Publications by authors named "Sourav Roy"

62 Publications

Tris(pentafluorophenyl)borane catalyzed C-C and C-heteroatom bond formation.

Org Biomol Chem 2021 Feb;19(6):1230-1267

Department of Chemistry, Indian Institute of Technology Ropar, Nangal Road, Rupnagar, Punjab-140001, India.

A series of boron based Lewis acids have been reported to date, but among them, tris(pentafluorophenyl)borane (BCF) has gained the most significant attention in the synthetic chemistry community. The viability of BCF as a potential Lewis acid catalyst has been vastly explored in organic and materials chemistry due to its thermal stability and commercial availability. Most explorations of BCF chemistry in organic synthesis has occurred in the last two decades and many new catalytic reactivities are currently under investigation. This review mainly focuses on recent reports from 2018 onwards and provides a concise knowledge to the readers about the role of BCF in metal-free catalysis. The review has mainly been categorized by different types of organic transformation mediated through BCF catalysis for the C-C and C-heteroatom bond formation.
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http://dx.doi.org/10.1039/d0ob02478cDOI Listing
February 2021

Hofmeister Ions Modulate the Autocatalytic Amyloidogenesis of an Intrinsically Disordered Functional Amyloid Domain via Unusual Biphasic Kinetics.

J Mol Biol 2020 11 15;432(23):6173-6186. Epub 2020 Oct 15.

Centre for Protein Science, Design and Engineering, Indian Institute of Science Education and Research (IISER) Mohali, Mohali 140306, Punjab, India; Department of Chemical Sciences, Indian Institute of Science Education and Research (IISER) Mohali, Mohali 140306, Punjab, India; Department of Biological Sciences, Indian Institute of Science Education and Research (IISER) Mohali, Mohali 140306, Punjab, India. Electronic address:

Hofmeister ions are thought to play fundamentally important roles in protein solubility, folding, stability, and function. Salt ions profoundly influence the course of protein misfolding, aggregation, and amyloid formation associated with devastating human diseases. However, the molecular origin of the salt-effect in protein aggregation remains elusive. Here, we report an unusual biphasic amyloidogenesis of a pH-responsive, intrinsically disordered, oligopeptide repeat domain of a melanosomal protein, Pmel17, that regulates the amyloid-assisted melanin synthesis in mammals via functional amyloid formation. We demonstrate that a symphony of molecular events involving charge-peptide interactions and hydration, in conjunction with secondary phenomena, critically governs the course of this biphasic amyloid assembly. We show that at mildly acidic pH, typical of melanosomes, highly amyloidogenic oligomeric units assemble into metastable, dendritic, fractal networks following the forward Hofmeister series. However, the subsequent condensation of fractal networks via conformational maturation into amyloid fibrils follows an inverse Hofmeister series due to fragmentation events coupled with secondary nucleation processes. Our results indicate that ions exert a strong influence on the aggregation kinetics as well as on the nanoscale morphology and also modulate the autocatalytic amplification processes during amyloid assembly via an intriguing dual Hofmeister effect. This unique interplay of molecular drivers will be of prime importance in delineating the aggregation pathways of a multitude of intrinsically disordered proteins involved in physiology and disease.
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http://dx.doi.org/10.1016/j.jmb.2020.10.015DOI Listing
November 2020

Utilization of CO Feedstock for Organic Synthesis by Visible-Light Photoredox Catalysis.

Chemistry 2021 Feb 30;27(7):2254-2269. Epub 2020 Nov 30.

Department of Chemistry, Indian Institute of Technology Ropar, Nangal Road, Rupnagar, Punjab, 140001, India.

CO is a highly abundant, green, and sustainable carbon feedstock. Despite its kinetic inertness and thermodynamic stability, the development of various catalytic techniques has enabled the conversion of CO to value-added products such as carboxylic acids, amino acids, and heterocyclic compounds, where visible-light photocatalysis has emerged to be an efficient promoter of these processes. This Minireview covers the progress in the areas of CO incorporation onto organic matters based on the combined venture of renewable resources of CO and light energy with significant emphasis on the last three years' developments.
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http://dx.doi.org/10.1002/chem.202003685DOI Listing
February 2021

Targeting the Initiator Protease of the Classical Pathway of Complement Using Fragment-Based Drug Discovery.

Molecules 2020 Sep 3;25(17). Epub 2020 Sep 3.

Department of Microbiology and Immunology, Brody School of Medicine, East Carolina University, Greenville, NC 27858, USA.

The initiating protease of the complement classical pathway, C1r, represents an upstream and pathway-specific intervention point for complement-related autoimmune and inflammatory diseases. Yet, C1r-targeted therapeutic development is currently underrepresented relative to other complement targets. In this study, we developed a fragment-based drug discovery approach using surface plasmon resonance (SPR) and molecular modeling to identify and characterize novel C1r-binding small-molecule fragments. SPR was used to screen a 2000-compound fragment library for binding to human C1r. This led to the identification of 24 compounds that bound C1r with equilibrium dissociation constants ranging between 160-1700 µM. Two fragments, termed CMP-1611 and CMP-1696, directly inhibited classical pathway-specific complement activation in a dose-dependent manner. CMP-1611 was selective for classical pathway inhibition, while CMP-1696 also blocked the lectin pathway but not the alternative pathway. Direct binding experiments mapped the CMP-1696 binding site to the serine protease domain of C1r and molecular docking and molecular dynamics studies, combined with C1r autoactivation assays, suggest that CMP-1696 binds within the C1r active site. The group of structurally distinct fragments identified here, along with the structure-activity relationship profiling of two lead fragments, form the basis for future development of novel high-affinity C1r-binding, classical pathway-specific, small-molecule complement inhibitors.
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http://dx.doi.org/10.3390/molecules25174016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7504721PMC
September 2020

The Association of Cardiovascular Diseases and Diabetes Mellitus with COVID-19 (SARS-CoV-2) and Their Possible Mechanisms.

SN Compr Clin Med 2020 Jun 25:1-6. Epub 2020 Jun 25.

Department of Pharmacy, Noakhali Science and Technology University, Noakhali, 3814 Bangladesh.

