Curated mode-of-action data and effect concentrations for chemicals relevant for the aquatic environment.

Chemicals in the aquatic environment can be harmful to organisms and ecosystems. Knowledge on effect concentrations as well as on mechanisms and modes of interaction with biological molecules and signaling pathways is necessary to perform chemical risk assessment and identify toxic compounds. To this end, we developed criteria and a pipeline for harvesting and summarizing effect concentrations from the US ECOTOX database for the three aquatic species groups algae, crustaceans, and fish and researched the modes of action of more than 3,300 environmentally relevant chemicals in literature and databases. We provide a curated dataset ready to be used for risk assessment based on monitoring data and the first comprehensive collection and categorization of modes of action of environmental chemicals. Authorities, regulators, and scientists can use this data for the grouping of chemicals, the establishment of meaningful assessment groups, and the development of in vitro and in silico approaches for chemical testing and assessment.

Effects of a Web-Based Behavioral Activation Intervention on Depressive Symptoms, Activation, Motivation, and Volition: Results of a Randomized Controlled Trial.

INTRODUCTION: Behavioral activation (BA) is effective for the treatment of depression. The Health Action Process Approach (HAPA), which is derived from health psychology, can provide a motivational-volitional framework of BA. OBJECTIVE: This study investigated the efficacy of a HAPA-based internet-delivered BA intervention (iBA; called InterAKTIV) in individuals with depression, also assessing HAPA-based motivational and volitional outcomes. METHODS: In a two-arm randomized controlled efficacy trial with a parallel design, 128 participants with a major depressive episode were randomly allocated to the intervention group (IG; TAU + immediate access to iBA) or control group (CG; TAU + access to iBA after follow-up). The primary outcome of clinician-rated depressive symptoms and secondary outcomes were assessed at baseline (T1), 8 weeks (T2), 6-month after randomization (T3). Data were analyzed on an intention-to-treat basis. RESULTS: Linear mixed model analyses revealed a significant group*time interaction effect on clinician-rated depressive symptoms favoring the IG (F2, 156.0 = 7.40; p < 0.001, d = 0.79 at T2, d = 0.25 at T3). The IG was also superior regarding self-rated depressive symptoms, BA, most motivational, and all volitional outcomes. CONCLUSION: This study shows that HAPA-based iBA can significantly improve clinician-rated depressive symptoms, as well as outcomes used in the HAPA model in people with depression. Building on these efficacy results, in the next step, the relationship between BA interventions and activity levels should be investigated, taking into account motivation and volition as potential mediators.

The unfolded protein response of the endoplasmic reticulum supports mitochondrial biogenesis by buffering nonimported proteins.

Almost all mitochondrial proteins are synthesized in the cytosol and subsequently targeted to mitochondria. The accumulation of nonimported precursor proteins occurring upon mitochondrial dysfunction can challenge cellular protein homeostasis. Here we show that blocking protein translocation into mitochondria results in the accumulation of mitochondrial membrane proteins at the endoplasmic reticulum, thereby triggering the unfolded protein response (UPRER). Moreover, we find that mitochondrial membrane proteins are also routed to the ER under physiological conditions. The level of ER-resident mitochondrial precursors is enhanced by import defects as well as metabolic stimuli that increase the expression of mitochondrial proteins. Under such conditions, the UPRER is crucial to maintain protein homeostasis and cellular fitness. We propose the ER serves as a physiological buffer zone for those mitochondrial precursors that cannot be immediately imported into mitochondria while engaging the UPRER to adjust the ER proteostasis capacity to the extent of precursor accumulation.

Internet-Based Behavioral Activation for Depression: Systematic Review and Meta-Analysis.

