Using brain cell-type-specific protein interactomes to interpret neurodevelopmental genetic signals in schizophrenia

Genetics have nominated many schizophrenia risk genes and identified convergent signals between schizophrenia and neurodevelopmental disorders. However, functional interpretation of the nominated genes in the relevant brain cell types is often lacking. We executed interaction proteomics for six schizophrenia risk genes that have also been implicated in neurodevelopment in human induced cortical neurons. The resulting protein network is enriched for common variant risk of schizophrenia in Europeans and East Asians, is down-regulated in layer 5/6 cortical neurons of individuals affected by schizophrenia, and can complement fine-mapping and eQTL data to prioritize additional genes in GWAS loci. A sub-network centered on HCN1 is enriched for common variant risk and contains proteins (HCN4 and AKAP11) enriched for rare protein-truncating mutations in individuals with schizophrenia and bipolar disorder. Our findings showcase brain cell-type-specific interactomes as an organizing framework to facilitate interpretation of genetic and transcriptomic data in schizophrenia and its related disorders

Structure-Function Analysis of STRUBBELIG, an Arabidopsis Atypical Receptor-Like Kinase Involved in Tissue Morphogenesis

Tissue morphogenesis in plants requires the coordination of cellular behavior across clonally distinct histogenic layers. The underlying signaling mechanisms are presently being unraveled and are known to include the cell surface leucine-rich repeat receptor-like kinase STRUBBELIG in Arabidopsis. To understand better its mode of action an extensive structure-function analysis of STRUBBELIG was performed. The phenotypes of 20 EMS and T-DNA-induced strubbelig alleles were assessed and homology modeling was applied to rationalize their possible effects on STRUBBELIG protein structure. The analysis was complemented by phenotypic, cell biological, and pharmacological investigations of a strubbelig null allele carrying genomic rescue constructs encoding fusions between various mutated STRUBBELIG proteins and GFP. The results indicate that STRUBBELIG accepts quite some sequence variation, reveal the biological importance for the STRUBBELIG N-capping domain, and reinforce the notion that kinase activity is not essential for its function in vivo. Furthermore, individual protein domains of STRUBBELIG cannot be related to specific STRUBBELIG-dependent biological processes suggesting that process specificity is mediated by factors acting together with or downstream of STRUBBELIG. In addition, the evidence indicates that biogenesis of a functional STRUBBELIG receptor is subject to endoplasmic reticulum-mediated quality control, and that an MG132-sensitive process regulates its stability. Finally, STRUBBELIG and the receptor-like kinase gene ERECTA interact synergistically in the control of internode length. The data provide genetic and molecular insight into how STRUBBELIG regulates intercellular communication in tissue morphogenesis

Sloan Digital Sky Survey IV: Mapping the Milky Way, Nearby Galaxies, and the Distant Universe

We describe the Sloan Digital Sky Survey IV (SDSS-IV), a project encompassing three major spectroscopic programs. The Apache Point Observatory Galactic Evolution Experiment 2 (APOGEE-2) is observing hundreds of thousands of Milky Way stars at high resolution and high signal-to-noise ratios in the near-infrared. The Mapping Nearby Galaxies at Apache Point Observatory (MaNGA) survey is obtaining spatially resolved spectroscopy for thousands of nearby galaxies (median $z\sim 0.03$). The extended Baryon Oscillation Spectroscopic Survey (eBOSS) is mapping the galaxy, quasar, and neutral gas distributions between $z\sim 0.6$ and 3.5 to constrain cosmology using baryon acoustic oscillations, redshift space distortions, and the shape of the power spectrum. Within eBOSS, we are conducting two major subprograms: the SPectroscopic IDentification of eROSITA Sources (SPIDERS), investigating X-ray AGNs and galaxies in X-ray clusters, and the Time Domain Spectroscopic Survey (TDSS), obtaining spectra of variable sources. All programs use the 2.5 m Sloan Foundation Telescope at the Apache Point Observatory; observations there began in Summer 2014. APOGEE-2 also operates a second near-infrared spectrograph at the 2.5 m du Pont Telescope at Las Campanas Observatory, with observations beginning in early 2017. Observations at both facilities are scheduled to continue through 2020. In keeping with previous SDSS policy, SDSS-IV provides regularly scheduled public data releases; the first one, Data Release 13, was made available in 2016 July

