Plasmon-emitter coupling in cytosine-rich hairpin DNA-templated silver nanoclusters: Thermal reversibility, white light emission, and dynamics inside live cells.

Bio-templated luminescent noble metal nanoclusters (NCs) have attracted great attention for their intriguing physicochemical properties. Continuous efforts are being made to prepare NCs with high fluorescence quantum yield (QY), good biocompatibility, and tunable emission properties for their widespread practical applications as new-generation environment-friendly photoluminescent materials in materials chemistry and biological systems. Herein, we explored the unique photophysical properties of silver nanoclusters (AgNCs) templated by cytosine-rich customized hairpin DNA. Our results indicate that a 36-nucleotide containing hairpin DNA with 20 cytosine (C20) in the loop can encapsulate photostable red-emitting AgNCs with an absolute QY of ∼24%. The luminescent properties in these DNA-templated AgNCs were found to be linked to the coupling between the surface plasmon and the emitter. These AgNCs exhibited excellent thermal sensitivity and were employed to produce high-quality white light emission with an impressive color rendering index of 90 in the presence of dansyl chloride. In addition, the as-prepared luminescent AgNCs possessing excellent biocompatibility can effectively mark the nuclear region of HeLa cells and can be employed as a luminescent probe to monitor the cellular dynamics at a single molecular resolution.

Mechanistic elucidation of the catalytic activity of silver nanoclusters: exploring the predominant role of electrostatic surface.

The core and the ligand shell of metal nanoclusters (MNCs) have an influential role in modulating their spectroscopic signatures and catalytic properties. The aspect of electrostatic interactions to regulate the catalytic properties of MNCs has not been comprehensively addressed to date. Our present work conclusively delineates the role of the metal core and the electrostatic surface of MNCs involved in the reduction of nitroarenes. A facile surface modification of mercaptosuccinic acid (MSA)-templated AgNCs has been selectively achieved through Mg2+ ions (Mg-AgNCs). Microscopic studies suggest that the size of Mg-AgNCs is ∼3.3 nm, which is considerably higher than that of MSA-templated AgNCs (∼1.75 nm), confirming the formation of a nano-assembled structure. Our spectroscopic and microscopic experiments revealed that the negatively charged AgNCs efficiently catalyze the reduction of 4-nitrophenol (4-NP) with a rate constant of 0.23 ± 0.01 min-1. However, upon surface modification, the catalytic efficiency almost doubles due to the formation of Mg-AgNCs. Catalysis through AgNCs and Mg-AgNCs collectively portrays the role of the core and electrostatic surfaces. Furthermore, the role of electrostatic interaction has been substantiated by varying the ionic strength of the medium, as well as employing different molecular systems. A quantitative assessment of the Debye screening length asserts the correlation between the ionic strength of the medium and the role of electrostatic interactions involved herein. This highly enhanced catalytic aspect has been utilized for the real sample analysis, wherein AgNCs unexpectedly outperform Mg-AgNCs. This approach of real sample analysis also emanates the role of electrostatics involved. This comprehensive investigation represents the influential role of the core and ligand shell of MNCs as well as the role of electrostatics on its catalytic activities, which is relevant for the rational design of highly efficient catalysts.

Plant growth promoting rhizobacterium Bacillus sp. BSE01 alleviates salt toxicity in chickpea (Cicer arietinum L.) by conserving ionic, osmotic, redox and hormonal homeostasis.

