Enteric Nervous System Progenitors Are Coordinately Controlled by the G Protein-Coupled Receptor EDNRB and the Receptor Tyrosine Kinase RET

AbstractThe enteric nervous system (ENS) in vertebrates is derived mainly from vagal neural crest cells that enter the foregut and colonize the entire wall of the gastrointestinal tract. Failure to completely colonize the gut results in the absence of enteric ganglia (Hirschsprung's disease). Two signaling systems mediated by RET and EDNRB have been identified as critical players in enteric neurogenesis. We demonstrate that interaction between these signaling pathways controls ENS development throughout the intestine. Activation of EDNRB specifically enhances the effect of RET signaling on the proliferation of uncommitted ENS progenitors. In addition, we reveal novel antagonistic roles of these pathways on the migration of ENS progenitors. Protein kinase A is a key component of the molecular mechanisms that integrate signaling by the two receptors. Our data provide strong evidence that the coordinate and balanced interaction between receptor tyrosine kinases and G protein-coupled receptors controls the development of the nervous system in mammals

Key principles for an integrated intercultural literary pedagogy: An educational design research project on arts integration for intercultural competence

Intercultural competence in foreign language teaching has gained importance in recent times. Although current work has highlighted the advantages of content and language integrated learning (CLIL) for intercultural development, little is known about its potential for teaching literature in secondary schools. Treating literature itself as an art form, the aim of this article is to formulate research-based design principles for an integrated intercultural literary pedagogy (IILP) that may foster intercultural competence through arts integration in foreign language classes. This article reports on the process of evaluating IILP-based pilot lesson materials in pre-university education in the Netherlands. Educational design research was applied as a method that encompasses the systematic study of designing, developing, and evaluating educational interventions through an iterative process of evaluation with stakeholders. Three iterations of formative evaluation were conducted, with additions to the tentative design principles following each of the first two iterations. The process resulted in a set of four refined principles. Results also illustrated the effectiveness of IILP-based lesson materials for intercultural competence. Although participating students encountered some difficulties relating to the functionality of the design, the students appreciated its social relevance and reported that the processing of literary texts through dialogic tasks with peers in the target language fostered intercultural language learning

Reconceptualizing critical cultural awareness for the context of FL literature education: The development of an assessment rubric for the secondary level

The construct of critical cultural awareness (CCA) is often regarded as an element pertaining to intercultural communicative competence (Byram, 1997, 2021). In this model, CCA is defined as the ability to “evaluate, critically, and on the basis of a systematic process of reasoning, values in one’s own culture and other cultures” (Byram, 2021, p. 90). Although the potential of literature to develop learners’ CCA is widely accepted by intercultural education scholars, Byram’s definition has some limitations as a theoretical basis for teaching students how to “evaluate and reason critically” about literary texts, as it does not take into account certain aspects of literary reading and critical interculturality that are essential in contemporary foreign language (FL) teaching and learning. This study aims to redefine CCA for the specific context of secondary literature education in a bottom-up manner, based on an analysis of student texts about migratory literature. To this end, 97 students learning Spanish as a FL in the upper forms of pre-university education (aged 15–19) at four schools in the Netherlands were asked to write an evaluation of two literary texts they read in class. Via qualitative analysis of these texts with Atlas.ti, three content categories – social justice, emotions and conflict – and two evaluative categories ­– cultural representation and transformation – were identified for CCA. The findings of this study have implications for other FL literature teaching settings, as a generic rubric for assessment of student texts was developed based on the criteria that emerged from the data

Peer Victimization, Internalizing Problems, and the Buffering Role of Friendship Quality: Disaggregating Between- and Within-Person Associations

