Notch signaling is required for maintaining stem-cell features of neuroprogenitor cells derived from human embryonic stem cells

<p>Abstract</p> <p>Background</p> <p>Studies have provided important findings about the roles of Notch signaling in neural development. Unfortunately, however, most of these studies have investigated the neural stem cells (NSCs) of mice or other laboratory animals rather than humans, mainly owing to the difficulties associated with obtaining human brain samples. It prompted us to focus on neuroectodermal spheres (NESs) which are derived from human embryonic stem cell (hESC) and densely inhabited by NSCs. We here investigated the role of Notch signaling with the hESC-derived NESs.</p> <p>Results</p> <p>From hESCs, we derived NESs, the <it>in-vitro </it>version of brain-derived neurospheres. NES formation was confirmed by increased levels of various NSC marker genes and the emergence of rosette structures in which neuroprogenitors are known to reside. We found that Notch signaling, which maintains stem cell characteristics of <it>in-vivo</it>-derived neuroprogenitors, is active in these hESC-derived NESs, similar to their <it>in-vivo </it>counterpart. Expression levels of Notch signaling molecules such as NICD, DLLs, JAG1, HES1 and HES5 were increased in the NESs. Inhibition of the Notch signaling by a γ-secretase inhibitor reduced rosette structures, expression levels of NSC marker genes and proliferation potential in the NESs, and, if combined with withdrawal of growth factors, triggered differentiation toward neurons.</p> <p>Conclusion</p> <p>Our results indicate that the hESC-derived NESs, which share biochemical features with brain-derived neurospheres, maintain stem cell characteristics mainly through Notch signaling, which suggests that the hESC-derived NESs could be an <it>in-vitro </it>model for <it>in-vivo </it>neurogenesis.</p

Achieving tolerant CO₂ electro-reduction catalyst in real water matrix

In order to achieve practical application of electrochemical CO₂ conversion technologies, the development of durable catalyst in real water matrix is essential because the use of catalysts only showing high performance within a well-refined environment cannot guarantee their feasibility in realistic conditions. Here, we report a design strategy for a catalyst, which shows excellent tolerance to deactivation factors, using a carbon-based material under more practical condition implemented by real tap water. Screening analyses on various components in tap water elucidated that the impurity group, which can be deposited on the catalyst surface and impede the active sites, such as copper, zinc, and especially iron are the main factors responsible for deactivation. Based on these findings, the structural modified nitrogen-doped carbon nanotube (denoted as ball mill N-CNT) was adopted as a catalyst design to secure durability. Consequently, the ball mill N-CNT revealed tolerance to the disclosed deactivation factors and showed stable performance during unprecedented long-time of 120 h in tap water media

PIAS1 regulates CP2c localization and active promoter complex formation in erythroid cell-specific α-globin expression

Data presented here extends our previous observations on α-globin transcriptional regulation by the CP2 and PIAS1 proteins. Using RNAi knockdown, we have now shown that CP2b, CP2c and PIAS1 are each necessary for synergistic activation of endogenous α-globin gene expression in differentiating MEL cells. In this system, truncated PIAS1 mutants lacking the ring finger domain recruited CP2c to the nucleus, as did wild-type PIAS1, demonstrating that this is a sumoylation-independent process. In vitro, recombinant CP2c, CP2b and PIAS1 bound DNA as a stable CBP (CP2c/CP2b/PIAS1) complex. Following PIAS1 knockdown in MEL cells, however, the association of endogenous CP2c and CP2b with the α-globin promoter simultaneously decreased. By mapping the CP2b- and CP2c-binding domains on PIAS1, and the PIAS1-binding domains on CP2b and CP2c, we found that two regions of PIAS1 that interact with CP2c/CP2b are required for its co-activator function. We propose that CP2c, CP2b, and PIAS1 form a hexametric complex with two units each of CP2c, CP2b, and PIAS1, in which PIAS1 serves as a clamp between two CP2 proteins, while CP2c binds directly to the target DNA and CP2b mediates strong transactivation

Efficacy of selenium supplementation for mild-to-moderate Graves ophthalmopathy in a selenium-sufficient area (SeGOSS trial): study protocol for a phase III, multicenter, open-label, randomized, controlled intervention trial

