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Characterization of SARS-CoV-2 public CD4+ αβ T cell clonotypes through reverse epitope discovery

Elisa Rosati, Mikhail Pogorelyy, Anastasia Minervina, Alexander Scheffold, Andre Franke, Petra Bacher, Paul Thomas,

The amount of scientific data and level of public sharing produced as a consequence of the COVID-19 pandemic, as well as the speed at which these data were produced, far exceeds any previous effort against a specific disease condition. This unprecedented situation allows for development and application of new research ... Read more >>

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Correction to: Prospective intra‑individual blinded comparison of [18F]PSMA‑1007 and [68 Ga]Ga‑PSMA‑11 PET/CT imaging in patients with confirmed prostate cancer.

David A Pattison, Maciej Debowski, Brook Gulhane, Evyn G Arnfield, Anita M Pelecanos, Peter L Garcia, Melissa J Latter, Charles Y Lin, Matthew J Roberts, Stuart C Ramsay, Paul A Thomas,

Eur J Nucl Med Mol Imaging (European journal of nuclear medicine and molecular imaging)
[2021, :]

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A novel approach to combine food production with carbon sequestration, biodiversity and conservation goals.

Paul W Thomas, Luis-Bernardo Vazquez,

Land use conflict is a major contributor to unsustainable deforestation rates, with agriculture being the primary driver. Demand for agricultural output is forecast to increase for years to come and the associated deforestation is a key driver in global declines of biodiversity. Moreover, deforestation is contributing to instability of agricultural ... Read more >>

Sci Total Environ (The Science of the total environment)
[2021, :151301]

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The Nestin neural enhancer is essential for normal levels of endogenous Nestin in neuroprogenitors but is not required for embryo development.

Ella Thomson, Ruby Dawson, Chee Ho H'ng, Fatwa Adikusuma, Sandra Piltz, Paul Q Thomas,

Enhancers are vitally important during embryonic development to control the spatial and temporal expression of genes. Recently, large scale genome projects have identified a vast number of putative developmental regulatory elements. However, the proportion of these that have been functionally assessed is relatively low. While enhancers have traditionally been studied ... Read more >>

PLoS One (PloS one)
[2021, 16(11):e0258538]

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SARS-CoV-2 Infection in Children Does Not Necessitate Establishment of Adaptive SARS- CoV-2-Specific Immunological Memory

Louise Rowntree, Thi Nguyen, Lukasz Kedzierski, Melanie Neeland, Jan Petersen, Jeremy Crawford, Lilith Allen, Anastasia Minervina, Mikhail Pogorelyy, Priyanka Chaurasia, T, Adam Wheatley, Hayley McQuilten, Bridie Clemens, Fatima Amanat, Florian Krammer, Sabrina Sonda, Katie Flanagan, Paul Licciardi, Stephen Kent, Jamie Rossjohn, Paul Thomas, Shidan Tosif, Nigel Crawford, van de Sandt, Katherine Kedzierska,

Children are at lower risk of developing severe COVID-19, yet the underlying immune mechanisms are understudied. While children’s innate immunity can drive rapid resolution of SARS-CoV-2 infection, the establishment of SARS-CoV-2-specific T-cell and B-cell memory in COVID-19 children remains unexplored. We recruited a household cohort to understand SARS-CoV-2-specific CD4<sup>+</sup> and ... Read more >>

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Fetal neural progenitors process TLR signals from bacterial components to enhance proliferation and rework brain development

Beth Mann, Jeremy Chase Crawford, Kavya Reddy, Josi Lott, Yong Ha Youn, Geli Gao, Cliff Guy, Ching-Heng Chou, Daniel Darnell, Sanchit Trivedi, Perrine Bomme, Allister Loughran, Paul Thomas, Young-Goo Han, Elaine Tuomanen,

<h4>Summary</h4> Bacterial cell wall, a universal pathogen-associated molecular pattern (PAMP), crosses the placenta into the fetal brain. We determined that PAMPs interact with TLR2/6 on murine fetal neural progenitor cells (NPCs) to induce overexpansion of all neocortical layers leading to a larger, folded cortex and abnormal postnatal behavior. The NPC ... Read more >>

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PANTHER: making genome-scale phylogenetics accessible to all.

