资源环境科技发展态势分析平台

Chromatin, the complex of DNA and protein in cell nuclei, can be modified by ubiquitin molecules. It emerges that this modification occurs in a molecular reaction chamber formed from an enzyme and a scaffold protein.

A phase-separated reaction chamber for chromatin ubiquitination.

A hexanucleotide-repeat expansion in C9ORF72 is the most common genetic variant that contributes to amyotrophic lateral sclerosis and frontotemporal dementia(1,2). The C9ORF72 mutation acts through gain- and loss-of-function mechanisms to induce pathways that are implicated in neural degeneration(3-9). The expansion is transcribed into a long repetitive RNA, which negatively sequesters RNA-binding proteins(5) before its non-canonical translation into neural-toxic dipeptide proteins(3,4). The failure of RNA polymerase to read through the mutation also reduces the abundance of the endogenous C9ORF72 gene product, which functions in endolysosomal pathways and suppresses systemic and neural inflammation(6-9). Notably, the effects of the repeat expansion act with incomplete penetrance in families with a high prevalence of amyotrophic lateral sclerosis or frontotemporal dementia, indicating that either genetic or environmental factors modify the risk of disease for each individual. Identifying disease modifiers is of considerable translational interest, as it could suggest strategies to diminish the risk of developing amyotrophic lateral sclerosis or frontotemporal dementia, or to slow progression. Here we report that an environment with reduced abundance of immune-stimulating bacteria(10,11) protects C9orf72-mutant mice from premature mortality and significantly ameliorates their underlying systemic inflammation and autoimmunity. Consistent with C9orf72 functioning to prevent microbiota from inducing a pathological inflammatory response, we found that reducing the microbial burden in mutant mice with broad spectrum antibiotics-as well as transplanting gut microflora from a protective environment-attenuated inflammatory phenotypes, even after their onset. Our studies provide further evidence that the microbial composition of our gut has an important role in brain health and can interact in surprising ways with well-known genetic risk factors for disorders of the nervous system.

Reduced abundance of immune-stimulating gut bacteria ameliorated the inflammatory and autoimmune phenotypes of mice with mutations in C9orf72, which in the human orthologue are linked to amyotrophic lateral sclerosis and frontotemporal dementia.

Data analysis workflows in many scientific domains have become increasingly complex and flexible. Here we assess the effect of this flexibility on the results of functional magnetic resonance imaging by asking 70 independent teams to analyse the same dataset, testing the same 9 ex-ante hypotheses(1). The flexibility of analytical approaches is exemplified by the fact that no two teams chose identical workflows to analyse the data. This flexibility resulted in sizeable variation in the results of hypothesis tests, even for teams whose statistical maps were highly correlated at intermediate stages of the analysis pipeline. Variation in reported results was related to several aspects of analysis methodology. Notably, a meta-analytical approach that aggregated information across teams yielded a significant consensus in activated regions. Furthermore, prediction markets of researchers in the field revealed an overestimation of the likelihood of significant findings, even by researchers with direct knowledge of the dataset(2-5). Our findings show that analytical flexibility can have substantial effects on scientific conclusions, and identify factors that may be related to variability in the analysis of functional magnetic resonance imaging. The results emphasize the importance of validating and sharing complex analysis workflows, and demonstrate the need for performing and reporting multiple analyses of the same data. Potential approaches that could be used to mitigate issues related to analytical variability are discussed.

The results obtained by seventy different teams analysing the same functional magnetic resonance imaging dataset show substantial variation, highlighting the influence of analytical choices and the importance of sharing workflows publicly and performing multiple analyses.

Our understanding of the earliest stages of crown bird evolution is hindered by an exceedingly sparse avian fossil record from the Mesozoic era. The most ancient phylogenetic divergences among crown birds are known to have occurred in the Cretaceous period(1-3), but stem-lineage representatives of the deepest subclades of crown birds-Palaeognathae (ostriches and kin), Galloanserae (landfowl and waterfowl) and Neoaves (all other extant birds)-are unknown from the Mesozoic era. As a result, key questions related to the ecology(4,5), biogeography(3,6,7) and divergence times(1,8-10) of ancestral crown birds remain unanswered. Here we report a new Mesozoic fossil that occupies a position close to the last common ancestor of Galloanserae and fills a key phylogenetic gap in the early evolutionary history of crown birds(10,11). Asteriornis maastrichtensis, gen. et sp. nov., from the Maastrichtian age of Belgium (66.8-66.7 million years ago), is represented by a nearly complete, three-dimensionally preserved skull and associated postcranial elements. The fossil represents one of the only well-supported crown birds from the Mesozoic era(12), and is the first Mesozoic crown bird with well-represented cranial remains. Asteriornis maastrichtensis exhibits a previously undocumented combination of galliform (landfowl)-like and anseriform (waterfowl)-like features, and its presence alongside a previously reported Ichthyornis-like taxon from the same locality(13) provides direct evidence of the co-occurrence of crown birds and avialan stem birds. Its occurrence in the Northern Hemisphere challenges biogeographical hypotheses of a Gondwanan origin of crown birds(3), and its relatively small size and possible littoral ecology may corroborate proposed ecological filters(4,5,9) that influenced the persistence of crown birds through the end-Cretaceous mass extinction.

A newly discovered fossil from the Cretaceous of Belgium is the oldest modern bird ever found, showing a unique combination of features and suggesting attributes shared by avian survivors of the end-Cretaceous extinction.