Aminobisphosphonates reactivate the latent reservoir in people living with HIV-1

Antiretroviral therapy (ART) is not curative due to the existence of cellular reservoirs of latent HIV-1 that persist during therapy. Current research efforts to cure HIV-1 infection include “shock and kill” strategies to disrupt latency using small molecules or latency-reversing agents (LRAs) to induce expression of HIV-1 enabling cytotoxic immune cells to eliminate infected cells. The modest success of current LRAs urges the field to identify novel drugs with increased clinical efficacy. Aminobisphosphonates (N-BPs) that include pamidronate, zoledronate, or alendronate, are the first-line treatment of bone-related diseases including osteoporosis and bone malignancies. Here, we show the use of N-BPs as a novel class of LRA: we found in ex vivo assays using primary cells from ART-suppressed people living with HIV-1 that N-BPs induce HIV-1 from latency to levels that are comparable to the T cell activator phytohemagglutinin (PHA). RNA sequencing and mechanistic data suggested that reactivation may occur through activation of the activator protein 1 signaling pathway. Stored samples from a prior clinical trial aimed at analyzing the effect of alendronate on bone mineral density, provided further evidence of alendronate-mediated latency reversal and activation of immune effector cells. Decay of the reservoir measured by IPDA was however not detected. Our results demonstrate the novel use of N-BPs to reverse HIV-1 latency while inducing immune effector functions. This preliminary evidence merits further investigation in a controlled clinical setting possibly in combination with therapeutic vaccination

Closing the Implementation Gap: Bringing Clean Air to the Region

This report identifies 25 clean air measures that can positively impact human health, crop yields, climate change and socio-economic development, as well as contribute to achieving the Sustainable Development Goals. Implementing these measures could help 1 billion people breathe cleaner air by 2030 and reduce global warming by a third of a degree Celsius by 2050

Teacher education at a distance : exploring meanings through dialogues with Nepalese teachers

Doctor of Philosoph

Guard Cell Purification and RNA Isolation Suitable for High-Throughput Transcriptional Analysis of Cell-Type Responses to Biotic Stresses

Stomata, the micro-pores on leaf surface, are formed by a pair of guard cells. In addition to control water loss and gas exchange between the plant and the environment, these cells act as immunity gates to prevent pathogen invasion of the plant apoplast. Here, we report a brief procedure to obtain highly pure guard cell preparations using conditions that preserve the guard cell transcriptome as much as possible for a robust high-throughput RNA sequence analysis. The advantages of this procedure included: 1) substantial shortening of the time required for obtaining high yield of >97% pure guard cell protoplasts (GCP), 2) extraction of enough amount of high quality RNA for direct sequencing, and 3) limited RNA decay during sample manipulation. Gene expression analysis by RT-qPCR revealed that wound-related genes were not induced during release of guard cells from leaves. To validate our approach, we performed a high throughput deep-sequencing of guard cell transcriptome (RNA-seq). A total of 18,994 nuclear-encoded transcripts was detected, which expanded the transcriptome by 70%. The optimized GCP isolation and RNA extraction protocols are simple, reproducible, and fast allowing the discovery of genes and regulatory networks inherent to the guard cells under various stresses

Probing the local structure and the role of protons in lithium sorption processes of a new lithium-rich manganese oxide

International audienc