GLP-1 receptor signalling promotes β-cell glucose metabolism via mTOR-dependent HIF-1α activation

Glucagon-like peptide-1 (GLP-1) promotes insulin secretion from pancreatic ß-cells in a glucose dependent manner. Several pathways mediate this action by rapid, kinase phosphorylation-dependent, but gene expression-independent mechanisms. Since GLP-1-induced insulin secretion requires glucose metabolism, we aimed to address the hypothesis that GLP-1 receptor (GLP-1R) signalling can modulate glucose uptake and utilization in ß-cells. We have assessed various metabolic parameters after short and long exposure of clonal BRIN-BD11 ß-cells and rodent islets to the GLP-1R agonist Exendin-4 (50 nM). Here we report for the first time that prolonged stimulation of the GLP-1R for 18 hours promotes metabolic reprogramming of ß-cells. This is evidenced by up-regulation of glycolytic enzyme expression, increased rates of glucose uptake and consumption, as well as augmented ATP content, insulin secretion and glycolytic flux after removal of Exendin-4. In our model, depletion of Hypoxia-Inducible Factor 1 alpha (HIF-1a) impaired the effects of Exendin-4 on glucose metabolism, while pharmacological inhibition of Phosphoinositide 3-kinase (PI3K) or mTOR completely abolished such effects. Considering the central role of glucose catabolism for stimulus-secretion coupling in ß-cells, our findings suggest that chronic GLP-1 actions on insulin secretion include elevated ß-cell glucose metabolism. Moreover, our data reveal novel aspects of GLP-1 stimulated insulin secretion involving de novo gene expression

Chinese Herbal Medicines for the Treatment of Type A H1N1 Influenza: A Systematic Review of Randomized Controlled Trials

Chinese herbs are thought to be effective for type A H1N1 influenza. Series of Chinese herbs have been authorized recommended by the Chinese government, and until now a number of clinical trials of Chinese herbs for H1N1 influenza have been conducted. However, there is no critically appraised evidence such as systematic reviews or metaanalyses on potential benefits and harms of medicinal herbs for H1N1 influenza to justify their clinical use and their recommendation. CENTRAL, MEDLINE, EMBASE, CBM, CNKI, VIP, China Important Conference Papers Database, China Dissertation Database, and online clinical trial registry websites were searched for published and unpublished randomized controlled trials (RCTs) of Chinese herbs for H1N1 influenza till 31 August, 2011. A total of 26 RCTs were identified and reviewed. Most of the RCTs were of high risk of bias with flawed study design and poor methodological quality. The combination of several Chinese herbal medicines with or without oseltamivir demonstrated positive effect on fever resolution, relief of symptoms, and global effectiveness rate compared to oseltamivir alone. However, only one herbal medicine showed positive effect on viral shedding. Most of the trials did not report adverse events, and the safety of herbal medicines is still uncertain. Some Chinese herbal medicines demonstrated potential positive effect for 2009 type A H1N1 influenza; however, due to the lack of placebo controlled trial and lack of repeated test of the intervention, we could not draw confirmative conclusions on the beneficial effect of Chinese herbs for H1N1 influenza. More rigorous trials are warranted to support their clinical use

Origin of Capacity Fading in Nano-Sized Co3O4Electrodes: Electrochemical Impedance Spectroscopy Study

Transition metal oxides have been suggested as innovative, high-energy electrode materials for lithium-ion batteries because their electrochemical conversion reactions can transfer two to six electrons. However, nano-sized transition metal oxides, especially Co3O4, exhibit drastic capacity decay during discharge/charge cycling, which hinders their practical use in lithium-ion batteries. Herein, we prepared nano-sized Co3O4with high crystallinity using a simple citrate-gel method and used electrochemical impedance spectroscopy method to examine the origin for the drastic capacity fading observed in the nano-sized Co3O4anode system. During cycling, AC impedance responses were collected at the first discharged state and at every subsequent tenth discharged state until the 100th cycle. By examining the separable relaxation time of each electrochemical reaction and the goodness-of-fit results, a direct relation between the charge transfer process and cycling performance was clearly observed

