Effects of Genetic Variants Previously Associated with Fasting Glucose and Insulin in the Diabetes Prevention Program

Common genetic variants have been recently associated with fasting glucose and insulin levels in white populations. Whether these associations replicate in pre-diabetes is not known. We extended these findings to the Diabetes Prevention Program, a clinical trial in which participants at high risk for diabetes were randomized to placebo, lifestyle modification or metformin for diabetes prevention. We genotyped previously reported polymorphisms (or their proxies) in/near G6PC2, MTNR1B, GCK, DGKB, GCKR, ADCY5, MADD, CRY2, ADRA2A, FADS1, PROX1, SLC2A2, GLIS3, C2CD4B, IGF1, and IRS1 in 3,548 Diabetes Prevention Program participants. We analyzed variants for association with baseline glycemic traits, incident diabetes and their interaction with response to metformin or lifestyle intervention. We replicated associations with fasting glucose at MTNR1B (P<0.001), G6PC2 (P = 0.002) and GCKR (P = 0.001). We noted impaired β-cell function in carriers of glucose-raising alleles at MTNR1B (P<0.001), and an increase in the insulinogenic index for the glucose-raising allele at G6PC2 (P<0.001). The association of MTNR1B with fasting glucose and impaired β-cell function persisted at 1 year despite adjustment for the baseline trait, indicating a sustained deleterious effect at this locus. We also replicated the association of MADD with fasting proinsulin levels (P<0.001). We detected no significant impact of these variants on diabetes incidence or interaction with preventive interventions. The association of several polymorphisms with quantitative glycemic traits is replicated in a cohort of high-risk persons. These variants do not have a detectable impact on diabetes incidence or response to metformin or lifestyle modification in the Diabetes Prevention Program

Multiple ITS Copies Reveal Extensive Hybridization within Rheum (Polygonaceae), a Genus That Has Undergone Rapid Radiation

During adaptive radiation events, characters can arise multiple times due to parallel evolution, but transfer of traits through hybridization provides an alternative explanation for the same character appearing in apparently non-sister lineages. The signature of hybridization can be detected in incongruence between phylogenies derived from different markers, or from the presence of two divergent versions of a nuclear marker such as ITS within one individual.In this study, we cloned and sequenced ITS regions for 30 species of the genus Rheum, and compared them with a cpDNA phylogeny. Seven species contained two divergent copies of ITS that resolved in different clades from one another in each case, indicating hybridization events too recent for concerted evolution to have homogenised the ITS sequences. Hybridization was also indicated in at least two further species via incongruence in their position between ITS and cpDNA phylogenies. None of the ITS sequences present in these nine species matched those detected in any other species, which provides tentative evidence against recent introgression as an explanation. Rheum globulosum, previously indicated by cpDNA to represent an independent origin of decumbent habit, is indicated by ITS to be part of clade of decumbent species, which acquired cpDNA of another clade via hybridization. However decumbent and glasshouse morphology are confirmed to have arisen three and two times, respectively.These findings suggested that hybridization among QTP species of Rheum has been extensive, and that a role of hybridization in diversification of Rheum requires investigation

U.S. academic libraries: understanding their web presence and their relationship with economic indicators

