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Article ; Online: Transcriptomic Analysis of Glycosylation and Neuroregulatory Pathways in Rodent Models in Response to Psychedelic Molecules.

Oommen, Anup M / Roberts, Katherine J / Joshi, Lokesh / Cunningham, Stephen

International journal of molecular sciences

2023 Volume 24, Issue 2

Abstract: The potential for psychedelic molecules in impacting cognitive flexibility has long been supported and acknowledged across scientific reports. In the current study, an approach leveraging knowledge-based gene-set information analysis has been adopted to ... ...

Abstract	The potential for psychedelic molecules in impacting cognitive flexibility has long been supported and acknowledged across scientific reports. In the current study, an approach leveraging knowledge-based gene-set information analysis has been adopted to explore the potential impact of psychedelic molecules on both glycosylation, (a post-translational modifications (PTM)) and on neuro-regulatory pathways. Though limitations and restrictions rise from the scarcity of publicly available 'omics' data, targeted analysis enabled us to identify a number of key glycogenes (
MeSH term(s)	Hallucinogens/pharmacology ; Glycosylation ; Transcriptome ; Gene Expression Profiling
Chemical Substances	Hallucinogens
Language	English
Publishing date	2023-01-07
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms24021200
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Article ; Online: Transcriptomic Analysis of Respiratory Tissue and Cell Line Models to Examine Glycosylation Machinery during SARS-CoV-2 Infection.

Oommen, Anup / Cunningham, Stephen / Joshi, Lokesh

Viruses

2021 Volume 13, Issue 1

Abstract: Glycosylation, being the most abundant post-translational modification, plays a profound role affecting expression, localization and function of proteins and macromolecules in immune response to infection. Presented are the findings of a transcriptomic ... ...

Abstract	Glycosylation, being the most abundant post-translational modification, plays a profound role affecting expression, localization and function of proteins and macromolecules in immune response to infection. Presented are the findings of a transcriptomic analysis performed using high-throughput functional genomics data from public repository to examine the altered transcription of the human glycosylation machinery in response to SARS-CoV-2 stimulus and infection. In addition to the conventional in silico functional enrichment analysis methods we also present results from the manual analysis of biomedical literature databases to bring about the biological significance of glycans and glycan-binding proteins in modulating the host immune response during SARS-CoV-2 infection. Our analysis revealed key immunomodulatory lectins, proteoglycans and glycan epitopes implicated in exerting both negative and positive downstream inflammatory signaling pathways, in addition to its vital role as adhesion receptors for SARS-CoV-2 pathogen. A hypothetical correlation of the differentially expressed human glycogenes with the altered host inflammatory response and the cytokine storm-generated in response to SARS-CoV-2 pathogen is proposed. These markers can provide novel insights into the diverse roles and functioning of glycosylation pathways modulated by SARS-CoV-2, provide avenues of stratification, treatment, and targeted approaches for COVID-19 immunity and other viral infectious agents.
MeSH term(s)	Biomarkers/metabolism ; COVID-19/genetics ; COVID-19/immunology ; COVID-19/metabolism ; COVID-19/pathology ; Databases, Genetic ; Epitopes/genetics ; Epitopes/metabolism ; Gene Expression Profiling ; Gene Expression Regulation ; Gene Regulatory Networks ; Glycosylation ; Host-Pathogen Interactions ; Humans ; Inflammation ; Lectins/genetics ; Lectins/metabolism ; Polysaccharides/genetics ; Polysaccharides/metabolism ; SARS-CoV-2/physiology ; Signal Transduction
Chemical Substances	Biomarkers ; Epitopes ; Lectins ; Polysaccharides
Language	English
Publishing date	2021-01-08
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v13010082
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Article ; Online: An integrative network analysis framework for identifying molecular functions in complex disorders examining major depressive disorder as a test case.

Oommen, Anup Mammen / Cunningham, Stephen / O'Súilleabháin, Páraic S / Hughes, Brian M / Joshi, Lokesh

Scientific reports

2021 Volume 11, Issue 1, Page(s) 9645

Abstract: In addition to the psychological depressive phenotype, major depressive disorder (MDD) patients are also associated with underlying immune dysregulation that correlates with metabolic syndrome prevalent in depressive patients. A robust integrative ... ...

