Impact of core polarity on smectic B-induced hydrogen bond liquid crystals.

The novel series of hydrogen bond liquid crystals were synthesized from the 2-methylglutaric acid (MGA) and 4-alkyloxybenzoic acid (nOBA) compounds. The induced smectic B phase with different texture (spine texture, needle texture, mosaic texture, natural mosaic texture and marble texture) were identified by polarizing optical microscope. Due to breaking of in-plane rotational symmetry within molecular layers, smectic B phase is tempted by suppressing other usual mesophases. The mesomorphic transition temperature, enthalpy and entropy values were calculated by differential scanning calorimeter which strongly proves the existence of mesomorphism. H-bond interaction and functional groups were confirmed by the observed peak between 2910 and 2954 cm-1 in the FTIR spectra. Thermal stability and extended mesophase width (for MGA + 12OBA = 31.1) of Sm B mesophase were reported and it clearly reveals the existence of mono-phase variance in the MGA + nOBA HBLC complex. Due to the steric effect, and the increased molecular core polarity, the highly stabilized Sm B phase with different textures were observed while varying alkyloxy carbon number n = 7 to 12. Further, the origination of Sm B phase and its detailed characteristics were reported.

Occurrence of Banana bract mosaic virus on Musa ornata Roxb based hybrids in India.

Musa ornata, wild species of banana is being used as a cut flower, potted plants and for landscape gardening etc., They are also being utilized in banana hybridization programmes for introgressing pest and disease tolerant traits into banana cultivars in addition to the development of inter specific ornamental banana hybrids. Symptoms of banana bract mosaic virus (BBrMV) was observed in the bracts of interspecific M. ornata based hybrid developed using another wild species i.e., Musa rubra Kurz at ICAR-National Research Centre for Banana (NRCB), Tiruchirapalli. Presence of the virus in the bracts, leaves and roots of symptomatic plants was confirmed through triple antibody sandwich enzyme linked immunosorbent assay with BBrMV monoclonal and polyclonal antibodies. BBrMV HC-Pro (1370 bp), CP (900 bp) and VPg (570 bp) genes were amplified from the infected bracts using reverse transcriptase polymerase chain reaction with BBrMV respective gene primers. The amplicons of these three genes were cloned and sequenced. Blastn analysis revealed that HC-Pro, VPg and CP gene sequences has 97.67%, 97.72% and 99.67% similarity with the respective gene sequences of BBrMV infecting banana. Phylogenetic analysis clustered the test isolate with other BBrMV isolates of banana and other hosts based on CP and HC-Pro and VPg gene sequences. The virus is transmitted through Pentalonia nigronervosa and the transmitted plants expressed symptoms under glass house conditions. To the best of our knowledge, this is the first report of BBrMV on ornamental M. ornata hybrid in India and its transmission occurs through Pentalonia nigronervosa. Supplementary Information: The online version contains supplementary material available at 10.1007/s13337-022-00788-6.

Characterization of Mungbean yellow mosaic India virus genome with a recombinant DNA-B in Southern Peninsular India.

BACKGROUND: Mungbean yellow mosaic India virus (MYMIV) is a representative of the genus begomovirus/Begomoviridae, which is prevalent in the northern part of Indian subcontinent causing yellow mosaic disease (YMD). This virus is rapidly evolving and breaking the resistance in the advanced lines causing huge economic losses in the pulse production. In this context, the present investigation on characterization of the causal organism of YMD was undertaken METHODS AND RESULTS: A novel recombinant isolate (YMV-BG-BPT) causing YMD was identified from blackgram in Andhra Pradesh, southern peninsular region of India. The association of a bipartite begomovirus with the disease was done by sequence analyses of the cloned full-length genome. The full length genome sequences were submitted in NCBI GenBank with accession numbers MZ235792 (DNA-A) and MZ356197 (DNA-B). The sequence analysis of DNA-A of YMV-BG-BPT showed maximum of 99.12% similarity at nucleotide level with Mungbean yellow mosaic India virus (MYMIV) isolate reported from Tamil Nadu (KC911719), India which is also confirmed by clustering pattern in phylogenic analysis and DNA-B showed 95.79% with Mungbean yellow mosaic virus (MYMV) isolate reported from Tamil Nadu (KP319016) and 95.05% with MYMIV isolate reported from Karnataka (MT027037). The huge variation in DNA-B lead us to suspect a recombination in DNA-B, where a recombination event in the CR, region coding for nuclear shuttle protein and movement protein of DNA B was detected in which MYMV-BG-AP-IND (KF928962) and MYMIV-GG-CH-IND (MN020536) have been identified as major and minor parents, respectively. CONCLUSION: Overall, the present study revealed occurrence of MYMIV with recombinant DNA B component in southern peneinsular India.

