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Article ; Online: Expression and Purification of Inflammasome Sensor NOD-Like Receptor Protein-1 Using the Baculovirus-Insect Cell Expression System.

Sivaraman, Hariharan / Wong, Wilson

Methods in molecular biology (Clifton, N.J.)

2023 Volume 2691, Page(s) 199–206

Abstract: Inflammasomes are innate immune sensing and signaling complexes critical for defense against pathogens and response to cellular stresses. A core component of inflammasomes is the sensor protein, which, upon sensing pathogen- or danger-associated ... ...

Abstract	Inflammasomes are innate immune sensing and signaling complexes critical for defense against pathogens and response to cellular stresses. A core component of inflammasomes is the sensor protein, which, upon sensing pathogen- or danger-associated molecular patterns (PAMPs or DAMPs), converts from inactive to active signaling platform for initiation of inflammatory signaling. A reliable source for the production and purification of recombinant inflammasome sensors is therefore invaluable for biochemical and structural characterizations, as well as drug screening for the development of therapeutics. Here, we describe an expression and purification protocol using the baculovirus-insect cell expression system to generate recombinant NLRP1, an important member of the NOD-like receptor (NLR) family of inflammasome sensors.
MeSH term(s)	Inflammasomes/metabolism ; NLR Proteins/genetics ; Signal Transduction ; Baculoviridae/genetics ; Baculoviridae/metabolism ; NLR Family, Pyrin Domain-Containing 3 Protein
Chemical Substances	Inflammasomes ; NLR Proteins ; NLR Family, Pyrin Domain-Containing 3 Protein
Language	English
Publishing date	2023-06-22
Publishing country	United States
Document type	Journal Article
ISSN	1940-6029
ISSN (online)	1940-6029
DOI	10.1007/978-1-0716-3331-1_15
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Cognition and Quality of Life of People with Spinal Cord Injury.

Houldsworth, Ceri / Nair, Krishnan Padmakumari Sivaraman / Hariharan, Ram Pankajam

Progress in rehabilitation medicine

2023 Volume 8, Page(s) 20230001

Abstract: Objectives: The aim of this study was to assess the cognitive abilities of people with spinal cord injury (SCI) using the Edinburgh Cognitive and Behavior Amyotrophic Lateral Sclerosis Screen (ECAS), a tool designed for testing cognition in individuals ... ...

Abstract	Objectives: The aim of this study was to assess the cognitive abilities of people with spinal cord injury (SCI) using the Edinburgh Cognitive and Behavior Amyotrophic Lateral Sclerosis Screen (ECAS), a tool designed for testing cognition in individuals with limited hand motor function. The impact of cognitive dysfunction on quality of life was also assessed. Methods: Forty-one patients with SCI were assessed using ECAS, the brief version of the World Health Organisation Quality of Life questionnaire (WHOQOL-BREF), and the Spinal Cord Independence Measure. Results: Overall, 28 of the 41 participants scored below the cut-off threshold for normal population in ECAS. The domains affected were language, 63%; memory, 51%; executive function, 44%; verbal fluency, 44%; and visuospatial skills, 24%. On multiple regression analysis, the ECAS total score moderately strongly explained the variance in the WHOQOL-BREF psychological (β = 0.428, t = 2.958, P = 0.005) and environmental (β = 0.411, t = 2.819, P = 0.008) domains. ECAS memory scores independently influenced WHOQOL-BREF physical (β = 0.398, t = 2.67, P = 0.011) and environmental (β = 0.37, t = 2.697, P = 0.010) domains. WHOQOL-BREF psychological scores were significantly influenced by ECAS executive scores (β = 0.415, t = 2.85, P = 0.007), whereas the social domain was not significantly influenced by ECAS scores. Conclusions: It was feasible to use ECAS in individuals with SCI. Cognitive ability influenced the quality of life of people with SCI.
Language	English
Publishing date	2023-01-14
Publishing country	Japan
Document type	Journal Article
ISSN	2432-1354
ISSN (online)	2432-1354
DOI	10.2490/prm.20230001
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Article ; Online: Coronavirus Disease 2019 Pandemic as Catalyst for Telemedicine Adoption: A Single-Center Experience.

