Author: "The University of Texas Medical Branch ( UTMB )" / Topic: 0302 clinical medicine - Searchworks@Jio Institute Digital Library Search Results

Your search keyword '"The University of Texas Medical Branch ( UTMB )"' showing total 30 results

Start Over Author "The University of Texas Medical Branch ( UTMB )" Topic 0302 clinical medicine

30 results on '"The University of Texas Medical Branch ( UTMB )"'

1. Dynamic interactions and Ca2+-binding modulate the holdase-type chaperone activity of S100B preventing tau aggregation and seeding

Author: Urmi Sengupta, Guilherme G. Moreira, Ana P. Carapeto, Filipa S. Carvalho, Andrea Quezada, Mário Rodrigues, Isabel Cardoso, Guenter Fritz, Nicha Puangmalai, Isabelle Landrieu, Federico Herrera, Rakez Kayed, Cláudio M. Gomes, Joana S. Cristóvão, François Xavier Cantrelle, Universidade de Lisboa = University of Lisbon (ULISBOA), Biologie Structurale Intégrative (ERL 9002 - BSI ), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 (RID-AGE), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), The University of Texas Medical Branch (UTMB), Universidade do Porto = University of Porto, Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), University of Hohenheim, This work was funded by Fundação para a Ciência e Tecnologia (Portugal) through research grants PTDC/NEU-NMC/2138/2014 (to C.M.G.), PTDC/BIA-BQM/29963/2017 (F.S.C.), PTDC/MED-NEU/31417/2017 (to F.H.), and POCI-01-0145-FEDER-007274 (to I.C.), investigator grants CEECIND/00031/2017 (to A.P.C.) and IF/00094/2013/CP1173/CT0005 (to F.H.), PhD fellowship SFRH/BD/101171/2014 (to J.S.C.) and DFA/BD/6443/2020 (to G.G.M.), and center grants UIDB/04046/2020 and UID/MULTI/04046/2020 (to BioISI) and Norte-01-0145-FEDER-000008 (to IBMC/I3S)., Landrieu, Isabelle, Universidade de Lisboa (ULISBOA), and Universidade do Porto
Subjects: [SDV.BBM.BS] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], Science, Tau protein, General Physics and Astronomy, tau Proteins, S100 Calcium Binding Protein beta Subunit, Protein Aggregation, Pathological, Article, Biophysical Phenomena, General Biochemistry, Genetics and Molecular Biology, Cell Line, 03 medical and health sciences, 0302 clinical medicine, Microtubule, Biophysical chemistry, Calcium-binding protein, mental disorders, Humans, Protein folding, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], Nuclear Magnetic Resonance, Biomolecular, [SDV.BBM.BC] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], 030304 developmental biology, 0303 health sciences, Multidisciplinary, biology, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], Chemistry, Neurodegenerative Diseases, General Chemistry, Kinetics, Proteostasis, Structural biology, Chaperone (protein), biology.protein, Biophysics, Protein Structural Elements, 030217 neurology & neurosurgery, Molecular Chaperones, Protein Binding, Binding domain
Abstract: The microtubule-associated protein tau is implicated in the formation of oligomers and fibrillar aggregates that evade proteostasis control and spread from cell-to-cell. Tau pathology is accompanied by sustained neuroinflammation and, while the release of alarmin mediators aggravates disease at late stages, early inflammatory responses encompass protective functions. This is the case of the Ca2+-binding S100B protein, an astrocytic alarmin which is augmented in AD and which has been recently implicated as a proteostasis regulator, acting over amyloid β aggregation. Here we report the activity of S100B as a suppressor of tau aggregation and seeding, operating at sub-stoichiometric conditions. We show that S100B interacts with tau in living cells even in microtubule-destabilizing conditions. Structural analysis revealed that tau undergoes dynamic interactions with S100B, in a Ca2+-dependent manner, notably with the aggregation prone repeat segments at the microtubule binding regions. This interaction involves contacts of tau with a cleft formed at the interface of the S100B dimer. Kinetic and mechanistic analysis revealed that S100B inhibits the aggregation of both full-length tau and of the microtubule binding domain, and that this proceeds through effects over primary and secondary nucleation, as confirmed by seeding assays and direct observation of S100B binding to tau oligomers and fibrils. In agreement with a role as an extracellular chaperone and its accumulation near tau positive inclusions, we show that S100B blocks proteopathic tau seeding. Together, our findings establish tau as a client of the S100B chaperone, providing evidence for neuro-protective functions of this inflammatory mediator across different tauopathies., The calcium binding protein S100B is an abundantly expressed protein in the brain and has neuro-protective functions by inhibiting Aβ aggregation and metal ion toxicity. Here, the authors combine cell biology and biochemical experiments with chemical kinetics and NMR measurements and show that S100B protein is an extracellular Tau chaperone and further characterize the interactions between S100B and Tau.
Published: 2021
Full Text: View/download PDF

2. Antioxidant Supplementation Does Not Affect Bone Turnover Markers During 60 Days of 6° Head-Down Tilt Bed Rest: Results from an Exploratory Randomized Controlled Trial

Author: Natalie Baecker, Jean-Pol Frippiat, Katharina Austermann, Peter Stehle, Scott M. Smith, Rolf Fimmers, Martina Heer, Sara R. Zwart, Rheinische Friedrich-Wilhelms-Universität Bonn, The University of Texas Medical Branch (UTMB), Stress, Immunité, Pathogènes (SIMPA), Université de Lorraine (UL), NASA Johnson Space Center (JSC), and NASA
Subjects: Adult, Male, 0301 basic medicine, medicine.medical_specialty, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Medicine (miscellaneous), Parathyroid hormone, 030209 endocrinology & metabolism, Antioxidants, Collagen Type I, Bone resorption, Bone remodeling, Head-Down Tilt, Selenium, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Fatty Acids, Omega-3, medicine, Humans, Vitamin E, Single-Blind Method, Bone Resorption, 2. Zero hunger, Calcium metabolism, 030109 nutrition & dietetics, Nutrition and Dietetics, biology, business.industry, Polyphenols, Urinary calcium, 3. Good health, Endocrinology, Dietary Supplements, Osteocalcin, biology.protein, Calcium, Bone Remodeling, business, Bed Rest, Biomarkers, Type I collagen
Abstract: International audience; Background Immobilization and related oxidative stress are associated with bone loss. Antioxidants like polyphenols, omega-3 fatty acids, vitamins, and micronutrients may mitigate these negative effects on bone metabolism through scavenging of free radicals. Objectives We hypothesized that antioxidant supplementation during 60 days of 6° head-down tilt bed rest (HDBR) would reduce bone resorption and increase bone formation compared to nonsupplemented controls. Methods This exploratory randomized, controlled, single-blind intervention study conducted in a parallel design included 20 healthy male volunteers (age, 34 ± 8 years; weight, 74 ± 6 kg). The study consisted of a 14-day adaptation phase [baseline data collection (BDC)], followed by 60 days of HDBR and a 14-day recovery period (R). In the antioxidant group, volunteers received an antioxidant cocktail (741 mg/d polyphenols, 2.1 g/d omega-3 fatty acids, 168 mg/d vitamin E, and 80 μg/d selenium) with their daily meals. In the control group, volunteers received no supplement. Based on their body weight, all volunteers received an individually tailored and strictly controlled diet, consistent with DRIs. We analyzed biomarkers of calcium homeostasis, bone formation, and bone resorption during BDC, HDBR, and R, as well as for 30 days after the end of HDBR. Data were analyzed by linear mixed models. Results The antioxidant supplement did not affect serum calcium, parathyroid hormone, urinary C-telopeptide of type I collagen (CTX), urinary N-telopeptide of type I collagen, serum β–C-telopeptide of type I collagen (β-CTX), bone alkaline phosphatase, aminoterminal propeptide of type I collagen, osteocalcin, or urinary calcium excretion. In both groups, typical bed rest–related changes were observed. Conclusions Supplementation of an antioxidant cocktail to a diet matching the DRIs did not affect bone resorption or formation during 60 days of HDBR in healthy young men. This trial was registered at clinicaltrials.gov as NCT03594799.
Published: 2021
Full Text: View/download PDF

3. Hepatitis C virus proteins induce lipogenesis and defective triglyceride secretion in transgenic mice

Author: Stanley M. Lemon, Emilie Mérour, Hervé Lerat, Hélène L. Kammoun, Celine Callens, Martin R. Higgs, Jean-Michel Pawlotsky, Fabienne Foufelle, Isabelle Hainault, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, Centre de Recherche des Cordeliers (CRC (UMR_S 872)), Université Paris Descartes - Paris 5 (UPD5)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institute of Human Infections and Immunity, The University of Texas Medical Branch (UTMB), Service de bactériologie, virologie, hygiène [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut Mondor de Recherche Biomédicale ( IMRB ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Centre de Recherche des Cordeliers ( CRC (UMR_S 872) ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), The University of Texas Medical Branch ( UTMB ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Guellaen, Georges
Subjects: Male, medicine.medical_specialty, Transgene, Blotting, Western, Mice, Transgenic, Lipids and Lipoproteins: Metabolism, Regulation, and Signaling, Hepacivirus, Biology, Endoplasmic Reticulum, Biochemistry, Mice, Viral Proteins, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, medicine, Animals, Humans, Secretion, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Molecular Biology, Triglycerides, 030304 developmental biology, Cytopathic effect, 0303 health sciences, Reverse Transcriptase Polymerase Chain Reaction, Lipogenesis, Fatty liver, virus diseases, Lipid metabolism, Cell Biology, medicine.disease, Hepatitis C, Virology, digestive system diseases, 3. Good health, Fatty Liver, Mice, Inbred C57BL, Disease Models, Animal, Endocrinology, Liver, Unfolded protein response, 030211 gastroenterology & hepatology, Steatosis, Sterol Regulatory Element Binding Protein 1
Abstract: This research was originally published in The Journal of Biological Chemistry. © the American Society for Biochemistry and Molecular Biology; International audience; Chronic hepatitis C virus (HCV) infection is associated with altered lipid metabolism and hepatocellular steatosis. Virus-induced steatosis is a cytopathic effect of HCV replication. The goal of this study was to examine the mechanisms underlying HCV-induced lipid metabolic defects in a transgenic mouse model expressing the full HCV protein repertoire at levels corresponding to natural human infection. In this model, expression of the HCV full-length open reading frame was associated with hepatocellular steatosis and reduced plasma triglyceride levels. Triglyceride secretion was impaired, whereas lipogenesis was activated. Increased lipogenic enzyme transcription was observed, resulting from maturational activation and nuclear translocation of sterol regulatory element-binding protein 1c (SREBP1c). However, endoplasmic reticulum (ER) stress markers were expressed at similar levels in both HCV transgenic mice and their wild type counterparts, suggesting that SREBP1c proteolytic cleavage in the presence of HCV proteins was independent of ER stress. In conclusion, transgenic mice expressing the HCV full-length polyprotein at low levels have decreased plasma triglyceride levels and develop hepatocellular steatosis in the same way as HCV-infected patients. In these mice, SREBP1c activation by one or several HCV proteins induces de novo triglyceride synthesis via the lipogenic pathway, in a manner independent of ER stress, whereas triglyceride secretion is simultaneously reduced.
Published: 2009
Full Text: View/download PDF

4. Behavioural responses of juvenile cuttlefish (Sepia officinalis) to local water movements

Author: Ludovic Dickel, Bernd U. Budelmann, Jean G. Boal, Spogmai Komak, National Resource Center for Cephalopods, The University of Texas Medical Branch (UTMB), Millersville University - Dpt of Biology, EA3211 Physiologie du Comportement des Céphalopodes, Groupe Mémoire et Plasticité comportementale (GMPc), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), The University of Texas Medical Branch ( UTMB ), Groupe Mémoire et Plasticité comportementale ( GMPc ), Université de Caen Normandie ( UNICAEN ), Normandie Université ( NU ) -Normandie Université ( NU ) -Université de Caen Normandie ( UNICAEN ), and Normandie Université ( NU ) -Normandie Université ( NU )
Subjects: Amphibian, Cuttlefish, Cephalopods, [ SDV.BA.ZI ] Life Sciences [q-bio]/Animal biology/Invertebrate Zoology, Physiology, Lateral line, Aquatic Science, Oceanography, Lolliguncula brevis, [ SDV.NEU.PC ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior, [ SDV.NEU.SC ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences, 03 medical and health sciences, 0302 clinical medicine, biology.animal, Juvenile, 14. Life underwater, Habituation, Sepia, 030304 developmental biology, 0303 health sciences, biology, [SDV.NEU.PC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior, Water Movements, [SCCO.NEUR]Cognitive science/Neuroscience, [SDV.NEU.SC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences, Anatomy, biology.organism_classification, lateral line, [SDV.BA.ZI]Life Sciences [q-bio]/Animal biology/Invertebrate Zoology, mechanoreception, hearing, [ SCCO.NEUR ] Cognitive science/Neuroscience, 030217 neurology & neurosurgery
Abstract: International audience; Physiological studies have shown that the epidermal head and arm lines in cephalopods are a mechanoreceptive system that is similar to the fish and amphibian lateral lines (Budelmann BU, Bleckmann H. 1988). A lateral line analogue in cephalopods: Water waves generate microphonic potentials in the epidermal head lines of Sepia officinalis and Lolliguncula brevis. J. Comp. Physiol. A, 164: 1–5. . A lateral line analogue in cephalopods: Water waves generate microphonic potentials in the epidermal head lines of Sepia officinalis and Lolliguncula brevis. J. Comp. Physiol. A 164:1–5.); however, the biological significance of the epidermal lines remains unclear. To test whether cuttlefish show behavioural responses to local water movements, juvenile Sepia officinalis were exposed to local sinusoidal water movements of different frequencies (0.01–1000 Hz) produced by a vibrating sphere. Five behavioural responses were recorded: body pattern changing, moving, burrowing, orienting, and swimming. Cuttlefish responded to a wide range of frequencies (20–600 Hz), but not to all of the frequencies tested within that range. No habituation to repeated stimuli was seen. Results indicate that cuttlefish can detect local water movements (most likely with the epidermal head and arm lines) and are able to integrate that information into behavioural responses.
Published: 2005
Full Text: View/download PDF

