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.

AUTORES: Daniel J Klionsky1745,1749*, Kotb Abdelmohsen840, Akihisa Abe1237, Md Joynal Abedin1762, Hagai Abeliovich425,
\nAbraham Acevedo Arozena789, Hiroaki Adachi1800, Christopher M Adams1669, Peter D Adams57, Khosrow Adeli1981,
\nPeter J Adhihetty1625, Sharon G Adler700, Galila Agam67, Rajesh Agarwal1587, Manish K Aghi1537, Maria Agnello1826,
\nPatrizia Agostinis664, Patricia V Aguilar1960, Julio Aguirre-Ghiso784,786, Edoardo M Airoldi89,422, Slimane Ait-Si-Ali1376,
\nTakahiko Akematsu2010, Emmanuel T Akporiaye1097, Mohamed Al-Rubeai1394, Guillermo M Albaiceta1294,
\nChris Albanese363, Diego Albani561, Matthew L Albert517, Jesus Aldudo128, Hana Alg€ul1164, Mehrdad Alirezaei1198,
\nIraide Alloza642,888, Alexandru Almasan206, Maylin Almonte-Beceril524, Emad S Alnemri1212, Covadonga Alonso544,
\nNihal Altan-Bonnet848, Dario C Altieri1205, Silvia Alvarez1497, Lydia Alvarez-Erviti1395, Sandro Alves107,
\nGiuseppina Amadoro860, Atsuo Amano930, Consuelo Amantini1554, Santiago Ambrosio1458, Ivano Amelio756,
\nAmal O Amer918, Mohamed Amessou2089, Angelika Amon726, Zhenyi An1538, Frank A Anania291, Stig U Andersen6,
\nUsha P Andley2079, Catherine K Andreadi1690, Nathalie Andrieu-Abadie502, Alberto Anel2027, David K Ann58,
\nShailendra Anoopkumar-Dukie388, Manuela Antonioli832,858, Hiroshi Aoki1791, Nadezda Apostolova2007,
\nSaveria Aquila1500, Katia Aquilano1876, Koichi Araki292, Eli Arama2098, Agustin Aranda456, Jun Araya591,
\nAlexandre Arcaro1472, Esperanza Arias26, Hirokazu Arimoto1225, Aileen R Ariosa1749, Jane L Armstrong1930,
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\nAgnieszka Bagniewska-Zadworna2, Hua Bai90, Jie Bai667, Xue-Yuan Bai1133, Yannick Bailly884,
\nKithiganahalli Narayanaswamy Balaji473, Walter Balduini2002, Andrea Ballabio316, Rena Balzan1711, Rajkumar Banerjee239,
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\nMartine Biard-Piechaczyk210, Viktor Billes298, Claudia Bincoletto1314, Baris Bingol350, Sara W Bird1128, Marc Bitoun1112,
\nIvana Bjedov1258, Craig Blackstone843, Lionel Blanc1183, Guillermo A Blanco1496, Heidi Kiil Blomhoff1812,
\nEmilio Boada-Romero1297, Stefan B€ockler1464, Marianne Boes1423, Kathleen Boesze-Battaglia1835, Lawrence H Boise286,287,
\nAlessandra Bolino2063, Andrea Boman693, Paolo Bonaldo1823, Matteo Bordi897, J€urgen Bosch608, Luis M Botana1308,
\nJoelle Botti1375, German Bou1405, Marina Bouch e1038, Marion Bouchecareilh1331, Marie-Jos ee Boucher1901,
\nMichael E Boulton481, Sebastien G Bouret1926, Patricia Boya133, Micha€el Boyer-Guittaut1345, Peter V Bozhkov1141,
\nNathan Brady374, Vania MM Braga469, Claudio Brancolini1997, Gerhard H Braus353, Jos e M Bravo-San Pedro299,393,508,1374,
\nLisa A Brennan322, Emery H Bresnick2022, Patrick Brest490, Dave Bridges1939, Marie-Agn es Bringer124, Marisa Brini1822,
\nGlauber C Brito1311, Bertha Brodin631, Paul S Brookes1872, Eric J Brown352, Karen Brown1690, Hal E Broxmeyer480,
\nAlain Bruhat486,1339, Patricia Chakur Brum1893, John H Brumell446, Nicola Brunetti-Pierri315,1171,
\nRobert J Bryson-Richardson781, Shilpa Buch1777, Alastair M Buchan1819, Hikmet Budak1022, Dmitry V Bulavin118,505,1789,
\nScott J Bultman1792, Geert Bultynck665, Vladimir Bumbasirevic1470, Yan Burelle1356, Robert E Burke216,217,
\nMargit Burmeister1750, Peter B€utikofer1473, Laura Caberlotto1987, Ken Cadwell896, Monika Cahova112, Dongsheng Cai24,
\nJingjing Cai2099, Qian Cai1018, Sara Calatayud2007, Nadine Camougrand1343, Michelangelo Campanella1700,
\nGrant R Campbell1525, Matthew Campbell1249, Silvia Campello556,1876, Robin Candau1769, Isabella Caniggia1983,
\nLavinia Cantoni560, Lizhi Cao116, Allan B Caplan1656, Michele Caraglia1051, Claudio Cardinali1043, Sandra Morais Cardoso1579, Jennifer S Carew208, Laura A Carleton874, Cathleen R Carlin101, Silvia Carloni2002,
\nSven R Carlsson1267, Didac Carmona-Gutierrez1643, Leticia AM Carneiro312, Oliana Carnevali971, Serena Carra1318,
\nAlice Carrier120, Bernadette Carroll900, Caty Casas1324, Josefina Casas1116, Giuliana Cassinelli324, Perrine Castets1462,
