Articles in 2013

The Shc1 scaffold mediates a switch in the signaling output of the epidermal growth factor receptor tyrosine kinase over time through recruitment of successive waves of proteins with distinct biological functions.

This study reports a global analysis of binding sites for over 200 RNA-binding proteins (RBPs) from 24 species; conserved RNA-binding motifs are identified, and their analysis allows prediction of interaction sites based on the sequence of the RNA-binding domain alone.

An in vivo genetic approach to generate mosaic expression of Myc in the mouse epiblast reveals evidence of cell competition, a tissue homeostasis mechanism first described in Drosophila by which viable but suboptimal cells are eliminated from metazoan tissues; during normal development Myc expression levels in the epiblast are heterogeneous, and endogenous cell competition refines the epiblast cell population through the apoptotic elimination of cells with low relative Myc levels.

Mycobacterium tuberculosis has the ability to survive within the host for months to decades in an asymptomatic state, and adaptations to hypoxia are thought to have an important role in pathogenesis; here a systems-wide reconstruction of the regulatory network provides a framework for understanding mycobacterial persistence in the host.

The Cancer Genome Atlas Research Network reports an integrative analysis of more than 400 samples of clear cell renal cell carcinoma based on genomic, DNA methylation, RNA and proteomic characterisation; frequent mutations were identified in the PI(3)K/AKT pathway, suggesting this pathway might be a potential therapeutic target, among the findings is also a demonstration of metabolic remodelling which correlates with tumour stage and severity.

Drosophila neural stem cells and their proliferative progeny are both shown to change over time, thus increasing the diversity of their neuronal and glial progeny; such temporal patterning may also contribute to neuronal complexity in the human neocortex.

Five transcription factors are sequentially expressed in a temporal cascade in Drosophila medulla neuroblasts of the visual system; cross-regulations between these transcription factors control the temporal transitions, and temporal switching of neural progenitors may be a common theme in neuronal specification, with different sequences of transcription factors being used in different contexts.

Realizing holographic video displays is proving far from straightforward, but it is shown here that it may be possible to overcome the limitations of present displays by harnessing the desirable optical manipulation properties of anisotropic leaky-mode spatial light modulators.

This study shows that 53BP1 recruitment to sites of DNA damage involves dual recognition of H4K20me2 and H2AK15 histone ubiquitination; the ubiquitin mark and the surrounding epitope on H2A are read by a region of 53BP1 designated the ubiquitination-dependent recruitment motif.

A novel tracking collar provides highly precise location, speed and acceleration data from 367 runs by five cheetahs in the wild; although a top speed of 58 m.p.h. was reported, few runs were above 45 m.p.h. with the average run around 31 m.p.h., and hunting success depended on grip, manoeuvrability and muscle power rather than outright speed.

Understanding the earliest phases of primate evolution is obscured by gaps in the fossil record, but some light is shed by the discovery of a nearly complete and substantially articulated skeleton of a tiny primate from the early Eocene; the new primate lies near the pivotal evolutionary dichotomy separating the tarsier and anthropoid lineages and it possesses features that are characteristic of subsequent members of both lineages.

An X-ray structure and electrophysiological analysis of mammalian G-protein-gated inward rectifier potassium channel GIRK2 in complex with βγ reveals a pre-open channel structure consistent with channel activation by membrane delimited G-protein subunits.

Cytosolic DNA arising from intracellular bacterial or viral infections induces type I interferon through activation of the DNA sensor cGAS, which catalyses the synthesis of cyclic dinucleotide which in turn activates STING; here the crystal structures of a carboxy-terminal fragment of cGAS alone and in complex with UTP and DNA–ATP–GTP complex are determined.

Cross-species genetic screens reveal that decreased mitogen-activated protein kinase signalling reduces polyglutamine-expanded ataxin 1 levels and toxicity in models of spinocerebellar ataxia type 1.

In freely moving rodents, eye movements serve to keep the visual fields of the two eyes continuously overlapping overhead at the expense of continuous alignment, a strategy that may have evolved to maintain constant overhead surveillance of predators.

KAT5 tyrosine phosphorylation, mediated by the tyrosine kinase c-Abl, increases after DNA damage, promoting KAT5 binding to histone H3K9me3, which triggers KAT5-mediated acetylation of the ATM kinase; this promotes the activation of the DNA damage checkpoint and cell survival.

This study identifies a deubiquitinase (DUB) that specifically recognises and cleaves linear ubiquitin chains, implicating linear (de)ubiquitination in Wnt signalling and angiogenesis; mutations in gumby cause defects in angiogenesis in mice, and structural and biochemical analysis shows that gumby encodes a linear-ubiquitin-specific DUB.

Mitochondrial ribosomal proteins have been identified as longevity regulators in C. elegans and mammalian systems, their role in longevity is linked to mitonuclear protein imbalance and the mitochondrial unfolded protein response.

The draft genome of the Norway spruce (P. abies) is presented; this is the first gymnosperm genome to be sequenced and reveals a large genome size (20 Gb) resulting from the accumulation of transposable elements, and comparative sequencing of five other gymnosperm genomes provides insights into conifer genome evolution.

When an animal is performing a cognitive task, individual neurons in the prefrontal cortex show a mixture of responses that is often difficult to decipher and interpret; here new computational methods to decode and extract rich sets of information from these neural responses are revealed and demonstrate how this mixed selectivity offers a computational advantage over specialized cells.