920 research outputs found

    The TCF7L2 locus and type 1 diabetes

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    <p>Abstract</p> <p>Background</p> <p><it>TCF7L2 </it>belongs to a subfamily of TCF7-like HMG box-containing transcription factors, and maps to human chromosome 10q25.3. A recent study identified genetic association of type 2 diabetes (T2D) with this gene, correlated with diminished insulin secretion. This study aimed to investigate the possibility of genetic association between <it>TCF7L2 </it>and type 1 diabetes (T1D).</p> <p>Methods</p> <p>The SNP most significantly associated with T2D, rs7903146, was genotyped in 886 T1D nuclear family trios with ethnic backgrounds of mixed European descent.</p> <p>Results</p> <p>This study found no T1D association with, and no age-of-onset effect from rs7903146.</p> <p>Conclusion</p> <p>This study suggests that a T2D mechanism mediated by <it>TCF7L2 </it>does not participate in the etiology of T1D.</p

    Solitary waves in the Nonlinear Dirac Equation

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    In the present work, we consider the existence, stability, and dynamics of solitary waves in the nonlinear Dirac equation. We start by introducing the Soler model of self-interacting spinors, and discuss its localized waveforms in one, two, and three spatial dimensions and the equations they satisfy. We present the associated explicit solutions in one dimension and numerically obtain their analogues in higher dimensions. The stability is subsequently discussed from a theoretical perspective and then complemented with numerical computations. Finally, the dynamics of the solutions is explored and compared to its non-relativistic analogue, which is the nonlinear Schr{\"o}dinger equation. A few special topics are also explored, including the discrete variant of the nonlinear Dirac equation and its solitary wave properties, as well as the PT-symmetric variant of the model

    Neutrophils in cancer: neutral no more

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    Neutrophils are indispensable antagonists of microbial infection and facilitators of wound healing. In the cancer setting, a newfound appreciation for neutrophils has come into view. The traditionally held belief that neutrophils are inert bystanders is being challenged by the recent literature. Emerging evidence indicates that tumours manipulate neutrophils, sometimes early in their differentiation process, to create diverse phenotypic and functional polarization states able to alter tumour behaviour. In this Review, we discuss the involvement of neutrophils in cancer initiation and progression, and their potential as clinical biomarkers and therapeutic targets

    Characterizing Genetic Diversity of Contemporary Pacific Chickens Using Mitochondrial DNA Analyses

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    Background\ud Mitochondrial DNA (mtDNA) hypervariable region (HVR) sequences of prehistoric Polynesian chicken samples reflect dispersal of two haplogroups—D and E—by the settlers of the Pacific. The distribution of these chicken haplogroups has been used as an indicator of human movement. Recent analyses suggested similarities between prehistoric Pacific and South American chicken samples, perhaps reflecting prehistoric Polynesian introduction of the chicken into South America. These analyses have been heavily debated. The current distribution of the D and E lineages among contemporary chicken populations in the Western Pacific is unclear, but might ultimately help to inform debates about the movements of humans that carried them.\ud \ud Objectives\ud We sought to characterize contemporary mtDNA diversity among chickens in two of the earliest settled archipelagoes of Remote Oceania, the Marianas and Vanuatu.\ud \ud Methods\ud We generated HVR sequences for 43 chickens from four islands in Vanuatu, and for 5 chickens from Guam in the Marianas.\ud \ud Results\ud Forty samples from Vanuatu and three from Guam were assigned to haplogroup D, supporting this as a Pacific chicken haplogroup that persists in the Western Pacific. Two haplogroup E lineages were observed in Guam and two in Vanuatu. Of the E lineages in Vanuatu, one was identical to prehistoric Vanuatu and Polynesian samples and the other differed by one polymorphism. Contrary to our expectations, we observed few globally distributed domesticate lineages not associated with Pacific chicken dispersal. This might suggest less European introgression of chickens into Vanuatu than expected. If so, the E lineages might represent lineages maintained from ancient Pacific chicken introductions. The Vanuatu sample might thus provide an opportunity to distinguish between maintained ancestral Pacific chicken lineages and replacement by global domesticates through genomic analyses, which could resolve questions of contemporary haplogroup E chicken relationships and inform interpretations of debated sequences from archaeological samples

    The Naturally Occurring YMDD Mutation among Patients Chronically Infected HBV and Untreated with Lamivudine: A Systematic Review and Meta-Analysis

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    Background: Several recent reports have demonstrated that tyrosine (Y)-methionine (M)-aspartic acid (D)-aspartic acid (D) (YMDD) motif mutations can naturally occur in chronic HBV patients without antiviral treatment such as lamivudine therapy. This paper aims to assess the overall spontaneous incidence and related risk factors of YMDD-motif mutations among lamivudine-naïve chronic HBV carriers, so as to provide some clue for clinical treatment of hepatitis B. Methodology/Principal Findings: Chinese and English literatures were searched for studies reporting natural YMDD mutations among untreated chronic HBV patients from 2001 to 2010. The incidence estimates were summarized and analyzed by meta-analyses. Forty-seven eligible articles from eight countries were selected in this review (13 in English and 34 in Chinese). The pooled incidence of YMDD-motif mutation among untreated chronic HBV patients from eight countries was 12.21 % (95 % CI: 9.69%–14.95%). China had an incidence of 13.38 % (95 % CI: 10.90%–16.07%) and seven other countries had an incidence of 9.90 % (95 % CI: 3.28%–19.55%), respectively. Lamivudine therapy would increase the risk of mutations 5.23 times higher than the untreated patients. A higher HBV DNA copy number was associated with increased incidence of natural YMDD mutation. No significant difference was found in YMDD mutation incidence between groups of different gender, age, HBeAg status, patients ’ ALT (alanine aminotransferase) level, and between the groups of HBV genotype B and C. Conclusions: The YMDD-motif mutations can occur spontaneously with a relatively high incidence in CHB patient

    A randomised trial of a 5 week, manual based, self-management programme for hypertension delivered in a cardiac patient club in Shanghai

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    <p>Abstract</p> <p>Background</p> <p>In Shanghai there are 1.2 million people with hypertension, many of whom have difficulty in affording medical treatment. Community based, anti-hypertensive clubs have been created to provide health education but education alone is often ineffective. Lifestyle change programmes have shown some potential for reducing blood pressure but in previous trials have required specialist staff and extensive contact. We have previously demonstrated that self-management programmes delivered by health professionals, such as a nurse who has had short training in self-management techniques can change health behaviour and reduce symptoms. This study was designed to evaluate the benefits of a simple, cognitive-behavioural, self-management programme for hypertension based around a hypertension manual and delivered in the setting of a community anti-hypertensive club in Shanghai.</p> <p>Method</p> <p>The method was a pragmatic randomised controlled trial with an intention-to-treat analysis. Adult patients with mild-to-moderate primary hypertension, waiting to join a neighbourhood anti-hypertension club, were randomised to the self-management programme or to an information only control procedure. They attended the group treatment sessions on 4 occasions over 5 weeks for education combined with goal setting for lifestyle change and an introduction to exercise. The main outcome measures were: changes in blood pressure; blood total cholesterol; diet; activity level and health related quality of life 1 month and 4 months after the end of treatment.</p> <p>Results</p> <p>A total of 140 adults with mild-to-moderate primary hypertension took part. All of the main outcomes showed beneficial changes. Four months after the end of treatment the mean blood pressure differences between groups were systolic 10.15 mm Hg (P < 0.001, 95% CI 7.25–13.05), and diastolic 8.29 mmHg (P < 0.001, 95% CI 6.71–9.88). Patients in the intervention group also had significantly reduced weight, lowered blood total cholesterol, increased physical activity and improved quality of life.</p> <p>Conclusion</p> <p>Patients with mild-to-moderate primary hypertension attending a 5 week, group and manual based, cognitive-behavioural self-management programme, delivered through a voluntary club in Shanghai experienced a significant reduction in blood pressure.</p> <p>Trial registration</p> <p>Current Controlled Trials ISRCTN73114566</p

    Analysis of the functional conservation of ethylene receptors between maize and Arabidopsis

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    Ethylene, a regulator of plant growth and development, is perceived by specific receptors that act as negative regulators of the ethylene response. Five ethylene receptors, i.e., ETR1, ERS1, EIN4, ETR2, and ERS2, are present in Arabidopsis and dominant negative mutants of each that confer ethylene insensitivity have been reported. In contrast, maize contains just two types of ethylene receptors: ZmERS1, encoded by ZmERS1a and ZmERS1b, and ZmETR2, encoded by ZmETR2a and ZmETR2b. In this study, we introduced a Cys to Tyr mutation in the transmembrane domain of ZmERS1b and ZmETR2b that is present in the etr1-1 dominant negative mutant and expressed each protein in Arabidopsis. Mutant Zmers1b and Zmetr2b receptors conferred ethylene insensitivity and Arabidopsis expressing Zmers1b or Zmetr2b were larger and exhibited a delay in leaf senescence characteristic of ethylene insensitive Arabidopsis mutants. Zmers1b and Zmetr2b were dominant and functioned equally well in a hemizygous or homozygous state. Expression of the Zmers1b N-terminal transmembrane domain was sufficient to exert dominance over endogenous Arabidopsis ethylene receptors whereas the Zmetr2b N-terminal domain failed to do so. Neither Zmers1b nor Zmetr2b functioned in the absence of subfamily 1 ethylene receptors, i.e., ETR1 and ERS1. These results suggest that Cys65 in maize ZmERS1b and ZmETR2b plays the same role that it does in Arabidopsis receptors. Moreover, the results demonstrate that the mutant maize ethylene receptors are functionally dependent on subfamily 1 ethylene receptors in Arabidopsis, indicating substantial functional conservation between maize and Arabidopsis ethylene receptors despite their sequence divergence
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