Coronavirus disease 2019 (COVID-19) has become a global concern and public health issue due to its higher infection and mortality rate; particularly, the risk is very higher among the patients who have cardiovascular diseases (CVD) and/or diabetes mellitus (DM). In this review, we analyzed the recently published literature on CVD and DM associated with COVD-19 infections and highlight their association with potential mechanisms. The findings revealed that without any previous history of CVD, the COVID-19 patients have developed some CVD complications like myocardial injury, cardiomyopathy, and venous thromboembolism after being infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and required for those patients an emergency clinical support to be aware to manage those complications. Though the association between DM and COVID-19-induced severe complications is still unclear, the limited data predict that different markers like interleukin (IL)-1, IL-6, C-reactive protein, and D-dimer linked with the severity of COVID-19 infection in diabetic individuals. Further studies on a large scale are urgently needed to explore the underlying mechanisms between CVD, DM, and COVID-19 for better treatment.
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http://dx.doi.org/10.1007/s42399-020-00376-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7316523PMC
June 2020

Role of Substituents at 3-position of Thienylethynyl Spacer on Electronic Properties in Diruthenium(II) Organometallic Wire-like Complexes.

Chem Asian J 2020 Oct 4;15(20):3304-3313. Epub 2020 Sep 4.

Department of Chemistry, Indian Institute of Technology Kharagpur, Kharagpur, 721302, WB, India.

A series of organometallic complexes [Cl(dppe) Ru-C≡C-(3-R-C H S)-C≡C-Ru(dppe) Cl] (3-R-C H S=3-substituted thienyl moiety; R=-H, -C H , -C H , -C H , -C H , -OMe, -CN in 5 a-5 g respectively) have been synthesized by systematic variation of 3-substituents at the thienylethynyl bridging unit. The diruthenum(II) wire-like complexes (5 a-5 g) have been achieved by the reaction of thienylethynyl bridging units, HC≡C-(3-R-C H S)-C≡CH (4 a-4 g) with cis-[Ru(dppe) Cl ]. The wire-like diruthenium(II) complexes undergo two consecutive electrochemical oxidation processes in the potential range of 0.0 - 0.8 V. Interestingly, the wave separation between the two redox waves is greatly influenced by the substituents at the 3-position of the thienylethynyl. Thus, the substitution on 3-position of the thienylethynyl bridging unit plays a pivotal role for tuning the electronic properties. To understand the electronic behavior, density functional theory (DFT) calculations of the selected diruthenium wire-like complexes (5 a-5 e) with different alkyl appendages are performed. The theoretical data demonstrate that incorporation of alkyl groups to the thienylethynyl entity leaves unsymmetrical spin densities, thus affecting the electronic properties. The voltammetric features of the other two Ru(II) alkynyl complexes 5 f and 5 g (with -OMe and -CN group respectively) show an apparent dependence on the electronic properties. The electronic properties in the redox conjugate, (5 a ) with K of 3.9×10 are further examined by UV-Vis-NIR and FTIR studies, showing optical responses in NIR region along with changes in "-Ru-C≡C-" vibrational stretching frequency. The origin of the observed electronic transition has been assigned based on time-dependent DFT (TDDFT) calculations.
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http://dx.doi.org/10.1002/asia.202000755DOI Listing
October 2020

Toward a Reliable Synaptic Simulation Using Al-Doped HfO RRAM.

ACS Appl Mater Interfaces 2020 Mar 20;12(9):10648-10656. Epub 2020 Feb 20.

Electronic Materials Research Laboratory, Key Laboratory of the Ministry of Education & International Center for Dielectric Research, School of Electronic Science and Engineering, Xi'an Jiaotong University, Xi'an 710049, China.

The potential in a synaptic simulation for neuromorphic computation has revived the research interest of resistive random access memory (RRAM). However, novel applications require reliable multilevel resistive switching (RS), which still represents a challenge. We demonstrate in this work the achievement of reliable HfO-based RRAM devices for synaptic simulation by performing the Al doping and the postdeposition annealing (PDA). Transmission electron microscopy and operando hard X-ray photoelectron spectroscopy results reveal the positive impact of Al doping on the formation of oxygen vacancies. Detailed - characterizations demonstrate that the 16.5% Al doping concentration leads to better RS properties of the device. In comparison with the other reported results based on HfO RRAM, our devices with 16.5% Al-doping and PDA at 450 °C show better reliable multilevel RS (∼20 levels) performance and an increased on/off ratio. The 16.5% Al:HfO sample with PDA at 450 °C shows good potentiation/depression characteristics with low pulse width (10 μs) along with a good On/Off ratio (>1000), good data retention at room temperature, and high temperature and good program/erase endurance characteristics with a pulse width of 50 ns. The synapse features including potentiation, depression, and spike time-dependent plasticity were successfully achieved using optimized Al-HfO RRAM devices. Our results demonstrate the beneficial effects of Al doping and PDA on the enhancement of the performances of RRAM devices for the synaptic simulation in neuromorphic computing applications.
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http://dx.doi.org/10.1021/acsami.9b21530DOI Listing
March 2020

Reliable resistive switching of epitaxial single crystalline cubic Y-HfO RRAMs with Si as bottom electrodes.

Nanotechnology 2020 May 4;31(20):205203. Epub 2020 Feb 4.

Electronic Materials Research Laboratory, Key Laboratory of the Ministry of Education & International Center for Dielectric Research, Xi'an Jiaotong University, School of Electronic Science and Engineering, Xi'an, People's Republic of China.

Previous studies have mainly focused on the resistive switching (RS) of amorphous or polycrystalline HfO-RRAM. The RS of single crystalline HfO films has been rarely reported. Yttrium doped HfO (YDH) thin films were fabricated and successful Y incorporation into HfO was confirmed by x-ray photoemission spectroscopy. A pure cubic phase of YDH and an abrupt YDH/Si interface were obtained and verified by x-ray diffraction, Raman spectroscopy and transmission electron microscopy. A Pt/YDH/n-Si heterostructure using Si as the bottom electrode was fabricated, which shows stable RS with an ON/OFF ratio of 100 and a reliable data retention (10 s). The electron transport mechanism was investigated in detail. It indicates that hopping conduction is dominating when the device is at a high resistance state, while space charge limited conduction acts as the dominant factor at a low resistance state. Such behavior, which is different from devices using TiN or Ti as electrodes, was attributed to the Y doping and specific YDH/Si interface. Our results demonstrate a proof of concept study to use highly doped Si as bottom electrodes along with single crystalline YDH as insulator layer for such RRAM applications as wireless sensors and synaptic simulation.
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http://dx.doi.org/10.1088/1361-6528/ab72b6DOI Listing
May 2020

Synergistic action of the transcription factors Krüppel homolog 1 and Hairy in juvenile hormone/Methoprene-tolerant-mediated gene-repression in the mosquito Aedes aegypti.

