A mutant ASXL1-EHMT complex contributes to heterochromatin dysfunction in clonal hematopoiesis and chronic monomyelocytic leukemia.

Unlabelled: is one of the three most frequently mutated genes in age-related clonal hematopoiesis (CH), alongside and . CH can progress to myeloid malignancies including chronic monomyelocytic leukemia (CMML), and is also strongly associated with inflammatory cardiovascular disease and all-cause mortality in humans. DNMT3A and TET2 regulate DNA methylation and demethylation pathways respectively, and loss-of-function mutations in these genes reduce DNA methylation in heterochromatin, allowing de-repression of silenced elements in heterochromatin.

A mutant ASXL1-BAP1-EHMT complex contributes to heterochromatin dysfunction in clonal hematopoiesis and chronic monomyelocytic leukemia.

is one of the three most frequently mutated genes in age-related clonal hematopoiesis (CH), alongside and (. CH can progress to myeloid malignancies including chronic monomyelocytic leukemia (CMML) and is also strongly associated with inflammatory cardiovascular disease and all-cause mortality in humans. DNMT3A and TET2 regulate DNA methylation and demethylation pathways, respectively, and loss-of-function mutations in these genes reduce DNA methylation in heterochromatin, allowing derepression of silenced elements in heterochromatin.

Management of Persistent Left Superior Vena Cava: Overcoming Lead and Vascular Complications With Transcatheter Pacing System Implantation.

Isolated persistent left superior vena cava (PLSVC) is a rare congenital anomaly typically found incidentally due to its asymptomatic nature. However, it can present technical challenges for device implanters. We report a case involving a patient with PLSVC, for whom the implantation of a transcatheter pacing system proved to be the most effective long-term solution.

The Role of Fatty Acid Synthase in the Vascular Smooth Muscle Cell to Foam Cell Transition.

Vascular smooth muscle cells (VSMCs), in their contractile and differentiated state, are fundamental for maintaining vascular function. Upon exposure to cholesterol (CHO), VSMCs undergo dedifferentiation, adopting characteristics of foam cells-lipid-laden, macrophage-like cells pivotal in atherosclerotic plaque formation. CHO uptake by VSMCs leads to two primary pathways: ABCA1-mediated efflux or storage in lipid droplets as cholesterol esters (CEs).

OGT prevents DNA demethylation and suppresses the expression of transposable elements in heterochromatin by restraining TET activity genome-wide.

The GlcNAc transferase OGT interacts robustly with all three mammalian TET methylcytosine dioxygenases. We show here that deletion of the gene in mouse embryonic stem cells (mESC) results in a widespread increase in the TET product 5-hydroxymethylcytosine (5hmC) in both euchromatic and heterochromatic compartments, with concomitant reduction of the TET substrate 5-methylcytosine (5mC) at the same genomic regions. mESC engineered to abolish the TET1-OGT interaction likewise displayed a genome-wide decrease of 5mC.

Subregional efforts to improve childhood cancer care in the Andean countries.

Cancer is one of the leading causes of death in children and adolescents younger than 19 years. An estimated 10 000 deaths are caused by this disease annually in this age group in Latin America and the Caribbean. In high-income countries, the survival of children and adolescents with neoplasms can reach 85%; however, in middle- and low-income countries, despite progress, survival rates are significantly lower (between 10% and 60%).

COVID-19 and human resources for health: analysis of planning, policy responses and actions in Latin American and Caribbean countries.

Background: The COVID-19 pandemic led to worldwide health service disruptions, due mainly to insufficient staff availability. To gain insight into policy responses and engage with policy-makers, the World Health Organization (WHO) developed a global approach to assess and measure the impact of COVID-19 on the health workforce. As part of this, WHO, together with the Pan American Health Organization (PAHO), supported an impact analysis of COVID-19 on health workers and policy responses, through country case studies in Latin America and the Caribbean (LAC).

OGT controls mammalian cell viability by regulating the proteasome/mTOR/ mitochondrial axis.

-GlcNAc transferase (OGT) modifies serine and threonine residues on nuclear and cytosolic proteins with -linked N-acetylglucosamine (GlcNAc). OGT is essential for mammalian cell viability, but the underlying mechanisms are still enigmatic. We performed a genome-wide CRISPR-Cas9 screen in mouse embryonic stem cells (mESCs) to identify candidates whose depletion rescued the block in cell proliferation induced by OGT deficiency.

