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

Association of eNOS polymorphisms with primary angle-closure glaucoma

Author version made available in accordance with the publisher's policy.Purpose: Recently, several studies have investigated genetic associations between Cytochrome P450 (CYP1B1), Endothelial nitric oxide synthase (eNOS) and Neurotrophin-4 (NTF4) with primary angle-closure glaucoma (PACG) in various ethnic groups. Here we investigate the association of these candidate genes with PACG in samples from Australia and Nepal. Method: A total of 235 patients with PACG (106 Nepalese and 129 Australian) and 492 controls (204 Nepalese and 288 Australian) were included. Tag single nucleotide polymorphisms (SNPs) were selected to cover the majority of common variation within the candidate genes and genotyped in DNA extracted from peripheral whole blood. Allele and haplotype analyses were conducted in PLINK. Bonferroni correction was applied for the total number of SNPs in this study (p=0.05/15=0.003) Results: In the Australian cohort, one eNOS SNP rs3793342 shows significance association with PACG in the Australian cohort after Bonferroni correction (p-value 0.003, OR 0.5 95% CI 0.3-0.8). After adjusting the results for sex and age both SNPs rs3793342 and rs7830 showed significance after Bonferroni correction (p-value of 0.001 and 0.003, respectively). The eNOS haplotype of all 7 typed SNPs showed significant association with a global p-value of 0.019, with the CGCAATC haplotype giving a specific p-value of 0.008 and odds ratio of 1.5 (95% CI 0.9-2.4). In the Nepalese cohort, SNPs in CYP1B1 and NTF4 genes showed borderline association with PACG but did not survive Bonferroni correction. Conclusions: The present data support the involvement of common variations in eNOS with PACG pathogenesis. Differences were observed in the two populations studied, and additional replication studies in other populations are necessary to confirm these association

A cross-ethnicity investigation of genes previously implicated in primary angle closure glaucoma

Purpose: To investigate the underlying genetic variation between candidate genes and primary angle closure glaucoma (PACG) in both Nepalese and Australian populations. Methods: A total of 213 patients with PACG (106 Nepalese and 107 Australian) and 492 age and sex matched controls (204 Nepalese and 288 Australian) were included in the current study. Three candidate genes were selected; methyltetrahydrofolate reductase (MTHFR), calcitonin receptor-like receptor gene (CALCRL), and membrane frizzled-related protein (MFRP). Tag single nucleotide polymorphisms (SNPs) were selected and genotyped to capture the majority of common variation across each locus. Allele and haplotype analyses were conducted using PLINK. Results: SNPs in the nanophthalmos gene MFRP were found to be nominally associated with PACG under the allelic model. Two SNPs were associated in the Australian cohort (rs948414; p=0.02 and rs36015759; p=0.02), and a single SNP in the Nepalese cohort (rs10790289; p=0.03), however these SNPs failed to remain significant after adjustment for sex and age. A haplotype at the CALCRL gene (AATACAGAT) was associated in the Australian cohort (corrected p-value= 0.024). No association was observed in either cohort for MTHFR. Conclusions: This study implicates genetic variation at the CALCRL gene in the pathogenesis of PACG in an Australian Caucasian cohort. Additionally, the MFRP gene shows tendency to be associated with PACG in both the Australian and Nepalese cohorts. Further investigation in a larger cohort is warranted to confirm these findings. No statistically significant associations were identified between MTHFR and PACG in either population

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

Association of genetic variants with primary angle closure glaucoma in two different populations

This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.PURPOSE: A recent large genome-wide association study (GWAS) identified multiple variants associated with primary angle-closure glaucoma (PACG). The present study investigated the role of these variants in two cohorts with PACG recruited from Australia and Nepal. METHOD: Patients with PACG and appropriate controls were recruited from eye clinics in Australia (n = 232 cases and n = 288 controls) and Nepal (n = 106 cases and 204 controls). Single nucleotide polymorphisms (SNPs) rs3753841 (COL11A1), rs1015213 (located between PCMTD1 and ST18), rs11024102 (PLEKHA7), and rs3788317 (TXNRD2) were selected and genotyped on the Sequenom. Analyses were conducted using PLINK and METAL. RESULTS: After adjustment for age and sex, SNP rs3753841 was found to be significantly associated with PACG in the Australian cohort (p = 0.017; OR = 1.34). SNPs rs1015213 (p = 0.014; OR 2.35) and rs11024102 (p = 0.039; OR 1.43) were significantly associated with the disease development in the Nepalese cohort. None of these SNPs survived Bonferroni correction (p = 0.05/4 = 0.013). However, in the combined analysis, of both cohorts, rs3753841 and rs1015213 showed significant association with p-values of 0.009 and 0.004, respectively both surviving Bonferroni correction. SNP rs11024102 showed suggestive association with PACG (p-value 0.035) and no association was found with rs3788317. CONCLUSION: The present results support the initial GWAS findings, and confirm the SNP's contribution to PACG. This is the first study to investigate these loci in both Australian Caucasian and Nepalese populations

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

DNA methylation landscape of ocular tissue relative to matched peripheral blood

This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/Epigenetic variation is implicated in a range of non-communicable diseases, including those of the eye. However, investigating the role of epigenetic variation in central tissues, such as eye or brain, remains problematic and peripheral tissues are often used as surrogates. In this study, matched human blood and eye tissue (n = 8) were obtained post-mortem and DNA methylation profiling performed on blood, neurosensory retina, retinal pigment epithelium (RPE)/choroid and optic nerve tissue using the Illumina Infinium HumanMethylation450 platform. Unsupervised clustering and principal components analysis revealed tissue of origin as the main driver of methylation variation. Despite this, there was a strong correlation of methylation profiles between tissues with >255,000 CpG sites found to have similar methylation levels. An additional ~16,000 show similarity across ocular tissues only. A small proportion of probes showing inter-individual variation in blood co-varied with eye tissues within individuals, however much of this variation may be genetically driven. An improved understanding of the epigenetic landscape of the eye will have important implications for understanding eye disease. Despite a generally high correlation irrespective of origin, tissue type is the major driver of methylation variation, with only limited covariation between blood and any specific ocular tissue