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Find video protocols related to scientific articles indexed in Pubmed.
Large-Scale Production of Graphene Nanoribbons from Electrospun Polymers.
J. Am. Chem. Soc.
PUBLISHED: 11-20-2014
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Graphene nanoribbons (GNRs) are promising building blocks for high-performance electronics due to their high electron mobility and dimensionality-induced bandgap. Despite many past efforts, direct synthesis of GNRs with controlled dimensions and scalability remains challenging. Here we report the scalable synthesis of GNRs using electrospun polymer nanofibers templates. Palladium-incorporated poly-(4-vinylphenol) nanofibers were prepared by electrospinning with controlled diameter and orientation. Highly graphitized GNRs as narrow as 10 nm were then synthesized from these templates by chemical vapor deposition. A transport gap can be observed in 30-nm-wide GNRs, enabling them to function as field-effect transistors at room temperature. Our results represent the first success on the scalable synthesis of highly graphitized GNRs from polymer templates. Furthermore, the generality of this method allows various polymers to be explored, which will lead to understanding of growth mechanism and rational control over crystallinity, feature size and bandgap to enable a new pathway for graphene electronics.
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Distinct aetiopathogenesis in subgroups of functional dyspepsia according to the Rome III criteria.
Gut
PUBLISHED: 11-20-2014
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Whether there is distinct pathogenesis in subgroups of functional dyspepsia (FD), the postprandial distress syndrome (PDS) and epigastric pain syndrome (EPS) remains controversial. We aimed to identify the risk factors of FD and its subgroups in the Chinese population.
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Effect of copper oxide oxidation state on the polymer-based solar cell buffer layers.
ACS Appl Mater Interfaces
PUBLISHED: 11-19-2014
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Transporting buffer layers are important components of the polymer-based organic photovoltaic devices. In this study, we have investigated the effects of the oxidation state in copper oxide based buffer layer in conjunction to its role in device performance. We have shown that variation in the oxidation state affects the band alignment and built-in voltage of the device, therefore, leading to variation in device performance. Specifically, the fully oxidized copper oxide buffer layer has a valence band position at 5.12 eV, much closer to the highest occupied molecular orbital of Poly(3-hexylthiophene-2,5-diyl) (P3HT) (~5.2 eV), giving a best fill factor and efficiency at 57% and 4.06%, respectively. Lastly, we also demonstrate significant enhancement in device stability, with power conversion efficiency maintained at 75% of the original value even after 40 days, and propose a strategy in recovering the device performance based on the observed property of the oxide buffer layer.
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Young capillary vessels rejuvenate aged pancreatic islets.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 11-19-2014
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Pancreatic islets secrete hormones that play a key role in regulating blood glucose levels (glycemia). Age-dependent impairment of islet function and concomitant dysregulation of glycemia are major health threats in aged populations. However, the major causes of the age-dependent decline of islet function are still disputed. Here we demonstrate that aging of pancreatic islets in mice and humans is notably associated with inflammation and fibrosis of islet blood vessels but does not affect glucose sensing and the insulin secretory capacity of islet beta cells. Accordingly, when transplanted into the anterior chamber of the eye of young mice with diabetes, islets from old mice are revascularized with healthy blood vessels, show strong islet cell proliferation, and fully restore control of glycemia. Our results indicate that beta cell function does not decline with age and suggest that islet function is threatened by an age-dependent impairment of islet vascular function. Strategies to mitigate age-dependent dysregulation in glycemia should therefore target systemic and/or local inflammation and fibrosis of the aged islet vasculature.
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High Electrochemical Selectivity of Edge versus Terrace Sites in Two-Dimensional Layered MoS2 Materials.
Nano Lett.
PUBLISHED: 11-06-2014
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Exploring the chemical reactivity of different atomic sites on crystal surface and controlling their exposures are important for catalysis and renewable energy storage. Here, we use two-dimensional layered molybdenum disulfide (MoS2) to demonstrate the electrochemical selectivity of edge versus terrace sites for Li-S batteries and hydrogen evolution reaction (HER). Lithium sulfide (Li2S) nanoparticles decorates along the edges of the MoS2 nanosheet versus terrace, confirming the strong binding energies between Li2S and the edge sites and guiding the improved electrode design for Li-S batteries. We also provided clear comparison of HER activity between edge and terrace sites of MoS2 beyond the previous theoretical prediction and experimental proof.
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miR-142 regulates the tumorigenicity of human breast cancer stem cells through the canonical WNT signaling pathway.
Elife
PUBLISHED: 10-16-2014
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MicroRNAs (miRNAs) are important regulators of stem and progenitor cell functions. We previously reported that miR-142 and miR-150 are upregulated in human breast cancer stem cells (BCSCs) as compared to the non-tumorigenic breast cancer cells. In this study, we report that miR-142 efficiently recruits the APC mRNA to an RNA-induced silencing complex, activates the canonical WNT signaling pathway in an APC-suppression dependent manner, and activates the expression of miR-150. Enforced expression of miR-142 or miR-150 in normal mouse mammary stem cells resulted in the regeneration of hyperproliferative mammary glands in vivo. Knockdown of endogenous miR-142 effectively suppressed organoid formation by BCSCs and slowed tumor growth initiated by human BCSCs in vivo. These results suggest that in some tumors, miR-142 regulates the properties of BCSCs at least in part by activating the WNT signaling pathway and miR-150 expression.
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?-Cell Ca(2+) dynamics and function are compromised in aging.
Adv Biol Regul
PUBLISHED: 09-11-2014
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Defects in pancreatic ?-cell function and survival are key components in type 2 diabetes (T2D). An age-dependent deterioration in ?-cell function has also been observed, but little is known about the molecular mechanisms behind this phenomenon. Our previous studies indicate that the regulation of cytoplasmic free Ca(2+) concentration ([Ca(2+)]i) may be critical and that this is dependent on the proper function of the mitochondria. The [Ca(2+)]i dynamics of the pancreatic ?-cell are driven by an interplay between glucose-induced influx of extracellular Ca(2+) via voltage-dependent Ca(2+) channels and the inositol 1,4,5-trisphosphate (Ins(1,4,5)P3)-mediated liberation of Ca(2+) from intracellular stores. Our previous work has indicated a direct relationship between disruption of Ins(1,4,5)P3-mediated Ca(2+) regulation and loss of ?-cell function, including disturbed [Ca(2+)]i dynamics and compromised insulin secretion. To investigate these processes in aging we used three mouse models, a premature aging mitochondrial mutator mouse, a mature aging phenotype (C57BL/6) and an aging-resistant phenotype (129). Our data suggest that age-dependent impairment in mitochondrial function leads to modest changes in [Ca(2+)]i dynamics in mouse ?-cells, particularly in the pattern of [Ca(2+)]i oscillations. These changes are driven by modifications in both PLC/Ins(1,4,5)P3-mediated Ca(2+) mobilization from intracellular stores and decreased ?-cell Ca(2+) influx over the plasma membrane. Our findings underscore an important concept, namely that even relatively small, time-dependent changes in ?-cell signal-transduction result in compromised insulin release and in a diabetic phenotype.
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Comparing HbA1c, fasting and 2-h plasma glucose for screening for abnormal glucose regulation in patients undergoing coronary angiography.
Clin. Chem. Lab. Med.
PUBLISHED: 08-27-2014
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Abstract Background: We aimed to investigate the prevalence of undiagnosed abnormal glucose regulation (AGR, including diabetes and prediabetes) in patients undergoing coronary angiography (CAG) by using both glycated hemoglobin (HbA1c) and oral glucose tolerance test (OGTT) to screen, and to compare the performance of fasting plasma glucose (FPG), 2-h plasma glucose (2hPG), and HbA1c for screening for AGR. Methods: Eligible patients were adults without known diabetes who were admitted for CAG. Patients' glucose regulation status was defined by conducting HbA1c and OGTT 2-4 weeks after hospital discharge. The performance of FPG, 2hPG, and HbA1c for detecting AGR was evaluated using receiver operating characteristic (ROC) analysis. Results: A total of 689 subjects were included. According to OGTT, the prevalence rates of diabetes and prediabetes were 19.9% and 41.7%, respectively. The corresponding values were 28.0% and 60.4%, respectively, when HbA1c was adopted as a diagnostic criterion in addition to OGTT. For detecting diabetes, the area under the ROC curve (AUC) was higher for HbA1c than for FPG (0.87 vs. 0.80, p=0.005), but was not significantly different from that for 2hPG (0.87 vs. 0.88, p=0.58). For detecting AGR, the AUC was higher for HbA1c than for either FPG (0.94 vs. 0.74, p<0.001) or 2hPG (0.94 vs. 0.83, p<0.001). Conclusions: Using HbA1c and OGTT to screen, we reported an extremely high prevalence of previously undiagnosed AGR (28.0% diabetes and 60.4% prediabetes) in patients admitted for CAG. HbA1c may be adopted as an alternative to OGTT for screening for AGR in patients undergoing CAG.
