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1,257 results on '"Pai, R"'

6. Homicide, Suicide, Cyber-Victimization, and Cyber-Bullying in Persons with Internet Gaming Disorder.

Author

Kulkarni, Ranganath R., Pandurangi, Swapna A., Pandurangi, Aditya A., Shantheri Pai R., and Sherigar, Divya K.

Subjects
CYBERBULLYING, MASSIVELY multiplayer online role-playing games, STRESS tolerance (Psychology), GAMING disorder, SELF-injurious behavior, INTERPERSONAL relations, PARENTING, HOME schooling
Abstract

The article discusses the prevalence of Internet Gaming Disorder (IGD) in India, highlighting the risks associated with excessive gaming, such as cyber-victimization, cyber-bullying, and medico-legal issues. The study presents four cases of individuals with IGD, detailing their socio-demographic, clinical, and psychosocial profiles, as well as their treatment outcomes. The findings suggest that early interventions and comprehensive management are crucial in addressing the complex psychosocial background of IGD, which can lead to serious consequences like violence, suicide, and cyber-crime. The article emphasizes the need for further research to better understand and manage IGD in vulnerable individuals. [Extracted from the article]

Published
2024
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7. Dibenzo‐Fused Heterocycles: A Decade Update on the Syntheses of Carbazole, Dibenzofuran, and Dibenzothiophene.

Author

Sreekumar, Anjana, Nair, Ajil R., Raksha, C., Gopika, S., Padmanabhan, S., Gopalakrishna Pai, R., and Sivan, Akhil

Subjects
BIOACTIVE compounds, HETEROCYCLIC compounds, CARBAZOLE derivatives, NATURAL products, DIBENZOTHIOPHENE
Abstract

Polycyclic heterocycles are the most common and critical structural motifs found in a variety of natural products, medicines, fertilizers, and advanced materials. Because of their widespread use in biologically active compounds and material chemistry, functionalised dibenzo heterocyclic compounds, especially dibenzofuran, dibenzothiophene, and carbazole derivatives, garnered much attention over time. Scientists are especially interested in elucidating more efficient techniques for developing these industrially essential compounds. Dibenzo‐fused heterocycles can rapidly be synthesised using highly efficient transition metal‐catalysed strategies as well as by economic metal‐free reaction conditions. This review includes a detailed overview of the most recent significant synthetic techniques, both metal‐catalysed and metal‐free, to produce these industrially significant and medicinally important dibenzo‐fused heterocycles. [ABSTRACT FROM AUTHOR]

Published
2024
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11. Finite Element Analysis of the Human Eye for a Range of Intraocular Pressure

Author

Vivek Suganthan, R., Meenatchi Sundaram, S., Ramesh, S. Ve, Rinu, Thomas, Pai, R., Khader, Shah Mohammed Abdul, Hazarika, Manali, Girish, H., Angrisani, Leopoldo, Series Editor, Arteaga, Marco, Series Editor, Panigrahi, Bijaya Ketan, Series Editor, Chakraborty, Samarjit, Series Editor, Chen, Jiming, Series Editor, Chen, Shanben, Series Editor, Chen, Tan Kay, Series Editor, Dillmann, Rüdiger, Series Editor, Duan, Haibin, Series Editor, Ferrari, Gianluigi, Series Editor, Ferre, Manuel, Series Editor, Hirche, Sandra, Series Editor, Jabbari, Faryar, Series Editor, Jia, Limin, Series Editor, Kacprzyk, Janusz, Series Editor, Khamis, Alaa, Series Editor, Kroeger, Torsten, Series Editor, Liang, Qilian, Series Editor, Martín, Ferran, Series Editor, Ming, Tan Cher, Series Editor, Minker, Wolfgang, Series Editor, Misra, Pradeep, Series Editor, Möller, Sebastian, Series Editor, Mukhopadhyay, Subhas, Series Editor, Ning, Cun-Zheng, Series Editor, Nishida, Toyoaki, Series Editor, Pascucci, Federica, Series Editor, Qin, Yong, Series Editor, Seng, Gan Woon, Series Editor, Speidel, Joachim, Series Editor, Veiga, Germano, Series Editor, Wu, Haitao, Series Editor, Zhang, Junjie James, Series Editor, George, V. I., editor, and Roy, B. K., editor

Published
2020
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17. A Systematic Review of Artificial Intelligence in Prostate Cancer

Author

Van Booven DJ, Kuchakulla M, Pai R, Frech FS, Ramasahayam R, Reddy P, Parmar M, Ramasamy R, and Arora H

Subjects
prostate cancer, active surveillance, clinical trials, artificial intelligence, Diseases of the genitourinary system. Urology, RC870-923
Abstract

