BIN1 in the Pursuit of Ousting the Alzheimer's Reign: Impact on Amyloid and Tau Neuropathology.

Alzheimer's disease contributes to 60-70% of all dementia cases in the general population. Belonging to the BIN1/amphiphysin/RVS167 (BAR) superfamily, the bridging integrator (BIN1) has been identified to impact two major pathological hallmarks in Alzheimer's disease (AD), i.e., amyloid beta (Aß) and tau accumulation. Aß accumulation is found to increase by BIN1 knockdown in cortical neurons in late-onset AD, due to BACE1 accumulation at enlarged early endosomes. Two BIN1 mutants, KR and PL, were identified to exhibit Aß accumulation. Furthermore, BIN1 deficiency by BIN1-related polymorphisms impairs the interaction with tau, thus elevating tau phosphorylation, altering synapse structure and tau function. Even though the precise role of BIN1 in the neuronal tissue needs further investigation, the authors aim to throw light on the potential of BIN1 and unfold its implications on tau and Aß pathology, to aid AD researchers across the globe to examine BIN1, as an appropriate target gene for disease management.

Molecular docking and simulation studies of natural compounds of Vitex negundo L. against papain-like protease (PLpro) of SARS CoV-2 (coronavirus) to conquer the pandemic situation in the world.

The severe acute respiratory syndrome coronavirus-2 (SARS CoV-2) is ß-coronavirus that is responsible for the pandemic coronavirus disease 2019 (COVID-19) all over the world. The rapid spread of the novel SARS CoV-2 worldwide is raising a significant global public health issue with nearly 61.86 million people infected and 1.4 million deaths. To date, no specific drugs are available for the treatment of COVID-19. The inhibition of proteases essential for the proteolytic treatment of viral polyproteins is a conventional therapeutic strategy for conquering viral infections. In the study, molecular docking approach was used to screen potential drug compounds among the phytochemicals of Vitex negundo L. against COVID-19 infection. Molecular docking analysis showed that oleanolic acid forms a stable complex and other phyto-compounds ursolic acid, 3ß-acetoxyolean-12-en-27-oic acid and isovitexin of V. negundo natural compounds form a less-stable complex. When compared with the control the synergistic interaction of these compounds shows inhibitory activity against papain-like protease (PLpro) of SARS CoV-2 (COVID-19). The molecular dynamics (MD) simulation (50 ns) were performed on the complexes of PLpro and the phyto-compounds viz. oleanolic acid, ursolic acid, 3ß-acetoxyolean-12-en-27-oic acid and isovitexin followed by the binding free energy calculations using MM-GBSA and these molecules have stable interactions with PLpro protein binding site. The MD simulation study provides more insight into the functional properties of the protein-ligand complex and suggests that these molecules can be considered as a potential drug molecule against COVID-19. In this pandemic situation, these herbal compounds provide a rich resource to produce new antivirals against COVID-19.Communicated by Ramaswamy H. Sarma.

A Turn-ON fluorometric biosensor based on ssDNA immobilized with a metal phenolic nanomaterial for the sequential detection of Pb(ii) and epirubicin cancer drug.

In this paper, we propose a fluorescent biosensor for the sequential detection of Pb2+ ions and the cancer drug epirubicin (Epn) using the interactions between label-free guanine-rich ssDNA (LFGr-ssDNA), acridine orange (AO), and a metal-phenolic nanomaterial (i.e., nano-monoclinic copper-tannic acid (NMc-CuTA)). An exploration of the sensing mechanism shows that LFGr-ssDNA and AO strongly adsorb on NMc-CuTA through π-π stacking and electrostatic interactions, and this results in the fluorescence quenching of AO. In order to sense the target Pb2+, initially, LFGr-ssDNA specifically binds with Pb2+ ions to form a G4 complex (G-Pb2+-G base pair), which was released from the surface of NMc-CuTA with strong AO fluorescence enhancement (Turn-ON). The subsequent addition of a biothiol, like cysteine (Cys), to the G4 complex decreases the fluorescence, as the Pb2+ ions released from the G4 complex have a higher interaction affinity with the sulfur atoms of Cys; this further induces the unwinding of the G4 complex to form LFGr-ssDNA. Finally, Epn was added to this, which intercalates with LFGr-ssDNA to form a G4 complex via G-Epn-G, resulting in fluorescence recovery (Turn-ON). Accordingly, the Turn-ON fluorescent probe had subsequent limits of detection of 1.5 and 5.6 nM for Pb2+ and Epn, respectively. Hence, the reported NMc-CuTA-based sensing platform has potential applications for the detection of Pb2+ and Epn in real samples with good sensitivity and selectivity.

