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Article ; Online: Endotype Characterization Reveals Mechanistic Differences Across Brain Regions in Sporadic Alzheimer's Disease.

Patel, Ashay O / Caldwell, Andrew B / Ramachandran, Srinivasan / Subramaniam, Shankar

Journal of Alzheimer's disease reports

2023 Volume 7, Issue 1, Page(s) 957–972

Abstract: Background: While Alzheimer's disease (AD) pathology is associated with altered brain structure, it is not clear whether gene expression changes mirror the onset and evolution of pathology in distinct brain regions. Deciphering the mechanisms which ... ...

Abstract	Background: While Alzheimer's disease (AD) pathology is associated with altered brain structure, it is not clear whether gene expression changes mirror the onset and evolution of pathology in distinct brain regions. Deciphering the mechanisms which cause the differential manifestation of the disease across different regions has the potential to help early diagnosis. Objective: We aimed to identify common and unique endotypes and their regulation in tangle-free neurons in sporadic AD (SAD) across six brain regions: entorhinal cortex (EC), hippocampus (HC), medial temporal gyrus (MTG), posterior cingulate (PC), superior frontal gyrus (SFG), and visual cortex (VCX). Methods: To decipher the states of tangle-free neurons across different brain regions in human subjects afflicted with AD, we performed analysis of the neural transcriptome. We explored changes in differential gene expression, functional and transcription factor target enrichment, and co-expression gene module detection analysis to discern disease-state transcriptomic variances and characterize endotypes. Additionally, we compared our results to tangled AD neuron microarray-based study and the Allen Brain Atlas. Results: We identified impaired neuron function in EC, MTG, PC, and VCX resulting from REST activation and reversal of mature neurons to a precursor-like state in EC, MTG, and SFG linked to SOX2 activation. Additionally, decreased neuron function and increased dedifferentiation were linked to the activation of SUZ12. Energetic deficit connected to NRF1 inactivation was found in HC, PC, and VCX. Conclusions: Our findings suggest that SAD manifestation varies in scale and severity in different brain regions. We identify endotypes, such as energetic shortfalls, impaired neuronal function, and dedifferentiation.
Language	English
Publishing date	2023-08-29
Publishing country	Netherlands
Document type	Journal Article
ISSN	2542-4823
ISSN (online)	2542-4823
DOI	10.3233/ADR-220098
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Phytovid19: a compilation of phytochemicals research in coronavirus.

Bhargav, Anasuya / Chaurasia, Pratibha / Kumar, Rohit / Ramachandran, Srinivasan

Structural chemistry

2022 Volume 33, Issue 6, Page(s) 2169–2177

Abstract: The COVID-19 pandemic has immensely impacted global health causing colossal damage. The recent outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has increased the quest to explore phytochemicals as treatment options. We summarize ... ...

Abstract	The COVID-19 pandemic has immensely impacted global health causing colossal damage. The recent outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has increased the quest to explore phytochemicals as treatment options. We summarize phytochemicals with activity against various coronaviruses including SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV). We compiled 705 phytochemical compounds through text mining of 893 PubMed articles. The physicochemical properties including molecular weight, lipophilicity, and the number of hydrogen bond donors and acceptors were determined from the structures of these compounds. A structure-based evaluation of these properties with respect to drug likeness showed that most compounds have a positive score of drug likeness. QSAR analysis showed that 5 descriptors, namely polar surface area, relative polar surface area, number of hydrogen bond donors, solubility, and lipophilicity, are significantly related to IC50. We envisage that these phytochemicals could be further explored for developing new potential therapeutic molecules for COVID-19. Supplementary information: The online version contains supplementary material available at 10.1007/s11224-022-02035-6.
Language	English
Publishing date	2022-08-25
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2018832-8
ISSN	1572-9001 ; 1040-0400
ISSN (online)	1572-9001
ISSN	1040-0400
DOI	10.1007/s11224-022-02035-6
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Article: Anesthetic management of a patient with apical hypertrophic cardiomyopathy, a not so rare variant of hypertrophic cardiomyopathy.

Ramachandran, Srinivasan / Velayudhan, Savitri / Kuppusamy, Sureshkumar / Shanmugam, Balasubramanian

Journal of anaesthesiology, clinical pharmacology

2022 Volume 39, Issue 2, Page(s) 327–328

Language	English
Publishing date	2022-02-21
Publishing country	India
Document type	Journal Article
ZDB-ID	1401760-x
ISSN	0970-9185
ISSN	0970-9185
DOI	10.4103/joacp.joacp_351_21
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Article ; Online: A computational approach to investigate constitutive activation of NF-κB.

