| | Myeloid disease: Another action of a thalidomide derivative
Lenalidomide effectively treats a blood disorder caused by the 5q chromosomal deletion. A study shows that the drug binds to its target, CRBN, to promote the breakdown of an enzyme encoded by a gene in the 5q region. | Protistology: How to build a microbial eye
Dissection of the subcellular eye of microorganisms called warnowiid dinoflagellates reveals that this structure is composed of elements of two cellular organelles — the plastid and the mitochondrion. | Developmental biology: Nanotubes in the niche
In fruit flies, protrusions can extend from stem cells in the testes to cells in a regulatory hub, mediating intercellular signalling and stem-cell maintenance. The implications of this finding are presented here from two angles. | Lenalidomide induces ubiquitination and degradation of CK1α in del(5q) MDS
Lenalidomide, a derivative of thalidomide, is an effective drug for myelodysplastic syndrome; lenalidomide binds the CRL4CRBN E3 ubiquitin ligase and promotes degradation of casein kinase 1a, on which the malignant cells rely for survival. | T-cell exhaustion, co-stimulation and clinical outcome in autoimmunity and infection
CD8 T-cell exhaustion, although a negative prognostic indicator during persistent infections, is shown to be associated with a good outcome in autoimmune and inflammatory diseases. | Molecular basis for 5-carboxycytosine recognition by RNA polymerase II elongation complex
Structural and biochemical studies of RNA polymerase II (Pol II) assembled on DNA containing 5-carboxycytosine reveals that Pol II can sense the oxidized methylation state of DNA and transiently slows down during transcription. | Identification of cis-suppression of human disease mutations by comparative genomics
Patterns of amino acid conservation have been used to guide the interpretation of the disease-causing potential of genetic variants in patients; now, an appreciable fraction of pathogenic alleles are shown to be fixed in the genomes of other species, suggesting that the genomic context has an important role in allele pathogenicity. | A hemi-fission intermediate links two mechanistically distinct stages of membrane fission
The GTPase dynamin provides the driving force for fission of membrane-bound vesicular structures; here, it is shown that dynamin-driven membrane fission proceeds in two mechanistically distinct stages that are separated by a metastable hemi-fission intermediate that requires GTP hydrolysis for progression to full fission. | Global-scale coherence modulation of radiation-belt electron loss from plasmaspheric hiss
Simultaneous measurements of structured radiation-belt electron losses (in the form of bremsstrahlung X-rays) and plasmaspheric hiss (which causes the losses) reveal that the loss dynamics is coherent with the hiss dynamics on spatial scales comparable to the size of the plasmasphere. | Eye-like ocelloids are built from different endosymbiotically acquired components
Dinoflagellate eye-like ocelloids are built from pre-existing organelles of disparate origin, including a cornea-like layer made of mitochondria and a retinal body made of anastomosing plastids. | Viral-genetic tracing of the input–output organization of a central noradrenaline circuit
To better understand the relationship between input and output connectivity for neurons of interest in specific brain regions, a viral-genetic tracing approach is used to identify input based on a combination of neurons’ projection and cell type, as illustrated in a study of locus coeruleus noradrenaline neurons. | Nanotubes mediate niche–stem-cell signalling in the Drosophila testis
Drosophila male germline stem cells form previously unrecognized structures, microtubule-based nanotubes, which extend into the hub, a major niche component, to mediate the niche–stem-cell signalling. | Influence maximization in complex networks through optimal percolation
A rigorous method to determine the most influential superspreaders in complex networks is presented—involving the mapping of the problem onto optimal percolation along with a scalable algorithm for big-data social networks—showing, unexpectedly, that many weak nodes can be powerful influencers. | Directional dominance on stature and cognition in diverse human populations
An analysis of 16 health-related quantitative traits in approximately 350,000 individuals reveals statistically significant associations between genome-wide homozygosity and four complex traits (height, lung function, cognitive ability and educational attainment); in each case increased homozygosity associates with a decreased trait value, but no evidence was seen of an influence on blood pressure, cholesterol, or ten other cardio-metabolic traits. | | Corrigendum: Greenland supraglacial lake drainages triggered by hydrologically induced basal slip | | The architecture of the spliceosomal U4/U6.U5 tri-snRNP
This study determines the structure of the spliceosomal tri-snRNP complex (containing three small nuclear RNAs and more than 30 proteins) by single-particle cryo-electron microscopy; the resolution is sufficient to discern the organization of RNA and protein components involved in spliceosome activation, exon alignment and catalysis.
Thi Hoang Duong Nguyen, Wojciech P. Galej, Xiao-chen Bai et al. | The core spliceosome as target and effector of non-canonical ATM signalling
Transcription-blocking DNA lesions result in chromatin displacement of core spliceosomes containing U2 and U5 snRNPs; consequently, R-loops containing the nascent transcript are formed, which activate ATM in a feed-forward fashion to influence spliceosome dynamics and alternative splicing.
