Large perturbations in CO2 flux and subsequent chemosynthesis are induced in agricultural soil by the addition of elemental sulfur

The microbial contribution to soil organic matter has been shown to be much larger than previously thought and thus it plays a major role in carbon cycling. Among soil microorganisms, chemoautotrophs can fix CO2 without sunlight and can glean energy through the oxidation of reduced elements such as sulfur. Here we show that the addition of sulfur to soil results in an initial surge in production of CO2 through microbial respiration, followed by an order of magnitude increase in the capture of carbon from the atmosphere as elemental sulfur is oxidised to sulfate. Thiobacillus spp., take advantage of specific conditions to become the dominant chemoautotrophic group that consumes CO2. We discern the direct incorporation of atmospheric carbon into soil carbohydrate, protein and aliphatic compounds and differentiate these from existing biomass. These results suggest that chemoautotrophs can play a large role in carbon cycling and that this carbon is heavily influenced by land management practises

Population Selection and Sequencing of Caenorhabditis elegans Wild Isolates Identifies a Region on Chromosome III Affecting Starvation Resistance

To understand the genetic basis of complex traits, it is important to be able to efficiently phenotype many genetically distinct individuals. In the nematode Caenorhabditis elegans, individuals have been isolated from diverse populations around the globe and whole-genome sequenced. As a result, hundreds of wild strains with known genome sequences can be used for genome-wide association studies (GWAS). However, phenotypic analysis of these strains can be laborious, particularly for quantitative traits requiring multiple measurements per strain. Starvation resistance is likely a fitness-proximal trait for nematodes, and it is related to metabolic disease risk in humans. However, natural variation in C. elegans starvation resistance has not been systematically characterized, and precise measurement of the trait is time-intensive. Here, we developed a population-selection-and-sequencing-based approach to phenotype starvation resistance in a pool of 96 wild strains. We used restriction site-associated DNA sequencing (RAD-seq) to infer the frequency of each strain among survivors in a mixed culture over time during starvation. We used manual starvation survival assays to validate the trait data, confirming that strains that increased in frequency over time are starvation-resistant relative to strains that decreased in frequency. Further, we found that variation in starvation resistance is significantly associated with variation at a region on chromosome III. Using a near-isogenic line (NIL), we showed the importance of this genomic interval for starvation resistance. This study demonstrates the feasibility of using population selection and sequencing in an animal model for phenotypic analysis of quantitative traits, documents natural variation of starvation resistance in C. elegans, and identifies a genomic region that contributes to such variation

Significance of herpesvirus immediate early gene expression in cellular immunity to cytomegalovirus infection

Interstitial pneumonia linked with reactivation of latent human cytomegalovirus due to iatrogenic immunosuppression can be a serious complication of bone marrow transplantation therapy of aplastic anaemia and acute leukaemia1. Cellular immunity plays a critical role in the immune surveillance of inapparent cytomegalovirus infections in man and the mouse1−7. The molecular basis of latency, however, and the interaction between latently or recurrently infected cells and the immune system of the host are poorfy understood. We have detected a so far unknown antigen in the mouse model. This antigen is found in infected cells in association with the expression of the herpesvirus 'immediate early' genes and is recognized by cytolytic T lymphocytes (CTL)8. We now demonstrate that an unexpectedly high proportion of the CTL precursors generated in vivo during acute murine cytomegalovirus infection are specific for cells that selectively synthesize immediate early proteins, indicating an immunodominant role of viral non-structural proteins

Women’s experiences of receiving care for pelvic organ prolapse: a qualitative study

