Ephrin-B1 transduces signals to activate integrin-mediated migration, attachment and angiogenesis.

Ephrin-B/EphB family proteins are implicated in bidirectional signaling and were initially defined through the function of their ectodomain sequences in activating EphB receptor tyrosine kinases. Ephrin-B1-3 are transmembrane proteins sharing highly conserved C-terminal cytoplasmic sequences. Here we use a soluble EphB1 ectodomain fusion protein (EphB1/Fc) to demonstrate that ephrin-B1 transduces signals that regulate cell attachment and migration. EphB1/Fc induced endothelial ephrin-B1 tyrosine phosphorylation, migration and integrin-mediated (alpha(v)beta(3) and alpha(5)beta(1)) attachment and promoted neovascularization, in vivo, in a mouse corneal micropocket assay. Activation of ephrin-B1 by EphB1/Fc induced phosphorylation of p46 JNK but not ERK-1/2 or p38 MAPkinases. By contrast, mutant ephrin-B1s bearing either a cytoplasmic deletion (ephrin-B1DeltaCy) or a deletion of four C-terminal amino acids (ephrin-B1DeltaPDZbd) fail to activate p46 JNK. Transient expression of intact ephin-B1 conferred EphB1/Fc migration responses on CHO cells, whereas the ephrin-B1DeltaCy and ephrin-B1DeltaPDZbd mutants were inactive. Thus ephrin-B1 transduces 'outside-in' signals through C-terminal protein interactions that affect integrin-mediated attachment and migration.

Surface densities of ephrin-B1 determine EphB1-coupled activation of cell attachment through alphavbeta3 and alpha5beta1 integrins.

Receptors of the Eph family and their ligands (ephrins) mediate developmental vascular assembly and direct axonal guidance. Migrating cell processes identify appropriate targets within migratory fields based on topographically displayed ephrin gradients. Here, EphB1 regulated cell attachment by discriminating the density at which ephrin-B1 was displayed on a reconstituted surface. EphB1-ephrin-B1 engagement did not promote cell attachment through mechanical tethering, but did activate integrin-mediated attachment. In endothelial cells, attachment to RGD peptides or fibrinogen was mediated through alphavbeta3 integrin. EphB1 transfection conferred ephrin-B1-responsive activation of alpha5beta1 integrin-mediated cell attachment in human embryonic kidney cells. Activation-competent but signaling-defective EphB1 point mutants failed to stimulate ephrin-B1 dependent attachment. These findings lead us to propose that EphB1 functions as a 'ligand density sensor' to signal integrin-mediated cell-matrix attachment.

A Biofilm Pocket Model to Evaluate Different Non-Surgical Periodontal Treatment Modalities in Terms of Biofilm Removal and Reformation, Surface Alterations and Attachment of Periodontal Ligament Fibroblasts.

BACKGROUND AND AIM There is a lack of suitable in vitro models to evaluate various treatment modalities intending to remove subgingival bacterial biofilm. Consequently, the aims of this in vitro-study were: a) to establish a pocket model enabling mechanical removal of biofilm and b) to evaluate repeated non-surgical periodontal treatment with respect to biofilm removal and reformation, surface alterations, tooth hard-substance-loss, and attachment of periodontal ligament (PDL) fibroblasts. MATERIAL AND METHODS Standardized human dentin specimens were colonized by multi-species biofilms for 3.5 days and subsequently placed into artificially created pockets. Non-surgical periodontal treatment was performed as follows: a) hand-instrumentation with curettes (CUR), b) ultrasonication (US), c) subgingival air-polishing using erythritol (EAP) and d) subgingival air-polishing using erythritol combined with chlorhexidine digluconate (EAP-CHX). The reduction and recolonization of bacterial counts, surface roughness (Ra and Rz), the caused tooth substance-loss (thickness) as well as the attachment of PDL fibroblasts were evaluated and statistically analyzed by means of ANOVA with Post-Hoc LSD. RESULTS After 5 treatments, bacterial reduction in biofilms was highest when applying EAP-CHX (4 log10). The lowest reduction was found after CUR (2 log10). Additionally, substance-loss was the highest when using CUR (128±40 µm) in comparison with US (14±12 µm), EAP (6±7 µm) and EAP-CHX (11±10) µm). Surface was roughened when using CUR and US. Surfaces exposed to US and to EAP attracted the highest numbers of PDL fibroblasts. CONCLUSION The established biofilm model simulating a periodontal pocket combined with interchangeable placements of test specimens with multi-species biofilms enables the evaluation of different non-surgical treatment modalities on biofilm removal and surface alterations. Compared to hand instrumentation the application of ultrasonication and of air-polishing with erythritol prevents from substance-loss and results in a smooth surface with nearly no residual biofilm that promotes the reattachment of PDL fibroblasts.

