Holographic calculation of hadronic contributions to muon g-2

Using the gauge/gravity duality, we compute the leading order hadronic (HLO) contribution to the anomalous magnetic moment of muon, amu(HLO). Holographic renormalization is used to obtain a finite vacuum polarization. We find amu(HLO) =470.5 x 10^{-10} in AdS/QCD with two light flavors, which is compared with the currently revised BABAR data estimated from e^+ e^- -> pi^+ pi^- events, amu(HLO)[pipi]=(514.1 +- 3.8) x 10^{-10}.Comment: 12 pages, latex, references adde

Bayesian naturalness of the CMSSM and CNMSSM

The recent discovery of the 125.5 GeV Higgs boson at the LHC has fueled interest in the next-to-minimal supersymmetric standard model (NMSSM) as it may require less fine-tuning than the minimal model to accommodate such a heavy Higgs. To this end we present Bayesian naturalness priors to quantify fine-tuning in the (N)MSSM. These priors arise automatically as Occam razors in Bayesian model comparison and generalize the conventional Barbieri-Giudice measure. In this paper we show that the naturalness priors capture features of both the Barbieri-Giudice fine-tuning measure and a simple ratio measure that has been used in the literature. We also show that according to the naturalness prior the constrained version of the NMSSM is less tuned than the CMSSM.Comment: 8 pages and 5 figure

Base extrusion is found at helical junctions between right- and left-handed forms of DNA and RNA

Base extrusion is a major structural feature at the junction between B- and Z-DNA (the B–Z junction) where a base pair is broken, and the two bases are extruded from the double helix. Despite the demonstration of base extrusion at the B–Z junction, it is not clear whether a similar base extrusion occurs at other types of junctions involving the left-handed Z conformation. Here, we investigate structural changes of bases at three Z-form junctions: DNA B–Z and Z–Z and RNA A–Z junctions. By monitoring fluorescently labeled duplex nucleic acids using 2-aminopurines at various positions relative to the junction point, we show that base extrusion occurs not only at the DNA B–Z junction, but also at the RNA A–Z and DNA Z–Z junctions. Our data suggest that base extrusion is a general feature of Z-form nucleic-acid junctions.Korean Science and Engineering Foundation (grant NRL-2006-02287)Korea (South). Ministry of Science and Technology (21C Frontier Functional Proteomics Program FPR08B2-270)Korean Science and Engineering Foundation (Ubiquitome Research Program M105 33010001-05N3301-00100)Korea Research Foundation (MOEHRD, Basic Research Promotion Fund; KRF-2005-070-C00078

Autosomal dominant transmission of complicated hereditary spastic paraplegia due to a dominant negative mutation of KIF1A, SPG30 gene.

KIF1A is a brain-specific anterograde motor protein that transports cargoes towards the plus-ends of microtubules. Many variants of the KIF1A gene have been associated with neurodegenerative diseases and developmental delay. Homozygous mutations of KIF1A have been identified in a recessive subtype of hereditary spastic paraplegia (HSP), SPG30. In addition, KIF1A mutations have been found in pure HSP with autosomal dominant inheritance. Here we report the first case of familial complicated HSP with a KIF1A mutation transmitted in autosomal dominant inheritance. A heterozygous p.T258M mutation in KIF1A was found in a Korean family through targeted exome sequencing. They displayed phenotypes of mild intellectual disability with language delay, epilepsy, optic nerve atrophy, thinning of corpus callosum, periventricular white matter lesion, and microcephaly. A structural modeling revealed that the p.T258M mutation disrupted the binding of KIF1A motor domain to microtubules and its movement along microtubules. Assays of peripheral accumulation and proximal distribution of KIF1A motor indicated that the KIF1A motor domain with p.T258M mutation has reduced motor activity and exerts a dominant negative effect on wild-type KIF1A. These results suggest that the p.T258M mutation suppresses KIF1A motor activity and induces complicated HSP accompanying intellectual disability transmitted in autosomal dominant inheritance. © The Author(s) 20171

