Wirkmechanismen sozial-interpersoneller Faktoren in einer Stichprobe ehemals politisch Inhaftierter der DDR

Social/interpersonal factors play a central role in PTSD. Previous studies have indicated the specific pathways along which these factors take effect. The study reported here investigates these pathways with reference to a sample of former political prisoners jailed in the GDR. It examines dysfunctional disclosure of traumatic experiences, social acknowledgement, general social support and forgiveness tendencies. For the study N = 86 non-treatment-seeking former political prisoners were recruited (average age 64 years). The instruments employed were the Disclosure of Trauma questionnaire, the Social Acknowledgement questionnaire, the Social Support questionnaire, the Tendency to Forgive scale and the Impact of Event scale (revised). Dysfunctional disclosure was proximally, social acknowledgement distally and general social support and forgiveness indirectly associated with PTSD symptomatologies. The study casts light on potential pathways to posttraumatic adjustment, with special reference to social/interpersonal factors.

Determinanten der Studierbereitschaft in Ostdeutschland. Eine empirische Anwendung der Humankapital- und Werterwartungstheorie am Beispiel sächsischer Abiturienten in den Jahren 1996 und 1998

Ausgangspunkt der empirischen Untersuchung ist die seit dem Zusammenbruch der DDR rückläufige Studierneigung ostdeutscher Abiturienten. Diese Entwicklung wird anhand der Humankapital- und Werterwartungstheorie zu erklären versucht. Demnach hängt die Studierneigung eines Individuums vom antizipierten Nutzen eines Studiums, von den erwarteten Kosten und der subjektiv eingeschätzeten Wahrscheinlichkeit, aufgrund eigener schulischer Leistungen erfolgreich studieren zu können, ab. Daraus wird die These abgeleitet, dass die Studierneigung wegen subjektiv wahrgenommener sinkender Bildungsnutzen und gleichzeitig antizipierter steigender Bildungskosten in der Zeit abgenommen hat. Für die empirische Überprüfung dieser These werden Querschnittsinformationen über sächsische Abiturienten der beiden Abschlussjahrgänge 1996 und 1998 herangezogen. Bei Kontrolle der sozialen Herkunft und des Geschlechts dieser befragten Abiturienten bestätigen die empirischen Befunde die These über die Veränderung in den subjektiv bewerteten Kosten-Nutzen-Relationen für oder gegen ein Studium nur teilweise. Ausschlaggebend für die abnehmende Studierwilligkeit ist die zunehmend ungünstige Einschätzung der beruflichen Verwertbarkeit eines Studiums. Offensichtlich lassen sich einerseits Abiturienten aus unteren und zunehmend auch aus mittleren Sozialschichten und andererseits Abiturientinnen wegen ungünstiger Arbeitsmarktentwicklungen vom Studium abschrecken.

Selektive Weiterbildungschancen und Exklusion von Arbeitslosen in Ostdeutschland

Seit dem Zusammenbruch der DDR und ihrer Integration in das Institutionengefüge der Bundesrepublik ist vor allem die Massen- und Langzeitarbeitslosigkeit ein gravierendes soziales Problem in Ostdeutschland (Buttler 1994). Ihre Persistenz hängt neben dem erzwungenen wirtschaftlichen und berufsstrukturellen Wandel und umfassenden Abbau von Arbeitsplätzen auch eng mit Schließungsprozessen auf dem Arbeitsmarkt zusammen, die in systematischer Weise bestimmte Gruppen von Erwerbspersonen benachteiligen (Mayer/Diewald/Solga 1996). Während in der DDR Arbeitslosigkeitsrisiken seit der späten Nachkriegszeit weitgehend unbekannt waren, liegt nunmehr für die noch nicht endgültig aus dem Erwerbsleben ausgeschiedenen Arbeitnehmer ein Großteil ihrer Anstrengungen im Berufsverlauf darin, nicht arbeitslos zu werden. Andererseits versuchen Arbeitslose trotz der ungünstigen Wirtschaftsentwicklung so rasch wie möglich in den Arbeitsmarkt zurückzukehren. Dies belegen sowohl die ungebrochen hohe Erwerbsorientierung ostdeutscher Männer und Frauen als auch die individuellen Weiterbildungsanstrengungen von Arbeitslosen.

