Department of Biotechnology

Heavy metal toxicity has proven to be a major threat and there are several health risks associated with it. The toxic effects of these metals, even though they do not have any biological role, remain present in some or the other form harmful for the human body and its proper functioning. They sometimes act as a pseudo element of the body while at certain times they may even interfere with metabolic processes. Few metals, such as aluminium, can be removed through elimination activities, while some metals get accumulated in the body and food chain, exhibiting a chronic nature. Various public health measures have been undertaken to control, prevent and treat metal toxicity occurring at various levels, such as occupational exposure, accidents and environmental factors. Metal toxicity depends upon the absorbed dose, the route of exposure and duration of exposure, i.e. acute or chronic. This can lead to various disorders and can also result in excessive damage due to oxidative stress induced by free radical formation. This review gives details about some heavy metals and their toxicity mechanisms, along with their health effects.

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. For example, a key point that needs to be emphasized is thatthere is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure flux through the autophagy pathway (i.e., the completeprocess including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defined as increasedautophagy induction coupled with increased delivery to, and degradation within, lysosomes (inmost higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in manycases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as forreviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multipleassays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation, it is imperative to target by gene knockout or RNA interference more than one autophagyrelated protein. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways implying that not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular assays, we hope to encourage technical innovation in the field.

Abstract Somatic mutations in cancer genomes are caused by multiple mutational processes, each of which generates a characteristic mutational signature 1 . Here, as part of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium 2 of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA), we characterized mutational signatures using 84,729,690 somatic mutations from 4,645 whole-genome and 19,184 exome sequences that encompass most types of cancer. We identified 49 single-base-substitution, 11 doublet-base-substitution, 4 clustered-base-substitution and 17 small insertion-and-deletion signatures. The substantial size of our dataset, compared with previous analyses 3–15 , enabled the discovery of new signatures, the separation of overlapping signatures and the decomposition of signatures into components that may represent associated—but distinct—DNA damage, repair and/or replication mechanisms. By estimating the contribution of each signature to the mutational catalogues of individual cancer genomes, we revealed associations of signatures to exogenous or endogenous exposures, as well as to defective DNA-maintenance processes. However, many signatures are of unknown cause. This analysis provides a systematic perspective on the repertoire of mutational processes that contribute to the development of human cancer.

Abstract Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale 1–3 . Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4–5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter 4 ; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation 5,6 ; analyses timings and patterns of tumour evolution 7 ; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity 8,9 ; and evaluates a range of more-specialized features of cancer genomes 8,10–18 .

autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.

Antibiotics have been used to cure bacterial infections for more than 70 years, and these low-molecular-weight bioactive agents have also been used for a variety of other medicinal applications. In the battle against microbes, antibiotics have certainly been a blessing to human civilization by saving millions of lives. Globally, infections caused by multidrug-resistant (MDR) bacteria are on the rise. Antibiotics are being used to combat diversified bacterial infections. Synthetic biology techniques, in combination with molecular, functional genomic, and metagenomic studies of bacteria, plants, and even marine invertebrates are aimed at unlocking the world's natural products faster than previous methods of antibiotic discovery. There are currently only few viable remedies, potential preventive techniques, and a limited number of antibiotics, thereby necessitating the discovery of innovative medicinal approaches and antimicrobial therapies. MDR is also facilitated by biofilms, which makes infection control more complex. In this review, we have spotlighted comprehensively various aspects of antibiotics viz. overview of antibiotics era, mode of actions of antibiotics, development and mechanisms of antibiotic resistance in bacteria, and future strategies to fight the emerging antimicrobial resistant threat.

Reactive oxygen species (ROS) are produced in plants as byproducts during many metabolic reactions, such as photosynthesis and respiration. Oxidative stress occurs when there is a serious imbalance between the production of ROS and antioxidant defense. Generation of ROS causes rapid cell damage by triggering a chain reaction. Cells have evolved an elaborate system of enzymatic and nonenzymatic antioxidants which help to scavenge these indigenously generated ROS. Various enzymes involved in ROS-scavenging have been manipulated, over expressed or downregulated to add to the present knowledge and understanding the role of the antioxidant systems. The present article reviews the manipulation of enzymatic and nonenzymatic antioxidants in plants to enhance the environmental stress tolerance and also throws light on ROS and redox signaling, calcium signaling, and ABA signaling.

