Efficient chemical synthesis of human complement protein C3a

We report the total chemical synthesis of human C3a by one-pot native chemical ligation of three unprotected peptide segments, followed by efficient in vitro folding that yielded the anaphylatoxin C3a in high yield and excellent purity. Synthetic C3a was fully active and its crystal structure at 2.1 Å resolution showed 3 helices and a C-terminal turn motif

Pairing Symmetry Competition in Organic Superconductors

A review is given on theoretical studies concerning the pairing symmetry in organic superconductors. In particular, we focus on (TMTSF)$_2$X and $\kappa$-(BEDT-TTF)$_2$X, in which the pairing symmetry has been extensively studied both experimentally and theoretically. Possibilities of various pairing symmetry candidates and their possible microscopic origin are discussed. Also some tests for determining the actual pairing symmtery are surveyed.Comment: 16 pages, 8 figures, to be published in J. Phys. Soc. Jpn., special issue on "Organic Conductors

Risk-adjusted cesarean section rates for the assessment of physician performance in Taiwan: a population-based study

BACKGROUND: Over the past decade, about one-third of all births nationwide in Taiwan were delivered by cesarean section (CS). Previous studies in the US and Europe have documented the need for risk adjustment for fairer comparisons among providers. In this study, we set out to determine the impact that adjustment for patient-specific risk factors has on CS among different physicians in Taiwan. METHODS: There were 172,511 live births which occurred in either hospitals or obstetrics/gynecology clinics between 1 January and 31 December 2003, and for whom birth certificate data could be linked with National Health Insurance (NHI) claims data, available as the sample for this study. Physicians were divided into four equivalent groups based upon the quartile distribution of their crude (actual) CS rates. Stepwise logistic regressions were conducted to develop a predictive model and to determine the expected (risk-adjusted) CS rate and 95% confidence interval (CI) for each physician. The actual rates were then compared with the expected CS rates to see the proportion of physicians whose actual rates were below, within, or above the predicted CI in each quartile. RESULTS: The proportion of physicians whose CS rates were above the predicted CI increased as the quartile moved to the higher level. However, more than half of the physicians whose actual rates were higher than the predicted CI were not in the highest quartile. Conversely, there were some physicians (40 of 258 physicians) in the highest quartile who were actually providing obstetric care that was appropriate to the risk. When a stricter standard was applied to the assessment of physician performance by excluding physicians in quartile 4 for predicting CS rates, as many as 60% of physicians were found to have higher CS rates than the predicted CI, and indeed, the CS rates of no physicians in either quartile 3 or quartile 4 were below the predicted CI. CONCLUSION: Overall, our study found that the comparison of unadjusted CS rates might not provide a valid reflection of the quality of obstetric care delivered by physicians, and may ultimately lead to biased judgments by purchasers. Our study has also shown that when we changed the standard of quality assessment, the evaluation results also changed

ENIGMA and global neuroscience: A decade of large-scale studies of the brain in health and disease across more than 40 countries.

This review summarizes the last decade of work by the ENIGMA (Enhancing NeuroImaging Genetics through Meta Analysis) Consortium, a global alliance of over 1400 scientists across 43 countries, studying the human brain in health and disease. Building on large-scale genetic studies that discovered the first robustly replicated genetic loci associated with brain metrics, ENIGMA has diversified into over 50 working groups (WGs), pooling worldwide data and expertise to answer fundamental questions in neuroscience, psychiatry, neurology, and genetics. Most ENIGMA WGs focus on specific psychiatric and neurological conditions, other WGs study normal variation due to sex and gender differences, or development and aging; still other WGs develop methodological pipelines and tools to facilitate harmonized analyses of "big data" (i.e., genetic and epigenetic data, multimodal MRI, and electroencephalography data). These international efforts have yielded the largest neuroimaging studies to date in schizophrenia, bipolar disorder, major depressive disorder, post-traumatic stress disorder, substance use disorders, obsessive-compulsive disorder, attention-deficit/hyperactivity disorder, autism spectrum disorders, epilepsy, and 22q11.2 deletion syndrome. More recent ENIGMA WGs have formed to study anxiety disorders, suicidal thoughts and behavior, sleep and insomnia, eating disorders, irritability, brain injury, antisocial personality and conduct disorder, and dissociative identity disorder. Here, we summarize the first decade of ENIGMA's activities and ongoing projects, and describe the successes and challenges encountered along the way. We highlight the advantages of collaborative large-scale coordinated data analyses for testing reproducibility and robustness of findings, offering the opportunity to identify brain systems involved in clinical syndromes across diverse samples and associated genetic, environmental, demographic, cognitive, and psychosocial factors

