Radioactive 26Al and massive stars in the Galaxy

Gamma-rays from radioactive 26Al (half life ~7.2 10^5 yr) provide a 'snapshot' view of ongoing nucleosynthesis in the Galaxy. The Galaxy is relatively transparent to such gamma-rays, and emission has been found concentrated along the plane of the Galaxy. This led to the conclusion1 that massive stars throughout the Galaxy dominate the production of 26Al. On the other hand, meteoritic data show locally-produced 26Al, perhaps from spallation reactions in the protosolar disk. Furthermore, prominent gamma-ray emission from the Cygnus region suggests that a substantial fraction of Galactic 26Al could originate in localized star-forming regions. Here we report high spectral resolution measurements of 26Al emission at 1808.65 keV, which demonstrate that the 26Al source regions corotate with the Galaxy, supporting its Galaxy-wide origin. We determine a present-day equilibrium mass of 2.8 (+/-0.8) M_sol of 26Al. We use this to estimate that the frequency of core collapse (i.e. type Ib/c and type II) supernovae to be 1.9(+/- 1.1) events per century.Comment: accepted for publication in Nature, 24 pages including Online Supplements, 11 figures, 1 tabl

What are the living conditions and health status of those who don't report their migration status? a population-based study in Chile

BACKGROUND: Undocumented immigrants are likely to be missing from population databases, making it impossible to identify an accurate sampling frame in migration research. No population-based data has been collected in Chile regarding the living conditions and health status of undocumented immigrants. However, the CASEN survey (Caracterizacion Socio- Economica Nacional) asked about migration status in Chile for the first time in 2006 and provides an opportunity to set the base for future analysis of available migration data. We explored the living conditions and health of self-reported immigrants and respondents who preferred not to report their migration status in this survey. METHODS: Cross-sectional secondary analysis of CASEN survey in Chile in 2006. Outcomes: any disability, illness/accident, hospitalization/surgery, cancer/chronic condition (all binary variables); and the number of medical/emergency attentions received (count variables). Covariates: Demographics (age, sex, marital status, urban/rural, ethnicity), socioeconomic status (education level, employment status and household income), and material standard of living (overcrowding, sanitation, housing quality). Weighted regression models were estimated for each health outcome, crude and adjusted by sets of covariates, in STATA 10.0. RESULTS: About 1% of the total sample reported being immigrants and 0.7% preferred not to report their migration status (Migration Status - Missing Values; MS-MV). The MS-MV lived in more deprived conditions and reported a higher rate of health problems than immigrants. Some gender differences were observed by health status among immigrants and the MS-MV but they were not statistically significant. Regressions indicated that age, sex, SES and material factors consistently affected MS-MVs’ chance of presenting poor health and these patterns were different to those found among immigrants. Great heterogeneity in both the MS-MV and the immigrants, as indicated by wide confidence intervals, prevented the identification of other significantly associated covariates. CONCLUSION: This is the first study to look at the living conditions and health of those that preferred not to respond their migration status in Chile. Respondents that do not report their migration status are vulnerable to poor health and may represent undocumented immigrants. Surveys that fail to identify these people are likely to misrepresent the experiences of immigrants and further quantitative and qualitative research is urgently required

FAK acts as a suppressor of RTK-MAP kinase signalling in Drosophila melanogaster epithelia and human cancer cells

Receptor Tyrosine Kinases (RTKs) and Focal Adhesion Kinase (FAK) regulate multiple signalling pathways, including mitogen-activated protein (MAP) kinase pathway. FAK interacts with several RTKs but little is known about how FAK regulates their downstream signalling. Here we investigated how FAK regulates signalling resulting from the overexpression of the RTKs RET and EGFR. FAK suppressed RTKs signalling in Drosophila melanogaster epithelia by impairing MAPK pathway. This regulation was also observed in MDA-MB-231 human breast cancer cells, suggesting it is a conserved phenomenon in humans. Mechanistically, FAK reduced receptor recycling into the plasma membrane, which resulted in lower MAPK activation. Conversely, increasing the membrane pool of the receptor increased MAPK pathway signalling. FAK is widely considered as a therapeutic target in cancer biology; however, it also has tumour suppressor properties in some contexts. Therefore, the FAK-mediated negative regulation of RTK/MAPK signalling described here may have potential implications in the designing of therapy strategies for RTK-driven tumours

Assessing the Quality of Reports about Randomized Controlled Trials of Acupuncture Treatment on Diabetic Peripheral Neuropathy

