Reduced recognition of dynamic facial emotional expressions and emotion-specific response bias in children with an autism spectrum disorder.

Emotion labelling was evaluated in two matched samples of 6-14-year old children with and without an autism spectrum disorder (ASD; N = 45 and N = 50, resp.), using six dynamic facial expressions. The Emotion Recognition Task proved to be valuable demonstrating subtle emotion recognition difficulties in ASD, as we showed a general poorer emotion recognition performance, in addition to some emotion-specific impairments in the ASD group.

Outward-facing conformers of LacY stabilized by nanobodies.

The lactose permease of Escherichia coli (LacY), a highly dynamic polytopic membrane protein, catalyzes stoichiometric galactoside/H(+) symport by an alternating access mechanism and exhibits multiple conformations, the distribution of which is altered by sugar binding. We have developed single-domain camelid nanobodies (Nbs) against a LacY mutant in an outward (periplasmic)-open conformation to stabilize this state of the WT protein. Twelve purified Nbs inhibit lactose transport in right-side-out membrane vesicles, indicating that the Nbs recognize epitopes on the periplasmic side of LacY.

[Paroxysmal events after anxiety treatment with fluoxetine in a child with autism spectrum disorder].

Anxiety is common in children and adolescents with autism spectrum disorders and can cause severe dysfunction and suffering. An 11-year-old boy with an autism spectrum disorder and suffering from anxiety and mood problems responded positively to treatment with fluoxetine. After four weeks he developed clinically observable paroxysmal events accompanied by absence and confusion.

Fragile spectral and temporal auditory processing in adolescents with autism spectrum disorder and early language delay.

We investigated low-level auditory spectral and temporal processing in adolescents with autism spectrum disorder (ASD) and early language delay compared to matched typically developing controls. Auditory measures were designed to target right versus left auditory cortex processing (i.e.

Llama immunization with full-length VAR2CSA generates cross-reactive and inhibitory single-domain antibodies against the DBL1X domain.

VAR2CSA stands today as the leading vaccine candidate aiming to protect future pregnant women living in malaria endemic areas against the severe clinical outcomes of pregnancy associated malaria (PAM). The rational design of an efficient VAR2CSA-based vaccine relies on a profound understanding of the molecular interactions associated with P. falciparum infected erythrocyte sequestration in the placenta.

Prevalence of Autism Spectrum Disorder symptoms in children with neurofibromatosis type 1.

Neurofibromatosis type 1 (NF1) is an autosomal dominant genetic condition. While considerable work has focused on cognitive functioning, several research groups also observed difficulties in social functioning as a prominent feature of NF1. These problems and the possible link between NF1 and Autism Spectrum Disorder (ASD) have become increasingly important in recent NF1 literature.

Production, crystallization and preliminary X-ray diffraction of the Gαs α-helical domain in complex with a nanobody.

GPCR-G-protein complexes are one of the most important components of cell-signalling cascades. Extracellular signals are sensed by membrane-associated G-protein-coupled receptors (GPCRs) and transduced via G proteins towards intracellular effector molecules. Structural studies of these transient complexes are crucial to understand the molecular details of these interactions.

Visual processing in adolescents with autism spectrum disorder: evidence from embedded figures and configural superiority tests.

The embedded figures test has often been used to reveal weak central coherence in individuals with autism spectrum disorder (ASD). Here, we administered a more standardized automated version of the embedded figures test in combination with the configural superiority task, to investigate the effect of contextual modulation on local feature detection in 23 adolescents with ASD and 26 matched typically developing controls. On both tasks both groups performed largely similarly in terms of accuracy and reaction time, and both displayed the contextual modulation effect.

Crystal structure of a SLC11 (NRAMP) transporter reveals the basis for transition-metal ion transport.

Members of the SLC11 (NRAMP) family transport iron and other transition-metal ions across cellular membranes. These membrane proteins are present in all kingdoms of life with a high degree of sequence conservation. To gain insight into the determinants of ion selectivity, we have determined the crystal structure of Staphylococcus capitis DMT (ScaDMT), a close prokaryotic homolog of the family.

A complex Xp11.22 deletion in a patient with syndromic autism: exploration of FAM120C as a positional candidate gene for autism.

We present a male patient with sporadic Aarskog syndrome, cleft palate, mild intellectual disability, and autism spectrum disorder (ASD). A submicroscopic discontiguous deletion was detected on chromosome Xp11.2 encompassing FGD1, FAM120C, and PHF8.

Measuring quantitative autism traits in families: informant effect or intergenerational transmission?

Autism spectrum disorders (ASD) have a high degree of heritability, but there is still much debate about specific causal genes and pathways. To gain insight into patterns of transmission, research has focused on the relatedness of quantitative autism traits (QAT) between family members, mostly using questionnaires. Yet, different kinds of bias may influence research results.

Disruptive CHD8 mutations define a subtype of autism early in development.

Autism spectrum disorder (ASD) is a heterogeneous disease in which efforts to define subtypes behaviorally have met with limited success. Hypothesizing that genetically based subtype identification may prove more productive, we resequenced the ASD-associated gene CHD8 in 3,730 children with developmental delay or ASD. We identified a total of 15 independent mutations; no truncating events were identified in 8,792 controls, including 2,289 unaffected siblings.

The metabolic cooperation between cells in solid cancer tumors.

Cancer cells cooperate with stromal cells and use their environment to promote tumor growth. Energy production depends on nutrient availability and O₂ concentration. Well-oxygenated cells are highly proliferative and reorient the glucose metabolism towards biosynthesis, whereas glutamine oxidation replenishes the TCA cycle coupled with OXPHOS-ATP production.

