Structural polymorphism of DNA has constantly been evolving from the time of illustration of the double helical model of DNA by Watson and Crick. A variety of non-canonical DNA structures have constantly been documented across the globe. DNA attracted worldwide attention as a carrier of genetic information. In addition to the classical Watson–Crick duplex, DNA can actually adopt diverse structures during its active participation in cellular processes like replication, transcription, recombination and repair. Structures like hairpin, cruciform, triplex, G-triplex, quadruplex, i-motif and other alternative non-canonical DNA structures have been studied at length and have also shown their in vivo occurrence. This review mainly focuses on non-canonical structures adopted by DNA oligonucleotides which have certain prerequisites for their formation in terms of sequence, its length, number and orientation of strands along with varied solution conditions. This conformational polymorphism of DNA might be the basis of different functional properties of a specific set of DNA sequences, further giving some insights for various extremely complicated biological phenomena. Many of these structures have already shown their linkages with diseases like cancer and genetic disorders, hence making them an extremely striking target for structure-specific drug designing and therapeutic applications.
CYP1A1 gene is involved in estrogen metabolism, and previously, we have reported association of variant rs2606345 with altered anti-epileptic drugs (AED) response in North Indian women with epilepsy (WWE). The present study aims to replicate the pharmacogenetic association, perform functional characterization and study its distribution within ethnically diverse Indian population. The variant was genotyped in 351 patients to assess the pharmacogenetic association and 552 healthy individuals belonging to 24 different ethnic groups to examine the distribution in Indian population. We observed significant overrepresentation of 'A' allele and 'AA' genotype in poor responders in WWE at Bonferroni-corrected significance levels. The recessive allele was found to lower the promoter activity by ~70-80% which was further substantiated by thermally less stable hairpin formed by it (ΔT=7 °C). Among all ethnic groups, west Indo-European (IE-W-LP2) subpopulation showed highest genotypic frequency of the variant making women from this community more prone to poor AED response. Our results indicate that rs2606345 influences drug response in WWE by lowering CYP1A1 expression.
Proteins as a biomolecule have been recognized as a "molecule with manifold biological functions". The functions not only include the structural, regulatory and transportation processes inside the body but also its capacity as an extremely specific catalyst for various biochemical reactions. Nature has been quite admirably using proteins as biocatalysts which are known as enzymes. Properties like higher reaction rate, good specificity, faster kinetics, production of lesser by-products and their non-hazardous nature make enzymes the most suitable targets for a process chemist to exploit. At the same time, limitations like a narrow range of substrates, requirement of coenzymes, lesser stability, smaller shelf-life, along with difficulties in procuring these enzymes, make this biocatalysis field quite challenging. For exploiting a broad range of applications related to therapeutics, biosensors, biotechnology, nanotechnology etc., de novo designing of proteins is of utmost importance. Enzymes with altered, specific and modified properties might be designed by utilizing the prior knowledge of structure and function of a protein with the help of computational modeling. Various protein engineering techniques like directed evolution, rational designing and immobilization strategies etc. have already been extensively used to address some of the issues. This review aims to update the repertoire of the advancements in the field of protein engineering, which can help in laying some guiding principles about designing, modifying and altering their usage for commercial industrial purposes. This possibility of effective and novel designing of peptides and proteins might further facilitate our understanding about the structure, function and folding patterns along with their inter-relationships. Copyright © 2016 John Wiley & Sons, Ltd.
Small size, stability, easy and inexpensive production, capability to migrate throughout the body, fast clearance from body and low immunogenicity, as well as the remarkable quality of peptides to mirror the change in protease expression or activation associated with a pathological process, have established them as a promising biomarker.
For deciphering the secrets of forensic science, nanotechnology has quite extensively been utilized. Generally, for identifying the fingerprints, a lot of combination of different materials and film assemblies have already been utilized. Since the mode of interaction between the nanoparticles and fingerprint marks, is still not clearly understood, fabricating the nanoparticle assemblies for their identification is quite challenging. Complete identification of fingerprint marks which are generally because of a combination of some kind of proteins and fatty acids, is still a difficult task and is only partially being done with the help of different techniques. Nanotechnology has already shown immense potential in many fields like medicine, molecular biology, genetics, material science etc. and it has also marked promising potential even in forensic analysis studies. This review aims to discuss the details of the process of fingerprint formation, their role in forensic analysis along with the latest advances in the field of nanotechnology for their identification. This information may enhance our understanding about the progress in the forensic analysis of fingerprints, which may further be utilized in solving the puzzle of various criminal cases.
With the completion of human genome project, a plethora of information had been available for exploring various unanswered questions related to cell and molecular biology. Bioinformatics has been instrumental in unravelling the genetic, phenotypic, structural and functional aspects of the whole genome by using this information. Genomics and proteomics have become one of the most relevant fields after the advancements in computational analysis, interpretation, and modelling software. It can not only quite categorically describe the position of nucleotides and amino acids throughout genomes and proteomes respectively, but it also helps in performing the phylogenetic analysis, search for associated transcription factors, multiple sequence alignments, and many other relevant explorations/hunts. The advances in the knowledge of genetics acquired from molecular biology and bioinformatics are applied and point towards potential therapeutic strategies such as genome editing. This review has an aim of discussing some of the bioinformatics databases and software, which has been utilized for exploring the position of a DNA sequence, any associated single nucleotide polymorphism (SNP) related to a disease, on or nearby situated transcription factor binding sites followed by multiple sequence alignment of this sequence with other organisms. This study provides the insights in to the functional elements of any DNA, RNA or Protein sequence prior to exploring the structural polymorphism, which may regulate the gene expression. Also, this review briefly discusses the tools used for programmable nuclease-based genome editing technology.
Background: With the advent of changes in lifestyle of people all around the world, cancer cases have been showing an exponential rise. Researchers from varied fields have been trying to solve this tricky issue. Methods: We undertook a systematic search of bibliographic databases of peer-reviewed research literature to evaluate the holistic blend of modern and traditional approaches, especially the Ayurvedic perspective of treatment of cancer along with the effect of our diet and lifestyle on the management (both prevention and cure) of cancer. Results: On the basis of extensive literature survey, it was found that Ayurveda as one of the ancient medicinal systems had been very well documented for utilizing its best practices for the treatment of various diseases including cancer, by utilization of several herbal plants and dietary interventions as therapeutics. Active components present in various herbs, which interfere with certain molecular targets to inhibit carcinogenesis are also summarized. Further, beneficial effects of yoga and exercise on psychological distress, cancer-related fatigue and global side-effects as well as their mechanism of action are also discussed. In addition, we recapitulate an upcoming field of Ayurgenomics to understand the possible correlation of Prakriti with genetics as well as epigenetics. Conclusion: Both genetic as well as environmental factors have shown their linkage with cancer. Substantial advancements in the field of targeted therapies have opened new horizons for the cancer patients. To fight with this grave situation, a combination of ancient and modern medicinal systems seems to be the need of the hour.
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