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There is a large body of research exploring therapeutic effectiveness for racially or ethnically minoritized college students. Prior literature highlights the unique mental health and academic challenges faced by Native American students in higher education; however, there is a paucity of research examining the effectiveness of counseling for Native American college students. The present study examined the effectiveness of counseling on psychological and academic distress among Native American college students, comparing their initial distress and rate of change to White students in counseling. Using naturalistic data from a large practice-research network spanning 2015-2019, we employed hierarchical linear modeling to evaluate the effect of race on psychological distress (N = 9,621) and academic distress (N = 9,643) scores during treatment. Results revealed that all clients demonstrated a significant decrease in both types of distress over the course of treatment. Native American and White clients presented to counseling with similar levels of psychological distress. However, Native American clients experienced more change and at a faster rate on psychological distress symptoms compared to White clients. On academic distress, Native American clients began and concluded counseling with higher levels of distress while experiencing a similar amount of change at a similar rate in their reduction of academic distress over the course of treatment. The study findings provide unique insight on the outcomes of treatment-seeking Native students by demonstrating a significant positive response to counseling, as well as novel comparisons between Native and White students receiving services within college counseling settings. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

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This article serves as an introduction to a special section devoted to the psychotherapy relationship and digital interventions. The nature of the therapy relationship is explored, and the question is raised as to whether machines can have relationships with their users. Finally, an overview and synthesis of the articles in the special section is provided.

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OBJECTIVE: Measurement of countertransference (CT) has proven challenging throughout the history of studying this construct. We sought to determine the potential value of using a common measure of transference, the Core Conflictual Relationship Theme (CCRT) method, as a means of studying CT. METHOD: The Relationship Anecdote Paradigm and the CCRT method were used to examine CT in two studies. In Study 1, we examined the correspondence between a therapist's wishes with significant people in her life (i.e., her parents and husband) and three long-term patients. In Study 2, we identified the interpersonal wishes of a different therapist and examined 14 of her sessions with 3 patients for evidence of how these wishes and needs were displayed in her clinical work. RESULTS: Analyses revealed that specific wishes in therapists' personal lives could be detected from projective interviews and these wishes were similar, but not necessarily identical, to wishes in therapists' descriptions of, and actual work with, their patients. Evidence of both chronic wishes and patient-specific wishes was revealed. CONCLUSIONS: These findings support the idea that the origins of CT reside in therapists' interpersonal wishes and that the CCRT may be a promising means of identifying CT in research, practice, and supervision.

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The highly positively charged and intrinsically disordered H1 C-terminal domain (CTD) undergoes extensive condensation upon binding to nucleosomes, and stabilizes nucleosomes and higher-order chromatin structures but its interactions in chromatin are not well defined. Using single-molecule FRET we found that about half of the H1 CTDs in H1-nucleosome complexes exhibit well-defined FRET values indicative of distinct, static conformations, while the remainder of the population exhibits exchange between multiple defined FRET structures. Moreover, crosslinking studies indicate that the first 30 residues of the H1 CTD participate in relatively localized contacts with the first ∼25 bp of linker DNA, and that two separate regions in the CTD contribute to H1-dependent organization of linker DNA. Finally, we show that acetylation mimetics within the histone H3 tail markedly reduce the overall extent of H1 CTD condensation and significantly increase the fraction of H1 CTDs undergoing dynamic exchange between FRET states. Our results indicate the nucleosome-bound H1 CTD adopts loosely defined structures that exhibit significantly enhanced dynamics and decondensation upon epigenetic acetylation within the H3 tail.