Soil salinity leading to sodium toxicity is developing into a massive challenge for agricultural productivity globally, inducing osmotic, ionic, and redox imbalances in plants. Considering the predicted increase in salinization risk with the ongoing climate change, applying plant growth-promoting rhizobacteria (PGPR) is an environmentally safe method for augmenting plant salinity tolerance. The present study examined the role of halotolerant Bacillus sp. BSE01 as a promising biostimulant for improving salt stress endurance in chickpea. Application of PGPR significantly increased the plant height, relative water content, and chlorophyll content of chickpea under both non-stressed and salt stress conditions. The PGPR-mediated tolerance towards salt stress was accomplished by the modulation of hormonal signaling and conservation of cellular ionic, osmotic, redox homeostasis. With salinity stress, the PGPR-treated plants significantly increased the indole-3-acetic acid and gibberellic acid contents more than the non-treated plants. Furthermore, the PGPR-inoculated plants maintained lower 1-aminocyclopropane-1-carboxylic acid and abscisic acid contents under salt treatment. The PGPR-inoculated chickpea plants also exhibited a decreased NADPH oxidase activity with reduced production of reactive oxygen species compared to the non-inoculated plants. Additionally, PGPR treatment led to increased antioxidant enzyme activities in chickpea under saline conditions, facilitating the reactive nitrogen and oxygen species detoxification, thereby limiting the nitro-oxidative damage. Following salinity stress, enhanced K+ /Na+ ratio and proline content were noted in the PGPR-inoculated chickpea plants. Therefore, Bacillus sp. BSE01, being an effective PGPR and salinity stress reducer, can further be considered to develop a bioinoculant for sustainable chickpea production under saline environments.

pH-Switchable phenylalanine-templated copper nanoclusters: CO2 probing and efficient peroxidase mimicking activity.

Inter-cluster conversion through the strategic tuning of external stimuli and thereby modulation of the optical properties of metal nanoclusters (MNCs) is an emerging domain for exploration. Herein, we report the preparation of blue-emitting CuNCs using phenylalanine (Phe) as a template under acidic conditions (pH ∼ 4). The as-prepared CuNCs exhibit a sequential tuning of the photophysical properties upon varying the pH of the solution from pH ∼4 to pH ∼12. Blue-emitting CuNCs (B-CuNCs, λem = 410 nm) are systematically converted to cyan-emitting CuNCs (C-CuNCs, λem = 490 nm) with a large red-shifted emission maximum by 80 nm as a function of pH. Our present investigation delineates an unprecedented switchability of the photoluminescence (PL) properties of the CuNCs with the variations of the pH from pH ∼4 to pH ∼12. Both the Phe-templated CuNCs (B-CuNCs and C-CuNCs) were broadly characterized by various spectroscopic and morphological techniques. The X-ray photoelectron spectroscopy (XPS) studies reveal the presence of different oxidation states in the metallic core of B-CuNCs and C-CuNCs. These results in turn substantiate the pH-induced intercluster conversion of CuNCs through the substantial change in their core composition as well as valence states. Owing to the pH sensitivity, the CuNCs act as an efficient and highly sensitive probe for CO2, and quantitative estimation of the dissolved CO2 in the form of bicarbonate ions has been achieved through the enhancement of the PL intensity, wherein a very low value of the limit of detection (LOD) of ∼60 µM was obtained. Furthermore, we demonstrated that the CuNCs act as an efficient bio-catalyst with peroxidase mimicking enzymatic activity which has been investigated using OPD as a substrate under physiological conditions (pH ∼7.4 and temperature ∼37 °C). The mechanistic investigations confirmed that the oxidation of OPD mainly proceeds through the generation of hydroxyl radicals (˙OH). We hope the present investigations shed light on a multidimensional aspect of MNCs and uncover an upsurging recent interest in MNCs to act as an artificial enzyme.

Solvent-Induced Modulation in the Optical Properties of Copper Nanoclusters and Revealing the Isomeric Effect of Templates.

