28 results on '"Srivastava, Ankit"'
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2. Cyanophages: interacting mechanism and evolutionary significance
- Author
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Srivastava, Ankit, primary, Gupta, Neha, additional, and Mishra, Arun Kumar, additional
- Published
- 2024
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3. Economic Assessment of Wind Energy Compared to Fossil Fuels
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Rajpurohit, Bharat S., primary, Srivastava, Ankit K., additional, and Singh, Sri N., additional
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- 2024
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4. Contributors
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Abdullaev, Bekhzod, primary, Afzal, Mohammad, additional, Ahmad, Faizan, additional, Ahmad, Javed, additional, Alam, Manzar, additional, Ali, Sabeeha, additional, Annadurai, Narendran, additional, Anwar, Saleha, additional, Ara, Shabnam Anjum, additional, Badar, Sufian, additional, Bagheri, Soghra, additional, Banerjee, Subhamoy, additional, Bhat, Eijaz Ahmed, additional, Bhatt, Hardik, additional, Bisht, Deepa, additional, Dan, Siddhartha, additional, Das, Debasis, additional, Das, Viswanath, additional, Dhankhar, Poonam, additional, Dube, Divya, additional, Gupta, Parth, additional, Gupta, Varsha, additional, Hassan, Md. Imtaiyaz, additional, Hekmat, Azadeh, additional, Hyderi, Zeeshan, additional, Islam, Asimul, additional, James, Michael N.G., additional, Jha, Hem Chandra, additional, Jit, Bimal Prasad, additional, Kashyap, Dharmendra, additional, Kaur, Lajpreet, additional, Khan, Md Khurshid Alam, additional, Khan, Mohammad Ahmed, additional, Kumar, Dhiraj, additional, Kumar, Pravindra, additional, Kumar, Vinod, additional, Kumari, Varsha, additional, Mishra, Parul, additional, Misra, Ashish, additional, Mittal, Disha, additional, Mittal, Pooja, additional, Mohammad, Taj, additional, Musvi, Syed Shahid, additional, Nagar, Garima, additional, Naqi, Asma, additional, Nayak, Chirasmita, additional, Niveria, Karishma, additional, Noor, Saba, additional, Ojha, Himanshu, additional, Padhy, Amrita Arpita, additional, Pathak, Mallika, additional, Pathak, Upasana, additional, Payoe, Roshani, additional, Rai, Sandhya, additional, Rani, Annu, additional, Rankawat, Sourbh, additional, Raut, Rajnikant, additional, Raza, Ali, additional, Rustagi, Vanshika, additional, Saboury, Ali Akbar, additional, Sachan, Manisha, additional, Sahoo, Subhashree, additional, Saini, Taruna, additional, Sajjad, Nasreena, additional, Shakeel, Ilma, additional, Shamsi, Anas, additional, Shamsi, Tooba Naz, additional, Sharma, Saroj, additional, Shaw, Suman, additional, Shivani, Kummari, additional, Singh, Archana, additional, Singh, Indrakant Kumar, additional, Singh, Sanjeev Kumar, additional, Singh, Vishakha, additional, Singhal, Rahul, additional, Srivastava, Ankit, additional, Srivastava, Sameer, additional, Tiwari, Deeksha, additional, Tiwari, Vishvanath, additional, Varshney, Nidhi, additional, Verma, Anita Kamra, additional, Vishwakarma, Keerti, additional, and Zaidi, Yeshfa, additional
- Published
- 2022
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5. Prion-like behavior of TDP-43 aggregates and its implication to disease
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Srivastava, Ankit, primary, Admane, Nikita, additional, Singh Yadav, Shiv Pratap, additional, and Kukrety, Himanshi, additional
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- 2022
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6. The potential role of microbes in the treatment of contaminated water bodies: Current trends and Case Studies
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Prathna, T.C., primary and Srivastava, Ankit, additional
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- 2022
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7. Contributors
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Alencastre, Inês, primary, Annapure, Uday S., additional, Araujo, Ricardo, additional, Arifa, Raquel D.N., additional, Aroco, Clara Lara, additional, Attri, Sampan, additional, Azevedo, Maria, additional, Bagul, Aaditi, additional, Bansal, Saurabh, additional, Batista, Rafaela R.A., additional, Blanco, Ana Moreno, additional, Brito, Camila B., additional, Choi, Eun-Ha, additional, Čoklo, Miran, additional, Costa, Carolina F.F.A., additional, Debnath, Nabendu, additional, del Campo Moreno, Rosa, additional, Dhandapani, Sunmathi, additional, Dolanc, Ivan, additional, Fagundes, Caio Tavares, additional, Fagundes, Micheli, additional, García-Fernández, Sergio, additional, Goel, Gunjan, additional, Gómez, Juan