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OBJECTIVE: The current study aimed to inform the varied and limited research on clinical variables in the context of teletherapy. Questions remain about the comparative quality of therapeutic alliance and clinical outcome in the context of teletherapy compared to in-person treatment. METHODS: We utilized a cohort design and a noninferiority statistical approach to study a large, matched sample of clients who reported therapeutic alliance as well as psychological distress before every session as part of routine clinical practice at a university counseling center. A cohort of 479 clients undergoing teletherapy after the emergence of the COVID-19 pandemic was compared to a cohort of 479 clients receiving in-person treatment before the onset of the pandemic. Tests of noninferiority were conducted to investigate the absence of meaningful differences between the two modalities of service delivery. Client characteristics were also examined as moderators of the association between modality and alliance or outcome. RESULTS: Clients receiving teletherapy showed noninferior alliance and clinical outcome when compared to clients receiving in-person psychotherapy. A significant main effect on alliance was found with regard to race and ethnicity. A significant main effect on outcome was found with regard to international student status. Significant interactions on alliance were found between cohort and current financial stress. CONCLUSIONS: Study findings support the continued use of teletherapy by demonstrating commensurate clinical process and outcome. Yet, it will be important for providers to be aware of existing mental health disparities that continue to accompany psychotherapy - in person and via teletherapy. Results and findings are discussed in terms of research and clinical implications. Future directions for researching teletherapy as a viable treatment delivery method are also discussed.

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Despite their importance, how linker histone H1s interact in chromatin and especially how the highly positively charged and intrinsically disordered H1 C-terminal domain (CTD) binds and stabilizes nucleosomes and higher-order chromatin structures remains unclear. Using single-molecule FRET we found that about half of the H1 CTDs in H1-nucleosome complexes exhibit well-defined FRET values indicative of distinct, static conformations, while the remainder of the population exhibits dynamically changing values, similar to that observed for H1 in the absence of nucleosomes. We also find that the first 30 residues of the CTD participate in relatively localized interactions with the first ∼20 bp of linker DNA, and that two separate regions in the CTD contribute to H1-dependent organization of linker DNA, consistent with some non-random CTD-linker DNA interactions. Finally, our data show that acetylation mimetics within the histone H3 tail induce decondensation and enhanced dynamics of the nucleosome-bound H1 CTD. (148 words).

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Linker histones (LH) are a critical component of chromatin in addition to the canonical histones (H2A, H2B, H3, and H4). In humans, 11 subtypes (7 somatic and 4 germinal) of linker histones have been identified, and their diverse cellular functions in chromatin structure, DNA replication, DNA repair, transcription, and apoptosis have been explored, especially for the somatic subtypes. Delineating the unique role of human linker histone (hLH) and their subtypes is highly tedious given their high homology and overlapping expression patterns. However, recent advancements in mass spectrometry combined with HPLC have helped in identifying the post-translational modifications (PTMs) found on the different LH subtypes. However, while a number of PTMs have been identified and their potential nuclear and non-nuclear functions explored in cellular processes, there are very few studies delineating the direct relevance of these PTMs in diseases. In addition, recent whole-genome sequencing of clinical samples from cancer patients and individuals afflicted with Rahman syndrome have identified high-frequency mutations and therefore broadened the perspective of the linker histone mutations in diseases. In this review, we compile the identified PTMs of hLH subtypes, current knowledge of the relevance of hLH PTMs in human diseases, and the correlation of PTMs coinciding with mutations mapped in diseases.

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Objective: The literature regarding dropout from psychotherapy has suffered from issues of diverse operationalization of the construct. Some have called for a more uniform definition to aid in generalization across research; this study aimed to assess the viability of such a definition by examining the rate of occurrence for three distinct definitions simultaneously. In addition, therapist and center level variances are explored to further understand the differences between definitions.Method: We compared the prevalence rates and overlap of three distinct operationalizations of dropout (based on last session attendance, therapist judgment, and symptom change) using data gathered from a national practice research network (N = 2977). Higher-order therapist and center-level effects were assessed for each definition.Results: There was very little overlap among definitions, with less than one percent of clients simultaneously meeting criteria for all three definitions. Additionally, therapist and center effects were found for each definition, especially notable for therapist-rated and last-session attendance definitions of dropout.Conclusion: Rather than a singular definition of dropout, these results instead suggest that multiple, specific, and unique definitions more accurately depict clinical reality, and future research might benefit from uncovering predictors of different "classes" of dropouts and examining the different practices of therapists and centers.

