Comparative Genomics, Evolutionary Epidemiology, and RBD-hACE2 Receptor Binding Pattern in B.1.1.7 (Alpha) and B.1.617.2 (Delta) Related to Their Pandemic Response in UK and India

BACKGROUND: The massive increase in COVID-19 infection had generated a second wave in India during May-June 2021 with a critical pandemic situation. The Delta variant (B.1.617.2) was a significant factor during the second wave. Conversely, the UK had passed through the crucial phase of the pandemic from November to December 2020 due to B.1.1.7. The study tried to comprehend the pandemic response in the UK and India to the spread of the B.1.1.7 (Alpha, UK) variant and B.1.617.2 (Delta, India) variant. METHODS: This study was performed in three directions to understand the pandemic response of the two emerging variants. First, we served comparative genomics, such as genome sequence submission patterns, mutational landscapes, and structural landscapes of significant mutations (N501Y, D614G, L452R, E484Q, and P681R). Second, we performed evolutionary epidemiology using molecular phylogenetics, scatter plots of the cluster evaluation, country-wise transmission pattern, and frequency pattern. Third, the receptor binding pattern was analyzed using the Wuhan reference strain and the other two variants. RESULTS: The study analyzed the country-wise and region-wise genome sequences and their submission pattern, molecular phylogenetics, scatter plot of the cluster evaluation, country-wise geographical distribution and transmission pattern, frequency pattern, entropy diversity, and mutational landscape of the two variants. The structural pattern was analyzed in the N501Y, D614G L452R, E484Q, and P681R mutations. The study found increased molecular interactivity between hACE2-RBD binding of B.1.1.7 and B.1.617.2 compared to the Wuhan reference strain. Our receptor binding analysis showed a similar indication pattern for hACE2-RBD of these two variants. However, B.1.617.2 offers slightly better stability in the hACE2-RBD binding pattern through MD simulation than B.1.1.7. CONCLUSION: The increased hACE2-RBD binding pattern of B.1.1.7 and B.1.617.2 might help to increase the infectivity compared to the Wuhan reference strain

Anti-vibrio potential of bacterial and fungal endophytes isolated from Datura metel

43-53Bacterial and fungal endophytes were isolated and characterized from root and shoot of Datura metel and studied for their antimicrobial properties. Molecular identification of the endophytes, both bacteria and fungi were done using 16S rDNA and 18S rDNA sequencing, respectively. Out of the total bacterial endophytes, Bacillus subtilis was predominant in both the tissues. Of the nine fungal endophytes isolated both from root and shoot, Aspergillus versicolor was found to be dominant. These two dominant species of endophytes, B. subtilis and A. versicolor, were subjected to mass multiplication, and secondary metabolites extraction of the host plant endophytes were performed using solvents of different polarity. The respective extracts were then studied for their antimicrobial activity against different Vibrio cholerae strains. Both bacterial and fungal extracts showed impressive activity against the V. cholerae strains P5, NE2 and VC7233

P.: A distance based clustering method for arbitrary shaped clusters in large datasets. Pattern Recognition 44(12

a b s t r a c t Clustering has been widely used in different fields of science, technology, social science, etc. Naturally, clusters are in arbitrary (non-convex) shapes in a dataset. One important class of clustering is distance based method. However, distance based clustering methods usually find clusters of convex shapes. Classical single-link is a distance based clustering method, which can find arbitrary shaped clusters. It scans dataset multiple times and has time requirement of Oðn 2 Þ, where n is the size of the dataset. This is potentially a severe problem for a large dataset. In this paper, we propose a distance based clustering method, l-SL to find arbitrary shaped clusters in a large dataset. In this method, first leaders clustering method is applied to a dataset to derive a set of leaders; subsequently single-link method (with distance stopping criteria) is applied to the leaders set to obtain final clustering. The l-SL method produces a flat clustering. It is considerably faster than the single-link method applied to dataset directly. Clustering result of the l-SL may deviate nominally from final clustering of the single-link method (distance stopping criteria) applied to dataset directly. To compensate deviation of the l-SL, an improvement method is also proposed. Experiments are conducted with standard real world and synthetic datasets. Experimental results show the effectiveness of the proposed clustering methods for large datasets

