[Food quality in pre-school and school children in Chile during the COVID-19 pandemic].

Introduction: the COVID-19 pandemic can affect the quality of food and nutrition of preschoolers and schoolchildren through an increase in food insecurity of families, by measures such as confinement and closure of educational establishments, which affects the daily structure, feeding schedules, and quality of food. Objectives: analyze the overall food quality of preschool and school children in Chile during the COVID-19 pandemic. Methods: five hundred and fifty-one schoolchildren (22.

Pbp1-Interacting Protein Mkt1 Regulates Virulence and Sexual Reproduction in .

The Mkt1-Pbp1 complex promotes mating-type switching by regulating the translation of mRNA in . Here, we performed immunoprecipitation assays and mass spectrometry analyses in the human fungal pathogen to show that Pbp1, a poly(A)-binding protein-binding protein, interacts with Mkt1 containing a PIN like-domain. Association of Pbp1 with Mkt1 was confirmed by co-immunoprecipitation assays.

Calcium-Calmodulin-Calcineurin Signaling: A Globally Conserved Virulence Cascade in Eukaryotic Microbial Pathogens.

Calcium is an abundant intracellular ion, and calcium homeostasis plays crucial roles in several cellular processes. The calcineurin signaling cascade is one of the major pathways governed by intracellular calcium. Calcineurin, a conserved protein from yeast to humans, is a calcium-calmodulin-dependent serine-threonine-specific phosphatase that orchestrates cellular stress responses.

Prognostic Value of MMP-9 -1562 C/T Gene Polymorphism in Patients With Sepsis.

Introduction: Matrix metalloproteinase-9 (MMP-9) plays an important role in the pathophysiology of sepsis. A single-nucleotide polymorphism (SNP) at position -1562 (C/T) in the MMP-9 gene has been associated with differential MMP-9 expression, being higher when the -1562 T allele is present. We evaluated the association of the SNP MMP9 -1562 C/T with severity and mortality in patients with sepsis to establish whether the prognosis of the disease is affected.

Mon1 Is Essential for Fungal Virulence and Stress Survival in .

Mon1 is a guanine nucleotide exchange factor subunit that activates the Ypt7 Rab GTPase and is essential for vacuole trafficking and autophagy in eukaryotic organisms. Here, we identified and characterized the function of Mon1, an ortholog of Mon1, in a human fungal pathogen, . Mutation in resulted in hypersensitivity to thermal stress.

Had1 Is Required for Cell Wall Integrity and Fungal Virulence in .

Calcineurin modulates environmental stress survival and virulence of the human fungal pathogen Previously, we identified 44 putative calcineurin substrates, and proposed that the calcineurin pathway is branched to regulate targets including Crz1, Pbp1, and Puf4 in In this study, we characterized Had1, which is one of the putative calcineurin substrates belonging to the ubiquitously conserved haloacid dehalogenase β-phosphoglucomutase protein superfamily. Growth of the ∆ mutant was found to be compromised at 38° or higher. In addition, the ∆ mutant exhibited increased sensitivity to cell wall perturbing agents, including Congo Red and Calcofluor White, and to an endoplasmic reticulum stress inducer dithiothreitol.

Dissecting the Roles of the Calcineurin Pathway in Unisexual Reproduction, Stress Responses, and Virulence in .

The Ca/calmodulin-dependent protein phosphatase calcineurin orchestrates sexual reproduction, stress responses, and virulence via branched downstream pathways in the opportunistic human fungal pathogen The calcineurin-binding protein Cbp1, the calcineurin temperature suppressor Cts1, the calcineurin-responsive zinc finger transcription factor Crz1, and the calcineurin targets Pbp1, Tif3, and Puf4, all function downstream of calcineurin to orchestrate distinct cellular processes. To elucidate how the calcineurin pathway regulatory network governs unisexual reproduction, stress responses, and virulence, we have analyzed the self-filamentous strain, XL280α, and generated double mutants of these calcineurin downstream genes. We demonstrated that calcineurin governs unisexual reproduction at different sexual developmental stages, in which the initiation of the yeast-hyphal morphological transition is independent of Crz1, whereas the sporulation process is dependent on Crz1.

Predictive Value of Matrix Metalloproteinases and Their Inhibitors for Mortality in Septic Patients: A Cohort Study.

Purpose: Over 170 biomarkers are being investigated regarding their prognostic and diagnostic accuracy in sepsis in order to find new tools to reduce morbidity and mortality. Matrix metalloproteinases (MMPs) and their inhibitors have been recently studied as promising new prognostic biomarkers in patients with sepsis. This study is aimed at determining the utility of several cutoff points of these biomarkers to predict mortality in patients with sepsis.

