Publications by authors named "Amit Das"

214 Publications

Evaluation of Chitinase 3-like 1 (CHI3L1) as a noninvasive biomarker of hepatic fibrosis in patients with Hepatitis B virus-related compensated chronic liver disease.

J Family Med Prim Care 2021 Apr 29;10(4):1694-1698. Epub 2021 Apr 29.

Department of Hepatology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh.

Background: Liver biopsy is the gold-standard method for diagnosing and staging liver fibrosis, but the procedure is invasive, not available in the primary health care facilities, and not free from complications. Noninvasive serum biomarkers of hepatic fibrosis are the current research focus.

Objectives: To assess the correlation between serum Chitinase 3-like 1 (CHI3L1) levels and histological severity in patients with Hepatitis B Virus (HBV)-related compensated chronic liver disease (CLD).

Material And Methods: This cross-sectional study evaluated 50 treatment-naïve patients with chronic hepatitis B with compensated CLD. Liver biopsy was done, and hepatic fibrosis was categorized using the METAVIR scoring system; we divided the study subjects into three groups; group 1 included subjects with F0 and F1, group 2 having F2 group 3 having F3 and F4. Serum CHI3L1 was measured in all by immunoassay.

Result: Among 50 patients, only one had METAVIR score F0, seven had F1, 33 had F2, nine had F3, and none had METAVIR score F4. The median value of CHI3L1 was 460.8 (IQR 340.1-570.3) in all study subjects; 359.5 (IQR 272.8-526.9) in group 1, 450.0 (IQR 307.75-5332.0) in group 2, and 1355.5 (IQR 530.75-1580.5) in the group 3. The difference in median CHI3L1 across the groups was statistically significant. Serum aspartate aminotransferase (AST) and the AST to Platelet Ratio Index (APRI) score had significant positive correlations with CHI3L1 levels. CHI3L1 also had significant positive correlations with METAVIR scores.

Conclusion: This study found a positive correlation between serum CHI3L1 level and hepatic histological severity in patients with HBV-related compensated CLD. Further larger-scale research is needed to establish the fact.
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http://dx.doi.org/10.4103/jfmpc.jfmpc_1922_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8144771PMC
April 2021

Design and development of a machine for continuous popping and puffing of grains.

J Food Sci Technol 2021 May 10;58(5):1703-1714. Epub 2020 Aug 10.

Department of Food Engineering, CSIR-Central Food Technological Research Institute, Mysore, 570 020 India.

Popping/puffing have been traditionally practiced for enhancing storage life, improving organoleptic properties and ease of incorporation in ready-to-eat-foods. Currently, batch type sand and electric popping/puffing machines involving conduction mode of heat transfer are employed. The major drawbacks of these methods are high-energy consumption, scorching of grains, non-uniform product quality, contamination (by sand/ash) and problems in scale-up. Since fluidization is known to increase heat and mass transfer, a continuous fluidized popping/puffing machine (capacity 10-20 kg/h) involving convective mode of heat transfer is designed/developed. Hot-flue gas generating from burning of LPG was used as the eco-friendly fuel. Process parameters such as expansion ratio, fluidization velocity, terminal velocity, carry over velocity, bulk density and voidage were estimated for un-popped and popped/puffed rice, maize, (sorghum) and paddy. Fluidization and carry over velocities for these grains were in the range of 4.18-5.78 m/s and 2.15-6.18 m/s, respectively. Based on the terminal velocity of the grains and volumetric air flow rate of the blower, fluidization chamber diameter was arrived. Chamber diameter of 0.15 m was found to be sufficient to generate required air velocity of 6.89 m/s which met the fluidization and carry over velocities of popped/puffed grains. The designed fluidization chamber was analyzed for heat and mass transfer during popping/puffing. Convective heat and mass transfer coefficients were estimated to be in the range of 103-187 W/m °C and 0.124-0.162 m/s, respectively. Theoretical values for total heat and mass transfer were similar to the experimental values.
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http://dx.doi.org/10.1007/s13197-020-04680-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8021677PMC
May 2021

Label-Free Method Development for Hydroxyproline PTM Mapping in Human Plasma Proteome.

Protein J 2021 Apr 11. Epub 2021 Apr 11.

Department of Biotechnology, Indian Institute of Technology Kharagpur, Kharagpur, 721302, India.

Post-translational modifications (PTMs) impart structural heterogeneities that can alter plasma proteins' functions in various pathophysiological processes. However, the identification and mapping of PTMs in untargeted plasma proteomics is still a challenge due to the presence of diverse components in blood. Here, we report a label-free method for identifying and mapping hydroxylated proteins using tandem mass spectrometry (MS/MS) in the human plasma sample. Our untargeted proteomics approach led us to identify 676 de novo sequenced peptides in human plasma that correspond to 201 proteins, out of which 11 plasma proteins were found to be hydroxylated. Among these hydroxylated proteins, Immunoglobulin A1 (IgA1) heavy chain was found to be modified at residue 285 (Pro to Hyp), which was further validated by MS/MS study. Molecular dynamics (MD) simulation analysis demonstrated that this proline hydroxylation in IgA1 caused both local and global structural changes. Overall, this study provides a comprehensive understanding of the protein profile containing Hyp PTMs in human plasma and shows the future perspective of identifying and discriminating Hyp PTM in the normal and the diseased proteomes.
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http://dx.doi.org/10.1007/s10930-021-09984-7DOI Listing
April 2021

Designing Supertough and Ultrastretchable Liquid Metal-Embedded Natural Rubber Composites for Soft-Matter Engineering.

ACS Appl Mater Interfaces 2021 Apr 29;13(13):15610-15620. Epub 2021 Mar 29.

Leibniz-Institut für Polymerforschung Dresden e. V, Hohe Straße 6, Dresden 01069, Germany.

