Catalogue Search | MBRL
Are you sure you want to remove the book from the shelf?
{{itemTitle}}
257
result(s) for
"Holland, Stephen J"
Sort by:
Treatment plans and interventions for depression and anxiety disorders
\"_This widely used book is packed with indispensable tools for treating the most common clinical problems encountered in outpatient mental health practice. Chapters provide basic information on depression and the six major anxiety disorders; step-by-step instructions for evidence-based assessment and intervention; illustrative case examples; and practical guidance for writing reports and dealing with third-party payers. In a convenient large-size format, the book features 125 reproducible client handouts, homework sheets, and therapist forms for assessment and record keeping. The included CD-ROM enables clinicians to rapidly generate individualized treatment plans, print extra copies of the forms, and find information on frequently prescribed medications._New to This Edition*The latest research on each disorder and its treatment.*Innovative techniques that draw on cognitive, behavioral, mindfulness, and acceptance-based approaches.*Two chapters offering expanded descriptions of basic behavioral and cognitive techniques.*47 of the 125 reproducibles are entirely new. __\"--Provided by publisher.
Book
Diversification of AID/APOBEC-like deaminases in metazoa
AID/APOBEC deaminases (AADs) convert cytidine to uridine in single-stranded nucleic acids. They are involved in numerous mutagenic processes, including those underpinning vertebrate innate and adaptive immunity. Using a multipronged sequence analysis strategy, we uncover several AADs across metazoa, dictyosteliida, and algae, including multiple previously unreported vertebrate clades, and versions from urochordates, nematodes, echinoderms, arthropods, lophotrochozoans, cnidarians, and porifera. Evolutionary analysis suggests a fundamental division of AADs early inmetazoan evolution into secreted deaminases (SNADs) and classical AADs, followed by diversification into several clades driven by rapid-sequence evolution, gene loss, lineage-specific expansions, and lateral transfer to various algae. Most vertebrate AADs, including AID and APOBECs1–3, diversified in the vertebrates, whereas the APOBEC4-like clade has a deeper origin in metazoa. Positional entropy analysis suggests that several AAD clades are diversifying rapidly, especially in the positions predicted to interact with the nucleic acid target motif, and with potential viral inhibitors. Further, several AADs have evolved neomorphic metal-binding inserts, especially within loops predicted to interact with the target nucleic acid. We also observe polymorphisms, driven by alternative splicing, gene loss, and possibly intergenic recombination between paralogs. We propose that biological conflicts of AADs with viruses and genomic retroelements are drivers of rapid AAD evolution, suggesting a widespread presence of mutagenesis-based immune-defense systems. Deaminases like AID represent versions “institutionalized” from the broader array of AADs pitted in such arms races for mutagenesis of self-DNA, and similar recruitment might have independently occurred elsewhere in metazoa.
Journal Article
Selection of the lamprey VLRC antigen receptor repertoire
The alternative adaptive immune system of jawless vertebrates is based on different isotypes of variable lymphocyte receptors (VLRs) that are composed of leucine-rich repeats (LRRs) and expressed by distinct B- and T-like lymphocyte lineages. VLRB is expressed by B-like cells, whereas VLRA and VLRC are expressed by two T-like lineages that develop in the thymoid, a thymus-like structure in lamprey larvae. In each case, stepwise combinatorial insertions of different types of short donor LRR cassettes into incomplete germ-line genes are required to generate functional VLR gene assemblies. It is unknown, however, whether the diverse repertoires of VLRs that are expressed by peripheral blood lymphocytes are shaped by selection after their assembly. Here, we identify signatures of selection in the peripheral repertoire of VLRC antigen receptors that are clonally expressed by one of the T-like cell types in lampreys. Selection strongly favors VLRC molecules containing four internal variable leucine-rich repeat (LRRV) modules, although VLRC assemblies encoding five internal modules are initially equally frequent. In addition to the length selection, VLRC molecules in VLRC⁺ peripheral lymphocytes exhibit a distinct pattern of high entropy sites in the N-terminal LRR1 module, which is inserted next to the germ-line-encoded LRRNT module. This is evident in comparisons to VLRC gene assemblies found in the thymoid and to VLRC gene assemblies found in some VLRA⁺ cells. Our findings are the first indication to our knowledge that selection operates on a VLR repertoire and provide a framework to establish the mechanism by which this selection occurs during development of the VLRC⁺ lymphocyte lineage.
Journal Article
Genomic donor cassette sharing during VLRA and VLRC assembly in jawless vertebrates
Significance Lampreys possess two T-like lymphocyte lineages that express either variable lymphocyte receptor (VLR) A or VLRC antigen receptors. Despite the mutually exclusive expression pattern of VLRA and VLRC, in some cases the sequences of the two receptors are partially identical. This is the result of the shared use of genomic donor cassettes that are required to convert the incomplete VLRA and VLRC genes into functional assemblies. This feature is reminiscent of T-cell receptors of jawed vertebrates that, despite being composed of different molecular structures, also share some variable parts. The shared use of variable segments in the different antigen receptor types for T cells of all vertebrates implies a conserved functional relationship between the two prototypic T-cell lineages.