\nSusana Castro-Obregon214, Gabriella Cavallini1841, Isabella Ceccherini568, Francesco Cecconi253,555,1884,
\nArthur I Cederbaum459, Valent ın Ce~na199,1281, Simone Cenci1323,2064, Claudia Cerella444, Davide Cervia1996,
\nSilvia Cetrullo1478, Hassan Chaachouay2028, Han-Jung Chae187, Andrei S Chagin634, Chee-Yin Chai626,628,
\nGopal Chakrabarti1502, Georgios Chamilos1601, Edmond YW Chan1142, Matthew TV Chan181, Dhyan Chandra1003,
\nPallavi Chandra548, Chih-Peng Chang818, Raymond Chuen-Chung Chang1653, Ta Yuan Chang345, John C Chatham1434,
\nSaurabh Chatterjee1910, Santosh Chauhan527, Yongsheng Che62, Michael E Cheetham1263, Rajkumar Cheluvappa1783,
\nChun-Jung Chen1153, Gang Chen598,1676, Guang-Chao Chen9, Guoqiang Chen1078, Hongzhuan Chen1077, Jeff W Chen1514,
\nJian-Kang Chen370,371, Min Chen249, Mingzhou Chen2104, Peiwen Chen1823, Qi Chen1674, Quan Chen172,
\nShang-Der Chen138, Si Chen325, Steve S-L Chen10, Wei Chen2125, Wei-Jung Chen829, Wen Qiang Chen979, Wenli Chen1113,
\nXiangmei Chen1133, Yau-Hung Chen1157, Ye-Guang Chen1250, Yin Chen1447, Yingyu Chen953,955, Yongshun Chen2135,
\nYu-Jen Chen712, Yue-Qin Chen1145, Yujie Chen1208, Zhen Chen339, Zhong Chen2123, Alan Cheng1702,
\nChristopher HK Cheng184, Hua Cheng1728, Heesun Cheong814, Sara Cherry1836, Jason Chesney1703,
\nChun Hei Antonio Cheung817, Eric Chevet1359, Hsiang Cheng Chi140, Sung-Gil Chi656, Fulvio Chiacchiera308,
\nHui-Ling Chiang958, Roberto Chiarelli1826, Mario Chiariello235,567,577, Marcello Chieppa835, Lih-Shen Chin290,
\nMario Chiong1285, Gigi NC Chiu878, Dong-Hyung Cho676, Ssang-Goo Cho650, William C Cho982, Yong-Yeon Cho105,
\nYoung-Seok Cho1064, Augustine MK Choi2095, Eui-Ju Choi656, Eun-Kyoung Choi387,400,685, Jayoung Choi1563,
\nMary E Choi2093, Seung-Il Choi2116, Tsui-Fen Chou412, Salem Chouaib395, Divaker Choubey1574, Vinay Choubey1936,
\nKuan-Chih Chow822, Kamal Chowdhury730, Charleen T Chu1856, Tsung-Hsien Chuang827, Taehoon Chun657,
\nHyewon Chung652, Taijoon Chung978, Yuen-Li Chung1194, Yong-Joon Chwae18, Valentina Cianfanelli254,
\nRoberto Ciarcia1775, Iwona A Ciechomska886, Maria Rosa Ciriolo1876, Mara Cirone1042, Sofie Claerhout1694,
\nMichael J Clague1698, Joan Cl aria1457, Peter GH Clarke1687, Robert Clarke361, Emilio Clementi1045,1398, C edric Cleyrat1781,
\nMiriam Cnop1366, Eliana M Coccia574, Tiziana Cocco1459, Patrice Codogno1375, J€orn Coers271, Ezra EW Cohen1533,
\nDavid Colecchia235,567,577, Luisa Coletto25, N uria S Coll123, Emma Colucci-Guyon516, Sergio Comincini1829,
\nMaria Condello578, Katherine L Cook2073, Graham H Coombs1929, Cynthia D Cooper2076, J Mark Cooper1395,
\nIsabelle Coppens601, Maria Tiziana Corasaniti1387, Marco Corazzari485,1884, Ramon Corbalan1566,
\nElisabeth Corcelle-Termeau251, Mario D Cordero1899, Cristina Corral-Ramos1289, Olga Corti507,1109, Andrea Cossarizza1767,
\nPaola Costelli1993, Safia Costes1518, Susan L Cotman721, Ana Coto-Montes946, Sandra Cottet566,1688, Eduardo Couve1301,
\nLori R Covey1015, L Ashley Cowart762, Jeffery S Cox1536, Fraser P Coxon1427, Carolyn B Coyne1846, Mark S Cragg1919,
\nRolf J Craven1679, Tiziana Crepaldi1995, Jose L Crespo1300, Alfredo Criollo1285, Valeria Crippa558, Maria Teresa Cruz1576,
\nAna Maria Cuervo26, Jose M Cuezva1277, Taixing Cui1907, Pedro R Cutillas987, Mark J Czaja27, Maria F Czyzyk-Krzeska1572,
\nRuben K Dagda2068, Uta Dahmen1404, Chunsun Dai800, Wenjie Dai1187, Yun Dai2059, Kevin N Dalby1940,
\nLuisa Dalla Valle1822, Guillaume Dalmasso1340, Marcello D’Amelio557, Markus Damme188, Arlette Darfeuille-Michaud1340,
\nCatherine Dargemont950, Victor M Darley-Usmar1433, Srinivasan Dasarathy205, Biplab Dasgupta202, Srikanta Dash1254,
\nCrispin R Dass242, Hazel Marie Davey8, Lester M Davids1560, David D avila227, Roger J Davis1731, Ted M Dawson604,
\nValina L Dawson606, Paula Daza1898, Jackie de Belleroche470, Paul de Figueiredo1180,1182,
\nRegina Celia Bressan Queiroz de Figueiredo135, Jos e de la Fuente1023, Luisa De Martino1775,
\nAntonella De Matteis1171, Guido RY De Meyer1443, Angelo De Milito631, Mauro De Santi2002,