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Intravital imaging of cytotoxic T lymphocytes.
Methods Mol. Biol.
PUBLISHED: 08-24-2014
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Intravital imaging approaches are proving to be essential to address new questions to better understand how the immune system operates. These approaches are especially valuable to characterize the complex organization of immune responses in vivo. Here, we examine how to take advantage of the cornea as a natural body window to apply noninvasive imaging techniques to assess cytotoxic T lymphocyte involvement in the immune rejection process in a model of intraocular allogeneic islet transplantation.
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MicroRNA-124a is hyperexpressed in type 2 diabetic human pancreatic islets and negatively regulates insulin secretion.
Acta Diabetol
PUBLISHED: 08-01-2014
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MicroRNAs are a class of negative regulators of gene expression, which have been shown to be involved in the development of endocrine pancreas and in the regulation of insulin secretion. Since type 2 diabetes (T2D) is characterized by beta cell dysfunction, we aimed at evaluating expression levels of miR-124a and miR-375, both involved in the control of beta cell function, in human pancreatic islets obtained from T2D and from age-matched non-diabetic organ donors.
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Electrolessly deposited electrospun metal nanowire transparent electrodes.
J. Am. Chem. Soc.
PUBLISHED: 07-17-2014
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Metal nanowire (MNW) transparent electrodes have been widely developed for their promising sheet resistance (R(s))-transmittance (T) performance, excellent mechanical flexibility, and facile synthesis. How to lower the junction resistance without compromising optical transmittance has become the key issue in enhancing their performance. Here we combine electrospinning and electroless deposition to synthesize interconnected, ultralong MNW networks. For both silver and copper nanowire networks, the R(s) and T values reach around 10 ?/sq and 90%, respectively. This process is scalable and takes place at ambient temperature and pressure, which opens new opportunities for flexible electronics and roll-to-roll large-scale manufacturing.
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Ciliary dysfunction impairs beta-cell insulin secretion and promotes development of type 2 diabetes in rodents.
Nat Commun
PUBLISHED: 07-16-2014
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Type 2 diabetes mellitus is affecting more than 382 million people worldwide. Although much progress has been made, a comprehensive understanding of the underlying disease mechanism is still lacking. Here we report a role for the ?-cell primary cilium in type 2 diabetes susceptibility. We find impaired glucose handling in young Bbs4(-/-) mice before the onset of obesity. Basal body/ciliary perturbation in murine pancreatic islets leads to impaired first phase insulin release ex and in vivo. Insulin receptor is recruited to the cilium of stimulated ?-cells and ciliary/basal body integrity is required for activation of downstream targets of insulin signalling. We also observe a reduction in the number of ciliated ?-cells along with misregulated ciliary/basal body gene expression in pancreatic islets in a diabetic rat model. We suggest that ciliary function is implicated in insulin secretion and insulin signalling in the ?-cell and that ciliary dysfunction could contribute to type 2 diabetes susceptibility.
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Mitochondrial GTP insensitivity contributes to hypoglycemia in hyperinsulinemia hyperammonemia by inhibiting glucagon release.
Diabetes
PUBLISHED: 07-14-2014
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Mitochondrial GTP (mtGTP)-insensitive mutations in glutamate dehydrogenase (GDH(H454Y)) result in fasting and amino acid-induced hypoglycemia in hyperinsulinemia hyperammonemia (HI/HA). Surprisingly, hypoglycemia may occur in this disorder despite appropriately suppressed insulin. To better understand the islet-specific contribution, transgenic mice expressing the human activating mutation in ?-cells (H454Y mice) were characterized in vivo. As in the humans with HI/HA, H454Y mice had fasting hypoglycemia, but plasma insulin concentrations were similar to the controls. Paradoxically, both glucose- and glutamine-stimulated insulin secretion were severely impaired in H454Y mice. Instead, lack of a glucagon response during hypoglycemic clamps identified impaired counterregulation. Moreover, both insulin and glucagon secretion were impaired in perifused islets. Acute pharmacologic inhibition of GDH restored both insulin and glucagon secretion and normalized glucose tolerance in vivo. These studies support the presence of an mtGTP-dependent signal generated via ?-cell GDH that inhibits ?-cells. As such, in children with activating GDH mutations of HI/HA, this insulin-independent glucagon suppression may contribute importantly to symptomatic hypoglycemia. The identification of a human mutation causing congenital hypoglucagonemic hypoglycemia highlights a central role of the mtGTP-GDH-glucagon axis in glucose homeostasis.
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Defects in ?-Cell Ca2+ Dynamics in Age-Induced Diabetes.
Diabetes
PUBLISHED: 07-01-2014
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Little is known about the molecular mechanisms underlying age-dependent deterioration in ?-cell function. We now demonstrate that age-dependent impairment in insulin release, and thereby glucose homeostasis, is associated with subtle changes in Ca(2+) dynamics in mouse ?-cells. We show that these changes are likely to be accounted for by impaired mitochondrial function and to involve phospholipase C/inositol 1,4,5-trisphosphate-mediated Ca(2+) mobilization from intracellular stores as well as decreased ?-cell Ca(2+) influx over the plasma membrane. We use three mouse models, namely, a premature aging phenotype, a mature aging phenotype, and an aging-resistant phenotype. Premature aging is studied in a genetically modified mouse model with an age-dependent accumulation of mitochondrial DNA mutations. Mature aging is studied in the C57BL/6 mouse, whereas the 129 mouse represents a model that is more resistant to age-induced deterioration. Our data suggest that aging is associated with a progressive decline in ?-cell mitochondrial function that negatively impacts on the fine tuning of Ca(2+) dynamics. This is conceptually important since it emphasizes that even relatively modest changes in ?-cell signal transduction over time lead to compromised insulin release and a diabetic phenotype.
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Hyperplastic polyps identified during screening endoscopy: reevaluated by histological examinations and genetic alterations.
J. Formos. Med. Assoc.
PUBLISHED: 06-26-2014
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Screening colonoscopy is one of the most effective methods to detect and prevent colorectal cancer by removing neoplastic polyps. The recent discovery of serrated polyps with neoplastic potential has reclassified these polyps into hyperplastic polyps (HPs), sessile serrated adenoma (SSA), and traditional serrated adenoma (TSA) on the basis of macroscopic morphology and microscopic histology. In this study, we aimed to revisit HPs identified during screening endoscopy by histological reevaluation and genetic alterations.
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Two-dimensional layered transition metal disulphides for effective encapsulation of high-capacity lithium sulphide cathodes.
Nat Commun
PUBLISHED: 06-18-2014
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Fully lithiated lithium sulphide (Li2S) is currently being explored as a promising cathode material for emerging energy storage applications. Like their sulphur counterparts, Li2S cathodes require effective encapsulation to reduce the dissolution of intermediate lithium polysulphide (Li2Sn, n=4-8) species into the electrolyte. Here we report, the encapsulation of Li2S cathodes using two-dimensional layered transition metal disulphides that possess a combination of high conductivity and strong binding with Li2S/Li2Sn species. In particular, using titanium disulphide as an encapsulation material, we demonstrate a high specific capacity of 503?mAh?g(-1)(Li2S) under high C-rate conditions (4C) as well as high areal capacity of 3.0?mAh?cm(-2) under high mass-loading conditions (5.3?mg(Li2S)?cm(-2)). This work opens up the new prospect of using transition metal disulphides instead of conventional carbon-based materials for effective encapsulation of high-capacity electrode materials.
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Consensus on control of risky nonvariceal upper gastrointestinal bleeding in Taiwan with National Health Insurance.
Biomed Res Int
PUBLISHED: 06-13-2014
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To compose upper gastrointestinal bleeding (UGIB) consensus from a nationwide scale to improve the control of UGIB, especially for the high-risk comorbidity group.
