Browsing by Author "Parimal Das"

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A new fluorescent pyrene-pyridine dithiocarbamate probe: A chemodosimeter to detect Hg2+ in pure aqueous medium and in live cells
(Elsevier, 2014) Vikram Singh; Priyanka Srivastava; Shiv Prakashverma; Arvind Misra; Parimal Das; Nanhai Singh
A new pyrene-pyridine dithiocarbamate based fluorescent chemodosimeter, potassium (pyren-1-ylmethyl)(pyridin-2-ylmethyl)dithiocarbamate (L1) has been designed and synthesized. The chemodosimeter shows high selectivity and sensitivity (5.2 ppb) for Hg2+ in pure aqueous medium in which emission intensity was quenched by.
A novel G to A transition at initiation codon and exon-intron boundary of PAX9 identified in association with familial isolated oligodontia
(Elsevier B.V., 2017) Tanmoy Sarkar; Rajesh Bansal; Parimal Das
Several studies on experimental animals indicate that the process of organogenesis crucially depends upon the spatiotemporal dose of certain critical bio-molecules. Tooth development is also not an exception. While most of the knowledge regarding the molecular mechanism of tooth development comes from the studies on mouse model, pathogenic variations identified in human tooth agenesis also provide valuable information on mammalian tooth development. Until now five major candidate genes have been identified for tooth agenesis in human. Among them, PAX9 plays the crucial role in tooth development and in non-syndromic congenital tooth agenesis. In this study, microsatellite and SNP based genotyping identifies a disease specific haplotype block, which includes PAX9 gene, segregates with autosomal dominant tooth agenesis phenotype. Direct sequencing of PAX9 identifies a novel heterozygous G to A transition at the third base (c.3G > A) of initiation codon leading to ATG to ATA shift in all affected individuals which is absent in all unaffected relatives and 200 control chromosomes. Further, in vitro functional analysis creating PAX9 minigene construct did apparently show no effect on the splice-site migration. It is therefore proposed that haploinsufficiency of PAX9 is the causal factor for tooth agenesis in this family. © 2017 Elsevier B.V.
A novel in-frame deletion in KIF5C gene causes infantile onset epilepsy and psychomotor retardation
(John Wiley and Sons Inc, 2024) Santasree Banerjee; Qiang Zhao; Bo Wang; Jiale Qin; Xin Yuan; Ziwei Lou; Weizeng Zheng; Huanguo Li; Xiaojun Wang; Xiawei Cheng; Yu Zhu; Fan Lin; Fan Yang; Junyu Xu; Anjana Munshi; Parimal Das; Yuanfeng Zhou; Kausik Mandal; Yi Wang; Muhammad Ayub; Nobutaka Hirokawa; Yongmei Xi; Guangfu Chen; Chen Li
Motor proteins, encoded by Kinesin superfamily (KIF) genes, are critical for brain development and plasticity. Increasing studies reported KIF’s roles in neurodevelopmental disorders. Here, a 6 years and 3 months-old Chinese boy with markedly symptomatic epilepsy, intellectual disability, brain atrophy, and psychomotor retardation was investigated. His parents and younger sister were phenotypically normal and had no disease-related family history. Whole exome sequencing identified a novel heterozygous in-frame deletion (c.265_267delTCA) in exon 3 of the KIF5C in the proband, resulting in the removal of evolutionarily highly conserved p.Ser90, located in its ATP-binding domain. Sanger sequencing excluded the proband's parents and family members from harboring this variant. The activity of ATP hydrolysis in vitro was significantly reduced as predicted. Immunofluorescence studies showed wild-type KIF5C was widely distributed throughout the cytoplasm, while mutant KIF5C was colocalized with microtubules. The live-cell imaging of the cargo-trafficking assay revealed that mutant KIF5C lost the peroxisome-transporting ability. Drosophila models also confirmed p.Ser90del's essential role in nervous system development. This study emphasized the importance of the KIF5C gene in intracellular cargo-transport as well as germline variants that lead to neurodevelopmental disorders and might enable clinicians for timely and accurate diagnosis and disease management in the future. © 2024 The Authors. MedComm published by Sichuan International Medical Exchange & Promotion Association (SCIMEA) and John Wiley & Sons Australia, Ltd.