Functional elastomers with incredible toughness and stretchability are indispensable for applications in soft robotics and wearable electronics. Furthermore, coupled with excellent electrical and thermal properties, these materials are at the forefront of recent efforts toward widespread use in cutting-edge electronics and devices. Herein, we introduce a highly deformable eutectic-GaIn liquid metal alloy-embedded natural rubber (NR) architecture employing, for the first time, industrially viable solid-state mixing and vulcanization. Standard methods of rubber processing and vulcanization allow us to fragment and disperse liquid metals into submicron-sized droplets in cross-linked NR without compromising the elastic properties of the base matrix. In addition to substantial boosts in mechanical (strain at failure of up to ∼650%) and elastic (negligible hysteresis loss) performances, the tearing energy of the composite was enhanced up to 6 times, and a fourfold reduction in the crack growth rate was achieved over a control vulcanizate. Moreover, we demonstrate improved thermal conductivity and dielectric properties for the resulting composites. Therefore, this work provides a facile and scalable pathway to develop liquid metal-embedded soft elastomeric composites that could be instrumental toward potential applications in soft-matter engineering.
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http://dx.doi.org/10.1021/acsami.1c00374DOI Listing
April 2021

Digital image analysis of ultrasound images using machine learning to diagnose pediatric nonalcoholic fatty liver disease.

Clin Imaging 2021 Feb 23;77:62-68. Epub 2021 Feb 23.

Department of Pediatrics, Valleywise Health Medical Center, Phoenix, AZ, United States of America.

Purpose: Prevalence of nonalcoholic fatty liver disease (NAFLD) in children is rising with the epidemic of childhood obesity. Our objective was to perform digital image analysis (DIA) of ultrasound (US) images of the liver to develop a machine learning (ML) based classification model capable of differentiating NAFLD from healthy liver tissue and compare its performance with pixel intensity-based indices.

Methods: De-identified hepatic US images obtained as part of a cross-sectional study examining pediatric NAFLD prevalence were used to build an image database. Texture features were extracted from a representative region of interest (ROI) selected from US images of subjects with normal liver and subjects with confirmed NAFLD using ImageJ and MAZDA image analysis software. Multiple ML classification algorithms were evaluated.

Results: Four-hundred eighty-four ROIs from images in 93 normal subjects and 260 ROIs from images in 39 subjects with NAFLD with 28 texture features extracted from each ROI were used to develop, train, and internally validate the model. An ensembled ML model comprising Support Vector Machine, Neural Net, and Extreme Gradient Boost algorithms was accurate in differentiating NAFLD from normal when tested in an external validation cohort of 211 ROIs from images in 42 children. The texture-based ML model was also superior in predictive accuracy to ML models developed using the intensity-based indices (hepatic-renal index and the hepatic echo-intensity attenuation index).

Conclusion: ML-based predictive models can accurately classify NAFLD US images from normal liver images with high accuracy using texture analysis features.
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http://dx.doi.org/10.1016/j.clinimag.2021.02.038DOI Listing
February 2021

Effect of iodine doping on the electrical, thermal and mechanical properties of SnSe for thermoelectric applications.

Phys Chem Chem Phys 2021 Feb;23(7):4230-4239

Soft Materials Laboratory, Department of Physics, Indian Institute of Technology Madras, Chennai - 600036, India.

We report the evolution of the thermoelectric and mechanical properties of n-type SnSe obtained by iodine doping at the Se site. The thermoelectric performance of n-type SnSe is detailed in the temperature range starting from 150 K ≤ T ≤ 700 K. The power factor of 0.25% iodine doped SnSe is found to be 0.33 mW m-1 K-2 at 700 K, comparable to that of the other monovalent doped n-type SnSe. The temperature-dependent electrical conductivity of the undoped and iodine doped SnSe samples is corroborated by using the adiabatic small polaron hopping model. A very low value of thermal conductivity, 0.62 W m-1 K-1, is obtained at 300 K and is comparable to that of SnSe single crystals. The low thermal conductivity of n-type polycrystalline SnSe is understood by taking into account the anharmonic phonon vibrations induced by the incorporation of heavy iodine atoms at the Se sites as well as the structural hierarchy of the compound. Besides, iodine doping is found to improve the reduced Young's modulus and hardness values of SnSe, which is highly desirable for thermoelectric device applications.
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http://dx.doi.org/10.1039/d0cp06130aDOI Listing
February 2021

Physicochemical and phytochemical properties of foam mat dried passion fruit () powder and comparison with fruit pulp.

J Food Sci Technol 2021 Feb 4;58(2):787-796. Epub 2020 Jul 4.

Department of Food Engineering and Technology, Tezpur University, Tezpur, Assam 784028 India.

The aim of the present study was to develop purple passion fruit powder using the foam mat dried process. The possible effect of whipping time, methylcellulose concentration, and drying temperature on physicochemical and phytochemical properties of foam mat dried passion fruit was evaluated and compared with fruit pulp. The drying process was optimized using central composite design and optimum conditions were whipping time 2.78 min, methylcellulose 2.58%, temperature 44.05 °C. At the optimum condition vitamin C, total phenolic compound and hygroscopicity were 34.67 mg/100 g, 258.12 mg GAE/100 g, and 21.12%, respectively. The artificial neural network was applied to predict experimental outcomes. The phytochemical properties in terms of (±)-α tocopherol, D-α-tocotrienol, β-carotene, and phenolic acid were determined using RP-HPLC. The foam mate dried powder contained a higher amount of β-carotene (13.26 mg/100 g), total phenolic compound (258.12 mg/100 g) and phenolic acids than fruit pulp whereas fruit pulp was contented higher amount of (±)-α tocopherol (171.1 mg/100 g) and D-α-tocotrienol (27.19 mg/100 g). The study manifested foam mate drying as an effective way to develop passion fruit powder.
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http://dx.doi.org/10.1007/s13197-020-04596-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7847913PMC
February 2021

Influence of extrusion cooking on phytochemical, physical and sorption isotherm properties of rice extrudate infused with microencapsulated anthocyanin.

Food Sci Biotechnol 2021 Jan 18;30(1):65-76. Epub 2020 Nov 18.

Department of Chemical Engineering, Indian Institute of Technology, Guwahati, Guwahati, Assam India.

