Evidence that Cd101 is an autoimmune diabetes gene in nonobese diabetic mice

We have previously proposed that sequence variation of the CD101 gene between NOD and C57BL/6 mice accounts for the protection from type 1 diabetes (T1D) provided by the insulin-dependent diabetes susceptibility region 10 (Idd10), a <1 Mb region on mouse chromosome 3. In this study, we provide further support for the hypothesis that Cd101 is Idd10 using haplotype and expression analyses of novel Idd10 congenic strains coupled to the development of a CD101 knockout mouse. Susceptibility to T1D was correlated with genotype-dependent CD101 expression on multiple cell subsets, including Foxp3(+) regulatory CD4(+) T cells, CD11c(+) dendritic cells, and Gr1(+) myeloid cells. The correlation of CD101 expression on immune cells from four independent Idd10 haplotypes with the development of T1D supports the identity of Cd101 as Idd10. Because CD101 has been associated with regulatory T and Ag presentation cell functions, our results provide a further link between immune regulation and susceptibility to T1D.     

Effects of divergent resistance exercise contraction mode and dietary supplementation type on anabolic signalling,muscle protein synthesis and muscle hypertrophy

Greater force produced with eccentric (ECC) compared to concentric (CONC) contractions, may comprise a stronger driver of muscle growth, which may be further augmented by protein supplementation. We investigated the effect of differentiated contraction mode with either whey protein hydrolysate and carbohydrate (WPH + CHO) or isocaloric carbohydrate (CHO) supplementation on regulation of anabolic signalling, muscle protein synthesis (MPS) and muscle hypertrophy. Twenty-four human participants performed unilateral isolated maximal ECC versus CONC contractions during exercise habituation, single-bout exercise and 12 weeks of training combined with WPH + CHO or CHO supplements. In the exercise-habituated state, p-mTOR, p-p70S6K, p-rpS6 increased by approximately 42, 206 and 213 %, respectively, at 1 h post-exercise, with resistance exercise per se; whereas, the phosphorylation was exclusively maintained with ECC at 3 and 5 h post-exercise. This acute anabolic signalling response did not differ between the isocaloric supplement types, neither did protein fractional synthesis rate differ between interventions. Twelve weeks of ECC as well as CONC resistance training augmented hypertrophy with WPH + CHO group compared to the CHO group (7.3 ± 1.0 versus 3.4 ± 0.8 %), independently of exercise contraction type. Training did not produce major changes in basal levels of Akt-mTOR pathway components. In conclusion, maximal ECC contraction mode may constitute a superior driver of acute anabolic signalling that may not be mirrored in the muscle protein synthesis rate. Furthermore, with prolonged high-volume resistance training, contraction mode seems less influential on the magnitude of muscle hypertrophy, whereas protein and carbohydrate supplementation augments muscle hypertrophy as compared to isocaloric carbohydrate supplementation .     

Land‐atmosphere exchange of methane from soil thawing to soil freezing in a high‐Arctic wet tundra ecosystem

The land‐atmosphere exchange of methane (CH₄) and carbon dioxide (CO₂) in a high‐Arctic wet tundra ecosystem (Rylekærene) in Zackenberg, north‐eastern Greenland, was studied over the full growing season and until early winter in 2008 and from before snow melt until early winter in 2009. The eddy covariance technique was used to estimate CO₂ fluxes and a combination of the gradient and eddy covariance methods was used to estimate CH₄ fluxes. Small CH₄ bursts were observed during spring thawing 2009, but these existed during short periods and would not have any significant effect on the annual budget. Growing season CH₄ fluxes were well correlated with soil temperature, gross primary production, and active layer thickness. The CH₄ fluxes remained low during the entire autumn, and until early winter. No increase in CH₄ fluxes were seen as the soil started to freeze. However, in autumn 2008 there were two CH₄ burst events that were highly correlated with atmospheric turbulence. They were likely associated with the release of stored CH₄ from soil and vegetation cavities. Over the measurement period, 7.6 and 6.5 g C m^?2 was emitted as CH₄ in 2008 and in 2009, respectively. Rylekærene acted as a C source during the warmer and wetter measurement period 2008, whereas it was a C sink for the colder and drier period of 2009. Wet tundra ecosystems, such as Rylekærene may thus play a more significant role for the climate in the future, as temperature and precipitation are predicted to increase in the high‐Arctic.     