Paul D Thomas, Dustin Ebert, Anushya Muruganujan, Tremayne Mushayahama, Laurent-Philippe Albou, Huaiyu Mi,

Phylogenetics is a powerful tool for analyzing protein sequences, by inferring their evolutionary relationships to other proteins. However, phylogenetics analyses can be challenging: they are computationally expensive and must be performed carefully in order to avoid systematic errors and artifacts. PANTHER (http://pantherdb.org) is a publicly available, user-focused knowledgebase that stores ... Read more >>

Protein Sci (Protein science : a publication of the Protein Society)
[2021, :]

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SAM Competitive PRMT5 Inhibitor PF-06939999 Demonstrates Antitumor Activity in Splicing Dysregulated NSCLC with Decreased Liability of Drug Resistance.

Kristen Jensen-Pergakes, John Tatlock, Karen A Maegley, Indrawan J McAlpine, Michele A McTigue, Tao Xie, Christopher P Dillon, Yuli Wang, Shinji Yamazaki, Noah Spiegel, Manli Shi, Amy Nemeth, Natalie Miller, Eleanore Hendrickson, Hieu Lam, John Sherrill, Chi-Yeh Chung, Elizabeth A McMillan, Shannon Karlicek Bryant, Prakash Palde, John Braganza, Alexei Brooun, Ya-Li Deng, Vesta Goshtasbi, Susan E Kephart, Robert A Kumpf, Wei Liu, Ryan L Patman, Eugene Rui, Stephanie Scales, Michelle Tran-Dube, Fen Wang, Martin Wythes, Thomas A Paul,

Protein arginine methyltransferase 5 (PRMT5) over-expression in hematological and solid tumors methylates arginine residues on cellular proteins involved in important cancer functions including cell cycle regulation, mRNA splicing, cell differentiation, cell signaling, and apoptosis. PRMT5 methyltransferase function has been linked with high rates of tumor cell proliferation and decreased overall ... Read more >>

Mol Cancer Ther (Molecular cancer therapeutics)
[2021, :]

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Corrigendum to "Isolation and characterization of bioactive xanthones from Hippocrateaafricana (Wild.)Loes.ex Engl. (Celastraceae) [J. Ethnopharmacol. 280 (2021) 114031].

Uwemedimo F Umoh, Paul S Thomas, Emmanuel E Essien, Jude E Okokon, Marinella DeLeo, Kola' K Ajibesin, Guido Flamini, Olorunfemi A Eseyin,

J Ethnopharmacol (Journal of ethnopharmacology)
[2021, 284:114703]

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The Gene Regulation Knowledge Commons: The action area of GREEKC.

Martin Kuiper, Joseph Bonello, Jesualdo Tomás Fernández-Breis, Philipp Bucher, Matthias E Futschik, Pascale Gaudet, Ivan V Kulakovskiy, Luana Licata, Colin Logie, Ruth C Lovering, Vsevolod J Makeev, Sandra Orchard, Simona Panni, Livia Perfetto, David Sant, Stefan Schulz, Daniel R Zerbino, Astrid Lægreid, ,

The COST Action Gene Regulation Ensemble Effort for the Knowledge Commons (GREEKC, CA15205, www.greekc.org) organized nine workshops in a four-year period, starting September 2016. The workshops brought together a wide range of experts from all over the world working on various parts of the knowledge cycle that is central to ... Read more >>

Biochim Biophys Acta Gene Regul Mech (Biochimica et biophysica acta. Gene regulatory mechanisms)
[2021, :194768]

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Low-dose in vivo protection and neutralization across SARS-CoV-2 variants by monoclonal antibody combinations.

Vincent Dussupt, Rajeshwer S Sankhala, Letzibeth Mendez-Rivera, Samantha M Townsley, Fabian Schmidt, Lindsay Wieczorek, Kerri G Lal, Gina C Donofrio, Ursula Tran, Nathaniel D Jackson, Weam I Zaky, Michelle Zemil, Sarah R Tritsch, Wei-Hung Chen, Elizabeth J Martinez, Aslaa Ahmed, Misook Choe, William C Chang, Agnes Hajduczki, Ningbo Jian, Caroline E Peterson, Phyllis A Rees, Magdalena Rutkowska, Bonnie M Slike, Christopher N Selverian, Isabella Swafford, I-Ting Teng, Paul V Thomas, Tongqing Zhou, Clayton J Smith, Jeffrey R Currier, Peter D Kwong, Morgane Rolland, Edgar Davidson, Benjamin J Doranz, Christopher N Mores, Theodora Hatziioannou, William W Reiley, Paul D Bieniasz, Dominic Paquin-Proulx, Gregory D Gromowski, Victoria R Polonis, Nelson L Michael, Kayvon Modjarrad, M Gordon Joyce, Shelly J Krebs,

