Anaemia as a critical health condition greatly upsurges the risk of pregnancy complications leading to preventable maternal mortalities and long-term morbidities. Therefore, identifying anaemia-associated factors is vital for planning relevant interventions in resource-constrained regions in Sahelian Africa. This study aimed to assess the prevalence and determinants of anaemia at 36 weeks of pregnancy among antenatal women in a peri-urban municipality of Ghana.
View Article and Find Full Text PDFHuman pluripotent stem cells serve as a robust model system to study disease pathogenesis in a dish and search for various targeted therapeutics. Collection of control lines from healthy individuals are essential for any study. Therefore, we have generated hiPSC line from a healthy male donor after episomal reprogramming of PBMCs.
View Article and Find Full Text PDFReprogramming somatic cells to pluripotent stem cells has revolutionized the biomedical field by providing enormous hopes and opportunities for the regeneration of tissues and organs for transplantation. Using a small molecule cocktail of epigenetic modifiers and cell signalling inhibitors, a chemical-based easy and controllable technique for converting human somatic cells into chemically induced pluripotent stem cells was recently reported (Guan, Nature 605:325-31, 2022). This novel approach offers well-defined, safe, simple, easy, and clinical-grade manufacturing strategies for modifying the fate of human cells required for regenerative therapeutics.
View Article and Find Full Text PDFHepatocytes store triglycerides (TGs) in the form of lipid droplets (LDs), which are increased in hepatosteatosis. The regulation of hepatic LDs is poorly understood and new therapies to reduce hepatosteatosis are needed. We performed a siRNA kinase and phosphatase screen in HuH-7 cells using high-content automated imaging of LDs.
View Article and Find Full Text PDFBackground And Aims: NASH will soon become the leading cause of liver transplantation in the United States and is also associated with increased COVID-19 mortality. Currently, there are no Food and Drug Administration-approved drugs available that slow NASH progression or address NASH liver involvement in COVID-19. Because animal models cannot fully recapitulate human NASH, we hypothesized that stem cells isolated directly from end-stage liver from patients with NASH may address current knowledge gaps in human NASH pathology.
View Article and Find Full Text PDFPathogenic mutations in LAMIN A/C (LMNA) cause abnormal nuclear structure and laminopathies. These diseases have myriad tissue-specific phenotypes, including dilated cardiomyopathy (DCM), but how LMNA mutations result in tissue-restricted disease phenotypes remains unclear. We introduced LMNA mutations from individuals with DCM into human induced pluripotent stem cells (hiPSCs) and found that hiPSC-derived cardiomyocytes, in contrast to hepatocytes or adipocytes, exhibit aberrant nuclear morphology and specific disruptions in peripheral chromatin.
View Article and Find Full Text PDFThe coronavirus disease 19 (COVID-19) pandemic, caused by severe acute respiratory distress syndrome coronavirus 2, has spread globally and requires effective preparedness within healthcare institutions. The British Columbia Simulation Network COVID-19 Simulation Guide was created to disseminate information throughout the province of British Columbia, Canada, and to allow simulation educators, from novice to expert, to participate in COVID-19 simulations. As of July 15, 2020, the guide had been downloaded 465 times from the British Columbia Simulation Network website, with downloads in 41 countries around the world.
View Article and Find Full Text PDFEstablishment of a physiologically relevant human hepatocyte-like cell system for translational research has been hampered by the limited availability of cell models that accurately reflect human biology and the pathophysiology of human disease. Here we report a robust, reproducible, and scalable protocol for the generation of hepatic organoids from human induced pluripotent stem cells (hiPSCs) using short exposure to nonengineered matrices. These hepatic organoids follow defined stages of hepatic development and express higher levels of early (hepatocyte nuclear factor 4A [HNF4A], prospero-related homeobox 1 [PROX1]) and mature hepatic and metabolic markers (albumin, asialoglycoprotein receptor 1 [ASGR1], CCAAT/enhancer binding protein α [C/EBPα]) than two-dimensional (2D) hepatocyte-like cells (HLCs) at day 20 of differentiation.
View Article and Find Full Text PDFDyslipidemias are strongly linked to the development of atherosclerotic cardiovascular disease. Most dyslipidemias find their origin in the liver. In recent years, the differentiation of induced pluripotent stem cells (iPSCs) into hepatocyte-like cells has provided a versatile platform for the functional study of various dyslipidemias, both rare genetic dyslipidemia as well as common lipid disorders associated with insulin resistance or non-alcoholic fatty liver disease.
View Article and Find Full Text PDFThe embryonic stem cell line derivation from nonpermissive mouse strains is a challenging and highly inefficient process. The cellular reprogramming strategy provides an alternative route for generating pluripotent stem cell (PSC) lines from such strains. In this study, we successfully derived an enhanced green fluorescent protein (EGFP)-transgenic "N9" induced pluripotent stem cell (iPS cell, iPSC) line from the FVB/N strain-derived mouse embryonic fibroblasts (MEFs).
View Article and Find Full Text PDFBackground: Organizational health literacy (OHL) is the degree to which health care organizations implement strategies to make it easier for patients to understand health information, navigate the health care system, engage in the health care process, and manage their health. Although resources exist to guide OHL-related quality improvement (QI) initiatives, little work has been done to establish measures that organizations can use to monitor their improvement efforts.
