Dataset on double mutation in PGIP of Glycine max improves defense to PG of Sclerotinia sclerotiorum.

The cell wall of the Glycine max altered by the polygalacturonases (PGs) secreted by the fungus Sclerotinia sclerotiorum, causes disease and quality losses. In soybeans, a resistance protein called polygalacturonases-inhibiting proteins (PGIPs) binds to the PG to block fungal infection. The active site residues of PGIP3, VAL170 and GLN242 are mutated naturally by various amino acids in different types of PGIPs. Therefore, the mutation of VAL170 to GLY is ineffective but the GLN242 amino acid mutation by LYS significantly alters the structure and is crucial for interacting with the PG protein. Docking and Molecular Dynamics simulation provide a comprehensive evaluation of the interactions between gmPGIP and ssPG. By elucidating the structural basis of the interaction between gmPGIP and ssPG, this investigation lays a foundation for the development of targeted strategies in-order to enhance soybean resistance against Sclerotinia sclerotiorum. By leveraging this knowledge, researchers can potentially engineer soybean varieties with improved resistance to the fungus, thereby reducing disease incidence and improving crop yields.

Classical molecular dynamics simulation identifies catechingallate as a promising antiviral polyphenol against MPOX palmitoylated surface protein.

Cumulative global prevalence of the emergent monkeypox (MPX) infection in the non-endemic countries has been professed as a global public health predicament. Lack of effective MPX-specific treatments sets the baseline for designing the current study. This research work uncovers the effective use of known antiviral polyphenols against MPX viral infection, and recognises their mode of interaction with the target F13 protein, that plays crucial role in formation of enveloped virions. Herein, we have employed state-of-the-art machine learning based AlphaFold2 to predict the three-dimensional structure of F13 followed by molecular docking and all-atoms molecular dynamics (MD) simulations to investigate the differential mode of F13-polyphenol interactions. Our extensive computational approach identifies six potent polyphenols Rutin, Epicatechingallate, Catechingallate, Quercitrin, Isoquecitrin and Hyperoside exhibiting higher binding affinity towards F13, buried inside a positively charged binding groove. Intermolecular contact analysis of the docked and MD simulated complexes divulges three important residues Asp134, Ser137 and Ser321 that are observed to be involved in ligand binding through hydrogen bonds. Our findings suggest that ligand binding induces minor conformational changes in F13 to affect the conformation of the binding site. Concomitantly, essential dynamics of the six-MD simulated complexes reveals Catechin gallate, a known antiviral agent as a promising polyphenol targeting F13 protein, dominated with a dense network of hydrophobic contacts. However, assessment of biological activities of these polyphenols need to be confirmed through in vitro and in vivo assays, which may pave the way for development of new novel antiviral drugs.

The Significance of Systemic Inflammatory Markers in Prognosis of Head and Neck Squamous Cell Cancers.

This present study aimed to assess the predictive significance of two systemic inflammatory markers, the neutrophilic to lymphocytic ratio (NLR) and platelet to lymphocytic ratio (PLR), in evaluating the prognosis of individuals. The research involved 47 patients diagnosed with head and neck squamous cell carcinoma, all of whom were histo-pathologically confirmed and aged over 18 years. The patients were monitored every 6 months for a period of 18 months. The average age of the study participants was 57.66 ± 13.5 years, with 42 (89.36%) being male and 5 (10.64%) female. After 6 months, the mean PLR in patients with residual/recurrence was 161.5 ± 8.5, which was significantly, exceeded that of patients without residual/recurrence (109.07 ± 36.29; p value < 0.0001). However, no significant correlation was seen between the NLR (p value = 0.822) and residual/recurrence after 6 months. After 12 months, the mean NLR in patients with recurrence was 4.89 ± 0.69, which was significantly higher compared to patients without recurrence (3.48 ± 1.01; p value = 0.025). Conversely, no significant association was found between the PLR (p value = 0.751) and recurrence after 12 months. Notably, there were no significant associations observed in NLR and PLR at the 18-month mark. Elevated levels of the NLR and PLR can serve as indicators of poor prognosis and the presence of residual/recurrent disease in head and neck malignancies.

In silico screening of phytoconstituents as potential anti-inflammatory agents targeting NF-κB p65: an approach to promote burn wound healing.

