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The cover image shows a paired helical filament of tau protein, which is the major component of tangles in Alzheimerâs disease. Tau filaments make up the protein inclusions seen inside nerve cells in the brains of people with many neurodegenerative conditions, including Alzheimerâs. In this issue, Sjors Scheres, Michel Goedert and their colleagues reveal the first high-resolution structures of the two forms of tau filaments in Alzheimerâs disease. The filaments were isolated from the brain of an individual with Alzheimerâs and imaged using cryo-electron microscopy. In both forms, the individual tau proteins form C shapes (white and blue), which stack together to form filaments. The high-resolution structures of these filaments may help the development of novel diagnostics and therapeutic compounds. Cover image: Thomas G. Martin
The hunt for treatments to halt Alzheimer’s disease has been frustrating; it is time to trial preventive drugs, urge Eric McDade and Randall J. Bateman.
Physicists should rethink interference experiments to reveal whether or not general relativity follows classical theory, argue Chiara Marletto and Vlatko Vedral.
Quantum physics ultimately constrains how well sensors of position, speed and acceleration can perform. A hybrid quantum system that avoids these constraints could give rise to improved sensor technologies. See Letter p.191
The T cells of the immune system can destroy tumours, but their activation can be inefficient. Vaccines that exploit tumour mutations elicit robust T-cell responses to tumours, with potential clinical benefits. See Letters p.217 & p.222
Trace elements are enriched in plants by natural processes, human activities or both. An analysis of mercury in Arctic tundra vegetation offers fresh insight into the uptake of trace metals from the atmosphere by plants. See Letter p.201
The protein HP1 mediates compaction of DNA into a repressive structure called heterochromatin. Analysis reveals that HP1 has liquid-like properties, offering a fresh perspective on genome organization. See Letters p.236 & p.241
The protein tau forms abnormal filamentous aggregates called tangles in the brains of people with neurodegeneration. Structures of two such filaments offer pathways to a deeper understanding of Alzheimer's disease. See Article p.185
The development of a protocol for isolating and expanding the cell population that lines bile ducts has enabled the in vitro generation of bioengineered ducts. These can replace native bile ducts when transplanted into mice.
The extracellular matrix protein agrin promotes cardiac regeneration in adult mice after myocardial infarction; it modulates cardiac differentiation and proliferation by interacting with the dystrophin–glycoprotein complex, Yap and ERK-mediated signalling.
By coupling a mechanical object to an ensemble of atomic spins with negative effective mass, the object’s position can be measured without the usual quantum back-action perturbation of its momentum.
A two-year study of mercury deposition in the Arctic finds that the main source of mercury is gaseous elemental mercury, which is deposited throughout the year and leads to very high soil mercury levels.
The pyrite-type high-pressure form of FeOOH is predicted from first principles, and found experimentally to be stable under the conditions at the base of the mantle, with implications for transport of water within Earth’s deep interior.
In contrast to the prevailing belief that the gut begins with the mouth and continues backwards from there, this work shows that substantial areas of the faces of ray-finned fishes originate from the pre-oral gut or endoderm.
The results of a phase I trial assessing a personal neoantigen multi-peptide vaccine in patients with melanoma, showing feasibility, safety, and immunogenicity.
After injury in the heart, postnatal mouse hearts deficient in the Hippo pathway show efficient repair, and in the hearts of Mdx mice (a model of Duchenne muscular dystrophy) Hippo deficiency protects against overload-induced heart failure.
A low-input Hi-C method is used to show that chromatin organization is markedly relaxed in pre-implantation mouse embryos after fertilization and that the subsequent maturation of 3D chromatin architecture is surprisingly slow.
Phosphorylation or DNA binding promotes the physical partitioning of HP1α out of a soluble aqueous phase into droplets, suggesting that the repressive action of heterochromatin may in part be mediated by the phase separation of HP1.
HP1a can nucleate into foci that display liquid properties during the early stages of heterochromatin domain formation in Drosophila embryos, suggesting that the repressive action of heterochromatin may be mediated in part by emergent properties of phase separation.