Biodegradation of acetaminophen: Microcosm centric genomic-proteomic-metabolomics evidences.

Acetaminophen (APAP) is a frequently used, over-the-counter analgesic and antipyretic medication. Considering increase in global consumption, its ubiquity in environment with potential toxic impacts has become a cause of great concern. Hence, bioremediation of this emerging contaminant is of paramount significance. The present study incorporates a microcosm centric omics approach to gain in-depth insights into APAP degradation by Paracoccus sp. APAP_BH8. It can metabolize APAP (300 mg kg-1) within 16 days in soil microcosms. Genome analysis revealed potential genes capable of mediating degradation includes M20 aminoacylase family protein, guanidine deaminase, 4-hydroxybenzoate 3-monooxygenase, and 4-hydroxyphenylpyruvate dioxygenase. Whole proteome analysis showed differential expression of enzymes and bioinformatics provided evidence for stable binding of intermediates at the active site of considered enzymes. Metabolites identified were 4-aminophenol, hydroquinone, and 3-hydroxy-cis, cis-muconate. Therefore, Paracoccus sp. APAP_BH8 with versatile enzymatic and genetic attributes can be a promising candidate for formulating improved in situ APAP bioremediation strategies.

Silver nanoparticle as an alternate to antibiotics in cattle semen during cryopreservation.

The proposed study was to determine if the silver nanoparticles can be used as potential antimicrobial agents and can replace the use of conventional antibiotics in semen without affecting the motility and fertility of semen. The silver nanoparticles prepared by chemical reduction method were confirmed by determination of the wavelength of surface plasmon resonance peak and further characterized using Zetasizer by determining their size, polydispersity index, and zeta potential. The nanoparticles were assessed for antibacterial activity and their concentration was optimized for use in semen extender for cryopreservation. Cryopreserved semen was further evaluated for seminal parameters, antioxidant parameter, and microbial load. Prepared silver NPs showed a plasmon resonance peak at 417 nm wavelength. NPs were found to possess antibacterial activity and were supplemented in semen extender @ 125 and 250 µg/ml for semen cryopreservation. There was a significant increase in pre and post-freezing motility and other seminal parameters. The microbial load of frozen-thawed semen of control and supplemented groups were well within the permissible limits. Lipid peroxidation levels were reduced in NPs supplemented groups, and reactive oxygen species (ROS) levels were significantly reduced in semen supplemented with 125 µg/ml NPs. Thus it can be conclude that silver NPs can be successfully used as a substitute for antibiotics in cattle bull semen cryopreservation with good antimicrobial activity and no adverse effects on sperm characteristics.

Synthesis of unsymmetrical ketones via dual catalysed cross-coupling of α,ß-unsaturated carboxylic acids with aryldiazonium salts.

A visible light-enabled synthesis of unsymmetrical ketones has been accomplished by the cross-coupling of α,ß-unsaturated carboxylic acids and aryldiazonium salts embracing a synergistic eosin Y and Co(OAc)2·4H2O catalysis. The reaction involves decarboxylative aerobic CC bond cleavage, and is endowed with the creation of new C-C and C-O bonds with good substrate scope.

Detection of the ß-lactoglobulin genotype in zebu cattle (Gangatiri) milk using high-resolution accurate mass spectroscopy.

We studied the genetic polymorphism of beta-lactoglobulin (ß-Lg) whey protein in Gangatiri zebu cows for this Research Communication. The polymorphic nature of milk protein fractions and their association with milk production traits, composition and quality has attracted several efforts in evaluating the allelic distribution of protein locus as a potential dairy trait marker. Genetic variants of ß-Lg have highly significant effects on casein number (B > A) and protein recovery (B > A) and also determine the yield of cheese dry matter (B > A). Molecular techniques of polyacrylamide gel electrophoresis and high-resolution accurate mass-spectroscopy were applied to characterize the ß-Lg protein obtained from the Gangatiri breed milk. Sequence analysis of ß-Lg showed the presence of variant B having UniProt database accession number P02754, coded on the PAEP gene. Our study can provide reference and guidance for the selection of superior milk (having ß-LgB) from this indigenous breed that could potentially give a good yield of ß-Lg for industrial applications.

Intensity of estrus expression - valuable obvious determinant of fertility in Bos indicus cows.

