Examining The Genetic, Social-Cognitive, And Neural Correlates Of Autism Spectrum Disorder Behaviors In Typically Developing Chi

Autism spectrum disorders (ASD) are pervasive developmental disorders that affect approximately 1 in 50 children (Blumberg et al., 2013). Due to the social nature of the deficits that characterize the disorders, many have classified them as disorders of social cognition, which is the process that individuals use in order to successfully interact with members of their own species (Frith & Frith, 2007). Previous research has typically neglected the spectrum nature of ASD in favor of a more categorical approach of ¿autistic¿ versus ¿non-autistic,¿ but the spectrum requires a more continuous approach. Thus, the present study sought to examine the genetic, social-cognitive, and neural correlates of ASD-like traits as well as the relationship between these dimensions in typically developing children. Parents and children completed several quantitative measures examining several areas of social-cognitive functioning, including theory of mind and social functioning, restricted/repetitive behaviors and interests, and adaptive/maladaptive functioning. Children were also asked to undergo an EEG and both parents and children contributed a saliva sample that was used to sequence four single nucleotide polymorphisms (SNPs) of the OXTR gene, rs1042778, rs53576, rs2254298, and rs237897. We successfully demonstrated a significant relationship between behavioral measures of social-cognition and differences in face perception via the N170. However, the directionality of these relationships varied based on the behavioral measure and particular N170 difference scores. We also found support for the associations between the G_G allelic combination of rs1042778 and the A_A and A_G allelic combinations of rs2254298 and increased ASD-like behavior with decreased social-cognitive functioning. In contrast, our results contradict previous findings with rs237897 and imply that individuals with the A_A and A_G genotypes are less similar to those with ASD and have higher social cognitive functioning than those with the G_G genotype. In conclusion, we have demonstrated the existence of ASD-like traits in typically developing children and have shown a link between behavioral, genetic, and neural correlates of social-cognition. These findings demonstrate the importance of considering autism as a spectrum disorder and provide support for the move to a more continuous approach to neurodevelopmental disorders.

Aspiration toxicology of hydrocarbons and lamp oils studied by in vitro technology

Medical literature regularly reports on accidental poisoning in children after aspiration of combustibles such as lamp oils which usually contain hydrocarbons or rape methyl esters (RMEs). We aimed to analyze the toxic potential of alkanes and different combustible classes in vitro with regard to biologic responses and mechanisms mediating toxicity. Two different in vitro models were used, i.e. (i) a captive bubble surfactometer (CBS) to assess direct influence of combustibles on biophysical properties of surfactant film and (ii) cell cultures (BEAS-2B and R3/1 cells, primary macrophages, re-differentiated epithelia) closely mimicking the inner lung surface. Biological endpoints included cell viability, cytotoxicity and inflammatory mediator release. CBS measurements demonstrate that combustibles affect film dynamics, i.e. the surface tension/area characteristics during compression and expansion, in a dose and molecular chain length dependent manner. Cell culture results confirm the dose dependent toxicity. Generally, cytotoxicity and cytokine release are higher in short-chained alkanes and hydrocarbon-based combustibles than in long-chained substances, e.g. highest inducible cytotoxicity in BEAS-2B was for hexane 84.6%, decane 74% and hexadecane 30.8%. Effects of RME-based combustibles differed between the cell models. Our results confirm data from animal experiments and give new insights into the mechanisms underlying the adverse health effects observed.

A deep dig--hindsight on Holocene vegetation composition from ancient environmental DNA

Want a glimpse at past vegetation? Studying pollen and other plant remains, which are preserved for example in lake sediments or mires for thousands of years, allows us to document regional occurrences of plant species over radiocarbon-dated time series. Such vegetation reconstructions derived from optical analyses of fossil samples are inherently incomplete because they only comprise taxa that contribute sufficient amounts of pollen, spores, macrofossil or other evidences. To complement optical analyses for paleoecological inference, molecular markers applied to ancient DNA (aDNA) may help in disclosing information hitherto inaccessible to biologists. Parducci et al. (2013) targeted aDNA from sediment cores of two lakes in the Scandes Mountains with generic primers in a meta-barcoding approach. When compared to palynological records from the same cores, respective taxon lists show remarkable differences in their compositions, but also in quantitative representation and in taxonomic resolution similar to a previous study (Jørgensen et al. 2012). While not free of assumptions that need critical and robust testing, notably the question of possible contamination, this study provides thrilling prospects to improve our knowledge about past vegetation composition, but also other organismic groups, stored as a biological treasure in the ground.

