Hybridization and speciation

Hybridization has many and varied impacts on the process of speciation. Hybridization may slow or reverse differentiation by allowing gene flow and recombination. It may accelerate speciation via adaptive introgression or cause near‐instantaneous speciation by allopolyploidization. It may have multiple effects at different stages and in different spatial contexts within a single speciation event. We offer a perspective on the context and evolutionary significance of hybridization during speciation, highlighting issues of current interest and debate. In secondary contact zones, it is uncertain if barriers to gene flow will be strengthened or broken down due to recombination and gene flow. Theory and empirical evidence suggest the latter is more likely, except within and around strongly selected genomic regions. Hybridization may contribute to speciation through the formation of new hybrid taxa, whereas introgression of a few loci may promote adaptive divergence and so facilitate speciation. Gene regulatory networks, epigenetic effects and the evolution of selfish genetic material in the genome suggest that the Dobzhansky–Muller model of hybrid incompatibilities requires a broader interpretation. Finally, although the incidence of reinforcement remains uncertain, this and other interactions in areas of sympatry may have knock‐on effects on speciation both within and outside regions of hybridization.     

Shadow enhancers flanking the HoxB cluster direct dynamic Hox expression in early heart and endoderm development

The products of Hox genes function in assigning positional identity along the anterior–posterior body axis during animal development. In mouse embryos, Hox genes located at the 3′ end of HoxA and HoxB complexes are expressed in nested patterns in the progenitors of the secondary heart field during early cardiogenesis and the combined activities of both of these clusters are required for proper looping of the heart. Using Hox bacterial artificial chromosomes (BACs), transposon reporters, and transgenic analyses in mice, we present the identification of several novel enhancers flanking the HoxB complex which can work over a long range to mediate dynamic reporter expression in the endoderm and embryonic heart during development. These enhancers respond to exogenously added retinoic acid and we have identified two retinoic acid response elements (RAREs) within these control modules that play a role in potentiating their regulatory activity. Deletion analysis in HoxB BAC reporters reveals that these control modules, spread throughout the flanking intergenic region, have regulatory activities that overlap with other local enhancers. This suggests that they function as shadow enhancers to modulate the expression of genes from the HoxB complex during cardiac development. Regulatory analysis of the HoxA complex reveals that it also has enhancers in the 3′ flanking region which contain RAREs and have the potential to modulate expression in endoderm and heart tissues. Together, the similarities in their location, enhancer output, and dependence on retinoid signaling suggest that a conserved cis-regulatory cassette located in the 3′ proximal regions adjacent to the HoxA and HoxB complexes evolved to modulate Hox gene expression during mammalian cardiac and endoderm development. This suggests a common regulatory mechanism, whereby the conserved control modules act over a long range on multiple Hox genes to generate nested patterns of HoxA and HoxB expression during cardiogenesis.     

Course of self-reported symptoms of 342 outpatients receiving medium- versus long-term psychodynamic psychotherapy

Background

The course of self-reported symptoms during medium- versus long-term psychodynamic psychotherapy has rarely been documented for outpatient settings. This observational study describes routine practice of ambulatory treatment in Germany and explores self-reported symptoms of a broad patient sample undergoing one (medium-term) versus two years (long-term) of psychodynamic psychotherapy.

Methods

Over four and a half years, longitudinal self-report symptom data were collected from 342 outpatients as part of a standardized documentation system. Self-report data were compared between patients receiving either medium-term or long-term psychodynamic psychotherapy.

Results

Routine care significantly decreased disease burden as reported by patients by small to medium effect sizes (ES) for depression (ES?=?0.58), anxiety (ES?=?0.49), obsessive-compulsive disorder (ES?=?0.54), somatoform disorder (ES?=?0.32), eating disorder (ES?=?0.38). The majority of patients completed treatment after one year and showed medium-size changes. For a subgroup of patients with depressive and/or obsessive-compulsive disorder symptoms for whom two years of therapy were deemed necessary, additional benefits were reported during the second year of treatment (ES?=?0.61 and ES??0.47, respectively).

Conclusions

Our findings suggest that both medium- and long-term psychodynamic psychotherapy decrease self-reported disease burden of patients with depression, anxiety, obsessive-compulsive, somatoform and/or eating disorders. For a subgroup of patients, additional benefits were gained in the second year of treatment.