The final publication is available at Springer via http://dx.doi.org/10.1007/s11192-013-1001-0The main goal of this research is to analyze the web structure and performance of units and services belonging to U.S. academic libraries in order to check their suitability for webometric studies. Our objectives include studying their possible correlation with economic data and assessing their use for complementary evaluation purposes. We conducted a survey of library homepages, institutional repositories, digital collections, and online catalogs (a total of 374 URLs) belonging to the 100 U.S. universities with the highest total expenditures in academic libraries according to data provided by the National Center for Education Statistics. Several data points were taken and analyzed, including web variables (page count, external links, and visits) and economic variables (total expenditures, expenditures on printed and electronic books, and physical visits). The results indicate that the variety of URL syntaxes is wide, diverse and complex, which produces a misrepresentation of academic libraries’ web resources and reduces the accuracy of web analysis. On the other hand, institutional and web data indicators are not highly correlated. Better results are obtained by correlating total library expenditures with URL mentions measured by Google (r = 0.546) and visits measured by Compete (r = 0.573), respectively. Because correlation values obtained are not highly significant, we estimate such correlations will increase if users can avoid linkage problems (due to the complexity of URLs) and gain direct access to log files (for more accurate data about visits).Orduña Malea, E.; Regazzi, JJ. (2014). U.S. academic libraries: understanding their web presence and their relationship with economic indicators. Scientometrics. 98(1):315-336. doi:10.1007/s11192-013-1001-0S315336981Adecannby, J. (2011). 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Search engine results over time—A case study on search engine stability”. Cybermetrics, 2/3. Retrieved February 18, 2013 from http://www.cindoc.csic.es/cybermetrics/articles/v2i1p1.html.Bar-Ilan, J. (2001). Data collection methods on the Web for informetric purposes: A review and analysis. Scientometrics, 50(1), 7–32.Bermejo, F. (2007). The internet audience: Constitution & measurement. New York: Peter Lang Pub Incorporated.Buigues-Garcia, M., & Gimenez-Chornet, V. (2012). Impact of Web 2.0 on national libraries. International Journal of Information Management, 32(1), 3–10.Chu, H., He, S., & Thelwall, M. (2002). Library and information science schools in Canada and USA: A Webometric perspective. Journal of education for Library and Information Science, 43(2), 110–125.Chua, Alton, Y. K., & Goh, D. H. (2010). A study of Web 2.0 applications in library websites. Library and Information Science Research, 32(3), 203–211.Gallego, I., García, I.-M., & Rodríguez, L. (2009). Universities’ websites: Disclosure practices and the revelation of financial information. The International Journal of Digital Accounting Research, 9(15), 153–192.Gomes, B. & Smith, B. T. (2003). Detecting query-specific duplicate documents. [Patent]. Retrieved February 18, 2013 from http://www.patents.com/Detecting-query-specific-duplicate-documents/US6615209/en-US .Harinarayana, N. S., & Raju, N. V. (2010). Web 2.0 features in university library web sites. Electronic Library, 28(1), 69–88.Lewandowski, D., Wahlig, H., & Meyer-Bautor, G. (2006). The freshness of web search engine databases. Journal of Information Science, 32(2), 131–148.Mahmood, K., & Richardson, J. V, Jr. (2012). Adoption of Web 2.0 in US academic libraries: A survey of ARL library websites. Program, 45(4), 365–375.Orduña-Malea, E., & Ontalba-Ruipérez, J-A. (2012). Selective linking from social platforms to university websites: A case study of the Spanish academic system. Scientometrics. (in press).Ortega, J. L., & Aguillo, I. F. (2009). Mapping World-class universities on the Web. Information Processing and Management, 45(2), 272–279.Ortega, José L. & Aguillo, Isidro F. (2009b). North America Academic Web Space: Multicultural Canada vs. The United States Homogeneity. In: ASIST & ISSI pre-conference symposium on informetrics and scientometrics.Phan, T., Hardesty, L., Sheckells, C., & George, A. (2009). Documentation for the academic libraries survey (ALS) public-use data file: Fiscal year 2008. Washington DC: National Center for Education Statistics. Institute of Education Sciences U.S. Department of Education.Qiu, J., Cheng, J., & Wang, Z. (2004). An analysis of backlinks counts and web impact factors for Chinese university websites. Scientometrics, 60(3), 463–473.Regazzi, J. J. (2012a). Constrained?—An analysis of U.S. Academic Libraries and shifts in spending, staffing and utilization, 1998–2008. College and Research Libraries, 73(5), 449–468.Regazzi, J. J. (2012b). Comparing Academic Library Spending with Public Libraries, Public K-12 Schools, Higher Education Public Institutions, and Public Hospitals Between 1998–2008. Journal of Academic Librarianship, 38(4), 205–216.Rousseau, R. (1999). Daily time series of common single word searches in AltaVista and NorthernLight. Cybermetrics, 2/3. Retrieved February 18, 2013 from http://www.cindoc.csic.es/cybermetrics/articles/v2i1p2.html .Sato, S., & Itsumura, H. (2011). How do people use open access papers in non-academic activities? A link analysis of papers deposited in institutional repositories. Library, Information and Media Studies, 9(1), 51–64.Scholze, F. (2007). Measuring research impact in an open access environment. Liber Quarterly: The Journal of European Research Libraries, 17(1–4), 220–232.Smith, A. G. (2011). Wikipedia and institutional repositories: An academic symbiosis? In: Proceedings of the ISSI 2011 conference. Durban, South Africa, 4–7 July 2011. 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Genetics of decayed sexual traits in a parasitoid wasp with endosymbiont-induced asexuality.