A new similarity measure using Bhattacharyya coefficient for collaborative filtering in sparse data

Collaborative filtering (CF) is the most successful approach for personalized product or service recommendations. Neighborhood based collaborative filtering is an important class of CF, which is simple, intuitive and efficient product recommender system widely used in commercial domain. Typically, neighborhood-based CF uses a similarity measure for finding similar users to an active user or similar products on which she rated. Traditional similarity measures utilize ratings of only co-rated items while computing similarity between a pair of users. Therefore, these measures are not suitable in a sparse data. In this paper, we propose a similarity measure for neighborhood based CF, which uses all ratings made by a pair of users. Proposed measure finds importance of each pair of rated items by exploiting Bhattacharyya similarity. To show effectiveness of the measure, we compared performances of neighborhood based CFs using state-of-the-art similarity measures with the proposed measured based CF. Recommendation results on a set of real data show that proposed measure based CF outperforms existing measures based CFs in various evaluation metrics

Mechanism of Amphotericin B Resistance in Clinical Isolates of Leishmania donovani

The clinical value of amphotericin B, the mainstay therapy for visceral leishmaniasis in sodium antimony gluconatenonresponsive zones of Bihar, India, is now threatened by the emergence of acquired drug resistance, and a comprehensive understanding of the underlying mechanisms is the need of the hour. We have selected an amphotericin B-resistant clinical isolate which demonstrated 8-fold-higher 50% lethal doses (LD50) than an amphotericin B-sensitive strain to explore the mechanism of amphotericin B resistance. Fluorimetric analysis demonstrated lower anisotropy in the motion of the diphenylhexatriene fluorescent probe in the resistant strain, which indicated a higher fluidity of the membrane for the resistant strain than for the sensitive strain. The expression patterns of the two transcripts of S-adenosyl-L-methionine:C-24-�-sterol methyltransferase and the absence of ergosterol, replaced by cholesta-5,7,24-trien-3�-ol in the membrane of the resistant parasite, indicate a decreased amphotericin B affinity, which is evidenced by decreased amphotericin B uptake. The expression level of MDR1 is found to be higher in the resistant strain, suggesting a higher rate of efflux of amphotericin B. The resistant parasite also possesses an upregulated tryparedoxin cascade and a more-reduced intracellular thiol level, which helps in better scavenging of reactive oxygen species produced by amphotericin B. The resistance to amphotericin B was partially reverted by the thiol metabolic pathway and ABC transporter inhibitors. Thus, it can be concluded that altered membrane composition, ATP-binding cassette transporters, and an upregulated thiol metabolic pathway have a role in conferring amphotericin B resistance in clinical isolates of Leishmania donovani

Polyamide-polyamine cryptand as dicarboxylate receptor : dianion binding studies in the solid state, in solution, and in the gas phase

Polyamide-polyamine hybrid macrobicycle L is explored with respect to its ability to bind α,?-dicarboxylate anions. Potentiometric studies of protonated L with the series of dianions from succinate (suc) through glutarate (glu), α-ketoglutarate (kglu), adipate (adi), pimelate (pim), suberate (sub), to azelate (aze) have shown adipate preference with association constant value of K = 4900 M-1 in a HO/DMSO (50:50 v/v) binary solvent mixture. The binding constant increases from glu2- to adi2- and then continuously decreases with the length of the anion chain. Further, potentiometric studies suggest that hydrogen bonding between the guest anions and the amide/ammonium protons of the receptor also contributes to the stability of the associations along with electrostatic interactions. Negative-mode electrospray ionization of aqueous solutions of host-guest complexes shows clear evidence for the selective formation of 1:1 complexes. Single-crystal X-ray structures of complexes of the receptor with glutaric acid, α-ketoglutaric acid, adipic acid, pimelic acid, suberic acid, and azelaic acid assist to understand the observed binding preferences. The solid-state structures reveal a size/shape complementarity between the host and the dicarboxylate anions, which is nicely reflected in the solution state binding studies