Structural and functional studies of the transcriptional regulator Seb1 in fission yeast

RNA polymerase II (Pol II) is responsible for the transcription of all protein-coding and some non-coding genes in eukaryotes. Its largest subunit, Rpb1, contains a unique C-terminal domain (CTD) which consists of repeats of the heptad YSPTSPS. It acts as a binding platform for proteins that control the different stages of transcription and their recruitment is regulated mainly by differential phosphorylation of residues contained within the CTD. Previous studies could unveil proteins containing a CTD-interacting domain (CID) as important players that specifically bind to certain phosphorylation types of the CTD. More precisely, they were shown to be important for the last step of transcription, termination. Despite extensive research over the past 30 years, the exact mechanism of how these proteins facilitate the dislodgement of Pol II from the DNA template, still remains unknown. The work presented here contains detailed studies of the CID-containing protein Seb1 from the fission yeast Schizosaccharomyces pombe, revealing an unexpectedly broad role of this protein in transcription termination. In addition to a CID, Seb1 also contains an RNA recognition motif (RRM) which allows direct binding to RNA. Here, I present high-resolution crystal structures of both domains of Seb1. While the CID has a very conserved fold, the RNA binding regions contains an unusual arrangement of a canonical RRM intertwined with a second domain that are both important for RNA binding. Structure-based mutations were introduced and a combination of in vitro and genome-wide in vivo studies uncover Seb1 as an essential player in transcription termination. Importantly, both domains are required to promote the full function of Seb1. Despite its homology to the well-studied budding yeast protein Nrd1, the role of Seb1 in fission yeast is quite different. This thesis therefore provides important insight into the mechanisms that underlie eukaryotic transcription termination.</p

School-based mental health screenings with Ukrainian adolescent refugees in Germany: Results from a pilot study

Catani C, Wittmann J, Schmidt TL, Wilker S, Neldner S, Neuner F. School-based mental health screenings with Ukrainian adolescent refugees in Germany: Results from a pilot study. Frontiers in Psychology. 2023;14.Since the Russian invasion of Ukraine in February 2022, high numbers of Ukrainians, mostly women and children, have left the country. As of today, Germany has accepted more than one million refugees fleeing from Ukraine including ~200,000 children and adolescents registered in German schools. Since refugee minors are typically affected by high rates of mental health issues, the identification of potential psychological problems at an early stage after arrival is essential in order to make timely referrals for vulnerable youth to diagnostic or treatment services possible. The aim of the present study was to test the feasibility of a classroom-based mental health screening procedure and to assess symptoms of PTSD, depression, and anxiety in a small sample of adolescents who had fled to Germany. Forty-two adolescents (n = 20 girls) took part in the study. Screening results showed that more than half of the sample had elevated ratings in the Refugee Health Screener (RHS) and about 45% reported clinically significant levels of PTSD. Overall, the amount of both mental health problems and current worries related to the war was significantly higher in girls compared to boys. In general, screenings were well received by the adolescents. The findings of this pilot study point to a considerable level of mental health problems and distress in adolescent refugees affected by the recent war in Ukraine. Brief psychological screenings within the school setting might represent a promising approach to identifying potential mental health disorders as early as possible in newly arriving refugee youth

Low access and inadequate treatment in mental health care for asylum seekers and refugees in Germany-A prospective follow-up study over 12months and a nationwide cross-sectional study

