The Role of Fibronectin in the Adherence and Inflammatory Response Induced by Enteroaggregative on Epithelial Cells.

Enteroaggregative (EAEC) infections are still one of the most important etiologic pathogens of diarrhea in children worldwide. EAEC pathogenesis comprises three stages: adherence and colonization, production of toxins, and diarrhea followed by inflammation. Previous studies have demonstrated that EAEC strains have the ability to bind to fibronectin (FN); however, the role this extracellular matrix protein plays in the inflammatory response induced by EAEC remains unknown.

Molecular and Cellular Mechanisms of Shigella flexneri Dissemination.

The intracellular pathogen Shigella flexneri is the causative agent of bacillary dysentery in humans. The disease is characterized by bacterial invasion of intestinal cells, dissemination within the colonic epithelium through direct spread from cell to cell, and massive inflammation of the intestinal mucosa. Here, we review the mechanisms supporting S.

Regulatory Crosstalk by Protein Kinases on CFTR Trafficking and Activity.

Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) is a member of the ATP binding cassette (ABC) transporter superfamily that functions as a cAMP-activated chloride ion channel in fluid-transporting epithelia. There is abundant evidence that CFTR activity (i.e.

Computational drug repositioning for peripheral arterial disease: prediction of anti-inflammatory and pro-angiogenic therapeutics.

Peripheral arterial disease (PAD) results from atherosclerosis that leads to blocked arteries and reduced blood flow, most commonly in the arteries of the legs. PAD clinical trials to induce angiogenesis to improve blood flow conducted in the last decade have not succeeded. We have recently constructed PADPIN, protein-protein interaction network (PIN) of PAD, and here we combine it with the drug-target relations to identify potential drug targets for PAD.

Assembly-driven activation of the AIM2 foreign-dsDNA sensor provides a polymerization template for downstream ASC.

AIM2 recognizes foreign dsDNA and assembles into the inflammasome, a filamentous supramolecular signalling platform required to launch innate immune responses. We show here that the pyrin domain of AIM2 (AIM2(PYD)) drives both filament formation and dsDNA binding. In addition, the dsDNA-binding domain of AIM2 also oligomerizes and assists in filament formation.

Involvement of calpains in adult neurogenesis: implications for stroke.

Calpains are ubiquitous proteases involved in cell proliferation, adhesion and motility. In the brain, calpains have been associated with neuronal damage in both acute and neurodegenerative disorders, but their physiological function in the nervous system remains elusive. During brain ischemia, there is a large increase in the levels of intracellular calcium, leading to the activation of calpains.

Out-of-body experiences associated with seizures.

Alterations of consciousness are critical factors in the diagnosis of epileptic seizures. With these alterations in consciousness, some persons report sensations of separating from the physical body, experiences that may in rare cases resemble spontaneous out-of-body experiences. This study was designed to identify and characterize these out-of-body-like subjective experiences associated with seizure activity.

Xenotropic MLV envelope proteins induce tumor cells to secrete factors that promote the formation of immature blood vessels.

Background: Xenotropic Murine leukemia virus-Related Virus (XMRV) is a γ-retrovirus initially reported to be present within familial human prostate tumors and the blood of patients with chronic fatigue syndrome. Subsequent studies however were unable to replicate these findings, and there is now compelling evidence that the virus evolved through rare retroviral recombination events in human tumor cell lines established through murine xenograft experiments. There is also no direct evidence that XMRV infection has any functional effects that contribute to tumor pathogenesis.

Lymphatic endothelial cells - key players in regulation of tolerance and immunity.

The lymphatic vasculature provides routes for dendritic cell and lymphocyte migration into and out of lymph nodes. Lymphatic endothelial cells (LEC) control these processes by expression of CCL21, sphingosine-1-phosphate, and adhesion molecules. LEC express MHC-I and MHC-II, but not costimulatory molecules, and present antigen on MHC-I via both direct and cross-presentation.

In vivo proliferative regeneration of balance hair cells in newborn mice.

The regeneration of mechanoreceptive hair cells occurs throughout life in non-mammalian vertebrates and allows them to recover from hearing and balance deficits that affect humans and other mammals permanently. The irreversibility of comparable deficits in mammals remains unexplained, but often has been attributed to steep embryonic declines in cellular production. However, recent results suggest that gravity-sensing hair cells in murine utricles may increase in number during neonatal development, raising the possibility that young mice might retain sufficient cellular plasticity for mitotic hair cell regeneration.

