SNP2GO: functional analysis of genome-wide association studies.

Genome-wide association studies (GWAS) are designed to identify the portion of single-nucleotide polymorphisms (SNPs) in genome sequences associated with a complex trait. Strategies based on the gene list enrichment concept are currently applied for the functional analysis of GWAS, according to which a significant overrepresentation of candidate genes associated with a biological pathway is used as a proxy to infer overrepresentation of candidate SNPs in the pathway. Here we show that such inference is not always valid and introduce the program SNP2GO, which implements a new method to properly test for the overrepresentation of candidate SNPs in biological pathways.

Climate and vegetation history of western Portugal inferred from Albian near-shore deposits (Gale Formation, Lusitanian Basin)

The late Early Cretaceous greenhouse climate has been studied intensively based on proxy data derived essentially from open marine archives. In contrast, information on continental climatic conditions and on the accompanying response of vegetation is relatively scarce, most notably owing to the stratigraphic uncertainties associated with many Lower Cretaceous terrestrial deposits. Here, we present a palynological record from Albian near-shore deposits of the Lusitanian Basin of W Portugal, which have been independently dated using Sr-isotope signals derived from low-Mg oyster shell calcite. Sr-87/Sr-86 values fluctuate between 0.707373 +/- 0.00002 and 0.707456 +/- 0.00003; absolute values and the overall stratigraphic trend match well with the global open marine seawater signature during Albian times. Based on the new Sr-isotope data, existing biostratigraphic assignments of the succession are corroborated and partly revised. Spore-pollen data provide information on the vegetation community structure and are flanked by sedimentological and clay mineralogical data used to infer the overall climatic conditions prevailing on the adjacent continent. Variations in the distribution of climate-sensitive pollen and spores indicate distinct changes in moisture availability across the studied succession with a pronounced increase in hygrophilous spores in late Early Albian times. Comparison with time-equivalent palynofloras from the Algarve Basin of southern Portugal shows pronounced differences in the xerophyte/hygrophyte ratio, interpreted to reflect the effect of a broad arid climate belt covering southern and southeastern Iberia during Early Albian times.

Characterization of a MexAB-OprM efflux system necessary for productive metabolism of Pseudomonas azelaica HBP1 on 2-hydroxybiphenyl.

Pseudomonas azelaica HBP1 is one of the few bacteria known to completely mineralize the biocide and toxic compound 2-hydroxybiphenyl (2-HBP), but the mechanisms of its tolerance to the toxicity are unknown. By transposon mutant analysis and screening for absence of growth on water saturating concentrations of 2-HBP (2.7 mM) we preferentially found insertions in three genes with high homology to the mexA, mexB, and oprM efflux system. Mutants could grow at 2-HBP concentrations below 100 μM but at lower growth rates than the wild-type. Exposure of the wild-type to increasing 2-HBP concentrations resulted in acute cell growth arrest and loss of membrane potential, to which the cells adapt after a few hours. By using ethidium bromide (EB) as proxy we could show that the mutants are unable to expel EB effectively. Inclusion of a 2-HBP reporter plasmid revealed that the wild-type combines efflux with metabolism at all 2-HBP concentrations, whereas the mutants cannot remove the compound and arrest metabolism at concentrations above 24 μM. The analysis thus showed the importance of the MexAB-OprM system for productive metabolism of 2-HBP.