Abstract Cancer develops through a process of somatic evolution 1,2 . Sequencing data from a single biopsy represent a snapshot of this process that can reveal the timing of specific genomic aberrations and the changing influence of mutational processes 3 . Here, by whole-genome sequencing analysis of 2,658 cancers as part of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA) 4 , we reconstruct the life history and evolution of mutational processes and driver mutation sequences of 38 types of cancer. Early oncogenesis is characterized by mutations in a constrained set of driver genes, and specific copy number gains, such as trisomy 7 in glioblastoma and isochromosome 17q in medulloblastoma. The mutational spectrum changes significantly throughout tumour evolution in 40% of samples. A nearly fourfold diversification of driver genes and increased genomic instability are features of later stages. Copy number alterations often occur in mitotic crises, and lead to simultaneous gains of chromosomal segments. Timing analyses suggest that driver mutations often precede diagnosis by many years, if not decades. Together, these results determine the evolutionary trajectories of cancer, and highlight opportunities for early cancer detection.

Abstract A key mutational process in cancer is structural variation, in which rearrangements delete, amplify or reorder genomic segments that range in size from kilobases to whole chromosomes 1–7 . Here we develop methods to group, classify and describe somatic structural variants, using data from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA), which aggregated whole-genome sequencing data from 2,658 cancers across 38 tumour types 8 . Sixteen signatures of structural variation emerged. Deletions have a multimodal size distribution, assort unevenly across tumour types and patients, are enriched in late-replicating regions and correlate with inversions. Tandem duplications also have a multimodal size distribution, but are enriched in early-replicating regions—as are unbalanced translocations. Replication-based mechanisms of rearrangement generate varied chromosomal structures with low-level copy-number gains and frequent inverted rearrangements. One prominent structure consists of 2–7 templates copied from distinct regions of the genome strung together within one locus. Such cycles of templated insertions correlate with tandem duplications, and—in liver cancer—frequently activate the telomerase gene TERT . A wide variety of rearrangement processes are active in cancer, which generate complex configurations of the genome upon which selection can act.

Interest in constructing composite materials from biosourced, recycled materials; waste resources; and their combinations is growing. Biocomposites have attracted the attention of automakers for the design of lightweight parts. Hybrid biocomposites made of petrochemical-based and bioresourced materials have led to technological advances in manufacturing. Greener biocomposites from plant-derived fiber and crop-derived plastics with higher biobased content are continuously being developed. Biodegradable composites have shown potential for major uses in sustainable packaging. Recycled plastic materials originally destined for landfills can be redirected and repurposed for blending in composite applications, thus leading to reduced dependence on virgin petro-based materials. Studies on compatibility of recycled and waste materials with other components in composite structure for improved interface and better mechanical performance pose major scientific challenges. This research holds the promise of advancing a key global sustainability goal.

Selenium (Se) is an essential micronutrient for humans and animals, but lead to toxicity when taken in excessive amounts. Plants are the main source of dietary Se, but essentiality of Se for plants is still controversial. However, Se at low doses protects the plants from variety of abiotic stresses such as cold, drought, desiccation, and metal stress. In animals, Se acts as an antioxidant and helps in reproduction, immune responses, thyroid hormone metabolism. Selenium is chemically similar to sulfur, hence taken up inside the plants via sulfur transporters present inside root plasma membrane, metabolized via sulfur assimilatory pathway, and volatilized into atmosphere. Selenium induced oxidative stress, distorted protein structure and function, are the main causes of Se toxicity in plants at high doses. Plants can play vital role in overcoming Se deficiency and Se toxicity in different regions of the world, hence, detailed mechanism of Se metabolism inside the plants is necessary for designing effective Se phytoremediation and biofortification strategies.

Chromothripsis is a mutational phenomenon characterized by massive, clustered genomic rearrangements that occurs in cancer and other diseases. Recent studies in selected cancer types have suggested that chromothripsis may be more common than initially inferred from low-resolution copy-number data. Here, as part of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA), we analyze patterns of chromothripsis across 2,658 tumors from 38 cancer types using whole-genome sequencing data. We find that chromothripsis events are pervasive across cancers, with a frequency of more than 50% in several cancer types. Whereas canonical chromothripsis profiles display oscillations between two copy-number states, a considerable fraction of events involve multiple chromosomes and additional structural alterations. In addition to non-homologous end joining, we detect signatures of replication-associated processes and templated insertions. Chromothripsis contributes to oncogene amplification and to inactivation of genes such as mismatch-repair-related genes. These findings show that chromothripsis is a major process that drives genome evolution in human cancer.