5. Excess all-cause mortality and COVID-19-related mortality:a temporal analysis in 22 countries, from January until August 2020

Author: Oscar Dario Martin Garzon, Fabrizio Stracci, Levan Kandelaki, Jose M. Rodriguez-Llanes, Julia A Critchley, Eva S. Schernhammer, Giuseppe Ambrosio, Neil Mehta, Cathy Bennett, Ourania Kolokotroni, Gleb Denissov, Qian Huang, Lucy Goldsmith, Maider Pagola Ugarte, Inbar Zucker, Jackeline Christiane Pinto Lobato, Petra Klepac, Constantina Constantinou, Alexandros Heraclides, Nolwenn Le Meur, Annalisa Quattrocchi, Kristi Rüütel, Antonio José Leal Costa, Claudia Zimmermann, Ángel Fernández Camporro, Ekaterina Bogatyreva, John Gabel, Pedro Arcos González, Christiana A. Demetriou, Ana Paula Semedo-Aguiar, Ivan Erzen, Laust Hvas Mortensen, Souzana Achilleos, Joan O'Donnell, Nicoletta Nicolaou, Zalman Kaufman, Terje P. Hagen, Shorena Tsiklauri, Gloria Ramírez, Nataliia Pidmurniak, Antonis Polemitis, Olesia Verstiuk, Ngibo Mubeta Fernandes, Ajay Oza, Bo Burström, Andreas Charalambous, University of Cyprus [Nicosia], European Commission - Joint Research Centre [Ispra] (JRC), Deakin University [Burwood], Medizinische Universität Wien = Medical University of Vienna, University of Copenhagen = Københavns Universitet (KU), St George’s University Hospitals, Recherche en Pharmaco-épidémiologie et Recours aux Soins (REPERES), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP), École des Hautes Études en Santé Publique [EHESP] (EHESP), Département Méthodes quantitatives en santé publique (METIS), Tel Aviv University [Tel Aviv], Università degli Studi di Perugia (UNIPG), University of Oslo (UiO), University of Oviedo, Karolinska Institutet [Stockholm], Bogomolets national medical university, University of South Carolina [Columbia], The University of Texas Medical Branch (UTMB), This work was supported by the University of Nicosia Medical School (internal funding), University of Cyprus [Nicosia] (UCY), University of Copenhagen = Københavns Universitet (UCPH), Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP), Tel Aviv University (TAU), and Università degli Studi di Perugia = University of Perugia (UNIPG)
Subjects: 0301 basic medicine, Coronavirus disease 2019 (COVID-19), Epidemiology, [SDV]Life Sciences [q-bio], Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Northern ireland, 03 medical and health sciences, 0302 clinical medicine, Pandemic, medicine, AcademicSubjects/MED00860, 030212 general & internal medicine, Excess mortality, business.industry, SARS-CoV-2, Mortality rate, pandemic, COVID-19, General Medicine, Seasonality, medicine.disease, mortality, infection control, 3. Good health, 030104 developmental biology, Original Article, business, All cause mortality, Demography
Abstract: This work was supported by the University of Nicosia Medical School (internal funding)., Achilleos S, Quattrocchi A, Gabel J, Heraclides A, Kolokotroni O, Constantinou C, Pagola Ugarte M, Nicolaou N, Rodriguez-Llanes JM, Bennett CM, Bogatyreva E, Schernhammer E, Zimmermann C, Costa AJL, Lobato JCP, Fernandes NM, Semedo-Aguiar AP, Jaramillo Ramirez GI, Martin Garzon OD, Mortensen LH, Critchley JA, Goldsmith LP, Denissov G, Rüütel K, Le Meur N, Kandelaki L, Tsiklauri S, O'Donnell J, Oza A, Kaufman Z, Zucker I, Ambrosio G, Stracci F, Hagen TP, Erzen I, Klepac P, Arcos González P, Fernández Camporro Á, Burström B, Pidmurniak N, Verstiuk O, Huang Q, Mehta NK, Polemitis A, Charalambous A, Demetriou CA.
Published: 2022
Full Text: View/download PDF

6. Pannexin-1 channel opening is critical for COVID-19 pathogenesis

Author: Geoffroy Lorin de la Grandmaison, Antonio Cibelli, David C. Spray, Juan E. Tichauer, Jean Dubuisson, Arielle Rosenberg, Ross H. Luu, Sandrine Belouzard, Eliana Scemes, Elisabeth Cramer-Bordé, Morgane Bomsel, Djillali Annane, Maximiliano Rovegno, Andrea Cottignies-Calamarte, Silvana Valdebenito, Eliseo A. Eugenin, Calude Capron, [Institut Cochin] Departement Infection, immunité, inflammation, Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), The University of Texas Medical Branch (UTMB), New York Medical College (NYMC), Albert Einstein College of Medicine [New York], Pontificia Universidad Católica de Chile (UC), Service de Virologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Ambroise Paré [AP-HP], Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Service des Maladies Infectieuses et Tropicales [CHU Raymond Poincaré], Hôpital Raymond Poincaré [AP-HP], Service médical des soins intensifs [CHU Raymond Poincaré], Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Médecine légale, Anatomo-pathologie et Paléopathologie [CHU Raymond Poincaré], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Raymond Poincaré [AP-HP], Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), The authors acknowledge financial support from the National Institutes of Health grant: MH096625/MH128082, The National Institute of Neurological Disorders and Stroke, NS105584, and UTMB internal funding (to E.A.E).Also, funding from the Flash COVID fund from both ANR and Fondation pour la Recherche Medicale (ANR-20-COVI-000 and AO2020- MUCOLUNG-ANR Flash COVID-19 - FRM) was provided to M.B., ANR-20-COVI-0024,MUCOLUNG,Rôle des cellules pulmonaires infectées par le SRAS-CoV-2 et réponse humoral dans l' évolution du COVID-19: de la physiopathologie au test de médicaments candidats dans les modèles de cellules muqueuses(2020), Bomsel, Morgane, and Rôle des cellules pulmonaires infectées par le SRAS-CoV-2 et réponse humoral dans l' évolution du COVID-19: de la physiopathologie au test de médicaments candidats dans les modèles de cellules muqueuses - - MUCOLUNG2020 - ANR-20-COVI-0024 - COVID-19 - VALID
Subjects: Cell biology, Human coronavirus 229E, [SDV.IMM] Life Sciences [q-bio]/Immunology, Science, viruses, Connexin, Endocytosis, medicine.disease_cause, Article, lung, Pathogenesis, 03 medical and health sciences, 0302 clinical medicine, Multiplicity of infection, Virology, medicine, purinergic, education, Furin, Molecular physiology, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Coronavirus, 0303 health sciences, education.field_of_study, Multidisciplinary, biology, Chemistry, COVID-19, virus diseases, Pannexin, biology.organism_classification, respiratory tract diseases, 3. Good health, ATP, Allograft inflammatory factor 1, biology.protein, [SDV.IMM]Life Sciences [q-bio]/Immunology, 030217 neurology & neurosurgery
Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) rapidly rampaged worldwide, causing a pandemic of coronavirus disease (COVID -19), but the biology of SARS-CoV-2 remains under investigation. We demonstrate that both SARS-CoV-2 spike protein and human coronavirus 229E (hCoV-229E) or its purified S protein, one of the main viruses responsible for the common cold, induce the transient opening of Pannexin-1 (Panx-1) channels in human lung epithelial cells. However, the Panx-1 channel opening induced by SARS-CoV-2 is greater and more prolonged than hCoV-229E/S protein, resulting in an enhanced ATP, PGE2, and IL-1β release. Analysis of lung lavages and tissues indicate that Panx-1 mRNA expression is associated with increased ATP, PGE2, and IL-1β levels. Panx-1 channel opening induced by SARS-CoV-2 spike protein is angiotensin-converting enzyme 2 (ACE-2), endocytosis, and furin dependent. Overall, we demonstrated that Panx-1 channel is a critical contributor to SARS-CoV-2 infection and should be considered as an alternative therapy., Graphical abstract, Cell biology; Molecular physiology; Virology
Published: 2021
Full Text: View/download PDF

7. Editorial: The Autophagy Pathway: Bacterial Pathogen Immunity and Evasion

Author: Jere W. McBride, Chinnaswamy Jagannath, Isabelle Vergne, Weill Medical College of Cornell University [New York], Institute for Human Infections and Immunity and Department of Pathology, The University of Texas Medical Branch (UTMB), Institut de pharmacologie et de biologie structurale (IPBS), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées
Subjects: Salmonella typhimurium, autophagy, Staphylococcus aureus, immunometabolism, Immunology, [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity, Microbiology, Mycobacterium tuberculosis, 03 medical and health sciences, 0302 clinical medicine, Immunity, Immunology and Allergy, Anaplasma, Pathogen, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 0303 health sciences, biology, Autophagy, RC581-607, biology.organism_classification, Evasion (ethics), Listeria monocytogenes, Anaplasmataceae, 030220 oncology & carcinogenesis, TFEB, Immunologic diseases. Allergy
Abstract: International audience
Published: 2021
Full Text: View/download PDF

8. Synaptic dysregulation and hyperexcitability induced by intracellular amyloid beta oligomers

Author: Christian Peters, Jérôme Epsztein, Luis G. Aguayo, Rakez Kayed, Denisse Bascuñán, Urmi Sengupta, Peter James Morgan, Nicolas O Riffo-Lepe, Caroline Filippi, Braulio Muñoz, María Paz Espinoza, Romain Bourboulou, Eduardo J Fernández-Pérez, Universidad de Concepción - University of Concepcion [Chile], Institut de Neurobiologie de la Méditerranée [Aix-Marseille Université] (INMED - INSERM U1249), Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), George and Cynthia Mitchell Center for Neurodegenerative diseases, University of Texas Medical Branch at Galveston, The University of Texas Medical Branch (UTMB), and pellegrino, Christophe
Subjects: AMPA‐R, Aging, neuronal nitric oxide synthase, amyloidβ peptide, CLR, synaptic dysregulation, amyloid precursor protein, Hippocampal formation, chemistry.chemical_compound, 0302 clinical medicine, human AD brain-derived Aβ oligomers, Amyloid precursor protein, miniature excitatory post-synaptic currents, miniature post-synaptic currents, chelerythrine, evoked excitatory post-synaptic currents, action potentials, Aβ, APs, 0303 health sciences, hyperexcitability, eEPSC, mIPSC, Alzheimer's disease, eIPSC, NOS, Original Papers, iNOS, mEPSC, eNOS, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Intracellular, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, synthetic Intracellular Aβ oligomers, Amyloid beta, Na v, nNOS, AMPA receptor, Biology, intracellular amyloid beta, Nitric oxide, voltage-dependent sodium channel, NO, 03 medical and health sciences, nitric oxide, nitric, mPSC, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], 030304 developmental biology, endothelial nitric oxide synthase, Original Paper, inducible nitric oxide synthase, Cell Biology, evoked inhibitory post-synaptic currents, Chelerythrine, chemistry, miniature inhibitory post-synaptic currents, biology.protein, Retrograde signaling, h-iAβo, Neuroscience, iAβo, 030217 neurology & neurosurgery
Abstract: Intracellular amyloid beta oligomer (iAβo) accumulation and neuronal hyperexcitability are two crucial events at early stages of Alzheimer's disease (AD). However, to date, no mechanism linking iAβo with an increase in neuronal excitability has been reported. Here, the effects of human AD brain‐derived (h‐iAβo) and synthetic (iAβo) peptides on synaptic currents and action potential firing were investigated in hippocampal neurons. Starting from 500 pM, iAβo rapidly increased the frequency of synaptic currents and higher concentrations potentiated the AMPA receptor‐mediated current. Both effects were PKC‐dependent. Parallel recordings of synaptic currents and nitric oxide (NO)‐associated fluorescence showed that the increased frequency, related to pre‐synaptic release, was dependent on a NO‐mediated retrograde signaling. Moreover, increased synchronization in NO production was also observed in neurons neighboring those dialyzed with iAβo, indicating that iAβo can increase network excitability at a distance. Current‐clamp recordings suggested that iAβo increased neuronal excitability via AMPA‐driven synaptic activity without altering membrane intrinsic properties. These results strongly indicate that iAβo causes functional spreading of hyperexcitability through a synaptic‐driven mechanism and offers an important neuropathological significance to intracellular species in the initial stages of AD, which include brain hyperexcitability and seizures., In the presence of iAβo, PKC is activated (a), which in turn allows the production of nitric oxide (NO) at the post‐synaptic level, increasing the release of neurotransmitters (b) (evidenced as an increase in the frequency of mPSC). PKC also increases AMPA receptor current (c), increasing post‐synaptic depolarization and neuronal excitability (d). Finally, iAβo increases synchronization NO production in nearby neurons that do not have iAβo (e).
Published: 2021
Full Text: View/download PDF