Miguel Rodríguez, additional, Han, Ihn, additional, Jonjić, Antonija, additional, Kataria, Arti, additional, Khan, Mudassir Azeez, additional, Kraljević Pavelić, Sandra, additional, Kumar, Ashwani, additional, Kumar, Manoj, additional, Martínez-Cuesta, M. Carmen, additional, Maurya, Pawan Kumar, additional, Merino-Ribas, Ana, additional, Nagpal, Ravinder, additional, Nair, Pratisha, additional, Peláez, Carmen, additional, Pestana, Manuel, additional, Ponce-Alonso, Manuel, additional, Requena, Teresa, additional, Rodríguez-Jiménez, Concepción, additional, Saini, Vikas, additional, Sampaio-Maia, Benedita, additional, Sangokunle, Oluwatoyin, additional, Sharma, Ayushi, additional, Shrivastava, Rahul, additional, Singh, Prashant, additional, Snehalatha, B.M., additional, Solo de Zaldívar, Beatriz, additional, Souza, Daniele G., additional, Srivastava, Ankit, additional, Verma, Anamika, additional, Yadav, Ashok Kumar, additional, and Yadav, Dharmendra Kumar, additional
- Published
- 2022
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8. List of contributors
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Ahmed, Mushtaque, primary, Anand, Abhishek, additional, Badiee, Amir, additional, Biwole, Pascal, additional, Campana, Pietro Elia, additional, Chand, Aneesh A., additional, Dahlke, Flemming, additional, Das, Gautham P., additional, Dhal, Ipsa Sweta, additional, Ebadi, Hossein, additional, Emami, Paria, additional, Eterafi, Sina, additional, Fakhraei, Omid, additional, Focken, Ulfert, additional, Ghalazman E., Amir, additional, Gorjian, Shiva, additional, Gould, Iain, additional, Hermann, Charis, additional, Heselden, James, additional, Jakobsson, Simson, additional, Jathar, Laxmikant D., additional, Kamrani, Fatemeh, additional, Kant, Karunesh, additional, Ketzer, Daniel, additional, Kumar, Nallapaneni Manoj, additional, Lal, Prashant P., additional, Mousavi, Seyed Sina, additional, Mousavi Ajarostaghi, Seyed Soheil, additional, Özdemir, Özal Emre, additional, Papic, Iva, additional, Pearson, Simon, additional, Pennec, Fabienne, additional, Prasad, Kushal A., additional, Rajendran S., Vishnu, additional, Rösch, Christine, additional, Samadi, Haniyeh, additional, Savoldi, Laura, additional, Shamseddine, Ibrahim, additional, Sharma, Atul, additional, Shukla, Amritanshu, additional, Srivastava, Ankit, additional, Tlaiji, Ghadie, additional, Trommsdorff, Max, additional, Vadiee, Amir, additional, Weinberger, Nora, additional, Wright, Isobel, additional, Yan, Jinyue, additional, and Zarafshan, Payam, additional
- Published
- 2022
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9. Solar applications for drying of agricultural and marine products
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Srivastava, Ankit, primary, Anand, Abhishek, additional, Shukla, Amritanshu, additional, and Sharma, Atul, additional
- Published
- 2022
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10. Interplay of alpha-synuclein pathology and gut microbiome in Parkinson’s disease
- Author
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Srivastava, Ankit, primary, Kataria, Arti, additional, Yadav, Dharmendra Kumar, additional, Han, Ihn, additional, and Choi, Eun-Ha, additional
- Published
- 2022
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11. Targeting the altered tyrosine kinases in colorectal cancer: From inhibitors to drugs
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Srivastava, Ankit, primary, Rai, Sandhya, additional, Bisht, Deepa, additional, Sachan, Manisha, additional, Jit, Bimal Prasad, additional, and Srivastava, Sameer, additional
- Published
- 2022
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12. List of contributors
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Admane, Nikita, primary, Anwar, Md Sheeraz, additional, Apontes, Pasha, additional, Bharathi, Vidhya, additional, Galzitskaya, Oxana V., additional, Girdhar, Amandeep, additional, Haque, Mohd Maksuf Ul, additional, Jaiswal, Manoj Kumar, additional, Kukrety, Himanshi, additional, Kumar, Vijay, additional, Malik, Md Zubbair, additional, Patel, Basant K., additional, Rahman, Samir, additional, Sharma, Saurabh Kumar, additional, Singh, R.K. Brojen, additional, Singh Yadav, Shiv Pratap, additional, Srivastava, Ankit, additional, Tomar, Anil Kumar, additional, Verma, Nidhi, additional, and Yadav, Savita, additional
- Published
- 2021
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13. Contributors