BACKGROUND: Behavioral activation is an effective treatment for reducing depression. As depressive disorders affect many people worldwide, internet-based behavioral activation (iBA) could provide enhanced treatment access. OBJECTIVE: This study aimed to investigate whether iBA is effective in reducing depressive symptoms and to assess the impact on secondary outcomes. METHODS: We systematically searched MEDLINE, PsycINFO, PSYNDEX, and CENTRAL up to December 2021 for eligible randomized controlled trials. In addition, a reference search was conducted. Title and abstract screening, as well as a full-text screening, was conducted by 2 independent reviewers. Randomized controlled trials that investigated the effectiveness of iBA for depression as a treatment or main component were included. Randomized controlled trials had to report depressive symptoms, with a quantitative outcome measure and assess an adult population with depressive symptoms above cutoff. Two independent reviewers performed the data extraction and risk of bias assessment. Data were pooled in random-effects meta-analyses. The primary outcome was self-reported depressive symptoms posttreatment. This systematic review and meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guidelines. RESULTS: A total of 12 randomized controlled trials, with 3274 participants (88% female, 43.61 years) were included. iBA was more effective in reducing depressive symptom severity posttreatment than inactive control groups (standardized mean difference -0.49; 95% CI -0.63 to -0.34; P<.001). The overall level of heterogeneity was moderate to substantial (I2=53%). No significant effect of iBA on depressive symptoms could be found at 6-month follow-up. Participants assigned to iBA also experienced a significant reduction of anxiety and a significant increase in quality of life and activation compared to the inactive control groups. The results remained robust in multiple sensitivity analyses. The risk of bias assessment revealed at least some concerns for all studies, and there was evidence of slight publication bias. CONCLUSIONS: This systematic review and meta-analysis implies that iBA is effective in reducing depressive symptoms. It represents a promising treatment option, providing treatment access where no treatment is available yet. TRIAL REGISTRATION: International Prospective Register of Systematic Reviews CRD42021236822; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=236822.

MitoStores: chaperone-controlled protein granules store mitochondrial precursors in the cytosol.

Hundreds of nucleus-encoded mitochondrial precursor proteins are synthesized in the cytosol and imported into mitochondria in a post-translational manner. However, the early processes associated with mitochondrial protein targeting remain poorly understood. Here, we show that in Saccharomyces cerevisiae, the cytosol has the capacity to transiently store mitochondrial matrix-destined precursors in dedicated deposits that we termed MitoStores. Competitive inhibition of mitochondrial protein import via clogging of import sites greatly enhances the formation of MitoStores, but they also form during physiological cell growth on nonfermentable carbon sources. MitoStores are enriched for a specific subset of nucleus-encoded mitochondrial proteins, in particular those containing N-terminal mitochondrial targeting sequences. Our results suggest that MitoStore formation suppresses the toxic potential of aberrantly accumulating mitochondrial precursor proteins and is controlled by the heat shock proteins Hsp42 and Hsp104. Thus, the cytosolic protein quality control system plays an active role during the early stages of mitochondrial protein targeting through the coordinated and localized sequestration of mitochondrial precursor proteins.

A risk based assessment approach for chemical mixtures from wastewater treatment plant effluents.

In this study, 56 effluent samples from 52 European wastewater treatment plants (WWTPs) were investigated for the occurrence of 499 emerging chemicals (ECs) and their associated potential risks to the environment. The two main objectives were (i) to extend our knowledge on chemicals occurring in treated wastewater, and (ii) to identify and prioritize compounds of concern based on three different risk assessment approaches for the identification of consensus mixture risk drivers of concern. Approaches include (i) PNEC and EQS-based regulatory risk quotients (RQs), (ii) species sensitivity distribution (SSD)-based hazard units (HUs) and (iii) toxic units (TUs) for three biological quality elements (BQEs) algae, crustacean, and fish. For this purpose, solid-phase extracts were analysed with wide-scope chemical target screening via liquid chromatography high-resolution mass spectrometry (LC-HRMS), resulting in 366 detected compounds, with concentrations ranging from < 1 ng/L to > 100 µg/L. The detected chemicals were categorized with respect to critical information relevant for risk assessment and management prioritization including: (1) frequency of occurrence, (2) measured concentrations, (3) use groups, (4) persistence & bioaccumulation, and (5) modes of action. A comprehensive assessment using RQ, HU and TU indicated exceedance of risk thresholds for the majority of effluents with RQ being the most sensitive metric. In total, 299 out of the 366 compounds were identified as mixture risk contributors in one of the approaches, while 32 chemicals were established as consensus mixture risk contributors of high concern, including a high percentage (66%) of pesticides and biocides. For samples which have passed an advanced treatment using ozonation or activated carbon (AC), consistently much lower risks were estimated.