Wohlfahrtsstaatsentwicklung und Lebenserwartung in Ost- und Westdeutschland

Im vorliegenden Beitrag wird die soziale Ungleichheit von Lebenserwartung in Deutschland untersucht. Es wird die These vertreten, daß der Wohlfahrtsstaat mit seinen institutionellen Vorgaben nicht nur zur Strukturierung von Lebensverläufen, sondern auch zur Verbesserung der individuellen Lebenserwartung beigetragen hat. Insbesondere die Durchsetzung der Schulpflicht und die Ausdehnung der Bildungsbeteiligung waren für diese demographische Entwicklung bedeutsam. Mit Hilfe von Längsschnittdaten des Sozio-ökonomischen Panels und der Lebensverlaufsstudie wurde gezeigt, daß sich die Lebensdauer von Männern und Frauen in der Generationenfolge erhöht hat. Während in der Bundesrepublik die Lebenszeiten zunahmen, verringerte sich in der DDR seit den 70er Jahren die Lebenserwartung. In Ostdeutschland hatten verheiratete Frauen geringere Mortalitätsrisiken als ledige Frauen. Wurden ostdeutsche Männer oder Frauen geschieden, stiegen ihre Sterbewahrscheinlichkeiten sprunghaft an. In der westdeutschen Population hatten insbesondere verwitwete Personen eine hohe Sterblichkeit. Bildung begünstigt die Lebensdauer. Mit zunehmendem Bildungsniveau sinkt das Risiko, vorzeitig zu sterben. Dieser Befund unterstreicht die Bedeutung des Wohlfahrtsstaates für Lebensverläufe und der Bildung als soziales und kulturelles Kapital.

The multifunctional FUS protein: Characterization of the biological effects of its depletion

FUS/TLS (fused in sarcoma/translocated in liposarcoma) protein, a ubiquitously expressed RNA-binding protein, has been linked to a variety of cellular processes, such as RNA metabolism, microRNA biogenesis and DNA repair. However, the precise role of FUS protein remains unclear. Recently, FUS has been linked to Amyotrophic Lateral Sclerosis (ALS), a neurodegenerative disorder characterized by the dysfunction and death of motor neurons. Based on the observation that some mutations in the FUS gene induce cytoplasmic accumulation of FUS aggregates, we decided to explore a loss-of-function situation (i.e. inhibition of FUS’ nuclear function) to unravel the role of this protein. To this purpose, we have generated a SH-SY5Y human neuroblastoma cell line which expresses a doxycycline induced shRNA targeting FUS and that specifically depletes the protein. In order to characterize this cell line, we have performed a whole transcriptome analysis by RNA deep sequencing. Preliminary results show that FUS depletion affects both expression and alternative splicing levels of several RNAs. When FUS is depleted we observed 330 downregulated and 81 upregulated genes. We also found that 395 splicing isoforms were downregulated, while 426 were upregulated. Currently, we are focusing our attention on the pathways which are mostly affected by FUS depletion. In addition, to further characterize the FUS-depleted cell line we have performed growth proliferation and survival assays. From these experiments emerge that FUS-depleted cells display growth proliferation alteration. In order to explain this observation, we have tested different hypothesis (e.g. apoptosis, senescence or slow-down growth). We observed that FUS-depleted cells growth slower than controls. Currently, we are looking for putative candidate targets causing this phenotype. Finally, since MEFs and B-lymphocytes derived from FUS knockdown mice display major sensitivity to ionizing radiation and chromosomal aberrations [1,2], we are exploring the effects of DNA damage in FUS-depleted cells by monitoring important components of DNA Damage Response (DDR). Taken together, these studies may contribute to our knowledge of the role of FUS in these cellular processes and will allow us to draw a clearer picture of mechanisms of neurodegenerative diseases.

The FUS protein is required for cell proliferation

FUS/TLS (fused in sarcoma/translocated in liposarcoma) protein, a ubiquitously expressed and highly conserved RNA binding protein, has been linked to a variety of cellular processes from mRNA processing to DNA repair. However, the precise function of FUS is not well understood. Recently, mutations in the FUS gene have been identified in familial and sporadic patients of Amyotrophic Lateral Sclerosis, a fatal neurodegenerative disorder characterized by dysfunction and death of motor neurons. Based on the observation that some mutations in the FUS gene induce cytoplasmic accumulation of FUS aggregates, we decided to explore a loss-of-function situation (i.e. inhibition of FUS’ nuclear function) to unravel the role of this protein. To this purpose, we have generated a SH-SY5Y human neuroblastoma cell line which expresses a doxycycline induced shRNA targeting FUS that efficiently depletes the protein. In order to characterize this cell line, we have characterized the poly(A) fraction by RNA deep sequencing. Preliminary results show that FUS depletion affects both mRNA expression and alternative splicing. Upon FUS depletion 330 genes are downregulated and 81 are upregulated. We also found that 395 splicing isoforms were downregulated, while 426 were upregulated. Currently, we are focusing our attention on the pathways which are mostly affected by FUS depletion. In addition, we are currently characterizing how FUS depletion affects cell proliferation and survival. We find that the lack of FUS impairs cell proliferation but does not induce apoptosis. Finally, since MEFs and B-lymphocytes derived from FUS knockdown mice display major sensitivity to ionizing radiation and chromosomal aberrations [1,2], we are exploring the effects of DNA damage in FUS-depleted cells by monitoring important components of DNA Damage Response (DDR). Taken together, these studies may contribute to our knowledge of the role of FUS in these cellular processes and will allow us to draw a clearer picture of mechanisms of neurodegenerative diseases.

