Learning enjoyment in early adolescence

There is empirical evidence showing that positive emotional and motivational factors in formal learning contexts decrease at the stage of young adolescence. According to Stage-Environment-Fit Theory and Self-Determination Theory, this change should be explained by a non-fulfilment of students' needs. By combining two different methods (questionnaires and day-to-day diaries) and applying a longitudinal design, this study aimed to explore the change in and the determinants of habitual and actual learning enjoyment. The sample consisted of 356 students. Quantitative results indicated that learning enjoyment and classroom practices decreased between Grades 6 and 7. Path analyses revealed that classroom practices are the source of students' learning enjoyment, while self-efficacy functions as a partial mediator. Data from students' diaries showed that a teacher's neglect of students' needs for competence and relatedness were significant sources of impeded learning enjoyment. Practical implications suggest the relevance of adjusting learning conditions to the needs of young adolescents in order to provide a facilitating basis for learning enjoyment.

Subjective well-being and exercise in the second halt of life: a critical review of theoretical approaches

Research has shown repeatedly that the “feeling better” effect of exercise is far more moderate than generally claimed. Examinations of subgroups in secondary analyses also indicate that numerous further variables influence this relationship. One reason for inconsistencies in this research field is the lack of adequate theoretical analyses. Well-being output variables frequently possess no construct definition, and little attention is paid to moderating and mediating variables. This article integrates the main models in an overview and analyzes how secondary analyses define well-being and which areas of the construct they focus on. It then applies a moderator and/or mediator framework to examine which person and environmental variables can be found in the existing explanatory approaches in sport science and how they specify the influence of these moderating and mediating variables. Results show that the broad understanding of well-being in many secondary analyses makes findings difficult to interpret. Moreover, physiological explanatory approaches focus more on affective changes in well-being, whereas psychological approaches also include cognitive changes. The approaches focus mostly on either physical or psychological person variables and rarely combine the two, as in, for example, the dual-mode model. Whereas environmental variables specifying the treatment more closely (e.g., its intensity) are comparatively frequent, only the social support model formulates variables such as the framework in which exercise is presented. The majority of explanatory approaches use simple moderator and/or mediator models such as the basic mediated (e.g., distraction hypothesis) or multiple mediated (e.g., monoamine hypotheses) model. The discussion draws conclusions for future research.

Elevated CSF histamine levels in multiple sclerosis patients.

BACKGROUND Histamine is an ubiquitous inflammatory mediator of numerous physiological processes. Histamine and its receptors have been implicated in multiple sclerosis (MS) disease pathogenesis. We prospectively enrolled 36 MS patients and 19 age and gender-matched healthy volunteers for cerebrospinal fluid (CSF) histamine analysis. FINDINGS CSF HISTAMINE LEVELS IN MS PATIENT SAMPLES WERE SIGNIFICANTLY HIGHER (MEDIAN: 35.6 pg/ml) than in controls (median: 5.5 pg/ml; Beta = 0.525, p < 0.001). In addition, histamine increased with age (Pearson's correlation, p < 0.003). CONCLUSIONS Histamine may be an important factor for both the initiation and maintenance of chronic inflammatory diseases of the central nervous system. Our observation encourages a deeper investigation of the role of histamine in MS.

Two Loci on Chromosome 5 Are Associated with Serum IgE Levels in Labrador Retrievers

Crosslinking of immunoglobulin E antibodies (IgE) bound at the surface of mast cells and subsequent mediator release is considered the most important trigger for allergic reactions. Therefore, the genetic control of IgE levels is studied in the context of allergic diseases, such as asthma, atopic rhinitis, or atopic dermatitis (AD). We performed genome-wide association studies in 161 Labrador Retrievers with regard to total and allergen-specific immunoglobulin E (IgE) levels. We identified a genome-wide significant association on CFA 5 with the antigen-specific IgE responsiveness to Acarus siro. We detected a second genome-wide significant association with respect to the antigen-specific IgE responsiveness to Tyrophagus putrescentiae at a different locus on chromosome 5. A. siro and T. putrescentiae both belong to the family Acaridae and represent so-called storage or forage mites. These forage mites are discussed as major allergen sources in canine AD. No obvious candidate gene for the regulation of IgE levels is located under the two association signals. Therefore our studies offer a chance of identifying a novel mechanism controlling the host's IgE response.