Effectiveness of a web-based behavioural activation intervention for individuals with depression based on the Health Action Process Approach: protocol for a randomised controlled trial with a 6-month follow-up.

INTRODUCTION: Behavioural activation is a highly effective treatment for depression. However, there is considerable heterogeneity of interventions grouped under the term 'behavioural activation'. A main reason for the heterogeneity is the lack of a unified theory in the intervention development: few of the established intervention manuals give a theoretical rationale for their intervention techniques. For the first time, this study will examine the effectiveness of a theory-based behavioural activation intervention (InterAKTIV) based on the Health Action Process Approach. The intervention is implemented online to ensure broad dissemination and standardisation. METHODS AND ANALYSIS: In a two-arm randomised controlled trial, the effectiveness of a guided web-based behavioural activation intervention for people with depression will be evaluated. Participants are recruited via the print and online media of a large German healthcare insurance company. Individuals (age 18-65), who meet criteria for major depressive episode in a clinical interview and no exclusion criteria are eligible for inclusion. A target sample of 128 participants is randomly allocated to either the intervention group (immediate access to InterAKTIV) or treatment as usual (access after follow-up assessment). The primary outcome of depressive symptom severity (Quick Inventory of Depressive Symptomatology Clinician Rating) and secondary outcomes, including behavioural activation, physical activity and motivational and volitional outcomes are assessed at baseline, post treatment and 6-month follow-up. Data will be analysed on an intention-to-treat basis with additional per-protocol analyses. ETHICS AND DISSEMINATION: This trial is approved by the ethics committee of the Albert-Ludwigs-University of Freiburg (no.: 20-1045). All participants are required to submit their informed consent online before study inclusion. The results will be submitted for publication in a peer-reviewed journal and presented at conferences. TRIAL REGISTRATION NUMBER: This trial was registered in the German Clinical Trials Register (DRKS): DRKS00024349 (date of registration: 29 January 2021).

Supporting patient adherence to physical activity and exercise: evaluation of a behavior change counseling training program for physiotherapists.

BACKGROUND: Physiotherapists promote physical activity and exercise, yet patient adherence is often poor. To support patient adherence, behavior change techniques (BCTs) should be applied. These are insufficiently covered in physiotherapy curricula. OBJECTIVE: The aim of this study was to evaluate a behavior change counseling training program for physiotherapists. The specific aims were to investigate: (1) physiotherapists' satisfaction with the training; (2) changes in physiotherapists' knowledge of BCTs and communication techniques immediately after the training and 6 weeks later; and (3) changes in physiotherapists' self-reported use of these techniques 6 weeks after the training. METHODS: We conducted a single-group pre-post intervention study. Data of 56 physiotherapists (47 female, mean age 48.0 years) who participated in the training program "BeFo" (German: "Bewegungstherapie-Fortbildungen") were analyzed. Knowledge of BCTs and communication techniques, intention to apply these techniques, action and coping planning were assessed at baseline (t1), after the training (t2), and 6 weeks later (t3) using questionnaires. Participants' satisfaction was evaluated at t2, their use of BCTs and communication techniques at t1 and t3. RESULTS: Fifty-four participants (96.4%) were satisfied with BeFo. One-way repeated-measures ANOVAs and Friedman's ANOVA revealed increased knowledge (Chi2(2) = 28.12, p < .001) and improved action planning (F(2, 98) = 22.65; p < .001) and coping planning (F(2, 100) = 19.28, p < .001) at t2 and t3. Higher use of BCTs and communication techniques at t3 was identified when participants with high baseline values were excluded. CONCLUSION: BeFo could be successfully implemented for physiotherapists. Our results imply that BeFo is a promising approach to improve physiotherapists' behavior change counseling skills.

