The triggering receptor expressed on myeloid cells 1 (TREM-1) is involved in the innate inflammatory response to microbial infections. Activation and expression of TREM-1 by polymorphonuclear neutrophils (PMN) occurs in concert with Toll-like receptors (TLR) such as TLR4 for bacterial lipopolysaccharide. However, it is currently unclear how this is mediated on a molecular level. Using pharmacol...

The signal transduction pathways associated with neural cell adhesion molecule (NCAM)-induced neuritogenesis are only partially characterized. We here demonstrate that NCAM-induced neurite outgrowth depends on activation of p59(fyn), focal adhesion kinase (FAK), phospholipase Cgamma (PLCgamma), protein kinase C (PKC), and the Ras-mitogen-activated protein (MAP) kinase pathway. This was done usi...

Organic synthesis is widely regarded as having begun nearly two centuries ago, with Friedrich Wöhler’s 1828 discovery that ammonium cyanate could be converted into urea [2]. Since that seminal finding, chemical synthesis has advanced to extents which must have been unimaginable to its early practitioners. The numerous paradigm-shifts which have taken place throughout the history of synthesis ha...

We have selected designed ankyrin repeat proteins (DARPins) from a synthetic library by using ribosome display that selectively bind to the mitogen-activated protein kinase ERK2 (extracellular signal-regulated kinase 2) in either its nonphosphorylated (inactive) or doubly phosphorylated (active) form. They do not bind to other kinases tested. Crystal structures of complexes with two DARPins, ea...

Creating conditions similar to those that occur during exposure of cells to microgravity induced a sixfold increase of apoptotic bodies and DNA fragments in human lymphocytes, paralleled by an early (within 2 h) fourfold increase in 5-lipoxygenase (5-LOX) activity and a fivefold decrease in mitochondrial membrane potential and increase in cytochrome c release (within 4 and 8 h, respectively). S...

Macrophage/microglia with heterogonous phenotype and function under physiological and pathological conditions are the main cell lineage involved in inducing immune responses in neuroinflammatory diseases which exhibit combined inflammatory and anti-inflammatory functions. An increase in the expression of iNOS triggers M1 phenotype that secrete high concentrations of inflammatory cytokines, whil...

Just as observing is more than just seeing, comparing is far more than mere matching. It takes understanding, and even inventiveness, to discern a useful basis for judging two ideas as similar in a particular context, especially when our perspective is shaped by an act of linguistic creativity such as metaphor, simile or analogy. Structured resources such as WordNet offer a convenient hierarchi...

An authentic sickness history is the vantage point for juxtaposing a biomedical and a biographical-phenomenological reading. What, in a biomedical framework, appears to be a longstanding state of comorbidity of different and unrelated types of diseases is rendered transparent in a biographical reading. This particular reading, evidencing the shortcomings of a biomedical framework regarding iden...

Focal adhesion kinase (FAK) is essential for vascular development as endothelial cell (EC)-specific knockout of FAK (conditional FAK knockout [CFKO] mice) leads to embryonic lethality. In this study, we report the differential kinase-independent and -dependent functions of FAK in vascular development by creating and analyzing an EC-specific FAK kinase-defective (KD) mutant knockin (conditional ...

Antiproliferative protein (APP) isolated from conditioned media of two androgen-independent prostatic carcinoma cell lines, PC3 and Du-145 was shown to inhibit selectively cell proliferation of androgen-dependent prostate cancer cell line LNCaP in a dose dependent manner. This protein was further purified with HPLC using hydrophobic interaction column (phenyl 5PW) and was used to study the modu...