Prevention of viral escape and increased coverage against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern require therapeutic monoclonal antibodies (mAbs) targeting multiple sites of vulnerability on the coronavirus spike glycoprotein. Here we identify several potent neutralizing antibodies directed against either the N-terminal domain (NTD) or the receptor-binding ... Read more >>

Nat Immunol (Nature immunology)
[2021, :]

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Allele-specific PCR and next generation sequencing based genetic screening for Congenital Adrenal Hyperplasia in India.

Lavanya Ravichandran, Sophy Korula, H S Asha, Deny Varghese, ParthibanR, Jabasteen Johnson, Janani Ishwarya, Sahana Shetty, Kripa Elizabeth Cherian, Felix Jebasingh, Nitin Kapoor, Divya Pachat, Sarah Mathai, Anna Simon, Simon Rajaratnam, Thomas V Paul, Nihal Thomas, Aaron Chapla,

Genetic screening of Congenital Adrenal Hyperplasia (CAH) is known to be challenging due to the complexities in CYP21A2 genotyping and has not been the first-tier diagnostic tool in routine clinical practice. Also, with the advent of massive parallel sequencing technology, there is a need for investigating its utility in screening ... Read more >>

Eur J Med Genet (European journal of medical genetics)
[2021, :104369]

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A SARS-CoV-2 spike ferritin nanoparticle vaccine protects hamsters against Alpha and Beta virus variant challenge.

Kathryn McGuckin Wuertz, Erica K Barkei, Wei-Hung Chen, Elizabeth J Martinez, Ines Lakhal-Naouar, Linda L Jagodzinski, Dominic Paquin-Proulx, Gregory D Gromowski, Isabella Swafford, Akshaya Ganesh, Ming Dong, Xiankun Zeng, Paul V Thomas, Rajeshwer S Sankhala, Agnes Hajduczki, Caroline E Peterson, Caitlin Kuklis, Sandrine Soman, Lindsay Wieczorek, Michelle Zemil, Alexander Anderson, Janice Darden, Heather Hernandez, Hannah Grove, Vincent Dussupt, Holly Hack, Rafael de la Barrera, Stasya Zarling, James F Wood, Jeffrey W Froude, Matthew Gagne, Amy R Henry, Elham Bayat Mokhtari, Prakriti Mudvari, Shelly J Krebs, Andrew S Pekosz, Jeffrey R Currier, Swagata Kar, Maciel Porto, Adrienne Winn, Kamil Radzyminski, Mark G Lewis, Sandhya Vasan, Mehul Suthar, Victoria R Polonis, Gary R Matyas, Eli A Boritz, Daniel C Douek, Robert A Seder, Sharon P Daye, Mangala Rao, Sheila A Peel, M Gordon Joyce, Diane L Bolton, Nelson L Michael, Kayvon Modjarrad,

The emergence of SARS-CoV-2 variants of concern (VOC) requires adequate coverage of vaccine protection. We evaluated whether a SARS-CoV-2 spike ferritin nanoparticle vaccine (SpFN), adjuvanted with the Army Liposomal Formulation QS21 (ALFQ), conferred protection against the Alpha (B.1.1.7), and Beta (B.1.351) VOCs in Syrian golden hamsters. SpFN-ALFQ was administered as ... Read more >>

NPJ Vaccines (NPJ vaccines)
[2021, 6(1):129]

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Intrinsic and acquired drug resistance to LSD1 inhibitors in small cell lung cancer occurs through a TEAD4-driven transcriptional state.

Wen Yan, Chi-Yeh Chung, Tao Xie, Mark Ozeck, Timothy C Nichols, Jessica Frey, Akshata R Udyavar, Shikhar Sharma, Thomas A Paul,

Small-cell lung cancer (SCLC) is a heterogeneous disease, consisting of intratumoral and intertumoral neuroendocrine (ASCL1 and/or NEUROD1), mesenchymal-like, and YAP-driven transcriptional states. Lysine-specific demethylase 1 (LSD1; also known as KDM1A) inhibitors have recently been progressed to clinical trials in SCLC based on a promising preclinical antitumor activity. A potential clinical ... Read more >>

Mol Oncol (Molecular oncology)
[2021, :]

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Optimized nickase- and nuclease-based prime editing in human and mouse cells.