The human IgG anti-carbohydrate repertoire exhibits a universal architecture and contains specificity for microbial attachment sites.

Despite the paradigm that carbohydrates are T cell-independent antigens, isotype-switched glycan-specific immunoglobulin G (IgG) antibodies and polysaccharide-specific T cells are found in humans. We used a systems-level approach combined with glycan array technology to decipher the repertoire of carbohydrate-specific IgG antibodies in intravenous and subcutaneous immunoglobulin preparations. A strikingly universal architecture of this repertoire with modular organization among different donor populations revealed an association between immunogenicity or tolerance and particular structural features of glycans. Antibodies were identified with specificity not only for microbial antigens but also for a broad spectrum of host glycans that serve as attachment sites for viral and bacterial pathogens and/or exotoxins. Tumor-associated carbohydrate antigens were differentially detected by IgG antibodies, whereas non-IgG2 reactivity was predominantly absent. Our study highlights the power of systems biology approaches to analyze immune responses and reveals potential glycan antigen determinants that are relevant to vaccine design, diagnostic assays, and antibody-based therapies.

A new measure for party coherence: Applying a physics-based concept to the Swiss party system

The paper revives a theoretical definition of party coherence as being composed of two basic elements, cohesion and factionalism, to propose and apply a novel empirical measure based on spin physics. The simultaneous analysis of both components using a single measurement concept is applied to data representing the political beliefs of candidates in the Swiss general elections of 2003 and 2007, proposing a connection between the coherence of the beliefs party members hold and the assessment of parties being at risk of splitting. We also compare our measure with established polarization measures and demonstrate its advantage with respect to multi-dimensional data that lack clear structure. Furthermore, we outline how our analysis supports the distinction between bottom-up and top-down mechanisms of party splitting. In this way, we are able to turn the intuition of coherence into a defined quantitative concept that, additionally, offers a methodological basis for comparative research of party coherence. Our work serves as an example of how a complex systems approach allows to get a new perspective on a long-standing issue in political science.

Estimating Intra-Party Preferences: Comparing Speeches to Votes

Well-established methods exist for measuring party positions, but reliable means for estimating intra-party preferences remain underdeveloped. While most efforts focus on estimating the ideal points of individual legislators based on inductive scaling of roll call votes, this data suffers from two problems: selection bias due to unrecorded votes and strong party discipline, which tends to make voting a strategic rather than a sincere indication of preferences. By contrast, legislative speeches are relatively unconstrained, as party leaders are less likely to punish MPs for speaking freely as long as they vote with the party line. Yet, the differences between roll call estimations and text scalings remain essentially unexplored, despite the growing application of statistical analysis of textual data to measure policy preferences. Our paper addresses this lacuna by exploiting a rich feature of the Swiss legislature: on most bills, legislators both vote and speak many times. Using this data, we compare text-based scaling of ideal points to vote-based scaling from a crucial piece of energy legislation. Our findings confirm that text scalings reveal larger intra-party differences than roll calls. Using regression models, we further explain the differences between roll call and text scalings by attributing differences to constituency-level preferences for energy policy.