Mobeen, Ahmed / Puniya, Bhanwar Lal / Ramachandran, Srinivasan

Proteins

2022 Volume 90, Issue 11, Page(s) 1944–1964

Abstract: Nuclear factor kappa B (NF-κB) signaling is the master regulator of inflammatory pathways; therefore, its regulation has been the subject of investigation since last two decades. Multiple models have been published that describes the dynamics of NF-κB ... ...

Abstract	Nuclear factor kappa B (NF-κB) signaling is the master regulator of inflammatory pathways; therefore, its regulation has been the subject of investigation since last two decades. Multiple models have been published that describes the dynamics of NF-κB activity by stimulated activation and feedback loops. However, there is also paramount evidence of the critical role of posttranslational modifications (PTMs) in the regulation of NF-κB pathway. With the premise that PTMs present alternate routes for activation or repression of the NF-κB pathway, we have developed a model including all PTMs known so far describing the system behavior. We present a pathway network model consisting of 171 proteins forming 315 molecular species and consisting of 482 reactions that describe the NF-κB activity regulation in totality. The overexpression or knockdown of interacting molecular partners that regulate NF-κB transcriptional activity by PTMs is used to infer the dynamics of NF-κB activity and offers qualitative agreement between model predictions and the experimental results heuristically. Finally, we have demonstrated an instance of NF-κB constitutive activation through positive upregulation of cytokines (the stimuli) and IKK complex (NF-κB activator), the characteristic features in several cancer types and metabolic disorders, and its reversal by employing combinatorial activation of PPARG, PIAS3, and P50-homodimer. For the first time, we have presented a NF-κB model that includes transcriptional regulation by PTMs and presented a theoretical strategy for the reversal of NF-κB constitutive activation. The presented model would be important in understanding the NF-κB system, and the described method can be used for other pathways as well.
MeSH term(s)	Cytokines ; I-kappa B Kinase/genetics ; I-kappa B Kinase/metabolism ; NF-kappa B/genetics ; NF-kappa B/metabolism ; PPAR gamma ; Signal Transduction
Chemical Substances	Cytokines ; NF-kappa B ; PPAR gamma ; I-kappa B Kinase (EC 2.7.11.10)
Language	English
Publishing date	2022-06-16
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	806683-8
ISSN	1097-0134 ; 0887-3585
ISSN (online)	1097-0134
ISSN	0887-3585
DOI	10.1002/prot.26388
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Zs.A 2291: Show issues

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Article ; Online: Computer-Aided Tools and Resources for Fungal Pathogens: An Application of Reverse Vaccinology for Mucormycosis.

Bhargav, Anasuya / Fatima, Firdaus / Chaurasia, Pratibha / Seth, Surabhi / Ramachandran, Srinivasan

Monoclonal antibodies in immunodiagnosis and immunotherapy

2022 Volume 41, Issue 5, Page(s) 243–254

Abstract: Increasing fungal infections in immunocompromised hosts are a growing concern for global public health. Along with treatments, preventive measures are required. The emergence of reverse vaccinology has opened avenues for using genomic and proteomic data ... ...

Abstract	Increasing fungal infections in immunocompromised hosts are a growing concern for global public health. Along with treatments, preventive measures are required. The emergence of reverse vaccinology has opened avenues for using genomic and proteomic data from pathogens in the design of vaccines. In this work, we present a comprehensive collection of various computational tools and databases with potential to aid in vaccine development. The ongoing pandemic has directed attention toward the increasing number of mucormycosis infections in COVID-19 patients. As a case study, we developed a computational pipeline for assisting vaccine development for mucormycosis. We obtained 6 proteins from 29,447 sequences from UniProtKB as potential vaccine candidates against mucormycosis, fulfilling multiple criteria. These criteria included potential characteristics, namely adhesin properties, surface or extracellular localization, antigenicity, no similarity to any human proteins, nonallergenicity, stability
MeSH term(s)	Humans ; Vaccinology ; Proteomics ; Mucormycosis ; COVID-19 ; Antibodies, Monoclonal ; Epitopes, T-Lymphocyte/genetics ; Computers ; Computational Biology
Chemical Substances	Antibodies, Monoclonal ; Epitopes, T-Lymphocyte
Language	English
Publishing date	2022-08-08
Publishing country	United States
Document type	Journal Article
ISSN	2167-9436
ISSN (online)	2167-9436
DOI	10.1089/mab.2021.0039
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Article ; Online: MetGENE: gene-centric metabolomics information retrieval tool.

