Uncoupling Caveolae From Intracellular Signaling In Vivo.

Rationale: Caveolin-1 (Cav-1) negatively regulates endothelial nitric oxide (NO) synthase-derived NO production, and this has been mapped to several residues on Cav-1, including F92. Herein, we reasoned that endothelial expression of an F92ACav-1 transgene would let us decipher the mechanisms and relationships between caveolae structure and intracellular signaling.

Objective: This study was designed to separate caveolae formation from its downstream signaling effects.

Cellularity and structure of fresh human coronary thrombectomy specimens; presence of cells with markers of progenitor cells.

Acute coronary syndromes and acute myocardial infarctions are often related to plaque rupture and the formation of thrombi at the site of the rupture. We examined fresh coronary thrombectomy specimens from patients with acute coronary syndromes and assessed their structure and cellularity. The thrombectomy specimens consisted of platelets, erythrocytes and inflammatory cells.

Reperfusion injury intensifies the adaptive human T cell alloresponse in a human-mouse chimeric artery model.

Objective: Perioperative nonimmune injuries to an allograft can decrease graft survival. We have developed a model for studying this process using human materials.

Methods And Results: Human artery segments were transplanted as infrarenal aortic interposition grafts into an immunodeficient mouse host, allowed to "heal in" for 30 days, and then retransplanted into a second mouse host.

The role of Nogo and the mitochondria-endoplasmic reticulum unit in pulmonary hypertension.

Pulmonary arterial hypertension (PAH) is caused by excessive proliferation of vascular cells, which occlude the lumen of pulmonary arteries (PAs) and lead to right ventricular failure. The cause of the vascular remodeling in PAH remains unknown, and the prognosis of PAH remains poor. Abnormal mitochondria in PAH PA smooth muscle cells (SMCs) suppress mitochondria-dependent apoptosis and contribute to the vascular remodeling.

Reticulon 4B (Nogo-B) is a novel regulator of hepatic fibrosis.

Unlabelled: Nogo-B, also known as Reticulon 4B, plays important roles in vascular injuries. Its function in the liver is not understood. The aim of this study was to characterize Nogo-B in liver fibrosis and cirrhosis.

An insight into the sialome of Glossina morsitans morsitans.

Background: Blood feeding evolved independently in worms, arthropods and mammals. Among the adaptations to this peculiar diet, these animals developed an armament of salivary molecules that disarm their host's anti-bleeding defenses (hemostasis), inflammatory and immune reactions. Recent sialotranscriptome analyses (from the Greek sialo = saliva) of blood feeding insects and ticks have revealed that the saliva contains hundreds of polypeptides, many unique to their genus or family.

Reticulon 4B (Nogo-B) is necessary for macrophage infiltration and tissue repair.

Blood vessel formation during ischemia and wound healing requires coordination of the inflammatory response with genes that regulate blood vessel assembly. Here we show that the reticulon family member 4B, aka Nogo-B, is upregulated in response to ischemia and is necessary for blood flow recovery secondary to ischemia and wound healing. Mice lacking Nogo-B exhibit reduced arteriogenesis and angiogenesis that are linked to a decrease in macrophage infiltration and inflammatory gene expression in vivo.

Urocortin2 inhibits tumor growth via effects on vascularization and cell proliferation.

The corticotropin-releasing factor (CRF) receptor CRFR2 is expressed widely in peripheral tissues and in the vasculature, although its functional roles in those tissues have only recently begun to be elucidated. Previously we found that genetic deletion of CRFR2 resulted in profound postnatal hypervascularization in mice, characterized by both an increase in total vessel number and a dramatic increase in vessel diameter. These data strongly suggested that ligands for CRFR2 act to limit tissue vascularity, perhaps as a counterbalance to factors that promote neovascularization.

Proventriculus (cardia) plays a crucial role in immunity in tsetse fly (Diptera: Glossinidiae).

Fat body and hemocytes play a central role in cellular and humoral responses for systemic infections in invertebrates, similar to the mammalian liver and blood cells. Epithelial surfaces, in particular the midgut, participate in the initial local immune responses in order to aid in the generation of the terminal cytotoxic molecules that mediate non-self recognition. Here, we describe for the first time the immune responses of a cluster of cells at the foregut/midgut junction--known as proventriculus (cardia) in the medically and agriculturally important insect, tsetse fly (Diptera: Glossinidae).

Proventriculus-specific cDNAs characterized from the tsetse, Glossina morsitans morsitans.

Peritrophic matrix (peritrophic membrane or PM) is an important structure in the gut of most insects at some stage in their development. It is composed of chitin, proteins and proteoglycans. Multiple roles for the PM ranging from partitioning of digestive enzymes and food to protection of gut epithelial cells from viral and parasitic invasion have been proposed.

What can we hope to gain for trypanosomiasis control from molecular studies on tsetse biology ?

At times of crisis when epidemics rage and begin to take their toll on affected populations, as we have been witnessing with African trypanosomiasis in subSahara, the dichotomy of basic versus applied research deepens. While undoubtedly the treatment of thousands of infected people is the top priority, without continued research and development on the biology of disease agents and on ecological and evolutionary forces impacting these epidemics, little progress can be gained in the long run for the eventual control of these diseases. Here, we argue the need for additional research in one under-investigated area, that is the biology of the tsetse vector.