المؤلفون: Hills, Rebecca, Ishii, Satoshi, Jancar, Sonia, McIntyre, Thomas, Ninio, Ewa, O'Neill, Chris, Oliveira Rios, Francisco Jose, Travers, Jeffery B., Whittaker, Mark

المصدر: IUPHAR/BPS Guide to Pharmacology CITE; Vol 2023 No 1 (2023) ; 2633-1020

الوصف: Platelet-activating factor (PAF, 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine) is an ether phospholipid mediator associated with platelet coagulation, but also subserves inflammatory roles. The PAF receptor (provisional nomenclature recommended by NC-IUPHAR [38]) is activated by PAF and other suggested endogenous ligands are oxidized phosphatidylcholine [74] and lysophosphatidylcholine [98]. It may also be activated by bacterial lipopolysaccharide [91].

وصف الملف: application/pdf; text/html

العلاقة: http://journals.ed.ac.uk/gtopdb-cite/article/view/8703/11503Test; http://journals.ed.ac.uk/gtopdb-cite/article/view/8703/11504Test; http://journals.ed.ac.uk/gtopdb-cite/article/view/8703/11505Test; http://journals.ed.ac.uk/gtopdb-cite/article/view/8703Test

الإتاحة: https://doi.org/10.2218/gtopdb/F55/2023.1Test
http://journals.ed.ac.uk/gtopdb-cite/article/view/8703Test

المؤلفون: Cao, Chuan, Zhang, Lingjun, Sorensen, Mia D., Reifenberger, Guido, Kristensen, Bjarne W., McIntyre, Thomas M., Lin, Feng

المصدر: Cao , C , Zhang , L , Sorensen , M D , Reifenberger , G , Kristensen , B W , McIntyre , T M & Lin , F 2023 , ' D-2-hydroxyglutarate regulates human brain vascular endothelial cell proliferation and barrier function ' , Journal of Neuropathology & Experimental Neurology , vol. 82 , no. 11 , pp. 921-933 . https://doi.org/10.1093/jnen/nlad072Test

مصطلحات موضوعية: (D)-2-hydroxyglutarate (D-2HG), Astrocytic glioma, Brain vascular endothelial cell, Glioblastoma, Isocitrate dehydrogenase (IDH), Microvascular proliferation

الوصف: Gain-of-function mutations in isocitrate dehydrogenase (IDH) genes result in excessive production of (D)-2-hydroxyglutarate (D-2HG) which intrinsically modifies tumor cell epigenetics and impacts surrounding noncancerous cells through nonepigenetic pathways. However, whether D-2HG has a paracrine effect on endothelial cells in the tumor microenvironment needs further clarification. We quantified microvessel density by immunohistochemistry using tissue sections from 60 high-grade astrocytic gliomas with or without IDH mutation. Microvessel density was found to be reduced in tumors carrying an IDH mutation. Ex vivo experiments showed that D-2HG inhibited endothelial cell migration, wound healing, and tube formation by suppressing cell proliferation but not viability, possibly through reduced activation of the mTOR/STAT3 pathway. Further, D-2HG reduced fluorescent dextran permeability and decreased paracellular T-cell transendothelial migration by augmenting expression of junctional proteins thereby collectively increasing endothelial barrier function. These results indicate that D-2HG may influence the tumor vascular microenvironment by reducing the intratumoral vasculature density and by inhibiting the transport of metabolites and extravasation of circulating cells into the astrocytoma microenvironment. These observations provide a rationale for combining IDH inhibition with antitumor immunological/angiogenic approaches and suggest a molecular basis for resistance to antiangiogenic drugs in patients whose tumors express a mutant IDH allele.

