Baryon charge from embedding topology and a continuous meson spectrum in a new holographic gauge theory

We study a new holographic gauge theory based on probe D4-branes in the background dual to D4-branes on a circle with antiperiodic boundary conditions for fermions. Field theory configurations with baryons correspond to smooth embeddings of the probe D4-branes with nontrivial winding around an S^4 in the geometry. As a consequence, physics of baryons and nuclei can be studied reliably in this model using the abelian Born-Infeld action. However, surprisingly, we find that the meson spectrum is not discrete. This is related to a curious result that the action governing small fluctuations of the gauge field on the probe brane is the five-dimensional Maxwell action in Minkowski space despite the non-trivial embedding of the probe brane in the curved background geometry.Comment: 24 pages, LaTeX, 10 figures, v4: previously ignored effects of coupling to RR-fields included, meson spectrum qualitatively changed, v5: journal versio

Regulation of neutrophil senescence by microRNAs

Neutrophils are rapidly recruited to sites of tissue injury or infection, where they protect against invading pathogens. Neutrophil functions are limited by a process of neutrophil senescence, which renders the cells unable to respond to chemoattractants, carry out respiratory burst, or degranulate. In parallel, aged neutrophils also undergo spontaneous apoptosis, which can be delayed by factors such as GMCSF. This is then followed by their subsequent removal by phagocytic cells such as macrophages, thereby preventing unwanted inflammation and tissue damage. Neutrophils translate mRNA to make new proteins that are important in maintaining functional longevity. We therefore hypothesised that neutrophil functions and lifespan might be regulated by microRNAs expressed within human neutrophils. Total RNA from highly purified neutrophils was prepared and subjected to microarray analysis using the Agilent human miRNA microarray V3. We found human neutrophils expressed a selected repertoire of 148 microRNAs and that 6 of these were significantly upregulated after a period of 4 hours in culture, at a time when the contribution of apoptosis is negligible. A list of predicted targets for these 6 microRNAs was generated from http://mirecords.biolead.org and compared to mRNA species downregulated over time, revealing 83 genes targeted by at least 2 out of the 6 regulated microRNAs. Pathway analysis of genes containing binding sites for these microRNAs identified the following pathways: chemokine and cytokine signalling, Ras pathway, and regulation of the actin cytoskeleton. Our data suggest that microRNAs may play a role in the regulation of neutrophil senescence and further suggest that manipulation of microRNAs might represent an area of future therapeutic interest for the treatment of inflammatory disease

Social and cultural efficacies of medicines: Complications for antiretroviral therapy

Using ethnographic examples of medicine use, prescription, distribution and production, the authors argue that social and cultural effects of pharmaceuticals should be taken into account. Non-medical effects deeply influence the medical outcome of medicine use. Complications around the advent of anti-AIDS medicines in poor countries are taken as a point in case. The authors are medical anthropologists specialised in the social and cultural analysis of pharmaceuticals

Tumour-derived alkaline phosphatase regulates tumour growth, epithelial plasticity and disease-free survival in metastatic prostate cancer

BACKGROUND: Recent evidence suggests that bone-related parameters are the main prognostic factors for overall survival in advanced prostate cancer (PCa), with elevated circulating levels of alkaline phosphatase (ALP) thought to reflect the dysregulated bone formation accompanying distant metastases. We have identified that PCa cells express ALPL, the gene that encodes for tissue nonspecific ALP, and hypothesised that tumour-derived ALPL may contribute to disease progression. METHODS: Functional effects of ALPL inhibition were investigated in metastatic PCa cell lines. ALPL gene expression was analysed from published PCa data sets, and correlated with disease-free survival and metastasis. RESULTS: ALPL expression was increased in PCa cells from metastatic sites. A reduction in tumour-derived ALPL expression or ALP activity increased cell death, mesenchymal-to-epithelial transition and reduced migration. Alkaline phosphatase activity was decreased by the EMT repressor Snail. In men with PCa, tumour-derived ALPL correlated with EMT markers, and high ALPL expression was associated with a significant reduction in disease-free survival. CONCLUSIONS: Our studies reveal the function of tumour-derived ALPL in regulating cell death and epithelial plasticity, and demonstrate a strong association between ALPL expression in PCa cells and metastasis or disease-free survival, thus identifying tumour-derived ALPL as a major contributor to the pathogenesis of PCa progression.British Journal of Cancer advance online publication, 22 December 2016; doi:10.1038/bjc.2016.402 www.bjcancer.com

Microbiological contamination of cubicle curtains in an out-patient podiatry clinic

<p>Abstract</p> <p>Background</p> <p>Exposure to potential pathogens on contaminated healthcare garments and curtains can occur through direct or indirect contact. This study aimed to identify the microorganisms present on podiatry clinic curtains and measure the contamination pre and post a standard hospital laundry process.</p> <p>Method</p> <p>Baseline swabs were taken to determine colony counts present on cubical curtains before laundering. Curtains were swabbed again immediately after, one and three weeks post laundering. Total colony counts were calculated and compared to baseline, with identification of micro-organisms.</p> <p>Results</p> <p>Total colony counts increased very slightly by 3% immediately after laundry, which was not statistically significant, and declined significantly (p = 0.0002) by 56% one-week post laundry. Three weeks post laundry colony counts had increased by 16%; although clinically relevant, this was not statistically significant. The two most frequent microorganisms present throughout were <it>Coagulase Negative Staphylococcus </it>and <it>Micrococcus </it>species. Laundering was not completely effective, as both species demonstrated no significant change following laundry.</p> <p>Conclusion</p> <p>This work suggests current laundry procedures may not be 100% effective in killing all microorganisms found on curtains, although a delayed decrease in total colony counts was evident. Cubicle curtains may act as a reservoir for microorganisms creating potential for cross contamination. This highlights the need for additional cleaning methods to decrease the risk of cross infection and the importance of maintaining good hand hygiene.</p