Trait decay may occur when selective pressures shift, owing to changes in environment or life style, rendering formerly adaptive traits non-functional or even maladaptive. It remains largely unknown if such decay would stem from multiple mutations with small effects or rather involve few loci with major phenotypic effects. Here, we investigate the decay of female sexual traits, and the genetic causes thereof, in a transition from haplodiploid sexual reproduction to endosymbiont-induced asexual reproduction in the parasitoid wasp Asobara japonica. We take advantage of the fact that asexual females cured of their endosymbionts produce sons instead of daughters, and that these sons can be crossed with sexual females. By combining behavioral experiments with crosses designed to introgress alleles from the asexual into the sexual genome, we found that sexual attractiveness, mating, egg fertilization and plastic adjustment of offspring sex ratio (in response to variation in local mate competition) are decayed in asexual A. japonica females. Furthermore, introgression experiments revealed that the propensity for cured asexual females to produce only sons (because of decayed sexual attractiveness, mating behavior and/or egg fertilization) is likely caused by recessive genetic effects at a single locus. Recessive effects were also found to cause decay of plastic sex-ratio adjustment under variable levels of local mate competition. Our results suggest that few recessive mutations drive decay of female sexual traits, at least in asexual species deriving from haplodiploid sexual ancestors

The Major Antigenic Membrane Protein of “Candidatus Phytoplasma asteris” Selectively Interacts with ATP Synthase and Actin of Leafhopper Vectors

Phytoplasmas, uncultivable phloem-limited phytopathogenic wall-less bacteria, represent a major threat to agriculture worldwide. They are transmitted in a persistent, propagative manner by phloem-sucking Hemipteran insects. Phytoplasma membrane proteins are in direct contact with hosts and are presumably involved in determining vector specificity. Such a role has been proposed for phytoplasma transmembrane proteins encoded by circular extrachromosomal elements, at least one of which is a plasmid. Little is known about the interactions between major phytoplasma antigenic membrane protein (Amp) and insect vector proteins. The aims of our work were to identify vector proteins interacting with Amp and to investigate their role in transmission specificity. In controlled transmission experiments, four Hemipteran species were identified as vectors of “Candidatus Phytoplasma asteris”, the chrysanthemum yellows phytoplasmas (CYP) strain, and three others as non-vectors. Interactions between a labelled (recombinant) CYP Amp and insect proteins were analysed by far Western blots and affinity chromatography. Amp interacted specifically with a few proteins from vector species only. Among Amp-binding vector proteins, actin and both the α and β subunits of ATP synthase were identified by mass spectrometry and Western blots. Immunofluorescence confocal microscopy and Western blots of plasma membrane and mitochondrial fractions confirmed the localisation of ATP synthase, generally known as a mitochondrial protein, in plasma membranes of midgut and salivary gland cells in the vector Euscelidius variegatus. The vector-specific interaction between phytoplasma Amp and insect ATP synthase is demonstrated for the first time, and this work also supports the hypothesis that host actin is involved in the internalization and intracellular motility of phytoplasmas within their vectors. Phytoplasma Amp is hypothesized to play a crucial role in insect transmission specificity

Extracellular ATP is a pro-angiogenic factor for pulmonary artery vasa vasorum endothelial cells