Background The therapeutic effect of selenium has been demonstrated in mild Graves ophthalmopathy (GO) in a European region where selenium status is suboptimal. However, there is a lack of evidence to support selenium use in selenium-sufficient areas. The aim of this study is to evaluate the therapeutic effect of selenium in mild-to-moderate GO in selenium-sufficient South Korea. Methods The SeGOSS trial is a multicenter, prospective, randomized, open-label trial in South Korea. Eighty-four patients aged 19years or older with mild-to-moderate GO will be randomized to receive either vitamin B complex alone or vitamin B complex with selenium for 6months with three monthly follow-up visits. The primary outcome is comparison of the improvement in quality of life at 6months from baseline between the control and selenium groups. The secondary outcomes are intergroup differences in changes in quality of life at 3months, clinical activity of GO at 3 and 6months, thyroid autoantibody titers at 3 and 6months, and the response rate at 3 and 6months from baseline. Quality of life will be measured by questionnaire for patients with GO, and the clinical activity of GO will be evaluated by the clinical activity score (CAS). A positive response is defined as either changes in the CAS < 0 or the changes in the GO-QOL score ≥ 6. Discussion The SeGOSS study will evaluate the therapeutic potential of selenium for mild-to-moderate GO in a selenium-sufficient area and provide support in tailoring better treatment for GO.

Clinical Experiences of Pheochromocytoma in Korea

∙ The authors have no financial conflicts of interest. Purpose: We report herein 119 patients with pheochromocytoma at our institute over the last 23 years. Materials and Methods: Between 1986 and 2009, 119 patients were diagnosed with pheochromocytoma at our institute. We reviewed the medical records of these patients. Results: Of 119 patients, 45 were male and 74 were female, and mean age was 43.83 ± 13.49 years. Forty-three patients (36.1%) were diagnosed incidentally, and 8 patients (6.7%) were found to have familial pheochromocytoma. The mean dimension of the tumors was 5.89 ± 3.18 cm. 4 patients had bilateral tumors; three of these patients were found to have familial pheochromocytoma and 1 patient was diagnosed with malignant pheochromocytoma. A total of eight patients (6.7%) were found to have malignant pheochromocytoma. In 1 patient, metastasis to a lymph node was found at the time of diagnosis. Metastases were found at a mean of 49 ± 25.83 (6-75) months after surgery in the other seven patients. 6 patients died of malignant pheochromocytoma at

Temporal Changes in Functional Magnetic Resonance Imaging Activation of Heterosexual Couples for Visual Stimuli of Loved Partners

ObjectiveaaPrevious neuroimaging studies on romantic love have focused on determining how the visual stimuli that serve as a representation of loved ones induce the neural activation patterns of romantic love. The purpose of this study was to investigate the temporal changes in romantic love over a period of 6 months and their correlated neurophysiological changes. MethodsaaFive heterosexual couples (n=10, mean age 21.1±1.97) who started dating not less than 100 days previously were recruited to measure their blood oxygen level dependent (BOLD) signals using functional magnetic resonance imaging (fMRI) while showing them pictures of their loved ones and their previously identified, opposite-sex friends. Subsequently, the subjects were scanned under the same experimental conditions to assess possible changes in their brain activities after 180 days. ResultsaaWe found that their Passionate Love Score (PLS) values (M: 118.6±9.1, F: 120.2 ±7.0) were significantly reduced after 6 months (M: 110.8±4.0, F: 106.2±3.0). Furthermore, significantly increased activations were found in the cingulate gyri, inferior frontal gyri, supramarginal gyri, etc., after 6 months, whereas the head and tail of the right caudate nucleus were deactivated, which is indicative of the inhibition of expression and sensory neglect. ConclusionaaThese findings suggest that dynamic neural processes in the cortical-subcortical regions are involved in temporal changes in romantic love

Temporal Changes in Functional Magnetic Resonance Imaging Activation of Heterosexual Couples for Visual Stimuli of Loved Partners

ObjectiveaaPrevious neuroimaging studies on romantic love have focused on determining how the visual stimuli that serve as a representation of loved ones induce the neural activation patterns of romantic love. The purpose of this study was to investigate the temporal changes in romantic love over a period of 6 months and their correlated neurophysiological changes. MethodsaaFive heterosexual couples (n=10, mean age 21.1±1.97) who started dating not less than 100 days previously were recruited to measure their blood oxygen level dependent (BOLD) signals using functional magnetic resonance imaging (fMRI) while showing them pictures of their loved ones and their previously identified, opposite-sex friends. Subsequently, the subjects were scanned under the same experimental conditions to assess possible changes in their brain activities after 180 days. ResultsaaWe found that their Passionate Love Score (PLS) values (M: 118.6±9.1, F: 120.2 ±7.0) were significantly reduced after 6 months (M: 110.8±4.0, F: 106.2±3.0). Furthermore, significantly increased activations were found in the cingulate gyri, inferior frontal gyri, supramarginal gyri, etc., after 6 months, whereas the head and tail of the right caudate nucleus were deactivated, which is indicative of the inhibition of expression and sensory neglect. ConclusionaaThese findings suggest that dynamic neural processes in the cortical-subcortical regions are involved in temporal changes in romantic love