Effectiveness of a psychological online training to promote physical activity among students: protocol of a randomized-controlled trial.

BACKGROUND: Many students in Germany do not meet recommended amounts of physical activity. In order to promote physical activity in students, web-based interventions are increasingly implemented. Yet, data on effectiveness of web-based interventions in university students is low. Our study aims at investigating a web-based intervention for students. The intervention is based on the Health Action Process Approach (HAPA), which discriminates between processes of intention formation (motivational processes) and processes of intention implementation (volitional processes). Primary outcome is change in physical activity; secondary outcomes are motivational and volitional variables as proposed by the HAPA as well as quality of life and depressive symptoms. METHODS: A two-armed randomized controlled trial (RCT) of parallel design is conducted. Participants are recruited via the internet platform StudiCare ( www.studicare.com ). After the baseline assessment (t1), participants are randomized to either intervention group (immediate access to web-based intervention) or control group (access only after follow-up assessment). Four weeks later, post-assessment (t2) is performed in both groups followed by a follow-up assessment (t3) 3 months later. Assessments take place online. Main outcome analyses will follow an intention-to-treat principle by including all randomized participants into the analyses. Outcomes will be analysed using a linear mixed model, assuming data are missing at random. The mixed model will include group, time, and the interaction of group and time as fixed effects and participant and university as random effect. DISCUSSION: This study is a high-quality RCT with three assessment points and intention-to-treat analysis meeting the state-of-the-art of effectiveness studies. Recruitment covers almost 20 universities in three countries, leading to high external validity. The results of this study will be of great relevance for student health campaigns, as they reflect the effectiveness of self-help interventions for young adults with regard to behaviour change as well as motivational and volitional determinants. From a lifespan perspective, it is important to help students find their way into regular physical activity. TRIAL REGISTRATION: The German clinical trials register (DRKS) DRKS00016889 . Registered on 28 February 2019.

Quality of Physical Activity Apps: Systematic Search in App Stores and Content Analysis.

BACKGROUND: Physical inactivity is a major contributor to the development and persistence of chronic diseases. Mobile health apps that foster physical activity have the potential to assist in behavior change. However, the quality of the mobile health apps available in app stores is hard to assess for making informed decisions by end users and health care providers. OBJECTIVE: This study aimed at systematically reviewing and analyzing the content and quality of physical activity apps available in the 2 major app stores (Google Play and App Store) by using the German version of the Mobile App Rating Scale (MARS-G). Moreover, the privacy and security measures were assessed. METHODS: A web crawler was used to systematically search for apps promoting physical activity in the Google Play store and App Store. Two independent raters used the MARS-G to assess app quality. Further, app characteristics, content and functions, and privacy and security measures were assessed. The correlation between user star ratings and MARS was calculated. Exploratory regression analysis was conducted to determine relevant predictors for the overall quality of physical activity apps. RESULTS: Of the 2231 identified apps, 312 met the inclusion criteria. The results indicated that the overall quality was moderate (mean 3.60 [SD 0.59], range 1-4.75). The scores of the subscales, that is, information (mean 3.24 [SD 0.56], range 1.17-4.4), engagement (mean 3.19 [SD 0.82], range 1.2-5), aesthetics (mean 3.65 [SD 0.79], range 1-5), and functionality (mean 4.35 [SD 0.58], range 1.88-5) were obtained. An efficacy study could not be identified for any of the included apps. The features of data security and privacy were mainly not applied. Average user ratings showed significant small correlations with the MARS ratings (r=0.22, 95% CI 0.08-0.35; P<.001). The amount of content and number of functions were predictive of the overall quality of these physical activity apps, whereas app store and price were not. CONCLUSIONS: Apps for physical activity showed a broad range of quality ratings, with moderate overall quality ratings. Given the present privacy, security, and evidence concerns inherent to most rated apps, their medical use is questionable. There is a need for open-source databases of expert quality ratings to foster informed health care decisions by users and health care providers.