Phosphate is the third nutrient monitored by TOR in and provides a target for fungal-specific indirect TOR inhibition.

The Target of Rapamycin (TOR) pathway regulates morphogenesis and responses to host cells in the fungal pathogen Eukaryotic Target of Rapamycin complex 1 (TORC1) induces growth and proliferation in response to nitrogen and carbon source availability. Our unbiased genetic approach seeking unknown components of TORC1 signaling in revealed that the phosphate transporter Pho84 is required for normal TORC1 activity. We found that mutants in are hypersensitive to rapamycin and in response to phosphate feeding, generate less phosphorylated ribosomal protein S6 (P-S6) than the WT.

Elucidation of the calcineurin-Crz1 stress response transcriptional network in the human fungal pathogen Cryptococcus neoformans.

Calcineurin is a highly conserved Ca2+/calmodulin-dependent serine/threonine-specific protein phosphatase that orchestrates cellular Ca2+ signaling responses. In Cryptococcus neoformans, calcineurin is activated by multiple stresses including high temperature, and is essential for stress adaptation and virulence. The transcription factor Crz1 is a major calcineurin effector in Saccharomyces cerevisiae and other fungi.

A non-canonical RNA degradation pathway suppresses RNAi-dependent epimutations in the human fungal pathogen Mucor circinelloides.

Mucorales are a group of basal fungi that includes the casual agents of the human emerging disease mucormycosis. Recent studies revealed that these pathogens activate an RNAi-based pathway to rapidly generate drug-resistant epimutant strains when exposed to stressful compounds such as the antifungal drug FK506. To elucidate the molecular mechanism of this epimutation pathway, we performed a genetic analysis in Mucor circinelloides that revealed an inhibitory role for the non-canonical RdRP-dependent Dicer-independent silencing pathway, which is an RNAi-based mechanism involved in mRNA degradation that was recently identified.

TIMP1 and MMP9 are predictors of mortality in septic patients in the emergency department and intensive care unit unlike MMP9/TIMP1 ratio: Multivariate model.

Introduction: Matrix metalloproteinases and tissue inhibitors of metalloproteinases could be promising biomarkers for establishing prognosis during the development of sepsis. It is necessary to clarify the relationship between matrix metalloproteinases and their tissue inhibitors. We conducted a cohort study with 563 septic patients, in order to elucidate the biological role and significance of these inflammatory biomarkers and their relationship to the severity and mortality of patients with sepsis.

Calcineurin Targets Involved in Stress Survival and Fungal Virulence.

Calcineurin governs stress survival, sexual differentiation, and virulence of the human fungal pathogen Cryptococcus neoformans. Calcineurin is activated by increased Ca2+ levels caused by stress, and transduces signals by dephosphorylating protein substrates. Herein, we identified and characterized calcineurin substrates in C.

Cancer-associated isocitrate dehydrogenase mutations induce mitochondrial DNA instability.

A major advance in understanding the progression and prognostic outcome of certain cancers, such as low-grade gliomas, acute myeloid leukaemia, and chondrosarcomas, has been the identification of early-occurring mutations in the NADP-dependent isocitrate dehydrogenase genes IDH1 and IDH2 These mutations result in the production of the onco-metabolite D-2-hydroxyglutarate (2HG), thought to contribute to disease progression. To better understand the mechanisms of 2HG pathophysiology, we introduced the analogous glioma-associated mutations into the NADPisocitrate dehydrogenase genes (IDP1, IDP2, IDP3) in Saccharomyces cerevisiae Intriguingly, expression of the mitochondrial IDP1 mutant allele results in high levels of 2HG production as well as extensive mtDNA loss and respiration defects. We find no evidence for a reactive oxygen-mediated mechanism mediating this mtDNA loss.

Vesicular Trafficking Systems Impact TORC1-Controlled Transcriptional Programs in Saccharomyces cerevisiae.

The Target of Rapamycin Complex I (TORC1) orchestrates global reprogramming of transcriptional programs in response to myriad environmental conditions, yet, despite the commonality of the TORC1 complex components, different TORC1-inhibitory conditions do not elicit a uniform transcriptional response. In Saccharomyces cerevisiae, TORC1 regulates the expression of nitrogen catabolite repressed (NCR) genes by controlling the nuclear translocation of the NCR transactivator Gln3. Moreover, Golgi-to-endosome trafficking was shown to be required for nuclear translocation of Gln3 upon a shift from rich medium to the poor nitrogen source proline, but not upon rapamycin treatment.

Branched-Chain Aminotransferases Control TORC1 Signaling in Saccharomyces cerevisiae.

