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ZusammenfassungMit der Selbstenttarnung des NSU entwickelte sich ein gesellschaftlicher und wissenschaftlicher Diskurs, der auf die Kontinuitäten rechtsextremen Terrors in der Bundesrepublik verweist. Nach aktuellem Kenntnisstand wurden seit 1945 ca. 300 Personen von rechtsextremen Täter:innen ermordet. Nur für wenige Opfer gibt es ein öffentliches und damit gesellschaftliches Gedenken und Erinnern. Der Beitrag nimmt einen praxeologischen Fokus ein und rekonstruiert anhand eines Falles in Baden-Württemberg Praktiken des doing memory. Dabei zeigt sich, wie der rechtsextreme Terroranschlag zum isolierten Problem konstruiert wird, das einer Lösung bedarf, um zu einer hegemonialen Vorstellung von Normalität zurückkehren zu können. Da Erinnern hier ein störendes Moment darstellen würde, lässt sich von einem undoing memory sprechen.

Chiral and enantiopure amines can be produced by enantioselective transaminases via kinetic resolution of amine racemates. This transamination reaction requires stoichiometric amounts of co-substrate. A dual-enzyme recycling system overcomes this limitation: L-amino acid oxidases (LAAO) recycle the accumulating co-product of ( S )-selective transaminases in the kinetic resolution of racemic amines to produce pure ( R )-amines. However, availability of suitable LAAOs is limited. Here we use the heterologously produced, highly active fungal hcLAAO4 with broad substrate spectrum. H 2 O 2 as by-product of hcLAAO4 is detoxified by a catalase. The final system allows using sub-stoichiometric amounts of 1mol% of the transaminase co-substrate as well as the initial application of L-amino acids instead of alpha-keto acids. With an optimized protocol, synthetic potential of this kinetic resolution cascade was proven at the preparative scale (>90mg) by the synthesis of highly enantiomerically pure ( R )-methylbenzylamine (>99%ee) at complete conversion (50%). © 2022 Wiley-VCH GmbH.

Pflegeberufe in stationären Einrichtungen lassen sich aufgrund ihrer formalen Verfasstheit mit Erwerbsverhältnissen außerhalb von Care-Arbeit vergleichen, gleichzeitig wohnt ihnen die Spezifik von Care-Tätigkeiten inne. Beides - Erwerbsarbeit und Care-Arbeit - unterlag in den letzten Jahrzehnten erheblichen Veränderungen. Wir fragen danach: Wie lassen sich die Veränderungen in der verberuflichten Pflege mit dem arbeitssoziologisch etablierten Diskurs der Subjektivierung von Arbeit zusammendenken? Relevant wird aus unserer Sicht dabei das Verhältnis der beiden Prozesse Subjektivierung von Arbeit und Ökonomisierung. Diese Frage diskutieren wir auf der Basis von multiperspektivischen qualitativen Betriebsfallstudien, die mit der Dokumentarischen Methode ausgewertet wurden. Als zentrales Ergebnis sehen wir eine kollektive Subjektiviertheit von Sorgetätigkeiten, die in den letzten Jahren Marktlogiken unterworfen wird. Die Unterscheidung in kollektive Subjektiviertheit im Care-Sektor und individualisierte Subjektivierung im Produktionsbereich scheint uns für die Analyse des Wandels von Erwerbsarbeit relevant. Sie hat auch Auswirkungen auf Verantwortung und Ertrag von Subjektivierung. This article deals with the nursing professions in inpatient facilities. Because they are formally constituted, they can be compared to non-carework. At the same time, though, they are characterised by specific care activities which are inherent to professional nursing. Both gainful employment and care work have undergone significant changes in recent decades. Our question is this: How can changes in professional nursing be reconciled with the discourse on the subjectivation of work which is now established in regard to the sociology of work? In our view, the relationship between the subjectivation of work and economisation is relevant here. We discuss this question on the basis of multi-perspective qualitative case studies which were analysed using the documentary method. Our key finding is that of a collective subjectivity of care activities which have been subjected to market logics in recent years. For us, the distinction between collective subjectivation in the care objectivation in the production sector appears relevant when it comes to an analysis of the transformation of gainful employment. It also has an impact on responsibility and the effects of subjectivation.