New record of mungbean yellow mosaic India virus in Desmodium laxiflorum and association of bhendi yellow vein mosaic betasatellite in Abelmoschus moschatus in Andhra Pradesh, India.

Mungbean yellow mosaic India virus (MYMIV) is one of the most serious commonly occurring yellow mosaic virus (YMV's) group in majority of the pulses especially black gram and green gram in southern India compared to previously reported mungbean yellow mosaic virus. In January 2020 Desmodium laxiflorum and Abelmoscus moschatus showing mosaic symptoms and vein yellowing were collected from Guntur and Prakasam districts respectively in Andhra Pradesh. PCR analysis using MYMIV and betasatellite specific primers gave desired expected amplification from the infected samples of A. moschatus (YMV-ABEL) whereas only MYMIV specific amplification was obtained in D. laxiflorum (YMV-DES). However, no PCR amplification was obtained in respective healthy leaf samples of both plants. Sequence analysis showed that the CP sequence of YMV-ABEL and YMV-DES showed a similarity of 99.19% with MYMIV (KP677496) and 99.75% with MYMIV (JN181003) respectively. The full-length betasatellite (1356 bp) showed highest identity of 90% with bhendi yellow vein mosaic betasatellite (BYVMB) (GU111977). Phylogenetic analysis clustered the test isolates with south Indian isolates of MYMIV whereas the betasatellite sequence clustered with various isolates of BYVMB, tomato leaf curl New Delhi virus betasatellite and okra leaf curl betasatellite reported from India and Pakistan. To the best of our knowledge, this is the first report of a MYMIV in D. laxiflorum and A. moschatus and MYMIV betasatellite complex in A. moschatus.

Azaindole Based Potentiator of Antibiotics against Gram-Negative Bacteria.

We discovered azaindole-based compounds with weak innate activity that exhibit substantial potentiation of antibacterial activities of different antibiotics, viz., rifampicin, erythromycin, solithromycin, and novobiocin in Gram-negative bacteria. In the presence of the azaindole derivatives, these antibiotics exhibited submicromolar minimum inhibitory concentrations (MICs) against Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii. The fold improvements in MIC of these antibiotics that were otherwise weak or inactive on their own against these bacteria were also observed against drug-resistant clinical isolates. Our studies indicate that this selective potentiation is probably through destabilization of the outer membrane's integrity, known to be regulated by the lipopolysaccharides (LPS). Thus, the azaindole based compounds described here open opportunities for those antibiotics that are otherwise ineffective due to LPS mediated entry barriers in Gram-negative bacteria.

Investigation of FSSW parameters on shear fracture load of AA6061 and copper alloy joints.

In this research, Friction stir spot welding (FSSW) is extensively employed to join dissimilar metals consisting of AA6061-T6 Aluminium Alloy and Commercial Copper Alloy. These alloys were friction stir spot welded using process parameters with the major impact, such as Dwell Time (DT), Rotational Speed (RS), Plunge Rate (PR) and Tool Diameter Ratio (D/d). Trail experiments have been carried out using Design of Experiments. Sound welded joints exhibiting a maximum shear fracture load of 4.79 kN were obtained at a RS of 2000 rpm, PR of 7 mm/min, DT of 25 s and D/d of 3.5, Balanced material flow around the pin was also observed at this condition, and it is evident that the superior metallurgical properties and geometric features at this condition results in the higher strength. Moreover, the joint also exhibited higher load-bearing capabilities due to an optimal hook height of 0.89 mm, hook width of 1.3 mm and hook initiation distance of 1.4 mm. The continuous formation of intermetallic compound such as ɤ2-Cu9Al4 in the Cu zone and ɳ2-CuAl in the Al zone may also enhance the shear fracture load.

