Administration of vorinostat disrupts HIV-1 latency in patients on antiretroviral therapy

Despite antiretroviral therapy, proviral latency of human immunodeficiency virus type 1 (HIV-1) remains a principal obstacle to curing the infection. Inducing the expression of latent genomes within resting CD4(+) T cells is the primary strategy to clear this reservoir. Although histone deacetylase inhibitors such as suberoylanilide hydroxamic acid (also known as vorinostat, VOR) can disrupt HIV-1 latency in vitro, the utility of this approach has never been directly proven in a translational clinical study of HIV-infected patients. Here we isolated the circulating resting CD4(+) T cells of patients in whom viraemia was fully suppressed by antiretroviral therapy, and directly studied the effect of VOR on this latent reservoir. In each of eight patients, a single dose of VOR increased both biomarkers of cellular acetylation, and simultaneously induced an increase in HIV RNA expression in resting CD4(+) cells (mean increase, 4.8-fold). This demonstrates that a molecular mechanism known to enforce HIV latency can be therapeutically targeted in humans, provides proof-of-concept for histone deacetylase inhibitors as a therapeutic class, and defines a precise approach to test novel strategies to attack and eradicate latent HIV infection directly.     

Effects of plant hormones on leucine aminotransferase in pea (Pisum sativum)

Summary The work reported here shows a specific effect of kinetin in enhancing LAT activity in pea buds and indicating its possible mode of action at the translational level. Other hormones tested did not show any appreciable effect on the enzyme activity.One of us (J. C.) is grateful to NCERT, India, for the grant of a fellowship to her.     

Development of lead-free multifunctional materials Bi(Co0.45Ti0.45Fe0.10)O3

A lead free multiferroic material,Bi(Co_(0.45)Ti_(0.45)Fe_(0.10))O_3(BCTF45/10)was synthesized by a solid-state reaction route at high temperatures.BCTF45/10 powder was prepared using appropriate raw maretials in oxide powders with methanol medium.As-prepared circular shaped pellets were sintered at 1053 K for 6 h to produce a compact form.Preliminary structural properties and elemental analysis were determined using X-ray diffraction and energy-dispersive X-ray spectroscopy techniques respectively at room temperature.The microstructure or surface morphology of the sintered sample was carried out by using field emission scanning electron microscope(FE-SEM).The XRD analysis shows that the compound exhibits the single-phase of orthorhombic symmetry.The average crystallite size estimated using the Scherrer's technique was found to be 30 nm.The influence of Co and Ti substitution(at Bi and Ti sites of Bi Fe O_3)on some physical and electrical properties of Bi Fe O_3was examined by using phase sensitive multimeter in a wide frequency and temperature ranges.The magnetic nature of the sample was studied using vibrating sample magnetometer.Study of room temperature magnetic hysteresis loop exhibits the enhanced ferromagnetic characteristic with saturation magnetization of 5.091 emu/g and coercive field of 0.213 k Oe respectively.The enhanced magnetic properties highlight various potential applications of Co/Ti doped BCTF45/10 materials.     

Efficiency of nonhomologous DNA end joining varies among somatic tissues,despite similarity in mechanism

Failure to repair DNA double-strand breaks (DSBs) can lead to cell death or cancer. Although nonhomologous end joining (NHEJ) has been studied extensively in mammals, little is known about it in primary tissues. Using oligomeric DNA mimicking endogenous DSBs, NHEJ in cell-free extracts of rat tissues were studied. Results show that efficiency of NHEJ is highest in lungs compared to other somatic tissues. DSBs with compatible and blunt ends joined without modifications, while noncompatible ends joined with minimal alterations in lungs and testes. Thymus exhibited elevated joining, followed by brain and spleen, which could be correlated with NHEJ gene expression. However, NHEJ efficiency was poor in terminally differentiated organs like heart, kidney and liver. Strikingly, NHEJ junctions from these tissues also showed extensive deletions and insertions. Hence, for the first time, we show that despite mode of joining being generally comparable, efficiency of NHEJ varies among primary tissues of mammals.