10 research outputs found
The Effect of Steel Industrial Residue-Enriched Soil on the Initial Growth and Heavy Metal Profiles of Elephantgrass
Heavy metal contamination of industrial sites are becoming a matter of growing concern. In spite of the substantial progress in the assessment of the influence of steel industrial plant waste on soil and water (Adamo et al., 2002), studies on the immediate responses of cultivated plants are still scarce. The objective of this experiment was to verify the short-term effects of soil added phosphate mud (P mud) or metallurgical scale (M scale), which are trace element-rich steel industry residues, on the initial uptake and heavy metal profiles of elephantgrass (Pennisetum purpureum
Gliotoxin, identified from a screen of fungal metabolites, disrupts 7SK snRNP, releases P-TEFb, and reverses HIV-1 latency
A leading pharmacological strategy toward HIV cure requires "shock" or activation of HIV gene expression in latently infected cells with latency reversal agents (LRAs) followed by their subsequent clearance. In a screen for novel LRAs, we used fungal secondary metabolites as a source of bioactive molecules. Using orthogonal mass spectrometry (MS) coupled to latency reversal bioassays, we identified gliotoxin (GTX) as a novel LRA. GTX significantly induced HIV-1 gene expression in latent ex vivo infected primary cells and in CD4+ T cells from all aviremic HIV-1+ participants. RNA sequencing identified 7SK RNA, the scaffold of the positive transcription elongation factor b (P-TEFb) inhibitory 7SK small nuclear ribonucleoprotein (snRNP) complex, to be significantly reduced upon GTX treatment of CD4+ T cells. GTX directly disrupted 7SK snRNP by targeting La-related protein 7 (LARP7), releasing active P-TEFb, which phosphorylated RNA polymerase II (Pol II) C-terminal domain (CTD), inducing HIV transcription
A phase I randomized therapeutic MVA-B vaccination improves the magnitude and quality of the T cell immune responses in HIV-1-infected subjects on HAART
Trial Design
Previous studies suggested that poxvirus-based vaccines might be instrumental in the therapeutic
HIV field. A phase I clinical trial was conducted in HIV-1-infected patients on highly
active antiretroviral therapy (HAART), with CD4 T cell counts above 450 cells/mm3 and
undetectable viremia. Thirty participants were randomized (2:1) to receive either 3 intramuscular
injections of MVA-B vaccine (coding for clade B HIV-1 Env, Gag, Pol and Nef antigens)
or placebo, followed by interruption of HAART.
Methods
The magnitude, breadth, quality and phenotype of the HIV-1-specific T cell response were
assayed by intracellular cytokine staining (ICS) in 22 volunteers pre- and post-vaccination.
Results
MVA-B vaccine induced newly detected HIV-1-specific CD4 T cell responses and expanded
pre-existing responses (mostly against Gag, Pol and Nef antigens) that were high in magnitude,
broadly directed and showed an enhanced polyfunctionality with a T effector memory
(TEM) phenotype, while maintaining the magnitude and quality of the pre-existing HIV-1-
specific CD8 T cell responses. In addition, vaccination also triggered preferential CD8+ T
cell polyfunctional responses to the MVA vector antigens that increase in magnitude after
two and three booster doses