An in vitro and computational validation of a novel loss-of-functional mutation in PAX9 associated with non-syndromic tooth agenesis
(Springer Science and Business Media Deutschland GmbH, 2023) Tanmoy Sarkar; Prashant Ranjan; Smitha Kanathur; Ankush Gupta; Parimal Das
Congenital tooth agenesis (CTA) is one of the most common craniofacial anomalies. Its frequency varies among different population depending upon the genetic heterogeneity. CTA could be of familial or sporadic and syndromic or non-syndromic. Five major genes are found to be associated with non-syndromic CTA, namely PAX9, MSX1, EDA1, AXIN2, and WNT10A. Very few studies have been carried out so far on CTA on this Indian population making this study unique and important. This study was initiated to identify potential pathogenic variant associated with congenital tooth agenesis in an India family with molar tooth agenesis. CTA was investigated and a novel c.336C > G variation was identified in the exon 3 of PAX9, leading to substitution of evolutionary conserved Cys with Trp at 112th amino acid position located at the functionally significant DNA-binding paired domain region. Functional analysis revealed that p.Cys112Trp mutation did not prevent the nuclear localization although mutant protein had higher cytoplasmic retention. EMSA using e5 probe revealed that mutant protein was unable to bind with the paired-domain-binding site. Subsequently, GST pull-down assay revealed lower binding activity of the mutant protein with its known interactor MSX1. These in vitro results were consistent with the computational results. The in vitro and computational observations altogether suggest that c.336C > G (p.Cys112Trp) variation leads to loss of function of PAX9 leading to CTA in this family. Graphical abstract: [Figure not available: see fulltext.]. © 2022, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.
An inclusive study of deleterious missense PAX9 variants using user-friendly tools reveals structural, functional alterations, as well as potential therapeutic targets.
(Elsevier B.V., 2023) Prashant Ranjan; Parimal Das
Mutations in the PAX9 are responsible for non-syndromic tooth agenesis in humans, although their structural and functional consequences on protein phenotype, stability, and posttranslational modifications (PTMs) have not yet been adequately investigated. This in silico study focuses on retrieving the six most deleterious mutations (L21P, R26W, R28P, G51S, I87F, and K91E) of PAX9 that has been linked to severe oligodontia. Several computational algorithm methods were used to determine the deleterious effects of PAX9 mutations. Analysis of gene ontology, protein interactions, and PTMs indicated significant functional changes caused by PAX9 mutations. The structural superimposition of the wild-type and mutant PAX9 variants revealed structural changes in locations that were present in the structures of all six variations. The conserved domain analysis revealed that the areas shared by all six variations contained unique sections that lacked DNA binding or protein-protein interaction sites, suggesting prospective drug target sites for functional restoration. The protein-protein interaction network showed KDM5B as PAX9's strongest interacting partner similar to MSX1. The PAX9 protein's structural conformations, compactness, stiffness, and function may all be impacted by changes, according to MD simulations. In addition, research on cell lines and animal models may be valuable in establishing their specific roles in functional annotations. © 2023 Elsevier B.V.
An integrative analysis of functional consequences of PKD2 missense variants on RNA and protein structures: a computational approach
(Springer Nature, 2024) Chandra Devi; Prashant Ranjan; Parimal Das
Background: The PKD2, encoding polycystin-2 (PC2) protein, is second major genetic determinant of autosomal dominant polycystic kidney disease (ADPKD) after PKD1. However, the structural and functional consequences of genetic variants in PKD2 remain poorly understood. Given the complexity and heterogeneous nature of ADPKD, understanding its pathogenesis at cellular and molecular levels is vital for deciphering genotype–phenotype correlations and disease severity, thus informing patient-centered treatments. We analyzed missense variants of PKD2 to assess their impact on RNA structure using computational tools and explored associated protein structure dynamics through MD simulation. Results: Our findings reveal distinct structural alterations and dynamic behaviors associated with specific missense variants. The variants such as c.1789C > A (p.L597M), c.1109G > A (p.S370N), c.1849C > A (p.L617I), and c.646 T > C (p.Y216H) induced major changes not only in RNA structure and accessibility profile but also in protein structure dynamics. In contrast, variants such as c.915C > A (p.N305K), c.1354A > G (p.I452V), and c.568G > A (p.A190T) resulted in minor alterations in RNA structure but exhibited noticeable effects on certain parameters of protein structure dynamics. Conclusion: This study suggests the multifaceted impact of these missense variants on both RNA and protein levels. It lays the groundwork in identifying high-impact variants in terms of pathogenicity and prioritizing these for further implications in understanding disease heterogeneity and eventually contributing to the development of targeted therapeutic interventions for ADPKD. Graphical Abstract: (Figure presented.) Study Highlights : PKD2 missense variants analyzed for impact on RNA and protein Structures Alterations in RNA Structures and protein dynamics observed Computational integration of analyses aids in prioritizing variants for further study Provide insights into disease heterogeneity and potential therapeutic targets © The Author(s) 2024.
Aqueous extract of anticancer drug CRUEL herbomineral formulation capsules exerts anti-proliferative effects in renal cell carcinoma cell lines
(Asian Pacific Organization for Cancer Prevention, 2016) Shiv Prakash Verma; Saumya Sisoudiya; Parimal Das
Purpose: Anti-cancer activity evaluation of aqueous extract of CRUEL (herbomineral formulation) capsules on renal cell carcinoma cell lines, and exploration of mechanisms of cell death. Materials and Methods: To detect the cytotoxic dose concentration in renal cell carcinoma (RCC) cells, MTT assays were performed and morphological changes after treatment were observed by inverted microscopy. Drug effects against RCC cell lines were assessed with reference to cell cycle distribution (flow cytometry), anti-metastatic potential (wound healing assay) and autophagy(RT-PCR). Results: CRUEL showed anti-proliferative effects against RCC tumor cell lines with an IC50 value of approximately 4mg/mL in vitro., while inducing cell cycle arrest at S-phase of cell cycle and inhibiting wound healing. LC3 was found to be up-regulated after drug treatment in RT-PCR resulting in an autophagy mode of cell death. Conclusions: This study provides the experimental validation for antitumor activity of CRUEL.