Srinivasan, Sumana / Maurya, Mano R / Ramachandran, Srinivasan / Fahy, Eoin / Subramaniam, Shankar

GigaScience

2023 Volume 12

Abstract: Background: Biomedical research often involves contextual integration of multimodal and multiomic data in search of mechanisms for improved diagnosis, treatment, and monitoring. Researchers need to access information from diverse sources, comprising ... ...

Abstract	Background: Biomedical research often involves contextual integration of multimodal and multiomic data in search of mechanisms for improved diagnosis, treatment, and monitoring. Researchers need to access information from diverse sources, comprising data in various and sometimes incongruent formats. The downstream processing of the data to decipher mechanisms by reconstructing networks and developing quantitative models warrants considerable effort. Results: MetGENE is a knowledge-based, gene-centric data aggregator that hierarchically retrieves information about the gene(s), their related pathway(s), reaction(s), metabolite(s), and metabolomic studies from standard data repositories under one dashboard to enable ease of access through centralization of relevant information. We note that MetGENE focuses only on those genes that encode for proteins directly associated with metabolites. All other gene-metabolite associations are beyond the current scope of MetGENE. Further, the information can be contextualized by filtering by species, anatomy (tissue), and condition (disease or phenotype). Conclusions: MetGENE is an open-source tool that aggregates metabolite information for a given gene(s) and presents them in different computable formats (e.g., JSON) for further integration with other omics studies. MetGENE is available at https://bdcw.org/MetGENE/index.php.
MeSH term(s)	Metabolomics ; Phenotype ; Proteins ; Information Storage and Retrieval
Chemical Substances	Proteins
Language	English
Publishing date	2023-11-20
Publishing country	United States
Document type	Journal Article
ZDB-ID	2708999-X
ISSN	2047-217X ; 2047-217X
ISSN (online)	2047-217X
ISSN	2047-217X
DOI	10.1093/gigascience/giad089
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Article: Comparison of conventional needle holding technique and pen holding method of needle holding for real-time ultrasound-guided internal jugular venous cannulation - A randomised parallel-group study.

Ramachandran, Srinivasan / Velayudhan, Savitri / Ramaraj, Krishna Prabu / Desingh, Dilip Chandar / Kuppusamy, Sureshkumar / Shanmugam, Balasubramanian

Indian journal of anaesthesia

2023 Volume 67, Issue 3, Page(s) 256–261

Abstract: Background and aims: Ultrasound-guided central venous (CV) cannulation is the standard of care for inserting CV catheter in the right internal jugular vein (RIJV). However, mechanical complications can still occur. The primary objective of this study ... ...

Abstract	Background and aims: Ultrasound-guided central venous (CV) cannulation is the standard of care for inserting CV catheter in the right internal jugular vein (RIJV). However, mechanical complications can still occur. The primary objective of this study was to compare the incidence of posterior vessel wall puncture (PVWP) using conventional needle holding technique with pen holding method of needle holding technique for IJV cannulation. Secondary objectives were comparison of other mechanical complications, access time and ease of the procedure. Methods: This prospective, randomised parallel-group study included 90 patients. Patients requiring ultrasound-guided RIJV cannulation under general anaesthesia were randomised into two groups P (n = 45) and C (n = 45). In group C, the RIJV was cannulated using the conventional needle holding technique. In group P, the pen holding method of needle holding technique was used. Incidence of PVWP, complications (arterial puncture, haematoma) number of attempts for successful cannulation, time to insertion of guidewire and performer's ease were compared. The data were analysed using Statistical Package for the Social Sciences (SPSS version 24.0). A Results: In our study, there was no significant difference in incidence of PVWP and complications between the two groups. Number of attempts and time for successful guidewire insertion were comparable. Ease of the procedure was scored a median of 10 in both the groups. Conclusion: There was no significant difference in the incidence of PVWP between the two techniques in this study, necessitating further evaluation of this novel technique.
Language	English
Publishing date	2023-03-16
Publishing country	India
Document type	Journal Article
ZDB-ID	412570-8
ISSN	0019-5049
ISSN	0019-5049
DOI	10.4103/ija.ija_704_22
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Article ; Online: Identification of perturbed pathways rendering susceptibility to tuberculosis in type 2 diabetes mellitus patients using BioNSi simulation of integrated networks of implicated human genes

Rani, Jyoti / Bhargav, Anasuya / Seth, Surabhi / Datta, Malabika / Bajpai, Urmi / Ramachandran, Srinivasan

J Biosci. 2022 Dec., v. 47, no. 4 p.69-69

2022

Abstract: In type 2 diabetes mellitus (T2DM) patients, chronic hyperglycemia and inflammation underlie susceptibility to tuberculosis (TB) and result in poor TB control. Here, an integrative pathway-based approach is used to investigate perturbed pathways in T2DM ... ...

