N-Heterocyclic carbene-stabilized gold nanoparticles with tunable sizes.

A simple and straightforward synthesis of N-heterocyclic carbene (NHC)-protected gold nanoparticles is derived from (benz)imidazolium-AuX4 complexes and NaBH4 only. The proposed method allows size tuning, from 3 to 6 nm, by adding (benz)imidazolium bromide. Changing the reducing agent to tBuNH2BH3 shifts the size range to ca. 6-12 nm. A one pot protocol is also reported from AuCl, (benz)imidazolium bromides and NaBH4, thereby providing an even more straightforward way of producing NHC-capped gold nanoparticles. In addition, X-ray photoelectron spectroscopy (XPS) is used to unambiguously evidence, on the nanoparticles, the covalent bond formed between the NHC and the surface gold atoms.

Chromosomal contacts connect loci associated with autism, BMI and head circumference phenotypes.

Copy number variants (CNVs) are major contributors to genomic imbalance disorders. Phenotyping of 137 unrelated deletion and reciprocal duplication carriers of the distal 16p11.2 220 kb BP2-BP3 interval showed that these rearrangements are associated with autism spectrum disorders and mirror phenotypes of obesity/underweight and macrocephaly/microcephaly. Such phenotypes were previously associated with rearrangements of the non-overlapping proximal 16p11.2 600 kb BP4-BP5 interval. These two CNV-prone regions at 16p11.2 are reciprocally engaged in complex chromatin looping, as successfully confirmed by 4C-seq, fluorescence in situ hybridization and Hi-C, as well as coordinated expression and regulation of encompassed genes. We observed that genes differentially expressed in 16p11.2 BP4-BP5 CNV carriers are concomitantly modified in their chromatin interactions, suggesting that disruption of chromatin interplays could participate in the observed phenotypes. We also identified cis- and trans-acting chromatin contacts to other genomic regions previously associated with analogous phenotypes. For example, we uncovered that individuals with reciprocal rearrangements of the trans-contacted 2p15 locus similarly display mirror phenotypes on head circumference and weight. Our results indicate that chromosomal contacts' maps could uncover functionally and clinically related genes.

16p11.2 Locus modulates response to satiety before the onset of obesity.

BACKGROUND: The 600 kb BP4-BP5 copy number variants (CNVs) at the 16p11.2 locus have been associated with a range of neurodevelopmental conditions including autism spectrum disorders and schizophrenia. The number of genomic copies in this region is inversely correlated with body mass index (BMI): the deletion is associated with a highly penetrant form of obesity (present in 50% of carriers by the age of 7 years and in 70% of adults), and the duplication with being underweight. Mechanisms underlying this energy imbalance remain unknown. OBJECTIVE: This study aims to investigate eating behavior, cognitive traits and their relationships with BMI in carriers of 16p11.2 CNVs. METHODS: We assessed individuals carrying a 16p11.2 deletion or duplication and their intrafamilial controls using food-related behavior questionnaires and cognitive measures. We also compared these carriers with cohorts of individuals presenting with obesity, binge eating disorder or bulimia. RESULTS: Response to satiety is gene dosage-dependent in pediatric CNV carriers. Altered satiety response is present in young deletion carriers before the onset of obesity. It remains altered in adolescent carriers and correlates with obesity. Adult deletion carriers exhibit eating behavior similar to that seen in a cohort of obesity without eating disorders such as bulimia or binge eating. None of the cognitive measures are associated with eating behavior or BMI. CONCLUSIONS: These findings suggest that abnormal satiety response is a strong contributor to the energy imbalance in 16p11.2 CNV carriers, and, akin to other genetic forms of obesity, altered satiety responsiveness in children precedes the increase in BMI observed later in adolescence.

The 16p11.2 locus modulates brain structures common to autism, schizophrenia and obesity.