This study aimed to characterize estrus response and to establish relationships between intensity of estrus, preovulatory follicle (POF) size and estradiol (E2) concentrations on day of AI, luteal profiles and pregnancy outcome in lactating Hariana breed of cows. 200 cyclic cows were subjected to Ovsynch (n = 54) and Pre-OV treatment (n = 146). Ovsynch: Buserelin acetate (BA; 10 µg), Cloprostenol (500 µg) and BA (10 µg) were injected i.m. on day 0, 7 and 9, respectively, irrespective of treatment. Pre-OV: BA (10 µg) and Cloprostenol (500 µg) was also injected i.m. simultaneously 7 days prior to initiate Ovsynch. On the basis of estrus behavior, the cows were classified into three groups: weak, moderate and intense. Artificial insemination performed at 18-24 hours after 2nd BA of Ovsynch in both treatments. The average duration of estrus did not differ (p > 0.05) between Ovsynch and Pre-OV treatment. A positive correlation was observed between estrus response and POF size, concentration of E2 on day of AI and luteal profiles on day 12 post-AI. First service conception rate was higher in cows exhibited intense (45.46%) and moderate (42.56%) estrus response than weak (28.57%) estrus response. In conclusion, intensity of estrus expression could be considered as important determinant for deciding pregnancy outcomes in Bos indicus cows.

Proteomics-based milk whey proteome profiling of Indian Jersey crossbreed cows followed by chromosomal mapping.

BACKGROUND: Milk contains a massive class of minor proteins that are known for their various biological and molecular functions. Many whey proteins transfer the host defense mechanism to the human body. In this assay, electrophoresis followed by a high-resolution mass spectrometry-based proteomic approach has been applied to identify the whey proteome of Indian Jersey crossbreed bovines. RESULTS: Two search engines, MS Amanda and Sequest HT, have shown more than 29 minor proteins. Chromosomal mapping revealed that chromosomes 5 and 9 are expressing maximum proteins in the whey proteome. The principal component analysis, outlier plots, scree plots, score plots, and loading plots were generated to further assess the results. CONCLUSION: The majorly expressed ones are glycosylation-dependent cell adhesion molecule-1, ubiquitin, desmoglein, annexin, glycoprotein, arginase, histones, peroxiredoxin, vimentin, desmin, catenin, peripherin, and 70 kDa heat shock protein. © 2023 Society of Chemical Industry.

Microcosm-omics centric investigation reveals elevated bacterial degradation of imidacloprid.

Imidacloprid, a broad-spectrum insecticide, is widely used against aphids and other sucking insects. As a result, its toxic effect is becoming apparent in non-targeted organisms. In-situ bioremediation of residual insecticide from the environment utilizing efficient microbes would be helpful in reducing its load. In the present work, in-depth genomics, proteomics, bioinformatics, and metabolomics analyses were employed to reveal the potential of Sphingobacterium sp. InxBP1 for in-situ degradation of imidacloprid. The microcosm study revealed ∼79% degradation with first-order kinetics (k = 0.0726 day-1). Genes capable of mediating oxidative degradation of imidacloprid and subsequent decarboxylation of intermediates were identified in the bacterial genome. Proteome analysis demonstrated significant overexpression of the enzymes coded by these genes. Bioinformatic analysis revealed significant affinity and binding of the identified enzymes for their respective substrates (the degradation pathway intermediates). The nitronate monooxygenase (K7A41 01745), amidohydrolase (K7A41 03835 and K7A41 07535), FAD-dependent monooxygenase (K7A41 12,275), and ABC transporter enzymes (K7A41 05325, and K7A41 05605) were found to be effective in facilitating the transport and intracellular degradation of imidacloprid. The metabolomic study identified the pathway intermediates and validated the proposed mechanism and functional role of the identified enzymes in degradation. Thus, the present investigation provides an efficient imidacloprid degrading bacterial species as evidenced by its genetic attributes which can be utilized or further improved to develop technologies for in-situ remediation.

Multi-omics approach reveals elevated potential of bacteria for biodegradation of imidacloprid.