Chronic burn wounds are frequently characterised by a prolonged and dysregulated inflammatory phase that is mediated by over-activation of NF-κB p65. Synthetic wound healing drugs used for treatment of inflammation are primarily associated with several shortcomings which reduce their therapeutic index. In this scenario, phytoconstituents that exhibit multifaceted biological activities including anti-inflammatory effects have emerged as a promising therapeutic alternative. However, identification and isolation of phytoconstituents from medicinal herbs is a cumbersome method that is linked to profound uncertainty. Hence, present study aimed to identify prospective phytoconstituents as inhibitors of RHD of NF-κB p65 by utilizing in silico approach. Virtual screening of 2821 phytoconstituents was performed against protein model. Out of 2821 phytoconstituents, 162 phytoconstituents displayed a higher binding affinity (≤ -8.0 kcal/mol). These 162 phytoconstituents were subjected to ADMET predictions, and 15 of them were found to satisfy Lipinski's rule of five and showed favorable pharmacokinetic properties. Among these 15 phytoconstituents, 5 phytoconstituents with high docking scores i.e. silibinin, bismurrayaquinone A, withafastuosin B, yuccagenin, (+)-catechin 3-gallate were selected for molecular dynamics (MD) simulation analysis. Results of MD simulation indicated that withafastuosin B, (+)-catechin 3-gallate and yuccagenin produced a compact and stable complex with protein without significant variations in conformation. Relative binding energy analysis of best hit molecules indicate that withafastuosin B, and (+)-catechin 3-gallate exhibit high binding affinity with target protein among other lead molecules. Findings of study suggest that these phytoconstituents could serve as promising anti-inflammatory agents for treatment of burn wounds by inhibiting the RHD of NF-κB p65.Communicated by Ramaswamy H. Sarma.

All-atoms molecular dynamics study to screen potent efflux pump inhibitors against KpnE protein of Klebsiella pneumoniae.

The Small Multidrug Resistance efflux pump protein KpnE, plays a pivotal role in multi-drug resistance in Klebsiella pneumoniae. Despite well-documented study of its close homolog, EmrE, from Escherichia coli, the mechanism of drug binding to KpnE remains obscure due to the absence of a high-resolution experimental structure. Herein, we exclusively elucidate its structure-function mechanism and report some of the potent inhibitors through drug repurposing. We used molecular dynamics simulation to develop a dimeric structure of KpnE and explore its dynamics in lipid-mimetic bilayers. Our study identified both semi-open and open conformations of KpnE, highlighting its importance in transport process. Electrostatic surface potential map suggests a considerable degree of similarity between KpnE and EmrE at the binding cleft, mostly occupied by negatively charged residues. We identify key amino acids Glu14, Trp63 and Tyr44, indispensable for ligand recognition. Molecular docking and binding free energy calculations recognizes potential inhibitors like acarbose, rutin and labetalol. Further validations are needed to confirm the therapeutic role of these compounds. Altogether, our membrane dynamics study uncovers the crucial charged patches, lipid-binding sites and flexible loop that could potentiate substrate recognition, transport mechanism and pave the way for development of novel inhibitors against K. pneumoniae.Communicated by Ramaswamy H. Sarma.

Identification of potential inhibitor against CTX-M-3 and CTX-M-15 proteins: an in silico and in vitro study.

Extended-spectrum beta-lactamase (ESBL) producing Enterobacteriaceae infection is a serious global threat. ESBLs target 3rd generation cephalosporin antibiotics, the most commonly prescribed medicine for gram-negative bacterial infections. As bacteria are prone to develop resistance against market-available ESBL inhibitors, finding a novel and effective inhibitor has become mandatory. Among ESBL, the worldwide reported two enzymes, CTX-M-15 and CTX-M-3, are selected for the present study. CTX-M-3 protein was modeled, and two thousand phyto-compounds were virtually screened against both proteins. After filtering through docking and pharmacokinetic properties, four phyto-compounds (catechin gallate, silibinin, luteolin, uvaol) were further selected for intermolecular contact analysis and molecular dynamics (MD) simulation. MD trajectory analysis results were compared, revealing that both catechin gallate and silibinin had a stabilizing effect against both proteins. Silibinin having the lowest docking score, also displayed the lowest MIC (128 µg/mL) against the bacterial strains. Silibinin was also reported to have synergistic activity with cefotaxime and proved to have bactericidal effect. Nitrocefin assay confirmed that silibinin could inhibit beta-lactamase enzyme only in living cells, unlike clavulanic acid. Thus the present study validated the CTX-M inhibitory activity of silibinin both in silico and in vitro and suggested its promotion for further studies as a potential lead. The present study adopted a protocol through the culmination of bioinformatics and microbiological analyses, which will help future researchers identify more potential leads and design new effective drugs.Communicated by Ramaswamy H. Sarma.