Abstract	In addition to the psychological depressive phenotype, major depressive disorder (MDD) patients are also associated with underlying immune dysregulation that correlates with metabolic syndrome prevalent in depressive patients. A robust integrative analysis of biological pathways underlying the dysregulated neural connectivity and systemic inflammatory response will provide implications in the development of effective strategies for the diagnosis, management and the alleviation of associated comorbidities. In the current study, focusing on MDD, we explored an integrative network analysis methodology to analyze transcriptomic data combined with the meta-analysis of biomarker data available throughout public databases and published scientific peer-reviewed articles. Detailed gene set enrichment analysis and complex protein-protein, gene regulatory and biochemical pathway analysis has been undertaken to identify the functional significance and potential biomarker utility of differentially regulated genes, proteins and metabolite markers. This integrative analysis method provides insights into the molecular mechanisms along with key glycosylation dysregulation underlying altered neutrophil-platelet activation and dysregulated neuronal survival maintenance and synaptic functioning. Highlighting the significant gap that exists in the current literature, the network analysis framework proposed reduces the impact of data gaps and permits the identification of key molecular signatures underlying complex disorders with multiple etiologies such as within MDD and presents multiple treatment options to address their molecular dysfunction.
MeSH term(s)	Biomarkers ; Brain/metabolism ; Depressive Disorder, Major/etiology ; Depressive Disorder, Major/genetics ; Depressive Disorder, Major/metabolism ; Disease/etiology ; Gene Expression Profiling ; Glycosylation ; Humans ; Metabolomics
Chemical Substances	Biomarkers
Language	English
Publishing date	2021-05-06
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-021-89040-7
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Article ; Online: An integrative network analysis framework for identifying molecular functions in complex disorders examining major depressive disorder as a test case

Anup Mammen Oommen / Stephen Cunningham / Páraic S. O’Súilleabháin / Brian M. Hughes / Lokesh Joshi

Scientific Reports, Vol 11, Iss 1, Pp 1-

2021 Volume 14

Abstract: Abstract In addition to the psychological depressive phenotype, major depressive disorder (MDD) patients are also associated with underlying immune dysregulation that correlates with metabolic syndrome prevalent in depressive patients. A robust ... ...

Abstract	Abstract In addition to the psychological depressive phenotype, major depressive disorder (MDD) patients are also associated with underlying immune dysregulation that correlates with metabolic syndrome prevalent in depressive patients. A robust integrative analysis of biological pathways underlying the dysregulated neural connectivity and systemic inflammatory response will provide implications in the development of effective strategies for the diagnosis, management and the alleviation of associated comorbidities. In the current study, focusing on MDD, we explored an integrative network analysis methodology to analyze transcriptomic data combined with the meta-analysis of biomarker data available throughout public databases and published scientific peer-reviewed articles. Detailed gene set enrichment analysis and complex protein–protein, gene regulatory and biochemical pathway analysis has been undertaken to identify the functional significance and potential biomarker utility of differentially regulated genes, proteins and metabolite markers. This integrative analysis method provides insights into the molecular mechanisms along with key glycosylation dysregulation underlying altered neutrophil-platelet activation and dysregulated neuronal survival maintenance and synaptic functioning. Highlighting the significant gap that exists in the current literature, the network analysis framework proposed reduces the impact of data gaps and permits the identification of key molecular signatures underlying complex disorders with multiple etiologies such as within MDD and presents multiple treatment options to address their molecular dysfunction.
Keywords	Medicine ; R ; Science ; Q
Subject code	306
Language	English
Publishing date	2021-05-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Vulnerability to stress: Personality facet of vulnerability is associated with cardiovascular adaptation to recurring stress.

O'Súilleabháin, Páraic S / Hughes, Brian M / Oommen, Anup M / Joshi, Lokesh / Cunningham, Stephen

International journal of psychophysiology : official journal of the International Organization of Psychophysiology

2019 Volume 144, Page(s) 34–39

Abstract: It is increasingly suggested that personality traits are critical to understanding patterns of cardiovascular stress adaptation. However, studies have focused on higher-order traits with no research having examined underlying facet effects to repeated ... ...