Handbook of LHC Higgs Cross Sections: 3. Higgs Properties. Report of the LHC Higgs Cross Section Working Group

This Report summarizes the results of the activities in 2012 and the first half of 2013 of the LHC Higgs Cross Section Working Group. The main goal of the working group was to present the state of the art of Higgs Physics at the LHC, integrating all new results that have appeared in the last few years. This report follows the first working group report Handbook of LHC Higgs Cross Sections: 1. Inclusive Observables (CERN-2011-002) and the second working group report Handbook of LHC Higgs Cross Sections: 2. Differential Distributions (CERN-2012-002). After the discovery of a Higgs boson at the LHC in mid-2012 this report focuses on refined prediction of Standard Model (SM) Higgs phenomenology around the experimentally observed value of 125-126 GeV, refined predictions for heavy SM-like Higgs bosons as well as predictions in the Minimal Supersymmetric Standard Model and first steps to go beyond these models. The other main focus is on the extraction of the characteristics and properties of the newly discovered particle such as couplings to SM particles, spin and CP-quantum numbers etc.

Present state of global wetland extent and wetland methane modelling: methodology of a model inter-comparison project (WETCHIMP)

The Wetland and Wetland CH4 Intercomparison of Models Project (WETCHIMP) was created to evaluate our present ability to simulate large-scale wetland characteristics and corresponding methane (CH4) emissions. A multi-model comparison is essential to evaluate the key uncertainties in the mechanisms and parameters leading to methane emissions. Ten modelling groups joined WETCHIMP to run eight global and two regional models with a common experimental protocol using the same climate and atmospheric carbon dioxide (CO2) forcing datasets. We reported the main conclusions from the intercomparison effort in a companion paper (Melton et al., 2013). Here we provide technical details for the six experiments, which included an equilibrium, a transient, and an optimized run plus three sensitivity experiments (temperature, precipitation, and atmospheric CO2 concentration). The diversity of approaches used by the models is summarized through a series of conceptual figures, and is used to evaluate the wide range of wetland extent and CH4 fluxes predicted by the models in the equilibrium run. We discuss relationships among the various approaches and patterns in consistencies of these model predictions. Within this group of models, there are three broad classes of methods used to estimate wetland extent: prescribed based on wetland distribution maps, prognostic relationships between hydrological states based on satellite observations, and explicit hydrological mass balances. A larger variety of approaches was used to estimate the net CH4 fluxes from wetland systems. Even though modelling of wetland extent and CH4 emissions has progressed significantly over recent decades, large uncertainties still exist when estimating CH4 emissions: there is little consensus on model structure or complexity due to knowledge gaps, different aims of the models, and the range of temporal and spatial resolutions of the models.

UPF1 RNA Immunoprecipitation from Mini-μ Construct–expressing Cells

UPF1, an RNA helicase and a core factor of nonsense-mediated mRNA decay (NMD), interacts with RNA independently of the sequence context. To investigate the influence of translation on the association of UPF1 with specific reporter transcripts, UPF1 RNA immunoprecipitations (RIPs) are performed from Hela cells that either express a normally translated immunoglobulin-µ (Ig-µ) reporter (mini µ) or a version with a stable stem loop in the 5' UTR (SL mini µ) that efficiently inhibit translation initiation (Zund et al., 2013). Both the cloning of the SL mini µ reporter construct and the UPF1 RIP experiment are described in detail.

