74 research outputs found
Platelet Serotonin Aggravates Myocardial Ischemia/Reperfusion Injury via Neutrophil Degranulation
Background: Platelets store large amounts of serotonin that they release during thrombus formation or acute inflammation. This facilitates hemostasis and modulates the inflammatory response. Methods: Infarct size, heart function, and inflammatory cell composition were analyzed in mouse models of myocardial reperfusion injury with genetic and pharmacological depletion of platelet serotonin. These studies were complemented by in vitro serotonin stimulation assays of platelets and leukocytes in mice and men, and by measuring plasma serotonin levels and leukocyte activation in patients with acute coronary syndrome. Results: Platelet-derived serotonin induced neutrophil degranulation with release of myeloperoxidase and hydrogen peroxide (H2O2) and increased expression of membrane-bound leukocyte adhesion molecule CD11b, leading to enhanced inflammation in the infarct area and reduced myocardial salvage. In patients hospitalized with acute coronary syndrome, plasmatic serotonin levels correlated with CD11b expression on neutrophils and myeloperoxidase plasma levels. Long-term serotonin reuptake inhibition - reported to protect patients with depression from cardiovascular events - resulted in the depletion of platelet serotonin stores in mice. These mice displayed a reduction in neutrophil degranulation and preserved cardiac function. In line, patients with depression using serotonin reuptake inhibition, presented with suppressed levels of CD11b surface expression on neutrophils and lower myeloperoxidase levels in blood. Conclusions: Taken together, we identify serotonin as a potent therapeutic target in neutrophil-dependent thromboinflammation during myocardial reperfusion injury.Fil: Mauler, Maximilian. No especifĂca;Fil: Herr, Nadine. No especifĂca;Fil: Schoenichen, Claudia. No especifĂca;Fil: Witsch, Thilo. No especifĂca;Fil: Marchini, Timoteo Oscar. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Oficina de CoordinaciĂłn Administrativa Houssay. Instituto de BioquĂmica y Medicina Molecular. Universidad de Buenos Aires. Facultad Medicina. Instituto de BioquĂmica y Medicina Molecular; ArgentinaFil: HĂ€rdtner, Carmen. No especifĂca;Fil: Koentges, Christoph. No especifĂca;Fil: Kienle, Korbinian. Max Planck Institute Of Immunobiology And Epigenetics; AlemaniaFil: Ollivier, VĂ©ronique. Inserm; FranciaFil: Schell, Maximilian. No especifĂca;Fil: Dorner, Ludwig. No especifĂca;Fil: Wippel, Christopher. No especifĂca;Fil: Stallmann, Daniela. No especifĂca;Fil: Normann, Claus. No especifĂca;Fil: Bugger, Heiko. No especifĂca;Fil: Walther, Paul. Universitat Ulm; AlemaniaFil: Wolf, Dennis. La Jolla Institute for Allergy and Immunology; Estados UnidosFil: Ahrens, Ingo. No especifĂca;Fil: LĂ€mmermann, Tim. Max Planck Institute Of Immunobiology And Epigenetics; AlemaniaFil: Ho-Tin-NoĂ©, BenoĂźt. Inserm; FranciaFil: Ley, Klaus. La Jolla Institute for Allergy and Immunology; Estados UnidosFil: Bode, Christoph. No especifĂca;Fil: Hilgendorf, Ingo. No especifĂca;Fil: Duerschmied, Daniel. No especifĂca
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Towards microbiome-informed dietary recommendations for promoting metabolic and mental health: opinion papers of the MyNewGut project
The gut microbiota coexists in partnership with the human host through adaptations to environmental and physiological changes that help maintain dynamic homeostatic healthy states. Break-down of this delicate balance under sustained exposure to stressors (e.g. unhealthy diets) can, however, contribute to the onset of disease. Diet is a key modifiable environmental factor that modulates the gut microbiota and its metabolic capacities that, in turn, could impact human physiology. On this basis, the diet and the gut microbiota could act as synergistic forces that provide resilience against disease or that speed the progress from health to disease states. Associations between unhealthy dietary patterns, non-communicable diseases and intestinal dysbiosis can be explained by this hypothesis. Translational studies showing that dietary-induced alterations in microbial communities recapitulate some of the pathological features of the original host further support this notion. In this introductory paper by the European project MyNewGut, we briefly summarize the investigations conducted to better understand the role of dietary patterns and food components in metabolic and mental health and the specificities of the microbiome-mediating mechanisms. We also discuss how advances in the understanding of the microbiome's role in dietary health effects can help to provide acceptable scientific grounds on which to base dietary advice for promoting healthy living