BACKGROUND: To evaluate the reports' qualities which are about randomized controlled trials (RCTs) of acupuncture treatment on Diabetic Peripheral Neuropathy (DPN). METHODOLOGY/PRINCIPAL FINDINGS: Eight databases including The Cochrane Library(1993-Sept.,2011), PubMed (1980-Sept., 2011), EMbase (1980-Sept.,2011), SCI Expanded (1998-Sept.,2011), China Biomedicine Database Disc (CBMdisc, 1978-Sept., 2011), China National Knowledge Infrastructure (CNKI, 1979-Sept., 2011 ), VIP (a full text issues database of China, 1989-Sept., 2011), Wan Fang (another full text issues database of China 1998-Sept., 2011) were searched systematically. Hand search for further references was conducted. Language was limited to Chinese and English. We identified 75 RCTs that used acupuncture as an intervention and assessed the quality of these reports with the Consolidated Standards for Reporting of Trials statement 2010 (CONSORT2010) and Standards for Reporting Interventions Controlled Trials of Acupuncture 2010(STRICTA2010). 24 articles (32%) applied the method of random allocation of sequences. No article gave the description of the mechanism of allocation concealment, no experiment applied the method of blinding. Only one article (1.47%) could be identified directly from its title as about the Randomized Controlled Trials, and only 4 articles gave description of the experimental design. No article mentioned the number of cases lost or eliminated. During one experiment, acupuncture syncope led to temporal interruption of the therapy. Two articles (2.94%) recorded the number of needles, and 8 articles (11.76%) mentioned the depth of needle insertion. None of articles reported the base of calculation of sample size, or has any analysis about the metaphase of an experiment or an explanation of its interruption. One (1.47%) mentioned intentional analysis (ITT). CONCLUSIONS/SIGNIFICANCE: The quality of the reports on RCTs of acupuncture for Diabetic Peripheral Neuropathy is moderate to low. The CONSORT2010 and STRICTA2010 should be used to standardize the reporting of RCTs of acupuncture in future

Alteration of gene expression profiles during mycoplasma-induced malignant cell transformation

BACKGROUND: Mycoplasmas are the smallest microorganisms capable of self-replication. Our previous studies show that some mycoplasmas are able to induce malignant transformation of host mammalian cells. This malignant transformation is a multistage process with the early infection, reversible and irreversible stages, and similar to human tumor development in nature. The purpose of this study is to explore mechanisms for this malignant transformation. METHODS: To better understand mechanisms for this unique process, we examined gene expression profiles of C3H cells at different stages of the mycoplasma-induced transformation using cDNA microarray technology. A total of 1185 genes involved in oncogenesis, apoptosis, cell growth, cell-cycle regulation, DNA repair, etc. were examined. Differences in the expression of these genes were compared and analyzed using the computer software AtlasImage. RESULTS: Among 1185 genes screened, 135 had aberrant expression at the early infection stage, 252 at the reversible stage and 184 at the irreversible stage. At the early infection stage, genes with increased expression (92 genes) were twice more than those with decreased expression (42 genes). The global gene expression at the reversible stage appeared to be more volatile than that at any other stages but still resembled the profile at the early infection stage. The expression profile at the irreversible stage shows a unique pattern of a wide range of expression levels and an increased number of expressing genes, especially the cancer-related genes. Oncogenes and tumor suppressors are a group of molecules that showed significant changes in expression during the transformation. The majority of these changes occurred in the reversible and irreversible stages. A prolonged infection by mycoplasmas lead to the expression of more cancer related genes at the irreversible stage. CONCLUSION: The results indicate that the expression profiles correspond with the phenotypic features of the cells in the mycoplasma induced transformation process. The early mycoplasma infection stage shares a common phenomenon with many other acute infections, genes with increased expression significantly outnumbering those with decreased expression. The reversible stage is a transition stage between benignancy and malignancy at the molecular level. Aberrant expression of oncogenes and tumor repressors plays a key role in mycoplasma-induced malignant transformation

Host Responses to Intestinal Microbial Antigens in Gluten-Sensitive Mice

BACKGROUND AND AIMS: Excessive uptake of commensal bacterial antigens through a permeable intestinal barrier may influence host responses to specific antigen in a genetically predisposed host. The aim of this study was to investigate whether intestinal barrier dysfunction induced by indomethacin treatment affects the host response to intestinal microbiota in gluten-sensitized HLA-DQ8/HCD4 mice. METHODOLOGY/PRINCIPAL FINDINGS: HLA-DQ8/HCD4 mice were sensitized with gluten, and gavaged with indomethacin plus gluten. Intestinal permeability was assessed by Ussing chamber; epithelial cell (EC) ultra-structure by electron microscopy; RNA expression of genes coding for junctional proteins by Q-real-time PCR; immune response by in-vitro antigen-specific T-cell proliferation and cytokine analysis by cytometric bead array; intestinal microbiota by fluorescence in situ hybridization and analysis of systemic antibodies against intestinal microbiota by surface staining of live bacteria with serum followed by FACS analysis. Indomethacin led to a more pronounced increase in intestinal permeability in gluten-sensitized mice. These changes were accompanied by severe EC damage, decreased E-cadherin RNA level, elevated IFN-gamma in splenocyte culture supernatant, and production of significant IgM antibody against intestinal microbiota. CONCLUSION: Indomethacin potentiates barrier dysfunction and EC injury induced by gluten, affects systemic IFN-gamma production and the host response to intestinal microbiota antigens in HLA-DQ8/HCD4 mice. The results suggest that environmental factors that alter the intestinal barrier may predispose individuals to an increased susceptibility to gluten through a bystander immune activation to intestinal microbiota