PLoS Genet 2019 10 29;15(10):e1008443. Epub 2019 Oct 29.

Department of Entomology and Institute of Integrative Biology, University of California, Riverside, California, United States of America.

Arthropod-specific juvenile hormones control numerous essential functions in development and reproduction. In the dengue-fever mosquito Aedes aegypti, in addition to its role in immature stages, juvenile hormone III (JH) governs post-eclosion (PE) development in adult females, a phase required for competence acquisition for blood feeding and subsequent egg maturation. During PE, JH through its receptor Methoprene-tolerant (Met) regulate the expression of many genes, causing either activation or repression. Met-mediated gene repression is indirect, requiring involvement of intermediate repressors. Hairy, which functions downstream of Met in the JH gene-repression hierarchy, is one such factor. Krüppel-homolog 1, a zinc-finger transcriptional factor, is directly regulated by Met and has been implicated in both activation and repression of JH-regulated genes. However, the interaction between Hairy and Kr-h1 in the JH-repression hierarchy is not well understood. Our RNAseq-based transcriptomic analysis of the Kr-h1-depleted mosquito fat body revealed that 92% of Kr-h1 repressed genes are also repressed by Met, supporting the existence of a hierarchy between Met and Kr-h1 as previously demonstrated in various insects. Notably, 130 genes are co-repressed by both Kr-h1 and Hairy, indicating regulatory complexity of the JH-mediated PE gene repression. A mosquito Kr-h1 binding site in genes co-regulated by this factor and Hairy was identified computationally. Moreover, this was validated using electrophoretic mobility shift assays. A complete phenocopy of the effect of Met RNAi depletion on target genes could only be observed after Kr-h1 and Hairy double RNAi knockdown, suggesting a synergistic action between these two factors in target gene repression. This was confirmed using a cell-culture-based luciferase reporter assay. Taken together, our results indicate that Hairy and Kr-h1 not only function as intermediate downstream factors, but also act together in a synergistic fashion in the JH/Met gene repression hierarchy.
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http://dx.doi.org/10.1371/journal.pgen.1008443DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6818763PMC
October 2019

Fabrication of an Active Electronic Device Using a Hetero-bimetallic Coordination Polymer.

ACS Omega 2018 Oct 8;3(10):12788-12796. Epub 2018 Oct 8.

Department of Chemistry, Inorganic Section and Department of Physics, Jadavpur University, Kolkata 700032, India.

A nickel(II)/lead(II) coordination polymer [(NCS)Pb(HO)LNi(NCS)] {HL = ,'-bis(3-methoxysalicylidene)propane-1,3-diamine} has been synthesized and characterized. The band gap (3.18 eV) calculated from Tauc's plot suggests the semiconducting nature of the complex. The material has a photosensitivity of 5.76, indicating its applicability in the fabrication of photosensitive devices. The complex has been successfully applied in a technologically challenging thin-film photosensitive Schottky device.
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http://dx.doi.org/10.1021/acsomega.8b02025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6644615PMC
October 2018

Molecular characterization and expression profile of an alternate proliferating cell nuclear antigen homolog PbPCNA2 in Plasmodium berghei.

IUBMB Life 2019 09 13;71(9):1293-1301. Epub 2019 Mar 13.

Special Centre for Molecular Medicine, Jawaharlal Nehru University, New Delhi, India.

Proliferative cell nuclear antigen (PCNA) is the processivity factor for various DNA polymerases and it functions in response to DNA damage in eukaryotic system. Plasmodium falciparum contains two PCNAs, while PCNA1 has been attributed to DNA replication, the role of PCNA2 has been assigned to DNA damage response in erythrocytic developmental stages. Although a recent transposon mediated knockout strategy qualified pcna2 as a nonessential gene in Plasmodium berghei, a conventional homologous recombination-based knockout strategy has not been employed for this gene yet. Moreover, the cellular dynamics of PCNA2 in extraerythrocytic stages still remain elusive in Plasmodium. We attempted multiple times to knock out PbPCNA2 from the parasite genome using homologous recombination strategy without much success. However, we were able to generate PbPCNA2-GFP tagged transgenic parasites confirming that the pcna2 locus is amenable to genetic manipulation. The GFP-tagged parasites showed similar growth phenotype, compared to wild-type parasites, in both erythrocytic and sporogonic cycle, suggesting that tagging had no effect on parasite physiology. PbPCNA2 expression was also observed during the sporogonic cycle in midgut oocyst and salivary gland sporozoites. The PbPCNA2 expression was upregulated in the presence of DNA damaging agents like hydroxyurea and methyl methanesulphonate. Our inability to knock out PCNA2 suggested its essentiality in the parasite development and elevated expression during DNA damaging condition hint at a critical role of the protein in parasite physiology. © 2019 IUBMB Life, 71(9):1293-1301, 2019.
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http://dx.doi.org/10.1002/iub.2036DOI Listing
September 2019

Improved reference genome of Aedes aegypti informs arbovirus vector control.

Nature 2018 11 14;563(7732):501-507. Epub 2018 Nov 14.

Laboratory of Neurogenetics and Behavior, The Rockefeller University, New York, NY, USA.

Female Aedes aegypti mosquitoes infect more than 400 million people each year with dangerous viral pathogens including dengue, yellow fever, Zika and chikungunya. Progress in understanding the biology of mosquitoes and developing the tools to fight them has been slowed by the lack of a high-quality genome assembly. Here we combine diverse technologies to produce the markedly improved, fully re-annotated AaegL5 genome assembly, and demonstrate how it accelerates mosquito science. We anchored physical and cytogenetic maps, doubled the number of known chemosensory ionotropic receptors that guide mosquitoes to human hosts and egg-laying sites, provided further insight into the size and composition of the sex-determining M locus, and revealed copy-number variation among glutathione S-transferase genes that are important for insecticide resistance. Using high-resolution quantitative trait locus and population genomic analyses, we mapped new candidates for dengue vector competence and insecticide resistance. AaegL5 will catalyse new biological insights and intervention strategies to fight this deadly disease vector.
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http://dx.doi.org/10.1038/s41586-018-0692-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6421076PMC
November 2018

Two new eriophyoid mites (Acari: Eriophyoidea) from West Bengal, India.