Derek J Van Booven,1 Manish Kuchakulla,2 Raghav Pai,2 Fabio S Frech,2 Reshna Ramasahayam,2 Pritika Reddy,2 Madhumita Parmar,2 Ranjith Ramasamy,2,3 Himanshu Arora1– 3 1John P Hussman Institute for Human Genomics, Miller School of Medicine, University of Miami, Miami, FL, USA; 2Department of Urology, Miller School of Medicine, University of Miami, Miami, FL, USA; 3The Interdisciplinary Stem Cell Institute, Miller School of Medicine, University of Miami, Miami, FL, USACorrespondence: Himanshu Arora Email Hxa287@miami.eduAbstract: The diagnosis and management of prostate cancer involves the interpretation of data from multiple modalities to aid in decision making. Tools like PSA levels, MRI guided biopsies, genomic biomarkers, and Gleason grading are used to diagnose, risk stratify, and then monitor patients during respective follow-ups. Nevertheless, diagnosis tracking and subsequent risk stratification often lend itself to significant subjectivity. Artificial intelligence (AI) can allow clinicians to recognize difficult relationships and manage enormous data sets, which is a task that is both extraordinarily difficult and time consuming for humans. By using AI algorithms and reducing the level of subjectivity, it is possible to use fewer resources while improving the overall efficiency and accuracy in prostate cancer diagnosis and management. Thus, this systematic review focuses on analyzing advancements in AI-based artificial neural networks (ANN) and their current role in prostate cancer diagnosis and management.Keywords: prostate cancer, active surveillance, clinical trials, artificial intelligence

Published
2021

18. A Systematic Review on the Investigation of SARS-CoV-2 in Semen

Author

Gonzalez DC, Khodamoradi K, Pai R, Guarch K, Connelly ZM, Ibrahim E, Arora H, and Ramasamy R

Subjects
covid-19, coronavirus, semen, semen parameters, Diseases of the genitourinary system. Urology, RC870-923
Abstract

Daniel C Gonzalez,1 Kajal Khodamoradi,1 Raghav Pai,1 Kristopher Guarch,2 Zachary M Connelly,3 Emad Ibrahim,1 Himanshu Arora,1 Ranjith Ramasamy1 1Department of Urology, Miller School of Medicine, University of Miami, Miami, FL 33136, USA; 2Florida International University, Miami, FL 33199, USA; 3Louisiana State University Health Shreveport, Shreveport, LA 71103, USA; 4The Interdisciplinary Stem Cell Institute, University of Miami, Miller School of Medicine, Miami, FL 33136, USACorrespondence: Ranjith RamasamyDepartment of Urology, Miller School of Medicine, University of Miami, 1120 NW 14th St, #1551, Miami, FL 33136, USATel +1 (305)-243-7200Email Ramasamy@miami.eduBackground: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a virus that is present in most bodily fluids. However, whether SARS-CoV-2 is present in the semen remains underexplored. Thus, we systematically reviewed the existing studies on the presence of SARS-CoV-2 in semen.Methods: A literature search of the PubMed, Embase, Cochrane, Web of Science, Google Scholar, and Ovid databases was performed for articles from the dates of their inception to August 2020 using the following keywords: COVID-19, SARS-CoV2, seminal, semen, and sperm. After excluding non-human studies and articles that were not in the English language, we identified 19 relevant studies. The full text of the articles were reviewed and a total of eight articles remained after applying our selection criteria.Results: After reviewing the presence of SARS-CoV-2 in the eight different studies using semen samples, only one reported the presence of the virus. Six out of 160 total semen samples with SARS-CoV-2 positive demonstrated the presence of viral RNA, of which 2 were from males in the recovery phase and 4 from the acute phase of the infection.Conclusion: The novel nature of SARS-CoV-2 has limited the number and size of studies on semen. Nevertheless, the current literature, while limited, has confirmed the presence of SARS-CoV-2 in semen in one out of the eight reported studies and totaling 4.3% of the population screened. Taken together, the risk of the presence of SARS-CoV-2 in semen appears to be extremely low and likely negligible in recovered men. Future studies need to focus on whether complete viral particles can be seen in semen and the possibility of sexual transmission.Keywords: COVID-19, coronavirus, semen, semen parameters

Published
2020

21. Acetylation of cell wall is required for structural integrity of the leaf surface and exerts a global impact on plant stress responses

Author

Nafisi, Majse, Stranne, Maria, Fimognari, Lorenzo, Atwell, Susanna, Martens, Helle J, Pedas, Pai R, Hansen, Sara F, Nawrath, Christiane, Scheller, Henrik V, Kliebenstein, Daniel J, and Sakuragi, Yumiko

Subjects
Plant Biology, Biological Sciences, Genetics, Biotechnology, cell wall acetylation, trichomes, cuticles, epidermis, Bobytis cinerea, peroxidase, mRNA sequencing, Botrytis cinerea, Crop and pasture production, Plant biology
Abstract

The epidermis on leaves protects plants from pathogen invasion and provides a waterproof barrier. It consists of a layer of cells that is surrounded by thick cell walls, which are partially impregnated by highly hydrophobic cuticular components. We show that the Arabidopsis T-DNA insertion mutants of REDUCED WALL ACETYLATION 2 (rwa2), previously identified as having reduced O-acetylation of both pectins and hemicelluloses, exhibit pleiotrophic phenotype on the leaf surface. The cuticle layer appeared diffused and was significantly thicker and underneath cell wall layer was interspersed with electron-dense deposits. A large number of trichomes were collapsed and surface permeability of the leaves was enhanced in rwa2 as compared to the wild type. A massive reprogramming of the transcriptome was observed in rwa2 as compared to the wild type, including a coordinated up-regulation of genes involved in responses to abiotic stress, particularly detoxification of reactive oxygen species and defense against microbial pathogens (e.g., lipid transfer proteins, peroxidases). In accordance, peroxidase activities were found to be elevated in rwa2 as compared to the wild type. These results indicate that cell wall acetylation is essential for maintaining the structural integrity of leaf epidermis, and that reduction of cell wall acetylation leads to global stress responses in Arabidopsis.

