7 research outputs found
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
Trap attributes influencing capture of Diabrotica speciosa (Coleoptera: Chrysomelidae) on common bean fields Atributos da armadilha influenciam captura de Diabrotica speciosa (Coleoptera: Chrysomelidae) em feijoeiro
Refinements in trap characteristics may improve ability to monitor and mass-trap beetles. Field assays were conducted in common bean fields to assess responses of Diabrotica speciosa (Germar) to some trap characteristics. Golden yellow plastic cups (750 mL) traps caught more D. speciosa females and males than did clear traps. Carrot slices in Petri dishes baited with Lagenaria vulagaris L. powder (cucurbitacin source - 0.28%) caught more beetles than did dishes with carrot alone. Dispensers for the floral volatile attractant 1,4-dimethoxybenze were also compared. Rubber septa dispenser attracted more beetles than did control (dental wicks saturated with acetone). Captures on dental wick, starch matrix and feminine pad dispensers were intermediate and did not differ from those on rubber septa and unbaited controls. Perforated bottle traps (2000 mL), when baited with the floral attractant, caught more beetles than did window bottle traps (both traps contained L. vulgaris powder) in most assessments done from two to ten days after trap placement in the field. Traps with the insecticide carbaryl captured more beetles than did traps without it, 2-4 and 8-10 days after trap placement in the field, but not in the remaining periods (0-2, 4-6 and 6-8 days). Traps baited with 1,4-dimethoxybenzene captured more beetles than did the unbaited ones in all assessments (each other day from two to ten days after trap placement in the field). Finally, similar amounts of beetles were captured using plastic bottle traps (2000 mL): perforated, window (both with cucurbitacin) and sticky (without cucurbitacin) traps, when were baited with the floral attractant.<br>Refinamentos em caraterĂsticas de armadilhas podem incrementar sua habilidade para monitorar e capturar em massa os insetos. Experimentos foram conduzidos em lavoura de feijoeiro para verificar as respostas de Diabrotica speciosa (Germar) a algumas caracterĂsticas de armadilhas. Armadilhas de copos plástico (750 mL) amarelo ouro capturaram mais fĂŞmeas e machos de D. speciosa do que transparentes. Placas de Petri com pedaços de cenoura, com pĂł seco de purungo, Lagenaria vulgaris L. (fonte de cucurbitacina - 0,28%) capturaram mais insetos do que placas com somente cenoura. Liberadores para o atraente floral 1,4-dimetoxibenzeno foram tambĂ©m comparados. Liberador de septo de borracha atraiu mais insetos do que o controle (flocos dentais saturados com acetona). Capturas nos tratamentos com liberadores de floco dental, matriz borato e absorvente higiĂŞnico foram intermediárias mas nĂŁo diferiram da testemunha e septo. Modelo de armadilha de garrafa (2000 mL) furada capturou mais insetos do que armadilha vazada ("janelas") (ambas contendo pĂł seco de purungo) na maioria das avaliações, dos dois atĂ© os dez dias apĂłs a instalação das armadilhas no campo. Armadilhas com inseticida carbaryl capturaram mais insetos do que armadilhas sem, nos intervalos de 2-4 e 9-10 dias apĂłs a instalação das armadilhas no campo. Nos perĂodos restantes (0-2, 4-6- e 6-8 dias), diferenças nĂŁo foram detectadas. Armadilhas com 1,4-dimetoxibenzeno capturaram mais insetos do que armadilhas sem o volátil (avaliações a cada dois dias dos dois aos dez dias apĂłs a instalação no campo). Finalmente, quantidades similares de insetos foram capturadas usando armadilhas de garrafa pet (2000 mL): vazadas ("janelas"), furadas (ambas com cucurbitacina) e adesivas quando estas foram iscadas com o atraente floral