Lawson criterion for ignition exceeded in an inertial fusion experiment

For more than half a century, researchers around the world have been engaged in attempts to achieve fusion ignition as a proof of principle of various fusion concepts. Following the Lawson criterion, an ignited plasma is one where the fusion heating power is high enough to overcome all the physical processes that cool the fusion plasma, creating a positive thermodynamic feedback loop with rapidly increasing temperature. In inertially confined fusion, ignition is a state where the fusion plasma can begin "burn propagation" into surrounding cold fuel, enabling the possibility of high energy gain. While "scientific breakeven" (i.e., unity target gain) has not yet been achieved (here target gain is 0.72, 1.37 MJ of fusion for 1.92 MJ of laser energy), this Letter reports the first controlled fusion experiment, using laser indirect drive, on the National Ignition Facility to produce capsule gain (here 5.8) and reach ignition by nine different formulations of the Lawson criterion

Sloan Digital Sky Survey IV: Mapping the Milky Way, Nearby Galaxies, and the Distant Universe

We describe the Sloan Digital Sky Survey IV (SDSS-IV), a project encompassing three major spectroscopic programs. The Apache Point Observatory Galactic Evolution Experiment 2 (APOGEE-2) is observing hundreds of thousands of Milky Way stars at high resolution and high signal-to-noise ratios in the near-infrared. The Mapping Nearby Galaxies at Apache Point Observatory (MaNGA) survey is obtaining spatially resolved spectroscopy for thousands of nearby galaxies (median $z\sim 0.03$). The extended Baryon Oscillation Spectroscopic Survey (eBOSS) is mapping the galaxy, quasar, and neutral gas distributions between $z\sim 0.6$ and 3.5 to constrain cosmology using baryon acoustic oscillations, redshift space distortions, and the shape of the power spectrum. Within eBOSS, we are conducting two major subprograms: the SPectroscopic IDentification of eROSITA Sources (SPIDERS), investigating X-ray AGNs and galaxies in X-ray clusters, and the Time Domain Spectroscopic Survey (TDSS), obtaining spectra of variable sources. All programs use the 2.5 m Sloan Foundation Telescope at the Apache Point Observatory; observations there began in Summer 2014. APOGEE-2 also operates a second near-infrared spectrograph at the 2.5 m du Pont Telescope at Las Campanas Observatory, with observations beginning in early 2017. Observations at both facilities are scheduled to continue through 2020. In keeping with previous SDSS policy, SDSS-IV provides regularly scheduled public data releases; the first one, Data Release 13, was made available in 2016 July

The Fourteenth Data Release of the Sloan Digital Sky Survey: First Spectroscopic Data from the Extended Baryon Oscillation Spectroscopic Survey and from the Second Phase of the Apache Point Observatory Galactic Evolution Experiment

The fourth generation of the Sloan Digital Sky Survey (SDSS-IV) has been in operation since 2014 July. This paper describes the second data release from this phase, and the 14th from SDSS overall (making this Data Release Fourteen or DR14). This release makes the data taken by SDSS-IV in its first two years of operation (2014–2016 July) public. Like all previous SDSS releases, DR14 is cumulative, including the most recent reductions and calibrations of all data taken by SDSS since the first phase began operations in 2000. New in DR14 is the first public release of data from the extended Baryon Oscillation Spectroscopic Survey; the first data from the second phase of the Apache Point Observatory (APO) Galactic Evolution Experiment (APOGEE-2), including stellar parameter estimates from an innovative data-driven machine-learning algorithm known as "The Cannon"; and almost twice as many data cubes from the Mapping Nearby Galaxies at APO (MaNGA) survey as were in the previous release (N = 2812 in total). This paper describes the location and format of the publicly available data from the SDSS-IV surveys. We provide references to the important technical papers describing how these data have been taken (both targeting and observation details) and processed for scientific use. The SDSS web site (www.sdss.org) has been updated for this release and provides links to data downloads, as well as tutorials and examples of data use. SDSS-IV is planning to continue to collect astronomical data until 2020 and will be followed by SDSS-V

