| | Molecular biology: It takes two to untangle
Yeast require the enzyme Hsp104 to untangle protein aggregates, which arise in stressed or aged cells. Animals lack Hsp104, but it emerges that proteins of the DNAJ family of molecular chaperones can fulfil this role.
| Structural biology: Hypoxia response becomes crystal clear
The crystal structures of two proteins that respond to reduced tissue oxygen levels — hypoxia-inducible factors — provide insight into their function and reveal sites for rational drug design.
| Cell biology: Surviving import failure
Two studies reveal that dysfunction in organelles called mitochondria causes the toxic accumulation of mitochondrial proteins in the cell's cytosolic fluid, and identify ways in which damage is mitigated.
| Regenerative biology: Maintaining liver mass
A previously under-appreciated subset of liver cells has been found to contribute to the day-to-day maintenance of liver mass in mice. The cells are induced and supported by signals from an adjacent vein.
| Self-renewing diploid Axin2+ cells fuel homeostatic renewal of the liver
In the uninjured liver, a population of self-renewing, diploid hepatocytes is identified near the central vein; these cells respond to Wnt signals that are provided by the adjacent central vein endothelial cells, and can give rise to all other hepatocytes to maintain liver homeostasis.
| Structural integration in hypoxia-inducible factors
This study describes the long-awaited crystal structures for hypoxia-inducible factor (HIF) heterodimers, including complexes bound to small molecules and DNA; the HIF–ARNT architecture is distinct from the bHLH-PAS-containing CLOCK–BMAL1 heterodimer, and HIF mutations linked to cancer can be mapped to important structural regions, with the structures providing future reference for small-molecule drug discovery efforts.
| Structural insights into µ-opioid receptor activation
X-ray crystallography and molecular dynamics simulations of the μ-opioid receptor reveal the conformational changes in the extracellular and intracellular domains of this G-protein-coupled receptor that are associated with its activation.
| A giant protogalactic disk linked to the cosmic web
A two-dimensional spectroscopic investigation of a large, luminous filament of the cosmic web near QSO UM287 reveals that the brightest emission region is an extended rotating hydrogen disk with a velocity profile that is characteristic of gas in a 1013-solar-mass dark-matter halo, with a geometry that is strongly suggestive of cold flow accretion.
| Reconstructing the reproductive mode of an Ediacaran macro-organism
The Ediacaran macrofossil Fractofusus reveals a complex life history of multigenerational, stolon-like asexual reproduction, interspersed with dispersal of waterborne propagules.
| Propagation of conformational changes during μ-opioid receptor activation
NMR spectroscopy reveals the conformational changes of the μ-opioid receptor that are associated with receptor activation, helping to explain why the allosteric coupling between the agonist-binding pocket and the cytoplasmic G-protein-coupling interface of this receptor is relatively weak.
| Crucial HSP70 co-chaperone complex unlocks metazoan protein disaggregation
An efficient protein disaggregation system uncovered in metazoan cells requires transient interactions between J-protein co-chaperones of classes A and B, which synergistically boost HSP70-dependent disaggregation activity, providing a flexible further level of regulation for metazoan protein quality control, with direct relevance to human diseases such as age-related neurodegeneration.
| Structural basis for stop codon recognition in eukaryotes
All eukaryotes utilize a single termination factor, eRF1, to halt translation when the ribosome encounters one of three possible stop codons; here electron cryo-microscopy structures of ribosome–eRF1 complexes in the process of recognizing each stop codon reveal how stop codons are discriminated from sense codons.
| Mistargeted mitochondrial proteins activate a proteostatic response in the cytosol
Mitochondrial dysfunction and cellular protein homeostasis failure are hallmarks of many diseases and age-associated pathologies; this study shows that the mitochondrial import defect of nuclear-encoded proteins triggers a cellular pathway, termed unfolded protein response activated by mistargeting of proteins (UPRam), that acts to minimize the stress caused by non-imported mitochondrial precursor proteins in order to sustain cellular protein homeostasis and organismal fitness.
| Corrigendum: Fatty acid carbon is essential for dNTP synthesis in endothelial cells
| Corrigendum: Progesterone receptor modulates ERα action in breast cancer
| | Comprehensive genomic profiles of small cell lung cancer
Genomic sequencing of 110 human small cell lung cancers identifies genomic signatures including nearly ubiquitous bi-allelic inactivation of TP53 and RB1, a role for NOTCH family genes, and somatic rearrangements that create an oncogenic version of TP73.
Julie George, Jing Shan Lim, Se Jin Jang et al. | HipBA–promoter structures reveal the basis of heritable multidrug tolerance
The molecular basis of multidrug tolerance in chronic urinary tract infections is mediated by mutations in the N-subdomain-1 of the Escherichia coli HipA protein kinase.