Objective: We sought to identify and evaluate existing OHL-related QI measures.
studies suggest that stress may generate random standing variation and that different cellular and ploidy states may evolve more rapidly under stress. Yet this idea has not been tested with pathogenic fungi growing within their host niche Here, we analyzed the generation of both genotypic and phenotypic diversity during exposure of to the mouse oral cavity. Ploidy, aneuploidy, loss of heterozygosity (LOH), and recombination were determined using flow cytometry and double digest restriction site-associated DNA sequencing.
View Article and Find Full Text PDFSoil and groundwater contamination are often managed by establishing on-site cleanup targets within the context of risk assessment or risk management measures. Decision-makers rely on modeling tools to provide insight; however, it is recognized that all models are subject to uncertainty. This case study compares suggested remediation requirements using a site-specific numerical model and a standardized analytical tool to evaluate risk to a downgradient wetland receptor posed by on-site chloride impacts.
View Article and Find Full Text PDFRecent advances in self-organizing, 3-dimensional tissue cultures of embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) provided an in vitro model that recapitulates many aspects of the in vivo developmental steps. Using Rax-GFP-expressing ESCs, newly generated Six3 iPSCs, and conditional null Six3;Rax-Cre ESCs, we identified Six3 repression of R-spondin 2 (Rspo2) as a required step during optic vesicle morphogenesis and neuroretina differentiation. We validated these results in vivo by showing that transient ectopic expression of Rspo2 in the anterior neural plate of transgenic mouse embryos was sufficient to inhibit neuroretina differentiation.
View Article and Find Full Text PDFGenome-wide association studies have identified a signal at the SLC22A1 locus for serum acylcarnitines, intermediate metabolites of mitochondrial oxidation whose plasma levels associate with metabolic diseases. Here, we refined the association signal, performed conditional analyses, and examined the linkage structure to find coding variants of SLC22A1 that mediate independent association signals at the locus. We also employed allele-specific expression analysis to find potential regulatory variants of SLC22A1 and demonstrated the effect of one variant on the splicing of SLC22A1.
View Article and Find Full Text PDFEmbryonic stem cells (ES-cells) provide a good model system to study lineage-specific differentiation. Though, the differentiation of ES-cells to cardiomyocytes is documented, a clear understanding of the molecular mechanism of differentiation and improved functional-differentiation efficiency are yet to be achieved. In this regard, ascorbic acid (Aa) is shown to be one of the effective cardiac inducers in ES-cells.
View Article and Find Full Text PDFThe interaction of Candida albicans with the host is of a complex nature involving fungal factors and host's response. In this study, we concentrated on the phenotypic expression of virulence attributes and genotypic characteristics of C. albicans isolates from two distinct clinical entities of candidiasis-blood stream and vaginal infections, and the possible role of these factors.
View Article and Find Full Text PDFGenome-wide association studies have struggled to identify functional genes and variants underlying complex phenotypes. We recruited a multi-ethnic cohort of healthy volunteers (n = 91) and used their tissue to generate induced pluripotent stem cells (iPSCs) and hepatocyte-like cells (HLCs) for genome-wide mapping of expression quantitative trait loci (eQTLs) and allele-specific expression (ASE). We identified many eQTL genes (eGenes) not observed in the comparably sized Genotype-Tissue Expression project's human liver cohort (n = 96).
View Article and Find Full Text PDFObjective: The research demonstrates that a conference slide presentation translated into non-English languages reaches significantly larger and different audiences than an English presentation alone.
Methods: The slides of a presentation from the Medical Library Association annual meeting were translated from English to Chinese, Japanese, and Russian and posted along with the English version to SlideShare, an open slide-hosting website. View counts, traffic sources, and geographic origins of the traffic for each language version were tracked over a twenty-two-month period.
Candida albicans is both a member of the healthy human microbiome and a major pathogen in immunocompromised individuals. Infections are typically treated with azole inhibitors of ergosterol biosynthesis often leading to drug resistance. Studies in clinical isolates have implicated multiple mechanisms in resistance, but have focused on large-scale aberrations or candidate genes, and do not comprehensively chart the genetic basis of adaptation.
View Article and Find Full Text PDFThe design of effective antimicrobial therapies for serious eukaryotic pathogens requires a clear understanding of their highly variable genomes. To facilitate analysis of copy number variations, single nucleotide polymorphisms and loss of heterozygosity events in these pathogens, we developed a pipeline for analyzing diverse genome-scale datasets from microarray, deep sequencing, and restriction site associated DNA sequence experiments for clinical and laboratory strains of Candida albicans, the most prevalent human fungal pathogen. The YMAP pipeline (http://lovelace.
View Article and Find Full Text PDFStem cells in cell based therapy for cardiac injury is being potentially considered. However, genetic regulatory networks involved in cardiac differentiation are not clearly understood. Among stem cell differentiation models, mouse P19 embryonic carcinoma (EC) cells, are employed for studying (epi)genetic regulation of cardiomyocyte differentiation.
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