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Distinct stages of the translation elongation cycle revealed by sequencing ribosome-protected mRNA fragments.
Elife
PUBLISHED: 05-21-2014
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During translation elongation, the ribosome ratchets along its mRNA template, incorporating each new amino acid and translocating from one codon to the next. The elongation cycle requires dramatic structural rearrangements of the ribosome. We show here that deep sequencing of ribosome-protected mRNA fragments reveals not only the position of each ribosome but also, unexpectedly, its particular stage of the elongation cycle. Sequencing reveals two distinct populations of ribosome footprints, 28-30 nucleotides and 20-22 nucleotides long, representing translating ribosomes in distinct states, differentially stabilized by specific elongation inhibitors. We find that the balance of small and large footprints varies by codon and is correlated with translation speed. The ability to visualize conformational changes in the ribosome during elongation, at single-codon resolution, provides a new way to study the detailed kinetics of translation and a new probe with which to identify the factors that affect each step in the elongation cycle.DOI: http://dx.doi.org/10.7554/eLife.01257.001.
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Expression of nucleobindin 1 (NUCB1) in pancreatic islets and other endocrine tissues.
Cell Tissue Res.
PUBLISHED: 05-02-2014
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The protein nucleobindin 1 (NUCB1; also known as CALNUC or Nuc) contains an intriguing combination of DNA- and calcium-binding motifs, a trait that it shares with the protein nucleobindin 2 (NUCB2; also known as nesfatin). NUCB2 has been implicated in several aspects of metabolic control and has been identified in a number of endocrine organs. No such comprehensive mapping of NUCB1 has been presented. We have explored the expression and distribution of NUCB1 in tissues and cells of the mouse endocrine system, with particular focus on the endocrine pancreas. Using reverse transcription plus the polymerase chain reaction (RT-PCR) and Western blot, we demonstrate that NUCB1 is present in the endocrine islets of Langerhans but absent from the exocrine acinar cells. Immunofluorescence studies have revealed that all islet cell types contain NUCB1, including the NUCB2-expressing beta cells. RT-PCR, Western blot and immunofluorescence have shown that NUCB1 is expressed in the pituitary, thyroid, parathyroid, gastrointestinal tract, adrenals and gonads. However, within these tissues, NUCB1 expression is not ubiquitous. For example, in the testis, NUCB1 occurs in the seminiferous tubules but not in the Leydig-cell-containing interstitial tissue. Similarly, the lamina propria of the duodenum lacks NUCB1, despite its presence in enterocytes. Where present, NUCB1 consistently appears to be associated with the Golgi apparatus. Thus, NUCB1 is broadly, but not ubiquitously, expressed in cells of the mouse endocrine system. Together with its location in the Golgi apparatus and its putative Ca(2+)-binding ability, this distribution suggests a role for NUCB1 in Ca(2+) handling/sensing in secretory cells.
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Weight loss reduces serum monocyte chemoattractant protein-1 concentrations in association with improvements in renal injury in obese men with metabolic syndrome.
Clin. Chem. Lab. Med.
PUBLISHED: 05-01-2014
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Abstract Background: Monocyte chemoattractant protein-1 (MCP-1) is involved in obesity-related renal injury. The aim of the present study was to examine the effects of weight loss on changes in MCP-1 and markers of renal injury, specifically serum cystatin C (S-CysC) and urinary N-acetyl glucosaminidase (UNAG), in obese people. Methods: In this prospective study, 40 obese men with metabolic syndrome (MetS) participated in a 3-month dietary and exercise intervention. Twenty-eight subjects completed the study with a ?5% weight loss. Circulating MCP-1, S-CysC and UNAG to creatinine ratio (UNCR) were determined before and after the weight loss program. Results: Obesity-associated components of MetS demonstrated significant improvements after the weight loss program. In addition, at baseline, circulating MCP-1 concentrations were positively correlated with UNCR and S-CysC levels. After weight loss, blood MCP-1 and UNCR levels were significantly decreased, but S-CysC was not affected. Using multiple linear regression analysis, there was a significant relationship between changes in UNCR and MCP-1 after adjusting for other potential confounding factors. Conclusions: Weight loss may improve renal tubular injury by ameliorating obesity-related inflammation in obese men with MetS.
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Short and prolonged exposure to hyperglycaemia in human fibroblasts and endothelial cells: metabolic and osmotic effects.
Int. J. Biochem. Cell Biol.
PUBLISHED: 04-25-2014
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High blood glucose levels are the main feature of diabetes. However, the underlying mechanism linking high glucose concentration to diabetic complications is still not fully elucidated, particularly with regard to human physiology. Excess of glucose is likely to trigger a metabolic response depending on the cell features, activating deleterious pathways involved in the complications of diabetes. In this study, we aim to elucidate how acute and prolonged hyperglycaemia alters the biology and metabolism in human fibroblasts and endothelial cells. We found that hyperglycaemia triggers a metabolic switch from oxidative phosphorylation to glycolysis that is maintained over prolonged time. Moreover, osmotic pressure is a major factor in the early metabolic response, decreasing both mitochondrial transmembrane potential and cellular proliferation. After prolonged exposure to hyperglycaemia we observed decreased mitochondrial steady-state and uncoupled respiration, together with a reduced ATP/ADP ratio. At the same time, we could not detect major changes in mitochondrial transmembrane potential and reactive oxygen species. We suggest that the physiological and metabolic alterations observed in healthy human primary fibroblasts and endothelial cells are an adaptive response to hyperglycaemia. The severity of metabolic and bioenergetics impairment associated with diabetic complications may occur after longer glucose exposure or due to interactions with cell types more sensitive to hyperglycaemia.
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CaV1.2 and CaV1.3 channel hyperactivation in mouse islet ? cells exposed to type 1 diabetic serum.
Cell. Mol. Life Sci.
PUBLISHED: 04-22-2014
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The voltage-gated Ca(2+) (CaV) channel acts as a key player in ? cell physiology and pathophysiology. ? cell CaV channels undergo hyperactivation subsequent to exposure to type 1 diabetic (T1D) serum resulting in increased cytosolic free Ca(2+) concentration and thereby Ca(2+)-triggered ? cell apoptosis. The present study was aimed at revealing the subtypes of CaV1 channels hyperactivated by T1D serum as well as the biophysical mechanisms responsible for T1D serum-induced hyperactivation of ? cell CaV1 channels. Patch-clamp recordings and single-cell RT-PCR analysis were performed in pancreatic ? cells from CaV1 channel knockout and corresponding control mice. We now show that functional CaV1.3 channels are expressed in a subgroup of islet ? cells from CaV1.2 knockout mice (CaV1.2(-/-)). T1D serum enhanced whole-cell CaV currents in islet ? cells from CaV1.3 knockout mice (CaV1.3(-/-)). T1D serum increased the open probability and number of functional unitary CaV1 channels in CaV1.2(-/-) and CaV1.3(-/-) ? cells. These data demonstrate that T1D serum hyperactivates both CaV1.2 and CaV1.3 channels by increasing their conductivity and number. These findings suggest CaV1.2 and CaV1.3 channels as potential targets for anti-diabetes therapy.
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Improving lithium-sulphur batteries through spatial control of sulphur species deposition on a hybrid electrode surface.
Nat Commun
PUBLISHED: 04-22-2014
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Lithium-sulphur batteries are attractive owing to their high theoretical energy density and reasonable kinetics. Despite the success of trapping soluble polysulphides in a matrix with high surface area, spatial control of solid-state sulphur and lithium sulphide species deposition as a critical aspect has not been demonstrated. Herein, we show a clear visual evidence that these solid species deposit preferentially onto tin-doped indium oxide instead of carbon during electrochemical charge/discharge of soluble polysuphides. To incorporate this concept of spatial control into more practical battery electrodes, we further prepare carbon nanofibers with tin-doped indium oxide nanoparticles decorating the surface as hybrid three-dimensional electrodes to maximize the number of deposition sites. With 12.5 ?l of 5 M Li2S8 as the catholyte and a rate of C/5, we can reach the theoretical limit of Li2S8 capacity ~\n1,470 mAh g(-1) (sulphur weight) under the loading of hybrid electrode only at 4.3 mg cm(-2).
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Normal values and symptom correlation of a simplified oatmeal-based gastric emptying study in the Chinese population.