Abstract	It is increasingly suggested that personality traits are critical to understanding patterns of cardiovascular stress adaptation. However, studies have focused on higher-order traits with no research having examined underlying facet effects to repeated stress. The examination of facets provides a more granular examination, which has the potential to identify specific personality components that are relevant within the context of psychophysiological stress adaptation. This study objective was to determine if the underlying facets which encapsulate the dimension of emotional stability, are associated with cardiovascular adaptation to recurring stress. Continuous cardiovascular monitoring and psychometric measures were collated from 79 healthy young male and female adults, across a protocol of recurring active stress tasks. Multiple regression analysis revealed that the facet of vulnerability was associated with systolic and diastolic blood pressure adaptation across the protocol. More specifically, vulnerability was negatively associated with adaptation to recurring stress, such that those highest in vulnerability displayed a sensitization to the recurring stressor. No significant effects emerged for any other facet. Importantly, this research adds to the existing literature examining stress adaptation and has implications for future research on the relevance of examining facet effects. This study is the first to implicate the personality facet of vulnerability which encapsulates an individual's tendency to feel unable to cope with stress and becoming hopeless when faced with emergency situations, in the context of cardiovascular stress adaptation. Taken together, this study suggests that the facet of vulnerability is a critical component to consider in the context of cardiovascular stress adaptation.
MeSH term(s)	Adaptation, Physiological/physiology ; Adolescent ; Adult ; Blood Pressure/physiology ; Disease Susceptibility/physiopathology ; Female ; Heart Rate/physiology ; Humans ; Male ; Neuroticism ; Personality/physiology ; Stress, Psychological/physiopathology ; Young Adult
Language	English
Publishing date	2019-06-20
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	605645-3
ISSN	1872-7697 ; 0167-8760
ISSN (online)	1872-7697
ISSN	0167-8760
DOI	10.1016/j.ijpsycho.2019.06.013
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Article ; Online: Correction: Dysregulation of multiple metabolic networks related to brain transmethylation and polyamine pathways in Alzheimer disease: A targeted metabolomic and transcriptomic study.

Mahajan, Uma V / Varma, Vijay R / Griswold, Michael E / Blackshear, Chad T / An, Yang / Oommen, Anup M / Varma, Sudhir / Troncoso, Juan C / Pletnikova, Olga / O'Brien, Richard / Hohman, Timothy J / Legido-Quigley, Cristina / Thambisetty, Madhav

PLoS medicine

2020 Volume 17, Issue 10, Page(s) e1003439

Abstract: This corrects the article DOI: 10.1371/journal.pmed.1003012.]. ...

Abstract	[This corrects the article DOI: 10.1371/journal.pmed.1003012.].
Language	English
Publishing date	2020-10-21
Publishing country	United States
Document type	Published Erratum
ZDB-ID	2185925-5
ISSN	1549-1676 ; 1549-1277
ISSN (online)	1549-1676
ISSN	1549-1277
DOI	10.1371/journal.pmed.1003439
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Article ; Online: Dimethylformamide interferes with Coomassie dye staining of proteins on blue native gel electrophoresis.

Raghupathy, V / Oommen, Anna / Ramachandran, Anup

Analytical biochemistry

2014 Volume 455, Page(s) 1–2

Abstract: Blue native gel electrophoresis (BN-PAGE) is used extensively for characterization of mitochondrial respiratory complexes and uses the binding of Coomassie brilliant blue G-250 to visualize proteins. Oxidative modification of sulfhydryl groups of such ... ...