Acute deletion of TET enzymes results in aneuploidy in mouse embryonic stem cells through decreased expression of Khdc3.

TET (Ten-Eleven Translocation) dioxygenases effect DNA demethylation through successive oxidation of the methyl group of 5-methylcytosine (5mC) in DNA. In humans and in mouse models, TET loss-of-function has been linked to DNA damage, genome instability and oncogenesis. Here we show that acute deletion of all three Tet genes, after brief exposure of triple-floxed, Cre-ERT2-expressing mouse embryonic stem cells (mESC) to 4-hydroxytamoxifen, results in chromosome mis-segregation and aneuploidy; moreover, embryos lacking all three TET proteins showed striking variation in blastomere numbers and nuclear morphology at the 8-cell stage.

The RabGEF ALS2 is a hypoxia inducible target associated with the acquisition of aggressive traits in tumor cells.

Tumor hypoxia and the hypoxia inducible factor-1, HIF-1, play critical roles in cancer progression and metastasis. We previously showed that hypoxia activates the endosomal GTPase Rab5, leading to tumor cell migration and invasion, and that these events do not involve changes in Rab protein expression, suggesting the participation of intermediate activators. Here, we identified ALS2, a guanine nucleotide exchange factor that is upregulated in cancer, as responsible for increased Rab5-GTP loading, cell migration and metastasis in hypoxia.

Ski Is Required for Tri-Methylation of H3K9 in Major Satellite and for Repression of Pericentromeric Genes: Mmp3, Mmp10 and Mmp13, in Mouse Fibroblasts.

Several mechanisms directing a rapid transcriptional reactivation of genes immediately after mitosis have been described. However, little is known about the maintenance of repressive signals during mitosis. In this work, we address the role of Ski in the repression of gene expression during M/G transition in mouse embryonic fibroblasts (MEFs).

Treatment, outcomes and costs of asthma exacerbations in Chilean children: a prospective multicenter observational study.

Objective: To describe potential regional variations in therapies for severe asthma exacerbations in Chilean children and estimate the associated health expenditures.

Methods: Observational prospective cohort study in 14 hospitals over a one-year period. Children five years of age or older were eligible for inclusion.

Mll-COMPASS complexes mediate H3K4me3 enrichment and transcription of the osteoblast master gene Runx2/p57 in osteoblasts.

Expression of Runx2/p57 is a hallmark of the osteoblast-lineage identity. Although several regulators that control the expression of Runx2/p57 during osteoblast-lineage commitment have been identified, the epigenetic mechanisms that sustain this expression in differentiated osteoblasts remain to be completely determined. Here, we assess epigenetic mechanisms associated with Runx2/p57 gene transcription in differentiating MC3T3 mouse osteoblasts.

Expression of the ectodomain-releasing protease ADAM17 is directly regulated by the osteosarcoma and bone-related transcription factor RUNX2.

Osteoblast differentiation is controlled by transcription factor RUNX2 which temporally activates or represses several bone-related genes, including those encoding extracellular matrix proteins or factors that control cell-cell, and cell-matrix interactions. Cell-cell communication in the many skeletal pericellular micro-niches is critical for bone development and involves paracrine secretion of growth factors and morphogens. This paracrine signaling is in part regulated by "A Disintegrin And Metalloproteinase" (ADAM) proteins.

Hospitalizations for asthma exacerbation in Chilean children: A multicenter observational study.

Background: Asthma hospitalization rates in Chilean children have increased in the last 14 years, but little is known about the factors associated with this.

Objective: Describe clinical characteristics of children hospitalized for asthma exacerbation.

Methods: Observational prospective cohort study in 14 hospitals.

Variable transcriptional responsiveness of the P2X3 receptor gene during CFA-induced inflammatory hyperalgesia.

The purinergic receptor P2X3 (P2X3-R) plays important roles in molecular pathways of pain, and reduction of its activity or expression effectively reduces chronic inflammatory and neuropathic pain sensation. Inflammation, nerve injury, and cancer-induced pain can increase P2X3-R mRNA and/or protein levels in dorsal root ganglia (DRG). However, P2X3-R expression is unaltered or even reduced in other pain studies.