The biogenic origin of needle fibre calcite

Needle fibre calcite is one of the most ubiquitous habits of calcite in vadose environments (caves deposits, soil pores, etc.). Its origin, either through inorganic, indirect or direct biological processes, has long been debated. In this study, investigations at 11 sites in Europe, Africa and Central America support arguments for its biogenic origin. The wide range of needle morphologies is the result of a gradual evolution of the simplest type, a rod. This rod is the elementary brick which, by aggregation and welding, builds more complex needles. The absence of cross-welded needles implies that they are welded in a mould, or under a longitudinal and unidirectional constraint, before being released inside the soil pores. The difference between the lengthening of the needles and the c axis can be explained by the existence of needles observed under a scanning electron microscope in organic sleeves, which can act as a mould during rod growth. Complex morphologies with epitaxial outgrowths on straight rods cannot have grown entirely inside organic microtubes; they must result from soil diagenesis after the release of straight rods in a soil-free medium. Whisker crystals are interpreted as the result of growth and coalescence of euhedral crystals on a rod. Rhomb chains are considered to be the consequence of successive epitaxial growth steps on a needle during variations in growth conditions. Isotopic signatures for needle fibre calcite vary from -16.63[per mille] to +1.10[per mille] and from -8.63[per mille] to -2.25[per mille] for Delta13C and Delta18O, respectively. The absence of high Delta18O values for needle fibre calcite precludes a purely physicochemical origin (evaporative) for this particular habit of calcite. As epitaxial growth cannot precipitate in the same conditions as initial needles, needle fibre calcite stable isotopic signatures should be used with caution as a proxy for palaeoenvironmental reconstructions. In addition, it is suggested that the term needle fibre calcite should be kept for the original biogenic form. The other habit should be referred to as epitaxial forms of needle fibre calcite.

Higher Risk of Incident Hepatitis C Virus Coinfection Among Men Who Have Sex With Men, in Whom the HIV Genetic Bottleneck at Transmission Was Wide.

BACKGROUND: High-risk sexual behaviors have been suggested as drivers of the recent dramatic increase of sexually transmitted hepatitis C virus (HCV) among human immunodeficiency virus (HIV)-infected men who have sex with men (MSM). METHODS: We assessed the association between the genetic bottleneck of HIV at transmission and the prevalence and incidence of HCV coinfection in HIV-infected MSM from the Swiss HIV Cohort Study (SHCS). As a proxy for the width of the transmission bottleneck, we used the fraction of ambiguous nucleotides detected by genotypic resistance tests sampled during early HIV infection. We defined a broad bottleneck as a fraction of ambiguous nucleotides exceeding a previously established threshold (0.5%). RESULTS: From the SHCS, we identified 671 MSM with available results of HCV serologic tests and with an HIV genotypic resistance test performed during early HIV infection. Of those, 161 (24.0%) exhibited a broad HIV transmission bottleneck, 38 (5.7%) had at least 1 positive HCV test result, and 26 (3.9%) had an incident HCV infection. Individuals with broad HIV transmission bottlenecks exhibited a 2-fold higher odds of having ever experienced an HCV coinfection (odds ratio, 2.2 [95% confidence interval {CI}, 1.1-4.3]) and a 3-fold higher hazard of having an incident HCV infection (hazard ratio, 3.0 [95% CI, 1.4-6.6]) than individuals with narrow HIV transmission bottlenecks. CONCLUSIONS: Our results indicate that the currently occurring sexual spread of HCV is focused on MSM who are prone to exhibit broad HIV transmission bottlenecks. This is consistent with an important role of high-risk behavior and mucosal barrier impairment in the transmission of HCV among MSM.

Early diagenesis of bone and tooth apatite in fluvial and marine settings: Constraints from combined oxygen isotope, nitrogen and REE analysis

