iPSC-Cardiomyocyte Models of Brugada Syndrome—Achievements,Challenges and Future Perspectives

Brugada syndrome (BrS) is an inherited cardiac arrhythmia that predisposes to ventricular fibrillation and sudden cardiac death. It originates from oligogenic alterations that affect cardiac ion channels or their accessory proteins. The main hurdle for the study of the functional effects of those variants is the need for a specific model that mimics the complex environment of human cardiomyocytes. Traditionally, animal models or transient heterologous expression systems are applied for electrophysiological investigations, each of these models having their limitations. The ability to create induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs), providing a source of human patient-specific cells, offers new opportunities in the field of cardiac disease modelling. Contemporary iPSC-CMs constitute the best possible in vitro model to study complex cardiac arrhythmia syndromes such as BrS. To date, thirteen reports on iPSC-CM models for BrS have been published and with this review we provide an overview of the current findings, with a focus on the electrophysiological parameters. We also discuss the methods that are used for cell derivation and data acquisition. In the end, we critically evaluate the knowledge gained by the use of these iPSC-CM models and discuss challenges and future perspectives for iPSC-CMs in the study of BrS and other arrhythmias.     

Estimating spine shape in lateral sleep positions using silhouette-derived body shape models

This study aims at evaluating spinal alignment during sleep by combining personalized human models with mattress indentation measurements. A generic surface model has been developed that can be personalized based on anthropometric parameters derived from silhouette extraction. Shape assessment of the personalized surface models, performed by comparison with 3-D surface scans of the trunk, showed a mean unsigned distance of 9.77 mm between modeled and scanned surface meshes. The surface model is combined with an inner skeleton model, allowing the model to simulate distinct sleep postures. An automatic fitting algorithm sets the appropriate degrees of freedom to position the model on the measured indentation according to the adopted sleep posture. Validation on lateral sleep positions showed good intraclass correlations (0.73–0.88) between estimated and measured angular spinal deformations, indicating that silhouette-derived body shape models provide a valuable tool for the unobtrusive assessment of spinal alignment during sleep.Relevance to industry: A common drawback of the available techniques to assess spinal deformation on bedding systems is that they interfere with the actual sleep process. The current study presents a novel method based on silhouette-derived body shape models in order to estimate spine shape during sleep unobtrusively.     

Longitudinal analysis of the formation and realisation of preferences to move into homeownership in the Netherlands

This study investigates how life course characteristics and housing market circumstances affect the formation and realisation of preferences to move into homeownership. Using a data set from the Netherlands in which data from three cross-sectional housing surveys are enriched with longitudinal register data for the period 1998–2008, we follow aspiring homeowners regarding their actual residential behaviour. We find that only 31 % of the aspiring homeowners became homeowners within 2 years, approximately 13 % moved to rental homes, and the vast majority did not move at all. Insufficient socioeconomic resources and a high house price-to-rent ratio hamper the realisation of preferences to move into homeownership. However, these hampering factors are at least as important as the extent to which individuals prefer to move into homeownership. This last finding suggests that housing tenure preferences cannot be viewed as ‘pure’ preferences.     

Individual differences in core affect variability and their relationship to personality and psychological adjustment.

How people's feelings change across time can be represented as trajectories in a core affect space defined by the dimensions of valence and activation. In this article, the authors analyzed individual differences in within-person affective variability defined as characteristics of core affect trajectories, introducing new ways to conceptualize affective variability. In 2 studies, participants provided multiple reports across time describing how they were feeling in terms of core affect. From these data, characteristics of participants' core affect trajectories were derived. Across both studies, core affect variability was negatively related to average valence, self-esteem, and agreeableness, and it was positively related to neuroticism and depression. Moreover, spin, a measure of how much people experienced qualitatively different feelings within the core affect space, was related more consistently to trait measures of adjustment and personality than other measures of within-person variability, including widely used measures of within-person single-dimension standard deviations. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Interdependent Regulation of Polycystin Expression Influences Starvation-Induced Autophagy and Cell Death

Autosomal dominant polycystic kidney disease (ADPKD) is mainly caused by deficiency of polycystin-1 (PC1) or polycystin-2 (PC2). Altered autophagy has recently been implicated in ADPKD progression, but its exact regulation by PC1 and PC2 remains unclear. We therefore investigated cell death and survival during nutritional stress in mouse inner medullary collecting duct cells (mIMCDs), either wild-type (WT) or lacking PC1 (PC1KO) or PC2 (PC2KO), and human urine-derived proximal tubular epithelial cells (PTEC) from early-stage ADPKD patients with PC1 mutations versus healthy individuals. Basal autophagy was enhanced in PC1-deficient cells. Similarly, following starvation, autophagy was enhanced and cell death reduced when PC1 was reduced. Autophagy inhibition reduced cell death resistance in PC1KO mIMCDs to the WT level, implying that PC1 promotes autophagic cell survival. Although PC2 expression was increased in PC1KO mIMCDs, PC2 knockdown did not result in reduced autophagy. PC2KO mIMCDs displayed lower basal autophagy, but more autophagy and less cell death following chronic starvation. This could be reversed by overexpression of PC1 in PC2KO. Together, these findings indicate that PC1 levels are partially coupled to PC2 expression, and determine the transition from renal cell survival to death, leading to enhanced survival of ADPKD cells during nutritional stress.     