A TBR1-K228E Mutation Induces Tbr1 Upregulation, Altered Cortical Distribution of Interneurons, Increased Inhibitory Synaptic Transmission, and Autistic-Like Behavioral Deficits in Mice

© Copyright © 2019 Yook, Kim, Kim, Kang, Kim, Kim and Kim.Mutations in Tbr1, a high-confidence ASD (autism spectrum disorder)-risk gene encoding the transcriptional regulator TBR1, have been shown to induce diverse ASD-related molecular, synaptic, neuronal, and behavioral dysfunctions in mice. However, whether Tbr1 mutations derived from autistic individuals cause similar dysfunctions in mice remains unclear. Here we generated and characterized mice carrying the TBR1-K228E de novo mutation identified in human ASD and identified various ASD-related phenotypes. In heterozygous mice carrying this mutation (Tbr1+/K228E mice), levels of the TBR1-K228E protein, which is unable to bind target DNA, were strongly increased. RNA-Seq analysis of the Tbr1+/K228E embryonic brain indicated significant changes in the expression of genes associated with neurons, astrocytes, ribosomes, neuronal synapses, and ASD risk. The Tbr1+/K228E neocortex also displayed an abnormal distribution of parvalbumin-positive interneurons, with a lower density in superficial layers but a higher density in deep layers. These changes were associated with an increase in inhibitory synaptic transmission in layer 6 pyramidal neurons that was resistant to compensation by network activity. Behaviorally, Tbr1+/K228E mice showed decreased social interaction, increased self-grooming, and modestly increased anxiety-like behaviors. These results suggest that the human heterozygous TBR1-K228E mutation induces ASD-related transcriptomic, protein, neuronal, synaptic, and behavioral dysfunctions in mice11Nsciescopu

SALM5 trans-synaptically interacts with LAR-RPTPs in a splicing-dependent manner to regulate synapse development

Synaptogenic adhesion molecules play critical roles in synapse formation. SALM5/Lrfn5, a SALM/Lrfn family adhesion molecule implicated in autism spectrum disorders (ASDs) and schizophrenia, induces presynaptic differentiation in contacting axons, but its presynaptic ligand remains unknown. We found that SALM5 interacts with the Ig domains of LAR family receptor protein tyrosine phosphatases (LAR-RPTPs; LAR, PTPδ, and PTPσ). These interactions are strongly inhibited by the splice insert B in the Ig domain region of LAR-RPTPs, and mediate SALM5-dependent presynaptic differentiation in contacting axons. In addition, SALM5 regulates AMPA receptor-mediated synaptic transmission through mechanisms involving the interaction of postsynaptic SALM5 with presynaptic LAR-RPTPs. These results suggest that postsynaptic SALM5 promotes synapse development by trans-synaptically interacting with presynaptic LAR-RPTPs and is important for the regulation of excitatory synaptic strength

SALM4 suppresses excitatory synapse development by cis-inhibiting trans-synaptic SALM3-LAR adhesion

Synaptic adhesion molecules regulate various aspects of synapse development, function and plasticity. These functions mainly involve trans-synaptic interactions and positive regulations, whereas cis-interactions and negative regulation are less understood. Here we report that SALM4, a member of the SALM/Lrfn family of synaptic adhesion molecules, suppresses excitatory synapse development through cis inhibition of SALM3, another SALM family protein with synaptogenic activity. Salm4-mutant (Salm4) mice show increased excitatory synapse numbers in the hippocampus. SALM4 cis-interacts with SALM3, inhibits trans-synaptic SALM3 interaction with presynaptic LAR family receptor tyrosine phosphatases and suppresses SALM3-dependent presynaptic differentiation. Importantly, deletion of Salm3 in Salm4 mice (Salm3, Salm4) normalizes the increased excitatory synapse number. These results suggest that SALM4 negatively regulates excitatory synapses via cis inhibition of the trans-synaptic SALM3-LAR adhesion. © The Author(s) 2016110101sciescopu