Maria Tresini, Daniël O. Warmerdam, Petros Kolovos et al. | | Self-similar energetics in large clusters of galaxies
Massive galaxy clusters are filled with a hot, turbulent and magnetized intra-cluster medium, whose energy is derived from gravitational energy; the energy components of this medium are now shown to be ordered according to a permanent hierarchy, in which the ratio of thermal to turbulent to magnetic energy densities remains virtually unaltered over time.
Francesco Miniati, Andrey Beresnyak | Large heterogeneities in comet 67P as revealed by active pits from sinkhole collapse
The size and spatial distribution of pits on comet 67P/Churyumov–Gerasimenko, which are active and probably created by a sinkhole process, imply that large heterogeneities exist in the physical, structural or compositional properties of the first few hundred metres below the current cometary surface.
Jean-Baptiste Vincent, Dennis Bodewits, Sébastien Besse et al. | A colloidal quantum dot spectrometer
An efficient, cost effective microspectrometer that consists of a two-dimensional absorptive filter array of 195 different colloidal quantum dots is presented, and its performance demonstrated by measuring shifts in spectral peak positions as small as one nanometre.
Jie Bao, Moungi G. Bawendi | A model-tested North Atlantic Oscillation reconstruction for the past millennium
The North Atlantic Oscillation (NAO) is an important source of climate variability in the Northern Hemisphere; here, a model-tested reconstruction of the NAO for the past millennium reveals that positive NAO phases were predominant during the thirteenth and fourteenth centuries, but not during the whole medieval period.
Pablo Ortega, Flavio Lehner, Didier Swingedouw et al. | Hallucigenia’s head and the pharyngeal armature of early ecdysozoans
A re-analysis of the 508-million-year-old stem-group onychophoran Hallucigenia sparsa from the Burgess Shale shows that its anterior gut has structures that indicate evolutionary links with more disparate phyla such as nematodes and kinorhynchs; Hallucigenia now provides concrete evidence of structures that might have existed in the last common ancestor of the Ecdysozoa, previously a matter of conjecture.
Martin R. Smith, Jean-Bernard Caron | Sex reversal triggers the rapid transition from genetic to temperature-dependent sex
The first report of reptile sex reversal in the wild and rapid transition between genetic and environmental sex determination in the Australian bearded dragon (Pogona vitticeps)
Clare E. Holleley, Denis O'Meally, Stephen D. Sarre et al. | Spatiotemporal control of a novel synaptic organizer molecule
Neuronal synapses need to be formed at the right time and the right place during nervous system development; here, three gene-regulatory factors (the UNC-30, LIN-14 and UNC-55 DNA-binding proteins) are shown to operate in an intersectional manner to control the expression of a novel synaptic organizer molecule, OIG-1.
Kelly Howell, John G. White, Oliver Hobert | Cell-intrinsic adaptation of lipid composition to local crowding drives social behaviour
Little is known about how individual cells within a group of cells exposed to the same external signals can produce a specific individual response to their local microenvironment; a quantitative analysis of cell crowding reveals that single cells can autonomously sense local crowding though their ability to spread and activate focal adhesion kinase (FAK), which ultimately results in changes in cellular lipid composition.
Mathieu Frechin, Thomas Stoeger, Stephan Daetwyler et al. | Mechanical induction of the tumorigenic β-catenin pathway by tumour growth pressure
Magnetically induced mechanical strain mimicking the pressure exerted by a growing tumour in the mouse colon is shown to activate the tumorigenic β-catenin pathway in healthy epithelia, suggesting an alternative pathway, mechanotransductive in nature, in the propagation of tumorigenesis and growth from tumour to healthy tissue.
María Elena Fernández-Sánchez, Sandrine Barbier, Joanne Whitehead et al. | MYC regulates the core pre-mRNA splicing machinery as an essential step in lymphomagenesis
The critical effectors of MYC overexpression during lymphomagenesis in transgenic mice are defined.
Cheryl M. Koh, Marco Bezzi, Diana H. P. Low et al. | Cytosolic extensions directly regulate a rhomboid protease by modulating substrate gating
Calcium potently stimulates proteolysis by endogenous rhomboid-4, an intramembrane protease that contains a cytoplasmic calcium-binding EF-hand domain.
Rosanna P. Baker, Siniša Urban | Structures of actin-like ParM filaments show architecture of plasmid-segregating spindles
Structures of actin-like ParM filaments at near-atomic resolution and their arrangements into doublets reveal how subunits and filaments come together to segregate low-copy-number plasmid R1 in Escherichia coli, producing the simplest known mitotic machinery.
Tanmay A. M. Bharat, Garib N. Murshudov, Carsten Sachse et al. | Structures of human phosphofructokinase-1 and atomic basis of cancer-associated mutations
The first structures of the mammalian phosphofructokinase-1 tetramer are reported, for the human platelet isoform, in complex with ATP–Mg2+ and ADP.
Bradley A. Webb, Farhad Forouhar, Fu-En Szu et al. | | | | |
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