Abstract The discovery of drivers of cancer has traditionally focused on protein-coding genes 1–4 . Here we present analyses of driver point mutations and structural variants in non-coding regions across 2,658 genomes from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium 5 of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). For point mutations, we developed a statistically rigorous strategy for combining significance levels from multiple methods of driver discovery that overcomes the limitations of individual methods. For structural variants, we present two methods of driver discovery, and identify regions that are significantly affected by recurrent breakpoints and recurrent somatic juxtapositions. Our analyses confirm previously reported drivers 6,7 , raise doubts about others and identify novel candidates, including point mutations in the 5′ region of TP53 , in the 3′ untranslated regions of NFKBIZ and TOB1 , focal deletions in BRD4 and rearrangements in the loci of AKR1C genes. We show that although point mutations and structural variants that drive cancer are less frequent in non-coding genes and regulatory sequences than in protein-coding genes, additional examples of these drivers will be found as more cancer genomes become available.

Nanotechnology has the potential to circumvent several drawbacks of conventional therapeutic formulations. In fact, significant strides have been made towards the application of engineered nanomaterials for the treatment of cancer with high specificity, sensitivity and efficacy. Tailor-made nanomaterials functionalized with specific ligands can target cancer cells in a predictable manner and deliver encapsulated payloads effectively. Moreover, nanomaterials can also be designed for increased drug loading, improved half-life in the body, controlled release, and selective distribution by modifying their composition, size, morphology, and surface chemistry. To date, polymeric nanomaterials, metallic nanoparticles, carbon-based materials, liposomes, and dendrimers have been developed as smart drug delivery systems for cancer treatment, demonstrating enhanced pharmacokinetic and pharmacodynamic profiles over conventional formulations due to their nanoscale size and unique physicochemical characteristics. The data present in the literature suggest that nanotechnology will provide next-generation platforms for cancer management and anticancer therapy. Therefore, in this critical review, we summarize a range of nanomaterials which are currently being employed for anticancer therapies and discuss the fundamental role of their physicochemical properties in cancer management. We further elaborate on the topical progress made to date toward nanomaterial engineering for cancer therapy, including current strategies for drug targeting and release for efficient cancer administration. We also discuss issues of nanotoxicity, which is an often-neglected feature of nanotechnology. Finally, we attempt to summarize the current challenges in nanotherapeutics and provide an outlook on the future of this important field.

Recent remarkable advances in the field of nanotechnology has been achieved in the last few years especially in the fabrication of sensors that have wide number of applications. Nanomaterials are the foundation of nanotechnology that are measured on nanoscale. Carbon nanotubes (CNTs) are tube-like materials that are made up of carbon with a diameter calculating on a nanometer scale. They are originated from graphite sheet and these graphite layers seems similar to a rolled up non-stop unbreakable hexagonal like mesh structure and the carbon molecules appears at the apexes of the hexagonal structures. Depending upon the number of carbon layers, carbon nanotubes can be single-walled carbon nanotubes (SWCNTs), double-walled carbon nanotubes (DWCNTs) and multi-walled carbon nanotubes (MWCNTs). Carbon nanotubes (CNTs) can be fabricated by three main methods i.e., chemical vapor deposition, electric arc method and laser deposition method. Carbon nanotubes exhibit various characteristic properties such as high elasticity, high thermal conductivity, low density and they are chemically more inert etc. Due to these interesting properties, carbon nanotubes have played a significant role in the field of nanotechnology, electronics, optics and other fields of materials science. Carbon nanotubes are being positively applied in drug delivery, sensing, water treatment etc. Functionalization of their surface can result in highly soluble materials, which can be further derivatized with active molecules, making them compatible with biological systems. Surface functionalization enables adsorption or attachment of various molecules or antigens, which subsequently can be targeted to the desired cell population for immune recognition or a therapeutic effect. In this review, properties of carbon nanotubes and their clinical applications such as medical diagnostics and drug delivery are being discussed. Here, antibacterial as well as antifungal activity of carbon nanotubes are also being reviewed.

The study provides a systematic literature review (SLR) encompassing industrial wastewater management research from the past decade, examining enablers, challenges, and prevailing practices. Originating from manufacturing, energy production, and diverse industrial processes, industrial wastewater's handling is critical due to its potential to impact the environment and public health. The research aims to comprehend the current state of industrial wastewater management, pinpoint gaps, and outline future research prospects. The SLR methodology involves scouring the Scopus database, yielding an initial pool of 253 articles. Refinement via search code leaves 101 articles, followed by abstract screening that reduces articles to 79, and finally 66 well-focused articles left for thorough full-text examination. Results underscore the significance of regulatory frameworks, technological innovation, and sustainability considerations as cornerstones for effective wastewater management. However, substantial impediments like; inadequate infrastructure, resource constraints and the necessity for stakeholder collaboration still exist. The study highlights emerging research domains, exemplified by advanced technologies like nanotechnology and bioremediation, alongside the pivotal role of circular economy principles in wastewater management. The SLR offers an exhaustive view of contemporary industrial wastewater management, accentuating the imperative of an all-encompassing approach that integrates regulatory, technological, and sustainability facets. Notably, the research identifies gaps and opportunities for forthcoming exploration, advocating for interdisciplinary research and intensified stakeholder collaboration. The study's insights cater to policymakers, practitioners, and researchers, equipping them to address the challenges and capitalize on prospects in industrial wastewater management effectively.