The residual imidacloprid, a widely used insecticide is causing serious environmental concerns. Knowledge of its biodegradation will help in assessing its residual mass in soil. In view of this, a soil microcosm-based study was performed to test the biodegradation potential of Agrobacterium sp. InxBP2. It achieved ∼88% degradation in 20 days and followed the pseudo-first-order kinetics (k = 0.0511 day-1 and t1/2=7 days). Whole genome sequencing of Agrobacterium sp. InxBP2 revealed a genome size of 5.44 Mbp with 5179 genes. Imidacloprid degrading genes at loci K7A42_07110 (ABC transporter substrate-binding protein), K7A42_07270 (amidohydrolase family protein), K7A42_07385 (ABC transporter ATP-binding protein), K7A42_16,845 (nitronate monooxygenase family protein), and K7A42_20,660 (FAD-dependent monooxygenase) having sequence and functional similarity with known counterparts were identified. Molecular docking of proteins encoded by identified genes with their respective degradation pathway intermediates exhibited significant binding energies (-6.56 to -4.14 kcal/mol). Molecular dynamic simulation discovered consistent interactions and binding depicting high stability of docked complexes. Proteome analysis revealed differential protein expression in imidacloprid treated versus untreated samples which corroborated with the in-silico findings. Further, the detection of metabolites proved the bacterial degradation of imidacloprid. Thus, results provided a mechanistic link between imidacloprid and associated degradative genes/enzymes of Agrobacterium sp. InxBP2. These findings will be of immense significance in carrying out the lifecycle analysis and formulating strategies for the bioremediation of soils contaminated with insecticides like imidacloprid.

Copper-Catalyzed Thiolation of Hydrazones with Sodium Sulfinates: A Straightforward Synthesis of Benzylic Thioethers.

A facile and sustainable protocol for the thiolation of hydrazones with sodium sulfinates has been developed in the presence of CuBr2 and DBU in DMF to afford diverse benzylic thioethers. Control experiments reveal a radical pathway involving a thiyl radical as a key intermediate.

Genome sequencing and in silico analysis of isoprene degrading monooxygenase enzymes of Sphingobium sp. BHU LFT2.

The whole genome sequencing of a novel isoprene degrading strain of Sphingobium sp. BHU LFT2, its in silico analysis for identifying and characterizing enzymes, especially isoprene monooxygenases (IsoMO), which initiate the degradation process, and in vitro validation with cell extract of optimal temperature and pH and analysis for utilizing isoprene as the preferential substrate, were conducted. The most efficient monooxygenase was identified through comparative analyses using molecular docking followed by molecular dynamics simulation approach. The in silico results revealed high thermostability for most of the monooxygenases. Most potent monooxygenase with locus ID JQK15_20300 exhibiting high sequence similarity with known monooxygenases of isoprene-degrading Rhodococcus sp. LB1 and SC4 strains was identified. Interaction energy of -17.25 kJ/mol for JQK15_20300 with isoprene, was almost similar as that analysed for above-mentioned similar known counterparts, was exhibited by the molecular docking. Molecular dynamic simulation of 100 ns and free energy analysis of JQK15_20300 in the complex with isoprene gave persistent interaction of isoprene with JQK15_20300 during the simulation with high average binding energy of -47.13 kJ/mol thus proving higher affinity of JQK15_20300 for isoprene. The study revealed that the highly efficient isoprene degrading strain of Sphingobium sp. BHU LFT2 having effective monooxygenase could be utilized for large-scale applications including detoxification of air contaminated with isoprene in closed working systems.Communicated by Ramaswamy H. Sarma.

5d CIDR-Heatsynch improves the circulatory estradiol levels, estrus expression and conception rate in anestrus buffalo (Bubalus bubalis).

The present study aimed to investigate whether increasing estradiol (E2) during preovulatory period would increase estrous expression, luteal profiles and conception rate in 5d CIDR based timed AI protocol. A total 156 anestrus buffalo allocated (78 per group) to either 5d CIDR-Cosynch (d-5: CIDR + GnRH; d0: PGF2α+CIDR removal; 72 h post-CIDR removal: GnRH) or 5d CIDR-Heatsynch (d-5: CIDR + GnRH; d0: PGF2α+CIDR removal; 24 h post-CIDR removal: estradiol benzoate) group. All the buffaloes inseminated at 72 and 84 h post-CIDR removal. A subset of buffalo (n = 58) were subjected to examination of the follicle diameter and luteal profile during protocol, post-AI on days 5 and 12. The buffalo in 5d CIDR-Heatsynch had greater (p < .05) E2 concentrations, estrus induction and increasing trend (p < .08) for conception rate (57.7% vs. 43.6%) than 5d CIDR-Cosynch. The percentage of pregnant buffalo that exhibited estrus signs was greater (p < .01) in 5d CIDR-Heatsynch than 5d CIDR-Cosynch. Positive correlation (p < .01) was observed between POF and E2 concentrations; POF and CL diameter, CL diameter and P4 concentrations. Estrus response and P4 concentrations were indicators of probability of pregnancy. In conclusion, 5d CIDR-Heatsynch tended to improve conception rate. The estrus expression and P4 concentrations (d5 and 12 post-first-AI) is the indicator of probability of pregnancy in buffalo.