Response of subfossil Cladocera in Gerzensee (Swiss Plateau) to early Late Glacial environmental change

Sub-fossil Cladocera were studied in a core from Gerzensee (Swiss Plateau) for the late-glacial periods of Oldest Dryas, Bølling, and Allerød. Cladocera assemblages were dominated by cold-tolerant littoral taxa Chydorus sphaericus, Acroperus harpae, Alonella nana, Alona affinis, and Alonella excisa. The rapid warming at the beginning of the Bølling (GI-1e) ca. 14,650 yr before present (BP: before AD 1950) was indicated by an abrupt 2‰ shift in carbonate δ18O and a clear change in pollen assemblages. Cladocera assemblages, in contrast, changed more gradually. C. sphaericus and A. harpae are the most cold-tolerant, and their abundance was highest in the earliest part of the record. Only 150–200 years after the beginning of the Bølling warming we observed an increase in less cold-tolerant A. excisa and A. affinis. The establishment of Alona guttata, A. guttata var. tuberculata, and Pleuroxus unicatus was delayed by ca. 350, 770, and 800 years respectively after the onset of the Bølling. The development of the Cladocera assemblages suggests increasing water temperatures during the Bølling/Allerød, which agrees with the interpretation by von Grafenstein et al. (2013-this issue) that decreasing δ18O values in carbonates in this period reflect increasing summer water temperatures at the sediment–water interface. Other processes also affected the Cladocera community, including the development and diversification of aquatic vegetation favourable for Cladocera. The record is clearly dominated by Chydoridae, as expected for a littoral core. Yet, the planktonic Eubosmina-group occurred throughout the core, with the exception of a period at ca. 13,760–13,420 yr BP. Lake levels reconstructed for this period are relatively low, indicating that the littoral location might have become too shallow for Eubosmina in that period.

The quiet eye and tasks demands: Do tougher shots need a quieter eye?

The Quiet Eye (QE; Vickers 1996) has been shown to underpin successful performance, differentiating both expertise (inter-individual) and proficiency (intra-individual), with experts and successful attempts characterised by longer QE durations. The QE is proposed to reflect the time needed to organise and fine tune the parameters of movement (e.g. force and direction). In order to examine this prediction and build upon previous research we experimentally manipulated the difficulty of a golf putting task; we hypothesised that if the QE is related to motor programming then a more difficult task should be associated with longer QE durations. 33 golfers (M age= 21.16, SD= 3.98) with an average handicap of 6.5 (SD= 6.02) performed putts in 4 conditions of increasing difficulty. We manipulated the length of the golf putt (short-4ft, long-8ft) and the contact point of the putter head (large-1.7cm, small-0.5cm,) giving increasingly difficult putting conditions of short-large [1], short-small [2], long-large [3] and long-small [4]. We measured performance (radial error from hole in cm) and QE (in ms) for 10 putts in each condition. A repeated measures ANOVA was performed on the performance and QE data. The performance data suggest that we were successful in increasing the difficulty of the task (F (3,93) = 26.46. p = .000), with the best performance in condition [1] (8.57cm), followed by [2] (9.10cm) followed by [3] (16.11cm) and finally the worst performance was in condition [4] (23.40cm). The QE data suggest that, in keeping with our hypothesis, the QE was lengthened as task difficulty increased (F (3,87) = 11.91, p = .043). The QE was shortest in condition [1] (1787.85ms) and increased to condition [2] (1939.78ms) and condition [3] (2076.51ms), with the longest QE in condition [4] (2164.08ms). More detailed analysis of the QE reveal that it was the proportion of the QE that occurred before movement initiation (pre-QE) which increased with shot difficulty, rather than the proportion that occurred during the swing (Online-QE; see Vine et al., 2013). Results support the notion that more complex tasks are associated with a longer QE duration, specifically participants appear to spend longer fixating the target prior to movement. This likely reflects the time needed to process visual information gathered in a pre-performance routine, to inhibit external distraction, and to pre-programme the increasingly difficult parameters of the movement. Vickers, J.N. (1996). Visual control when aiming at a far target. Journal of Experimental Psychology: Human Perception and Performance, 22, 342-354. Vine, S.J. et al. (2013). Quiet eye and choking: Online control breaks down at the point of performance failure. Medicine and Science in Sports and Exercise, 45, 1988-1994.

