Investigation of sex-specific effects of apolipoprotein E on severity of EAE and MS.

BACKGROUND: Despite pleiotropic immunomodulatory effects of apolipoprotein E (apoE) in vitro, its effects on the clinical course of experimental autoimmune encephalomyelitis (EAE) and multiple sclerosis (MS) are still controversial. As sex hormones modify immunomodulatory apoE functions, they may explain contentious findings. This study aimed to investigate sex-specific effects of apoE on disease course of EAE and MS. METHODS: MOG(35-55) induced EAE in female and male apoE-deficient mice was assessed clinically and histopathologically. apoE expression was investigated by qPCR. The association of the MS severity score (MSSS) and APOE rs429358 and rs7412 was assessed across 3237 MS patients using linear regression analyses. RESULTS: EAE disease course was slightly attenuated in male apoE-deficient (apoE (-/-) ) mice compared to wildtype mice (cumulative median score: apoE (-/-) = 2 [IQR 0.0-4.5]; wildtype = 4 [IQR 1.0-5.0]; n = 10 each group, p = 0.0002). In contrast, EAE was more severe in female apoE (-/-) mice compared to wildtype mice (cumulative median score: apoE (-/-) = 3 [IQR 2.0-4.5]; wildtype = 3 [IQR 0.0-4.0]; n = 10, p = 0.003). In wildtype animals, apoE expression during the chronic EAE phase was increased in both females and males (in comparison to naïve animals; p < 0.001). However, in MS, we did not observe a significant association between MSSS and rs429358 or rs7412, neither in the overall analyses nor upon stratification for sex. CONCLUSIONS: apoE exerts moderate sex-specific effects on EAE severity. However, the results in the apoE knock-out model are not comparable to effects of polymorphic variants in the human APOE gene, thus pinpointing the challenge of translating findings from the EAE model to the human disease.

Global information pickup underpins anticipation of tennis shot direction.

The authors examined the importance of local dynamical information when anticipating tennis shot direction. In separate experiments, they occluded the arm and racket, shoulders, hips, trunk, and legs and locally neutralized dynamical differences between shot directions, respectively. The authors examined the impact of these manipulations on resulting (display) dynamics and the ability of participants with varying perceptual skills to anticipate shot direction. The occlusion manipulation affected the display dynamics to a larger extent than did the neutralization manipulation. Although the authors observed a decrement in performance when local information from the arm and racket was occluded or neutralized and when information from the trunk and legs was neutralized, the results generally suggest that participants anticipated shot direction through a more global perceptual approach, particularly in perceptually skilled participants.

Analysis of Driving Factors of Willingness to Use and Willingness to Pay for Existing Pharmacological Smoking Cessation Aids Among Young and Middle-Aged Adults in Germany.

BACKGROUND: Smoking cessation is a challenging task with a high risk of relapse. Depending on the choice of medication and duration of therapy, the costs of using a smoking cessation aid can be high. Additionally, these costs are not covered by health insurance in Germany. Information on willingness to use (WTU) and willingness to pay (WTP) for smoking cessation aids is valuable for developing different smoking cessation strategies. OBJECTIVES: The study analyses WTU and WTP for three pharmacological smoking cessation aids (nicotine replacement therapy (NRT), bupropion and varenicline) among young and middle-aged adults in Germany and attempts to determine their major driving factors. METHODS: Two cross-sectional internet-based surveys of smokers over 18 years of age were conducted in 2014 and 2015 in Germany. Respondents were asked about smoking-related issues and WTU and WTP for each therapy. The contingent valuation method with payment cards was used to measure WTP. Descriptive statistics, logistical regression and accelerated failure-time regression models were performed. RESULTS: The total sample size is 505. Half of the respondents are willing to use NRT and one-third are willing to use bupropion and/or varenicline. WTU induces positive WTP; however, the magnitude of WTP is beneath the market price. WTU significantly increases with a higher addiction level and if smokers have previously heard about the therapy. CONCLUSION: This study indicates different points to be considered for policy development. Promotion information and improving awareness about medication aids might increase WTU, and development of monetary incentives for young smokers could create a better chance for successful smoking cessation.

The serologically defined colon cancer antigen-3 interacts with the protein tyrosine phosphatase PTPN13 and is involved in the regulation of cytokinesis.

Cytokinesis is the final step of cell division. Increasing evidence suggests failure of cytokinesis might contribute to the development of cancer. Here, we demonstrate that the serologically defined colon cancer antigen-3 (SDCCAG3) forms a complex with PTPN13, a protein tyrosine phosphatase known to be involved in the regulation of cytokinesis, carcinogenesis and tumor aggressiveness. We show that SDCCAG3 is a novel endosomal protein, primarily localized at the early/recycling endosomal compartment. SDCCAG3 undergoes dynamic localization during cell division with strong accumulation at the midbody during cytokinesis. Overexpression as well as downregulation correlates with the generation of multinucleate cells. Furthermore, we show interaction of SDCCAG3 with the Arf GTPase activating protein GIT1 (G protein-coupled receptor kinase interactor-1). Overexpression of an ArfGAP-negative version of GIT1 also results in an increased number of multinucleate cells suggesting regulation of Arf-mediated vesicular trafficking or signaling via SDCCAG3. Finally, we demonstrate that SDCCAG3 expression levels are elevated in colon cancers. In summary, we have established SDCCAG3 as a novel endosomal protein, which is involved in the regulation of cytokinesis.

Conditions of practice in perceptual skill learning.

This study uses three experiments with different kinds of training conditions to investigate the "easy-to-hard" principle, context interference conditions, and feedback effects for learning anticipatory skills in badminton. Experiment 1 (N = 60) showed that a training program that gradually increases the difficulty level has no advantage over the randomized variant. Experiment 2 (N = 60) pointed out that when comparing the blocked (lateral before depth dimension) perceptual training group with the random perceptual training group a significant advantage for the random group was found in the retention test (depth error). Experiment 3 (N = 40) demonstrated that training with reduced feedback (66 %) is no more effective than 100% feedback training in a group of novice performers.

Anorexia Nervosa: the hospital's role in family treatment.

When an anorexia nervosa patient requires hospitalization for her medical condition the treatment team faces the problem of integrating the individual focus of inpatient care with the systems focus of family therapy. In this paper we propose a family-systems model of hospitalization, the aim of which is to facilitate such integration. The model draws on current theories of anorexia nervosa, as well as general concepts from psychodynamic, developmental, and family systems theories. The major hypothesis of the model is that all members of the anorexic family are developmentally arrested in the area of separation-individuation. On this assumption, we propose that the entire treatment team (including medical professionals and therapist) needs to function as "parents" to the anorexic family in much the same way that two cotherapists become parental figures in a family therapy. Specifically, the team needs to provide those parenting the responses that facilitate the family's individuation process.