Large-scale association analyses identify new loci influencing glycemic traits and provide insight into the underlying biological pathways.

Through genome-wide association meta-analyses of up to 133,010 individuals of European ancestry without diabetes, including individuals newly genotyped using the Metabochip, we have increased the number of confirmed loci influencing glycemic traits to 53, of which 33 also increase type 2 diabetes risk (q < 0.05). Loci influencing fasting insulin concentration showed association with lipid levels and fat distribution, suggesting impact on insulin resistance. Gene-based analyses identified further biologically plausible loci, suggesting that additional loci beyond those reaching genome-wide significance are likely to represent real associations. This conclusion is supported by an excess of directionally consistent and nominally significant signals between discovery and follow-up studies. Functional analysis of these newly discovered loci will further improve our understanding of glycemic control.

Spatial pattern and process at the plant neighbourhood scale: insights from communities dominated by the clonal grass Elymus repens (L.) Gould.

Question: How do clonal traits of a locally dominant grass (Elymus repens (L.) Gould.) respond to soil heterogeneity and shape spatial patterns of its tillers? How do tiller spatial patterns constrain seedling recruitment within the community?Locations: Artificial banks of the River Rhone, France.Material and Methods: We examined 45 vegetation patches dominated by Elymus repens. During a first phase we tested relationships between soil variables and three clonal traits (spacer length, number of clumping tillers and branching rate), and between the same clonal traits and spatial patterns (i.e. density and degree of spatial aggregation) of tillers at a very fine scale. During a second phase, we performed a sowing experiment to investigate effects of density and spatial patterns of E. repens on recruitment of eight species selected from the regional species pool.Results: Clonal traits had clear effects - especially spacer length - on densification and aggregation of E. repens tillers and, at the same time, a clear response of these same clonal traits as soil granulometry changed. The density and degree of aggregation of E. repens tillers was positively correlated to total seedling cover and diversity at the finest spatial scales.Conclusions: Spatial patterning of a dominant perennial grass responds to soil heterogeneity through modifications of its clonal morphology as a trade-off between phalanx and guerrilla forms. In turn, spatial patterns have strong effects on abundance and diversity of seedlings. Spatial patterns of tillers most probably led to formation of endogenous gaps in which the recruitment of new plant individuals was enhanced. Interestingly, we also observed more idiosyncratic effects of tiller spatial patterns on seedling cover and diversity when focusing on different growth forms of the sown species.

SDF 1-alpha (CXCL12) triggers glutamate exocytosis from astrocytes on a millisecond time scale: Imaging analysis at the single-vesicle level with TIRF microscopy

Chemokines are small chemotactic molecules widely expressed throughout the central nervous system. A number of papers, during the past few years, have suggested that they have physiological functions in addition to their roles in neuroinflammatory diseases. In this context, the best evidence concerns the CXC-chemokine stromal cell-derived factor (SDF-1alpha or CXCL12) and its receptor CXCR4, whose signalling cascade is also implicated in the glutamate release process from astrocytes. Recently, astrocytic synaptic like microvesicles (SLMVs) that express vesicular glutamate transporters (VGLUTs) and are able to release glutamate by Ca(2+)-dependent regulated exocytosis, have been described both in tissue and in cultured astrocytes. Here, in order to elucidate whether SDF-1alpha/CXCR4 system can participate to the brain fast communication systems, we investigated whether the activation of CXCR4 receptor triggers glutamate exocytosis in astrocytes. By using total internal reflection (TIRF) microscopy and the membrane-fluorescent styryl dye FM4-64, we adapted an imaging methodology recently developed to measure exocytosis and recycling in synaptic terminals, and monitored the CXCR4-mediated exocytosis of SLMVs in astrocytes. We analyzed the co-localization of VGLUT with the FM dye at single-vesicle level, and observed the kinetics of the FM dye release during single fusion events. We found that the activation of CXCR4 receptors triggered a burst of exocytosis on a millisecond time scale that involved the release of Ca(2+) from internal stores. These results support the idea that astrocytes can respond to external stimuli and communicate with the neighboring cells via fast release of glutamate.

Construction of a scale to evaluate the diurnal impact of insomnia

The objective of this study was to develop and validate a scale to assess the diurnal impact of insomnia. The Insomnia Diurnal Impact Scale (IDIS) comprises six items designed to evaluate the daytime effects of insomnia. The sychometric properties of the original scale were analysed in a sample of 172 students, while its ability to differentiate insomniacs and non-insomniacs (according to the International Classification of Diseases (ICD)-10 criteria) was examined in a sample of 79 psychiatric patients and 82 individuals from the community. The psychometric properties of the English version were then analysed in a sample of 44 Englishspeaking participants. The results showed the internal consistency coefficient to be very good (0.86), with testretest reliability at 1 month being 0.79. A single factor explained almost 60% of the variance. Correlation of the IDIS with other scales varied between moderate and high values. Sensitivity was 78% and specificity 57% in the community sample, while the corresponding figures for the psychiatric population were 83% and 63%. Cronbach's ¿ coefficient for the English version reached a value of 0.93. These results indicate that the IDIS shows adequate reliability and validity with both general and psychiatric populations, and also that it can discriminate between the presence and absence of insomnia. The English version presents good preliminary results regarding item-corrected total correlation and internal consistency. In conclusion, the IDIS appears to be a useful tool in the primary care and mental health contexts for assessing insomnia-related diurnal dysfunction.