The solvent plays an influential role in controlling the nucleation process of metal nanoclusters (MNCs) and thereby significantly modulates their optical signatures. Herein, we have demonstrated the solvent-induced modulation in the optical properties of copper nanoclusters (CuNCs), primarily governed by the solvent polarity. During the preparation of para-mercaptobenzoic acid (p-MBA)-templated CuNCs, the simultaneous formation of blue-emitting CuNCs (B-CuNCs) and red-emitting CuNCs (R-CuNCs) were observed up to 7 h of reaction time, reflected from the systematic increment in the photoluminescence (PL) intensity at 420 nm and 615 nm, respectively. However, after 7 h of reaction time, the exclusive formation of B-CuNCs was observed. Such simultaneous growth and depletion dynamics of CuNCs result in a significant modulation in their optical properties. The variation of the solvent from water to less polar solvents such as DMSO and DMF restricts this inter-cluster dynamics by stabilizing both the CuNCs (B-CuNCs and R-CuNCs). Thereby, a single-component White Light Emission (WLE) was realized in DMSO with CIE coordinates (0.37, 0.36). The isomeric effect of the templates has also been investigated which extensively controls the optical and catalytic properties of the CuNCs.

Overexpression of flowering locus D (FLD) in Indian mustard (Brassica juncea) enhances tolerance to Alternaria brassicae and Sclerotinia sclerotiorum.

KEY MESSAGE: Overexpression of BjFLD in Brassica juncea imparts resistance against fungal pathogens and increases the yield. These transgenics could lower the use of fungicides, which have detrimental effects on the environment. Productivity of Indian mustard (Brassica juncea) is adversely affected by fungal phytopathogens, Alternaria brassicae and Sclerotinia sclerotiorum. Arabidopsis flowering locus D (FLD) positively regulates jasmonic acid signaling and defense against necrotrophic pathogens. In this study, the endogenous FLD (B. juncea FLD; BjFLD) in Indian mustard was overexpressed in B. juncea to determine its role in biotic stress tolerance. We report the isolation, characterization, and functional validation of BjFLD. The transgene expression was confirmed by qRT-PCR. The constitutive overexpression of BjFLD enhanced the tolerance of B. juncea to A. brassicae and S. sclerotiorum, which was manifested as delayed appearance of symptom, impeded disease progression, and enhanced percentage of disease protection. The transgenic lines maintained a higher photosynthetic capacity and redox potential under biotic stress and could detoxify reactive oxygen species (ROS) by modulating the antioxidant machinery and physiochemical attributes. The BjFLD-overexpressing lines showed enhanced SA level as well higher NPR1 expression. The overexpression of BjFLD induced early flowering and higher seed yield in the transgenic lines. These findings indicate that overexpression of BjFLD enhances the tolerance of B. juncea to A. brassicae and S. sclerotiorum by induction of systemic acquired resistance and mitigating the damage caused by stress-induced ROS.

Game Theory-Based Authentication Framework to Secure Internet of Vehicles with Blockchain.

The Internet of Vehicles (IoV) is a new paradigm for vehicular networks. Using diverse access methods, IoV enables vehicles to connect with their surroundings. However, without data security, IoV settings might be hazardous. Because of the IoV's openness and self-organization, they are prone to malevolent attack. To overcome this problem, this paper proposes a revolutionary blockchain-enabled game theory-based authentication mechanism for securing IoVs. Here, a three layer multi-trusted authorization solution is provided in which authentication of vehicles can be performed from initial entry to movement into different trusted authorities' areas without any delay by the use of Physical Unclonable Functions (PUFs) in the beginning and later through duel gaming, and a dynamic Proof-of-Work (dPoW) consensus mechanism. Formal and informal security analyses justify the framework's credibility in more depth with mathematical proofs. A rigorous comparative study demonstrates that the suggested framework achieves greater security and functionality characteristics and provides lower transaction and computation overhead than many of the available solutions so far. However, these solutions never considered the prime concerns of physical cloning and side-channel attacks. However, the framework in this paper is capable of handling them along with all the other security attacks the previous work can handle. Finally, the suggested framework has been subjected to a blockchain implementation to demonstrate its efficacy with duel gaming to achieve authentication in addition to its capability of using lower burdened blockchain at the physical layer, which current blockchain-based authentication models for IoVs do not support.

Sequential asymmetric third order rotatable designs (SATORDs).