9. Rational design of universal immunotherapy for TfR1-tropic arenaviruses

Author: Thomas W. Geisbert, Vered Padler-Karavani, Sylvain Baize, Hadas Cohen-Dvashi, Ron Amon, Krystle N. Agans, Aliza Borenstein-Katz, Ron Diskin, Robert W. Cross, Mathieu Mateo, Weizmann Institute of Science [Rehovot, Israël], Tel Aviv University (TAU), The University of Texas Medical Branch (UTMB), Biologie des Infections Virales Émergentes - Biology of Emerging Viral Infections (UBIVE), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris] (IP), BSL-4 experiments using MACV were supported by the Pasteur-Weizmann joint research program collaborative research grant S-CR18069-02 to M.M. and R.D. BSL-4 operations of the Galveston National Laboratory and Department of Microbiology and Immunology are supported by NIAID/NIH Grant No. UC7AI094660 to T.W.G. The lab of R.D. is supported by research grants from the Enoch Foundation, from the Abramson Family Center for Young Scientists, from Ms. Rudolfine Steindling, and from the I-CORE Program of the Planning and Budgeting Committee and The Israel Science Foundation (grants no. 1775/12 and 682/16)., Tel Aviv University [Tel Aviv], Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris] (IP), and Bodescot, Myriam
Subjects: 0301 basic medicine, New World Arenavirus, Viral protein, medicine.medical_treatment, Science, viruses, General Physics and Astronomy, Transferrin receptor, Biologics, Biology, Antibodies, Viral, medicine.disease_cause, Article, General Biochemistry, Genetics and Molecular Biology, Viral Proteins, 03 medical and health sciences, 0302 clinical medicine, Virology, Receptors, Transferrin, medicine, Arenaviridae Infections, Humans, lcsh:Science, X-ray crystallography, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Multidisciplinary, Transmission (medicine), Rational design, virus diseases, Arenavirus, General Chemistry, Immunotherapy, Antibodies, Neutralizing, Arenaviruses, 3. Good health, Hemorrhagic Fevers, 030104 developmental biology, Drug Design, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Biological warfare, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Receptors, Virus, lcsh:Q, 030217 neurology & neurosurgery
Abstract: Certain arenaviruses that circulate in rodent populations can cause life-threatening hemorrhagic fevers when they infect humans. Due to their efficient transmission, arenaviruses pose a severe risk for outbreaks and might be exploited as biological weapons. Effective countermeasures against these viruses are highly desired. Ideally, a single remedy would be effective against many or even all the pathogenic viruses in this family. However, despite the fact that all pathogenic arenaviruses from South America utilize transferrin receptor 1 (TfR1) as a cellular receptor, their viral glycoproteins are highly diversified, impeding efforts to isolate cross-neutralizing antibodies. Here we address this problem using a rational design approach to target TfR1-tropic arenaviruses with high potency and breadth. The pan-reactive molecule is highly effective against all arenaviruses that were tested, offering a universal therapeutic approach. Our design scheme avoids the shortcomings of previous immunoadhesins and can be used to combat other zoonotic pathogens., New World arenaviruses utilize the cellular transferrin receptor 1 (TfR1) to enter host cells. Here, the authors develop a TfR1-mimetic immunoadhesin, Arenacept, that targets viral spike complexes and exerts effective pan-reactive neutralization against pathogenic mammarenaviruses.
Published: 2020
Full Text: View/download PDF

10. Antiviral activity of oleandrin and a defined extract of Nerium oleander against SARS-CoV-2

Author: Rick Matos, Divya Mirchandani, Scott C. Weaver, Diana Fernández, Jordi B. Torrelles, Varun Dwivedi, Jennifer Delgado, Nathen E. Bopp, Kenneth S. Plante, Vinay Shivanna, Patricia V. Aguilar, Jun Gyu Park, Luis Martinez-Sobrido, Jessica A. Plante, Paula Pino Tamayo, Robert A. Newman, K. Jagannadha Sastry, The University of Texas Medical Branch (UTMB), World Reference Center for Emerging Viruses and Arboviruses (WRCEVA), Institute for Human Infections and Immunity and Department of Pathology, Texas Biomedical Research Institute [San Antonio, TX], Innovar LLC, Phoenix Biotechnology, Inc., The University of Texas M.D. Anderson Cancer Center [Houston], and This research was supported in part by NIH grant R24 AI120942 to SCW. We thank Natalie Thornburg (Centers 305 for Disease Control and Prevention, Atlanta, GA, USA) and the World Reference Center for Emerging Viruses and Arboviruses for providing the SARS-CoV-2 USA_WA1/2020 isolate. Research was also supported by Phoenix Biotechnology, Inc. Experimental design, conduct of the experiments, and interpretation of the data were the independent products of scientists at University of Texas Medical Branch (Galveston) and Texas Biomedical Research Institute with consulting comments from R. A. Newman, PhD, and K. Jagannadha Sastry, PhD. The authors thank Bev Newman, M.S., R.N. for graphic art support.
Subjects: 0301 basic medicine, Oleandrin, NP, nucleocapsid protein, LDH, lactic dehydrogenase, [SDV]Life Sciences [q-bio], DPI, day post infection, Pharmacology, DMSO, dimethyl sulfoxide, medicine.disease_cause, law.invention, chemistry.chemical_compound, 0302 clinical medicine, HTLV-1, human T-lymphotropic virus, law, Cricetinae, Chlorocebus aethiops, Mab, monoclonal antibody, Antiviral activity, Coronavirus, General Medicine, 3. Good health, HIV, human immunodeficiency virus, Cardenolides, Titer, CPE, cytopathic effect, Reduced infectivity, 030220 oncology & carcinogenesis, BDNF, brain-derived neurotrophic factor, EC50, half maximal effective concentration, Female, Original Article, ATP, adenosine triphosphate, ALT, alanine transaminase, Genome, Viral, RM1-950, Antiviral Agents, Virus, MERS, middle east respiratory syndrome, 03 medical and health sciences, FBS, fetal bovine serum, In vivo, medicine, DPBS, Dulbecco’s phosphate-buffered saline, Animals, Nerium, SARS, severe acute respiratory syndrome, Vero Cells, EC50, ELISA, enzyme-linked immunoassay, ALP, alkaline phosphatase, Plant Extracts, business.industry, SARS-CoV-2, COVID-19, Nrf-2, nuclear factor erythroid 2-related factor 2, Nerium oleander, COVID-19 Drug Treatment, 030104 developmental biology, chemistry, qRT-PCR, real-time quantitative polymerase chain reaction, Vero cell, RNA, ribonucleic acid, H&E, hematoxylin and eosin, BSA, bovine serum albumin, Therapeutics. Pharmacology, business, Phytotherapy, PFU, plaque-forming unit
Abstract: International audience; With continued expansion of the coronavirus disease (COVID-19) pandemic, caused by severe acute respiratory syndrome 2 (SARS-CoV-2), both antiviral drugs as well as effective vaccines are desperately needed to treat patients at high risk of life-threatening disease. Here, we present in vitro evidence for significant inhibition of SARS-CoV-2 by oleandrin and a defined extract of N. oleander (designated as PBI-06150). Using Vero cells, we found that prophylactic (pre-infection) oleandrin (as either the pure compound or as the active principal ingredient in PBI-06150) administration at concentrations as low as 0.05g/ml exhibited potent antiviral activity against SARS-CoV-2, with an 800-fold reduction in virus production, and a 0.1g/ml concentration resulted in a greater than 3000-fold reduction in infectious virus production. The half maximal effective concentration (EC50) values were 11.98ng/ml when virus output was measured at 24h post-infection, and 7.07ng/ml measured at 48h post-infection. Therapeutic (post-infection) treatment up to 24h after SARS-CoV-2 infection of Vero cells also reduced viral titers, with 0.1g/ml and 0.05g/ml concentrations causing greater than 100-fold reduction as measured at 48h, and the 0.05g/ml concentration resulting in a 78-fold reduction. Concentrations of oleandrin up to 10g/ml were well tolerated in Vero cells. We also present in vivo evidence of the safety and efficacy of defined N. oleander extract (PBI-06150), which was administered to golden Syrian hamsters in a preparation containing as high as 130g/ml of oleandrin. In comparison to administration of control vehicle, PBI-06150 provided a statistically significant reduction of the viral titer in the nasal turbinates (nasal conchae). The potent prophylactic and therapeutic antiviral activities demonstrated here, together with initial evidence of its safety and efficacy in a relevant hamster model of COVID-19, support the further development of oleandrin and/or defined extracts containing this molecule for the treatment of SARS-CoV-2 and associated COVID-19 disease and potentially also for reduction of virus spread by persons diagnosed early after infection.
Published: 2021
Full Text: View/download PDF

11. Mosquito‐bacteria interactions during larval development trigger metabolic changes with carry‐over effects on adult fitness

Author: Émilie Giraud, Hugo Varet, Rachel Legendre, Odile Sismeiro, Fabien Aubry, Stéphanie Dabo, Laura B. Dickson, Claire Valiente Moro, Louis Lambrechts, Interactions Virus-Insectes - Insect-Virus Interactions (IVI), Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Biomics (plateforme technologique), Institut Pasteur [Paris], Biologie des Bactéries pathogènes à Gram-positif - Biology of Gram-Positive Pathogens, The University of Texas Medical Branch (UTMB), Laboratoire d'Ecologie Microbienne - UMR 5557 (LEM), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Ecole Nationale Vétérinaire de Lyon (ENVL)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), This work was primarily funded by the Agence Nationale de la Recherche (grant ANR-16-CE35-0004-01). It was also supported by the French Government’s Investissement d’Avenir program Laboratoire d’Excellence Integrative Biology of Emerging Infectious Diseases (grant ANR-10-LABX-62-IBEID to LL), and the City of Paris Emergence(s) program in Biomedical Research (to LL). The Biomics platform was supported by France Génomique (ANR-10-INBS-09-09) and IBISA., ANR-16-CE35-0004,MOSQUIBIOTA,Contribution de la diversité bactérienne intestinale à la capacité vectorielle d'Aedes aegypti(2016), ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-10-INBS-0009,France-Génomique,Organisation et montée en puissance d'une Infrastructure Nationale de Génomique(2010), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), and Institut Pasteur [Paris] (IP)
Subjects: 0303 health sciences, vector competence, Bacteria, Microbiota, [SDV]Life Sciences [q-bio], 030231 tropical medicine, fungi, gnotobiotic, 03 medical and health sciences, 0302 clinical medicine, Aedes aegypti, Aedes, Larva, Genetics, Animals, triglyceride, transcriptome, Ecosystem, Ecology, Evolution, Behavior and Systematics, 030304 developmental biology
Abstract: International audience; In animals with distinct life stages such as holometabolous insects, adult phenotypic variation is often shaped by the environment of immature stages, including their interactions with microbes colonizing larval habitats. Such carry-over effects were previously observed for several adult traits of the mosquito Aedes aegypti after larval exposure to different bacteria, but the mechanistic underpinnings are unknown. Here, we investigated the molecular changes triggered by gnotobiotic larval exposure to different bacteria in Ae. aegypti. We initially screened a panel of 16 bacterial isolates from natural mosquito breeding sites to determine their ability to influence adult life-history traits. We subsequently focused on four bacterial isolates (belonging to Flavobacterium, Lysobacter, Paenibacillus, and Enterobacteriaceae) with significant carry-over effects on adult survival and found that they were associated with distinct transcriptomic profiles throughout mosquito development. Moreover, we detected carry-over effects at the level of gene expression for the Flavobacterium and Paenibacillus isolates. The most prominent transcriptomic changes in gnotobiotic larvae reflected a profound remodeling of lipid metabolism, which translated into phenotypic differences in lipid storage and starvation resistance at the adult stage. Together, our findings indicate that larval exposure to environmental bacteria trigger substantial physiological changes that impact adult fitness, uncovering a possible mechanism underlying carry-over effects of mosquito-bacteria interactions during larval development.
Published: 2021
Full Text: View/download PDF