The conserved target of rapamycin complex 1 (TORC1) integrates nutrient signals to orchestrate cell growth and proliferation. Leucine availability is conveyed to control TORC1 activity via the leu-tRNA synthetase/EGOC-GTPase module in yeast and mammals, but the mechanisms sensing leucine remain only partially understood. We show here that both leucine and its α-ketoacid metabolite, α-ketoisocaproate, effectively activate the yeast TORC1 kinase via both EGOC GTPase-dependent and -independent mechanisms.

L-leucine partially rescues translational and developmental defects associated with zebrafish models of Cornelia de Lange syndrome.

Cohesinopathies are human genetic disorders that include Cornelia de Lange syndrome (CdLS) and Roberts syndrome (RBS) and are characterized by defects in limb and craniofacial development as well as mental retardation. The developmental phenotypes of CdLS and other cohesinopathies suggest that mutations in the structure and regulation of the cohesin complex during embryogenesis interfere with gene regulation. In a previous project, we showed that RBS was associated with highly fragmented nucleoli and defects in both ribosome biogenesis and protein translation.

Antifungal drug resistance evoked via RNAi-dependent epimutations.

Microorganisms evolve via a range of mechanisms that may include or involve sexual/parasexual reproduction, mutators, aneuploidy, Hsp90 and even prions. Mechanisms that may seem detrimental can be repurposed to generate diversity. Here we show that the human fungal pathogen Mucor circinelloides develops spontaneous resistance to the antifungal drug FK506 (tacrolimus) via two distinct mechanisms.

Estrogen receptor antagonists are anti-cryptococcal agents that directly bind EF hand proteins and synergize with fluconazole in vivo.

Unlabelled: Cryptococcosis is an infectious disease of global significance for which new therapies are needed. Repurposing previously developed drugs for new indications can expedite the translation of new therapies from bench to beside. Here, we characterized the anti-cryptococcal activity and antifungal mechanism of estrogen receptor antagonists related to the breast cancer drugs tamoxifen and toremifene.

Endolysosomal membrane trafficking complexes drive nutrient-dependent TORC1 signaling to control cell growth in Saccharomyces cerevisiae.

The rapamycin-sensitive and endomembrane-associated TORC1 pathway controls cell growth in response to nutrients in eukaryotes. Mutations in class C Vps (Vps-C) complexes are synthetically lethal with tor1 mutations and confer rapamycin hypersensitivity in Saccharomyces cerevisiae, suggesting a role for these complexes in TORC1 signaling. Vps-C complexes are required for vesicular trafficking and fusion and comprise four distinct complexes: HOPS and CORVET and their minor intermediaries (i)-CORVET and i-HOPS.

Genomic insights into the atopic eczema-associated skin commensal yeast Malassezia sympodialis.

Unlabelled: Malassezia commensal yeasts are associated with a number of skin disorders, such as atopic eczema/dermatitis and dandruff, and they also can cause systemic infections. Here we describe the 7.67-Mbp genome of Malassezia sympodialis, a species associated with atopic eczema, and contrast its genome repertoire with that of Malassezia globosa, associated with dandruff, as well as those of other closely related fungi.

Rapamycin exerts antifungal activity in vitro and in vivo against Mucor circinelloides via FKBP12-dependent inhibition of Tor.

The zygomycete Mucor circinelloides is an opportunistic fungal pathogen that commonly infects patients with malignancies, diabetes mellitus, and solid organ transplants. Despite the widespread use of antifungal therapy in the management of zygomycosis, the incidence of infections continues to rise among immunocompromised individuals. In this study, we established that the target and mechanism of antifungal action of the immunosuppressant rapamycin in M.

Association of calcineurin with the COPI protein Sec28 and the COPII protein Sec13 revealed by quantitative proteomics.

Calcineurin is a calcium-calmodulin-dependent serine/threonine specific protein phosphatase operating in key cellular processes governing responses to extracellular cues. Calcineurin is essential for growth at high temperature and virulence of the human fungal pathogen Cryptococcus neoformans but the underlying mechanism is unknown. We performed a mass spectrometry analysis to identify proteins that associate with the calcineurin A catalytic subunit (Cna1) in C.

Calcineurin colocalizes with P-bodies and stress granules during thermal stress in Cryptococcus neoformans.

Calcineurin is a calcium-calmodulin-activated serine/threonine-specific phosphatase that operates during cellular responses to stress and plays a prominent role in transcriptional control, whereas regulatory events beyond transcription are less well characterized. This study reveals a novel transcription-independent role of calcineurin during the temperature stress response in the human fungal pathogen Cryptococcus neoformans. The diffusely cytoplasmic calcineurin catalytic subunit Cna1 relocates to endoplasmic reticulum (ER)-associated puncta and the mother-bud neck when cells are subjected to 37°C.