Different Gain/Loss Sensitivity and Social Adaptation Ability in Gifted Adolescents during a Public Goods Game

Gifted adolescents are considered to have high IQs with advanced mathematical and logical performances, but are often thought to suffer from social isolation or emotional mal-adaptation to the social group. The underlying mechanisms that cause stereotypic portrayals of gifted adolescents are not well known. We aimed to investigate behavioral performance of gifted adolescents during social decision-making tasks to assess their affective and social/non-social cognitive abilities. We examined cooperation behaviors of 22 gifted and 26 average adolescents during an iterative binary public goods (PG) game, a multi-player social interaction game, and analyzed strategic decision processes that include cooperation and free-riding. We found that the gifted adolescents were more cooperative than average adolescents. Particularly, comparing the strategies for the PG game between the two groups, gifted adolescents were less sensitive to loss, yet were more sensitive to gain. Additionally, the behavioral characteristics of average adolescents, such as low trust of the group and herding behavior, were not found in gifted adolescents. These results imply that gifted adolescents have a high cognitive ability but a low ability to process affective information or to adapt in social groups compared with average adolescents. We conclude that gain/loss sensitivity and the ability to adapt in social groups develop to different degrees in average and gifted adolescents

A network-based target overlap score for characterizing drug combinations: High correlation with cancer clinical trial results

Drug combinations are highly efficient in systemic treatment of complex multigene diseases such as cancer, diabetes, arthritis and hypertension. Most currently used combinations were found in empirical ways, which limits the speed of discovery for new and more effective combinations. Therefore, there is a substantial need for efficient and fast computational methods. Here, we present a principle that is based on the assumption that perturbations generated by multiple pharmaceutical agents propagate through an interaction network and can cause unexpected amplification at targets not immediately affected by the original drugs. In order to capture this phenomenon, we introduce a novel Target Overlap Score (TOS) that is defined for two pharmaceutical agents as the number of jointly perturbed targets divided by the number of all targets potentially affected by the two agents. We show that this measure is correlated with the known effects of beneficial and deleterious drug combinations taken from the DCDB, TTD and Drugs.com databases. We demonstrate the utility of TOS by correlating the score to the outcome of recent clinical trials evaluating trastuzumab, an effective anticancer agent utilized in combination with anthracycline- and taxane-based systemic chemotherapy in HER2-receptor (erb-b2 receptor tyrosine kinase 2) positive breast cancer. © 2015 Ligeti et al

Interactive Rhythmic Auditory Stimulation Reinstates Natural 1/f Timing in Gait of Parkinson's Patients

Parkinson's disease (PD) and basal ganglia dysfunction impair movement timing, which leads to gait instability and falls. Parkinsonian gait consists of random, disconnected stride times—rather than the 1/f structure observed in healthy gait—and this randomness of stride times (low fractal scaling) predicts falling. Walking with fixed-tempo Rhythmic Auditory Stimulation (RAS) can improve many aspects of gait timing; however, it lowers fractal scaling (away from healthy 1/f structure) and requires attention. Here we show that interactive rhythmic auditory stimulation reestablishes healthy gait dynamics in PD patients. In the experiment, PD patients and healthy participants walked with a) no auditory stimulation, b) fixed-tempo RAS, and c) interactive rhythmic auditory stimulation. The interactive system used foot sensors and nonlinear oscillators to track and mutually entrain with the human's step timing. Patients consistently synchronized with the interactive system, their fractal scaling returned to levels of healthy participants, and their gait felt more stable to them. Patients and healthy participants rarely synchronized with fixed-tempo RAS, and when they did synchronize their fractal scaling declined from healthy 1/f levels. Five minutes after removing the interactive rhythmic stimulation, the PD patients' gait retained high fractal scaling, suggesting that the interaction stabilized the internal rhythm generating system and reintegrated timing networks. The experiment demonstrates that complex interaction is important in the (re)emergence of 1/f structure in human behavior and that interactive rhythmic auditory stimulation is a promising therapeutic tool for improving gait of PD patients

Evolutionarily Conserved Substrate Substructures for Automated Annotation of Enzyme Superfamilies