12. Resurgence of Ebola Virus in 2021 in Guinea Suggests a New Paradigm for Outbreaks

Author: Fodé B. Sako, Jacob Camara, Amadou A. Sall, Ariane Düx, Giuditta Annibaldis, Meike Pahlmann, Abdoulaye Toure, Ousmane Faye, Mamadou Condé, Haby Diallo, Steven T. Pullan, Amadou Sidibe, Moriba Povogui, Fara Raymond Koundouno, Christophe Peyrefitte, Liana E. Kafetzopoulou, Alpha Kabinet Keita, Saa L. Millimono, Mandiou Diakite, Ahmadou Doré, Karla Pietro, N'. Faly Magassouba, Fabian H. Leendertz, Nicole Vidal, Stephan Günther, Anke Thielebein, Julia Hinzmann, Dembo Diakite, Ahidjo Ayouba, Cheikh Loucoubar, Kaka Kourouma, Martin Faye, Philippe Lemey, Moussa Moïse Diagne, Mamadou D. Barry, Fodé Y. Soumah, Annick Renevey, Georges Ki-Zerbo, Kékoura Ifono, Andrew Rambaut, Abdoul K. Soumah, Miles W. Carroll, Mamadou S. Bah, Joseph Akoi Bore, Ibrahima Camara, Mamadou S. Sow, Sébastien Calvignac-Spencer, Fodé A. Traore, Sophie Duraffour, Assaïtou Bah, John T. McCrone, Nathalie J. Vielle, Joshua Quick, Noël Tordo, Moussa Baldé, Mamadou Diop, Youssouf Sidibé, Martine Peeters, Madeleine Kourouma, Sakoba Keita, Mamadou B. Keita, Frédéric Le Marcis, Cé D. Saouromou, Anais Legand, Amadou Diallo, Pierre Formenty, Almudena Mari-Saez, Michael R. Wiley, Karifa Kourouma, Eric Delaporte, Barré Soropogui, Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques et émergentes (TransVIHMI), Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I-Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Université Gamal Abdel Nasser de Conakry, Laboratoire des Fièvres Hémorragiques en Guinée, Bernhard Nocht Institute for Tropical Medicine - Bernhard-Nocht-Institut für Tropenmedizin [Hamburg, Germany] (BNITM), Institut Pasteur de Dakar, Réseau International des Instituts Pasteur (RIIP), Robert Koch Institute [Berlin] (RKI), German Center for Infection Research - Partner Site Hamburg-Lübeck-Borstel-Riems, German Centre for Infection Research (DZIF), Centre de Recherche et de Formation en Infectiologie de Guinée [Conakry, Guinée] (CERFIG), Triangle : action, discours, pensée politique et économique (TRIANGLE), École normale supérieure de Lyon (ENS de Lyon)-Université Lumière - Lyon 2 (UL2)-Sciences Po Lyon - Institut d'études politiques de Lyon (IEP Lyon), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Centre National de la Recherche Scientifique (CNRS), Hôpital National Donka, The Wellcome Trust Centre for Human Genetics [Oxford], University of Oxford, Epidemiology of Highly Pathogenic Microorganisms, Vecteurs - Infections tropicales et méditerranéennes (VITROME), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut de Recherche Biomédicale des Armées [Brétigny-sur-Orge] (IRBA), CEA Tech Grand-Est (DGDE), CEA Tech en régions (CEA-TECH-Reg), Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Institut National de Santé Publique [Conakry, Guinée] (INSP), Ministère de la Santé [Conakry, Guinea], Laboratoire de Physique de l'Atmosphère et de l'Océan Siméon Fongang (LPAO-SF), École Supérieure Polytechnique de Dakar (ESP), Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD), Public Health England, University of Birmingham [Birmingham], Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), World Health Organization [Geneva], The University of Texas Medical Branch (UTMB), University of Nebraska Medical Center, University of Nebraska System, Institut Pasteur de Guinée, Unité des Virus Emergents (UVE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Recherche Biomédicale des Armées [Antenne Marseille] (IRBA), University of Edinburgh, Division Prévention et Lutte contre la Maladie, Ministère de la Santé et de l’Hygiène Publique, Ecole Nationale Superieure de Lyon, Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Infectious and Tropical Diseases Department [Montpellier], Institut de Recherche pour le Développement (IRD)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD), Max Planck Institute for Evolutionary Anthropology [Leipzig], Max-Planck-Gesellschaft, ANR-16-IDEX-0006,MUSE,MUSE(2016), Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques er émergentes (TransVIHMI), Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Université Montpellier 1 (UM1), Centre National de la Recherche Scientifique (CNRS)-Sciences Po Lyon - Institut d'études politiques de Lyon (IEP Lyon), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Université Lumière - Lyon 2 (UL2)-École normale supérieure - Lyon (ENS Lyon), University of Oxford [Oxford], Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes (URMITE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR48, INSB-INSB-Centre National de la Recherche Scientifique (CNRS), CEA Tech Alsace Champagne-Ardenne Lorraine, École normale supérieure - Lyon (ENS Lyon)-Université Lumière - Lyon 2 (UL2)-Sciences Po Lyon - Institut d'études politiques de Lyon (IEP Lyon), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Centre National de la Recherche Scientifique (CNRS), Aix Marseille Université (AMU)-Institut de Recherche pour le Développement (IRD)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Michel de l'Hospital : laboratoire de recherche en sciences juridiques et politiques (CMH ), and Université Clermont Auvergne (UCA)
Subjects: Male, Zaire ebolavirus, Time Factors, viruses, Disease, Biology, medicine.disease_cause, Disease cluster, Models, Biological, Viral Zoonoses, Virus, Disease Outbreaks, 03 medical and health sciences, Ebola virus, 0302 clinical medicine, medicine, Animals, Humans, Survivors, 030212 general & internal medicine, Clade, Phylogeny, 030304 developmental biology, 0303 health sciences, Multidisciplinary, Transmission (medicine), Guinea-2021, High-Throughput Nucleotide Sequencing, Outbreak, Hemorrhagic Fever, Ebola, [SHS.ANTHRO-SE]Humanities and Social Sciences/Social Anthropology and ethnology, Ebolavirus, Virology, 3. Good health, Democratic Republic of the Congo, Female, Persistent Infection, epidemiology, Guinea, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie
Abstract: Seven years after the declaration of the first epidemic of Ebola virus disease in Guinea, the country faced a new outbreak—between 14 February and 19 June 2021—near the epicentre of the previous epidemic1,2. Here we use next-generation sequencing to generate complete or near-complete genomes of Zaire ebolavirus from samples obtained from 12 different patients. These genomes form a well-supported phylogenetic cluster with genomes from the previous outbreak, which indicates that the new outbreak was not the result of a new spillover event from an animal reservoir. The 2021 lineage shows considerably lower divergence than would be expected during sustained human-to-human transmission, which suggests a persistent infection with reduced replication or a period of latency. The resurgence of Zaire ebolavirus from humans five years after the end of the previous outbreak of Ebola virus disease reinforces the need for long-term medical and social care for patients who survive the disease, to reduce the risk of re-emergence and to prevent further stigmatization. The viral lineage responsible for the February 2021 outbreak of Ebola virus disease in Guinea is nested within a clade that predominantly consists of genomes sampled during the 2013–2016 epidemic, suggesting that the virus might have re-emerged after a long period of latency within a previously infected individual.
Published: 2021
Full Text: View/download PDF

13. Specific Immunologic Countermeasure Protocol for Deep-Space Exploration Missions

Author: George Makedonas, Satish Mehta, Alexander Choukèr, Richard J. Simpson, Gailen Marshall, Jordan S. Orange, Serena Aunon-Chancellor, Scott M. Smith, Sara R. Zwart, Raymond P. Stowe, Martina Heer, Sergey Ponomarev, Alexandra Whitmire, Jean P. Frippiat, Grace L. Douglas, Stephanie S. Krieger, Hernan Lorenzi, Judith-Irina Buchheim, Geoffrey S. Ginsburg, C. Mark Ott, Meghan Downs, Duane Pierson, Natalie Baecker, Clarence Sams, Brian Crucian, JES Tech, University Hospital of the Ludwig-Maximilians University, The University of Arizona Medical Center, University of Arizona, University of Mississippi Medical Center (UMMC), Department of Pediatrics (University of British Columbia), NASA Johnson Space Center (JSC), NASA, The University of Texas Medical Branch (UTMB), Institute of Human Nutrition and Food Science, Rheinische Friedrich-Wilhelms-Universität Bonn, Institute of biomedical problems, Russian Academy of Sciences [Moscow] (RAS), Stress, Immunité, Pathogènes (SIMPA), Université de Lorraine (UL), J. Craig Venter Institute, Duke Center for Applied Genomics and Precision Medicine [Durham, NC, USA], Duke University School of Medicine [Durham, NC, USA], Aerospace Medical Institute, and German Aerospace Center (DLR)
Subjects: 0301 basic medicine, lcsh:Immunologic diseases. Allergy, Opinion, stress management, T-Lymphocytes, Immunology, 03 medical and health sciences, 0302 clinical medicine, Aeronautics, Political science, Herpesvirus reactivation, Agency (sociology), Humans, Immunology and Allergy, Protocol (object-oriented programming), ComputingMilieux_MISCELLANEOUS, Inflammation, Immunity, Cellular, immune countermeasures, immune surveillance, DNA Methylation, Space Flight, Immune surveillance, 3. Good health, 030104 developmental biology, Deep space exploration, Twin Studies as Topic, Space program, [SDV.IMM]Life Sciences [q-bio]/Immunology, space immunology, lcsh:RC581-607, Countermeasure (computer), 030215 immunology
Abstract: German National Space Program [50WB1622]; European Space Agency (ESA)'s Topical Team Stress and Immunity - ESA ELIPS 4 program; European Space Agency (ESA)'s Topical Team Stress and Immunity - ESA SciSpacE program
Published: 2019
Full Text: View/download PDF

14. NLRP3 inflammasome activation drives tau pathology

Author: Shuangshuang Zhang, David Blum, Ana Vieira-Saecker, Carmen Venegas, Rakez Kayed, Hannah Scheiblich, Douglas T. Golenbock, Maximilian Merten, Shadi Albasset, Susanne V. Schmidt, Eicke Latz, Luc Buée, Frederic Brosseron, Sabine Opitz, Angelika Griep, Francesco Santarelli, Christina Ising, James Stunden, Róisín M. McManus, Michael T. Heneka, Dario Tejera, Stephanie Schwartz, Blum, David, Centre de recherche en Biologie cellulaire de Montpellier (CRBM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centers for Disease Control and Prevention [Atlanta] (CDC), Centers for Disease Control and Prevention, Institute of Innate Immunity, Bonn, Department of Neurology, The University of Texas Medical Branch (UTMB), Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 (JPArc), Université Lille Nord de France (COMUE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Rheinische Friedrich-Wilhelms-Universität Bonn, Centre de recherche en Biologie Cellulaire (CRBM), Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U1172 Inserm - U837 (JPArc), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Lille Nord de France (COMUE)-Université de Lille
Subjects: 0301 basic medicine, Inflammasomes, metabolism [NLR Family, Pyrin Domain-Containing 3 Protein], physiopathology [Protein Aggregation, Pathological], Protein aggregation, genetics [Gene Expression Regulation], Mice, 0302 clinical medicine, genetics [Inflammasomes], Phosphorylation, Multidisciplinary, Microglia, integumentary system, Chemistry, Kinase, Caspase 1, Neurodegeneration, pathology [Microglia], Inflammasome, medicine.anatomical_structure, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], ddc:500, medicine.drug, tau Proteins, Protein Aggregation, Pathological, Article, 03 medical and health sciences, Alzheimer Disease, mental disorders, NLR Family, Pyrin Domain-Containing 3 Protein, medicine, Animals, Humans, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Neuroinflammation, genetics [NLR Family, Pyrin Domain-Containing 3 Protein], Amyloid beta-Peptides, Cyclin-dependent kinase 5, [SCCO.NEUR]Cognitive science/Neuroscience, [SCCO.NEUR] Cognitive science/Neuroscience, Cyclin-Dependent Kinase 5, medicine.disease, metabolism [tau Proteins], Mice, Inbred C57BL, genetics [tau Proteins], 030104 developmental biology, Gene Expression Regulation, metabolism [Cyclin-Dependent Kinase 5], Neuroscience, metabolism [Inflammasomes], 030217 neurology & neurosurgery
Abstract: International audience; Alzheimer's disease is characterized by the accumulation of amyloid-beta in plaques, aggregation of hyperphosphorylated tau in neurofibrillary tangles and neuroinflammation, together resulting in neurodegeneration and cognitive decline1. The NLRP3 inflammasome assembles inside of microglia on activation, leading to increased cleavage and activity of caspase-1 and downstream interleukin-1β release2. Although the NLRP3 inflammasome has been shown to be essential for the development and progression of amyloid-beta pathology in mice3, the precise effect on tau pathology remains unknown. Here we show that loss of NLRP3 inflammasome function reduced tau hyperphosphorylation and aggregation by regulating tau kinases and phosphatases. Tau activated the NLRP3 inflammasome and intracerebral injection of fibrillar amyloid-beta-containing brain homogenates induced tau pathology in an NLRP3-dependent manner. These data identify an important role of microglia and NLRP3 inflammasome activation in the pathogenesis of tauopathies and support the amyloid-cascade hypothesis in Alzheimer's disease, demonstrating that neurofibrillary tangles develop downstream of amyloid-beta-induced microglial activation.
Published: 2019
Full Text: View/download PDF