Dumke L, Schmidt TL, Wittmann J, et al. Low access and inadequate treatment in mental health care for asylum seekers and refugees in Germany-A prospective follow-up study over 12months and a nationwide cross-sectional study. Applied Psychology: Health and Well-Being . 2024.Refugees experience elevated rates of mental health problems, but little is known about mental health service utilization and quality among asylum seekers and refugees in Europe. In a 12-month follow-up study of newly arrived refugees (N=166, Mage =32.38years, 30.7% female) and a nationwide cross-sectional study (N=579, Mage =33.89years, 36.2% female) of refugees who had been living in Germany for an average of 6years, we examined objective need for mental health treatment, perceived need, access to treatment services, and adequacy of treatment. We defined minimally adequate mental health treatment according to the WHO World Mental Health Survey as ≥8 sessions of psychotherapy (minimally adequate psychotherapy) or pharmacotherapy plus ≥4 medical visits (minimally adequate pharmacotherapy). In both studies, two in three individuals screened for mental health symptoms and additionally perceived a need for professional treatment. Of those, less than half had contact to any service provider, with only 1 in 14 receiving minimally adequate psychotherapy. Overall, no more than one in seven of refugees in need received minimally adequate treatment. Despite a comprehensive mental health-care system, refugees' access to mental health care and the treatment provided are inadequate. Health policies are urgently needed to provide equitable mental health care for all. © 2024 The Authors. Applied Psychology: Health and Well-Being published by John Wiley & Sons Ltd on behalf of International Association of Applied Psychology

Mental health of war-affected and forcibly displaced individuals and their families - Associations of risk factors and symptomatology

Ibrahim H, Iffland B, Neldner S, et al. Mental health of war-affected and forcibly displaced individuals and their families - Associations of risk factors and symptomatology. In: Abstract book: The 17th biennial conference of the European Society for Traumatic Stress Studies. Trauma and resilience through the ages: A life course perspective. European Journal of Psychotraumatology . Vol 14. Abingdon: Taylor &amp; Francis ; 2023.While the dose-effect association between the number of experienced war traumatic events andnegative mental ill-health outcomes is well-documented within current psychotraumatologyliterature, there is a dearth of scientific research on the impacts of non-war and life adversityevents (such as family-childhood trauma and intimate partner violence, and resources loss)on the mental health of war-affected populations. This symposium will present four empiricaldata on the contribution of family, childhood violence, and loss of resources to the mentalhealth of displacement families and genocide survivors in the Middle Ea

The Bielefeld Screening Approach - A screen-and-treat approach for newly arrived refugees conducted by trained multilingual lay staff

Schmidt TL, Catani C, Dumke L, et al. The Bielefeld Screening Approach - A screen-and-treat approach for newly arrived refugees conducted by trained multilingual lay staff. In: Abstract book: The 17th biennial conference of the European Society for Traumatic Stress Studies. Trauma and resilience through the ages: A life course perspective. European Journal of Psychotraumatology . Vol 14. Abingdon: Taylor &amp; Francis ; 2023.Background:Adequate health care provision for newly arrived refugees remains a challengeeven in countries with a highly developed health care system such as Germany and many otherEuropean countries. Care structures building on the principles of task-shifting and screen-and-treat may represent a cost-effective way to bridge the existing treatment gap.Objective:A manualized training program for so-called Intercultural Therapy Assistants (ITAs)will be presented. ITAs are intercultural mediators who are trained to conduct screenings andtake over other delegable tasks under the supervision of health care professionals.Furthermore, results of a feasibility study on a systematic screening approach conducted byITAs at a refugee reception camp in Bielefeld, Germany, will be presented.Method:ITAs were trained by the training manual. 167 newly arrived refugees underwent ascreening interview with the Refugee Health Screener (RHS). Afterwards, post-traumaticstress disorder (PTSD) and depression were assessed in a subsample of 48 persons by meansof structured validation interviews conducted by psychologists.Results:Findings demonstrated that it was feasible to conduct a systematic screeningprocedure during the initial immigration phase. However, adjustments of the screeningprocedure were necessary in order to meet the needs of a significant number of refugees insevere psychological crises and established cut-offvalues of the RHS had to be adapted.Conclusions:The Bielefeld Screening Approach conducted by ITAs may facilitate the earlysystematic identification of persons in need of mental health care and, thus, enable targetedinterventions that can help to prevent chronification of symptoms and consequentialproblems

Histone deacetylation promotes transcriptional silencing at facultative heterochromatin

International audienc

The efficacy of Narrative Exposure Therapy for Children (KIDNET) as a treatment for traumatized young refugees versus treatment as usual: update to the study protocol for the multi-center randomized controlled trial YOURTREAT