Combined VEGF and LMP-1 delivery enhances osteoprogenitor cell differentiation and ectopic bone formation.

A novel strategy to enhance bone repair is to combine angiogenic factors and osteogenic factors. We combined vascular endothelial growth factor (VEGF) and LIM mineralization protein-1 (LMP-1) by using an internal ribosome entry site to link the genes within a single plasmid. We then evaluated the effects on osteoblastic differentiation in vitro and ectopic bone formation in vivo with a subcutaneously placed PLAGA scaffold loaded with a cloned mouse osteoprogenitor cell line, D1, transfected with plasmids containing VEGF and LMP-1 genes.

Binding of phosphatase inhibitor-2 to prolyl isomerase Pin1 modifies specificity for mitotic phosphoproteins.

Inhibitor-2 (I-2) is the most ancient protein that selectively recognizes type-1 protein phosphatase and is phosphorylated by CDK1-cyclinB during mitosis at Thr72 in a conserved PXTP site. Pin1 is a peptide prolyl cis/trans isomerase conserved among eukaryotes that specifically reacts with proteins phosphorylated at Ser/Thr-Pro sites. We tested phospho-T72-I-2 as a substrate for Pin1 and discovered that unphosphorylated I-2 bound Pin1 with micromolar affinity and phosphorylation of the PXTP site or truncation of I-2 reduced binding 10-fold.

Fungal infections in neonates: update on prevention and treatment.

Neonates with gastrointestinal diseases and extremely preterm infants are at highest risk for developing invasive fungal infections. Candida species are commensal organisms that colonize skin and mucosal surfaces as well as adhere to catheter surfaces. Due to the immature immune system of neonates including compromise of the developing barrier defenses of the skin or mucosal membranes, Candida can invade into the bloodstream and disseminate, often making these infections difficult to eradicate.

Phosphorylation of the Pro-X-Thr-Pro site in phosphatase inhibitor-2 by cyclin-dependent protein kinase during M-phase of the cell cycle.

Protein phosphorylation serves as a primary mechanism for triggering events during mitosis and depends on coordinated regulation of kinases and phosphatases. Protein Ser-Thr phosphatase-1 (PP1) activity is essential for the metaphase to anaphase transition and the most ancient regulator of PP1 conserved from yeast to human is inhibitor-2 (I-2), an unstructured heat-stable protein. A unique sequence motif in I-2 from various species surrounds a phosphorylation site PXTP that can be phosphorylated in biochemical assays by GSK3, MAPK and CDK kinases.

Combined histone deacetylase and NF-kappaB inhibition sensitizes non-small cell lung cancer to cell death.

Background: Non-small cell lung cancer (NSCLC) remains resistant to traditional and novel chemotherapeutic agents, relating, in part, to the activation of the antiapoptotic transcription factor NF-kappaB. We hypothesize that inhibition of NF-kappaB using BAY-11-7085 will sensitize NSCLC cells to death, induced by the histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA).

Methods: Five tumorigenic NSCLC cell lines (A549, H157, H358, H460, H1299) were treated with nothing, SAHA, BAY-11-7085, or both compounds.

Effect of mannitol on the permeability of cultured endothelial cells.

The effect of mannitol on the permeability of the endothelial monolayer was investigated. Endothelial cells from bovine major cerebral arteries were cultured on a polycarbonate membranes of the double chamber culture system. After the monolayers reached confluence, they were incubated with three kinds of mannitol solution either on the upper chamber or the lower chamber.

Histone H4 and the maintenance of genome integrity.

The normal progression of Saccharomyces cerevisiae through nuclear division requires the function of the amino-terminal domain of histone H4. Mutations that delete the domain, or alter 4 conserved lysine residues within the domain, cause a marked delay during the G2+M phases of the cell cycle. Site-directed mutagenesis of single and multiple lysine residues failed to map this phenotype to any particular site; the defect was only observed when all four lysines were mutated.

Impaired skeletal muscle glycogen synthase activation by insulin in the Goto-Kakizaki (G/K) rat.

The Goto-Kakizaki (G/K) rat is an animal model of non-insulin-dependent diabetes mellitus, with early hyperglycaemia, hyperinsulinaemia, and insulin resistance. We have studied the effect of insulin on the activation of glycogen synthase in the G/K rat and in the original parent strain, the Wistar rat. After insulin injection, glycogen synthase I activity, glycogen synthase phosphatase activity and glucose 6-phosphate content in skeletal muscle were significantly increased in the Wistar rats.