Aims Oral opioid preparations combined with naloxone are intended to induce a transient acute withdrawal syndrome to avoid intravenous misuse. This trial aimed to establish an appropriate morphine–naloxone dose ratio for an abuse‐deterrent oral opioid formulation. Methods In a randomized, double‐blinded, 2 × 2 cross‐over trial, 43 patients with opioid use disorder were challenged with intravenous morphine HCl Ph.Eur. (75 mg; [morphine mono]) or morphine HCl Ph.Eur. and naloxone HCl Ph.Eur. at ratios of 100:1 (75 mg: 0.75 mg; [morphine–naloxone 100:1]) or 200:1 (75 mg: 0.375 mg; [morphine–naloxone 200:1]). Acute naloxone‐induced opioid withdrawal was evaluated using subjective (Short Opiate Withdrawal Scale–German [SOWS‐G]) and observer‐rated (Objective Opiate Withdrawal Scale [OOWS], Wang scale) questionnaires, and physiological parameters. For statistical analysis, the area under the curve between baseline and 20 minutes after drug administration of the outcome variables was calculated. Results Intravenous morphine–naloxone caused rapid withdrawal symptoms. Coadministration of naloxone dose‐dependently (morphine–naloxone 100:1 > morphine–naloxone 200:1) increased SOWS‐G, OOWS and Wang Scale area under the curve when compared to morphine mono, respectively (all P < .0001). A similar response was detectable for changes of pupil diameter. Blood pressure and respiratory rate changed heterogeneously, and heart rate was unaltered by morphine without or with naloxone. Conclusion Morphine–naloxone 100:1 effectively suppresses the pleasurable effects of intravenous morphine and results in an aversive withdrawal reaction. A lower naloxone concentration as used in morphine–naloxone 200:1 does not appear to be appropriate to prevent intravenous morphine misuse.

l-Amino acid oxidases (LAAOs) are flavoproteins, which use oxygen to deaminate l-amino acids and produce the corresponding α-keto acids, ammonia, and hydrogen peroxide. Here we describe the heterologous expression of LAAO4 from the fungus Hebeloma cylindrosporum without signal sequence as fusion protein with a 6His tag in Escherichia coli and its purification. 6His-hcLAAO4 could be activated by exposure to acidic pH, the detergent sodium dodecyl sulfate, or freezing. The enzyme converted 14 proteinogenic l-amino acids with l-glutamine, l-leucine, l-methionine, l-phenylalanine, l-tyrosine, and l-lysine being the best substrates. Methyl esters of these l-amino acids were also accepted. Even ethyl esters were converted but with lower activity. Km values were below 1 mM and vmax values between 19 and 39 U mg−1 for the best substrates with the acid-activated enzyme. The information for an N-terminal aldehyde tag was added to the coding sequence. Co-expressed formylglycine-generating enzyme was used to convert a cysteine residue in the aldehyde tag to a Cα-formylglycine residue. The aldehyde tag did not change the properties of the enzyme. Purified Ald-6His-hcLAAO4 was covalently bound to a hexylamine resin via the Cα-formylglycine residue. The immobilized enzyme could be reused repeatedly to generate phenylpyruvate from l-phenylalanine with a total turnover number of 17,600 and was stable for over 40 days at 25 °C.

Cortical morphogenesis entails several neurobiological events, including proliferation and differentiation of progenitors, migration of neuroblasts, and neuronal maturation leading to functional neural circuitry. These neurodevelopmental processes are delicately regulated by many factors. Endosomal SNAREs have emerged as formidable modulators of neuronal growth, aside their well-known function in membrane/vesicular trafficking. However, our understanding of their influence on cortex formation is limited. Here, we report that the SNAREs Vti1a and Vti1b (Vti1a/1b) are critical for proper cortical development. Following null mutation of Vti1a/1b in mouse, the late-embryonic mutant cortex appeared dysgenic, and the cortical progenitors therein were depleted beyond normal. Notably, cortical layer 5 (L5) is distinctively disorganized in the absence of Vti1a/1b. The latter defect, coupled with an overt apoptosis of Ctip2-expressing L5 neurons, likely contributed to the substantial loss of corticospinal and callosal projections in the Vti1a/1b-deficient mouse brain. These findings suggest that Vti1a/1b serve key neurodevelopmental functions during cortical histogenesis, which when mechanistically elucidated, can lend clarity to how endosomal SNAREs regulate brain development, or how their dysfunction may have implications for neurological disorders. Copyright © 2021 IBRO. Published by Elsevier Ltd. All rights reserved.