Effects of water deficit stress on agronomic and physiological responses of rice and greenhouse gas emission from rice soil under elevated atmospheric CO2.

Rice is the foremost staple food in the world, safeguarding the global food and nutritional security. Rise in atmospheric carbon dioxide (CO2) and water deficits are threatening global rice productivity and sustainability. Under real field conditions these climatic factors often interact with each other resulting in impacts that are remarkably different compared to individual factor exposure. Rice soils exposed to drought and elevated CO2 (eCO2) alters the biomass, diversity and activity of soil microorganisms affecting greenhouse gas (GHG) emission dynamics. In this review we have discussed the impacts of eCO2 and water deficit on agronomic, biochemical and physiological responses of rice and GHGs emissions from rice soils. Drought usually results in oxidative stress due to stomatal closure, dry weight reduction, formation of reactive oxygen species, decrease in relative water content and increase in electrolyte leakage at almost all growth and developmental phases of rice. Elevated atmospheric CO2 concentration reduces the negative effects of drought by improving plant water relations, reducing stomatal opening, decreasing transpiration, increasing canopy photosynthesis, shortening crop growth period and increasing the antioxidant metabolite activities in rice. Increased scientific understanding of the effects of drought and eCO2 on rice agronomy, physiology and GHG emission dynamics of rice soil is essential for devising adaptation options. Integration of novel agronomic practices viz., crop establishment methods and alternate cropping systems with improved water and nutrient management are important steps to help rice farmers cope with drought and eCO2. The review summarizes future research needs for ensuring sustained global food security under future warmer, drier and high CO2 conditions.

T-cell death following immune activation is mediated by mitochondria-localized SARM.

Following acute-phase infection, activated T cells are terminated to achieve immune homeostasis, failure of which results in lymphoproliferative and autoimmune diseases. We report that sterile α- and heat armadillo-motif-containing protein (SARM), the most conserved Toll-like receptors adaptor, is proapoptotic during T-cell immune response. SARM expression is significantly reduced in natural killer (NK)/T lymphoma patients compared with healthy individuals, suggesting that decreased SARM supports NK/T-cell proliferation. T cells knocked down of SARM survived and proliferated more significantly compared with wild-type T cells following influenza infection in vivo. During activation of cytotoxic T cells, the SARM level fell before rising, correlating inversely with cell proliferation and subsequent T-cell clearance. SARM knockdown rescued T cells from both activation- and neglect-induced cell deaths. The mitochondria-localized SARM triggers intrinsic apoptosis by generating reactive oxygen species and depolarizing the mitochondrial potential. The proapoptotic function is attributable to the C-terminal sterile alpha motif and Toll/interleukin-1 receptor domains. Mechanistically, SARM mediates intrinsic apoptosis via B cell lymphoma-2 (Bcl-2) family members. SARM suppresses B cell lymphoma-extra large (Bcl-xL) and downregulates extracellular signal-regulated kinase phosphorylation, which are cell survival effectors. Overexpression of Bcl-xL and double knockout of Bcl-2 associated X protein and Bcl-2 homologous antagonist killer substantially reduced SARM-induced apoptosis. Collectively, we have shown how T-cell death following infection is mediated by SARM-induced intrinsic apoptosis, which is crucial for T-cell homeostasis.