Aryl selenonium vs. aryl sulfonium counterions in polyoxometalate chemistry: the impact of Se+ cationic centers on the photocatalytic reduction of dichromate.

A selenonium organic counter ion has been used in polyoxometalate chemistry to develop a new aryl selenonium polyoxometalate (POM) hybrid, and its photocatalytic properties have been explored in comparison with an aryl sulfonium POM-hybrid counterpart for the first time. The chalcogenonium counterions, namely, methyldiphenylsulfonium trifluoromethane sulfonate (MDPST) and methyldiphenylselenonium trifluoromethane sulfonate (MDPSeT), and their octamolybdate ([Mo8O26]4-) hybrids, 1 and 2, with the general formula (C13H13X)4[Mo8O26] (where X = S for 1 and Se for 2) were synthesized and characterized. Hybrids 1 and 2 vary in their chalcogenonium cationic center (S+vs. Se+), which enabled a direct comparison of their photocatalytic properties as a function of the cationic center. The photocatalytic activities of hybrids 1 and 2 were tested using the reduction of dichromate (Cr2O72-) as a model reaction under UV irradiation. A 99% photocatalytic reduction of Cr2O72- with a rate constant of 0.0305 min-1 was achieved with hybrid 2, while only a 67% reduction with a rate constant of 0.0062 min-1 was observed with hybrid 1 in 180 minutes. The better catalytic performance of hybrid 2 may be correlated to the larger atomic radii of Se than S, which helps in better stabilizing the photogenerated electron-hole (e--h+) pair on the POM cluster by polarizing its lone pair more efficiently compared to S. The catalytic recyclability was tested for up to 4 cycles using hybrid 2, and up to 98% reduction was obtained even after the 4th cycle. Recyclability tests and control experiments also indicated the generation of some elemental Se through possible cleavage of some C-Se bonds of MDPSe under prolonged UV exposure during catalysis, and the Se thus generated was found to contribute to the catalytic reduction of dichromate. This study, therefore, opens new avenues for aryl selenonium moieties and their POM hybrids for potential catalytic applications.

Illuminating the structural basis of human neurokinin 1 receptor (NK1R) antagonism through classical all-atoms molecular dynamics simulations.

Advances in structural biology have bestowed insights into the pleiotropic effects of neurokinin 1 receptors (NK1R) in diverse patho-physiological processes, thereby highlighting the potential therapeutic value of antagonists directed against NK1R. Herein, we investigate the mode of antagonist recognition to discern the obscure atomic facets germane for the function and molecular determinants of NK1R. To commence discernment of potent antagonists and the conformational changes in NK1R, induced upon antagonist binding, state-of-the-art classical all-atoms molecular dynamics (MD) simulations in lipid mimetic bilayers have been utilized. MD simulations of structural ensembles reveals the involvement of TM5 and TM6 in tight anchoring of antagonists through a network of interhelical hydrogen-bonds, while, the extracellular loop 2 (ECL2) governs the overall size and nature of the pocket, thereby modulating NK1R. Consistent comparison between experiments and MD simulation results discerns the predominant role of TM3, TM4, and TM6 in lipid-NK1R interaction. Correlation between hydrophobic index and helicity of TM domains elucidates their importance in maintaining the structural stability in addition to regulating NK1R antagonism. Taken together, we anticipate that our computational study marks a comprehensive structural basis of NK1R antagonism in lipid bilayers, which may facilitate designing of new therapeutics against associated diseases targeting human neurokinin receptors.

Reproducibility and Reliability of Computing Models in Segmentation and Volumetric Measurement of Brain.