Zootaxa 2018 Jun 14;4434(1):193-200. Epub 2018 Jun 14.

Post-Graduate Department of Zoology, Vidyasagar College, 39 Sankar Ghosh Lane, Kolkata 700006..

Two new species of eriophyoid mites viz. Abacarus sundarbanensis n. sp. infesting Pongamia glabra L. (Fabaceae) and Diptilomiopus augustifoliae n. sp. infesting Ambroma augusta (L.) (Sterculiaceae) respectively, are described from West Bengal, India.
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http://dx.doi.org/10.11646/zootaxa.4434.1.13DOI Listing
June 2018

Glucocorticoids Induce Stress Oncoproteins Associated with Therapy-Resistance in African American and European American Prostate Cancer Cells.

Sci Rep 2018 10 10;8(1):15063. Epub 2018 Oct 10.

Center for Health Disparities and Molecular Medicine and Department of Basic Sciences, Loma Linda University School of Medicine, Loma Linda, CA, USA.

Glucocorticoid receptor (GR) is emerging as a key driver of prostate cancer (PCa) progression and therapy resistance in the absence of androgen receptor (AR) signaling. Acting as a bypass mechanism, GR activates AR-regulated genes, although GR-target genes contributing to PCa therapy resistance remain to be identified. Emerging evidence also shows that African American (AA) men, who disproportionately develop aggressive PCa, have hypersensitive GR signaling linked to cumulative stressful life events. Using racially diverse PCa cell lines (MDA-PCa-2b, 22Rv1, PC3, and DU145) we examined the effects of glucocorticoids on the expression of two stress oncoproteins associated with PCa therapy resistance, Clusterin (CLU) and Lens Epithelium-Derived Growth Factor p75 (LEDGF/p75). We observed that glucocorticoids upregulated LEDGF/p75 and CLU in PCa cells. Blockade of GR activation abolished this upregulation. We also detected increased GR transcript expression in AA PCa tissues, compared to European American (EA) tissues, using Oncomine microarray datasets. These results demonstrate that glucocorticoids upregulate the therapy resistance-associated oncoproteins LEDGF/p75 and CLU, and suggest that this effect may be enhanced in AA PCa. This study provides an initial framework for understanding the contribution of glucocorticoid signaling to PCa health disparities.
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http://dx.doi.org/10.1038/s41598-018-33150-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6180116PMC
October 2018

RNA sequencing reveals upregulation of a transcriptomic program associated with stemness in metastatic prostate cancer cells selected for taxane resistance.

Oncotarget 2018 Jul 13;9(54):30363-30384. Epub 2018 Jul 13.

Center for Health Disparities and Molecular Medicine, Loma Linda University School of Medicine, Loma Linda, CA, USA.

Patients with metastatic castration-resistant prostate cancer (mCRPC) develop resistance to conventional therapies including docetaxel (DTX). Identifying molecular pathways underlying DTX resistance is critical for developing novel combinatorial therapies to prevent or reverse this resistance. To identify transcriptomic signatures associated with acquisition of chemoresistance we profiled gene expression in DTX-sensitive and -resistant mCRPC cells using RNA sequencing (RNA-seq). PC3 and DU145 cells were selected for DTX resistance and this phenotype was validated by immunoblotting using DTX resistance markers (e.g. clusterin, ABCB1/P-gp, and LEDGF/p75). Overlapping genes differentially regulated in the DTX-sensitive and -resistant cells were ranked by Gene Set Enrichment Analysis (GSEA) and validated to correlate transcript with protein expression. GSEA revealed that genes associated with cancer stem cells (CSC) (e.g., ) were highly ranked and comprised 70% of the top 25 genes differentially upregulated in the DTX-resistant cells. Established markers of epithelial-to-mesenchymal transition (EMT) and CSCs were used to evaluate the stemness of adherent DTX-resistant cells (2D cultures) and tumorspheres (3D cultures). Increased formation and frequency of cells expressing CSC markers were detected in DTX-resistant cells. DU145-DR cells showed a 2-fold increase in tumorsphere formation and increased DTX resistance compared to DU145-DR 2D cultures. These results demonstrate the induction of a transcriptomic program associated with stemness in mCRPC cells selected for DTX resistance, and strengthen the emerging body of evidence implicating CSCs in this process. In addition, they provide additional candidate genes and molecular pathways for potential therapeutic targeting to overcome DTX resistance.
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http://dx.doi.org/10.18632/oncotarget.25744DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6084384PMC
July 2018

Regulatory Pathways Controlling Female Insect Reproduction.

Annu Rev Entomol 2018 01 20;63:489-511. Epub 2017 Oct 20.

Department of Entomology, Institute for Integrative Genome Biology, and Center for Disease Vector Research, University of California, Riverside, California 92521, USA; email: , ,

The synthesis of vitellogenin and its uptake by maturing oocytes during egg maturation are essential for successful female reproduction. These events are regulated by the juvenile hormones and ecdysteroids and by the nutritional signaling pathway regulated by neuropeptides. Juvenile hormones act as gonadotropins, regulating vitellogenesis in most insects, but ecdysteroids control this process in Diptera and some Hymenoptera and Lepidoptera. The complex crosstalk between the juvenile hormones, ecdysteroids, and nutritional signaling pathways differs distinctly depending on the reproductive strategies adopted by various insects. Molecular studies within the past decade have revealed much about the relationships among, and the role of, these pathways with respect to regulation of insect reproduction. Here, we review the role of juvenile hormones, ecdysteroids, and nutritional signaling, along with that of microRNAs, in regulating female insect reproduction at the molecular level.
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http://dx.doi.org/10.1146/annurev-ento-020117-043258DOI Listing
January 2018

The 22Rv1 prostate cancer cell line carries mixed genetic ancestry: Implications for prostate cancer health disparities research using pre-clinical models.

