[Cognition and driving ability in chronic pain syndrome]. / Kognition und Kraftfahreignung bei chronischem Schmerzsyndrom.

Cognitive impairments in patients with chronic pain are increasingly attracting interest in scientific research. The consequences of these cognitive impairments on coping with pain, everyday life and the driving ability are rarely included in clinical practice although half of all patients are affected. This article summarizes the current research situation and discusses possibilities of the integration in clinical and therapeutic care.

Death receptor-based enrichment of Cas9-expressing cells.

BACKGROUND: The CRISPR/Cas9 genome editing system has greatly facilitated and expanded our capacity to engineer mammalian genomes, including targeted gene knock-outs. However, the phenotyping of the knock-out effect requires a high DNA editing efficiency. RESULTS: Here, we report a user-friendly strategy based on the extrinsic apoptosis pathway that allows enrichment of a polyclonal gene-edited cell population, by selecting Cas9-transfected cells that co-express dominant-negative mutants of death receptors. The extrinsic apoptosis pathway can be triggered in many mammalian cell types, and ligands are easy to produce, do not require purification and kill much faster than the state-of-the-art selection drug puromycin. Stringent assessment of our advanced selection strategy via Sanger sequencing, T7 endonuclease I (T7E1) assay and direct phenotyping confirmed a strong and rapid enrichment of Cas9-expressing cell populations, in some cases reaching up to 100 % within one hour. Notably, the efficiency of target DNA cleavage in these enriched cells reached high levels that exceeded the reliable range of the T7E1 assay, a conclusion that can be generalized for editing efficiencies above 30 %. Moreover, our data emphasize that the insertion and deletion pattern induced by a specific gRNA is reproducible across different cell lines. CONCLUSIONS: The workflow and the findings reported here should streamline a wide array of future low- or high-throughput gene knock-out screens, and should largely improve data interpretation from CRISPR experiments.

[Cognitive remediation in clinical routine: a study on psychiatric patients' acceptance]. / Kognitive Remediation im klinischen Alltag: Eine Studie zur Akzeptanz bei psychiatrischen Patienten.

BACKGROUND: Cognitive remediation represents an effective treatment for improving functional outcome of psychiatric diseases like schizophrenia or depression. However, in clinical routine the therapeutic approach has not been established continuously. This can be partly attributed to doubts about the reasonableness of cognitive remediation for psychiatric patients. Therefore the current study investigates psychiatric patients' acceptance of, motivation for, and exhaustion due to cognitive remediation compared to an established treatment programme. METHODS: 21 psychiatric patients who simultaneously participated in occupational therapy and cognitive remediation rated the motivation, exhaustion, enjoyment, and effort on a visual analogue scale (VAS) over five weeks with regard to the respective therapy. RESULTS: The ratings of occupational therapy and cognitive remediation did not differ relating to motivation, exhaustion, and enjoyment. The subjective effort in cognitive remediation was higher than that in occupational therapy. DISCUSSION: Cognitive remediation is evaluated as being equivalent to an already established treatment programme by psychiatric patients concerning motivation, enjoyment, and exhaustion. Doubts about the acceptance and reasonableness of cognitive remediation could not be confirmed. In clinical routine cognitive remediation as an effective and accepted therapeutic approach should be integrated as a standard procedure for various disorders.

[Rehabilitation in persons with schizophrenic spectrum disorders: the impact of cognition and cognitive remediation therapy]. / Rehabilitation von Menschen mit schizophrenen Psychosen: Die Bedeutung von Kognition und Training kognitiver Funktionen.

Schizophrenia is a chronic disorder, which severely limits the social and occupational functioning. Employment, education, relationships, housing and health are among the most frequently stated life and treatment goals among persons suffering from schizophrenia. Rehabilitation for persons with schizophrenia aims at preservation and improvement of psychosocial functions in areas such as work, social relationship and independent living skills, promotes recovery-oriented interventions and, therefore, serves the central goals of affected persons. Cognitive functioning, education, negative symptoms, social support and skills, age, work history, and rehabilitation service to restore community functioning have proven to be strong predictors for successful psychiatric rehabilitation. It makes sense to concentrate on these predictors when improvement of psychiatric rehabilitation is targeted. Cognitive remediation produces moderate improvements in cognitive performance and, when combined with functional training and embedded in comprehensive psychiatric rehabilitation, also enhances functional outcome. Germany provides a highly differentiated system of psychosocial support for schizophrenic patients. However, the "German disease" with different care providers being in charge in subsequent stages of recovery hampers efficient organisation of psychiatric rehabilitation. Improvement of overall organisation, i.e., configuration of interfaces, understanding of the complex interactions of measures, design of disease specific programmes, research and economic evaluation constitute major challenges in the field of psychiatric rehabilitation.

Caspase-8 cleaves its substrates from the plasma membrane upon CD95-induced apoptosis.

Apoptosis occurs through a tightly regulated cascade of caspase activation. In the context of extrinsic apoptosis, caspase-8 is activated by dimerization inside a death receptor complex, cleaved by auto-proteolysis and subsequently released into the cytosol. This fully processed form of caspase-8 is thought to cleave its substrates BID and caspase-3. To test if the release is required for substrate cleavage, we developed a novel approach based on localization probes to quantitatively characterize the spatial-temporal activity of caspases in living single cells. Our study reveals that caspase-8 is significantly more active at the plasma membrane than within the cytosol upon CD95 activation. This differential activity is controlled by the cleavage of caspase-8 prodomain. As a consequence, targeting of caspase-8 substrates to the plasma membrane can significantly accelerate cell death. Subcellular compartmentalization of caspase-8 activity may serve to restrict enzymatic activity before mitochondrial pathway activation and offers new possibilities to interfere with apoptotic sensitivity of the cells.