Das offene Selbstgespräch des Teampartners - Einfluss auf die wahrgenommene Kompetenz und die eigene Anstrengungsbereitschaft

Einleitung und Fragestellung In der Forschung zum Selbstgespräch im Sport dominiert die Frage nach dessen Wir-kung auf die Leistung. Der Einfluss des während der Leistungserbringung geäußerten Selbstgesprächs auf (un-)beteiligte Personen (z.B. Zuschauer, Gegenspieler oder Dop-pelpartner) wurde bislang kaum untersucht. Van Raalte, Brewer, Cornelius und Petitpas (2006) konnten immerhin zeigen, dass Zuschauer einen Tennisspieler als kompetenter einschätzen, wenn er in einem Laborexperiment mit positivem statt mit negativem Selbst-gespräch gezeigt wurde. In unserer Studie stehen Dyaden im Zentrum, in der eine Person eine andere beobach-tet, die mit sich selbst spricht. Untersucht wird, ob bei einer additiven Teamaufgabe sol-che Beobachtungen einen Effekt auf die Kompetenzeinschätzung und die Anstren-gungsbereitschaft haben. Es wird vermutet, dass die beobachtende Person dann eine höhere Anstrengungsbereitschaft (AV) zeigt, wenn sie einen Teampartner mit positivem Selbstgespräch (UV) beobachtet, da sie ihren Partner als kompetenter einschätzt und diese Einschätzung als Mediator wirkt. Methode Es wurde ein randomisierter Zweigruppen-Versuchsplan mit zwei Experimentalgruppen (je n=20) durchgeführt. Das Treatment bestand aus einem Video, das den (jeweils identi-schen) Teampartner bei der Bewältigung der zu absolvierenden visuomotorisch-koordinativen Testaufgabe zeigt (Test 2HAND des Wiener Testsystems). Das Video wur-de abhängig von der Gruppenzugehörigkeit mit negativen respektive positiven Selbstge-sprächsaussagen unterlegt. Die Mediatorvariable wahrgenommene Kompetenz wurde mittels eines Fragebogens erhoben, der in Anlehnung an Van Raalte et al. (2006) entwi-ckelt wurde. Das Vorgehen zur Erhebung der abhängigen Variable Anstrengungsbereit-schaft wurde von Ohlert (2009) übernommen: Die Probanden erhielten die Möglichkeit, sich auf die spätere Testphase vorzubereiten. Erfasst wurde dabei die Zeit, die sie für die Vorbereitung in Anspruch nahmen, und die Genauigkeit, mit der sie eine Reihe von Aufwärmaufgaben absolvierten. Ergebnisse Die Datenerhebung wurde soeben abgeschlossen. Die Ergebnisse der noch ausstehen-den regressionsanalytischen Auswertung werden auf der Tagung präsentiert. Literatur Ohlert, J. (2009). Teamleistung. Social Loafing in der Vorbereitung auf eine Gruppenaufgabe. Hamburg: Dr. Kovac. Van Raalte, J. L., Brewer, B. W., Cornelius, A. E. & Petitpas, A. J. (2006). Self-presentational effects of self-talk on perceptions of tennis players. Hellenic Journal of Psychology, 3, 134-149.

Childhood Trauma and PTSD symptoms increase the risk of cognitive impairment in a sample of former indetured child laborers in old Age.

A growing body of evidence suggests a link between early childhood trauma, post-traumatic stress disorder (PTSD) and higher risk for dementia in old age. The aim of the present study was to investigate the association between childhood trauma exposure, PTSD and neurocognitive function in a unique cohort of former indentured Swiss child laborers in their late adulthood. To the best of our knowledge this is the first study ever conducted on former indentured child laborers and the first to investigate the relationship between childhood versus adulthood trauma and cognitive function. According to PTSD symptoms and whether they experienced childhood trauma (CT) or adulthood trauma (AT), participants (n = 96) were categorized as belonging to one of four groups: CT/PTSD+, CT/PTSD-, AT/PTSD+, AT/PTSD-. Information on cognitive function was assessed using the Structured Interview for Diagnosis of Dementia of Alzheimer Type, Multi-infarct Dementia and Dementia of other Etiology according to ICD-10 and DSM-III-R, the Mini-Mental State Examination, and a vocabulary test. Depressive symptoms were investigated as a potential mediator for neurocognitive functioning. Individuals screening positively for PTSD symptoms performed worse on all cognitive tasks compared to healthy individuals, independent of whether they reported childhood or adulthood adversity. When controlling for depressive symptoms, the relationship between PTSD symptoms and poor cognitive function became stronger. Overall, results tentatively indicate that PTSD is accompanied by cognitive deficits which appear to be independent of earlier childhood adversity. Our findings suggest that cognitive deficits in old age may be partly a consequence of PTSD or at least be aggravated by it. However, several study limitations need to considered. Consideration of cognitive deficits when treating PTSD patients and victims of lifespan trauma (even without a diagnosis of a psychiatric condition) is crucial. Furthermore, early intervention may prevent long-term deficits in memory function and development of dementia in adulthood.