The brain’s pre-stimulus default state interacts with working memory in a load-dependent manner

Recently, multiple studies showed that spatial and temporal features of a task-negative default mode network (DMN) (Greicius et al., 2003) are important markers for psychiatric diseases (Balsters et al., 2013). Another prominent indicator of cognitive functioning, yielding information about the mental condition in health and disease, is working memory (WM) processing. In EEG and MEG studies, frontal-midline theta power has been shown to increase with load during WM retention in healthy subjects (Brookes et al., 2011). Negative correlations between DMN activity and theta amplitude have been found during resting state (Jann et al., 2010) as well as during WM (Michels et al., 2010). Likewise, WM training resulted in higher resting state theta power as well as increased small-worldness of the resting brain (Langer et al., 2013). Further, increased fMRI connectivity between nodes of the DMN correlated with better WM performance (Hampson et al., 2006). Hence, the brain’s default state might influence it’s functioning during task. We therefore hypothesized correlations between pre-stimulus DMN activity and EEG-theta power during WM maintenance, depending on the WM load. 17 healthy subjects performed a Sternberg WM task while being measured simultaneously with EEG and fMRI. Data was recorded within a multicenter-study: 12 subjects were measured in Zurich with a 64-channels MR-compatible system (Brain Products) in a 3T Philips scanner, 5 subjects with a 96-channel MR-compatible system (Brain Products) in a 3T Siemens Scanner in Bern. The DMN components was obtained by a group BOLD-ICA approach over the full task duration (figure 1). The subject-wise dynamics were obtained by back-reconstructed onto each subject’s fMRI data and normalized to percent signal change values. The single trial pre-stimulus-DMN activation was then temporally correlated with the single trial EEG-theta (3-8 Hz) spectral power during retention intervals. This so-called covariance mapping (Jann et al., 2010) yielded the spatial distribution of the theta EEG fluctuations during retention associated with the dynamics of the pre-stimulus DMN. In line with previous findings, theta power was increased at frontal-midline electrodes in high- versus low-load conditions during early WM retention (figure 2). However, correlations of DMN with theta power resulted in primarily positive correlations in low-load conditions, while during high-load conditions negative correlations of DMN activity and theta power were observed at frontal-midline electrodes. This DMN-dependent load effect reached significance in the middle of the retention period (TANOVA, p<0.05) (figure 3). Our results show a complex and load-dependent interaction of pre-stimulus DMN activity and theta power during retention, varying over time. While at a more global, load-independent view pre-stimulus DMN activity correlated positively with theta power during retention, the correlation was inversed during certain time windows in high-load trials, meaning that in trials with enhanced pre-stimulus DMN activity theta power decreases during retention. Since both WM performance and DMN activity are markers of mental health our results could be important for further investigations of psychiatric populations.

