Single nucleotide polymorphism rs6716901 in SLC25A12 gene is associated with Asperger syndrome

BACKGROUND: Autism Spectrum Conditions (ASC) are a group of developmental conditions which affect communication, social interactions and behaviour. Mitochondrial oxidative dysfunction has been suggested as a mechanism of autism based on the results of multiple genetic association and expression studies. SLC25A12 is a gene encoding a calcium-binding carrier protein that localizes to the mitochondria and is involved in the exchange of aspartate for glutamate in the inner membrane of the mitochondria regulating the cytosolic redox state. rs2056202 SNP in this gene has previously been associated with ASC. SNPs rs6716901 and rs3765166 analysed in this study have not been previously explored in association with AS. METHODS: We genotyped three SNPs (rs2056202, rs3765166, and rs6716901) in SLC25A12 in n?=?117 individuals with Asperger syndrome (AS) and n?=?426 controls, all of Caucasian ancestry. RESULTS: rs6716901 showed significant association with AS (P?=?0.008) after correcting for multiple testing. We did not replicate the previously identified association between rs2056202 and AS in our sample. Similarly, rs3765166 (P?=?0.11) showed no significant association with AS. CONCLUSION: The present study, in combination with previous studies, provides evidence for SLC25A12 as involved in the etiology of AS. Further cellular and molecular studies are required to elucidate the role of this gene in ASC.

Risk-taking and inhibitory control in behaviourally inhibited and disinhibited preschool children

The temperament style Behavioural Inhibition (BI) has been implicated as a risk factor for the development of internalising disorders such as anxiety. Of interest is what factors influence the developmental trajectories of both inhibited and disinhibited children and the development of psychopathology. One such factor is risk-taking behaviour. Using the computer based Balloon Analogue Risk Task, we assessed risk taking behaviour in behaviourally inhibited (n = 27) and behaviourally disinhibited (n = 43) children. This is the first study to examine the relationship between BI, executive functioning and risk-taking. The results indicated Behavioural Inhibition was not related to risk-taking but that inhibitory control predicted reward focused results. These findings illustrate how inhibitory control affects risk-taking and risk avoidance in both inhibited and disinhibited children.

Le développement de la prosodie dans le syndrome de Williams et le syndrome de Down chez des enfants de langue anglaise

The aim of the present study is to investigate the developmental profile of three aspects of prosody function, i.e. affect, focus and turn-endings in children with Williams and in those with Down’s syndrome compared to typically developing English speaking children. The tasks used were part of the computer-based battery, Profiling Elements of Prosody for Speech Communication (Peppe, McCann & Gibon, 2003). Cross-sectional developmental trajectories linking chronological and non-verbal mental age and affects and turn-ending functions of prosody were constructed. The results showed an atypical profile in both clinical populations. More interestingly, the profiles were atypical for different reasons, suggesting multiple and possibly different developmental pathways to the acquisition of prosody in these two populations.

FUNCTIONAL ALPHA-TROPOMYOSIN PRODUCED IN ESCHERICHIA-COLI - A DIPEPTIDE EXTENSION CAN SUBSTITUTE THE AMINO-TERMINAL ACETYL GROUP

Unlike the muscle protein, alpha-tropomyosin expressed in Escherichia coli does not bind actin, does not exhibit head-to-tail polymerization, and does not inhibit actomyosin ATPase activity in the absence of troponin. The only chemical difference between recombinant and muscle tropomyosins is that the first methionine is not acetylated in the recombinant protein (Hitchcock-DeGregori, S. E., and Heald, R. W. (1987) J. Biol. Chem. 262, 9730-9735). We expressed three fusion tropomyosins in E. coli with 2, 3, and 17 amino acids fused to its amino terminus. Ah three fusions restored actin binding, head-to-tail polymerization, and the capacity to inhibit the actomyosin ATPase to these unacetylated tropomyosins. Unlike larger fusions, the small fusions of 2 and 3 amino acids do not interfere with regulatory function. Therefore the presence of a fused dipeptide at the amino terminus of unacetylated tropomyosin is sufficient to replace the function of the N-acetyl group present in muscle tropomyosin. A structural interpretation for the function of the acetyl group, based on our results and the coiled coil structure of tropomyosin, is presented.