Prostate 2017 Dec 14;77(16):1601-1608. Epub 2017 Oct 14.

Department of Basic Sciences, Center for Health Disparities and Molecular Medicine, Loma Linda University School of Medicine, Loma Linda, California.

Background: Understanding how biological factors contribute to prostate cancer (PCa) health disparities requires mechanistic functional analysis of specific genes or pathways in pre-clinical cellular and animal models of this malignancy. The 22Rv1 human prostatic carcinoma cell line was originally derived from the parental CWR22R cell line. Although 22Rv1 has been well characterized and used in numerous mechanistic studies, no racial identifier has ever been disclosed for this cell line. In accordance with the need for racial diversity in cancer biospecimens and recent guidelines by the NIH on authentication of key biological resources, we sought to determine the ancestry of 22RV1 and authenticate previously reported racial identifications for four other PCa cell lines.

Methods: We used 29 established Ancestry Informative Marker (AIM) single nucleotide polymorphisms (SNPs) to conduct DNA ancestry analysis and assign ancestral proportions to a panel of five PCa cell lines that included 22Rv1, PC3, DU145, MDA-PCa-2b, and RC-77T/E.

Results: We found that 22Rv1 carries mixed genetic ancestry. The main ancestry proportions for this cell line were 0.41 West African (AFR) and 0.42 European (EUR). In addition, we verified the previously reported racial identifications for PC3 (0.73 EUR), DU145 (0.63 EUR), MDA-PCa-2b (0.73 AFR), and RC-77T/E (0.74 AFR) cell lines.

Conclusions: Considering the mortality disparities associated with PCa, which disproportionately affect African American men, there remains a burden on the scientific community to diversify the availability of biospecimens, including cell lines, for mechanistic studies on potential biological mediators of these disparities. This study is beneficial by identifying another PCa cell line that carries substantial AFR ancestry. This finding may also open the door to new perspectives on previously published studies using this cell line.
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http://dx.doi.org/10.1002/pros.23437DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5687283PMC
December 2017

Understanding of multi-level resistive switching mechanism in GeO through redox reaction in HO/sarcosine prostate cancer biomarker detection.

Sci Rep 2017 09 11;7(1):11240. Epub 2017 Sep 11.

Department of Physics, Indian Institute of Technology, Kharagpur, 721302, India.

Formation-free multi-level resistive switching characteristics by using 10 nm-thick polycrystalline GeO film in a simple W/GeO/W structure and understanding of switching mechanism through redox reaction in HO/sarcosine sensing (or changing Ge°/Ge oxidation states under external bias) have been reported for the first time. Oxidation states of Ge/Ge are confirmed by both XPS and HO sensing of GeO membrane in electrolyte-insulator-semiconductor structure. Highly repeatable 1000 dc cycles and stable program/erase (P/E) endurance of >10 cycles at a small pulse width of 100 ns are achieved at a low operation current of 0.1 µA. The thickness of GeO layer is found to be increased to 12.5 nm with the reduction of polycrystalline grain size of <7 nm after P/E of 10 cycles, which is observed by high-resolution TEM. The switching mechanism is explored through redox reaction in GeO membrane by sensing 1 nM HO, which is owing to the change of oxidation states from Ge to Ge because of the enhanced O ions migration in memory device under external bias. In addition, sarcosine as a prostate cancer biomarker with low concentration of 50 pM to 10 µM is also detected.
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http://dx.doi.org/10.1038/s41598-017-11657-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5593955PMC
September 2017

MicroRNA-275 targets sarco/endoplasmic reticulum Ca2+ adenosine triphosphatase (SERCA) to control key functions in the mosquito gut.

PLoS Genet 2017 Aug 7;13(8):e1006943. Epub 2017 Aug 7.

Department of Entomology and Institute for Integrative Genome Biology, University of California Riverside, Riverside, California, United States of America.

The yellow fever mosquito Aedes aegypti is the major vector of arboviruses, causing numerous devastating human diseases, such as dengue and yellow fevers, Chikungunya and Zika. Female mosquitoes need vertebrate blood for egg development, and repeated cycles of blood feeding are tightly linked to pathogen transmission. The mosquito's posterior midgut (gut) is involved in blood digestion and also serves as an entry point for pathogens. Thus, the mosquito gut is an important tissue to investigate. The miRNA aae-miR-275 (miR-275) has been shown to be required for normal blood digestion in the female mosquito; however, the mechanism of its action has remained unknown. Here, we demonstrate that miR-275 directly targets and positively regulates sarco/endoplasmic reticulum Ca2+ adenosine triphosphatase, which is implicated in active transport of Ca2+ from the cytosol to the sarco/endoplasmic reticulum. We utilized a combination of the gut-specific yeast transcription activator protein Gal4/upstream activating sequence (Gal4/UAS) system and miRNA Tough Decoy technology to deplete the endogenous level of miR-275 in guts of transgenic mosquitoes. This gut-specific reduction of miR-275 post blood meal decreased SERCA mRNA and protein levels of the digestive enzyme late trypsin. It also resulted in a significant reduction of gut microbiota. Moreover, the decrease of miR-275 and SERCA correlated with defects in the Notch signaling pathway and assembly of the gut actin cytoskeleton. The adverse phenotypes caused by miR-275 silencing were rescued by injections of miR-275 mimic. Thus, we have discovered that miR-275 directly targets SERCA, and the maintenance of its level is critical for multiple gut functions in mosquitoes.
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http://dx.doi.org/10.1371/journal.pgen.1006943DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5560755PMC
August 2017

Estimation of conventional C-Hπ (arene), unconventional C-Hπ (chelate) and C-Hπ (thiocyanate) interactions in hetero-nuclear nickel(ii)-cadmium(ii) complexes with a compartmental Schiff base.

Dalton Trans 2017 Apr;46(16):5384-5397

Department of Chemistry, Inorganic Section, Jadavpur University, Kolkata - 700032, India.