EcoTILLING in Capsicum species: searching for new virus resistances

<p>Abstract</p> <p>Background</p> <p>The EcoTILLING technique allows polymorphisms in target genes of natural populations to be quickly analysed or identified and facilitates the screening of genebank collections for desired traits. We have developed an EcoTILLING platform to exploit <it>Capsicum </it>genetic resources. A perfect example of the utility of this EcoTILLING platform is its application in searching for new virus-resistant alleles in <it>Capsicum </it>genus. Mutations in translation initiation factors (eIF4E, eIF(iso)4E, eIF4G and eIF(iso)4G) break the cycle of several RNA viruses without affecting the plant life cycle, which makes these genes potential targets to screen for resistant germplasm.</p> <p>Results</p> <p>We developed and assayed a cDNA-based EcoTILLING platform with 233 cultivated accessions of the genus <it>Capsicum</it>. High variability in the coding sequences of the <it>eIF4E </it>and <it>eIF(iso)4E </it>genes was detected using the cDNA platform. After sequencing, 36 nucleotide changes were detected in the CDS of <it>eIF4E </it>and 26 in <it>eIF(iso)4E</it>. A total of 21 <it>eIF4E </it>haplotypes and 15 <it>eIF(iso)4E </it>haplotypes were identified. To evaluate the functional relevance of this variability, 31 possible eIF4E/eIF(iso)4E combinations were tested against <it>Potato virus Y</it>. The results showed that five new <it>eIF4E </it>variants (<it>pvr2¹⁰</it>, <it>pvr2¹¹</it>, <it>pvr2¹²</it>, <it>pvr2¹³</it>and <it>pvr2¹⁴</it>) were related to PVY-resistance responses.</p> <p>Conclusions</p> <p>EcoTILLING was optimised in different <it>Capsicum </it>species to detect allelic variants of target genes. This work is the first to use cDNA instead of genomic DNA in EcoTILLING. This approach avoids intronic sequence problems and reduces the number of reactions. A high level of polymorphism has been identified for initiation factors, showing the high genetic variability present in our collection and its potential use for other traits, such as genes related to biotic or abiotic stresses, quality or production. Moreover, the new <it>eIF4E </it>and <it>eIF(iso)4E </it>alleles are an excellent collection for searching for new resistance against other RNA viruses.</p

Utilization patterns of Chinese medicine and Western medicine under the National Health Insurance Program in Taiwan, a population-based study from 1997 to 2003

<p>Abstract</p> <p>Background</p> <p>In 1995, Taiwan has launched a national health-care system (the National Health Insurance Program, NHI) covering the use of both Western medicine (WM) and Chinese medicine (CM). This population-based study was conducted to understand the role of CM in this dual medical system by determining the utilization patterns of CM and WM and to analyze the demographic characteristics and primary indications influencing the choice of the medical services for the development of strategies to enhance the appropriate use and reduce unnecessary use of CM.</p> <p>Methods</p> <p>This study used the NHI sample files from 1997 to 2003 consisting of comprehensive utilization and enrolment information for a random sample of 200,432 NHI beneficiaries of the total enrolees from 1995 to 2000. A total of 136,720 subjects with valid and complete enrolment and utilization data were included in this study. The logistic regression method was employed to estimate the odds ratios (ORs) for utilization of CM and WM. The usage, frequency of services, and primary indications for CM and WM were evaluated. A significance level of α = 0.05 was selected.</p> <p>Results</p> <p>Compared with WM, the odds of CM increased from 1997 to 2003. The odds of using CM (OR = 1.48; 95% CI: 1.45–1.50; p < 0.001) and WM (OR = 1.74; 95% CI: 1.72–1.77; p < 0.001) were higher in females and that of CM increased with age to a peak in the 45–54-year-group (OR = 1.75; 95% CI: 1.68–1.82; p < 0.001) and WM (OR = 1.09; 95% CI: 1.05–1.13; p < 0.001) in the elderly subjects (≥ 65 years). The odds of CM and WM were similar in all income groups. However, those of CM were higher in Central (OR = 1.65; 95% CI: 1.56–1.74; p < 0.001) and Southern Taiwan (OR = 1.18; 95% CI: 1.12–1.25; p < 0.001) and lower in the remote areas (OR = 0.57; 95% CI: 0.52–0.63; p < 0.001). Most of the patients had one ambulatory visit of both medical services annually. However, the utilization of WM predominated over CM. Over 90% of CM service was provided by clinics, whereas over 60% of WM service by hospitals. Diseases of the respiratory system was the most frequent primary indication in CM and WM. Herbal medication was the most commonly used form of CM (68.4–72.7%).</p> <p>Conclusion</p> <p>In recent years, there is an increasing trend in the utilization of CM in Taiwan. This increasing trend may be due to the covering of CM in the national health insurance system.</p