Increased levels of mitochondrial import factor Mia40 prevent the aggregation of polyQ proteins in the cytosol.

The formation of protein aggregates is a hallmark of neurodegenerative diseases. Observations on patient samples and model systems demonstrated links between aggregate formation and declining mitochondrial functionality, but causalities remain unclear. We used Saccharomyces cerevisiae to analyze how mitochondrial processes regulate the behavior of aggregation-prone polyQ protein derived from human huntingtin. Expression of Q97-GFP rapidly led to insoluble cytosolic aggregates and cell death. Although aggregation impaired mitochondrial respiration only slightly, it considerably interfered with the import of mitochondrial precursor proteins. Mutants in the import component Mia40 were hypersensitive to Q97-GFP, whereas Mia40 overexpression strongly suppressed the formation of toxic Q97-GFP aggregates both in yeast and in human cells. Based on these observations, we propose that the post-translational import of mitochondrial precursor proteins into mitochondria competes with aggregation-prone cytosolic proteins for chaperones and proteasome capacity. Mia40 regulates this competition as it has a rate-limiting role in mitochondrial protein import. Therefore, Mia40 is a dynamic regulator in mitochondrial biogenesis that can be exploited to stabilize cytosolic proteostasis.

Effectiveness of a Guided Web-Based Intervention to Reduce Depressive Symptoms before Outpatient Psychotherapy: A Pragmatic Randomized Controlled Trial.

INTRODUCTION: Psychotherapy is a first-line treatment for depression. However, capacities are limited, leading to long waiting times for outpatient psychotherapy in health care systems. Web-based interventions (WBI) could help to bridge this treatment gap. OBJECTIVE: This study investigates the effectiveness of a guided cognitive-behavioral WBI in depressive patients seeking face-to-face psychotherapy. METHODS: A 2-arm randomized controlled trial was conducted. Depressive patients (n = 136) recruited from the waiting lists of outpatient clinics were randomly assigned to an intervention group (IG; treatment as usual [TAU] + immediate access to WBI) or a control group (CG; TAU + access to WBI after follow-up). Depressive symptoms and secondary outcomes were assessed at baseline, 7 weeks, and 5 months after randomization. RESULTS: Mixed-model analyses revealed a significant group × time interaction effect on depressive symptoms (F2, 121.5 = 3.91; p < 0.05). Between-group effect sizes were d = 0.55 at 7 weeks and d = 0.52 at 5 months. The IG was superior regarding psychological symptoms and mental health quality of life but not on physical health quality of life, attitudes, motivation for psychotherapy, or subjective need and uptake of psychotherapy. CONCLUSIONS: Patients waiting for face-to-face psychotherapy can benefit from a WBI when compared to TAU. Despite the reduction of depressive symptoms in the IG, the uptake of subsequent psychotherapy was still high in both groups. The effects remained stable at the 5-month follow-up. However, this study could not determine the proportion of specific intervention effects vs. nonspecific effects, such as positive outcome expectations or attention. Future research should focus on the long-term effects and cost-effectiveness of WBI before psychotherapy.

The chaperone-binding activity of the mitochondrial surface receptor Tom70 protects the cytosol against mitoprotein-induced stress.

Most mitochondrial proteins are synthesized as precursors in the cytosol and post-translationally transported into mitochondria. The mitochondrial surface protein Tom70 acts at the interface of the cytosol and mitochondria. In vitro import experiments identified Tom70 as targeting receptor, particularly for hydrophobic carriers. Using in vivo methods and high-content screens, we revisit the question of Tom70 function and considerably expand the set of Tom70-dependent mitochondrial proteins. We demonstrate that the crucial activity of Tom70 is its ability to recruit cytosolic chaperones to the outer membrane. Indeed, tethering an unrelated chaperone-binding domain onto the mitochondrial surface complements most of the defects caused by Tom70 deletion. Tom70-mediated chaperone recruitment reduces the proteotoxicity of mitochondrial precursor proteins, particularly of hydrophobic inner membrane proteins. Thus, our work suggests that the predominant function of Tom70 is to tether cytosolic chaperones to the outer mitochondrial membrane, rather than to serve as a mitochondrion-specifying targeting receptor.