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Ahmad, Harith, primary, Bowden, Stuart, additional, Brabazon, Dermot, additional, Chacko, Jenu V., additional, Chandra, Balu, additional, Dawes, Judith M., additional, Dutta, Joydeep, additional, Eapen, Nitin, additional, Fleischer, Karsten, additional, Goodnick, Stephen, additional, Grohens, Yves, additional, Gupta, Banshi D., additional, Harun, Sulaiman Wadi, additional, Honsberg, Christiana, additional, James, Jemy, additional, Jose, Jerry, additional, Joseph, Blessy, additional, Kalarikkal, Nandakumar, additional, Lee, Changhyoup, additional, Lee, Kwang-Geol, additional, Mathew, Juby Alphonsa, additional, McCarthy, Éanna, additional, Mohammed, Waleed Soliman, additional, Nair, Rajesh V., additional, Nancy, Parvathy, additional, Pathak, Anisha, additional, Rahim, Hazli Rafis Abdul, additional, Reduan, Siti Aisyah, additional, Rockstuhl, Carsten, additional, Saxena, Swasti, additional, Semwal, Vivek, additional, Shaji, Ashin, additional, Sreenilayam, Sithara P., additional, Srivastava, Ankit Kumar, additional, Tame, Mark, additional, Thambiratnam, Kavintheran, additional, Thokchom, Siddharth, additional, Thomas, Sabu, additional, Tiu, Zian Cheak, additional, Ulahannan, Jijo P., additional, and Vignaud, Guillaume, additional
- Published
- 2020
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14. Carbon nanotube-based sensors and their application
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Saxena, Swasti, primary and Srivastava, Ankit Kumar, additional
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- 2020
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15. List of Contributors
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Agarwal, Nidhi B., primary, Bedi, Geeta O., additional, Bhardwaj, Subodh, additional, Goyal, Richa, additional, Guin, Debleena, additional, Jalali, Rajinder K., additional, Karwa, Manoj, additional, Khanna, Bharti, additional, Khurana, Lalit K., additional, Kukreti, Ritushree, additional, Narang, Sunita, additional, Nell, Gerfried K.H., additional, Olsson, Sten, additional, Rai, Mahendra, additional, Rasaily, Deepa, additional, Saha, Nilanjan, additional, Sharma, Bindu, additional, Sharma, Sangeeta, additional, Singh, Gursharan, additional, Singh, Harinder, additional, Singh, Romi, additional, Sinha, Sandeep, additional, Srivastava, Ankit, additional, Vohora, Divya, additional, and Vyas, Preeti, additional
- Published
- 2018
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16. Pharmacogenomics
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Srivastava, Ankit, primary, Guin, Debleena, additional, Kukreti, Ritushree, additional, and Vohora, Divya, additional
- Published
- 2018
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17. Unravelling a novel CTNND1-RAB6A fusion transcript: Implications in colon cancer cell migration.
- Author
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Rai S, Singh MP, Sinha A, Srivastava A, Datta D, and Srivastava S
- Subjects
- Humans, HCT116 Cells, Cell Movement genetics, Biomarkers, Colorectal Neoplasms metabolism, Colonic Neoplasms genetics
- Abstract
The interchange of DNA sequences between genes may occur because of chromosomal rearrangements leading to the formation of chimeric genes. These chimeric genes have been linked to various cancers, accumulated significant interest in recent times. We used paired-end RNA-seq. data of four CRC and one normal sample generated from our previous study. The STAR-Fusion pipeline was utilized to identify the fusion genes unique to CRC. The in-silico identified fusion gene(s) were explored for their diagnostic, prognostic and therapeutic biomarker potential using TCGA-datasets, then validated through PCR and DNA sequencing. Further, cell line-based studies were performed to gain functional insights of the novel fusion transcript CTNND1-RAB6A, which was amplified in one sample. Sequencing revealed that there was a total loss of the CTNND1 gene, whereas RAB6A retained its coding sequence. Further, RAB6A was functionally characterized for its oncogenic potential in HCT116 cell line. RAB6A under-expression was found to be significantly associated with increased cell migration and is proposed to be regulated via the RAB6A-ECR1-Liprin-α axis. We conclude that RAB6A gene may play significant role in CRC oncogenesis, and could be used as a potential biomarker and therapeutic target in future for better management of a subset of CRCs harbouring this fusion., Competing Interests: Declaration of competing interest Authors declare there is no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)
- Published
- 2024
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18. Multiomics data identifies RSPO2 as a prognostic biomarker in human tumors associated with pan-cancer.