Malhotra, Kunal / Sivaraman, Aparna / Regunath, Hariharan

Telemedicine reports

2020 Volume 1, Issue 1, Page(s) 16–21

Abstract: Background: ...

Abstract	Background:
Language	English
Publishing date	2020-11-18
Publishing country	United States
Document type	Journal Article
ISSN	2692-4366
ISSN (online)	2692-4366
DOI	10.1089/tmr.2020.0003
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Book ; Online: ML-based Modeling to Predict I/O Performance on Different Storage Sub-systems

Xu, Yiheng / Sivaraman, Pranav / Devarajan, Hariharan / Mohror, Kathryn / Bhatele, Abhinav

2023

Abstract: Parallel applications can spend a significant amount of time performing I/O on large-scale supercomputers. Fast near-compute storage accelerators called burst buffers can reduce the time a processor spends performing I/O and mitigate I/O bottlenecks. ... ...

Abstract	Parallel applications can spend a significant amount of time performing I/O on large-scale supercomputers. Fast near-compute storage accelerators called burst buffers can reduce the time a processor spends performing I/O and mitigate I/O bottlenecks. However, determining if a given application could be accelerated using burst buffers is not straightforward even for storage experts. The relationship between an application's I/O characteristics (such as I/O volume, processes involved, etc.) and the best storage sub-system for it can be complicated. As a result, adapting parallel applications to use burst buffers efficiently is a trial-and-error process. In this work, we present a Python-based tool called PrismIO that enables programmatic analysis of I/O traces. Using PrismIO, we identify bottlenecks on burst buffers and parallel file systems and explain why certain I/O patterns perform poorly. Further, we use machine learning to model the relationship between I/O characteristics and burst buffer selections. We run IOR (an I/O benchmark) with various I/O characteristics on different storage systems and collect performance data. We use the data as the input for training the model. Our model can predict if a file of an application should be placed on BBs for unseen IOR scenarios with an accuracy of 94.47% and for four real applications with an accuracy of 95.86%.
Keywords	Computer Science - Distributed ; Parallel ; and Cluster Computing
Subject code	004
Publishing date	2023-12-11
Publishing country	us
Document type	Book ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Structural Basis of SARS-CoV-2 and SARS-CoV Antibody Interactions.

Gavor, Edem / Choong, Yeu Khai / Er, Shi Yin / Sivaraman, Hariharan / Sivaraman, J

Trends in immunology

2020 Volume 41, Issue 11, Page(s) 1006–1022

Abstract: The 2019 coronavirus pandemic remains a major public health concern. Neutralizing antibodies (nAbs) represent a cutting-edge antiviral strategy. We focus here on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and SARS-CoV, and discuss ... ...

Abstract	The 2019 coronavirus pandemic remains a major public health concern. Neutralizing antibodies (nAbs) represent a cutting-edge antiviral strategy. We focus here on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and SARS-CoV, and discuss current progress in antibody research against rampant SARS-CoV-2 infections. We provide a perspective on the mechanisms of SARS-CoV-2-derived nAbs, comparing these with existing SARS-CoV-derived antibodies. We offer insight into how these antibodies cross-react and cross-neutralize by analyzing available structures of spike (S) glycoprotein-antibody complexes. We also propose ways of adopting antibody-based strategies - such as cocktail antibody therapeutics against SARS-CoV-2 - to overcome the possible resistance of currently identified mutants and mitigate possible antibody-dependent enhancement (ADE) pathologies. This review provides a platform for the progression of antibody and vaccine design against SARS-CoV-2, and possibly against future coronavirus pandemics.
MeSH term(s)	Animals ; Antibodies, Monoclonal/immunology ; Antibodies, Monoclonal/metabolism ; Antibodies, Neutralizing/immunology ; Antibodies, Neutralizing/metabolism ; Antibodies, Viral/immunology ; Antibodies, Viral/metabolism ; Betacoronavirus/immunology ; Betacoronavirus/metabolism ; Betacoronavirus/physiology ; COVID-19 ; COVID-19 Vaccines ; Coronavirus Infections/immunology ; Coronavirus Infections/prevention & control ; Coronavirus Infections/virology ; Humans ; Pandemics/prevention & control ; Pneumonia, Viral/immunology ; Pneumonia, Viral/prevention & control ; Pneumonia, Viral/virology ; Protein Binding ; Severe acute respiratory syndrome-related coronavirus/immunology ; Severe acute respiratory syndrome-related coronavirus/metabolism ; SARS-CoV-2 ; Viral Vaccines/administration & dosage ; Viral Vaccines/immunology
Chemical Substances	Antibodies, Monoclonal ; Antibodies, Neutralizing ; Antibodies, Viral ; COVID-19 Vaccines ; Viral Vaccines
Keywords	covid19
Language	English
Publishing date	2020-09-17
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2036831-8
ISSN	1471-4981 ; 1471-4906
ISSN (online)	1471-4981
ISSN	1471-4906
DOI	10.1016/j.it.2020.09.004
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Article ; Online: Structural Basis of SARS-CoV-2- and SARS-CoV-Receptor Binding and Small-Molecule Blockers as Potential Therapeutics.