J. Gastroenterol. Hepatol.
PUBLISHED: 04-10-2014
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Instant oatmeal has been proposed as a good alternative to the standardized low-fat egg white test meal for gastric emptying studies. We aim to establish normal values of oatmeal-based gastric emptying scintigraphy and test its correlation with gastroparesis symptoms in the Chinese population.
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Large cell anaplastic medulloblastoma metastatic to the scalp: tumor and derived stem-like cells features.
BMC Cancer
PUBLISHED: 04-09-2014
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Extraneural metastases (ENM) rarely occur in medulloblastoma (MBL) patients and only few cases of subcutaneous localizations have been described. ENM indicate an aggressive disease associated with a worse prognosis. The characterization of metastatic tumours might be useful to understand their pathogenesis and to identify the most appropriate therapeutic strategies.
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Control of insulin secretion by cholinergic signaling in the human pancreatic islet.
Diabetes
PUBLISHED: 03-21-2014
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Acetylcholine regulates hormone secretion from the pancreatic islet and is thus crucial for glucose homeostasis. Little is known, however, about acetylcholine (cholinergic) signaling in the human islet. We recently reported that in the human islet, acetylcholine is primarily a paracrine signal released from ?-cells rather than primarily a neural signal as in rodent islets. In this study, we demonstrate that the effects acetylcholine produces in the human islet are different and more complex than expected from studies conducted on cell lines and rodent islets. We found that endogenous acetylcholine not only stimulates the insulin-secreting ?-cell via the muscarinic acetylcholine receptors M3 and M5, but also the somatostatin-secreting ?-cell via M1 receptors. Because somatostatin is a strong inhibitor of insulin secretion, we hypothesized that cholinergic input to the ?-cell indirectly regulates ?-cell function. Indeed, when all muscarinic signaling was blocked, somatostatin secretion decreased and insulin secretion unexpectedly increased, suggesting a reduced inhibitory input to ?-cells. Endogenous cholinergic signaling therefore provides direct stimulatory and indirect inhibitory input to ?-cells to regulate insulin secretion from the human islet.
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Adipsin is an adipokine that improves ? cell function in diabetes.
Cell
PUBLISHED: 03-19-2014
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A hallmark of type 2 diabetes mellitus (T2DM) is the development of pancreatic ? cell failure, which results in insulinopenia and hyperglycemia. We show that the adipokine adipsin has a beneficial role in maintaining ? cell function. Animals genetically lacking adipsin have glucose intolerance due to insulinopenia; isolated islets from these mice have reduced glucose-stimulated insulin secretion. Replenishment of adipsin to diabetic mice treated hyperglycemia by boosting insulin secretion. We identify C3a, a peptide generated by adipsin, as a potent insulin secretagogue and show that the C3a receptor is required for these beneficial effects of adipsin. C3a acts on islets by augmenting ATP levels, respiration, and cytosolic free Ca(2+). Finally, we demonstrate that T2DM patients with ? cell failure are deficient in adipsin. These findings indicate that the adipsin/C3a pathway connects adipocyte function to ? cell physiology, and manipulation of this molecular switch may serve as a therapy in T2DM.
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Carbon dioxide insufflation can significantly reduce toilet use after colonoscopy: a double-blind randomized controlled trial.
Endoscopy
PUBLISHED: 02-26-2014
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Carbon dioxide (CO2) insufflation during colonoscopy can significantly decrease abdominal pain and bloating after the procedure, but its impact on the frequency and duration of toilet use remains unknown. The aim of this study was to assess the impact of CO2 insufflation on toilet use after screening colonoscopy.
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Ionic mechanisms in pancreatic ? cell signaling.
Cell. Mol. Life Sci.
PUBLISHED: 02-22-2014
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The function and survival of pancreatic ? cells critically rely on complex electrical signaling systems composed of a series of ionic events, namely fluxes of K(+), Na(+), Ca(2+) and Cl(-) across the ? cell membranes. These electrical signaling systems not only sense events occurring in the extracellular space and intracellular milieu of pancreatic islet cells, but also control different ? cell activities, most notably glucose-stimulated insulin secretion. Three major ion fluxes including K(+) efflux through ATP-sensitive K(+) (KATP) channels, the voltage-gated Ca(2+) (CaV) channel-mediated Ca(2+) influx and K(+) efflux through voltage-gated K(+) (KV) channels operate in the ? cell. These ion fluxes set the resting membrane potential and the shape, rate and pattern of firing of action potentials under different metabolic conditions. The KATP channel-mediated K(+) efflux determines the resting membrane potential and keeps the excitability of the ? cell at low levels. Ca(2+) influx through CaV1 channels, a major type of ? cell CaV channels, causes the upstroke or depolarization phase of the action potential and regulates a wide range of ? cell functions including the most elementary ? cell function, insulin secretion. K(+) efflux mediated by KV2.1 delayed rectifier K(+) channels, a predominant form of ? cell KV channels, brings about the downstroke or repolarization phase of the action potential, which acts as a brake for insulin secretion owing to shutting down the CaV channel-mediated Ca(2+) entry. These three ion channel-mediated ion fluxes are the most important ionic events in ? cell signaling. This review concisely discusses various ionic mechanisms in ? cell signaling and highlights KATP channel-, CaV1 channel- and KV2.1 channel-mediated ion fluxes.
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CXCL12 secreted from adipose tissue recruits macrophages and induces insulin resistance in mice.
Diabetologia
PUBLISHED: 02-15-2014
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Obesity-induced inflammation is initiated by the recruitment of macrophages into adipose tissue. The recruited macrophages, called adipose tissue macrophages, secrete several proinflammatory cytokines that cause low-grade systemic inflammation and insulin resistance. The aim of this study was to find macrophage-recruiting factors that are thought to provide a crucial connection between obesity and insulin resistance.
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Brain-derived neurotrophic factor, but not body weight, correlated with a reduction in depression scale scores in men with metabolic syndrome: a prospective weight-reduction study.
Diabetol Metab Syndr
PUBLISHED: 02-11-2014
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Obesity, a critical component of metabolic syndrome (MetS), is associated with depression. Deficiency of brain-derived neurotrophic factor (BDNF) is involved in the mechanism of depression. We hypothesized that weight reduction would improve depressive symptoms via increasing BDNF levels in obese men.
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Electrochemical tuning of layered lithium transition metal oxides for improvement of oxygen evolution reaction.
Nat Commun
PUBLISHED: 01-31-2014
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Searching for low-cost and efficient catalysts for the oxygen evolution reaction has been actively pursued owing to its importance in clean energy generation and storage. While developing new catalysts is important, tuning the electronic structure of existing catalysts over a wide electrochemical potential range can also offer a new direction. Here we demonstrate a method for electrochemical lithium tuning of catalytic materials in organic electrolyte for subsequent enhancement of the catalytic activity in aqueous solution. By continuously extracting lithium ions out of LiCoO2, a popular cathode material in lithium ion batteries, to Li0.5CoO2 in organic electrolyte, the catalytic activity is significantly improved. This enhancement is ascribed to the unique electronic structure after the delithiation process. The general efficacy of this methodology is demonstrated in several mixed metal oxides with similar improvements. The electrochemically delithiated LiCo0.33Ni0.33Fe0.33O2 exhibits a notable performance, better than the benchmark iridium/carbon catalyst.
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Current management of diminutive colorectal polyps in Taiwan.
Dig Endosc
PUBLISHED: 01-17-2014
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The majority of polyps detected during colonoscopy are diminutive polyps, for which the cost of pathological analysis is substantial. In our analysis of a screening cohort of 10737 subjects undergoing screening colonoscopy, a total of 15877 neoplastic lesions were detected, of which 10816 (68.1%) were diminutive lesions. Of those diminutive lesions, 90 (0.83%) had a villous component, 14 (0.1%) had high-grade dysplasia, and none had invasive cancer. Only 1.3% of patients were advised to decrease their surveillance interval because of unfavorable histology. Laws regulating medical practice, uncertainty regarding the accuracy of endoscopic diagnosis of diminutive polyps outside of academic centers, and the relatively low cost of pathological analysis are among the barriers to adopting a 'resect and discard' practice in Taiwan.
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Distribution and abundance of schistosomiasis and fascioliasis host snails along the Mara River in Kenya and Tanzania.
