| | Ophthalmology: Cataracts dissolved
Mutations underlying hereditary cataracts in two families impair the function of an enzyme that synthesizes the lens molecule lanosterol. The finding may lead to non-surgical prevention and treatment of cataracts. | Sustainability: Bypassing the methane cycle
A genetically modified rice with more starch in its grains also provides fewer nutrients for methane-producing soil microbes. This dual benefit might help to meet the urgent need for globally sustainable food production. | Structural biology: Arresting developments in receptor signalling
The first crystal structure of a G-protein-coupled receptor in complex with an arrestin protein provides insight into how the signalling pathways activated by these receptors are switched off through desensitization. | Molecular biology: Salvaging the genome
Overexpression of the enzyme cytidine deaminase allows the incorporation of abnormally modified nucleotides into DNA, leading to cell death. This discovery might point the way to treating some cancers. | Crystal structure of rhodopsin bound to arrestin by femtosecond X-ray laser
G protein-coupled receptors are a large family of signalling proteins that mediate cellular responses primarily via G proteins or arrestins, and they are targets of one-third of the current clinically used drugs; here, an active form of human rhodopsin bound to a pre-activated form of the mouse visual arrestin-1 is determined, revealing unique structural features that may constitute essential elements for arrestin-biased signalling. | Metabolic co-dependence gives rise to collective oscillations within biofilms
The emergence of long-range metabolic co-dependence within a biofilm drives oscillations in growth that resolve a social conflict between cooperation and competition, thereby increasing community-level fitness against chemical attack. | Non-coding recurrent mutations in chronic lymphocytic leukaemia
Genomic approaches in more than 500 patients are used to extend the number of chronic lymphocytic leukaemia (CLL) driver alterations, and also identify novel recurrent mutations in non-coding regions, including an enhancer of PAX5 and the 3′ untranslated region of NOTCH1, which lead to aberrant splicing events, increased NOTCH1 protein stability and activity, and an adverse clinical outcome. | Biogenesis and structure of a type VI secretion membrane core complex
The assembly, architecture and role of the bacterial type VI secretion system (T6SS) membrane core complex is presented. | 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. | Lanosterol reverses protein aggregation in cataracts
Exploring the genetic basis of congenital cataracts in two families identifies a molecule, lanosterol, which prevents intracellular protein aggregation of various cataract-causing mutant crystallins, and which can reduce cataract severity and increase lens transparency in vivo in dogs. | Expression of barley SUSIBA2 transcription factor yields high-starch low-methane rice
Expression of a barley transcription factor SUSIBA2 in rice generates a plant with high-starch content and low-methane emissions by conferring a shift in the carbon flux that favours the allocation of photosynthates to aboveground biomass rather than to the roots. | A cytosolic network suppressing mitochondria-mediated proteostatic stress and cell death
A new pathway of mitochondria-mediated cell death termed mitochondrial precursor over-accumulation stress (mPOS) is identified that could explain the link between mitochondrial dysfunction and misfolding of cytosolic proteins during ageing and disease; the pathway is triggered not only by mutations affecting the core protein import machineries, but also by conditions that interfere with mitochondrial inner membrane integrity and function, and a large network of genes that suppress mPOS in favour of cell survival is also identified. | Genetic evidence for two founding populations of the Americas
Previous genetic studies have suggested that the Americas were peopled by a single founding population of Eurasian origin, but a genome-wide study of 30 Native American groups shows that Amazonian Native Americans also have a second source of ancestry that is deeply related to indigenous Australians, New Guineans and Andaman Islanders. | 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. | | Structure of the TRPA1 ion channel suggests regulatory mechanisms | | Speed cells in the medial entorhinal cortex
On the basis of neural firing rates a specific class of neuron is identified in the medial entorhinal cortex that linearly encodes information on running speed in a context-independent manner and that is distinct from other functionally specific entorhinal neurons.
Emilio Kropff, James E. Carmichael, May-Britt Moser et al. | Crystal structures of a polypeptide processing and secretion transporter
Gram-positive bacteria use peptidase-containing ATP-binding cassette transporters (PCATs) to export quorum-sensing and antimicrobial polypeptides; here, the X-ray crystal structures of PCAT1 from Clostridium thermocellum in the absence and presence of ATP are reported.
David Yin-wei Lin, Shuo Huang, Jue Chen | Antibody against early driver of neurodegeneration cis P-tau blocks brain injury and tauopathy
Here the cis form of tau protein, which disrupts axonal microtubules and transport, spreads to other neurons, and leads to apoptosis in vitro and in vivo, is found to be produced by neurons immediately after traumatic brain injury (TBI); treating TBI mice with cis antibody blocks early production of cis tau, prevents tauopathy and spread and restores brain structural and functional outcomes, and may be further developed to treat TBI and to prevent neurodegeneration after injury.