Fossil bones and teeth of Late Pleistocene terrestrial mammals from Rhine River gravels (RS) and the North Sea (NS), that have been exposed to chemically and isotopically distinct diagenetic fluids (fresh water versus seawater), were investigated to study the effects of early diagenesis on biogenic apatite. Changes in phosphate oxygen isotopic composition (delta O-18(PO4)), nitrogen content (wt.% N) and rare earth element (REE) concentrations were measured along profiles within bones that have not been completely fossilized, and in skeletal tissues (bone, dentine, enamel) with different susceptibilities to diagenetic alteration. Early diagenetic changes of elemental and isotopic compositions of apatite in fossil bone are related to the loss of the stabilizing collagen matrix. The REE concentration is negatively correlated with the nitrogen content, and therefore the amount of collagen provides a sensitive proxy for early diagenetic alteration. REE patterns of RS and NS bones indicate initial fossilization in a fresh water fluid with similar REE compositions. Bones from both settings have nearly collagen-free, REE-, U-, F- and Sr-enriched altered outer rims, while the collagen-bearing bone compacta in the central part often display early diagenetic pyrite void-fillings. However, NS bones exposed to Holocene seawater have outer rim delta O-18(PO4) values that are 1.1 to 2.6 parts per thousand higher compared to the central part of the same bones (delta O-18(PO4) = 18.2 +/- 0.9 parts per thousand, n = 19). Surprisingly, even the collagen-rich bone compacta with low REE contents and apatite crystallinity seems altered, as NS tooth enamel (delta O-18(PO4) =15.0 +/- 0.3 parts per thousand, n=4) has about 3%. lower delta O-18(PO4) values, values that are also similar to those of enamel from RS teeth. Therefore, REE concentration, N content and apatite crystallinity are in this case only poor proxies for the alteration of delta O-18(PO4) values. Seawater exposure of a few years up to 8 kyr can change the delta O-18(PO4) values of the bone apatite by > 3 parts per thousand. Therefore, bones fossilized in marine settings must be treated with caution for palaeoclimatic reconstructions. However, enamel seems to preserve pristine delta O-18(PO4) values on this time scale. Using species-specific calibrations for modern mammals, a mean delta O-18(H2O) value can be reconstructed for Late Pleistocene mammalian drinking water of around -9.2 +/- 0.5 parts per thousand, which is similar to that of Late Pleistocene groundwater from central Europe. (c) 2008 Elsevier B.V. All rights reserved.

Disentangling the link between health and social capital: A comparison of immigrant and native-born populations in Spain

An increasing body of research has pointed to the relevance of social capital in studying a great variety of socio-economic phenomena, ranging from economics growth and development to educational attainment and public health. Conceptually, our paper is framed within the debates about the possible links between health and social capital, on one hand, and within the hypotheses regarding the importance of social and community networks in all stages of the dynamics of international migration, on the other hand. Our primary objective is to explore the ways social relations contribute to health differences between the immigrants and the native-born population of Spain. We also try to reveal differences in the nature of the social networks of foreign-born, as compared to that of the native-born persons. The empirical analysis is based on an individual-level data coming from the 2006 Spanish Health Survey, which contains a representative sample of the immigrant population. To assess the relationship between various health indicators (self-assessed health, chronic conditions and long-term illness) and social capital, controlling for other covariates, we estimate multilevel models separately for the two population groups of interest. In the estimates we distinguish between individual and community-level social capital. While the Health Survey contains information that allows us to define individual social capital measures, the collective indicators come from other official sources. In particular, for the subsample of immigrants, we proxy community-level networks and relationships by variables contained in the Spanish National Survey of Immigrants 2007. The results obtained so far point to the relevance of social capital as a covariate in the health equation, although, the significance varies according to the specific health indicator used. Additionally, and contrary to what is expected, immigrants’ social networks seem to be inferior to those of the native-born population in many aspects; and they also affect immigrant’s health to a lesser extent. Policy implications of the findings are discussed. Keywords: health status, social capital, immigration, Spain