Background Pelvic organ prolapse is a common urogenital condition affecting 41–50% of women over the age of 40. To achieve early diagnosis and appropriate treatment, it is important that care is sensitive to and meets women’s needs, throughout their patient journey. This study explored women’s experiences of seeking diagnosis and treatment for prolapse and their needs and priorities for improving person-centred care. Methods Twenty-two women receiving prolapse care through urogynaecology services across three purposefully selected NHS UK sites took part in three focus groups and four telephone interviews. A topic guide facilitated discussions about women’s experiences of prolapse, diagnosis, treatment, follow-up, interactions with healthcare professionals, overall service delivery, and ideals for future services to meet their needs. Data were analysed thematically. Results Three themes emerged relating to women’s experiences of a) Evaluating what is normal b) Hobson’s choice of treatment decisions, and c) The trial and error of treatment and technique. Women often delayed seeking help for their symptoms due to lack of awareness, embarrassment and stigma. When presented to GPs, their symptoms were often dismissed and unaddressed until they became more severe. Women reported receiving little or no choice in treatment decisions. Choices were often influenced by health professionals’ preferences which were subtly reflected through the framing of the offer. Women’s embodied knowledge of their condition and treatment was largely unheeded, resulting in decisions that were inconsistent with women’s preferences and needs. Physiotherapy based interventions were reported as helping women regain control over their symptoms and life. A need for greater awareness of prolapse and physiotherapy interventions among women, GPs and consultants was identified alongside greater focus on prevention, early diagnosis and regular follow-up. Greater choice and involvement in treatment decision making was desired. Conclusions As prolapse treatment options expand to include more conservative choices, greater awareness and education is needed among women and professionals about these as a first line treatment and preventive measure, alongside a multi-professional team approach to treatment decision making. Women presenting with prolapse symptoms need to be listened to by the health care team, offered better information about treatment choices, and supported to make a decision that is right for them

Shallow water methane-derived authigenic carbonate mounds at the Codling Fault Zone, western Irish Sea

Methane-derived authigenic carbonate (MDAC) mound features at the Codling Fault Zone (CFZ), located in shallow waters (50–120 m) of the western Irish Sea were investigated and provide a comparison to deep sea MDAC settings. Carbonates consisted of aragonite as the major mineral phase, with δ13C depletion to −50‰ and δ18O enrichment to ~ 2‰. These isotope signatures, together with the co-precipitation of framboidal pyrite confirm that anaerobic oxidation of methane (AOM) is an important process mediating methane release to thewater column and the atmosphere in this region. 18O-enrichment could be a result ofMDAC precipitation with seawater in colder than present day conditions, or precipitation with 18O-enriched water transported from deep petroleum sources. The 13C depletion of bulk carbonate and sampled gas(−70‰) suggests a biogenic source, but significant mixing of thermogenic gas and depletion of the original isotope signature cannot be ruled out. Active seepage was recorded from one mound and together with extensive areas of reduced sediment, confirms that seepage is ongoing. The mounds appear to be composed of stacked pavements that are largely covered by sand and extensively eroded. The CFZ mounds are colonized by abundant Sabellaria polychaetes and possible Nemertesia hydroids, which benefit indirectly from available hard substrate. In contrast to deep sea MDAC settings where seep-related macrofauna are commonly reported, seep-specialist fauna appear to be lacking at the CFZ. In addition, unlike MDAC in deep waters where organic carbon input from photosynthesis is limited, lipid biomarkers and isotope signatures related to marine planktonic production (e.g. sterols, alkanols) were most abundant. Evidence for microbes involved in AOM was limited from samples taken; possibly due to this dilution effect from organic matter derived from the photic zone, and will require further investigation

Tubulin binding cofactor C (TBCC) suppresses tumor growth and enhances chemosensitivity in human breast cancer cells

