Articles in 2015

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.

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.

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.

A global geochemical data set of volcanic and plutonic rocks indicates that differentiation trends from primitive basaltic to felsic compositions for volcanic versus plutonic samples are generally indistinguishable in subduction-zone settings, but are divergent in continental rifts.

The SLC2 family glucose transporters facilitate the transport of glucose and other monosaccharides across biological membranes; the X-ray crystal structure of human GLUT3 has been solved in outward-open and outward-occluded conformations and a model for how the membrane protein rearranges itself during a complete transport cycle has been proposed.

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.

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.

Ice-core and tree-ring data show that large volcanic eruptions in the tropics and high latitudes were primary drivers of temperature variability in the Northern Hemisphere during the past 2,500 years, firmly implicating such eruptions as catalysts in major sixth-century pandemics, famines, and socioeconomic disruptions.

This paper describes the discovery of the exopolysaccharide receptor (Epr3) in plants, and shows that its expression is induced upon perception of the bacterial Nod factors; the EPR3 receptor recognizes exopolysaccharides on the surface of rhizobia, thus controlling the symbiotic infection of the roots of legumes.

Progesterones, oestrogens and their receptors (PR, ERα and ERβ) are essential in normal breast development and homeostasis, as well as in breast cancer; here it is shown that PR controls ERα function by redirecting where ERα binds to the chromatin, acting as a proliferative brake in ERα⁺ breast tumours.

Lenalidomide, a derivative of thalidomide, is an effective drug for myelodysplastic syndrome; lenalidomide binds the CRL4^CRBN E3 ubiquitin ligase and promotes degradation of casein kinase 1a, on which the malignant cells rely for survival.

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.

Glypican-1 identifies cancer exosomes and serves as a biomarker for detection of early pancreatic cancer in patients and mouse models of the disease; the findings may enable early and non-invasive identification, and prevention of malignant cancer.

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.

Myocardial hypoxia activates HIF1α, which activates the splicing factor SF3B1, which mediates a splice switch of the fructose-metabolising enzyme KHK, so that the C isoform that has superior affinity for fructose is expressed in the heart—pathological heart growth and contractile dysfunction can therefore be suppressed by depleting SF3B1 or deleting KHK.

The description of a compound (DDD107498) with antimalarial activity against multiple life-cycle stages of Plasmodium falciparum and good pharmacokinetic and safety properties, with potential for single-dose treatment, chemoprotection and prevention of transmission.

An investigation of the molecular mechanism of stomatal development and patterning finds an unexpected signalling mechanism: two signalling peptides (STOMAGEN, a positive regulator of stomatal development; and EPF2, a negative regulator of this process) use the same receptor kinase, ERECTA, to fine-tune stomatal development.

A cryo-electron microscopy determination of the atomic structures of anaphase-promoting complex (APC/C)–coactivator complexes with either Emi1 or a UbcH10–ubiquitin conjugate.

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.

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.