15. GloPID-R report on chikungunya, o'nyong-nyong and Mayaro virus, part 3: Epidemiological distribution of Mayaro virus

Author: Pezzi, L., Rodriguez-Morales, A.J., Reusken, C.B., Ribeiro, G.S., Labeaud, A.D., Lourenço-De-Oliveira, R., Brasil, P., Lecuit, M., Failloux, Anna-Bella, Gallian, P., Jaenisch, T., Simon, F., Siqueira, A.M., Rosa-Freitas, M.G., Vega Rua, A., Weaver, S.C., Drexler, J.F., Vasilakis, N., de Lamballerie, Xavier, Boyer, Sébastien, Busch, M., Diallo, M., Diamond, M.S., Drebot, M.A., Kohl, A., Neyts, J., Ng, L.F.P., Rios, M., Sall, A., Simmons, G., Virology, Unité des Virus Emergents (UVE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Virologie [UNIV Corse-Inserm] (EA7310), Université Pascal Paoli (UPP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Universidad Tecnológica de Pereira [Colombie] (UTP), National Institute for Public Health and the Environment [Bilthoven] (RIVM), Erasmus University Medical Center [Rotterdam] (Erasmus MC), Universidade Federal da Bahia (UFBA), Stanford School of Medicine [Stanford], Stanford Medicine, Stanford University-Stanford University, Fundação Oswaldo Cruz (FIOCRUZ), Réseau International des Instituts Pasteur (RIIP), Biologie des Infections - Biology of Infection, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Arbovirus et Insectes Vecteurs - Arboviruses and Insect Vectors, Institut Pasteur [Paris] (IP), Etablissement Français du Sang - Alpes-Méditerranée (EFS - Alpes-Méditerranée), Etablissement Français du Sang, Heidelberg University Hospital [Heidelberg], Hôpital d'Instruction des Armées Laveran, Service de Santé des Armées, Institut Pasteur de la Guadeloupe, The University of Texas Medical Branch (UTMB), German Center for Infection Research - partner site Hannover-Braunschweig (DZIF), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Humboldt University Of Berlin, Berlin Institute of Health (BIH), Institut Pasteur du Cambodge, University of California [San Francisco] (UC San Francisco), University of California (UC), Institut Pasteur de Dakar, Washington University in Saint Louis (WUSTL), Public Health Agency of Canada, MRC - University of Glasgow Centre for Virus Research, Laboratory of Virology and Chemotherapy [KU Leuven], Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven)-Rega Institute of Medical Research [Leuven, Belgium], Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Agency for science, technology and research [Singapore] (A*STAR), U.S. Food and Drug Administration (FDA), Publication fees were covered by the Global Research Collaboration for Infectious Disease Preparedness (GloPID-R)., DEMESLAY GOUGAM, MARIE, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pascal Paoli (UPP), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Institut Pasteur [Paris], Humboldt-Universität zu Berlin, University of California [San Francisco] (UCSF), University of California, and Fundação Oswaldo Cruz / Oswaldo Cruz Foundation (FIOCRUZ)
Subjects: Primates, GloPID-R chikungunya, o'nyong-nyong and Mayaro virus Working Group, 030231 tropical medicine, Alphavirus, Genome, Viral, Mosquito Vectors, Disease Outbreaks, 03 medical and health sciences, 0302 clinical medicine, Seroepidemiologic Studies, Virology, Zoonoses, Animals, Humans, O'nyong-nyong Virus, Serologic Tests, 030212 general & internal medicine, Pathology, Molecular, ComputingMilieux_MISCELLANEOUS, Phylogeny, Disease Reservoirs, Pharmacology, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Alphavirus Infections, 3. Good health, Caribbean Region, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Chikungunya Fever, Americas, Chikungunya virus
Abstract: ispartof: ANTIVIRAL RESEARCH vol:172 ispartof: location:Netherlands status: published
Published: 2019
Full Text: View/download PDF

16. Meeting the challenge of tick-borne disease control: A proposal for 1000 Ixodes genomes

Author: Timothy J. Kurtti, Karen D. McCoy, Ala E. Tabor, Lesley Bell-Sakyi, Claude Rispe, Manuel Rodriguez Valle, Ulrike G. Munderloh, Benjamin L. Makepeace, Catherine A. Hill, Jyothi Thimmapuram, José de la Fuente, Maria V. Murgia, Saravanan Thangamani, Olivier Plantard, Ben J. Mans, Purdue University [West Lafayette], University of Liverpool, Instituto de Investigación en Recursos Cinegéticos (IREC), University of Minnesota [Twin Cities] (UMN), University of Minnesota System, University of South Africa (UNISA), Evolution of host-microbe communities (MIVEGEC-EVCO), Processus Écologiques et Évolutifs au sein des Communautés (PEEC), Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), Biologie, Epidémiologie et analyse de risque en Santé Animale (BIOEPAR), Institut National de la Recherche Agronomique (INRA)-École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS), University of Queensland [Brisbane], The University of Texas Medical Branch (UTMB), University of Minnesota [Twin Cities], Institut de Recherche pour le Développement (IRD [France-Sud])-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), and Institut National de la Recherche Agronomique (INRA)
Subjects: Ixodes ricinus, [SDV]Life Sciences [q-bio], education, 030231 tropical medicine, Tick, Microbiology, Genome, 03 medical and health sciences, 0302 clinical medicine, medicine, Animals, Humans, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 0303 health sciences, Tick-borne disease, biology, Ixodes, Genomics, biology.organism_classification, medicine.disease, Infectious Diseases, Evolutionary biology, Tick-Borne Diseases, Insect Science, Parasitology
Abstract: International audience
Published: 2019
Full Text: View/download PDF

17. Changes in the Transmission Dynamic of Chikungunya Virus in Southeastern Senegal

Author: Scott C. Weaver, Oumar Ndiaye, Abdourahmane Sow, Mawlouth Diallo, Bakary Djilocalisse Sadio, Amadou A. Sall, Ousmane Faye, Anta Tall Dia, Birgit Nikolay, Oumar Faye, Denis Malvy, Jorge Cano, Simon Cauchemez, Arbovirus et Virus de Fièvres Hémorragiques [Dakar, Sénégal], Institut Pasteur de Dakar, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD), Team MORPH3EUS (INSERM U1219 - UB - ISPED), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Modélisation mathématique des maladies infectieuses, Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), London School of Hygiene and Tropical Medicine (LSHTM), Unité d'Entomologie Médicale [Dakar] (UEM), The University of Texas Medical Branch (UTMB), The research was supported by the National Institutes of Health (NIH), Grant Number AI1069145., Modélisation mathématique des maladies infectieuses - Mathematical modelling of Infectious Diseases, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), and Limouzin, Cécile
Subjects: Male, Rural Population, 0301 basic medicine, Veterinary medicine, lcsh:QR1-502, environmental risk, MESH: Chikungunya Fever, Forests, Antibodies, Viral, medicine.disease_cause, Logistic regression, spatial autocorrelation, Population density, lcsh:Microbiology, law.invention, MESH: Aged, 80 and over, 0302 clinical medicine, MESH: Rural Population, Seroepidemiologic Studies, [MATH.MATH-ST]Mathematics [math]/Statistics [math.ST], law, MESH: Child, Chikungunya, Child, [MATH.MATH-ST] Mathematics [math]/Statistics [math.ST], Aged, 80 and over, MESH: Aged, MESH: Immunoglobulin G, MESH: Middle Aged, Age Factors, virus diseases, Middle Aged, MESH: Forests, MESH: Mining, MESH: Infant, Senegal, 3. Good health, Infectious Diseases, Transmission (mechanics), MESH: Young Adult, Child, Preschool, Female, Sylvatic cycle, Adult, Adolescent, MESH: Population Density, 030231 tropical medicine, Environment, Biology, Article, Mining, gold mining, Young Adult, 03 medical and health sciences, MESH: Senegal, Virology, medicine, Humans, Seroprevalence, MESH: Environment, Aged, Population Density, MESH: Adolescent, MESH: Age Factors, MESH: Seroepidemiologic Studies, MESH: Humans, MESH: Child, Preschool, Infant, Outbreak, MESH: Adult, Odds ratio, 15. Life on land, MESH: Male, 030104 developmental biology, Immunoglobulin G, Chikungunya Fever, MESH: Female, MESH: Antibodies, Viral
Abstract: In Senegal, chikungunya virus (CHIKV) is maintained in a sylvatic cycle and causes sporadic cases or small outbreaks in rural areas. However, little is known about the influence of the environment on its transmission. To address the question, 120 villages were randomly selected in the Kedougou region of southeastern Senegal. In each selected village, 10 persons by randomly selected household were sampled and tested for specific anti-CHIKV IgG antibodies by ELISA. We investigated the association of CHIKV seroprevalence with environmental variables using logistic regression analysis and the spatial correlation of village seroprevalence based on semivariogram analysis. Fifty-four percent (51%&ndash, 57%) of individuals sampled during the survey tested positive for CHIKV-specific IgG. CHIKV seroprevalence was significantly higher in populations living close to forested areas (Normalized Difference Vegetation Index (NDVI), Odds Ratio (OR) = 1.90 (1.42&ndash, 2.57)), and was negatively associated with population density (OR = 0.76 (0.69&ndash, 0.84)). In contrast, in gold mining sites where population density was &gt, 400 people per km2, seroprevalence peaked significantly among adults (46% (27%&ndash, 67%)) compared to all other individuals (20% (12%&ndash, 31%)). However, traditional gold mining activities significantly modify the transmission dynamic of CHIKV, leading to a potential increase of the risk of human exposition in the region.
Published: 2020
Full Text: View/download PDF

18. Novel Wolbachia strains in Anopheles malaria vectors from Sub-Saharan Africa

Author: James Orsborne, Thomas Walker, Fara Nantenaina Raharimalala, Francis Wat’senga, Kamil Khanipov, Mojca Kristan, Yuriy Fofanov, Yaw A. Afrane, Grant L. Hughes, Emile Z Manzambi, Kalil Keita, Seth R. Irish, Gena G. Lawrence, Eliot Hurn, Denka Camara, Claire L. Jeffries, Janvier Bandibabone, Georgiy Golovko, Shivanand Hegde, Sébastien Boyer, Tarekegn A. Abeku, Yaya Barry, Kirstin Spence, Luciano Michaël Tantely, Abdul Rahim Mohammed, Maria Pimenova, London School of Hygiene and Tropical Medicine (LSHTM), Centers for Disease Control and Prevention [Atlanta] (CDC), Centers for Disease Control and Prevention, The University of Texas Medical Branch (UTMB), Centre de Recherche en Sciences Naturelles [Lwiro, Congo] (CRSN), Unité d'Entomologie Médicale [Antananarivo, Madagascar] (IPM), Institut Pasteur de Madagascar, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Ministère de la Santé [Conakry, Guinea], Institut National de Recherche Biomédicale [Kinshasa] (INRB), University of Ghana, Malaria Consortium, London, UK, and CLJ and TW were supported by a Wellcome Trust /Royal Society grant awarded to TW (101285): http://www.wellcome.ac.uk
Subjects: 0301 basic medicine, Range (biology), media_common.quotation_subject, Anopheles gambiae, 030231 tropical medicine, malaria, Prevalence, Zoology, Medicine (miscellaneous), Asaia, Insect, Plasmodium, General Biochemistry, Genetics and Molecular Biology, symbols.namesake, 03 medical and health sciences, endosymbionts, 0302 clinical medicine, Anopheles, parasitic diseases, medicine, Parasite hosting, Microbiome, reproductive and urinary physiology, mosquitoes, 030304 developmental biology, media_common, Sanger sequencing, 0303 health sciences, biology, fungi, Articles, biochemical phenomena, metabolism, and nutrition, biology.organism_classification, medicine.disease, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 3. Good health, 030104 developmental biology, symbols, Multilocus sequence typing, bacteria, Wolbachia, Malaria, Research Article
Abstract: Background: Wolbachia, a common insect endosymbiotic bacterium that can influence pathogen transmission and manipulate host reproduction, has historically been considered absent from the Anopheles (An.) genera, but has recently been found in An. gambiae s.l. populations in West Africa. As there are numerous Anopheles species that have the capacity to transmit malaria, we analysed a range of species across five malaria endemic countries to determine Wolbachia prevalence rates, characterise novel Wolbachia strains and determine any correlation between the presence of Plasmodium, Wolbachia and the competing bacterium Asaia. Methods: Anopheles adult mosquitoes were collected from five malaria-endemic countries: Guinea, Democratic Republic of the Congo (DRC), Ghana, Uganda and Madagascar, between 2013 and 2017. Molecular analysis was undertaken using quantitative PCR, Sanger sequencing, Wolbachia multilocus sequence typing (MLST) and high-throughput amplicon sequencing of the bacterial 16S rRNA gene. Results: Novel Wolbachia strains were discovered in five species: An. coluzzii, An. gambiae s.s., An. arabiensis, An. moucheti and An. species A, increasing the number of Anopheles species known to be naturally infected. Variable prevalence rates in different locations were observed and novel strains were phylogenetically diverse, clustering with Wolbachia supergroup B strains. We also provide evidence for resident strain variants within An. species A. Wolbachia is the dominant member of the microbiome in An. moucheti and An. species A but present at lower densities in An. coluzzii. Interestingly, no evidence of Wolbachia/Asaia co-infections was seen and Asaia infection densities were shown to be variable and location dependent. Conclusions: The important discovery of novel Wolbachia strains in Anopheles provides greater insight into the prevalence of resident Wolbachia strains in diverse malaria vectors. Novel Wolbachia strains (particularly high-density strains) are ideal candidate strains for transinfection to create stable infections in other Anopheles mosquito species, which could be used for population replacement or suppression control strategies.
Published: 2018
Full Text: View/download PDF

19. i-BLESS is an ultra-sensitive method for detection of DNA double-strand breaks

