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Presently, immunoinformatics and bioinformatics approaches are contributing actively to COVID-19 vaccine research. The first immunoinformatics-based vaccine construct against SARS-CoV-2 was published in February 2020. Following this, immunoinformatics and bioinformatics approaches have created a new direction in COVID-19 vaccine research. Several researchers have designed the next-generation COVID-19 vaccines using these approaches. Presently, immunoinformatics has accelerated immunology research immensely in the area of COVID-19. Hence, we have tried to depict the current scenario of immunoinformatics and bioinformatics in COVID-19 vaccine research. [ABSTRACT FROM AUTHOR]

The diverse, evolutionary architectures of proteins can be regarded as molecular fossils, tracing a historical path that marks important milestones across life. The B1-subfamily of GPCRs (G-protein-coupled receptors) are medically significant proteins that comprise 15 transmembrane receptor proteins in Homo sapiens. These proteins control the intracellular concentration of cyclic AMP as well as various vital processes in the body. However, little is known about the evolutionary correlation and conservational blueprint of this GPCR subfamily. We performed a comprehensive analysis to understand the evolutionary architecture among 13 members of the B1-subfamily. Multiple sequence alignment analysis exhibited six multiple sequence aligned blocks and five highly aligned blocks. Molecular phylogenetics indicated that CRHR1 and CRHR2 share a typical ancestral relationship and are siblings in 100% bootstrap replications with a total of 24 nodes observed in the cladogram. CRHR2 has the maximum number of extremely conserved amino acids followed by ADCYAP1R1. The longest continuous number sequence logos (74) were found between sequence location 349 and 423, and consequently, the maximum and minimum logo height recorded was 3.6 bits and 0.18 bits, respectively. Finally, to understand the model and pattern of evolutionary relatedness, the conservation blueprint, and the diversification among the members of a protein family, GPCR distribution from several species throughout the animal kingdom was analysed. Together, the study provides an evolutionary insight and offers a rapid method to explore the potential of depicting the evolutionary relationship, conservation blueprint, and diversification among the B1-subfamily of GPCRs using bioinformatics, algorithm analysis, and mathematical models. [ABSTRACT FROM AUTHOR]

Phosphoinositide 3-kinase (PI3K) is an essential regulatory protein of the insulin signaling pathway and several other pathways that govern cell survival, cell proliferation, cell differentiation and oncogene regulation. The protein has main two subunits; regulatory p85 and catalytic p110. Other regulatory subunits are p50, p55. The catalytic activity of p110 is stabilized by the regulatory subunit p85α. This regulatory subunit is composed of five domains; the SH3, BCR-homology (BH), N-terminal SH2 (nSH2), C-terminal SH2 (cSH2), and inter-SH2 (iSH2). In the current study, we executed comparative analysis of the computational proteomic and molecular evolution of these five domains. Our results reveal that faster and more cost-effective methods for forming intricate relationships between the domains are worth pursuing according to vital proteomic parameters such as physico-chemical properties, evolution and post-translational modification (PTM). The results show variation instability, grand average of hydrophobicity (GRAVY), aliphatic index, globularity, PTM among the five domains, and strongly indicate a likeness between the nSH2 and cSH2 domains. The study provides vital information for the structural and functional aspects of PI3K regulatory subunit p85α. Many of these property changes might be defined as protein–protein interactions, protein folding structures and structure–function correlations in future. [ABSTRACT FROM AUTHOR]

In the recent advancement of cancer therapy, mortality of the immortal cancer cells begins to decline, and it shows great promise for the chemotherapy regimen supported by targeted therapy. In this post-genomic era boosted by the discovery of microRNA (miRNA), it has been understood that miRNA regulates gene expression at the post-transcriptional level. On the other hand, some studies have also indicated that miRNA expression level has changed during the treatment of chemotherapy. Data based on various previous studies, we propose that the chemotherapeutic agents modulate miRNA expression that might perform anticancerous activities through cellular changes such as DNA repair, cell cycle arrest, or apoptosis. [ABSTRACT FROM AUTHOR]

We performed canonical correlation analysis as an unsupervised statistical tool to describe related views of the same semantic object for identifying patterns. A pattern recognition technique based on canonical correlation analysis (CCA) was proposed for finding required genetic code in the DNA sequence. Two related but different objects were considered: one was a particular pattern, and other was test DNA sequence. CCA found correlations between two observations of the same semantic pattern and test sequence. It is concluded that the relationship possesses maximum value in the position where the pattern exists. As a case study, the potential of CCA was demonstrated on the sequence found from HIV-1 preferred integration sites. The subsequences on the left and right flanking from the integration site were considered as the two views, and statistically significant relationships were established between these two views to elucidate the viral preference as an important factor for the correlation. [ABSTRACT FROM AUTHOR]