Histamine and its receptors (H1R-H4R) play a crucial and significant role in the development of various allergic diseases. Mast cells are multifunctional bone marrow-derived tissue-dwelling cells that are the major producer of histamine in the body. H1R are expressed in many cells, including mast cells, and are involved in Type 1 hypersensitivity reactions. H2R are involved in Th1 lymphocyte cytokine production. H3R are mainly involved in blood-brain barrier function. H4R are highly expressed on mast cells where their stimulation exacerbates histamine and cytokine generation. Both H1R and H4R have important roles in the progression and modulation of histamine-mediated allergic diseases. Antihistamines that target H1R alone are not entirely effective in the treatment of acute pruritus, atopic dermatitis, allergic asthma, and other allergic diseases. However, antagonists that target H4R have shown promising effects in preclinical and clinical studies in the treatment of several allergic diseases. In the present review, we examine the accumulating evidence suggesting novel therapeutic approaches that explore both H1R and H4R as therapeutic targets for histamine-mediated allergic diseases.

Copper oxide (CuO) nanoparticles were synthesized by green chemistry approach using different plant extracts obtained from the leaves of Azadirachta indica, Hibiscus rosa-sinensis, Murraya koenigii, Moringa oleifera and Tamarindus indica. In order to compare their efficiency, the same copper oxide nanoparticles was also synthesized by chemical method. Phytochemical screening of the leaf extracts showed the presence of carbohydrates, flavonoids, glycosides, phenolic compounds, saponins, tannins, proteins and amino acids. FT IR spectra confirmed the possible biomolecules responsible for the formation of copper oxide nanoparticles. The surface plasmon resonance absorption band at 220-235nm in the UV-vis spectra also supports the formation of copper oxide nanoparticles. XRD patterns revealed the monoclinic phase of the synthesized copper oxide nanoparticles. The average size, shape and the crystalline nature of the nanoparticles were determined by SEM, TEM and SAED analysis. EDX analysis confirmed the presence of elements in the synthesized nanoparticles. The antioxidant activity was evaluated by three different free radical scavenging assays. The cytotoxicity of copper oxide nanoparticles was evaluated against four cancer cell lines such as human breast (MCF-7), cervical (HeLa), epithelioma (Hep-2) and lung (A549), and one normal human dermal fibroblast (NHDF) cell line. The morphological changes were evaluated using Hoechst 33258 staining assay. Copper oxide nanoparticles synthesized by green method exhibited high antioxidant and cytotoxicity than that synthesized by chemical method.

In the industrialized world, functional foods have become a part of an everyday diet and are demonstrated to offer potential health benefits beyond the widely accepted nutritional effects. Currently, the most important and frequently used functional food compounds are probiotics and prebiotics, or they are collectively known as 'synbiotics'. Moreover, with an already healthy image, dairy products appear to be an excellent mean for inventing nutritious foods. Such probiotic dairy foods beneficially affect the host by improving survival and implantation of live microbial dietary supplements in the gastrointestinal flora, by selectively stimulating the growth or activating the catabolism of one or a limited number of health-promoting bacteria in the intestinal tract, and by improving the gastrointestinal tract's microbial balance. Hence, the paper reviews the current scenario of probiotics and their prospective potential applications for functional foods for better health and nutrition of the society. Lactose metabolism & food digestion Cholesterol normalization B vitamins Diabetes Antioxidative activity Antibioticassociated diarrhea Oral health Immune response & Parasitic infections Reduction in blood pressure Constipation & ulcers

The upsurge in the need of targeted controlled drug delivery (TCDD) has led to the invention of remarkable biomaterials with improved biocompatibility and biodegradability. In recent years, "Smart Polymers" have emerged as a potential candidate, competing with the existing hydrogel systems used for controlled drug delivery. This article is an effort to highlight the diverse applications of hydrogels for revolutionizing the present research on drug delivery systems. This article summarizes the role of hydrogels as delivery vehicles for drugs used in various disorders related to the brain and other distinct parts of the human body. The clinical application and toxicological aspects of hydrogels are also highlighted. Their potential for diagnostics and various therapeutic interventions against tuberculosis have been reviewed. In addition, the limitations and future prospectives in the development of biopolymeric hydrogels are discussed.