[Evidence for Psychodynamic Therapy for Children and Adolescents]. / Evidenz für psychoanalytisch begründete Verfahren für Kinder und Jugendliche.

In Germany, cognitive-behavioral therapy, psychodynamic therapy, and systemic therapy are scientifically and legally approved as suitable procedures for treating mental disorders. While all methods have provided empirical evidence of their effectiveness in adults according to defined criteria of the "Scientific Advisory Board for Psychotherapy" (in German: "Wissenschaftlicher Beirat Psychotherapie"), i. e., the official board which decides upon the formal scientific approval of psychotherapeutic approaches in Germany, an evaluation is lacking for the psychodynamic methods in children and adolescents. Against this background, we evaluated the available empirical data for psychodynamic therapy in children and adolescents based on the methods paper of the "Scientific Advisory Board for Psychotherapy" (2019; version 2.9). Published reviews served as the basis for identifying relevant studies, supplemented by a systematic literature search. We identified 91 potentially relevant studies but could not consider the majority of these due to formal exclusion criteria (mainly not disorder-specific, no control group). Up to 26 of the remaining studies provide evidence of efficacy as defined by the "Scientific Advisory Board for Psychotherapy". These cover 10 of the 18 areas of application as defined by the "Scientific Advisory Board for Psychotherapy". According to our evaluation, the reviewed studies provide empirical evidence for the three most relevant areas of application (i. e., affective disorders; anxiety disorders and obsessive-compulsive disorders; hyperkinetic disorders and conduct disorders). Thus, the available evidence supports the suitability of psychodynamic therapy as a method for the treatment of children and adolescents.

Activation of a Plant NLR Complex through Heteromeric Association with an Autoimmune Risk Variant of Another NLR.

When independently evolved immune receptor variants meet in hybrid plants, they can activate immune signaling in the absence of non-self recognition. Such autoimmune risk alleles have recurrently evolved at the DANGEROUS MIX2 (DM2) nucleotide-binding domain and leucine-rich repeat (NLR)-encoding locus in A. thaliana. One of these activates signaling in the presence of a particular variant encoded at another NLR locus, DM1. We show that the risk variants of DM1 and DM2d NLRs signal through the same pathway that is activated when plant NLRs recognize non-self elicitors. This requires the P loops of each protein and Toll/interleukin-1 receptor (TIR)-domain-mediated heteromeric association of DM1 and DM2d. DM1 and DM2d each resides in a multimeric complex in the absence of signaling, with the DM1 complex shifting to higher molecular weight when heteromerizing DM2 variants are present. The activation of the DM1 complex appears to be sensitive to the conformation of the heteromerizing DM2 variant. Autoimmunity triggered by interaction of this NLR pair thus suggests that activity of heteromeric NLR signaling complexes depends on the sum of activation potentials of partner NLRs.

Genetic architecture of nonadditive inheritance in Arabidopsis thaliana hybrids.

The ubiquity of nonparental hybrid phenotypes, such as hybrid vigor and hybrid inferiority, has interested biologists for over a century and is of considerable agricultural importance. Although examples of both phenomena have been subject to intense investigation, no general model for the molecular basis of nonadditive genetic variance has emerged, and prediction of hybrid phenotypes from parental information continues to be a challenge. Here we explore the genetics of hybrid phenotype in 435 Arabidopsis thaliana individuals derived from intercrosses of 30 parents in a half diallel mating scheme. We find that nonadditive genetic effects are a major component of genetic variation in this population and that the genetic basis of hybrid phenotype can be mapped using genome-wide association (GWA) techniques. Significant loci together can explain as much as 20% of phenotypic variation in the surveyed population and include examples that have both classical dominant and overdominant effects. One candidate region inherited dominantly in the half diallel contains the gene for the MADS-box transcription factor AGAMOUS-LIKE 50 (AGL50), which we show directly to alter flowering time in the predicted manner. Our study not only illustrates the promise of GWA approaches to dissect the genetic architecture underpinning hybrid performance but also demonstrates the contribution of classical dominance to genetic variance.

Species-wide genetic incompatibility analysis identifies immune genes as hot spots of deleterious epistasis.

Intraspecific genetic incompatibilities prevent the assembly of specific alleles into single genotypes and influence genome- and species-wide patterns of sequence variation. A common incompatibility in plants is hybrid necrosis, characterized by autoimmune responses due to epistatic interactions between natural genetic variants. By systematically testing thousands of F1 hybrids of Arabidopsis thaliana strains, we identified a small number of incompatibility hot spots in the genome, often in regions densely populated by nucleotide-binding domain and leucine-rich repeat (NLR) immune receptor genes. In several cases, these immune receptor loci interact with each other, suggestive of conflict within the immune system. A particularly dangerous locus is a highly variable cluster of NLR genes, DM2, which causes multiple independent incompatibilities with genes that encode a range of biochemical functions, including NLRs. Our findings suggest that deleterious interactions of immune receptors limit the combinations of favorable disease resistance alleles accessible to plant genomes.