During the last two decades, the DNA barcode development towards microbial community has increased dramatically. DNA barcode development is related to error-free and quick species identification which aid in understanding the microbial biodiversity, as well as the diseases related to microbial species. Here, we seek to evaluate the so-called barcoding initiatives for the microbial communities and the emerging trends in this field. In this paper, we describe the development of DNA marker-based DNA barcoding system, comparison between routine species identification and DNA barcode, and microbial biodiversity and DNA barcode for microbial communities. Two major topics, such as the molecular diversity of viruses and barcode for viruses have been discussed at the same time. We demonstrate the current status and the maker of DNA barcode for bacteria, algae, fungi, and protozoa. Furthermore, we argue about the promises, limitations, and present and future challenges of microbial barcode development. [ABSTRACT FROM AUTHOR]

Understanding and predicting the significance of novel genetic variants revealed by DNA sequencing is a major challenge to integrate and interpret in medical genetics with medical practice. Recent studies have afforded significant advances in characterization and predicting the association of single nucleotide polymorphisms in human TERT with various disorders, but the results remain inconclusive. In this context, a comparative study between disease causing and novel mutations in hTERT gene was performed computationally. Out of 59 missense mutations, five variants were predicted to be less stable with the most deleterious effect on hTERT gene by in silico tools, in which two mutations (L584W and M970T) were not previously reported to be involved in any of the human disorders. To get insight into the structural and functional impact due to the mutation, docking study and interaction analysis was performed followed by 6 ns molecular dynamics simulation. These results may provide new perspectives for the targeted drug discovery in the coming future. [ABSTRACT FROM AUTHOR]

Cluster of differentiation (CD) is a group of proteins with highly immunological and medical importance, and some are established therapeutics. These membrane proteins are used to investigate of cell surface molecules of blood cells especially WBC. We selected a population of fifteen members with most medical importance, which includes CD2, CD4, CD5, CD6, CD7, CD9, CD14, CD16, CD19, CD22, CD28, CD33, CD36, CD38, and CD44 and performed in silico analysis using algorithm analysis and mathematical models. The results suggest that LEU (L) is well aligned. CD16 is rooted with CD22 and likewise, CD4 is closely related to CD44. Notably, highest number of highly conserved amino acids is recorded in CD22. WebLogo were formed up to 350 amino acid position and Met (M) is found to be tallest logo. Our results would be useful for upcoming researchers to obtain fundamental idea about the particular regions CD proteins which is having the structural and functional significance related to the evolutionary biology. [ABSTRACT FROM AUTHOR]

A correction to the article "Can the chemotherapeutic agents performanticancer activity through miRNA expression regulation? Proposing a new hypothesis" that was published in the 2015 issue is presented.

A letter to the editor is presented regarding the control of electronic waste in India.

Some individuals with non-small-cell lung cancer (NSCLC) benefit from therapies targeting epidermal growth factor receptor (EGFR), and the characterization of a new mechanism of resistance to the EGFR-specific antibody gefitinib will provide valuable insight into how therapeutic strategies might be designed to overcome this particular resistance mechanism. The G719S and T790M mutations and their combination were involved in causing different conformational redistribution of EGFR. In the present computational study, we analyzed the impact and structural influence of G719S/T790M double mutation (DM) in EGFR with ligand (gefitinib) through molecular dynamic simulation (50 ns) and docking analysis. We observed the escalation in distance between the functional loop and activation loop with respect to T790M mutation compared to the G719S mutation. Furthermore, we confirmed that the G719S mutation causes the ligand to move closer to the hinge region, whereas T790M makes the ligand escape from the binding pocket. Obtained results provide with an explanation for the resistance induced by T790M and a vital clue for the design of drugs to combat gefitinib resistance. [ABSTRACT FROM AUTHOR]

Bunyamwera orthobunyavirus and its serogroup can cause several diseases in humans, cattle, ruminants, and birds. The viral M-polyprotein helps the virus to enter the host body. Therefore, this protein might serve as a potential vaccine target against Bunyamwera orthobunyavirus. The present study applied the immunoinformatics technique to design an epitopic vaccine component that could protect against Bunyamwera infection. Phylogenetic analysis revealed the presence of conserved patterns of M-polyprotein within the viral serogroup. Three epitopes common for both B-cell and T-cell were identified, i.e., YQPTELTRS, YKAHDKEET, and ILGTGTPKF merged with a specific linker peptide to construct an active vaccine component. The low atomic contact energy value of docking complex between human TLR4 (TLR4/MD2 complex) and vaccine construct confirms the elevated protein–protein binding interaction. Molecular dynamic simulation and normal mode analysis illustrate the docking complex's stability, especially by the higher Eigenvalue. In silico cloning of the vaccine construct was applied to amplify the desired vaccine component. Structural allocation of both the vaccine and epitopes also show the efficacy of the developed vaccine. Hence, the computational research design outcomes support that the peptide-based vaccine construction is a crucial drive target to limit the infection of Bunyamwera orthobunyavirus to an extent. [ABSTRACT FROM AUTHOR]

