Dynamic Force Spectroscopy on Supported Lipid Bilayers: Effect ofTemperature and Sample Preparation

Biological membranes are constantly exposed to forces. The stress-strain relation in membranes determines thebehavior of many integral membrane proteins or other membrane related-proteins that show a mechanosensitive behavior. Here, we studied by force spectroscopy the behavior of supported lipid bilayers (SLBs) subjected to forces perpendicular to their plane. We measured the lipid bilayer mechanical properties and the force required for the punch-through event characteristic of atomic force spectroscopy on SLBs as a function of the interleaflet coupling. We found that for an uncoupled bilayer, the overall tip penetration occurs sequentially through the two leaflets, giving rise to two penetration events. In the case of a bilayer with coupled leaflets, penetration of the atomic force microscope tip always occurred in a single step. Considering the dependence of the jump-through force value on the tip speed, we also studied the process in the context of dynamic force spectroscopy (DFS). We performed DFS experiments by changing the temperature and cantilever spring constant, and analyzed the resultsin the context of the developed theories for DFS. We found that experiments performed at different temperatures and withdifferent cantilever spring constants enabled a more effective comparison of experimental data with theory in comparisonwith previously published data

The Vicious Cycle Towards Violence: Focus on the Negative Feedback Mechanisms of Brain Serotonin Neurotransmission

Violence can be defined as a form of escalated aggressive behavior that is expressed out of context and out of inhibitory control, and apparently has lost its adaptive function in social communication. Little is known about the social and environmental factors as well as the underlying neurobiological mechanisms involved in the shift of normal adaptive aggression into violence. In an effort to model the harmful acts of aggression and violence in humans, we recently (re)developed an animal model that is focused on engendering uncontrolled forms of maladaptive aggressive behavior in laboratory-bred feral rats and mice. We show that certain (8–12%) constitutionally aggressive individuals gradually develop, over the course of repetitive exposures to victorious social conflicts, escalated (short-latency, high-frequency and ferocious attacks), persistent (lack of attack inhibition by defeat/submission signals and perseverance of the aggressive attack-biting bout), indiscriminating (attacking female and anesthetized male intruders) and injurious (enhanced vulnerable-body region attacks and inflicted wounding) forms of offensive aggression. Based on the neurobiological results obtained using this model, a revised view is presented on the key role of central serotonergic (auto)regulatory mechanisms in this transition of normal aggression into violence

Development of violence in mice through repeated victory along with changes in prefrontal cortex neurochemistry

Recent reviews on the validity of rodent aggression models for human violence have addressed the dimension of pathological, maladaptive, violent forms of aggression in male rodent aggressive behaviour. Among the neurobiological mechanisms proposed for the regulation of aggressive behaviour in its normal and pathological forms, serotonin plays a major role. However, the results on the detailed mechanism are still confusing and controversial, mainly because of difficulties in extrapolating from rodent to human psychopathological behaviour. Our aim was to investigate the involvement of serotonin in pathological aggression. We subjected mice genetically selected for high (SAL, TA, NC900 lines) and low (LAL, TNA, NC100) aggression levels to a repeated resident-intruder experience (RRI mice) or to handling as a control procedure (CTR mice). Pathological aggression parameters we recorded were aggression towards females and lack of communication between the resident and its opponent. In the same mice, we measured the monoamine levels in the prefrontal cortex, a brain region strongly involved in the regulation of motivated behaviour. Our results show that SAL mice augmented their proneness to attack and showed the most pathological phenotype, with disregard of the opponent's sex, high territorial behavioural patterns, and low sensitivity to signals of subordination. In contrast, TA and NC900 augmented their proneness to attack and low discrimination of the opponent's signals, without showing offence towards females. After repeated resident-intruder experience, serotonin levels in the prefrontal cortex were significantly lower in SAL than in LAL whereas dopamine turnover was significantly higher, compared to CTR mice. Serotonin turnover was significantly reduced in all RRI mice, with no strain differences. Noradrenaline was significantly lower in aggressive mice of the TA and NC900 lines compared to their low-aggressive counterparts, with no effect of the repeated resident-intruder experience. We conclude that social experience changes prefrontal cortex neurochemistry and elicits pathologically aggressive phenotypes. (C) 2008 Elsevier B.V. All rights reserved