Fur Deutschland lasst sich eine Diskrepanz zwischen der Kontinuitat rechtsextremer Terrorakte und der offentlichen Auseinandersetzung damit feststellen. Ein Erinnern an die Opfer und damit ein offentliches Thematisieren der Taten fehlen in vielen Fallen. Ausgehend von einem Verstandnis von Erinnern als machtvollem Aushandlungsprozess wird in dem folgenden Beitrag anhand eines Mordes 1992 in Baden-Wurttemberg nachgezeichnet, wie ein rechtsextremer Mord aus dem offentlichen Diskurs verschwindet. Fur die Dethematisierung rechtsextremer Gewalt ist dieser Fall besonders interessant, da die Tat vor Gericht eindeutig als rechtsextrem und rassistisch eingeordnet wurde, was fur deutsche Rechtsprechung in diesem Feld eher unublich ist. Trotzdem erinnert bis heute vor Ort nichts an die Tat.

The aldehyde tag is appropriate to selectively label proteins, prepare antibody-drug conjugates or to immobilize enzymes or antibodies for biotechnological and medical applications. The cysteine within the consensus sequence CxPxR of the aldehyde tag is specifically oxidized by the formylglycine-generating enzyme (FGE) to the non-canonical and electrophilic amino acid C-alpha-formylglycine (FGly). Subsequent reductive amination is a common method for site-directed immobilization, which usually results in poor immobilization efficiency due to the reaction conditions. Here, we introduce a new solid support like agarose modified with an aryl substituted pyrazolone (Knoevenagel reagent) that was obtained in a facile and efficient 2-step synthesis. The modified agarose allowed the site-selective and efficient immobilization of aldehyde-containing small molecules, peptides and proteins - in particular enzymes - at physiological pH (6.2-8.2) without any additive or catalyst needed. In comparison to reductive amination, higher loadings and activities were achieved in various buffers at different concentrations and temperatures.

Cytostatic metallo-drugs mostly bind to the nucleobases of DNA. A new family of dinuclear transition metal complexes was rationally designed to selectively target the phosphate diesters of the DNA backbone by covalent bonding. The synthesis and characterization of the first dinuclear NiII2 complex of this family are presented, and its DNA binding and interference with DNA synthesis in polymerase chain reaction (PCR) are investigated and compared to those of the analogous CuII2 complex. The NiII2 complex also binds to DNA but forms fewer intermolecular DNA cross-links, while it interferes with DNA synthesis in PCR at lower concentrations than CuII2. To simulate possible competing phosphate-based ligands in vivo, these effects have been studied for both complexes with 100-200-fold excesses of phosphate and ATP, which provided no disturbance. The cytotoxicity of both complexes has been studied for human cancer cells and human stem cells with similar rates of proliferation. CuII2 shows the lowest IC50 values and a remarkable preference for killing the cancer cells. Three different assays show that the CuII2 complex induces apoptosis in cancer cells. These results are discussed to gain insight into the mechanisms of action and demonstrate the potential of this family of dinuclear complexes as anticancer drugs acting by a new binding target.