Framework and baseline examination of the German National Cohort (NAKO)
The German National Cohort (NAKO) is a multidisciplinary, population-based prospective cohort study that aims to investigate the causes of widespread diseases, identify risk factors and improve early detection and prevention of disease. Specifically, NAKO is designed to identify novel and better characterize established risk and protection factors for the development of cardiovascular diseases, cancer, diabetes, neurodegenerative and psychiatric diseases, musculoskeletal diseases, respiratory and infectious diseases in a random sample of the general population. Between 2014 and 2019, a total of 205,415 men and women aged 19â74Â years were recruited and examined in 18 study centres in Germany. The baseline assessment included a face-to-face interview, self-administered questionnaires and a wide range of biomedical examinations. Biomaterials were collected from all participants including serum, EDTA plasma, buffy coats, RNA and erythrocytes, urine, saliva, nasal swabs and stool. In 56,971 participants, an intensified examination programme was implemented. Whole-body 3T magnetic resonance imaging was performed in 30,861 participants on dedicated scanners. NAKO collects follow-up information on incident diseases through a combination of active follow-up using self-report via written questionnaires at 2â3Â year intervals and passive follow-up via record linkages. All study participants are invited for re-examinations at the study centres in 4â5Â year intervals. Thereby, longitudinal information on changes in risk factor profiles and in vascular, cardiac, metabolic, neurocognitive, pulmonary and sensory function is collected. NAKO is a major resource for population-based epidemiology to identify new and tailored strategies for early detection, prediction, prevention and treatment of major diseases for the next 30Â years. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10654-022-00890-5
Selbstberichtete Krebserkrankungen in der NAKO Gesundheitsstudie: Erfassungsmethoden und erste Ergebnisse
BACKGROUND: In the German National Cohort (NAKO Gesundheitsstudie), the largest prospective cohort study in Germany, data on self-reported cancer diagnoses are now available for the first half of participants. OBJECTIVES: Description of the methods to assess self-reported cancer diagnoses and type of cancer in the NAKO and presentation of first results. MATERIALS AND METHODS: In a computer-assisted, standardized personal interview, 101,787 participants (54,526 women, 47,261 men) were asked whether they had ever been diagnosed with cancer (malignant tumors including in situ) by a physician and how many cancer diagnoses they had. The type of cancer was classified with a list. Absolute and relative frequencies of self-reported cancer diagnoses and types of cancer were calculated and compared with cancer registry data. RESULTS: A physician-diagnosed cancer was reported by 9.4% of women and 7.0% of men. Of the participants who reported a cancer diagnosis, 88.3% reported to have had only one cancer diagnosis. In women, the most frequent malignancies were breast cancer, cervical cancer, and melanoma. In men, the most frequent malignancies were prostate cancer, melanoma, and colorectal cancer. Comparing the frequencies of cancer diagnoses reported by 45- to 74-year-old NAKO participants within the last five years to cancer registry-based 5âyear prevalences, most types of cancer were less frequent in the NAKO, with the exception of melanoma in men and women, cervical cancer and liver cancer in women, and bladder cancer and breast cancer in men. CONCLUSIONS: The NAKO is a rich data basis for future investigations of incident cancer
Messung der körperlichen Fitness in der NAKO Gesundheitsstudie: Methoden, QualitÀtssicherung und erste deskriptive Ergebnisse
Die körperliche Fitness ist das MaĂ fĂŒr die individuelle FĂ€higkeit, körperlich aktiv zu sein. Ihre wesentlichen Komponenten sind die kardiorespiratorische Fitness (Cardiorespiratory Fitness, CRF), die Muskelkraft und die Beweglichkeit. Neben der körperlichen AktivitĂ€t ist die körperliche Fitness ein wesentlicher PrĂ€diktor fĂŒr MorbiditĂ€t und MortalitĂ€t. Ziel der Arbeit sind die Beschreibung der Erhebungsmethoden körperlicher Fitness in der NAKO Gesundheitsstudie und die Darstellung erster deskriptiver Ergebnisse. In der NAKO-Basiserhebung wurden die maximale Handgreifkraft (Grip Strength, GS) und die CRF als Komponenten der körperlichen Fitness ĂŒber ein Handdynamometer bzw. ĂŒber einen Fahrradergometertest mit submaximaler Belastung erhoben. Daraus wurde die maximale Sauerstoffaufnahme (VO2max) zur Beurteilung der CRF abgeleitet. Die Ergebnisse von insgesamt 99.068 GS-Messungen