Data set on prediction of friction stir welding parameters to achieve maximum strength of AA2014-T6 aluminium alloy joints.

Statistical tools such as design of experiments (DoE), analysis of variance (ANOVA) were used to develop the empirical relationship, to predict the ultimate tensile strength of the joint at the 95% percent confidence level. Response surface graph and contour plots were constructed using response surface methodology (RSM) concept. From this investigation, it is found that the joint fabricated with a tool rotational speed of 1500 rpm, welding speed of 40 mm/min, tool tilt angle of 1.5° and tool shoulder diameter of 6 mm, exhibited maximum tensile strength of 380 MPa.

Complete genome sequence of sacbrood virus isolated from Asiatic honey bee Apis cerana indica in India.

We determined the complete genome sequence of a sacbrood virus (SBV) infecting Indian honey bee (Apis cerana indica) from Tamil Nadu, India named as AcSBV-IndTN1. The genome of AcSBV-IndTN1 comprised of 8740 nucleotides, encoding a single large ORF containing 2849 amino acids flanked by 5' and 3' untranslated regions. Results of phylogenetic tree analysis based on complete genomes of SBV isolates indicated that the virus isolates from India isolated from the Asiatic honey bee A. cerana (AcSBVs) formed a separate group along with six Vietnam isolates and three Chinese isolates. The AcSBV-IndTN1 isolate showed closer genetic relationship with other isolates from India. The second major group had both AcSBVs and AmSBVs (virus isolated from European honey bee, Apis mellifera SBV) of Korea, China and Vietnam. The third and a distantly related group had AmSBVs of Australia, UK, USA and Korea. The results obtained from phylogenetic analysis were further supported with evolutionary distance analysis. AcSBV-IndTN1 isolate open reading frame had 95-99% amino acid sequence similarity with other Indian isolates and 92-96% with AcSBVs and AmSBVs of other geographical locations. In addition, sequence difference count matrix ranged from 154 to 907 nt among all the SBV isolates. This suggests that the virus isolates have evolved significantly in different geographical locations but isolates on different hosts in a given location/country are closely related. The high similarity in the genome among the AcSBV and AmSBV isolates indicate possible cross-infections and recombination of SBV isolates in Asian continent where both the honey bee species are reared in close proximity. Gene flow between SBV population indicating that an infrequent gene flow occur between them. The pattern of molecular diversity in SBV population revealed that the occurrence of recent population expansion of SBV. To the best of our knowledge this is the first report of the complete nucleotide sequence of AcSBV from Tamil Nadu, India. This study provided an opportunity to establish the molecular evolution of SBV isolates and shall be useful in the development of diagnostics and effective disease control strategies.

Hot tensile properties and constant load stress corrosion cracking test data of autogenous weld joints of super 304HCu stainless steel in boiling MgCl2 solution.

Hot tensile test data of Gas Tungsten Arc Welded (GTAW) autogenous joints of Super 304HCu tubes tested at their operating temperature are presented along with the microstructure of the weld joint. The GTAW joints exhibited lower tensile strength than the parent metal and the failure occurred in the weld metal region for all test temperatures. Constant load Stress Corrosion Cracking (SCC) test data of the GTAW weld joints tested in boiling MgCl2 environment at different applied stress level are presented. SCC curves obtained from the test were analyzed to derive SCC parameters such as rate of steady state elongation, the time required for set-in of tertiary region, and time to complete fracture. The fracture surfaces of SCC samples were examined using Scanning Electron Microscope to reveal the mode of fracture. Super 304HCu stainless steel being used as construction material for super heaters and reheaters of advanced ultra super critical boilers, this data will be an addition to the design data available for material selection in design of power plants.

Nitrothiophene carboxamides, a novel narrow spectrum antibacterial series: Mechanism of action and Efficacy.