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Candida albicans is an opportunistic human fungal pathogen that causes invasive infections in immunocompromised individuals. Despite the high anticandidal activity among the echinocandins (ECNs), a first-line therapy, resistance remains an issue. Furthermore, many clinical isolates display decreased ECN susceptibility, a physiological state which is thought to lead to resistance. Determining the factors that can decrease susceptibility is of high importance. We searched for such factors genome-wide by comparing the transcriptional profiles of five mutants that acquired decreased caspofungin susceptibility in vitro in the absence of canonical FKS1 resistance mutations. The mutants were derived from two genetic backgrounds and arose due to independent mutational events, some with monosomic chromosome 5 (Ch5). We found that the mutants exhibit common transcriptional changes. In particular, all mutants upregulate five genes from Ch2 in concert. Knockout experiments show that all five genes positively influence caspofungin and anidulafungin susceptibility and play a role in regulating the cell wall mannan and glucan contents. The functions of three of these genes, orf19.1766, orf19.6867, and orf19.5833, were previously unknown, and our work expands the known functions of LEU42 and PR26. Importantly, orf19.1766 and LEU42 have no human orthologues. Our results provide important clues as to basic mechanisms of survival in the presence of ECNs while identifying new genes controlling ECN susceptibility and revealing new targets for the development of novel antifungal drugs.

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Chromatin remodeling enzymes use energy derived from ATP hydrolysis to mobilize nucleosomes and alter their structure to facilitate DNA access. The Remodels the Structure of Chromatin (RSC) complex has been extensively studied, yet aspects of how this complex functionally interacts with nucleosomes remain unclear. We introduce a steric mapping approach to determine how RSC activity depends on interaction with specific surfaces within the nucleosome. We find that blocking SHL + 4.5/-4.5 via streptavidin binding to the H2A N-terminal tail domains results in inhibition of RSC nucleosome mobilization. However, restriction enzyme assays indicate that remodeling-dependent exposure of an internal DNA site near the nucleosome dyad is not affected. In contrast, occlusion of both protein faces of the nucleosome by streptavidin attachment near the acidic patch completely blocks both remodeling-dependent nucleosome mobilization and internal DNA site exposure. However, we observed partial inhibition when only one protein surface is occluded, consistent with abrogation of one of two productive RSC binding orientations. Our results indicate that nucleosome mobilization requires RSC access to the trailing but not the leading protein surface, and reveals a mechanism by which RSC and related complexes may drive unidirectional movement of nucleosomes to regulate cis-acting DNA sequences in vivo.

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As a key structural component of the chromatin of higher eukaryotes, linker histones (H1s) are involved in stabilizing the folding of extended nucleosome arrays into higher-order chromatin structures and function as a gene-specific regulator of transcription in vivo. The H1 C-terminal domain (CTD) is essential for high-affinity binding of linker histones to chromatin and stabilization of higher-order chromatin structure. Importantly, the H1 CTD is an intrinsically disordered domain that undergoes a drastic condensation upon binding to nucleosomes. Moreover, although phosphorylation is a prevalent post-translational modification within the H1 CTD, exactly where this modification is installed and how phosphorylation influences the structure of the H1 CTD remains unclear for many H1s. Using novel mass spectrometry techniques, we identified six phosphorylation sites within the CTD of the archetypal linker histone Xenopus H1.0. We then analyzed nucleosome-dependent CTD condensation and H1-dependent linker DNA organization for H1.0 in which the phosphorylated serine residues were replaced by glutamic acid residues (phosphomimics) in six independent mutants. We find that phosphomimetics at residues S117E, S155E, S181E, S188E, and S192E resulted in a significant reduction in nucleosome-bound H1.0 CTD condensation compared with unphosphorylated H1.0, whereas S130E did not alter CTD structure. Furthermore, we found distinct effects among the phosphomimetics on H1-dependent linker DNA trajectory, indicating unique mechanisms by which this modification can influence H1 CTD condensation. These results bring to light a novel role for linker histone phosphorylation in directly altering the structure of nucleosome-bound H1 and a potential novel mechanism for its effects on chromatin structure and function.