und 3094 Messungen der CRF beruhen auf einem Datensatz zur Halbzeit der Basiserhebung der NAKO (Alter 20â73 Jahre, 47âŻ% MĂ€nner). MĂ€nner zeigten im Vergleich zu Frauen höhere Werte der körperlichen Fitness (MĂ€nner: GSâŻ=â47,8âŻkg, VO2maxâŻ=â36,4âŻml·minâ1âŻÂ·âkgâ1; Frauen: GSâŻ=â29,9âŻkg, VO2maxâŻ=â32,3âŻml·minâ1âŻÂ·âkgâ1). UngefĂ€hr ab dem 50. Lebensjahr konnte ein RĂŒckgang der GS verzeichnet werden, wohingegen die CRF ab der Altersgruppe 20â29 Jahre bis zu den â„60-JĂ€hrigen kontinuierlich abfiel. Die GS und die VO2max zeigten nach Korrektur fĂŒr das Körpergewicht einen linear positiven Zusammenhang (MĂ€nner ÎČâŻ=â0,21; Frauen ÎČâŻ=â0,35). Die Analysen zeigten eine gute Ăbereinstimmung der Verteilung der körperlichen Fitness in der NAKO im Vergleich zu anderen bevölkerungsbasierten Studien. ZukĂŒnftige Auswertungen werden insbesondere die unabhĂ€ngige Bedeutung der GS und CRF bei der PrĂ€diktion von MorbiditĂ€t und MortalitĂ€t beleuchten.Physical fitness is defined as an individualâs ability to be physically active. The main components are cardiorespiratory fitness (CRF), muscle strength, and flexibility. Regardless of physical activity level, physical fitness is an important determinant of morbidity and mortality. The aim of the current study was to describe the physical fitness assessment methodology in the German National Cohort (NAKO) and to present initial descriptive results in a subsample of the cohort. In the NAKO, hand grip strength (GS) and CRF as physical fitness components were assessed at baseline using a hand dynamometer and a submaximal bicycle ergometer test, respectively. Maximum oxygen uptake (VO2max) was estimated as a result of the bicycle ergometer test. The results of a total of 99,068 GS measurements and 3094 CRF measurements are based on a data set at halftime of the NAKO baseline survey (age 20â73 years, 47% men). Males showed higher values of physical fitness compared to women (males: GSâŻ=â47.8âŻkg, VO2maxâŻ=â36.4âŻml·minâ1âŻÂ·âkgâ1; females: GSâŻ=â29.9âŻkg, VO2maxâŻ=â32.3âŻmlâŻÂ·âminâ1âŻÂ·âkgâ1). GS declined from the age of 50 onwards, whereas VO2max levels decreased continuously between the age groups of 20â29 and â„60 years. GS and VO2max showed a linear positive association after adjustment for body weight (males ÎČâŻ=â0.21; females ÎČâŻ=â0.35). These results indicate that the physical fitness measured in the NAKO are comparable to other population-based studies. Future analyses in this study will focus on examining the independent relations of GS and CRF with risk of morbidity and mortality
Die Basiserhebung der NAKO Gesundheitsstudie: Teilnahme an den Untersuchungsmodulen, QualitÀtssicherung und Nutzung von SekundÀrdaten
BACKGROUND: The German National Cohort (NAKO) is an interdisciplinary health study aimed at elucidating causes for common chronic diseases and detecting their preclinical stages. This article provides an overview of design, methods, participation in the examinations, and their quality assurance based on the midterm baseline dataset (MBD) of the recruitment. METHODS: More than 200,000 women and men aged 20â69 years derived from random samples of the German general population were recruited in 18 study centers (2014â2019). The data collection comprised physical examinations, standardized interviews and questionnaires, and the collection of biomedical samples for all participants (level 1). At least 20% of all participants received additional in-depth examinations (level 2), and 30,000 received whole-body magnet resonance imaging (MRI). Additional information will be collected through secondary data sources such as medical registries, health insurances, and pension funds. This overview is based on the MBD, which included 101,839 participants, of whom 11,371 received an MRI. RESULTS: The mean response proportion was 18%. The participation in the examinations was high with most of the modules performed by over 95%. Among MRI participants, 96% completed all 12 MRI sequences. More than 90% of the participants agreed to the use of complementary secondary and registry data. DISCUSSION: Individuals selected for the NAKO were willing to participate in all examinations despite the time-consuming program. The NAKO provides a central resource for population-based epidemiologic research and will contribute to developing innovative strategies for prevention, screening and prediction of chronic diseases.HINTERGRUND: Die NAKO Gesundheitsstudie ist ein bundesweites interdisziplinĂ€res Forschungsvorhaben mit dem Ziel, die Ursachen fĂŒr chronische Krankheiten und deren vorklinische Stadien zu untersuchen. Der Artikel gibt einen Ăberblick ĂŒber das Studiendesign, die Methoden, die Teilnahme an den Untersuchungen und ihre QualitĂ€tssicherung zur Halbzeit der Basiserhebung.