Published
2015

23. Three body on-site interactions in ultracold bosonic atoms in optical lattices and superlattices

Author

Singh, Manpreet, Dhar, Arya, Mishra, Tapan, Pai, R. V., and Das, B. P.

Subjects
Condensed Matter - Quantum Gases
Abstract

The Mott insulator-superfluid transition for ultracold bosonic atoms in an optical lattice has been extensively studied in the framework of the Bose-Hubbard model with two-body on-site interactions. In this paper, we analyze the additional effect of the three-body on-site interactions on this phase transition in optical lattice and the transitions between the various phases that arise in an optical superlattice. Using the mean-field theory and the density matrix renormalization group method, we find the phase diagrams depicting the relationships between various physical quantities in an optical lattice and superlattice. We also suggest possible experimental signatures to observe the three-body interactions., Comment: 5 pages, 9 figures Resubmitted after a few changes. http://pra.aps.org/abstract/PRA/v85/i5/e051604 http://pra.aps.org/abstract/PRA/v85/i5/e051604

Published
2012
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24. Bose Hubbard Model in a Strong Effective Magnetic Field: Emergence of a Chiral Mott Insulator Ground State

Author

Dhar, Arya, Maji, Maheswar, Mishra, Tapan, Pai, R. V., Mukerjee, Subroto, and Paramekanti, Arun

Subjects
Condensed Matter - Quantum Gases, Condensed Matter - Superconductivity
Abstract

Motivated by experiments on Josephson junction arrays, and cold atoms in an optical lattice in a synthetic magnetic field, we study the "fully frustrated" Bose-Hubbard (FFBH) model with half a magnetic flux quantum per plaquette. We obtain the phase diagram of this model on a two-leg ladder at integer filling via the density matrix renormalization group approach, complemented by Monte Carlo simulations on an effective classical XY model. The ground state at intermediate correlations is consistently shown to be a chiral Mott insulator (CMI) with a gap to all excitations and staggered loop currents which spontaneously break time reversal symmetry. We characterize the CMI state as a vortex supersolid or an indirect exciton condensate, and discuss various experimental implications., Comment: 4 pages, 4 figs, Significantly revised version, to appear in PRA-Rapid

Published
2011
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26. UNAMBIGUOUS IDENTIFICATION OF THE STAR ĀRDRĀ.

Author

Shylaja, B. S. and Pai, R. Venketeswara

Subjects
*ZODIAC
Abstract

The names of the stars in old Indian texts are listed in the manuals for the use of astrolabes--for example in the Yantrarāja, Sarvasiddhāntarāja and Yantra Kiraṇāvalī--with coordinates and magnitudes. They were forgotten and the names of the stars too were forgotten, leading to confusion in the identification of stars in recent years. Betelgeuse is omitted in the list of 27 bright stars in the old texts. Recent studies have associated it with Ārdrā, while the coordinates from the old manuals clearly point to γ Gem (Alhena). [ABSTRACT FROM AUTHOR]

Published
2024
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31. Are We Missing Early-onset Frontotemporal Dementia as Late-onset Primary Psychiatric Disorder? A Case Series.

Author

Kulkarni, Ranganath R., Pai, R. Shantheri, Pandurangi, Swapna A., and Kalachari, Manjunath B.

Subjects
*PROGRESSIVE supranuclear palsy, *MENTAL illness, *FRONTOTEMPORAL dementia, *NEUROBEHAVIORAL disorders, *SYMPTOMS, *NEUROLOGICAL disorders
Abstract

Frontotemporal dementia (FTD) presents with a wide variability in clinical progressive syndromes, genetic etiologies, and underlying pathologies. Early diagnosis of combined features of behavioral and language variants of FTD poses a clinical challenge due to its complex heterogeneous clinical presentations, phenotypical overlap, and frequent normal neuroimaging during the initial phase. This masquerading nature has often led to unintended "misdiagnoses," as typical dementia features evolve late. The enigmatic resemblance of early-onset (<65 years of age) FTD with a range of late-onset (>45 years of age) primary psychiatric disorders emphasizes the need for high index of clinical suspicion, thorough family history for neurocognitive disorders, and regular follow-up of such individuals. We describe the clinical profile and management of four cases of combined variant FTD (cvFTD) that clinically mimicked late-onset psychiatric disorders such as catatonia, depressive disorder, psychosis, and personality changes. Parkinsonian-like features and mid-brain atrophy in FTD may indicate phenotypical overlap and shared neuropathology with progressive supranuclear palsy. [ABSTRACT FROM AUTHOR]

Published
2024
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35. TGF-beta signaling pathway: its role in gastrointestinal pathophysiology and modulation of ulcer healing.

