Identification of Campylobacter jejuni genes contributing to acid adaptation by transcriptional profiling and genome-wide mutagenesis

In order to cause disease, the food- and waterborne pathogen Campylobacter jejuni must face the extreme acidity of the host stomach as well as cope with pH fluctuations in the intestine. In the present study, C. jejuni NCTC 11168 was grown under mildly acidic conditions mimicking those encountered in the intestine. The resulting transcriptional profiles revealed how this bacterium fine-tunes gene expression in response to acid stress. This adaptation involves the differential expression of respiratory pathways, the induction of genes for phosphate transport, and the repression of energy generation and intermediary metabolism genes. We also generated and screened a transposon-based mutant library to identify genes required for wild-type levels of growth under mildly acidic conditions. This screen highlighted the important role played by cell surface components (flagella, the outer membrane, capsular polysaccharides, and lipooligosaccharides) in the acid stress response of C. jejuni. Our data also revealed that a limited correlation exists between genes required for growth under acidic conditions and genes differentially expressed in response to acid. To gain a comprehensive picture of the acid stress response of C. jejuni, we merged transcriptional profiles obtained from acid-adapted cells and cells subjected to acid shock. Genes encoding the transcriptional regulator PerR and putative oxidoreductase subunits Cj0414 and Cj0415 were among the few up-regulated under both acid stress conditions. As a Cj0415 mutant was acid sensitive, it is likely that these genes are crucial to the acid stress response of C. jejuni and consequently are important for host colonization.Peer reviewedVeterinary Pathobiolog

Examining sustainability in a hospital setting: Case of smoking cessation

<p>Abstract</p> <p>Background</p> <p>The Ottawa Model of Smoking Cessation (OMSC) is a hospital-based smoking cessation program that is expanding across Canada. While the short-term effectiveness of hospital cessation programs has been documented, less is known about long-term sustainability. The purpose of this exploratory study was to understand how hospitals using the OMSC were addressing sustainability and determine if there were critical factors or issues that should be addressed as the program expanded.</p> <p>Methods</p> <p>Six hospitals that differed on OMSC program activities (identify and document smokers, advise quitting, provide medication, and offer follow-up) were intentionally selected, and two key informants per hospital were interviewed using a semi-structured interview guide. Key informants were asked to reflect on the initial decision to implement the OMSC, the current implementation process, and perceived sustainability of the program. Qualitative analysis of the interview transcripts was conducted and themes related to problem definition, stakeholder influence, and program features emerged.</p> <p>Results</p> <p>Sustainability was operationalized as higher performance of OMSC activities than at baseline. Factors identified in the literature as important for sustainability, such as program design, differences in implementation, organizational characteristics, and the community environment did not explain differences in program sustainability. Instead, key informants identified factors that reflected the interaction between how the health problem was defined by stakeholders, how priorities and concerns were addressed, features of the program itself, and fit within the hospital context and resources as being influential to the sustainability of the program.</p> <p>Conclusions</p> <p>Applying a sustainability model to a hospital smoking cessation program allowed for an examination of how decisions made during implementation may impact sustainability. Examining these factors during implementation may provide insight into issues affecting program sustainability, and foster development of a sustainability plan. Based on this study, we suggest that sustainability plans should focus on enhancing interactions between the health problem, program features, and stakeholder influence.</p

Midgut microbiota of the malaria mosquito vector Anopheles gambiae and Interactions with plasmodium falciparum Infection

The susceptibility of Anopheles mosquitoes to Plasmodium infections relies on complex interactions between the insect vector and the malaria parasite. A number of studies have shown that the mosquito innate immune responses play an important role in controlling the malaria infection and that the strength of parasite clearance is under genetic control, but little is known about the influence of environmental factors on the transmission success. We present here evidence that the composition of the vector gut microbiota is one of the major components that determine the outcome of mosquito infections. A. gambiae mosquitoes collected in natural breeding sites from Cameroon were experimentally challenged with a wild P. falciparum isolate, and their gut bacterial content was submitted for pyrosequencing analysis. The meta-taxogenomic approach revealed a broader richness of the midgut bacterial flora than previously described. Unexpectedly, the majority of bacterial species were found in only a small proportion of mosquitoes, and only 20 genera were shared by 80% of individuals. We show that observed differences in gut bacterial flora of adult mosquitoes is a result of breeding in distinct sites, suggesting that the native aquatic source where larvae were grown determines the composition of the midgut microbiota. Importantly, the abundance of Enterobacteriaceae in the mosquito midgut correlates significantly with the Plasmodium infection status. This striking relationship highlights the role of natural gut environment in parasite transmission. Deciphering microbe-pathogen interactions offers new perspectives to control disease transmission.Institut de Recherche pour le Developpement (IRD); French Agence Nationale pour la Recherche [ANR-11-BSV7-009-01]; European Community [242095, 223601]info:eu-repo/semantics/publishedVersio

Protocol for stage 1 of the GaP study (Genetic testing acceptability for Paget's disease of bone): an interview study about genetic testing and preventive treatment: would relatives of people with Paget's disease want testing and treatment if they were available?