The mechanism of efflux is a tour-de-force in the bacterial armoury that has thwarted the development of novel antibiotics. We report the discovery of a novel chemical series with potent antibacterial properties that was engineered to overcome efflux liability. Compounds liable to efflux specifically via the Resistance Nodulation and cell Division (RND) pump, AcrAB-TolC were chosen for a hit to lead progression. Using structure-based design, the compounds were optimised to lose their binding to the efflux pump, thereby making them potent on wild-type bacteria. We discovered these compounds to be pro-drugs that require activation in E. coli by specific bacterial nitroreductases NfsA and NfsB. Hit to lead chemistry led to the generation of compounds that were potent on wild-type and multi-drug resistant clinical isolates of E. coli, Shigella spp., and Salmonella spp. These compounds are bactericidal and efficacious in a mouse thigh infection model.

Cyclohexylation of Resorcinol with Cyclohexanol Catalyzed by Tungstophosphoric Acid Supported Zirconia Catalysts.

We demonstrate a highly active and reusable heterogeneous catalyst system, tungstophosphoric acid (TPA) supported on zirconia (ZrO2), for the cyclohexylation of resorcinol by cyclohexanol to produce value added chemicals such as 2-cyclohexyl resorcinol, 4-cyclohexyl resorcinol and 3-Hydroxy cyclohexyl phenyl ether under liquid phase reaction condition. TPA/ZrO2 catalysts prepared with different TPA loadings (5-30 wt.%) by wet impregnation method and calcined in the temperature range of 650-850 °C were characterized by Nitrogen sorption analysis, XRD, FTIR, DTG and DTA, and 31P MAS NMR spectroscopy. Among the catalysts studied, 15 wt.%TPA/ZrO2 catalyst calcined at 750 °C gave the highest conversion of resorcinol (51.2%) with the selectivities for 3-Hydroxy cyclohexyl phenyl ether (53.9%) and 2-cyclohexyl resorcinol and 4-cyclohexyl resorcinol together (46.1%) under optimum reaction conditions. However, the selectivity of the products were controlled by varying the reaction conditions. At higher conversion of resorcinol (78.9%), only C-alkylated products were formed at 200 °C with 15 wt.%TPA/ZrO2 catalyst calcined at 750 °C. The combination of TPA and ZrO2 coupled with calcination temperature offered an excellent platform for the conversion of resorcinol into O- or C-alkylated products.

Post-Transcriptional Regulation of Hepatic DDAH1 with TNF Blockade Leads to Improved eNOS Function and Reduced Portal Pressure In Cirrhotic Rats.

Portal hypertension (PH) is a major cause of morbidity and mortality in chronic liver disease. Infection and inflammation play a role in potentiating PH and pro-inflammatory cytokines, including TNF, are associated with severity of PH. In this study, cirrhotic bile duct ligated (BDL) rats with PH were treated with Infliximab (IFX, a monoclonal antibody against TNF) and its impact on modulation of vascular tone was assessed. BDL rats had increased TNF and NFkB compared to sham operated rats, and their reduction by IFX was associated with a reduction in portal pressure. IFX treatment also reduced hepatic oxidative stress, and biochemical markers of hepatic inflammation and injury. IFX treatment was associated with an improvement in eNOS activity and increased L-arginine/ADMA ratio and DDAH1 expression. In vitro analysis of HepG2 hepatocytes showed that DDAH1 protein expression is reduced by oxidative stress, and this is in part mediated by post-transcriptional regulation by the 3'UTR. This study supports a role for the DDAH1/ADMA axis on the effect of inflammation and oxidative stress in PH and provides insight for new therapies.

Discovery of Imidazo[1,2-a]pyridine Ethers and Squaramides as Selective and Potent Inhibitors of Mycobacterial Adenosine Triphosphate (ATP) Synthesis.

The approval of bedaquiline to treat tuberculosis has validated adenosine triphosphate (ATP) synthase as an attractive target to kill Mycobacterium tuberculosis (Mtb). Herein, we report the discovery of two diverse lead series imidazo[1,2-a]pyridine ethers (IPE) and squaramides (SQA) as inhibitors of mycobacterial ATP synthesis. Through medicinal chemistry exploration, we established a robust structure-activity relationship of these two scaffolds, resulting in nanomolar potencies in an ATP synthesis inhibition assay. A biochemical deconvolution cascade suggested cytochrome c oxidase as the potential target of IPE class of molecules, whereas characterization of spontaneous resistant mutants of SQAs unambiguously identified ATP synthase as its molecular target. Absence of cross resistance against bedaquiline resistant mutants suggested a different binding site for SQAs on ATP synthase. Furthermore, SQAs were found to be noncytotoxic and demonstrated efficacy in a mouse model of tuberculosis infection.