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Srivastava A and Srivastava S
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- Humans, Prognosis, Carcinogenesis, Biomarkers, Tumor Microenvironment, Multiomics, Neoplasms diagnosis, Neoplasms genetics
- Abstract
RSPO2 protein may provide valuable insights into the mechanism underlying various types of tumorigenesis. The role of RSPO2 in pan-cancer has not been reported so far. Therefore, this study aimed to provide a comprehensive analysis of RSPO2 from a pan-cancer perspective employing multiomics data. The expression profile and function of RSPO2 across different tumors were investigated using various web-based tools UALCAN, GEPIA, TIMER, Human Protein Atlas, cBioPortal, TISIDB, STRING, and Metascape to interpret the expression profile, promoter methylation status, genomic alterations, survival analysis, protein-protein interaction, correlation with immune cell subtypes, tumor immune microenvironment and enrichment analysis. Comprehensive pan-cancer analysis indicated that RSPO2 was significantly downregulated in eleven and upregulated in five tumor types compared to normal tissues, validation results further suggest RSPO2 was downregulated in most of the tumors. The protein level expression of RSPO2 was mostly low in malignant tissues. We found that RSPO2 was significantly related to individual pathological stages in BLCA, COAD, LUAD and LUSC. Prognostic analysis indicates that the high RSPO2 expression was significantly correlated with the poor prognosis in BRCA, KICH, KIRP, READ, and UCES. Furthermore, RSPO2 is frequently amplified, exhibits hypermethylated promoter in most cancers, and is associated with immune subtypes, molecular subtypes and immune cell infiltration. Finally, enrichment analysis showed that RSPO2 is involved in the regulation of the canonical Wnt pathway and neuronal development. The overall comprehensive pan-cancer analysis affirms that RSPO2 could be a promising diagnostic and prognostic biomarker and latent therapy target in the future., (Copyright © 2024. Published by Elsevier Inc.)
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- 2024
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19. HIF-1α regulates the expression of the non-conventional isoform of the cd5 gene in T cells under the hypoxic condition: A potential mechanism for CD5 neg/low phenotype of infiltrating cells in solid tumors.
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Kumari S, Sahu S, Singh B, Gupta S, Kureel AK, Srivastava A, Rikhari D, Srivastava S, and Rai AK
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- Humans, Hypoxia genetics, Protein Isoforms genetics, Exons, Phenotype, Hypoxia-Inducible Factor 1, alpha Subunit genetics, Hypoxia-Inducible Factor 1, alpha Subunit metabolism, Cell Hypoxia genetics, Cell Line, Tumor, Tumor Microenvironment, Neoplasms genetics
- Abstract
CD5, a T-cell receptor (TCR) negative regulator, is reduced on the surface of CD8+ lymphocytes in the tumor microenvironment (TME). Reduced surface CD5 expression (sCD5) occurs due to the preferential transcription of HERV-E derived exon E1B, i.e., anon-conventional formofthe cd5gene instead of its conventional exon E1A. A tumor employs several mechanisms to evade anti-tumor response, and hypoxia is one such mechanism that prevails in the TME and modulates the infiltrated T lymphocytes. We identified hypoxia response elements (HREs) upstream of E1B. We showed binding of HIF-1α onto these HREs and increased E1B mRNA expression in hypoxic T cells. This results in decreased sCD5 expression and increased cytoplasmic accumulation in T cells. We also validated our study in a solid tumor, i.e., colorectal cancer (CRC) patient samples. This hypoxia-driven mechanism reduces the surface CD5 expression on infiltrated T-cells in solid tumors., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)
- Published
- 2023
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20. The Long Noncoding RNA LINC00958 Is Induced in Psoriasis Epidermis and Modulates Epidermal Proliferation.
