Adenosine receptor expression and function in bladder uroepithelium

The uroepithelium of the bladder forms an impermeable barrier that is maintained in part by regulated membrane turnover in the outermost umbrella cell layer. Other than bladder filling, few physiological regulators of this process are known. Western blot analysis established that all four adenosine receptors (A₁, A_2a, A_2b, and A₃) are expressed in the uroepithelium. A₁ receptors were prominently localized to the apical membrane of the umbrella cell layer, whereas A_2a, A_2b, and A₃ receptors were localized intracellularly or on the basolateral membrane of umbrella cells and the plasma membrane of the underlying cell layers. Adenosine was released from the uroepithelium, which was potentiated 10-fold by stretching the tissue. Administration of adenosine to the serosal or mucosal surface of the uroepithelium led to increases in membrane capacitance (where 1 µF 1 cm² tissue area) of 30% or 24%, respectively, after 5 h. Although A₁, A_2a, and A₃ selective agonists all stimulated membrane capacitance after being administrated serosally, only the A₁ agonist caused large increases in capacitance after being administered mucosally. Adenosine receptor antagonists as well as adenosine deaminase had no effect on stretch-induced capacitance increases, but adenosine potentiated the effects of stretch. Treatment with U-73122, 2-aminoethoxydiphenylborate, or xestospongin C or incubation in calcium-free Krebs solution inhibited adenosine-induced increases in capacitance. These data indicate that the uroepithelium is a site of adenosine biosynthesis, that adenosine receptors are expressed in the uroepithelium, and that one function of these receptors may be to modulate exocytosis in umbrella cells. capacitance; exocytosis     

Role of specific innate immune responses in herpes simplex virus infection of the central nervous system

Herpes simplex virus 1 (HSV-1) causes a spectrum of disease, including herpes labialis, herpes keratitis, and herpes encephalitis, which can be lethal. Viral recognition by pattern recognition receptors plays a central role in cytokine production and in the generation of antiviral immunity. The relative contributions of different Toll-like receptors (TLRs) in the innate immune response during central nervous system infection with HSV-1 have not been fully characterized. In this study, we investigate the roles of TLR2, TLR9, UNC93B1, and the type I interferon (IFN) receptor in a murine model of HSV-1 encephalitis. TLR2 is responsible for detrimental inflammatory cytokine production following intracranial infection with HSV-1, and the absence of TLR2 expression leads to increased survival in mice. We prove that inflammatory cytokine production by microglial cells, astrocytes, neutrophils, and monocytes is mediated predominantly by TLR2. We also demonstrate that type I IFNs are absolutely required for survival following intracranial HSV-1 infection, as mice lacking the type I IFN receptor succumb rapidly following infection and have high levels of HSV in the brain. However, the absence of TLR9 does not impact survival, type I IFN levels, or viral replication in the brain following infection. The absence of UNC93B1 leads to a survival disadvantage but does not impact viral replication or type I IFN levels in the brain in HSV-1-infected mice. These results illustrate the complex but important roles that innate immune receptors play in host responses to HSV-1 during infection of the central nervous system.     

Estimation of Maximum Sustainable Yield for Lesser Sciaenids Fishery of North-Eastern Arabian Sea using Surplus Production Model with Environmental Effects

Journal of Ichthyology - Fishes of family Sciaenidae, popularly known as croakers, form a major fishery along the north-west coast of India. In general, sciaenids can be divided in to two major...     

4-Cyano-2-butenyl Group: A New Type of Protecting Group in Oligonucleotide Synthesis via Phosphoramidite Approach

Abstract

4-Cyano-2-butenyl (CB) is a new type of protecting group for the intemucleotidic bonds in the synthesis of oligodeoxyribonucleotides by the phosphoramidite approach. This group is stable to acidic conditions and can be removed under mild conditions by a δ-elimination pathway using aqueous ammonium hydroxide.