Induction of Glucose Metabolism in Stimulated T Lymphocytes Is Regulated by Mitogen-Activated Protein Kinase Signaling

T lymphocytes play a critical role in cell-mediated immune responses. During activation, extracellular and intracellular signals alter T cell metabolism in order to meet the energetic and biosynthetic needs of a proliferating, active cell, but control of these phenomena is not well defined. Previous studies have demonstrated that signaling from the costimulatory receptor CD28 enhances glucose utilization via the phosphatidylinositol-3-kinase (PI3K) pathway. However, since CD28 ligation alone does not induce glucose metabolism in resting T cells, contributions from T cell receptor-initiated signaling pathways must also be important. We therefore investigated the role of mitogen-activated protein kinase (MAPK) signaling in the regulation of mouse T cell glucose metabolism. T cell stimulation strongly induces glucose uptake and glycolysis, both of which are severely impaired by inhibition of extracellular signal-regulated kinase (ERK), whereas p38 inhibition had a much smaller effect. Activation also induced hexokinase activity and expression in T cells, and both were similarly dependent on ERK signaling. Thus, the ERK signaling pathway cooperates with PI3K to induce glucose utilization in activated T cells, with hexokinase serving as a potential point for coordinated regulation

Trypanosoma cruzi Epimastigotes Are Able to Store and Mobilize High Amounts of Cholesterol in Reservosome Lipid Inclusions

Reservosomes are lysosome-related organelles found in Trypanosoma cruzi epimastigotes. They represent the last step in epimastigote endocytic route, accumulating a set of proteins and enzymes related to protein digestion and lipid metabolism. The reservosome matrix contains planar membranes, vesicles and lipid inclusions. Some of the latter may assume rectangular or sword-shaped crystalloid forms surrounded by a phospholipid monolayer, resembling the cholesterol crystals in foam cells.Using Nile Red fluorimetry and fluorescence microscopy, as well as electron microscopy, we have established a direct correlation between serum concentration in culture medium and the presence of crystalloid lipid inclusions. Starting from a reservosome purified fraction, we have developed a fractionation protocol to isolate lipid inclusions. Gas-chromatography mass-spectrometry (GC-MS) analysis revealed that lipid inclusions are composed mainly by cholesterol and cholesterol esters. Moreover, when the parasites with crystalloid lipid-loaded reservosomes were maintained in serum free medium for 48 hours the inclusions disappeared almost completely, including the sword shaped ones.Taken together, our results suggest that epimastigote forms of T. cruzi store high amounts of neutral lipids from extracellular medium, mostly cholesterol or cholesterol esters inside reservosomes. Interestingly, the parasites are able to disassemble the reservosome cholesterol crystalloid inclusions when submitted to serum starvation

Structural Conservation Despite Huge Sequence Diversity Allows EPCR Binding by the PfEMP1 Family Implicated in Severe Childhood Malaria

SummaryThe PfEMP1 family of surface proteins is central for Plasmodium falciparum virulence and must retain the ability to bind to host receptors while also diversifying to aid immune evasion. The interaction between CIDRα1 domains of PfEMP1 and endothelial protein C receptor (EPCR) is associated with severe childhood malaria. We combine crystal structures of CIDRα1:EPCR complexes with analysis of 885 CIDRα1 sequences, showing that the EPCR-binding surfaces of CIDRα1 domains are conserved in shape and bonding potential, despite dramatic sequence diversity. Additionally, these domains mimic features of the natural EPCR ligand and can block this ligand interaction. Using peptides corresponding to the EPCR-binding region, antibodies can be purified from individuals in malaria-endemic regions that block EPCR binding of diverse CIDRα1 variants. This highlights the extent to which such a surface protein family can diversify while maintaining ligand-binding capacity and identifies features that should be mimicked in immunogens to prevent EPCR binding

Determinants of women's satisfaction with maternal health care: a review of literature from developing countries.

BACKGROUND: Developing countries account for 99 percent of maternal deaths annually. While increasing service availability and maintaining acceptable quality standards, it is important to assess maternal satisfaction with care in order to make it more responsive and culturally acceptable, ultimately leading to enhanced utilization and improved outcomes. At a time when global efforts to reduce maternal mortality have been stepped up, maternal satisfaction and its determinants also need to be addressed by developing country governments. This review seeks to identify determinants of women's satisfaction with maternity care in developing countries. METHODS: The review followed the methodology of systematic reviews. Public health and social science databases were searched. English articles covering antenatal, intrapartum or postpartum care, for either home or institutional deliveries, reporting maternal satisfaction from developing countries (World Bank list) were included, with no year limit. Out of 154 shortlisted abstracts, 54 were included and 100 excluded. Studies were extracted onto structured formats and analyzed using the narrative synthesis approach. RESULTS: Determinants of maternal satisfaction covered all dimensions of care across structure, process and outcome. Structural elements included good physical environment, cleanliness, and availability of adequate human resources, medicines and supplies. Process determinants included interpersonal behavior, privacy, promptness, cognitive care, perceived provider competency and emotional support. Outcome related determinants were health status of the mother and newborn. Access, cost, socio-economic status and reproductive history also influenced perceived maternal satisfaction. Process of care dominated the determinants of maternal satisfaction in developing countries. Interpersonal behavior was the most widely reported determinant, with the largest body of evidence generated around provider behavior in terms of courtesy and non-abuse. Other aspects of interpersonal behavior included therapeutic communication, staff confidence and competence and encouragement to laboring women. CONCLUSIONS: Quality improvement efforts in developing countries could focus on strengthening the process of care. Special attention is needed to improve interpersonal behavior, as evidence from the review points to the importance women attach to being treated respectfully, irrespective of socio-cultural or economic context. Further research on maternal satisfaction is required on home deliveries and relative strength of various determinants in influencing maternal satisfaction