Genetic Engineering of Induced Pluripotent Stem Cells and Reprogramming to Motor Neurons to Elucidate Selective Motor Neuron Death in Amyotrophic Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is a progressive motor neuron disease, fatal within 1 to 5 years after onset of symptoms. About 3 out of 100’000 persons are diagnosed with ALS and there is still no cure available [1, 2]. 95% of all cases occur sporadically and the aetiology remains largely unknown [3]. However, up to now 16 genes were identified to play a role in the development of familial ALS. One of these genes is FUS that encodes for the protein fused in sarcoma (FUS). Mutations in this gene are responsible for some cases of sporadic as well as of inherited ALS [4]. FUS belongs to the family of heterogeneous nuclear ribonucleoproteins and is predicted to be involved in several cellular functions like transcription regulation, RNA splicing, mRNA transport in neurons and microRNA processing [5] Aberrant accumulation of mutated FUS has been found in the cytoplasm of motor neurons from ALS patients [6]. The mislocalization of FUS is based on a mutation in the nuclear localization signal of FUS [7]. However, it is still unclear if the cytoplasmic localization of FUS leads to a toxic gain of cytoplasmic function and/or a loss of nuclear function that might be crucial in the course of ALS. The goal of this project is to characterize the impact of ALS-associated FUS mutations on in vitro differentiated motor neurons. To this end, we edit the genome of induced pluripotent stem cells (iPSC) using transcription activator-like effector nucleases (TALENs) [8,9] to create three isogenic cell lines, each carrying an ALS-associated FUS mutation (G156E, R244C and P525L). These iPSC’s will then be differentiated to motor neurons according to a recently established protocol [10] and serve to study alterations in the transcriptome, proteome and metabolome upon the expression of ALS-associated FUS. With this approach, we hope to unravel the molecular mechanism leading to FUS-associated ALS and to provide new insight into the emerging connection between misregulation of RNA metabolism and neurodegeneration, a connection that is currently implied in a variety of additional neurological diseases, including spinocerebellar ataxia 2 (SCA-2), spinal muscular atrophy (SMA), fragile X syndrome, and myotonic dystrophy. [1] Cleveland, D.W. et al. (2001) Nat Rev Neurosci 2(11): 806-819 [2] Sathasivam, S. (2010) Singapore Med J 51(5): 367-372 [3] Schymick, J.C. et al. (2007) Hum Mol Genet Vol 16: 233-242 [4] Pratt, A.J. et al. (2012). Degener Neurol Neuromuscul Dis 2012(2): 1-14 [5] Lagier-Tourenne, C. Hum Mol Genet, 2010. 19(R1): p. R46-64 [6] Mochizuki, Y. et al. (2012) J Neurol Sci 323(1-2): 85-92 [7] Dormann, D. et al. (2010) EMBO J 29(16): 2841-2857 [8] Hockemeyer, D. et al. (2011) Nat Biotech 29(8): 731-734 [9] Joung, J.K. and J.D. Sander (2013) Nat Rev Mol Cell Biol 14(1): 49-55 [10]Amoroso, M.W. et al. (2013) J Neurosci 33(2): 574-586.

CTIF is involved in mRNA export in human cells

In eukaryotic cells translation initiation of messenger RNA (mRNA) transcripts can be initiated either by the cap-binding complex (CBC) consisting of CBP80 and CBP20, or by the eukaryotic translation initiation factor (eIF) 4E. Together with eIF4G and eIF4A, eIF4E forms the eIF4F-complex, which mediates translation initiation during the bulk of cellular protein synthesis [1,2]. Functionally analogous to eIF4G, the CBP80/20-dependent translation initiation factor (CTIF) has been reported to be part of the CBC-dependent translation initiation complex [3,4]. CTIF consists of a N-terminal CBP80-binding domain and a conserved C-terminal MIF4G domain [3]. This MIF4G domain has been shown to mediate the interaction between CTIF and different factors such as eIF3g and the stem-loop binding protein (SLBP) [4,5]. Here we show data indicating that CTIF, besides its function in translation initiation, is involved in mRNA translocation from the nucleus to the cytoplasm, possibly through a direct interaction with the nuclear export factor NFX1/TAP. Taken together our results suggest that CTIF can function as a platform that interacts with proteins involved in different steps of the mRNA metabolism. [1] Haghighat A. and Sonenberg N. (1997) JBC 272:21677-21680 [2] Gross J.D. et al. (2003) Cell 115:739-750 [3] Kim K.M. et al. (2009) Genes Dev 23:2033-2045 [4] Choe J. et al. (2012) JBC 287:18500-18509 [5] Choe J. et al. (2013) NAR 41:1307-1318

What does professionalisation mean? Perceptions of professionalisation in swiss sport federations