Vectors for efficient and high-throughput construction of fluorescent drosophila reporters using the PhiC31 site-specific integration system.

The fruit fly Drosophila is a leading model system for the study of transcriptional control by cis-regulatory elements or enhancers. Here, we present a rapid and highly efficient system for the large-scale analysis of enhancer elements, site-specifically integrated into the Drosophila genome. This system, which is scalable for either small projects or high-throughput approaches, makes use of the Gateway cloning technology and the PhiC31 site-specific integration system, which allows the insertion of constructs at predetermined genomic locations. Thus, this system allows not only a fast and easy analysis of reporter gene expression in live animals, but also the simultaneous analysis of different regulatory outputs on a cellular resolution by recombining in the same animal distinct enhancer elements fused to different fluorescent proteins.

Role of translational coupling in robustness of bacterial chemotaxis pathway.

Chemotaxis allows bacteria to colonize their environment more efficiently and to find optimal growth conditions, and is consequently under strong evolutionary selection. Theoretical and experimental analyses of bacterial chemotaxis suggested that the pathway has been evolutionarily optimized to produce robust output under conditions of such physiological perturbations as stochastic intercellular variations in protein levels while at the same time minimizing complexity and cost of protein expression. Pathway topology in Escherichia coli apparently evolved to produce an invariant output under concerted variations in protein levels, consistent with experimentally observed transcriptional coupling of chemotaxis genes. Here, we show that the pathway robustness is further enhanced through the pairwise translational coupling of adjacent genes. Computer simulations predicted that the robustness of the pathway against the uncorrelated variations in protein levels can be enhanced by a selective pairwise coupling of individual chemotaxis genes on one mRNA, with the order of genes in E. coli ranking among the best in terms of noise compensation. Translational coupling between chemotaxis genes was experimentally confirmed, and coupled expression of these genes was shown to improve chemotaxis. Bioinformatics analysis further revealed that E. coli gene order corresponds to consensus in sequenced bacterial genomes, confirming evolutionary selection for noise reduction. Since polycistronic gene organization is common in bacteria, translational coupling between adjacent genes may provide a general mechanism to enhance robustness of their signaling and metabolic networks. Moreover, coupling between expression of neighboring genes is also present in eukaryotes, and similar principles of noise reduction might thus apply to all cellular networks.

Multifactorial regulation of a hox target gene.

Hox proteins play fundamental roles in controlling morphogenetic diversity along the anterior-posterior body axis of animals by regulating distinct sets of target genes. Within their rather broad expression domains, individual Hox proteins control cell diversification and pattern formation and consequently target gene expression in a highly localized manner, sometimes even only in a single cell. To achieve this high-regulatory specificity, it has been postulated that Hox proteins co-operate with other transcription factors to activate or repress their target genes in a highly context-specific manner in vivo. However, only a few of these factors have been identified. Here, we analyze the regulation of the cell death gene reaper (rpr) by the Hox protein Deformed (Dfd) and suggest that local activation of rpr expression in the anterior part of the maxillary segment is achieved through a combinatorial interaction of Dfd with at least eight functionally diverse transcriptional regulators on a minimal enhancer. It follows that context-dependent combinations of Hox proteins and other transcription factors on small, modular Hox response elements (HREs) could be responsible for the proper spatio-temporal expression of Hox targets. Thus, a large number of transcription factors are likely to be directly involved in Hox target gene regulation in vivo.

Reaction patterns of the tracheobronchial wall to implanted noncovered metal stents.

BACKGROUND: Endoluminal implantation of stents has evolved as a nonsurgical treatment option for stenosis of the central airways. Based on the favorable results in treatment of tumorous tracheobronchial stenosis, stenting has been introduced into the therapy of nonmalignant stenosis. AIM: To study the long-term biocompatibility and incorporation of implanted bronchial stents based on the pathoanatomic reaction of the tracheobronchial system in humans. The incorporation of bronchial stents was documented, with specific interest in transformation or induction of dysplasia in the implantation zone. METHODS: The tracheobronchial reaction was studied in 18 patients 2 days to 18 months after implantation of 24 noncovered metal stents (Wallstent; Schneider; Bülach, Switzerland; n = 8; and Ultraflex; Boston Scientific; Natick, MA; n = 16). RESULTS: Stenting produced slow papillomatous growth of granulative tissue through the interfilamentary space of the stents. A nonspecific inflammatory response of nontumorous tissue could be documented. Sparse spots of superficial squamous cells occurred. No epithelial dysplasia or giant cells were detected within the stented region. The number of superficial ciliated cells in the implantation zone was markedly reduced. CONCLUSION: After stent insertion in the upper airways, no malignant transformation of initially nontumorous tissue occurs. Stenting seems to be a safe therapy option when considered even for nonmalignant airway stenoses.