@article {3716, title = {Omicron infection increases IgG binding to spike protein of predecessor variants.}, journal = {J Med Virol}, year = {2022}, month = {2022 Dec 22}, abstract = {

BACKGROUND: SARS-CoV-2 transmission in India in 2020-2022 was driven predominantly by Wild (Wuhan-Hu-1and D614G), Delta, and Omicron variants. The aim of this study was to examine the effect of infections on the humoral immune response and cross-reactivity to spike proteins of Wuhan-Hu-1, Delta, C.1.2., and Omicron.

OBJECTIVES: Residual archival sera (N=81) received between January 2020 and March 2022 were included. Infection status was inferred by a positive SARS-CoV-2 RT-PCR and/or serology (anti-N and anti-S antibodies) and sequencing of contemporaneous samples (N=18) to infer lineage. We estimated the levels and cross-reactivity of infection-induced sera including Wild, Delta, Omicron as well as vaccine breakthrough infections (Delta and Omicron).

RESULTS: We found ~2-fold increase in spike-specific IgG antibody binding in post-Omicron infection compared to the pre-Omicron period, whilst the change in pre- and post-Delta infections were similar. Further investigation of Omicron-specific humoral responses revealed primary Omicron infection as an inducer of cross-reactive antibodies against predecessor variants, in spite of weaker degree of humoral response compared to Wuhan-Hu-1 and Delta infection. Intriguingly, Omicron vaccine-breakthrough infections when compared with primary infections, exhibited increased humoral responses against RBD (7.7-fold) and Trimeric S (Trimeric form of spike protein) (34.6-fold) in addition to increased binding of IgGs towards previously circulating variants (4.2 - 6.5-fold). Despite Delta breakthrough infections showing a higher level of humoral response against RBD (2.9-fold) and Trimeric S (5.7-fold) compared to primary Delta sera, a demonstrably reduced binding (36-49\%) was observed to Omicron spike protein.

CONCLUSIONS: Omicron vaccine breakthrough infection results in increased intensity of humoral response and wider breadth of IgG binding to spike proteins of antigenically-distinct, predecessor variants. This article is protected by copyright. All rights reserved.

}, issn = {1096-9071}, doi = {10.1002/jmv.28419}, author = {Mahalingam, Gokulnath and Periyasami, Yogapriya and Arjunan, Porkizhi and Subaschandrabose, Rajesh Kumar and Mathivanan, Tamil Venthan and Mathew, Roshlin Susan and Ramya Devi, Kt and Premkumar, Prasanna Samuel and Muliyil, Jayaprakash and Srivastava, Alok and Moorthy, Mahesh and Marepally, Srujan} } @article {2244, title = {Oxylipin biosynthesis reinforces cellular senescence and allows detection of senolysis.}, journal = {Cell Metab}, year = {2021}, month = {2021 Mar 31}, abstract = {

Cellular senescence is a stress or damage response that causes a permanent proliferative arrest and secretion of numerous factors with potent biological activities. This senescence-associated secretory phenotype (SASP) has been characterized largely for secreted proteins that participate in embryogenesis, wound healing, inflammation, and many age-related pathologies. By contrast, lipid components of the SASP are understudied. We show that senescent cells activate the biosynthesis of several oxylipins that promote segments of the SASP and reinforce the proliferative arrest. Notably, senescent cells synthesize and accumulate an unstudied intracellular prostaglandin, 1a,1b-dihomo-15-deoxy-delta-12,14-prostaglandin J2. Released 15-deoxy-delta-12,14-prostaglandin J2 is a biomarker of senolysis in culture and in\ vivo. This and other prostaglandin D2-related lipids promote the senescence arrest and SASP by activating RAS signaling. These data identify an important aspect of cellular senescence and a method to detect senolysis.

}, issn = {1932-7420}, doi = {10.1016/j.cmet.2021.03.008}, author = {Wiley, Christopher D and Sharma, Rishi and Davis, Sonnet S and Lopez-Dominguez, Jose Alberto and Mitchell, Kylie P and Wiley, Samantha and Alimirah, Fatouma and Kim, Dong Eun and Payne, Therese and Rosko, Andrew and Aimontche, Eliezer and Deshpande, Sharvari M and Neri, Francesco and Kuehnemann, Chisaka and Demaria, Marco and Ramanathan, Arvind and Campisi, Judith} } @article {2152, title = {Optimization of Protocols for Detection of De Novo Protein Synthesis in Whole Blood Samples via Azide-Alkyne Cycloaddition.}, journal = {J Proteome Res}, volume = {19}, year = {2020}, month = {2020 Sep 04}, pages = {3856-3866}, abstract = {

