The transcellular propagation of the aberrantly modified protein tau along the functional brain network is a key hallmark of Alzheimer's disease and related tauopathies. Inoculation-based tau ...propagation models can recapitulate the stereotypical spread of tau and reproduce various types of tau inclusions linked to specific tauopathy, albeit with varying degrees of fidelity. With this systematic review, we underscore the significance of judicious selection and meticulous functional, biochemical, and biophysical characterization of various tau inocula. Furthermore, we highlight the necessity of choosing suitable animal models and inoculation sites, along with the critical need for validation of fibrillary pathology using confirmatory staining, to accurately recapitulate disease-specific inclusions. As a practical guide, we put forth a framework for establishing a benchmark of inoculation-based tau propagation models that holds promise for use in preclinical testing of disease-modifying drugs.
The persistence of latent HIV-1 reservoirs in cells presents a formidable challenge towards a complete HIV cure. Edelfosine is an FDA-approved investigational, anti-neoplastic drug. In this study, we ...aimed to investigate its role as a HIV-1 Latency Reversal Agent (LRA) using latency model cell lines. Our findings demonstrated that edelfosine reactivated latent HIV-1 viruses in myeloid cells in a dose and time-dependent manner. The mechanism of reactivation by edelfosine involved the activation of NF-κB and AP1 pathways in these cells. The reactivated virus was non-infectious. Delineating the mechanism of non-infectious virus production revealed an increased stabilization of cellular APOBEC3G protein as well as its enhanced incorporation into the released viruses. Thus, our study demonstrated for the first time an additional role of edelfosine in reactivation of latent HIV-1 and production of non-infectious virus. Our results have paved the way for repurposing of edelfosine as a novel HIV-1 latency reversal agent.
•Edelfosine reactivated latent HIV-1 in myeloid cells in a dose and time-dependent manner.•The mechanism of reactivation involved the activation of NF-κB and AP1 pathways.•The reactivated virus was non-infectious due to enhanced APOBEC3G packaging.•Our results shows edelfosine may be repurposed as a novel LRA.
Cereals are staple food for many countries and are grown on millions of hectares of land, but much of the harvest is wasted due to losses by pests. To minimize these losses, many pesticides are used ...which are damaging to the environment and human health. There are debates to get rid of these chemicals but they are still in use at large scale. An alternative control strategy for insect pests in storage houses is the use of botanicals. In this study, four plant essential oils, two plant extracts, two herbicides, and two insecticides were used against Tribolium confusum and the comparison of toxicity was made by calculating LC50 and LT50 values. LC50 values were higher for abamectin (2.09–10.23 mg/L) and cypermethrin (3.41–11.78 mg/L) insecticides followed by neem essential oil (7.39–19.24 mg/L) and citrus extract (10.14–24.50 mg/L). However, LC50 values were maximum in case of jaman plant extract (22.38–176.42 mg/L) followed by two herbicides, Logran (19.66–39.72 mg/L) and Topik (29.09–47.67 mg/L) However, LC50 values were higher for topic herbicide (24.098 ppm) and jaman essential oil (16.383 ppm) after four days of treatment. Abamectin and cypermethrin insecticides, neem essential oil and citrus plant extract also killed adults of T. confusum quicker as compared other essential oils, extracts and herbicides. Results revealed that botanical formulations being environmentally safe could be used instead of highly hazardous pesticides for stored products’ pests. This study also elaborates the non-host toxicity of herbicides commonly applied in our agroecosystem.
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