Functional characterisation of in vitro synthesised G-protein coupled receptors in polymersomes

Membrane proteins play an indispensable role in physiological processes. It is, therefore, not surprising that many diseases are based on the malfunction of membrane proteins. Hence membrane proteins and especially G-protein coupled receptors(GPCRs)- the largest subfamily- have become an important drug target. Due to their high selectivity and sensitivity membrane proteins are also feasible for the detection of small quantities of substances with biosensors. Despite this widespread interest in GPCRs due to their importance as drug targets and biosensors there is still a lack of knowledge of structure, function and endogenous ligands for quiet a few of the previously identified receptors.rnBottlenecks in over-expression, purification, reconstitution and handling of membrane proteins arise due to their hydrophobic nature. Therefore the production of reasonable amounts of functional membrane proteins for structural and functional studies is still challenging. Also the limited stability of lipid based membrane systems hampers their application as platforms forrnscreening applications and biosensors.rnIn recent years the in vitro protein synthesis became a promising alternative to gain better yields for expression of membrane proteins in bio-mimetic membrane systems. These expression systems are based on cell extracts. Therefore cellular effects on protein expression are reduced. The open nature of the cell-free expression systems easily allows for the adjustment of reactionrnconditions for the protein of interest. The cell-free expression in the presence of bio-mimetic membrane systems allows the direct incorporation of the membrane proteins and therefore skips the time-consuming purification and reconstitution processes. Amphiphilic block-copolymers emerged as promising alternative for the less stable lipid-based membrane systems. They, likernlipids, form membraneous structures in aqueous solutions but exhibit increased mechanical and chemical stability.rnThe aim of this work was the generation of a GPCR-functionalised membrane system by combining both promising alternatives: in vitro synthesis and polymeric membrane systems. This novel platform should be feasible for the characterisation of the incorporated GPCR. Immunodetection of Dopamine receptor 1 and 2 expressed in diblock- and triblock-polymersomes demonstrated the successful in vitro expression of GPCRs in polymeric membranes. Antibodyrnbinding studies suggested a favoured orientation of dopamine receptors in triblockpolymersomes.rnA dopamine-replacement assay on DRD2-functionalised immobilised triblockpolymersomes confirmed functionality of the receptor in the polymersomes. The altered binding curve suggests an effect of the altered hydrophobic environment presented by the polymer membrane on protein activity.

Adulthood with Turner Syndrome: Quality of life, psychosocial adjustment and clinical management in 70 Italian women

Abstract Background: Turner syndrome (TS) is a chromosomal abnormality (total or partial absence of one of the sexual chromosomes in some or all cells of the body), which affects approximately 1:2000 female. Principal characteristics are short stature and gonadal disgenesis. Clinical management consist of Growth Hormone (GH) treatment and oestrogen replacement therapy (HRT), to induce development of secondary characteristics and to avoid the sequelae of oestrogen deficiency. Aim of the study: To assess clinical management, quality of life (QoL) and general psychosocial adjustment of women with TS. Population: 70 adult Caucasian females with TS (mean age: 27.8, ± 7.6; range 18-48 y.). Setting: Specialist service for Rare Disease care, University Hospital. Methods: Subjects were required to fill in questionnaires collecting ASR, WHOQOL, and 8 open questions. Data were compared with those of the Italian population or to those collected in a comparison group (70 healthy females, mean age: 27.9, ±7.3, range 21-48 y.). Results: Women with TS are educated as well as the Italian Population, but they have a less successful professional life. They show good QoL in general, but they appeared less satisfied in social area. They had statistically higher scores than the comparison group for depression, anxiety and withdrawal. Are less involved in a love relationship. Diagnosis communication was mostly performed by doctors or parents, satisfaction was higher when information was given by parents. Main preoccupation about TS are infertility, feeling of being different and future health problem. Conclusions: Italian people with TS were generally well adapted and have a good QoL, but lived more often with parents and show impaired sentimental and sexual life. They have higher degree of psychological distress compared to a comparison group. Psychological intervention should firstly address parents in order to encourage an open communication on diagnosis issues and on sexual education.

Patient adjustment to reduced olfactory function

To compare the importance of olfaction in daily life between patients with olfactory disorders and healthy normosmic individuals.

Retrospective adjustment of self-assessed medical competencies - noteworthy in the evaluation of postgraduate practical training courses

The efficacy of postgraduate practical training courses is frequently evaluated by self-assessment instruments. The present study analyses the effect of a basic course in laparoscopic surgery on self-assessed medical competencies.

Dose adjustment in patients with liver cirrhosis: impact on adverse drug reactions and hospitalizations

To assess drug-related problems in patients with liver cirrhosis by investigating the prevalence of inadequately dosed drugs and their association with adverse drug reactions (ADRs) and hospitalizations.

Prospective effects of emotion regulation on emotional adjustment

Deficits in emotion-regulation skills have widely been shown to be associated with poor emotional adjustment. However, it is still unclear whether these deficits are a cause or a consequence of poor adjustment. The purpose of the present research was to clarify the reciprocal effects between these 2 concepts. In 2 studies (Ns = 446 and 635), self-reports of emotion regulation and emotional adjustment were assessed twice with a 2-week interval. Cross-lagged regression analyses demonstrated that self-reports of emotion regulation predicted subsequent adjustment, over and above the effects of previous adjustment, whereas emotional adjustment did not predict subsequent emotion regulation. Thus, a focus on emotion-regulation skills may be important in the prevention and treatment of affect-related mental health problems.

Forgiveness and psychological adjustment following interpersonal transgressions: A longitudinal analysis

Forgiveness is often assumed to be adaptive for psychological adjustment following interpersonal transgressions. Three hundred and forty seven individuals who had experienced a recent interpersonal transgression were surveyed on four occasions over the course of six weeks. Forgiveness was assessed with scales measuring interpersonal avoidance and revenge motivation and psychological adjustment was assessed with scales measuring depression and rumination. Latent growth curve analyses showed that intraindividual changes in forgiveness were positively correlated with changes in adjustment. Latent difference score analyses indicated that adjustment predicted subsequent change in forgiveness, but that forgiveness did not predict subsequent change in adjustment. The results suggest that adjustment facilitates forgiveness, but not that forgiveness facilitates adjustment.

A neural network approach for insulin regime and dose adjustment in type 1 diabetes

A decision support system based on a neural network approach is proposed to advise on insulin regime and dose adjustment for type 1 diabetes patients.