Runt-Related Transcription Factor 2 Induction During Differentiation of Wharton's Jelly Mesenchymal Stem Cells to Osteoblasts Is Regulated by Jumonji AT-Rich Interactive Domain 1B Histone Demethylase.

Novel bone regeneration approaches aim to obtain immature osteoblasts from somatic stem cells. Umbilical cord Wharton's jelly mesenchymal stem cells (WJ-MSCs) are an ideal source for cell therapy. Hence, the study of mechanisms involved in WJ-MSC osteoblastic differentiation is crucial to exploit their developmental capacity.

A functional IL1RL1 variant regulates corticosteroid-induced sST2 expression in ulcerative colitis.

The ST2/IL33 signalling pathway has been associated with ulcerative colitis (UC). ST2, encoded by the IL1RL1 gene, is expressed as both a membrane-anchored receptor (ST2L) activated by IL33 and as a soluble receptor (sST2) with anti-inflammatory properties. In UC patients, sST2 is further increased by corticosteroid treatment; however, the glucocorticoid-mediated molecular regulation remains unknown.

Tet-Mediated DNA Demethylation Is Required for SWI/SNF-Dependent Chromatin Remodeling and Histone-Modifying Activities That Trigger Expression of the Sp7 Osteoblast Master Gene during Mesenchymal Lineage Commitment.

Here we assess histone modification, chromatin remodeling, and DNA methylation processes that coordinately control the expression of the bone master transcription factor Sp7 (osterix) during mesenchymal lineage commitment in mammalian cells. We find that Sp7 gene silencing is mediated by DNA methyltransferase1/3 (DNMT1/3)-, histone deacetylase 1/2/4 (HDAC1/2/4)-, Setdb1/Suv39h1-, and Ezh1/2-containing complexes. In contrast, Sp7 gene activation involves changes in histone modifications, accompanied by decreased nucleosome enrichment and DNA demethylation mediated by SWI/SNF- and Tet1/Tet2-containing complexes, respectively.

Largest baleen whale mass mortality during strong El Niño event is likely related to harmful toxic algal bloom.

While large mass mortality events (MMEs) are well known for toothed whales, they have been rare in baleen whales due to their less gregarious behavior. Although in most cases the cause of mortality has not been conclusively identified, some baleen whale mortality events have been linked to bio-oceanographic conditions, such as harmful algal blooms (HABs). In Southern Chile, HABs can be triggered by the ocean-atmosphere phenomenon El Niño.

Mercury contamination in breast milk of nursing mothers in gold mining municipalities of Antioquia, Colombia.

Introduction: Breast milk is essential for human development, but it may contain toxics derived from environmental pollution, especially in mining areas. Objective: To assess the prevalence of mercury contamination in breast milk and factors associated with its transfer to nursing mothers living in municipalities with gold mining. Materials and methods: We conducted a cross-sectional study with 150 nursing mothers in four municipalities of Antioquia (El Bagre, Segovia, Remedios and Zaragoza) with a mining tradition.

Epigenetic Signatures at the RUNX2-P1 and Sp7 Gene Promoters Control Osteogenic Lineage Commitment of Umbilical Cord-Derived Mesenchymal Stem Cells.

Wharton's Jelly mesenchymal stem cells (WJ-MSCs) are an attractive potential source of multipotent stem cells for bone tissue replacement therapies. However, the molecular mechanisms involved in their osteogenic conversion are poorly understood. Particularly, epigenetic control operating at the promoter regions of the two master regulators of the osteogenic program, RUNX2/P57 and SP7 has not yet been described in WJ-MSCs.

The oceanic concordance of phylogeography and biogeography: a case study in Notochthamalus.

Dispersal and adaptation are the two primary mechanisms that set the range distributions for a population or species. As such, understanding how these mechanisms interact in marine organisms in particular - with capacity for long-range dispersal and a poor understanding of what selective environments species are responding to - can provide useful insights for the exploration of biogeographic patterns. Previously, the barnacle Notochthamalus scabrosus has revealed two evolutionarily distinct lineages with a joint distribution that suggests an association with one of the two major biogeographic boundaries (~30°S) along the coast of Chile.