Infect Ecol Epidemiol
PUBLISHED: 01-01-2014
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We purposively selected 39 sampling sites along the Mara River and its two perennial tributaries of Amala and Nyangores and sampled snails. In addition, water physicochemical parameters (temperature, turbidity, dissolved oxygen, conductivity, alkalinity, salinity and pH) were taken to establish their influence on the snail abundance and habitat preference. Out of the 39 sites sampled, 10 (25.6%) had snails. The snail species encountered included Biomphalaria pfeifferi Krauss - the intermediate host of Schistosoma mansoni Sambon, Bulinus africanus - the intermediate host of Schistosoma haematobium, and Lymnaea natalensis Krauss - the intermediate host of both Fasciola gigantica and F. hepatica Cobbold. Ceratophallus spp., a non-vector snail was also encountered. Most (61.0%) of the snails were encountered in streamside pools. Schistosomiasis-transmitting host snails, B. pfeifferi and B. africanus, were fewer than fascioliasis-transmitting Lymnaea species. All the four different snail species were found to be attached to different aquatic weeds, with B. pfeifferi accounting for over half (61.1%) of the snails attached to the sedge, followed by B. africanus and Lymnaea spp., accounting for 22.2 and 16.7%, respectively. Ceratophallus spp. were non-existent in sedge. The results from this preliminary study show that snails intermediate hosts of schistosomiasis and fascioliasis exists in different habitats, in few areas along the Mara River, though their densities are still low to have any noticeable impacts on disease transmission in case they are infected. The mere presence of the vector snails in these focal regions calls for their immediate control and institution of proper regulations, management, and education among the locals that can help curtail the spread of the snails and also schistosomiasis and fascioliasis within the Mara River basin.
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Correlation between reduction of superior interventricular groove epicardial fat thickness and improvement of insulin resistance after weight loss in obese men.
Diabetol Metab Syndr
PUBLISHED: 01-01-2014
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It has been recognized that reduction of abdominal visceral fat and subcutaneous fat are associated with improvement in insulin-resistance (IR) after weight loss. However, few studies have investigated the correlation of reduction in epicardial adipose tissue (EAT) with improvement of IR index after weight loss in obese non-diabetic men with metabolic syndrome (MetS).
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Transcriptome-Wide Mapping of Pseudouridines: Pseudouridine Synthases Modify Specific mRNAs in S. cerevisiae.
PLoS ONE
PUBLISHED: 01-01-2014
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We developed a novel technique, called pseudouridine site identification sequencing (PSI-seq), for the transcriptome-wide mapping of pseudouridylation sites with single-base resolution from cellular RNAs based on the induced termination of reverse transcription specifically at pseudouridines following CMCT treatment. PSI-seq analysis of RNA samples from S. cerevisiae correctly detected all of the 43 known pseudouridines in yeast 18S and 25S ribosomal RNA with high specificity. Moreover, application of PSI-seq to the yeast transcriptome revealed the presence of site-specific pseudouridylation within dozens of mRNAs, including RPL11a, TEF1, and other genes implicated in translation. To identify the mechanisms responsible for mRNA pseudouridylation, we genetically deleted candidate pseudouridine synthase (Pus) enzymes and reconstituted their activities in vitro. These experiments demonstrated that the Pus1 enzyme was necessary and sufficient for pseudouridylation of RPL11a mRNA, whereas Pus4 modified TEF1 mRNA, and Pus6 pseudouridylated KAR2 mRNA. Finally, we determined that modification of RPL11a at ? -68 was observed in RNA from the related yeast S. mikitae, and ? -239 in TEF1 mRNA was maintained in S. mikitae as well as S. pombe, indicating that these pseudouridylations are ancient, evolutionarily conserved RNA modifications. This work establishes that site-specific pseudouridylation of eukaryotic mRNAs is a genetically programmed RNA modification that naturally occurs in multiple yeast transcripts via distinct mechanisms, suggesting that mRNA pseudouridylation may provide an important novel regulatory function. The approach and strategies that we report here should be generally applicable to the discovery of pseudouridylation, or other RNA modifications, in diverse biological contexts.
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Contribution of endothelial injury and inflammation in early phase to vein graft failure: the causal factors impact on the development of intimal hyperplasia in murine models.
PLoS ONE
PUBLISHED: 01-01-2014
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Autologous veins are preferred conduits in by-pass surgery. However, long-term results are hampered by limited patency due to intimal hyperplasia. Although mechanisms involved in development of intimal hyperplasia have been established, the role of inflammatory processes is still unclear. Here, we studied leukocyte recruitment and intimal hyperplasia in inferior vena cava grafts transferred to abdominal aorta in mice.
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Association of esophageal inflammation, obesity and gastroesophageal reflux disease: from FDG PET/CT perspective.
PLoS ONE
PUBLISHED: 01-01-2014
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Gastroesophageal reflux disease (GERD) is associated with bothersome symptoms and neoplastic progression into Barrett's esophagus and esophageal adenocarcinoma. We aim to determine the correlation between GERD, esophageal inflammation and obesity with 18F-Fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT).
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Circular RNA is expressed across the eukaryotic tree of life.
PLoS ONE
PUBLISHED: 01-01-2014
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An unexpectedly large fraction of genes in metazoans (human, mouse, zebrafish, worm, fruit fly) express high levels of circularized RNAs containing canonical exons. Here we report that circular RNA isoforms are found in diverse species whose most recent common ancestor existed more than one billion years ago: fungi (Schizosaccharomyces pombe and Saccharomyces cerevisiae), a plant (Arabidopsis thaliana), and protists (Plasmodium falciparum and Dictyostelium discoideum). For all species studied to date, including those in this report, only a small fraction of the theoretically possible circular RNA isoforms from a given gene are actually observed. Unlike metazoans, Arabidopsis, D. discoideum, P. falciparum, S. cerevisiae, and S. pombe have very short introns (? 100 nucleotides or shorter), yet they still produce circular RNAs. A minority of genes in S. pombe and P. falciparum have documented examples of canonical alternative splicing, making it unlikely that all circular RNAs are by-products of alternative splicing or 'piggyback' on signals used in alternative RNA processing. In S. pombe, the relative abundance of circular to linear transcript isoforms changed in a gene-specific pattern during nitrogen starvation. Circular RNA may be an ancient, conserved feature of eukaryotic gene expression programs.
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High-throughput microRNA profiling of pediatric high-grade gliomas.
Neuro-oncology
PUBLISHED: 12-04-2013
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BackgroundHigh-grade gliomas (HGGs) account for 15% of all pediatric brain tumors and are a leading cause of cancer-related mortality and morbidity. Pediatric HGGs (pHGGs) are histologically indistinguishable from their counterpart in adulthood. However, recent investigations indicate that differences occur at the molecular level, thus suggesting that the molecular path to gliomagenesis in childhood is distinct from that of adults. MicroRNAs (miRNAs) have been identified as key molecules in gene expression regulation, both in development and in cancer. miRNAs have been investigated in adult high-grade gliomas (aHGGs), but scant information is available for pHGGs.MethodsWe explored the differences in microRNAs between pHGG and aHGG, in both fresh-frozen and paraffin-embedded tissue, by high-throughput miRNA profiling. We also evaluated the biological effects of miR-17-92 cluster silencing on a pHGG cell line.ResultsComparison of miRNA expression patterns in formalin versus frozen specimens resulted in high correlation between both types of samples. The analysis of miRNA profiling revealed a specific microRNA pattern in pHGG with an overexpression and a proliferative role of the miR-17-92 cluster. Moreover, we highlighted a possible quenching function of miR-17-92 cluster on its target gene PTEN, together with an activation of tumorigenic signaling such as sonic hedgehog in pHGG.ConclusionsOur results suggest that microRNA profiling represents a tool to distinguishing pediatric from adult HGG and that miR-17-92 cluster sustains pHGG.
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Electrochemical tuning of vertically aligned MoS2 nanofilms and its application in improving hydrogen evolution reaction.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 11-18-2013
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The ability to intercalate guest species into the van der Waals gap of 2D layered materials affords the opportunity to engineer the electronic structures for a variety of applications. Here we demonstrate the continuous tuning of layer vertically aligned MoS2 nanofilms through electrochemical intercalation of Li(+) ions. By scanning the Li intercalation potential from high to low, we have gained control of multiple important material properties in a continuous manner, including tuning the oxidation state of Mo, the transition of semiconducting 2H to metallic 1T phase, and expanding the van der Waals gap until exfoliation. Using such nanofilms after different degree of Li intercalation, we show the significant improvement of the hydrogen evolution reaction activity. A strong correlation between such tunable material properties and hydrogen evolution reaction activity is established. This work provides an intriguing and effective approach on tuning electronic structures for optimizing the catalytic activity.