Knockdown of the Halloween Genes spook,shadow and shade Influences Oocyte Development,Egg Shape,Oviposition and Hatching in the Desert Locust

Ecdysteroids are widely investigated for their role during the molting cascade in insects; however, they are also involved in the development of the female reproductive system. Ecdysteroids are synthesized from cholesterol, which is further converted via a series of enzymatic steps into the main molting hormone, 20-hydoxyecdysone. Most of these biosynthetic conversion steps involve the activity of cytochrome P450 (CYP) hydroxylases, which are encoded by the Halloween genes. Three of these genes, spook (spo), phantom (phm) and shade (shd), were previously characterized in the desert locust, Schistocerca gregaria. Based on recent sequencing data, we have now identified the sequences of disembodied (dib) and shadow (sad), for which we also analyzed spatiotemporal expression profiles using qRT-PCR. Furthermore, we investigated the possible role(s) of five different Halloween genes in the oogenesis process by means of RNA interference mediated knockdown experiments. Our results showed that depleting the expression of SchgrSpo, SchgrSad and SchgrShd had a significant impact on oocyte development, oviposition and hatching of the eggs. Moreover, the shape of the growing oocytes, as well as the deposited eggs, was very drastically altered by the experimental treatments. Consequently, it can be proposed that these three enzymes play an important role in oogenesis.     

State of the Art and Perspectives of Hierarchical Zeolites: Practical Overview of Synthesis Methods and Use in Catalysis

Microporous zeolites have proven to be of great importance in many chemical processes. Yet, they often suffer from diffusion limitations causing inefficient use of the available catalytically active sites. To address this problem, hierarchical zeolites have been developed, which extensively improve the catalytic performance. There is a multitude of recent literature describing synthesis of and catalysis with these hierarchical zeolites. This review attempts to organize and overview this literature (of the last 5 years), with emphasis on the most important advances with regard to synthesis and application of such zeolites. Special attention is paid to the most common and important 10- and 12-membered ring zeolites (MTT, TON, FER, MFI, MOR, FAU, and *BEA). In contrast to previous reviews, the research per zeolite topology is brought together and discussed here. This allows the reader to instantly find the best synthesis method in accordance to the desired zeolite properties. A summarizing graph is made available to enable the reader to select suitable synthesis procedures based on zeolite acidity and mesoporosity, the two most important tunable properties.     

Diagnostic validity of the Eppendorf Schizophrenia Inventory (ESI): A self-report screen for ultrahigh risk and acute psychosis.

[Correction Notice: An erratum for this article was reported in Vol 23(1) of Psychological Assessment (see record 2011-04411-006). Presents changes that are very small and do not in any way affect the findings of the research. These changes are explained in the correction.] Providers of mental health services need tools to screen for acute psychosis and ultrahigh risk (UHR) for transition to psychosis in help-seeking individuals. In this study, the Eppendorf Schizophrenia Inventory (ESI) was examined as a screening tool and for its ability to correctly predict diagnostic group membership (e.g., help seeking, mild psychiatric complaints, highly symptomatic mood or anxiety disorder, UHR, acute psychosis). Diagnostic evaluation with established instruments was used for diagnosis in 3 research samples. UHR status was assessed with the Structured Interview for Prodromal Symptoms/Scale of Prodromal Symptoms (Miller et al., 1999) and the Bonn Scale for the Assessment of Basic Symptoms Prediction list (Gross, Huber, Klosterk?tter, & Linz, 1987; Klosterk?tter, Hellmich, Steinmeyer, & Schulze-Lutter, 2001). This study showed that members of different diagnostic groups rate themselves significantly differently on the ESI and its subscales. A new subscale was constructed, the UHR–Psychosis scale, that showed good utility in detecting individuals with interview-diagnosed UHR status and acute psychosis. The scale is also sensitive to the threshold between UHR and acute psychosis. Practical applications of the ESI include use as a diagnostic tool within various settings. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Acetylsalicylic Acid Reduces Passive Aortic Wall Stiffness and Cardiovascular Remodelling in a Mouse Model of Advanced Atherosclerosis

Acetylsalicylic acid (ASA) is widely used in secondary prevention of cardiovascular (CV) disease, mainly because of its antithrombotic effects. Here, we investigated whether ASA can prevent the progression of vessel wall remodelling, atherosclerosis, and CV complications in apolipoprotein E deficient (ApoE^−/−) mice, a model of stable atherosclerosis, and in ApoE^−/− mice with a mutation in the fibrillin-1 gene (Fbn1^C1039G+/−), which is a model of elastic fibre fragmentation, accompanied by exacerbated unstable atherosclerosis. Female ApoE^−/− and ApoE^−/−Fbn1^C1039G+/− mice were fed a Western diet (WD). At 10 weeks of WD, the mice were randomly divided into four groups, receiving either ASA 5 mg/kg/day in the drinking water (ApoE^−/− (n = 14), ApoE^−/−Fbn1^C1039G+/− (n = 19)) or plain drinking water (ApoE^−/− (n = 15), ApoE^−/−Fbn1^C1039G+/− (n = 21)) for 15 weeks. ApoE^−/−Fbn1^C1039G+/− mice showed an increased neutrophil–lymphocyte ratio (NLR) compared to ApoE^−/− mice, and this effect was normalised by ASA. In the proximal ascending aorta wall, ASA-treated ApoE^−/−Fbn1^C1039G+/− mice showed less p-SMAD2/3 positive nuclei, a lower collagen percentage and an increased elastin/collagen ratio, consistent with the values measured in ApoE^−/− mice. ASA did not affect plaque progression, incidence of myocardial infarction and survival of ApoE^−/−Fbn1^C1039G+/− mice, but systolic blood pressure, cardiac fibrosis and hypertrophy were reduced. In conclusion, ASA normalises the NLR, passive wall stiffness and cardiac remodelling in ApoE^−/−Fbn1^C1039G+/− mice to levels observed in ApoE^−/− mice, indicating additional therapeutic benefits of ASA beyond its classical use.