Searching for Dark Matter Annihilation in the Smith High-Velocity Cloud

Recent observations suggest that some high-velocity clouds may be confined by massive dark matter halos. In particular, the proximity and proposed dark matter content of the Smith Cloud make it a tempting target for the indirect detection of dark matter annihilation. We argue that the Smith Cloud may be a better target than some Milky Way dwarf spheroidal satellite galaxies and use gamma-ray observations from the Fermi Large Area Telescope to search for a dark matter annihilation signal. No significant gamma-ray excess is found coincident with the Smith Cloud, and we set strong limits on the dark matter annihilation cross section assuming a spatially-extended dark matter profile consistent with dynamical modeling of the Smith Cloud. Notably, these limits exclude the canonical thermal relic cross section ($\sim 3\times10^{-26}{\rm cm}^{3}{\rm s}^{-1}$) for dark matter masses $\lesssim 30$ GeV annihilating via the $b \bar b$ or $\tau^{+}\tau^{-}$ channels for certain assumptions of the dark matter density profile; however, uncertainties in the dark matter content of the Smith Cloud may significantly weaken these constraints.Comment: 7 pages, 5 figures. Published in Ap

Plurality in multi-disciplinary research: multiple institutional affiliations are associated with increased citations

Background The institutional affiliations and associated collaborative networks that scientists foster during their research careers are salient in the production of high-quality science. The phenomenon of multiple institutional affiliations and its relationship to research output remains relatively unexplored in the literature. Methods We examined 27,612 scientific articles, modelling the normalized citation counts received against the number of authors and affiliations held. Results In agreement with previous research, we found that teamwork is an important factor in high impact papers, with average citations received increasing concordant with the number of co-authors listed. For articles with more than five co-authors, we noted an increase in average citations received when authors with more than one institutional affiliation contributed to the research. Discussion Multiple author affiliations may play a positive role in the production of high-impact science. This increased researcher mobility should be viewed by institutional boards as meritorious in the pursuit of scientific discovery

Ethical Considerations for the Return of Incidental Findings in Ophthalmic Genomic Research

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. Available from PubMed Central (PMC).http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4757467/Whole genome and whole exome sequencing technologies are being increasingly used in research. However, they have the potential to identify incidental findings (IF), findings not related to the indication of the test, raising questions regarding researchers' responsibilities toward the return of this information to participants. In this study we discuss the ethical considerations related to the return of IF to research participants, emphasizing that the type of the study matters and describing the current practice standards. There are currently no legal obligations for researchers to return IF to participants, but some viewpoints consider that researchers might have an ethical one to return IF of clinical validity and clinical utility and that are actionable. The reality is that most IF are complex to interpret, especially since they were not the indication of the test. The clinical utility often depends on the participants' preferences, which can be challenging to conciliate and relies on participants' understanding. In summary, in the context of a lack of clear guidance, researchers need to have a clear plan for the disclosure or nondisclosure of IF from genomic research, balancing their research goals and resources with the participants' rights and their duty not to harm

Role of the TCF4 gene intronic variant in normal variation of corneal endothelium

PURPOSE: To identify early features of Fuchs endothelial dystrophy (FED) in carriers of the rs613872(G) transcription factor 4 gene (TCF4) aged 20 to 21 years. METHODS: Prospective cohort study of people aged 20 to 21 years previously enrolled in the Western Australia Pregnancy (Raine) Cohort. Specular microscopy was performed using a noncontact specular microscopy (EM-3000; Tomey, Nagoya, Japan). Individual genotype data were extracted from the genome-wide Illumina 660 Quad Array. Analysis of the association between the rs613872 risk allele in TCF4 and specular microscopic measurements was conducted. RESULTS: Association between the rs613872 risk allele and corneal endothelial cell density (CD) as well as the coefficient of variation in cell shape was the main outcome measure. Genotype and specular microscopic data were available for a total of 445 participants (46% women). The median CD was 2851 and 2850 cells per square millimeter in the right and left eyes, respectively. No significant differences between intereye variability in endothelial CD were seen (right eye to left eye correlation = 0.64); however, a significant difference in variability of endothelial CD between men and women was observed (male: OD, 2839 ± 124 cells/mm and OS, 2845 ± 124 cells/mm vs. female: OD, 2838 ± 134 cells/mm and OS, 2842 ± 132 cells/mm; OD, P = 0.0013 and OS, P = 0.0016). Eleven individuals were homozygous for the rs613872 risk allele. We found no association between rs613872 genotype and CD or coefficient of variation. One of 11 homozygous GG individuals was found to have a gutta in 1 sample field on specular microscopy, whereas 2 of 297 TT individuals also had a gutta each in 1 sample field. CONCLUSIONS: We were unable to detect an association between TCF4 rs613872 genotype and the variation in corneal endothelial CD or variation in cell morphology in a healthy young adult population. Copyrigh