BACKGROUND: Paget's disease of bone (PDB) is characterised by focal increases in bone turnover, affecting one or more bones throughout the skeleton. This disrupts normal bone architecture and causes pain, deformity, deafness, osteoarthritis, and fractures. Genetic factors are recognised to play a role in PDB and it is now possible to carry out genetic tests for research. In view of this, it is timely to investigate the clinical potential for a programme of genetic testing and preventative treatment for people who have a family history of PDB, to prevent or delay the development of PDB. Evidence from non-genetic conditions, that have effective treatments, demonstrates that patients' beliefs may affect the acceptability and uptake of treatment. Two groups of beliefs (illness and treatment representations) are likely to be influential. Illness representations describe how people see their illness, as outlined in Leventhal's Self-Regulation Model. Treatment representations describe how people perceive potential treatment for their disease. People offered a programme of genetic testing and treatment will develop their own treatment representations based on what is offered, but the beliefs rather than the objective programme of treatment are likely to determine their willingness to participate. The Theory of Planned Behaviour is a theoretical model that predicts behaviours from people's beliefs about the consequences, social pressures and perceived control over the behaviour, including uptake of treatment. METHODS/DESIGN: This study aims to examine the acceptability of genetic testing, followed by preventative treatment, to relatives of people with PDB. We aim to interview people with Paget's disease, and their families, from the UK. Our research questions are: 1. What do individuals with Paget's disease think would influence the involvement of their relatives in a programme of genetic testing and preventative treatment? 2. What do relatives of Paget's disease sufferers think would influence them in accepting an offer of a programme of genetic testing and preventative treatment? DISCUSSION: Our research will be informed by relevant psychological theory: primarily the Self-Regulation Model and the Theory of Planned Behaviour. The results of these interviews will inform the development of a separate questionnaire-based study to explore these research questions in greater detail

Surface Dimming by the 2013 Rim Fire Simulated by a Sectional Aerosol Model

The Rim Fire of 2013, the third largest area burned by fire recorded in California history, is simulated by a climate model coupled with a size-resolved aerosol model. Modeled aerosol mass, number and particle size distribution are within variability of data obtained from multiple airborne in-situ measurements. Simulations suggest Rim Fire smoke may block 4-6 of sunlight energy reaching the surface, with a dimming efficiency around 120-150 W m(exp -2) per unit aerosol optical depth in the mid-visible at 13:00-15:00 local time. Underestimation of simulated smoke single scattering albedo at mid-visible by 0.04 suggests the model overestimates either the particle size or the absorption due to black carbon. This study shows that exceptional events like the 2013 Rim Fire can be simulated by a climate model with one-degree resolution with overall good skill, though that resolution is still not sufficient to resolve the smoke peak near the source region

Community views about routine HIV testing and antiretroviral treatment in Botswana: signs of progress from a cross sectional study

<p>Abstract</p> <p>Background</p> <p>The Botswana government began providing free antiretroviral therapy (ART) in 2002 and in 2004 introduced routine HIV testing (RHT) in government health facilities, aiming to increase HIV testing and uptake of ART. There have been concerns that the RHT programme might be coercive, lead to increased partner violence, and drive people away from government health services.</p> <p>Methods</p> <p>We conducted a household survey of 1536 people in a stratified random sample of communities across Botswana, asking about use and experience of government health services, views about RHT, views about ART, and testing for HIV in the last 12 months. Focus groups further discussed issues about ART.</p> <p>Results</p> <p>Some 81% of respondents had visited a government clinic within the last 24 months. Of these 92% were satisfied with the service, 96% felt they were treated with respect and 90% were comfortable about confidentiality. Almost all respondents said they would choose a government clinic for treatment of AIDS.</p> <p>Nearly one half (47%) thought they were at risk of HIV. Those who had experienced partner violence within the last 12 months were more likely to think themselves at risk. One half of those who had visited a government facility in the last 24 months were offered HIV tests, and nearly half were tested. A few (8%) of those who were not asked thought they were tested. Most people (79%) had heard of RHT and 94% were in favour of it. Over one half (55%) of the entire sample had been tested for HIV within the last 12 months, one half of these through RHT. Women were more likely to have been tested.</p> <p>Nearly everyone (94%) had heard of ART and thought it could help AIDS. Focus groups identified problems of access to ART due to distance from treatment centres and long queues in the centres.</p> <p>Conclusion</p> <p>Public awareness and approval of RHT was very high. The high rate of RHT has contributed to the overall high rate of HIV testing. The government's programme to increase HIV testing and uptake of ART is apparently working well. However, turning the tide of the epidemic will also require further concerted efforts to reduce the rate of new HIV infections.</p

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

The state of the Martian climate

60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes

The Role of Body Mass Index, Insulin, and Adiponectin in the Relation Between Fat Distribution and Bone Mineral Density

Despite the positive association between body mass index (BMI) and bone mineral density (BMD) and content (BMC), the role of fat distribution in BMD/BMC remains unclear. We examined relationships between BMD/BMC and various measurements of fat distribution and studied the role of BMI, insulin, and adiponectin in these relations. Using a cross-sectional investigation of 2631 participants from the Erasmus Rucphen Family study, we studied associations between BMD (using dual-energy X-ray absorptiometry (DXA]) at the hip, lumbar spine, total body (BMD and BMC), and fat distribution by the waist-to-hip ratio (WHR), waist-to-thigh ratio (WTR), and DXA-based trunk-to-leg fat ratio and android-to-gynoid fat ratio. Analyses were stratified by gender and median age (48.0 years in women and 49.2 years in men) and were performed with and without adjustment for BMI, fasting insulin, and adiponectin. Using linear regression (adjusting for age, height, smoking, and use of alcohol), most relationships between fat distribution and BMD and BMC were positive, except for WTR. After BMI adjustment, most correlations were negative except for trunk-to-leg fat ratio in both genders. No consistent influence of age or menopausal status was found. Insulin and adiponectin levels did not explain either positive or negative associations. In conclusion, positive associations between android fat distribution and BMD/BMC are explained by higher BMI but not by higher insulin and/or lower adiponectin levels. Inverse associations after adjustment for BMI suggest that android fat deposition as measured by the WHR, WTR, and DXA-based android-to-gynoid fat ratio is not beneficial and possibly even deleterious for bone