John Benjamins Publishing Company (Netherlands)

Long noncoding RNAs (lncRNA) have emerged as critical regulators in cardiovascular biology, influencing cardiac development, remodeling, and regeneration. Zeb2os (zeb2 opposite strand), a natural antisense transcript of the Zeb2 (zinc finger E-box-binding homeobox 2) gene, has been linked to these processes in various organs. Although ZEB2 promotes cardiac repair, the role of Zeb2os in these processes remains unclear. This study investigates the role of Zeb2os in modulating ZEB2 expression and cardiac remodeling after ischemic injury. We used adeno-associated virus vectors to overexpress Zeb2os in mouse models of cardiac IR (ischemia/reperfusion) injury. RNA sequencing, immunofluorescence, and high-resolution respirometry were used to evaluate the effects of Zeb2os delivery on gene expression, ZEB2 reactivation, cardiomyocyte phenotype, scar composition, and mitochondrial function. Experiments in cultured cardiomyocytes under hypoxia further explored the regulatory dynamics between Zeb2os and Zeb2. We identified Zeb2os as a hypoxia-responsive lncRNA that displays an inverse and oscillatory expression pattern with Zeb2 in both in vitro and in vivo models of cardiac injury. Functional experiments revealed that Zeb2os negatively regulates ZEB2 expression, impairing the cardiomyocyte dedifferentiation and metabolic remodeling necessary for effective repair. Adeno-associated virus-mediated delivery of Zeb2os resulted in preserved sarcomere structure, altered scar composition, reduced expression of regenerative genes, and diminished cardiac function following injury. In contrast, silencing of Zeb2os increased ZEB2 protein expression, suggesting a potential therapeutic strategy to enhance repair. Mechanistically, modulation of Zeb2os levels inversely regulated ZEB2 protein expression, whereas ZEB2 modulation did not affect Zeb2os levels, indicating a unidirectional regulatory axis between the 2 transcripts. Our findings identify Zeb2os as a stress-responsive inhibitor of ZEB2 reactivation that limits cardiomyocyte plasticity and hinders repair following ischemic injury. Given its specific activity under ischemic conditions, targeting Zeb2os may represent a novel therapeutic strategy to enhance endogenous cardiac regeneration.

To enhance social interaction of residents living with dementia and their (in)formal carers in nursing homes, we examined the effects of a digital, person-centred, Photo-Activity (PA) versus a conversation activity (control). An explorative randomized controlled trial was conducted in 81 resident-informal carer (IC) dyads and 51 formal carers (FC) with three measurements (pre/post-test, 2-week follow-up). Intervention effects were tested using Mann–Whitney U’s, and ANCOVA’s with pre-test scores as covariates. Interaction effects were examined between dementia severity (DS; less/more) and condition (PA/control). A post-test effect was observed in social interaction (INTERACT-subscale: Mood [p = 0.037, ηp2 = 0.07]), with PA residents showing better mood than controls. Residents with less DS showed more positive effects of PA than residents with more DS (interaction effects: INTERACT-subscales Mood [p = 0.017, ηp2 = 0.092], Stimulation Level [p = 0.011, ηp2 = 0.106], and Need for Prompting [p = 0.013, ηp2 = 0.099]). Higher QUALIDEM Positive Affect scores were observed in the PA group, post-test (p = 0.025, ηp2 = 0.082), and follow-up (p = 0.042, d = 0.39). PA FC showed less empathy (IRI; p = 0.006, ηp2 = 0.185;) than controls, but reported getting to know the residents better (p = 0.035, r = 0.299). PA improved mood and positive affect of residents with dementia and led to FC knowing the residents better. Less empathy was observed in FC providing PA, requiring further investigation.

