murine cryptococcal IRIS.

Cryptococcal immune reconstitution inflammatory syndrome (C-IRIS) is a condition that affects immunosuppressed individuals recruited to antiretroviral therapy. In a recent publication, Kawano and colleagues used a mouse model to demonstrate that pulmonary dysfunction, one of the fatal complications of C-IRIS, is caused by T cell-driven neurodegeneration in a vital medullary nucleus of the brain responsible for respiratory control.

Qualitative interviews to understand methods and systems used to collect ethnicity information in health administrative data sources in England.

 This article is one of a series aiming to inform analytical methods to improve comparability of estimates of ethnic health disparities based on different sources. This article explores the quality of ethnicity data and identifies potential sources of bias when ethnicity information is collected in three key NHS data sources. Future research can build on these findings to explore analytical methods to mitigate biases.

Efficacy and predictors of success on laryngomalacia surgery: experience from a tertiary pediatric care center in Brazil.

Objectives: Laryngomalacia is the most common congenital cause of stridor; the natural history of the disease runs through to complete resolution by the age of two. Severe cases are characterized by cyanosis, hypoxia, apnea, furcular and/or subcostal retractions, aspirations, pulmonary hypertension, and failure to thrive and must undergo surgery. This study aimed to evaluate the success rates of supraglottoplasty in our hospital and evaluate the predictive factors for surgical success.

A North Star Vision: Results from a Deliberative Dialogue to Identify Policy Strategies to Improve Value in Healthcare.

We hosted a deliberative dialogue with citizens ( = 3), policy researchers ( = 3), government decision makers ( = 3) and health system leaders ( = 3) to identify evidence-informed policy options to improve the value of Canadian healthcare. The analysis resulted in three themes: (1) the need for a vision to guide reforms, (2) community-based care and (3) community-engaged care. Results suggest the need for a new paradigm: community-focused health systems.

Meningeal Whole Mounts for Imaging CNS Fungal Infection.

Invasive fungal infections may involve the brain and central nervous system (CNS), leading to often fatal meningitis in immunocompromised individuals. Recent technological advances have allowed us to move beyond studying the brain parenchyma to understanding the immune mechanisms of the meninges, the protective layer that surrounds the brain and spinal cord. Specifically, advanced microscopy techniques have enabled researchers to begin to visualize the anatomy of the meninges and the cellular mediators of meningeal inflammation.

Adoptive Transfer of Cryptococcus neoformans-Specific CD4 T-Cells to Study Anti-fungal Lymphocyte Responses In Vivo.

CD4 T-cells are important for long-term control and clearance of several fungal infections in humans, particularly those caused by Cryptococcus species. Understanding the mechanisms underlying protective T-cell immunity against fungal infection is critical for developing mechanistic insights into the pathogenesis of the disease. Here, we describe a protocol that enables analysis of fungal-specific CD4 T-cell responses in vivo, using adoptive transfer of fungal-specific T-cell receptor (TCR) transgenic CD4 T-cells.

One population, multiple lifestyles: Commensalism and pathogenesis in the human mycobiome.

Candida auris and Candida albicans can result in invasive fungal diseases. And yet, these species can stably and asymptomatically colonize human skin and gastrointestinal tracts. To consider these disparate microbial lifestyles, we first review factors shown to influence the underlying microbiome.

What fungal CNS infections can teach us about neuroimmunology and CNS-specific immunity.

Immunity to fungal infections of the central nervous system (CNS) is one of the most poorly understood subjects within the field of medical mycology. Yet, the majority of deaths from invasive fungal infections are caused by brain-tropic fungi. In recent years, there have been several significant discoveries in the regulation of neuroinflammation and the role of the immune system in tissue homeostasis within the CNS.