The co-evolution of social institutions, demography, and large-scale human cooperation.

Human cooperation is typically coordinated by institutions, which determine the outcome structure of the social interactions individuals engage in. Explaining the Neolithic transition from small- to large-scale societies involves understanding how these institutions co-evolve with demography. We study this using a demographically explicit model of institution formation in a patch-structured population. Each patch supports both social and asocial niches. Social individuals create an institution, at a cost to themselves, by negotiating how much of the costly public good provided by cooperators is invested into sanctioning defectors. The remainder of their public good is invested in technology that increases carrying capacity, such as irrigation systems. We show that social individuals can invade a population of asocials, and form institutions that support high levels of cooperation. We then demonstrate conditions where the co-evolution of cooperation, institutions, and demographic carrying capacity creates a transition from small- to large-scale social groups.

Modelling of vegetative filter strips in catchment scale erosin control

Selostus: Valuma-aluetason mallisovellus suojakaistojen käytöstä eroosion torjunnassa

Feasibility Study of Dynamic Overload and Ultimate Load Tests of Full-Scale Highway Bridges, HR-160, 1973

As a result of the construction of the Saylorville Dam and Reservoir on the Des Moines River, six highway bridges are scheduled for removal. Five of these are old high-truss single-lane bridges, each bridge having several simple spans. The other bridge is a fairly modern (1955) double 4-span continuous beam-and-slab composite highway bridge. The availability of these bridges affords an unusual opportunity for study of the behavior of full-scale bridges. Because of the magnitude of the potential testing program, a feasibility study was initiated and the results are presented in this two-part final report. Part I summarizes the findings and Part II presents the supporting detailed information.

Ultimate Load Behavior of Full-Scale Highway Truss Bridges, Summary Report, HR-169, 1975

As a result of the construction of the Saylorville Dam and Reservoir on the Des Moines River, six highway bridges crossing the river were scheduled for removal. One of these, an old pin-connected, high-truss, single-lane bridge, was selected for a comprehensive testing program which included ultimate load tests, service load tests, and a supplementary test program. A second bridge was used for a limited service load test program. The results of the research are detailed in two interim reports. The first interim report outlines the ultimate load tests and the second interim report details the results of the service load and supplementary test program. This report presents a summary of these findings along with recommendations for implementation of the findings.

Large-scale clustering through functional embedding

We present a new framework for large-scale data clustering. The main idea is to modify functional dimensionality reduction techniques to directly optimize over discrete labels using stochastic gradient descent. Compared to methods like spectral clustering our approach solves a single optimization problem, rather than an ad-hoc two-stage optimization approach, does not require a matrix inversion, can easily encode prior knowledge in the set of implementable functions, and does not have an ?out-of-sample? problem. Experimental results on both artificial and real-world datasets show the usefulness of our approach.

Exploring the proposed DSM-5 diagnostic threshold and severity scale for the alcohol use disorder

Aims :¦Several studies have questioned the validity of separating the diagnosis of alcohol abuse from that of alcohol dependence, and the DSM-5 task force has proposed combining the criteria from these two diagnoses to assess a single category of alcohol use disorders (AUD). Furthermore, the DSM-5 task force has proposed including a new 2-symptom threshold and a severity scale based on symptom counts for the AUD diagnosis. The current study aimed to examine these modifications in a large population-based sample.¦Method :¦Data stemmed from an adult sample (N=2588 ; mean age 51.3 years (s.d.: 0.2), 44.9% female) of current and lifetime drinkers from the PsyCoLaus study, conducted in the Lausanne area in Switzerland. AUDs and validating variables were assessed using a semi-structured diagnostic interview for the assessment of alcohol¦and other major psychiatric disorders. First, the adequacy of the proposed 2- symptom threshold was tested by comparing threshold models at each possible cutoff and a linear model, in relation to different validating variables. The model with the smallest Akaike Criterion Information (AIC) value was established as the best¦model for each validating variable. Second, models with varying subsets of individual AUD symptoms were created to assess the associations between each symptom and the validating variables. The subset of symptoms with the smallest AIC value was established as the best subset for each validator.¦Results :¦1) For the majority of validating variables, the linear model was found to be the best fitting model. 2) Among the various subsets of symptoms, the symptoms most frequently associated with the validating variables were : a) drinking despite having knowledge of a physical or psychological problem, b) having had a persistent desire or unsuccessful efforts to cut down or control drinking and c) craving. The¦least frequent symptoms were : d) drinking in larger amounts or over a longer period than was intended, e) spending a great deal of time in obtaining, using or recovering from alcohol use and f) failing to fulfill major role obligations.¦Conclusions :¦The proposed DSM-5 2-symptom threshold did not receive support in our data. Instead, a linear AUD diagnosis was supported with individuals receiving an increasingly severe AUD diagnosis. Moreover, certain symptoms were more frequently associated with the validating variables, which suggests that these¦symptoms should be considered as more severe.

Bioinformatics: making large-scale science happen

Bionformatics is a rapidly evolving research field dedicated toanalyzing and managing biological data with computational resources. This paperaims to overview some of the processes and applications currently implementedat CCiT-UB¿s Bioinformatics Unit, focusing mainly on the areas of Genomics,Transcriptomics and Proteomics