The progression of the COVID-19 pandemic has generated numerous emerging variants of SARS-CoV-2 on a global scale. These variants have gained evolutionary advantages, comprising high virulence and serious infectivity due to multiple spike glycoprotein mutations. As a reason, variants are demonstrating significant abilities to escape the immune responses of the host. The D614G mutation in the S-glycoprotein of SARS-CoV-2 variants has shown the most efficient interaction with the ACE2 receptor of the cells. This explicit mutation at amino acid position 614 (aspartic acid-to-glycine substitution) is the prime cause of infection and re-infection. It changes the conformation of RBD and cleavage patterns S-glycoprotein with higher stability, replication fitness, and fusion efficiencies. Therefore, this review aims to provide several crucial pieces of information associated with the D614 mutational occurrence of SARS-CoV-2 variants and their infectivity patterns. This review will also effectively emphasize the mechanism of action of D614G mutant variants, immune escape, and partial vaccine escape of this virus. Furthermore, the viral characteristic changes leading to the current global pandemic condition have been highlighted. Here, we have tried to illustrate a novel direction for future researchers to develop effective therapeutic approaches and counterweight strategies to minimize the spread of COVID-19. Key points • D614G mutation arises within the S-glycoprotein of significant SARS-CoV-2 variants. • The D614G mutation affects infection, re-infection, cleavage patterns of S-glycoprotein, and replication fitness of SARS-CoV-2 variants. • The D614G mutation influences the immunity and partial vaccine escape. [ABSTRACT FROM AUTHOR]

We describe a novel algorithm for information recovery from DNA sequences by using a digital filter. This work proposes a three-part algorithm to decide the k-mer or q-gram word density. Employing a finite impulse response digital filter, one can calculate the sequence's k-mer or q-gram word density. Further principal component analysis is used on word density distribution to analyze the dissimilarity between sequences. A dissimilarity matrix is thus formed and shows the appearance of cluster formation. This cluster formation is constructed based on the alignment-free sequence method. Furthermore, the clusters are used to build phylogenetic relations. The cluster algorithm is in good agreement with alignment-based algorithms. The present algorithm is simple and requires less time for computation than other currently available algorithms. We tested the algorithm using beta hemoglobin coding sequences (HBB) of 10 different species and 18 primate mitochondria genome (mtDNA) sequences. [ABSTRACT FROM AUTHOR]

Helicobacter pylori is a highly potential pathogen to colonize in the human stomach. This bacterial strain is now alarming serious health concern all over the world. Combating through available drugs is a difficult task due to lack of appropriate common targets against genetically diverse strains. Therefore, the developments of effective targets vaccines require alternative strategies to eliminate the H. pylori infection. In this study, we developed a novel vaccine construct using B-cell derived T-cell epitopes from four target antigenic proteins (HpaA, FlaA, FlaB and Omp18), and found the induction of possible immune response using advanced immunoinformatics approaches. In order to boost immune system, we tagged adjuvant (50S ribosomal protein L7/L12) with a suitable linker at the N-terminus side of vaccine sequence. Protein–protein docking between human Toll like receptor 5 (TLR5) and vaccine construct help to predict the way of inductive signaling that leads to immune-response. The calculated negative score (− 151.4, + / − 8.7) of molecular docking complex signify the best binding interface. Molecular dynamics simulation studies confirmed the proper docking between TLR5 and vaccine candidate. Moreover, Normal mode analysis (NMA) calculates the molecular motion of the docking complex. The low eigenvalue (2.935e−05) indicates the stable and flexible molecular motion in the binding interaction side. Finally, in-silico cloning of vaccine candidate was performed using expression vector pET28b (+) with the optimized restriction sites. [ABSTRACT FROM AUTHOR]