Author

Tanigawa, T, Pai, R, Arakawa, T, Higuchi, K, and Tarnawski, A S

Subjects
Animals, Gastrointestinal Diseases: metabolism, physiopathology, Humans, Peptic Ulcer: metabolism, physiopathology, Signal Transduction: physiology, Transforming Growth Factor beta: physiology, Wound Healing, TGF-beta, smad, gastrointestinal ulcer healingtransforming-growth-factor, gastric-mucosa, epithelial-cells, expression, growth-factor-beta-1, localization, tgf-beta-1, receptors, wounds, mice, Animals, Gastrointestinal Diseases: metabolism, physiopathology, Humans, Peptic Ulcer: metabolism, physiopathology, Signal Transduction: physiology, Transforming Growth Factor beta: physiology, Wound Healing, TGF-beta, smad, gastrointestinal ulcer healingtransforming-growth-factor, gastric-mucosa, epithelial-cells, expression, growth-factor-beta-1, localization, tgf-beta-1, receptors, wounds, mice
Abstract

Gastrointestinal ulcer healing is a complex process, involving cell migration, proliferation, angiogenesis and extracellular matrix deposition, all ultimately leading to reconstruction of tissue architecture within the ulcer scar. These processes are controlled by growth factors, cytokines and hormones. Transforming growth factor-beta (TGF-beta), one of the multifunctional peptide growth factors, has been reported to positively regulate gastrointestinal ulcer healing. Although TGF-beta inhibits cell proliferation in a variety of cells, it induces cell migration, angiogenesis, and enhances extracellular matrix production necessary for gastrointestinal ulcer healing. TGF-beta exerts its action by binding to its transmembrane serine/threonine kinase receptors, which in turn triggers activation of various intracellular signaling pathways. Smads are intermediate effector proteins that play key roles in biological activities of TGF-beta by transmitting the signals from the cell surface directly into the nucleus and initiating transcription. New insight into the mechanisms underlying TGF-beta-Smad modulation of gastrointestinal ulcer healing will likely enhance our understanding of the mechanisms controlling the healing processes of gastrointestinal ulcers.

Published
2005

37. Deciphering colorectal cancer genetics through multi-omic analysis of 100,204 cases and 154,587 controls of European and east Asian ancestries

