Generation of Functional CLL-Specific Cord Blood CTL Using CD40-Ligated CLL APC

PMCID: PMC3526610This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Atypical audiovisual speech integration in infants at risk for autism

The language difficulties often seen in individuals with autism might stem from an inability to integrate audiovisual information, a skill important for language development. We investigated whether 9-month-old siblings of older children with autism, who are at an increased risk of developing autism, are able to integrate audiovisual speech cues. We used an eye-tracker to record where infants looked when shown a screen displaying two faces of the same model, where one face is articulating/ba/and the other/ga/, with one face congruent with the syllable sound being presented simultaneously, the other face incongruent. This method was successful in showing that infants at low risk can integrate audiovisual speech: they looked for the same amount of time at the mouths in both the fusible visual/ga/− audio/ba/and the congruent visual/ba/− audio/ba/displays, indicating that the auditory and visual streams fuse into a McGurk-type of syllabic percept in the incongruent condition. It also showed that low-risk infants could perceive a mismatch between auditory and visual cues: they looked longer at the mouth in the mismatched, non-fusible visual/ba/− audio/ga/display compared with the congruent visual/ga/− audio/ga/display, demonstrating that they perceive an uncommon, and therefore interesting, speech-like percept when looking at the incongruent mouth (repeated ANOVA: displays x fusion/mismatch conditions interaction: F(1,16) = 17.153, p = 0.001). The looking behaviour of high-risk infants did not differ according to the type of display, suggesting difficulties in matching auditory and visual information (repeated ANOVA, displays x conditions interaction: F(1,25) = 0.09, p = 0.767), in contrast to low-risk infants (repeated ANOVA: displays x conditions x low/high-risk groups interaction: F(1,41) = 4.466, p = 0.041). In some cases this reduced ability might lead to the poor communication skills characteristic of autism

A genome-wide scan for common alleles affecting risk for autism

Although autism spectrum disorders (ASDs) have a substantial genetic basis, most of the known genetic risk has been traced to rare variants, principally copy number variants (CNVs). To identify common risk variation, the Autism Genome Project (AGP) Consortium genotyped 1558 rigorously defined ASD families for 1 million single-nucleotide polymorphisms (SNPs) and analyzed these SNP genotypes for association with ASD. In one of four primary association analyses, the association signal for marker rs4141463, located within MACROD2, crossed the genome-wide association significance threshold of P < 5 × 10−8. When a smaller replication sample was analyzed, the risk allele at rs4141463 was again over-transmitted; yet, consistent with the winner's curse, its effect size in the replication sample was much smaller; and, for the combined samples, the association signal barely fell below the P < 5 × 10−8 threshold. Exploratory analyses of phenotypic subtypes yielded no significant associations after correction for multiple testing. They did, however, yield strong signals within several genes, KIAA0564, PLD5, POU6F2, ST8SIA2 and TAF1C

Parent-reported and clinician-observed autism spectrum disorder (ASD) symptoms in children with attention deficit/hyperactivity disorder (ADHD): implications for practice under DSM-5

BACKGROUND: Children with attention deficit/hyperactivity disorder (ADHD) often present with social difficulties, though the extent to which these clearly overlap with symptoms of autism spectrum disorder (ASD) is not well understood. METHODS: We explored parent-reported and directly-observed ASD symptoms on the Autism Diagnostic Interview-Revised (ADI-R) and the Autism Diagnostic Observation Schedule (ADOS) in children referred to ASD-specialty clinics who received diagnoses of either ADHD (n = 48) or ASD (n = 164). RESULTS: Of the ADHD sample, 21 % met ASD cut-offs on the ADOS and 30 % met ASD cut-offs on all domains of the ADI-R. Four social communication ADOS items (Quality of Social Overtures, Unusual Eye Contact, Facial Expressions Directed to Examiner, and Amount of Reciprocal Social Communication) adequately differentiated the groups while none of the items on the ADI-R met the criteria for adequate discrimination. CONCLUSIONS: Results of this work highlight the challenges that clinicians and researchers face when distinguishing ASD from other disorders in verbally fluent, school-age children

Individual common variants exert weak effects on the risk for autism spectrum disorders.

While it is apparent that rare variation can play an important role in the genetic architecture of autism spectrum disorders (ASDs), the contribution of common variation to the risk of developing ASD is less clear. To produce a more comprehensive picture, we report Stage 2 of the Autism Genome Project genome-wide association study, adding 1301 ASD families and bringing the total to 2705 families analysed (Stages 1 and 2). In addition to evaluating the association of individual single nucleotide polymorphisms (SNPs), we also sought evidence that common variants, en masse, might affect the risk. Despite genotyping over a million SNPs covering the genome, no single SNP shows significant association with ASD or selected phenotypes at a genome-wide level. The SNP that achieves the smallest P-value from secondary analyses is rs1718101. It falls in CNTNAP2, a gene previously implicated in susceptibility for ASD. This SNP also shows modest association with age of word/phrase acquisition in ASD subjects, of interest because features of language development are also associated with other variation in CNTNAP2. In contrast, allele scores derived from the transmission of common alleles to Stage 1 cases significantly predict case status in the independent Stage 2 sample. Despite being significant, the variance explained by these allele scores was small (Vm&lt; 1%). Based on results from individual SNPs and their en masse effect on risk, as inferred from the allele score results, it is reasonable to conclude that common variants affect the risk for ASD but their individual effects are modest

The Impact of Hydrogen Bonding on Amide 1H Chemical Shift Anisotropy Studied by Cross-Correlated Relaxation and Liquid Crystal NMR Spectroscopy

Site-specific (1)H chemical shift anisotropy (CSA) tensors have been derived for the well-ordered backbone amide moieties in the B3 domain of protein G (GB3). Experimental input data include residual chemical shift anisotropy (RCSA), measured in six mutants that align differently relative to the static magnetic field when dissolved in a liquid crystalline Pf1 suspension, and cross-correlated relaxation rates between the (1)H(N) CSA tensor and either the (1)H-(15)N, the (1)H-(13)C&#39;, or the (1)H-(13)C(alpha) dipolar interactions. Analyses with the assumption that the (1)H(N) CSA tensor is symmetric with respect to the peptide plane (three-parameter fit) or without this premise (five-parameter fit) yield very similar results, confirming the robustness of the experimental input data, and that, to a good approximation, one of the principal components orients orthogonal to the peptide plane. (1)H(N) CSA tensors are found to deviate strongly from axial symmetry, with the most shielded tensor component roughly parallel to the N-H vector, and the least shielded component orthogonal to the peptide plane. DFT calculations on pairs of N-methyl acetamide and acetamide in H-bonded geometries taken from the GB3 X-ray structure correlate with experimental data and indicate that H-bonding effects dominate variations in the (1)H(N) CSA. Using experimentally derived (1)H(N) CSA tensors, the optimal relaxation interference effect needed for narrowest (1)H(N) TROSY line widths is found at similar to 1200 MHz