The proteasome: friend and foe of mitochondrial biogenesis.

Most mitochondrial proteins are synthesized in the cytosol and subsequently translocated as unfolded polypeptides into mitochondria. Cytosolic chaperones maintain precursor proteins in an import-competent state. This post-translational import reaction is under surveillance of the cytosolic ubiquitin-proteasome system, which carries out several distinguishable activities. On the one hand, the proteasome degrades nonproductive protein precursors from the cytosol and nucleus, import intermediates that are stuck in mitochondrial translocases, and misfolded or damaged proteins from the outer membrane and the intermembrane space. These surveillance activities of the proteasome are essential for mitochondrial functionality, as well as cellular fitness and survival. On the other hand, the proteasome competes with mitochondria for nonimported cytosolic precursor proteins, which can compromise mitochondrial biogenesis. In order to balance the positive and negative effects of the cytosolic protein quality control system on mitochondria, mitochondrial import efficiency directly regulates the capacity of the proteasome via transcription factor Rpn4 in yeast and nuclear respiratory factor (Nrf) 1 and 2 in animal cells. In this review, we provide a thorough overview of how the proteasome regulates mitochondrial biogenesis.

[Implementation of a Web-Based Self-Help Intervention for Mood Enhancement during Waiting Times for Outpatient Psychotherapy - A Qualitative Study Exploring Participants' Perspectives]. / Webbasierte Selbsthilfe zur Stimmungsverbesserung in der Wartezeit auf ambulante Psychotherapie ­ Eine qualitative Erhebung der Teilnehmerperspektive.

OBJECTIVE: In Germany, waiting times for outpatient psychotherapy are on average 5 months long. Guided web-based interventions can be implemented to reduce depressive symptoms during waiting times. The study aims to explore how patients experience the usage of a web-based intervention for mood enhancement. METHODS: Patients on the waiting lists of cooperating outpatient clinics were invited to participate in the study and apply a web-based intervention for mood enhancement. Eleven participating patients were interviewed about their experiences with the intervention. The data was analyzed based on the Grounded-Theory methodology. RESULTS: Three categories could be derived from the data: prior expectations, experiences with the intervention and factors influencing adherence. The web-based intervention was experienced very differently and was associated with both positive and negative experiences. The participants could be grouped into 3 user types. DISCUSSION: Not all patients report positive experiences with the intervention and some fail to adhere. In order to prepare patients adequately, they should be informed about the application and goals of the intervention in advance. Interventions should be implemented in accordance with the individual's need of support in order to enhance adherence and allow positive experiences.

The intermembrane space protein Mix23 is a novel stress-induced mitochondrial import factor.

The biogenesis of mitochondria requires the import of hundreds of precursor proteins. These proteins are transported post-translationally with the help of chaperones, meaning that the overproduction of mitochondrial proteins or the limited availability of chaperones can lead to the accumulation of cytosolic precursor proteins. This imposes a severe challenge to cytosolic proteostasis and triggers a specific transcription program called the mitoprotein-induced stress response, which activates the proteasome system. This coincides with the repression of mitochondrial proteins, including many proteins of the intermembrane space. In contrast, herein we report that the so-far-uncharacterized intermembrane space protein Mix23 is considerably up-regulated when mitochondrial import is perturbed. Mix23 is evolutionarily conserved and a homolog of the human protein CCDC58. We found that, like the subunits of the proteasome, Mix23 is under control of the transcription factor Rpn4. It is imported into mitochondria by the mitochondrial disulfide relay. Mix23 is critical for the efficient import of proteins into the mitochondrial matrix, particularly if the function of the translocase of the inner membrane 23 is compromised such as in temperature-sensitive mutants of Tim17. Our observations identify Mix23 as a novel regulator or stabilizer of the mitochondrial protein import machinery that is specifically up-regulated upon mitoprotein-induced stress conditions.