Nitroarenes as Antitubercular Agents: Stereoelectronic Modulation to Mitigate Mutagenicity.

Nitroarenes are less preferred in drug discovery due to their potential to be mutagenic. However, several nitroarenes were shown to be promising antitubercular agents with specific modes of action, namely, nitroimidazoles and benzothiazinones. The nitro group in these compounds is activated through different mechanisms, both enzymatic and non-enzymatic, in mycobacteria prior to binding to the target of interest. From a whole-cell screening program, we identified a novel lead nitrobenzothiazole (BT) series that acts by inhibition of decaprenylphosphoryl-ß-d-ribose 2'-epimerase (DprE1) of Mycobacterium tuberculosis (Mtb). The lead was found to be mutagenic to start with. Our efforts to mitigate mutagenicity resulted in the identification of 6-methyl-7-nitro-5-(trifluoromethyl)-1,3-benzothiazoles (cBTs), a novel class of antitubercular agents that are non-mutagenic and exhibit an improved safety profile. The methyl group ortho to the nitro group decreases the electron affinity of the series, and is hence responsible for the non-mutagenic nature of these compounds. Additionally, the co-crystal structure of cBT in complex with Mtb DprE1 established the mode of binding. This investigation led to a new non-mutagenic antitubercular agent and demonstrates that the mutagenic nature of nitroarenes can be solved by modulation of stereoelectronic properties.

Complete coverage of space favors modularity of the grid system in the brain.

Grid cells in the entorhinal cortex fire when animals that are exploring a certain region of space occupy the vertices of a triangular grid that spans the environment. Different neurons feature triangular grids that differ in their properties of periodicity, orientation, and ellipticity. Taken together, these grids allow the animal to maintain an internal, mental representation of physical space. Experiments show that grid cells are modular, i.e., there are groups of neurons which have grids with similar periodicity, orientation, and ellipticity. We use statistical physics methods to derive a relation between variability of the properties of the grids within a module and the range of space that can be covered completely (i.e., without gaps) by the grid system with high probability. Larger variability shrinks the range of representation, providing a functional rationale for the experimentally observed comodularity of grid cell periodicity, orientation, and ellipticity. We obtain a scaling relation between the number of neurons and the period of a module, given the variability and coverage range. Specifically, we predict how many more neurons are required at smaller grid scales than at larger ones.

Discovery of benzothiazoles as antimycobacterial agents: Synthesis, structure-activity relationships and binding studies with Mycobacterium tuberculosis decaprenylphosphoryl-ß-D-ribose 2'-oxidase.

We report the discovery of benzothiazoles, a novel anti-mycobacterial series, identified from a whole cell based screening campaign. Benzothiazoles exert their bactericidal activity against Mycobacterium tuberculosis (Mtb) through potent inhibition of decaprenylphosphoryl-ß-d-ribose 2'-oxidase (DprE1), the key enzyme involved in arabinogalactan synthesis. Specific target linkage and mode of binding were established using co-crystallization and protein mass spectrometry studies. Most importantly, the current study provides insights on the utilization of systematic medicinal chemistry approaches to mitigate safety liabilities while improving potency during progression from an initial genotoxic hit, the benzothiazole N-oxides (BTOs) to the lead-like AMES negative, crowded benzothiazoles (cBTs). These findings offer opportunities for development of safe clinical candidates against tuberculosis. The design strategy adopted could find potential application in discovery of safe drugs in other therapy areas too.

In silico-based high-throughput screen for discovery of novel combinations for tuberculosis treatment.