Fatwa Adikusuma, Caleb Lushington, Jayshen Arudkumar, Gelshan I Godahewa, Yu C J Chey, Luke Gierus, Sandra Piltz, Ashleigh Geiger, Yatish Jain, Daniel Reti, Laurence O W Wilson, Denis C Bauer, Paul Q Thomas,

Precise genomic modification using prime editing (PE) holds enormous potential for research and clinical applications. In this study, we generated all-in-one prime editing (PEA1) constructs that carry all the components required for PE, along with a selection marker. We tested these constructs (with selection) in HEK293T, K562, HeLa and mouse ... Read more >>

Nucleic Acids Res (Nucleic acids research)
[2021, 49(18):10785-10795]

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Network Diffusion Embedding Reveals Transdiagnostic Subnetwork Disruption and Potential Treatment Targets in Internalizing Psychopathologies.

Paul J Thomas, Alex Leow, Heide Klumpp, K Luan Phan, Olusola Ajilore,

Network diffusion models are a common and powerful way to study the propagation of information through a complex system and they offer straightforward approaches for studying multimodal brain network data. We developed an analytic framework to identify brain subnetworks with perturbed information diffusion capacity using the structural basis that best ... Read more >>

Cereb Cortex (Cerebral cortex (New York, N.Y. : 1991))
[2021, :]

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Immune responses in COVID-19 respiratory tract and blood reveal mechanisms of disease severity

Wuji Zhang, Brendon Chua, Kevin Selva, Lukasz Kedzierski, Thomas Ashhurst, Ebene Haycroft, Suzanne Shoffner, Luca Hensen, David Boyd, Fiona James, Effie Mouhtouris, Jason Kwong, Kyra Chua, George Drewett, Ana Copaescu, Julie Dobson, Louise Rowntree, Jennifer Habel, Lilith Allen, Hui-Fern Koay, Jessica Neil, Matthew Gartner, Christina Lee, Patiyan Andersson, Torsten Seemann, Norelle Sherry, Fatima Amanat, Florian Krammer, Sarah Londrigan, Linda Wakim, Nicholas J.C. King, Dale Godfrey, Laura Mackay, Paul Thomas, Suellen Nicholson, Kelly Arnold, Amy Chung, Natasha Holmes, Olivia Smibert, Jason Trubiano, Claire Gordon, Thi H.O. Nguyen, Katherine Kedzierska,

<h4>ABSTRACT</h4> Although the respiratory tract is the primary site of SARS-CoV-2 infection and the ensuing immunopathology, respiratory immune responses are understudied and urgently needed to understand mechanisms underlying COVID-19 disease pathogenesis. We collected paired longitudinal blood and respiratory tract samples (endotracheal aspirate, sputum or pleural fluid) from hospitalized COVID-19 patients ... Read more >>

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Combining genotypes and T cell receptor distributions to infer genetic loci determining V(D)J recombination probabilities

Magdalena Russell, Aisha Souquette, David Levine, Kaitlynn Allen, Guillermina Kuan, Noah Simon, Angel Balmaseda, Aubree Gordon, Paul Thomas, Frederick Matsen, Philip Bradley,

Every T cell receptor (TCR) repertoire is shaped by a complex probabilistic tangle of genetically determined biases and immune exposures. T cells combine a random V(D)J recombination process with a selection process to generate highly diverse and functional TCRs. The extent to which an individual’s genetic background is associated with ... Read more >>

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SARS-CoV-2 vaccination modelling for safe surgery to save lives: data from an international prospective cohort study.

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<h4>Background</h4>Preoperative SARS-CoV-2 vaccination could support safer elective surgery. Vaccine numbers are limited so this study aimed to inform their prioritization by modelling.<h4>Methods</h4>The primary outcome was the number needed to vaccinate (NNV) to prevent one COVID-19-related death in 1 year. NNVs were based on postoperative SARS-CoV-2 rates and mortality in an ... Read more >>

Br J Surg (The British journal of surgery)
[2021, 108(9):1056-1063]

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The prevalence of vertebral fractures among Indian perimenopausal women and its association with ovarian biomarkers.