Background and aimsWe investigated whether improving the cognitive accessibility of a widely used self-report measure leads to better understanding and more accurate answers in a sample of adults with mild intellectual disability and borderline intellectual functioning. Methods and proceduresWe undertook a series of cognitive interviews before and after adaptation of the instructions and selected items of an existing self-report measure of adaptive functioning. Interview results and participant feedback were supplemented with quantitative comparisons between participant and carer scores. Outcomes and resultsAdaptation based on participant experiences and preferences combined with evidence-informed guidelines improved understanding and accuracy. Self-report and carer-report scores showed greater convergence after adaptation; this occurred because people with intellectual disabilities appeared to understand the self-report measure more effectively. Conclusions and implicationsThe results show that adaptation of the self-report instrument to suit the needs and preferences of people with mild intellectual disability or borderline intellectual functioning leads to a more accessible measure and more reliable and valid results. Results also highlight the importance of complementing proxy reports with a first-person perspective in assessment as clients and informants may differ in their assessment of behavior and skills.

BACKGROUND:High heritability of salt sensitivity suggests an essential role for genetics in the relationship between sodium intake and blood pressure (BP). The role of glycosaminoglycan genes, which are crucial for salinity tolerance, remains to be elucidated.METHODS:Interactions between 54 126 variants in 130 glycosaminoglycan genes and daily sodium excretion on BP were explored in 20 420 EPIC-Norfolk (European Prospective Investigation Into Cancer in Norfolk) subjects. The UK Biobank (n=414 132) and the multiethnic HELIUS study (Healthy Life in an Urban Setting; n=2239) were used for validation. Afterward, the urinary glycosaminoglycan composition was studied in HELIUS participants (n=57) stratified by genotype and upon dietary sodium loading in a time-controlled crossover intervention study (n=12).RESULTS:rs2892799 in NDST3 (heparan sulfate N-deacetylase/N-sulfotransferase 3) showed the strongest interaction with sodium on mean arterial pressure (false discovery rate 0.03), with higher mean arterial pressure for the C allele in high sodium conditions. Also, rs9654628 in HS3ST5 (heparan sulfate-glucosamine 3-sulfotransferase 5) showed an interaction with sodium on systolic BP (false discovery rate 0.03). These interactions were multiethnically validated. Stratifying for the rs2892799 genotype showed higher urinary expression of N-sulfated heparan sulfate epitope D0S0 for the T allele. Conversely, upon dietary sodium loading, urinary D0S0 expression was higher in participants with stable BP after sodium loading, and sodium-induced effects on this epitope were opposite in individuals with and without BP response to sodium.CONCLUSIONS:The C allele of rs2892799 in NDST3 exhibits higher BP in high sodium conditions when compared with low sodium conditions, whereas no differences were detected for the T allele. Concomitantly, both alleles demonstrate distinct expressions of D0S0, which, in turn, correlates with sodium-mediated BP elevation. These findings underscore the potential significance of genetic glycosaminoglycan variation in human BP regulation.

Drug isomer differentiation has become a relevant problem in forensic drug testing laboratories as new psychoactive substances include many closely related and isomeric forms. Both legislative and public safety requirements demand unambiguous identification of the isomers. A novel approach for ring-isomeric differentiation using GC–MS by means of low energy Electron Ionization (EI) in combination with chemometric data analysis was developed. An ionization energy of 15 eV combined with a high efficiency EI source yields more information rich and thus discriminating mass spectra for ring-isomeric, cathinone-type drugs. Through multivariate statistics using Principal Component Analysis (PCA) followed by Linear Discriminant Analysis (LDA) mass spectral data can be exploited to confidently distinguish isomeric classes. Including feature selection of the mass spectra further enhanced the discriminative power of these models. In this way, all examined classes of cathinone and fluoroamphetamine isomers could be robustly identified, even through their conventional 70 eV mass spectrum from a quadrupole-MS instrument. A characteristic Likelihood Ratio (LR) based indicator was developed to quantify the selectivity of the models which proved to be useful for comparison, optimization and identification purposes. The potential of the method was demonstrated with six forensic case samples, providing 100% correct isomer identification. In general, this new approach enables robust classification of drug isomers that is currently not possible with conventional GC–MS methods without the use of additional spectroscopic analyses.