Optimal low-cost transfer to L4 and L5 lagrangian points based on G-family of periodic orbits

An alternative transfer strategy to send spacecrafts to stable orbits around the Lagrangian equilibrium points L4 and L5 based in trajectories derived from the periodic orbits around LI is presented in this work. The trajectories derived, called Trajectories G, are described and studied in terms of the initial generation requirements and their energy variations relative to the Earth through the passage by the lunar sphere of influence. Missions for insertion of spacecrafts in elliptic orbits around L4 and L5 are analysed considering the Restricted Three-Body Problem Earth- Moon-particle and the results are discussed starting from the thrust, time of flight and energy variation relative to the Earth. Copyright© (2012) by the International Astronautical Federation.

Grupo de apoiadores e cooperlix em Presidente Prudente-SP, Brasil: modelo e evolução de suas relações durante quinze anos

Pós-graduação em Geografia - FCT

Executive functions and their differential contribution to sustained attention in 5- to 8-year-old children

ABSTRACT Everyday routine in general and school settings in particular make high demands on children's abilities to sustain their focus of attention over longer time periods. School tasks thus require the child to accomplish the task on an appropriate level of performance while maintaining the focus of attention even under repetitious or distracting conditions. However, sustained attention (SA) may be a more heterogeneous construct than commonly assumed as it requires the individual not only to sustain attentional capacities but also to store and maintain the task rule (working memory), to inhibit inappropriate responses (inhibition), and to switch according to requirements (switching). It might thus involve processes counted among executive functions (EF). In the present study, performance in EF tasks (covering the core components inhibition, switching, and working memory) and in a SA task was assessed in 118 children, aged between 5;0 and 8;11 years. Similar age-dependent performance trajectories were found in EF components and SA, indicating ongoing performance improvements between 5 until at least 8 years of age in SA and in EF. Interrelations between single EF components and SA showed to be small to moderate. Finally, different patterns of SA performance predictions were found in age-homogeneous subgroups with inhibition being crucial for SA performance in the youngest and switching in the oldest age group. Taken as a whole, even though similarities in assumed developmental trajectories and substantial interrelations point to common underlying processes in EF and SA, age-dependent patterns of explained variance indicate clear discriminability.

The SasS -SasR two-component signal transduction system required for early Myxococcus xanthus multicellular *development

Initiation of Myxococcus xanthus multicellular development requires both nutrient limitation and high cell density. The extracellular signal, A signal, which consists of a set of amino acids at specific concentrations, serves as a cell density signal in M. xanthus early development. A reporter gene, designated 4521, that requires both starvation and A signal for developmental expression was used to identify mutations in the signal transduction pathways. A group of point mutations located in the chromosomal sasB locus that bypasses both requirements was previously isolated. One of these point mutations, sasB7, was mapped to the sasS gene, which is predicted to encode a transmembrane histidine protein kinase required for normal development. SasS is a positive regulator of 4521 and a candidate A signal sensor. This dissertation continues the characterization of the sasB locus, focusing on the sasR gene and the functional relationship of SasS and SasR. ^ The sasR gene is located 2.2-kb downstream of sasS. It is predicted to encode an NtrC-like response regulator, which belongs to the family of sigma54 transcriptional activators. SasR is a positive regulator of 4521 gene and is required for normal development. The sasR mutant displays phenotypes similar to that of sasS mutant. Both SasS and SasR are required for the A-signal-dependent 4521 expression. Genetic epistasis analysis indicates that SasR functions downstream of SasS. Biochemical studies show that SasS has autokinase activity, and phosphorylated SasS is able to transfer its phosphate to SasR. We propose that SasS and SasR form a two-component signal transduction system in the A signal transduction pathway. ^ To search for the genes regulated by SasS and SasR, expression patterns of a group of developmental genes were compared in wild-type and sasS null mutant backgrounds. SasS and SasR were found to positively regulate sasN and 4521. The sasN gene was previously identified as a negative regulator of 4521, located at about 170-bp downstream of sasR. It is required for normal fruiting body development. Based on the above data, a regulatory network consisting of sasS, sasR, sasN, and 4521 is hypothesized, and the interactions of the components in this network can now be further studied. ^

Grouping genetic operators for the delineation of functional areas based on spatial interaction

The delineation of functional economic areas, or market areas, is a problem of high practical relevance, since the delineation of functional sets such as economic areas in the US, Travel-to-Work Areas in the United Kingdom, and their counterparts in other OECD countries are the basis of many statistical operations and policy making decisions at local level. This is a combinatorial optimisation problem defined as the partition of a given set of indivisible spatial units (covering a territory) into regions characterised by being (a) self-contained and (b) cohesive, in terms of spatial interaction data (flows, relationships). Usually, each region must reach a minimum size and self-containment level, and must be continuous. Although these optimisation problems have been typically solved through greedy methods, a recent strand of the literature in this field has been concerned with the use of evolutionary algorithms with ad hoc operators. Although these algorithms have proved to be successful in improving the results of some of the more widely applied official procedures, they are so time consuming that cannot be applied directly to solve real-world problems. In this paper we propose a new set of group-based mutation operators, featuring general operations over disjoint groups, tailored to ensure that all the constraints are respected during the operation to improve efficiency. A comparative analysis of our results with those from previous approaches shows that the proposed algorithm systematically improves them in terms of both quality and processing time, something of crucial relevance since it allows dealing with most large, real-world problems in reasonable time.