Abstract	Blue native gel electrophoresis (BN-PAGE) is used extensively for characterization of mitochondrial respiratory complexes and uses the binding of Coomassie brilliant blue G-250 to visualize proteins. Oxidative modification of sulfhydryl groups of such proteins can be evaluated by labeling with iodoacetamide conjugated to biotin (BIAM) and detected with streptavidin peroxidase on Western blots following BN-PAGE. However, dissolving BIAM in dimethylformamide, a recommended solvent, reduces Coomassie blue G staining to proteins during BN-PAGE. This interference is prevented by dissolving BIAM in dimethyl sulfoxide. Precautions in the use of the dye for protein staining subsequent to BIAM labeling are discussed.
MeSH term(s)	Animals ; Biotin/chemistry ; Dimethylformamide/chemistry ; Electrophoresis, Polyacrylamide Gel ; Iodoacetamide/chemistry ; Mitochondria, Muscle/metabolism ; Mitochondrial Proteins/analysis ; Proteins/analysis ; Proteins/metabolism ; Rats ; Rosaniline Dyes/chemistry ; Rosaniline Dyes/metabolism ; Solvents/chemistry ; Staining and Labeling/methods
Chemical Substances	Mitochondrial Proteins ; Proteins ; Rosaniline Dyes ; Solvents ; Biotin (6SO6U10H04) ; Dimethylformamide (8696NH0Y2X) ; coomassie Brilliant Blue (M1ZRX790SI) ; Iodoacetamide (ZRH8M27S79)
Language	English
Publishing date	2014-06-15
Publishing country	United States
Document type	Journal Article
ZDB-ID	1110-1
ISSN	1096-0309 ; 0003-2697
ISSN (online)	1096-0309
ISSN	0003-2697
DOI	10.1016/j.ab.2014.03.010
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Article ; Online: Investigating correlations in the altered metabolic profiles of obese and diabetic subjects in a South Indian Asian population using an NMR-based metabolomic approach.

Gogna, Navdeep / Krishna, Murahari / Oommen, Anup Mammen / Dorai, Kavita

Molecular bioSystems

2015 Volume 11, Issue 2, Page(s) 595–606

Abstract: It is well known that obesity/high body mass index (BMI) plays a key role in the evolution of insulin resistance and type-2 diabetes mellitus (T2DM). However, the exact mechanism underlying its contribution is still not fully understood. This work ... ...

Abstract	It is well known that obesity/high body mass index (BMI) plays a key role in the evolution of insulin resistance and type-2 diabetes mellitus (T2DM). However, the exact mechanism underlying its contribution is still not fully understood. This work focuses on an NMR-based metabolomic investigation of the serum profiles of diabetic, obese South Indian Asian subjects. (1)H 1D and 2D NMR experiments were performed to profile the altered metabolic patterns of obese diabetic subjects and multivariate statistical methods were used to identify metabolites that contributed significantly to the differences in the samples of four different subject groups: diabetic and non-diabetic with low and high BMIs. Our analysis revealed that the T2DM-high BMI group has higher concentrations of saturated fatty acids, certain amino acids (leucine, isoleucine, lysine, proline, threonine, valine, glutamine, phenylalanine, histidine), lactic acid, 3-hydroxybutyric acid, choline, 3,7-dimethyluric acid, pantothenic acid, myoinositol, sorbitol, glycerol, and glucose, as compared to the non-diabetic-low BMI (control) group. Of these 19 identified significant metabolites, the levels of saturated fatty acids, lactate, valine, isoleucine, and phenylalanine are also higher in obese non-diabetic subjects as compared to control subjects, implying that this set of metabolites could be identified as potential biomarkers for the onset of diabetes in subjects with a high BMI. Our work validates the utility of NMR-based metabolomics in conjunction with multivariate statistical analysis to provide insights into the underlying metabolic pathways that are perturbed in diabetic subjects with a high BMI.
MeSH term(s)	Adult ; Body Mass Index ; Diabetes Mellitus, Type 2/blood ; Diabetes Mellitus, Type 2/metabolism ; Discriminant Analysis ; Female ; Humans ; India ; Least-Squares Analysis ; Magnetic Resonance Spectroscopy/methods ; Male ; Metabolic Networks and Pathways ; Metabolome ; Metabolomics/methods ; Multivariate Analysis ; Obesity/blood ; Obesity/metabolism
Language	English
Publishing date	2015-02
Publishing country	England
Document type	Journal Article
ZDB-ID	2188635-0
ISSN	1742-2051 ; 1742-206X
ISSN (online)	1742-2051
ISSN	1742-206X
DOI	10.1039/c4mb00507d
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Article: Abnormal brain cholesterol homeostasis in Alzheimer's disease-a targeted metabolomic and transcriptomic study.