Asparagus racemosus leaf extract inhibits growth of UOK 146 Renal cell carcinoma cell line: Simultaneous oncogenic PRCCTFE3 fusion transcript inhibition and apoptosis independent cell death
(Asian Pacific Organization for Cancer Prevention, 2014) Shiv Prakash Verma; Vikash Chandra Tripathi; Parimal Das
Aims: To evaluate anti-cancer activity of Asparagus racemosus (AR) leaf extract on UOK146, a renal cell carcinoma cell line, and explore its mechanism of action. Materials and Methods: Dried AR leaves were extracted with chloroform and dissolved in DMSO. This extract was applied to UOK146 and cell death was estimated by MTT assay. In addition PRCC-TFE3 fusion transcripts were detected by real time PCR. Results: Extract was found to be cytotoxic with an IC50 of 0.9 mg/ml as estimated by dose response curve. Antitumor activity of the permissible doses of the extract was assessed by the down regulation of PRCC-TFE3 fusion transcript (38%) responsible for oncogenicity of the UOK146 cell line. No increment in the BAX, a proapoptotic marker level was observed. Conclusions: Evidence of antiproliferative effect, PRCC-TFE3 fusion transcript inhibition and static BAX level clearly indicate that AR extract provides or elicits an apoptosis independent anticancer effect on RCC cells by some specific mechanism of regulation.
Calcimycin mediates apoptosis in breast and cervical cancer cell lines by inducing intracellular calcium levels in a P2RX4-dependent manner
(Elsevier B.V., 2024) Neha; Prashant Ranjan; Parimal Das
Background: Calcimycin (A23187) is a polyether antibiotic and divalent cation ionophore, extracted from Streptomyces chartrecensis. With wide variety of antimicrobial activities, it also exhibits cytotoxicity of tumor cells. Calcimycin exhibit therapeutic potential against tumor cell growth; however, the molecular mechanism remains to be fully elucidated. Present study explores the mechanism of calcimycin-induced apoptosis cancer cell lines. Methods: Apoptotic induction in a dose-dependent manner were recorded with MTT assays, Phase contrast imaging, wound healing assay, fluorescence imaging by DAPI and AO/EB staining and FACS using cell line model. Mitochondrial potential was analyzed by TMRM assay as Ca2+ signaling is well known to be influenced and synchronized by mitochondria also. Results: Calcimycin induces apoptosis in dose dependent manner, also accompanied by increased intracellular calcium-level and expression of purinergic receptor-P2RX4, a ligand-gated ion channel. Conclusion: Calcimycin tends to increase the intracellular calcium level, mRNA expression of ATP receptor P2RX4, and phosphorylation of p38. Blocking of either intracellular calcium by BAPTA-AM, P2RX4 expression by antagonist 5-BDBD, and phospho-p38 by SB203580, abrogated the apoptotic activity of calcimycin. General significance: Taken together, these results show that calcimycin induces apoptosis in P2RX4 and ATP mediated intracellular Ca2+ and p38 MAPK mediated pathway in both the cancer cell lines. This study explored a new mode of action for calcimycin in cancer that could be potentially employed in future studies for cancer therapeutic research. This study disentangles that the calcimycin-induced apoptotic cell death is P2RX4 and ATP involved, intracellular Ca2+ and p38 MAPK mediated pathway. © 2023
Computational exploration of protein structure dynamics and RNA structural consequences of PKD1 missense variants: implications in ADPKD pathogenesis
(Springer Science and Business Media Deutschland GmbH, 2024) Chandra Devi; Prashant Ranjan; Sonam Raj; Parimal Das
We analyzed the impact of nine previously identified missense PKD1 variants from our studies, including c.6928G > A p.G2310R, c.8809G > A p.E2937K, c.2899 T > C p.W967R, c.6284A > G p.D2095G, c.6644G > A p.R2215Q, c.7810G > A p.D2604N, c.11249G > C p.R3750P, c.1001C > T p.T334M, and c.3101A > G p.N1034S on RNA structures and PC1 protein structure dynamics utilizing computational tools. RNA structure analysis was done using short RNA snippets of 41 nucleotides with the variant position at the 21st nucleotide, ensuring 20 bases on both sides. The secondary structures of these RNA snippets were predicted using RNAstructure. Structural changes of the mutants compared to the wild type were analyzed using the MutaRNA webserver. Molecular dynamics (MD) simulation of PC1 wild-type and mutant protein regions were performed using GROMACS 2018 (GROMOS96 54a7 force field). Findings revealed that five variants including c.8809G > A (p.E2937K), c.11249G > C (p.R3750P), c.3101A > G (p.N1034S), c.6928G > A (p.G2310R), c.6644G > A (p.R2215Q) exhibited major alterations in RNA structures and thereby their interactions with other proteins or RNAs affecting protein structure dynamics. While certain variants have minimal impact on RNA conformations, their observed alterations in MD simulations indicate impact on protein structure dynamics highlighting the importance of evaluating the functional consequences of genetic variants by considering both RNA and protein levels. The study also emphasizes that each missense variant exerts a unique impact on RNA stability, and protein structure dynamics, potentially contributing to the heterogeneous clinical manifestations and progression observed in Autosomal Dominant Polycystic Kidney Disease (ADPKD) patients offering a novel perspective in this direction. Thus, the utility of studying the structure dynamics through computational tools can help in prioritizing the variants for their functional implications, understanding the molecular mechanisms underlying variability in ADPKD presentation and developing targeted therapeutic interventions. © King Abdulaziz City for Science and Technology 2024.