Maria A. Schumacher, Pooja Balani, Jungki Min et al. | RNA degradation paths in a 12-subunit nuclear exosome complex
Solving the crystal structure of an exosome complex from yeast, bound to different RNA substrates, offers insights into how the exosome can be utilized for precise processing of some 3′ ends, such as that of the 5.8S rRNA, while other RNAs are degraded to completion.
Debora Lika Makino, Benjamin Schuch, Elisabeth Stegmann et al. | | Distinct lineages of Ebola virus in Guinea during the 2014 West African epidemic OPEN
An analysis of 85 Ebola virus sequences collected in Guinea from July to November 2014 provides insight into the evolution of the Ebola virus responsible for the epidemic in West Africa; the results show sustained transmission of three co-circulating lineages, each defined by multiple mutations.
Etienne Simon-Loriere, Ousmane Faye, Oumar Faye et al. | Conversion of amides to esters by the nickel-catalysed activation of amide C–N bonds
Although enzymes are able to cleave amide bonds in nature, it is difficult to selectively break the carbon–nitrogen bond of an amide using synthetic chemistry; now the activation and cleavage of these bonds using nickel catalysts is used to convert amides to esters.
Liana Hie, Noah F. Fine Nathel, Tejas K. Shah et al. | Cyanate as an energy source for nitrifiers
The ammonia-oxidizing archaeon Nitrososphaera gargensis can utilize cyanate as the only source of energy for growth due to the presence of a cyanase enzyme, and cyanase-encoding nitrite-oxidizing bacteria can work together with cyanase-negative ammonia oxidizers to collectively grow on cyanate via reciprocal feeding; cyanases are widespread in the environment according to metagenomic data sets, pointing to the potential importance of cyanate in the nitrogen cycle.
Marton Palatinszky, Craig Herbold, Nico Jehmlich et al. | 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.
Juha-Pekka Mattila, Anna V. Shnyrova, Anna C. Sundborger et al. | 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.
Flaviano Morone, Hernán A. Makse | Beating the Stoner criterion using molecular interfaces
By harnessing the charge transfer that takes place at the interface between a metal and a layer of molecules, the usually non-magnetic materials copper and manganese are made magnetic at room temperature.
Fatma Al Ma'Mari, Timothy Moorsom, Gilberto Teobaldi et al. | A zeolite family with expanding structural complexity and embedded isoreticular structures
The complex structure of zeolite ZSM-25 is determined and a family of related structures are identified by using electron diffraction to uncover the structural 'coding' within them; this enabled the synthesis of two more-complex zeolites in the family.
Peng Guo, Jiho Shin, Alex G. Greenaway et al. | Erosion of organic carbon in the Arctic as a geological carbon dioxide sink
Measurements of sediments eroded by the Mackenzie River reveal the widespread export of permafrost-derived biospheric carbon that is several thousand years old, and demonstrate its burial in the Arctic Ocean, suggesting that high-latitude rivers can act as important carbon dioxide sinks.
Robert G. Hilton, Valier Galy, Jérôme Gaillardet et al. | 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.
Lindsay A. Schwarz, Kazunari Miyamichi, Xiaojing J. Gao et al. | Genetic diversity and evolutionary dynamics of Ebola virus in Sierra Leone OPEN
The genome sequences of 175 Ebola virus from five districts in Sierra Leone, collected during September–November 2014, show that the rate of virus evolution seems to be similar to that observed during previous outbreaks and that the genetic diversity of the virus has increased substantially, with the emergence of several novel lineages.
Yi-Gang Tong, Wei-Feng Shi, Di Liu et al. | Temporal and spatial analysis of the 2014–2015 Ebola virus outbreak in West Africa OPEN
Analysis of 179 new Ebola virus sequences from patient samples collected in Guinea between March 2014 and January 2015 shows how different lineages evolved and spread in West Africa.
Miles W. Carroll, David A. Matthews, Julian A. Hiscox et al. | CDA directs metabolism of epigenetic nucleosides revealing a therapeutic window in cancer
Enzymes of the nucleotide salvage pathway are shown to have substrate selectivity that protects newly synthesized DNA from random incorporation of epigenetically modified forms of cytosine; a subset of cancer cell lines that overexpress cytidine deaminase (CDA) are sensitive to treatment with 5hmdC or 5fdC (oxidized forms of 5-methyl-cytosine), which leads to DNA damage and cell death, indicating the chemotherapeutic potential of these nucleoside variants for CDA-overexpressing cancers.
Melania Zauri, Georgina Berridge, Marie-Laëtitia Thézénas et al. | Protein synthesis by ribosomes with tethered subunits
A ribosome with tethered subunits, 'Ribo-T', is engineered by making a hybrid RNA composed of ribosomal RNA of large and small subunits; Ribo-T can support cell growth in vivo in the absence of wild-type ribosomes, and is used to establish a fully orthogonal ribosome–mRNA system.
Cédric Orelle, Erik D. Carlson, Teresa Szal et al. | | | | |
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