Isolation and amino acid sequence analysis of a 4,000-dalton dynorphin from porcine pituitary

A 4,000-dalton dynorphin was isolated from porcine pituitary. It has 32 amino acids (Mr = 3,986), with the previously described heptadecapeptide (now called dynorphin A) at its amino terminus and a related tridecapeptide, dynorphin B, at its carboxyl terminus. The two peptides are separated by the "processing signal" Lys-Arg

Empowering Digital Democracy

This article examines the role of digital technology in enabling and enhancing democratic practices and forms of governance. It contributes to emerging debates on democratic innovations by proposing a novel theoretical account of decentralized participatory democracy. To develop our account, we draw on the experience of two EU-funded projects, D-CENT and DECODE, which produced innovative citizen participation platforms and digital public infrastructure. Bringing democratic theory into conversation with critical data studies and the new municipalism movement, we theorize how these projects advanced three political aims: organizing political communities to build collective power, empowering citizens through direct participation in decision making, and transforming political institutions. The article then analyzes the strengths and limitations of these projects to draw lessons for policy makers and practitioners for future digital democratic experiments

Trix und Robert Haussmann

Die Monografie Robert & Trix Haussmann eröffnet die Publikationsreihe STUDIOLO / Edition Patrick Frey, eine Kollaboration des Verlags mit dem Ausstellungsraum STUDIOLO. Die Kuratoren Fredi Fischli und Niels Olsen betreiben in einem Atelierhaus in Zürich ein vielfältiges Programm gegenwärtiger Kunstproduktion. Die Ausstellung The Log-O-Rhythmic Slide Rule im Frühjahr 2012 widmete sich dem Werk von Trix und Robert Haussmann und ist Ausgangspunkt für die folgende Publikation, die mit Bildern, Essays, Künstlerbeiträgen und einem Gespräch vertieften Einblick in das reiche Schaffen des Schweizer Architekten- und Designerpaars bietet. Trix und Robert Haussmann gehören zu den wichtigsten Architekten, Designern und Theoretikern in der Prägung und Ablösung der klassischen Moderne in der Schweiz. Ihr Lebenswerk umfasst derzeit rund 650 realisierte Projekte; in Zürich u.a. die Da-Capo-Bar, den neuen Hauptbahnhof, die Boutique Weinberg und die Kronenhallenbar. Das Jahr 1967 markiert mit ihrer Heirat und der Gründung des Büros Allgemeine Entwurfsanstalt den Beginn ihrer langjährigen gemeinsamen Tätigkeit, aus der Arbeiten hervorgegangen sind, die mit den Dogmen erstarrter Architekturpraktiken brechen. Neben Bauten und Möbeln entstand ein reiches theoretisches OEuvre, das in dieser Publikation erstmals präsentiert wird und die Grundlage für eine zukünftige Auseinandersetzung mit ihrem Werk schafft

Negative symptoms in alcohol use disorder: A pilot study applying the two-factor model of negative symptoms to patients with alcohol use disorder

Background and aimsAlcohol Use Disorder (AUD) is characterized by a reduction in goal-directed behavior, with alcohol use taking precedence over other areas of life. These features in AUD resemble negative symptoms in schizophrenia, especially the reduction in motivation and pleasure (MAP). Given the clinical similarities of negative symptoms across diagnostic categories, it comes as a surprise that there are few investigations on negative symptoms in alcohol and other substance use disorders. To our knowledge, our study is the first to assess negative symptoms in AUD based on a two-factorial approach, and to investigate the interrelation of these dimensions with the severity of AUD, and alcohol craving.Materials and methodsWe examined a sample of 42 patients with AUD at the Psychiatric University Hospital in Zurich. Participants provided self-report and interview-based measures of the severity of AUD, negative symptoms, and alcohol craving. Finally, we used data from the electronic health records of the patients.ResultsPatients with AUD show negative symptoms to a similar extent as patients with schizophrenia or bipolar disorder. We found a positive correlation between the extent of impairment within the MAP factor and overall severity of AUD. Furthermore, MAP negative symptoms were correlated with alcohol craving. In a linear regression, negative symptoms predicted alcohol craving whereas depression did not.SummaryNegative symptoms as conceptualized for schizophrenia are prevalent in patients with AUD and associated with the severity of AUD. More specifically, severity of AUD correlates with diminished motivation and pleasure, highlighting the importance of disturbances in motivational functions in AUD. This is further supported by the correlation between negative symptoms and craving, a hallmark of AUD. Taken together, our findings suggest that negative symptoms might be a highly relevant but hitherto often neglected therapeutic target in AUD