Lampreys possess two T-like lymphocyte lineages that express either variable lymphocyte receptor (VLR) A or VLRC antigen receptors. VLRA ⁺ and VLRC ⁺ lymphocytes share many similarities with the two principal T-cell lineages of jawed vertebrates expressing the αβ and γδ T-cell receptors (TCRs). During the assembly of VLR genes, several types of genomic cassettes are inserted, in step-wise fashion, into incomplete germ-line genes to generate the mature forms of antigen receptor genes. Unexpectedly, the structurally variable components of VLRA and VLRC receptors often possess partially identical sequences; this phenomenon of module sharing between these two VLR isotypes occurs in both lampreys and hagfishes. By contrast, VLRA and VLRC molecules typically do not share their building blocks with the structurally analogous VLRB receptors that are expressed by B-like lymphocytes. Our studies reveal that VLRA and VLRC germ-line genes are situated in close proximity to each other in the lamprey genome and indicate the interspersed arrangement of isotype-specific and shared genomic donor cassettes; these features may facilitate the shared cassette use. The genomic structure of the VLRA/VLRC locus in lampreys is reminiscent of the interspersed nature of the TCRA / TCRD locus in jawed vertebrates that also allows the sharing of some variable gene segments during the recombinatorial assembly of TCR genes.
Journal Article
T-cell receptor is not hardwired to engage MHC ligands
The bias of αβ T cells for MHC ligands has been proposed to be intrinsic to the T-cell receptor (TCR). Equally, the CD4 and CD8 coreceptors contribute to ligand restriction by colocalizing Lck with the TCR when MHC ligands are engaged. To determine the importance of intrinsic ligand bias, the germ-line TCR complementarity determining regions were extensively diversified in vivo. We show that engagement with MHC ligands during thymocyte selection and peripheral T-cell activation imposes remarkably little constraint over TCR structure. Such versatility is more consistent with an opportunist, rather than a predetermined, mode of interface formation. This hypothesis was experimentally confirmed by expressing a hybrid TCR containing TCR-γ chain germ-line complementarity determining regions, which engaged efficiently with MHC ligands.
Journal Article
Expansions, diversification, and interindividual copy number variations of AID/APOBEC family cytidine deaminase genes in lampreys
Cytidine deaminases of the AID/APOBEC family catalyze C-to-U nucleotide transitions in mRNA or DNA. Members of the APOBEC3 branch are involved in antiviral defense, whereas AID contributes to diversification of antibody repertoires in jawed vertebrates via somatic hypermutation, gene conversion, and class switch recombination. In the extant jawless vertebrate, the lamprey, two members of the AID/APOBEC family are implicated in the generation of somatic diversity of the variable lymphocyte receptors (VLRs). Expression studies linked CDA1 and CDA2 genes to the assembly of VLRA/C genes in T-like cells and the VLRB genes in B-like cells, respectively. Here, we identify and characterize several CDA1-like genes in the larvae of different lamprey species and demonstrate that these encode active cytidine deaminases. Structural comparisons of the CDA1 variants highlighted substantial differences in surface charge; this observation is supported by our finding that the enzymes require different conditions and substrates for optimal activity in vitro. Strikingly, we also found that the number of CDA-like genes present in individuals of the same species is variable. Nevertheless, irrespective of the number of different CDA1-like genes present, all lamprey larvae have at least one functional CDA1-related gene encoding an enzyme with predicted structural and chemical features generally comparable to jawed vertebrate AID. Our findings suggest that, similar to APOBEC3 branch expansion in jawed vertebrates, the AID/APOBEC family has undergone substantial diversification in lamprey, possibly indicative of multiple distinct biological roles.
Journal Article
Development and validation of a scale to assess patient progress in brief psychodynamic therapy
The Rutgers Psychotherapy Progress Scale (RPPS) was developed to measure in-session patient progress as psychoanalytically conceived. It assesses eight aspects of patient progress: Significant Material, Insight, Focus on Emotion, New Behavior, Direct Reference to the Therapist and/or Therapy, Collaboration, Clarity and Vividness, and Focus on the Self. A concurrent validity study was undertaken comparing the RPPS to three subscales of the Vanderbilt Psychotherapy Process Scale (VPPS): Patient Participation, Patient Exploration and Patient Hostility. The study employed strategies consistent with the emerging new paradigm in psychotherapy research, including use of context, single case design, and quantitative and qualitative analysis. Both scales were applied to two cases of brief (15 to 16 session) psychodynamic therapy, one with a very good outcome and one with a less positive outcome. Four raters for each scale scored every other five minute block of material in all but the first session of each case. Both scales had adequate reliability: intraclass correlations for the RPPS Total Score were.74 and.80; for the three subscales of the VPPS they were.79 to.81. As predicted, the RPPS Total Score was positively correlated with the VPPS subscales Patient Participation, Patient Exploration, and the composite score Patient Involvement, and negatively correlated with Patient Hostility. Correlations among most individual RPPS items and the VPPS were also as predicted. Factor analyses of the RPPS and the VPPS found both similarities and differences between the two cases. A qualitative analysis indicated that discussion of transference material was typically initiated by the therapist when the patients were resistant and that such discussions may have been helpful for the more resistant patient. Overall, the results suggest that, with minor modifications, the RPPS is a reliable and valid scale that can be used in a variety of future research.
Dissertation