- Author
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Luo L, Pasquali L, Srivastava A, Freisenhausen JC, Pivarcsi A, and Sonkoly E
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- Humans, Interleukin-17 genetics, Interleukin-17 metabolism, Epidermis metabolism, Keratinocytes metabolism, Cell Proliferation genetics, RNA, Long Noncoding genetics, Psoriasis genetics, Psoriasis metabolism
- Abstract
Psoriasis is a common, immune-mediated skin disease characterized by epidermal hyperproliferation and chronic skin inflammation. Long noncoding RNAs are >200 nucleotide-long transcripts that possess important regulatory functions. To date, little is known about the contribution of long noncoding RNAs to psoriasis. In this study, we identify LINC00958 as a long noncoding RNA overexpressed in keratinocytes (KCs) from psoriasis skin lesions, in a transcriptomic screen performed on KCs sorted from psoriasis and healthy skin. Increased levels of LINC00958 in psoriasis KCs were confirmed by RT-qPCR and single-molecule in situ hybridization. Confocal microscopy and analysis of subcellular fractions showed that LINC00958 is mainly localized in the cytoplasm of KCs. IL-17A, a key psoriasis cytokine, induced LINC00958 in KCs through C/EBP-β and the p38 pathway. The inhibition of LINC00958 led to decreased proliferation as measured by Ki-67 expression, live cell analysis imaging, and 5-ethynyl-2-deoxyuridine assays. Transcriptomic analysis of LINC00958-depleted KCs revealed enrichment of proliferation- and cell cycle‒related genes among differentially expressed transcripts. Moreover, LINC00958 depletion led to decreased basal and IL-17A‒induced phosphorylation of p38. Furthermore, IL-17A‒induced KC proliferation was counteracted by the inhibition of LINC00958. In summary, our data support a role for the IL-17A‒induced long noncoding RNA, LINC00958, in the pathological circuits of psoriasis by reinforcing IL-17A‒induced epidermal hyperproliferation., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2023
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21. Molecular insights into the critical role of gallate moiety of green tea catechins in modulating prion fibrillation, cellular internalization, and neuronal toxicity.
- Author
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Admane N, Srivastava A, Jamal S, Sharma R, Kundu B, and Grover A
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- Humans, Prion Proteins chemistry, Tea, Molecular Docking Simulation, Prions chemistry, Prion Diseases, Catechin pharmacology
- Abstract
Transmissible spongiform encephalopathies (TSEs) or prion diseases are fatal neurodegenerative diseases with no approved therapeutics. TSE pathology is characterized by abnormal accumulation of amyloidogenic and infectious prion protein conformers (PrP
Sc ) in the central nervous system. Herein, we examined the role of gallate group in green tea catechins in modulating the aggregation of human prion protein (HuPrP) using two green tea constituents i.e., epicatechin 3-gallate (EC3G; with intact gallate ring) and epigallocatechin (EGC; without gallate ring). Molecular docking indicated distinct differences in hydrogen bonding and hydrophobic interactions of EC3G and EGC at the β2-α2 loop of HuPrP. These differences were substantiated by 44-fold higher KD for EC3G as compared to EGC with the former significantly reducing Thioflavin T (ThT) binding aggregates of HuPrP. Conformational alterations in HuPrP aggregates were validated by particle sizing, AFM analysis and A11 and OC conformational antibodies. As compared to EGC, EC3G showed relatively higher reduction in toxicity and cellular internalization of HuPrP oligomers in Neuro-2a cells. Additionally, EC3G also displayed higher fibril disaggregating properties as observed by ThT kinetics and electron microscopy. Our observations were supported by molecular dynamics (MD) simulations that showed markedly reduced α2-α3 and β2-α2 loop mobilities in presence of EC3G that may lead to constriction of HuPrP conformational space with lowered β-sheet conversion. In totality, gallate moiety of catechins play key role in modulating HuPrP aggregation, and toxicity and could be a new structural motif for designing therapeutics against prion diseases and other neurodegenerative disorders., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial or personal interests that could appear to have influenced the work reported in this paper., (Copyright © 2022. Published by Elsevier B.V.)- Published
- 2022
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22. IL-22 Downregulates Peptidylarginine Deiminase-1 in Human Keratinocytes: Adding Another Piece to the IL-22 Puzzle in Epidermal Barrier Formation.
