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  1. Article ; Online: Loss of Prom1 impairs autophagy and promotes epithelial-mesenchymal transition in mouse retinal pigment epithelial cells.

    Bhattacharya, Sujoy / Yin, Jinggang / Huo, Weihong / Chaum, Edward

    Journal of cellular physiology

    2023  Volume 238, Issue 10, Page(s) 2373–2389

    Abstract: Mutations in the Prominin-1 (Prom1) gene disrupt photoreceptor disk morphogenesis, leading to macular dystrophies. We have shown that human retinal pigment epithelial (RPE) homeostasis is under the control of Prom1-dependent autophagy, demonstrating that ...

    Abstract Mutations in the Prominin-1 (Prom1) gene disrupt photoreceptor disk morphogenesis, leading to macular dystrophies. We have shown that human retinal pigment epithelial (RPE) homeostasis is under the control of Prom1-dependent autophagy, demonstrating that Prom1 plays different roles in the photoreceptors and RPE. It is unclear if retinal and macular degeneration caused by the loss of Prom1 function is a cell-autonomous feature of the RPE or a generalized disease of photoreceptor degeneration. In this study, we investigated whether Prom1 is required for mouse RPE (mRPE) autophagy and phagocytosis, which are cellular processes essential for photoreceptor survival. We found that Prom1-KO decreases autophagy flux, activates mTORC1, and concomitantly decreases transcription factor EB (TFEB) and Cathepsin-D activities in mRPE cells. In addition, Prom1-KO reduces the clearance of bovine photoreceptor outer segments in mRPE cells due to increased mTORC1 and reduced TFEB activities. Dysfunction of Prom1-dependent autophagy correlates with both a decrease in ZO-1 and E-cadherin and a concomitant increase in Vimentin, SNAI1, and ZEB1 levels, consistent with induction of epithelial-mesenchymal transition (EMT) in Prom1-KO mRPE cells. Our results demonstrate that Prom1-mTORC1-TFEB signaling is a central driver of cell-autonomous mRPE homeostasis. We show that Prom1-KO in mRPE leads to RPE defects similar to that seen in atrophic age-related macular degeneration and opens new avenues of investigation targeting Prom1 in retinal degenerative diseases.
    Language English
    Publishing date 2023-08-23
    Publishing country United States
    Document type Journal Article
    ZDB-ID 3116-1
    ISSN 1097-4652 ; 0021-9541
    ISSN (online) 1097-4652
    ISSN 0021-9541
    DOI 10.1002/jcp.31094
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Modeling of mitochondrial bioenergetics and autophagy impairment in MELAS-mutant iPSC-derived retinal pigment epithelial cells.

    Bhattacharya, Sujoy / Yin, Jinggang / Huo, Weihong / Chaum, Edward

    Stem cell research & therapy

    2022  Volume 13, Issue 1, Page(s) 260

    Abstract: Background: Mitochondrial dysfunction and mitochondrial DNA (mtDNA) damage in the retinal pigment epithelium (RPE) have been implicated in the pathogenesis of age-related macular degeneration (AMD). However, a deeper understanding is required to ... ...

    Abstract Background: Mitochondrial dysfunction and mitochondrial DNA (mtDNA) damage in the retinal pigment epithelium (RPE) have been implicated in the pathogenesis of age-related macular degeneration (AMD). However, a deeper understanding is required to determine the contribution of mitochondrial dysfunction and impaired mitochondrial autophagy (mitophagy) to RPE damage and AMD pathobiology. In this study, we model the impact of a prototypical systemic mitochondrial defect, mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS), in RPE health and homeostasis as an in vitro model for impaired mitochondrial bioenergetics.
    Methods: We used induced pluripotent stem cells (iPSCs) derived from skin biopsies of MELAS patients (m.3243A > G tRNA leu mutation) with different levels of mtDNA heteroplasmy and differentiated them into RPE cells. Mitochondrial depletion of ARPE-19 cells (p
    Results: We found that MELAS iPSC-derived RPE cells exhibited key characteristics of native RPE. We observed heteroplasmy-dependent impairment of mitochondrial bioenergetics and reliance on glycolysis for generating energy in the MELAS iPSC-derived RPE. The degree of heteroplasmy was directly associated with increased activation of signal transducer and activator of transcription 3 (STAT3), reduced adenosine monophosphate-activated protein kinase α (AMPKα) activation, and decreased autophagic activity. In addition, impaired autophagy was associated with aberrant lysosomal function, and failure of mitochondrial recycling. The mitochondria-depleted p
    Conclusions: Our studies demonstrate that the MELAS iPSC-derived disease models are powerful tools for dissecting the molecular mechanisms by which mitochondrial DNA alterations influence RPE function in aging and macular degeneration, and for testing novel therapeutics in patients harboring the MELAS genotype.
    MeSH term(s) Autophagy/genetics ; DNA, Mitochondrial/genetics ; Energy Metabolism/genetics ; Epithelial Cells/metabolism ; Humans ; Induced Pluripotent Stem Cells/metabolism ; MELAS Syndrome/genetics ; MELAS Syndrome/metabolism ; MELAS Syndrome/pathology ; Macular Degeneration/metabolism ; Mitochondria/genetics ; Mitochondria/metabolism ; Retinal Pigment Epithelium/metabolism ; Retinal Pigments/metabolism
    Chemical Substances DNA, Mitochondrial ; Retinal Pigments
    Language English
    Publishing date 2022-06-17
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 2548671-8
    ISSN 1757-6512 ; 1757-6512
    ISSN (online) 1757-6512
    ISSN 1757-6512
    DOI 10.1186/s13287-022-02937-6
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Lens Aquaporin-5 Inserts Into Bovine Fiber Cell Plasma Membranes Via Unconventional Protein Secretion.

    Gletten, Romell B / Cantrell, Lee S / Bhattacharya, Sujoy / Schey, Kevin L

    Investigative ophthalmology & visual science

    2022  Volume 63, Issue 8, Page(s) 5

    Abstract: Purpose: To spatially map aquaporin-5 (AQP5) expression in the bovine lens, molecularly characterize cytoplasmic AQP5-containing vesicles in the outer cortex, and elucidate AQP5 membrane trafficking mechanisms.: Methods: Immunofluorescence was ... ...

    Abstract Purpose: To spatially map aquaporin-5 (AQP5) expression in the bovine lens, molecularly characterize cytoplasmic AQP5-containing vesicles in the outer cortex, and elucidate AQP5 membrane trafficking mechanisms.
    Methods: Immunofluorescence was performed on bovine lens cryosections using AQP5, TOMM20, COX IV, calnexin, LC3B, Sec22β, LIMP-2, and connexin 50 antibodies and the membrane dye CM-DiI. AQP5 plasma membrane insertion was defined via line expression profile analysis. Transmission electron microscopy (TEM) was performed on bovine lens sections to examine cytoplasmic organelle morphology and subcellular localization in cortical fiber cells. Bovine lenses were treated with 10-nM bafilomycin A1 or 0.1% dimethyl sulfoxide vehicle control for 24 hours in ex vivo culture to determine changes in AQP5 plasma membrane expression.
    Results: Immunofluorescence analysis revealed cytoplasmic AQP5 expression in lens epithelial cells and differentiating fiber cells. In the lens cortex, complete AQP5 plasma membrane insertion occurs at r/a = 0.951 ± 0.005. AQP5-containing cytoplasmic vesicles are spheroidal in morphology with linear extensions, express TOMM20, and contain LC3B and LIMP-2, but not Sec22β, as fiber cells mature. TEM analysis revealed complex vesicular assemblies with congruent subcellular localization to AQP5-containing cytoplasmic vesicles. AQP5-containing cytoplasmic vesicles appear to dock with the plasma membrane. Bafilomycin A1 treatment reduced AQP5 plasma membrane expression by 27%.
    Conclusions: AQP5 localizes to spheroidal, linear cytoplasmic vesicles in the differentiating bovine lens fiber cells. During fiber cell differentiation, these vesicles incorporate LC3B and presumably fuse with LIMP-2-positive lysosomes. Our data suggest that AQP5 to the plasma membrane through lysosome-associated unconventional protein secretion, a novel mechanism of AQP5 trafficking.
    MeSH term(s) Animals ; Aquaporin 5/metabolism ; Cattle ; Cell Membrane/metabolism ; Lens Cortex, Crystalline/metabolism ; Lens, Crystalline/metabolism ; Protein Transport
    Chemical Substances Aquaporin 5
    Language English
    Publishing date 2022-07-09
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 391794-0
    ISSN 1552-5783 ; 0146-0404
    ISSN (online) 1552-5783
    ISSN 0146-0404
    DOI 10.1167/iovs.63.8.5
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 45: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
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    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

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  4. Article: Family firms, board structure and firm performance

    Bhatt, R. Rathish / Bhattacharya, Sujoy

    International journal of law and management : IJLMA Vol. 59, No. 5 , p. 699-717

    evidence from top Indian firms

    2017  Volume 59, Issue 5, Page(s) 699–717

    Author's details R. Rathish Bhatt and Sujoy Bhattacharya
    Keywords India ; Family firms ; Corporate governance ; Firm performance
    Language English
    Publisher Emerald
    Publishing place Bingley
    Document type Article
    ZDB-ID 2428717-9 ; 2424409-0
    ISSN 1754-2448 ; 1754-243X
    ISSN (online) 1754-2448
    ISSN 1754-243X
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  5. Article: Postservice recovery customer satisfaction in Indian retail banking

    Mandal, Pratap Chandra / Bhattacharya, Sujoy

    Journal of Asia Pacific business Vol. 17, No. 4 , p. 272-292

    scale development and validation

    2016  Volume 17, Issue 4, Page(s) 272–292

    Author's details Pratap Chandra Mandal and Sujoy Bhattacharya
    Keywords India ; post-service recovery customer satisfaction ; retail banking ; scale development ; scale reliability ; scale validity
    Language English
    Dates of publication 2016-9999
    Publisher Routledge, Taylor & Francis Group
    Publishing place Philadelphia, Pa
    Document type Article
    ZDB-ID 1305579-3
    ISSN 1059-9231
    Database ECONomics Information System

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  6. Article: Modeling time-varying volatility in Indian commodity futures return

    Bhattacharya, Sujoy / Gupta, Pulkit

    The IUP journal of financial risk management : IJFRM Bd. XIII , 4 (December), Seite 28-46

    some empirical evidence

    2016  

    Author's details Sujoy Bhattacharya and Pulkit Gupta
    Language English
    Publisher IUP Publ.
    Publishing place Hyderabad
    Document type Article
    ZDB-ID 2615394-4 ; 2571369-3
    ISSN 0972-916X
    ISSN 0972-916X
    Database ECONomics Information System

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  7. Article ; Online: STAT3 suppresses the AMPKα/ULK1-dependent induction of autophagy in glioblastoma cells.

    Bhattacharya, Sujoy / Yin, Jinggang / Yang, Chuanhe / Wang, Yinan / Sims, Michelle / Pfeffer, Lawrence M / Chaum, Edward

    Journal of cellular and molecular medicine

    2022  Volume 26, Issue 14, Page(s) 3873–3890

    Abstract: Despite advances in molecular characterization, glioblastoma (GBM) remains the most common and lethal brain tumour with high mortality rates in both paediatric and adult patients. The signal transducer and activator of transcription 3 (STAT3) is an ... ...

    Abstract Despite advances in molecular characterization, glioblastoma (GBM) remains the most common and lethal brain tumour with high mortality rates in both paediatric and adult patients. The signal transducer and activator of transcription 3 (STAT3) is an important oncogenic driver of GBM. Although STAT3 reportedly plays a role in autophagy of some cells, its role in cancer cell autophagy remains unclear. In this study, we found Serine-727 and Tyrosine-705 phosphorylation of STAT3 was constitutive in GBM cell lines. Tyrosine phosphorylation of STAT3 in GBM cells suppresses autophagy, whereas knockout (KO) of STAT3 increases ULK1 gene expression, increases TSC2-AMPKα-ULK1 signalling, and increases lysosomal Cathepsin D processing, leading to the stimulation of autophagy. Rescue of STAT3-KO cells by the enforced expression of wild-type (WT) STAT3 reverses these pathways and inhibits autophagy. Conversely, expression of Y705F- and S727A-STAT3 phosphorylation deficient mutants in STAT3-KO cells did not suppress autophagy. Inhibition of ULK1 activity (by treatment with MRT68921) or its expression (by siRNA knockdown) in STAT3-KO cells inhibits autophagy and sensitizes cells to apoptosis. Taken together, our findings suggest that serine and tyrosine phosphorylation of STAT3 play critical roles in STAT3-dependent autophagy in GBM, and thus are potential targets to treat GBM.
    MeSH term(s) AMP-Activated Protein Kinases/genetics ; AMP-Activated Protein Kinases/metabolism ; Autophagy/genetics ; Autophagy-Related Protein-1 Homolog/genetics ; Autophagy-Related Protein-1 Homolog/metabolism ; Glioblastoma/pathology ; Humans ; Intracellular Signaling Peptides and Proteins/genetics ; Intracellular Signaling Peptides and Proteins/metabolism ; Phosphorylation ; STAT3 Transcription Factor/metabolism ; Serine/metabolism ; Tyrosine/metabolism
    Chemical Substances Intracellular Signaling Peptides and Proteins ; STAT3 Transcription Factor ; STAT3 protein, human ; Tyrosine (42HK56048U) ; Serine (452VLY9402) ; Autophagy-Related Protein-1 Homolog (EC 2.7.11.1) ; ULK1 protein, human (EC 2.7.11.1) ; AMP-Activated Protein Kinases (EC 2.7.11.31)
    Language English
    Publishing date 2022-06-06
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2074559-X
    ISSN 1582-4934 ; 1582-4934 ; 1582-1838
    ISSN (online) 1582-4934
    ISSN 1582-4934 ; 1582-1838
    DOI 10.1111/jcmm.17421
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 5752: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
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  8. Article: Do board characteristics impact firm performance?

    Bhatt, R. Rathish / Bhattacharya, Sujoy

    Asia-Pacific journal of management research and innovation : APJMRI Vol. 11, No. 4 , p. 274-287

    an agency and resource dependency theory perspective

    2015  Volume 11, Issue 4, Page(s) 274–287

    Author's details R. Rathish Bhatt, Sujoy Bhattacharya
    Keywords Corporate governance ; firm performance ; board of directors ; agency theory ; resource dependency theory
    Language English
    Publisher Sage
    Publishing place Los Angeles [u.a.]
    Document type Article
    ZDB-ID 2838029-0 ; 2694545-9
    ISSN 2321-0729 ; 2319-510X
    ISSN (online) 2321-0729
    ISSN 2319-510X
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  9. Article: Recent Advances in Retinal Stem Cell Therapy.

    Bhattacharya, Sujoy / Gangaraju, Rajashekhar / Chaum, Edward

    Current molecular biology reports

    2017  Volume 3, Issue 3, Page(s) 172–182

    Abstract: Purpose of review: Progress in stem cell research for blinding diseases over the past decade is now being applied to patients with retinal degenerative diseases and soon perhaps, glaucoma. However, the field still has much to learn about the conversion ... ...

    Abstract Purpose of review: Progress in stem cell research for blinding diseases over the past decade is now being applied to patients with retinal degenerative diseases and soon perhaps, glaucoma. However, the field still has much to learn about the conversion of stem cells into various retinal cell types, and the potential delivery methods that will be required to optimize the clinical efficacy of stem cells delivered into the eye.
    Recent findings: Recent groundbreaking human clinical trials have demonstrated both the opportunities and current limitations of stem cell transplantation for retinal diseases. New progress in developing
    Summary: While promising progress is being made, meticulous clinical trials with cells derived using good manufacturing practice, novel surgical methods, and improved methods to derive all of the neuronal cell types present in the retina will be indispensable for developing stem cell transplantation as a paradigm shift for the treatment of blinding diseases.
    Language English
    Publishing date 2017-07-10
    Publishing country Switzerland
    Document type Journal Article
    ISSN 2198-6428
    ISSN 2198-6428
    DOI 10.1007/s40610-017-0069-3
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  10. Article ; Online: Genomic regulation of senescence and innate immunity signaling in the retinal pigment epithelium.

    Chaum, Edward / Winborn, Christina S / Bhattacharya, Sujoy

    Mammalian genome : official journal of the International Mammalian Genome Society

    2015  Volume 26, Issue 5-6, Page(s) 210–221

    Abstract: The tumor suppressor p53 is a major regulator of genes important for cell cycle arrest, senescence, apoptosis, and innate immunity, and has recently been implicated in retinal aging. In this study we sought to identify the genetic networks that regulate ... ...

    Abstract The tumor suppressor p53 is a major regulator of genes important for cell cycle arrest, senescence, apoptosis, and innate immunity, and has recently been implicated in retinal aging. In this study we sought to identify the genetic networks that regulate p53 function in the retina using quantitative trait locus (QTL) analysis. First we examined age-associated changes in the activation and expression levels of p53; known p53 target proteins and markers of innate immune system activation in primary retinal pigment epithelial (RPE) cells that were harvested from young and aged human donors. We observed increased expression of p53, activated caspase-1, CDKN1A, CDKN2A (p16INK4a), TLR4, and IFNα in aged primary RPE cell lines. We used the Hamilton Eye Institute (HEI) retinal dataset ( www.genenetwork.org ) to identify genomic loci that modulate expression of genes in the p53 pathway in recombinant inbred BXD mouse strains using a QTL systems biology-based approach. We identified a significant trans-QTL on chromosome 1 (region 172-177 Mb) that regulates the expression of Cdkn1a. Many of the genes in this QTL locus are involved in innate immune responses, including Fc receptors, interferon-inducible family genes, and formin 2. Importantly, we found an age-related increase in FCGR3A and FMN2 and a decrease in IFI16 levels in RPE cultures. There is a complex multigenic innate immunity locus that controls expression of genes in the p53 pathway in the RPE, which may play an important role in modulating age-related changes in the retina.
    MeSH term(s) Adult ; Aged, 80 and over ; Aging ; Animals ; Apoptosis ; Caspases/genetics ; Caspases/metabolism ; Cell Line ; Cyclin-Dependent Kinase Inhibitor p16/genetics ; Cyclin-Dependent Kinase Inhibitor p16/metabolism ; Cyclin-Dependent Kinase Inhibitor p21/genetics ; Cyclin-Dependent Kinase Inhibitor p21/metabolism ; Gene Expression Regulation ; Humans ; Immunity, Innate/genetics ; Interferon-alpha/genetics ; Interferon-alpha/metabolism ; Interferon-gamma/genetics ; Interferon-gamma/metabolism ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Mice, Inbred DBA ; Primary Cell Culture ; Quantitative Trait Loci ; Retinal Pigment Epithelium/cytology ; Retinal Pigment Epithelium/metabolism ; Signal Transduction ; Toll-Like Receptor 4/genetics ; Toll-Like Receptor 4/metabolism ; Tumor Suppressor Protein p53/genetics ; Tumor Suppressor Protein p53/metabolism
    Chemical Substances CDKN1A protein, human ; Cdkn1a protein, mouse ; Cdkn2a protein, mouse ; Cyclin-Dependent Kinase Inhibitor p16 ; Cyclin-Dependent Kinase Inhibitor p21 ; Ifna2 protein, mouse ; Interferon-alpha ; TLR4 protein, human ; Tlr4 protein, mouse ; Toll-Like Receptor 4 ; Tumor Suppressor Protein p53 ; Interferon-gamma (82115-62-6) ; Casp11 protein, mouse (EC 3.4.22.-) ; Caspases (EC 3.4.22.-)
    Language English
    Publishing date 2015-06
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 1058547-3
    ISSN 1432-1777 ; 0938-8990
    ISSN (online) 1432-1777
    ISSN 0938-8990
    DOI 10.1007/s00335-015-9568-9
    Database MEDical Literature Analysis and Retrieval System OnLINE

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