The rapid development of Information and Communication Technology (ICT) has an impact on the innovation of new technology that gives benefits for health. One of its latest development is wearable device technology. No...
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Standardising the representation of biomedical knowledge among all researchers is an insurmountable task, hindering the effectiveness of many computational methods. To facilitate harmonisation and interoperability des...
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Combinatorial control by transcription factors (TFs) is central to eukaryotic gene regulation, yet its mechanism, evolution, and regulatory impact are not well understood. Here we use natural variation in the yeast ph...
Combinatorial control by transcription factors (TFs) is central to eukaryotic gene regulation, yet its mechanism, evolution, and regulatory impact are not well understood. Here we use natural variation in the yeast phosphate starvation (PHO) response to examine the genetic basis and species variation in TF interdependence. In Saccharomyces cerevisiae, the main TF Pho4 relies on the co-TF Pho2 to regulate ~28 genes, whereas in the related pathogen Candida glabrata, Pho4 has reduced Pho2 dependence and regulates ~70 genes. We found C. glabrata Pho4 (CgPho4) binds the same motif with 3-4 fold higher affinity. Machine learning and yeast one-hybrid assay identify two intrinsically disordered regions (IDRs) in CgPho4 that boost its activation domain's activity. In ScPho4, an IDR next to the DNA binding domain both allows for enhanced activity with Pho2 and inhibits activity without Pho2. This study reveals how IDR divergence drives TF interdependence evolution by influencing activation potential and autoinhibition.
Massively parallel sequencing techniques have revolutionized biological and medical sciences by providing unprecedented insight into the genomes of humans, animals, and microbes. Modern sequencing platforms generate e...
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Predicting how genetic variation affects phenotypic outcomes at the organismal, cellular, and molecular levels requires deciphering the cis-regulatory code, the sequence rules by which non-coding regions regulate gene...
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Channa striata or the striped snakehead fish is one of snakehead fish species which inhabits all types of freshwater bodies distributed across Asian countries. Because this fish is known to have higher albumin fractio...
Channa striata or the striped snakehead fish is one of snakehead fish species which inhabits all types of freshwater bodies distributed across Asian countries. Because this fish is known to have higher albumin fraction (64.61%) of protein and other economic values, domestication, and cultivation of this fish has been done in many Asian countries such as Indonesia, China, Malaysia, Thailand, Bangladesh, and India. Environmental factors such as temperature, water pH, dissolved oxygen, total dissolved solids, and turbidity are important parameters must be considered inbreeding and growing this type of fish. The aim of this paper is to propose an IoT solution to automatically monitor these environmental factors. It is designed with affordable and open-source electrical components to provide a cost-efficient solution for farmers. Five sensors are used to measure each parameter. A web application prototype is also presented as a companion application for the users to get useful information from the IoT device. It is developed using a Pythonframework. By accessing this web application, the users can immediately detect any abnormal conditions of the pond.
Post-traumatic stress disorder (PTSD) is a polygenic disorder occurring after extreme trauma exposure. Recent studies have begun to detail the molecular biology of PTSD. However, given the array of PTSD-perturbed mole...
Post-traumatic stress disorder (PTSD) is a polygenic disorder occurring after extreme trauma exposure. Recent studies have begun to detail the molecular biology of PTSD. However, given the array of PTSD-perturbed molecular pathways identified so far, it is implausible that a single cell type is responsible. Here we profile the molecular responses in over two million nuclei from the dorsolateral prefrontal cortex of 111 human brains, collected post-mortem from individuals with and without PTSD and major depressive disorder. We identify neuronal and non-neuronal cell-type clusters, gene expression changes and transcriptional regulators, and map the epigenomic regulome of PTSD in a cell-type-specific manner. Our analysis revealed PTSD-associated gene alterations in inhibitory neurons, endothelial cells and microglia and uncovered genes and pathways associated with glucocorticoid signalling, GABAergic transmission and neuroinflammation. We further validated these findings using cell-type-specific spatial transcriptomics, confirming disruption of key genes such as SST and FKBP5. By integrating genetic, transcriptomic and epigenetic data, we uncovered the regulatory mechanisms of credible variants that disrupt PTSD genes, including ELFN1, MAD1L1 and KCNIP4, in a cell-type-specific context. Together, these findings provide a comprehensive characterization of the cell-specific molecular regulatory mechanisms that underlie the persisting effects of traumatic stress response on the human prefrontal cortex.
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