SAFO, FRAGMENTO 2: TRADUÇÃO E COMENTÁRIO

Safo destaca-se entre os maiores poetas da Lírica Grega Arcaica. Neste artigo, apresentamos uma tradução do Fragmento 2 (Lobel-Page) de um poema seu e oferecemos informações sobre essa lírica, uma biografia resumida da poetisa e sua obra. Descrevemos também como o Fragmento 2 chegou até nós. Por derradeiro, incluímos o texto grego original e um comentário

Plasma concentrations of SSRI/SNRI after bariatric surgery and the effects on depressive symptoms.

BACKGROUND Depression and treatment with antidepressants SSRI/SNRI are common in people with morbid obesity who are candidates for bariatric surgery. There is few and inconsistent data about the postoperative plasma concentrations of SSRI/SNRI. The aims of our study were to provide comprehensive data about the postoperative bioavailability of SSRI/SNRI, and the clinical effects on depressive symptoms. METHODS Prospective multicenter study including 63 patients with morbid obesity and therapy with fixed doses of SSRI/SNRI: participants filled the Beck Depression Inventory (BDI) questionnaire, and plasma levels of SSRI/SNRI were measured by HPLC, preoperatively (T0), and 4 weeks (T1) and 6 months (T2) postoperatively. RESULTS The plasma concentrations of SSRI/SNRI dropped significantly in the bariatric surgery group from T0 to T2 by 24.7% (95% confidence interval [CI], -36.8 to -16.6, p = 0.0027): from T0 to T1 by 10.5% (95% 17 CI, -22.7 to -2.3; p = 0.016), and from T1 to T2 by 12.8% (95% CI, -29.3 to 3.5, p = 0.123), respectively.There was no significant change in the BDI score during follow-up (-2.9, 95% CI, -7.4 to 1.0; p = 0.13).The clinical outcome with respect to SSRI/SNRI plasma concentrations, weight change, and change of BDI score were similar in the subgroups undergoing gastric bypass surgery and sleeve gastrectomy, respectively. In the conservative group the plasma concentrations of SSRI/SNRI remained unchanged throughout the 6 months follow-up (-14.7, 95% CI, -32.6 to 1.7; p = 0.076). CONCLUSION In patients undergoing bariatric surgery plasma concentrations of SSRI/SNRI decrease significantly by about 25% mainly during the first 4 weeks postoperatively with wide individual variation, but without correlation to the severity of depression or weight loss

Translation of liver stage activity of M5717, a Plasmodium elongation factor 2 inhibitor: from bench to bedside

© The Author(s) 2022. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativeco mmons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.Background: Targeting the asymptomatic liver stage of Plasmodium infection through chemoprevention could become a key intervention to reduce malaria-associated incidence and mortality. Methods: M5717, a Plasmodium elongation factor 2 inhibitor, was assessed in vitro and in vivo with readily accessible Plasmodium berghei parasites. In an animal refinement, reduction, replacement approach, the in vitro IC99 value was used to feed a Population Pharmacokinetics modelling and simulation approach to determine meaningful effective doses for a subsequent Plasmodium sporozoite-induced volunteer infection study. Results: Doses of 100 and 200 mg would provide exposures exceeding IC99 in 96 and 100% of the simulated population, respectively. Conclusions: This approach has the potential to accelerate the search for new anti-malarials, to reduce the number of healthy volunteers needed in a clinical study and decrease and refine the animal use in the preclinical phase.This work was funded by the healthcare business of Merck KGaA, Darmstadt, Germany (CrossRef Funder ID: https://doi.org/10.13039/100009945). F.A. is the recipient of an individual Ph.D. fellowship funded by FCT (PD/BD/128371/2017).info:eu-repo/semantics/publishedVersio