Neural-immune-effector (NIE) cross-talk in vascular trophobiology: proposal for new and not yet exploited purinergic regulatory mechanisms

In a state-of-the-art approach, Dr. Hasséssian presents purinoceptor-mediated vasoconstriction/vasodilation mechanisms of the pulmonary circulation. He focuses on P2 purinoceptors of smooth muscle cells, endothelial cells, platelets and mast cells, without addressing P1 (adenosine) purinoceptors. Recently, the Burnstock's purinoceptorology is "arborizing" into a variety of members of P1 and P2 purinoceptor families classified by the International Union of Pharmacology. Here we would like to add some possible, new and not yet exploited, purinergic regulatory mechanisms to the Hasséssian's work. Accordingly, we shall briefly focus on the involvement of connective tissue (adventitial) mast cells and their interactions with perivascular nerves and medial smooth muscle cells.Biomedical Reviews 1994; 3: 81-86

Conformational Reorganization of the SARS Coronavirus Spike Following Receptor Binding: Implications for Membrane Fusion

The SARS coronavirus (SARS-CoV) spike is the largest known viral spike molecule, and shares a similar function with all class 1 viral fusion proteins. Previous structural studies of membrane fusion proteins have largely used crystallography of static molecular fragments, in isolation of their transmembrane domains. In this study we have produced purified, irradiated SARS-CoV virions that retain their morphology, and are fusogenic in cell culture. We used cryo-electron microscopy and image processing to investigate conformational changes that occur in the entire spike of intact virions when they bind to the viral receptor, angiotensin-converting enzyme 2 (ACE2). We have shown that ACE2 binding results in structural changes that appear to be the initial step in viral membrane fusion, and precisely localized the receptor-binding and fusion core domains within the entire spike. Furthermore, our results show that receptor binding and subsequent membrane fusion are distinct steps, and that each spike can bind up to three ACE2 molecules. The SARS-CoV spike provides an ideal model system to study receptor binding and membrane fusion in the native state, employing cryo-electron microscopy and single-particle image analysis

Institutional investors and corporate governance

We provide a comprehensive overview of the role of institutional investors in corporate governance with three main components. First, we establish new stylized facts documenting the evolution and importance of institutional ownership. Second, we provide a detailed characterization of key aspects of the legal and regulatory setting within which institutional investors govern portfolio firms. Third, we synthesize the evolving response of the recent theoretical and empirical academic literature in finance to the emergence of institutional investors in corporate governance. We highlight how the defining aspect of institutional investors – the fact that they are financial intermediaries – differentiates them in their governance role from standard principal blockholders. Further, not all institutional investors are identical, and we pay close attention to heterogeneity amongst institutional investors as blockholders

Effect of ribavirin on hepatitis A virus replication in vitro

The effect of ribavirin on fetal Rhesus monkey kidney cells (FRhK-4) acutely or chronically infected with hepatitis A virus was studied. The effect of ribavirin on hepatitis A virus yield as detected by radioimmunoassay in acutely infected FRhK-4 cells was dependent on hepatitis A virus inoculum dose. Treatment with 100 μg/mL ribavirin completely inhibited hepatitis A virus growth in cultures infected with 100 to 800 tissue culture infectious dose 50 (TCID50) hepatitis A virus, but inocula of 800 to 1600 TCID50 resulted in limited production of virus. The effect was time dependent and required more than 96 h of treatment to inhibit the virus completely. Ribavirin was less effective in treating cells persistently infected with hepatitis A virus, although there was significant inhibition of hepatitis A virus (82%) in persistently infected cells as well. Ribavirin had some inhibitory effect on cell growth; treatment with 25, 50 or 100 μg/mL ribavirin reduced cell growth by approximately 0, 20 and 40%, respectively

Pretreatment Resistance to Hepatitis C Virus Protease Inhibitors Boceprevir/Telaprevir in Hepatitis C Subgenotype 1A-Infected Patients from Manitoba

BACKGROUND: Traditional therapy with pegylated interferon and ribavirin combined with the new protease inhibitors boceprevir or telaprevir has demonstrated improved outcomes in hepatitis C virus (HCV)-infected patients. Prevalence data regarding pre-existing drug-resistant variants to these two new virus inhibitors in the Canadian population are not available

A topology of grid connected photovoltaic inverter with variable power factor

By outlying renewable energy sources, the reactive electric power of local consumers at the same area must be carried by the grid. This loads and causes losses in the same grid. This can be avoided if the necessary reactive power is generated on the spot by the inverter. For that purpose is proposed and investigated a new modified topology for operating with variable power factor. Features of this topology are: transformerless connection to single-phase grid, symmetrical operation in both half waves and the presence of flying inductor, which eliminate the necessity from a separate boost converter, if the input voltage is smaller than the grid peak voltage. The simulation analysis is done on the model elaborated on the SIMETRIX software environment. The results show that the suggested topology can operate with variable power factor and has many additional advantages