Author: Benjamin Pardo, Anna Biernacka, Krzysztof Ginalski, Jules Nde, Andrzej Kudlicki, Nicola Crosetto, Magdalena Skrzypczak, Marta Grzelak, Abhishek Mitra, Maga Rowicka, Romain Forey, Yingjie Zhu, Philippe Pasero, Laboratory of Bioinformatics and Systems Biology, Centre of New Technologies, University of Warsaw, 02-089 Warsaw, Poland, Department of Biochemistry and Molecular Biology, University of Texas Medical Branch at Galveston, Galveston, TX 77555 USA., Institut de génétique humaine (IGH), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), University of Texas Medical Branch at Galveston, The University of Texas Medical Branch (UTMB), and Science for Life Laboratory, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, SE-17165 Sweden.
Subjects: 0301 basic medicine, Double strand, [SDV.GEN]Life Sciences [q-bio]/Genetics, [SDV]Life Sciences [q-bio], Medicine (miscellaneous), Chromosome deletions, High resolution, Cell fate determination, Article, General Biochemistry, Genetics and Molecular Biology, 3. Good health, Cell biology, 03 medical and health sciences, chemistry.chemical_compound, 030104 developmental biology, 0302 clinical medicine, chemistry, lcsh:Biology (General), Agarose, General Agricultural and Biological Sciences, lcsh:QH301-705.5, 030217 neurology & neurosurgery, DNA, Ultra sensitive, Genome stability
Abstract: Maintenance of genome stability is a key issue for cell fate that could be compromised by chromosome deletions and translocations caused by DNA double-strand breaks (DSBs). Thus development of precise and sensitive tools for DSBs labeling is of great importance for understanding mechanisms of DSB formation, their sensing and repair. Until now there has been no high resolution and specific DSB detection technique that would be applicable to any cells regardless of their size. Here, we present i-BLESS, a universal method for direct genome-wide DNA double-strand break labeling in cells immobilized in agarose beads. i-BLESS has three key advantages: it is the only unbiased method applicable to yeast, achieves a sensitivity of one break at a given position in 100,000 cells, and eliminates background noise while still allowing for fixation of samples. The method allows detection of ultra-rare breaks such as those forming spontaneously at G-quadruplexes., Anna Biernacka, Yingjie Zhu et al. present i-BLESS, a universal method for detecting genome-wide DNA double strand breaks, optimized here for yeast. By immobilizing cells on agarose beads, the authors are able to achieve efficient diffusion of reagents and labeling of double strand breaks, including ultra-rare breaks such as those at G-quadruplexes.
Published: 2018
Full Text: View/download PDF

20. Zika, Chikungunya, and Other Emerging Vector-Borne Viral Diseases

Author: Scott C. Weaver, Caroline Charlier, Nikos Vasilakis, Marc Lecuit, The University of Texas Medical Branch (UTMB), Biologie des Infections - Biology of Infection, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5), CHU Necker - Enfants Malades [AP-HP], Institut des Maladies Génétiques Imagine [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)
Subjects: 0301 basic medicine, chikungunya, viruses, 030231 tropical medicine, mosquito, Aedes aegypti, Mosquito Vectors, Biology, medicine.disease_cause, Arbovirus, Communicable Diseases, Emerging, General Biochemistry, Genetics and Molecular Biology, Article, Dengue fever, yellow fever, 03 medical and health sciences, 0302 clinical medicine, Zika, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, medicine, Animals, Humans, Chikungunya, Rift Valley fever, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Zika Virus Infection, Yellow fever, virus diseases, General Medicine, Japanese encephalitis, medicine.disease, biology.organism_classification, Virology, dengue, 3. Good health, 030104 developmental biology, arbovirus, Virus Diseases, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Enzootic, Chikungunya Fever, Arboviruses, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Arthropod-borne viruses (arboviruses) have a long history of emerging to infect humans, but during recent decades, they have been spreading more widely and affecting larger populations. This is due to several factors, including increased air travel and uncontrolled mosquito vector populations. Emergence can involve simple spillover from enzootic (wildlife) cycles, as in the case of West Nile virus accompanying geographic expansion into the Americas; secondary amplification in domesticated animals, as seen with Japanese encephalitis, Venezuelan equine encephalitis, and Rift Valley fever viruses; and urbanization, in which humans become the amplification hosts and peridomestic mosquitoes, mainly Aedes aegypti, mediate human-to-human transmission. Dengue, yellow fever, chikungunya, and Zika viruses have undergone such urban emergence. We focus mainly on the latter two, which are recent arrivals in the Western Hemisphere. We also discuss a few other viruses with the potential to emerge through all of these mechanisms.
Published: 2018
Full Text: View/download PDF

21. Chikungunya Outbreak in Kedougou, Southeastern Senegal in 2009-2010

Author: Manfred Weidmann, Cheikh Tidiane Diagne, Abdourahmane Sow, Rubing Chen, Amadou A. Sall, Oumar Ndiaye, Mathilde Guerbois, Scott C. Weaver, Ousmane Faye, Diawo Diallo, Abdourahmane Faye, Cheikh Sadibou Senghor, Youssoupha Ndiaye, Mawlouth Diallo, Bakary Djilocalisse Sadio, Anta Tall Dia, Oumar Faye, Denis Malvy, Kathryn A. Hanley, Douglas M. Watts, Ousmane M. Diop, Arbovirus et Virus de Fièvres Hémorragiques [Dakar, Sénégal], Institut Pasteur de Dakar, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Réseau International des Instituts Pasteur (RIIP), The University of Texas Medical Branch (UTMB), University Medical Center Göttingen (UMG), District sanitaire de Saraya, District sanitaire de Kedougou, University of Texas [El Paso] (UTEP ), New Mexico State University, and The research was funded by the National Institutes of Health (Grant Number 5R01A 1069145).
Subjects: 0301 basic medicine, sylvatic circulation, 030231 tropical medicine, medicine.disease_cause, Chikungunya fever, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, medicine, Major Article, Chikungunya, Viral isolation, Aedes, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, School age child, biology, outbreak, business.industry, Outbreak, virus diseases, biology.organism_classification, Senegal, 3. Good health, Kedougou, 030104 developmental biology, Infectious Diseases, Oncology, Ethnology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, Chikungunya virus
Abstract: Background In Senegal, Chikungunya virus (CHIKV), which is an emerging mosquito-borne alphavirus, circulates in a sylvatic and urban/domestic cycle and has caused sporadic human cases and epidemics since 1960s. However, the real impact of the CHIKV sylvatic cycle in humans and mechanisms underlying its emergence still remains unknown. Methodology One thousand four hundred nine suspect cases of CHIKV infection, recruited from 5 health facilities located in Kedougou region, south-eastern Senegal, between May 2009 to March 2010, together with 866 serum samples collected from schoolchildren from 4 elementary schools in May and November 2009 from Kedougou were screened for anti-CHIKV immunoglobulin (Ig)M antibodies and, when appropriate, for viral nucleic acid by real-time polymerase chain reaction (rPCR) and virus isolation. In addition, mosquitoes collected in the same area from May 2009 to January 2010 were tested for CHIKV by rPCR and by virus isolation, and 116 monkeys sera collected from March 2010 to May 2010 were tested for anti-CHIKV IgM and neutralizing antibodies. Results The main clinical manifestations of the CHIKV suspect cases were headache, myalgia, and arthralgia. Evidence for CHIKV infection was observed in 1.4% (20 of 1409) of patients among suspect cases. No significant difference was observed among age or sex groups. In addition, 25 (2.9%) students had evidence of CHIKV infection in November 2009. Chikungunya virus was detected in 42 pools of mosquitoes, mainly from Aedes furcifer, and 83% of monkeys sampled were seropositive. Conclusions Our findings further documented that CHIKV is maintained in a sylvatic transmission cycle among monkeys and Aedes mosquitoes in Kedougou, and humans become infected by exposure to the virus in the forest.
Published: 2018
Full Text: View/download PDF

22. Lactobacillus rhamnosus GG increases cyclooxygenase-2 expression and prostaglandin E2 secretion in colonic myofibroblasts via a MyD88-dependent mechanism during homeostasis

Author: Daniel L. Worthley, Maria C. Urdaci, Philippe Bressollier, Romain Villeger, Rachel Dillard, Don W. Powell, Gabriela Uribe, Irina V. Pinchuk, Timothy C. Wang, The University of Texas Medical Branch (UTMB), Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne), Laboratoire de Chimie des Substances Naturelles (LCSN), Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503), Daniel Guggenheim School of Aerospace Engineering (GA TECH), Georgia Institute of Technology [Atlanta], Chimie et Biologie des Membranes et des Nanoobjets (CBMN), Université de Bordeaux (UB)-École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne)-Institut National de la Recherche Agronomique (INRA), École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie du CNRS (INC)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte - Clermont Auvergne (M2iSH), Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne), and Université Sciences et Technologies - Bordeaux 1-École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Stromal cell, Colon, Immunology, Prostaglandin, Administration, Oral, Mice, Transgenic, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], Biology, Microbiology, [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity, Article, Dinoprostone, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Downregulation and upregulation, Virology, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], medicine, Animals, Homeostasis, Humans, Prostaglandin E2, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], Myofibroblasts, ComputingMilieux_MISCELLANEOUS, Leukotriene, Innate immune system, Arachidonate 5-Lipoxygenase, Arachidonic Acid, Lacticaseibacillus rhamnosus, Probiotics, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], Mice, Inbred C57BL, 030104 developmental biology, Eicosanoid, chemistry, Cyclooxygenase 2, 030220 oncology & carcinogenesis, Myeloid Differentiation Factor 88, Cancer research, Caco-2 Cells, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, medicine.drug
Abstract: Prostaglandin E2 (PGE2 ) plays a critical role in intestinal mucosal tolerance and barrier integrity. Cyclooxygenase-2 (COX-2)-dependent PGE2 production involves mobilisation of arachidonic acid. Lactobacillus rhamnosus GG (LbGG) is one of the most widely used probiotics reported to colonise the colonic mucosa. LbGG contributes to the protection of the small intestine against radiation injury through the repositioning of mucosal COX-2 expressing cells. However, it is unknown if LbGG modulates PGE2 production in the colonic mucosa under homeostasis and the major cellular elements involved in these processes. Colonic epithelial and CD90+ mesenchymal stromal cells, also known as (myo) fibroblasts (CMFs), are abundant innate immune cells in normal colonic mucosa able to produce PGE2 . Herein, we tested the hypothesis that under colonic mucosal homeostasis, LbGG modulates the eicosanoid pathway resulting in increased PGE2 production in both epithelial and stromal cells. Among the five tested human colonic epithelial cell lines, only exposure of Caco-2 to LbGG for 24 hr led to the mobilisation of arachidonic acid with concomitant increase in the components within the leukotriene and COX-2-dependent PGE2 pathways. By contrast, CMFs isolated from the normal human colonic mucosa responded to LbGG with increased expression of COX-2 and PGE2 in the prostaglandin pathway, but not 5-LO in the leukotriene pathway. Oral gavage of C57BL/6 mice for 5 days with LbGG (5 × 108 Colony-Forming Unit (CFU)/dose) increased COX-2 expression in the colonic mucosa. The majority of cells upregulating COX-2 protein expression were located in the colonic lamina propria and colocalised with α-SMA+ cells corresponding to the CMF phenotype. This process was myeloid differentiation factor-88-dependent, because silencing of myeloid differentiation factor-88 expression in CMFs abrogated LbGG-induced upregulation of COX-2 in culture and in vivo. Taken together, our data suggest that LbGG increases release of COX-2-mediated PGE2 , contributing to the maintenance of mucosal homeostasis in the colon and CMFs are among the major contributors to this process.
Published: 2017
Full Text: View/download PDF

23. Dual Inhibition of EGFR and c-Src by Cetuximab and Dasatinib Combined with FOLFOX Chemotherapy in Patients with Metastatic Colorectal Cancer

Author: Alain R. Thierry, Christine Megerdichian Parseghian, Ji Yuan Wu, Kanwal Pratap Singh Raghav, Feng Tian, Laura Henderson, Nila U. Parikh, Anastasia D. Katsiampoura, Marc Ychou, Scott Kopetz, Zhi-Qin Jiang, David G. Menter, Gary E. Gallick, Cathy Eng, David R. Fogelman, Robert A. Wolff, Michael J. Overman, Arvind Dasari, Brice Pastor, The University of Texas M.D. Anderson Cancer Center [Houston], The University of Texas Medical Branch (UTMB), Tsinghua University [Beijing] (THU), Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), and CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)
Subjects: 0301 basic medicine, Oncology, Adult, Male, Cancer Research, medicine.medical_specialty, Maximum Tolerated Dose, Organoplatinum Compounds, Colorectal cancer, medicine.medical_treatment, Dasatinib, Leucovorin, Cetuximab, [SDV.CAN]Life Sciences [q-bio]/Cancer, medicine.disease_cause, Disease-Free Survival, Article, CSK Tyrosine-Protein Kinase, Proto-Oncogene Proteins p21(ras), 03 medical and health sciences, 0302 clinical medicine, FOLFOX, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, Medicine, Humans, Aged, Chemotherapy, business.industry, Cancer, Middle Aged, medicine.disease, digestive system diseases, 3. Good health, ErbB Receptors, 030104 developmental biology, src-Family Kinases, 030220 oncology & carcinogenesis, Female, KRAS, Fluorouracil, business, Colorectal Neoplasms, MESH: Colorectal Neoplasms, medicine.drug, Proto-oncogene tyrosine-protein kinase Src
Abstract: Purpose: Aberrant activation of the intracellular tyrosine kinase Src has been implicated as a mechanism of acquired chemotherapy resistance in metastatic colorectal cancer (mCRC). Here, the oral tyrosine kinase Src inhibitor, dasatinib, was investigated in combination with FOLFOX and cetuximab. Experimental Design: We performed a phase IB/II study of 77 patients with previously treated mCRC. Primary objectives were to determine the maximum tolerated dose, dose-limiting toxicities (DLT), pharmacodynamics, and efficacy. Using a 3 + 3 design, patients received FOLFOX6 with cetuximab and escalating doses of dasatinib (100, 150, 200 mg daily), followed by a 12-patient expansion cohort at 150 mg. Phase II studies evaluated FOLFOX plus dasatinib 100 mg in KRAS c12/13mut patients or in combination with cetuximab if KRAS c12/13WT. FAK and paxillin were utilized as surrogate blood biomarkers of Src inhibition, and paired biopsies of liver metastases were obtained in patients in the expansion cohort. Results: In phase IB, the DLTs were grade 3/4 fatigue (20%) and neutropenia (23%). In phase II, grade 3/4 fatigue (23%) and pleural effusions (11%) were present. Response rates were 20% (6 of 30) in the phase IB escalation and expansion cohort and 13% (3 of 24) and 0% (0 of 23) in the KRAS c12/13WT and mutant cohorts of phase II, respectively. Median progression-free survival was 4.6, 2.3, and 2.3 months, respectively. There was no evidence of Src inhibition based on surrogate blood biomarkers or paired tumor biopsies. Conclusions: The combination of dasatinib plus FOLFOX with or without cetuximab showed only modest clinical activity in refractory colorectal cancer. This appears to be primarily due to a failure to fully inhibit Src at the achievable doses of dasatinib. The combination of dasatinib plus FOLFOX with or without cetuximab did not show meaningful clinical activity in refractory colorectal cancer due to failure to fully inhibit Src. Clin Cancer Res; 23(15); 4146–54. ©2017 AACR.
Published: 2017
Full Text: View/download PDF