A comparative analysis of high-throughput platforms for validation of a circulating microRNA signature in diabetic retinopathy

MicroRNAs are now increasingly recognized as biomarkers of disease progression. Several quantitative real-time PCR (qPCR) platforms have been developed to determine the relative levels of microRNAs in biological fluids. We systematically compared the detection of cellular and circulating microRNA using a standard 96-well platform, a high-content microfluidics platform and two ultrahigh content platforms. We used extensive analytical tools to compute inter- and intra-run variability and concordance measured using fidelity scoring, coefficient of variation and cluster analysis. We carried out unprejudiced next generation sequencing to identify a microRNA signature for Diabetic Retinopathy (DR) and systematically assessed the validation of this signature on clinical samples using each of the above four qPCR platforms. The results indicate that sensitivity to measure low copy number microRNAs is inversely related to qPCR reaction volume and that the choice of platform for microRNA biomarker validation should be made based on the abundance of miRNAs of interest

The telomere of human chromosome 1p contains at least two independent autosomal dominant congenital cataract genes.

AIMS: Multiple genetic causes of congenital cataract have been identified, both as a component of syndromes and in families that present with isolated congenital cataract. Linkage analysis was used to map the genetic locus in a six generation Australian family presenting with total congenital cataract. METHODS: Microsatellite markers located across all known autosomal dominant congenital cataract loci were genotyped in all recruited family members of the Tasmanian family. Both two point and multipoint linkage analysis were used to assess each locus under an autosomal dominant model. RESULTS: Significant linkage was detected at the telomere of the p arm of chromosome 1, with a maximum two point LOD of 4.21 at marker D1S507, a maximum multipoint exact LOD of 5.44, and an estimated location score of 5.61 at marker D1S507. Haplotype analysis places the gene inside a critical region between D1S228 and D1S199, a distance of approximately 6 megabases. The candidate gene PAX7 residing within the critical interval was excluded by direct sequencing in affected individuals. CONCLUSION: This is the third report of congenital cataract linkage to 1ptel. The critical region as defined by the shared haplotype in this family is clearly centromeric from the Volkmann cataract locus identified through study of a Danish family, indicating that two genes causing autosomal dominant congenital cataract map to the telomeric region of chromosome 1p

Primary open angle glaucoma due to T377M MYOC: Population mapping of a Greek founder mutation in Northwestern Greece

BACKGROUND: Mutations in the MYOC gene have been shown to explain 5% of unrelated primary open angle glaucoma (POAG) in different populations. In particular, the T377M MYOC mutation has arisen at least three separate times in history, in Great Britain, India, and Greece. The purpose of this study is to investigate the distribution of the mutation among different population groups in the northwestern region of Greece. MATERIALS AND METHODS: We explored the distribution of the "Greek" T377M founder mutation in the Epirus region in Northwestern Greece, which could be its origin. Genotyping was performed in POAG cases and controls by PCR amplification of the MYOC gene, followed by digestion with restriction enzyme. Statistical analyses were performed by an exact test, the Kaplan-Meier method and the t-test. RESULTS: In the isolated Chrysovitsa village in the Pindus Mountains, a large POAG family demonstrated the T377M mutation in 20 of 66 family members while no controls from the Epirus region (n = 124) carried this mutation (P < 0.001). Among other POAG cases from Epirus, 2 out of 14 familial cases and 1 out of 80 sporadic cases showed the mutation (P = 0.057). The probability of POAG diagnosis with advancing age among mutation carriers was 23% at age 40, and reached 100% at age 75. POAG patients with the T377M mutation were diagnosed at a mean age of 51 years (SD +/- 13.9), which is younger than the sporadic or familial POAG cases: 63.1 (SD +/- 11) and 66.8 (SD +/- 9.8) years, respectively. CONCLUSIONS: The T377M mutation was found in high proportion in members of the Chrysovitsa family (30.3%), in lower proportion in familial POAG cases (14.2%) and seems rare in sporadic POAG cases (1.2%), while no controls (0%) from the Epirus region carried the mutation. Historical and geographical data may explain the distribution of this mutation within Greece and worldwide