Cijoy Kuriakose, Kripa Elizabeth Cherian, Felix Jebasingh, Nitin Kapoor, Hesarghatta S Asha, Arun Jose, Nihal Thomas, Thomas V Paul,

<h4>Introduction</h4>There is dearth of data on prevalent vertebral fractures in perimenopausal women in India and limited literature on the utility of FSH, AMH and estradiol in evaluating bone health them. The objective was to study the prevalence of vertebral fractures (VF) and to assess the utility of FSH, estradiol and ... Read more >>

J Bone Miner Metab (Journal of bone and mineral metabolism)
[2021, :]

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Preclinical Molecular PET-CT Imaging Targeting CDCP1 in Colorectal Cancer.

Tahleesa J Cuda, Yaowu He, Thomas Kryza, Tashbib Khan, Brian W Tse, Kamil A Sokolowski, Cheng Liu, Nicholas Lyons, Madeline Gough, Cameron E Snell, David K Wyld, Stephen Rose, Andrew D Riddell, Andrew R L Stevenson, Paul A Thomas, David A Clark, Simon Puttick, John D Hooper,

Colorectal cancer (CRC) is the third most common malignancy in the world, with 22% of patients presenting with metastatic disease and a further 50% destined to develop metastasis. Molecular imaging uses antigen-specific ligands conjugated to radionuclides to detect and characterise primary cancer and metastases. Expression of the cell surface protein ... Read more >>

Contrast Media Mol Imaging (Contrast media & molecular imaging)
[2021, 2021:3153278]

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Characterization of a Copper-Chelating Natural Product from the Methanotroph Methylosinus sp. LW3.

Yun Ji Park, Gerri M Roberts, Rana Montaser, Grace E Kenney, Paul M Thomas, Neil L Kelleher, Amy C Rosenzweig,

Methanobactins (Mbns) are ribosomally produced, post-translationally modified peptidic natural products that bind copper with high affinity. Methanotrophic bacteria use Mbns to acquire copper needed for enzymatic methane oxidation. Despite the presence of Mbn operons in a range of methanotroph and other bacterial genomes, few Mbns have been isolated and structurally ... Read more >>

Biochemistry (Biochemistry)
[2021, 60(38):2845-2850]

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Integrating T cell receptor sequences and transcriptional profiles by clonotype neighbor graph analysis (CoNGA).

Stefan A Schattgen, Kate Guion, Jeremy Chase Crawford, Aisha Souquette, Alvaro Martinez Barrio, Michael J T Stubbington, Paul G Thomas, Philip Bradley,

Links between T cell clonotypes, as defined by T cell receptor (TCR) sequences, and phenotype, as reflected in gene expression (GEX) profiles, surface protein expression and peptide:major histocompatibility complex binding, can reveal functional relationships beyond the features shared by clonally related cells. Here we present clonotype neighbor graph analysis (CoNGA), ... Read more >>

Nat Biotechnol (Nature biotechnology)
[2021, :]

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Risk of Metastatic Disease Using [18F]PSMA-1007 PET/CT for Primary Prostate Cancer Staging

Venkata Avinash Chikatamarla, Satomi Okano, Peter Jenvey, Alexander Ansaldo, Matthew Roberts, Stuart Ramsay, Paul Thomas, David Pattison,

<h4>Purpose: </h4> Accurate prostate cancer imaging is critical for patient management. Multiple studies have demonstrated superior diagnostic accuracy of [ 68 Ga]-PSMA-11 PET/CT over conventional imaging for disease detection, with validated clinical and biochemical predictors of disease detection. More recently [ 18 F]PSMA-1007 offers theoretical imaging advantages, but there is ... Read more >>

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Gene Ontology representation for transcription factor functions.

Pascale Gaudet, Colin Logie, Ruth C Lovering, Martin Kuiper, Astrid Lægreid, Paul D Thomas,

Transcription plays a central role in defining the identity and functionalities of cells, as well as in their responses to changes in the cellular environment. The Gene Ontology (GO) provides a rigorously defined set of concepts that describe the functions of gene products. A GO annotation is a statement about ... Read more >>

Biochim Biophys Acta Gene Regul Mech (Biochimica et biophysica acta. Gene regulatory mechanisms)
[2021, 1864(11-12):194752]

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