Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Hsa-mir-145 is the top EWS-FLI1-repressed microRNA involved in a positive feedback loop in Ewing's sarcoma

EWS-FLI1 is a chromosome translocation-derived chimeric transcription factor that has a central and rate-limiting role in the pathogenesis of Ewing's sarcoma. Although the EWS-FLI1 transcriptomic signature has been extensively characterized on the mRNA level, information on its impact on non-coding RNA expression is lacking. We have performed a genome-wide analysis of microRNAs affected by RNAi-mediated silencing of EWS-FLI1 in Ewing's sarcoma cell lines, and differentially expressed between primary Ewing's sarcoma and mesenchymal progenitor cells. Here, we report on the identification of hsa-mir-145 as the top EWS-FLI1-repressed microRNA. Upon knockdown of EWS-FLI1, hsa-mir-145 expression dramatically increases in all Ewing's sarcoma cell lines tested. Vice versa, ectopic expression of the microRNA in Ewing's sarcoma cell lines strongly reduced EWS-FLI1 protein, whereas transfection of an anti-mir to hsa-mir-145 increased the EWS-FLI1 levels. Reporter gene assays revealed that this modulation of EWS-FLI1 protein was mediated by the microRNA targeting the FLI1 3'-untranslated region. Mutual regulations of EWS-FLI1 and hsa-mir-145 were mirrored by an inverse correlation between their expression levels in four of the Ewing's sarcoma cell lines tested. Consistent with the role of EWS-FLI1 in Ewing's sarcoma growth regulation, forced hsa-mir-145 expression halted Ewing's sarcoma cell line growth. These results identify feedback regulation between EWS-FLI1 and hsa-mir-145 as an important component of the EWS-FLI1-mediated Ewing's sarcomagenesis that may open a new avenue to future microRNA-mediated therapy of this devastating malignant disease

Reasons for receiving or not receiving HPV vaccination in primary schoolgirls in Tanzania: a case control study.

BACKGROUND: There are few data on factors influencing human papillomavirus (HPV) vaccination uptake in sub-Saharan Africa. We examined the characteristics of receivers and non-receivers of HPV vaccination in Tanzania and identified reasons for not receiving the vaccine. METHODS: We conducted a case control study of HPV vaccine receivers and non-receivers within a phase IV cluster-randomised trial of HPV vaccination in 134 primary schools in Tanzania. Girls who failed to receive vaccine (pupil cases) and their parents/guardians (adult cases) and girls who received dose 1 (pupil controls) of the quadrivalent vaccine (Gardasil™) and their parents/guardians (adult controls) were enrolled from 39 schools in a 1∶1 ratio and interviewed about cervical cancer, HPV vaccine knowledge and reasons why they might have received or not received the vaccine. Conditional logistic regression was used to determine factors independently associated with not receiving HPV vaccine. RESULTS: We interviewed 159 pupil/adult cases and 245 pupil/adult controls. Adult-factors independently associated with a daughter being a case were older age, owning fewer household items, not attending a school meeting about HPV vaccine, and not knowing anyone with cancer. Pupil-factors for being a case included having a non-positive opinion about the school de-worming programme, poor knowledge about the location of the cervix, and not knowing that a vaccine could prevent cervical cancer. Reasons for actively refusing vaccination included concerns about side effects and infertility. Most adult and pupil cases reported that they would accept the HPV vaccine if it were offered again (97% and 93% respectively). CONCLUSIONS: Sensitisation messages, especially targeted at older and poorer parents, knowledge retention and parent meetings are critical for vaccine acceptance in Tanzania. Vaccine side effects and fertility concerns should be addressed prior to a national vaccination program. Parents and pupils who initially decline vaccination should be given an opportunity to reconsider their decision

Nuclear structure with radioactive muonic atoms

Muonic atoms have been used to extract the most accurate nuclear charge radii based on the detection of X-rays from the muonic cascades. Most stable and a few un- stable isotopes have been investigated with muonic atom spectroscopy techniques. A new research project recently started at the Paul Scherrer Institut aims to extend the high- resolution muonic atom spectroscopy for the precise determination of nuclear charge radii and other nuclear structure properties of radioactive isotopes. The challenge to combine the high-energy muon beam with small quantity of stopping mass is being addressed by developing the concept of stopping the muon in a high-density, a high-pressure hydrogen cell and subsequent transfer of the muon to the element of interest. Status and perspectives of the project will be presented.status: Published onlin

A qualitative study of HPV vaccine acceptability among health workers, teachers, parents, female pupils, and religious leaders in northwest Tanzania

Background As human papillomavirus (HPV) vaccines become available in developing countries, acceptability studies can help to better understand potential barriers and facilitators of HPV vaccination and guide immunisation programs. Methods Prior to a cluster-randomised phase IV trial of HPV vaccination delivery strategies in Mwanza Region, Tanzania, qualitative research was conducted to assess attitudes and knowledge about cervical cancer and HPV, and acceptability of and potential barriers to HPV vaccination of Tanzanian primary schoolgirls. Semi-structured interviews (n = 31) and group discussions (n = 12) were conducted with a total of 169 respondents (parents, female pupils, teachers, health workers and religious leaders). Results While participants had heard of cancer in general, most respondents had no knowledge of cervical cancer, HPV, or HPV vaccines. Only health workers had heard of cervical cancer but very few knew its cause or had any awareness about HPV vaccines. After participants were provided with information about cervical cancer and HPV vaccination, the majority stated that they would support HPV vaccination of their daughter to protect them against cervical cancer. Opt-out consent for vaccination was considered acceptable. Most preferred age-based vaccination, saying this would target more girls before sexual debut than class-based vaccination. Potential side effects and infertility concerns were raised by 5/14 of participating male teachers. Discussion Reported acceptability of HPV vaccination amongst parents, teachers and other community members was high in this population. Respondents stressed the need to provide adequate information about the vaccine to parents, that also addresses side effects and infertility concerns

Can we identify patients with high risk of osteoarthritis progression who will respond to treatment? A focus on biomarkers ans frailty

Osteoarthritis (OA), a disease affecting different patient phenotypes, appears as an optimal candidate for personalized healthcare. The aim of the discussions of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) working group was to explore the value of markers of different sources in defining different phenotypes of patients with OA. The ESCEO organized a series of meetings to explore the possibility of identifying patients who would most benefit from treatment for OA, on the basis of recent data and expert opinion. In the first meeting, patient phenotypes were identified according to the number of affected joints, biomechanical factors, and the presence of lesions in the subchondral bone. In the second meeting, summarized in the present article, the working group explored other markers involved in OA. Profiles of patients may be defined according to their level of pain, functional limitation, and presence of coexistent chronic conditions including frailty status. A considerable amount of data suggests that magnetic resonance imaging may also assist in delineating different phenotypes of patients with OA. Among multiple biochemical biomarkers identified, none is sufficiently validated and recognized to identify patients who should be treated. Considerable efforts are also being made to identify genetic and epigenetic factors involved in OA, but results are still limited. The many potential biomarkers that could be used as potential stratifiers are promising, but more research is needed to characterize and qualify the existing biomarkers and to identify new candidates