<p>Abstract</p> <p>Background</p> <p>Microtubules are considered major therapeutic targets in patients with breast cancer. In spite of their essential role in biological functions including cell motility, cell division and intracellular transport, microtubules have not yet been considered as critical actors influencing tumor cell aggressivity. To evaluate the impact of microtubule mass and dynamics on the phenotype and sensitivity of breast cancer cells, we have targeted tubulin binding cofactor C (TBCC), a crucial protein for the proper folding of α and β tubulins into polymerization-competent tubulin heterodimers.</p> <p>Methods</p> <p>We developed variants of human breast cancer cells with increased content of TBCC. Analysis of proliferation, cell cycle distribution and mitotic durations were assayed to investigate the influence of TBCC on the cell phenotype. <it>In vivo </it>growth of tumors was monitored in mice xenografted with breast cancer cells. The microtubule dynamics and the different fractions of tubulins were studied by time-lapse microscopy and lysate fractionation, respectively. <it>In vitro </it>sensitivity to antimicrotubule agents was studied by flow cytometry. <it>In vivo </it>chemosensitivity was assayed by treatment of mice implanted with tumor cells.</p> <p>Results</p> <p>TBCC overexpression influenced tubulin fraction distribution, with higher content of nonpolymerizable tubulins and lower content of polymerizable dimers and microtubules. Microtubule dynamicity was reduced in cells overexpressing TBCC. Cell cycle distribution was altered in cells containing larger amounts of TBCC with higher percentage of cells in G2-M phase and lower percentage in S-phase, along with slower passage into mitosis. While increased content of TBCC had little effect on cell proliferation <it>in vitro</it>, we observed a significant delay in tumor growth with respect to controls when TBCC overexpressing cells were implanted as xenografts <it>in vivo</it>. TBCC overexpressing variants displayed enhanced sensitivity to antimicrotubule agents both <it>in vitro </it>and in xenografts.</p> <p>Conclusion</p> <p>These results underline the essential role of fine tuned regulation of tubulin content in tumor cells and the major impact of dysregulation of tubulin dimer content on tumor cell phenotype and response to chemotherapy. A better understanding of how the microtubule cytoskeleton is dysregulated in cancer cells would greatly contribute to a better understanding of tumor cell biology and characterisation of resistant phenotypes.</p

Dengue Virus Inhibits Immune Responses in Aedes aegypti Cells

The ability of many viruses to manipulate the host antiviral immune response often results in complex host-pathogen interactions. In order to study the interaction of dengue virus (DENV) with the Aedes aegypti immune response, we have characterized the DENV infection-responsive transcriptome of the immune-competent A. aegypti cell line Aag2. As in mosquitoes, DENV infection transcriptionally activated the cell line Toll pathway and a variety of cellular physiological systems. Most notably, however, DENV infection down-regulated the expression levels of numerous immune signaling molecules and antimicrobial peptides (AMPs). Functional assays showed that transcriptional induction of AMPs from the Toll and IMD pathways in response to bacterial challenge is impaired in DENV-infected cells. In addition, Escherichia coli, a Gram-negative bacteria species, grew better when co-cultured with DENV-infected cells than with uninfected cells, suggesting a decreased production of AMPs from the IMD pathway in virus-infected cells. Pre-stimulation of the cell line with Gram-positive bacteria prior to DENV infection had no effect on DENV titers, while pre-stimulation with Gram-negative bacteria resulted in an increase in DENV titers. These results indicate that DENV is capable of actively suppressing immune responses in the cells it infects, a phenomenon that may have important consequences for virus transmission and insect physiology

Might Depression, Psychosocial Adversity, and Limited Social Assets Explain Vulnerability to and Resistance against Violent Radicalisation?