- Author
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Padhi A, Srivastava A, Ramesh A, Ehrström M, Simon M, Sonkoly E, Eidsmo L, Bergman P, and Lysell J
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- Acitretin pharmacology, Acitretin therapeutic use, Biopsy, Cell Differentiation drug effects, Cell Differentiation genetics, Cell Line, Citrullination drug effects, Citrullination genetics, Dermatitis, Atopic drug therapy, Dermatitis, Atopic genetics, Dermatitis, Atopic pathology, Down-Regulation, Epidermis drug effects, Epidermis enzymology, Filaggrin Proteins metabolism, Humans, Keratin-1 metabolism, Keratinocytes drug effects, Keratinocytes enzymology, Keratinocytes pathology, Primary Cell Culture, Protein-Arginine Deiminase Type 1 metabolism, Psoriasis drug therapy, Psoriasis pathology, Vitamin D pharmacology, Vitamin D therapeutic use, Interleukin-22, Epidermis pathology, Interleukins metabolism, Protein-Arginine Deiminase Type 1 genetics, Psoriasis genetics
- Abstract
Increased presence of IL-22
+ cells in the skin is a characteristic finding in skin barrier defects, such as psoriasis and atopic dermatitis. However, mechanistic insight into effects of IL-22 on epidermal functioning is yet to be elucidated. One crucial step during epidermal differentiation is deimination or citrullination. Here, we show reduced levels of peptidylarginine deiminase 1, an enzyme that converts peptidylarginine into citrulline in lesional psoriatic skin. IL-22 signaling through the IL-22 receptor complex was found to suppress expression of peptidylarginine deiminase 1 in epidermal keratinocytes. Subsequently, total peptidylarginine deiminase activity and extent of protein deimination in keratinocytes treated with IL-22 were reduced together with a significant decrease in deimination of keratin 1 and FLG, both important for epidermal differentiation. Vitamin D and acitretin partly restored the peptidylarginine deiminase 1 defect caused by IL-22. Collectively, we show that IL-22 downregulates deimination, thus identifying a potential target for treatment of skin barrier defects., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)- Published
- 2022
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23. Prion protein transcription is auto-regulated through dynamic interactions with G-quadruplex motifs in its own promoter.
- Author
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Pradhan P, Srivastava A, Singh J, Biswas B, Saini A, Siddique I, Kumari P, Khan MA, Mishra A, Yadav PK, Kumar S, Bhavesh NS, Venkatraman P, Vivekanandan P, and Kundu B
- Subjects
- Cells, Cultured, Feedback, Physiological, Humans, Prion Proteins biosynthesis, Prion Proteins chemistry, Prion Proteins metabolism, G-Quadruplexes, Gene Expression Regulation, Prion Proteins genetics, Promoter Regions, Genetic, Transcription, Genetic
- Abstract
Cellular prion protein (PrP) misfolds into an aberrant and infectious scrapie form (PrP
Sc ) that lead to fatal transmissible spongiform encephalopathies (TSEs). Association of prions with G-quadruplex (GQ) forming nucleic acid motifs has been reported, but implications of these interactions remain elusive. Herein, we show that the promoter region of the human prion gene (PRNP) contains two putative GQ motifs (Q1 and Q2) that assume stable, hybrid, intra-molecular quadruplex structures and bind with high affinity to PrP. Here, we investigate the ability of PrP to bind to the quadruplexes in its own promoter. We used a battery of techniques including SPR, NMR, CD, MD simulations and cell culture-based reporter assays. Our results show that PrP auto-regulates its expression by binding and resolving the GQs present in its own promoter. Furthermore, we map this resolvase-like activity to the N-terminal region (residues 23-89) of PrP. Our findings highlight a positive transcriptional-translational feedback regulation of the PRNP gene by PrP through dynamic unwinding of GQs in its promoter. Taken together, our results shed light on a yet unknown mechanism of regulation of the PRNP gene. This work provides the necessary framework for a plethora of studies on understanding the regulation of PrP levels and its implications in prion pathogenesis., Competing Interests: Declaration of competing interest The authors declare no competing financial interests., (Copyright © 2019. Published by Elsevier B.V.)- Published
- 2020
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24. Next-Generation Sequencing Identifies the Keratinocyte-Specific miRNA Signature of Psoriasis.
- Author
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Srivastava A, Meisgen F, Pasquali L, Munkhammar S, Xia P, Ståhle M, Landén NX, Pivarcsi A, and Sonkoly E
- Subjects
- Biopsy, Humans, Keratinocytes pathology, MicroRNAs metabolism, Psoriasis metabolism, Psoriasis pathology, Sequence Analysis, RNA, High-Throughput Nucleotide Sequencing methods, Keratinocytes metabolism, MicroRNAs genetics, Psoriasis genetics
- Published
- 2019
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25. Exploring the aggregation-prone regions from structural domains of human TDP-43.