Rotatable designs that are available for process/ product optimization trials are mostly symmetric in nature. In many practical situations, response surface designs (RSDs) with mixed factor (unequal) levels are more suitable as these designs explore more regions in the design space but it is hard to get rotatable designs with a given level of asymmetry. When experimenting with unequal factor levels via asymmetric second order rotatable design (ASORDs), the lack of fit of the model may become significant which ultimately leads to the estimation of parameters based on a higher (or third) order model. Experimenting with a new third order rotatable design (TORD) in such a situation would be expensive as the responses observed from the first stage runs would be kept underutilized. In this paper, we propose a method of constructing asymmetric TORD by sequentially augmenting some additional points to the ASORDs without discarding the runs in the first stage. The proposed designs will be more economical to obtain the optimum response as the design in the first stage can be used to fit the second order model and with some additional runs, third order model can be fitted without discarding the initial design.

Preferential Binding of Epirubicin Hydrochloride with Single Nucleotide Mismatched DNA and Subsequent Sequestration by a Mixed Micelle.

Targeting mismatched base pairs containing DNA using small molecules and exploring the underlying mechanism involved during the binding interactions is one of the fundamental aspects of drug design. These molecules in turn are used in nucleic acid targeted therapeutics and cancer diagnosis. In this work, we systematically delineate the binding of the anticancer drug, epirubicin hydrochloride (EPR) with 20-mer duplex DNA, having both natural nucleobase pairing and thermodynamically least stable non-Watson-Crick base pairing. From the thermal denaturation studies, we observed that EPR can remarkably enhance the thermal stability of cytosine-cytosine (CC) and cytosine-thymine (CT) mismatched (MM) DNA over other 20-mer duplex DNA. From steady-state fluorescence spectroscopy and isothermal titration calorimetry studies, we concluded that EPR binds strongly with the mismatched duplex DNA through the intercalation binding mode. The interaction of EPR and duplex DNA has also been monitored at a single molecular resolution using fluorescence correlation spectroscopy (FCS). Dynamic quantitates such as diffusion coefficients and hydrodynamic radii obtained from an FCS study along with association and dissociation rate constants estimated from intensity time trace analyses further substantiate the stronger binding affinity of EPR to the thermally less stable mismatched DNA, formed by the most discriminating nucleobase (viz. cytosine). Additionally, we have shown that EPR can be sequestered from nucleic acids using a mixed micellar system of an anionic surfactant and a triblock copolymer. From thermal denaturation studies and circular dichroism spectroscopy, we found that the extent of drug sequestration depends on the binding affinity of EPR to the duplex DNA, and this mixed micellar system can be employed for the removal of excess drug in the case of a drug overdose.

Exploring the Nucleobase-Specific Hydrophobic Interaction of Cryptolepine Hydrate with RNA and Its Subsequent Sequestration.

The study of the interactions of drug molecules with genetic materials plays a key role underlying the development of new drugs for many life-threatening diseases in pharmaceutical industries. Understanding their fundamental base-specific and/or groove-binding interaction is crucial to target the genetic material with an external drug, which can pave the way to curing diseases related to the genetic material. Here, we studied the interaction of cryptolepine hydrate (CRYP) with RNA under physiological conditions knowing the antimalarial and anticancer activities of the drug. Our experiments explicitly demonstrate that CRYP interacts with the guanine- and adenine-rich region within the RNA duplex. The pivotal role of the hydrophobic interaction governing the interaction is substantiated by temperature-dependent isothermal titration calorimetry experiments and spectroscopic studies. Circular dichroism study underpins a principally intercalative mode of binding of CRYP with RNA. This interaction is found to be drastically affected in the presence of magnesium salt, which has a strong propensity to coordinate with RNA nucleobases, which can in turn modulate the interaction of the drug with RNA. The temperature-dependent calorimetric results substantiate the occurrence of entropy-enthalpy compensation, which enabled us to rule out the possibility of groove binding of the drug with RNA. Furthermore, our results also show the application of host-guest chemistry in sequestering the RNA-bound drug, which is crucial to the development of safer therapeutic applications.