Tradução e adaptação cultural do WORC: um questionário de qualidade de vida para alterações do manguito rotador Translation and cultural adaptation of WORC: a quality-of-life questionnaire for rotator cuff disorders

OBJETIVO: Realizar a tradução e a adaptação cultural do questionário WORC (The Western Ontario Rotator Cuff Index) para a língua portuguesa para ulterior validação no Brasil. MÉTODOS: O protocolo aplicado consistiu em: 1) Preparação, 2) Tradução, 3) Tradução de volta à língua original (retro-tradução), 4) Interrogatório Cognitivo e 5) Relato de Informações. Ao serem concluídas as etapas de tradução e retro-tradução, as versões foram enviadas para os autores do WORC original, que as aprovaram para continuação do estudo. A versão em Português foi aplicada a 35 pacientes com disfunções do manguito rotador para verificar o nível de compreensão do instrumento. A idade média foi 57 anos (DP=13), 63% eram do sexo feminino e 74% tinham nível de escolaridade de primeiro grau incompleto. A versão brasileira final do WORC foi definida após se conseguir menos que 15% de "não compreensão" em cada item. Para análise das variáveis, foi utilizada estatística descritiva. RESULTADOS: Realizaram-se mudanças e substituições de termos e expressões para obter equivalência cultural do WORC. Alteraram-se também os termos "não compreendidos" pelos pacientes de acordo com as sugestões feitas por eles. CONCLUSÃO: Após a tradução e adaptação cultural do questionário, foi concluída a versão em Português do WORC que está em processo de validação para ser utilizada no Brasil.<br>OBJECTIVE: To accomplish the translation of WORC (The Western Ontario Rotator Cuff Index) into Portuguese and its cultural adaptation, for future validation in Brazil. METHOD: The protocol applied consisted of: 1) Preparation; 2) Forward translation; 3) Back translation; 4) Cognitive Debriefing; and 5) Information report. After concluding the forward and back-translations, the versions were sent to the authors of the original questionnaire, who gave their approval for the study to be continued. The Portuguese version was applied to 35 patients with rotator cuff dysfunctions to verify the level of understanding of the instrument. The mean age of these patients was 57 years (SD = 13); 63% were female and 74% had not completed elementary school. The final Brazilian version of WORC was defined after achieving a "no comprehension" rate of less than 15% for each item. Descriptive statistics were used to analyze the variables. RESULTS: Some terms and expressions were changed or replaced to obtain cultural equivalence for WORC. The terms that were incomprehensible to the patients were changed in accordance with their own suggestions. CONCLUSION: After the translation and cultural adaptation of the questionnaire, the final Portuguese version of WORC was concluded and it is now undergoing validation for use in Brazil

A mechanical comparison between conventional and modified angular plates for proximal humeral fractures

The objective of this study is to present a modified angular blade plate for fixing 2-part and even 3-part fractures of the proximal humerus, as well as the results of the comparative mechanical test between the conventional angular blade plate and this new modified plate. The plates were tested in flexion and rotational trials in a wooden model that simulated a 2-part humeral fracture of the proximal extremity. The results (mean +/- SD) of bending strength and stiffness obtained after testing showed findings of 601 +/- 349 N and 0.5 +/- 0.2 N/mm, respectively, for the conventional plate and 4005 +/- 164 N and 3.9 +/- 0.7 N/mm, respectively, for the modified plate. The torsional stiffness test showed findings of 1.26 +/- 0.09 KN.mm degrees for the conventional plate and 1.74 +/- 0.21 KN.mm degrees for the modified plate. The test of torsional moment showed findings of 57.0 +/- 7.6 KN.mm for the conventional plate and 115.2 +/- 9.3 KN.mm for the modified plate. The test of angular displacement of the torsional moment showed findings of 50.8 degrees +/- 7.2 degrees for the conventional plate and 70.2 degrees +/- 2.6 degrees for the modified plate. The results of the mechanical trials of flexion and rotation were superior for the modified angular blade plate compared with the conventional angular blade plate.17463163