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Psychotherapy is an interpersonal process of collaboration toward specified treatment goals. The therapeutic alliance is well established as an important factor of psychotherapeutic change. However, the experience of distress in social interactions, commonly referred to as interpersonal problems, might be interfering with the collaborative process during psychotherapy. This study systematically reviews the literature and obtains an estimate of the relationship between pretreatment interpersonal problems and the quality of the therapeutic alliance. Overall, 27 studies with 48 correlation coefficients were included in the final analysis. Due to the nested structure of the data, a three-level meta-analytic approach with a restricted maximum likelihood estimator was applied. Alliance assessment phase, alliance rater, alliance measure instrument, and treatment type were tested as potential moderators. Heterogeneity and publication bias test were performed. The meta-analysis showed a small, but significant negative relationship between interpersonal problems at the beginning of psychotherapy and subsequent therapeutic alliance ( r = -.12, SE = .02, 95% CI [-.16, -.08], p < .001, d = -.27). Only alliance assessment phase accounted for significant variability. There were no indications for a substantial publication bias. Interpersonal problems of patients before psychotherapy are a robust predictor for lower therapeutic alliance quality, albeit a small effect size. Consequently, patients who experience interpersonal problems may face greater challenges in developing a strong alliance with their therapists, especially in early stages of the treatment. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Transcription factors (TFs) bind specific DNA sequences to regulate transcription. Apart from DNA sequences, local factors such as DNA accessibility and chromatin structure determine the affinity of a TF for any given locus. Including these factors when measuring TF-DNA affinities has proven difficult. To address this challenge, we recently developed a method called binding affinities in native chromatin by sequencing (BANC-seq). In BANC-seq, intact mammalian nuclei are incubated with a concentration range of epitope-tagged TF, followed by either chromatin immunoprecipitation or cleavage under target and release using nuclease with spike-in DNA. This allows determination of apparent dissociation constant (K d App ) values, defined by the concentration of TF at which half-maximum binding occurs, across the genome. Here we present a detailed stepwise protocol for BANC-seq, including downstream data analysis. In principle, any molecular biologist should be able to perform a BANC-seq experiment in as little as 1.5 d (excluding analysis). However, preprocessing and analysis of the sequencing data does require some experience in command-line shell and R programming., (© 2024. Springer Nature Limited.)

Objective: This study aimed to provide evidence for treatment credibility (TC) as a potential mechanism of change in cognitive behavioral therapy (CBT). Therefore, it focused on within-person effects that are free of the influence of stable characteristics and thus allow to exclude certain alternative explanations for the association under study., Method: The sample included 1,423 patients receiving outpatient CBT, who presented a wide variety of psychiatric diagnoses (mostly affective and anxiety disorders). TC, depression, and anxiety were measured every fifth session from Session 5 to 25 using the Credibility Expectancy Questionnaire (CEQ), the Patient Health Questionnaire-9 (PHQ-9), and the General Anxiety Disorder-7 (GAD-7), respectively. Symptom severity was assessed every session using the Hopkins Symptom Checklist-11. Within- and between-person effects of TC, depression, and anxiety were analyzed using the latent curve model with structured residuals (LCM-SRs). In exploratory analyses, within-person effects of TC on next-session symptom severity were assessed using a modification of the LCM-SR., Results: LCM-SRs exhibited excellent fit in main analyses. There were significant negative correlations of both intercepts and slopes (between-person level) of CEQ and PHQ-9 as well GAD-7. No significant cross-lagged effects (within-person level) were found over the five-session interval. However, session-wise analyses revealed significant cross-lagged effects of CEQ on Hopkins Symptom Checklist-11., Conclusions: This study is the first to find significant within-person effects of TC in session-wise analyses. This lends preliminary support to the notion of TC as a mechanism of change. The lack of significant findings at the five-session interval is discussed considering the specific design used in this study. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Transcription factor binding across the genome is regulated by DNA sequence and chromatin features. However, it is not yet possible to quantify the impact of chromatin context on transcription factor binding affinities. Here, we report a method called binding affinities to native chromatin by sequencing (BANC-seq) to determine absolute apparent binding affinities of transcription factors to native DNA across the genome. In BANC-seq, a concentration range of a tagged transcription factor is added to isolated nuclei. Concentration-dependent binding is then measured per sample to quantify apparent binding affinities across the genome. BANC-seq adds a quantitative dimension to transcription factor biology, which enables stratification of genomic targets based on transcription factor concentration and prediction of transcription factor binding sites under non-physiological conditions, such as disease-associated overexpression of (onco)genes. Notably, whereas consensus DNA binding motifs for transcription factors are important to establish high-affinity binding sites, these motifs are not always strictly required to generate nanomolar-affinity interactions in the genome., (© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)