Corrigendum to “Layered double hydroxides as effective carrier for anticancer drugs and tailoring of release rate through interlayer anions” [Journal of Controlled Release 224 (2106) 186–198] (Layered double hydroxides as effective carrier for anticancer drugs and tailoring of release rate through interlayer anions (2016) 224 (186–198), (S016836591630013X), (10.1016/j.jconrel.2016.01.016))
(Elsevier B.V., 2021) Sudipta Senapati; Ravi Thakur; Shiv Prakash Verma; Shivali Duggal; Durga Prasad Mishra; Parimal Das; T. Shripathi; Mohan Kumar; Dipak Rana; Pralay Maiti
The authors regret that the initial published version of this article an error in the assembly of Fig. 7b resulted in some image duplications. The corrected Fig. 7b includes the correct images of the experiment. This correction/omission doesn't alter any conclusion of the article as quantitative analysis of the experiment has been performed through MTT assay, presented in Fig. 7a. [Figure Presented] The figure legend remains the same. The corrections made in this corrigendum do not affect the original conclusions of the article. The author's apologies for any inconvenience caused. © 2016 Elsevier B.V.
COVID-19 and Mucosal Immunization: Assessing Current Efforts, Challenges, and Future Opportunities for Vaccine Development
(Springer Science and Business Media Deutschland GmbH, 2025) Syed Muhammad Faheem Afzal; Zakaria Ahmed Mohamed; Mainak Sengupta; Rakesh Kumar Panjaliya; Parimal Das; Anjana Munshi; Jinghua Li; Jianping Wen; Fan Li; Santasree Banerjee
Purpose of the Review: This review aims to provide a comprehensive overview of the mucosal immune system and assess the potential of mucosal vaccines, particularly for COVID-19, as a promising approach in combating respiratory pathogens like SARS-CoV-2. Recent Findings: Mucosal immunization has emerged as a viable strategy for COVID-19 vaccination. Various mucosal vaccines, including oral and intranasal formulations, are currently undergoing clinical evaluation in multiple countries. This review examines these vaccine strategies, their status, and highlights recent advancements in the field. Summary: This review focuses on mucosal vaccination as a strategic defense against respiratory pathogens by leveraging innate immunity, mucosal antibodies, and memory lymphocytes. While the approach offers significant potential, it faces substantial challenges that limit the effectiveness of current COVID-19 mucosal vaccines. The article outlines these obstacles and proposes targeted strategies to overcome them, contributing to improved pandemic control measures. © The Author(s), under exclusive licence to Springer Nature Switzerland AG 2025.
Development of a robust and generalizable algorithm "gQuant" for accurate normalizer gene selection in qRT-PCR analysis
(Nature Research, 2024) Abhay Kumar Pathak; Sukhad Kural; Shweta Singh; Lalit Kumar; Mahima Yadav; Manjari Gupta; Parimal Das; Garima Jain
The emergent role of nucleic acid-based biomarkers—microRNAs(miRNAs), long non-coding RNAs(lncRNAs), and messenger RNAs(mRNAs), is becoming increasingly prominent in disease diagnostics and risk assessment. qRT-PCR is the primary analytical method for quantitative measurement of biomarkers. Yet, the relative infancy of non-coding RNAs recognition as biomarkers poses a challenge due to the absence of a consensus on a universally accepted normalizer gene, an absolute requirement for accurate quantification. Current tools normalizer selection are fraught with statistical limitations and suboptimal graphical user interface for data visualisation. These deficiencies underscore the necessity for a balanced tool tailored to handle qRT-PCR datasets. Addressing the identified challenges, we have developed 'gQuant' tool crafted to address these limitations. We employed voting classifiers that combine predictions from multiple statistical methods. Tool's efficacy was validated through different available and in house data derived from urinary exosomal miRNAs datasets. Comparative analysis with existing tools revealed that their integrated methodologies could skew the ranking of normalizer genes, whereas 'gQuant' consistently yielded rankings characterised by lower standard-deviation, reduced covariance, and enhanced kernel density estimation values. Given 'gQuant's' promising performance, normalizer gene identification will be greatly improved, improving precision of gene expression quantification in a variety of research scenarios. The gQuant tool developed for this study is available for public use and can be accessed at [https://github.com/ABHAYHBB/gQuant-Tool]." © The Author(s) 2024.