Author

Fernandez-Rozadilla, C, Timofeeva, M, Chen, Z, Law, P, Thomas, M, Bien, S, Diez-Obrero, V, Li, L, Fernandez-Tajes, J, Palles, C, Sherwood, K, Harris, S, Svinti, V, McDonnell, K, Farrington, S, Studd, J, Vaughan-Shaw, P, Shu, X-O, Long, J, Cai, Q, Guo, X, Lu, Y, Scacheri, P, Huyghe, J, Harrison, T, Shibata, D, Haiman, C, Devall, M, Schumacher, F, Melas, M, Rennert, G, Obon-Santacana, M, Martin-Sanchez, V, Moratalla-Navarro, F, Oh, JH, Kim, J, Jee, SH, Jung, KJ, Kweon, S-S, Shin, M-H, Shin, A, Ahn, Y-O, Kim, D-H, Oze, I, Wen, W, Matsuo, K, Matsuda, K, Tanikawa, C, Ren, Z, Gao, Y-T, Jia, W-H, Potter, J, Jenkins, M, Win, AK, Pai, R, Figueiredo, J, Haile, R, Gallinger, S, Woods, M, Newcomb, P, Cheadle, J, Kaplan, R, Maughan, T, Kerr, R, Kerr, D, Kirac, I, Boehm, J, Mecklin, L-P, Jousilahti, P, Knekt, P, Aaltonen, L, Rissanen, H, Pukkala, E, Eriksson, J, Cajuso, T, Hanninen, U, Kondelin, J, Palin, K, Tanskanen, T, Renkonen-Sinisalo, L, Zanke, B, Mannisto, S, Albanes, D, Weinstein, S, Ruiz-Narvaez, E, Palmer, J, Buchanan, D, Platz, E, Visvanathan, K, Ulrich, C, Siegel, E, Brezina, S, Gsur, A, Campbell, P, Chang-Claude, J, Hoffmeister, M, Brenner, H, Slattery, M, Tsilidis, K, Schulze, M, Gunter, M, Murphy, N, Castells, A, Castellvi-Bel, S, Moreira, L, Arndt, V, Shcherbina, A, Stern, M, Pardamean, B, Bishop, T, Giles, G, Southey, M, Idos, G, Abu-Ful, Z, Greenson, J, Shulman, K, Lejbkowicz, F, Offit, K, Su, Y-R, Steinfelder, R, Keku, T, van Guelpen, B, Hudson, T, Hampel, H, Pearlman, R, Berndt, S, Hayes, R, Martinez, ME, Thomas, S, Corley, D, Pharoah, P, Larsson, S, Yen, Y, Lenz, H-J, White, E, Doheny, K, Pugh, E, Shelford, T, Chan, A, Cruz-Correa, M, Lindblom, A, Joshi, A, Schafmayer, C, Kundaje, A, Nickerson, D, Schoen, R, Hampe, J, Stadler, Z, Vodicka, P, Vodickova, L, Vymetalkova, V, Papadopoulos, N, Edlund, C, Gauderman, W, Thomas, D, Toland, A, Markowitz, S, Kim, A, Gruber, S, van Duijnhoven, F, Feskens, E, Sakoda, L, Gago-Dominguez, M, Wolk, A, Naccarati, A, Pardini, B, FitzGerald, L, Lee, SC, Ogino, S, Kooperberg, C, Li, C, Lin, Y, Prentice, R, Qu, C, Bezieau, S, Tangen, C, Mardis, E, Yamaji, T, Sawada, N, Iwasaki, M, Le Marchand, L, Wu, A, McNeil, C, Coetzee, G, Hayward, C, Deary, I, Theodoratou, E, Reid, S, Walker, M, Ooi, LY, Moreno, V, Casey, G, Tomlinson, I, Zheng, W, Dunlop, M, Houlston, R, Peters, U, Fernandez-Rozadilla, C, Timofeeva, M, Chen, Z, Law, P, Thomas, M, Bien, S, Diez-Obrero, V, Li, L, Fernandez-Tajes, J, Palles, C, Sherwood, K, Harris, S, Svinti, V, McDonnell, K, Farrington, S, Studd, J, Vaughan-Shaw, P, Shu, X-O, Long, J, Cai, Q, Guo, X, Lu, Y, Scacheri, P, Huyghe, J, Harrison, T, Shibata, D, Haiman, C, Devall, M, Schumacher, F, Melas, M, Rennert, G, Obon-Santacana, M, Martin-Sanchez, V, Moratalla-Navarro, F, Oh, JH, Kim, J, Jee, SH, Jung, KJ, Kweon, S-S, Shin, M-H, Shin, A, Ahn, Y-O, Kim, D-H, Oze, I, Wen, W, Matsuo, K, Matsuda, K, Tanikawa, C, Ren, Z, Gao, Y-T, Jia, W-H, Potter, J, Jenkins, M, Win, AK, Pai, R, Figueiredo, J, Haile, R, Gallinger, S, Woods, M, Newcomb, P, Cheadle, J, Kaplan, R, Maughan, T, Kerr, R, Kerr, D, Kirac, I, Boehm, J, Mecklin, L-P, Jousilahti, P, Knekt, P, Aaltonen, L, Rissanen, H, Pukkala, E, Eriksson, J, Cajuso, T, Hanninen, U, Kondelin, J, Palin, K, Tanskanen, T, Renkonen-Sinisalo, L, Zanke, B, Mannisto, S, Albanes, D, Weinstein, S, Ruiz-Narvaez, E, Palmer, J, Buchanan, D, Platz, E, Visvanathan, K, Ulrich, C, Siegel, E, Brezina, S, Gsur, A, Campbell, P, Chang-Claude, J, Hoffmeister, M, Brenner, H, Slattery, M, Tsilidis, K, Schulze, M, Gunter, M, Murphy, N, Castells, A, Castellvi-Bel, S, Moreira, L, Arndt, V, Shcherbina, A, Stern, M, Pardamean, B, Bishop, T, Giles, G, Southey, M, Idos, G, Abu-Ful, Z, Greenson, J, Shulman, K, Lejbkowicz, F, Offit, K, Su, Y-R, Steinfelder, R, Keku, T, van Guelpen, B, Hudson, T, Hampel, H, Pearlman, R, Berndt, S, Hayes, R, Martinez, ME, Thomas, S, Corley, D, Pharoah, P, Larsson, S, Yen, Y, Lenz, H-J, White, E, Doheny, K, Pugh, E, Shelford, T, Chan, A, Cruz-Correa, M, Lindblom, A, Joshi, A, Schafmayer, C, Kundaje, A, Nickerson, D, Schoen, R, Hampe, J, Stadler, Z, Vodicka, P, Vodickova, L, Vymetalkova, V, Papadopoulos, N, Edlund, C, Gauderman, W, Thomas, D, Toland, A, Markowitz, S, Kim, A, Gruber, S, van Duijnhoven, F, Feskens, E, Sakoda, L, Gago-Dominguez, M, Wolk, A, Naccarati, A, Pardini, B, FitzGerald, L, Lee, SC, Ogino, S, Kooperberg, C, Li, C, Lin, Y, Prentice, R, Qu, C, Bezieau, S, Tangen, C, Mardis, E, Yamaji, T, Sawada, N, Iwasaki, M, Le Marchand, L, Wu, A, McNeil, C, Coetzee, G, Hayward, C, Deary, I, Theodoratou, E, Reid, S, Walker, M, Ooi, LY, Moreno, V, Casey, G, Tomlinson, I, Zheng, W, Dunlop, M, Houlston, R, and Peters, U

Abstract

Colorectal cancer (CRC) is a leading cause of mortality worldwide. We conducted a genome-wide association study meta-analysis of 100,204 CRC cases and 154,587 controls of European and east Asian ancestry, identifying 205 independent risk associations, of which 50 were unreported. We performed integrative genomic, transcriptomic and methylomic analyses across large bowel mucosa and other tissues. Transcriptome- and methylome-wide association studies revealed an additional 53 risk associations. We identified 155 high-confidence effector genes functionally linked to CRC risk, many of which had no previously established role in CRC. These have multiple different functions and specifically indicate that variation in normal colorectal homeostasis, proliferation, cell adhesion, migration, immunity and microbial interactions determines CRC risk. Crosstissue analyses indicated that over a third of effector genes most probably act outside the colonic mucosa. Our findings provide insights into colorectal oncogenesis and highlight potential targets across tissues for new CRC treatment and chemoprevention strategies.