METHODEN: FĂŒr die Basiserhebung wurden mehr als 200.000 Frauen und MĂ€nner im Alter von 20â69 Jahren aus Zufallsstichproben der Allgemeinbevölkerung in 18 Studienzentren rekrutiert (2014â2019). Die Basiserhebung beinhaltet Untersuchungen, Befragungen und Biomaterialien fĂŒr alle Teilnehmerinnen und Teilnehmer (Level 1), ein erweitertes Programm fĂŒr mindestens 20âŻ% (Level 2) und eine Magnetresonanztomografie (MRT) fĂŒr 30.000 Teilnehmerinnen und Teilnehmer. SekundĂ€r- und Registerdaten werden ĂŒber Krankheitsregister, Kranken- und Rentenversicherungen erhoben. Die Auswertung bezieht die Datenbasis zur Halbzeit der Basiserhebung mit 101.839 Teilnehmerinnen und Teilnehmern ein, davon 11.371 mit einer MRT-Untersuchung. ERGEBNISSE: Die mittlere Responsequote zur Halbzeit betrug insgesamt 18âŻ%. Die Teilnahme an den Untersuchungen lag ĂŒberwiegend bei mehr als 95âŻ%. Bei 96âŻ% der MRT-Teilnehmerinnen und Teilnehmer konnten alle 12 MRT-Sequenzen vollstĂ€ndig durchgefĂŒhrt werden. Der ErschlieĂung und wissenschaftlichen Nutzung ergĂ€nzender SekundĂ€r- und Registerdaten stimmten mehr als 90âŻ% der Teilnehmerinnen und Teilnehmer zu. DISKUSSION: Die Bereitschaft, möglichst alle Untersuchungsmodule durchzufĂŒhren, war trotz des zeitlichen Aufwandes auĂerordentlich hoch. Dadurch wird die NAKO zu einer zentralen Ressource fĂŒr die epidemiologische Forschung in Deutschland. Sie wird es ermöglichen, neue Strategien zur FrĂŒherkennung, Vorhersage und PrimĂ€rprĂ€vention chronischer Krankheiten zu entwickeln
Herbicide-Resistant Field Crops
This chapter reviews information about how crop plants resist herbicides and how resistance is selected for in plants and surveys specific herbicide-resistant crops by chemical family. The discussion in the chapter includes HRCs derived from both traditional and biotechnological selection methodologies. Plants avoid the effects of herbicides they encounter by several different mechanisms. These mechanisms can be grouped into two categories: those that exclude the herbicide molecule from the site in the plant where they induce the toxic response and those that render the specific site of herbicide action resistant to the chemical. The chapter presents herbicide-resistant crops by the herbicide chemical familyâsuch as, triazine, acetolactate synthatase, acetyl-CoA carboxylase, glyphosate, bromoxynil, phenoxycarboxylic acids, and glufosinate. Resistant crops are listed in the chapter regardless of whether they have been commercialized or were developed for experimental purposes only, and are provided regardless of their âsuccessâ as resistant plants
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