Variations in the Biological Functions of HIV-1 Clade C Envelope in a SHIV-Infected Rhesus Macaque during Disease Progression

A better understanding of how the biological functions of the HIV-1 envelope (Env) changes during disease progression may aid the design of an efficacious anti-HIV-1 vaccine. Although studies from patient had provided some insights on this issue, the differences in the study cohorts and methodology had make it difficult to reach a consensus of the variations in the HIV-1 Env functions during disease progression. To this end, an animal model that can be infected under controlled environment and reflect the disease course of HIV-1 infection in human will be beneficial. Such an animal model was previously demonstrated by the infection of macaque with SHIV, expressing HIV-1 clade C Env V1-V5 region. By using this model, we examined the changes in biological functions of Env in the infected animal over the entire disease course. Our data showed an increase in the neutralization resistance phenotype over time and coincided with the decrease in the net charges of the V1-V5 region. Infection of PBMC with provirus expressing various Env clones, isolated from the infected animal over time, showed a surprisingly better replicative fitness for viruses expressing the Env from early time point. Biotinylation and ELISA data also indicated a decrease of cell-surface-associated Env and virion-associated gp120 content with disease progression. This decrease did not affect the CD4-binding capability of Env, but were positively correlated with the decrease of Env fusion ability. Interestingly, some of these changes in biological functions reverted to the pre-AIDS level during advance AIDS. These data suggested a dynamic relationship between the Env V1-V5 region with the host immune pressure. The observed changes of biological functions in this setting might reflect and predict those occurring during natural disease progression in human.     

Accurate and rapid estimation of phosphene thresholds (REPT)

To calibrate the intensity of transcranial magnetic stimulation (TMS) at the occipital pole, the phosphene threshold is used as a measure of cortical excitability. The phosphene threshold (PT) refers to the intensity of magnetic stimulation that induces illusory flashes of light (phosphenes) on a proportion of trials. The existing PT estimation procedures lack the accuracy and mathematical rigour of modern threshold estimation methods. We present an improved and automatic procedure for estimating the PT which is based on the well-established Ψ Bayesian adaptive staircase approach. To validate the new procedure, we compared it with another commonly used procedure for estimating the PT. We found that our procedure is more accurate, reliable, and rapid when compared with an existing PT measurement procedure. The new procedure is implemented in Matlab and works automatically with the Magstim Rapid(2) stimulator using a convenient graphical user interface. The Matlab program is freely available for download.     

Potentiometric sensor for dipicolinic acid

A potentiometric chemosensor for selective determination of dipicolinic acid (2,6-pyridinedicarboxylic acid, DPA) was developed based on the surface imprinting technique coupled with a nanoscale transducer: an indium tin oxide (ITO)-coated glass plate. The sensor fabrication conditions, optimal recognition condition, as well as selectivity, sensitivity, and stability of the DPA sensor have been investigated. The DPA sensor could recognize DPA from 3,5-pyridinedicarboxylic acid. Potentiometric measurements demonstrated selective detection of DPA in a concentration range of 1.5 x 10(-6) to 0.0194 M. The response time of DPA sensor for 4 x 10(-4) M DPA was 25 s. The potentiometric response of the DPA sensor to DPA is at 90% of its initial magnitude after 550 times measurement. The viability of such a modified ITO electrode in the presence of other inorganic, organic, and biological materials was probed.     

Infant mortality in Armenia, 1992–2003

Health system reforms have been taken in Armenia during a time of dramatic economic and fiscal distress. It is important to assess trends in health indicators and ascertain if the changes in socio-economic systems affected the health status of infants as the most vulnerable part of the population. We find that infant mortality has fallen during the period c. 1992-2003 in spite of the difficult economic circumstances because of health-care procedures that were introduced. Particular attention is paid to the underreporting of infants' death cases in the state registration system as well as to estimating the role of different factors influencing infant mortality in Armenia.     

Receptors and ionic transporters in nuclear membranes: new targets for therapeutical pharmacological interventions

Work from our group and other laboratories showed that the nucleus could be considered as a cell within a cell. This is based on growing evidence of the presence and role of nuclear membrane G-protein coupled receptors and ionic transporters in the nuclear membranes of many cell types, including vascular endothelial cells, endocardial endothelial cells, vascular smooth muscle cells, cardiomyocytes, and hepatocytes. The nuclear membrane receptors were found to modulate the functioning of ionic transporters at the nuclear level, and thus contribute to regulation of nuclear ionic homeostasis. Nuclear membranes of the mentioned types of cells possess the same ionic transporters; however, the type of receptors is cell-type dependent. Regulation of cytosolic and nuclear ionic homeostasis was found to be dependent upon a tight crosstalk between receptors and ionic transporters of the plasma membranes and those of the nuclear membrane. This crosstalk seems to be the basis for excitation-contraction coupling, excitation-secretion coupling, and excitation - gene expression coupling. Further advancement in this field will certainly shed light on the role of nuclear membrane receptors and transporters in health and disease. This will in turn enable the successful design of a new class of drugs that specifically target such highly vital nuclear receptors and ionic transporters.