Published
2023

38. Open science discovery of potent noncovalent SARS-CoV-2 main protease inhibitors.

Author

Boby, M.L., Fearon, D., Ferla, M., Filep, M., Koekemoer, L., Robinson, M.C., Chodera, J.D., Lee, A.A., London, N., Delft, A. von, Delft, F. von, Achdout, H., Aimon, A., Alonzi, D.S., Arbon, R., Aschenbrenner, J.C., Balcomb, B.H., Bar-David, E., Barr, H., Ben-Shmuel, A., Bennett, J., Bilenko, V.A., Borden, B., Boulet, P., Bowman, G.R., Brewitz, L., Brun, J., Bvnbs, S., Calmiano, M., Carbery, A., Carney, D.W., Cattermole, E., Chang, E., Chernyshenko, E., Clyde, A., Coffland, J.E., Cohen, G., Cole, J.C., Contini, A., Cox, L., Croll, T.I., Cvitkovic, M., Jonghe, S. De, Dias, A., Donckers, K., Dotson, D.L., Douangamath, A., Duberstein, S., Dudgeon, T., Dunnett, L.E., Eastman, P., Erez, N., Eyermann, C.J., Fairhead, M., Fate, G., Fedorov, O., Fernandes, R.S., Ferrins, L., Foster, R., Foster, H., Fraisse, L., Gabizon, R., García-Sastre, A., Gawriljuk, V.O., Gehrtz, P., Gileadi, C., Giroud, C., Glass, W.G., Glen, R.C., Glinert, I., Godoy, A.S., Gorichko, M., Gorrie-Stone, T., Griffen, E.J., Haneef, A., Hassell Hart, S, Heer, J., Henry, M., Hill, M., Horrell, S., Huang, Q.Y.J., Huliak, V.D., Hurley, M.F.D., Israely, T., Jajack, A., Jansen, J, Jnoff, E., Jochmans, D., John, T., Kaminow, B., Kang, L., Kantsadi, A.L., Kenny, P.W., Kiappes, J.L., Kinakh, S.O., Kovar, B., Krojer, T., La, V.N.T., Laghnimi-Hahn, S., Lefker, B.A., Levy, H., Lithgo, R.M., Logvinenko, I.G., Lukacik, P., Macdonald, H.B., MacLean, E.M., Makower, L.L., Malla, T.R., Marples, P.G., Matviiuk, T., McCorkindale, W., McGovern, B.L., Melamed, S., Melnykov, K.P., Michurin, O., Miesen, P., Mikolajek, H., Milne, B.F., Minh, D., Morris, A., Morris, G.M., Morwitzer, M.J., Moustakas, D., Mowbray, C.E., Nakamura, A.M., Neto, J.B., Neyts, J., Nguyen, L, Noske, G.D., Oleinikovas, V., Oliva, G., Overheul, G.J., Owen, C.D., Pai, R., Pan, J., Paran, N., Payne, A.M., Perry, B., Pingle, M., Pinjari, J., Politi, B., Powell, A., Pšenák, V., Pulido, I., Puni, R., Rangel, V.L., Reddi, R.N., Rees, P., Reid, S.P., Reid, L., Resnick, E., Ripka, E.G., Robinson, R.P., Rodriguez-Guerra, J., Rosales, R., Rufa, D.A., Saar, K., Saikatendu, K.S., Salah, E., Schaller, D., Scheen, J., Schiffer, C.A., Schofield, C.J., Shafeev, M., Shaikh, A., Shaqra, A.M., Shi, J., Shurrush, K., Singh, S., Sittner, A., Sjö, P., Skyner, R., Smalley, A., Smeets, B., Smilova, M.D., Solmesky, L.J., Spencer, J., Strain-Damerell, C., Swamy, V., Tamir, H., Taylor, J.C., Tennant, R.E., Thompson, W., Thompson, A., Tomásio, S., Tomlinson, C.W.E., Tsurupa, I.S., Tumber, A., Vakonakis, I., Rij, R.P. van, Vangeel, L., Varghese, F.S., Vaschetto, M., Vitner, E.B., Voelz, V., Volkamer, A., Walsh, M.A., Ward, W., Weatherall, C., Weiss, S., White, K.M., Wild, C.F., Witt, K.D., Wittmann, M., Wright, N., Yahalom-Ronen, Y., Yilmaz, N.K., Zaidmann, D., Zhang, I., Zidane, H., Zitzmann, N., Zvornicanin, S.N., Boby, M.L., Fearon, D., Ferla, M., Filep, M., Koekemoer, L., Robinson, M.C., Chodera, J.D., Lee, A.A., London, N., Delft, A. von, Delft, F. von, Achdout, H., Aimon, A., Alonzi, D.S., Arbon, R., Aschenbrenner, J.C., Balcomb, B.H., Bar-David, E., Barr, H., Ben-Shmuel, A., Bennett, J., Bilenko, V.A., Borden, B., Boulet, P., Bowman, G.R., Brewitz, L., Brun, J., Bvnbs, S., Calmiano, M., Carbery, A., Carney, D.W., Cattermole, E., Chang, E., Chernyshenko, E., Clyde, A., Coffland, J.E., Cohen, G., Cole, J.C., Contini, A., Cox, L., Croll, T.I., Cvitkovic, M., Jonghe, S. De, Dias, A., Donckers, K., Dotson, D.L., Douangamath, A., Duberstein, S., Dudgeon, T., Dunnett, L.E., Eastman, P., Erez, N., Eyermann, C.J., Fairhead, M., Fate, G., Fedorov, O., Fernandes, R.S., Ferrins, L., Foster, R., Foster, H., Fraisse, L., Gabizon, R., García-Sastre, A., Gawriljuk, V.O., Gehrtz, P., Gileadi, C., Giroud, C., Glass, W.G., Glen, R.C., Glinert, I., Godoy, A.S., Gorichko, M., Gorrie-Stone, T., Griffen, E.J., Haneef, A., Hassell Hart, S, Heer, J., Henry, M., Hill, M., Horrell, S., Huang, Q.Y.J., Huliak, V.D., Hurley, M.F.D., Israely, T., Jajack, A., Jansen, J, Jnoff, E., Jochmans, D., John, T., Kaminow, B., Kang, L., Kantsadi, A.L., Kenny, P.W., Kiappes, J.L., Kinakh, S.O., Kovar, B., Krojer, T., La, V.N.T., Laghnimi-Hahn, S., Lefker, B.A., Levy, H., Lithgo, R.M., Logvinenko, I.G., Lukacik, P., Macdonald, H.B., MacLean, E.M., Makower, L.L., Malla, T.R., Marples, P.G., Matviiuk, T., McCorkindale, W., McGovern, B.L., Melamed, S., Melnykov, K.P., Michurin, O., Miesen, P., Mikolajek, H., Milne, B.F., Minh, D., Morris, A., Morris, G.M., Morwitzer, M.J., Moustakas, D., Mowbray, C.E., Nakamura, A.M., Neto, J.B., Neyts, J., Nguyen, L, Noske, G.D., Oleinikovas, V., Oliva, G., Overheul, G.J., Owen, C.D., Pai, R., Pan, J., Paran, N., Payne, A.M., Perry, B., Pingle, M., Pinjari, J., Politi, B., Powell, A., Pšenák, V., Pulido, I., Puni, R., Rangel, V.L., Reddi, R.N., Rees, P., Reid, S.P., Reid, L., Resnick, E., Ripka, E.G., Robinson, R.P., Rodriguez-Guerra, J., Rosales, R., Rufa, D.A., Saar, K., Saikatendu, K.S., Salah, E., Schaller, D., Scheen, J., Schiffer, C.A., Schofield, C.J., Shafeev, M., Shaikh, A., Shaqra, A.M., Shi, J., Shurrush, K., Singh, S., Sittner, A., Sjö, P., Skyner, R., Smalley, A., Smeets, B., Smilova, M.D., Solmesky, L.J., Spencer, J., Strain-Damerell, C., Swamy, V., Tamir, H., Taylor, J.C., Tennant, R.E., Thompson, W., Thompson, A., Tomásio, S., Tomlinson, C.W.E., Tsurupa, I.S., Tumber, A., Vakonakis, I., Rij, R.P. van, Vangeel, L., Varghese, F.S., Vaschetto, M., Vitner, E.B., Voelz, V., Volkamer, A., Walsh, M.A., Ward, W., Weatherall, C., Weiss, S., White, K.M., Wild, C.F., Witt, K.D., Wittmann, M., Wright, N., Yahalom-Ronen, Y., Yilmaz, N.K., Zaidmann, D., Zhang, I., Zidane, H., Zitzmann, N., and Zvornicanin, S.N.