Three new heteronuclear nickel(ii)/cadmium(ii) complexes, [(SCN)(Cl)Cd(L)Ni(DMF)] (1), [(SCN)(CHCO)Cd(L)Ni(CHOH)] (2) and [(SCN)(Cl)Cd(L)Ni(NHCHCHCHNH)] (3) {where HL = N,N'-bis(3-ethoxy-salicylidene)propane-1,3-diamine is a NO compartmental Schiff base}, have been synthesized and characterized. The structures of the complexes have been confirmed by single crystal X-ray diffraction studies. In each complex, nickel(ii) is placed in the inner NO environment and cadmium(ii) is placed in the outer O compartment of the compartmental Schiff base. Furthermore, the importance of unconventional C-Hπ (chelate) interactions in the solid state of both complexes and C-Hπ (thiocyanate) interaction in complex 2 has been described by means of DFT and MEP calculations and characterized using NCI plots. All complexes show photoluminescence at room temperature upon irradiation by ultraviolet light. The lifetimes of excited states are in the range of 2-6 ns.
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http://dx.doi.org/10.1039/c6dt04906kDOI Listing
April 2017

Two new genera and two new species of eriophyoid mites (Acari: Eriophyoidea) from North Bengal, India.

Zootaxa 2017 Feb 21;4236(1):zootaxa.4236.1.10. Epub 2017 Feb 21.

Post-Graduate Department of Zoology, Vidyasagar College, 39 Sankar Ghosh Lane, Kolkata 700006, India..

Two new genera and two new species of eriophyoid mites viz., Propeaciota genusetosis n. gen. and n. sp. infesting Acer sp. (Aceraceae) and Spinaephyes alnus n. gen. and n. sp. infesting Alnus nepalensis D. Don (Betulaceae) are described in the tribe Tegonotini (Eriophyidae: Phyllocoptinae) from North Bengal, India. Aciota secundum Flechtmann et al.1995 is re-assigned (n. comb.) to Propeaciota. Relationships of the new genera with other eriophyoid genera are discussed.
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http://dx.doi.org/10.11646/zootaxa.4236.1.10DOI Listing
February 2017

Role of W181 in modulating kinetic properties of Plasmodium falciparum hypoxanthine guanine xanthine phosphoribosyltransferase.

Proteins 2016 11 13;84(11):1658-1669. Epub 2016 Aug 13.

Molecular Biology and Genetics Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Jakkur, Bangalore, 560064, India.

Hypoxanthine-guanine-xanthine phosphoribosyltransference (HGXPRT), a key enzyme in the purine salvage pathway of the malarial parasite, Plasmodium falciparum (Pf), catalyses the conversion of hypoxanthine, guanine, and xanthine to their corresponding mononucleotides; IMP, GMP, and XMP, respectively. Out of the five active site loops (I, II, III, III', and IV) in PfHGXPRT, loop III' facilitates the closure of the hood over the core domain which is the penultimate step during enzymatic catalysis. PfHGXPRT mutants were constructed wherein Trp 181 in loop III' was substituted with Ser, Thr, Tyr, and Phe. The mutants (W181S, W181Y and W181F), when examined for xanthine phosphoribosylation activity, showed an increase in K for PRPP by 2.1-3.4 fold under unactivated condition and a decrease in catalytic efficiency by more than 5-fold under activated condition as compared to that of the wild-type enzyme. The W181T mutant showed 10-fold reduced xanthine phosphoribosylation activity. Furthermore, molecular dynamics simulations of WT and in silico W181S/Y/F/T PfHGXPRT mutants bound to IMP.PPi.Mg have been carried out to address the effect of the mutation of W181 on the overall dynamics of the systems and identify local changes in loop III'. Dynamic cross-correlation analyses show a communication between loop III' and the substrate binding site. Differential cross-correlation maps indicate altered communication among different regions in the mutants. Changes in the local contacts and hydrogen bonding between residue 181 with the nearby residues cause altered substrate affinity and catalytic efficiency of the mutant enzymes. Proteins 2016; 84:1658-1669. © 2016 Wiley Periodicals, Inc.
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http://dx.doi.org/10.1002/prot.25107DOI Listing
November 2016

A combined experimental and computational study on supramolecular assemblies in hetero-tetranuclear nickel(ii)-cadmium(ii) complexes with NO-donor compartmental Schiff bases.

Dalton Trans 2016 Sep;45(38):15048-15059

Department of Chemistry, Inorganic Section, Jadavpur University, Kolkata - 700032, India.

Two new hetero-tetranuclear nickel(ii)/cadmium(ii) complexes, a cubane [(CHCO)Ni(L)Cd(NCS)] (1) and a linear tetramer [(DMSO)NiLCd(NCS)(μ-SCN)Ni(DMSO)LCd(NCS)] (2) {where HL = N,N'-bis(3-methoxysalicylidene)propane-1,3-diamine and HL = N,N'-bis(3-ethoxysalicylidene)propane-1,3-diamine are potential octadentate compartmental Schiff bases}, were synthesized and characterized. The structures of both complexes were confirmed by single crystal X-ray diffraction studies. Complex 1 contained a NiCdO cubane core, whereas complex 2 featured an end-to-end thiocyanate-bridged tetranuclear moiety. Furthermore, complex 1 showed C-HH-C interactions, whereas a unique Sπ interaction was observed in complex 2. Theoretical studies were performed using several computational tools such as NBO and AIM analyses. Both complexes showed photoluminescence in DMSO medium at room temperature upon irradiation with ultraviolet light. The lifetimes of the excited states were ∼27 ns.
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http://dx.doi.org/10.1039/c6dt02587kDOI Listing
September 2016

NMR Scalar Couplings across Intermolecular Hydrogen Bonds between Zinc-Finger Histidine Side Chains and DNA Phosphate Groups.

J Phys Chem B 2016 Oct 10;120(41):10679-10685. Epub 2016 Oct 10.

Department of Biochemistry and Molecular Biology, Sealy Center for Structural Biology and Molecular Biophysics, University of Texas Medical Branch , Galveston, Texas 77555-1068, United States.