Dual metal ion (Fe3+ and As3+) sensing and cell bioimaging using fluorescent carbon quantum dots synthesised from Cynodon dactylon
(Elsevier Ltd, 2023) Sweta Gurung; Neha; Nimmala Arun; Mayank Joshi; Tanya Jaiswal; Anand P. Pathak; Parimal Das; Amaresh Kumar Singh; Ajay Tripathi; Archana Tiwari
In this study, water dispersible fluorescent carbon quantum dot (CQD) has been synthesised, having an average size of 8.6 ± 0.4 nm using Cynodon dactylon (CD) following microwave assisted green synthetic one-step method. As-prepared CQD fluoresces strongly at 444 nm having a quantum yield of 1% in water when excited at 350 nm. This fluorescence of CQD is sensitive toward As3+ and Fe3+ metal ions. These CQD are utilized for dual metal ion fluorescence sensing; turn-on fluorescence sensing for As3+ and turn-off fluorescence sensing for Fe3+ ions. Limit of detection for As3+ and Fe3+ ions has been found to be 19 nM and 0.10 μM respectively, which is the lowest value reported for As3+ without any functionalization. The adsorption kinetics of As3+ and Fe3+ ions on CQD have been examined using pseudo-first-order-kinetic model revealing that physical adsorption is dominant over chemical processes in this work. For 0.41 g/L and 1.90 g/L dose of CQD, the equilibrium adsorption capacity was found to be 1.57 × 10−6 mg/g, 2.91 × 10−7 mg/g, and 1.01 × 10−5 mg/g, 1.69 × 10−6 mg/g respectively for As3+ and Fe3+ ions. Despite having low quantum yield in water, as-prepared CQD showed low cytotoxicity and good tolerance against photodegradation of biological cells at concentrations lower than 62.5 μg/mL and when the cells are illuminated up to 12 h. Owing to this, the synthesised CQD have been utilized as fluorescent probes for in itro cell imaging. © 2023 Elsevier Ltd
Dual role of G-quadruplex in translocation renal cell carcinoma: Exploring plausible Cancer therapeutic innovation
(Elsevier B.V., 2020) Neha; Parimal Das; Shiv Prakash Verma
Background: Renal Cell Carcinoma (RCC) is the ninth leading cause of death among kidney cancer. Xp11.2 translocation harboring TFE3 fusion proteins, act as an oncogene in translocation cancers that constitute the hallmark of translocation renal cell carcinoma (tRCC). G-quadruplex (G4), an alternative nucleic acid structure is an emerging and promising factor in cancer. The presence of G4 within the genome plays a pioneering role in cancer as it contributes to genomic aberration as well as inhibition in cell proliferation. Scope of review: Here we discuss the link between G4 and tRCC. We compile the available information of G-quadruplex & propose their dual role in tRCC, suggesting both stabilization and destabilization of G-quadruplex could be considered targets for tRCC. Major conclusions: Our in Silico analysis of TFE3 and their three fusions partner's PRCC, SFPQ, and ASPSCR1 discloses a few putative G4 forming sequences (PQS) in their corresponding fusion gene or fusion transcript. Stabilization of G4 structure within fusion gene/transcript can be of great use towards potential therapeutics targeting fusion protein derived oncogenesis, as G4 is a serious menace for DNA polymerization, transcription & translation. G-quadruplex at intron-2 of the TFE3 has been reported to mediate its translocation also. Both stabilization and destabilization of the G4 structure would be a promising approach in the suppression of cancerous cell proliferation. General significance: Pioneering studies discovered the relevance of G4 in cancer therapy and explore our approaches towards therapeutic innovation against oncogenic fusion protein and tRCC. Selectively targeting G4 in oncogenic fusion transcript will emerge as potential druggable structures. © 2020
Efficient water soluble nanostructured ZnO grafted O-carboxymethyl chitosan/curcumin-nanocomposite for cancer therapy
(Elsevier Ltd, 2015) Laxmi Upadhyaya; Jay Singh; Vishnu Agarwal; A.C. Pandey; Shiv P. Verma; Parimal Das; R.P. Tewari
The present work deals with the synthesis of efficient water soluble O-carboxymethyl chitosan (O-CMCS) based nanocomposites (NCs) with nanostructured zinc oxide (n-ZnO) by ex-situ grafting method for the delivery of anticancer drug curcumin (Cr). The phase identification, morphology and thermal stability of prepared Cr/O-CMCS/n-ZnO NCs have been investigated by FT-IR, XRD, SEM, TEM and TGA/DTA techniques. The drug entrapment efficiency have found to be 74% and in vitro drug release study performed at 37 °C at pH 4.5 and 7.4 indicated slow and controlled release in the initial phase and sustained in later phase. The MTT assay showed higher and preferential toxicity of the Cr/O-CMCS/n-ZnO NCs against cancer cells (MA104). The cellular uptake study by FACS revealed concentration dependent uptake of the NCs. The utilization of this Cr/O-CMCS/n-ZnO nanoformulation offers an efficient strategy and a novel promising soluble nanomatrix for anticancer therapy and other biomedical applications. © 2015 Elsevier Ltd. All rights reserved.