Season-Long Examination of the Intervention Tone of Coach-Athlete Interactions and Athlete Development in Youth Sport

Objectives: Coaches are a primary influence on athletes' development in youth sport (Horn, 2008). However, the intervention tone of coaches' behaviour has not been directly observed. The purpose of this study was to examine associations between the intervention tone exhibited by youth sport coaches and athletes' individual developmental trajectories over the course of a season. Design: Short-term longitudinal study with behavioural observation. Method: Fifty-five athletes and their coaches from five youth volleyball teams were observed at three time points, and the intervention tone of interactive behaviour was systematically coded and organized by coach-athlete dyad. Athletes completed measures of the 4C's of athlete development (competence, confidence, connection, character) at each time point, which were used to create individualized developmental trajectories. Person-centred analyses were used to examine associations between athletes' developmental trajectories and their unique interactive experiences with their coach. Results: Cluster analysis revealed the presence of three distinct clusters based on athletes' developmental trajectories: 1) high and increasing, 2) low and decreasing, and 3) moderate and maintaining, with athletes from each team distributed across clusters. Analysis of dyadic interaction profiles revealed significant differences in interactive behaviour between clusters. Conclusions: Results suggest that differences in coach-athlete interactive experiences are associated with different developmental trajectories over the course of a season, even for athletes working with the same coach, highlighting the individualized nature of coaches' influence on young athletes. Practical implications for coaches include a critical awareness of their unique interactive relationship with each athlete independently, as well as the importance of fostering these relationships with regard to young people as more than just athletes.

Moderators of two Indicated Cognitive-Behavioral Depression Prevention Approaches for Adolescents in a School-Based Effectiveness Trial

Objective: Our aim was to identify moderators of the effects of a cognitive behavioral group-based prevention program (CB group) and CB bibliotherapy, relative to an educational brochure control condition and to one another, in a school-based effectiveness randomized controlled prevention trial. Method: 378 adolescents (M age ¼ 15.5, 68% female) with elevated depressive symptoms were randomized in one of three conditions and were assessed at pretest, posttest, and 6-month follow-up. We tested the moderating effect of three individual (baseline depressive symptoms, negative attributional style, substance use), three environmental (negative life events, parental support, peer support), and two sociodemographic (sex, age) characteristics. Results: Baseline depressive symptoms interacted with condition and time. Decomposition indicated that elevated baseline depressive symptoms amplified the effect of CB bibliotherapy at posttest (but not 6-month follow-up) relative to the control condition, but did not modify the effect of CB group relative to the control condition or relative to bibliotherapy. Specifically, CB bibliotherapy resulted in lower posttest depressive symptoms than the control condition in individuals with elevated, but not average or low baseline symptoms. We found no interaction effect for other putative moderators. Conclusions: Our findings suggest that bibliotherapy is effective only in participants who have elevated depressive symptoms at baseline. The fact that no study variable moderated the effects of CB group, which had a significant main effect in reducing depressive symptoms relative to the control condition, suggests that this indicated prevention intervention is effective for a wide range of adolescents.

Moderators of two Indicated Cognitive-Behavioral Depression Prevention Approaches for Adolescents in a School-Based Effectiveness Trial