العلاقة: https://portal.findresearcher.sdu.dk/da/publications/569c94ef-90df-4647-bbf7-6e5c69ea561bTest

الإتاحة: https://doi.org/10.1093/jnen/nlad072Test
https://portal.findresearcher.sdu.dk/da/publications/569c94ef-90df-4647-bbf7-6e5c69ea561bTest
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3444730/pdf/2038.pdfTest

المؤلفون: Jeon, Hye-Min, Kim, Jeong-Yub, Cho, Hee Jin, Lee, Won Jun, Nguyen, Dayna, Kim, Sung Soo, Oh, Young Taek, Kim, Hee-Jin, Jung, Chan-Woong, Pinero, Gonzalo, Joshi, Tanvi, Hambardzumyan, Dolores, Sakaguchi, Takuya, Hubert, Christopher G., McIntyre, Thomas M., Fine, Howard A., Gladson, Candece L., Wang, Bingcheng, Purow, Benjamin W., Park, Jong Bae, Park, Myung Jin, Nam, Do-Hyun, Lee, Jeongwu

المساهمون: National Institutes of Health

المصدر: Cancer Cell ; volume 41, issue 8, page 1480-1497.e9 ; ISSN 1535-6108

مصطلحات موضوعية: Cancer Research, Oncology

الإتاحة: https://doi.org/10.1016/j.ccell.2023.06.007Test
https://api.elsevier.com/content/article/PII:S1535610823002179?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S1535610823002179?httpAccept=text/plainTest

المؤلفون: McIntyre, Thomas, Seres, David, Chiasson, Mary Ann

المصدر: Current Developments in Nutrition ; volume 7, page 101146 ; ISSN 2475-2991

مصطلحات موضوعية: Nutrition and Dietetics, Food Science, Medicine (miscellaneous)

الإتاحة: https://doi.org/10.1016/j.cdnut.2023.101146Test
https://api.elsevier.com/content/article/PII:S2475299123258552?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S2475299123258552?httpAccept=text/plainTest

المؤلفون: McIntyre, Thomas Jeremiah

مرشدي الرسالة: Ghaleigh, Navraj ; Brown, Abbe

مصطلحات موضوعية: 343.09, internet, blocking, filtering, censorship, child protection, regulation, governance

الوصف: This thesis examines the legal and governance issues presented by internet blocking (“filtering”) systems through the use of the United Kingdom’s Cleanfeed system as a national case study. The Cleanfeed system – which aims to block access to child abuse images – has been influential both domestically and internationally but has been the subject of relatively little sustained scrutiny in the literature. Using a mixed doctrinal and empirical methodology this work discusses the evolution of Cleanfeed and considers the way in which government pressure has led to a private body without any express legislative basis (the Internet Watch Foundation) being given the power to control what UK internet users can view. The thesis argues that the Cleanfeed system sits at the intersection of three distinct trends – the use of architectural regulation, regulation through intermediaries and self-regulation – which individually and collectively present significant risks for freedom of expression and good governance online. It goes on to identify and examine the fundamental rights norms and governance standards which should apply to internet blocking and tests the system against them, arguing in particular that Cleanfeed fails to meet the requirements developed by the European Court of Human Rights under Articles 6 and 10 ECHR. It considers the extent to which Cleanfeed might be made amenable to these principles through the use of judicial review or actions under the Human Rights Act 1998 and concludes that the diffuse structure of the system and the limited availability of horizontal effect against private bodies will leave significant aspects beyond the effective reach of the courts. This work also assesses claims that the Cleanfeed system is a proof of concept which should be extended so as to block other material considered objectionable (such as websites which “glorify terrorism”). It argues that the peculiar features of the system mean that it represents a best case scenario and does not support blocking of other types of content which are significantly more problematic. The thesis concludes by considering proposals for reform of the Cleanfeed system and the extent to which greater public law oversight might undermine the desirable features associated with self-regulation.

الإتاحة: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.699982Test

المؤلفون: Aggarwal, Anu, Singh, Tamanna K, Pham, Michael, Godwin, Matthew, Chen, Rui, McIntyre, Thomas M, Scalise, Alliefair, Chung, Mina K, Jennings, Courtney, Ali, Mariya, Park, Hiijun, Englund, Kristin, Khorana, Alok A, Svensson, Lars G, Kapadia, Samir, McCrae, Keith R, Cameron, Scott J

المصدر: Vasc Med ; ISSN:1477-0377 ; Volume:29 ; Issue:2

مصطلحات موضوعية: COVID-19, long COVID-19, platelets, thrombosis

الوصف: Postacute sequelae of COVID-19 (PASC), also referred to as "Long COVID", sometimes follows COVID-19, a disease caused by SARS-CoV-2. Although SARS-CoV-2 is well known to promote a prothrombotic state, less is known about the thrombosis risk in PASC. Our objective was to evaluate platelet function and thrombotic potential in patients following recovery from SARS-CoV-2, but with clear symptoms of patients with PASC.