[Responses of German-speaking voice assistants to questions about health issues]. / Antwortverhalten von deutschsprachigen Sprachassistenten auf Gesundheitsfragen.

BACKGROUND: In Germany, there is widespread use of smartphones that can be operated via voice assistants (VAs). Due to their increasing distribution, they hold the potential to influence health behavior at a population level. OBJECTIVES: This study examines the response behavior of German-speaking VAs to questions on mental and physical health as well as interpersonal violence. METHODS: Common VAs received nine standardized health questions. Responses were evaluated in terms of the categories "Recognizing the question," "Respectful responsiveness," and "Referring to support services." RESULTS: Fifty-one VAs were tested on 44 devices. Mental health issues were mostly recognized and answered with respect. Regarding expressed suicidal thoughts, only one VA did not refer to a specific crisis line. With respect to "interpersonal violence," only one VA recognized the expressed problems. In terms of physical health, only one VA showed respectful responses in all three tested healthcare areas, leading help seekers to additional healthcare services (e.g., hospitals, pharmacies). For some complaints, the VAs gave behavioral advice. CONCLUSION: VAs are able to recognize health issues, to respond respectably, and to guide those in need of care to specific healthcare and counselling services. However, responsiveness is insufficient and inconsistent. Future research should investigate how the responsiveness of VAs can be improved to provide the best possible support to people in crisis.

Publisher Correction: Mitochondrial protein-induced stress triggers a global adaptive transcriptional programme.

In the version of this article originally published, parts of Figure 5 were misaligned because of a shift during production. In a, one data point was outside of the graph border. In b, axes lines were not connected, and graph lines did not reach the data points. In c and d, the axes lines were not connected. In e and g, the axes lines were not connected, and error bars and columns were not aligned. Shown below are the original and corrected versions of Figure 5. The errors have been corrected in the PDF and HTML versions of the paper.

[New Media in Psychotherapy: Blended Therapy from the Perspective of Outpatient Psychotherapists]. / Neue Medien in der Psychotherapie: Blended Therapy aus der Sicht ambulanter Psychotherapeuten.

The aim of the study was to generate a model describing psychotherapists' use of new media in outpatient psychotherapy. Problem-centered interviews were conducted with 12 outpatient psychotherapists. Data was analyzed following the Grounded Theory approach. The interviews revealed five categories that were integrated into the model "Use of new media in outpatient therapy" (MAP): First, psychotherapists' characteristics determine whether new media use is considered. When new media is in use, patient characteristics define its intensity and content. Additionally, decision making rules and communication rules shape therapists' use of new media. MAP identifies barriers and facilitators of new media application in outpatient psychotherapy and describes psychotherapists' decision making process. Options for implementing blended therapy in outpatient psychotherapeutic care are discussed.

Mitochondrial protein-induced stress triggers a global adaptive transcriptional programme.

The cytosolic accumulation of mitochondrial precursors is hazardous to cellular fitness and is associated with a number of diseases. However, it is not observed under physiological conditions. Individual mechanisms that allow cells to avoid cytosolic accumulation of mitochondrial precursors have recently been discovered, but their interplay and regulation remain elusive. Here, we show that cells rapidly launch a global transcriptional programme to restore cellular proteostasis after induction of a 'clogger' protein that reduces the number of available mitochondrial import sites. Cells upregulate the protein folding and proteolytic systems in the cytosol and downregulate both the cytosolic translation machinery and many mitochondrial metabolic enzymes, presumably to relieve the workload of the overstrained mitochondrial import system. We show that this transcriptional remodelling is a combination of a 'wideband' core response regulated by the transcription factors Hsf1 and Rpn4 and a unique mitoprotein-induced downregulation of the oxidative phosphorylation components, mediated by an inactivation of the HAP complex.