Aberrant protein synthesis and protein expression are a hallmark of many conditions ranging from cancer to Alzheimer{\textquoteright}s. Blood-based biomarkers indicative of changes in proteomes have long been held to be potentially useful with respect to disease prognosis and treatment. However, most biomarker efforts have focused on unlabeled plasma proteomics that include nonmyeloid origin proteins with no attempt to dynamically tag acute changes in proteomes. Herein we report a method for evaluating de novo protein synthesis in whole blood liquid biopsies. Using a modification of the "bioorthogonal noncanonical amino acid tagging" (BONCAT) protocol, rodent whole blood samples were incubated with l-azidohomoalanine (AHA) to allow incorporation of this selectively reactive non-natural amino acid within nascent polypeptides. Notably, failure to incubate the blood samples with EDTA prior to implementation of azide-alkyne "click" reactions resulted in the inability to detect probe incorporation. This live-labeling assay was sensitive to inhibition with anisomycin and nascent, tagged polypeptides were localized to a variety of blood cells using FUNCAT. Using labeled rodent blood, these tagged peptides could be consistently identified through standard LC/MS-MS detection of known blood proteins across a variety of experimental conditions. Furthermore, this assay could be expanded to measure de novo protein synthesis in human blood samples. Overall, we present a rapid and convenient de novo protein synthesis assay that can be used with whole blood biopsies that can quantify translational change as well as identify differentially expressed proteins that may be useful for clinical applications.

}, issn = {1535-3907}, doi = {10.1021/acs.jproteome.0c00299}, author = {Bowling, Heather L and Kasper, Amanda and Patole, Chhaya and Venkatasubramani, Janani Priya and Leventer, Sarah Parker and Carmody, Erin and Sharp, Kevin and Berry-Kravis, Elizabeth and Kirshenbaum, Kent and Klann, Eric and Bhattacharya, Aditi} } @article {1589, title = {OCIAD1 Controls Electron Transport Chain Complex I Activity to Regulate Energy Metabolism in Human Pluripotent Stem Cells.}, journal = {Stem Cell Reports}, volume = {11}, year = {2018}, month = {2018 Jul 10}, pages = {128-141}, abstract = {

Pluripotent stem cells (PSCs) derive energy predominantly from glycolysis and not the energy-efficient oxidative phosphorylation (OXPHOS). Differentiation is initiated with energy metabolic shift from glycolysis to OXPHOS. We investigated the role of mitochondrial energy metabolism in human PSCs using molecular, biochemical, genetic, and pharmacological approaches. We show that the carcinoma protein OCIAD1 interacts with and regulates mitochondrial complex I activity. Energy metabolic assays on live pluripotent cells showed that OCIAD1-depleted cells have increased OXPHOS and may be poised for differentiation. OCIAD1 maintains human embryonic stem cells, and its depletion by CRISPR/Cas9-mediated knockout leads to rapid and increased differentiation upon induction, whereas OCIAD1 overexpression has the opposite effect. Pharmacological alteration of complex I activity was able to rescue the defects of OCIAD1 modulation. Thus, hPSCs can exist in energy metabolic substates. OCIAD1 provides a target to screen for additional modulators of mitochondrial activity to promote transient multipotent precursor expansion or enhance differentiation.

}, issn = {2213-6711}, doi = {10.1016/j.stemcr.2018.05.015}, author = {Shetty, Deeti K and Kalamkar, Kaustubh P and Inamdar, Maneesha S} } @article {1206, title = {{One enzyme, many reactions: structural basis for the various reactions catalyzed by naphthalene 1,2-dioxygenase}}, journal = {IUCrJ}, volume = {4}, year = {2017}, month = {Sep}, pages = {648{\textendash}656}, abstract = {

Rieske nonheme iron oxygenases (ROs) are a well studied class of enzymes. Naphthalene 1,2-dioxygenase (NDO) is used as a model to study ROs. Previous work has shown how side-on binding of oxygen to the mononuclear iron provides this enzyme with the ability to catalyze stereospecific and regiospecific {\i}t cis}-dihydroxylation reactions. It has been well documented that ROs catalyze a variety of other reactions, including mono-oxygenation, desaturation, O- and N-dealkylation, sulfoxidation {\i}t etc}. NDO itself catalyzes a variety of these reactions. Structures of NDO in complex with a number of different substrates show that the orientation of the substrate in the active site controls not only the regiospecificity and stereospecificity, but also the type of reaction catalyzed. It is proposed that the mononuclear iron-activated dioxygen attacks the atoms of the substrate that are most proximal to it. The promiscuity of delivering two products (apparently by two different reactions) from the same substrate can be explained by the possible binding of the substrate in slightly different orientations aided by the observed flexibility of residues in the binding pocket.

}, keywords = {2-dioxygenase, deoxygenation, monooxygenation, naphthalene 1, substrate orientation, sulfoxidation}, doi = {10.1107/S2052252517008223}, url = {https://doi.org/10.1107/S2052252517008223}, author = {Ferraro, Daniel J. and Okerlund, Adam and Brown, Eric and Ramaswamy, S.} }