Abstract

Item does not contain fulltext, We report the results of the COVID Moonshot, a fully open-science, crowdsourced, and structure-enabled drug discovery campaign targeting the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease. We discovered a noncovalent, nonpeptidic inhibitor scaffold with lead-like properties that is differentiated from current main protease inhibitors. Our approach leveraged crowdsourcing, machine learning, exascale molecular simulations, and high-throughput structural biology and chemistry. We generated a detailed map of the structural plasticity of the SARS-CoV-2 main protease, extensive structure-activity relationships for multiple chemotypes, and a wealth of biochemical activity data. All compound designs (>18,000 designs), crystallographic data (>490 ligand-bound x-ray structures), assay data (>10,000 measurements), and synthesized molecules (>2400 compounds) for this campaign were shared rapidly and openly, creating a rich, open, and intellectual property-free knowledge base for future anticoronavirus drug discovery.

Published
2023

39. Expression of endothelin-1, and endothelin A and B receptors in portal hypertensive esophagus of rats.

Author

Ohta, M, Pai, R, Kawanaka, H, Ma, T, Sugimachi, K, Sarfeh, I J, and Tarnawski, A S

Subjects
Animals, Endothelin-1: genetics, metabolism, Esophagus: metabolism, Hypertension, Portal: metabolism, physiopathology, Mucous Membrane: metabolism, Portal Vein: physiopathology, RNA, Messenger: metabolism, Rats, Rats, Sprague-Dawley, Receptor, Endothelin A, Receptor, Endothelin B, Receptors, Endothelin: genetics, metabolism, Venous Pressure, portal hypertension, esophageal varices, endothelin-1, endothelin receptornecrosis-factor-alpha, smooth-muscle cells, nitric-oxide, messenger-rna, hyperdynamic circulation, clinical-significance, plasma endothelin-1, cirrhotic rats, growth-factor, cloning
Abstract

Nitric oxide synthase is overexpressed in the portal hypertensive (PHT) esophagus, suggesting that expression of other vasoactive mediatora could also be affected. Therefore, in the present study we determined the expression of endothelin-1 (ET-1) and endothelin receptors, which could contribute to the regulation of the vascular tone in PHT esophagus. In esophageal specimens of PHT and sham operated rats, expression of ET-1 and its receptors A and B (ET(A)R and ET(B)R) mRNAs was studied by reverse transcription-polymerase chain reactions. ET-1 protein expression was assessed by immunostaining and enzyme immunoassay. In PHT esophagus, expression of ET-1, ET(A)R and ET(B)R mRNAs was significantly increased by 2.2-, 2.5- and 1.5-fold, respectively, compared with sham operated. The ET-1 protein was significantly increased by 2.2-fold vs. controls as measured by enzyme immunoassay. ET-1 protein was predominantly localized to endothelia of submucosal veins. Thus, portal hypertension induces over-expression of ET-1 in endothelia of esophageal submucosal vessels. Since ET-1 and its receptors could promote vascular proliferation and induce mucosal damage, the overexpressed ET-1 may play an important role in the development and rupture of esophageal varices in portal hypertension.

