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Defects of motile cilia cause primary ciliary dyskinesia (PCD), characterized by recurrent respiratory infections and male infertility. Using whole-exome resequencing and high-throughput mutation analysis, we identified recessive biallelic mutations in ZMYND10 in 14 families and mutations in the recently identified LRRC6 in 13 families. We show that ZMYND10 and LRRC6 interact and that certain ZMYND10 and LRRC6 mutations abrogate the interaction between the LRRC6 CS domain and the ZMYND10 C-terminal domain. Additionally, ZMYND10 and LRRC6 colocalize with the centriole markers SAS6 and PCM1. Mutations in ZMYND10 result in the absence of the axonemal protein components DNAH5 and DNALI1 from respiratory cilia. Animal models support the association between ZMYND10 and human PCD, given that zmynd10 knockdown in zebrafish caused ciliary paralysis leading to cystic kidneys and otolith defects and that knockdown in Xenopus interfered with ciliogenesis. Our findings suggest that a cytoplasmic protein complex containing ZMYND10 and LRRC6 is necessary for motile ciliary function. © 2013 The American Society of Human Genetics.

Interferometric detectors will very soon give us an unprecedented view of the gravitational-wave sky, and in particular of the explosive and transient Universe. Now is the time to challenge our theoretical understanding of short-duration gravitational-wave signatures from cataclysmic events, their connection to more traditional electromagnetic and particle astrophysics, and the data analysis techniques that will make the observations a reality. This paper summarizes the state of the art, future science opportunities, and current challenges in understanding gravitational-wave transients. 33 pages, 2 figures

We present a comprehensive description of the population synthesis code StarTrack. The original code has been significantly modified and updated. Special emphasis is placed here on processes leading to the formation and further evolution of compact objects (white dwarfs, neutron stars, and black holes). Both single and binary star populations are considered. The code now incorporates detailed calculations of all mass-transfer phases, a full implementation of orbital evolution due to tides, as well as the most recent estimates of magnetic braking. This updated version of StarTrack can be used for a wide variety of problems, with relevance to many current and planned observatories, e.g., studies of X-ray binaries (Chandra, XMM-Newton), gravitational radiation sources (LIGO, LISA), and gamma-ray burst progenitors (HETE-II, Swift). The code has already been used in studies of Galactic and extra-galactic X-ray binary populations, black holes in young star clusters, Type Ia supernova progenitors, and double compact object populations. Here we describe in detail the input physics, we present the code calibration and tests, and we outline our current studies in the context of X-ray binary populations. 40 pages, 14 figures, accepted to ApJS (major extensions/revisions)

We report the detection of the far-infrared (FIR) fine-structure line of singly ionised nitrogen, \Nplusa, within the peak epoch of galaxy assembly, from a strongly lensed galaxy, hereafter ``The Red Radio Ring''; the RRR, at z = 2.55. We combine new observations of the ground-state and mid-J transitions of CO (J$_{\rm up} =$ 1,5,8), and the FIR spectral energy distribution (SED), to explore the multi-phase interstellar medium (ISM) properties of the RRR. All line profiles suggest that the HII regions, traced by \Nplusa, and the (diffuse and dense) molecular gas, traced by the CO, are co-spatial when averaged over kpc-sized regions. Using its mid-IR-to-millimetre (mm) SED, we derive a non-negligible dust attenuation of the \Nplusa line emission. Assuming a uniform dust screen approximation results a mean molecular gas column density $> 10^{24}$\, cm$^{-2}$, with a molecular gas-to-dust mass ratio of 100. It is clear that dust attenuation corrections should be accounted for when studying FIR fine-structure lines in such systems. The attenuation corrected ratio of $L_{\rm NII205} / L_{\rm IR(8-1000��m)} = 2.7 \times 10^{-4}$ is consistent with the dispersion of local and $z >$ 4 SFGs. We find that the lower-limit, \Nplusa -based star-formation rate (SFR) is less than the IR-derived SFR by a factor of four. Finally, the dust SED, CO line SED and $L_{\rm NII205}$ line-to-IR luminosity ratio of the RRR is consistent with a starburst-powered ISM. 13 pages, 6 figures, accepted to MNRAS