- Author
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Kumar V, Wahiduzzaman, Prakash A, Tomar AK, Srivastava A, Kundu B, Lynn AM, and Imtaiyaz Hassan M
- Subjects
- Molecular Dynamics Simulation, Protein Domains, DNA-Binding Proteins chemistry, Oligopeptides chemistry, Protein Aggregates
- Abstract
TDP-43 (transactive- response DNA binding protein) amazes structural biologist as its aberrant ubiquitinated cytosolic inclusions is largely involved in neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). An important question in TDP-43 research is to identify the structural region mediating the formation of cytoplasmic pathological aggregates. In this study, we attempted to delineate the aggregation-prone sequences of the structural domain of TDP-43. Here, we investigated the self-assembly of peptides of TDP-43 using aggregation prediction algorithms, Zipper DB and AMYLPRED2. The three aggregation-prone peptides identified were from N-terminal domain (
24 GTVLLSTV31 ), and RNA recognition motifs, RRM1 (128 GEVLMVQV135 ) and RRM2 (247 DLIIKGIS254 ). Furthermore, the amyloid fibril forming propensities of these peptides were analyzed through different biophysical techniques and molecular dynamics simulation. Our study shows the different aggregation ability of conserved stretches in structural domain of TDP-43 that will possibly induce full-length aggregation of TDP-43 in vivo. The peptide form RRM2 demonstrates the higher intrinsic amyloid forming propensity and suggests that RRM2 might form the structural core of TDP-43 aggregation seen in vivo. The results of this study would help in designing peptide based inhibitors of TDP-43 aggregation., (Copyright © 2018 Elsevier B.V. All rights reserved.)- Published
- 2019
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26. L-Asparaginase of Leishmania donovani: Metabolic target and its role in Amphotericin B resistance.
- Author
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Singh J, Khan MI, Singh Yadav SP, Srivastava A, Sinha KK, Ashish, Das P, and Kundu B
- Subjects
- Antiprotozoal Agents pharmacology, Asparaginase metabolism, Inhibitory Concentration 50, Kinetics, Leishmania donovani genetics, Leishmaniasis, Visceral parasitology, Metabolic Networks and Pathways drug effects, Models, Molecular, Protozoan Proteins genetics, Real-Time Polymerase Chain Reaction, Scattering, Small Angle, X-Ray Diffraction, Amphotericin B pharmacology, Asparaginase chemistry, Asparaginase drug effects, Drug Resistance genetics, Leishmania donovani drug effects, Leishmania donovani enzymology
- Abstract
Emergence of Amphotericin B (AmB) resistant Leishmania donovani has posed major therapeutic challenge against the parasite. Consequently, combination therapy aimed at multiple molecular targets, based on proteome wise network analysis has been recommended. In this regard we had earlier identified and proposed L-asparaginase of Leishmania donovani (LdAI) as a crucial metabolic target. Here we report that both LdAI overexpressing axenic amastigote and promastigote forms of L. donovani survives better when challenged with AmB as compared to wild type strain. Conversely, qRT-PCR analysis showed an upregulation of LdAI in both forms upon AmB treatment. Our data demonstrates the importance of LdAI in imparting immediate protective response to the parasite upon AmB treatment. In the absence of structural and functional information, we modeled LdAI and validated its solution structure through small angle X-ray scattering (SAXS) analysis. We identified its specific inhibitors through ligand and structure-based approach and characterized their effects on enzymatic properties (K
m , Vmax , Kcat ) of LdAI. We show that in presence of two of the inhibitors L1 and L2, the survival of L. donovani is compromised whereas overexpression of LdAI in these cells restores viability. Taken together, our results conclusively prove that LdAI is a crucial metabolic enzyme conferring early counter measure against AmB treatment by Leishmania., (Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.)- Published
- 2017
- Full Text
- View/download PDF
27. Stable self-assembled nanostructured hen egg white lysozyme exhibits strong anti-proliferative activity against breast cancer cells.