Molecular Epidemiology of Campylobacter Isolates from Poultry Production Units in Southern Ireland

This study aimed to identify the sources and routes of transmission of Campylobacter in intensively reared poultry farms in the Republic of Ireland. Breeder flocks and their corresponding broilers housed in three growing facilities were screened for the presence of Campylobacter species from November 2006 through September 2007. All breeder flocks tested positive for Campylobacter species (with C. jejuni and C. coli being identified). Similarly, all broiler flocks also tested positive for Campylobacter by the end of the rearing period. Faecal and environmental samples were analyzed at regular intervals throughout the rearing period of each broiler flock. Campylobacter was not detected in the disinfected house, or in one-day old broiler chicks. Campylobacter jejuni was isolated from environmental samples including air, water puddles, adjacent broiler flocks and soil. A representative subset of isolates from each farm was selected for further characterization using flaA-SVR sub-typing and multi-locus sequence typing (MLST) to determine if same-species isolates from different sources were indistinguishable or not. Results obtained suggest that no evidence of vertical transmission existed and that adequate cleaning/disinfection of broiler houses contributed to the prevention of carryover and cross-contamination. Nonetheless, the environment appears to be a potential source of Campylobacter. The population structure of Campylobacter isolates from broiler farms in Southern Ireland was diverse and weakly clonal

EFSA NDA Panel (EFSA Panel on Dietetic Products, Nutrition and Allergies), 2013 . Scientific opinion on Dietary Reference Values for fluoride

Following a request from the European Commission, the Panel on Dietetic Products, Nutrition and Allergies (NDA) derived Dietary Reference Values (DRVs) for fluoride, which are provided as Adequate Intake (AI) from all sources, including non-dietary sources. Fluoride is not an essential nutrient. Therefore, no Average Requirement for the performance of essential physiological functions can be defined. Nevertheless, the Panel considered that the setting of an AI is appropriate because of the beneficial effects of dietary fluoride on prevention of dental caries. The AI is based on epidemiological studies (performed before the 1970s) showing an inverse relationship between the fluoride concentration of water and caries prevalence. As the basis for defining the AI, estimates of mean fluoride intakes of children via diet and drinking water with fluoride concentrations at which the caries preventive effect approached its maximum whilst the risk of dental fluorosis approached its minimum were chosen. Except for one confirmatory longitudinal study in US children, more recent studies were not taken into account as they did not provide information on total dietary fluoride intake, were potentially confounded by the use of fluoride-containing dental hygiene products, and did not permit a conclusion to be drawn on a dose-response relationship between fluoride intake and caries risk. The AI of fluoride from all sources (including non-dietary sources) is 0.05 mg/kg body weight per day for both children and adults, including pregnant and lactating women. For pregnant and lactating women, the AI is based on the body weight before pregnancy and lactation. Reliable and representative data on the total fluoride intake of the European population are not available

Generation and characterization of two immortalized human osteoblastic cell lines useful for epigenetic studies

Different model systems using osteoblastic cell lines have been developed to help understand the process of bone formation. Here, we report the establishment of two human osteoblastic cell lines obtained from primary cultures upon transduction of immortalizing genes. The resulting cell lines had no major differences to their parental lines in their gene expression profiles. Similar to primary osteoblastic cells, osteocalcin transcription increased following 1,25-dihydroxyvitamin D3 treatment and the immortalized cells formed a mineralized matrix, as detected by Alizarin Red staining. Moreover, these human cell lines responded by upregulating ALPL gene expression after treatment with the demethylating agent 5-aza-2 Œ-deoxycytidine (AzadC), as shown before for primary osteoblasts. We further demonstrate that these cell lines can differentiate in vivo, using a hydroxyapatite/tricalcium phosphate composite as a scaffold, to produce bone matrix. More importantly, we show that these cells respond to demethylating treatment, as shown by the increase in SOST mRNA levels, the gene encoding sclerostin, upon treatment of the recipient mice with AzadC. This also confirms, in vivo, the role of DNA methylation in the regulation of SOST expression previously shown in vitro. Altogether our results show that these immortalized cell lines constitute a particularly useful model system to obtain further insight into bone homeostasis, and particularly into the epigenetic mechanisms regulating sclerostin production

Search for a narrow charmed baryonic state decaying to D^*+/- p^-/+ in ep collisions at HERA

A resonance search has been made in the D^*+/- p^-/+ invariant-mass spectrum with the ZEUS detector at HERA using an integrated luminosity of 126 pb^-1. The decay channels D^*+ -> D^0 pi^+_s -> (K^- pi^+) pi^+_s and D^*+ -> D^0 pi^+_s -> (K^- pi^+ pi^+ pi^-) pi^+_s (and the corresponding antiparticle decays) were used to identify D^*+/- mesons. No resonance structure was observed in the D^*+/- p^-/+ mass spectrum from more than 60000 reconstructed D^*+/- mesons. The results are not compatible with a report of the H1 Collaboration of a charmed pentaquark, Theta^0_c.Comment: 22 pages, 7 figures, 1 table; minor text revisions; 2 references adde