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Defining the genome-wide chromatin landscape has been a goal of experimentalists for decades. Here we review highlights of these efforts, from seminal experiments showing discontinuities in chromatin structure related to gene activation to extensions of these methods elucidating general features of chromatin related to gene states by exploiting deep sequencing methods. We also review chromatin conformational capture methods to identify patterns in long-range interactions between genomic loci.

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Candida albicans is a prevalent fungal pathogen of humans. Understanding the development of decreased susceptibility to ECN drugs of this microbe is of substantial interest, as it is viewed as an intermediate step allowing the formation of FKS1 resistance mutations. We used six previously characterized mutants that decreased caspofungin susceptibility either by acquiring aneuploidy of chromosome 5 (Ch5) or by aneuploidy-independent mechanisms. When we exposed these caspofungin-adapted mutants to caspofungin again, we obtained 60 evolved mutants with further decreases in caspofungin susceptibility, as determined with CLSI method. We show that the initial adaptation to caspofungin is coupled with the adaptation to other ECNs, such as micafungin and anidulafungin, in mutants with no ploidy change, but not in aneuploid mutants, which become more susceptible to micafungin and anidulafungin. Furthermore, we find that the initial mechanism of caspofungin adaptation determines the pattern of further adaptation as parentals with no ploidy change further adapt to all ECNs by relatively small decreases in susceptibility, whereas aneuploid parentals adapt to all ECNs, primarily by large decrease in susceptibilities. Our data suggest that either distinct or common mechanisms can govern adaptation to different ECNs.

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Physarum polycephalum belongs to Mycetozoans, a phylogenetic clade apart from the animal, plant and fungus kingdoms. Histones are nuclear proteins involved in genome organization and regulation and are among the most evolutionary conserved proteins within eukaryotes. Therefore, this raises the question of their conservation in Physarum and the position of this organism within the eukaryotic phylogenic tree based on histone sequences. We carried out a comprehensive study of histones in Physarum polycephalum using genomic, transcriptomic and molecular data. Our results allowed to identify the different isoforms of the core histones H2A, H2B, H3 and H4 which exhibit strong conservation of amino acid residues previously identified as subject to post-translational modifications. Furthermore, we also identified the linker histone H1, the most divergent histone, and characterized a large number of its PTMs by mass spectrometry. We also performed an in-depth investigation of histone genes and transcript structures. Histone proteins are highly conserved in Physarum and their characterization will contribute to a better understanding of the polyphyletic Mycetozoan group. Our data reinforce that P. polycephalum is evolutionary closer to animals than plants and located at the crown of the eukaryotic tree. Our study provides new insights in the evolutionary history of Physarum and eukaryote lineages.

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Purpose: Campus counseling centers, which oversee the provision of mental health services, can play a vital role in supporting positive outcomes among college students in general; however, little remains known about the effectiveness of campus-based counseling for reducing academic and psychological distress among college students with disabilities. The purpose of the current study was to examine the effectiveness of individual campus-based counseling for students with disabilities and to determine whether the effectiveness of counseling varied by student disability status. Method: Data for the present study were gathered by the Center for Collegiate Mental Health from the 2016-2019 academic years. Participants consisted of help-seeking students with only psychiatric disabilities (n = 643), students with disabilities other than only psychiatric disabilities (n = 3,833), and students without a disability (n = 54,576). Results: Results indicated that students with disabilities demonstrated significantly fewer reductions in levels of psychological and academic distress than their nondisabled peers, and analyses further revealed variation by disability type. Conclusions: These findings advance our understanding of the effectiveness of campus counseling services for improving pertinent outcomes among help-seeking college students with disabilities. Implications for clinical practice, theory, and future research are discussed. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

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Considerable progress has been made recently in defining the interactions of linker histones (H1s) within nucleosomes. Major advancements include atomic resolution structures of the globular domain of full-length H1s in the context of nucleosomes containing full-length linker DNA. Although these studies have led to a detailed understanding of the interactions and dynamics of H1 globular domains in the canonical on-dyad nucleosome binding pocket, more information regarding the intrinsically disordered N-terminal and C-terminal domains is needed. In this review, we highlight studies supporting our current understanding of the structures and interactions of the N-terminal, globular, and C-terminal domains of linker histones within the nucleosome.

