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AbstractWe have recently described a class of 756 genes that are widely expressed in cancer, while normally restricted to adult germ cells, referred to as germ cell cancer genes (GC-genes). We hypothesized that carcinogenesis involves reactivation of biomolecular processes and regulatory mechanisms that, under normal circumstances, are restricted to germline development. This would imply that cancer cells share gene expression profiles with primordial germ cells (PGCs). We therefore compared the transcriptomes of human PGCs (hPGCs) and PGC-like cells (PGCLCs) with 17 382 samples from 54 healthy somatic tissues (GTEx) and 11 003 samples from 33 tumor types (TCGA), and identified 672 GC-genes, expanding the known GC-gene pool by 387 genes (51%). Because GC-genes specific to the embryonic germline are not expressed in any adult tissue, targeting these in cancer treatment may result in fewer side effects than targeting conventional cancer/testis (CT) or GC-genes and may preserve fertility. We anticipate that our extended GC-dataset enables improved understanding of tumor development and may provide multiple novel targets for cancer treatment development.

Background:\ud Campylobacter jejuni is the most common bacterial cause of human infectious intestinal disease.\ud \ud Methods:\ud We genome sequenced 601 human C. jejuni isolates, obtained from two large prospective studies of infectious intestinal disease (IID1 [isolates from 1993–1996; n = 293] and IID2 [isolates from 2008–2009; n = 93]), the INTEGRATE project [isolates from 2016–2017; n = 52] and the ENIGMA project [isolates from 2017; n = 163].\ud \ud Results:\ud There was a significant increase in the prevalence of the T86I mutation conferring resistance to fluoroquinolone between each of the three later studies (IID2, INTEGRATE and ENIGMA) and IID1. Although the distribution of major multilocus sequence types (STs) was similar between the studies, there were changes in both the abundance of minority STs associated with the T86I mutation, and the abundance of clones within single STs associated with the T86I mutation.\ud \ud Discussion:\ud Four population-based studies of community diarrhoea over a 25 year period revealed an increase over time in the prevalence of the T86I amongst isolates of C. jejuni associated with human gastrointestinal disease in the UK. Although associated with many STs, much of the increase is due to the expansion of clones associated with the resistance mutation.

Background Active travel (walking or cycling for transport) is associated with favourable health outcomes in adults. However, little is known about the concurrent patterns of health behaviour associated with active travel. We used compositional data analysis to explore differences in how people doing some active travel used their time compared to those doing no active travel, incorporating physical activity, sedentary behaviour and sleep. Methods We analysed cross-sectional data from the 2014/15 United Kingdom Harmonised European Time Use Survey. Participants recorded two diary days of activity, and we randomly selected one day from participants aged 16 years or over. Activities were categorised into six mutually exclusive sets, accounting for the entire 24 h: (1) sleep; (2) leisure moderate to vigorous physical activity (MVPA); (3) leisure sedentary screen time; (4) non-discretionary time (work, study, chores and caring duties); (5) travel and (6) other. This mixture of activities was defined as a time-use composition. A binary variable was created indicating whether participants reported any active travel on their selected diary day. We used compositional multivariate analysis of variance (MANOVA) to test whether mean time-use composition differed between individuals reporting some active travel and those reporting no active travel, adjusted for covariates. We then used adjusted linear regression models and bootstrap confidence intervals to identify which of the six activity sets differed between groups. Results 6143 participants (mean age 48 years; 53% female) provided a valid diary day. There was a statistically significant difference in time-use composition between those reporting some active travel and those reporting no active travel. Those undertaking active travel reported a relatively greater amount of time in leisure MVPA and travel, and a relatively lower amount of time in leisure sedentary screen time and sleep. Conclusions Compared to those not undertaking active travel, those who did active travel reported 11 min more in leisure MVPA and 18 min less in screen time per day, and reported lower sleep. From a health perspective, higher MVPA and lower screen time is favourable, but the pattern of sleep is more complex. Overall, active travel was associated with a broadly health-promoting composition of time across multiple behavioural domains, which supports the public health case for active travel. Electronic supplementary material The online version of this article (10.1186/s12966-018-0662-8) contains supplementary material, which is available to authorized users.

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 Despite its contribution to global disease burden, diarrhoeal disease is still a relatively neglected area for research funding, especially in low-income country settings. The SNOWS consortium (Scientists Networked for Outcomes from Water and Sanitation) is funded by the Wellcome Trust under an initiative to build the necessary research skills in Africa. This paper focuses on the research training needs of the consortium as identified during the first three years of the project. Methods We reviewed the reports of two needs assessments. The first was a detailed needs assessment led by one northern partner, with follow-up visits which included reciprocal representation from the African universities. The second assessment, led by another northern partner, focused primarily on training needs. The reports from both needs assessments were read and stated needs were extracted and summarised. Results Key common issues identified in both assessments were supervisory skills, applications for external research funding, research management, and writing for publication in the peer-reviewed scientific literature. The bureaucratisation of university processes and inconsistencies through administration processes also caused problems. The lack of specialist laboratory equipment presented difficulties, particularly of inaccessibility through a lack of skilled staff for operation and maintenance, and of a budget provision for repairs and running costs. The lack of taught PhD modules and of research training methods also caused problems. Institutionally, there were often no mechanisms for identifying funding opportunities. On the other hand, grantees were often unable to understand or comply with the funders’ financial and reporting requirements and were not supported by their institution. Skills in staff recruitment, retention, and performance were poor, as were performance in proposal and paper writing. The requirements for ethical clearance were often not known and governance issues not understood, particularly those required by funders. Conclusions SNOWS believes that working with African universities to develop networks that support African-led research driven by the local context is an effective approach to develop and retain research skills needed to change policy and practice in water, sanitation, and hygiene in Africa. Electronic supplementary material The online version of this article (doi:10.1186/1478-4505-12-68) contains supplementary material, which is available to authorized users.

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.