The philosophical problem of the Inside -Outside duality has a long history.In this paper I recall that not only this duality caught the attention of philosophers like F. Nietzsche, G.W.F.Hegel and J.-P.Sartre, but it also formed the pièce de résistance in the famous controversy between S.A. Kierkegaard and Th.W. Adorno.In Nietzsche's early work Menschliches, allzumenschliches (1878), an interesting starting point is found that reminded me of the also famous, original viewpoint of M. Proust as expressed in À la Recherche du Temps Perdu (1914).Doing so, these re-collections brought me to a re-formulation of my 1992 paper on the problem of the linearity of written language and the nature of communication.This paper aims at showing that the translation of the Inside-Outside duality in a contemporary context together with a non-linear topography of natural communication, allows us to answer T. Morton's (2016) challenging logic of the hyper-real and so-called agrilogistics view on ecology.It is concluded that this debate is indeed important to distillate a logic of future coexistence.

Abstract In this article, we challenge the (implicit) dogmas of the current trend towards a business rescue culture within Europe. It is unclear why this trend – as a logical consequence of the desire to create increasingly debtor friendly insolvency regimes – keeps revealing and reinforcing itself in this time frame. Many different approaches take this concept for granted. The idea thus risks becoming an end in itself. The assumptions behind the current trend of business rescue culture should reflect the stylized facts of a firm embedded in its business ecology. An implicit dogma of current business rescue culture is that a firm is an entity that must survive and will create value indefinitely and, accordingly, deserves a second chance. However, the ability to create value and therefore the viability of a firm are the outcome of an uncertain economic process. Capitalism is a process of trial and error. Failure is a normal outcome and should be considered an essential part of capitalism. In general, the life span of firms is finite because they have to cope with many uncertainties and trade‐offs. The firm itself is only a tiny temporary (legal) shell within a self‐organized value chain that continuously reallocates resources as competition intensifies and the rate of innovation accelerates. The implicit assumptions or dogmas of the current business rescue culture contradict the accelerating destructive forces of capitalism and therefore can be labelled as an anachronism. Instead of focusing on the specific micro‐level of the firm, insolvency regimes should aim to provide a solution at the higher meso‐level. Copyright © 2018 The Authors International Insolvency Review published by INSOL International and John Wiley & Sons, Ltd.

Ce petit essai vise d’abord à contester la mauvaise façon endémique de poser la question du « monde arabo-musulman méditerranéen ». Il propose ensuite une réflexion sur la nature même du phénomène religieux, y compris la charia, et de sa constitution en facteur explicatif du devenir de ce monde. Enfin, il insiste sur le fait que parler en termes de révolution et d’illusion n’est avantageux qu’à la condition d’être engagé dans une démarche de production militante d’un maître-récit global visant à imposer une lecture de l’histoire plutôt qu’à décrire ce que l’histoire donne à voir.

Stöber silica particles are used in a diverse range of applications. Despite their widespread industrial and scientific uses, information on the internal structure of the particles is non-trivial to obtain and is not often reported. In this work we have used spin-echo small angle neutron scattering (SESANS) in conjunction with ultra small angle X-ray scattering (USAXS) and pycnometry to study an aqueous dispersion of Stöber particles. Our results are in agreement with models which propose that Stöber particles have a porous core, with a significant fraction of the pores inaccessible to solvent. For samples prepared from the same master sample in a range of H2O : D2O ratio solutions we were able to model the SESANS results for the solution series assuming monodisperse, smooth surfaced spheres of radius 83 nm with an internal open pore volume fraction of 32% and a closed pore fraction of 10%. Our results are consistent with USAXS measurements. The protocol developed and discussed here shows that the SESANS technique is a powerful way to investigate particles much larger than those studied using conventional small angle scattering methods.