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Reporter islets in the eye reveal the plasticity of the endocrine pancreas.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 11-18-2013
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The islets of Langerhans constitute the endocrine part of the pancreas and are responsible for maintenance of blood glucose homeostasis. They are deeply embedded in the exocrine pancreas, limiting their accessibility for functional studies. Understanding regulation of function and survival and assessing the clinical outcomes of individual treatment strategies for diabetes requires a monitoring system that continuously reports on the endocrine pancreas. We describe the application of a natural body window that successfully reports on the properties of in situ pancreatic islets. As proof of principle, we transplanted "reporter islets" into the anterior chamber of the eye of leptin-deficient mice. These islets displayed obesity-induced growth and vascularization patterns that were reversed by leptin treatment. Hence, reporter islets serve as optically accessible indicators of islet function in the pancreas, and also reflect the efficacy of specific treatment regimens aimed at regulating islet plasticity in vivo.
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Accuracy of faecal occult blood test and Helicobacter pylori stool antigen test for detection of upper gastrointestinal lesions.
BMJ Open
PUBLISHED: 11-02-2013
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Highly sensitive guaiac-based faecal occult blood (Hemoccult SENSA) and Helicobacter pylori stool antigen testing might help detect upper gastrointestinal lesions when appended to a colorectal cancer screening programme with faecal immunochemical testing. We evaluated the diagnostic accuracies of two stool tests in detecting upper gastrointestinal lesions.
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Computer-aided diagnosis in endoscopy: A novel application toward automatic detection of abnormal lesions on magnifying narrow-band imaging endoscopy in the stomach.
Conf Proc IEEE Eng Med Biol Soc
PUBLISHED: 10-11-2013
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Gastric cancer is the fourth common cancer and the second major cause of cancer death worldwide. Early detection of gastric cancer by endoscopy surveillance is actively investigated to improve patient survival, especially using the newly developed magnifying narrow-band imaging endoscopy in the stomach. However, meticulous examination of the aforementioned images is both time and experience demanding and interpretation could be variable among different doctors, which hindered its widespread application. In this study, we developed a new image analysis system by adopting local binary pattern and vector quantization to perform pattern comparison between known training abnormal images and testing images of magnifying narrow band endoscopy images in the stomach. Our preliminary results demonstrated promising potential for automatically labeled region of interest for endoscopy doctors to focus on abnormal lesions for subsequent targeted biopsy, with the rates of recall 0.46-1.00 and precision 0.39-0.87.
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TNF-? and IFN-? promote lymphocyte adhesion to endothelial junctional regions facilitating transendothelial migration.
J. Leukoc. Biol.
PUBLISHED: 09-26-2013
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Inflammatory conditions induce redistribution of junctional adhesion receptors toward the apical regions of endothelial cells promoting lymphocyte TEM. Much of the molecular structures of TEM have been revealed; however, the biophysical mechanisms underlying this process remain to be fully elucidated. Here, we used immunofluorescence microscopy and AFM to study endothelial distribution of adhesion molecules upon lymphocyte activation and transmigration. Our immunofluorescence results revealed redistribution of JAM-A and PECAM-1 but not ICAM-1 or VCAM-1 toward the apical junctional regions of HUVECs following a 6-h stimulation with TNF-? and IFN-?. Consistently, our SCFS studies revealed that Jurkat cell adhesion to stimulated HUVEC monolayers was significantly greater in junctional regions. Enhanced adhesion was mediated mostly by JAM-A receptors. Further AFM adhesion mapping of the homophilic JAM-A/JAM-A interaction on the surfaces of HUVECs revealed a greater number of JAM-A receptors available for binding along junctional regions after TNF-? and IFN-? stimulation. Our data reveal for the first time that adhesion "hot spots" of JAM-A receptors are involved in initiating lymphocyte TEM under inflammatory conditions.
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Microbial battery for efficient energy recovery.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 09-16-2013
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By harnessing the oxidative power of microorganisms, energy can be recovered from reservoirs of less-concentrated organic matter, such as marine sediment, wastewater, and waste biomass. Left unmanaged, these reservoirs can become eutrophic dead zones and sites of greenhouse gas generation. Here, we introduce a unique means of energy recovery from these reservoirs-a microbial battery (MB) consisting of an anode colonized by microorganisms and a reoxidizable solid-state cathode. The MB has a single-chamber configuration and does not contain ion-exchange membranes. Bench-scale MB prototypes were constructed from commercially available materials using glucose or domestic wastewater as electron donor and silver oxide as a coupled solid-state oxidant electrode. The MB achieved an efficiency of electrical energy conversion of 49% based on the combustion enthalpy of the organic matter consumed or 44% based on the organic matter added. Electrochemical reoxidation of the solid-state electrode decreased net efficiency to about 30%. This net efficiency of energy recovery (unoptimized) is comparable to methane fermentation with combined heat and power.
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Adjuvant treatments for resected pancreatic adenocarcinoma: a systematic review and network meta-analysis.
Lancet Oncol.
PUBLISHED: 09-12-2013
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Major adjuvant treatments for pancreatic adenocarcinoma include fluorouracil, gemcitabine, chemoradiation, and chemoradiation plus fluorouracil or gemcitabine. Since the optimum regimen remains inconclusive, we aimed to compare these treatments in terms of overall survival after tumour resection and in terms of grade 3-4 toxic effects with a systematic review and random-effects Bayesian network meta-analysis.
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Cell-type specific features of circular RNA expression.
PLoS Genet.
PUBLISHED: 09-01-2013
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Thousands of loci in the human and mouse genomes give rise to circular RNA transcripts; at many of these loci, the predominant RNA isoform is a circle. Using an improved computational approach for circular RNA identification, we found widespread circular RNA expression in Drosophila melanogaster and estimate that in humans, circular RNA may account for 1% as many molecules as poly(A) RNA. Analysis of data from the ENCODE consortium revealed that the repertoire of genes expressing circular RNA, the ratio of circular to linear transcripts for each gene, and even the pattern of splice isoforms of circular RNAs from each gene were cell-type specific. These results suggest that biogenesis of circular RNA is an integral, conserved, and regulated feature of the gene expression program.
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Coached practice using ERCP mechanical simulator improves trainees ERCP performance: a randomized controlled trial.
Endoscopy
PUBLISHED: 07-29-2013
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Preliminary data suggested that simulation practice using an endoscopic retrograde cholangiopancreatography (ERCP) mechanical simulator (EMS) improved trainees skill. The aims of the current study were to confirm the impact of coached EMS practice at the beginning of ERCP training and to investigate whether subsequent uncoached EMS practice provides additional benefit.
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Leptin promotes K(ATP) channel trafficking by AMPK signaling in pancreatic ?-cells.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 07-15-2013
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Leptin is a pivotal regulator of energy and glucose homeostasis, and defects in leptin signaling result in obesity and diabetes. The ATP-sensitive potassium (K(ATP)) channels couple glucose metabolism to insulin secretion in pancreatic ?-cells. In this study, we provide evidence that leptin modulates pancreatic ?-cell functions by promoting K(ATP) channel translocation to the plasma membrane via AMP-activated protein kinase (AMPK) signaling. K(ATP) channels were localized mostly to intracellular compartments of pancreatic ?-cells in the fed state and translocated to the plasma membrane in the fasted state. This process was defective in leptin-deficient ob/ob mice, but restored by leptin treatment. We discovered that the molecular mechanism of leptin-induced AMPK activation involves canonical transient receptor potential 4 and calcium/calmodulin-dependent protein kinase kinase ?. AMPK activation was dependent on both leptin and glucose concentrations, so at optimal concentrations of leptin, AMPK was activated sufficiently to induce K(ATP) channel trafficking and hyperpolarization of pancreatic ?-cells in a physiological range of fasting glucose levels. There was a close correlation between phospho-AMPK levels and ?-cell membrane potentials, suggesting that AMPK-dependent K(ATP) channel trafficking is a key mechanism for regulating ?-cell membrane potentials. Our results present a signaling pathway whereby leptin regulates glucose homeostasis by modulating ?-cell excitability.
