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Neurodegeneration: Aggregates feel the strain
Aggregates of α-synuclein protein can form in various cell types and cause different neurodegenerative disorders. The existence of strains with distinct structural conformations might explain this variability.
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Neurodegeneration: Evolved protection against human prions
A genetic variant of PrP, the protein that forms prions, confers protection against the human prion disease kuru by inhibiting the conversion of functional isoforms to the abnormal, disease-causing conformation.
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Hippocampal–prefrontal input supports spatial encoding in working memory
Spatial working memory is known to involve the prefrontal cortex and the hippocampus, but the specificities of the connection have been unclear; now, a direct path between these two areas is defined that is necessary for the encoding of spatial cues in mice, but is not required for the maintenance or retrieval of these cues.
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Global circulation patterns of seasonal influenza viruses vary with antigenic drift
The analysis of more than 9,000 haemagglutinin sequences of human seasonal influenza viruses over a 12-year time period shows that the global circulation patterns of A/H1N1 and B viruses are different from those of the well characterised A/H3N2 viruses; in particular the A/H1N1 and B viruses are shown to persist locally across several seasons and do not display the same degree of global movement as the H3N2 viruses.
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Supramolecular assemblies underpin turnover of outer membrane proteins in bacteria
Fluorescent labelling is used to show that in E. coli, outer membrane protein (OMP) turnover is passive and binary in nature, and OMPs cluster to form islands in which diffusion of individual proteins is restricted owing to lateral interactions with other OMPs; new OMPs are inserted mostly at mid-cell, meaning that old OMP islands are displaced to the poles of growing cells.
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HDL-bound sphingosine-1-phosphate restrains lymphopoiesis and neuroinflammation
Apolipoprotein-M-bound sphingosine-1-phosphate (S1P) is found to restrain the generation of new lymphocytes—and, consequently, adaptive immune responses—by activating the S1P1 receptor on bone marrow lymphocyte progenitors in mice.
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Structural basis for retroviral integration into nucleosomes
Retroviruses such as HIV rely on the intasome, a tetramer of integrase protein bound to the viral DNA ends interacting with host chromatin, for integration into the host genome; the structure of the intasome as it interacts with a nucleosome is now solved, giving insight into the integration process.
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A naturally occurring variant of the human prion protein completely prevents prion disease
This study looks at a polymorphism of the human prion protein gene, which results in a G-to-V substitution at residue 127, in transgenic mice expressing different human prion proteins, finding that mice heterozygous for the G127V polymorphism are resistant to both kuru and classical CJD prions, but there is some transmission of variant CJD prions; most remarkable, however, is that mice homozygous for V127 are completely resistant to all prion strains.
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α-Synuclein strains cause distinct synucleinopathies after local and systemic administration
Brain α-synuclein deposits are the hallmark of various distinct neurodegenerative diseases, and it is proposed that α-synuclein assemblies with different structural characteristics or 'strains' (ribbons or fibrils) could account for pathological differences between these diseases; here different human α-synuclein strains are injected into rat brain, and are shown to propagate in a strain-dependent manner and cause different pathological and neurotoxic phenotypes.
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Population genomics of Bronze Age Eurasia
An analysis of 101 ancient human genomes from the Bronze Age (3000–1000 bc) reveals large-scale population migrations in Eurasia consistent with the spread of Indo-European languages; individuals frequently had light skin pigmentation but were not lactose tolerant.
Morten E. Allentoft, Martin Sikora, Karl-Göran Sjögren et al. |
Cloning and variation of ground state intestinal stem cells
Novel technology to rapidly clone patient-specific, ‘ground state’ stem cells of columnar epithelia reveals their proliferative potential, remarkably precise and origin-dependent lineage commitment as well as genomic stability, despite extensive culturing, thereby skirting limitations associated with pluripotent stem cells.
Xia Wang, Yusuke Yamamoto, Lane H. Wilson et al. |
Chromothripsis from DNA damage in micronuclei
The mechanism for chromothripsis, “shattered” chromosomes that can be observed in cancer cells, is unknown; here, using live-cell imaging and single-cell sequencing, chromothripsis is shown to occur after a chromosome is isolated into a micronucleus, an abnormal nuclear structure.
Cheng-Zhong Zhang, Alexander Spektor, Hauke Cornils et al. |
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Visible-frequency hyperbolic metasurface
Visible-frequency hyperbolic metasurfaces defined on single-crystal silver exhibit negative refraction and diffraction-free propagation, as well as strong, dispersion-dependent spin–orbit coupling for propagating surface plasmon polaritons, with device performance greatly exceeding those of previous bulk metamaterial demonstrations.