Expansion of the vasa vasorum network has been observed in a variety of systemic and pulmonary vascular diseases. We recently reported that a marked expansion of the vasa vasorum network occurs in the pulmonary artery adventitia of chronically hypoxic calves. Since hypoxia has been shown to stimulate ATP release from both vascular resident as well as circulatory blood cells, these studies were undertaken to determine if extracellular ATP exerts angiogenic effects on isolated vasa vasorum endothelial cells (VVEC) and/or if it augments the effects of other angiogenic factors (VEGF and basic FGF) known to be present in the hypoxic microenvironment. We found that extracellular ATP dramatically increases DNA synthesis, migration, and rearrangement into tube-like networks on Matrigel in VVEC, but not in pulmonary artery (MPAEC) or aortic (AOEC) endothelial cells obtained from the same animals. Extracellular ATP potentiated the effects of both VEGF and bFGF to stimulate DNA synthesis in VVEC but not in MPAEC and AOEC. Analysis of purine and pyrimidine nucleotides revealed that ATP, ADP and MeSADP were the most potent in stimulating mitogenic responses in VVEC, indicating the involvement of the family of P2Y1-like purinergic receptors. Using pharmacological inhibitors, Western blot analysis, and Phosphatidylinositol-3 kinase (PI3K) in vitro kinase assays, we found that PI3K/Akt/mTOR and ERK1/2 play a critical role in mediating the extracellular ATP-induced mitogenic and migratory responses in VVEC. However, PI3K/Akt and mTOR/p70S6K do not significantly contribute to extracellular ATP-induced tube formation on Matrigel. Our studies indicate that VVEC, isolated from the sites of active angiogenesis, exhibit distinct functional responses to ATP, compared to endothelial cells derived from large pulmonary or systemic vessels. Collectively, our data support the idea that extracellular ATP participates in the expansion of the vasa vasorum that can be observed in hypoxic conditions

Hemichordate genomes and deuterostome origins

Acorn worms, also known as enteropneust (literally, ‘gut-breathing’) hemichordates, are marine invertebrates that share features with echinoderms and chordates. Together, these three phyla comprise the deuterostomes. Here we report the draft genome sequences of two acorn worms, Saccoglossus kowalevskii and Ptychodera flava. By comparing them with diverse bilaterian genomes, we identify shared traits that were probably inherited from the last common deuterostome ancestor, and then explore evolutionary trajectories leading from this ancestor to hemichordates, echinoderms and chordates. The hemichordate genomes exhibit extensive conserved synteny with amphioxus and other bilaterians, and deeply conserved non-coding sequences that are candidates for conserved gene-regulatory elements. Notably, hemichordates possess a deuterostome-specific genomic cluster of four ordered transcription factor genes, the expression of which is associated with the development of pharyngeal ‘gill’ slits, the foremost morphological innovation of early deuterostomes, and is probably central to their filter-feeding lifestyle. Comparative analysis reveals numerous deuterostome-specific gene novelties, including genes found in deuterostomes and marine microbes, but not other animals. The putative functions of these genes can be linked to physiological, metabolic and developmental specializations of the filter-feeding ancestor

Protein Docking by the Interface Structure Similarity: How Much Structure Is Needed?

The increasing availability of co-crystallized protein-protein complexes provides an opportunity to use template-based modeling for protein-protein docking. Structure alignment techniques are useful in detection of remote target-template similarities. The size of the structure involved in the alignment is important for the success in modeling. This paper describes a systematic large-scale study to find the optimal definition/size of the interfaces for the structure alignment-based docking applications. The results showed that structural areas corresponding to the cutoff values <12 Å across the interface inadequately represent structural details of the interfaces. With the increase of the cutoff beyond 12 Å, the success rate for the benchmark set of 99 protein complexes, did not increase significantly for higher accuracy models, and decreased for lower-accuracy models. The 12 Å cutoff was optimal in our interface alignment-based docking, and a likely best choice for the large-scale (e.g., on the scale of the entire genome) applications to protein interaction networks. The results provide guidelines for the docking approaches, including high-throughput applications to modeled structures