Predicting Continental Scale Malaria With Land Surface Water Predictors Based on Malaria Dispersal Mechanisms and High-Resolution Earth Observation Data.

Despite malaria prevalence being linked to surface water through vector breeding, spatial malaria predictors representing surface water often predict malaria poorly. Furthermore, precipitation, which precursors surface water, often performs better. Our goal is to determine whether novel surface water exposure indices that take malaria dispersal mechanisms into account, derived from new high-resolution surface water data, can be stronger predictors of malaria prevalence compared to precipitation.

Point-of-Care: Roadmap for Analytical Characterization and Validation of a High-Sensitivity Cardiac Troponin I Assay in Plasma and Whole Blood Matrices.

Background: High-sensitivity cardiac troponin (hs-cTn) assays enable more precise use of traditional diagnostic strategies and earlier rule-out/rule-in at 0/1 h or 0/2 h after presentation of acute myocardial infarction (AMI). Availability of hs-cTn measurements at point-of-care (POC) can improve timely management of AMI patients. A roadmap for regulatory and analytical validation is exemplified with studies with the Atellica VTLi hs-cTnI at POC.

p38 inhibition and not MK2 inhibition enhances the secretion of chemokines from TNF-α activated rheumatoid arthritis fibroblast-like synoviocytes.

Objectives: For many years the p38 MAP kinase (MAPK) has been a major anti-inflammatory target for the development of an oral therapy for rheumatoid arthritis (RA). However, disappointing results from Phase II clinical studies suggest that adaptations may occur, which allow escape from blockade of the p38 pathway. In this study we investigated whether p38 inhibition mediated JNK activation represents such an escape mechanism.

Molecular pathway profiling of T lymphocyte signal transduction pathways; Th1 and Th2 genomic fingerprints are defined by TCR and CD28-mediated signaling.

Background: T lymphocytes are orchestrators of adaptive immunity. Naïve T cells may differentiate into Th1, Th2, Th17 or iTreg phenotypes, depending on environmental co-stimulatory signals. To identify genes and pathways involved in differentiation of Jurkat T cells towards Th1 and Th2 subtypes we performed comprehensive transcriptome analyses of Jurkat T cells stimulated with various stimuli and pathway inhibitors.

Discovery of selective and orally available spiro-3-piperidyl ATP-competitive MK2 inhibitors.

The identification of a potent, selective, and orally available MK2 inhibitor series is described. The initial absence of oral bioavailability was successfully tackled by moving the basic nitrogen of the spiro-4-piperidyl moiety towards the electron-deficient pyrrolepyridinedione core, thereby reducing the pK(a) and improving Caco-2 permeability. The resulting racemic spiro-3-piperidyl analogues were separated by chiral preparative HPLC, and the activity towards MK2 inhibition was shown to reside mostly in the first eluting stereoisomer.

Membrane-bound HLA-G activates proliferation and interferon-gamma production by uterine natural killer cells.

The expression of HLA-G by invading trophoblasts suggests a role for this molecule in embryo implantation. Putative targets for HLA-G are the uterine natural killer cells (uNK) that are abundantly present at the time of implantation. Since NK cells are potent producers of a variety of cytokines, interaction with HLA-G may result in the production of cytokines involved in trophoblast differentiation or tissue remodelling.

Detection of HLA-G by a specific sandwich ELISA using monoclonal antibodies G233 and 56B.

Human leukocyte antigen (HLA)-G, which is mainly expressed at the maternal-fetal interface, may play a role in the immune tolerance of the semi-allogenic fetus by the mother. Functional studies have shown that HLA-G is indeed a potential modulator of different immune responses. Therefore, it is of interest to study the level of expression of soluble HLA-G in several biological fluids derived from women with and without fertility problems.