Exploring the boundaries in an interdisciplinary context through the Family Resemblance Approach: The Dialogue Between Physics and Mathematics

Among the relevant aspects of the family resemblance approach (FRA), our study focuses on the potential of the approach to elaborate on disciplinary identities in an interdisciplinary context, specifically regarding the interplay between physics and mathematics. We present and discuss how the FRA wheel can be used and intertwined with the framework of boundary objects and boundary crossing mechanisms (Akkerman & Bakker, Review of Educational Research, 81, 132–169, 2011), which is well-known in STEM education for dealing with interdisciplinarity. The role of the FRA discussed in the article is dual: both practical and theoretical. It is practical in that we show how its use, in combination with the Akkerman and Bakker framework, appears effective in fostering productive discussions among prospective teachers on disciplinary identities and interdisciplinarity in historical cases. It is theoretical in that the combination of the two frameworks provides the vocabulary to characterise the ‘ambiguous nature’ of interdisciplinarity: like boundaries, interdisciplinarity both separates disciplines, making their identities emerge, and connects them, fostering mechanisms of crossing and transgressing the boundaries. This empirical study reveals how the theoretical elaboration took advantage of the prospective teachers’ contributions. We initially presented the FRA to characterise disciplinary identities, but the prospective teachers highlighted its potential to characterise also the boundary zone and the dialogue between physics and mathematics. The data analysis showed that the combination of the two frameworks shaped a complex learning space where there was room for very different epistemic demands of the prospective teachers: from those who feel better within the identity cores of the disciplines, to those who like to inhabit the boundary zone and others who like to re-shape boundary spaces and move dynamically across them

Making sense of youth futures narratives: Recognition of emerging tensions in students' imagination of the future

In this era of great uncertainty, imagining the future may be challenging, especially for young people. In science education, the interest in future-oriented education is now emerging, research needs, however, to keep eyes on youngsters' future perceptions and on the development of a future literacy. In this article, starting from a sample of individual students' narratives about their future daily life in 2040, we aim to delineate which ways of grappling with the future can be observed in the essays and which methodological tools are suited to operationalize their identification and characterization. The analysis led to the definition of "polarization" and "complexification" attitudes that represent the ways in which the students' narratives are positioned with respect to a bunch of dichotomies: personal-societal, functional-aesthetics oriented, good-bad, natural-artificial, and certain-uncertain. Moreover, with this study, we provide a contribution to the methodological reflection that deals with the collection and analysis of data, when students' future perceptions need to be investigated. Discussing the limits of the current data collection tool, we introduce the design of a SenseMaker (R) questionnaire which contributed to feeding a collaboration with #OurFutures project, recently launched by the European Commission to collect future narratives all around Europe

Epidemiology of Strongyloides stercoralis in northern Italy: Results of a multicentre case-control study, February 2013 to July 2014

Strongyloides stercoralis is a soil-transmitted helminth widely diffused in tropical and subtropical regions of the world. Autochthonous cases have been also diagnosed sporadically in areas of temperate climate. We aimed at defining the epidemiology of strongyloidiasis in immigrants and Italians living in three northern Italian Regions. Screening for S. stercoralis infection was done with serology, confirmation tests were a second serological method or stool agar culture. A case-control approach was adopted and patients with a peripheral eosinophil count 65 500/mcL were classified as cases. Of 2,701 individuals enrolled here 1,351 were cases and 1,350 controls; 86% were Italians, 48% women. Italians testing positive were in 8% (97/1,137) cases and 1% (13/1,178) controls (adjusted odds ratio (aOR) 8.2; 95% confidence interval (CI): 4.5-14.8), while positive immigrants were in 17% (36/214) cases and in 2% (3/172) controls (aOR 9.6; 95% CI: 2.9-32.4). Factors associated with a higher risk of infection for all study participants were eosinophilia (p < 0.001) and immigration (p = 0.001). Overall, strongyloidiasis was nine-times more frequent in individuals with eosinophilia than in those with normal eosinophil count

Physiotherapists and Osteopaths’ Attitudes: Training in Management of Temporomandibular Disorders