The effect of extrusion cooking on the quality of rice extrudate with infused microencapsulated anthocyanin was investigated. The moisture sorption isotherm of the extrudate was also studied. The rotatable central composite design was used to optimize the extrusion process and the optimized conditions were: screw speed, 121 rpm; barrel temperature, 91.89 °C; and moisture content, 22.03%. The extrudate showed anthocyanin content of 0.218 mg/L; true density, 1.48 g/cc; water activity 0.51, water solubility index, 7.49%; and specific mechanical energy, 31.39 kJ/kg. The antioxidant activity and solubility of the extrudate were higher as compared with native extrudate. The moisture sorption isotherm of the extrudate was found to follow type III isotherm behavior according to the Brunauer-Emmett-Teller classification. The sorption isotherm was analyzed using several models and the Caurie and Peleg models were best fitted with the extrudate isotherm data. The present work manifested a way to develop antioxidant rich extrudate.
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http://dx.doi.org/10.1007/s10068-020-00841-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7847424PMC
January 2021

Targeting RECQL5 Functions, by a Small Molecule, Selectively Kills Breast Cancer o and .

J Med Chem 2021 02 2;64(3):1524-1544. Epub 2021 Feb 2.

Bio-Organic Division, Bhabha Atomic Research Centre, Trombay, Mumbai 400085, India.

Clinical and preclinical data reveal that RECQL5 protein overexpression in breast cancer was strongly correlated with poor prognosis, survival, and therapeutic resistance. In the current investigation, we report design, synthesis, and specificity of a small molecule, , which can preferentially kill RECQL5-expressing breast cancers but not RECQL5 knockout. Our stringent analysis showed that compound specifically sensitizes RECQL5-expressing cancers, while it did not have any effect on other members of DNA RECQL-helicases. Integrated approaches of organic synthesis, biochemical, molecular simulation, knockouts, functional mutation, and rescue experiments showed that potently inhibits RECQL5-helicase activity and stabilizes RECQL5-RAD51 physical interaction, leading to impaired HRR and preferential killing of RECQL5-expressing breast cancer. Moreover, treatment led to the efficient sensitization of cisplatin-resistant breast cancers but not normal mammary epithelial cells. Pharmacologically, compound was orally effective in reducing the growth of RECQL5-expressing breast tumors (human xenograft) in NUDE-mice with no appreciable toxicity to the vital organs.
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http://dx.doi.org/10.1021/acs.jmedchem.0c01692DOI Listing
February 2021

Morphology and Physico-Mechanical Threshold of α-Cellulose as Filler in an E-SBR Composite.

Molecules 2021 Jan 28;26(3). Epub 2021 Jan 28.

Department of Elastomers, Leibniz Institute of Polymer Research Dresden, HoheStraße 6, 01069 Dresden, Germany.

In the current context of green mobility and sustainability, the use of new generation natural fillers, namely, α-cellulose, has gained significant recognition. The presence of hydroxyl groups on α-cellulose has generated immense eagerness to map its potency as filler in an elastomeric composite. In the present work, α-cellulose-emulsion-grade styrene butadiene rubber (E-SBR) composite is prepared by conventional rubber processing method by using variable proportions of α-cellulose (1 to 40 phr) to assess its reinforce ability. Rheological, physical, visco-elastic and dynamic-mechanical behavior have clearly established that 10 phr loading of α-cellulose can be considered as an optimized dosage in terms of performance parameters. Morphological characterization with the aid of scanning electron microscope (SEM) and transmission electron microscopy (TEM) also substantiated that composite with 10 phr loading of α-cellulose has achieved the morphological threshold. With this background, synthetic filler (silica) is substituted by green filler (α-cellulose) in an E-SBR-based composite. Characterization of the compound has clearly established the reinforcement ability of α-cellulose.
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http://dx.doi.org/10.3390/molecules26030694DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7866042PMC
January 2021

Genome Editing of Rice by CRISPR-Cas: End-to-End Pipeline for Crop Improvement.

Methods Mol Biol 2021 ;2238:115-134

Formerly at Corteva Agriscience™, DuPont Knowledge Centre, Hyderabad, Telangana, India.

CRISPR-Cas resonates a revolutionary genome editing technology applicable through a horizon spreading across microbial organism to higher plant and animal. This technology can be harnessed with ease to understand the basic genetics of a living system by altering sequence of individual genes and characterizing their functions. The precision of this technology is unparallel. It allows very precise and targeted base pair level edits in the genome. Here, in the current chapter, we have provided end-to-end process outline on how to generate genome edited plants in crops like rice to evaluate for agronomic traits associated with yield, disease resistance and abiotic stress tolerance, etc. Genome editing process includes designing of gene editing strategy, vector construction, plant transformation, molecular screening, and phenotyping under control environment conditions. Furthermore, its application for development of commercial crop product may require additional processes, including field trials in the target geography for evaluation of product efficacy. Evaluation of genome edited lines in controlled greenhouse/net house or open field condition requires few generations for outcrossing with wild-type parent to eliminate and/or reduce any potential pleiotropic effect in the edited genome which may arise during the process. The genome edited plant selected for advancement shall harbor the genome with only the intended changes, which can be analyzed by various molecular techniques, advanced sequencing methods, and genomic data analysis tools. CRISPR-Cas-based genome editing has opened a plethora of opportunities in agriculture as well as human health.
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http://dx.doi.org/10.1007/978-1-0716-1068-8_8DOI Listing
March 2021

Decellularized bone matrix/oleoyl chitosan derived supramolecular injectable hydrogel promotes efficient bone integration.

Mater Sci Eng C Mater Biol Appl 2021 Feb 9;119:111604. Epub 2020 Oct 9.