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Effectiveness of intragastric balloon treatment for obese patients: one-year follow-up after balloon removal.
Obes Surg
PUBLISHED: 07-09-2013
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The Bioenterics Intragastric Balloon (BIB) is effective for weight loss. However, comparisons of its effectiveness between groups with different body mass index (BMI) are rare. This study compared the effectiveness of BIB treatment in patients with BMI <32 kg/m(2) and those with BMI ? 32 kg/m(2) at the time of BIB removal and at 1 year later.
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Usefulness of PET/CT for the differentiation and characterization of periampullary lesions.
Clin Nucl Med
PUBLISHED: 07-03-2013
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At present, there is no ideal imaging modality for the diagnosis of periampullary lesions. We prospectively evaluated the preoperative diagnostic usefulness of PET/CT for differentiating malignant from benign periampullary lesions.
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Differential regulation of mouse pancreatic islet insulin secretion and Smad proteins by activin ligands.
Diabetologia
PUBLISHED: 06-14-2013
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Glucose-stimulated insulin secretion (GSIS) from pancreatic beta cells is regulated by paracrine factors, the identity and mechanisms of action of which are incompletely understood. Activins are expressed in pancreatic islets and have been implicated in the regulation of GSIS. Activins A and B signal through a common set of intracellular components, but it is unclear whether they display similar or distinct functions in glucose homeostasis.
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Quantitative proteomic analysis reveals concurrent RNA-protein interactions and identifies new RNA-binding proteins in Saccharomyces cerevisiae.
Genome Res.
PUBLISHED: 05-01-2013
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A growing body of evidence supports the existence of an extensive network of RNA-binding proteins (RBPs) whose combinatorial binding affects the post-transcriptional fate of every mRNA in the cell-yet we still do not have a complete understanding of which proteins bind to mRNA, which of these bind concurrently, and when and where in the cell they bind. We describe here a method to identify the proteins that bind to RNA concurrently with an RBP of interest, using quantitative mass spectrometry combined with RNase treatment of affinity-purified RNA-protein complexes. We applied this method to the known RBPs Pab1, Nab2, and Puf3. Our method significantly enriched for known RBPs and is a clear improvement upon previous approaches in yeast. Our data reveal that some reported protein-protein interactions may instead reflect simultaneous binding to shared RNA targets. We also discovered more than 100 candidate RBPs, and we independently confirmed that 77% (23/30) bind directly to RNA. The previously recognized functions of the confirmed novel RBPs were remarkably diverse, and we mapped the RNA-binding region of one of these proteins, the transcriptional coactivator Mbf1, to a region distinct from its DNA-binding domain. Our results also provided new insights into the roles of Nab2 and Puf3 in post-transcriptional regulation by identifying other RBPs that bind simultaneously to the same mRNAs. While existing methods can identify sets of RBPs that interact with common RNA targets, our approach can determine which of those interactions are concurrent-a crucial distinction for understanding post-transcriptional regulation.
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Imaging dynamics of CD11c? cells and Foxp3? cells in progressive autoimmune insulitis in the NOD mouse model of type 1 diabetes.
Diabetologia
PUBLISHED: 04-24-2013
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The aim of this study was to visualise the dynamics and interactions of the cells involved in autoimmune-driven inflammation in type 1 diabetes.
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Performance enhancement of metal nanowire transparent conducting electrodes by mesoscale metal wires.
Nat Commun
PUBLISHED: 04-23-2013
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For transparent conducting electrodes in optoelectronic devices, electrical sheet resistance and optical transmittance are two of the main criteria. Recently, metal nanowires have been demonstrated to be a promising type of transparent conducting electrode because of low sheet resistance and high transmittance. Here we incorporate a mesoscale metal wire (1-5??m in diameter) into metal nanowire transparent conducting electrodes and demonstrate at least a one order of magnitude reduction in sheet resistance at a given transmittance. We realize experimentally a hybrid of mesoscale and nanoscale metal nanowires with high performance, including a sheet resistance of 0.36???sq(-1) and transmittance of 92%. In addition, the mesoscale metal wires are applied to a wide range of transparent conducting electrodes including conducting polymers and oxides with improvement up to several orders of magnitude. The metal mesowires can be synthesized by electrospinning methods and their general applicability opens up opportunities for many transparent conducting electrode applications.
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A transparent electrode based on a metal nanotrough network.
Nat Nanotechnol
PUBLISHED: 04-11-2013
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Transparent conducting electrodes are essential components for numerous flexible optoelectronic devices, including touch screens and interactive electronics. Thin films of indium tin oxide-the prototypical transparent electrode material-demonstrate excellent electronic performances, but film brittleness, low infrared transmittance and low abundance limit suitability for certain industrial applications. Alternatives to indium tin oxide have recently been reported and include conducting polymers, carbon nanotubes and graphene. However, although flexibility is greatly improved, the optoelectronic performance of these carbon-based materials is limited by low conductivity. Other examples include metal nanowire-based electrodes, which can achieve sheet resistances of less than 10? ?(-1) at 90% transmission because of the high conductivity of the metals. To achieve these performances, however, metal nanowires must be defect-free, have conductivities close to their values in bulk, be as long as possible to minimize the number of wire-to-wire junctions, and exhibit small junction resistance. Here, we present a facile fabrication process that allows us to satisfy all these requirements and fabricate a new kind of transparent conducting electrode that exhibits both superior optoelectronic performances (sheet resistance of ~2? ?(-1) at 90% transmission) and remarkable mechanical flexibility under both stretching and bending stresses. The electrode is composed of a free-standing metallic nanotrough network and is produced with a process involving electrospinning and metal deposition. We demonstrate the practical suitability of our transparent conducting electrode by fabricating a flexible touch-screen device and a transparent conducting tape.
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microRNA-17-92 cluster is a direct Nanog target and controls neural stem cell through Trp53inp1.
EMBO J.
PUBLISHED: 04-05-2013
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The transcription factor Nanog plays a critical role in the self-renewal of embryonic stem cells as well as in neural stem cells (NSCs). microRNAs (miRNAs) are also involved in stemness regulation. However, the miRNA network downstream of Nanog is still poorly understood. High-throughput screening of miRNA expression profiles in response to modulated levels of Nanog in postnatal NSCs identifies miR-17-92 cluster as a direct target of Nanog. Nanog controls miR-17-92 cluster by binding to the upstream regulatory region and maintaining high levels of transcription in NSCs, whereas Nanog/promoter association and cluster miRNAs expression are lost alongside differentiation. The two miR-17 family members of miR-17-92 cluster, namely miR-17 and miR-20a, target Trp53inp1, a downstream component of p53 pathway. To support a functional role, the presence of miR-17/20a or the loss of Trp53inp1 is required for the Nanog-induced enhancement of self-renewal of NSCs. We unveil an arm of the Nanog/p53 pathway, which regulates stemness in postnatal NSCs, wherein Nanog counteracts p53 signals through miR-17/20a-mediated repression of Trp53inp1.
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Genome-wide association study in a Chinese population with diabetic retinopathy.
Hum. Mol. Genet.
PUBLISHED: 04-04-2013
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Diabetic retinopathy (DR) is a leading cause of preventable blindness in adults. To identify genetic contributions in DR, we studied 2071 type 2 diabetics. We first conducted a genome-wide association study of 1007 individuals, comparing 570 subjects with ?8 years duration without DR (controls) with 437 PDR (cases) in the Chinese discovery cohort. Cases and controls were similar for HbA1c, diabetes duration and body mass index. Association analysis with imputed data identified three novel loci: TBC1D4-COMMD6-UCHL3 (rs9565164, P = 1.3 × 10(-7)), LRP2-BBS5 (rs1399634, P = 2.0 × 10(-6)) and ARL4C-SH3BP4 (rs2380261, P = 2.1 × 10(-6)). Analysis of an independent cohort of 585 Hispanics diabetics with or without DR though did not confirm these signals. These genes are still of particular interest because they are involved in insulin regulation, inflammation, lipid signaling and apoptosis pathways, all of which are possibly involved with DR. Our finding nominates possible novel loci as potential DR susceptibility genes in the Chinese that are independent of the level of HbA1c and duration of diabetes and may provide insight into the pathophysiology of DR.
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Multiscale cross-approximate entropy analysis as a measure of complexity among the aged and diabetic.