Embracing Monogenic Parkinson's Disease: The MJFF Global Genetic PD Cohort
(John Wiley and Sons Inc, 2023) Eva-Juliane Vollstedt; Susen Schaake; Katja Lohmann; Shalini Padmanabhan; Alexis Brice; Suzanne Lesage; Christelle Tesson; Marie Vidailhet; Isabel Wurster; Faycel Hentati; Anat Mirelman; Nir Giladi; Karen Marder; Cheryl Waters; Stanley Fahn; Meike Kasten; Norbert Brüggemann; Max Borsche; Tatiana Foroud; Eduardo Tolosa; Alicia Garrido; Grazia Annesi; Monica Gagliardi; Maria Bozi; Leonidas Stefanis; Joaquim J. Ferreira; Leonor Correia Guedes; Micol Avenali; Simona Petrucci; Lorraine Clark; Ekaterina Y. Fedotova; Natalya Y. Abramycheva; Victoria Alvarez; Manuel Menéndez-González; Silvia Jesús Maestre; Pilar Gómez-Garre; Pablo Mir; Andrea Carmine Belin; Caroline Ran; Chin-Hsien Lin; Ming-Che Kuo; David Crosiers; Zbigniew K. Wszolek; Owen A. Ross; Joseph Jankovic; Kenya Nishioka; Manabu Funayama; Jordi Clarimon; Caroline H. Williams-Gray; Marta Camacho; Mario Cornejo-Olivas; Luis Torres-Ramirez; Yih-Ru Wu; Guey-Jen Lee-Chen; Ana Morgadinho; Teeratorn Pulkes; Pichet Termsarasab; Daniela Berg; Gregor Kuhlenbäumer; Andrea A. Kühn; Friederike Borngräber; Giuseppe de Michele; Anna De Rosa; Alexander Zimprich; Andreas Puschmann; George D. Mellick; Jolanta Dorszewska; Jonathan Carr; Rosangela Ferese; Stefano Gambardella; Bruce Chase; Katerina Markopoulou; Wataru Satake; Tatsushi Toda; Malco Rossi; Marcelo Merello; Timothy Lynch; Diana A. Olszewska; Shen-Yang Lim; Azlina Ahmad-Annuar; Ai Huey Tan; Bashayer Al-Mubarak; Hasmet Hanagasi; Dariusz Koziorowski; Sibel Ertan; Gençer Genç; Patricia de Carvalho Aguiar; Melinda Barkhuizen; Marcia M.G. Pimentel; Rachel Saunders-Pullman; Bart van de Warrenburg; Susan Bressman; Mathias Toft; Silke Appel-Cresswell; Anthony E. Lang; Matej Skorvanek; Agnita J.W. Boon; Rejko Krüger; Esther M. Sammler; Vitor Tumas; Bao-rong Zhang; Gaetan Garraux; Sun Ju Chung; Yun Joong Kim; Juliane Winkelmann; Carolyn M. Sue; Eng-King Tan; Joana Damásio; Péter Klivényi; Vladimir S. Kostic; David Arkadir; Mika Martikainen; Vanderci Borges; Jens Michael Hertz; Laura Brighina; Mariana Spitz; Oksana Suchowersky; Olaf Riess; Parimal Das; Brit Mollenhauer; Emilia M. Gatto; Maria Skaalum Petersen; Nobutaka Hattori; Ruey-Meei Wu; Sergey N. Illarioshkin; Enza Maria Valente; Jan O. Aasly; Anna Aasly; Roy N. Alcalay; Avner Thaler; Matthew J. Farrer; Kathrin Brockmann; Jean-Christophe Corvol; Christine Klein; Alberto Albanese; Amaal Aldakheel; Thamer Alkhairallah; Nada Al-tassan; Victoria Alvarez; Paolo Amami; Grazia Annesi; Marco Antonio Araujo Leite; Henrique Ballalai Ferraz; Soraya Bardien; Matthew J. Barrett; A. Nazlı Başak; Basar Bilgic; Bastiaan R. Bloem; Vincenzo Bonifati; Jonathan Carr; Martin Emiliano Cesarini; Leonor Correia Guedes; Anna De Rosa; Elena Dieguez; Stanley Fahn; Rosangela Ferese; Victor S. C. Fung; Monica Gagliardi; Alicia Garrido; Nobutaka Hattori; Cristina Januario; Silvia Jesús Maestre; Valtteri Kaasinen; Hiroshi Kataoka; Anneke A. Kievit; Guey-Jen Lee-Chen; Jia Lun Lim; Timothy Lynch; Patrick May; Allan McCarthy; Hugo Morales Briceno; Huw Morris; Alexandra Mosejova; Özgür Öztop Çakmak; Avi Orr-Urtreger; Sinthuja Pachchek; Maria Teresa Periñán; Radha Procopio; Owen A. Ross; Javier Ruiz-Martinez; João Santos Pereira; Alexandra I. Soto-Beasley; Mário Sousa; Fatih Tepgeç; Tatsushi Toda; Oya Uyguner; Ronald L. Walton; Juliane Winkelmann; Zbigniew K. Wszolek
Background: As gene-targeted therapies are increasingly being developed for Parkinson's disease (PD), identifying and characterizing carriers of specific genetic pathogenic variants is imperative. Only a small fraction of the estimated number of subjects with monogenic PD worldwide are currently represented in the literature and availability of clinical data and clinical trial-ready cohorts is limited. Objective: The objectives are to (1) establish an international cohort of affected and unaffected individuals with PD-linked variants; (2) provide harmonized and quality-controlled clinical characterization data for each included individual; and (3) further promote collaboration of researchers in the field of monogenic PD. Methods: We conducted a worldwide, systematic online survey to collect individual-level data on individuals with PD-linked variants in SNCA, LRRK2, VPS35, PRKN, PINK1, DJ-1, as well as selected pathogenic and risk variants