Sivaraman, Hariharan / Er, Shi Yin / Choong, Yeu Khai / Gavor, Edem / Sivaraman, J

Annual review of pharmacology and toxicology

2020 Volume 61, Page(s) 465–493

Abstract: Over the past two decades, deadly coronaviruses, with the most recent being the severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) 2019 pandemic, have majorly challenged public health. The path for virus invasion into humans and other ... ...

Abstract	Over the past two decades, deadly coronaviruses, with the most recent being the severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) 2019 pandemic, have majorly challenged public health. The path for virus invasion into humans and other hosts is mediated by host-pathogen interactions, specifically virus-receptor binding. An in-depth understanding of the virus-receptor binding mechanism is a prerequisite for the discovery of vaccines, antibodies, and small-molecule inhibitors that can interrupt this interaction and prevent or cure infection. In this review, we discuss the viral entry mechanism, the known structural aspects of virus-receptor interactions (SARS-CoV-2 S/humanACE2, SARS-CoV S/humanACE2, and MERS-CoV S/humanDPP4), the key protein domains and amino acid residues involved in binding, and the small-molecule inhibitors and other drugs that have (as of June 2020) exhibited therapeutic potential. Specifically, we review the potential clinical utility of two transmembrane serine protease 2 (TMPRSS2)-targeting protease inhibitors, nafamostat mesylate and camostat mesylate, as well as two novel potent fusion inhibitors and the repurposed Ebola drug, remdesivir, which is specific to RNA-dependent RNA polymerase, against human coronaviruses, including SARS-CoV-2.
MeSH term(s)	Angiotensin-Converting Enzyme 2/drug effects ; Antiviral Agents/pharmacology ; Antiviral Agents/therapeutic use ; COVID-19/drug therapy ; Humans ; Protease Inhibitors/therapeutic use ; Receptors, Virus/drug effects ; Small Molecule Libraries
Chemical Substances	Antiviral Agents ; Protease Inhibitors ; Receptors, Virus ; Small Molecule Libraries ; ACE2 protein, human (EC 3.4.17.23) ; Angiotensin-Converting Enzyme 2 (EC 3.4.17.23)
Keywords	covid19
Language	English
Publishing date	2020-08-21
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	196587-6
ISSN	1545-4304 ; 0362-1642
ISSN (online)	1545-4304
ISSN	0362-1642
DOI	10.1146/annurev-pharmtox-061220-093932
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Article ; Online: Structural Basis of SARS-CoV-2 and SARS-CoV Antibody Interactions

Gavor, Edem / Choong, Yeu Khai / Er, Shi Yin / Sivaraman, Hariharan / Sivaraman, J.

Trends in Immunology

2020 Volume 41, Issue 11, Page(s) 1006–1022

Keywords	Immunology ; Immunology and Allergy ; covid19
Language	English
Publisher	Elsevier BV
Publishing country	us
Document type	Article ; Online
ZDB-ID	2036831-8
ISSN	1471-4981 ; 1471-4906
ISSN (online)	1471-4981
ISSN	1471-4906
DOI	10.1016/j.it.2020.09.004
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Article ; Online: Structure of

Gavor, Edem / Choong, Yeu Khai / Tulsian, Nikhil Kumar / Nayak, Digant / Idris, Fakhriedzwan / Sivaraman, Hariharan / Ting, Donald Heng Rong / Sylvie, Alonso / Mok, Yu Keung / Kini, R Manjunatha / Sivaraman, J

Life science alliance

2021 Volume 5, Issue 1

Abstract: Metallocarboxypeptidases play critical roles in the development of mosquitoes and influence pathogen/parasite infection of the mosquito midgut. Here, we report the crystal structure ... ...