Wittmann J, Groß M, Catani C, et al. The efficacy of Narrative Exposure Therapy for Children (KIDNET) as a treatment for traumatized young refugees versus treatment as usual: update to the study protocol for the multi-center randomized controlled trial YOURTREAT. Trials. 2022;23(1): 360.BACKGROUND: The trial YOURTREAT aims to compare the pragmatic, short-term psychotherapy Narrative Exposure Therapy for Children (KIDNET) with treatment as usual (TAU) for the treatment of young refugees in Germany. This update outlines changes made to the study protocol in response to the current COVID-19 pandemic with the aim of allowing the continuation of the clinical trial while ensuring the safety of the staff and the participants, maintaining methodological quality, and ensuring compliance with legal regulations.; METHODS: The major amendments to the original study protocol include (1) the possibility of using telehealth technology for the conduction of diagnostic and therapy sessions, (2) a reduction of the diagnostic set, and (3) an increased flexibility in the time frame of the study protocol.; DISCUSSION: The adaptations to the study protocol made it feasible to continue with the trial YOURTREAT during the COVID-19 pandemic. Although the diagnostic set had to be shortened, the primary outcomes and the main secondary outcomes remain unimpaired by the amendment. Therefore, we expect the trial to provide evidence regarding effective treatment options for young refugees in Germany, a population that has received little scientific attention so far and has only very limited access to mental health care in the German health care system. In light of the current pandemic, which globally increases the risk of mental problems, the situation for young refugees is likely to aggravate further. Thus, the clinical and social relevance of the present trial YOURTREAT is even more important in these particular times.; TRIAL REGISTRATION: German Clinical Trials Register (Deutsches Register Klinischer Studien; DRKS) DRKS00017222 . Registered on May 15, 2019. © 2022. The Author(s)

Welcome, how are you doing? – towards a systematic mental health screening and crisis management for newly arriving refugees

Background: Compared to the general German population, refugees in Germany are a high-risk group for trauma spectrum disorders. Currently, many barriers exist for the implementation of a screen-and-treat approach for mental disorders as part of the routine health care provision during the early stage of the immigration process. Objective: The aim of the present study was to develop and test a systematic screening approach to identify individual refugees in need of mental health care during the initial immigration phase. Method: 167 newly arrived refugees underwent a screening interview with the Refugee Health Screener (RHS) carried out by Intercultural Therapy Assistants (ITAs). The ITAs were super­vised by psychologists at a reception centre in Bielefeld, Germany. A subsample of 48 persons partici­pated in clinical validation interviews. Results: Findings demonstrated the need for and feasibility of a systematic screening during the initial immigration phase. However, established cut-off values of the RHS had to be adapted and the screening procedure had to be adjusted due to the needs of a significant number of refugees in severe psychological crises. Conclusion: A systematic screening that is applied shortly after arrival facilitates the early identification of refugees at risk of developing mental disorders and may be helpful to prevent chronic symptom development and an aggravation of psychological crises

Reentrant liquid condensate phase of proteins is stabilized by hydrophobic and non-ionic interactions.

Liquid-liquid phase separation of proteins underpins the formation of membraneless compartments in living cells. Elucidating the molecular driving forces underlying protein phase transitions is therefore a key objective for understanding biological function and malfunction. Here we show that cellular proteins, which form condensates at low salt concentrations, including FUS, TDP-43, Brd4, Sox2, and Annexin A11, can reenter a phase-separated regime at high salt concentrations. By bringing together experiments and simulations, we demonstrate that this reentrant phase transition in the high-salt regime is driven by hydrophobic and non-ionic interactions, and is mechanistically distinct from the low-salt regime, where condensates are additionally stabilized by electrostatic forces. Our work thus sheds light on the cooperation of hydrophobic and non-ionic interactions as general driving forces in the condensation process, with important implications for aberrant function, druggability, and material properties of biomolecular condensates