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- 저자 : Clevers, H. (검색결과 4 건)
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Lee, M.,Yoon, J.,Song, H.,Lee, B.,Lam, D.T.,Yoon, J.,Baek, K.,Clevers, H.,Jeong, Y. Academic Press 2017 Developmental biology Vol.424 No.1
<P>The thalamus acts as a central integrator for processing and relaying sensory and motor information to and from the cerebral cortex, and the habenula plays pivotal roles in emotive decision making by modulating dopaminergic and serotonergic circuits. These neural compartments are derived from a common developmental progenitor domain, called prosomere 2, in the caudal forebrain. Thalamic and habenular neurons exhibit distinct molecular profile, neurochemical identity, and axonal circuitry. However, the mechanisms of how their progenitors in prosomere 2 give rise to these two populations of neurons and contribute to the forebrain circuitry remains unclear. In this study, we discovered a previously unrecognized role for Tcf7l2, a transcription factor known as the canonical Wnt nuclear effector and diabetes risk-conferring gene, in establishing neuronal identity and circuits of the caudal forebrain. Using genetic and chemical axon tracers, we showed that efferent axons of the thalamus, known as the thalamocortical axons (TCAs), failed to elongate normally and strayed from their normal course to inappropriate locations in the absence of Tcf7l2. Further experiments with thalamic explants revealed that the pathfinding defects of Tcf7l2-deficient TCAs were associated at least in part with downregulation of guidance receptors Robol and Robo2 expression. Moreover, the fasciculus retroflexus, the main habenular output tract, was missing in embryos lacking Tcf7l2. These axonal defects may result from dysregulation of Nrp2 guidance receptor. Strikingly, loss of Tcf7l2 caused a post-mitotic identity switch between thalamic and habenular neurons. Despite normal acquisition of progenitor identity in prosomere 2, Tcf7l2-deficient thalamic neurons adopted a molecular profile of a neighboring forebrain derivative, the habenula. Conversely, habenular neurons failed to maintain their normal post-mitotic neuronal identity and acquired a subset of thalamic neuronal features in the absence of Tcf7l2. Our findings suggest a unique role for Tcf7l2 in generating distinct neuronal phenotypes from homogeneous progenitor population, and provide a better understanding of the mechanism underlying neuronal specification, differentiation, and connectivity of the developing caudal forebrain.</P>
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Tumour suppressor RNF43 is a stem-cell E3 ligase that induces endocytosis of Wnt receptors
Koo, Bon-Kyoung,Spit, Maureen,Jordens, Ingrid,Low, Teck Y.,Stange, Daniel E.,van de Wetering, Marc,van Es, Johan H.,Mohammed, Shabaz,Heck, Albert J. R.,Maurice, Madelon M.,Clevers, Hans Nature Publishing Group, a division of Macmillan P 2012 Nature Vol.488 No.7413
LGR5<SUP>+</SUP> stem cells reside at crypt bottoms, intermingled with Paneth cells that provide Wnt, Notch and epidermal growth factor signals. Here we find that the related RNF43 and ZNRF3 transmembrane E3 ubiquitin ligases are uniquely expressed in LGR5<SUP>+</SUP> stem cells. Simultaneous deletion of the two genes encoding these proteins in the intestinal epithelium of mice induces rapidly growing adenomas containing high numbers of Paneth and LGR5<SUP>+</SUP> stem cells. In vitro, growth of organoids derived from these adenomas is arrested when Wnt secretion is inhibited, indicating a dependence of the adenoma stem cells on Wnt produced by adenoma Paneth cells. In the HEK293T human cancer cell line, expression of RNF43 blocks Wnt responses and targets surface-expressed frizzled receptors to lysosomes. In the RNF43-mutant colorectal cancer cell line HCT116, reconstitution of RNF43 expression removes its response to exogenous Wnt. We conclude that RNF43 and ZNRF3 reduce Wnt signals by selectively ubiquitinating frizzled receptors, thereby targeting these Wnt receptors for degradation.
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Substrate Mixture Optimization of Nutrients Needed for Methane Yield
Peter Tumutegyereize,Clever Ketlogetswe,Jerekias Gandure,Noble Banadda 한국농업기계학회 2019 바이오시스템공학 Vol.44 No.2
Purpose The twofold aim of this study was to optimize nutrients important for methane yield in substrate mixtures and to assess the effect of the optimized nutrients on methane production. Method Augmented simplex lattice design was used on three substrates, i.e., matooke peels (MPs), cassava peels (CPs), and sweet potato peels (SPs) wherein 16 ratio combinations were assessed for their macro- and micronutrient compositions and methane production potential. Experimental data was simulated using canonical polynomial models to determine mixture combinations with optimal nutrients stimulatory to methane yield. Results Six optimization solutions with the global optimal having a desirability of 0.93 and a ratio of 0.611:0.375:0.015 were observed to be localized over the design space. Biomethane experiments were in agreement with the optimized mixture ratios as ratios that gave the highest methane yield of 0.3 Nm3CH4/kg VS and above lay in the optimized design region. Conclusion Therefore, charts showing optimized regions of different substrate mixtures in terms of their nutrients can be a tool in biogas digester operations.
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Mnyawi, Richard,Kombe, Cleverence,Sam, Anael,Nyambo, Devotha International Journal of Computer ScienceNetwork S 2022 International journal of computer science and netw Vol.22 No.3
Health information systems (HIS) are facing security challenges on data privacy and confidentiality. These challenges are based on centralized system architecture creating a target for malicious attacks. Blockchain technology has emerged as a trending technology with the potential to improve data security. Despite the effectiveness of this technology, still HIS are suffering from a lack of data privacy and confidentiality. This paper presents a blockchain-based data storage security architecture integrated with an e-Health care system to improve its security. The study employed a qualitative research method where data were collected using interviews and document analysis. Execute-order-validate Fabric's storage security architecture was implemented through private data collection, which is the combination of the actual private data stored in a private state, and a hash of that private data to guarantee data privacy. The key findings of this research show that data privacy and confidentiality are attained through a private data policy. Network peers are decentralized with blockchain only for hash storage to avoid storage challenges. Cost-effectiveness is achieved through data storage within a database of a Hyperledger Fabric. The overall performance of Fabric is higher than Ethereum. Ethereum's low performance is due to its execute-validate architecture which has high computation power with transaction inconsistencies. E-Health care system administrators should be trained and engaged with blockchain architectural designs for health data storage security. Health policymakers should be aware of blockchain technology and make use of the findings. The scientific contribution of this study is based on; cost-effectiveness of secured data storage, the use of hashes of network data stored in each node, and low energy consumption of Fabric leading to high performance.
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