- Author
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Mahanta S, Paul S, Srivastava A, Pastor A, Kundu B, and Chaudhuri TK
- Subjects
- 3T3 Cells, Animals, Breast Neoplasms metabolism, Breast Neoplasms pathology, Cell Line, Cell Line, Tumor, Chickens, Circular Dichroism, Enzyme Stability, Female, Hemolysis drug effects, Humans, Hydrogen-Ion Concentration, MCF-7 Cells, Mice, Microscopy, Atomic Force, Microscopy, Electron, Scanning methods, Microscopy, Fluorescence, Muramidase chemistry, Nanostructures ultrastructure, Reactive Oxygen Species metabolism, Spectrometry, Fluorescence methods, Temperature, Cell Proliferation drug effects, Egg White chemistry, Muramidase pharmacology, Nanostructures chemistry
- Abstract
Chemotherapy side effects have long been a matter of great concern. Here we describe a structurally stable self-assembled nanostructured lysozyme (snLYZ) synthesized using a simple desolvation technique that exhibited anticancer activity, as well as excellent hemocompatibility. Field emission scanning electron microscopy; atomic force microscopy and dynamic particle size analyzer were used for analyzing the synthesized snLYZ. The analysis revealed spherical shape with an average size of 300 nm. Circular dichroism and tryptophan fluorescence spectroscopic analysis revealed its gross change in secondary as well as the tertiary level of the structure. snLYZ also demonstrated excellent structural as well as the functional stability of LYZ in a wide range of pH and temperature with a fair level of protection against proteinase K digestion. When applied to MCF-7 breast cancer cells, it exhibited approximately 95% cell death within 24h, involving a reactive oxygen species (ROS) based mechanism, and showed excellent hemocompatibility. Fluorescence microscopy imaging revealed distinct cellular internalization of snLYZ and the formation of cytoplasmic granules, which initiated a cell-killing process through membrane damage. In order to mimic targeted therapy, we tagged folic acid with snLYZ, which further enhanced cytotoxicity against MCF-7 cells. Therefore, this is the first report of its kind where we demonstrated the preparation of a highly stable self-assembled nanostructured lysozyme with a strong anti-proliferative activity against breast cancer cells., (Copyright © 2015 Elsevier B.V. All rights reserved.)
- Published
- 2015
- Full Text
- View/download PDF
28. Tributyltin chloride induced testicular toxicity by JNK and p38 activation, redox imbalance and cell death in sertoli-germ cell co-culture.
- Author
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Mitra S, Srivastava A, and Khandelwal S
- Subjects
- Animals, Apoptosis drug effects, Blood-Testis Barrier drug effects, Calcium metabolism, Calcium Channel Blockers pharmacology, Coculture Techniques, Coloring Agents, DNA Fragmentation drug effects, Enzyme Activation drug effects, Free Radical Scavengers pharmacology, Glutathione metabolism, Male, Membrane Potential, Mitochondrial drug effects, Metallothionein metabolism, Necrosis, Oxidation-Reduction, Phosphorylation, Rats, Reactive Oxygen Species metabolism, Testicular Diseases pathology, Testis drug effects, Testis metabolism, Testis pathology, Cell Death drug effects, Germ Cells drug effects, MAP Kinase Kinase 4 metabolism, Sertoli Cells drug effects, Testicular Diseases chemically induced, Trialkyltin Compounds toxicity, p38 Mitogen-Activated Protein Kinases metabolism
- Abstract
The widespread use of tributyltin (TBT) as biocides in antifouling paints and agricultural chemicals has led to environmental and marine pollution. Human exposure occurs mainly through TBT contaminated seafood and drinking water. It is a well known endocrine disruptor in mammals, but its molecular mechanism in testicular damage is largely unexplored. This study was therefore, designed to ascertain effects of tributyltin chloride (TBTC) on sertoli-germ cell co-culture in ex-vivo and in the testicular tissue in-vivo conditions. An initial Ca(2+) rise followed by ROS generation and glutathione depletion resulted in oxidative damage and cell death. We observed p38 and JNK phosphorylation, stress proteins (Nrf2, MT and GST) induction and mitochondrial depolarization leading to caspase-3 activation. Prevention of TBTC reduced cell survival and cell death by Ca(2+) inhibitors and free radical scavengers specify definitive role of Ca(2+) and ROS. Sertoli cells were found to be more severely affected which in turn can hamper germ cells functionality. TBTC exposure in-vivo resulted in increased tin content in the testis with enhanced Evans blue leakage into the testicular tissue indicating blood-testis barrier disruption. Tesmin levels were significantly diminished and histopathological studies revealed marked tissue damage. Our data collectively indicates the toxic manifestations of TBTC on the male reproductive system and the mechanisms involved., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)
- Published
- 2013
- Full Text
- View/download PDF
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