Biomaterials and Tissue Engineering Laboratory, School of Medical Science and Technology, Indian Institute of Technology Kharagpur, Kharagpur 721302, India. Electronic address:

Hydrogels derived from decellularized extracellular matrix (ECM) have been widely used as a bioactive matrix for facilitating functional bone tissue regeneration. However, its poor mechanical strength and fast degradation restricts the extensive use for clinical application. Herein, we present a crosslinked decellularized bone ECM (DBM) and fatty acid modified chitosan (oleoyl chitosan, OC) based biohybrid hydrogel (DBM/OC) for delivering human amnion-derived stem cells (HAMSCs) for bone regeneration. DBM/OC hydrogel were benchmarked against collagen-I/OC (Col-I/OC) based hydrogel in terms of their morphological characteristics, rheological analysis, and biological performances. DBM/OC hydrogel with its endogenous growth factors recapitulates the nanofibrillar 3D tissue microenvironment with improved mechanical strength and also exhibited antimicrobial potential along with superior proliferation/differentiation ability. HAMSCs encapsulation potential of DBM/OC hydrogel was established by well spread cytoskeleton morphology post 14 days of cultivation. Further, ex-vivo chick chorioallantoic membrane (CAM) assay revealed excellent neovascularization potential of DBM/OC hydrogel. Subcutaneously implanted DBM/OC hydrogel did not trigger any severe immune response or infection in the host after 21 days. Also, DBM/OC hydrogels and HAMSCs encapsulated DBM/OC hydrogels were implanted at the tibial defect in a rabbit model to assess the bone regeneration ability. Quantitative micro-CT and histomorphological analysis demonstrated that HAMSCs encapsulated DBM/OC hydrogel can support more mature mineralized bone formation at the defect area compared to DBM/OC hydrogel or SHAM. These findings manifested the efficacy of DBM/OC hydrogel as a functional cell-delivery vehicle and osteoinductive template to accelerate bone regeneration.
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http://dx.doi.org/10.1016/j.msec.2020.111604DOI Listing
February 2021

Dual Functionalized Injectable Hybrid Extracellular Matrix Hydrogel for Burn Wounds.

Biomacromolecules 2021 02 8;22(2):514-533. Epub 2020 Dec 8.

Biomaterials and Tissue Engineering Laboratory, School of Medical Science and Technology, Indian Institute of Technology Kharagpur, Kharagpur 721302, India.

Low strength and rapid biodegradability of acellular dermal matrix (ADM) restrict its wider clinical application as a rapid cell delivery platform for management of burn wounds. Herein, the extracted ADM was modified by a dual cross-linking approach with ionic crosslinking using chitosan and covalent cross-linking using an iodine-modified 2,5-dihydro-2,5-dimethoxy-furan cross-linker, termed as CsADM-Cl. In addition, inherent growth factors and cytokines were found to be preserved in CsADM-Cl, irrespective of ionic/covalent crosslinking. CsADM-Cl demonstrated improvement in post crosslinking stiffness with a decreased biodegradation rate. This hybrid crosslinked hydrogel supported adhesion, proliferation, and migration of human foreskin-derived fibroblasts and keratinocytes. Also, the angiogenic potential of CsADM-Cl was manifested by chick chorioallantoic membrane assay. CsADM-Cl showed excellent antibacterial activity against and . Moreover, CsADM-Cl treated full thickness burn wounds and demonstrated rapid healing marked with superior angiogenesis, well-defined dermal-epidermal junctions, mature basket weave collagen deposition, and development of more pronounced secondary appendages. Altogether, the bioactive CsADM-Cl hydrogel established significant clinical potential to support wound healing as an apt injectable antibacterial matrix to encounter unmet challenges concerning critical burn wounds.
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http://dx.doi.org/10.1021/acs.biomac.0c01400DOI Listing
February 2021

Combination of QSAR, molecular docking, molecular dynamic simulation and MM-PBSA: analogues of lopinavir and favipiravir as potential drug candidates against COVID-19.

J Biomol Struct Dyn 2020 Nov 30:1-20. Epub 2020 Nov 30.

Department of Genetic Engineering and Biotechnology, Jashore University of Science and Technology, Jashore, Bangladesh.

Pandemic COVID-19 infections have spread throughout the world. There is no effective treatment against this disease. Viral RNA-dependent RNA polymerase (RdRp) catalyzes the replication of RNA from RNA and the main protease (M) has a role in the processing of polyproteins that are translated from the RNA of SARS-CoV-2, and thus these two enzymes are strong candidates for targeting by anti-viral drugs. Small molecules such as lopinavir and favipiravir significantly inhibit the activity of M and RdRp . Studies have shown that structurally modified lopinavir, favipiravir, and other similar compounds can inhibit COVID-19 main protease (M) and RNA-dependent RNA polymerase (RdRp). In this study, lopinavir and its structurally similar compounds were chosen to bind the main protease, and favipiravir was chosen to target RNA-dependent RNA polymerase. Molecular docking and the quantitative structure-activity relationships (QSAR) study revealed that the selected candidates have favorable binding affinity but less druggable properties. To improve the druggability, four structural analogues of lopinavir and one structural analogue of favipiravir was designed by structural modification. Molecular interaction analyses have displayed that lopinavir and favipiravir analogues interact with the active site residues of M and RdRp, respectively. Absorption, distribution, metabolism, excretion and toxicity (ADMET) properties, medicinal chemistry profile, and physicochemical features were shown that all structurally modified analogues are less toxic and contain high druggable properties than the selected candidates. Subsequently, 50 ns molecular dynamics simulation of the top four docked complexes demonstrated that CID44271905, a lopinavir analogue, forms the most stable complex with the M. Further MMPBSA analyses using the MD trajectories also confirmed the higher binding affinity of CID44271905 towards M. In summary, this study demonstrates a new way to identify leads for novel anti-viral drugs against COVID-19. Communicated by Ramaswamy H. Sarma.
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http://dx.doi.org/10.1080/07391102.2020.1850355DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7754938PMC
November 2020

Structural insights into SARS-CoV-2 proteins.

J Mol Biol 2021 01 24;433(2):166725. Epub 2020 Nov 24.