The evolution of enzymes affects how well a species can adapt to new environmental conditions. During enzyme evolution, certain aspects of molecular function are conserved while other aspects can vary. Aspects of function that are more difficult to change or that need to be reused in multiple contexts are often conserved, while those that vary may indicate functions that are more easily changed or that are no longer required. In analogy to the study of conservation patterns in enzyme sequences and structures, we have examined the patterns of conservation and variation in enzyme function by analyzing graph isomorphisms among enzyme substrates of a large number of enzyme superfamilies. This systematic analysis of substrate substructures establishes the conservation patterns that typify individual superfamilies. Specifically, we determined the chemical substructures that are conserved among all known substrates of a superfamily and the substructures that are reacting in these substrates and then examined the relationship between the two. Across the 42 superfamilies that were analyzed, substantial variation was found in how much of the conserved substructure is reacting, suggesting that superfamilies may not be easily grouped into discrete and separable categories. Instead, our results suggest that many superfamilies may need to be treated individually for analyses of evolution, function prediction, and guiding enzyme engineering strategies. Annotating superfamilies with these conserved and reacting substructure patterns provides information that is orthogonal to information provided by studies of conservation in superfamily sequences and structures, thereby improving the precision with which we can predict the functions of enzymes of unknown function and direct studies in enzyme engineering. Because the method is automated, it is suitable for large-scale characterization and comparison of fundamental functional capabilities of both characterized and uncharacterized enzyme superfamilies

The Relationship between Phytoplankton Distribution and Water Column Characteristics in North West European Shelf Sea Waters

Phytoplankton underpin the marine food web in shelf seas, with some species having properties that are harmful to human health and coastal aquaculture. Pressures such as climate change and anthropogenic nutrient input are hypothesized to influence phytoplankton community composition and distribution. Yet the primary environmental drivers in shelf seas are poorly understood. To begin to address this in North Western European waters, the phytoplankton community composition was assessed in light of measured physical and chemical drivers during the “Ellett Line” cruise of autumn 2001 across the Scottish Continental shelf and into adjacent open Atlantic waters. Spatial variability existed in both phytoplankton and environmental conditions, with clear differences not only between on and off shelf stations but also between different on shelf locations. Temperature/salinity plots demonstrated different water masses existed in the region. In turn, principal component analysis (PCA), of the measured environmental conditions (temperature, salinity, water density and inorganic nutrient concentrations) clearly discriminated between shelf and oceanic stations on the basis of DIN∶DSi ratio that was correlated with both salinity and temperature. Discrimination between shelf stations was also related to this ratio, but also the concentration of DIN and DSi. The phytoplankton community was diatom dominated, with multidimensional scaling (MDS) demonstrating spatial variability in its composition. Redundancy analysis (RDA) was used to investigate the link between environment and the phytoplankton community. This demonstrated a significant relationship between community composition and water mass as indexed by salinity (whole community), and both salinity and DIN∶DSi (diatoms alone). Diatoms of the Pseudo-nitzschia seriata group occurred at densities potentially harmful to shellfish aquaculture, with the potential for toxicity being elevated by the likelihood of DSi limitation of growth at most stations and depths

Modulatory effects of heparin and short-length oligosaccharides of heparin on the metastasis and growth of LMD MDA-MB 231 breast cancer cells in vivo

Expression of the chemokine receptor CXCR4 allows breast cancer cells to migrate towards specific metastatic target sites which constitutively express CXCL12. In this study, we determined whether this interaction could be disrupted using short-chain length heparin oligosaccharides. Radioligand competition binding assays were performed using a range of heparin oligosaccharides to compete with polymeric heparin or heparan sulphate binding to I125 CXCL12. Heparin dodecasaccharides were found to be the minimal chain length required to efficiently bind CXCL12 (71% inhibition; P<0.001). These oligosaccharides also significantly inhibited CXCL12-induced migration of CXCR4-expressing LMD MDA-MB 231 breast cancer cells. In addition, heparin dodecasaccharides were found to have less anticoagulant activity than either a smaller quantity of polymeric heparin or a similar amount of the low molecular weight heparin pharmaceutical product, Tinzaparin. When given subcutaneously in a SCID mouse model of human breast cancer, heparin dodecasaccharides had no effect on the number of lung metastases, but did however inhibit (P<0.05) tumour growth (lesion area) compared to control groups. In contrast, polymeric heparin significantly inhibited both the number (P<0.001) and area of metastases, suggesting a differing mechanism for the action of polymeric and heparin-derived oligosaccharides in the inhibition of tumour growth and metastases

Essential Domains of Anaplasma phagocytophilum Invasins Utilized to Infect Mammalian Host Cells