S-nitroso albumin enhances bone formation in a rabbit calvaria model.

Nitric oxide (NO) is a mediator involved in bone regeneration. We therefore examined the effect of the novel NO donor, S-nitroso human serum albumin (S-NO-HSA) on bone formation in a rabbit calvaria augmentation model. Circular grooves (8 mm diameter, two per animal) were created by a trephine drill in the cortical bone of 40 rabbits and titanium caps were placed on the rabbit calvaria bone filled with a collagen sponge soaked with either 100 μL S-NO-HSA (5%, 20%) or human albumin (5%, 20%). After 4 weeks the titanium hemispheres were subjected to histological and histomorphometric analysis. Bone formation and the volume of the residual collagen sponge were evaluated. S-NO-HSA treatment groups had a significantly higher volume of newly formed bone underneath the titanium hemispheres compared to the albumin control groups (5%: 15.5 ± 4.0% versus 10.6 ± 2.9%; P < 0.05; 20%: 14.0 ± 4.6% versus 6.0 ± 3.8%; P < 0.01). The volume of residual collagen sponge was also significantly lower in the S-NO-HSA groups compared to the control groups (5%: 0.4 ± 0.5% versus 2.6 ± 2.4%; P < 0.05 and 20%: 1.5 ± 2.7% versus 13.0 ± 18.7%; P < 0.01). This study demonstrates for the first time that S-NO-HSA promotes bone formation by slow NO release. Additionally, S-NO-HSA increases collagen sponge degradation.

BID-dependent release of mitochondrial SMAC dampens XIAP-mediated immunity against Shigella

The X‐linked inhibitor of apoptosis protein (XIAP) is a potent caspase inhibitor, best known for its anti‐apoptotic function in cancer. During apoptosis, XIAP is antagonized by SMAC, which is released from the mitochondria upon caspase‐mediated activation of BID. Recent studies suggest that XIAP is involved in immune signaling. Here, we explore XIAP as an important mediator of an immune response against the enteroinvasive bacterium Shigella flexneri, both in vitro and in vivo. Our data demonstrate for the first time that Shigella evades the XIAP‐mediated immune response by inducing the BID‐dependent release of SMAC from the mitochondria. Unlike apoptotic stimuli, Shigella activates the calpain‐dependent cleavage of BID to trigger the release of SMAC, which antagonizes the inflammatory action of XIAP without inducing apoptosis. Our results demonstrate how the cellular death machinery can be subverted by an invasive pathogen to ensure bacterial colonization.

Memo has a novel role in S1P signaling and crucial for vascular development

Memo is a conserved protein that was identified as an essential mediator of tumor cell motility induced by receptor tyrosine kinase activation. Here we show that Memo null mouse embryonic fibroblasts (MEFs) are impaired in PDGF-induced migration and this is due to a defect in sphingosine-1-phosphate (S1P) signaling. S1P is a bioactive phospholipid produced in response to multiple stimuli, which regulates many cellular processes. S1P is secreted to the extracellular milieu where it exerts its function by binding a family of G-protein coupled receptors (S1PRs), causing their activation in an autocrine or paracrine manner. The process, termed cell-autonomous S1PR signaling, plays a role in survival and migration. Indeed, PDGF uses cell-autonomous S1PR signaling to promote cell migration; we show here that this S1P pathway requires Memo. Using vascular endothelial cells (HUVECs) with Memo knock-down we show that their survival in conditions of serum-starvation is impaired. Furthermore, Memo loss in HUVECs causes a reduction of junctional VE-cadherin and an increase in sprout formation. Each of these phenotypes is rescued by S1P or S1P agonist addition, showing that Memo also plays an important role in cell-autonomous S1PR signaling in endothelial cells. We also produced conventional and endothelial cell-specific conditional Memo knock-out mouse strains and show that Memo is essential for embryonic development. Starting at E13.5 embryos of both strains display bleeding and other vascular problems, some of the phenotypes that have been described in mouse strains lacking S1PRs. The essential role of Memo in embryonic vascular development may be due in part to alterations in S1P signaling. Taken together our results show that Memo has a novel role in the S1P pathway and that Memo is needed to promote cell-autonomous S1PR activation.