Structural Compactness in Hen Egg White Lysozyme Induced by Bisphenol†S: A†Spectroscopic and Molecular Dynamics Simulation Approach.

The endocrine disrupting compound Bisphenol and its analogues are widely used in food packaging products and can cause serious health hazards. The protein, Lysozyme (Lyz), showing anti-microbial properties, is used as a "natural" food and dairy preservative. Herein, we explored the interaction between Lyz and Bisphenol S (BPS) by multi-spectroscopic and theoretical approaches. Lyz interacts with BPS through static quenching, where hydrophobic force governed the underlying interaction. Molecular docking results reveal that tryptophan plays a vital role in binding, corroborated well with near UV-CD studies. A decrease in the radius of gyration (from 1.43 nm to 1.35 nm) of Lyz substantiates the compactness of the protein conformation owing to such an interaction. This structural alteration experienced by Lyz may alter its functional properties as a food preservative. Consequently, this can degrade the quality of the food products and thereby lead to severe health issues.

Rotational diffusion and rotational correlations in frictional amorphous disk packings under shear.

We show here that rotations of round particles in amorphous disk packing reveal various nontrivial microscopic features when the packing is close to rigidification. We analyze experimental measurements on disk packing subjected to simple shear deformation with various inter-particle friction coefficients and across a range of volume fractions where the system is known to stiffen. The analysis of measurements indicates that shear induces diffusive microrotation, that can be both enhanced and suppressed depending upon the volume fraction as well as the inter-particle friction. Rotations also display persistent anticorrelated motion. Spatial correlations in microrotation are observed to be directly correlated with system pressure. These observations point towards the broader mechanical relevance of collective dynamics in the rotational degree of freedom of particles.

Thermal Reversibility and Structural Stability in Lysozyme Induced by Epirubicin Hydrochloride.

Herein we report the binding interactions between lysozyme (Lyz) and an anthracycline drug, epirubicin hydrochloride (EPR), through an extensive spectroscopic approach at both ensemble average and single molecular resolution. Our steady-state and time-resolved fluorescence spectroscopy reveals that the drug-induced fluorescence quenching of the protein proceeds through a static quenching mechanism. Isothermal titration calorimetry (ITC) and steady-state experiments reveal almost similar thermodynamic signatures of the drug-protein interactions. The underlying force that plays pivotal roles in the said interaction is hydrophobic in nature, which is enhanced in the presence of a strong electrolyte (NaCl). Circular dichroism (CD) spectra indicate that there is a marginal increase in the secondary structure of the native protein (α-helical content increases from 26.9 to 31.4% in the presence of 100 µM EPR) upon binding with the drug. Fluorescence correlation spectroscopy (FCS) was used to monitor the changes in structure and conformational dynamics of Lyz upon interaction with EPR. The individual association (Kass = 0.33 × 106 ms-1 M-1) and dissociation (Kdiss = 1.79 ms-1) rate constants and the binding constant (Kb = 1.84 × 105 M-1) values, obtained from fluctuations of fluorescence intensity of the EPR-bound protein, have also been estimated. AutoDock results demonstrate that the drug molecule is encapsulated within the hydrophobic pocket of the protein (in close proximity to both Trp62 and Trp108) and resides ∼20 Å apart from the covalently labelled CPM dye. Förster resonance energy transfer (FRET) studies proved that the distance between the donor (CPM) and the acceptor (EPR) is ∼22 Å, which is very similar to that obtained from molecular docking analysis (∼20 Å). The system also shows temperature-dependent reversible FRET, which may be used as a thermal sensor for the temperature-sensitive biological systems.

Contrasting Thermodynamics Governs the Interaction of 3-Hydroxyflavone with the N-Isoform and B-Isoform of Human Serum Albumin.