Temporomandibular disorders (TMDs) are a condition which has multifactorial etiology. The most acknowledged method to classify TMDs is the diagnostic criteria (DC) introduced firstly by Dworkin. This protocol considers different aspects that are not only biological, but even psychosocial. Diagnosis is often based on anamnesis, physical examination and instrumental diagnosis. TMDs are classified as intra-articular and/or extra-articular disorders. Common signs and symptoms include jaw pain and dysfunction, earache, headache, facial pain, limitation to opening the mouth, ear pain and temporomandibular joint (TMJ) noises. This study regards two kind of clinicians that started in the last years to be more involved in the treatment of TMDs: osteopaths (OOs) and physiotherapists (PTs). The purpose is to analyze their attitude and clinical approach on patients affected by TMDs. Four hundred therapists answered an anonymous questionnaire regarding TMJ and TMDs. OOs showed greater knowledges on TMDs and TMJ and, the therapists with both qualifications seemed to be most confident in treating patients with TMDs. In conclusion this study highlights OOs and all the clinicians with this qualification, have a higher confidence in treating patients with TMD than the others. Dentists and orthodontists, according to this study, should co-work with OOs and PTs, because they are the specialists more requested by them than other kinds of specialists

Value of systolic pulmonary arterial pressure as a prognostic factor of death in the systemic sclerosis EUSTAR population.

The aim of this study was to assess the prognostic value of systolic pulmonary artery pressure (sPAP) estimated by echocardiography in the multinational European League Against Rheumatism Scleroderma Trial and Research (EUSTAR) cohort.Data for patients with echocardiography documented between 1 January 2005 and 31 December 2011 were extracted from the EUSTAR database. Stepwise forward multivariable statistical Cox pulmonary hypertension analysis was used to examine the independent effect on survival of selected variables.Based on our selection criteria, 1476 patients were included in the analysis; 87\% of patients were female, with a mean age of 56.3 years (s.d. 13.5) and 31\% had diffuse SSc. The mean duration of follow-up was 2.0 years (s.d. 1.2, median 1.9). Taking index sPAP of 50 mmHg. In a multivariable Cox model, sPAP and the diffusing capacity for carbon monoxide (DLCO) were independently associated with the risk of death [HR 1.833 (95\% CI 1.035, 3.247) and HR 0.973 (95\% CI 0.955, 0.991), respectively]. sPAP was an independent risk factor for death with a HR of 3.02 (95\% CI 1.91, 4.78) for sPAP ≥36 mmHg.An estimated sPAP >36 mmHg at baseline echocardiography was significantly and independently associated with reduced survival, regardless of the presence of pulmonary hypertension based on right heart catheterization

Peripheral SLC6A4 DNA Methylation Is Associated with In Vivo Measures of Human Brain Serotonin Synthesis and Childhood Physical Aggression

The main challenge in addressing the role of DNA methylation in human behaviour is the fact that the brain is inaccessible to epigenetic analysis in living humans. Using positron emission tomography (PET) measures of brain serotonin (5-HT) synthesis, we found in a longitudinal sample that adult males with high childhood-limited aggression (C-LHPA) had lower in vivo 5-HT synthesis in the orbitofrontal cortex (OBFC). Here we hypothesized that 5-HT alterations associated with childhood aggression were linked to differential DNA methylation of critical genes in the 5-HT pathway and these changes were also detectable in peripheral white blood cells. Using pyrosequencing, we determined the state of DNA methylation of SLC6A4 promoter in T cells and monocytes isolated from blood of cohort members (N = 25) who underwent a PET scan, and we examined whether methylation status in the blood is associated with in vivo brain 5-HT synthesis. Higher levels of methylation were observed in both T cells and monocytes at specific CpG sites in the C-LHPA group. DNA methylation of SLC6A4 in monocytes appears to be associated more reliably with group membership than T cells. In both cell types the methylation state of these CpGs was associated with lower in vivo measures of brain 5-HT synthesis in the left and right lateral OBFC (N = 20) where lower 5-HT synthesis in C-LHPA group was observed. Furthermore, in vitro methylation of the SLC6A4 promoter in a luciferase reporter construct suppresses its transcriptional activity supporting a functional role of DNA methylation in SLC6A4 promoter regulation. These findings indicate that state of SLC6A4 promoter methylation is altered in peripheral white blood cells of individuals with physical aggression during childhood. This supports the relevance of peripheral DNA methylation for brain function and suggests that peripheral SLC6A4 DNA methylation could be a marker of central 5-HT function