Abstract	Metallocarboxypeptidases play critical roles in the development of mosquitoes and influence pathogen/parasite infection of the mosquito midgut. Here, we report the crystal structure of
MeSH term(s)	Aedes/enzymology ; Aedes/virology ; Amino Acid Sequence ; Animals ; Binding Sites ; Carboxypeptidase B/chemistry ; Carboxypeptidase B/genetics ; Carboxypeptidase B/metabolism ; Catalytic Domain ; Dengue/prevention & control ; Dengue/transmission ; Dengue/virology ; Dengue Virus/physiology ; Host Microbial Interactions ; Infection Control ; Models, Biological ; Models, Molecular ; Protein Binding ; Protein Conformation ; Protein Interaction Domains and Motifs ; Sequence Analysis, DNA ; Structure-Activity Relationship ; Substrate Specificity ; Viral Envelope Proteins/chemistry ; Viral Envelope Proteins/metabolism
Chemical Substances	Viral Envelope Proteins ; Carboxypeptidase B (EC 3.4.17.2)
Language	English
Publishing date	2021-11-08
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2575-1077
ISSN (online)	2575-1077
DOI	10.26508/lsa.202101211
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Article: Structural Basis of SARS-CoV-2 and SARS-CoV Antibody Interactions

Gavor, Edem / Choong, Yeu Khai / Er, Shi Yin / Sivaraman, Hariharan / Sivaraman, J

Trends Immunol

Abstract	The 2019 coronavirus pandemic remains a major public health concern. Neutralizing antibodies (nAbs) represent a cutting-edge antiviral strategy. We focus here on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and SARS-CoV, and discuss current progress in antibody research against rampant SARS-CoV-2 infections. We provide a perspective on the mechanisms of SARS-CoV-2-derived nAbs, comparing these with existing SARS-CoV-derived antibodies. We offer insight into how these antibodies cross-react and cross-neutralize by analyzing available structures of spike (S) glycoprotein-antibody complexes. We also propose ways of adopting antibody-based strategies - such as cocktail antibody therapeutics against SARS-CoV-2 - to overcome the possible resistance of currently identified mutants and mitigate possible antibody-dependent enhancement (ADE) pathologies. This review provides a platform for the progression of antibody and vaccine design against SARS-CoV-2, and possibly against future coronavirus pandemics.
Keywords	covid19
Publisher	WHO
Document type	Article
Note	WHO #Covidence: #844007
Database	COVID19

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Article ; Online: Halochromic Isoquinoline with Mechanochromic Triphenylamine: Smart Fluorescent Material for Rewritable and Self-Erasable Fluorescent Platform.

Hariharan, Palamarneri Sivaraman / Mothi, Ebrahim M / Moon, Dohyun / Anthony, Savarimuthu Philip

ACS applied materials & interfaces

2016 Volume 8, Issue 48, Page(s) 33034–33042

Abstract: Halochromic isoquinoline attached mechanochromic triphenylamine, N-phenyl-N-(4-(quinolin-2-yl)phenyl)benzenamine (PQPBA) and tris(4-(quinolin-2-yl)phenyl)amine (TQPA), smart fluorescent materials exhibit thermo/mechanochromism and tunable solid state ... ...

Abstract	Halochromic isoquinoline attached mechanochromic triphenylamine, N-phenyl-N-(4-(quinolin-2-yl)phenyl)benzenamine (PQPBA) and tris(4-(quinolin-2-yl)phenyl)amine (TQPA), smart fluorescent materials exhibit thermo/mechanochromism and tunable solid state fluorescence and their unusual halochromic response in PMMA matrix have been used for fabricating rewritable and self-erasable fluorescent platforms. PQPBA and TQPA showed strong fluorescence in solution (Φ
Language	English
Publishing date	2016-12-07
Publishing country	United States
Document type	Journal Article
ISSN	1944-8252
ISSN (online)	1944-8252
DOI	10.1021/acsami.6b11939
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