Similar outcome of upfront-unrelated and matched sibling stem cell transplantation in idiopathic paediatric aplastic anaemia. A study on behalf of the UK Paediatric BMT Working Party, Paediatric Diseases Working Party and Severe Aplastic Anaemia Working Party of EBMT

Abstract We explored the feasibility of unrelated donor haematopoietic stem cell transplant (HSCT) upfront without prior immunosuppressive therapy (IST) in paediatric idiopathic severe aplastic anaemia (SAA). This cohort was then compared to matched historical controls who had undergone first-line therapy with a matched sibling/family donor (MSD) HSCT (n = 87) or IST with horse antithymocyte globulin and ciclosporin (n = 58) or second-line therapy with unrelated donor HSCT post-failed IST (n = 24). The 2-year overall survival in the upfront cohort was 96 ± 4% compared to 91 ± 3% in the MSD controls (P = 0·30) and 94 ± 3% in the IST controls (P = 0·68) and 74 ± 9% in the unrelated donor HSCT post-IST failure controls (P = 0·02).The 2-year event-free survival in the upfront cohort was 92 ± 5% compared to 87 ± 4% in MSD controls (P = 0·37), 40 ± 7% in IST controls (P = 0·0001) and 74 ± 9% in the unrelated donor HSCT post-IST failure controls (n = 24) (P = 0·02). Outcomes for upfront-unrelated donor HSCT in paediatric idiopathic SAA were similar to MSD HSCT and superior to IST and unrelated donor HSCT post-IST failure. Front-line therapy with matched unrelated donor HSCT is a novel treatment approach and could be considered as first-line therapy in selected paediatric patients who lack a MSD. © 2015 John Wiley & Sons Ltd.

Dislocated Tongue Muscle Attachment and Cleft Palate Formation

In Pierre Robin sequence, a retracted tongue due to micrognathia is thought to physically obstruct palatal shelf elevation and thereby cause cleft palate. However, micrognathia is not always associated with palatal clefting. Here, by using the Bmp7-null mouse model presenting with cleft palate and severe micrognathia, we provide the first causative mechanism linking the two. In wild-type embryos, the genioglossus muscle, which mediates tongue protrusion, originates from the rostral process of Meckel's cartilage and later from the mandibular symphysis, with 2 tendons positive for Scleraxis messenger RNA. In E13.5 Bmp7-null embryos, a rostral process failed to form, and a mandibular symphysis was absent at E17.5. Consequently, the genioglossus muscle fibers were diverted toward the lingual surface of Meckel's cartilage and mandibles, where they attached in an aponeurosis that ectopically expressed Scleraxis. The deflection of genioglossus fibers from the anterior-posterior toward the medial-lateral axis alters their direction of contraction and necessarily compromises tongue protrusion. Since this muscle abnormality precedes palatal shelf elevation, it is likely to contribute to clefting. In contrast, embryos with a cranial mesenchyme-specific deletion of Bmp7 (Bmp7:Wnt1-Cre) exhibited some degree of micrognathia but no cleft palate. In these embryos, a rostral process was present, indicating that mesenchyme-derived Bmp7 is dispensable for its formation. Moreover, the genioglossus appeared normal in Bmp7:Wnt1-Cre embryos, further supporting a role of aberrant tongue muscle attachment in palatal clefting. We thus propose that in Pierre Robin sequence, palatal shelf elevation is not impaired simply by physical obstruction by the tongue but by a specific developmental defect that leads to functional changes in tongue movements.