l‐amino acid oxidases (LAAOs) are flavoenzymes that catalyze the oxidative deamination of l‐amino acids to the corresponding α‐keto acids, ammonia, and hydrogen peroxide. Here, we show the overexpression, purification, and the characterization of LAAO4 from the fungus Hebeloma cylindrosporum in the yeast Pichia pastoris with a 9His‐tag and compare this with the recently characterized 6His‐hcLAAO4 expressed in E. coli. The expression of the enzyme with an ER‐signal sequence in P. pastoris resulted in a glycosylated, secreted protein. The enzymatic activity without activation was higher after expression in P. pastoris compared to E. coli. Due to treatment with acidic pH, a striking increase of activity could be detected for both expression systems resulting in similar specific activities after acid activation. Regarding the substrate spectrum, temperature stability, K m, and v max values, hcLAAO4 showed very few differences when produced in these two expression systems. A higher yield of hcLAAO4 could be obtained by fermentation., hcLAAO4 was successfully expressed in Pichia pastoris as a secreted, glycosylated enzyme. K m and v max values, substrate spectrum, and temperature stability were similar when expressed in E. coli or in P. pastoris. Expression of hcLAAO4 could be drastically increased when fermented in bioreactors compared to shaking flasks in both expression systems with much higher values obtained regarding activity per gram dry mass and activity per liter for P. pastoris.

Ethische Fragen von Verantwortung werden in der Sozialen Arbeit oftmals individualisiert. Unsere rekonstruktive Analyse eines Praktikumsberichts einer/eines Studierenden Sozialer Arbeit zeigt, wie subjektivierende Anteile professionsethischen Denkens zutage treten und welche Bilder von Verantwortung und Verantwortlichkeiten auf diesen unterschiedlichen Ebenen transportiert werden. Ausgehend von der Rekonstruktion der Adressierungs- und Zuordnungspraxen der Hilfeempfanger*innen fragen wir danach, wie diese mit institutionellen und subjektiven Verantwortungshorizonten korrespondieren und welche Bedeutung dem jeweiligen Grad an Institutionalisierung dabei zukommt. Wir sehen dies als eine Moglichkeit, fur eine menschenrechtlich inspirierte Kritik an nicht rechtfertigbaren Verhaltnissen einzutreten und verstehen diesen Beitrag als ein Pladoyer fur das Einbeziehen einer Organisations- und Institutionenethik in den Diskurs um professionelles Handeln in der Sozialen Arbeit.

Background. Lifestyle interventions have shown to be effective when continuous personal support was provided. However, there is lack of knowledge whether a telemedical-approach with personal coaching contributes to long-term weight losses in overweight employees. We, therefore, tested the hypothesis that telemedical-based lifestyle interventions accompanied with telemedical coaching lead to larger weight losses in overweight persons in an occupational health care setting. Methods. Overweight employees (n=180) with a body mass index (BMI) of >27 kg/m2 were randomized into either a telemedical (TM) group (n=61), a telemedical coaching (TMC) group (n=58), or a control group (n=61). Both intervention groups were equipped with scales and pedometers automatically transferring the data into a personalized online portal, which could be monitored from participants and coaches. Participants of the TMC group received additionally one motivational care call per week by mental coaches to discuss the current data (current weight and steps) and achieving goals such as a healthy lifestyle or weight reduction. The control group remained in routine care. Clinical and anthropometric data were determined after the 12-week intervention. Additionally, weight change was followed up after 12 months. Results. Participants of TMC (-3.1 ± 4.8 kg, p Conclusions. Telemedical devices in combination with telemedical coaching lead to significant long-term weight reductions in overweight persons in an occupational health care setting. This study is registered with NCT01868763, ClinicalTrials.gov.