[Adsorption therapy in sepsis.]

BACKGROUND The activation of multiple pro- and anti-inflammatory mediators is a key feature in the pathophysiology of sepsis. Many of these mediators may directly contribute to organ dysfunction and determine disease severity. So far our ability to modulate these upregulated mediator pathways is very limited. Therefore the adsorption of such mediators via an extracorporeal circuit may be a beneficial intervention during sepsis. OBJECTIVES Recent technical innovations have made this intervention feasible. Both systems for exclusive mediator adsorption and for adsorption beside a conventional renal replacement therapy are now available. Some of the membranes can adsorb a broad range of mediators by rather unspecific binding, whereas others specifically adsorb endotoxin or mediators. DISCUSSION Whilst biochemical efficacy could be demonstrated by some of the systems, controlled and randomized studies demonstrating improved clinical endpoints are still lacking. Therefore the use of such therapies outside clinical studies cannot yet be recommended.

Von Willebrand Factor Improves Risk Prediction in Addition to N-Terminal Pro-B-type Natriuretic Peptide in Patients Referred to Coronary Angiography and Signs and Symptoms of Heart Failure and Preserved Ejection Fraction.

BACKGROUND Heart failure with preserved ejection fraction (HFpEF) represents a growing health burden associated with substantial mortality and morbidity. Consequently, risk prediction is of highest importance. Endothelial dysfunction has been recently shown to play an important role in the complex pathophysiology of HFpEF. We therefore aimed to assess von Willebrand factor (vWF), a marker of endothelial damage, as potential biomarker for risk assessment in patients with HFpEF. METHODS AND RESULTS Concentrations of vWF were assessed in 457 patients with HFpEF enrolled as part of the LUdwigshafen Risk and Cardiovascular Health (LURIC) study. All-cause mortality was observed in 40% of patients during a median follow-up time of 9.7 years. vWF significantly predicted mortality with a hazard ratio (HR) per increase of 1 SD of 1.45 (95% confidence interval, 1.26-1.68; P<0.001) and remained a significant predictor after adjustment for age, sex, body mass index, N-terminal pro-B-type natriuretic peptide (NT-proBNP), renal function, and frequent HFpEF-related comorbidities (adjusted HR per 1 SD, 1.22; 95% confidence interval, 1.05-1.42; P=0.001). Most notably, vWF showed additional prognostic value beyond that achievable with NT-proBNP indicated by improvements in C-Statistic (vWF×NT-proBNP: 0.65 versus NT-proBNP: 0.63; P for comparison, 0.004) and category-free net reclassification index (37.6%; P<0.001). CONCLUSIONS vWF is an independent predictor of long-term outcome in patients with HFpEF, which is in line with endothelial dysfunction as potential mediator in the pathophysiology of HFpEF. In particular, combined assessment of vWF and NT-proBNP improved risk prediction in this vulnerable group of patients.

Dsh homolog DVL3 mediates resistance to IGFIR inhibition by regulating IGF-RAS signaling

Drugs that inhibit insulin-like growth factor 1 (IGFI) receptor IGFIR were encouraging in early trials, but predictive biomarkers were lacking and the drugs provided insufficient benefit in unselected patients. In this study, we used genetic screening and downstream validation to identify the WNT pathway element DVL3 as a mediator of resistance to IGFIR inhibition. Sensitivity to IGFIR inhibition was enhanced specifically in vitro and in vivo by genetic or pharmacologic blockade of DVL3. In breast and prostate cancer cells, sensitization tracked with enhanced MEK-ERK activation and relied upon MEK activity and DVL3 expression. Mechanistic investigations showed that DVL3 is present in an adaptor complex that links IGFIR to RAS, which includes Shc, growth factor receptor-bound-2 (Grb2), son-of-sevenless (SOS), and the tumor suppressor DAB2. Dual DVL and DAB2 blockade synergized in activating ERKs and sensitizing cells to IGFIR inhibition, suggesting a nonredundant role for DVL3 in the Shc-Grb2-SOS complex. Clinically, tumors that responded to IGFIR inhibition contained relatively lower levels of DVL3 protein than resistant tumors, and DVL3 levels in tumors correlated inversely with progression-free survival in patients treated with IGFIR antibodies. Because IGFIR does not contain activating mutations analogous to EGFR variants associated with response to EGFR inhibitors, we suggest that IGF signaling achieves an equivalent integration at the postreceptor level through adaptor protein complexes, influencing cellular dependence on the IGF axis and identifying a patient population with potential to benefit from IGFIR inhibition.