in GBA and corresponding demographic, clinical, and genetic data. All registered cases underwent thorough quality checks, and pathogenicity scoring of the variants and genotype–phenotype relationships were analyzed. Results: We collected 3888 variant carriers for our analyses, reported by 92 centers (42 countries) worldwide. Of the included individuals, 3185 had a diagnosis of PD (ie, 1306 LRRK2, 115 SNCA, 23 VPS35, 429 PRKN, 75 PINK1, 13 DJ-1, and 1224 GBA) and 703 were unaffected (ie, 328 LRRK2, 32 SNCA, 3 VPS35, 1 PRKN, 1 PINK1, and 338 GBA). In total, we identified 269 different pathogenic variants; 1322 individuals in our cohort (34%) were indicated as not previously published. Conclusions: Within the MJFF Global Genetic PD Study Group, we (1) established the largest international cohort of affected and unaffected individuals carrying PD-linked variants; (2) provide harmonized and quality-controlled clinical and genetic data for each included individual; (3) promote collaboration in the field of genetic PD with a view toward clinical and genetic stratification of patients for gene-targeted clinical trials. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Enhancing tomato growth and early blight disease resistance through green-synthesized silver nanoparticles: Insights into plant physiology
(Elsevier B.V., 2024) Jeetu Narware; Satyendra P. Singh; Jharjhari chakma; Prashant Ranjan; Lopamudra Behera; Parimal Das; Nazia Manzar; Abhijeet Shankar Kashyap
Tomato (Solanum lycopersicum) is a globally significant crop, but its cultivation is challenged by the devastating Early Blight disease caused by Alternaria solani, leading to substantial yield losses. Silver nanoparticles (AgNPs) have emerged as potential antifungal agents, garnering increasing attention. In this study, we investigated the impact of biogenic AgNPs on tomato plant defense mechanisms during a three-way interaction with plant pathogens and nanoparticles. Additionally, the study explored the integration of biochemical markers to assess plant response. Histochemical analyses confirmed the presence of oxidative stress markers (H2O2 and O−2), as well as callose and lignin deposition, supporting the involvement of defensive responses in this study. Metabolic profiling revealed that tomato plants exposed to 20 ppm AgNPs exhibited maximal accumulation levels of various secondary metabolites compared to the control group. Remarkably, the concurrent application of AgNPs and plants resulted in enhanced plant resistance against biotic stress, as evidenced by reduced stress parameters and stress enzyme activity. The antioxidant enzymes (PO, SOD, CAT, LPX) exhibited significant variations among treatments, emphasizing the influence of AgNPs on maintaining reactive oxygen species (ROS) homeostasis in plant cells. These findings highlight the potential of nanotechnology-based approaches in bolstering food supply and promoting sustainable agriculture. Our study underscores the significance of integrating biochemical markers to monitor and assess plant response during the interaction with nanoparticles and pathogens. This integration offers a promising avenue for elucidating the underlying mechanisms of plant defense and optimizing agricultural practices. In conclusion, our research elucidates the potential of silver nanoparticles in augmenting plant resistance against Early Blight disease in tomato, ultimately contributing to sustainable agriculture. The incorporation of biochemical markers further advances our understanding of the intricate interplay between nanoparticles, plant pathogens, and plant defense mechanisms. © 2024 SAAB
Establishing an online resource to facilitate global collaboration and inclusion of underrepresented populations: Experience from the MJFF Global Genetic Parkinson’s Disease Project