Memory performance in acute and weight-restored anorexia nervosa patients.

BACKGROUND: Anorexia nervosa (AN), at the stage of starvation and emaciation, is characterized by abnormalities in cognitive function, including memory performance. It is unclear whether memory impairment persists or is reversible following weight restoration, and whether memory function differs between AN subtypes. The aim of the present study was to investigate general memory performance in currently ill and fully weight-restored patients of different AN subtypes. METHOD: Memory performance was assessed using the Wechsler Memory Scale-Revised (WMS-R) in a total of 99 participants, including 34 restricting-type AN patients (AN-RESTR), 19 binge-eating/purging-type AN patients (AN-PURGE), 16 weight-restored AN patients (AN-W-R) and 30 healthy controls (CONTROL). Cognitive evaluation included a battery of standardized neuropsychological tasks for validating the findings on memory function. RESULTS: Deficits were found with respect to immediate and delayed story recall in currently ill AN patients irrespective of AN subtype. These deficits persisted in weight-restored AN patients. Currently ill and weight-restored AN patients did not differ significantly from healthy controls with respect to working memory or other measures of neuropsychological functioning. CONCLUSIONS: The findings suggest that impaired memory performance is either a stable trait characteristic or a scar effect of chronic starvation that may play a role in the development and/or persistence of the disorder.

Mirror writing and handedness.

It has been reported that left-handed subjects are better able to write in mirror-reversed script than right-handers (Tankle & Heilman, 1983). Vaid and Stiles Davis (1989) conducted studies which led them to contradict the supposed superiority of left-handers in this area. In these studies, left as well as right-handed subjects were examined under normal- and mirror-writing conditions. Both examinations included the analysis of writing time and the accuracy of mirror writing (error rates). Using a digitizing tablet, we examined normal- and mirror-writing performance of left-handers, right-handers, and left-handed subjects who habitually write with their right hand. Our results support the finding of Tankle and Heilman (1983) that left-handers perform better in mirror-writing tasks.

Pleated septate junctions in leech photoreceptors: ultrastructure, arrangement of septa, gate and fence functions.

The leech photoreceptor forms a unicellular epithelium: every cell surrounds an extracellular "vacuole" that is connected to the remaining extracellular space via narrow clefts containing pleated septate junctions. We analyzed the complete structural layout of all septa within the junctional complex in elastic brightfield stereo electron micrographs of semithin serial sections from photoreceptors infiltrated with colloidal lanthanum. The septa form tortuous interseptal corridors that are spatially continuous, and open ended basally and apically. Individual septa seem to be impermeable to lanthanum; interseptal corridors form the only diffusional pathway for this ion. The junctions form no diffusion barrier for the electron-dense tracer Ba2+, but they hinder the diffusion of various hydrophilic fluorescent dyes as demonstrated by confocal laser scanning microscopy (CLSM) of live cells. Even those dyes that penetrate gap junctions do not diffuse beyond the septate junctions. The aqueous diffusion pathway within the septal corridors is, therefore, less permeable than the gap-junctional pore. Our morphological results combined with published electrophysiological data suggest that the septa themselves are not completely tight for small physiologically relevant ions. We also examined, by CLSM, whether the septate junctions create a permeability barrier for the lateral diffusion of fluorescent lipophilic dyes incorporated into the peripheral membrane domain. AFC16, claimed to remain in the outer membrane leaflet, does not diffuse beyond the junctional region, whereas DiIC16, claimed to flip-flop, does. Thus, pleated septate junctions, like vertebrate tight junctions, contribute to the maintenance of cell polarity.

The ontogeny of the canary HVC revealed by the expression of androgen and oestrogen receptors.

The vocal control nucleus HVC (nucleus hyperstriatalis ventrale, pars caudale) of the canary (Serinus canaria) is a model in which to study the relationship between anatomical plasticity and vocal developmental learning. Much of the structural plasticity of the HVC is sensitive to the action of androgenic and oestrogenic gonadal hormones that affect the brain by binding to androgen receptors (AR) and oestrogen receptors (ER). Here we report developmental changes of AR and ER expression in the HVC using in situ hybridization with avian specific cRNA probes. AR and ER are first expressed in the HVC at post-hatching day 10 (P10) and P30, respectively and are, therefore, present in the HVC throughout the singing-learning period of the canary. Because AR occur only in the caudal neostriatum of the HVC we mapped the size of the HVC with this marker. The size and neurone number of the AR-defined HVC reaches adult values at P30 and differentiates, therefore, independently of the singing activity and probably independently of oestrogens. Continuing neurogenesis in the HVC requires neuronal death and replacement from P30 on.

Paleogeographic reconstructions of coastal aegean archaeological sites.

Many studies have been made of ancient Greek topography, some of the more recent ones based on modern techniques. However, most still ignore the subsurface dimension of coastal and other environments and hence fail to fully explain coastal and alluvial-colluvial processes, rates of change of geomorphology, and the effects of coastal change on humans. In this article subsurface geological analyses have been used to elucidate paleogeographic coastal settings of major archaeological sites around the Aegean Sea. Similar approaches could be applied in the Middle and Far East and elsewhere in the Mediterranean.