24. Chikungunya Virus Infections

Author: Fabrice, Simon, Emilie, Javelle, Philippe, Gasque, The University of Texas Medical Branch (UTMB), Biologie des Infections - Biology of Infection, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), and Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: viruses, [SDV]Life Sciences [q-bio], education, MESH: Chikungunya Fever, MESH: Insect Vectors, Chikungunya fever, medicine.disease_cause, Virus, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, parasitic diseases, Medicine, Animals, Humans, MESH: Animals, 030212 general & internal medicine, Chikungunya, 030304 developmental biology, 0303 health sciences, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, MESH: Humans, business.industry, virus diseases, MESH: Chikungunya virus, General Medicine, Virology, 3. Good health, Insect Vectors, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Culicidae, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Chikungunya Fever, Animals, Chikungunya Fever, Chikungunya virus, CULICIDAE, Humans, Insect Vectors, business, MESH: Culicidae, Chikungunya virus, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Comment on Chikungunya virus and the global spread of a mosquito-borne disease. [N Engl J Med. 2015] Chikungunya Virus Infections. [N Engl J Med. 2015] Chikungunya Virus Infections. [N Engl J Med. 2015]; International audience; To the Editor and Response
Published: 2015
Full Text: View/download PDF

25. Chikungunya Virus and the Global Spread of a Mosquito-Borne Disease

Author: Marc Lecuit, Scott C. Weaver, The University of Texas Medical Branch (UTMB), Global Virus Network, Biologie des Infections - Biology of Infection, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5), CHU Necker - Enfants Malades [AP-HP], Service des Maladies infectieuses et tropicales [CHU Necker], Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP]-Institut des Maladies Génétiques Imagine [Paris], Institut des Maladies Génétiques Imagine [Paris], We thank Therese Couderc, the members of the Biology of Infection Unit, and the members of the Chikungunya Task Force at Institut Pasteur, and Rose Langsjoen for assistance with graphics., University of South Florida [Tampa] (USF), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)
Subjects: musculoskeletal diseases, myalgia, viruses, [SDV]Life Sciences [q-bio], 030231 tropical medicine, Disease, Alphavirus, MESH: Chikungunya Fever, MESH: Insect Vectors, medicine.disease_cause, Virus, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, parasitic diseases, medicine, MESH: Animals, Chikungunya, MESH: Disease Outbreaks, MESH: Travel, 030304 developmental biology, Mosquito-borne disease, 0303 health sciences, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, MESH: Humans, biology, business.industry, virus diseases, MESH: Chikungunya virus, General Medicine, medicine.disease, biology.organism_classification, Virology, Rash, 3. Good health, body regions, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Chikungunya Virus Infection, Immunology, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, MESH: Disease Progression, medicine.symptom, business, MESH: Culicidae, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Comment in Chikungunya Virus Infections. [N Engl J Med. 2015] Chikungunya Virus Infections. [N Engl J Med. 2015] Chikungunya Virus Infections. [N Engl J Med. 2015]; International audience; Chikungunya virus is a mosquito-borne alphavirus; its name comes from a Makonde word describing the bent posture of persons with the severe arthralgia that is a hallmark of chikungunya fever, the disease caused by the virus.1 Chikungunya virus was first isolated after a 1952–1953 epidemic in present-day Tanzania. Outbreaks were subsequently identified in Asia during the 1950s and 1960s [...]
Published: 2015
Full Text: View/download PDF

26. Lack of evidence for Zika virus transmission by Culex mosquitoes

Author: Scott C. Weaver, Scott A. Ritchie, Aaron C. Brault, Nikos Vasilakis, Ricardo Lourenço-de-Oliveira, Guilherme S. Ribeiro, Gregory D. Ebel, Laura Beatriz Tauro, Jorge E. Osorio, Gonzalo M. Vazquez-Prokopec, Laura D. Kramer, Christopher M. Roundy, Igor Adolfo Dexheimer Paploski, Uriel Kitron, Ildefonso Fernández-Salas, Sasha R. Azar, Anna-Bella Failloux, The University of Texas Medical Branch (UTMB), Centers for Disease Control and Prevention, Colorado State University [Fort Collins] (CSU), Arbovirus et Insectes Vecteurs - Arboviruses and Insect Vectors, Institut Pasteur [Paris], Centro Regional de Investigación en Salud Pública = Regional Centre of Research in Public Health [Tapachula, Mexique] (CRISP), National Institute of Public Health = Instituto Nacional de Salud Pública [Cuernavaca, Mexique] (INSP), Emory University [Atlanta, GA], Wadsworth Center, New York State Department of Health [Albany], Fundação Oswaldo Cruz (FIOCRUZ), Réseau International des Instituts Pasteur (RIIP), University of Wisconsin-Madison, Universidade Federal da Bahia (UFBA), James Cook University (JCU), Institut Pasteur [Paris] (IP), and Fundação Oswaldo Cruz / Oswaldo Cruz Foundation (FIOCRUZ)
Subjects: 0301 basic medicine, Epidemiology, Culex, 030231 tropical medicine, Immunology, Microbiology, Zika virus, law.invention, 03 medical and health sciences, 0302 clinical medicine, Aedes, law, Virology, parasitic diseases, Drug Discovery, Animals, Humans, Letter to the Editor, biology, Zika Virus Infection, fungi, Zika Virus, General Medicine, biology.organism_classification, Insect Vectors, 3. Good health, 030104 developmental biology, Infectious Diseases, Transmission (mechanics), [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Parasitology
Abstract: Response to: ‘Lack of evidence for Zika virus transmission by Culex mosquitoes’https://www.nature.com/articles/emi201786doi:10.1038/emi.2017.86; International audience; LETTER TO THE EDITORDear Editor,Since Zika virus (ZIKV) emerged in the Americas, major research efforts have been focused on identifying the mosquito species responsible for transmission. [...]
Published: 2017
Full Text: View/download PDF

27. SNMIB/Apollo protects leading-strand telomeres against NHEJ-mediated repair

Author: Sandy Chang, Eric Gilson, Anaïs Poulet, Yung C. Lam, Randy J. Legerski, Peili Gu, Marie Josèphe Giraud-Panis, Shamima Akhter, Susan M. Bailey, Jing Ye, Department of Genetics, The University of Texas Medical Branch (UTMB), Laboratoire de biologie et pathologie des génomes, Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Environmental and Radiological Health Sciences, Colorado State University [Fort Collins] (CSU), Department of Medical Genetics, Centre Hospitalier Universitaire de Nice (CHU Nice), Department of Hematopathology, Ganivet, Agnès, Laboratory of Biology and Pathology of Genomes, and Centre National de la Recherche Scientifique (CNRS)
Subjects: Exonuclease, chromosomes, DNA Repair, DNA damage, Telomere-Binding Proteins, Cell Cycle Proteins, Ataxia Telangiectasia Mutated Proteins, Protein Serine-Threonine Kinases, Biology, Aminopeptidases, Shelterin Complex, Article, General Biochemistry, Genetics and Molecular Biology, Mice, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Animals, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Dipeptidyl-Peptidases and Tripeptidyl-Peptidases, Molecular Biology, 030304 developmental biology, Mice, Knockout, 0303 health sciences, Nuclease, Tripeptidyl-Peptidase 1, General Immunology and Microbiology, DNA synthesis, Tumor Suppressor Proteins, General Neuroscience, DNA replication, Fibroblasts, Telomere, Embryo, Mammalian, telomeres, Molecular biology, DNA-Binding Proteins, Exodeoxyribonucleases, chemistry, 030220 oncology & carcinogenesis, Knockout mouse, biology.protein, Serine Proteases, DNA
Abstract: Progressive telomere attrition or deficiency of the protective shelterin complex elicits a DNA damage response as a result of a cell's inability to distinguish dysfunctional telomeric ends from DNA double-strand breaks. SNMIB/Apollo is a shelterin-associated protein and a member of the SMN1/PSO2 nuclease family that localizes to telomeres through its interaction with TRF2. Here, we generated SNMIB/Apollo knockout mouse embryo fibroblasts (MEFs) to probe the function of SNMIB/Apollo at mammalian telomeres. SNMIB/Apollo null MEFs exhibit an increased incidence of G2 chromatid-type fusions involving telomeres created by leading-strand DNA synthesis, reflective of a failure to protect these telomeres after DNA replication. Mutations within SNMIB/Apollo's conserved nuclease domain failed to suppress this phenotype, suggesting that its nuclease activity is required to protect leading-strand telomeres. SNMIB/Apollo(-/-)ATM(-/-) MEFs display robust telomere fusions when Trf2 is depleted, indicating that ATM is dispensable for repair of uncapped telomeres in this setting. Our data implicate the 5'-3' exonuclease function of SNM1B/Apollo in the generation of 3' single-stranded overhangs at newly replicated leading-strand telomeres to protect them from engaging the non-homologous end-joining pathway.
Published: 2010

28. Beta-catenin/Tcf-4 inhibition after progastrin targeting reduces growth and drives differentiation of intestinal tumors

Author: Julie Pannequin, Arthur Shulkes, André Pèlegrin, Fanny Surrel, Graham S. Baldwin, Pomila Singh, Frédéric Hollande, Nathalie Delaunay, Dominique Joubert, Joanne Ryan, Gérard Lambeau, Christine Pignodel, Philippe Jay, Stéphanie Boireau, Mildred Yim, Jean-François Bourgaux, Jessica Coelho, Michael Buchert, Institut de Génomique Fonctionnelle (IGF), Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), Institut de pharmacologie moléculaire et cellulaire (IPMC), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS), Service d'Hépato Gastroentérologie, Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Immunociblage des tumeurs et ingénierie des anticorps, Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Neuroscience & Cell Biology, The University of Texas Medical Branch (UTMB), and Service d'Anatomopathologie
Subjects: MESH: Signal Transduction, Small interfering RNA, MESH: Protein Precursors, MESH: Random Allocation, MESH: beta Catenin, Apoptosis, Cell Cycle Proteins, MESH: Gastrins, Mice, Phosphatidylinositol 3-Kinases, Random Allocation, 0302 clinical medicine, Differentiation therapy, MESH: RNA, Small Interfering, MESH: Animals, RNA, Small Interfering, beta Catenin, Regulation of gene expression, 0303 health sciences, MESH: Genes, APC, biology, Gastroenterology, MESH: Transcription Factors, MESH: Gene Expression Regulation, Neoplastic, Gene Expression Regulation, Neoplastic, Cell Transformation, Neoplastic, Adenomatous Polyposis Coli, 030220 oncology & carcinogenesis, Colorectal Neoplasms, TCF Transcription Factors, Transcription Factor 7-Like 2 Protein, Signal Transduction, Adenoma, Transcriptional Activation, Genes, APC, Beta-catenin, MESH: Cell Line, Tumor, Adenomatous polyposis coli, Transplantation, Heterologous, Mice, Nude, [SDV.CAN]Life Sciences [q-bio]/Cancer, 03 medical and health sciences, MESH: Cell Cycle Proteins, Cell Line, Tumor, MESH: Cell Proliferation, Gastrins, MESH: Mice, Nude, Animals, Humans, Protein Precursors, MESH: Transplantation, Heterologous, MESH: Mice, PI3K/AKT/mTOR pathway, Adaptor Proteins, Signal Transducing, Cell Proliferation, 030304 developmental biology, MESH: Adenoma, MESH: Humans, Hepatology, Cell growth, MESH: Apoptosis, MESH: 1-Phosphatidylinositol 3-Kinase, Molecular biology, MESH: Adenomatous Polyposis Coli, Repressor Proteins, MESH: Cell Transformation, Neoplastic, Catenin, Cancer research, biology.protein, MESH: TCF Transcription Factors, MESH: Colorectal Neoplasms, Transcription Factors
Abstract: BACKGROUND & AIMS: Aberrant activation of the beta-catenin/Tcf-4 transcriptional complex represents an initiating event for colorectal carcinogenesis, shifting the balance from differentiation toward proliferation in colonic crypts. Here, we assessed whether endogenous progastrin, encoded by a target gene of this complex, was in turn able to regulate beta-catenin/Tcf-4 activity in adenomatous polyposis coli (APC)-mutated cells, and we analyzed the impact of topical progastrin depletion on intestinal tumor growth in vivo. METHODS: Stable or transient RNA silencing of the GAST gene was induced in human tumor cells and in mice carrying a heterozygous Apc mutation (APCDelta14), which overexpress progastrin but not amidated or glycine-extended gastrin. RESULTS: Depletion of endogenous progastrin production strongly decreased intestinal tumor growth in vivo through a marked inhibition of constitutive beta-catenin/Tcf-4 activity in tumor cells. This effect was mediated by the de novo expression of the inhibitor of beta-catenin and Tcf-4 (ICAT), resulting from a down-regulation of integrin-linked kinase in progastrin-depleted cells. Accordingly, ICAT down-regulation was correlated with progastrin overexpression and Tcf-4 target gene activation in human colorectal tumors, and ICAT repression was detected in the colon epithelium of tumor-prone, progastrin-overexpressing mice. In APCDelta14 mice, small interfering RNA-mediated progastrin depletion not only reduced intestinal tumor size and numbers, but also increased goblet cell lineage differentiation and cell apoptosis in the remaining adenomas. CONCLUSIONS: Thus, depletion of endogenous progastrin inhibits the tumorigenicity of APC-mutated colorectal cancer cells in vivo by promoting ICAT expression, thereby counteracting Tcf-4 activity. Progastrin targeting strategies should provide an exciting prospect for the differentiation therapy of colorectal cancer.
Published: 2007
Full Text: View/download PDF