Herein we report the interaction of 3-hydroxyflavone (3HF) with various isomeric forms of Human Serum Albumin (HSA), namely, the N-isoform (or native HSA at pH 7.4) and the B-isoform (at pH 9.2). Spectroscopic signatures of 3HF reveal that the interaction of 3HF with the N-isoform of HSA results in significant lowering of absorbance of the neutral species (λabs ∼ 345 nm) with concomitant increase of the anionic species (λabs ∼ 416 nm) whereas interaction with the B-isoform of HSA leads to selective enhancement of absorbance of the anionic species. The fluorescence profile of 3HF displays marked increase of intensity of the proton transferred tautomer (λem ∼ 538 nm) as well as the anionic species (λem ∼ 501 nm) for both the forms of the protein. However, analyses of the associated thermodynamics through temperature-dependent isothermal titration calorimetric (ITC) indicate that the interaction of 3HF with the N-isoform of HSA is more enthalpic in the lower temperature limit while the entropy contribution predominates in the higher temperature limit. Consequently, the 3HF-HSA (N-isoform at pH 7.4) interaction reveals an unusual thermodynamic signature of a positive heat capacity change (ΔCp = 3.84 kJ mol-1K-1) suggesting the instrumental role of hydrophobic hydration. On the contrary, the 3HF-HSA (B-isoform at pH 9.2) interaction shows qualitatively reverse effect. Consequently, the interaction is found to be characterized by an enthalpy-dominated hydrophobic effect (negative heat capacity change, ΔCp = -1.15 kJ mol-1K-1) which is rationalized on the basis of the nonclassical hydrophobic effect.

Groundnut AhcAPX conferred abiotic stress tolerance in transgenic banana through modulation of the ascorbate-glutathione pathway.

A stress inducible cytosolic ascorbate peroxidase gene (AhcAPX) was ectopically expressed in banana (cv. Grand naine) plants to strengthen their antioxidant capacity. High level of AhcAPX gene transcripts and enzyme suggested constitutive and functional expression of candidate gene in transgenic (TR) plants. The tolerance level of in vitro and in vivo grown TR banana plantlets were assessed against salt and drought stress. The TR banana plants conferred tolerance against the abiotic stresses by maintaining a high redox state of ascorbate and glutathione, which correlated with lower accumulation of H2O2, O2 ⋅- and higher level of antioxidant enzyme (SOD, APX, CAT, GR, DHAR and MDHAR) activities. The efficacy of AhcAPX over-expression was also investigated in terms of different physiochemical attributes of TR and untransformed control plants, such as, proline content, membrane stability, electrolyte leakage and chlorophyll retention. The TR plants showed higher photochemical efficiency of PSII (Fv/Fm), and stomatal attributes under photosynthesis generated reactive oxygen species (ROS) stress. The outcome of present investigation suggest that ectopic expression of AhcAPX gene in banana enhances the tolerance to drought and salt stress by annulling the damage caused by ROS.

Meeting the challenge of developing food crops with improved nutritional quality and food safety: leveraging proteomics and related omics techniques.

Eliminating malnutrition remains an imminent priority in our efforts to achieve food security and providing adequate calories, proteins, and micronutrients to the growing world population. Malnutrition may be attributed to socio-economic factors (poverty and limited accessibility to nutritional food), dietary preferences, inherent nutrient profiles of traditional food crops, and to a combination of all such factors. Modern advancements in "omics" technology have made it possible to reliably predict, diagnose, and suggest ways to remedy the low protein content and bioavailability of key micronutrients in food crops. In this review, we briefly describe how proteomics techniques can potentially be used for improving the nutrient profile of major crops, through high throughput multiplexed assays. Food safety is another important issue where proteomics and related platforms can offer solution for absolute quantitation of food allergens and mycotoxins present in the plant-based food. The purpose of the present review is to discuss the proteomic-based strategies in food crops to meet the challenges of overcoming malnutrition throughout the world.

Ube3a deficiency inhibits amyloid plaque formation in APPswe/PS1δE9 mouse model of Alzheimer's disease.

