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Editorial
(2004)
Reduced expression of the Indy ("I am Not Dead, Yet") gene in lower organisms promotes longevity in a manner akin to caloric restriction. Deletion of the mammalian homolog of Indy (mIndy, Slc13a5) encoding for a plasma membrane-associated citrate transporter expressed highly in the liver, protects mice from high-fat diet-induced and aging-induced obesity and hepatic fat accumulation through a mechanism resembling caloric restriction. We studied a possible role of mIndy in human hepatic fat metabolism. In obese, insulin-resistant patients with nonalcoholic fatty liver disease, hepatic mIndy expression was increased and mIndy expression was also independently associated with hepatic steatosis. In nonhuman primates, a 2-year high-fat, high-sucrose diet increased hepatic mIndy expression. Liver microarray analysis showed that high mIndy expression was associated with pathways involved in hepatic lipid metabolism and immunological processes. Interleukin-6 (IL-6) was identified as a regulator of mIndy by binding to its cognate receptor. Studies in human primary hepatocytes confirmed that IL-6 markedly induced mIndy transcription through the IL-6 receptor and activation of the transcription factor signal transducer and activator of transcription 3, and a putative start site of the human mIndy promoter was determined. Activation of the IL-6-signal transducer and activator of transcription 3 pathway stimulated mIndy expression, enhanced cytoplasmic citrate influx, and augmented hepatic lipogenesis in vivo. In contrast, deletion of mIndy completely prevented the stimulating effect of IL-6 on citrate uptake and reduced hepatic lipogenesis. These data show that mIndy is increased in liver of obese humans and nonhuman primates with NALFD. Moreover, our data identify mIndy as a target gene of IL-6 and determine novel functions of IL-6 through mINDY. Conclusion: Targeting human mINDY may have therapeutic potential in obese patients with nonalcoholic fatty liver disease. German Clinical Trials Register: DRKS00005450.
Editorial: Wir greifen im vorliegenden Heft eine Reihe von eher praxisorientierten Fragestellungen auf, behandeln aber auch grundlegende Themen. Carolin König widmet sich in ihrem Beitrag über das TRIPS-Übereinkommen menschenrechtlichen Implikationen des geistigen Eigentums, wie sie vor allem für den Handel mit und die Entwicklung von Medikamenten von Bedeutung sind. Johannes Freudenreich und Florian Ranft liefern eine statistische Analyse der 29 Wahrheitskommissionen, die ihre Arbeit beendet haben. Dabei werden Variablen zu Ressourcen, Mandat, Inhalt und Ergebnis von Wahrheitskommissionen untersucht. Die Autoren wollten herausfinden, ob es ein Standardmodell für Wahrheitskommissionen gibt, kommen aber zu dem Ergebnis, dass sich ein solches noch nicht erkennbar herausgebildet hat. Unter dem Titel „Rechtsstaatlichkeit in Europa: Dogmatik im (Kon)text“ beschäftigen sich Philippe Gréciano und Norman Weiß mit dem diesbezüglichen Entwicklungsstand der Europäischen Union und versuchen, aus rechtsvergleichender Perspektive Anregungen für die weitere Entwicklung zu gewinnen. Silke Bruchmüller untersucht in ihrem Beitrag die Aktivitäten des Deutschen Bundestages im Zusammenhang mit der „Terrorismusbekämpfung in der 14. und 15. Legislaturperiode“. Der Beitrag „Menschsein als Teilhabe an innerer und äußerer Würde“ von Linda Pickny behandelt das Thema Menschenwürde aus rechtsphilosophischer Sicht. Anne Dieter ruft dazu auf, die „Menschenrechte leben [zu] lernen“, und erinnert so daran, den wohlweislich bereits in der Präambel der Allgemeinen Erklärung der Menschenrechte geforderten fortschreitenden Prozess der Anerkennung und Verwirklichung von Menschenrechten voranzutreiben. Der Dokumentationsteil enthält den traditionellen Bericht über die Arbeit des Menschenrechtsausschusses der Vereinten Nationen im Jahre 2008. Der erste Teil, verfasst von Anne Foith, behandelt vorrangig das Staatenberichtsverfahren. Corinna Dau und Gunda Meyer führen die Reihe „Mitgliedstaaten des Europarates“ mit einem Artikel über Lettland fort. Alexander Dietz und Frank Martin Brunn beschreiben Inhalte und Strukturen der „Interdisziplinäre[n] Forschung zum Thema Menschenwürde an der Universität Heidelberg“. Dem Problem der „Zirkulären Migration“ ist schließlich der Bericht von Julia Vespermann gewidmet. Buchbesprechungen runden das Heft ab, bei dessen Herstellung uns Jutta Wickenhäuser und Tim Reiß redaktionell unterstützt haben. Gunda Meyer scheidet mit diesem Heft aus der Redaktion aus, um sich ganz auf das Referendariat zu konzentrieren. Ihre Nachfolgerin, Anne Foith, gehört bereits zum Kreis unserer Autorinnen und Autoren. Wir wünschen unseren Lesern eine anregende Lektüre.
