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Damaged mitochondria are removed by mitophagy, and defects in mitophagy are linked to Parkinson’s disease; here it is shown that USP30, a deubiquitinase localized to mitochondria, antagonizes mitophagy by removing the ubiquitin tags put in place by Parkin, USP30 inhibition is therefore potentially beneficial for Parkinson’s disease by promoting mitochondrial clearance and quality control.
Ubiquitin, known for its role in post-translational modification of other proteins, undergoes post-translational modification itself; after a decrease in mitochondrial membrane potential, the kinase enzyme PINK1 phosphorylates ubiquitin at Ser 65, and the phosphorylated ubiquitin then interacts with ubiquitin ligase (E3) enzyme parkin, which is also phosphorylated by PINK1, and this process is sufficient for full activation of parkin enzymatic activity.
Whole-genome sequencing is used to identify genetic alterations in patients with severe intellectual disability for whom all other tests, including array and exome sequencing, returned negative results; de novo single-nucleotide and copy number variations affecting the coding region seem to be a major cause of this disorder.
Neutrinos are known to have mass, in contradiction to the predictions of the standard model, and one explanation of this mass is that they are Majorana fermions; this conjecture could be proved by observation of the neutrinoless double-β decay process, but new experiments with 136Xe find no statistically significant evidence for this process.
Intracranial germ cell tumours are rare tumours affecting mainly male adolescents, mainly in Asia; here the authors identify frequent mutations in the KIT/RAS and AKT/mTOR signalling pathways as well as rare germline variants in JMJD1C, suggesting potential therapeutic strategies focusing on the inhibition of KIT/RAS activation and the AKT1/mTOR pathway.
Loss-of-function studies of the miR-34/449 microRNA family in mouse and Xenopus reveal their evolutionarily conserved role in ciliogenesis by repressing expression of the centriolar protein Cp110.
Bacterial species whose representation defines healthy postnatal assembly of the gut microbiota in Bangladeshi children during their first 2 years are identified, and a model is constructed to compare healthy children to those with severe acute malnutrition (SAM); results show that SAM is associated with microbiota immaturity that is only partially ameliorated by existing nutritional interventions.
A new mass-spectrometry method has been developed to obtain high-resolution spectra of folded proteins bound to lipids; using this technique as well as X-ray crystallography provides evidence for membrane protein conformational change as a result of lipid–protein interaction.
Systematically assaying the activity of 7,705 candidate enhancers during Drosophila embryogenesis shows that nearly half are active in the embryo and display dynamic spatial patterns during development; enhancer activity is matched to expression patterns of putative target genes and predictive cis-regulatory motifs are identified.
BRCA2, the breast cancer susceptibility gene factor, interacts with TREX-2, a protein complex involved in the biogenesis and export of messenger ribonucleoprotein, to process DNA–RNA hybrid structures called R-loops that can trigger genome instability; these may be a central cause of the stress occurring in early cancer cells that drives oncogenesis.
A rodent study using optogenetics to induce long-term potentiation and long-term depression provides a causal link between synaptic plasticity and memory.
Two presynaptically secreted isoforms of the protein Punctin in the nematode Caenorhabditis elegans determine the postsynaptic accumulation of acetylcholine versus GABA receptors, raising the question of whether the related human punctin-2 gene, which has been associated with schizophrenia, may also control synaptic organization.
A palladium-catalysed C–H bond activation process is reported that proceeds through a four-membered-ring cyclopalladation pathway; it allows a methyl group that is adjacent to an unprotected secondary amine to be transformed into a synthetically versatile nitrogen heterocycle.
Analysis of the metallicities of more than 400 stars hosting 600 candidate extrasolar planets shows that the planets can be categorized by size into three populations — terrestrial-like planets, gas dwarf planets with rocky cores and hydrogen–helium envelopes, and ice or gas giant planets — on the basis of host star metallicity.
Concurrent observations at multiple locations indicate that storm-generated ocean waves propagating through Antarctic sea ice can transport enough energy to break first-year sea ice hundreds of kilometres from the ice edge, which is much farther than would be predicted by the commonly assumed exponential wave decay.
Large annual variation in the stimulation of above-ground biomass by elevated carbon dioxide in a mixed C3/C4 temperate grassland can be predicted accurately using seasonal rainfall totals.
A mass-spectrometry-based draft of the human proteome and a public database for analysis of proteome data are presented; assembled information is used to estimate the size of the protein-coding genome, to identify organ-specific proteins, proteins predicting drug resistance or sensitivity, and many translated long intergenic non-coding RNAs, and to reveal conserved control of protein abundance.
Two well-dated, high-resolution records of iceberg-rafted debris are presented that document variability in Antarctic Ice Sheet discharge during the last deglaciation.