We report BRITE-Constellation photometry of the beta Cep pulsator xi 1 CMa. Analysis of these data reveals a single pulsation period of 0.2095781(3) d, along with its first and second harmonics. We find no evidence for any other frequencies, limiting the value of this star as a target for magneto-asteroseismology. We em- ploy the 17-year database of RV measurements of xi 1 CMa to evaluate evidence for the reported change in pulsation period, and interpret this period change in terms of stellar evolution. We measure a rate-of-change of the period equal to 0.009(1) s/yr, consistent with that reported in the literature. 5 pages, proceedings of the 3rd BRITE-Constellation Science Conference, Lac Taureau, 2017

Estrogen receptor (ER)-negative tumors represent 20-30% of all breast cancers, with a higher proportion occurring in younger women and women of African ancestry. The etiology and clinical behavior of ER-negative tumors are different from those of tumors expressing ER (ER positive), including differences in genetic predisposition. To identify susceptibility loci specific to ER-negative disease, we combined in a metaanalysis 3 genome-wide association studies of 4,193 ER-negative breast cancer cases and 35,194 controls with a series of 40 follow-up studies (6,514 cases and 41,455 controls), genotyped using a custom Illumina array, iCOGS, developed by the Collaborative Oncological Gene-environment Study (COGS). SNPs at four loci, 1q32.1 (MDM4, P= 2.1 x 10(-12) and LGR6, P = 1.4 x 10(-8)), 2p24.1 (P = 4.6 x 10(-8)) and 16q12.2 (FTO, P = 4.0 x 10(-8)), were associated with ER-negative but not ER-positive breast cancer (P> 0.05). These findings provide further evidence for distinct etiological pathways associated with invasive ER-positive and ER-negative breast cancers.

Background Recent progress in selective breeding of maize (Zea mays L.) towards adaptation to temperate climate has allowed the production of inbred lines withstanding cold springs with temperatures below 8 °C or even close to 0 °C, indicating that despite its tropical origins maize is not inherently cold-sensitive. Results Here we studied the acclimatory response of three maize inbred lines of contrasting cold-sensitivity selected basing on multi-year routine field data. The field observations were confirmed in the growth chamber. Under controlled conditions the damage to the photosynthetic apparatus due to severe cold treatment was the least in the cold-tolerant line provided that it had been subjected to prior moderate chilling, i.e., acclimation. The cold-sensitive lines performed equally poorly with or without acclimation. To uncover the molecular basis of the attained cold-acclimatability we performed comparative transcriptome profiling of the response of the lines to the cold during acclimation phase by means of microarrays with a statistical and bioinformatic data analysis. Conclusions The analyses indicated three mechanisms likely responsible for the cold-tolerance: acclimation-dependent modification of the photosynthetic apparatus, cell wall properties, and developmental processes. Those conclusions supported the observed acclimation of photosynthesis to severe cold at moderate chilling and were further confirmed by experimentally showing specific modification of cell wall properties and repression of selected miRNA species, general regulators of development, in the cold-tolerant line subjected to cold stress. Electronic supplementary material The online version of this article (doi:10.1186/s12864-016-2453-4) contains supplementary material, which is available to authorized users.

Quantitative Phase Imaging (QPI) provides unique means for the imaging of biological or technical microstructures, merging beneficial features identified with microscopy, interferometry, holography, and numerical computations. This roadmap article reviews several digital holography-based QPI approaches developed by prominent research groups. It also briefly discusses the present and future perspectives of 2D and 3D QPI research based on digital holographic microscopy, holographic tomography, and their applications.