Anatomical structures and mechanisms linking genes to neuropsychiatric disorders are not deciphered. Reciprocal copy number variants at the 16p11.2 BP4-BP5 locus offer a unique opportunity to study the intermediate phenotypes in carriers at high risk for autism spectrum disorder (ASD) or schizophrenia (SZ). We investigated the variation in brain anatomy in 16p11.2 deletion and duplication carriers. Beyond gene dosage effects on global brain metrics, we show that the number of genomic copies negatively correlated to the gray matter volume and white matter tissue properties in cortico-subcortical regions implicated in reward, language and social cognition. Despite the near absence of ASD or SZ diagnoses in our 16p11.2 cohort, the pattern of brain anatomy changes in carriers spatially overlaps with the well-established structural abnormalities in ASD and SZ. Using measures of peripheral mRNA levels, we confirm our genomic copy number findings. This combined molecular, neuroimaging and clinical approach, applied to larger datasets, will help interpret the relative contributions of genes to neuropsychiatric conditions by measuring their effect on local brain anatomy.

Emotional contagion for pain is intact in autism spectrum disorders.

Perceiving others in pain generally leads to empathic concern, consisting of both emotional and cognitive processes. Empathy deficits have been considered as an element contributing to social difficulties in individuals with autism spectrum disorders (ASD). Here, we used functional magnetic resonance imaging and short video clips of facial expressions of people experiencing pain to examine the neural substrates underlying the spontaneous empathic response to pain in autism. Thirty-eight adolescents and adults of normal intelligence diagnosed with ASD and 35 matched controls participated in the study. In contrast to general assumptions, we found no significant differences in brain activation between ASD individuals and controls during the perception of pain experienced by others. Both groups showed similar levels of activation in areas associated with pain sharing, evidencing the presence of emotional empathy and emotional contagion in participants with autism as well as in controls. Differences between groups could be observed at a more liberal statistical threshold, and revealed increased activations in areas involved in cognitive reappraisal in ASD participants compared with controls. Scores of emotional empathy were positively correlated with brain activation in areas involved in embodiment of pain in ASD group only. Our findings show that simulation mechanisms involved in emotional empathy are preserved in high-functioning individuals with autism, and suggest that increased reappraisal may have a role in their apparent lack of caring behavior.

Social reasoning skills in adults with Down syndrome: the role of language, executive functions and socio-emotional behaviour.

BACKGROUND: Although the prevalence of mental illness and behaviour problems is lower in adults with Down syndrome (DS) than in other populations with intellectual disabilities, they do present emotional and relational problems, as well as social integration difficulties. However, studies reporting on specific competences known to be central in developing appropriate social relationships (e.g. social reasoning, emotion processing, theory of mind) remain rare in the adult DS population and the mechanisms underlying these people's emotional and relational difficulties are unclear. METHOD: The present study investigated the ability to understand the appropriateness of others' social behaviour in 34 adults with DS, using the Social Resolution Task (SRT). Their results were compared with those of 34 typically developing (TD) children matched for gender and receptive vocabulary. The relationships among the SRT experimental task, cognitive competences (receptive and productive vocabulary, non-verbal reasoning, inhibition, selective attention) and a caregiver-rated measure of socio-emotional behaviour were examined in the DS group. RESULTS: The DS participants' global SRT scores did not differ from those of the controls. However, analyses of the SRT subscores revealed that the DS group identified significantly fewer inappropriate situations than the control group. Nevertheless, when they correctly identified the behaviour as inappropriate, they were as well as the controls to explain the rules underlying their responses. Regression analyses showed that receptive vocabulary and selective attention and a specific dimension of the socio-emotional profile (social relating skills) constituted the best predictors of the DS adults' performance on the SRT. CONCLUSIONS: The main findings show that the DS participants demonstrate relatively good social reasoning skills in comparison with TD children matched for verbal age. However, the two groups present distinctions in their response patterns, and the influence of cognitive variables on success on the SRT also appears different. While selective attention skills are found to be significant predictors for both groups, the influence of receptive vocabulary level is much stronger in the DS group. The implications of particular cognitive and socio-emotional factors for success on the SRT in this group are considered in more detail.