Magnetic nanoparticle (Fe3O4) impregnated onto tea waste for the removal of nickel(II) from aqueous solution.

The removal of Ni(II) from aqueous solution by magnetic nanoparticles prepared and impregnated onto tea waste (Fe(3)O(4)-TW) from agriculture biomass was investigated. Magnetic nanoparticles (Fe(3)O(4)) were prepared by chemical precipitation of a Fe(2+) and Fe(3+) salts from aqueous solution by ammonia solution. These magnetic nanoparticles of the adsorbent Fe(3)O(4) were characterized by surface area (BET), Scanning Electron Microscopy (SEM), Transmission Electron Microscopy (TEM) and Fourier Transform-Infrared Spectroscopy (FT-IR). The effects of various parameters, such as contact time, pH, concentration, adsorbent dosage and temperature were studied. The kinetics followed is first order in nature, and the value of rate constant was found to be 1.90×10(-2) min(-1) at 100 mg L(-1) and 303 K. Removal efficiency decreases from 99 to 87% by increasing the concentration of Ni(II) in solution from 50 to 100 mg L(-1). It was found that the adsorption of Ni(II) increases by increasing temperature from 303 to 323 K and the process is endothermic in nature. The adsorption isotherm data were fitted to Langmuir and Freundlich equation, and the Langmuir adsorption capacity, Q°, was found to be (38.3)mgg(-1). The results also revealed that nanoparticle impregnated onto tea waste from agriculture biomass, can be an attractive option for metal removal from industrial effluent.

Influence of edaphic factors on the mineralization of neem oil coated urea in four Indian soils.

The utility of neem (Azadirachta indica A Juss) oil coated urea as a value-added nitrogenous fertilizer has been now widely accepted by Indian farmers and the fertilizer industry. In the present study, the expeller grade (EG) and hexane-extracted (HE) neem oils, the two most common commercial grades, were used to prepare neem oil coated urea (NOCU) of various oil doses, for which mineralization rates were assessed in four soils at three incubation temperatures (20, 27, and 35 degrees C). Neem oil dose-dependent conservation of ammonium N was observed in NOCU treatments in all of the soils. However, a longer incubation period and a higher soil temperature caused depletion of ammonium N. Overall, the nitrification in NOCU treatment averaged 56.6% against 77.3% for prilled urea in four soils. NOCU prepared from EG neem oil was consistently superior to that derived from hexane-extracted oil. The performance of NOCUs was best in coarse-textured soil and poorest in sodic soil. The nitrification rate (NR) of the NOCUs in the soils followed the order sodic > fine-textured > medium-textured > coarse-textured. The influence of edaphic factors on NR of NOCUs has been highlighted. The utility of the present study in predicting the performance of NOCU in diverse Indian soils was highlighted through the use of algorithms for computation of the optimum neem oil dose that would cause maximum inhibition of nitrification in any soil.

Survey on ochratoxin A in Indian green coffee destined for export.

Ochratoxin A (OTA) is a toxic metabolite, produced by Aspergillus spp. and Penicillium verrucosum, that is nephrotoxic and possibly carcinogenic to humans. The aim of this study was to evaluate OTA contamination in batches of green coffee destined for export. Analysis of 80 green coffee samples indicated that, although a high incidence (74%) of OTA contamination (0.2-13.5 ng g⁻¹) was recorded, the overall mean OTA level (2.17 ± 2.45 ng g⁻¹) was low. The highest recorded OTA concentration was 13.5 ng g⁻¹ in a robusta cherry sample and only five samples had OTA above 5 ng g⁻¹ level. The mean OTA level was higher in cherry (range: 1.63 ± 0.97-4.8 ± 3.90) than parchment (0.56 ± 0.35-1.10 ± 0.28), indicating a correlation between processing method and OTA contamination.