Although many studies have shown an association between peer victimization and internalizing problems, which may be buffered by friendship quality, it is unclear whether these associations apply to within-person processes as well. This would mean that at times when adolescents experience more victimization than they usually do, they also experience more internalizing problems. The current study disaggregated between- and within-person variation to examine the association between peer victimization and symptoms of depression and anxiety, and the protective effect of friend support and conflict. Participants were 497 Dutch adolescents (56% boys) with a mean age of 13.03 (SDage = 0.45, ranging from 11.68 to 15.56 at Wave 1). They participated in a 6-wave questionnaire study, with each wave taking place approximately one year after the previous. The results showed that peer victimization was associated with depressive symptoms and anxiety across adolescence, both between and within persons. Friend support buffered this association at the between-person level, but not the within-person level. This study highlights the impact of peer victimization and suggests that friend support may partly protect adolescents from the effects of peer victimization

Integrated Index of Women's Participation in Agricultural Community by Prefecture

textabstractObjective: Anti-Tr is among the better described autoantibodies in paraneoplastic cerebellar degeneration (PCD) combined with Hodgkin lymphoma (HL); however, the Tr antigen remains unidentified. Methods: We used immunoprecipitation of total rat brain extract followed by mass spectrometry to identify the antigen recognized by anti-Tr-positive sera. By Western blotting and cell-based assays, we tested a total of 12 anti-Tr-positive and 246 control sera and determined the region of the epitope recognized by the anti-Tr antibodies. Deletion and mutant constructs were generated to further map the antigenic region. Results: Mass spectrometry analysis of immunopurified rat brain extract using 4 different anti-Tr-positive sera led to the identification of Delta/Notch-like epidermal growth factor-related receptor (DNER) as the Tr antigen. All but 1 of 246 control samples were negative in the HeLa cell-based screening assay, whereas 12 of the 12 anti-Tr-positive sera stained hemagglutinin-tagged DNER-expressing cells. Only 1 control subject with HL but no ataxia was found to be both DNER and Tr positive. Using deletion constructs, we pinpointed the main epitope to the extracellular domain. Knockdown of endogenous DNER in hippocampal and N-glycosylation mutations abolished the anti-Tr staining, indicating that glycosylation of DNER is required for it to be recognized by anti-Tr antibodies. Interpretation: DNER is the antigen detected by anti-Tr-positive sera. Presence of anti-Tr antibodies in patients with PCD and HL or HL only can now be screened quickly and reliably by using a cell-based screening assay

Activities of daily living in lower limb amputees with a bone-anchored prosthesis:a retrospective case series with 24 months’ follow-up

Background and purpose:Little is known about the activities of daily living (ADL) of patients with a bone-anchored prosthesis (BAP). We aimed to objectively measure ADL without and with BAP during standard care of follow-up. Our secondary aim was to measure mobility and walking ability. Patients and methods:Patients aged 18–99 years who underwent surgery for transfemoral or transtibial BAP between September 11, 2017, and February 11, 2021, were eligible for inclusion in this retrospective case series of patients with socket prosthesis. ADL was measured with a continuous recording activity monitor (hours [h]) before surgery, and at 6, 12, and 24 months with BAP. Mobility and walking ability were assessed by the Timed Up and Go test (TUG) (seconds [s]) and 6 Minute Walk Test (6MWT) (meters [m]), respectively. Results:48 of the 57 eligible patients provided informed consent and were included. Their age was 59 (1st quartile to 3rd quartile 51–63) years. Total daily activity before BAP was 1.6 h (0.82–2.1) and increased to 2.1 h (1.4–2.5) at 6, 2.0 h (1.5–2.7) at 12, and 2.7 h (2.0–3.3) at 24 months with BAP. Daily walking increased from 1.3 h (0.79–1.9) before BAP to 1.8 h (1.6–2.3) at 6, to 1.7 h (1.2–2.4) at 12, and 2.0 h (1.6–2.6) at 24 months. Median TUG decreased from 12 s (9.1–14) before BAP to 8.9 s (7.7–10) at 24 months. Mean 6MWT increased from 272 m (SD 92) before BAP to 348 m (SD 68) at 24 months.Conclusion:Objective measurements on ADL positively changed in patients with BAP. This effect was also seen in mobility and walking ability at 24 months.</p