High‐Throughput DNA sequencing of ancient wood

Reconstructing the colonization and demographic dynamics that gave rise to extant forests is essential to forecasts of forest responses to environmental changes. Classical approaches to map how population of trees changed through space and time largely rely on pollen distribution patterns, with only a limited number of studies exploiting DNA molecules preserved in wooden tree archaeological and subfossil remains. Here, we advance such analyses by applying high‐throughput (HTS) DNA sequencing to wood archaeological and subfossil material for the first time, using a comprehensive sample of 167 European white oak waterlogged remains spanning a large temporal (from 550 to 9,800 years) and geographical range across Europe. The successful characterization of the endogenous DNA and exogenous microbial DNA of 140 (~83%) samples helped the identification of environmental conditions favouring long‐term DNA preservation in wood remains, and started to unveil the first trends in the DNA decay process in wood material. Additionally, the maternally inherited chloroplast haplotypes of 21 samples from three periods of forest human‐induced use (Neolithic, Bronze Age and Middle Ages) were found to be consistent with those of modern populations growing in the same geographic areas. Our work paves the way for further studies aiming at using ancient DNA preserved in wood to reconstruct the micro‐evolutionary response of trees to climate change and human forest management.     

Improving ancient DNA read mapping against modern reference genomes

ABSTRACT: BACKGROUND: Next-Generation Sequencing has revolutionized our approach to ancient DNA (aDNA) research, by providing complete genomic sequences of ancient individuals and extinct species. However, the recovery of genetic material from long-dead organisms is still complicated by a number of issues, including post-mortem DNA damage and high levels of environmental contamination. Together with error profiles specific to the type of sequencing platforms used, these specificities could limit our ability to map sequencing reads against modern reference genomes and therefore limit our ability to identify endogenous ancient reads, reducing the efficiency of shotgun sequencing aDNA. RESULTS: In this study, we compare different computational methods for improving the accuracy and sensitivity of aDNA sequence identification, based on shotgun sequencing reads recovered from Pleistocene horse extracts using Illumina GAIIx and Helicos Heliscope platforms. We show that the performance of the Burrows Wheeler Aligner (BWA), that has been developed for mapping of undamaged sequencing reads using platforms with low rates of indel-types of sequencing errors, can be employed at acceptable run-times by modifying default parameters in a platform-specific manner. We also examine if trimming likely damaged positions at read ends can increase the recovery of genuine aDNA fragments and if accurate identification of human contamination can be achieved using a strategy previously suggested based on best hit filtering. We show that combining our different mapping and filtering approaches can increase the number of high-quality endogenous hits recovered by up to 33%. CONCLUSIONS: We have shown that Illumina and Helicos sequences recovered from aDNA extracts could not be aligned to modern reference genomes with the same efficiency unless mapping parameters are optimized for the specific types of errors generated by these platforms and by post-mortem DNA damage. Our findings have important implications for future aDNA research, as we define mapping guidelines that improve our ability to identify genuine aDNA sequences, which in turn could improve the genotyping accuracy of ancient specimens. Our framework provides a significant improvement to the standard procedures used for characterizing ancient genomes, which is challenged by contamination and often low amounts of DNA material.     