Alexander A. High, Robert C. Devlin, Alan Dibos et al. |
Bipolar seesaw control on last interglacial sea level
A synthesis of new and existing data allows Heinrich Stadial 11 (HS11), a prominent Northern Hemisphere cold event, to be linked to the timing of peak sea-level rise during glacial termination T-II, whereas rapid sea-level rise in T-I is shown to clearly post-date Heinrich Stadial 1, so fundamentally different mechanisms seem to be at work during glacial terminations.
G. Marino, E. J. Rohling, L. Rodríguez-Sanz et al. |
Experimental constraints on the electrical anisotropy of the lithosphere–asthenosphere system
Electrical anisotropy measurements at high temperatures and quasi-hydrostatic pressures on previously deformed olivine plus melt samples show that electrical conductivity is much higher in the direction of deformation; this is confirmed with a layered electrical model of the asthenosphere and lithosphere that reproduces existing field data.
Anne Pommier, Kurt Leinenweber, David L. Kohlstedt et al. |
Epicardial regeneration is guided by cardiac outflow tract and Hedgehog signalling
Using a genetic approach in zebrafish, the mesothelial covering of the heart—the epicardium—is shown to have a high regenerative ability after injury, a process that is driven by Hedgehog signalling originating from the outflow tract.
Jinhu Wang, Jingli Cao, Amy L. Dickson et al. |
ESCRT-III controls nuclear envelope reformation
The ESCRT-III complex is implicated in the reformation of the nuclear envelope; the CHMP2A component of ESCRT-III is directed to the forming nuclear envelope through classical ESCRT-assembly mechanisms, with the help of the p97 complex component UFD1, and provides an activity essential for nuclear envelope reformation.
Yolanda Olmos, Lorna Hodgson, Judith Mantell et al. |
Small-scale dynamo magnetism as the driver for heating the solar atmosphere
A model of the heating of the quiet Sun, in which magnetic fields are generated by a subphotospheric fluid dynamo intrinsically connected to granulation, shows fields expanding into the chromosphere, where plasma is heated at the rate required to match observations by small-scale eruptions that release magnetic energy and drive sonic motions, while the corona is heated by the dissipation of Alfvén waves.
Tahar Amari, Jean-François Luciani, Jean-Jacques Aly |
Reducing the energy cost of human walking using an unpowered exoskeleton
The attachment of a simple, unpowered, mechanical exoskeleton to the foot and ankle results in a net saving of 7% of the metabolic energy expended in human walking.
Steven H. Collins, M. Bruce Wiggin, Gregory S. Sawicki |
Small particles dominate Saturn’s Phoebe ring to surprisingly large distances
Infrared imaging reveals all of Saturn’s faint, outermost ring, showing that it is composed principally of small dust particles and suggesting that particle temperatures are increased because of the radiative inefficiency of the smallest grains.
Douglas P. Hamilton, Michael F. Skrutskie, Anne J. Verbiscer et al. |
Massive migration from the steppe was a source for Indo-European languages in Europe
A genome-wide analysis of 69 ancient Europeans reveals the history of population migrations around the time that Indo-European languages arose in Europe, when there was a large migration into Europe from the Eurasian steppe in the east (providing a genetic ancestry still present in Europeans today); these findings support a ‘steppe origin’ hypothesis for how some Indo-European languages arose.
Wolfgang Haak, Iosif Lazaridis, Nick Patterson et al. |
Drug-based modulation of endogenous stem cells promotes functional remyelination in vivo
Two drugs, miconazole and clobetasol, have functions that modulate differentiation of oligodendrocyte progenitor cells directly, enhance remyelination, and significantly reduce disease severity in mouse models of multiple sclerosis.
Fadi J. Najm, Mayur Madhavan, Anita Zaremba et al. |
Intrinsic retroviral reactivation in human preimplantation embryos and pluripotent cells
The human endogenous retrovirus HERVK is normally silenced, but here the surprising discovery is made that in early human embryo development it is expressed, producing retroviral-like particles.
Edward J. Grow, Ryan A. Flynn, Shawn L. Chavez et al. |
Spastin and ESCRT-III coordinate mitotic spindle disassembly and nuclear envelope sealing
ESCRT-III, a protein complex best known for membrane constriction and sealing during various cellular processes, mediates reassembly of the nuclear envelope during late anaphase.
Marina Vietri, Kay O. Schink, Coen Campsteijn et al. |
Histone H3.3 is required for endogenous retroviral element silencing in embryonic stem cells
Transposable elements in mammalian genomes need to be silenced to avoid detrimental genome instability; here, the histone variant H3.3 is shown to have an important role in silencing endogenous retroviral elements.
Simon J. Elsässer, Kyung-Min Noh, Nichole Diaz et al. |
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