Protein Crystallography Section, Radiation Biology & Health Sciences Division, Bhabha Atomic Research Centre, Trombay, Mumbai 400085, India; Homi Bhabha National Institute, Anushaktinagar, Mumbai 400094, India. Electronic address:

The unprecedented scale of the ongoing COVID-19 pandemic has catalyzed an intense effort of the global scientific community to unravel different aspects of the disease in a short time. One of the crucial aspects of these developments is the determination of more than three hundred experimental structures of SARS-CoV-2 proteins in the last few months. These include structures of viral non-structural, structural, and accessory proteins and their complexes determined by either X-ray diffraction or cryo-electron microscopy. These structures elucidate the intricate working of different components of the viral machinery at the atomic level during different steps of the viral life cycle, including attachment to the host cell, viral genome replication and transcription, and genome packaging and assembly of the virion. Some of these proteins are also potential targets for drug development against the disease. In this review, we discuss important structural features of different SARS-CoV-2 proteins with their function, and their potential as a target for therapeutic interventions.
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http://dx.doi.org/10.1016/j.jmb.2020.11.024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7685130PMC
January 2021

Effect of Prestrain on the Actuation Characteristics of Dielectric Elastomers.

Polymers (Basel) 2020 Nov 16;12(11). Epub 2020 Nov 16.

Leibniz-Institut für Polymerforschung Dresden e.V., 01069 Dresden, Germany.

Dielectric elastomers (DEs) represent a class of electroactive polymers that deform due to electrostatic attraction between oppositely charged electrodes under a varying electric field. Over the last couple of decades, DEs have garnered considerable attention due to their much-coveted actuation properties. As far as the precise measurement systems are concerned, however, there is no standard instrument or interface to quantify various related parameters, e.g., actuation stress, strain, voltage and creeping etc. In this communication, we present an in-depth study of dielectric actuation behavior of dielectric rubbers by the state-of-the-art , designed and developed in-house. The instrument allowed us to elucidate various factors that could influence the output efficiency of the DEs. Herein, several non-conventional DEs such as hydrogenated nitrile rubber, nitrile rubber with different acrylonitrile contents, were employed as an electro-active matrix. The effect of viscoelastic creeping on the prestrain, molecular architecture of the matrices, e.g., nitrile content of nitrile-butadiene rubber (NBR) etc., are also discussed in detail.
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http://dx.doi.org/10.3390/polym12112694DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7696614PMC
November 2020

Characterization of two sugar transporters responsible for efficient xylose uptake in an oleaginous yeast Candida tropicalis SY005.

Arch Biochem Biophys 2020 11 22;695:108645. Epub 2020 Oct 22.

Department of Biotechnology, Indian Institute of Technology Kharagpur, Kharagpur, 721302, India. Electronic address:

Microbial conversion of lignocellulosic feedstock to the target bioproduct requires efficient assimilation of its constituent sugars, a large part of which comprises of glucose and xylose. This study aims to identify and characterize sugar transporters capable of xylose uptake in an oleaginous strain of the industrially relevant yeast Candida tropicalis. In silico database mining resulted in two sugar transporter proteins- CtStp1 and CtStp2, containing conserved amino acid residues and motifs that have been previously reported to be involved in xylose transport in other organisms. Several softwares predicted the likelihood of 10-12 transmembrane (TM) helices to be present in both the Stps, while molecular modelling showed 12 TM helices that were organized into a typical structure found in the major facilitator superfamily of transporters. Docking with different sugars also predicted favorable interactions. Heterologous expression in a Saccharomyces cerevisiae strain harboring functional xylose metabolic genes validated the broad substrate specificity of the two Stps. Each transporter supported prominent growth of recombinant S. cerevisiae strains on six sugars including xylose at various concentrations. Expression of CtSTP1 and CtSTP2 along with the xylose metabolic genes in yeast transformants grown in presence of xylose was confirmed by transcript detection. Growth curve and sugar consumption profiles revealed uptake of both glucose and xylose simultaneously by the recombinant yeast strains, though CtStp1 showed relatively less effect of glucose repression in mixed sugars and was a better transporter of xylose than CtStp2. Such glucose-xylose utilizing efficient transporters can be effective tools for developing co-fermenting yeasts through genetic engineering in future, with noteworthy applications in renewable biomass utilization.
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http://dx.doi.org/10.1016/j.abb.2020.108645DOI Listing
November 2020

In primary airway epithelial cells, the unjamming transition is distinct from the epithelial-to-mesenchymal transition.

Nat Commun 2020 10 7;11(1):5053. Epub 2020 Oct 7.

Harvard T.H. Chan School of Public Health, Boston, MA, USA.

The epithelial-to-mesenchymal transition (EMT) and the unjamming transition (UJT) each comprises a gateway to cellular migration, plasticity and remodeling, but the extent to which these core programs are distinct, overlapping, or identical has remained undefined. Here, we triggered partial EMT (pEMT) or UJT in differentiated primary human bronchial epithelial cells. After triggering UJT, cell-cell junctions, apico-basal polarity, and barrier function remain intact, cells elongate and align into cooperative migratory packs, and mesenchymal markers of EMT remain unapparent. After triggering pEMT these and other metrics of UJT versus pEMT diverge. A computational model attributes effects of pEMT mainly to diminished junctional tension but attributes those of UJT mainly to augmented cellular propulsion. Through the actions of UJT and pEMT working independently, sequentially, or interactively, those tissues that are subject to development, injury, or disease become endowed with rich mechanisms for cellular migration, plasticity, self-repair, and regeneration.
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http://dx.doi.org/10.1038/s41467-020-18841-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7542457PMC
October 2020

Study of relationship of posterior tibial slope in anterior cruciate ligament injury.

J Orthop 2020 Sep-Oct;21:487-490. Epub 2020 Sep 11.

Department of Radiodiagnosiss, AHRCC, Cuttack, India.

Objective: To determine the relationship between Posterior Tibial slope in terms of medial and lateral in Anterior cruciate ligament deficient patients.

Methods: Magnetic resonance images (MRI) of the knee of 100 ACL injured patients and 100 ACL intact patients were studied. Their medial and lateral posterior tibial slopes were measured using MRI. Of 200 subjects, 100 (Male- 63, Female- 37) were controls, other 100 (Male - 68, Female-32) were ACL injured cases. Using DIACOM viewer software,the slopes of both medial and lateral slopes were measured. Range of Variation, mean value and standard deviation of medial tibial plateau slope (MTS), lateral tibia plateau slope (LTS) of controls and ACL injured patients were measured. The data collected were entered into Microsoft excel worksheet and analysed using statistical package for social sciences, Version 15.0 (SPSS Inc. Chicago, IL, USA). Distribution of data was confirmed using Shapiro's Wilk Test and appropriate parametric statistics were applied. For all analysis p value < 0.05 was set to be significant.