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive decline in memory and cognitive function. Pathological hallmark of AD includes aberrant aggregation of amyloid beta (Aß) peptide, which is produced upon sequential cleavage of amyloid precursor protein (APP) by ß- and γ -secretases. On the contrary, α-secretase cleaves APP within the Aß sequence and thereby prevents Aß generation. Here, we investigated the role of ubiquitin ligase Ube3a (involved in synaptic function and plasticity) in the pathogenesis of AD using APPswe/PS1δE9 transgenic mouse model and first noticed that soluble pool of Ube3a was age-dependently decreased in AD mouse in comparison with wild type controls. To further explore the role of Ube3a in AD patho-mechanism, we generated brain Ube3a-deficient AD mice that exhibited accelerated cognitive and motor deficits compared with AD mice. Interestingly, these Ube3a-deficient AD mice were excessively obese from their age of 12 months and having shorter lifespan. Biochemical analysis revealed that the Ube3a-deficient AD mice had significantly reduced level of Aß generation and amyloid plaque formation in their brain compared with age-matched AD mice and this effect could be due to the increased activity of α-secretase, ADAM10 (a disintegrin and metalloproteinase-10) that shift the proteolysis of APP towards non-amyloidogenic pathway. These findings suggest that aberrant function of Ube3a could influence the progression of AD and restoring normal level of Ube3a might be beneficial for AD.

Rescue of altered HDAC activity recovers behavioural abnormalities in a mouse model of Angelman syndrome.

Angelman syndrome (AS) is a neurodevelopmental disorder characterized by severe intellectual and developmental disabilities. The disease is caused by the loss of function of maternally inherited UBE3A, a gene that exhibits paternal-specific imprinting in neuronal tissues. Ube3a-maternal deficient mice (AS mice) display many classical features of AS, although, the underlying mechanism of these behavioural deficits is poorly understood. Here we report that the absence of Ube3a in AS mice brain caused aberrant increase in HDAC1/2 along with decreased acetylation of histone H3/H4. Partial knockdown of Ube3a in cultured neuronal cells also lead to significant up-regulation of HDAC1/2 and consequent down-regulation of histones H3/H4 acetylation. Treatment of HDAC inhibitor, sodium valproate, to AS mice showed significant improvement in social, cognitive and motor impairment along with restoration of various proteins linked with synaptic function and plasticity. Interestingly, HDAC inhibitor also significantly increased the expression of Ube3a in cultured neuronal cells and in the brain of wild type mice but not in AS mice. These results indicate that anomalous HDAC1/2 activity might be linked with synaptic dysfunction and behavioural deficits in AS mice and suggests that HDAC inhibitors could be potential therapeutic molecule for the treatment of the disease.

Sugar-Terminated Nanoparticle Chaperones Are 102-105 Times Better Than Molecular Sugars in Inhibiting Protein Aggregation and Reducing Amyloidogenic Cytotoxicity.

Sugar-based osmolyte molecules are known to stabilize proteins under stress, but usually they have poor chaperone performance in inhibiting protein aggregation. Here, we show that the nanoparticle form of sugars molecule can enhance their chaperone performance typically by 102-105 times, compared to molecular sugar. Sugar-based plate-like nanoparticles of 20-40 nm hydrodynamic size have been synthesized by simple heating of acidic aqueous solution of glucose/sucrose/maltose/trehalose. These nanoparticles have excitation-dependent green/yellow/orange emission and surface chemistry identical to the respective sugar molecule. Fibrillation of lysozyme/insulin/amyloid beta in extracellular space, aggregation of mutant huntingtin protein inside model neuronal cell, and cytotoxic effect of fibrils are investigated in the presence of these sugar nanoparticles. We found that sugar nanoparticles are 102-105 times efficient than respective sugar molecules in inhibiting protein fibrillation and preventing cytotoxicity arising of fibrils. We propose that better performance of the nanoparticle form is linked to its stronger binding with fibril structure and enhanced cell uptake. This result suggests that nanoparticle form of osmolyte can be an attractive option in prevention and curing of protein aggregation-derived diseases.