1,253 research outputs found

    Preventing and Treating Type 2 Diabetes Through a Physically Active Lifestyle

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    By the late 1960s, the increasing number of type 2 diabetic cases in children and adolescents rapidly presented a signifi cant public health issue recognized by the American Diabetes Association (2000). Since then, the prevalence of pediatric type 2 diabetes appears to be on the rise not only in the United States but all around the world (Gungor et al., 2005). In the United States, an increase from fewer than four percent to more than 50 percent of new cases of type 2 diabetes in the pediatric population was reported between the years of 1982 and 1998 (American Diabetes Association, 2000). An increasing percentage of pediatric cases of newly diagnosed type 2 diabetes were also reported in population-based data (Gungor et al., 2005). Therefore, the purpose of this article is to discuss how regular physical activity can help to prevent and treat type 2 diabetes

    Understanding NF-ÎșB signaling via mathematical modeling

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    Mammalian inflammatory signaling, for which NF-ÎșB is a principal transcription factor, is an exquisite example of how cellular signaling pathways can be regulated to produce different yet specific responses to different inflammatory insults. Mathematical models, tightly linked to experiment, have been instrumental in unraveling the forms of regulation in NF-ÎșB signaling and their underlying molecular mechanisms. Our initial model of the IÎșB–NF-ÎșB signaling module highlighted the role of negative feedback in the control of NF-ÎșB temporal dynamics and gene expression. Subsequent studies sparked by this work have helped to characterize additional feedback loops, the input–output behavior of the module, crosstalk between multiple NF-ÎșB-activating pathways, and NF-ÎșB oscillations. We anticipate that computational techniques will enable further progress in the NF-ÎșB field, and the signal transduction field in general, and we discuss potential upcoming developments

    Computation and measurement of cell decision making errors using single cell data

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    Author summary Cell continuously receives signals from the surrounding environment and is supposed to make correct decisions, i.e., respond properly to various signals and initiate certain cellular functions. Modeling and quantification of decision making processes in a cell have emerged as important areas of research in recent years. Due to signal transduction noise, cells respond differently to similar inputs, which may result in incorrect cell decisions. Here we develop a novel method for characterization of decision making processes in cells, using statistical signal processing and decision theory concepts. To demonstrate the utility of the method, we apply it to an important signaling pathway that regulates molecules which play key roles in cell survival. Our method reveals that cells can make two types of incorrect decisions, namely, false alarm and miss events. We measure the likelihood of these decisions using single cell experimental data, and demonstrate how these incorrect decisions are related to the signal transduction noise or absence of certain molecular functions. Using our method, decision making errors in other molecular systems can be modeled. Such models are useful for understanding and developing treatments for pathological processes such as inflammation, various cancers and autoimmune diseases

    Flexibility and Control of Protein-DNA Loops

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    Combined research report and review article on our work in DNA looping. Presented at the Asia and Pacific Workshop on Biological Physics, Singapore, July 2006.Protein-DNA loops are essential for efficient transcriptional repression and activation. The geometry and stability of the archetypal Lac repressor tetramer (LacI)-DNA loop were investigated using designed hyperstable loops containing lac operators bracketing a sequence-directed bend. Electrophoretic mobility shift assays, DNA cyclization, and bulk and single-molecule fluorescence resonance energy transfer (FRET) demonstrate that the DNA sequence controls whether the LacI-DNA loop forms a compact loop with positive writhe or an open loop with little writhe. Monte Carlo methods for simulation of DNA ring closure were extended to DNA loops, including treatment of variable protein hinge angles. The observed distribution of topoisomer products upon cyclization provides a strong constraint on possible models. The experiments and modeling imply that LacI-DNA can adopt a wide range of geometries but has a strong intrinsic preference for an open form. The flexibility of LacI helps explain in vivo observations that DNA looping is less sensitive to DNA length and shape than would be expected from the physical properties of DNA. While DNA cyclization suggests two pools of precursor loops for the 9C14 construct, single-molecule FRET demonstrates a single population. This discrepancy suggests that the LacI-DNA structure is strongly influenced by flanking DNA.NSF, NI

    Entomologic and molecular investigation into Plasmodium vivax transmission in Singapore, 2009

