Hematopoietic but Not Endothelial Cell MyD88 Contributes to Host Defense during Gram-negative Pneumonia Derived Sepsis

Klebsiella pneumoniae is an important cause of sepsis. The common Toll-like receptor adapter myeloid differentiation primary response gene (MyD)88 is crucial for host defense against Klebsiella. Here we investigated the role of MyD88 in myeloid and endothelial cells during Klebsiella pneumosepsis. Mice deficient for MyD88 in myeloid (LysM-Myd88^−/−) and myeloid plus endothelial (Tie2-Myd88^−/−) cells showed enhanced lethality and bacterial growth. Tie2-Myd88^−/− mice reconstituted with control bone marrow, representing mice with a selective MyD88 deficiency in endothelial cells, showed an unremarkable antibacterial defense. Myeloid or endothelial cell MyD88 deficiency did not impact on lung pathology or distant organ injury during late stage sepsis, while LysM-Myd88^−/− mice demonstrated a strongly attenuated inflammatory response in the airways early after infection. These data suggest that myeloid but not endothelial MyD88 is important for host defense during gram-negative pneumonia derived sepsis.     

Enhanced operation of femtosecond lasers and applications in cell transfection

In this work we present a review and discussion on the enhancement of femtosecond (fs) lasers for use within biophotonics with a particular focus on their use in optical transfection techniques. We describe the broad range of source options now available for the generation of femtosecond pulses before briefly reviewing the application of fs laser in optical transfection studies. We show that major performance enhancements may be obtained by optimising the spatial and temporal performance of the laser source before considering possible future directions in this field. In relation to optical transfection we describe how such laser sources initiate a multiphoton process to permeate the cell membrane in a transient fashion. We look at aspects of this technique including the ability to combine transfection with optical trapping. For future implementation of such transfection we explore the role of new sources and “nondiffracting” light fields. (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

FitSNPs: highly differentially expressed genes are more likely to have variants associated with disease

Background  

Candidate single nucleotide polymorphisms (SNPs) from genome-wide association studies (GWASs) were often selected for validation based on their functional annotation, which was inadequate and biased. We propose to use the more than 200,000 microarray studies in the Gene Expression Omnibus to systematically prioritize candidate SNPs from GWASs.     

3-Acrylamide-4-aryloxyindoles: Synthesis,biological evaluation and metabolic stability of potent and selective EP3 receptor antagonists

A series of potent and selective EP₃ receptor antagonists are described. Utilizing a pharmacophore model developed for the EP₃ receptor, a series of 3,4-disubstituted indoles were found to be efficient ligands for this target. These compounds showed high selectivity over IP, FP and other EP receptors. An optimized molecule 7c featured a sound profile and potency in the functional rat and human platelet aggregation assays.