Evolutionary Signatures amongst Disease Genes Permit Novel Methods for Gene Prioritization and Construction of Informative Gene-Based Networks

Genes involved in the same function tend to have similar evolutionary histories, in that their rates of evolution covary over time. This coevolutionary signature, termed Evolutionary Rate Covariation (ERC), is calculated using only gene sequences from a set of closely related species and has demonstrated potential as a computational tool for inferring functional relationships between genes. To further define applications of ERC, we first established that roughly 55% of genetic diseases posses an ERC signature between their contributing genes. At a false discovery rate of 5% we report 40 such diseases including cancers, developmental disorders and mitochondrial diseases. Given these coevolutionary signatures between disease genes, we then assessed ERC's ability to prioritize known disease genes out of a list of unrelated candidates. We found that in the presence of an ERC signature, the true disease gene is effectively prioritized to the top 6% of candidates on average. We then apply this strategy to a melanoma-associated region on chromosome 1 and identify MCL1 as a potential causative gene. Furthermore, to gain global insight into disease mechanisms, we used ERC to predict molecular connections between 310 nominally distinct diseases. The resulting “disease map” network associates several diseases with related pathogenic mechanisms and unveils many novel relationships between clinically distinct diseases, such as between Hirschsprung's disease and melanoma. Taken together, these results demonstrate the utility of molecular evolution as a gene discovery platform and show that evolutionary signatures can be used to build informative gene-based networks

Is Bariatric Surgery an Effective Treatment for Type II Diabetic Kidney Disease?

Type II diabetic kidney disease is devastating to patients and society alike. This review will evaluate bariatric surgery as a treatment for diabetic kidney disease primarily through its ability to induce and maintain regression of type II diabetes. The review begins by outlining the global challenge of diabetic kidney disease, its link to obesity, and the comparative benefits of bariatric surgery on weight and type II diabetes. It then surveys comprehensively the relevant literature, which reports that although bariatric surgery is associated with reductions in albuminuria, its effect on harder clinical end points like progression of diabetic kidney disease is not known. The review also includes a critical assessment of the risks and costs of bariatric surgery and concludes by acknowledging the major knowledge gaps in the field and providing research strategies to overcome them. Until these knowledge gaps are filled, clinicians will be forced to rely on their own subjective judgment in determining the benefit-risk ratio of bariatric surgery for patients with diabetic kidney disease

A complete sample of 21-cm absorbers at z~1.3: Giant Metrewave Radio Telescope Survey Using MgII Systems

We present the results of a systematic Giant Metrewave Radio Telescope (GMRT) survey of 21-cm absorption in a representative and unbiased sample of 35 strong MgII systems in the redshift range: zabs~1.10-1.45, 33 of which have W_r>1 \AA. The survey using ~400hrs of telescope time has resulted in 9 new 21-cm detections and stringent 21-cm optical depth upper limits (median 3-sigma optical depth per 10 km/s of 0.017) for the remaining 26 systems. This is by far the largest number of 21-cm detections from any single survey of intervening absorbers. Prior to our survey no intervening 21-cm system was known in the above redshift range and only one system was known in the redshift range 0.7<z<1.5. We discuss the relation between the detectability of 21-cm absorption and various properties of UV absorption lines. We show that if MgII systems are selected with the following criteria, MgII doublet ratio <1.3 and W_r(MgI)/W_r(MgII)>0.3, then a detection rate of 21-cm absorption up to 90% can be achieved. We estimate n_{21}, the number per unit redshift of 21-cm absorbers with W_r(Mg(II)>W_o and integrated optical depth Tau_{21}>Tau_o and show that n_{21} decreases with increasing redshift. In particular, for W_o=1.0 \AA and Tau_o>0.3 km\s, n_{21} falls by a factor 4 from =0.5 to =1.3. The evolution seems to be stronger for stronger MgII systems. Using a subsample of systems for which high frequency VLBA images are available, we show that the effect is not related to the structure of the background radio sources and is most probably due to the evolution of the cold neutral medium filling factor in MgII systems. We find no correlation between the velocity spread of the 21-cm absorption feature and W_r(MgII) at z~1.3.Comment: 22 pages, 8 tables, 12 figures, accepted for publication in MNRA

Open-access theology : introducing the St Andrews Encyclopaedia of Theology’s digital publishing model

The St Andrews Encyclopaedia of Theology (SAET) is an online multi-author reference work designed as a resource for those engaged with, or wishing to learn more about, the academic study of theology. The SAET seeks to provide a suite of comprehensive, fully open-access peer-reviewed articles with no fees or sign-up requirements. In doing so, the editors aim to improve the availability of high-quality information for readers worldwide, especially those for whom access to resources through traditional academic publishing is restricted by cost, lack of institutional affiliation, or limited library resources. This article introduces the SAET’s digital publishing model, discussing the scholarly and editorial principles that have informed the development of the project. In particular, the article examines the ways in which the SAET’s commitment to providing quality open-access scholarship has significantly shaped the project’s information management and publishing processes. Technical strategies for widening access to theological knowledge are discussed, focusing on information discovery through the Encyclopaedia’s faceted search and in-article hyperlinks, as well as available article formats (HTML and PDF). This is accompanied by an explanation of strategies for long-term curation and preservation of theological knowledge within the SAET, namely capturing and preserving conceptual information through enriched XML mark-up and embedded metadata. The SAET’s article lifecycle is then conceptualized in reference to digital curation and preservation actions described by the Digital Curation Centre’s ‘DCC Curation Lifecycle Model’, leading to conclusions about the distinctive character of the SAET article workflow, in which curation and preservation of theological knowledge is integrated into its creation and production.Publisher PDFPeer reviewe

Metallicity Evolution in the Early Universe

Observations of the damped Lya systems provide direct measurements on the chemical enrichment history of neutral gas in the early universe. In this Letter, we present new measurements for four damped Lya systems at high redshift. Combining these data with [Fe/H] values culled from the literature, we investigate the metallicity evolution of the universe from z~1.5-4.5. Contrary to our expectations and the predictions of essentially every chemical evolution model, the N(HI)-weighted mean [Fe/H] metallicity exhibits minimal evolution over this epoch. For the individual systems, we report tentative evidence for an evolution in the unweighted [Fe/H] mean and the scatter in [Fe/H] with the higher redshift systems showing lower scatter and lower typical [Fe/H] values. We also note that no damped Lya system has [Fe/H] < -2.7 dex. Finally, we discuss the potential impact of small number statistics and dust on our conclusions and consider the implications of these results on chemical evolution in the early universe.Comment: 6 pages, 2 encapsulated figures, Latex2e, uses emulateapj.sty and onecolfloat.sty. Accepted for publication in ApJ Letters: Feb 28, 200

Heat pumping in nanomechanical systems

We propose using a phonon pumping mechanism to transfer heat from a cold to a hot body using a propagating modulation of the medium connecting the two bodies. This phonon pump can cool nanomechanical systems without the need for active feedback. We compute the lowest temperature that this refrigerator can achieve.Comment: 4 pages, 1 figure, published versio

A Bioclimatic Laboratory in Southern Ohio

Author Institution: Department of Botany and Plant Pathology, The Ohio State University, Columbus 1