Results: In control (ACL uninjured) population mean MTS was 5.95° with SD 3.09°, mean LTS was 6.08° with SD 3.48°. In ACL injured population mean MTS 6.41° with SD 2.66°, mean LTS was 8.12° with SD 3.65°. So ACL injured population had MTS steeper than control population with no statistical significance (p value < 0.27) and LTS was steeper than control population with statistical significance (p value < 0.001),where as there were comparable results between male and females.

Conclusion: Our current results indicate that lateral PTS is a risk factor for patients with primary ACL tears as compared with ligament-intact controls. Therefore,PTS should be considered as independent modifiable risk factors in ACL injury.
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http://dx.doi.org/10.1016/j.jor.2020.08.032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7501475PMC
September 2020

Carbon nanodot decorated acellular dermal matrix hydrogel augments chronic wound closure.

J Mater Chem B 2020 10;8(40):9277-9294

Biomaterials and Tissue Engineering, Laboratory School of Medical Science and Technology, Indian Institute of Technology Kharagpur, Kharagpur-721302, India.

Impaired skin regeneration in chronic wounds like in diabetes corresponds to high oxidative stress, poor angiogenesis and insufficient collagen hyperplasia. Therefore, a multifaceted strategy for treatment is required to address critical issues associated with chronic wound healing. Fascinating application of nanomaterials in chronic wounds is still limited; hence, in the present work bioactive solubilized decellularized dermal matrix (sADM) was employed to form a hydrogel with chitosan (CTS) at physiological pH/temperature and modified with reactive oxygen species (ROS) scavenging carbon nanodots (ND). A detailed in vitro investigation found that the ND modified bioactive hydrogel (CsADMND) is suitable for human amniotic membrane derived stem cell (hAMSC) delivery. Also, CsADMND was observed to possess a good ROS scavenging property, hemocompatibility and pro-angiogenic potential as demonstrated by 2,2-diphenyl-1-picrylhydrazyl (DPPH), haemolysis and chick chorioallantoic membrane (CAM) assay, respectively. The hybrid hydrogel promoted migration of cells in vitro in scratch assay owing to its antioxidant potential and the presence of bioactive moieties. Further, its efficacy in healing full thickness (FT) chronic wounds was evaluated in a streptozotocin (STZ) induced diabetic model. The CsADMND hydrogel after association with hAMSCs led to stimulation of early angiogenesis, superior collagen deposition, rapid wound closure, complete reepithelialisation, and formation of distinct organized dermal epidermal junctions (DEJ) post 21 days of healing. These results suggest that the hAMSC laden CsADMND hydrogel may serve as a promising therapeutic strategy for the management of chronic wounds.
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http://dx.doi.org/10.1039/d0tb01574aDOI Listing
October 2020

Poly(acrylonitrile-co-butadiene) as polymeric crosslinking accelerator for sulphur network formation.

Heliyon 2020 Aug 26;6(8):e04659. Epub 2020 Aug 26.

Leibniz-Institut für Polymerforschung Dresden e.V., D-01069 Dresden, Germany.

The major controlling factors that determine the various mechanical properties of an elastomer system are type of chemical crosslinking and crosslink density of the polymer network. In this study, a catalytic amount of acrylonitrile butadiene copolymer (NBR) was used as a co-accelerator for the curing of polybutadiene (BR) elastomer. After the addition of this copolymer along with other conventional sulphur ingredients in polybutadiene compounds, a clear and distinct effect on the curing and other physical characteristics was noticed. The crosslinking density of BR was increased, as evidenced by rheometric properties, solid-state NMR and swelling studies. The vulcanization kinetics study revealed a substantial lowering of the activation energy of the sulphur crosslinking process when acrylonitrile butadiene copolymer was used in the formulation. The compounds were also prepared in the presence of carbon black and silica, and it was found that in the carbon black filled system the catalytic effect of the NBR was eminent. The effect was not only reflected in the mechanical performance but also the low-temperature crystallization behavior of BR systems was altered.
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http://dx.doi.org/10.1016/j.heliyon.2020.e04659DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7452554PMC
August 2020

Dry-Jet Wet Spinning of Thermally Stable Lignin-Textile Grade Polyacrylonitrile Fibers Regenerated from Chloride-Based Ionic Liquids Compounds.

Materials (Basel) 2020 Aug 20;13(17). Epub 2020 Aug 20.

Leibniz-Institut für Polymerforschung Dresden e. V., D-01069 Dresden, Germany.

In this paper, we report on the use of amorphous lignin, a waste by-product of the paper industry, for the production of high performance carbon fibers (CF) as precursor with improved thermal stability and thermo-mechanical properties. The precursor was prepared by blending of lignin with polyacrylonitrile (PAN), which was previously dissolved in an ionic liquid. The fibers thus produced offered very high thermal stability as compared with the fiber consisting of pure PAN. The molecular compatibility, miscibility, and thermal stability of the system were studied by means of shear rheological measurements. The achieved mechanical properties were found to be related to the temperature-dependent relaxation time (consistence parameter) of the spinning dope and the diffusion kinetics of the ionic liquids from the fibers into the coagulation bath. Furthermore, thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), and dynamic mechanical tests (DMA) were utilized to understand in-depth the thermal and the stabilization kinetics of the developed fibers and the impact of lignin on the stabilization process of the fibers. Low molecular weight lignin increased the thermally induced physical shrinkage, suggesting disturbing effects on the semi-crystalline domains of the PAN matrix, and suppressed the chemically induced shrinkage of the fibers. The knowledge gained throughout the present paper allows summarizing a novel avenue to develop lignin-based CF designed with adjusted thermal stability.
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http://dx.doi.org/10.3390/ma13173687DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7504658PMC
August 2020

Effect of ionic liquid on sol-gel phase transition, kinetics and rheological properties of high amylose starch.

Int J Biol Macromol 2020 Nov 22;162:685-692. Epub 2020 Jun 22.