Introduction: Organisational changes in sports federations are often associated with a drift from a volunteer driven to an increasingly business-like phenomenon (Shilbury & Ferkins, 2011). This process of transfor-mation is be called as “professionalization”. Accordingly, professionalization seems to be an appropriate strategy for sport organisations in order to meet organizational pressure due to challenges of a more complex and dynamic changing environment adequately. Despite the increasing research interest and the attempts for systematization on the phenomenon of professionalization it still remains unclear what does the term professionalization exactly mean (Dowling et al., 2014). Thus, there is a lack of a consistent concept of professionalization that is needed in order to explore different facets and perspectives of this phenomenon more validly. Against this background following question emerged: What is the suitable concept of professionalization for analyzing the actual ongoing processes of change, adaption or transformation in sport federations? Methods: Dealing with this question, following two-step approach was choosen: (1) In a first step a scholar’s perspective at professionalisation of sport organisations will be displayed in order to explore both the common ground as well as divergences and inconsistencies in previous approaches. Therefore, a literature review is indicated. (2) In a second step, and in contrast to previous studies we will consider a practical point of view by a so called second-order observation of experts to gain valuable insights into current thinking and acting towards professionalization in sport federations. In doing so, a hermeneutical approach is used, which is about understanding the meaning of contexts by grasping the everyday world, and draw insight and meaning from it (Shilbury et al., 2013). Accordance with hermeneutics, the explorative interpretive knowledge of expert interviews was used. The interviews were conducted with a sample of six selected experts, who have both dedicated insider knowledge and the overall view of all Swiss sport federations. Results and discussion: The summaries of literature review could be categorized into two research currents. The one defines professionalization as a structural process towards professional status of occupations. The other defines it in a broader sense as an organisational change towards a business-like approach. Whereas the first perspective there is a broad scientific consensus that second isn’t that clear, however. Explorative analysis of interview data reveals different themes in relation to professionalization of sports federation. First theme deals with a changed philosophy as more strategic alignment towards for-profit, efficiency and quality orientation. Second theme refers to paid work associated with more competence orientation and balanced governance between paid and voluntary work. Third theme deals with acting shift towards more rationalization and efficiency by implementation of innovative management and communication tools. Based on findings of both our review of scholar`s perspective as well insights from experts we will provide – in the sense of synthesis – a more clear understanding of what does professionalization mean that can be useful in terms of further studies. References: Dowling, M., Edwards, J. & Washington, M. (2014). Understanding the concept of professionalisation in sport management research. Sport Management Review, 17 (4), 520–529. Shilbury, D., Ferkins, L. & Smythe, L. (2013). Sport governance encounters: Insights from lived experiences. Sport Management Review, 16,349–363. Shilbury, D., & Ferkins, L. (2011). Professionalisation, sport governance and strategic capability. Managing Leisure, 16, 108–127.

Gender-Fair Language in Organizations: Attracting Potential Leaders and Promoting the Organizational Image of Gender Equality

In many languages, masculine generics are the traditional way of referring to women and men. However, gender-fair forms (e.g., feminine-masculine word pairs) can enhance gender equality: for instance, they counteract male biases in mental associations (Stahlberg et al., 2007) and evoke more neutral perceptions of gender-stereotypical professions (Merkel et al., 2013). Compared to masculine forms, use of gender-fair language in advertisements for leadership positions also helps to achieve gender equality in hiring decisions (e.g., use of German Geschäftsführerin/Geschäftsführer 'CEO fem/masc' instead of Geschäftsführer 'CEO masc', cf. Horvath & Sczesny, 2012). The present research investigates how potential applicants react to the use of gender-fair vs. masculine forms in German job ads for leadership positions (Study 1) and how the respective organization is perceived in response to these forms (Study 2). In Study 1, 251 participants showed higher intentions to apply for a leadership position when it was advertised with a feminine-masculine word pair instead of a masculine form; this was mediated by job appeal and organizational attraction. In Study 2, 154 participants perceived the organization as more discriminatory when masculine forms were used. This was mediated by the organizational image of gender equality. Thus, gender-fair language affects the social perception of a job and the respective organization and can impact social behavior in an organizational context.