Graphene Quantum Dot-Based Optical Sensing Platform for Aflatoxin B1 Detection via the Resonance Energy Transfer Phenomenon.

An optical sensing platform for the detection of an important mycotoxin, aflatoxin B1 (AFB1), in the absence of a bioactive environment is explored. In this work, a fluorescence-based sensing technique was designed by combining graphene quantum dots (GQDs) and AFB1 via fluorescence quenching, where AFB1 acts as the quencher of GQD fluorescence. GQDs were synthesized through a single-step hydrothermal reaction from the leaves of "curry tree" (Murraya Koenigii) at 200 °C. The fluorescent GQDs were quenched by AFB1 (quencher), which itself is detecting the analyte. Hence, this study reports the direct sensing of the mycotoxin AFB1 without the involvement of inhibitors or biological entities. The possible mode of quenching is the nonradiative resonance energy transfer between the GQDs and the AFB1 molecules. This innovative sensor could detect AFB1 in the range from 5 to 800 ng mL-1 with a detection limit of 0.158 ng mL-1. The interferent study was also carried out in the presence of different mycotoxins and carbohydrates (d-fructose, cellulose, and starch), which demonstrated the high selectivity and robustness of the sensor in the complex sample matrix. The recovery percentage of the spiked samples was also calculated to be up to 106.8%. Thus, this study reports the first GQD based optical sensor for AFB1.

Soluble 4R0N Tau Abrogates Endocytic Vesicular Dynamics.

Aggregated tau is a hallmark neuropathological feature in numerous neurodegenerative disorders. Previous studies aiming to validate aggregated tau pathology as a pathogenic driver of neurodegeneration in correlation to characteristic behavioral phenotypes have had shortcomings. Although studies on soluble tau pathology have effectively addressed these shortcomings, the role of soluble tau in the molecular pathogenesis of neurodegeneration is not yet unequivocally established. In sporadic Alzheimer's disease (AD), the relevance of soluble tau pathology in endolysosomal dysfunction and autophagic stress, some of the earliest disease manifestations, is unclear. In this study, we report that soluble 4R0N tau overexpression affects the expression levels of certain markers associated with the endolysosomal system and autophagy. Moreover, through live-cell imaging, we found that the vesicular dynamics of early endosomes were affected with respect to spatiotemporal parameters and vesicle maturation. Additionally, we observed the localization of amyloid precursor protein (APP) along the endocytic pathway and found that upon overexpression of soluble 4R0N tau, APP was preferentially localized to the endocytic compartments implicated in the amyloidogenic pathway. Overall, our observations indicate that soluble 4R0N tau abrogates the dynamics of the endolysosomal system, autophagy, and affects the trafficking of APP. Since the amyloidogenic processing of APP occurs during its progression through the endocytic pathway, our results suggest that the generation of amyloid-ß (Aß) might also be modulated.

Pharmacological Tools to Modulate Autophagy in Neurodegenerative Diseases.

Considerable evidences suggest a link between autophagy dysfunction, protein aggregation, and neurodegenerative diseases. Given that autophagy is a conserved intracellular housekeeping process, modulation of autophagy flux in various model organisms have highlighted its importance for maintaining proteostasis. In postmitotic cells such as neurons, compromised autophagy is sufficient to cause accumulation of ubiquitinated aggregates, neuronal dysfunction, degeneration, and loss of motor coordination-all hallmarks of neurodegenerative diseases. Reciprocally, enhanced autophagy flux augments cellular and organismal health, in addition to extending life span. These genetic studies not-withstanding a plethora of small molecule modulators of autophagy flux have been reported that alleviate disease symptoms in models of neurodegenerative diseases. This review summarizes the potential of such molecules to be, perhaps, one of the first autophagy drugs for treating these currently incurable diseases.

One-Step Synthesized ZnO np-Based Optical Sensors for Detection of Aldicarb via a Photoinduced Electron Transfer Route.

Pesticides are used in agriculture for crop production enhancement by controlling pests, but they have acute toxicological effects on other life forms. Thus, it becomes imperative to detect their concentration in food products in a fast and accurate manner. In this study, ZnO nanoparticles (ZnO nps) have been used as optical sensors for the detection of pesticide Aldicarb via a photoinduced electron transfer (PET) route. ZnO nps were synthesized directly by calcining zinc acetate at 450, 500, and 550 °C for 2 h. ZnO nps were characterized by X-ray diffraction (XRD), Raman spectroscopy, scanning electron microscopy (SEM), and UV-vis absorption and photoluminescence (PL) spectroscopies to study the phase, crystallinity, shape, morphology, absorbance, and fluorescence of the prepared ZnO nps. XRD and Raman studies confirmed the crystalline nature of ZnO nps. The average crystallite size obtained was 13-20 nm from the XRD study. The SEM study confirmed spherical-shaped ZnO nps with average sizes in the range of 70-150 nm. The maximum absorbance was obtained in the 200-500 nm regions with a prominent peak absorbance at 372 nm from UV-vis spectra. The corresponding band gap for ZnO nps was calculated using Tauc's plots and was found to be 3.8, 3.67, and 3.45 eV for the 450, 500, and 550 °C calcined samples, respectively. The fluorescence spectra showed an increase in the intensity along with the increase in the size of ZnO nps. The ZnO nps (samples calcined at 500 and 550 °C) exhibited a response toward Aldicarb, owing to their pure phase and higher PL intensity. Both the samples showed systematic detection of Aldicarb in the range of 250 pM to 2 nM (500 °C) and 250 pM to 5 nM (550 °C). Among the various quenching mechanisms, PET was found to be the dominant process for the detection of Aldicarb. This method can be used for the detection of Aldicarb in real (food) samples using a portable fluorimeter.

Small molecule modulator of aggrephagy regulates neuroinflammation to curb pathogenesis of neurodegeneration.

BACKGROUND: Plethora of efforts fails to yield a single drug to reverse the pathogenesis of Parkinson's disease (PD) and related α-synucleopathies. METHODS: Using chemical biology, we identified a small molecule inhibitor of c-abl kinase, PD180970 that could potentially clear the toxic protein aggregates. Genetic, molecular, cell biological and immunological assays were performed to understand the mechanism of action. In vivo preclinical disease model of PD was used to assess its neuroprotection efficacy. FINDINGS: In this report, we show the ability of a small molecule inhibitor of tyrosine kinases, PD180970, to induce autophagy (cell lines and mice midbrain) in an mTOR-independent manner and ameliorate the α-synuclein mediated toxicity. PD180970 also exerts anti-neuroinflammatory potential by inhibiting the release of proinflammatory cytokines such as IL-6 (interleukin-6) and MCP-1 (monocyte chemoattractant protein-1) through reduction of TLR-4 (toll like receptor-4) mediated NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) activation. In vivo studies show that PD180970 is neuroprotective by degrading the toxic protein oligomers through induction of autophagy and subsiding the microglial activation. INTERPRETATION: These protective mechanisms ensure the negation of Parkinson's disease related motor impairments. FUND: This work was supported by Wellcome Trust/DBT India Alliance Intermediate Fellowship (500159-Z-09-Z), DST-SERB grant (EMR/2015/001946), DBT (BT/INF/22/SP27679/2018) and JNCASR intramural funds to RM, and SERB, DST (SR/SO/HS/0121/2012) to PAA, and DST-SERB (SB/YS/LS-215/2013) to JPC and BIRAC funding to ETA C-CAMP.