(Public Library of Science, 2023) Eva-Juliane Vollstedt; Harutyun Madoev; Anna Aasly; Azlina Ahmad-Annuar; Bashayer Al-Mubarak; Roy N. Alcalay; Victoria Alvarez; Ignacio Amorin; Grazia Annesi; David Arkadir; Soraya Bardien; Roger A. Barker; Melinda Barkhuizen; A. Nazli Basak; Vincenzo Bonifati; Agnita Boon; Laura Brighina; Kathrin Brockmann; Andrea Carmine Belin; Jonathan Carr; Jordi Clarimon; Mario Cornejo-Olivas; Leonor Correia Guedes; Jean-Christophe Corvol; David Crosiers; Joana Damásio; Parimal Das; Patricia de Carvalho Aguiar; Anna De Rosa; Jolanta Dorszewska; Sibel Ertan; Rosangela Ferese; Joaquim Ferreira; Emilia Gatto; Gençer Genç; Nir Giladi; Pilar Gómez-Garre; Hasmet Hanagasi; Nobutaka Hattori; Faycal Hentati; Dorota Hoffman-Zacharska; Sergey N. Illarioshkin; Joseph Jankovic; Silvia Jesús; Valtteri Kaasinen; Anneke Kievit; Peter Klivenyi; Vladimir Kostic; Dariusz Koziorowski; Andrea A. Kühn; Anthony E. Lang; Shen-Yang Lim; Chin-Hsien Lin; Katja Lohmann; Vladana Markovic; Mika Henrik Martikainen; George Mellick; Marcelo Merello; Lukasz Milanowski; Pablo Mir; Özgür Öztop-Çakmak; Márcia Mattos Gonçalves Pimentel; Teeratorn Pulkes; Andreas Puschmann; Ekaterina Rogaeva; Esther M. Sammler; Maria Skaalum Petersen; Matej Skorvanek; Mariana Spitz; Oksana Suchowersky; Ai Huey Tan; Pichet Termsarasab; Avner Thaler; Vitor Tumas; Enza Maria Valente; Bart van de Warrenburg; Caroline H. Williams-Gray; Ruey-Mei Wu; Baorong Zhang; Alexander Zimprich; Justin Solle; Shalini Padmanabhan; Christine Klein
Parkinson’s disease (PD) is the fastest-growing neurodegenerative disorder, currently affecting ~7 million people worldwide. PD is clinically and genetically heterogeneous, with at least 10% of all cases explained by a monogenic cause or strong genetic risk factor. However, the vast majority of our present data on monogenic PD is based on the investigation of patients of European White ancestry, leaving a large knowledge gap on monogenic PD in underrepresented populations. Gene-targeted therapies are being developed at a fast pace and have started entering clinical trials. In light of these developments, building a global network of centers working on monogenic PD, fostering collaborative research, and establishing a clinical trial-ready cohort is imperative. Based on a systematic review of the English literature on monogenic PD and a successful team science approach, we have built up a network of 59 sites worldwide and have collected information on the availability of data, biomaterials, and facilities. To enable access to this resource and to foster collaboration across centers, as well as between academia and industry, we have developed an interactive map and online tool allowing for a quick overview of available resources, along with an option to filter for specific items of interest. This initiative is currently being merged with the Global Parkinson’s Genetics Program (GP2), which will attract additional centers with a focus on underrepresented sites. This growing resource and tool will facilitate collaborative research and impact the development and testing of new therapies for monogenic and potentially for idiopathic PD patients. Copyright: © 2023 Vollstedt et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Exploring G-quadruplex structure in PRCC-TFE3 fusion oncogene: Plausible use as anti cancer therapy for translocation Renal cell carcinoma (tRCC)
(Elsevier B.V., 2024) Neha Neha; Parimal Das
The TFE3 fusion gene, byproduct of Xp11.2 translocation, is the diagnostic marker for translocation renal cell carcinoma (tRCC). Absence of any clinically recognized therapy for tRCC, pressing a need to create novel and efficient therapeutic approaches. Previous studies shown that stabilization of the G-quadruplex structure in oncogenes suppresses their expression machinery. To combat the oncogenesis caused by fusion genes, our objective is to locate and stabilize the G-quadruplex structure within the PRCC-TFE3 fusion gene. Using the Quadruplex-forming G Rich Sequences (QGRS) mapper and the Non-B DNA motif search tool (nBMST) online server, we found putative G-quadruplex forming sequences (PQS) in the PRCC-TFE3 fusion gene. Circular dichroism demonstrating a parallel G-quadruplex in the targeted sequence. Fluorescence and UV–vis spectroscopy results suggest that pyridostatin binds to this newly discovered G-quadruplex. The PCR stop assay, as well as transcriptional or translational inhibition using real time PCR and Dual luciferase assay, revealed that stable G-quadruplex formation affects biological processes. Confocal microscopy of HEK293T cells transfected with the fusion transcript confirmed G-quadruplexes formation in cell. This investigation may shed light on G-quadruplex's functions in fusion genes and may help in the development of therapies specifically targeted against fusion oncogenes, which would enhance the capability of current tRCC therapy approach. © 2024