Department of Food Engineering and Technology, Tezpur University, Tezpur 784028, India. Electronic address:

The effect of 1-butyl-3-methylimidazolium chloride (BMIMCl) as a plasticizer on sol-gel phase transition, rheological, and physical properties of high amylose rice starch was studied. The inter-relationships of parameters were determined using principal component analysis. The sol-gel phase transition temperature and storage modulus of starch was varied significantly (p ≤ 0.05) in the presence of BMIMCl. The sol-gel phase transition temperature of native starch was varied between 53.99 and 39.7 °C, whereas, for starch with ionic liquid varied between 49.50 and 40.6 °C. The changes in storage modulus (G') during the sol-gel phase transition were suitable with first order kinetics. The temperature dependent rheology of starch during the sol-gel phase transition was efficiently (0.93 ≤ R ≤ 0.98) explained using the Arrhenius model. The thermal stability of the gel was improved in the presence of BMIMCl. The textural and electrical properties of the gel were significantly affected by the presence of BMIMCl. The inter-relationships between the parameters were developed and the initial temperature, resistance, and storage modulus showed a strong interrelation.
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http://dx.doi.org/10.1016/j.ijbiomac.2020.06.186DOI Listing
November 2020

Mithramycin suppresses DNA damage repair via targeting androgen receptor in prostate cancer.

Cancer Lett 2020 09 30;488:40-49. Epub 2020 May 30.

Eugene McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center, Dallas, TX, USA; Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA; Department of Pharmacology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA; Green Center for Reproductive Biology Sciences, University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA. Electronic address:

The dependency of prostate cancer (PCa) growth on androgen receptor (AR) signaling has been harnessed to develop first-line therapies for high-risk localized and metastatic PCa treatment. However, the occurrence of aberrant expression, mutated or splice variants of AR confers resistance to androgen ablation therapy (ADT), radiotherapy or chemotherapy in AR-positive PCa. Therapeutic strategies that effectively inhibit the expression and/or transcriptional activity of full-length AR, mutated AR and AR splice variants have remained elusive. In this study, we report that mithramycin (MTM), an antineoplastic antibiotic, suppresses cell proliferation and exhibits dual inhibitory effects on expression and transcriptional activity of AR and AR splice variants. MTM blocks AR recruitment to its genomic targets by occupying AR enhancers and causes downregulation of AR target genes, which includes key DNA repair factors in DNA damage repair (DDR). We show that MTM significantly impairs DDR and enhances the effectiveness of ionizing radiation or the radiomimetic agent Bleomycin in PCa. Thus, the combination of MTM treatment with RT or radiomimetic agents, such as bleomycin, may present a novel effective therapeutic strategy for patients with high-risk, clinically localized PCa.
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http://dx.doi.org/10.1016/j.canlet.2020.05.027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7370677PMC
September 2020

Visualizing Tetrahedral Oxyanion Bound in HIV-1 Protease Using Neutrons: Implications for the Catalytic Mechanism and Drug Design.

ACS Omega 2020 May 14;5(20):11605-11617. Epub 2020 May 14.

Neutron Scattering Division, Oak Ridge National Laboratory, Oak Ridge, Tennessee 37830, United States.

HIV-1 protease is indispensable for virus propagation and an important therapeutic target for antiviral inhibitors to treat AIDS. As such inhibitors are transition-state mimics, a detailed understanding of the enzyme mechanism is crucial for the development of better anti-HIV drugs. Here, we used room-temperature joint X-ray/neutron crystallography to directly visualize hydrogen atoms and map hydrogen bonding interactions in a protease complex with peptidomimetic inhibitor KVS-1 containing a reactive nonhydrolyzable ketomethylene isostere, which, upon reacting with the catalytic water molecule, is converted into a tetrahedral intermediate state, KVS-1. We unambiguously determined that the resulting tetrahedral intermediate is an oxyanion, rather than the -diol, and both catalytic aspartic acid residues are protonated. The oxyanion tetrahedral intermediate appears to be unstable, even though the negative charge on the oxyanion is delocalized through a strong n → π* hyperconjugative interaction into the nearby peptidic carbonyl group of the inhibitor. To better understand the influence of the ketomethylene isostere as a protease inhibitor, we have also examined the protease structure and binding affinity with keto-darunavir (keto-DRV), which similar to KVS-1 includes the ketomethylene isostere. We show that keto-DRV is a significantly less potent protease inhibitor than DRV. These findings shed light on the reaction mechanism of peptide hydrolysis catalyzed by HIV-1 protease and provide valuable insights into further improvements in the design of protease inhibitors.
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http://dx.doi.org/10.1021/acsomega.0c00835DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7254801PMC
May 2020

Discovery of Potent, Selective, and State-Dependent Na1.7 Inhibitors with Robust Oral Efficacy in Pain Models: Structure-Activity Relationship and Optimization of Chroman and Indane Aryl Sulfonamides.

J Med Chem 2020 06 19;63(11):6107-6133. Epub 2020 May 19.

Novel Drug Discovery & Development, Lupin Ltd., Lupin Research Park, Survey No. 46 A/47 A, Village Nande, Taluka Mulshi, Pune 412115, India.

Voltage-gated sodium channel Na1.7 is a genetically validated target for pain. Identification of Na1.7 inhibitors with all of the desired properties to develop as an oral therapeutic for pain has been a major challenge. Herein, we report systematic structure-activity relationship (SAR) studies carried out to identify novel sulfonamide derivatives as potent, selective, and state-dependent Na1.7 inhibitors for pain. Scaffold hopping from benzoxazine to chroman and indane bicyclic system followed by thiazole replacement on sulfonamide led to identification of lead molecules with significant improvement in solubility, selectivity over Na1.5, and CYP2C9 inhibition. The lead molecules , , , , and showed a favorable pharmacokinetics (PK) profile across different species and robust efficacy in veratridine and formalin-induced inflammatory pain models in mice. Compound also showed significant effects on the CCI-induced neuropathic pain model. The profile of indicated that it has the potential for further evaluation as a therapeutic for pain.
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http://dx.doi.org/10.1021/acs.jmedchem.0c00361DOI Listing
June 2020

Efficient Chemical Protein Synthesis using Fmoc-Masked N-Terminal Cysteine in Peptide Thioester Segments.