Guidelines for Removal of Traffic Control Devices in Rural Areas, TR-527, 2005

It is commonly regarded that the overuse of traffic control devices desensitizes drivers and leads to disrespect, especially for low-volume secondary roads with limited enforcement. The maintenance of traffic signs is also a tort liability concern, exacerbated by unnecessary signs. The Federal Highway Administration’s (FHWA) Manual on Uniform Traffic Control Devices (MUTCD) and the Institute of Transportation Engineer’s (ITE) Traffic Control Devices Handbook provide guidance for the implementation of STOP signs based on expected compliance with right-of-way rules, provision of through traffic flow, context (proximity to other controlled intersections), speed, sight distance, and crash history. The approach(es) to stop is left to engineering judgment and is usually dependent on traffic volume or functional class/continuity of system. Although presently being considered by the National Committee on Traffic Control Devices, traffic volume itself is not given as a criterion for implementation in the MUTCD. STOP signs have been installed at many locations for various reasons which no longer (or perhaps never) met engineering needs. If in fact the presence of STOP signs does not increase safety, removal should be considered. To date, however, no guidance exists for the removal of STOP signs at two-way stop-controlled intersections. The scope of this research is ultra-low-volume (< 150 daily entering vehicles) unpaved intersections in rural agricultural areas of Iowa, where each of the 99 counties may have as many as 300 or more STOP sign pairs. Overall safety performance is examined as a function of a county excessive use factor, developed specifically for this study and based on various volume ranges and terrain as a proxy for sight distance. Four conclusions are supported: (1) there is no statistical difference in the safety performance of ultra-low-volume stop-controlled and uncontrolled intersections for all drivers or for younger and older drivers (although interestingly, older drivers are underrepresented at both types of intersections); (2) compliance with stop control (as indicated by crash performance) does not appear to be affected by the use or excessive use of STOP signs, even when adjusted for volume and a sight distance proxy; (3) crash performance does not appear to be improved by the liberal use of stop control; (4) safety performance of uncontrolled intersections appears to decline relative to stop-controlled intersections above about 150 daily entering vehicles. Subject to adequate sight distance, traffic professionals may wish to consider removal of control below this threshold. The report concludes with a section on methods and legal considerations for safe removal of stop control.

Mining the human phenome using allelic scores that index biological intermediates.

It is common practice in genome-wide association studies (GWAS) to focus on the relationship between disease risk and genetic variants one marker at a time. When relevant genes are identified it is often possible to implicate biological intermediates and pathways likely to be involved in disease aetiology. However, single genetic variants typically explain small amounts of disease risk. Our idea is to construct allelic scores that explain greater proportions of the variance in biological intermediates, and subsequently use these scores to data mine GWAS. To investigate the approach's properties, we indexed three biological intermediates where the results of large GWAS meta-analyses were available: body mass index, C-reactive protein and low density lipoprotein levels. We generated allelic scores in the Avon Longitudinal Study of Parents and Children, and in publicly available data from the first Wellcome Trust Case Control Consortium. We compared the explanatory ability of allelic scores in terms of their capacity to proxy for the intermediate of interest, and the extent to which they associated with disease. We found that allelic scores derived from known variants and allelic scores derived from hundreds of thousands of genetic markers explained significant portions of the variance in biological intermediates of interest, and many of these scores showed expected correlations with disease. Genome-wide allelic scores however tended to lack specificity suggesting that they should be used with caution and perhaps only to proxy biological intermediates for which there are no known individual variants. Power calculations confirm the feasibility of extending our strategy to the analysis of tens of thousands of molecular phenotypes in large genome-wide meta-analyses. We conclude that our method represents a simple way in which potentially tens of thousands of molecular phenotypes could be screened for causal relationships with disease without having to expensively measure these variables in individual disease collections.

Heritability and quantitative genetic divergence of serotiny, a fire-persistence plant trait.

BACKGROUND AND AIMS: Although it is well known that fire acts as a selective pressure shaping plant phenotypes, there are no quantitative estimates of the heritability of any trait related to plant persistence under recurrent fires, such as serotiny. In this study, the heritability of serotiny in Pinus halepensis is calculated, and an evaluation is made as to whether fire has left a selection signature on the level of serotiny among populations by comparing the genetic divergence of serotiny with the expected divergence of neutral molecular markers (QST-FST comparison). METHODS: A common garden of P. halepensis was used, located in inland Spain and composed of 145 open-pollinated families from 29 provenances covering the entire natural range of P. halepensis in the Iberian Peninsula and Balearic Islands. Narrow-sense heritability (h(2)) and quantitative genetic differentiation among populations for serotiny (QST) were estimated by means of an 'animal model' fitted by Bayesian inference. In order to determine whether genetic differentiation for serotiny is the result of differential natural selection, QST estimates for serotiny were compared with FST estimates obtained from allozyme data. Finally, a test was made of whether levels of serotiny in the different provenances were related to different fire regimes, using summer rainfall as a proxy for fire regime in each provenance. KEY RESULTS: Serotiny showed a significant narrow-sense heritability (h(2)) of 0·20 (credible interval 0·09-0·40). Quantitative genetic differentiation among provenances for serotiny (QST = 0·44) was significantly higher than expected under a neutral process (FST = 0·12), suggesting adaptive differentiation. A significant negative relationship was found between the serotiny level of trees in the common garden and summer rainfall of their provenance sites. CONCLUSIONS: Serotiny is a heritable trait in P. halepensis, and selection acts on it, giving rise to contrasting serotiny levels among populations depending on the fire regime, and supporting the role of fire in generating genetic divergence for adaptive traits.