Abstract	In type 2 diabetes mellitus (T2DM) patients, chronic hyperglycemia and inflammation underlie susceptibility to tuberculosis (TB) and result in poor TB control. Here, an integrative pathway-based approach is used to investigate perturbed pathways in T2DM patients that render susceptibility to TB. We obtained 36 genes implicated in type 2 diabetes-associated tuberculosis (T2DMTB) from the literature. Gene expression analysis on T2DM patient data (GSE26168) showed that DEFA1 is differentially expressed at Pₐdⱼ<0.05. The human host TB susceptibility genes TNFRSF10A, MSRA, GPR148, SLC37A3, PXK, PROK2, REV3L, PGM1, HIST3H2A, PLAC4, LETM2, and EMP2 and hsa-miR-146a microRNA were also differentially expressed at Pₐdⱼ<0.05. We included all these genes and added the remaining 28 genes from the T2DMTB set and the remaining differentially expressed genes at Pₐdⱼ<0.05 in STRING and obtained a well-connected network with high confidence score (≥0.7). Further, we extracted the KEGG pathways at FDR<0.05 and retained only the diabetes and TB pathways. The network was simulated with BioNSi using gene expression data. It is evident from BioNSi analysis that the NF-kappa B and Toll-like receptor pathways are commonly perturbed with high ranking in multiple gene expression datasets of type 2 diabetes versus healthy controls. The other pathways, necroptosis pathway and FoxO signalling pathway, appear perturbed with high ranking in different gene expression datasets. These pathways likely underlie susceptibility to TB in T2DM patients.
Keywords	Toll-like receptors ; data collection ; gene expression ; gene expression regulation ; humans ; hyperglycemia ; inflammation ; microRNA ; necroptosis ; noninsulin-dependent diabetes mellitus ; patients ; tuberculosis
Language	English
Dates of publication	2022-12
Size	p. 69.
Publishing place	Springer India
Document type	Article ; Online
ZDB-ID	756157-x
ISSN	0973-7138 ; 0250-5991
ISSN (online)	0973-7138
ISSN	0250-5991
DOI	10.1007/s12038-022-00309-z
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Plant-based release system of negative air ions and its application on particulate matter removal.

Jiang, Shu-Ye / Ma, Ali / Ramachandran, Srinivasan

Indoor air

2020 Volume 31, Issue 2, Page(s) 574–586

Abstract: Particulate matter (PM, especially ... ...

Abstract	Particulate matter (PM, especially PM
MeSH term(s)	Air Pollution, Indoor ; Environmental Monitoring ; Ions ; Particle Size ; Particulate Matter ; Plants
Chemical Substances	Ions ; Particulate Matter
Language	English
Publishing date	2020-12-23
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1081722-0
ISSN	1600-0668 ; 0905-6947
ISSN (online)	1600-0668
ISSN	0905-6947
DOI	10.1111/ina.12729
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Article ; Online: Identification of perturbed pathways rendering susceptibility to tuberculosis in type 2 diabetes mellitus patients using BioNSi simulation of integrated networks of implicated human genes.

Rani, Jyoti / Bhargav, Anasuya / Seth, Surabhi / Datta, Malabika / Bajpai, Urmi / Ramachandran, Srinivasan

Journal of biosciences

2022 Volume 47

Abstract	In type 2 diabetes mellitus (T2DM) patients, chronic hyperglycemia and inflammation underlie susceptibility to tuberculosis (TB) and result in poor TB control. Here, an integrative pathway-based approach is used to investigate perturbed pathways in T2DM patients that render susceptibility to TB. We obtained 36 genes implicated in type 2 diabetes-associated tuberculosis (T2DMTB) from the literature. Gene expression analysis on T2DM patient data (GSE26168) showed that DEFA1 is differentially expressed at P
MeSH term(s)	Humans ; Diabetes Mellitus, Type 2/complications ; Diabetes Mellitus, Type 2/genetics ; Tuberculosis/genetics ; DNA-Directed DNA Polymerase ; DNA-Binding Proteins ; Membrane Glycoproteins
Chemical Substances	REV3L protein, human (EC 2.7.7.7) ; DNA-Directed DNA Polymerase (EC 2.7.7.7) ; DNA-Binding Proteins ; EMP2 protein, human ; Membrane Glycoproteins
Language	English
Publishing date	2022-12-07
Publishing country	India
Document type	Journal Article
ZDB-ID	756157-x
ISSN	0973-7138 ; 0250-5991
ISSN (online)	0973-7138
ISSN	0250-5991
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