العلاقة: https://doi.org/10.1177/1358863X231224383Test; https://pubmed.ncbi.nlm.nih.gov/38334067Test; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11164201Test/

الإتاحة: https://doi.org/10.1177/1358863X231224383Test
https://pubmed.ncbi.nlm.nih.gov/38334067Test
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11164201Test/

المؤلفون: Chen, Lechuang, Chen, Rui, Yao, Min, Feng, Zhimin, Yuan, Guoxiang, Ye, Fengchun, Nguyen, Kien, Karn, Jonathan, McComsey, Grace A., McIntyre, Thomas M., Jin, Ge

المساهمون: National Institutes of Health

المصدر: Scientific Reports ; volume 12, issue 1 ; ISSN 2045-2322

مصطلحات موضوعية: Multidisciplinary

الوصف: Elevated serum cytokine production in COVID-19 patients is associated with disease progression and severity. However, the stimuli that initiate cytokine production in patients remain to be fully revealed. Virus-infected cells release virus-associated exosomes, extracellular vesicles of endocytic origin, into the blood to deliver viral cargoes able to regulate immune responses. Here, we report that plasma exosomes of COVID-19 patients contain SARS-CoV-2 double stranded RNA (dsRNA) and stimulate robust production of interleukin-6 (IL-6), IL-8, tumor necrosis factor-α (TNF-α), and other inflammatory cytokines and chemokines by human peripheral mononuclear cells. Exosome depletion abolished these stimulated responses. COVID-19 plasma exosomes induced proinflammatory responses in CD4 + T cells, CD8 + T cells, and CD14 + monocytes but not significantly in regulatory T cells, Th17 T cells, or central memory T cells. COVID-19 plasma exosomes protect the SARS-CoV-2 dsRNA cargo from RNase and deliver the dsRNA into recipient cells. These exosomes significantly increase expression of endosomal toll-like receptor 3 (TLR3), TLR7, TLR8, and TLR9 in peripheral T cells and monocytes. A pharmacological inhibitor of TLR3 considerably reduced cytokine and chemokine production by CD4 + and CD8 + T cells but not by CD14 + monocytes, highlighting divergent signaling pathways of immune cells in response to COVID-19 plasma exosomes. Our results identify a novel model of intercellular crosstalk following SARS-CoV-2 infection that evoke immune responses positioned to contribute to elevated cytokine production associated with COVID-19 progression, severity, and long-haul symptoms.

الإتاحة: https://doi.org/10.1038/s41598-022-26457-8Test
https://www.nature.com/articles/s41598-022-26457-8.pdfTest
https://www.nature.com/articles/s41598-022-26457-8Test

المؤلفون: McIntyre, Thomas, Barowsky, Ellis I., Tong, Virginia

المصدر: Journal of the American Academy of Special Education Professionals. Fall 2011:4-21.

تمت مراجعته من قبل الزملاء: Y

Page Count: 18

الواصفات: Immigrants, Student Adjustment, Behavior Problems, Emotional Disturbances, Behavior Disorders, Cultural Differences, Student Needs, Psychological Needs, English Language Learners, Student Evaluation, Teaching Styles, Cognitive Style, Teacher Education, Intervention, Foreign Countries

مصطلحات جغرافية: North America

مستخلص: Educators' lack of knowledge of the cultural and immigration overlays on behaviors presents a quandary. It makes it difficult, given the present state of assessment in this area, to determine whether an emotional or behavioral disorder exists, or whether the behavior is acceptable to the newcomer's culture and therefore reflects a cultural marker. This article addresses factors to be considered in making this differentiation, and provides information and guidance in meeting the psychological, emotional, and social needs of recent immigrant students.

Abstractor: As Provided

المؤلفون: Sumanth, M. S., Shancy P. Jacob, Abhilasha, K. V., Manne, Bhanu Kanth, Venkatesha, B., Lehoux, Sylvain, Campbell, Robert A., Yost, Christian C., McIntyre, Thomas M., Cummings, Richard D., Weyrich, Andrew S., Rondina, Matthew T., Marathe, Gopal K.