Characterization of the role of the RNA-binding protein FUS in the DNA damage response

FUS/TLS (fused in sarcoma/translocated in liposarcoma), a ubiquitously expressed RNA-binding protein, has been linked to a variety of cellular processes, including RNA metabolism, microRNA biogenesis and DNA repair. However, the precise cellular function of FUS remains unclear. Recently, mutations in the FUS gene have been found in ∼5% of familial Amyotrophic Lateral Sclerosis, a neurodegenerative disorder characterized by the dysfunction and death of motor neurons. Since MEFs and B-lymphocytes derived from FUS knockdown mice display major sensitivity to ionizing radiation and chromosomal aberrations [1,2], we are investigating the effects of DNA damage both in the presence or in the absence of FUS. To this purpose, we have generated a SH-SY5Y human neuroblastoma cell line expressing a doxycycline-induced shRNA targeting FUS, which specifically depletes the protein. We have found that FUS depletion induces an activation of the DNA damage response (DDR). However, treatment with genotoxic agents did not induce any strong changes in ATM (Ataxia Telangiectasia Mutated)-mediated DDR signaling. Interestingly, genotoxic treatment results in changes in the subcellular localization of FUS in normal cells. We are currently exploring on one hand the mechanism by which FUS depletion leads to DNA damage, and on the other the functional significance of FUS relocalization after genotoxic stress.

Buparvaquone is active against Neospora caninum in vitro and in experimentally infected mice.

The naphthoquinone buparvaquone is currently the only drug used against theileriosis. Here, the effects of buparvaquone were investigated in vitro and in an experimental mouse model for Neospora caninum infection. In 4-day proliferation assays, buparvaquone efficiently inhibited N. caninum tachyzoite replication (IC50 = 4.9 nM; IC100 = 100 nM). However, in the long term tachyzoites adapted and resumed proliferation in the presence of 100 nM buparvaquone after 20 days of cultivation. Parasiticidal activity was noted after 9 days of culture in 0.5 µM or 6 days in 1 µM buparvaquone. TEM of N. caninum infected fibroblasts treated with 1 µM buparvaquone showed that the drug acted rather slowly, and ultrastructural changes were evident only after 3-5 days of treatment, including severe alterations in the parasite cytoplasm, changes in the composition of the parasitophorous vacuole matrix and a diminished integrity of the vacuole membrane. Treatment of N. caninum infected mice with buparvaquone (100 mg/kg) either by intraperitoneal injection or gavage prevented neosporosis symptoms in 4 out of 6 mice in the intraperitoneally treated group, and in 6 out of 7 mice in the group receiving oral treatment. In the corresponding controls, all 6 mice injected intraperitoneally with corn oil alone died of acute neosporosis, and 4 out of 6 mice died in the orally treated control group. Assessment of infection intensities in the treatment groups showed that, compared to the drug treated groups, the controls showed a significantly higher parasite load in the lungs while cerebral parasite load was higher in the buparvaquone-treated groups. Thus, although buparvaquone did not eliminate the parasites infecting the CNS, the drug represents an interesting lead with the potential to eliminate, or at least diminish, fetal infection during pregnancy.

A DNA probe for the detection of Dicrocoelium dendriticum in ants of Formica spp. and Lasius spp

Repetitive DNA sequences present in the genome of Dicrocoelium dendriticum were identified by hybridization of genomic DNA that had been digested with different restriction enzymes with 32P-labeled genomic D. dendriticum DNA. DNA fragments containing repetitive sequences were isolated from PstI-digested D. dendriticum DNA and were subcloned into a plasmid vector. Plasmids containing repetitive sequences were identified by colony hybridization. One of these plasmids, designated Ddr-IV, was isolated and used as a probe in further studies. Ddr-IV is specific for D. dendriticum since it does not hybridize to DNA isolated from other trematodes. In addition, Ddr-IV was capable of detecting D. dendriticum metacercariae in ants (Formica cunicularia, F. rufibarbis, and Lasius sp.), which act as second intermediate hosts in the parasite's life cycle. Since metacercariae constitute the infectious stage of the parasite for grazing animals, Ddr-IV will provide a useful tool for epidemiology studies of dicrocoeliosis.