A Meta-Analysis of Genome-Wide Association Scans Identifies IL18RAP, PTPN2, TAGAP, and PUS10 As Shared Risk Loci for Crohn's Disease and Celiac Disease

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ANIA:ANnotation and Integrated Analysis of the 14-3-3 interactome

The dimeric 14-3-3 proteins dock onto pairs of phosphorylated Ser and Thr residues on hundreds of proteins, and thereby regulate many events in mammalian cells. To facilitate global analyses of these interactions, we developed a web resource named ANIA: ANnotation and Integrated Analysis of the 14-3-3 interactome, which integrates multiple data sets on 14-3-3-binding phosphoproteins. ANIA also pinpoints candidate 14-3-3-binding phosphosites using predictor algorithms, assisted by our recent discovery that the human 14-3-3-interactome is highly enriched in 2R-ohnologues. 2R-ohnologues are proteins in families of two to four, generated by two rounds of whole genome duplication at the origin of the vertebrate animals. ANIA identifies candidate ‘lynchpins’, which are 14-3-3-binding phosphosites that are conserved across members of a given 2R-ohnologue protein family. Other features of ANIA include a link to the catalogue of somatic mutations in cancer database to find cancer polymorphisms that map to 14-3-3-binding phosphosites, which would be expected to interfere with 14-3-3 interactions. We used ANIA to map known and candidate 14-3-3-binding enzymes within the 2R-ohnologue complement of the human kinome. Our projections indicate that 14-3-3s dock onto many more human kinases than has been realized. Guided by ANIA, PAK4, 6 and 7 (p21-activated kinases 4, 6 and 7) were experimentally validated as a 2R-ohnologue family of 14-3-3-binding phosphoproteins. PAK4 binding to 14-3-3 is stimulated by phorbol ester, and involves the ‘lynchpin’ site phosphoSer99 and a major contribution from Ser181. In contrast, PAK6 and PAK7 display strong phorbol ester-independent binding to 14-3-3, with Ser113 critical for the interaction with PAK6. These data point to differential 14-3-3 regulation of PAKs in control of cell morphology. Database URL: https://ania-1433.lifesci.dundee.ac.uk/prediction/webserver/index.p

Mid-infrared plasmons in scaled graphene nanostructures

Plasmonics takes advantage of the collective response of electrons to electromagnetic waves, enabling dramatic scaling of optical devices beyond the diffraction limit. Here, we demonstrate the mid-infrared (4 to 15 microns) plasmons in deeply scaled graphene nanostructures down to 50 nm, more than 100 times smaller than the on-resonance light wavelength in free space. We reveal, for the first time, the crucial damping channels of graphene plasmons via its intrinsic optical phonons and scattering from the edges. A plasmon lifetime of 20 femto-seconds and smaller is observed, when damping through the emission of an optical phonon is allowed. Furthermore, the surface polar phonons in SiO2 substrate underneath the graphene nanostructures lead to a significantly modified plasmon dispersion and damping, in contrast to a non-polar diamond-like-carbon (DLC) substrate. Much reduced damping is realized when the plasmon resonance frequencies are close to the polar phonon frequencies. Our study paves the way for applications of graphene in plasmonic waveguides, modulators and detectors in an unprecedentedly broad wavelength range from sub-terahertz to mid-infrared.Comment: submitte

Giant capsids from lattice self-assembly of cyclodextrin complexes

Proteins can readily assemble into rigid, crystalline and functional structures such as viral capsids and bacterial compartments. Despite ongoing advances, it is still a fundamental challenge to design and synthesize protein-mimetic molecules to form crystalline structures. Here we report the lattice self-assembly of cyclodextrin complexes into a variety of capsidlike structures such as lamellae, helical tubes and hollow rhombic dodecahedra. The dodecahedral morphology has not hitherto been observed in self-assembly systems. The tubes can spontaneously encapsulate colloidal particles and liposomes. The dodecahedra and tubes are respectively comparable to and much larger than the largest known virus. In particular, the resemblance to protein assemblies is not limited to morphology but extends to structural rigidity and crystallinity-a well-defined, 2D rhombic lattice of molecular arrangement is strikingly universal for all the observed structures. We propose a simple design rule for the current lattice self-assembly, potentially opening doors for new protein-mimetic materials

Condições de vida e vocabulário receptivo em crianças de dois a cinco anos

OBJECTIVE: To assess the receptive vocabulary of children aged between two years and six months and five years and eleven months who were attending childcare centers and kindergarten schools. METHODS: An analytical cross-sectional study was carried out in the municipality of Embu, Southeastern Brazil. The Peabody Picture Vocabulary Test and analysis of factors associated with children's performance were applied. The sample consisted of 201 children of both genders, aged between two and six years. Statistical analysis was performed using multivariate analysis and logistic regression model. The dependent variable analyzed was test performance and the independent variables were child's age, mother's level of education and family socio-demographic characteristics. RESULTS: It was observed that 44.3% of the children had performances in the test that were below what would be expected for their age. The factors associated with the best performances in the test were child's age (OR=2.4; 95% CI: 1.6-3.5) and mother's education level (OR= 3.2; 95% CI: 1.3-7.4). CONCLUSIONS: Mother's education level is important for child's language development. Settings such as childcare and kindergarten schools are protective factors for child development in families of low income and education.OBJETIVO: Avaliar o vocabulário receptivo de crianças de dois anos e seis meses a cinco anos e 11 meses que freqüentam creches e pré-escolas. MÉTODOS: Estudo transversal e analítico realizado no município de Embu, Estado de São Paulo. Utilizou-se o Teste de Vocabulário por Imagem Peabody e análise de fatores associados ao desempenho. A amostra foi constituída de 201 crianças de ambos os sexos, com idade entre dois e seis anos. Foram realizados análise multivariada e modelo de regressão logística. A variável dependente analisada foi o desempenho no teste e as variáveis independentes foram a idade da criança, tempo de escolaridade e série, e características sociodemográficas de suas famílias. RESULTADOS: Observou-se que 44,3% das crianças apresentaram desempenho inferior ao esperado para a idade no teste e os fatores associados ao melhor desempenho foram a idade da criança (OR=2,4; IC 95%: 1,6-3,5) e a escolaridade materna (OR=3,2; IC 95%: 1,3-7,4). CONCLUSÕES: A escolaridade maternal é importante no desenvolvimento de linguagem da criança. As instituições como creches e pré- escolas são fatores de proteção do desenvolvimento infantil em famílias de baixa renda e com baixa escolaridade.Universidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Departamento de FonoaudiologiaUniversidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Departamento de PediatriaUNIFESP, EPM, Depto. de FonoaudiologiaUNIFESP, EPM, Depto. de PediatriaSciEL