Angew Chem Int Ed Engl 2020 08 26;59(35):14796-14801. Epub 2020 May 26.

TIFR Centre for Interdisciplinary Sciences, Tata Institute of Fundamental Research Hyderabad, 36/p Gopanpally, Hyderabad, 500046, Telangana, India.

We report an operationally simple method to facilitate chemical protein synthesis by fully convergent and one-pot native chemical ligations utilizing the fluorenylmethyloxycarbonyl (Fmoc) moiety as an N-masking group of the N-terminal cysteine of the middle peptide thioester segment(s). The Fmoc group is stable to the harsh oxidative conditions frequently used to generate peptide thioesters from peptide hydrazide or o-aminoanilide. The ready availability of Fmoc-Cys(Trt)-OH, which is routinely used in Fmoc solid-phase peptide synthesis, where the Fmoc group is pre-installed on cysteine residue, minimizes additional steps required for the temporary protection of the N-terminal cysteinyl peptides. The Fmoc group is readily removed after ligation by short exposure (<7 min) to 20 % piperidine at pH 11 in aqueous conditions at room temperature. Subsequent native chemical ligation reactions can be performed in presence of piperidine in the same solution at pH 7.
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http://dx.doi.org/10.1002/anie.202000491DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7891605PMC
August 2020

Identification and functional characterization of a lipid droplet protein CtLDP1 from an oleaginous yeast Candida tropicalis SY005.

Biochim Biophys Acta Mol Cell Biol Lipids 2020 08 19;1865(8):158725. Epub 2020 Apr 19.

Department of Biotechnology, Indian Institute of Technology Kharagpur, Kharagpur 721302, India. Electronic address:

Proteins residing in lipid droplets (LDs) of organisms exhibit diverse physiological roles. Since the LD proteins of yeasts are largely unexplored, we have identified a putative LD protein gene, CtLDP1 in the oleaginous yeast Candida tropicalis SY005 and characterized its function. The increased lipid accumulation in SY005 could be correlated with enhanced (~2.67-fold) expression of the CtLDP1 after low-nitrogen stress. The N-terminal transmembrane domain similar to perilipin proteins and the amphipathic α-helices predicted in silico, presumably aid in targeting the CtLDP1 to LD membranes. Heterologous expression of CtLDP1-mCherry fusion in Saccharomyces cerevisiae revealed localization in LDs, yet the expression of CtLDP1 did not show significant effect on LD formation in transformed cells. Molecular docking showed favourable interactions of the protein with sterol class of molecules, but not with triacylglycerol (TAG); and this was further experimentally verified by co-localization of the mCherry-tagged protein in TAG-deficient (but steryl ester containing) LDs. While oleic acid supplementation caused coalescence of LDs into supersized ones (average diameter = 1.19 ± 0.12 μm; n = 160), this effect was suppressed due to CtLDP1 expression, and the cells mostly exhibited numerous smaller LDs (average diameter = 0.46 ± 0.05 μm; n = 160). Moreover, CtLDP1 expression in pet10Δ knockout strain of S. cerevisiae restored multiple LD formation, indicating functional complementation of the protein. Overall, this study documents functional characterization of an LD-stabilizing protein from an oleaginous strain of Candida genus for the first time, and provides insights on the characteristics of LD proteins in oleaginous yeasts for future metabolic engineering.
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http://dx.doi.org/10.1016/j.bbalip.2020.158725DOI Listing
August 2020

Zirconia: A Superior Reinforcing Filler for High-Performance Nitrile Rubber Composites.

ACS Omega 2020 Apr 3;5(14):7751-7761. Epub 2020 Apr 3.

Department of Chemistry, Visvesvaraya National Institute of Technology, Nagpur 440010, Maharashtra, India.

Zirconia particles are generated into a nitrile rubber (NBR) matrix via a solution sol-gel method in a controlled manner. Formation of zirconia particles from their precursor (zirconium(IV) propoxide) occurs under optimized reaction conditions. As a result, the nanoparticles are embedded and well dispersed in the NBR matrix that results in a remarkable improvement in mechanical and thermal properties of the composite. Such reinforcement is not realized when the composites are prepared following the conventional technique of filler loading by physical mixing, although the filler content remains the same. Use of a surface active coupling agent TESPT (bis-(3-triethoxysilylpropyl) tetrasulfide) in the reactive sol-gel system is found to further boost the mechanical performance of the composites. In order to ensure the practical application of the developed composites, a series of studies have been performed that consist of dynamic performance, swelling, thermal degradation, and resistance to oil, ozone, and abrasion. Analysis of the results reveals that zirconia could be an excellent filler for the NBR composites to withstand in a harsh and adverse environment.
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http://dx.doi.org/10.1021/acsomega.9b03495DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7160828PMC
April 2020

Biochemical Characterization of VapC46 Toxin from Mycobacterium tuberculosis.

Mol Biotechnol 2020 Jul;62(6-7):335-343

Department of Biotechnology, Indian Institute of Technology, Kharagpur, India.

Emergence of multidrug resistant strains and extremely drug resistant strains of Mycobacterium tuberculosis is due to its ability to form persister cells. The formation of persister cells is assumed to be triggered due to the presence of large number of toxin-antitoxin (TA) systems in its genome. Mtb genome encodes 47 VapBC TA systems. In this work, we aim to biochemically characterize VapC46 toxin of the VapBC46 TA operon from Mycobacterium tuberculosis. Heterologous expression of VapC46 in E. coli is shown to exhibit bacteriostasis and toxicity alters the surface morphology of the E. coli cells. VapC46 is shown to possess ribonuclease activity in a magnesium-dependent manner. Using FRET and pull down assay, VapC46 is shown to interact with VapB46 antitoxin. A model of VapC46 is shown to resemble PIN domain family of proteins and reveals the putative active site required for its ribonuclease activity.
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http://dx.doi.org/10.1007/s12033-020-00253-zDOI Listing
July 2020