Presynchronization with simultaneous administration of GnRH and prostaglandin F2α (PGF2α) 7 days prior to Ovsynch improves reproductive profile in Hariana zebu cow.

This study is aimed at assessing the impact of simultaneous administration of GnRH and prostaglandin F2α (PGF2α) 7 days prior to Ovsynch in Hariana cow. Two hundred cyclic cows (> 4 months postpartum) were assigned to control (n = 54) and pre-OV (n = 146). As per Ovsynch protocol, buserelin acetate (10 µg), cloprostenol (500 µg), and buserelin acetate (10 µg) were injected i.m. on days 0, 7, and 9, respectively, in cows irrespective of treatment. But in pre-OV cows, buserelin acetate (10 µg) and cloprostenol (500 µg) were also injected i.m. simultaneously 7 days prior to initiate the Ovsynch protocol. Artificial insemination was performed between 18 and 24 h after the 2nd GnRH of Ovsynch in both treatments. Ultrasonography and blood sampling for hormonal analysis were done on each day of treatment, on day of AI, and 12 days post-AI. Pre-OV treatment resulted to increased (45.20% vs 29.62%; P < 0.05) pregnancy outcomes and higher (P < 0.01) ovulation rate to first GnRH of Ovsynch than control. Cows showing complete luteolysis in response to PGF2α of Ovsynch were also higher (P < 0.05) in pre-OV than control. Greater (P < 0.05) synchronization rate was recorded in pre-OV than control (86.76% and 68.75%). The circulating concentrations of estradiol on day of AI and progesterone on day 12 post-AI were higher (P < 0.01) in cows diagnosed pregnant than non-pregnant in both control and pre-OV treatment. In conclusion, simultaneous administration of GnRH and PGF2α 7 days before Ovsynch improved the synchronization rate and luteal profile in terms of CL area and hence resulted in higher conception rate in Hariana zebu cow.

In silico structural inhibition of ACE-2 binding site of SARS-CoV-2 and SARS-CoV-2 omicron spike protein by lectin antiviral dyad system to treat COVID-19.

Spike glycoprotein of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) binds angiotensin-converting enzyme-2 (ACE-2) receptors via its receptor-binding domain (RBD) and mediates virus-to-host cell fusion. Recently emerged omicron variant of SARS-CoV-2 possesses around 30 mutations in spike protein where N501Y tremendously increases viral infectivity and transmission. Lectins interact with glycoproteins and mediate innate immunity displaying antiviral, antibacterial, and anticarcinogenic properties. In this study, we analyzed the potential of lectin, and lectin-antibody (spike-specific) complex to inhibit the ACE-2 binding site of wild and N501Y mutated spike protein by utilizing in silico molecular docking and simulation approach. Docking of lectin at reported ACE-2 binding spike-RBD residues displayed the ZDock scores of 1907 for wild and 1750 for N501Y mutated spike-RBD. Binding of lectin with antibody to form proposed dyad complex gave ZDock score of 1174 revealing stable binding. Docking of dyad complex with wild and N501Y mutated spike-RBD, at lectin and antibody individually, showed high efficiency binding hence, effective structural inhibition of spike-RBD. MD simulation of 100 ns of each complex proved high stability of complexes with RMSD values ranging from 0.2 to 1.5 nm. Consistent interactions of lead ACE-2 binding spike residues with lectin during simulation disclosed efficient structural inhibition by lectin against formation of spike RBD-ACE-2 complex. Hence, lectins along with their ability to induce innate immunity against spike glycoprotein can structurally inhibit the spike-RBD when given as lectin-antibody dyad system and thus can be developed into a dual effect treatment against COVID-19. Moreover, the high binding specificity of this system with spike-RBD can be exploited for development of diagnostic and drug-delivery systems.

