Articles in 2015

Sequencing the genomes of two enteropneusts reveals complex genomic organization and developmental innovation in the ancestor of deuterostomes, a group of animals including echinoderms (starfish and their relatives) and chordates (which includes humans).

Haematopoietic stem cells normally reside in a bone marrow niche but they are recruited to the spleen after physiological stresses; here, endothelial cells and stromal cells around sinusoidal blood vessels of the spleen are shown to secrete key niche factors to support this process.

An epithelial-to-mesenchymal transition (EMT) lineage-tracing system in a mouse model of breast-to-lung metastasis reveals that although some cells undergo EMT in a primary epithelial tumour, the lung metastases mainly arise from cells that have not undergone EMT; in addition, cells that have undergone EMT appear more resistant to chemotherapy.

How marine communities will respond to climate change depends on the thermal sensitivities of existing communities; existing reef communities do not show a perfect fit between current temperatures and the thermal niches of the species within them and this thermal bias is a major contributor to projected local species loss.

Yeast-based screening identifies the benzodiazepine drug lorazepam as a non-selective positive allosteric modulator of the G-protein-coupled receptor (GPCR) GPR68; homology modelling and molecular docking of 3.1 million molecules found a new compound, ‘ogerin’, as a potent GPR68 modulator, which suppressed recall in fear conditioning in wild-type mice, and the general method of combining physical and structure-based screening may lead to the discovery of selective ligands for other GPCRs.

The morphogen Decapentaplegic (Dpp) has been implicated in both wing patterning and growth in fruitflies; here, a nanobody-based morphotrap approach has been developed that rules out a role for the Dpp gradient in regulating lateral wing growth.

Antibiotic-resistant strains of Staphylococcus aureus, such as MRSA, are proving increasingly difficult to treat; here, one reason for this is confirmed to be the fact that S. aureus bacteria can reside in intracellular reservoirs where they are protected from antibiotics, but a new strategy—based on an antibody–antibiotic conjugate—can specifically target these reservoirs.

A multi-model framework that accounts for climate, water, energy, food, biodiversity and economic activity in Australia reveals that a sustainable society that enjoys economic improvement without ecological deterioration is possible, but that specific political and economic choices need to be made to achieve this.

Brain tumours are difficult to treat because of their propensity to infiltrate brain tissue; here long processes, or tumour microtubes, extended by astrocytomas are shown to promote brain infiltration and to create an interconnected network that enables multicellular communication and that protects the tumours from radiotherapy-induced cell death, suggesting that disruption of the network could be a new therapeutic approach.

Activation of the ventral medial prefrontal cortex–basomedial amygdala pathway is shown to suppress anxiety and fear-related freezing in mice, thus identifying the basomedial amygdala (and not intercalated cells, as posited by earlier models) as a novel target of top-down control.

Exosomes originating from lung-, liver- and brain-tropic tumour cells are preferentially incorporated by specific resident cells of the target organs, thus preparing the site for metastasis; the expression of distinct combinations of exosomal integrin proteins determines the exosomal targeting to each of the three organs, and blocking these integrins reduces organotropic exosome uptake by the target organs, thereby reducing the likelihood of organotropic metastasis.

Ion channels in bacterial biofilms are shown to conduct long-range electrical signals within the biofilm community through the propagation of potassium ions; as predicted by a simple mathematical model, potassium channel gating is shown to coordinate metabolic states between distant cells via electrical communication.

In the worm C. elegans, a previously unidentified pair of bilateral neurons in the male (termed MCMs) are shown to arise from differentiated glial cells upon sexual maturation; these neurons are essential for a male-specific form of associative learning which balances chemotactic responses with reproductive priorities.

Many gene-regulatory proteins have been shown to activate in pulses, but whether cells exploit the dynamic interaction between pulses of different regulatory proteins has remained unexplored; here single-cell videos show that yeast cells modulate the relative timing between the pulsatile transcription factors Msn2 and Mig1—a gene activator and a repressor, respectively—to control the expression of target genes in response to diverse environmental conditions.

Description of a well-preserved 125-million-year-old fossil of a triconodont mammal from Spain, which extends the record of mammalian soft-tissue preservation back into the Mesozoic era.

This study reports exome sequencing of samples from 538 individuals with chronic lymphocytic leukaemia (CLL), including 278 collected as part of a prospective clinical trial; recurrently mutated genes are identified and pathways involved in CLL are highlighted, as well as their evolution in progression and disease relapse.

Human melanoma cells grown in mice experience high levels of oxidative stress in the bloodstream such that few metastasizing cells survive to form tumours; the rare melanoma cells that successfully metastasize undergo metabolic changes that increase their capacity to withstand this stress, and antioxidant treatments increase metastasis formation by human melanoma cells, while inhibiting antioxidant pathways had the reverse effect.

This study has determined the electron cryomicroscopy structure of the mammalian type 1 InsP₃ receptor in a ligand-free state at 4.7 Å resolution; although the central Ca²⁺-conduction pathway is similar to other ion channels, the unique architecture of the C-terminal domains of the tetrameric channel suggests that a distinctive allosteric mechanism underlies the activation of InsP₃ gating.

Here, a sparse neuronal projection from a part of the prefrontal cortex, the anterior cingulate, to the hippocampus is identified that, when activated, can elicit memory retrieval in mice.

The structure of the full-length Slo2.2 Na⁺-activated K⁺ channel is determined by cryo-electron microscopy, revealing features that explain the high conductance and gating mechanism of the Slo K⁺ channel family.