Depression Socialization in Early Adolescent Friendships: The Role of Baseline Depressive Symptoms and Autonomous Functioning

There is mixed evidence for depression socialization, a process by which friends affect each other’s level of depressive symptoms. The current study examined whether adolescents’ baseline depressive symptoms and three dimensions of autonomous functioning (autonomy, peer resistance, and friend adaptation) make adolescents more or less sensitive to depression socialization, and how these dimensions of autonomous functioning were connected. In this preregistered, two-wave longitudinal study, participants completed questionnaires on depressive symptoms, autonomy, and peer resistance and participated in a task to assess friend adaptation. Participants were 416 Dutch adolescents (Mage = 11.60, 52.8% girls) across 230 close friend dyads. In contrast to expectations, results showed no significant depression socialization nor significant moderation. Furthermore, autonomy and peer resistance were related but distinct constructs, and not related to friend adaptation. These findings suggest that there is no depression socialization in early adolescence, regardless of level of autonomous functioning

Ventilation with lower tidal volumes as compared with conventional tidal volumes for patients without acute lung injury: a preventive randomized controlled trial

Introduction: Recent cohort studies have identified the use of large tidal volumes as a major risk factor for development of lung injury in mechanically ventilated patients without acute lung injury (ALI). We compared the effect of conventional with lower tidal volumes on pulmonary inflammation and development of lung injury in critically ill patients without ALI at the onset of mechanical ventilation. Methods: We performed a randomized controlled nonblinded preventive trial comparing mechanical ventilation with tidal volumes of 10 ml versus 6 ml per kilogram of predicted body weight in critically ill patients without ALI at the onset of mechanical ventilation. The primary end point was cytokine levels in bronchoalveolar lavage fluid and plasma during mechanical ventilation. The secondary end point was the development of lung injury, as determined by consensus criteria for ALI, duration of mechanical ventilation, and mortality. Results: One hundred fifty patients (74 conventional versus 76 lower tidal volume) were enrolled and analyzed. No differences were observed in lavage fluid cytokine levels at baseline between the randomization groups. Plasma interleukin-6 (IL-6) levels decreased significantly more strongly in the lower-tidal-volume group ((from 51 (20 to 182) ng/ml to 11 (5 to 20) ng/ml versus 50 (21 to 122) ng/ml to 21 (20 to 77) ng/ml; P = 0.01)). The trial was stopped prematurely for safety reasons because the development of lung injury was higher in the conventional tidal-volume group as compared with the lower tidal-volume group (13.5% versus 2.6%; P = 0.01). Univariate analysis showed statistical relations between baseline lung-injury score, randomization group, level of positive end-expiratory pressure (PEEP), the number of transfused blood products, the presence of a risk factor for ALI, and baseline IL-6 lavage fluid levels and the development of lung injury. Multivariate analysis revealed the randomization group and the level of PEEP as independent predictors of the development of lung injury. Conclusions: Mechanical ventilation with conventional tidal volumes is associated with sustained cytokine production, as measured in plasma. Our data suggest that mechanical ventilation with conventional tidal volumes contributes to the development of lung injury in patients without ALI at the onset of mechanical ventilation. (aut. ref.

Antibodies to TRIM46 are associated with paraneoplastic neurological syndromes.

Paraneoplastic neurological syndromes (PNS) are often characterized by the presence of antineuronal antibodies in patient serum or cerebrospinal fluid. The detection of antineuronal antibodies has proven to be a useful tool in PNS diagnosis and the search for an underlying tumor. Here, we describe three patients with autoantibodies to several epitopes of the axon initial segment protein tripartite motif 46 (TRIM46). We show that anti-TRIM46 antibodies are easy to detect in routine immunohistochemistry screening and can be confirmed by western blotting and cell-based assay. Anti-TRIM46 antibodies can occur in patients with diverse neurological syndromes and are associated with small-cell lung carcinoma