Objective: Our aim was to identify moderators of the effects of a cognitive behavioral group-based prevention program (CB group) and CB bibliotherapy, relative to an educational brochure control condition and to one another, in a school-based effectiveness randomized controlled prevention trial. Method: 378 adolescents (M age ¼ 15.5, 68% female) with elevated depressive symptoms were randomized in one of three conditions and were assessed at pretest, posttest, and 6-month follow-up. We tested the moderating effect of three individual (baseline depressive symptoms, negative attributional style, substance use), three environmental (negative life events, parental support, peer support), and two sociodemographic (sex, age) characteristics. Results: Baseline depressive symptoms interacted with condition and time. Decomposition indicated that elevated baseline depressive symptoms amplified the effect of CB bibliotherapy at posttest (but not 6-month follow-up) relative to the control condition, but did not modify the effect of CB group relative to the control condition or relative to bibliotherapy. Specifically, CB bibliotherapy resulted in lower posttest depressive symptoms than the control condition in individuals with elevated, but not average or low baseline symptoms. We found no interaction effect for other putative moderators. Conclusions: Our findings suggest that bibliotherapy is effective only in participants who have elevated depressive symptoms at baseline. The fact that no study variable moderated the effects of CB group, which had a significant main effect in reducing depressive symptoms relative to the control condition, suggests that this indicated prevention intervention is effective for a wide range of adolescents.

A developmental dissociation of view-dependent and view-invariant object recognition in adolescence

Spatial generalization skills in school children aged 8-16 were studied with regard to unfamiliar objects that had been previously learned in a cross-modal priming and learning paradigm. We observed a developmental dissociation with younger children recognizing objects only from previously learnt perspectives whereas older children generalized acquired object knowledge to new viewpoints as well. Haptic and - to a lesser extent - visual priming improved spatial generalization in all but the youngest children. The data supports the idea of dissociable, view-dependent and view-invariant object representations with different developmental trajectories that are subject to modulatory effects of priming. Late-developing areas in the parietal or the prefrontal cortex may account for the retarded onset of view-invariant object recognition. © 2006 Elsevier B.V. All rights reserved.

Leadership and the negotiation of order in small groups

This thesis is focussed on the role differentiationhypothesis as it relates to small groups (Bales, 1958). The hypothesis is systematically examined, both conceptually and empirically, in the light of the Equilibrium Hypothesis (Bales, 1953) and the Negotiated Order Theory of leadership (e.g. Hosking, 1988). Chapter 1 sketches in a context for the research,which was stimulated by attempts during the 60s and 70s to organise small groups without leaders (the leaderless group, based on isocratic principles). Chapter 2 gives a conceptual and developmental overview of Bales' work, concentrating on the Equilibrium Hypothesis. It is argued that Bales' conceptual approach, if developed, can potentially integrate the disparate small groups and leadership literatures. Chapters 3 and 4 examine the concepts `group', `leader' and `leadership' in terms of the Negotiated Order perspective. In chapter 3 it is argued that two aspects of the concept group need to be taken separately into account; physical attributes and social psychological aspects (the metaphysical glue). It is further argued that a collection of people becomes a group only when they begin to establish a shared sense of social order. In chapter 4 it is argued that leadership is best viewed as a process of negotiation between those who influence and those who are influenced, in the context of shared values about means and ends. It is further argued that leadership is the process by which a shared sense of social order is established and maintained, thus linking the concepts `leadership' and `group' in a single formulation. The correspondences with Bales' approach are discussed at the end of the chapter. Chapters 5 to 8 present a detailed critical description and evaluation of the empirical work which claims to show role differentiation or test the hypothesis, both Bales original work and subsequent studies. It is argued here, that the measurement and analytical procedures adopted by Bales and others, in particular the use of simple means as summaries of group structures, are fundamentally flawed, and that role differentiation in relation to particular identifiable groups has not been demonstrated clearly anywhere in the literature. Chapters 9 to 13 present the empirical work conducted for the thesis. 18 small groups are examined systematically for evidence of role differentiation using an approach based on early sociometry (Moreno, 1934). The results suggest that role differentiation, as described by Bales, does not occur as often as is implied in the literature, and not equivocally in any case. In particular structures derived from Liking are typically distributed or weak. This suggests that one of Bales' principal findings, that Liking varies independently of his other main dimensions, is the product of statistical artifact. Chapter 14 presents a general summary of results and presents some considerations about future research.

Toddlers' prosocial behavior: from instrumental to empathic to altruistic helping.

The study explored how the meaning of prosocial behavior changes over toddlerhood. Sixty-five 18- and 30-month-olds could help an adult in 3 contexts: instrumental (action based), empathic (emotion based), and altruistic (costly). Children at both ages helped readily in instrumental tasks. For 18-month-olds, empathic helping was significantly more difficult than instrumental helping and required greater communication from the adult about her needs. Altruistic helping, which involved giving up an object of the child's own, was the most difficult for children at both ages. Findings suggest that over the 2nd year of life, prosocial behavior develops from relying on action understanding and explicit communications to understanding others' emotions from subtle cues. Developmental trajectories of social-cognitive and motivational components of early helping are discussed.