Convergent cerebrospinal fluid proteomes and metabolic ontologies in humans and animal models of Rett syndrome

MECP2 loss-of-function mutations cause Rett syndrome, a neurodevelopmental disorder resulting from a disrupted brain transcriptome. How these transcriptional defects are decoded into a disease proteome remains unknown. We studied the proteome of Rett cerebrospinal fluid (CSF) to identify consensus Rett proteome and ontologies shared across three species. Rett CSF proteomes enriched proteins annotated to HDL lipoproteins, complement, mitochondria, citrate/pyruvate metabolism, synapse compartments, and the neurosecretory protein VGF. We used shared Rett ontologies to select analytes for orthogonal quantification and functional validation. VGF and ontologically selected CSF proteins had genotypic discriminatory capacity as determined by receiver operating characteristic analysis in Mecp2(-/y) and Mecp2(−/+). Differentially expressed CSF proteins distinguished Rett from a related neurodevelopmental disorder, CDKL5 deficiency disorder. We propose that Mecp2 mutant CSF proteomes and ontologies inform putative mechanisms and biomarkers of disease. We suggest that Rett syndrome results from synapse and metabolism dysfunction

Reaction rate for carbon burning in massive stars

Carbon burning is a critical phase for nucleosynthesis in massive stars. The conditions for igniting this burning stage, and the subsequent isotope composition of the resulting ashes, depend strongly on the reaction rate for C12+C12 fusion at very low energies. Results for the cross sections for this reaction are influenced by various backgrounds encountered in measurements at such energies. In this paper, we report on a new measurement of C12+C12 fusion cross sections where these backgrounds have been minimized. It is found that the astrophysical S factor exhibits a maximum around Ecm=3.5-4.0 MeV, which leads to a reduction of the previously predicted astrophysical reaction rate

Fusion measurements of 12C+12C at energies of astrophysical interest

The cross section of the 12C+12C fusion reaction at low energies is of paramount importance for models of stellar nucleosynthesis in different astrophysical scenarios, such as Type Ia supernovae and Xray superbursts, where this reaction is a primary route for the production of heavier elements. In a series of experiments performed at Argonne National Laboratory, using Gammasphere and an array of Silicon detectors, measurements of the fusion cross section of 12C+12C were successfully carried out with the γ and charged-particle coincidence technique in the center-of-mass energy range of 3-5 MeV. These were the first background-free fusion cross section measurements for 12C+12C at energies of astrophysical interest. Our results are consistent with previous measurements in the high-energy region; however, our lowest energy measurement indicates a fusion cross section slightly lower than those obtained with other techniques

How well do we understand the reaction rate of C burning?

Carbon burning plays a crucial role in stellar evolution, where this reaction is an important route for the production of heavier elements. A particle-γ coincidence technique that minimizes the backgrounds to which this reaction is subject and provides reliable cross sections has been used at the Argonne National Laboratory to measure fusion cross-sections at deep sub-barrier energies in the 12C+12C system. The corresponding excitation function has been extracted down to a cross section of about 6 nb. This indicates the existence of a broad S-factor maximum for this system. Experimental results are presented and discussed

European Red List of Marine Fishes

The European Red List is a review of the conservation status of European species according to IUCN regional Red Listing guidelines. It identifies those species that are threatened with extinction at the regional level, so that appropriate conservation action can be taken to improve their status. This Red List publication summarises results for all described native European marine fishes.Postprin

Creating a multi-center rare disease consortium - the Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR).

 Eosinophilic gastrointestinal disorders (EGIDs) affect various segments of the gastrointestinal tract. Since these disorders are rare, collaboration is essential to enroll subjects in clinical studies and study the broader population. The Rare Diseases Clinical Research Network (RDCRN), a program of the National Center for Advancing Translational Sciences (NCATS), funded the Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR) in 2014 to advance the field of EGIDs. CEGIR facilitates collaboration among various centers, subspecialties, patients, professional organizations and patient-advocacy groups and includes 14 clinical sites. It has successfully initiated two large multi-center clinical studies looking to refine EGID diagnoses and management. Several pilot studies are underway that focus on various aspects of EGIDs including novel therapeutic interventions, diagnostic and monitoring methods, and the role of the microbiome in pathogenesis. CEGIR currently nurtures five physician-scholars through a career training development program and has published more than 40 manuscripts since its inception. This review focuses on CEGIR's operating model and progress and how it facilitates a framework for exchange of ideas and stimulates research and innovation. This consortium provides a model for progress on other potential clinical areas

New approaches using mass spectrometry to investigate changes to cytokinin and abscisic acid (ABA) concentrations in soil

Phytohormones such as cytokinins, abscisic acid (ABA) and auxins play a vital role in plant development and regulatory processes. Their role within the plant is a focus for much research, with studies using recent advances in mass spectrometry performance allowing the quantification of low levels of phytohormones extracted from plant tissues. Despite these advances, external factors influencing the production of phytohormones are less well studied. Here, a new approach is presented for the extraction of a range of phytohormones from plant growth media (soil and hydroponic solution), their identification using high mass accuracy mass spectrometry and subsequent quantification using multiple reaction monitoring (MRM). The ability to detect phytohormones in matrices other than plant tissue presents the opportunity to study further the influence of factors such as below ground organisms and soil bacteria on phytohormone production. This novel approach was therefore applied to the plant growth media from a series of experiments comparing plant growth in the presence and absence of earthworms. A small but significant increase in ABA concentration was observed in the presence of earthworms, increasing even further when plants were also present. This finding suggests that earthworms could stimulate plant ABA production. This experiment and its outcomes demonstrate the value of studying phytohormones outside plant tissue, and the potential value of further research in this area