Development of a Subgrade Drainage Model for Unpaved Roads, TR-654, 2015

With over 68 thousand miles of gravel roads in Iowa and the importance of these roads within the farm-to-market transportation system, proper water management becomes critical for maintaining the integrity of the roadway materials. However, the build-up of water within the aggregate subbase can lead to frost boils and ultimately potholes forming at the road surface. The aggregate subbase and subgrade soils under these gravel roads are produced with material opportunistically chosen from local sources near the site and, many times, the compositions of these sublayers are far from ideal in terms of proper water drainage with the full effects of this shortcut not being fully understood. The primary objective of this project was to provide a physically-based model for evaluating the drainability of potential subbase and subgrade materials for gravel roads in Iowa. The Richards equation provided the appropriate framework to study the transient unsaturated flow that usually occurs through the subbase and subgrade of a gravel road. From which, we identified that the saturated hydraulic conductivity, Ks, was a key parameter driving the time to drain of subgrade soils found in Iowa, thus being a good proxy variable for accessing roadway drainability. Using Ks, derived from soil texture, we were able to identify potential problem areas in terms of roadway drainage . It was found that there is a threshold for Ks of 15 cm/day that determines if the roadway will drain efficiently, based on the requirement that the time to drain, Td, the surface roadway layer does not exceed a 2-hr limit. Two of the three highest abundant textures (loam and silty clay loam), which cover nearly 60% of the state of Iowa, were found to have average Td values greater than the 2-hr limit. With such a large percentage of the state at risk for the formation of boils due to the soil with relatively low saturated hydraulic conductivity values, it seems pertinent that we propose alternative design and/or maintenance practices to limit the expensive repair work in Iowa. The addition of drain tiles or French mattresses my help address drainage problems. However, before pursuing this recommendation, a comprehensive cost-benefit analysis is needed.

Fact-sheet National Comparison of Jointly Enrolled Students, February 3, 2015

This fact sheet attempts to address the following question: where does Iowa rank nationally in terms of the enrollment of high school students in post-secondary coursework? The division gathered national statistics from the Integrated Post-secondary Education Data System (IPEDS) on the age of the enrolled student population at two–year and four-year public institutions during the fall of 2013. The division utilized the percent of students under the age of 18 as a proxy for joint enrollment since most high school students would fall into this age bracket.

Fetal testosterone (2D:4D) as predictor of cognitive reflection

The Cognitive Reflection Test (CRT) is a test introduced by S. Frederick (2005) Cognitive reflection and decision making, J Econ Perspect 19(4): 25-42. The task is designed to measure the tendency to override an intuitive response that is incorrect and to engage in further reflection that leads to the correct response. The consistent sex differences in CRT performance may suggest a role for gonadal hormones, particularly testosterone. A now widely studied putative marker for fetal testosterone is the second-to-fourth digit ratio (2D:4D). This paper tests to what extent 2D:4D, as a proxy for prenatal exposure to testosterone, can predict CRT scores in a sample of 623 students. After controlling for sex, we observe that a lower 2D:4D (reflecting a higher exposure to testosterone) is significantly associated with a higher number of correct answers. The result holds for both hands? 2D:4Ds. In addition, the effect appears to be sharper for females than for males. We also control for patience and math proficiency, which are significantly related to performance in the CRT. But the effect of 2D:4D on performance in CRT is not reduced with these controls, implying that these variables are not mediating the relationship between digit ratio and CRT.

Am I shrinking? On clothing size and body size.

Comment on: Hughes LA, Schouten LJ, Goldbohm RA, van den Brandt PA, Weijenberg MP. Self-reported clothing size as a proxy measure for body size. Epidemiology. 2009 Sep;20(5):673-6. PMID: 19451821