Visible-Light Photoredox-Catalyzed Synthesis of trans-Oxiranes via Decarboxylative Stereospecific Epoxidation of trans-Cinnamic Acids by Aryldiazonium Salts.

An efficient visible-light-induced synthesis of trans-oxiranes has been accomplished via decarboxylative stereospecific epoxidation of trans-cinnamic acids by aryldiazonium salts using CuCl, eosin Y, TBHP, and DBU. The reaction is facile, straightforward, and endowed with good functional group tolerability and a good substrate scope.

An in-silico evaluation of dietary components for structural inhibition of SARS-Cov-2 main protease.

The main protease (Mpro) of SARS-CoV-2 is responsible for the cleavage of viral replicase polyproteins 1a and 1ab into their mature form and is highly specific and exclusive in its activity. Many studies have targeted this enzyme by small molecule inhibitors to develop therapeutics against the highly infectious disease Covid-19. Our diet contains many natural antioxidants which along with providing support for proper growth and functioning of the body, pose additional health benefits. Present in-silico analysis depicted that natural antioxidants like sesamin, ellagic acid, capsaisin, and epicatechin along with galangin, exhibited significant binding at the catalytic site of the Mpro enzyme. They interacted with excellent efficiency with the chief active site residue Cys145 and thus seem to possess the remarkable potential to act as drug candidates for the treatment of Covid-19. Such dietary compounds can be easily administered orally with least toxicity related concern and thus yell for urgent exhaustive research to develop into efficient therapies.Communicated by Ramaswamy H. Sarma.

A molecular genetics view on Mucopolysaccharidosis Type II.

Mucopolysaccharidosis Type II (MPS II) is an X-linked recessive genetic disorder that primarily affects male patients. With an incidence of 1 in 100,000 male live births, the disease is one of the orphan diseases. MPS II symptoms are caused by mutations in the lysosomal iduronate-2-sulfatase (IDS) gene. The mutations cause a loss of enzymatic performance and result in the accumulation of glycosaminoglycans (GAGs), heparan sulfate and dermatan sulfate, which are no longer degradable. This inadvertent accumulation causes damage in multiple organs and leads either to a severe neurological course or to an attenuated course of the disease, although the exact relationship between mutation, extent of GAG accumulation and disease progression is not yet fully understood. This review is intended to present current diagnostic procedures and therapeutic interventions. In times when the genetic profile of patients plays an increasingly important role in the assessment of therapeutic success and future drug design, we chose to further elucidate the impact of genetic diversity within the IDS gene on disease phenotype and potential implications in current diagnosis, prognosis and therapy. We report recent advances in the structural biological elucidation of I2S enzyme that that promises to improve our future understanding of the molecular damage of the hundreds of IDS gene variants and will aid damage prediction of novel mutations in the future.

Retraction notice to "Melatonin renders neuroprotection by protein kinase C mediated aquaporin-4 inhibition in animal model of focal cerebral ischemia" [Life Sci. 100 (2014) 97-109].

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). This article has been retracted at the request of the Editor-in-Chief. Panels from Figures 2a and 3a appear similar to panels from Figures 2A and 3A of the article that the authors et al. have previously published in PLoS One 8(9) (2013) e73481 https://doi.org/10.1371/journal.pone.0073481 and Figures 1c and 2c of the article that Vikas Mishra, Rajkumar Verma and Ram Raghubir have published in Neuropharmacology 59 (2010) 582-588 https://doi.org/10.1016/j.neuropharm.2010.08.015. One of the conditions of submission of a paper for publication is that authors declare explicitly that the work is original. Re-use of any data should be appropriately cited. As such this article represents a misuse of the scientific publishing system. The scientific community takes a very strong view on this matter and apologies are offered to readers of the journal that this was not detected during the submission process.

Visible-Light-Induced Photocatalytic Oxidative Decarboxylation of Cinnamic Acids to 1,2-Diketones.

A concerted metallophotoredox catalysis has been realized for the efficient decarboxylative functionalization of α,ß-unsaturated carboxylic acids with aryl iodides in the presence of perylene bisimide dye to afford 1,2-diketones.