Semienzymatic cyclization of disulfide-rich peptides using sortase A

Background: Sortase A (SrtA) is a transpeptidase capable of catalyzing the formation of amide bonds. Results: SrtA was used to backbone-cyclize disulfide-rich peptides, including kalata B1, -conotoxin Vc1.1, and SFTI-1. Conclusion: SrtA-mediated cyclization is applicable to small disulfide-rich peptides. Significance: SrtA-mediated cyclization is an alternative to native chemical ligation for the cyclization of small peptides of therapeutic interest

Novel Two-Component Systems Implied in Antibiotic Production in Streptomyces coelicolor

The abundance of two-component systems (TCSs) in Streptomyces coelicolor A3(2) genome indicates their importance in the physiology of this soil bacteria. Currently, several TCSs have been related to antibiotic regulation, and the purpose in this study was the characterization of five TCSs, selected by sequence homology with the well-known absA1A2 system, that could also be associated with this important process. Null mutants of the five TCSs were obtained and two mutants (ΔSCO1744/1745 and ΔSCO4596/4597/4598) showed significant differences in both antibiotic production and morphological differentiation, and have been renamed as abr (antibiotic regulator). No detectable changes in antibiotic production were found in the mutants in the systems that include the ORFs SCO3638/3639, SCO3640/3641 and SCO2165/2166 in any of the culture conditions assayed. The system SCO1744/1745 (AbrA1/A2) was involved in negative regulation of antibiotic production, and acted also as a negative regulator of the morphological differentiation. By contrast, the system SCO4596/4597/4598 (AbrC1/C2/C3), composed of two histidine kinases and one response regulator, had positive effects on both morphological development and antibiotic production. Microarray analyses of the ΔabrC1/C2/C3 and wild-type transcriptomes revealed downregulation of actII-ORF4 and cdaR genes, the actinorhodin and calcium-dependent antibiotic pathway-specific regulators respectively. These results demonstrated the involvement of these new two-component systems in antibiotic production and morphological differentiation by different approaches. One is a pleiotropic negative regulator: abrA1/A2. The other one is a positive regulator composed of three elements, two histidine kinases and one response regulator: abrC1/C2/C3

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 July 2014. This paper describes the second data release from this phase, and the fourteenth from SDSS overall (making this, Data Release Fourteen or DR14). This release makes public data taken by SDSS-IV in its first two years of operation (July 2014-2016). 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 (eBOSS); 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 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 website (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.Comment: SDSS-IV collaboration alphabetical author data release paper. DR14 happened on 31st July 2017. 19 pages, 5 figures. Accepted by ApJS on 28th Nov 2017 (this is the "post-print" and "post-proofs" version; minor corrections only from v1, and most of errors found in proofs corrected

Classification and function of small open reading frames

Small open reading frames (smORFs) of 100 codons or fewer are usually - if arbitrarily - excluded from proteome annotations. Despite this, the genomes of many metazoans, including humans, contain millions of smORFs, some of which fulfil key physiological functions. Recently, the transcriptome of Drosophila melanogaster was shown to contain thousands of smORFs of different classes that actively undergo translation, which produces peptides of mostly unknown function. Here, we present a comprehensive analysis of smORFs in flies, mice and humans. We propose the existence of several functional classes of smORFs, ranging from inert DNA sequences to transcribed and translated cis-regulators of translation and peptides with a propensity to function as regulators of membrane-associated proteins, or as components of ancient protein complexes in the cytoplasm. We suggest that the different smORF classes could represent steps in gene, peptide and protein evolution. Our analysis introduces a distinction between different peptide-coding classes of smORFs in animal genomes, and highlights the role of model organisms for the study of small peptide biology in the context of development, physiology and human disease

The Second Data Release of the Sloan Digital Sky Survey

The Sloan Digital Sky Survey (SDSS) has validated and made publicly available its Second Data Release. This data release consists of 3324 deg2 of five-band (ugriz) imaging data with photometry for over 88 million unique objects, 367,360 spectra of galaxies, quasars, stars, and calibrating blank sky patches selected over 2627 deg2 of this area, and tables of measured parameters from these data. The imaging data reach a depth of r ≈ 22.2 (95% completeness limit for point sources) and are photometrically and astrometrically calibrated to 2% rms and 100 mas rms per coordinate, respectively. The imaging data have all been processed through a new version of the SDSS imaging pipeline, in which the most important improvement since the last data release is fixing an error in the model fits to each object. The result is that model magnitudes are now a good proxy for point-spread function magnitudes for point sources, and Petrosian magnitudes for extended sources. The spectroscopy extends from 3800 to 9200 Å at a resolution of 2000. The spectroscopic software now repairs a systematic error in the radial velocities of certain types of stars and has substantially improved spectrophotometry. All data included in the SDSS Early Data Release and First Data Release are reprocessed with the improved pipelines and included in the Second Data Release. Further characteristics of the data are described, as are the data products themselves and the tools for accessing them

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson’s disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder