32 results on '"Sreenivasan U"'
Search Results
2. The impact of mental health legislation on psychiatric services
- Author
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Hoenig, J., Sreenivasan, U., and Leiberman, D.
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Mental health law -- Evaluation ,Health ,Law ,Psychology and mental health - Published
- 1983
3. The impact of mental health legislation on psychiatric services
- Author
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Hoenig, J., Sreenivasan, U., and Leiberman, D.
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Mental health law -- Evaluation ,Health ,Law ,Psychology and mental health - Published
- 1982
4. Book Review: Psychosomatic Disorders in Childhood
- Author
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Sreenivasan, U., primary
- Published
- 1979
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5. Sexual Exploitation of Patients: The Position of the Canadian Psychiatric Association
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Sreenivasan, U., primary
- Published
- 1989
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6. Epilepsy-Aphasia Syndrome in Children: An Unusual Presentation to Psychiatry*
- Author
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White, H., primary and Sreenivasan, U., additional
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- 1987
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7. Book Review: Psychotherapy and Growth. A Family Systems Perspective.
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Sreenivasan, U., primary
- Published
- 1980
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8. Exploitation Sexuelle des Patients
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Sreenivasan, U., primary
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- 1989
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9. Book Review: Experience and Experiment: A Collection of Essays.
- Author
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Sreenivasan, U., primary
- Published
- 1981
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10. Book Review: Children's Learning and Attention Problems
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Sreenivasan, U., primary
- Published
- 1980
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- View/download PDF
11. Book Review: Fingernail Biting: Theory, Research and Treatment
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Sreenivasan, U., primary
- Published
- 1986
- Full Text
- View/download PDF
12. Development of Certified Reference Material Solutions for Phytochemicals in Ginger and Kava.
- Author
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Aijaz SM, Ruan Z, Leija C, Lytwak LA, Waddell S, Kuszak AJ, Wise SA, and Sreenivasan U
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- Catechols analysis, Catechols chemistry, Catechols standards, Chromatography, High Pressure Liquid methods, Dietary Supplements analysis, Dietary Supplements standards, Zingiber officinale chemistry, Kava chemistry, Reference Standards, Phytochemicals analysis, Phytochemicals standards, Phytochemicals chemistry, Fatty Alcohols analysis, Fatty Alcohols chemistry
- Abstract
Background: Dietary supplements derived from botanicals are commonly consumed and investigated in biomedical studies for their potential health benefits. Accurate identification and quantification of key chemical constituents from botanical ingredients is necessary for consistent product preparations and reproducible research results. Manufacturers need quantitative reference materials of the chemical constituents of interest to verify the content of ingredients and products. The rigor and reproducibility of biomedical research is enhanced through thorough characterization of the interventions used in mechanistic, clinical, and safety investigations. Quantitative reference materials enable reliable product quality assessments and reproducible research results., Objective: Solution-based certified reference material (CRM) mixes were developed as calibrants for phytochemicals in ginger and kava. The kava CRM contained yangonin, desmethoxyyangonin, dihydrokavain, DL-kavain, methysticin, dihydromethysticin, flavokawain A, flavokawain B, and flavokawain C. The ginger CRM contained 6-gingerol, 8-gingerol, 10-gingerol, 6-shogaol, 8-shogaol, and 10-shogaol., Methods: Each phytochemical was sourced as an isolated compound and assigned a purity factor by a mass balance approach accounting for residual impurities. The solution standard mixes were formulated by gravimetric addition of each phytochemical incorporating the purity factor and diluting with acetonitrile to the target concentrations of 500 µg/mL for the gingerols and shogaols, 250 µg/mL for the kavalactones, and 25 µg/mL for the flavokawains., Results: The concentration accuracy of each component in the solution mixes was analytically verified by ultra high performance liquid chromatography with ultraviolet detection (UHPLC-UV) assay comparison to an independently prepared calibration solution. Each component in the ginger and kava CRMs were within 5 and 7% of the target concentrations, respectively., Conclusion: Homogeneous kava and ginger phytochemical solution mixes were produced with accurate constituent concentrations and demonstrated good stability over 2 years. These solution mixes were launched as commercially available CRMs., Highlights: These mixes can be used as accurate concentration stock solutions to prepare calibrators and controls for botanical dietary supplement product testing and standardization., (© The Author(s) 2024. Published by Oxford University Press on behalf of AOAC INTERNATIONAL. All rights reserved. For permissions, please email: journals.permissions@oup.com.)
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- 2024
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13. Determination of psilocybin and psilocin content in multiple Psilocybe cubensis mushroom strains using liquid chromatography - tandem mass spectrometry.
- Author
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Goff R, Smith M, Islam S, Sisley S, Ferguson J, Kuzdzal S, Badal S, Kumar AB, Sreenivasan U, and Schug KA
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- Chromatography, Liquid, Tandem Mass Spectrometry, Psilocybin analysis, Psilocybin chemistry, Agaricales chemistry, Psilocybe
- Abstract
A method for clinical potency determination of psilocybin and psilocin in hallucinogenic mushroom species Psilocybe cubensis was developed using liquid chromatography with tandem mass spectrometry (LC-MS/MS). Five strains of dried, intact mushrooms were obtained and analyzed: Blue Meanie, Creeper, B-Plus, Texas Yellow, and Thai Cubensis. An extraction protocol was developed; this included an evaluation of sample milling technique, extraction solvents, and recovery/stability. Reversed phase chromatography on fused-core particle phases was developed for the determination of the two analytes using internal standard calibration with deuterated isotopologues of each analyte. The separation takes less than 5 min. Matrix effects were investigated by comparing signal response of calibration samples in neat solution and several mushroom matrices; no significant matrix effects were observed. The limit of detection for psilocybin was 1.5 ng/mL (1.5 pg on-column; 300 ng/g mushroom) and for psilocin was 0.15 ng/mL (0.15 pg on-column; 30 ng/g mushroom) using a Shimadzu LCMS-8050 triple quadrupole mass spectrometer. Assessment of the accuracy and precision of the method indicated percent error and RSD were <6 % at all concentration levels. Three whole, intact mushrooms from each strain were analyzed individually to obtain average content differences both between strains and between mushrooms of the same strain. From most to least potent, the study found that the average total psilocybin and psilocin concentrations for the Creeper, Blue Meanie, B+, Texas Yellow, and Thai Cubensis strains were 1.36, 1.221, 1.134, 1.103, and 0.879 % (w/w), respectively. A subset of these mushrooms was also tested in a separate non-affiliated laboratory, and the results were comparable between the two laboratories. Results from the secondary laboratory showed improved precision when multiple mushrooms were homogenized together, prior to extraction., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: JF and SK are employees of Shimadzu Scientific Instruments, the manufacturer of the instrumentation used in this study. SB, ABK, and US are employees of Millipore-Sigma. They performed the secondary potency study and provided chemical standards for this research., (Copyright © 2023 Elsevier B.V. All rights reserved.)
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- 2024
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14. Impaired Reorganization of Centrosome Structure Underlies Human Infantile Dilated Cardiomyopathy.
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Chun YW, Miyamoto M, Williams CH, Neitzel LR, Silver-Isenstadt M, Cadar AG, Fuller DT, Fong DC, Liu H, Lease R, Kim S, Katagiri M, Durbin MD, Wang KC, Feaster TK, Sheng CC, Neely MD, Sreenivasan U, Cortes-Gutierrez M, Finn AV, Schot R, Mancini GMS, Ament SA, Ess KC, Bowman AB, Han Z, Bichell DP, Su YR, and Hong CC
- Subjects
- Female, Pregnancy, Animals, Humans, Zebrafish, Stroke Volume, Ventricular Function, Left, Centrosome metabolism, Myocytes, Cardiac, Cardiomyopathy, Dilated genetics
- Abstract
Background: During cardiomyocyte maturation, the centrosome, which functions as a microtubule organizing center in cardiomyocytes, undergoes dramatic structural reorganization where its components reorganize from being localized at the centriole to the nuclear envelope. This developmentally programmed process, referred to as centrosome reduction, has been previously associated with cell cycle exit. However, understanding of how this process influences cardiomyocyte cell biology, and whether its disruption results in human cardiac disease, remains unknown. We studied this phenomenon in an infant with a rare case of infantile dilated cardiomyopathy (iDCM) who presented with left ventricular ejection fraction of 18% and disrupted sarcomere and mitochondria structure., Methods: We performed an analysis beginning with an infant who presented with a rare case of iDCM. We derived induced pluripotent stem cells from the patient to model iDCM in vitro. We performed whole exome sequencing on the patient and his parents for causal gene analysis. CRISPR/Cas9-mediated gene knockout and correction in vitro were used to confirm whole exome sequencing results. Zebrafish and Drosophila models were used for in vivo validation of the causal gene. Matrigel mattress technology and single-cell RNA sequencing were used to characterize iDCM cardiomyocytes further., Results: Whole exome sequencing and CRISPR/Cas9 gene knockout/correction identified RTTN , the gene encoding the centrosomal protein RTTN (rotatin), as the causal gene underlying the patient's condition, representing the first time a centrosome defect has been implicated in a nonsyndromic dilated cardiomyopathy. Genetic knockdowns in zebrafish and Drosophila confirmed an evolutionarily conserved requirement of RTTN for cardiac structure and function. Single-cell RNA sequencing of iDCM cardiomyocytes showed impaired maturation of iDCM cardiomyocytes, which underlie the observed cardiomyocyte structural and functional deficits. We also observed persistent localization of the centrosome at the centriole, contrasting with expected programmed perinuclear reorganization, which led to subsequent global microtubule network defects. In addition, we identified a small molecule that restored centrosome reorganization and improved the structure and contractility of iDCM cardiomyocytes., Conclusions: This study is the first to demonstrate a case of human disease caused by a defect in centrosome reduction. We also uncovered a novel role for RTTN in perinatal cardiac development and identified a potential therapeutic strategy for centrosome-related iDCM. Future study aimed at identifying variants in centrosome components may uncover additional contributors to human cardiac disease.
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- 2023
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15. Absolute Protein Quantification by Mass Spectrometry: Not as Simple as Advertised.
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Shuford CM, Walters JJ, Holland PM, Sreenivasan U, Askari N, Ray K, and Grant RP
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- HEK293 Cells, Humans, Mass Spectrometry, Thyroglobulin analysis
- Abstract
Stable isotopically labeled (SIL) tryptic peptides, cleavable SIL peptides, and a full-length SIL protein were compared for internal calibration (i.e., as internal calibrators) and external calibration (i.e., as internal standards) when quantifying three forms of unlabeled, human thyroglobulin (Tg) by bottom-up protein analysis. All SIL materials and human proteins were standardized by amino acid analysis to ensure traceability of measurements and allow confident assignment of accuracy. The three forms of human Tg quantified were (1) the primary reference material BCR457-a native protein purified from human thyroids, (2) a commercially available form also purified from human thyroids, and (3) a full-length recombinant form expressed and purified from a human embryonic kidney 293 cell-line. Collectively, the results unequivocally demonstrate the lack of commutability of tryptic and cleavable SIL peptides as internal calibrators across various bottom-up assays (i.e., denaturing/digestion conditions). Further, the results demonstrate the potential during external calibration for surrogate protein calibrators (i.e., recombinant proteins) to produce inaccurate concentration assignments of native protein analytes by bottom-up analysis due to variance in digestion efficiency, which is not alleviated by altering denaturation/digestion stringency and indicates why protein calibrators may not be commutable in bottom-up protein assays. These results have implications regarding the veracity of "absolute" protein concentration assignments by bottom-up assays using peptide calibrators, as well as protein calibrators, given that absolute accuracy was not universally observed. Nevertheless, these results support the use of recombinant SIL proteins as internal standards over SIL peptides due to their ability to better mimic the digestion of human-derived proteins and mitigate bias due to digestion-based matrix effects that were observed during external calibration.
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- 2017
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16. TM6SF2 rs58542926 impacts lipid processing in liver and small intestine.
- Author
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O'Hare EA, Yang R, Yerges-Armstrong LM, Sreenivasan U, McFarland R, Leitch CC, Wilson MH, Narina S, Gorden A, Ryan KA, Shuldiner AR, Farber SA, Wood GC, Still CD, Gerhard GS, Robishaw JD, Sztalryd C, and Zaghloul NA
- Subjects
- Animals, Base Sequence, Caco-2 Cells, Enterocytes metabolism, Fatty Liver genetics, Female, Hepatocytes metabolism, Homeostasis, Humans, Intestine, Small ultrastructure, Male, Membrane Proteins metabolism, Mice, Middle Aged, Molecular Sequence Data, Polymorphism, Single Nucleotide, Postprandial Period, Triglycerides biosynthesis, Triglycerides blood, Tunicamycin, Zebrafish, Endoplasmic Reticulum Stress, Intestine, Small metabolism, Lipid Metabolism genetics, Liver metabolism, Membrane Proteins genetics
- Abstract
The transmembrane 6 superfamily member 2 (TM6SF2) loss-of-function variant rs58542926 is a genetic risk factor for nonalcoholic fatty liver disease and progression to fibrosis but is paradoxically associated with lower levels of hepatically derived triglyceride-rich lipoproteins. TM6SF2 is expressed predominantly in liver and small intestine, sites for triglyceride-rich lipoprotein biogenesis and export. In light of this, we hypothesized that TM6SF2 may exhibit analogous effects on both liver and intestine lipid homeostasis. To test this, we genotyped rs58542926 in 983 bariatric surgery patients from the Geisinger Medical Center for Nutrition and Weight Management, Geisinger Health System, in Pennsylvania and from 3,556 study participants enrolled in the Amish Complex Disease Research Program. Although these two cohorts have different metabolic profiles, carriers in both cohorts had improved fasting lipid profiles. Importantly, following a high-fat challenge, carriers in the Amish Complex Disease Research Program cohort exhibited significantly lower postprandial serum triglycerides, suggestive of a role for TM6SF2 in the small intestine. To gain further insight into this putative role, effects of TM6SF2 deficiency were studied in a zebrafish model and in cultured human Caco-2 enterocytes. In both systems TM6SF2 deficiency resulted in defects in small intestine metabolism in response to dietary lipids, including significantly increased lipid accumulation, decreased lipid clearance, and increased endoplasmic reticulum stress., Conclusions: These data strongly support a role of TM6SF2 in the regulation of postprandial lipemia, potentially through a similar function for TM6SF2 in the lipidation and/or export of both hepatically and intestinally derived triglyceride-rich lipoproteins. (Hepatology 2017;65:1526-1542)., (© 2016 by the American Association for the Study of Liver Diseases.)
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- 2017
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17. A Class of Diacylglycerol Acyltransferase 1 Inhibitors Identified by a Combination of Phenotypic High-throughput Screening, Genomics, and Genetics.
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Tschapalda K, Zhang YQ, Liu L, Golovnina K, Schlemper T, Eichmann TO, Lal-Nag M, Sreenivasan U, McLenithan J, Ziegler S, Sztalryd C, Lass A, Auld D, Oliver B, Waldmann H, Li Z, Shen M, Boxer MB, and Beller M
- Subjects
- Animals, COS Cells, Cell Differentiation drug effects, Cell Line, Chlorocebus aethiops, Diacylglycerol O-Acyltransferase antagonists & inhibitors, Diacylglycerol O-Acyltransferase genetics, Drosophila metabolism, Enzyme Inhibitors chemistry, Enzyme Inhibitors pharmacology, Epistasis, Genetic, Fatty Acids metabolism, Female, Humans, Lipid Peroxidation, Male, Mice, Phenotype, Pyrroles chemistry, Pyrroles metabolism, Pyrroles pharmacology, Sequence Analysis, RNA, Small Molecule Libraries chemistry, Small Molecule Libraries metabolism, Small Molecule Libraries pharmacology, Structure-Activity Relationship, Diacylglycerol O-Acyltransferase metabolism, Enzyme Inhibitors metabolism, Genomics
- Abstract
Excess lipid storage is an epidemic problem in human populations. Thus, the identification of small molecules to treat or prevent lipid storage-related metabolic complications is of great interest. Here we screened >320.000 compounds for their ability to prevent a cellular lipid accumulation phenotype. We used fly cells because the multifarious tools available for this organism should facilitate unraveling the mechanism-of-action of active small molecules. Of the several hundred lipid storage inhibitors identified in the primary screen we concentrated on three structurally diverse and potent compound classes active in cells of multiple species (including human) and negligible cytotoxicity. Together with Drosophila in vivo epistasis experiments, RNA-Seq expression profiles suggested that the target of one of the small molecules was diacylglycerol acyltransferase 1 (DGAT1), a key enzyme in the production of triacylglycerols and prominent human drug target. We confirmed this prediction by biochemical and enzymatic activity tests., (Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.)
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- 2016
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18. Development challenges in the preparation of solution-based phytochemical and vitamin certified reference materials.
- Author
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Johnson D, Rettinger M, Tarbox T, Marek B, Pogue S, Dilek I, and Sreenivasan U
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- Camellia sinensis chemistry, Dietary Supplements analysis, Food Storage, Ginkgo biloba chemistry, Humans, Plant Extracts analysis, Plants, Medicinal chemistry, Practice Guidelines as Topic, Quality Control, Reference Standards, United States, United States Food and Drug Administration legislation & jurisprudence, Vitamins analysis, Dietary Supplements standards, Plant Extracts standards, Vitamins standards
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- 2013
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19. Cardiomyocyte-specific perilipin 5 overexpression leads to myocardial steatosis and modest cardiac dysfunction.
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Wang H, Sreenivasan U, Gong DW, O'Connell KA, Dabkowski ER, Hecker PA, Ionica N, Konig M, Mahurkar A, Sun Y, Stanley WC, and Sztalryd C
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- Animals, Blotting, Western, Cardiomyopathies genetics, Cell Line, Cricetinae, DNA, Mitochondrial genetics, Mice, Mice, Transgenic, Microscopy, Electron, Transmission, Molecular Sequence Data, Perilipin-5, Proteins genetics, Reactive Oxygen Species metabolism, Triglycerides metabolism, Cardiomyopathies metabolism, Myocardium metabolism, Myocytes, Cardiac metabolism, Proteins metabolism
- Abstract
Presence of ectopic lipid droplets (LDs) in cardiac muscle is associated to lipotoxicity and tissue dysfunction. However, presence of LDs in heart is also observed in physiological conditions, such as when cellular energy needs and energy production from mitochondria fatty acid β-oxidation are high (fasting). This suggests that development of tissue lipotoxicity and dysfunction is not simply due to the presence of LDs in cardiac muscle but due at least in part to alterations in LD function. To examine the function of cardiac LDs, we obtained transgenic mice with heart-specific perilipin 5 (Plin5) overexpression (MHC-Plin5), a member of the perilipin protein family. Hearts from MHC-Plin5 mice expressed at least 4-fold higher levels of plin5 and exhibited a 3.5-fold increase in triglyceride content versus nontransgenic littermates. Chronic cardiac excess of LDs was found to result in mild heart dysfunction with decreased expression of peroxisome proliferator-activated receptor (PPAR)α target genes, decreased mitochondria function, and left ventricular concentric hypertrophia. Lack of more severe heart function complications may have been prevented by a strong increased expression of oxidative-induced genes via NF-E2-related factor 2 antioxidative pathway. Perilipin 5 regulates the formation and stabilization of cardiac LDs, and it promotes cardiac steatosis without major heart function impairment.
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- 2013
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20. Perilipin 5, a lipid droplet-associated protein, provides physical and metabolic linkage to mitochondria.
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Wang H, Sreenivasan U, Hu H, Saladino A, Polster BM, Lund LM, Gong DW, Stanley WC, and Sztalryd C
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- Amino Acid Sequence, Animals, Carrier Proteins chemistry, Cattle, Cell Line, Humans, Hydrolysis, Lipid Metabolism, Lipids chemistry, Male, Mice, Molecular Sequence Data, Oxidation-Reduction, Palmitates metabolism, Protein Structure, Tertiary, Rats, Triglycerides metabolism, Carrier Proteins metabolism, Mitochondria metabolism
- Abstract
Maintaining cellular lipid homeostasis is crucial to oxidative tissues, and it becomes compromised in obesity. Lipid droplets (LD) play a central role in lipid homeostasis by mediating fatty acid (FA) storage in the form of triglyceride, thereby lowering intracellular levels of lipids that mediate cellular lipotoxicity. LDs and mitochondria have interconnected functions, and anecdotal evidence suggests they physically interact. However, the mechanisms of interaction have not been identified. Perilipins are LD-scaffolding proteins and potential candidates to play a role in their interaction with mitochondria. We examined the contribution of LD perilipin composition to the physical and metabolic interactions between LD and mitochondria using multiple techniques: confocal imaging, electron microscopy (EM), and lipid storage and utilization measurements. Using neonatal cardiomyocytes, reconstituted cell culture models, and rodent heart tissues, we found that perilipin 5 (Plin5) recruits mitochondria to the LD surface through a C-terminal region. Compared with control cells, Plin5-expressing cells show decreased LD hydrolysis, decreased palmitate β-oxidation, and increased palmitate incorporation into triglycerides in basal conditions, whereas in stimulated conditions, LD hydrolysis inhibition is lifted and FA released for β-oxidation. These results suggest that Plin5 regulates oxidative LD hydrolysis and controls local FA flux to protect mitochondria against excessive exposure to FA during physiological stress.
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- 2011
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21. Unique regulation of adipose triglyceride lipase (ATGL) by perilipin 5, a lipid droplet-associated protein.
- Author
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Wang H, Bell M, Sreenivasan U, Sreenevasan U, Hu H, Liu J, Dalen K, Londos C, Yamaguchi T, Rizzo MA, Coleman R, Gong D, Brasaemle D, and Sztalryd C
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- 1-Acylglycerol-3-Phosphate O-Acyltransferase genetics, 1-Acylglycerol-3-Phosphate O-Acyltransferase metabolism, 3T3-L1 Cells, Adipocytes cytology, Animals, CHO Cells, Carrier Proteins, Cricetinae, Cricetulus, Cyclic AMP-Dependent Protein Kinases genetics, Cyclic AMP-Dependent Protein Kinases metabolism, Enzyme Activation physiology, Humans, Lipase genetics, Male, Mice, Oxidative Stress physiology, Perilipin-1, Phosphoproteins genetics, Adipocytes metabolism, Energy Metabolism physiology, Lipase metabolism, Lipolysis physiology, Phosphoproteins metabolism
- Abstract
Lipolysis is a critical metabolic pathway contributing to energy homeostasis through degradation of triacylglycerides stored in lipid droplets (LDs), releasing fatty acids. Neutral lipid lipases act at the oil/water interface. In mammalian cells, LD surfaces are coated with one or more members of the perilipin protein family, which serve important functions in regulating lipolysis. We investigated mechanisms by which three perilipin proteins control lipolysis by adipocyte triglyceride lipase (ATGL), a key lipase in adipocytes and non-adipose cells. Using a cell culture model, we examined interactions of ATGL and its co-lipase CGI-58 with perilipin 1 (perilipin A), perilipin 2 (adipose differentiation-related protein), and perilipin 5 (LSDP5) using multiple techniques as follows: anisotropy Forster resonance energy transfer, co-immunoprecipitation, [(32)P]orthophosphate radiolabeling, and measurement of lipolysis. The results show that ATGL interacts with CGI-58 and perilipin 5; the latter is selectively expressed in oxidative tissues. Both proteins independently recruited ATGL to the LD surface, but with opposite effects; interaction of ATGL with CGI-58 increased lipolysis, whereas interaction of ATGL with perilipin 5 decreased lipolysis. In contrast, neither perilipin 1 nor 2 interacted directly with ATGL. Activation of protein kinase A (PKA) increased [(32)P]orthophosphate incorporation into perilipin 5 by 2-fold, whereas neither ATGL nor CGI-58 was labeled under the incubation conditions. Cells expressing both ectopic perilipin 5 and ATGL showed a 3-fold increase in lipolysis following activation of PKA. Our studies establish perilipin 5 as a novel ATGL partner and provide evidence that the protein composition of perilipins at the LD surface regulates lipolytic activity of ATGL.
- Published
- 2011
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22. Resistance to the antilipolytic effect of insulin in adipocytes of African-American compared to Caucasian postmenopausal women.
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Fried SK, Tittelbach T, Blumenthal J, Sreenivasan U, Robey L, Yi J, Khan S, Hollender C, Ryan AS, and Goldberg AP
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- Abdominal Fat drug effects, Abdominal Fat metabolism, Adipocytes drug effects, Adult, Aged, Buttocks, Fatty Acids, Nonesterified metabolism, Female, Humans, Insulin pharmacology, Isoproterenol pharmacology, Middle Aged, Phenylisopropyladenosine pharmacology, Adipocytes metabolism, Black or African American, Insulin metabolism, Insulin Resistance ethnology, Lipolysis drug effects, Postmenopause metabolism, White People
- Abstract
High fatty acid (FA) flux is associated with systemic insulin resistance, and African-American (AA) women tend to be more insulin resistant. We assessed possible depot and race difference in the antilipolytic effect of insulin in adipocytes isolated from abdominal (Abd) and gluteal (Glt) subcutaneous (sc) adipose tissue of overweight, postmenopausal AA and Caucasian (C) women. Percent body fat, fasting insulin, visceral adiposity, and adipocyte size was higher in AA women. Disinhibited lipolysis (presence of adenosine deaminase) per unit adipocyte surface area was similar in Abd and Glt and in AA and C. However, rates of 'basal' [submaximal phenylisopropyl adenosine (PIA)-suppressed] and insulin-suppressed lipolysis were higher in Abd of AA compared with C women even after adjustment for percent fat and visceral fat area. The race difference in rates of PIA- and insulin-suppressed lipolysis in AA were correlated with their hyperinsulinemia, but AA race, independent of fasting insulin, was associated with lower responsiveness (percent suppression) to submaximal insulin concentrations, although sensitivity (ED50) was not affected. Overall, these data are consistent with the hypothesis that decreased responsiveness of Abd adipocytes to antilipolytic effectors may contribute to higher FA availability and thereby to racial differences in insulin resistance.
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- 2010
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23. Simulated dipeptide recognition by vancomycin.
- Author
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Li D, Sreenivasan U, Juranic N, Macura S, Puga FJ 2nd, Frohnert PM, and Axelsen PH
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- Anti-Bacterial Agents chemistry, Computer-Aided Design, Ligands, Magnetic Resonance Spectroscopy, Models, Molecular, Peptides metabolism, Protein Binding, Protein Conformation, Structure-Activity Relationship, Vancomycin chemistry, Anti-Bacterial Agents metabolism, Drug Design, Vancomycin metabolism
- Abstract
The antimicrobial activity of vancomycin and related glycopeptide antibiotics is due to stereospecific recognition of polypeptide components in bacterial cell walls. To better understand how these antibiotics recognize polypeptide determinants, we have developed dynamic models of the complexes formed by the vancomycin aglycon and two different dipeptide ligands, Ac-D-ala-D-ala and Ac-D-ala-gly. Molecular dynamics simulations of the two complexes, initially conditioned with distance constraints derived from two-dimensional nuclear magnetic resonance (NMR) studies, are conformationally stable and propagate in a manner consistent with the NMR-derived constraints after the constraints are removed. Free energy calculations accurately predict the relative binding affinity of these two complexes and help validate the simulation models for detailed structural analysis. Although the two ligands adopt similar conformations when bound to the antibiotic, there are clear differences in the configuration of intermolecular hydrogen bonds, the overall shape of the antibiotic, and other structural features of the two complexes. This analysis illustrates how complex structural and dynamic factors interrelate and contribute to differences in binding affinity.
- Published
- 1997
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24. Synthesis and dopamine receptor modulating activity of lactam conformationally constrained analogues of Pro-Leu-Gly-NH2.
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Sreenivasan U, Mishra RK, and Johnson RL
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- Amino Acid Sequence, Animals, Cattle, Dopamine Agents metabolism, Dopamine Agents pharmacology, Lactams metabolism, Lactams pharmacology, Molecular Sequence Data, Oligopeptides chemistry, Oligopeptides metabolism, Oligopeptides pharmacology, Receptors, Dopamine metabolism, Structure-Activity Relationship, Tetrahydronaphthalenes metabolism, Dopamine Agents chemical synthesis, Lactams chemical synthesis, Oligopeptides chemical synthesis
- Abstract
A series of analogues of the potent analogue of Pro-Leu-Gly-NH2 (PLG), 2-oxo-3(R)-[(2(S)-pyrrolidinylcarbonyl)amino]-1-pyrrolidineacet amide (2) were synthesized in which the (R)-gamma-lactam residue of 2 was replaced with a (R)-beta-lactam, (R)-aminosuccinimide, (R)-cycloseryl, (R)-delta-lactam, (R)-epsilon-lactam, or (S)-epsilon-lactam residue to give analogues 3-8, respectively. These substitutions were made so as to vary the psi 2 torsion angle. The analogues were tested for their ability to enhance the binding of the dopamine receptor agonist ADTN to the dopamine receptor. Analogues 3-6 and 8 exhibited dose-response curves that were bell-shaped in nature with the maximum effect occurring at a concentration of 1 microM. Analogue 7 was inactive. Analogues 3 and 4 were found to be as effective as PLG, while analogues 5, 6, and 8 appeared to be more effective than PLG in terms of enhancing the binding of ADTN to dopamine receptors. The activity of analogues 3-6 and 8 with their psi 2 angles in the vicinity of that observed in a type II beta-turn is consistent with the hypothesis that this type of turn is the bioactive conformation of PLG.
- Published
- 1993
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25. Buried water in homologous serine proteases.
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Sreenivasan U and Axelsen PH
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- Animals, Chymases, Chymotrypsin chemistry, Chymotrypsinogen chemistry, Crystallization, Histidine chemistry, Humans, Hydrogen Bonding, Kallikreins chemistry, Molecular Structure, Pancreatic Elastase chemistry, Peptidyl-Dipeptidase A chemistry, Rats, Thrombin chemistry, Trypsin chemistry, Trypsinogen chemistry, X-Ray Diffraction, Serine Endopeptidases chemistry, Water chemistry
- Abstract
Buried water molecules in the structurally homologous family of eukaryotic serine proteases were examined to determine whether buried waters and their protein environments are conserved in these proteins. We found 16 equivalent water sites conserved in trypsin/ogen, chymotrypsin/ogen, elastase, kallikrein, thrombin, rat tonin and rat mast cell protease, and 5 additional water sites in enzymes which share the primary specificity of trypsin. Based on an alignment of 30 serine protease sequences, it appears that the protein environments of these 21 conserved buried waters are highly conserved. The protein environments of buried waters are comprised primarily of atoms from highly conserved residues or main chain atoms from nonconserved residues. In one instance, the protein environment of a water is conserved even in the presence of an unlikely Pro/Ala substitution. We also note 3 instances in which a histidine side chain substitutes for water, suggesting that the structural role of water at these sites is satisfied by the presence of an alternative hydrogen bonding partner. Buried waters appear to be integral structural components of these proteins and should be incorporated into protein structures predicted on the basis of sequence homology to this family, including the catalytic domains of coagulation proteases.
- Published
- 1992
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26. Encopresis in Hirschsprung's disease: a report on two cases.
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Sreenivasan U and Manocha SN
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- Child, Colostomy, Humans, Male, Token Economy, Behavior Therapy methods, Encopresis rehabilitation, Megacolon surgery, Postoperative Complications rehabilitation
- Abstract
Two patients with persistent severe encopresis after surgery for Hirschsprung's disease were treated with a token economy type of behavior modification therapy. After eight weeks there was very marked improvement, which persisted after discharge home without relapse after four and eight months respectively.
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- 1978
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27. Anorexia nervosa associated with energy-wasting disorders.
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Sreenivasan U
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- Adolescent, Anorexia Nervosa psychology, Body Weight, Child, Female, Humans, Anorexia Nervosa complications, Colitis, Ulcerative complications, Diabetes Complications
- Abstract
Some patients with anorexia nervosa and energy-wasting disorders have been found to be able to use their illness to lose weight. This paper presents two patients with diabetes mellitus and one with ulcerative colitis in whom the illness was complicated by anorexia nervosa.
- Published
- 1984
28. Effeminate boys in a child psychiatric clinic: prevalence and associated factors.
- Author
-
Sreenivasan U
- Subjects
- Age Factors, Child, Family, Humans, Male, Mental Disorders complications, Socioeconomic Factors, Child Behavior Disorders complications, Gender Identity, Identification, Psychological
- Published
- 1985
- Full Text
- View/download PDF
29. Treatment of severe dog phobia in childhood by flooding: a case report.
- Author
-
Sreenivasan U, Manocha SN, and Jain VK
- Subjects
- Animals, Child, Desensitization, Immunologic, Female, Humans, Phobic Disorders genetics, Residential Treatment, Behavior Therapy, Dogs, Implosive Therapy, Phobic Disorders rehabilitation
- Published
- 1979
- Full Text
- View/download PDF
30. Anorexia nervosa in boys.
- Author
-
Sreenivasan U
- Subjects
- Adolescent, Child, Humans, Male, Obsessive Behavior psychology, Parent-Child Relations, Psychotherapy, Sex Factors, Anorexia Nervosa psychology
- Abstract
The literature on primary anorexia nervosa in the male is reviewed and the case histories of 3 new patients are reported. Most surveys comment on the rarity of the syndrome in the male, with the sex ratio in the range of 1 in 10 to 1 in 20. The patients reported here had certain features in common. All the mothers and fathers were overweight, but obesity was marked only in the fathers, who also showed moderate to severe degrees of alcoholism. The mothers were oversensitive, insecure individuals, and the marriages suffered in proportion to the severity of the husband's alcoholism. Preoccupation with food was observed on home visits. There was overt mutual hostility between each father and anorexic son; the boys showed pronounced obsessional traits in their personalities. Dieting in order to ameliorate real or feared obesity was a first step in the development of the syndrome in each boy. In the past 3 years an equal number of boys and girls (new patients) have been referred for treatment in the psychiatric unit. Speculative reasons for this are discussed.
- Published
- 1978
- Full Text
- View/download PDF
31. Mental hospital admissions in Mysore State, India.
- Author
-
HOENIG J and SREENIVASAN U
- Subjects
- Humans, India, Hospitalization, Hospitals, Hospitals, Psychiatric, Mental Disorders statistics & numerical data
- Published
- 1959
- Full Text
- View/download PDF
32. Caste and mental hospital admissions in Mysore State, India.
- Author
-
SREENIVASAN U and HOENIG J
- Subjects
- Humans, India, Hospitals, Psychiatric statistics & numerical data, Social Class
- Published
- 1960
- Full Text
- View/download PDF
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