Metabolite profiles of medulloblastoma for rapid and non-invasive detection of molecular disease groups

\ua9 2024 The AuthorsBackground: The malignant childhood brain tumour, medulloblastoma, is classified clinically into molecular groups which guide therapy. DNA-methylation profiling is the current classification ‘gold-standard’, typically delivered 3–4 weeks post-surgery. Pre-surgery non-invasive diagnostics thus offer significant potential to improve early diagnosis and clinical management. Here, we determine tumour metabolite profiles of the four medulloblastoma groups, assess their diagnostic utility using tumour tissue and potential for non-invasive diagnosis using in vivo magnetic resonance spectroscopy (MRS). Methods: Metabolite profiles were acquired by high-resolution magic-angle spinning NMR spectroscopy (MAS) from 86 medulloblastomas (from 59 male and 27 female patients), previously classified by DNA-methylation array (WNT (n = 9), SHH (n = 22), Group3 (n = 21), Group4 (n = 34)); RNA-seq data was available for sixty. Unsupervised class-discovery was performed and a support vector machine (SVM) constructed to assess diagnostic performance. The SVM classifier was adapted to use only metabolites (n = 10) routinely quantified from in vivo MRS data, and re-tested. Glutamate was assessed as a predictor of overall survival. Findings: Group-specific metabolite profiles were identified; tumours clustered with good concordance to their reference molecular group (93%). GABA was only detected in WNT, taurine was low in SHH and lipids were high in Group3. The tissue-based metabolite SVM classifier had a cross-validated accuracy of 89% (100% for WNT) and, adapted to use metabolites routinely quantified in vivo, gave a combined classification accuracy of 90% for SHH, Group3 and Group4. Glutamate predicted survival after incorporating known risk-factors (HR = 3.39, 95% CI 1.4–8.1, p = 0.025). Interpretation: Tissue metabolite profiles characterise medulloblastoma molecular groups. Their combination with machine learning can aid rapid diagnosis from tissue and potentially in vivo. Specific metabolites provide important information; GABA identifying WNT and glutamate conferring poor prognosis. Funding: Children with Cancer UK, Cancer Research UK, Children\u27s Cancer North and a Newcastle University PhD studentship

Feasibility and acceptability of point of care HIV testing in community outreach and GUM drop-in services in the North West of England: A programmatic evaluation

Background: In Liverpool, injecting drug users (IDUs), men-who-have-sex-with-men (MSM) and UK Africans experience a disproportionate burden of HIV, yet services do not reach out to these groups and late presentations continue. We set out to: increase testing uptake in targeted marginalized groups through a community and genitourinary medicine (GUM)-based point of care testing (POCT) programme; and conduct a process evaluation to examine service provider inputs and document service user perceptions of the programme. Methods: Mixed quantitative, qualitative and process evaluation methods were used. Service providers were trained to use fourth generation rapid antibody/antigen HIV tests. Existing outreach services incorporated POCT into routine practice. Clients completed a semi-structured questionnaire and focus group discussions (FGDs) were held with service providers. Results: Between September 2009 and June 2010, 953 individuals underwent POCT (GUM: 556 [59%]; communitybased sites: 397 [42%]). Participants in the community were more likely to be male (p = 0.028), older (p < 0.001), of UK African origin (p < 0.001) and IDUs (p < 0.001) than participants from the GUM clinic. Seventeen new HIV diagnoses were confirmed (prevalence = 1.8%), 16 of whom were in risk exposure categories (prevalence: 16/517, 3.1%). Questionnaires and FGDs showed that clients and service providers were supportive of POCT, highlighting benefits of reaching out to marginalised communities and incorporating HIV prevention messages. Conclusions: Community and GUM clinic-based POCT for HIV was feasible and acceptable to clients and service providers in a low prevalence setting. It successfully reached target groups, many of whom would not have otherwise tested. We recommend POCT be considered among strategies to increase the uptake of HIV testing among groups who are currently underserved