Varma, Vijay R / Büşra Lüleci, H / Oommen, Anup M / Varma, Sudhir / Blackshear, Chad T / Griswold, Michael E / An, Yang / Roberts, Jackson A / O'Brien, Richard / Pletnikova, Olga / Troncoso, Juan C / Bennett, David A / Çakır, Tunahan / Legido-Quigley, Cristina / Thambisetty, Madhav

NPJ aging and mechanisms of disease

2021 Volume 7, Issue 1, Page(s) 11

Abstract: The role of brain cholesterol metabolism in Alzheimer's disease (AD) remains unclear. Peripheral and brain cholesterol levels are largely independent due to the impermeability of the blood brain barrier (BBB), highlighting the importance of studying the ... ...

Abstract	The role of brain cholesterol metabolism in Alzheimer's disease (AD) remains unclear. Peripheral and brain cholesterol levels are largely independent due to the impermeability of the blood brain barrier (BBB), highlighting the importance of studying the role of brain cholesterol homeostasis in AD. We first tested whether metabolite markers of brain cholesterol biosynthesis and catabolism were altered in AD and associated with AD pathology using linear mixed-effects models in two brain autopsy samples from the Baltimore Longitudinal Study of Aging (BLSA) and the Religious Orders Study (ROS). We next tested whether genetic regulators of brain cholesterol biosynthesis and catabolism were altered in AD using the ANOVA test in publicly available brain tissue transcriptomic datasets. Finally, using regional brain transcriptomic data, we performed genome-scale metabolic network modeling to assess alterations in cholesterol biosynthesis and catabolism reactions in AD. We show that AD is associated with pervasive abnormalities in cholesterol biosynthesis and catabolism. Using transcriptomic data from Parkinson's disease (PD) brain tissue samples, we found that gene expression alterations identified in AD were not observed in PD, suggesting that these changes may be specific to AD. Our results suggest that reduced de novo cholesterol biosynthesis may occur in response to impaired enzymatic cholesterol catabolism and efflux to maintain brain cholesterol levels in AD. This is accompanied by the accumulation of nonenzymatically generated cytotoxic oxysterols. Our results set the stage for experimental studies to address whether abnormalities in cholesterol metabolism are plausible therapeutic targets in AD.
Language	English
Publishing date	2021-06-01
Publishing country	England
Document type	Journal Article
ZDB-ID	2836493-4
ISSN	2056-3973
ISSN	2056-3973
DOI	10.1038/s41514-021-00064-9
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Article ; Online: Blood Metabolite Signature of Metabolic Syndrome Implicates Alterations in Amino Acid Metabolism: Findings from the Baltimore Longitudinal Study of Aging (BLSA) and the Tsuruoka Metabolomics Cohort Study (TMCS).

Roberts, Jackson A / Varma, Vijay R / Huang, Chiung-Wei / An, Yang / Oommen, Anup / Tanaka, Toshiko / Ferrucci, Luigi / Elango, Palchamy / Takebayashi, Toru / Harada, Sei / Iida, Miho / Thambisetty, Madhav

International journal of molecular sciences

2020 Volume 21, Issue 4

Abstract: Rapid lifestyle and dietary changes have contributed to a rise in the global prevalence of metabolic syndrome (MetS), which presents a potential healthcare crisis, owing to its association with an increased burden of multiple cardiovascular and ... ...

Abstract	Rapid lifestyle and dietary changes have contributed to a rise in the global prevalence of metabolic syndrome (MetS), which presents a potential healthcare crisis, owing to its association with an increased burden of multiple cardiovascular and neurological diseases. Prior work has identified the role that genetic, lifestyle, and environmental factors can play in the prevalence of MetS. Metabolomics is an important tool to study alterations in biochemical pathways intrinsic to the pathophysiology of MetS. We undertook a metabolomic study of MetS in serum samples from two ethnically distinct, well-characterized cohorts-the Baltimore Longitudinal Study of Aging (BLSA) from the U.S. and the Tsuruoka Metabolomics Cohort Study (TMCS) from Japan. We used multivariate logistic regression to identify metabolites that were associated with MetS in both cohorts. Among the top 25 most significant (lowest
MeSH term(s)	Aged ; Aged, 80 and over ; Aging/genetics ; Aging/metabolism ; Aging/pathology ; Amino Acids/metabolism ; Female ; Humans ; Longitudinal Studies ; Male ; Metabolic Syndrome/blood ; Metabolic Syndrome/pathology ; Metabolome/genetics ; Metabolomics
Chemical Substances	Amino Acids
Language	English
Publishing date	2020-02-13
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms21041249
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