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BACKGROUND: The vast majority of methods available to characterize genome-wide chromatin structure exploit differences in DNA accessibility to nucleases or chemical crosslinking. We developed a novel method to gauge genome-wide accessibility of histone protein surfaces within nucleosomes by assessing reactivity of engineered cysteine residues with a thiol-specific reagent, biotin-maleimide (BM). RESULTS: Yeast nuclei were obtained from cells expressing the histone mutant H2B S116C, in which a cysteine resides near the center of the external flat protein surface of the nucleosome. BM modification revealed that nucleosomes are generally equivalently accessible throughout the S. cerevisiae genome, including heterochromatic regions, suggesting limited, higher-order chromatin structures in which this surface is obstructed by tight nucleosome packing. However, we find that nucleosomes within 500 bp of transcription start sites exhibit the greatest range of accessibility, which correlates with the density of chromatin remodelers. Interestingly, accessibility is not well correlated with RNA polymerase density and thus the level of gene expression. We also investigated the accessibility of cysteine mutations designed to detect exposure of histone surfaces internal to the nucleosome thought to be accessible in actively transcribed genes: H3 102, is at the H2A-H2B dimer/H3-H4 tetramer interface, and H3 A110C, resides at the H3-H3 interface. However, in contrast to the external surface site, we find that neither of these internal sites were found to be appreciably exposed. CONCLUSIONS: Overall, our finding that nucleosomes surfaces within S. cerevisiae chromatin are equivalently accessible genome-wide is consistent with a globally uncompacted chromatin structure lacking substantial higher-order organization. However, we find modest differences in accessibility that correlate with chromatin remodelers but not transcription, suggesting chromatin poised for transcription is more accessible than actively transcribed or intergenic regions. In contrast, we find that two internal sites remain inaccessible, suggesting that such non-canonical nucleosome species generated during transcription are rapidly and efficiently converted to canonical nucleosome structure and thus not widely present in native chromatin.

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Objective: There is a paucity of studies examining the experience of clients who undergo multiple courses of psychotherapy. Conducted within a large practice research network, this study demonstrated that returning therapy clients comprise a considerable portion of the clinical population in university counseling settings, and identified variables associated with return to therapy. Method: Utilizing data spanning 2013 to 2017, statistical variable selection for predicting return to therapy was conducted via grouped least absolute shrinkage and selection operator (grouped LASSO) applied to logistic regression. The grouped LASSO approach is described in detail to facilitate learning and replication. The paper also addresses methodological considerations related to this approach, such as sample size, generalizability, as well as general strengths and limitations. Results: Attendance rate, duration of initial treatment course, social anxiety, perceived social support, academic distress, and alcohol use were identified as predictive of return to therapy. Conclusions: Findings could help inform more cost-effective policies for session limits (e.g., extending session limits for clients with social anxiety), referral decisions (e.g., for clients with alcohol use problems), and appointment reminders (based on the association between poor attendance rate and return to therapy). Taking into account the many reasons that can explain why clients do or do not return to therapy, these findings also could inform clinicians' early case conceptualizations and treatment interventions.

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Linker histones (H1s) are key structural components of the chromatin of higher eukaryotes. However, the mechanisms by which the intrinsically disordered linker histone carboxy-terminal domain (H1 CTD) influences chromatin structure and gene regulation remain unclear. We previously demonstrated that the CTD of H1.0 undergoes a significant condensation (reduction of end-to-end distance) upon binding to nucleosomes, consistent with a transition to an ordered structure or ensemble of structures. Here, we show that deletion of the H3 N-terminal tail or the installation of acetylation mimics or bona fide acetylation within H3 N-terminal tail alters the condensation of the nucleosome-bound H1 CTD. Additionally, we present evidence that the H3 N-tail influences H1 CTD condensation through direct protein-protein interaction, rather than alterations in linker DNA trajectory. These results support an emerging hypothesis wherein the H1 CTD serves as a nexus for signaling in the nucleosome.

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