Mitochondrial heat shock protein 70, a molecular chaperone for proteins encoded by mitochondrial DNA

Mitochondrial heat shock protein 70 (mt-Hsp70) has been shown to play an important role in facilitating import into, as well as folding and assembly of nuclear-encoded proteins in the mitochondrial matrix. Here, we describe a role for mt-Hsp70 in chaperoning proteins encoded by mitochondrial DNA and synthesized within mitochondria. The availability of mt-Hsp70 function influences the pattern of proteins synthesized in mitochondria of yeast both in vivo and in vitro. In particular, we show that mt-Hsp70 acts in maintaining the var1 protein, the only mitochondrially encoded subunit of mitochondrial ribosomes, in an assembly competent state, especially under heat stress conditions. Furthermore, mt-Hsp70 helps to facilitate assembly of mitochondrially encoded subunits of the ATP synthase complex. By interacting with the ATP-ase 9 oligomer, mt-Hsp70 promotes assembly of ATP-ase 6, and thereby protects the latter protein from proteolytic degradation. Thus mt-Hsp70 by acting as a chaperone for proteins encoded by the mitochondrial DNA, has a critical role in the assembly of supra- molecular complexes

Literatur nach der Dystopie : Ein Zukunftsbericht in Zeiten der COVID-19- Krise

Based on theoretical considerations of Aristotle's law of probability and necessity, this contribution examines the long-term influence of a global historical event like the COVID-19 crisis on our perception of reality. What happens if an unprecedented situation previously conceivable purely as fiction suddenly becomes real and literature is caught up by reality? Then, according to the thesis put forward here, this is the end of dystopia and the beginning of a new reality, accompanied by a blatant ‘reality shock’. In the form of an essay, the article first describes the historical event of the COVID-19 pandemic in its affective component and explains why and how it has been experienced as a crisis. The article further examines what effects this crisis experience might have on our perception of reality and fiction, and on future literature. Special attention is given to the literary form of speculative realism which opens up new forms of thinking and enables reflection on how we can re-conceptualize our passive 'being in the world' as an involved 'acting in this world' thus taking responsibility not only for the present but also for the future

Freier Zugang zu KrimLit : Kriminologische Literaturdokumentation in der Kriminologischen Zentralstelle Wiesbaden

Literatur- und Forschungsdokumentation in der Kriminologischen Zentralstelle Wiesbaden (KrimZ) seit der Gründung der KrimZ vor 30 Jahren werden beschrieben. In Zusammenarbeit mit dem juristischen Fachinformationssystem JURIS wurde die Kriminologische Literaturdatenbank (KrimLit) entwickelt, in welcher die in Kooperation erschlossenen Daten seit Anfang 2016 über die Webseite der KrimZ frei verfügbar sind. Sie enthält neben dem Bücherbestand der Bibliothek durch Abstracts erschlossene Aufsatznachweise aus Fachzeitschriften. Die Richtlinien für die Aufsatzdokumentation werden beschrieben. Veranschaulicht durch Abbildungen wird eine Anleitung zur Recherche in KrimLit mittels Schlagwörtern gegeben

Prenatal ultrasound screening for fetal anomalies and outcomes in high-risk pregnancies due to maternal HIV infection : a retrospective study

Objective: To assess the prevalence of prenatal screening and of adverse outcome in high-risk pregnancies due to maternal HIV infection. Study design: The prevalence of prenatal screening in 330 pregnancies of HIV-positive women attending the department for prenatal screening and/or during labour between January 1, 2002 and December 31, 2012, was recorded. Screening results were compared with the postnatal outcome and maternal morbidity, and mother-to-child transmission (MTCT) was evaluated. Results: One hundred of 330 women (30.5%) had an early anomaly scan, 252 (74.5%) had a detailed scan at 20–22 weeks, 18 (5.5%) had a detailed scan prior to birth, and three (0.9%) had an amniocentesis. In seven cases (2.12%), a fetal anomaly was detected prenatally and confirmed postnatally, while in eight (2.42%) an anomaly was only detected postnatally, even though a prenatal scan was performed. There were no anomalies in the unscreened group. MTCT occurred in three cases (0.9%) and seven fetal and neonatal deaths (2.1%) were reported. Conclusion: The overall prevalence of prenatal ultrasound screening in our cohort is 74.5%, but often the opportunity for prenatal ultrasonography in the first trimester is missed. In general, the aim should be to offer prenatal ultrasonography in the first trimester in all pregnancies. This allows early reassurance or if fetal disease is suspected, further steps can be taken