To comprehend the events during developmental biology, fundamental knowledge about the basic machinery of regulation is a prerequisite. MicroRNA (miRNAs) act as regulators in most of the biological processes and recently, it has been concluded that miRNAs can act as modulatory factors even during developmental process from lower to higher animal. Zebrafish, because of its favorable attributes like tiny size, transparent embryo, and rapid external embryonic development, has gained a preferable status among all other available experimental animal models. Currently, zebrafish is being utilized for experimental studies related to stem cells, regenerative molecular medicine as well drug discovery. Therefore, it is important to understand precisely about the various miRNAs that controls developmental biology of this vertebrate model. In here, we have discussed about the miRNA-controlled zebrafish developmental stages with a special emphasis on different miRNA families such as miR-430, miR-200, and miR-133. Moreover, we have also reviewed the role of various miRNAs during embryonic and vascular development stages of zebrafish. In addition, efforts have been made to summarize the involvement of miRNAs in the development of different body parts such as the brain, eye, heart, muscle, and fin, etc. In each section, we have tried to fulfill the gaps of zebrafish developmental biology with the help of available knowledge of miRNA research. We hope that precise knowledge about the miRNA-regulated developmental stages of zebrafish may further help the researchers to efficiently utilize this vertebrate model for experimental purpose. [ABSTRACT FROM AUTHOR]

Purpose: To overcome the therapeutic restrictions offered by hydrophobic quercetin (Qu), this study aims to synthesize MPEG-PLA encapsulated Qu nanoparticle and to evaluate their anticancer efficacy. Materials and Methods: In vitro anticancer potential and apoptotic studies were done by cell cytotoxicity assay and flow cytometry, respectively . MPEG-PLA-Qu nanoparticles were evaluated for anticancer efficacy in vivo using xenograft mice model. TUNEL assay was performed to observe the frequency of apoptotic cells in vivo. Results: The hydrodynamic particle size, polydispersity index, zeta potential and drug loading % of MPEG-PLA-Qu nanoparticle was 155.3 ± 3.2 nm, 0.2 ± 0.05, −3.14 mV and 5.3 ± 1.1%, respectively. Also, MPEG-PLA-Qu showed sustained drug release for 10 days. In vitro results showed that MPEG-PLA-Qu could efficiently induce apoptosis in triple negative breast cancer cell line (MDA-MB-231) with higher amount of quercetin in cell lysate treated with MPEG-PLA-Qu in comparison to free quercetin. In xenograft model for breast cancer, peritumorally injected MPEG-PLA-Qu significantly inhibited the tumor growth. Moreover, TUNEL assay showed more occurrence of apoptotic cells in MPEG-PLA-Qu treated tumors compared to free quercetin at similar dose. Conclusion: Our data suggest that MPEG-PLA-Qu nanoparticle can have a promising clinical potential for the treatment of breast cancer. [ABSTRACT FROM AUTHOR]

India's Gujarat state has a long coastline with rich maritime history. The entrepreneurial nature of its citizens enabled Gujarat to emerge as the most aggressive industrial development state in the country. Due to the availability of vast land resource for industrial expansion along the coast, affordable labor cost, sparse human density and liberal state government policies have significantly contributed towards the outburst of the industrial sector's growth across Gujarat. Ecologically fragile ecosystems such as mangroves, coral reefs, mudflats, salt marshes, sea grass beds and nesting sites of winter migratory birds are increasingly threatened due to direct and indirect pressure induced by the industrial and allied development projects. This article reviews the status of coastal environment in Gujarat state with an emphasis on integrated coastal management associated laws and regulations. [ABSTRACT FROM AUTHOR]

The bacterial phosphoenolpyruvate (PEP)-dependent group translocation system (PTS) requires the presence of both membrane-bound and cytoplasmic components to phosphorylate and translocate sugar. Deinococcus radiodurans has a functional fruA gene coding for the membrane-bound components of the fructose-specific PTS. However, fruB gene coding for the fructose-specific cytosolic components of PTS is a pseudogene. Yet, this bacterium metabolized fructose readily. In vitro studies showed that both cell membranes and cytoplasmic fractions of the cells were needed for fructose phosphorylation. Further studies showed that fructose phosphorylation required ATP, not PEP, as the phosphate donor. Unlike most PEP-dependent PTS systems, fructose phosphorylation is sensitive to sodium fluoride, a kinase inhibitor. Fructose phosphorylation was also inhibited in the presence of antiserum against a kinase phosphorylation site. Rhodobacter capsulatus has a functional fruA- fruB system. Complementation assays by reconstituting the membrane fraction of D. radiodurans to the cytoplasmic fraction of R. capsulatus resulted in a PEP-dependent fructose phosphorylation, whereas mixing the membranes of R. capsulatus and the deinococcal cytosol in vitro resulted in an ATP-dependent fructose phosphorylation. [ABSTRACT FROM AUTHOR]