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.

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.

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.

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.

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.

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.

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.

Chitin, the second most abundant polysaccharide in nature after cellulose, is found in the exoskeleton of insects, fungi, yeast, and algae, and in the internal structures of other vertebrates. Chitinases are enzymes that degrade chitin. Chitinases contribute to the generation of carbon and nitrogen in the ecosystem. Chitin and chitinolytic enzymes are gaining importance for their biotechnological applications, especially the chitinases exploited in agriculture fields to control pathogens. Chitinases have a use in human health care, especially in human diseases like asthma. Chitinases have wide-ranging applications including the preparation of pharmaceutically important chitooligosaccharides and N-acetyl D glucosamine, preparation of single-cell protein, isolation of protoplasts from fungi and yeast, control of pathogenic fungi, treatment of chitinous waste, mosquito control and morphogenesis, etc. In this review, the various types of chitinases and the chitinases found in different organisms such as bacteria, plants, fungi, and mammals are discussed.

Abstract Transcript alterations often result from somatic changes in cancer genomes 1 . Various forms of RNA alterations have been described in cancer, including overexpression 2 , altered splicing 3 and gene fusions 4 ; however, it is difficult to attribute these to underlying genomic changes owing to heterogeneity among patients and tumour types, and the relatively small cohorts of patients for whom samples have been analysed by both transcriptome and whole-genome sequencing. Here we present, to our knowledge, the most comprehensive catalogue of cancer-associated gene alterations to date, obtained by characterizing tumour transcriptomes from 1,188 donors of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA) 5 . Using matched whole-genome sequencing data, we associated several categories of RNA alterations with germline and somatic DNA alterations, and identified probable genetic mechanisms. Somatic copy-number alterations were the major drivers of variations in total gene and allele-specific expression. We identified 649 associations of somatic single-nucleotide variants with gene expression in cis , of which 68.4% involved associations with flanking non-coding regions of the gene. We found 1,900 splicing alterations associated with somatic mutations, including the formation of exons within introns in proximity to Alu elements. In addition, 82% of gene fusions were associated with structural variants, including 75 of a new class, termed ‘bridged’ fusions, in which a third genomic location bridges two genes. We observed transcriptomic alteration signatures that differ between cancer types and have associations with variations in DNA mutational signatures. This compendium of RNA alterations in the genomic context provides a rich resource for identifying genes and mechanisms that are functionally implicated in cancer.