BACKGROUND: Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. METHODS: We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. RESULTS: Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. CONCLUSIONS: Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders. Statistical analyses were carried out on the NL Genetic Cluster Computer (http://www.geneticcluster.org) hosted by SURFsara and the Mount Sinai high performance computing cluster (http://hpc.mssm.edu), which is supported by the Office of Research Infrastructure of the National Institutes of Health (Grant Nos. S10OD018522 and S10OD026880). This work was conducted in part using the resources of the Advanced Computing Center for Research and Education at Vanderbilt University, Nashville, TN. This work was funded by the National Institutes of Health (Grant Nos. R01MH116269 and R01MH121455 [to DMR]), NIGMS of the National Institutes of Health (Grant No. T32GM007347 [to JK]), and the Brain & Behavior Research Foundation (NARSAD Young Investigator Award No. 29551 [to NM]). Office of Research Infrastructure of the National Institutes of Health S10OD018522 S10OD026880 NIH National Institute of General Medical Sciences (NIGMS) T32GM007347 NARSAD 29551 National Institutes of Health (NIH) - USA R01MH116269 R01MH121455 United States Department of Health & Human Services

الملخص: أهداف البحث: يعد فقر الدم المنجلي من أكثر أمراض خضاب الدم المنتشرة في العالم. ومن مضاعفات المرض تكون حصى المرارة وتتفاوت الأعراض المصاحبة لحصى المرارة من كونها صامتة ولا تظهر على المريض أي أعراض، إلى حدوث التهابات المرارة، والقنوات الصفراوية وكذلك البنكرياس. تهدف هذه الدراسة إلى تحديد نسبة حدوث حصوات المرارة لدى الأطفال المصابين بفقر الدم المنجلي في السعودية. طرق البحث: تمت الدراسة عن طريق مراجعة السجلات الطبية لجميع المرضى الذين تتراوح أعمارهم ما بين عامين إلى ثمانية عشر عاما المصابين بفقر الدم المنجلي. ودراسة عوامل الخطورة المرتبطة بتكوين حصوات المرارة. النتائج: أظهرت النتائج حدوث حصوات المرارة بنسبة ٢٧٪ لدى المرضى المصابين بفقر الدم المنجلي عند متوسط عمر سبعة سنوات تقريبا. ومن عوامل الخطورة التي ساهمت في زيادة تكون الحصوات بشكل ملحوظ هي زيادة العمر، وارتفاع نسبة خضاب الدم من النوع ''س'' وزيادة حجم كريات الدم الحمراء. كما لوحظت زيادة نسبة الحصى لدى الذكور عن الاناث، والسعوديين عن غيرهم، ومرضى فقر الدم المنجلي عن فقر الدم المنجلي والبحر المتوسط، لكن هذه الاختلافات لم تكن ذات مدلولات إحصائية. الاستنتاجات: وجدت الدراسة أن نسبة حدوث حصى المرارة عالية لدى الأطفال المصابين بفقر الدم المنجلي. وكانت العلاقة مع العمر وزيادة نسبة خضاب الدم من النوع ''س'' وزيادة حجم كريات الدم الحمراء علاقة ذات دلالة إحصائية. Abstract: Objective: Sickle cell disease is one of the most common inherited hemoglobinopathies in the world. Chronic haemolysis predisposes individuals to the development of bilirubinate cholelithiasis, which can be asymptomatic or can result in cholecystitis, choledocholithiasis, cholangitis, and gallstone pancreatitis. We aimed to determine the prevalence of cholelithiasis and associated gallstone disease among patients with paediatric sickle cell disease in a Saudi hospital. Methods: This retrospective study was conducted among all patients aged between 2 and 18 years. We reviewed the medical records of patients diagnosed with sickle cell anaemia. Mean and standard deviation were calculated for quantitative variables, and the Student t-test was used to compare means. The chi-square test was used to assess those risk factors possibly associated with cholelithiasis. A P-value of ≤0.05 was considered statistically significant. Results: Approximately 75% of participants developed cholelithiasis (27.5%) at a mean age of 6.9 ± 3.4 years. The frequency of cholelithiasis was significantly higher with increasing age (40.8% in participants 12 years and older) and among those with high levels of haemoglobin S (Hb S) and mean corpuscular volume (MCV). Moreover, cholelithiasis was more frequent among males than females, Saudis than non-Saudis, and in those with sickle cell disease than in those with sickle thalassemia. However, these differences were not statistically significant. Conclusion: In this study, the prevalence of cholelithiasis among children with sickle cell anaemia was found to be high. This association was significantly increased with age and high levels of MCV and Hb S. الكلمات المفتاحية: حصى المرارة, فقر الدم المنجلي, Keywords: Cholelithiasis, Gallstones, Sickle cell anaemia