Association of a MET genetic variant with autism-associated maternal autoantibodies to fetal brain proteins and cytokine expression.

The contribution of peripheral immunity to autism spectrum disorders (ASDs) risk is debated and poorly understood. Some mothers of children with ASD have autoantibodies that react to fetal brain proteins, raising the possibility that a subset of ASD cases may be associated with a maternal antibody response during gestation. The mechanism by which the maternal immune system breaks tolerance has not been addressed. We hypothesized that the mechanism may involve decreased expression of the MET receptor tyrosine kinase, an ASD risk gene that also serves as a key negative regulator of immune responsiveness. In a sample of 365 mothers, including 202 mothers of children with ASD, the functional MET promoter variant rs1858830 C allele was strongly associated with the presence of an ASD-specific 37+73-kDa band pattern of maternal autoantibodies to fetal brain proteins (P=0.003). To determine the mechanism of this genetic association, we measured MET protein and cytokine production in freshly prepared peripheral blood mononuclear cells from 76 mothers of ASD and typically developing children. The MET rs1858830 C allele was significantly associated with MET protein expression (P=0.025). Moreover, decreased expression of the regulatory cytokine IL-10 was associated with both the MET gene C allele (P=0.001) and reduced MET protein levels (P=0.002). These results indicate genetic distinction among mothers who produce ASD-associated antibodies to fetal brain proteins, and suggest a potential mechanism for how a genetically determined decrease in MET protein production may lead to a reduction in immune regulation

New outcomes of Lewis base addition to diboranes(4): electronic effects override strong steric disincentives

Two surprising new outcomes of the reaction of Lewis bases with dihalodiboranes(4) are presented, including sp2–sp3 diboranes in which the Lewis base unit is bound to a highly sterically congested boron atom, and a rearranged double base adduct. The results provide a fuller understanding of the reactivity of diboranes, a poorly-understood class of molecule of critical importance to synthetic organic chemistry

Maternal antibodies from mothers of children with autism alter brain growth and social behavior development in the rhesus monkey.

Antibodies directed against fetal brain proteins of 37 and 73 kDa molecular weight are found in approximately 12% of mothers who have children with autism spectrum disorder (ASD), but not in mothers of typically developing children. This finding has raised the possibility that these immunoglobulin G (IgG) class antibodies cross the placenta during pregnancy and impact brain development, leading to one form of ASD. We evaluated the pathogenic potential of these antibodies by using a nonhuman primate model. IgG was isolated from mothers of children with ASD (IgG-ASD) and of typically developing children (IgG-CON). The purified IgG was administered to two groups of female rhesus monkeys (IgG-ASD; n=8 and IgG-CON; n=8) during the first and second trimesters of pregnancy. Another control group of pregnant monkeys (n=8) was untreated. Brain and behavioral development of the offspring were assessed for 2 years. Behavioral differences were first detected when the macaque mothers responded to their IgG-ASD offspring with heightened protectiveness during early development. As they matured, IgG-ASD offspring consistently deviated from species-typical social norms by more frequently approaching familiar peers. The increased approach was not reciprocated and did not lead to sustained social interactions. Even more striking, IgG-ASD offspring displayed inappropriate approach behavior to unfamiliar peers, clearly deviating from normal macaque social behavior. Longitudinal magnetic resonance imaging analyses revealed that male IgG-ASD offspring had enlarged brain volume compared with controls. White matter volume increases appeared to be driving the brain differences in the IgG-ASD offspring and these differences were most pronounced in the frontal lobes

Uncovering latent behaviors in ant colonies

Many biological systems exhibit collective behaviors that strengthen their adaptability to their environment, compared to more solitary species. Describing these behaviors is challenging yet necessary in order to understand these biological systems. We propose a probabilistic model that enables us to uncover the collective behaviors observed in a colony of ants. This model is based on the assumption that the behavior of an individual ant is a time-dependent mixture of latent behaviors that are specific to the whole colony. We apply this model to a large-scale dataset obtained by observing the mobility of nearly 1000 Camponotus fellah ants from six different colonies. Our results indicate that a colony typically exhibits three classes of behaviors, each characterized by a specific spatial distribution and a level of activity. Moreover, these spatial distributions, which are uncovered automatically by our model, match well with the ground truth as manually annotated by domain experts. We further explore the evolution of the behavior of individual ants and show that it is well captured by a second order Markov chain that encodes the fact that the future behavior of an ant depends not only on its current behavior but also on its preceding one