BACKGROUND: This study tests whether depression, psychosocial adversity, and limited social assets offer protection or suggest vulnerability to the process of radicalisation. METHODS: A population sample of 608 men and women of Pakistani or Bangladeshi origin, of Muslim heritage, and aged 18-45 were recruited by quota sampling. Radicalisation was measured by 16 questions asking about sympathies for violent protest and terrorism. Cluster analysis of the 16 items generated three groups: most sympathetic (or most vulnerable), most condemning (most resistant), and a large intermediary group that acted as a reference group. Associations were calculated with depression (PHQ9), anxiety (GAD7), poor health, and psychosocial adversity (adverse life events, perceived discrimination, unemployment). We also investigated protective factors such as the number social contacts, social capital (trust, satisfaction, feeling safe), political engagement and religiosity. RESULTS: Those showing the most sympathy for violent protest and terrorism were more likely to report depression (PHQ9 score of 5 or more; RR = 5.43, 1.35 to 21.84) and to report religion to be important (less often said religion was fairly rather than very important; RR = 0.08, 0.01 to 0.48). Resistance to radicalisation measured by condemnation of violent protest and terrorism was associated with larger number of social contacts (per contact: RR = 1.52, 1.26 to 1.83), less social capital (RR = 0.63, 0.50 to 0.80), unavailability for work due to housekeeping or disability (RR = 8.81, 1.06 to 37.46), and not being born in the UK (RR = 0.22, 0.08 to 0.65). CONCLUSIONS: Vulnerability to radicalisation is characterised by depression but resistance to radicalisation shows a different profile of health and psychosocial variables. The paradoxical role of social capital warrants further investigation

Efficacy of conservative treatment regimes for hip osteoarthritis - Evaluation of the therapeutic exercise regime "Hip School": A protocol for a randomised, controlled trial

<p>Abstract</p> <p>Background</p> <p>Hip osteoarthritis (hip OA) is a disease with a major impact on both national economy and the patients themselves. Patients suffer from pain and functional impairment in activities of daily life which are associated with a decrease in quality of life. Conservative therapeutic interventions such as physical exercises aim at reducing pain and increasing function and health-related quality of life. However, there is only silver level evidence for efficacy of land-based physical exercise in the treatment of hip OA. The purpose of this randomized controlled trial is to determine whether the specific 12-week exercise regime "Hip School" can decrease bodily pain and improve physical function and life quality in subjects with hip osteoarthritis.</p> <p>Methods/Design</p> <p>217 participants with hip OA, confirmed using the clinical score of the American College of Rheumatology, are recruited from the community and randomly allocated to one of the following groups: (1) exercise regime "Hip School", n = 70; (2) Non-intervention control group, n = 70; (3) "Sham" ultrasound group, n = 70; (4) Ultrasound group, n = 7. The exercise regime combines group exercises (1/week, 60-90') and home-based exercises (2/week, 30-40'). Sham ultrasound and ultrasound are given once a week, 15'. Measures are taken directly prior to (M1) and after (M2) the 12-week intervention period. Two follow-ups are conducted by phone 16 and 40 weeks after the intervention period. The primary outcome measure is the change in the subscale <it>bodily pain </it>of the SF36 from M1 to M2. Secondary outcomes comprise the WOMAC score, SF36, isometric strength of hip muscles, spatial-temporal and discrete measures derived from clinical gait analysis, and the length of the centre of force path in different standing tasks. An intension-to-treat analysis will be performed using multivariate statistics (group × time).</p> <p>Discussion</p> <p>Results from this trial will contribute to the evidence regarding the effect of a hip-specific exercise regime on physical function, pain, and health-related quality of life in patients with hip osteoarthritis.</p> <p>Trial registration</p> <p>German Clinical Trial Register DRKS00000651.</p

Lack of Association between Y-Chromosomal Haplogroups and Prostate Cancer in the Korean Population

The Y chromosome has recently been suggested to have an association with prostate cancer risk in human populations. Since this chromosome is haploid and lacks recombination over most of its length, haplotypes constructed from binary markers throughout the chromosome can be used for association studies. To assess the possible Y-chromosomal contribution to prostate cancer risk, we have therefore analyzed 14 Y-chromosomal binary markers in 106 prostate cancer cases and 110 controls from the Korean population. In contrast to previous findings in the Japanese population, no statistically significant difference in the distribution of Y-chromosomal haplogroup frequencies was observed between the case and control groups of Koreans. Thus, our data imply that the previously reported associations between Y-chromosomal lineages and a predisposition to, or protection against, prostate cancer might be explained by statistical fluctuations, or by genetic effects that are seen only in some environments