Metabolic footprint and intestinal microbial changes in response to dietary proteins in a pig model
(2019)
Epidemiological studies revealed that dietary proteins can contribute to the modulation of the cardiovascular disease risk. Still, direct effects of dietary proteins on serum metabolites and other health-modulating factors have not been fully explored. Here, we compared the effects of dietary lupin protein with the effects of beef protein and casein on the serum metabolite profile, cardiovascular risk markers and the fecal microbiome. Pigs were fed diets containing 15% of the respective proteins for 4 weeks. A classification analysis of the serum metabolites revealed six biomarker sets of two metabolites each that discriminated between the intake of lupin protein, lean beef or casein. These biomarker sets included 1- and 3-methylhistidine, betaine, carnitine, homoarginine and methionine. The study revealed differences in the serum levels of the metabolites 1- and 3- methylhistidine, homoarginine, methionine and homocysteine, which are involved in the one-carbon cycle. However, these changes were not associated with differences in the methylation capacity or the histone methylation pattern. With the exception of serum homocysteine and homoarginine levels, other cardiovascular risk markers, such as the homeostatic model assessment index, trimethylamine-N-oxide and lipids, were not influenced by the dietary protein source. However, the composition of the fecal microorganisms was markedly changed by the dietary protein source. Lupin-protein-fed pigs exhibited more species from the phyla Bacteroidetes and Firmicutes than the other two groups. In conclusion, different dietary protein sources induce distinct serum metabolic fingerprints, have an impact on the cardiovascular risk and modulate the composition of the fecal microbiome. (C) 2019 Elsevier Inc. All rights reserved.
Objectives-Sonography of muscle architecture provides physicians and researchers with information about muscle function and muscle-related disorders. Inter-rater reliability is a crucial parameter in daily clinical routines. The aim of this study was to assess the inter-rater reliability of sonographic muscle architecture assessments and quantification of errors that arise from inconsistent probe positioning and image interpretation.
Results-Inter-rater reliability was good overall (ICC, 0.77-0.90; IRV, 9.0%-13.4%; bias LoA, 0.2 +/- 0.2-1.7 +/- 3.0). Superior and inferior pennation angles showed high systematic bias and LoA in all setups, ranging from 2.0 degrees +/- 2.2 degrees to 3.4 degrees +/- 4.1 degrees. The highest IRV was found for muscle thickness (13.4%). "When the probe position was standardized, the SEM for muscle thickness decreased from 0.1 to 0.05 cm.
Conclusions-Sonographic examination of muscle architecture of the medial gastrocnemius has good to high reliability. In contrast to pennation angle measurements, length measurements can be improved by standardization of the probe position.
In dynamic H-reflex measurements, the standardisation of the nerve stimulation to the gait cycle is crucial to avoid misinterpretation due to altered pre-synaptic inhibition. In this pilot study, a plantar pressure sole was used to trigger the stimulation of the tibialis nerve with respect to the gait cycle. Consequently, the intersession reliability of the soleus muscle H-reflex during treadmill walking was investigated.
Seven young participants performed walking trials on a treadmill at 5 km/h. The stimulating electrode was placed on the tibial nerve in the popliteal fossa. An EMG was recorded from the soleus muscle. To synchronize the stimulus to the gait cycle, initial heel strike was detected with a plantar pressure sole. Maximum H-reflex amplitude and M-wave amplitude were obtained and the Hmax/Mmax ratio was calculated.
Data reveals excellent reliability, ICC = 0.89. Test-retest variability was 13.0% (+/- 11.8). The Bland-Altman analysis showed a systematic error of 2.4%.
The plantar pressure sole was capable of triggering the stimulation of the tibialis nerve in a reliable way and offers a simple technique for the evaluation of reflex activity during walking.