Characterization of two homologous 2'-O-methyltransferases showing different specificities for their tRNA substrates.

The 2'-O-methylation of the nucleoside at position 32 of tRNA is found in organisms belonging to the three domains of life. Unrelated enzymes catalyzing this modification in Bacteria (TrmJ) and Eukarya (Trm7) have already been identified, but until now, no information is available for the archaeal enzyme. In this work we have identified the methyltransferase of the archaeon Sulfolobus acidocaldarius responsible for the 2'-O-methylation at position 32.

Association of CDH11 with non-syndromic ASD.

We report a sporadic patient with Autism Spectrum Disorder (ASD), mild intellectual disability and attention deficit hyperactivity disorder (ADHD) with a de novo partial deletion of CADHERIN 11 (CDH11). The deletion is associated with one of the breakpoints of a de novo complex chromosomal rearrangement 46,XY,t(3;16;5)(q29;q22;q15)inv4(p14;q21)ins(4;5)(q21;q14.3q15).

SAXS analysis of the tRNA-modifying enzyme complex MnmE/MnmG reveals a novel interaction mode and GTP-induced oligomerization.

Transfer ribonucleic acid (tRNA) modifications, especially at the wobble position, are crucial for proper and efficient protein translation. MnmE and MnmG form a protein complex that is implicated in the carboxymethylaminomethyl modification of wobble uridine (cmnm(5)U34) of certain tRNAs. MnmE is a G protein activated by dimerization (GAD), and active guanosine-5'-triphosphate (GTP) hydrolysis is required for the tRNA modification to occur.

Inhibition of ligand exchange kinetics via active-site trapping with an antibody fragment.

We describe the first example of an inhibitory antibody fragment (nanobody ca1697) that binds simultaneously to an enzyme (the enzyme dihydrofolate reductase from Escherichia coli) and its bound substrate (folate). Binding of the antibody to the substrate causes a 20-fold reduction in the rate of folate exchange kinetics. This work opens up the prospect of designing new types of antibody-based inhibitors of enzymes and receptors through suitable design of immunogens.

A general protocol for the generation of Nanobodies for structural biology.

There is growing interest in using antibodies as auxiliary tools to crystallize proteins. Here we describe a general protocol for the generation of Nanobodies to be used as crystallization chaperones for the structural investigation of diverse conformational states of flexible (membrane) proteins and complexes thereof. Our technology has a competitive advantage over other recombinant crystallization chaperones in that we fully exploit the natural humoral response against native antigens.

Altered functional connectivity of the language network in ASD: role of classical language areas and cerebellum.

The development of language, social interaction and communicative skills is remarkably different in the child with autism spectrum disorder (ASD). Atypical brain connectivity has frequently been reported in this patient population. However, the neural correlates underlying their disrupted language development and functioning are still poorly understood.

No differences in emotion recognition strategies in children with autism spectrum disorder: evidence from hybrid faces.

Emotion recognition problems are frequently reported in individuals with an autism spectrum disorder (ASD). However, this research area is characterized by inconsistent findings, with atypical emotion processing strategies possibly contributing to existing contradictions. In addition, an attenuated saliency of the eyes region is often demonstrated in ASD during face identity processing.

Crystal structure of the proteasomal deubiquitylation module Rpn8-Rpn11.

The ATP-dependent degradation of polyubiquitylated proteins by the 26S proteasome is essential for the maintenance of proteome stability and the regulation of a plethora of cellular processes. Degradation of substrates is preceded by the removal of polyubiquitin moieties through the isopeptidase activity of the subunit Rpn11. Here we describe three crystal structures of the heterodimer of the Mpr1-Pad1-N-terminal domains of Rpn8 and Rpn11, crystallized as a fusion protein in complex with a nanobody.

Metabolic treatment of cancer: intermediate results of a prospective case series.

Background: The combination of hydroxycitrate and lipoic acid has been demonstrated by several laboratories to be effective in reducing murine cancer growth.

Patients And Methods: All patients had failed standard chemotherapy and were offered only palliative care by their referring oncologist. Karnofsky status was between 50 and 80.

Probing the N-terminal β-sheet conversion in the crystal structure of the human prion protein bound to a nanobody.

Prions are fatal neurodegenerative transmissible agents causing several incurable illnesses in humans and animals. Prion diseases are caused by the structural conversion of the cellular prion protein, PrP(C), into its misfolded oligomeric form, known as prion or PrP(Sc). The canonical human PrP(C) (HuPrP) fold features an unstructured N-terminal part (residues 23-124) and a well-defined C-terminal globular domain (residues 125-231).

Brief report: Reduced grouping interference in children with ASD: evidence from a Multiple Object Tracking Task.

This study was inspired by the more locally oriented processing style in autism spectrum disorders (ASD). A modified multiple object tracking (MOT) task was administered to a group of children with and without ASD. Participants not only had to distinguish moving targets from distracters, but they also had to track targets when they were visually grouped to distracters, a manipulation which has a detrimental effect on tracking performance in adults.

Regulation of β2-adrenergic receptor function by conformationally selective single-domain intrabodies.

The biologic activity induced by ligand binding to orthosteric or allosteric sites on a G protein-coupled receptor (GPCR) is mediated by stabilization of specific receptor conformations. In the case of the β2 adrenergic receptor, these ligands are generally small-molecule agonists or antagonists. However, a monomeric single-domain antibody (nanobody) from the Camelid family was recently found to allosterically bind and stabilize an active conformation of the β2-adrenergic receptor (β2AR).