708 research outputs found

    Tgif1 Counterbalances The Activity Of Core Pluripotency Factors In Mouse Embryonic Stem Cells

    Get PDF
    Core pluripotency factors, such as Oct4, Sox2, and Nanog, play important roles in maintaining embryonic stem cell (ESC) identity by autoregulatory feedforward loops. Nevertheless, the mechanism that provides precise control of the levels of the ESC core factors without indefinite amplification has remained elusive. Here, we report the direct repression of core pluripotency factors by Tgif1, a previously known terminal repressor of TGF beta/activin/nodal signaling. Overexpression of Tgif1 reduces the levels of ESC core factors, whereas its depletion leads to the induction of the pluripotency factors. We confirm the existence of physical associations between Tgif1 and Oct4, Nanog, and HDAC1/2 and further show the level of Tgif1 is not significantly altered by treatment with an activator/inhibitor of the TGF beta/activin/nodal signaling. Collectively, our findings establish Tgif1 as an integral member of the core regulatory circuitry of mouse ESCs that counterbalances the levels of the core pluripotency factors in a TGF beta/activin/nodal-independent manner.Cancer Prevention Research Institute of Texas (CPRIT) R1106Molecular Bioscience

    miTarget: microRNA target gene prediction using a support vector machine

    Get PDF
    BACKGROUND: MicroRNAs (miRNAs) are small noncoding RNAs, which play significant roles as posttranscriptional regulators. The functions of animal miRNAs are generally based on complementarity for their 5' components. Although several computational miRNA target-gene prediction methods have been proposed, they still have limitations in revealing actual target genes. RESULTS: We implemented miTarget, a support vector machine (SVM) classifier for miRNA target gene prediction. It uses a radial basis function kernel as a similarity measure for SVM features, categorized by structural, thermodynamic, and position-based features. The latter features are introduced in this study for the first time and reflect the mechanism of miRNA binding. The SVM classifier produces high performance with a biologically relevant data set obtained from the literature, compared with previous tools. We predicted significant functions for human miR-1, miR-124a, and miR-373 using Gene Ontology (GO) analysis and revealed the importance of pairing at positions 4, 5, and 6 in the 5' region of a miRNA from a feature selection experiment. We also provide a web interface for the program. CONCLUSION: miTarget is a reliable miRNA target gene prediction tool and is a successful application of an SVM classifier. Compared with previous tools, its predictions are meaningful by GO analysis and its performance can be improved given more training examples

    Digital public health leadership in the global fight for health security

    Get PDF
    The COVID-19 pandemic highlighted the need to prioritise mature digital health and data governance at both national and supranational levels to guarantee future health security. The Riyadh Declaration on Digital Health was a call to action to create the infrastructure needed to share effective digital health evidence-based practices and high-quality, real-time data locally and globally to provide actionable information to more health systems and countries. The declaration proposed nine key recommendations for data and digital health that need to be adopted by the global health community to address future pandemics and health threats. Here, we expand on each recommendation and provide an evidence-based roadmap for their implementation. This policy document serves as a resource and toolkit that all stakeholders in digital health and disaster preparedness can follow to develop digital infrastructure and protocols in readiness for future health threats through robust digital public health leadership.Peer reviewe

    Effect of Magnetic Pulsed Compaction (MPC) on sintering behavior of materials

    Get PDF
    Soon-Jik Hong, Md. Raihanuzzaman Rumman and Chang Kyu Rhe

    Acute-Onset Bilateral Myopia and Ciliochoroidal Effusion Induced by Hydrochlorothiazide

    Get PDF
    The authors experienced two cases of hydrochlorothiazide (HCTZ)-induced acute-onset bilateral myopia and shallowing of the anterior chambers. Two middle-aged women taking HCTZ, a sulfa derivative, visited our clinic complaining of acute bilateral visual deterioration. Both had good visual acuity without corrective lenses before taking HCTZ. A complete ophthalmologic examination revealed bilateral myopic shift, intraocular pressure elevation, shallowing of the anterior chambers, choroidal effusions, radiating retinal folds, and conjunctival chemosis. Approximately one week after HCTZ discontinuance, all ocular changes disappeared completely. Physicians should be aware of the adverse ocular effects of HCTZ and should manage patients accordingly
    corecore