Background: Segmentation and morphometric measurement of brain tissue and regions from non-invasive magnetic resonance images have clinical and research applications. Several software tools and models have been developed by different research groups which are increasingly used for segmentation and morphometric measurements. Variability in results has been observed in the imaging data processed with different neuroimaging pipelines which have increased the focus on standardization. Purpose: The availability of several tools and models for brain morphometry poses challenges as an analysis done on the same set of data using different sets of tools and pipelines may result in different results and interpretations and there is a need for understanding the reliability and accuracy of such models. Methods: T1-weighted (T1-w) brain volumes from the publicly available OASIS3 dataset have been analysed using recent versions of FreeSurfer, FSL-FAST, CAT12, and ANTs pipelines. grey matter (GM), white matter (WM), and estimated total intracranial volume (eTIV) have been extracted and compared for inter-method variability and accuracy. Results: All four methods are consistent and strongly reproducible in their measurement across subjects however there is a significant degree of variability between these methods. Conclusion: CAT12 and FreeSurfer methods have the highest degree of agreement in tissue class segmentation and are most reproducible compared to others.

Insilico generation of novel ligands for the inhibition of SARS-CoV-2 main protease (3CLpro) using deep learning.

The recent emergence of novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing the coronavirus disease (COVID-19) has become a global public health crisis, and a crucial need exists for rapid identification and development of novel therapeutic interventions. In this study, a recurrent neural network (RNN) is trained and optimized to produce novel ligands that could serve as potential inhibitors to the SARS-CoV-2 viral protease: 3 chymotrypsin-like protease (3CLpro). Structure-based virtual screening was performed through molecular docking, ADMET profiling, and predictions of various molecular properties were done to evaluate the toxicity and drug-likeness of the generated novel ligands. The properties of the generated ligands were also compared with current drugs under various phases of clinical trials to assess the efficacy of the novel ligands. Twenty novel ligands were selected that exhibited good drug-likeness properties, with most ligands conforming to Lipinski's rule of 5, high binding affinity (highest binding affinity: -9.4 kcal/mol), and promising ADMET profile. Additionally, the generated ligands complexed with 3CLpro were found to be stable based on the results of molecular dynamics simulation studies conducted over a 100 ns period. Overall, the findings offer a promising avenue for the rapid identification and development of effective therapeutic interventions to treat COVID-19.

Exploiting the potential of natural polyphenols as antivirals against monkeypox envelope protein F13 using machine learning and all-atoms MD simulations.

The re-emergence of monkeypox (MPX), in the era of COVID-19 pandemic is a new global menace. Regardless of its leniency, there are chances of MPX expediting severe health deterioration. The role of envelope protein, F13 as a critical component for production of extracellular viral particles makes it a crucial drug target. Polyphenols, exhibiting antiviral properties have been acclaimed as an effective alternative to the traditional treatment methods for management of viral diseases. To facilitate the development of potent MPX specific therapeutics, herein, we have employed state-of-the-art machine learning techniques to predict a highly accurate 3-dimensional structure of F13 as well as identify binding hotspots on the protein surface. Additionally, we have effectuated high-throughput virtual screening methodology on 57 potent natural polyphenols having antiviral activities followed by all-atoms molecular dynamics (MD) simulations, to substantiate the mode of interaction of F13 protein and polyphenol complexes. The structure-based virtual screening based on Glide SP, XP and MM/GBSA scores enables the selection of six potent polyphenols having higher binding affinity towards F13. Non-bonded contact analysis, of pre- and post- MD complexes propound the critical role of Glu143, Asp134, Asn345, Ser321 and Tyr320 residues in polyphenol recognition, which is well supported by per-residue decomposition analysis. Close-observation of the structural ensembles from MD suggests that the binding groove of F13 is mostly hydrophobic in nature. Taken together, this structure-based analysis from our study provides a lead on Myricetin, and Demethoxycurcumin, which may act as potent inhibitors of F13. In conclusion, our study provides new insights into the molecular recognition and dynamics of F13-polyphenol bound states, offering new promises for development of antivirals to combat monkeypox. However, further in vitro and in vivo experiments are necessary to validate these results.

A study on the seasonal cyclicity of ovarian development in adult Himalayan snow trout, Schizothorax plagiostomus.