Published
2000

43. P479 Reliability and responsiveness of histologic disease activity indices in Crohn’s Disease

Author

Solitano, V, primary, Schaeffer, D F, additional, Hogan, M, additional, Pai, R K, additional, Zou, G, additional, Vande Casteele, N, additional, Parker, C E, additional, Remillard, J, additional, Christensen, B, additional, Panaccione, R, additional, Sands, B E, additional, D’Haens, G, additional, Feagan, B G, additional, Ma, C, additional, and Jairath, V, additional

Published
2023
Full Text
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49. A subset of Kupffer cells regulates metabolism through the expression of CD36

Author

Bleriot, C, Barreby, E, Dunsmore, G, Ballaire, R, Chakarov, S, Ficht, X, De Simone, G, Andreata, F, Fumagalli, V, Guo, W, Wan, G, Gessain, G, Khalilnezhad, A, Zhang, X, Ang, N, Chen, P, Morgantini, C, Azzimato, V, Kong, W, Liu, Z, Pai, R, Lum, J, Shihui, F, Low, I, Xu, C, Malleret, B, Kairi, M, Balachander, A, Cexus, O, Larbi, A, Lee, B, Newell, E, Ng, L, Phoo, W, Sobota, R, Sharma, A, Howland, S, Chen, J, Bajenoff, M, Yvan-Charvet, L, Venteclef, N, Iannacone, M, Aouadi, M, Ginhoux, F, Bleriot C., Barreby E., Dunsmore G., Ballaire R., Chakarov S., Ficht X., De Simone G., Andreata F., Fumagalli V., Guo W., Wan G., Gessain G., Khalilnezhad A., Zhang X. M., Ang N., Chen P., Morgantini C., Azzimato V., Kong W. T., Liu Z., Pai R., Lum J., Shihui F., Low I., Xu C., Malleret B., Kairi M. F. M., Balachander A., Cexus O., Larbi A., Lee B., Newell E. W., Ng L. G., Phoo W. W., Sobota R. M., Sharma A., Howland S. W., Chen J., Bajenoff M., Yvan-Charvet L., Venteclef N., Iannacone M., Aouadi M., Ginhoux F., Bleriot, C, Barreby, E, Dunsmore, G, Ballaire, R, Chakarov, S, Ficht, X, De Simone, G, Andreata, F, Fumagalli, V, Guo, W, Wan, G, Gessain, G, Khalilnezhad, A, Zhang, X, Ang, N, Chen, P, Morgantini, C, Azzimato, V, Kong, W, Liu, Z, Pai, R, Lum, J, Shihui, F, Low, I, Xu, C, Malleret, B, Kairi, M, Balachander, A, Cexus, O, Larbi, A, Lee, B, Newell, E, Ng, L, Phoo, W, Sobota, R, Sharma, A, Howland, S, Chen, J, Bajenoff, M, Yvan-Charvet, L, Venteclef, N, Iannacone, M, Aouadi, M, Ginhoux, F, Bleriot C., Barreby E., Dunsmore G., Ballaire R., Chakarov S., Ficht X., De Simone G., Andreata F., Fumagalli V., Guo W., Wan G., Gessain G., Khalilnezhad A., Zhang X. M., Ang N., Chen P., Morgantini C., Azzimato V., Kong W. T., Liu Z., Pai R., Lum J., Shihui F., Low I., Xu C., Malleret B., Kairi M. F. M., Balachander A., Cexus O., Larbi A., Lee B., Newell E. W., Ng L. G., Phoo W. W., Sobota R. M., Sharma A., Howland S. W., Chen J., Bajenoff M., Yvan-Charvet L., Venteclef N., Iannacone M., Aouadi M., and Ginhoux F.

Abstract

Tissue macrophages are immune cells whose phenotypes and functions are dictated by origin and niches. However, tissues are complex environments, and macrophage heterogeneity within the same organ has been overlooked so far. Here, we used high-dimensional approaches to characterize macrophage populations in the murine liver. We identified two distinct populations among embryonically derived Kupffer cells (KCs) sharing a core signature while differentially expressing numerous genes and proteins: a major CD206loESAM– population (KC1) and a minor CD206hiESAM+ population (KC2). KC2 expressed genes involved in metabolic processes, including fatty acid metabolism both in steady-state and in diet-induced obesity and hepatic steatosis. Functional characterization by depletion of KC2 or targeted silencing of the fatty acid transporter Cd36 highlighted a crucial contribution of KC2 in the liver oxidative stress associated with obesity. In summary, our study reveals that KCs are more heterogeneous than anticipated, notably describing a subpopulation wired with metabolic functions.

Published
2021

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