Site-specific interaction of the murine pre-replicative complex with origin DNA: assembly and disassembly during cell cycle transit and differentiation

Eukaryotic DNA replication initiates at origins of replication by the assembly of the highly conserved pre-replicative complex (pre-RC). However, exact sequences for pre-RC binding still remain unknown. By chromatin immunoprecipitation we identified in vivo a pre-RC-binding site within the origin of bidirectional replication in the murine rDNA locus. At this sequence, ORC1, -2, -4 and -5 are bound in G1 phase and at the G1/S transition. During S phase, ORC1 is released. An ATP-dependent and site-specific assembly of the pre-RC at origin DNA was demonstrated in vitro using partially purified murine pre-RC proteins in electrophoretic mobility shift assays. By deletion experiments the sequence required for pre-RC binding was confined to 119 bp. Nucleotide substitutions revealed that two 9 bp sequence elements, CTCGGGAGA, are essential for the binding of pre-RC proteins to origin DNA within the murine rDNA locus. During myogenic differentiation of C2C12 cells, we demonstrated a reduction of ORC1 and ORC2 by immunoblot analyses. ChIP analyses revealed that ORC1 completely disappears from chromatin of terminally differentiated myotubes, whereas ORC2, -4 and -5 still remain associated

Mycophenolic acid counteracts B cell proliferation and plasmablast formation in patients with systemic lupus erythematosus

INTRODUCTION: Clinical trials revealed a high efficacy of mycophenolate mofetil (MMF) in inducing and maintaining remission in patients with class III-V-lupus nephritis. Also extrarenal manifestations respond to MMF treatment. However, few attempts have been undertaken to delineate its mechanism of action in systemic lupus erythematosus (SLE) a disease characterized by enhanced B cell activation. METHODS: Clinical and paraclinical parameters of 107 patients with SLE were recorded consecutively and analyzed retrospectively. Patients were divided into treatment groups (MMF: n = 39, azathioprine (AZA) n = 30 and controls without immunosuppressive therapy n = 38). To further delineate the effect of mycophenolic acid (MPA) on naive and memory B cells in vitro assays were performed. RESULTS: Although patients taking AZA flared more frequently than patients on MMF or controls, the analysis of clinical parameters did not reveal significant differences. However, profound differences in paraclinical parameters were found. B cell frequencies and numbers were significantly higher in patients taking MMF compared to those on AZA but lower numbers and frequencies of plasmablasts were detected compared to AZA-treated patients or controls. Notably, MMF treatment was associated with a significantly higher frequency and number of transitional B cells as well as naive B cells compared to AZA treatment. Differences in T cell subsets were not significant. MPA abrogated in vitro proliferation of purified B cells completely but had only moderate impact on B cell survival. CONCLUSIONS: The thorough inhibition of B cell activation and plasma cell formation by MMF might explain the favorable outcomes of previous clinical trials in patients with SLE, since enhanced B cell proliferation is a hallmark of this disease

General practitioner care in nursing homes during the first wave of the COVID-19 pandemic in Germany: a retrospective survey among nursing home managers