Comput Math Methods Med
PUBLISHED: 03-22-2013
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Complex fluctuations within physiological signals can be used to evaluate the health of the human body. This study recruited four groups of subjects: young healthy subjects (Group 1, n = 32), healthy upper middle-aged subjects (Group 2, n = 36), subjects with well-controlled type 2 diabetes (Group 3, n = 31), and subjects with poorly controlled type 2 diabetes (Group 4, n = 24). Data acquisition for each participant lasted 30 minutes. We obtained data related to consecutive time series with R-R interval (RRI) and pulse transit time (PTT). Using multiscale cross-approximate entropy (MCE), we quantified the complexity between the two series and thereby differentiated the influence of age and diabetes on the complexity of physiological signals. This study used MCE in the quantification of complexity between RRI and PTT time series. We observed changes in the influences of age and disease on the coupling effects between the heart and blood vessels in the cardiovascular system, which reduced the complexity between RRI and PTT series.
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Assessment of autonomic dysfunction in patients with type 2 diabetes using reactive hyperemia.
J. Theor. Biol.
PUBLISHED: 03-13-2013
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It is known that aging and type 2 diabetes mellitus contribute to atherosclerosis and autonomic dysfunction. By using the air pressure sensing system (APSS), peak-peak intervals (PPIs) of wrist arterial waveforms from baseline and reactive hyperemia (RH) were obtained. Through frequency domain analysis of heart rate variability (HRV) and nonlinear Poincaré method, the HRV of healthy young individuals (Group 1, n=25), healthy upper middle-aged individuals (Group 2, n=22), and patients with type 2 diabetes (Group 3, n=28) were assessed. By using the standard deviation (SD) of the instantaneous PPI variability (SD1)/the SD of the long PPI variability (SD2) ratio (SSR), PPIs of the same individuals before and after RH induction were compared. Reduced SSR???? was noted only in patients with diabetes. Moreover, a significient correlation between SSR???? and endothelial function was observed in all subjects (r=0.290, p=0.033) after RH. However, no correlation with low-frequency to high-frequency power ratio (LHR) was noted before and after RH. In conclusion, according to our results, campared to the baseline, there were more significant changes of SSR???? after RH in patients with diabetes; and, a significient correlation between SSR???? and endothelial function at the moment of RH was noted.
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Screening for precancerous lesions of upper gastrointestinal tract: from the endoscopists viewpoint.
Gastroenterol Res Pract
PUBLISHED: 02-19-2013
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Upper gastrointestinal tract cancers are one of the most important leading causes of cancer death worldwide. Diagnosis at late stages always brings about poor outcome of these malignancies. The early detection of precancerous or early cancerous lesions of gastrointestinal tract is therefore of utmost importance to improve the overall outcome and maintain a good quality of life of patients. The desire of endoscopists to visualize the invisibles under conventional white-light endoscopy has accelerated the advancements in endoscopy technologies. Nowadays, image-enhanced endoscopy which utilizes optical- or dye-based contrasting techniques has been widely applied in endoscopic screening program of gastrointestinal tract malignancies. These contrasting endoscopic technologies not only improve the visualization of early foci missed by conventional endoscopy, but also gain the insight of histopathology and tumor invasiveness, that is so-called optical biopsy. Here, we will review the application of advanced endoscopy technique in screening program of upper gastrointestinal tract cancers.
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Apolipoprotein CIII hyperactivates ? cell CaV1 channels through SR-BI/?1 integrin-dependent coactivation of PKA and Src.
Cell. Mol. Life Sci.
PUBLISHED: 02-18-2013
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Apolipoprotein CIII (ApoCIII) not only serves as an inhibitor of triglyceride hydrolysis but also participates in diabetes-related pathological events such as hyperactivation of voltage-gated Ca(2+) (CaV) channels in the pancreatic ? cell. However, nothing is known about the molecular mechanisms whereby ApoCIII hyperactivates ? cell CaV channels. We now demonstrate that ApoCIII increased CaV1 channel open probability and density. ApoCIII enhanced whole-cell Ca(2+) currents and the CaV1 channel blocker nimodipine completely abrogated this enhancement. The effect of ApoCIII was not influenced by individual inhibition of PKA, PKC, or Src. However, combined inhibition of PKA, PKC, and Src counteracted the effect of ApoCIII, similar results obtained by coinhibition of PKA and Src. Moreover, knockdown of ?1 integrin or scavenger receptor class B type I (SR-BI) prevented ApoCIII from hyperactivating ? cell CaV channels. These data reveal that ApoCIII hyperactivates ? cell CaV1 channels through SR-BI/?1 integrin-dependent coactivation of PKA and Src.
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The benefit of pretreatment esophageal screening with image-enhanced endoscopy on the survival of patients with hypopharyngeal cancer.
Oral Oncol.
PUBLISHED: 02-12-2013
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Synchronous esophageal cancers can suppress the survival of patients with hypopharyngeal cancers. Esophageal screening with the image-enhanced endoscopy may identify more synchronous cancers while there is no evidence to support its benefit on survival.
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Improved discovery of molecular interactions in genome-scale data with adaptive model-based normalization.
PLoS ONE
PUBLISHED: 01-22-2013
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High throughput molecular-interaction studies using immunoprecipitations (IP) or affinity purifications are powerful and widely used in biology research. One of many important applications of this method is to identify the set of RNAs that interact with a particular RNA-binding protein (RBP). Here, the unique statistical challenge presented is to delineate a specific set of RNAs that are enriched in one sample relative to another, typically a specific IP compared to a non-specific control to model background. The choice of normalization procedure critically impacts the number of RNAs that will be identified as interacting with an RBP at a given significance threshold - yet existing normalization methods make assumptions that are often fundamentally inaccurate when applied to IP enrichment data.
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Use of transnasal endoscopy for screening of esophageal squamous cell carcinoma in high-risk patients: Yield rate, completion rate, and safety.
Dig Endosc
PUBLISHED: 01-21-2013
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Patients with head and neck squamous cell carcinoma are at high risk for synchronous and/or metachronous esophageal cancer. The present study aimed to evaluate the feasibility and safety of unsedated transnasal endoscopy (TNE) for screening these high-risk patients.
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Sulphur-TiO2 yolk-shell nanoarchitecture with internal void space for long-cycle lithium-sulphur batteries.
Nat Commun
PUBLISHED: 01-10-2013
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Sulphur is an attractive cathode material with a high specific capacity of 1,673?mAh?g(-1), but its rapid capacity decay owing to polysulphide dissolution presents a significant technical challenge. Despite much efforts in encapsulating sulphur particles with conducting materials to limit polysulphide dissolution, relatively little emphasis has been placed on dealing with the volumetric expansion of sulphur during lithiation, which will lead to cracking and fracture of the protective shell. Here, we demonstrate the design of a sulphur-TiO(2) yolk-shell nanoarchitecture with internal void space to accommodate the volume expansion of sulphur, resulting in an intact TiO(2) shell to minimize polysulphide dissolution. An initial specific capacity of 1,030?mAh?g(-1) at 0.5?C and Coulombic efficiency of 98.4% over 1,000 cycles are achieved. Most importantly, the capacity decay after 1,000 cycles is as small as 0.033% per cycle, which represents the best performance for long-cycle lithium-sulphur batteries so far.
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Combined multichannel intraluminal impedance and pH monitoring assists the diagnosis of sliding hiatal hernia in children with gastroesophageal reflux disease.
J. Gastroenterol.
PUBLISHED: 01-04-2013
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The role of combined multichannel intraluminal impedance and pH monitoring (MII-pH) in diagnosing sliding hiatal hernia in gastroesophageal reflux disease (GERD) children remains unclear. We aimed to explore the clinical efficacy of MII-pH as a supplement diagnostic method for sliding hiatal hernia.
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Effects of weight loss on epicardial adipose tissue thickness and its relationship between serum soluble CD40 ligand levels in obese men.
Clin. Chim. Acta
PUBLISHED: 01-03-2013
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Epicardial adipose tissue (EAT) induces activated inflammatory cells secreting cytokines, including soluble CD40 ligand (sCD40L). In turn, the serum sCD40L can trigger inflammatory responses. We examined the reduction of EAT in response to weight loss (WL) and its relationship with alterations in sCD40L in obese men.
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What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

How does it work?

We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

Video X seems to be unrelated to Abstract Y...

In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.