Enter exitrons

Staiger D, Simpson GG. Enter exitrons. Genome Biology. 2015;16(1): 136.Exitrons are exon-like introns located within protein-coding exons. Removal or retention of exitrons through alternative splicing increases proteome complexity and thus adds to phenotypic diversity

Superconformal constraints for QCD conformal anomalies

Anomalous superconformal Ward identities and commutator algebra in N = 1 super-Yang-Mills theory give rise to constraints between the QCD special conformal anomalies of conformal composite operators. We evaluate the superconformal anomalies that appear in the product of renormalized conformal operators and the trace anomaly in the supersymmetric spinor current and check the constraints at one-loop order. In this way we prove the universality of QCD conformal anomalies, which define the non-diagonal part of the anomalous dimension matrix responsible for scaling violations of exclusive QCD amplitudes at the next-to-leading order.Comment: 30 pages, 2 figures, LaTe

An SU(3) model for octet baryon and meson fragmentation

The production of the octet of baryons and mesons in e^+ e^- collisions is analysed, based on considerations of SU(3) symmetry and a simple model for SU(3) symmetry breaking in fragmentation functions. All fragmentation functions, D_q^h(x, Q^2), describing the fragmentation of quarks into a member of the baryon octet (and similarly for fragmentation into members of the meson octet) are expressed in terms of three SU(3) symmetric functions, \alpha(x, Q^2), \beta(x, Q^2), and \gamma(x, Q^2). With the introduction of an SU(3) breaking parameter, \lambda, the model is successful in describing hadroproduction data at the Z pole. The fragmentation functions are then evolved using leading order evolution equations and good fits to currently available data at 34 GeV and at 161 GeV are obtained.Comment: 24 pages LaTeX file including 11 postscript figure file

Direct access to a cAAC-supported dihydrodiborene and its dianion

The two-fold reduction of (cAAC)BHX2 (cAAC = 1-(2,6-diisopropylphenyl)-3,3,5,5-tetramethylpyrrolidin-2-ylidene); X = Cl, Br) provides a facile, high-yielding route to the dihydrodiborene (cAAC)2B2H2. The (chloro)hydroboryl anion reduction intermediate was successfully isolated using a crown ether. Overreduction of the diborene to its dianion [(cAAC)2B2H2]2– causes a decrease in the B-B bond order whereas the B-C bond orders increase

Pion and Kaon Production in e+e−e^+e^- and epep Collisions at Next-to-Leading Order

We present new sets of fragmentation functions for charged pions and kaons, both at leading and next-to-leading order. They are fitted to data on inclusive charged-hadron production in $e^+e^-$ annihilation taken by TPC at PEP ($\sqrt s=29$~GeV) and to similar data by ALEPH at LEP, who discriminated between events with charm, bottom, and light- flavour fragmentation in their charged-hadron sample. We treat all partons independently and to properly incorporate the charm and bottom thresholds. Due to the sizeable energy gap between PEP and LEP, we are sensitive to the scaling violation in the fragmentation process, which allows us to extract a value for the asymptotic scale parameter of QCD, $\Lambda$. Recent data on inclusive charged-hadron production in tagged three-jet events by OPAL and similar data for longitudinal electron polarization by ALEPH allow us to pin down the gluon fragmentation functions. Our new fragmentation functions lead to an excellent description of a multitude of other $e^+e^-$ data on inclusive charged-hadron production, ranging from $\sqrt s=5.2$~GeV to LEP energy. In addition, they agree nicely with the transverse-momentum spectra of single charged hadrons measured by H1 and ZEUS in photoproduction at the $ep$ collider HERA, which represents a nontrivial check of the factorization theorem of the QCD-improved parton model.Comment: 22 pages, latex, 13 compressed ps figures in separate fil