Leseprobe ----- Zusammenfassung Berufsorientierung, Geschlechterverhaltnisse, Erwerbsarbeit und Care-Verhaltnisse beschreiben eine Matrix, innerhalb derer gesellschaftliche Hierarchien ausgehandelt werden. Individuen sind gefordert, innerhalb dieser Hierarchien Selbstentwurfe zu gestalten. Der vorliegende Beitrag schlagt vor, diese Selbstbildungsprozesse annerkennungstheoretisch zu analysieren und legt dabei den Fokus auf Anerkennungspraktiken. Dazu wird das Konzept von Anerkennungspraktiken theoretisch entwickelt und empirisch angewendet. In biographischen Erzahlungen von Chirurg_innen und Friseur_innen, die in vergeschlechtlichten und hierarchisch weit auseinander liegenden Berufen tatig sind, werden Anerkennungspraktiken rekonstruiert. Diese haben unterschiedliche und hierarchisierte Subjektpositionen zur Folge, die fur die Individuen jeweils Handlungsbeschrankungen darstellen, aber auch Chancen zur Selbstermachtigung bieten. Hierin wird deutlich, wie Hierarchien in konkrete Praktiken des Selbst einfliesen. Schlagworter: Berufshierarchie; Anerkennung; soziale Praxis; Subjektivierung; Selbstbildung. ----- Mother, bad mother, rebel, surgeon – critical positioning between subjection and empowerment The matrix of work, care and gender norms with a theoretical perspective of recognition Abstract Occupational orientation, gender, work and care build up a matrix of social hierarchies. Individuals are forced to create a perspective of their Self within those intersected social hierarchies. This article focusses on selfbuilding processes in this field with a theoretical framework of recognition and, more specifically, recognition understood as a form of social practice. On the empirical base of biographical narratives of male and female surgeons and hairdressers, social practices of recognition are being reconstructed by analyzing which different hierarchical social positions are gathered. The theoretical and empirical analysis shows that different hierarchical positions are being constructed and both of them imply moments of constraints as well as moments of empowerment. This results underline that social hierarchies need to be seen as relevant parts of selfbuilding processes. Keywords: Hierarchy of professions; recognition; social practice; subjectification; self-building. ----- Bibliographie: Fischer , Gabriele: Mutter, Rabenmutter, Rebell, Chirurgin – kritische Positionierungen zwischen Macht und Ermachtigung. Eine anerkennungstheoretische Perspektive auf die Matrix Erwerbsarbeit, Care-Verhaltnisse und Geschlechternormen, FZG, 1-2017, S. 71-86. https://doi.org/10.3224/fzg.v23i1.05

With the breadth of new psychoactive substances and international policy changes, an analysis of specific responses in all areas of drug supply and demand is beyond the resources of a single country. The Scientific Committee of the European Monitoring Centre for Drugs and Drug Addiction calls for a strengthening of global monitoring and evidence synthesis and a renewed vigour in collaborative efforts to expand training, research and the quality and comparability of data across Europe and beyond.

Objective: Psychiatric comorbidities are highly prevalent among individuals affected by substance use disorders and those with non-substance-related addictive disorders such as gambling disorder. M...

This microreview summarizes a study aiming at the development of a novel family of metal complexes that binds to the phosphate esters of the DNA backbone inspired by the cytotoxicity of the anticancer drug cisplatin and by the phosphate ester cleaving reactivity of metalloenzymes and their biomimetic model complexes. A rational design is presented that is based on the requirements to establish a molecular recognition for the phosphate esters of the DNA backbone and to suppress binding to the less exposed nucleobases. Two phosphate binding sites should be preoriented and fixed by a rigid backbone to the distance of two neighboring phosphate ester in the DNA backbone of 6-7 angstrom. Sterical demand close to the phosphate binding sites should inhibit coordination to the nucleobases. This was molecularly translated into an unprecedented family of dinuclear complexes based on 1,8-naphthalenediol ligands with sterically demanding chelate arms in 2,7-position. The synthesis of the ligand and its first dinuclear Cull complex is described. The binding of this complex to DNA has been studied by biochemical ensemble methods and biophysical single-molecule methods. The incubation of DNA with the Cull complex results in interstrand interactions forming aggregates that prevent the DNA to enter the gel in the electrophoresis experiments. AFM experiments show an increase of the DNA diameter and local entanglements of the DNA by intrastrand interactions. The stretching of a single DNA molecule by optical tweezers exhibits distinct force peaks upon treatment with the complex necessary to break the intrastrand interactions. Torsional measurements of a single DNA molecule by magnetic tweezers showed a shortening of the effective DNA length due to the intrastrand interactions. Incubation with the Cull complex suggests inhibition of DNA synthesis in polymerase chain reaction experiments and strong cytotoxicity to human HeLa cancer cells, both at lower concentration than with cisplatin. A coherent model is provided that explains all experimental observations by the intended binding of the Cull complex to two neighboring phosphates of the DNA backbone and the formation of intra- or interstrand interactions by pi-pi interactions of the outward oriented and freely exposed naphthalene rings. (C) 2016 Elsevier B.V. All rights reserved.