Background: Though evidence on the detrimental impact of the COVID-19 pandemic in nursing homes is vast, research focusing on general practitioners' (GP) care during the pandemic in nursing homes is still scarce. Methods: A retrospective online survey among 1,010 nursing home managers in Germany was conducted during the first wave of the COVID-19 pandemic between November 2020 and February 2021. Associations between perceived deficits in GP care (routine and acute visits) and both general and COVID-19-related characteristics of nursing homes were analysed using multiple logistic regression analyses. Results: The majority of nursing home managers reported no deficits in GP care (routine visits, 84.3%; acute visits, 92.9%). Logistic regression analyses revealed that deficits in GP care (routine visits) were significantly associated with visiting restrictions for GPs and nursing home size. Small nursing homes (1-50 residents) were significantly more likely to report deficits in GP care (routine visits) compared to medium (51-100 residents) and large nursing homes (> 100 residents). Further, deficits in GP care (acute visits) were significantly associated with dementia as a focus of care and the burden of insufficient testing for SARS-CoV-2 among residents. Moreover, visiting restrictions for GPs were significantly associated with dementia as the focus of care and the COVID-19 incidence at the federal state level. Finally, COVID-19 cases in nursing homes were significantly associated with size of nursing homes, COVID-19-incidence on the federal state level and the burden of insufficient testing capacities for SARS-CoV-2 among residents. Conclusion: We found structural factors associated with GP care deficits during the pandemic. New concepts for GP care should be implemented in pandemic preparedness plans to ensure high quality, consistent, and reliable GP care as well as effective infection prevention measures in nursing homes

Kultursensible Suchtprävention: Ein Projekt des SPIKE DRESDEN e. V.

Mit dem Projekt „Kultursensible Suchtprävention“ wurde ein neuer Weg beschritten, um Erfahrungen zu sammeln, Methoden zu erproben, Vernetzung voranzutreiben, einen Überblick über die Situation zur kultursensiblen Suchtpräventionsarbeit in Dresden zu erlangen und das daraus entstandene Wissen für Fachkräfte zugänglich zu machen. In dieser Broschüre werden die gewonnenen Erkenntnisse und Erfahrungen aus dem Projekt, die aus der Zusammenarbeit mit der Zielgruppe im SPIKE Dresden entstanden sind, gebündelt und interessierten Fachkräften zur Verfügung gestellt. Die Broschüre dient dabei als Wissensspeicher und Werkzeugkiste für all jene, die sich mit der Materie befassen. Dabei wird kein Anspruch auf Vollständigkeit und Allgemeingültigkeit erhoben, vielmehr basiert diese Broschüre auf den im Rahmen des Projektes erlangten Erfahrungen, die in dem spezifischen Setting des SPIKE Dresden gemacht wurden. Auch wenn die erprobten Möglichkeiten den Fokus auf Suchtprävention legen, lassen sich viele der Erkenntnisse auch auf weitere Arbeitsfelder übertragen. Die Broschüre soll dazu einladen, sich mit den Ergebnissen auseinanderzusetzen, sie im Team zu diskutieren, mit ihnen weiterzuarbeiten und eigene Ideen zu entwickeln. Stand: Dezember 202

Status Quo of Progress Testing in Veterinary Medical Education and Lessons Learned

Progress testing is an assessment tool for longitudinal measurement of increase in knowledge of a specific group, e.g., students, which is well-known in medical education. This article gives an overview of progress testing in veterinary education with a focus on the progress test of the German-speaking countries. The "progress test veterinary medicine" (PTT) was developed in 2013 as part of a project by the Competence Centre for E-Learning, Didactics and Educational Research in Veterinary Medicine-a project cooperation of all German-speaking institutes for veterinary medicine in Germany, Austria, and Switzerland. After the end of the project, the PTT was still continued at six locations, at each of the five German schools for veterinary medicine and additionally in Austria. Further changes to the PTT platform and the analysis were carried out to optimize the PTT for continuing to offer the test from 2017 to 2019. The PTT is an interdisciplinary, formative electronic online test. It is taken annually and is composed of 136 multiple-choice single best answer questions. In addition, a "don't know" option is given. The content of the PTT refers to the day 1 competencies described by the European Association of Establishments for Veterinary Education. The platform Q-Exam (R) Institutions (IQuL GmbH, Bergisch Gladbach, Germany) is used for creating and administrating the PTT questions, the review processes and organizing of the online question database. After compiling the test by means of a blueprint, the PTT file is made available at every location. After the last PTT in 2018, the link to an evaluation was sent to the students from four out of these six partner Universities. The 450 analyzed questionnaires showed that the students mainly use the PTT to compare their individual results with those of fellow students in the respective semester. To conclude our study, a checklist with our main findings for implementing progress testing was created