     

Hox genes: Downstream “effectors” of retinoic acid signaling in vertebrate embryogenesis

One of the major regulatory challenges of animal development is to precisely coordinate in space and time the formation, specification, and patterning of cells that underlie elaboration of the basic body plan. How does the vertebrate plan for the nervous and hematopoietic systems, heart, limbs, digestive, and reproductive organs derive from seemingly similar population of cells? These systems are initially established and patterned along the anteroposterior axis (AP) by opposing signaling gradients that lead to the activation of gene regulatory networks involved in axial specification, including the Hox genes. The retinoid signaling pathway is one of the key signaling gradients coupled to the establishment of axial patterning. The nested domains of Hox gene expression, which provide a combinatorial code for axial patterning, arise in part through a differential response to retinoic acid (RA) diffusing from anabolic centers established within the embryo during development. Hence, Hox genes are important direct effectors of retinoid signaling in embryogenesis. This review focuses on describing current knowledge on the complex mechanisms and regulatory processes, which govern the response of Hox genes to RA in several tissue contexts including the nervous system during vertebrate development.     

Identification of selective sweeps using a dynamically adjusted number of linked microsatellites

There is currently large interest in distinguishing the signatures of genetic variation produced by demographic events from those produced by natural selection. We propose a simple multilocus statistical test to identify candidate sites of selective sweeps with high power. The test is based on the variability profile measured in an array of linked microsatellites. We also show that the analysis of flanking markers drastically reduces the number of false positives among the candidates that are identified in a genomewide survey of unlinked loci and find that this property is maintained in many population-bottleneck scenarios. However, for a certain range of intermediately severe population bottlenecks we find genomic signatures that are very similar to those produced by a selective sweep. While in these worst-case scenarios the power of the proposed test remains high, the false-positive rate reaches values close to 50%. Hence, selective sweeps may be hard to identify even if multiple linked loci are analyzed. Nevertheless, the integration of information from multiple linked loci always leads to a considerable reduction of the false-positive rate compared to a genome scan of unlinked loci. We discuss the application of this test to experimental data from Drosophila melanogaster.     

Design and evaluation of a cryogenic soft tissue fixation device -- load tolerances and thermal aspects

Mechanical studies of soft connective tissues often encounter methodological difficulties, particularly in the secure fixation of the tissues. A simple, inexpensive technique which allowed stable cryofixation of soft tissues in uniaxial loading machines was developed. The cryogenic fixation device was evaluated in terms of its fixation strength and the temperature gradients within the tested tissues. Human patellar ligaments and quadriceps tendons were tested successfully to an average failure load of 2219N (S.D. 448N) with mid-substance failures occurring in 90% of the specimens. The temperature gradients within porcine flexor and extensor tendons were determined and found to exhibit a typical diffusion profile. The fixation quality was dependent upon the initial block temperature and the desired testing time. In summary, the cryofixation device presented here is an effective tool for soft tissue fixation but the effect of this type of fixation on internal tissue temperatures and possible testing times must be acknowledged.     

Immunolocalization of the neural cell adhesion molecule L1 in epithelia of rodents

The expression of the neural cell adhesion molecule L1 was analyzed in several non-neural tissues of the mouse using immunohistochemical and immunochemical techniques. In the adult mouse, L1 immunoreactivity was detectable in the basal and intermediate layers of epidermal and lingual epithelia, in the outer sheath of hair roots and in the single-layered endodermal epithelia of lung, small intestine, and colon. Epithelia of salivary glands also showed L1 immunoreactivity, while endothelial cells of blood vessels did not express detectable levels of L1. The epithelia of the kidney showed expression only in the collecting tubule system. In single-layered kidney epithelia and stratified epithelia, L1 expression was confined to lateral cell contacts and basal infoldings of the epithelial cells but was absent from apical and basal cell surface membranes. Also, in cultured keratinocytes L1 was confined to cell-cell contacts. During development of the epidermis, L1 immunoreactivity was first detectable at the onset of keratinization around embryonic day 16. At this age LI was detectable in the kidney on branching tubules of the ureter. Western blot analysis showed that L1 immunoreactivity in epidermis and kidney appeared as two bands of 190-210 and 210-230 kDa. Northern blot analysis of mRNA from the L1-immunopositive HEL-30 keratinocyte cell line revealed a single band with the expected size of 6 kb. The presence of L1 in epithelia indicates that this molecule may be involved in interactions between epithelial cells and thereby may affect differentiation and maintenance of epithelial tissues.