Anaplasma phagocytophilum causes granulocytic anaplasmosis, an emerging disease of humans and domestic animals. The obligate intracellular bacterium uses its invasins OmpA, Asp14, and AipA to infect myeloid and non-phagocytic cells. Identifying the domains of these proteins that mediate binding and entry, and determining the molecular basis of their interactions with host cell receptors would significantly advance understanding of A. phagocytophilum infection. Here, we identified the OmpA binding domain as residues 59 to 74. Polyclonal antibody generated against a peptide spanning OmpA residues 59 to 74 inhibited A. phagocytophilum infection of host cells and binding to its receptor, sialyl Lewis x (sLex-capped P-selectin glycoprotein ligand 1. Molecular docking analyses predicted that OmpA residues G61 and K64 interact with the two sLex sugars that are important for infection, α2,3-sialic acid and α1,3-fucose. Amino acid substitution analyses demonstrated that K64 was necessary, and G61 was contributory, for recombinant OmpA to bind to host cells and competitively inhibit A. phagocytophilum infection. Adherence of OmpA to RF/6A endothelial cells, which express little to no sLex but express the structurally similar glycan, 6-sulfo-sLex, required α2,3-sialic acid and α1,3-fucose and was antagonized by 6-sulfo-sLex antibody. Binding and uptake of OmpA-coated latex beads by myeloid cells was sensitive to sialidase, fucosidase, and sLex antibody. The Asp14 binding domain was also defined, as antibody specific for residues 113 to 124 inhibited infection. Because OmpA, Asp14, and AipA each contribute to the infection process, it was rationalized that the most effective blocking approach would target all three. An antibody cocktail targeting the OmpA, Asp14, and AipA binding domains neutralized A. phagocytophilumbinding and infection of host cells. This study dissects OmpA-receptor interactions and demonstrates the effectiveness of binding domain-specific antibodies for blocking A. phagocytophilum infection

Healthcare professionals' intentions and behaviours: A systematic review of studies based on social cognitive theories

<p>Abstract</p> <p>Background</p> <p>There is an important gap between the implications of clinical research evidence and the routine clinical practice of healthcare professionals. Because individual decisions are often central to adoption of a clinical-related behaviour, more information about the cognitive mechanisms underlying behaviours is needed to improve behaviour change interventions targeting healthcare professionals. The aim of this study was to systematically review the published scientific literature about factors influencing health professionals' behaviours based on social cognitive theories. These theories refer to theories where individual cognitions/thoughts are viewed as processes intervening between observable stimuli and responses in real world situations.</p> <p>Methods</p> <p>We searched psycINFO, MEDLINE, EMBASE, CIHNAL, Index to theses, PROQUEST dissertations and theses and Current Contents for articles published in English only. We included studies that aimed to predict healthcare professionals' intentions and behaviours with a clear specification of relying on a social cognitive theory. Information on percent of explained variance (R²) was used to compute the overall frequency-weighted mean R²to evaluate the efficacy of prediction in several contexts and according to different methodological aspects. The cognitive factors most consistently associated with prediction of healthcare professionals' intention and behaviours were documented.</p> <p>Results</p> <p>Seventy eight studies met the inclusion criteria. Among these studies, 72 provided information on the determinants of intention and 16 prospective studies provided information on the determinants of behaviour. The theory most often used as reference was the Theory of Reasoned Action (TRA) or its extension the Theory of Planned Behaviour (TPB). An overall frequency-weighted mean R²of 0.31 was observed for the prediction of behaviour; 0.59 for the prediction of intention. A number of moderators influenced the efficacy of prediction; frequency-weighted mean R²varied from 0.001 to 0.58 for behaviour and 0.19 to 0.81 for intention.</p> <p>Conclusion</p> <p>Our results suggest that the TPB appears to be an appropriate theory to predict behaviour whereas other theories better capture the dynamic underlying intention. In addition, given the variations in efficacy of prediction, special care should be given to methodological issues, especially to better define the context of behaviour performance.</p

Influenza vaccination for immunocompromised patients: systematic review and meta-analysis from a public health policy perspective.

Immunocompromised patients are vulnerable to severe or complicated influenza infection. Vaccination is widely recommended for this group. This systematic review and meta-analysis assesses influenza vaccination for immunocompromised patients in terms of preventing influenza-like illness and laboratory confirmed influenza, serological response and adverse events