New Implications on Genomic Adaptation Derived from the Helicobacter pylori Genome Comparison

BACKGROUND: Helicobacter pylori has a reduced genome and lives in a tough environment for long-term persistence. It evolved with its particular characteristics for biological adaptation. Because several H. pylori genome sequences are available, comparative analysis could help to better understand genomic adaptation of this particular bacterium. PRINCIPAL FINDINGS: We analyzed nine H. pylori genomes with emphasis on microevolution from a different perspective. Inversion was an important factor to shape the genome structure. Illegitimate recombination not only led to genomic inversion but also inverted fragment duplication, both of which contributed to the creation of new genes and gene family, and further, homological recombination contributed to events of inversion. Based on the information of genomic rearrangement, the first genome scaffold structure of H. pylori last common ancestor was produced. The core genome consists of 1186 genes, of which 22 genes could particularly adapt to human stomach niche. H. pylori contains high proportion of pseudogenes whose genesis was principally caused by homopolynucleotide (HPN) mutations. Such mutations are reversible and facilitate the control of gene expression through the change of DNA structure. The reversible mutations and a quasi-panmictic feature could allow such genes or gene fragments frequently transferred within or between populations. Hence, pseudogenes could be a reservoir of adaptation materials and the HPN mutations could be favorable to H. pylori adaptation, leading to HPN accumulation on the genomes, which corresponds to a special feature of Helicobacter species: extremely high HPN composition of genome. CONCLUSION: Our research demonstrated that both genome content and structure of H. pylori have been highly adapted to its particular life style

Use frequency of traditional Chinese medicine in Taiwan

BACKGROUND: Use of Traditional Chinese medicine (TCM), an important category of complementary and alternative medicine (CAM), has increased substantially in Western countries during the past decade. Use of TCM is also widespread in the Chinese population. However, few informative data have been obtained to date by large-scale investigations of TCM use in the Chinese population. This study was aimed at elucidating the demographics and patterns of TCM use in Taiwan. METHODS: We employed the complete datasets of TCM outpatient reimbursement claims from 1996 to 2001, including the use of Chinese herbal remedies, acupuncture and traumatology manipulative therapy, to analyse use frequencies, the characteristics of TCM users, and the disease categories that were treated by TCM in Taiwan. RESULTS: At the end of 2001, 6,142,829 (28.4%) among the 21,653,555 valid beneficiaries of the National Health Insurance in Taiwan had used TCM during the year. However, 13,536,266 subjects (62.5%) had used TCM at least once during the whole 6-year period from 1996 to 2001, with a total of 156,224,266 visits (mean 11.5 visits per user). The mean number of TCM users per annum was 5,733,602, with a mean increment of 1,671,476 (29.2%) of new users yearly. Among TCM users, female was higher than male (female:male = 1.13:1), and the age distribution displayed a peak at around the 30s, followed by the 20s and 40s. Chinese herbal remedies (85.9%) were the most common TCM modality used by this population, followed by acupuncture (11.0%) and traumatology manipulative therapies (3.1%). Private TCM clinics provided most of the TCM care (82.6%), followed by private TCM hospitals (12.0%). The top ten major disease categories for TCM visits were diseases of the respiratory system, musculoskeletal system and connective tissue; symptoms, signs and ill-defined conditions; injury and poisoning; diseases of the digestive system, genitourinary system, skin and subcutaneous tissue, nervous system and sense organs, circulatory and endocrine system; nutritional and metabolic diseases; and immunological disorders. CONCLUSION: TCM was popular among the Chinese population in Taiwan during the period studied. More than 60% of all subjects had used TCM during the 6-year interval. TCM was widely used by the Chinese population to treat problems and diseases of major human organ systems recognised by western medicine. This study provides information about the use frequencies of TCM and the disease categories treated by TCM, which should be useful for health policy makers and for those considering the integration of TCM and Western medicine

Measurement of electron antineutrino oscillation based on 1230 days of operation of the Daya Bay experiment

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Improved Search for a Light Sterile Neutrino with the Full Configuration of the Daya Bay Experiment

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