Early adolescents’ enjoyment experienced in learning situations at school and its relation to student achievement

While many studies confirm that positive emotions, including enjoyment, lead to better student achievement, less empirical evidence exists about possible mediator variables that link achievement to enjoyment. It is proposed that achievement and enjoyment form a circular dependency; enjoyment in learning leads to higher achievement but a degree of achievement is required to enjoy learning. This study provides insight into the reverse of the much studied enjoyment to achievement link and provides practical recommendations on how to use these findings. Founded in Control-value theory, which suggests that control and value cognitions are important variables that mediate the connection between enjoyment and achievement, this study explores the reciprocal achievement-cognition-enjoyment link. The reciprocal link was investigated by applying a one year longitudinal design to students of grade 6 and 7 (N = 356). This age group was chosen because early adolescence represents a critical period during which a strong decrease in positive learning emotions is observed. Part of the work involved identifying factors that might be responsible for this negative development. Results of cross-lagged path analysis identified reciprocal effects between student achievement and enjoyment with control and value cognitions functioning as partial mediators. High achievement goes with high control and value cognitions, which in turn positively affect enjoyment. However, cross-lagged correlations could only be partly confirmed. The results are discussed in terms of theoretical and practical implications

Expanding the Mutation Spectrum Affecting αIIbβ3 Integrin in Glanzmann Thrombasthenia: Screening of the ITGA2B and ITGB3 Genes in a Large International Cohort.

We report the largest international study on Glanzmann thrombasthenia (GT), an inherited bleeding disorder where defects of the ITGA2B and ITGB3 genes cause quantitative or qualitative defects of the αIIbβ3 integrin, a key mediator of platelet aggregation. Sequencing of the coding regions and splice sites of both genes in members of 76 affected families identified 78 genetic variants (55 novel) suspected to cause GT. Four large deletions or duplications were found by quantitative real-time PCR. Families with mutations in either gene were indistinguishable in terms of bleeding severity that varied even among siblings. Families were grouped into type I and the rarer type II or variant forms with residual αIIbβ3 expression. Variant forms helped identify genes encoding proteins mediating integrin activation. Splicing defects and stop codons were common for both ITGA2B and ITGB3 and essentially led to a reduced or absent αIIbβ3 expression; included was a heterozygous c.1440-13_c.1440-1del in intron 14 of ITGA2B causing exon skipping in 7 unrelated families. Molecular modeling revealed how many missense mutations induced subtle changes in αIIb and β3 domain structure across both subunits thereby interfering with integrin maturation and/or function. Our study extends knowledge of Glanzmann thrombasthenia and the pathophysiology of an integrin. This article is protected by copyright. All rights reserved.

A Missense Change in the ATG4D Gene Links Aberrant Autophagy to a Neurodegenerative Vacuolar Storage Disease.

Inherited neurodegenerative disorders are debilitating diseases that occur across different species. We have performed clinical, pathological and genetic studies to characterize a novel canine neurodegenerative disease present in the Lagotto Romagnolo dog breed. Affected dogs suffer from progressive cerebellar ataxia, sometimes accompanied by episodic nystagmus and behavioral changes. Histological examination revealed unique pathological changes, including profound neuronal cytoplasmic vacuolization in the nervous system, as well as spheroid formation and cytoplasmic aggregation of vacuoles in secretory epithelial tissues and mesenchymal cells. Genetic analyses uncovered a missense change, c.1288G>A; p.A430T, in the autophagy-related ATG4D gene on canine chromosome 20 with a highly significant disease association (p = 3.8 x 10-136) in a cohort of more than 2300 Lagotto Romagnolo dogs. ATG4D encodes a poorly characterized cysteine protease belonging to the macroautophagy pathway. Accordingly, our histological analyses indicated altered autophagic flux in affected tissues. The knockdown of the zebrafish homologue atg4da resulted in a widespread developmental disturbance and neurodegeneration in the central nervous system. Our study describes a previously unknown canine neurological disease with particular pathological features and implicates the ATG4D protein as an important autophagy mediator in neuronal homeostasis. The canine phenotype serves as a model to delineate the disease-causing pathological mechanism(s) and ATG4D function, and can also be used to explore treatment options. Furthermore, our results reveal a novel candidate gene for human neurodegeneration and enable the development of a genetic test for veterinary diagnostic and breeding purposes.