Schizothorax plagiostomus, commonly known as snow trout, is a popular food fish found in parts of Central Asia and the Indo-Himalayan region. Despite such a broad range of distribution and potential financial value, it is a highly neglected cold-water ichthyofauna. Furthermore, an alarming decline in Schizothoracine population has been reported in the recent past due to climate change and uncontrolled anthropogenic interference. In this study, the seasonal variations in ovarian architecture and development were examined in adult S. plagiostomus from Garhwal Himalayan region, Uttarakhand, India. Ovarian-somatic index ranged from 16.86 ± 0.29 to 0.31 ± 0.56, with a maximal value in September and a minimal value in April. Ovarian histology revealed the abundance of primary growth oocytes in resting and preparatory stages; primary/secondary vitellogenic oocytes with numerous cortical alveoli were predominant in the developing stage of pre-spawning ovaries; secondary/tertiary vitellogenic oocytes were conspicuous in actively spawning ovaries; and atretic follicles/oocytes were discernible during the regressing stage of spent ovaries. Scanning electron microscopy of mature ova (mean diameter 2.003 ± 0.01 mm) prominently showed the structure micropyle (mean diameter 12.93 ± 3.38 µm). Fecundity analyses suggested that September was the principal breeding season, whereas residual spawning occurred with fresh rain in late winter during February-March. Collectively, this is the first comprehensive qualitative and quantitative report of the seasonal variations in the ovarian development and function for S. plagiostomus. These data may provide valuable information towards the captive breeding programme as well as conservation and management for Schizothoracine fishes in normal and altered climatic conditions.

Machine learning and classical MD simulation to identify inhibitors against the P37 envelope protein of monkeypox virus.

Monkeypox virus (MPXV) outbreak is a serious public health concern that requires international attention. P37 of MPXV plays a pivotal role in DNA replication and acts as one of the promising targets for antiviral drug design. In this study, we intent to screen potential analogs of existing FDA approved drugs of MPXV against P37 using state-of-the-art machine learning and computational biophysical techniques. AlphaFold2 guided all-atoms molecular dynamics simulations optimized P37 structure is used for molecular docking and binding free energy calculations. Similar to members of Phospholipase-D family , the predicted P37 structure also adopts a ß-α-ß-α-ß sandwich fold, harbouring strongly conserved HxKxxxxD motif. The binding pocket comprises of Tyr48, Lys86, His115, Lys117, Ser130, Asn132, Trp280, Asn240, His325, Lys327 and Tyr346 forming strong hydrogen bonds and dense hydrophobic contacts with the screened analogs and is surrounded by positively charged patches. Loops connecting the two domains and C-terminal region exhibit high degree of flexibility. In some structural ensembles, the partial disorderness in the C-terminal region is presumed to be due to its low confidence score, acquired during structure prediction. Transition from loop to ß-strands (244-254 aa) in P37-Cidofovir and its analog complexes advocates the need for further investigations. MD simulations support the accuracy of the molecular docking results, indicating the potential of analogs as potent binders of P37. Taken together, our results provide preferable understanding of molecular recognition and dynamics of ligand-bound states of P37, offering opportunities for development of new antivirals against MPXV. However, the need of in vitro and in vivo assays for confirmation of these results still persists.Communicated by Ramaswamy H. Sarma.

Genome size estimation and its associations with body length, chromosome number and evolution in teleost fishes.

Precise estimation of genome size (GS) is vital for various genomic studies, such as deciding genome sequencing depth, genome assembly, biodiversity documentation, evolution, genetic disorders studies, duplication events etc. Animal Genome Size Database provides GS of over 2050 fish species, which ranges from 0.35 pg in pufferfish (Tetraodon nigroviridis) to 132.83 pg in marbled lungfish (Protopterus aethiopicus). The GS of majority of the fishes inhabiting waters of Indian subcontinent are still missing. In present study, we estimated GS of 51 freshwater teleost (31 commercially important, 7 vulnerable and 13 ornamental species) that ranged from 0.58 pg in banded gourami (Trichogaster fasciata) to 1.92 pg in scribbled goby (Awaous grammepomus). Substantial variation in GS was observed within the same fish orders (0.64-1.45 pg in cypriniformes, 0.70-1.41 pg in siluriformes and 0.58-1.92 pg in perciformes). We examined the relationship between the GS, chromosome number and body length across all the fishes. Body length was found to be associated with GS, whereas no relationship was noticed between the GS and the chromosome number. The analysis using ancestral information revealed haploid chromosome number 25, 27 and 24 for the most recent common ancestor of cypriniformes, siluriformes and perciformes, respectively. The study led to generation of new records on GS of 43 fish species and revalidated records for 8 species. The finding is valuable resource for further research in the areas of fish genomics, molecular ecology and evolutionary conservation genetics.