Rebound effects of price differences

Goal, Scope and Background  Traditionally, comparative life cycle assessments (LCA) have not considered rebound effects, for instance in case of significant price differences among the compared products. No justifications have been made for this delimitation in scope. This article shows that price differences and the consequent effects of marginal consumer expenditure may influence the conclusions of comparative LCA significantly. We also show that considerations about rebound effects of price differences can be included in LCAs. Methods  The direct rebound effect of a price difference is marginal consumption. Based on statistical data on private consumption in different income groups (Statistics Denmark 2005a, 2005b), the present article provides an estimate of how an average Danish household will spend an additional 1 DKK for further consumer goods, when the household has gained money from choosing a cheaper product alternative. The approach is to use marginal income changes and the following changes in consumption patterns as an expression for marginal consumption. Secondly, the environmental impact potentials related to this marginal consumption are estimated by the use of environmental impact intensity data from an IO-LCA database (Weidema et al. 2005). Finally, it is discussed whether, and in which ways the conclusions of comparative LCAs can be affected by including the price difference between product alternatives. This is elucidated in a case study of a comparative LCA screening of two different kinds of Danish cheese products (Fricke et al. 2004). Results  Car purchase and driving, use and maintenance of dwelling, clothing purchase and insurance constitutes the largest percentages of the marginal consumption. In a case study of two cheeses, the including the impact potentials related to the price difference results in significant changes in the total impact potentials. Considering the relatively small price difference of the two products, it is likely also to have a significant influence on the results of comparative LCAs more generally. Discussion  The influence of marginal consumption in comparative LCAs is relevant to consider in situations with large differences in the price of the product alternatives being compared, and in situations with minor differences in the impact potentials related to the alternatives. However, different uncertainties are linked to determining the pattern for marginal consumption and the environmental impact potential related to this. These are first of all related to the method used, but also include inaccurate data of consumption in households, aggregation and weighting of income groups, aggregation of product groups, estimation and size of the price difference, and the general applicability of the results. Conclusion  Incorporating marginal consumption in consequential LCAs is possible in practice. In the case study used, including the rebound effects of the price difference has a significant influence on the result of the comparative LCA, as the result for the impact categories acidification and nutrient enrichment changes in favour of the expensive product. Recommendations and Perspectives  It is recommended that the rebound effects of price differences should be included more frequently in LCAs. In order to ensure this, further research in marginal consumption and investment patterns and IO data for different countries or regions is required. Furthermore, this study does not consider the economic distributional consequences of buying an expensive product instead of a cheaper product (e.g. related to how the profit is spent by those who provided the product). It should also be noted, that more expensive products not necessarily result in less consumption, as those who provided the product also will spend the money they have earned from the sale. Ideally, these consequences should also be further investigated. Likewise, the development of databases to include marginal consumption in PC-tools is needed. In general, considerations of marginal consumption would favour expensive product alternatives, depending, however, on the type of consumer. ESS-Submission Editor: Dr. David Hunkeler (david.hunkeler@aquaplustech.ch)     

X-Ray Crystal Structure of a Highly Functionalized Thiophene as a New Backbone Amide Linker for Solid-phase Peptide Synthesis. Relationship between Crystal Structure and Reactivity

The development of new linkers (handles) for solid-phase synthesis provides new chemical opportunities for peptide synthesis. To understand the chemical properties of a recently developed backbone amide linker from a structural perspective, the crystal structure of S-((5-formyl-3,4-ethylenedioxy)thiophene-2-yl)-3-thiopropionic acid (T-BAL2) was studied. Specifically, we wished to address whether this highly substituted thiophene retained planarity in the aromatic ring as well as between the aromatic ring and the aldehyde carbonyl. Furthermore, we sought an explanation for the relatively low reactivity in reductive aminations of the thienylaldehyde with amines in solution and on solid phase. Based on the crystal structure of T-BAL2, the thienyl-C (aldehyde) and C–O (aldehyde) bond lengths were applied as measures for the electron-deficiency (electrophilicity) of the aldehyde and compared to similar bond lengths found in previously reported formylated homo- and hetero-aromatic systems, which show significantly higher reactivity towards imine formation. The bond lengths found in the present structure are in accordance with normal C–C single bond and C–O double bond lengths. The high similarity in aldehyde bond lengths in the present system and in the reported systems indicates similar electron distribution in these systems. The lower reactivity of the present system may therefore not be attributed to electronic factors.     

Whole genome association mapping by incompatibilities and local perfect phylogenies

Background  

With current technology, vast amounts of data can be cheaply and efficiently produced in association studies, and to prevent data analysis to become the bottleneck of studies, fast and efficient analysis methods that scale to such data set sizes must be developed.     

Diurnal variation in methane emission in relation to the water table,soil temperature,climate and vegetation cover in a Swedish acid mire

Diurnal variation in the rate of methane emission and its relation to water table depth and macro climate was studied in several plant communities within an acid,Sphagnum dominated, mixed mire in Northern Sweden. Provided that diurnal variation in solar radiation and air temperature occurred, methane fluxes differed during day and night. Diurnal patterns in methane emission rates were found to differ among mire plant communities. In relatively dry plant communities (ridges, minerotrophic lawn), the average nighttime emission rates were 2–3 times higher than the daytime rates during the two periods with high diurnal variation in solar radiation and air temperature. Methane emission was significantly (p < 0.05) related to solar radiation and soil temperature at depths of 5 and 10 cm at all sampling points in the dry plant communities. In the wetter plant communities, no significant difference between daytime and nighttime average methane emission rates were found even though methane emissions were significantly related with radiation and soil temperature at approximately 70% of the sampling points. The increased emission rate for methane at night in the comparatively dry plant communities was probably caused by an inhibition of methane oxidation, owing to the lower nighttime temperatures or to a delay in the supply of root-exuded substrate for the anaerobic bacteria, or by both. The pattern observed in the wet plant communities indicated that methane production were positively related either to soil temperature or light-regulated root exudation.