Oleate but not stearate induces the regulatory phenotype of myeloid suppressor cells

Tumor infiltrating myeloid cells play contradictory roles in the tumor development. Dendritic cells and classical activated macrophages support anti- tumor immune activity via antigen presentation and induction of pro- inflammatory immune responses. Myeloid suppressor cells (MSCs), for instance myeloid derived suppressor cells (MDSCs) or tumor associated macrophages play a critical role in tumor growth. Here, treatment with sodium oleate, an unsaturated fatty acid, induced a regulatory phenotype in the myeloid suppressor cell line MSC-2 and resulted in an increased suppression of activated T cells, paralleled by increased intracellular lipid droplets formation. Furthermore, sodium oleate potentiated nitric oxide (NO) production in MSC-2, thereby increasing their suppressive capacity. In primary polarized bone marrow cells, sodium oleate (C18:1) and linoleate (C18:2), but not stearate (C18:0) were identified as potent FFA to induce a regulatory phenotype. This effect was abrogated in MSC-2 as well as primary cells by specific inhibition of droplets formation while the inhibition of de novo FFA synthesis proved ineffective, suggesting a critical role for exogenous FFA in the functional induction of MSCs. Taken together our data introduce a new unsaturated fatty acid-dependent pathway shaping the functional phenotype of MSCs, facilitating the tumor escape from the immune system

Human resource management interventions to improve health workers' performance in low and middle income countries: a realist review

Contains fulltext : 80429.pdf (publisher's version ) (Open Access)BACKGROUND: Improving health workers' performance is vital for achieving the Millennium Development Goals. In the literature on human resource management (HRM) interventions to improve health workers' performance in Low and Middle Income Countries (LMIC), hardly any attention has been paid to the question how HRM interventions might bring about outcomes and in which contexts. Such information is, however, critical to assess the transferability of results. Our aim was to explore if realist review of published primary research provides better insight into the functioning of HRM interventions in LMIC. METHODOLOGY: A realist review not only asks whether an intervention has shown to be effective, but also through which mechanisms an intervention produces outcomes and which contextual factors appear to be of critical influence. Forty-eight published studies were reviewed. Results : The results show that HRM interventions can improve health workers' performance, but that different contexts produce different outcomes. Critical implementation aspects were involvement of local authorities, communities and management; adaptation to the local situation; and active involvement of local staff to identify and implement solutions to problems. Mechanisms that triggered change were increased knowledge and skills, feeling obliged to change and health workers' motivation. Mechanisms to contribute to motivation were health workers' awareness of local problems and staff empowerment, gaining acceptance of new information and creating a sense of belonging and respect. In addition, staff was motivated by visible improvements in quality of care and salary supplements. Only a limited variety of HRM interventions have been evaluated in the health sector in LMIC. Assumptions underlying HRM interventions are usually not made explicit, hampering our understanding of how HRM interventions work. CONCLUSION: Application of a realist perspective allows identifying which HRM interventions might improve performance, under which circumstances, and for which groups of health workers. To be better able to contribute to an understanding of how HRM interventions could improve health workers' performance, a combination of qualitative and quantitative research methods would be needed and the use of common indicators for evaluation and a common reporting format would be required

Factors Influencing Conception Rates of Cameroonian Zebu Cattle (Bos Indicus) following Oestrus Synchronisation and Artificial Insemination

A study was carried out to identify and evaluate factors affecting variation in conception rate (CR) in Cameroonian Zebu cattle following oestrus synchronisation and artificial insemination (AI). Two hundred and six local female Zebu cattle were evaluated to determine relationship between factors such as lactation number, age, body condition score (BCS), days postpartum and conception rate. Animals received an intravaginal progesterone release device (PRID®) containing 1.55mg of progesterone and a capsule with 10mg estradiol benzonate for 10 days and were treated with luteolytic dose of PGF2α and 1000mg IU PMSG at the time of PRIDt withdrawal. Animals were inseminated 48 hours after PGF2α and PMSG injection. Pregnancy status was assessed by observed non-return to oestrus and confirmed by rectal palpation 55-60 days after insemination. The overall CR was 47.6%. CR was influenced (p< 0.05) by lactation number, age and days postpartum of cows. The multivariate logistic regression model used revealed that CR was optimum in primiparous cows, those between 4.5 -7 years old and 151-300 days postpartum

Conserved amphipathic helices mediate lipid droplet targeting of perilipins 1-3

Perilipins (PLINs) play a key role in energy storage by orchestrating the activity of lipases on the surface of lipid droplets. Failure of this activity results in severe metabolic disease in humans. Unlike all other lipid droplet-associated proteins, PLINs localize almost exclusively to the phospholipid monolayer surrounding the droplet. To understand how they sense and associate with the unique topology of the droplet surface, we studied the localization of human PLINs in Saccharomyces cerevisiae, demonstrating that the targeting mechanism is highly conserved and that 11-mer repeat regions are sufficient for droplet targeting. Mutations designed to disrupt folding of this region into amphipathic helices (AHs) significantly decreased lipid droplet targeting in vivo and in vitro. Finally, we demonstrated a substantial increase in the helicity of this region in the presence of detergent micelles, which was prevented by an AH-disrupting missense mutation. We conclude that highly conserved 11-mer repeat regions of PLINs target lipid droplets by folding into AHs on the droplet surface, thus enabling PLINs to regulate the interface between the hydrophobic lipid core and its surrounding hydrophilic environment

Arf1/COPI machinery acts directly on lipid droplets and enables their connection to the ER for protein targeting

Lipid droplets (LDs) are ubiquitous organelles that store neutral lipids, such as triacylglycerol (TG), as reservoirs of metabolic energy and membrane precursors. The Arf1/COPI protein machinery, known for its role in vesicle trafficking, regulates LD mor

Treatment of cheese whey wastewater by combined electrochemical processes

This study shows the good performance of a sequential electrochemical methodology, consisting in electrocoagulation (EC) followed by an electrochemical advanced oxidation process (EAOP), to treat raw cheese whey wastewater at laboratory and pre-pilot scales. In EC, different electrode materials like Fe, Al and stainless steel (AISI 304 and ASI 316L) were tested. Among EAOPs, photoelectro-Fenton (PEF) and electrochemical oxidation (EO) with active anodes like Pt or DSA((R)) and non-active ones like boron-doped diamond (BDD) were studied. At both scales, the optimum anode/cathode combination in EC was Fe/AISI 304, which yielded the highest total organic carbon (TOC) removal of 22.0-27.0%. This is due to various effects on organic compounds: (i) coagulation promoted by Fe(OH)(3) flocs, (ii) cathodic reduction, and (iii) oxidation with generated active chlorine. At small scale, the resulting wastewater was further treated by PEF at pH 3.0. The highest TOC removal was achieved using the BDD, owing to the great oxidation power of hydroxyl radicals. In contrast, total nitrogen was abated much more rapidly with active anodes because of the attack of active chlorine on N-compounds. At pre-pilot scale, the post-treatment of conditioned wastewater made by EO with a BDD/Pt flow cell combined with UVA irradiation yielded the highest TOC removal, i.e., 49.1%. The high energy consumed by the UVA lamp would be a drawback at industrial scale, which could be overcome by using sunlight