Resolving the phylogenetic relationship of Himalayan snow trout Schizothorax plagiostomus with other species of Schizothoracine using mitochondrial CO-I and Cyt b genes.

BACKGROUND: The classification of the sub-family Schizothoracinae has been debatable due to the overlap in morphological characters. There are discrepancies between classical taxonomy and molecular taxonomy, as well. In the present study, mitochondrial genes CO-I and Cyt b were sequenced to elucidate the phylogenetic status of three species of the genus Schizothorax. METHODS AND RESULTS: In total, 29 samples of three species viz., S. plagiostomus, S. progastus, and S. richardsonii, were collected from rivers of Uttarakhand, India. For phylogenetic analyses, 40 sequences of CO-I and 41 sequences of Cyt b of Schizothoracinae species were downloaded from NCBI. The highest genetic divergence based on CO-I (16.08%) is between S. plagiostomus and Ptychobarbus dipogon, while the lowest divergence (0.00%) is between 10 pairs of species. The highest divergence based on Cyt b (19.43%), is between S. niger and Gymnocypris eckloni, while the lowest divergence (0.00%) is between four pairs of species. The divergence (0.00% for CO-I and 2.38% for Cyt b) between S. chongi and S. kozlovi, seems a case of convergent molecular evolution of the CO-I gene and in this case, CO-I alone cannot be used to differentiate these two species. CONCLUSION: The simultaneous use of two molecular markers along with morphomeristic data is a better strategy for the classification of the sub-family Schizothoracinae. These results will be a resource dataset for determining the taxonomical status of Schizothoracine species and will help in the conservation and commercial production of these commercially important fish species.

Keggin Cluster Modulated Photocatalytic Activity of Aryl Sulfonium Polyoxometalate Hybrids toward Dichromate Reduction.

Dichromate (Cr2O72-) ion having chromium in its +6 oxidation state is a carcinogen and a potential threat to humans and aquatic life. The photocatalytic reduction of toxic Cr(VI) species into less toxic Cr(III) is an important target in heterogeneous catalysis. In this work, the catalytic activities of a series of Keggin cluster-based aryl sulfonium polyoxometalate hybrids, (FPDS)3[PMo12O40] (1), (FPDS)3[PW12O40] (2), (FPDS)4[SiMo12O40] (3), and (FPDS)4[SiW12O40] (4), toward the photocatalytic reduction of Cr(VI) have been analyzed and compared. Here, we used the aryl sulfonium counterions to modulate the POM cluster's solubility in water and stabilize the photogenerated e--h+ pair on the cluster. All of the hybrids 1-4 catalyzed the reduction of Cr(VI) to Cr(III) under ultraviolet (UV) irradiation, and their photocatalytic efficiencies followed the order hybrid 1 > hybrid 3 > hybrid 2 > hybrid 4, with the rate-constant values of 0.048, 0.0056, 0.0035, and 0.0028 min-1, respectively. Hybrid 1 with [PMo12O40]3- Keggin cluster exhibited the best photocatalytic activity in the series yielding a 99% reduction in 120 min. The reasons behind the best photocatalytic activity of hybrid 1 are identified as its low band gap, less charge recombination, and fast photoresponse. The electron-trapping analyses performed using AgNO3 revealed electrons as the main reactive species responsible for the photocatalytic reduction of Cr(VI). A plausible photocatalytic mechanism has also been proposed based on electron-trapping experiments. The present study shows that aryl sulfonium Keggin hybrids can function as efficient photocatalysts for Cr(VI) reduction, and their catalytic efficiency varies with the nature of the Keggin cluster.

Glomus Tumor of the Pterygopalatine Fossa: A Rare Case Report.

The pterygopalatine fossa (PPF) is a challenging space and pathological processes in this anatomical space are uncommon. This report presents a case of glomus tumor right PPF in a 65 years old female patient who underwent tumor removal by endoscopic transnasal-transmaxillary approach with preoperative selective embolization of the right internal maxillary artery.