29. Insulin sensitivity and mitochondrial function are improved in children with burn injury during a randomized controlled trial of fenofibrate

Author: Ting Qian, Asle Aarsland, David N. Herndon, Melanie G. Cree, Béatrice Morio, Arthur P. Sanford, Ricki Y. Fram, Robert R. Wolfe, Jennifer J. Zwetsloot, University of Texas Medical Branch, Partenaires INRAE, East Carolina University, Shriners Hospitals for Children [Boston], Department of Cell Physiology, Unité de Nutrition Humaine (UNH), Institut National de la Recherche Agronomique (INRA)-Université d'Auvergne - Clermont-Ferrand I (UdA)-Clermont Université, Centre de Recherche en Nutrition Humaine, Department of Anesthesiology, and The University of Texas Medical Branch (UTMB)
Subjects: Blood Glucose, medicine.medical_specialty, Adolescent, medicine.medical_treatment, Biopsy, [SDV]Life Sciences [q-bio], 03 medical and health sciences, 0302 clinical medicine, Insulin resistance, Double-Blind Method, Fenofibrate, Diabetes mellitus, Intensive care, Internal medicine, medicine, Humans, PPAR alpha, Myocardial infarction, Prospective Studies, Child, Muscle, Skeletal, 030304 developmental biology, Hypolipidemic Agents, 0303 health sciences, Trauma Severity Indices, business.industry, Insulin, 030208 emergency & critical care medicine, Glucose clamp technique, medicine.disease, 3. Good health, Metformin, Mitochondria, Muscle, Endocrinology, Treatment Outcome, Liver, Child, Preschool, Randomized Controlled Trial, Cardiology, Glucose Clamp Technique, Surgery, Animal studies, Insulin Resistance, business, Burns, medicine.drug, Follow-Up Studies
Abstract: Multiple studies have documented hyperglycemia and insulin resistance following trauma, myocardial infarction, stroke, or surgery.1–4 Both are of serious clinical concern, as hyperglycemia is associated with increased morbidity and mortality of critically ill, surgical, and burned patients.3–5 These outcome studies emphasize the importance of better understanding insulin resistance in this large patient population. Pediatric burns provide a unique model for studying acute onset insulin resistance, since the nature of the injury is severe and quantifiable and the timing of onset is exactly known. Further, lean children are much less likely to have preexisting comorbid conditions such as diabetes, or to have been taking medications prior to injury. We have recently demonstrated that mitochondrial oxidative function is impaired in burned children by more than 70% at 1 week postburn.6 A limited number of animal studies have found that mitochondrial genes, protein, and function are also decreased in skeletal muscle, liver, and cardiac muscle following burn injury.7–9 Similar findings were reported from the liver of patients who died after prolonged stays in intensive care for nonsurgical illness.10 In patients with type II diabetes, correlations between mitochondrial function and insulin sensitivity have been documented.11,12 These studies indicate that improving mitochondrial function may be a potential treatment target for improving insulin sensitivity. There are limited proven therapies for treating acute injury-induced insulin resistance. Insulin therapy to prevent hyperglycemia has been shown to reduce mortality and/or morbidity in intensive care patients, patients undergoing surgical procedures and in burns.4,10 However, intensive insulin therapy requires constant vigilance and does not alter the underlying pathology. One study found that metformin decreased muscle loss after burn,13 but other medications that are typically prescribed for treatment of insulin resistance have not been tested in these populations. PPAR-γ agonists, or thioglitazones, have been shown to improve insulin sensitivity in patients with diabetes.14 The mechanism of action apparently involves suppression of peripheral lipolysis and redistribution of triglyceride stores to subcutaneous fat cells.14 However, burned children often have a large amount of their subcutaneous triglyceride stores destroyed or removed, decreasing the availability for redistribution sites. Further, burn patients may be treated with the beta-blocking agent propranolol to reduce myocardial stress, which also suppresses lipolysis.15 Therefore, a PPAR-γ agonist would be anticipated to be redundant in children given propranolol. PPAR-α agonists have been shown in numerous animal studies and a few human studies to improve insulin sensitivity by enhancing mitochondrial function.16–18 We therefore hypothesized that PPAR-α agonism would stimulate mitochondrial function and improve insulin sensitivity in pediatric burn patients.
Published: 2007
Full Text: View/download PDF

30. PPAR-α agonism improves whole body and muscle mitochondrial fat oxidation, but does not alter intracellular fat concentrations in burn trauma children in a randomized controlled trial

Author: Ronald P. Mlcak, Dayoung Sun, Asle Aarsland, Béatrice Morio, Melanie G. Cree, G. Lynis Dohm, Ricki Y. Fram, Jennifer J. Zwetsloot, Ting Qian, Bradley R. Newcomer, Robert R. Wolfe, David N. Herndon, University of Texas Medical Branch, Partenaires INRAE, University of Alabama, Department of Finance, Shriners Hospitals for Children [Boston], Unité de Nutrition Humaine (UNH), Institut National de la Recherche Agronomique (INRA)-Université d'Auvergne - Clermont-Ferrand I (UdA)-Clermont Université, Centre de Recherche en Nutrition Humaine, East Carolina University, Department of Anesthesiology, and The University of Texas Medical Branch (UTMB)
Subjects: Agonist, medicine.medical_specialty, medicine.drug_class, [SDV]Life Sciences [q-bio], Endocrinology, Diabetes and Metabolism, Peroxisome proliferator-activated receptor, Medicine (miscellaneous), lcsh:TX341-641, 030209 endocrinology & metabolism, 03 medical and health sciences, chemistry.chemical_compound, Acyl-CoA, 0302 clinical medicine, Insulin resistance, Internal medicine, medicine, Carnitine, lcsh:RC620-627, 030304 developmental biology, Diacylglycerol kinase, chemistry.chemical_classification, 0303 health sciences, Nutrition and Dietetics, Triglyceride, business.industry, Research, medicine.disease, 3. Good health, lcsh:Nutritional diseases. Deficiency diseases, Endocrinology, chemistry, lipids (amino acids, peptides, and proteins), business, lcsh:Nutrition. Foods and food supply, Intracellular, medicine.drug
Abstract: Article n.9 Open access : http://www.nutritionandmetabolism.com/content/4/1/9 http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=17451602; International audience; BACKGROUND: Insulin resistance is often associated with increased levels of intracellular triglycerides, diacylglycerol and decreased fat beta-oxidation. It was unknown if this relationship was present in patients with acute insulin resistance induced by trauma. METHODS: A double blind placebo controlled trial was conducted in 18 children with severe burn injury. Metabolic studies to assess whole body palmitate oxidation and insulin sensitivity, muscle biopsies for mitochondrial palmitate oxidation, diacylglycerol, fatty acyl Co-A and fatty acyl carnitine concentrations, and magnetic resonance spectroscopy for muscle and liver triglycerides were compared before and after two weeks of placebo or PPAR-alpha agonist treatment. RESULTS: Insulin sensitivity and basal whole body palmitate oxidation as measured with an isotope tracer increased significantly (P = 0.003 and P = 0.004, respectively) after PPAR-alpha agonist treatment compared to placebo. Mitochondrial palmitate oxidation rates in muscle samples increased significantly after PPAR-alpha treatment (P = 0.002). However, the concentrations of muscle triglyceride, diacylglycerol, fatty acyl CoA, fatty acyl carnitine, and liver triglycerides did not change with either treatment. PKC-theta activation during hyper-insulinemia decreased significantly following PPAR-alpha treatment. CONCLUSION: PPAR-alpha agonist treatment increases palmitate oxidation and decreases PKC activity along with reduced insulin sensitivity in acute trauma, However, a direct link between these responses cannot be attributed to alterations in intracellular lipid concentrations.
Full Text: View/download PDF

Catalog

Books, media, physical & digital resources

See catalog results

Searchworks

Select search scope, currently: Articles

Catalog

books, media & more in Jio Institute collections

Articles

journal articles & other e-resources

Refine your results

30 results on '"The University of Texas Medical Branch ( UTMB )"'

1. Dynamic interactions and Ca2+-binding modulate the holdase-type chaperone activity of S100B preventing tau aggregation and seeding

2. Antioxidant Supplementation Does Not Affect Bone Turnover Markers During 60 Days of 6° Head-Down Tilt Bed Rest: Results from an Exploratory Randomized Controlled Trial

3. Hepatitis C virus proteins induce lipogenesis and defective triglyceride secretion in transgenic mice

4. Behavioural responses of juvenile cuttlefish (Sepia officinalis) to local water movements

5. Excess all-cause mortality and COVID-19-related mortality:a temporal analysis in 22 countries, from January until August 2020

6. Pannexin-1 channel opening is critical for COVID-19 pathogenesis

7. Editorial: The Autophagy Pathway: Bacterial Pathogen Immunity and Evasion

8. Synaptic dysregulation and hyperexcitability induced by intracellular amyloid beta oligomers

9. Rational design of universal immunotherapy for TfR1-tropic arenaviruses

10. Antiviral activity of oleandrin and a defined extract of Nerium oleander against SARS-CoV-2

11. Mosquito‐bacteria interactions during larval development trigger metabolic changes with carry‐over effects on adult fitness

12. Resurgence of Ebola Virus in 2021 in Guinea Suggests a New Paradigm for Outbreaks

13. Specific Immunologic Countermeasure Protocol for Deep-Space Exploration Missions

14. NLRP3 inflammasome activation drives tau pathology

15. GloPID-R report on chikungunya, o'nyong-nyong and Mayaro virus, part 3: Epidemiological distribution of Mayaro virus

16. Meeting the challenge of tick-borne disease control: A proposal for 1000 Ixodes genomes

17. Changes in the Transmission Dynamic of Chikungunya Virus in Southeastern Senegal

18. Novel Wolbachia strains in Anopheles malaria vectors from Sub-Saharan Africa

19. i-BLESS is an ultra-sensitive method for detection of DNA double-strand breaks

20. Zika, Chikungunya, and Other Emerging Vector-Borne Viral Diseases

21. Chikungunya Outbreak in Kedougou, Southeastern Senegal in 2009-2010

22. Lactobacillus rhamnosus GG increases cyclooxygenase-2 expression and prostaglandin E2 secretion in colonic myofibroblasts via a MyD88-dependent mechanism during homeostasis

23. Dual Inhibition of EGFR and c-Src by Cetuximab and Dasatinib Combined with FOLFOX Chemotherapy in Patients with Metastatic Colorectal Cancer

24. Chikungunya Virus Infections

25. Chikungunya Virus and the Global Spread of a Mosquito-Borne Disease

26. Lack of evidence for Zika virus transmission by Culex mosquitoes

27. SNMIB/Apollo protects leading-strand telomeres against NHEJ-mediated repair

28. Beta-catenin/Tcf-4 inhibition after progastrin targeting reduces growth and drives differentiation of intestinal tumors

29. Insulin sensitivity and mitochondrial function are improved in children with burn injury during a randomized controlled trial of fenofibrate

30. PPAR-α agonism improves whole body and muscle mitochondrial fat oxidation, but does not alter intracellular fat concentrations in burn trauma children in a randomized controlled trial

Catalog

Searchworks

Select search scope, currently: Articles Catalog books, media & more in Jio Institute collections Articles journal articles & other e-resources

Search

Search Constraints

Refine your results

Search Limiters

Topic

Publication Year Range

Language

Journal

Database

Publisher

30 results on '"The University of Texas Medical Branch ( UTMB )"'

Search Results

Catalog

Select search scope, currently: Articles

Catalog

books, media & more in Jio Institute collections

Articles

journal articles & other e-resources