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    <p>Abstract</p> <p>Background</p> <p>Singapore has been certified malaria free since November 1982 by the World Health Organization and despite occasional local transmission, the country has maintained the standing. In 2009, three clusters of malaria cases were reported in Singapore.</p> <p>Methods</p> <p>Epidemiological, entomological and molecular studies were carried out to investigate the three clusters, namely Mandai-Sungei Kadut, Jurong Island and Sembawang.</p> <p>Results</p> <p>A total of 29 malaria patients, with no recent travel history, were reported in the three clusters. Molecular analysis based on the <it>msp3α </it>and <it>msp1 </it>genes showed two independent local transmissions: one in Mandai-Sungei Kadut and another in Sembawang. Almost all cases within each cluster were epidemiologically linked. In Jurong Island cluster, epidemiological link remains uncertain, as almost all cases had a unique genetic profile. Only two cases shared a common profile and were found to be linked to the Mandai-Sungei Kadut cluster. Entomological investigation found <it>Anopheles sinensis </it>to be the predominant Anopheline in the two areas where local transmission of <it>P. vivax </it>was confirmed. <it>Anopheles sinensis </it>was found to be attracted to human bait and bites as early as 19:45 hrs. However, all <it>Anopheles </it>mosquitoes caught were negative for sporozoites and oocysts by dissection.</p> <p>Conclusion</p> <p>Investigation of <it>P. vivax </it>cases from the three cluster areas confirmed the occurrence of local transmission in two areas. Although <it>An. sinensis </it>was the predominant Anopheline found in areas with confirmed transmission, the vector/s responsible for the outbreaks still remains cryptic.</p

    Wild and Hatchery Populations of Korean Starry Flounder (Platichthys stellatus) Compared Using Microsatellite DNA Markers

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    Starry flounder (Platichthys stellatus) is an important sport and food fish found around the margins of the North Pacific. Aquaculture production of this species in Korea has increased because of its commercial value. Microsatellite DNA markers are a useful DNA-based tool for monitoring the genetic variation of starry flounder populations. In this study, 12 polymorphic microsatellite DNA markers were identified from a partial genomic starry flounder DNA library enriched in CA repeats, and used to compare allelic variation between wild and hatchery starry flounder populations in Korea. All loci were readily amplified and demonstrated high allelic diversity, with the number of alleles ranging from 6 to 18 in the wild population and from 2 to 12 in the farmed population. A total of 136 alleles were detected at the 12 microsatellite loci in the two populations. The mean observed and expected heterozygosities were 0.62 and 0.68, respectively, in the hatchery samples and 0.67 and 0.75, respectively, in the wild samples. These results indicate lower genetic variability in the hatchery population as compared to the wild population. Significant shifts in allelic frequencies were detected at eight loci, which resulted in a small but significant genetic differences between the wild and hatchery populations (FST = 0.043, P < 0.05). Further studies with additional starry flounder sample collections are needed for comprehensive determinations of the genetic varieties between the wild and hatchery populations. These microsatellite loci may be valuable for future population genetic studies, monitoring the genetic variation for successful aquaculture management and the preservation of aquatic biodiversity

    Measurement of the inclusive and dijet cross-sections of b-jets in pp collisions at sqrt(s) = 7 TeV with the ATLAS detector

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    The inclusive and dijet production cross-sections have been measured for jets containing b-hadrons (b-jets) in proton-proton collisions at a centre-of-mass energy of sqrt(s) = 7 TeV, using the ATLAS detector at the LHC. The measurements use data corresponding to an integrated luminosity of 34 pb^-1. The b-jets are identified using either a lifetime-based method, where secondary decay vertices of b-hadrons in jets are reconstructed using information from the tracking detectors, or a muon-based method where the presence of a muon is used to identify semileptonic decays of b-hadrons inside jets. The inclusive b-jet cross-section is measured as a function of transverse momentum in the range 20 < pT < 400 GeV and rapidity in the range |y| < 2.1. The bbbar-dijet cross-section is measured as a function of the dijet invariant mass in the range 110 < m_jj < 760 GeV, the azimuthal angle difference between the two jets and the angular variable chi in two dijet mass regions. The results are compared with next-to-leading-order QCD predictions. Good agreement is observed between the measured cross-sections and the predictions obtained using POWHEG + Pythia. MC@NLO + Herwig shows good agreement with the measured bbbar-dijet cross-section. However, it does not reproduce the measured inclusive cross-section well, particularly for central b-jets with large transverse momenta.Comment: 10 pages plus author list (21 pages total), 8 figures, 1 table, final version published in European Physical Journal
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