BAC-FISH Based Physical Map of Endangered Catfish Clarias magur for Chromosome Cataloguing and Gene Isolation through Positional Cloning.

Construction of a physical chromosome map of a species is important for positional cloning, targeted marker development, fine mapping of genes, selection of candidate genes for molecular breeding, as well as understanding the genome organization. The genomic libraries in the form of bacterial artificial chromosome (BAC) clones are also a very useful resource for physical mapping and identification and isolation of full-length genes and the related cis acting elements. Some BAC-FISH based studies reported in the past were gene based physical chromosome maps of Clarias magur (magur) to understand the genome organization of the species and to establish the relationships with other species in respect to genes' organization and evolution in the past. In the present study, we generated end sequences of the BAC clones and analyzed those end sequences within the scaffolds of the draft genome of magur to identify and map the genes bioinformatically for each clone. A total of 36 clones mostly possessing genes were identified and used in probe construction and their subsequent hybridization on the metaphase chromosomes of magur. This study successfully mapped all 36 specific clones on 16 chromosome pairs, out of 25 pairs of magur chromosomes. These clones are now recognized as chromosome-specific makers, which are an aid in individual chromosome identification and fine assembly of the genome sequence, and will ultimately help in developing anchored genes' map on the chromosomes of C. magur for understanding their organization, inheritance of important fishery traits and evolution of magur with respect to channel catfish, zebrafish and other species.

Identification of phytocompounds as newer antiviral drugs against COVID-19 through molecular docking and simulation based study.

COVID-19 pandemic has emerged as a global threat with its highly contagious and mutating nature. Several existing antiviral drugs has been worked on, without proper results and meanwhile the virus is mutating rapidly to create more infectious variant. In order to find some alternatives, phytocompounds can be opted as good one. In this study, three hundred phytocompounds were screened virtually against two viral proteins namely main protease and spike protein. Molecular docking and dynamic simulation study was used to find binding affinity, structural stability and flexibility of the complex. Pharmacokinetic properties were studied through ADMET analysis. To understand energy variation of the complex structure free energy landscape analysis was performed. Among three hundred phytocompounds virtual screening, three phytocompounds were selected for detailed molecular interaction analysis. Oleanderolide, Proceragenin A and Balsaminone A, showed strong binding affinity against both the target proteins and reflected conformational stability throughout the MD run. Oleanderolide, proceragenin A and balsaminone A has docking score -9.4 kcal/mol, -8.6 kcal/mol, and -8.1 kcal/mol respectively against main protease and same -8.3 kcal/mol docking score against spike protein. These three phytocompounds has high gastrointestinal absorption capacity. They were unexplored till now for their antiviral activity. Their promising in silico results suggests that they can be promoted in the long run for development of new antiviral drugs.

Integrative taxonomy peeps a new torrent catfish species of genus Amblyceps (Siluriformes: Amblycipitidae) in Kaladan River of Mizoram, India.

BACKGROUND: Explorations of the Kaladan River of Mizoram, India during the last decade have given a large number of new species. Integrative taxonomy, when used at the time of discovery of new species, can correlate the morphological characters with the species-specific DNA signatures and ameliorate the process of species identification. Based on this approach, Amblyceps hmolaii sp. nov., a new torrent catfish species is described from the Kaladan River drainage. METHODS AND RESULTS: The new species is distinguished from all twenty-two congeners by morphometric measurements and meristic counts. Sequence analysis of mitochondrial gene cytochrome c oxidase subunit I (COI), generated in this study and those available in NCBI, separated A. hmolaii sp. nov. from seven species of Amblyceps. Analysis of COI sequences, with ABGD software to delimit the species, also provided eight stable groups corresponding to the eight species of Amblyceps. The new species was separated from its congeners with an average genetic distance of 11.77%. Maximum-likelihood (ML) phylogenetic tree was constructed using the best fit nucleotide substitution model HKY + G + I. CONCLUSION: This study used all the twenty-two congeners in morphomeristic analysis and seven congeners in molecular analysis, for comparison with the new species. This approach unambiguously resolved the new species from other species of Amblyceps and created its species-specific DNA signatures. The discovery of new species even marked the first record of genus Amblyceps from the Kaladan drainage.