There are currently 18 drug classes for the treatment of tuberculosis, including those in the development pipeline. An in silico simulation enabled combing the innumerably large search space to derive multidrug combinations. Through the use of ordinary differential equations (ODE), we constructed an in silico kinetic platform in which the major metabolic pathways in Mycobacterium tuberculosis and the mechanisms of the antituberculosis drugs were integrated into a virtual proteome. The optimized model was used to evaluate 816 triplets from the set of 18 drugs. The experimentally derived cumulative fractional inhibitory concentration (∑FIC) value was within twofold of the model prediction. Bacterial enumeration revealed that a significant number of combinations that were synergistic for growth inhibition were also synergistic for bactericidal effect. The in silico-based screen provided new starting points for testing in a mouse model of tuberculosis, in which two novel triplets and five novel quartets were significantly superior to the reference drug triplet of isoniazid, rifampin, and ethambutol (HRE) or the quartet of HRE plus pyrazinamide (HREZ).

Triaminopyrimidine is a fast-killing and long-acting antimalarial clinical candidate.

The widespread emergence of Plasmodium falciparum (Pf) strains resistant to frontline agents has fuelled the search for fast-acting agents with novel mechanism of action. Here, we report the discovery and optimization of novel antimalarial compounds, the triaminopyrimidines (TAPs), which emerged from a phenotypic screen against the blood stages of Pf. The clinical candidate (compound 12) is efficacious in a mouse model of Pf malaria with an ED99 <30 mg kg(-1) and displays good in vivo safety margins in guinea pigs and rats. With a predicted half-life of 36 h in humans, a single dose of 260 mg might be sufficient to maintain therapeutic blood concentration for 4-5 days. Whole-genome sequencing of resistant mutants implicates the vacuolar ATP synthase as a genetic determinant of resistance to TAPs. Our studies highlight the potential of TAPs for single-dose treatment of Pf malaria in combination with other agents in clinical development.

Highly ordered nanoporous carbon films with tunable pore diameters and their excellent sensing properties.

Ordered porous carbon films with tunable pore diameters, immobilized with glucose oxidase (GOD) have been fabricated and employed for the construction of a biosensor for glucose molecules. The as-prepared porous films have large specific surface areas and highly ordered porous structure with uniform pore sizes, which are critical for the immobilization of large amounts of GOD and support the promotion of heterogeneous electron transfer. The developed biosensors give enough room for the encapsulation of a high amount of GOD molecules and show excellent biosensing performance with a linear response to glucose concentration ranging from 0.5 to 9 mM and a detection limit of 1.5 µM. It is also demonstrated that the sensitivity of the biosensor can be easily tuned by modulating the pore size of carbon film as it dictates the amount of immobilization of GOD in the porous channels. The fabricated carbon-film-based biosensor has a good stability and a high reproducibility, which opens the gateway for the commercialization of this excellent technology.

Simple and rapid method to determine antimycobacterial potency of compounds by using autoluminescent Mycobacterium tuberculosis.

A major obstacle in the process of discovery of drugs against Mycobacterium tuberculosis is its extremely slow growth rate and long generation time (∼20 to 24 h). Consequently, determination of MICs and minimum bactericidal concentrations (MBCs) of potential drug candidates using current methods requires 7 days (resazurin-based MIC assay [REMA]) and 1 month (CFU enumeration), respectively. We employed a synthetic luciferase operon optimized for expression in high-GC-content bacteria and adapted it for use in mycobacteria. Using luminescence-based readouts, we were able to determine the MICs and bactericidal activities of approved tuberculosis (TB) drugs, which correlated well with currently used methods. Although luminescence-based readouts have been used previously to determine the MICs and bactericidal activities of approved TB drugs, in this study we adapted this assay to carry out a pilot screen using a library of 1,114 compounds belonging to diverse chemical scaffolds. We found that MICs derived from a 3-day luminescence assay matched well with REMA-based MIC values. To determine the bactericidal potencies of compounds, a 1:10 dilution of the cultures from the MIC plate was carried out on day 7, and the bactericidal concentrations determined based on time to positivity in 2 weeks were found to be comparable with MBC values determined by the conventional CFU approach. Thus, the luminescent mycobacterium-based approach not only is very simple and inexpensive but also allowed us to generate the information in half the time required by conventional methods.