مصطلحات موضوعية: Biochemistry

الوصف: Alpha-1-acid glycoprotein (AGP-1) is a positive acute phase glycoprotein with uncertain functions. Serum AGP-1 (sAGP-1) is primarily derived from hepatocytes and circulates as 12-20 different glycoforms. We isolated a glycoform secreted from platelet-activating factor (PAF)-stimulated human neutrophils (nAGP-1). Its peptide sequence was identical to hepatocyte-derived sAGP-1, but nAGP-1 differed from sAGP-1 in its chromatographic behavior, electrophoretic mobility, and pattern of glycosylation. The function of these 2 glycoforms also differed. sAGP-1 activated neutrophil adhesion, migration, and neutrophil extracellular traps (NETosis) involving myeloperoxidase, peptidylarginine deiminase 4, and phosphorylation of ERK in a dose-dependent fashion, whereas nAGP-1 was ineffective as an agonist for these events. Furthermore, sAGP-1, but not nAGP-1, inhibited LPS-stimulated NETosis. Interestingly, nAGP-1 inhibited sAGP-1-stimulated neutrophil NETosis. The discordant effect of the differentially glycosylated AGP-1 glycoforms was also observed in platelets where neither of the AGP-1 glycoforms alone stimulated aggregation of washed human platelets, but sAGP-1, and not nAGP-1, inhibited aggregation induced by PAF or ADP, but not by thrombin. These functional effects of sAGP-1 correlated with intracellular cAMP accumulation and phosphorylation of the protein kinase A substrate vasodilator-stimulated phosphoprotein and reduction of Akt, ERK, and p38 phosphorylation. Thus, the sAGP-1 glycoform limits platelet reactivity, whereas nAGP-1 glycoform also limits proinflammatory actions of sAGP-1. These studies identify new functions for this acute phase glycoprotein and demonstrate that the glycosylation of AGP-1 controls its effects on 2 critical cells of acute inflammation.

العلاقة: Sumanth, M. S. and Shancy P. Jacob and Abhilasha, K. V. and Manne, Bhanu Kanth and Venkatesha, B. and Lehoux, Sylvain and Campbell, Robert A. and Yost, Christian C. and McIntyre, Thomas M. and Cummings, Richard D. and Weyrich, Andrew S. and Rondina, Matthew T. and Marathe, Gopal K. (2021) Different glycoforms of alpha-1-acid glycoprotein contribute to its functional alterations in platelets and neutrophils. Journal of Leukocyte Biology, 109 (5). pp. 915-930. ISSN 1938-3673

الإتاحة: https://doi.org/10.1002/JLB.3A0720-422RTest
http://eprints.uni-mysore.ac.in/15490Test/

المؤلفون: Sahai, Aditya, Bhandari, Rohan, Godwin, Matthew, McIntyre, Thomas, Chung, Mina K, Iskandar, Jean-Pierre, Kamran, Hayaan, Hariri, Essa, Aggarwal, Anu, Burton, Robert, Kalra, Ankur, Bartholomew, John R, McCrae, Keith R, Elbadawi, Ayman, Bena, James, Svensson, Lars G, Kapadia, Samir, Cameron, Scott J

المساهمون: National Heart, Lung, and Blood Institute

المصدر: Vascular Medicine ; volume 26, issue 6, page 626-632 ; ISSN 1358-863X 1477-0377

مصطلحات موضوعية: Cardiology and Cardiovascular Medicine

الوصف: Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 is an ongoing viral pandemic marked by increased risk of thrombotic events. However, the role of platelets in the elevated observed thrombotic risk in COVID-19 and utility of antiplatelet agents in attenuating thrombosis is unknown. We aimed to determine if the antiplatelet effect of aspirin may mitigate risk of myocardial infarction, cerebrovascular accident, and venous thromboembolism in COVID-19. We evaluated 22,072 symptomatic patients tested for COVID-19. Propensity-matched analyses were performed to determine if treatment with aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs) affected thrombotic outcomes in COVID-19. Neither aspirin nor NSAIDs affected mortality in COVID-19. Thus, aspirin does not appear to prevent thrombosis and death in COVID-19. The mechanisms of thrombosis in COVID-19, therefore, appear distinct and the role of platelets as direct mediators of SARS-CoV-2-mediated thrombosis warrants further investigation.

الإتاحة: https://doi.org/10.1177/1358863x211012754Test