The expanded version of the Inventory of Depression and Anxiety Symptoms (IDAS-II) is a 99-item self-report measure containing 18 nonoverlapping dimensional scales assessing symptoms of depression, anxiety, and mania. The aim of this study was to develop and validate a German adaptation of the IDAS-II. Participants from a community sample (N = 1,054) completed the IDAS-II (German version). In addition, part of the sample (N = 550) completed a series of additional measures of depression (Patient Health Questionnaire-9, WHO-Five Well-Being Index, Symptom Checklist-90 Revised-Short Version) and anxiety disorders (Generalized Anxiety Disorder Scale-7, Fear of Negative Evaluation Scale-5, Dimensional Obsessive-Compulsive Scale, The International Trauma Questionnaire). We conducted item-level confirmatory factor analyses (CFA) separately for the 15 nonsaturated IDAS-II scales, which confirmed unidimensionality. McDonald's ω indicated good internal consistency (ω > .8) of all symptom scales except Euphoria (ω = .751) and Ordering (ω = .728). A CFA of the IDAS-II scales, based on exploratory results by Watson et al. (2012), confirmed a three-factor model of "Distress," "Obsessions/Fear," and "Positive Mood." Correlational analyses with additional symptom measures supported the convergent and discriminant validity of the IDAS-II scales. The IDAS-II (German version) allows for a reliable assessment of the severity of depression, anxiety, and bipolar symptoms and is one of the first clinical measures for German-speaking samples that is consistent with the Hierarchical Taxonomy of Psychopathology (HiTOP). (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Retinoic acid (RA) signaling is an important and conserved pathway that regulates cellular proliferation and differentiation. Furthermore, perturbed RA signaling is implicated in cancer initiation and progression. However, the mechanisms by which RA signaling contributes to homeostasis, malignant transformation, and disease progression in the intestine remain incompletely understood. Here, we report, in agreement with previous findings, that activation of the Retinoic Acid Receptor and the Retinoid X Receptor results in enhanced transcription of enterocyte-specific genes in mouse small intestinal organoids. Conversely, inhibition of this pathway results in reduced expression of genes associated with the absorptive lineage. Strikingly, this latter effect is conserved in a human organoid model for colorectal cancer (CRC) progression. We further show that RXR motif accessibility depends on progression state of CRC organoids. Finally, we show that reduced RXR target gene expression correlates with worse CRC prognosis, implying RA signaling as a putative therapeutic target in CRC., Competing Interests: The authors declare no competing interests., (© 2021 The Author(s).)

Loss-of-function (LOF) screens provide a powerful approach to identify regulators in biological processes. Pioneered in laboratory animals, LOF screens of human genes are currently restricted to two-dimensional cell cultures, which hinders the testing of gene functions requiring tissue context. Here, we present CRISPR-lineage tracing at cellular resolution in heterogeneous tissue (CRISPR-LICHT), which enables parallel LOF studies in human cerebral organoid tissue. We used CRISPR-LICHT to test 173 microcephaly candidate genes, revealing 25 to be involved in known and uncharacterized microcephaly-associated pathways. We characterized IER3IP1 , which regulates the endoplasmic reticulum (ER) function and extracellular matrix protein secretion crucial for tissue integrity, the dysregulation of which results in microcephaly. Our human tissue screening technology identifies microcephaly genes and mechanisms involved in brain-size control., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Pluripotency can be captured in vitro in the form of Embryonic Stem Cells (ESCs). These ESCs can be either maintained in the unrestricted "naïve" state of pluripotency, adapted to developmentally more constrained "primed" pluripotency or differentiated towards each of the three germ layers. Epigenetic protein complexes and transcription factors have been shown to specify and instruct transitions from ESCs to distinct cell states. In this study, proteomic profiling of the chromatin landscape by chromatin enrichment for proteomics (ChEP) is used in mouse naive pluripotent ESCs, primed pluripotent Epiblast stem cells (EpiSCs), and cells in early stages of differentiation. A comprehensive overview of epigenetic protein complexes associated with the chromatin is provided and proteins associated with the maintenance and loss of pluripotency are identified. The data reveal major compositional alterations of epigenetic complexes during priming and differentiation of naïve pluripotent ESCs. These results contribute to the understanding of ESC differentiation and provide a framework for future studies of lineage commitment of ESCs., (© 2019 The Authors. Proteomics published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The ground state of pluripotency is defined as a minimal unrestricted epigenetic state as present in the Inner Cell Mass. Mouse embryonic stem cells (ESCs) grown in a defined serum-free medium with two kinase inhibitors ("2i ESCs") have been postulated to reflect ground-state pluripotency, whereas ESCs grown in the presence of serum ("serum ESCs") share more similarities with post-implantation epiblast cells. Pluripotency results from an intricate interplay between cytoplasmic, nuclear and chromatin-associated proteins. Here, we perform quantitative subcellular proteomics to gain insight in the molecular mechanisms sustaining the pluripotent states reflected by 2i and serum ESCs. We describe a full SILAC workflow and quality controls for proteomic comparison of 2i and serum ESCs, allowing subcellular proteomics of the cytoplasm, nucleoplasm and chromatin. The obtained quantitative information revealed increased levels of naïve pluripotency factors on the chromatin of 2i ESCs. Surprisingly, the cytoplasmic proteome suggests that 2i and serum ESCs utilize distinct metabolic programs, which include upregulation of free radical buffering by the glutathione pathway in 2i ESCs. Through induction of intracellular radicals, we show that the altered metabolic environment renders 2i ESCs less sensitive to oxidative stress. Altogether, this work provides novel insights into the proteomic landscape underlying ground state pluripotency., (Copyright © 2018 Radboud University Nijmegen. Published by Elsevier B.V. All rights reserved.)