Assessing perceptions of environmental risk and environmental justice and their impacts on neighborhood attachment in a predominately Hispanic community

This study examines and relates concepts from environmental risk perception and environmental justice and focuses on the perception of environmental problems, their consequent health risks and their impact on neighborhood attachment in a predominately Hispanic community along the U.S.-Mexico border. The findings indicate that the perception of environmental problems in the immediate area varies by problem and demographic subgroup. Ethnicity and income have the highest number of statistically significant associations across ten environmental problems. This result lies in the fact that Hispanics in El Paso County and those with low annual incomes live in neighborhoods that are faced with more severe environmental problems. Thus the findings lend support to the environmental justice claim that the poor and minorities bear the brunt of environmental degradation. ^ The findings also provide evidence that public perception of health risks from an environmental problem is influenced by the perceived severity of an environmental problem in the immediate area. Those who believe the problem is serious on a local level are the ones who are most likely to believe that they could become ill or injured from that problem and that the illness/injury will be serious. ^ The findings of this study also indicate that the young, Hispanics, those who perceive considerable environmental problems in their neighborhood, those who believe that their neighborhood has more environmental problems than others, and those who are angry about those problems are most likely to want to move from their neighborhood. ^ Efforts need to be made to enact policies and programs designed to reduce the environmental hazards in disadvantaged Hispanic communities along the U.S.-Mexico border. Future environmental education campaigns need to complement community-based projects with the media. Programs that involve and empower the community, particularly the youth, in improving the neighborhood could provide a sense of control and pride within their community in solving these problems. These neighborhood improvement efforts could also lead to the development and strengthening of social ties within the community, as well as enhanced community cohesiveness in tackling these problems. ^

Emotional Content in Autobiographical Memory through an Attachment Theory Framework

The current study investigates the relationship between individual differences in attachment style and the recall of autobiographical memories. According to attachment theory, affect regulation strategies employed by individuals high in attachment anxiety and high in attachment avoidance are likely to influence how information about the past is recalled. This study examines how attachment anxiety and attachment avoidance relate to the presence of negative emotions in autobiographical memories of upsetting events with important relationship figures (i.e., mother, father, or roommate). Participants included 248 undergraduate students ranging from ages 18-22 that attend a public university in the northeast. As hypothesized, individuals with an avoidant attachment expressed less sadness in their responses to the written narrative task, especially when prompted for memories involving their primary caregiver. Contrary to the hypothesis, anxiously attached individuals did not display higher levels of worry/fear emotions in their responses to the written narrative. Attachment anxiety was related to some differences in emotional content; however, this varied by relationship partner. The results provide evidence linking attachment style to emotion selection and retrieval in autobiographical memories of ‘upsetting’ events. Implications for close relationships and therapy are discussed.

Das geheime Bataillon : eine Untersuchung über das kommunistische Verhalten zur Labour-Party

von Harold J. Laski

Journeying Beyond the Balcony to the Block Party and Up to 50,000 Feet: Disparities in Children’s Health and Healthcare

Invited Commentary on “Observations from the Balcony: Directions for Pediatric Health Disparities Research and Policy".

Cyberbullying and school attachment: An analysis of the 2005-2006 U.S. health behavior in school-aged children (HBSC) study

Despite a lack of consistent research, the possible association between school attachment and cyberbullying suggests that targeting school attachment as a method of increasing help-seeking behaviors may be important in intervention strategies for cyberbullying. The present study sought to fill the gap in current literature by examining cyberbullying and school attachment in a nationally representative sample of U.S. adolescents, grades 6-10 (n=9,227). Results found that negative school attachment was significantly associated with greater odds of cyberbullying victimization (OR=4.71, p<0.001), perpetration (OR=2.95, p<0.001), and cyberbully-victim status (OR=3.38, p<0.001). After adjustment for confounding variables, cyberbullying victimization remained significant (OR=1.90, p=0.002). Overall, the present analyses suggest that higher negative school attachment may be associated with higher frequency of cyberbullying behaviors. These findings provide evidence for an association between school attachment and cyberbullying, and support considerations that improving school attachment may be a potential source of intervention against cyberbullying in an adolescent population.^