NMR scalar couplings across hydrogen bonds represent direct evidence for the partial covalent nature of hydrogen bonds and provide structural and dynamic information on hydrogen bonding. In this article, we report heteronuclear N-P and H-P scalar couplings across the intermolecular hydrogen bonds between protein histidine (His) imidazole and DNA phosphate groups. These hydrogen-bond scalar couplings were observed for the Egr-1 zinc-finger-DNA complex. Although His side-chain NH protons are typically undetectable in heteronuclear H-N correlation spectra due to rapid hydrogen exchange, this complex exhibited two His side-chain NH signals around H 14.3 ppm and N 178 ppm at 35 °C. Through various heteronuclear multidimensional NMR experiments, these signals were assigned to two zinc-coordinating His side chains in contact with DNA phosphate groups. The data show that the N atoms of these His side chains are protonated and exhibit the H-N cross-peaks. Using heteronuclear H, N, and P NMR experiments, we observed the hydrogen-bond scalar couplings between the His N/H and DNA phosphate P nuclei. These results demonstrate the direct involvement of the zinc-coordinating His side chains in the recognition of DNA by the CysHis-class zinc fingers in solution.
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http://dx.doi.org/10.1021/acs.jpcb.6b08137DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5386832PMC
October 2016

microRNA-309 targets the Homeobox gene SIX4 and controls ovarian development in the mosquito Aedes aegypti.

Proc Natl Acad Sci U S A 2016 08 3;113(33):E4828-36. Epub 2016 Aug 3.

Department of Entomology, University of California, Riverside, CA 92521; Institute for Integrative Genomic Biology, University of California, Riverside, CA 92521

Obligatory blood-triggered reproductive strategy is an evolutionary adaptation of mosquitoes for rapid egg development. It contributes to the vectorial capacity of these insects. Therefore, understanding the molecular mechanisms underlying reproductive processes is of particular importance. Here, we report that microRNA-309 (miR-309) plays a critical role in mosquito reproduction. A spatiotemporal expression profile of miR-309 displayed its blood feeding-dependent onset and ovary-specific manifestation in female Aedes aegypti mosquitoes. Antagomir silencing of miR-309 impaired ovarian development and resulted in nonsynchronized follicle growth. Furthermore, the genetic disruption of miR-309 by CRISPR/Cas9 system led to the developmental failure of primary follicle formation. Examination of genomic responses to miR-309 depletion revealed that several pathways associated with ovarian development are down-regulated. Comparative analysis of genes obtained from the high-throughput RNA sequencing of ovarian tissue from the miR-309 antagomir-silenced mosquitoes with those from the in silico computation target prediction identified that the gene-encoding SIX homeobox 4 protein (SIX4) is a putative target of miR-309. Reporter assay and RNA immunoprecipitation confirmed that SIX4 is a direct target of miR-309. RNA interference of SIX4 was able to rescue phenotypic manifestations caused by miR-309 depletion. Thus, miR-309 plays a critical role in mosquito reproduction by targeting SIX4 in the ovary and serves as a regulatory switch permitting a stage-specific degradation of the ovarian SIX4 mRNA. In turn, this microRNA (miRNA)-targeted degradation is required for appropriate initiation of a blood feeding-triggered phase of ovarian development, highlighting involvement of this miRNA in mosquito reproduction.
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http://dx.doi.org/10.1073/pnas.1609792113DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4995966PMC
August 2016

Product Release Pathways in Human and Plasmodium falciparum Phosphoribosyltransferase.

J Chem Inf Model 2016 08 21;56(8):1528-38. Epub 2016 Jul 21.

Chemistry and Physics of Materials Unit, ‡Molecular Biology and Genetics Unit, and §Theoretical Sciences Unit, Jawaharlal Nehru Centre for Advanced Scientific Research , Bangalore 560 064, India.

Atomistic molecular dynamics (MD) simulations coupled with the metadynamics technique were carried out to delineate the product (PPi.2Mg and IMP) release mechanisms from the active site of both human (Hs) and Plasmodium falciparum (Pf) hypoxanthine-guanine-(xanthine) phosphoribosyltransferase (HG(X)PRT). An early movement of PPi.2Mg from its binding site has been observed. The swinging motion of the Asp side chain (D134/D145) in the binding pocket facilitates the detachment of IMP, which triggers the opening of flexible loop II, the gateway to the bulk solvent. In PfHGXPRT, PPi.2Mg and IMP are seen to be released via the same path in all of the biased MD simulations. In HsHGPRT too, the product molecules follow similar routes from the active site; however, an alternate but minor escape route for PPi.2Mg has been observed in the human enzyme. Tyr 104 and Phe 186 in HsHGPRT and Tyr 116 and Phe 197 in PfHGXPRT are the key residues that mediate the release of IMP, whereas the motion of PPi.2Mg away from the reaction center is guided by the negatively charged Asp and Glu and a few positively charged residues (Lys and Arg) that line the product release channels. Mutations of a few key residues present in loop II of Trypanosoma cruzi (Tc) HGPRT have been shown to reduce the catalytic efficiency of the enzyme. Herein, in silico mutation of corresponding residues in loop II of HsHGPRT and PfHGXPRT resulted in partial opening of the flexible loop (loop II), thus exposing the active site to bulk water, which offers a rationale for the reduced catalytic activity of these two mutant enzymes. Investigations of the product release from these HsHGPRT and PfHGXPRT mutants delineate the role of these important residues in the enzymatic turnover.
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http://dx.doi.org/10.1021/acs.jcim.6b00203DOI Listing
August 2016

Changes in conformational dynamics of basic side chains upon protein-DNA association.

Nucleic Acids Res 2016 08 10;44(14):6961-70. Epub 2016 Jun 10.

Department of Biochemistry and Molecular Biology, Sealy Center for Structural Biology and Molecular Biophysics, University of Texas Medical Branch, Galveston, TX 77555-1068, USA

Basic side chains play major roles in recognition of nucleic acids by proteins. However, dynamic properties of these positively charged side chains are not well understood. In this work, we studied changes in conformational dynamics of basic side chains upon protein-DNA association for the zinc-finger protein Egr-1. By nuclear magnetic resonance (NMR) spectroscopy, we characterized the dynamics of all side-chain cationic groups in the free protein and in the complex with target DNA. Our NMR order parameters indicate that the arginine guanidino groups interacting with DNA bases are strongly immobilized, forming rigid interfaces. Despite the strong short-range electrostatic interactions, the majority of the basic side chains interacting with the DNA phosphates exhibited high mobility, forming dynamic interfaces. In particular, the lysine side-chain amino groups exhibited only small changes in the order parameters upon DNA-binding. We found a similar trend in the molecular dynamics (MD) simulations for the free Egr-1 and the Egr-1-DNA complex. Using the MD trajectories, we also analyzed side-chain conformational entropy. The interfacial arginine side chains exhibited substantial entropic loss upon binding to DNA, whereas the interfacial lysine side chains showed relatively small changes in conformational entropy. These data illustrate different dynamic characteristics of the interfacial arginine and lysine side chains.
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http://dx.doi.org/10.1093/nar/gkw531DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5001603PMC
August 2016

Kinetic mechanism of Plasmodium falciparum hypoxanthine-guanine-xanthine phosphoribosyltransferase.

Mol Biochem Parasitol 2015 Dec 21;204(2):111-120. Epub 2016 Feb 21.

Molecular Biology and Genetics Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Jakkur, Bangalore 560064, India. Electronic address:

Plasmodium falciparum hypoxanthine-guanine-xanthine phosphoribosyltransferase (PfHGXPRT) exhibits a kinetic mechanism that differs from that of the human homolog. Human HGPRT follows a steady-state ordered mechanism, wherein PRPP binding precedes the binding of hypoxanthine/guanine and release of product IMP/GMP is the rate limiting step. In the current study, initial velocity kinetics with PfHGXPRT indicates a steady-state ordered mechanism, wherein xanthine binding is conditional to the binding of PRPP. The value of the rate constant for IMP dissociation is greater by 183-fold than the kcat for hypoxanthine phosphoribosylation and this results in the absence of burst in progress curves from pre-steady-state kinetics. Further, IMP binding is 1000 times faster (4s(-1) at 0.5μM IMP) when compared to the kcat (3.9±0.2×10(-3)s(-1)) for the reverse IMP pyrophosphorolysis reaction. These results lend support to the fact that in both forward and reverse reactions, the process of chemical conversion (formation of IMP/hypoxanthine) is slow and the events of ligand association and dissociation are faster.
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http://dx.doi.org/10.1016/j.molbiopara.2016.02.006DOI Listing
December 2015

Hairy and Groucho mediate the action of juvenile hormone receptor Methoprene-tolerant in gene repression.

Proc Natl Acad Sci U S A 2016 Feb 7;113(6):E735-43. Epub 2016 Jan 7.

Department of Entomology, University of California, Riverside, CA 92521; The Institute for Integrative Genome Biology, University of California, Riverside, CA 92521;

The arthropod-specific juvenile hormone (JH) controls numerous essential functions. Its involvement in gene activation is known to be mediated by the transcription factor Methoprene-tolerant (Met), which turns on JH-controlled genes by directly binding to E-box-like motifs in their regulatory regions. However, it remains unclear how JH represses genes. We used the Aedes aegypti female mosquito, in which JH is necessary for reproductive maturation, to show that a repressor, Hairy, is required for the gene-repressive action of JH and Met. The RNA interference (RNAi) screen for Met and Hairy in the Aedes female fat body revealed a large cohort of Met- and Hairy-corepressed genes. Analysis of selected genes from this cohort demonstrated that they are repressed by JH, but RNAi of either Met or Hairy renders JH ineffective in repressing these genes in an in vitro fat-body culture assay. Moreover, this JH action was prevented by the addition of the translational inhibitor cycloheximide (CHX) to the culture, indicating the existence of an indirect regulatory hierarchy. The lack of Hairy protein in the CHX-treated tissue was verified using immunoblot analysis, and the upstream regions of Met/Hairy-corepressed genes were shown to contain common binding motifs that interact with Hairy. Groucho (gro) RNAi silencing phenocopied the effect of Hairy RNAi knockdown, indicating that it is involved in the JH/Met/Hairy hierarchy. Finally, the requirement of Hairy and Gro for gene repression was confirmed in a cell transfection assay. Thus, our study has established that Hairy and its cofactor Gro mediate the repressive function of JH and Met.
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http://dx.doi.org/10.1073/pnas.1523838113DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4760797PMC
February 2016

Ultra-highly diluted plant extracts of Hydrastis canadensis and Marsdenia condurango induce epigenetic modifications and alter gene expression profiles in HeLa cells in vitro.

J Integr Med 2015 Nov;13(6):400-11

Cytogenetics and Molecular Biology Laboratory, Department of Zoology, University of Kalyani, Kalyani-741235, West Bengal, India.

Objective: Methylation-specific epigenetic process and gene expression profiles of HeLa cells treated with ultra-high dilutions (HDs) of two plant extracts, Hydrastis canadensis (HC-30) and Marsdenia condurango (Condu-30), diluted 1060 times, were analyzed against placebo 30C (Pl-30) for alterations in gene profiles linked to epigenetic modifications.

Methods: Separate groups of cells were subjected to treatment of Condu-30, HC-30, and Pl-30 prepared by serial dilutions and succussions. Global microarray data recorded on Affymetrix platform, using 25-mer probes were provided by iLifeDiscoveries, India. Slides were scanned with 3000 7G microarray scanner and raw data sets were extracted from Cel (raw intensity) files. Analyses of global microarray data profile, differential gene expression, fold change and clusters were made using GeneSpring GX12.5 software and standard normalization procedure. Before microarray study, concentration of RNA (ng/μL), RIN value and rRNA ratio for all the samples were analysed by Agilant Bioanalyzer 2100. Reverse transcriptase polymerase chain reaction (RT-PCR) and quantitative RT-PCR were done for analyzing SMAD-4 expression. Fluorescence-activated cell sorting study was further made to elucidate fate of cells at divisional stages. Methylation-specific restriction enzyme assay was conducted for ascertaining methylation status of DNA at specific sites.

Results: HDs of HC-30 and Condu-30 differentially altered methylation in specific regions of DNA and expression profiles of certain genes linked to carcinogenesis, as compared to Pl-30. Two separate cut sites were found in genomic DNA of untreated and placebo-treated HeLa cells when digested with McrBC, compared to a single cut observed in Condu-30-treated genomic DNA. SMAD-4 gene expression validated the expression pattern observed in microarray profile. Methylation-specific restriction enzyme assay elucidated differential epigenetic modifications in drug-treated and control cells.

Conclusion: HDs triggered epigenetic modifications and alterations in microarray gene expression profiles of many genes associated with carcinogenesis in HeLa cells in vitro.
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http://dx.doi.org/10.1016/S2095-4964(15)60201-1DOI Listing
November 2015