Greater response variability in adolescents is associated with increased white matter development.

Adolescence is a period of learning, exploration, and continuous adaptation to fluctuating environments. Response variability during adolescence is an important, understudied, and developmentally appropriate behavior. The purpose of this study was to identify the association between performance on a dynamic risky decision making task and white matter microstructure in a sample of 48 adolescents (14-16 years). Individuals with the greatest response variability on the task obtained the widest range of experience with potential outcomes to risky choice. When compared with their more behaviorally consistent peers, adolescents with greater response variability rated real-world examples of risk taking behaviors as less risky via self-report. Tract-Based Spatial Statistics (TBSS) were used to examine fractional anisotropy (FA) and mean diffusivity (MD). Greater FA in long-range, late-maturing tracts was associated with higher response variability. Greater FA and lower MD were associated with lower riskiness ratings of real-world risky behaviors. Results suggest that response variability and lower perceived risk attitudes of real-world risk are supported by neural maturation in adolescents

Frequency drives lexical access in reading but not in speaking: the frequency-lag hypothesis

To contrast mechanisms of lexical access in production versus comprehension we compared the effects of word frequency (high, low), context (none, low constraint, high constraint), and level of English proficiency (monolingual, Spanish-English bilingual, Dutch-English bilingual) on picture naming, lexical decision, and eye fixation times. Semantic constraint effects were larger in production than in reading. Frequency effects were larger in production than in reading without constraining context but larger in reading than in production with constraining context. Bilingual disadvantages were modulated by frequency in production but not in eye fixation times, were not smaller in low-constraint contexts, and were reduced by high-constraint contexts only in production and only at the lowest level of English proficiency. These results challenge existing accounts of bilingual disadvantages and reveal fundamentally different processes during lexical access across modalities, entailing a primarily semantically driven search in production but a frequency-driven search in comprehension. The apparently more interactive process in production than comprehension could simply reflect a greater number of frequency-sensitive processing stages in production

High-level production of animal-free recombinant transferrin from saccharomyces cerevisiae

<p>Abstract</p> <p>Background</p> <p>Animal-free recombinant proteins provide a safe and effective alternative to tissue or serum-derived products for both therapeutic and biomanufacturing applications. While recombinant insulin and albumin already exist to replace their human counterparts in cell culture media, until recently there has been no equivalent for serum transferrin.</p> <p>Results</p> <p>The first microbial system for the high-level secretion of a recombinant transferrin (rTf) has been developed from <it>Saccharomyces cerevisiae </it>strains originally engineered for the commercial production of recombinant human albumin (Novozymes' Recombumin^®USP-NF) and albumin fusion proteins (Novozymes' albufuse^®). A full-length non-N-linked glycosylated rTf was secreted at levels around ten-fold higher than from commonly used laboratory strains. Modification of the yeast 2 μm-based expression vector to allow overexpression of the ER chaperone, protein disulphide isomerase, further increased the secretion of rTf approximately twelve-fold in high cell density fermentation. The rTf produced was functionally equivalent to plasma-derived transferrin.</p> <p>Conclusions</p> <p>A <it>Saccharomyces cerevisiae </it>expression system has enabled the cGMP manufacture of an animal-free rTf for industrial cell culture application without the risk of prion and viral contamination, and provides a high-quality platform for the development of transferrin-based therapeutics.</p

Neural mechanisms of social influence in adolescence

During the transformative period of adolescence, social influence plays a prominent role in shaping young people’s emerging social identities, and can impact their propensity to engage in prosocial or risky behaviors. In this study, we examine the neural correlates of social influence from both parents and peers, two important sources of influence. Nineteen adolescents (age 16–18 years) completed a social influence task during a functional magnetic resonance imaging (fMRI) scan. Social influence from both sources evoked activity in brain regions implicated in mentalizing (medial prefrontal cortex, left temporoparietal junction, right temporoparietal junction), reward (ventromedial prefrontal cortex), and self-control (right ventrolateral prefrontal cortex). These results suggest that mental state reasoning, social reward and self-control processes may help adolescents to evaluate others’ perspectives and overcome the prepotent force of their own antecedent attitudes to shift their attitudes toward those of others. Findings suggest common neural networks involved in social influence from both parents and peers

Fifteen years of research on oral–facial–digital syndromes: from 1 to 16 causal genes

Oral–facial–digital syndromes (OFDS) gather rare genetic disorders characterised by facial, oral and digital abnormalities associated with a wide range of additional features (polycystic kidney disease, cerebral malformations and several others) to delineate a growing list of OFDS subtypes. The most frequent, OFD type I, is caused by a heterozygous mutation in the OFD1 gene encoding a centrosomal protein. The wide clinical heterogeneity of OFDS suggests the involvement of other ciliary genes. For 15 years, we have aimed to identify the molecular bases of OFDS. This effort has been greatly helped by the recent development of whole-exome sequencing (WES). Here, we present all our published and unpublished results for WES in 24 cases with OFDS. We identified causal variants in five new genes (C2CD3, TMEM107, INTU, KIAA0753 and IFT57) and related the clinical spectrum of four genes in other ciliopathies (C5orf42, TMEM138, TMEM231 and WDPCP) to OFDS. Mutations were also detected in two genes previously implicated in OFDS. Functional studies revealed the involvement of centriole elongation, transition zone and intraflagellar transport defects in OFDS, thus characterising three ciliary protein modules: the complex KIAA0753-FOPNL-OFD1, a regulator of centriole elongation; the Meckel-Gruber syndrome module, a major component of the transition zone; and the CPLANE complex necessary for IFT-A assembly. OFDS now appear to be a distinct subgroup of ciliopathies with wide heterogeneity, which makes the initial classification obsolete. A clinical classification restricted to the three frequent/well-delineated subtypes could be proposed, and for patients who do not fit one of these three main subtypes, a further classification could be based on the genotype