Asami Kondo, Koorosh Shahpasand, Rebekah Mannix et al. | | Small-scale filament eruptions as the driver of X-ray jets in solar coronal holes
A study of the formation of X-ray jets in solar coronal holes suggests that this process does not follow the popular ‘emerging-flux’ model, but instead results from a minifilament eruption akin to the larger-scale filament eruptions that drive larger solar flares and mass ejections.
Alphonse C. Sterling, Ronald L. Moore, David A. Falconer et al. | DNA rendering of polyhedral meshes at the nanoscale
A general method of folding arbitrary polygonal digital meshes in DNA uses a routeing algorithm based on graph theory and a relaxation simulation that traces scaffold strands through the target structures to produce complex structures with an open conformation that are stable under biological assay conditions.
Erik Benson, Abdulmelik Mohammed, Johan Gardell et al. | Catalytic asymmetric umpolung reactions of imines
Imines conventionally act as electrophiles towards carbon nucleophiles in the synthesis of amines, but the range of amines could be much extended if the carbon atom of the imine could be rendered electron-rich to allow it to act as a nucleophile toward a carbon electrophile; such a reaction can be promoted by new phase-transfer catalysts, leading to highly efficient asymmetric reactions of imines with enals.
Yongwei Wu, Lin Hu, Zhe Li et al. | Statistical analysis of iron geochemical data suggests limited late Proterozoic oxygenation
Iron-based proxies are used to track the redox chemistry of ancient oceans, but do not reveal the sharp oxygenation event in the late Proterozoic eon that is expected from previous evaluations of proxy records.
Erik A. Sperling, Charles J. Wolock, Alex S. Morgan et al. | The ancestry and affiliations of Kennewick Man OPEN
Kennewick Man, a 8,500-year-old male human skeleton discovered in Washington state, USA, has been the subject of scientific and legal controversy; here a DNA analysis shows that Kennewick Man is closer to modern Native Americans than to any other extant population worldwide.
Morten Rasmussen, Martin Sikora, Anders Albrechtsen et al. | 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.
Peter K. Joshi, Tonu Esko, Hannele Mattsson et al. | Parent–progeny sequencing indicates higher mutation rates in heterozygotes
Mutation rates vary within genomes; here, by calling mutation events directly using a parent–offspring sequencing strategy in Arabidopsis, replicated in the rice and honey bee genomes, mutation rates are found to be higher in heterozygotes and in proximity to crossover events.
Sihai Yang, Long Wang, Ju Huang et al. | Epoxyeicosatrienoic acids enhance embryonic haematopoiesis and adult marrow engraftment
An in vivo imaging-based competitive transplant screen in zebrafish identifies epoxyeicosatrienoic acids as enhancers of haematopoietic stem and progenitor cell (HSPC) engraftment; these derivatives of arachidonic acid also promote zebrafish developmental HSPC specification through a PI(3)K-dependent AP-1 and runx1 transcriptional program and their pro-engraftment effect is conserved in mammals (indicating clinical potential).
Pulin Li, Jamie L. Lahvic, Vera Binder et al. | Redox rhythm reinforces the circadian clock to gate immune response
The master immune regulator NPR1 of Arabidopsis is a sensor of the plant’s redox state and regulates transcription of core circadian clock genes even in the absence of pathogen challenge.
Mian Zhou, Wei Wang, Sargis Karapetyan et al. | Genetic modification of the diarrhoeal pathogen Cryptosporidium parvum
Cryptosporidium is an important cause of diarrhoeal disease in young children but until now it has been difficult to study; here, the parasite is genetically modified, paving the way for in-depth investigation and the development of effective treatments.
Sumiti Vinayak, Mattie C. Pawlowic, Adam Sateriale et al. | Engineered CRISPR-Cas9 nucleases with altered PAM specificities
CRISPR-Cas9 nucleases are widely used for genome editing, but the range of sequences that Cas9 can recognize is constrained by the need for a specific protospacer adjacent motif (PAM); here the commonly used Streptococcus pyogenes Cas9 (SpCas9) is modified to recognize alternative PAM sequences, enabling robust editing of endogenous gene sites in zebrafish and human cells not currently targetable by wild-type SpCas9.
Benjamin P. Kleinstiver, Michelle S. Prew, Shengdar Q. Tsai et al. | Single-cell chromatin accessibility reveals principles of regulatory variation
A single-cell method for probing genome-wide chromatin accessibility has been developed; the results provide insight into the relationship between cell-to-cell variation associated with specific trans-factors and cis-elements, as well insights into the relationship between chromatin accessibility and three-dimensional genome organization.
Jason D. Buenrostro, Beijing Wu, Ulrike M. Litzenburger et al. | | | | |
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