13,740 research outputs found

    The role of coactivators in oestrogen action

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    Mitochondrial heteroplasmy and DNA barcoding in Hawaiian Hylaeus (Nesoprosopis) bees (Hymenoptera: Colletidae)

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    <p>Abstract</p> <p>Background</p> <p>The past several years have seen a flurry of papers seeking to clarify the utility and limits of DNA barcoding, particularly in areas such as species discovery and paralogy due to nuclear pseudogenes. Heteroplasmy, the coexistence of multiple mitochondrial haplotypes in a single organism, has been cited as a potentially serious problem for DNA barcoding but its effect on identification accuracy has not been tested. In addition, few studies of barcoding have tested a large group of closely-related species with a well-established morphological taxonomy. In this study we examine both of these issues, by densely sampling the Hawaiian <it>Hylaeus </it>bee radiation.</p> <p>Results</p> <p>Individuals from 21 of the 49 <it>a priori </it>morphologically-defined species exhibited coding sequence heteroplasmy at levels of 1-6% or more. All homoplasmic species were successfully identified by COI using standard methods of analysis, but only 71% of heteroplasmic species. The success rate in identifying heteroplasmic species was increased to 86% by treating polymorphisms as character states rather than ambiguities. Nuclear pseudogenes (numts) were also present in four species, and were distinguishable from heteroplasmic sequences by patterns of nucleotide and amino acid change.</p> <p>Conclusions</p> <p>Heteroplasmy significantly decreased the reliability of species identification. In addition, the practical issue of dealing with large numbers of polymorphisms- and resulting increased time and labor required - makes the development of DNA barcode databases considerably more complex than has previously been suggested. The impact of heteroplasmy on the utility of DNA barcoding as a bulk specimen identification tool will depend upon its frequency across populations, which remains unknown. However, DNA barcoding is still likely to remain an important identification tool for those species that are difficult or impossible to identify through morphology, as is the case for the ecologically important solitary bee fauna.</p

    Regression of murine lung tumors by the let-7 microRNA.

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    MicroRNAs (miRNAs) have recently emerged as an important new class of cellular regulators that control various cellular processes and are implicated in human diseases, including cancer. Here, we show that loss of let-7 function enhances lung tumor formation in vivo, strongly supporting the hypothesis that let-7 is a tumor suppressor. Moreover, we report that exogenous delivery of let-7 to established tumors in mouse models of non-small-cell lung cancer (NSCLC) significantly reduces the tumor burden. These results demonstrate the therapeutic potential of let-7 in NSCLC and point to miRNA replacement therapy as a promising approach in cancer treatment

    The importance of social worlds: an investigation of peer relationships

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    In the following report, we investigate the developing social worlds in late primary school, exploring the patterns in children?s general peer relationships, their closer and more significant friendships and bullying behaviours. Using cluster analysis, we identify unique groups of children characterized not only by their experiences of bullying and victimization, but the support and satisfaction they receive from their friendships and interactions between the ages of 8 and 10. We also expand past research by examining how children?s early development (ages 3 to 4) may predict their later designation as bullies and/or victims, and whether peer clusters relate to children?s contemporaneous and later adjustment

    Epithelial cell shedding and barrier function: a matter of life and death at the small intestinal villus tip

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    The intestinal epithelium is a critical component of the gut barrier. Composed of a single layer of intestinal epithelial cells (IECs) held together by tight junctions, this delicate structure prevents the transfer of harmful microorganisms, antigens, and toxins from the gut lumen into the circulation. The equilibrium between the rate of apoptosis and shedding of senescent epithelial cells at the villus tip, and the generation of new cells in the crypt, is key to maintaining tissue homeostasis. However, in both localized and systemic inflammation, this balance may be disturbed as a result of pathological IEC shedding. Shedding of IECs from the epithelial monolayer may cause transient gaps or microerosions in the epithelial barrier, resulting in increased intestinal permeability. Although pathological IEC shedding has been observed in mouse models of inflammation and human intestinal conditions such as inflammatory bowel disease, understanding of the underlying mechanisms remains limited. This process may also be an important contributor to systemic and intestinal inflammatory diseases and gut barrier dysfunction in domestic animal species. This review aims to summarize current knowledge about intestinal epithelial cell shedding, its significance in gut barrier dysfunction and host-microbial interactions, and where research in this field is directed

    Nurturing parenting capability: the early years

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    This report examines parenting from babyhood to early childhood. We first consider what previous studies have revealed about the nature of good parenting and the determinants of parenting in the early years. Using data from the Avon Longitudinal Study of Parents and Children we then set out to establish whether the individual characteristics of mothers and children, and factors such as mothers? social networks and marital relations, predict certain types of parenting behaviours. We do this by examining how 1,136 mothers interacted with their child when asked to share a picture book with them. This observation exercise, which measured parental warmth and teaching behaviours, took place when the child was aged one, then again at age five. Lastly, we address the implications of our findings for policy and practice

    Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes

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    Background The cardiovascular effect of liraglutide, a glucagon-like peptide 1 analogue, when added to standard care in patients with type 2 diabetes, remains unknown. Methods In this double-blind trial, we randomly assigned patients with type 2 diabetes and high cardiovascular risk to receive liraglutide or placebo. The primary composite outcome in the time-to-event analysis was the first occurrence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. The primary hypothesis was that liraglutide would be noninferior to placebo with regard to the primary outcome, with a margin of 1.30 for the upper boundary of the 95% confidence interval of the hazard ratio. No adjustments for multiplicity were performed for the prespecified exploratory outcomes. Results A total of 9340 patients underwent randomization. The median follow-up was 3.8 years. The primary outcome occurred in significantly fewer patients in the liraglutide group (608 of 4668 patients [13.0%]) than in the placebo group (694 of 4672 [14.9%]) (hazard ratio, 0.87; 95% confidence interval [CI], 0.78 to 0.97; P<0.001 for noninferiority; P=0.01 for superiority). Fewer patients died from cardiovascular causes in the liraglutide group (219 patients [4.7%]) than in the placebo group (278 [6.0%]) (hazard ratio, 0.78; 95% CI, 0.66 to 0.93; P=0.007). The rate of death from any cause was lower in the liraglutide group (381 patients [8.2%]) than in the placebo group (447 [9.6%]) (hazard ratio, 0.85; 95% CI, 0.74 to 0.97; P=0.02). The rates of nonfatal myocardial infarction, nonfatal stroke, and hospitalization for heart failure were nonsignificantly lower in the liraglutide group than in the placebo group. The most common adverse events leading to the discontinuation of liraglutide were gastrointestinal events. The incidence of pancreatitis was nonsignificantly lower in the liraglutide group than in the placebo group. Conclusions In the time-to-event analysis, the rate of the first occurrence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke among patients with type 2 diabetes mellitus was lower with liraglutide than with placebo. (Funded by Novo Nordisk and the National Institutes of Health; LEADER ClinicalTrials.gov number, NCT01179048 .)

    Random‑telegraph‑noise‑enabled true random number generator for hardware security

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    The future security of Internet of Things is a key concern in the cyber-security field. One of the key issues is the ability to generate random numbers with strict power and area constrains. “True Random Number Generators” have been presented as a potential solution to this problem but improvements in output bit rate, power consumption, and design complexity must be made. In this work we present a novel and experimentally verified “True Random Number Generator” that uses exclusively conventional CMOS technology as well as offering key improvements over previous designs in complexity, output bitrate, and power consumption. It uses the inherent randomness of telegraph noise in the channel current of a single CMOS transistor as an entropy source. For the first time multilevel and abnormal telegraph noise can be utilised, which greatly reduces device selectivity and offers much greater bitrates. The design is verified using a breadboard and FPGA proof of concept circuit and passes all 15 of the NIST randomness tests without any need for post-processing of the generated bitstream. The design also shows resilience against machine learning attacks performed by the LSTM neural network
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