Articles in 2014

Specialized ribosomes (with a particular protein composition) carry out translation of specific transcripts; analysis of Hox mRNA translation in mice reveals that unique RNA structural elements within their 5′ UTRs, including internal ribosome entry sites and translation inhibitory elements, are responsible for this specialized mode of translation.

The crystal structure of the bat-specific influenza A polymerase in complex with the viral RNA promoter is presented, revealing how binding of the 5′ end of the viral RNA is required to activate or enhance the polymerase allosterically.

The mosquito Aedes aegypti includes two subspecies, one of which shows a preference for biting humans, whereas the other prefers to bite non-human animals; genetic analysis reveals that changes in the mosquito odorant receptor Or4 contribute to the behavioural difference—in human-preferring mosquitoes, Or4 is more highly expressed and more sensitive to sulcatone, a compound present at high levels in human odour.

Here β-catenin, which has been implicated in neurological and psychiatric diseases, including depression, is shown to mediate resilience to chronic stress in mice through induction of Dicer and microRNAs in nucleus accumbens, a key brain reward region.

The authors describe the structure of a Ca²⁺-activated lipid scramblase which catalyses the passive movement of lipids between the two leaflets of a lipid bilayer; the structure reveals the location of a regulatory calcium-binding site embedded within the membrane and the presence of a hydrophilic membrane-traversing cavity that is exposed to the lipid bilayer, where catalysis is likely to occur.

As incomes grow, diets change, with varying impacts on human health and the environment; here the links are examined and suggestions made for diets that both improve health and minimize environmental impacts.

Simple cooperating groups of bacteria reproduced either by embracing or purging cheating types; those that embraced cheats adopted a life cycle of alternating phenotypic states, underpinned by a developmental switch that allowed the fitness of collectives to decouple from the fitness of constituent cells.

The gondwanatherians were mammals known only from teeth and some jaw fragments that lived in the southern continents alongside dinosaurs; here the entire cranium of a bizarre and badger-sized fossil mammal from the Cretaceous of Madagascar shows that gondwanatherians were related to the better-known multituberculates, a long-lived and successful group of now-extinct rodent-like mammals.

Body axis elongation from head to tail is essential for animal development, however, the spatial cues that direct cell rearrangements relative to the anterior–posterior axis were unknown; this Drosophila study of convergent extension reveals that three Toll family receptors, expressed in overlapping stripes, modulate the contractile properties of cells to generate the polarized cell rearrangements that lead to body axis elongation.

Genome-wide association studies combined with data from epigenomic maps for immune cells have been used to fine-map causal variants for 21 autoimmune diseases; disease risk tends to be linked to single nucleotide polymorphisms in cell-type-specific enhancers, often in regions adjacent to transcription factor binding motifs.

Family-based exome sequencing in a large autism study has identified 27 high-confidence gene targets and accurately estimates the contribution of both de novo gene-disrupting and missense mutations to the incidence of simplex autism, with target genes in affected females overlapping those in males of lower but not higher IQ; targets also overlap known targets for intellectual disability and schizophrenia, and are enriched for chromatin modifiers, FMRP-associated genes and embryonically expressed genes.

Whole-exome sequencing in a large autism study identifies over 100 autosomal genes that are likely to affect risk for the disorder; these genes, which show unusual evolutionary constraint against mutations, carry de novo loss-of-function mutations in over 5% of autistic subjects and many function in synaptic, transcriptional and chromatin-remodelling pathways.

The crystal structure of the PRC1 ubiquitylation module bound to its nucleosome core substrate is determined, revealing how a histone-modifying enzyme achieves substrate specificity by recognizing nucleosome surfaces distinct from the site of catalysis, and uncovering a unique role for the ubiquitin E2 enzyme in substrate recognition.

The high-quality genome sequence of a 45,000-year-old modern human from Siberia reveals that gene flow from Neanderthals into the ancestors of this individual had already occurred about 7,000 to 13,000 years earlier; genomic comparisons show that he belonged to a population that lived close in time to the separation of populations in east and west Eurasia and that may represent an early modern human radiation out of Africa that has no direct descendants today.

The X-ray crystal structure of a eukaryotic Ca²⁺-activated chloride channel, BEST1, and its function in liposomes are described; the structure shows that Ca²⁺ binds to the cytosolic region of this pentameric channel and reveals that the pore is approximately 95 Å long with at least 15 distinct anion-binding sites.

This study shows that cardiac injury induces cardiac fibroblasts to undergo mesenchymal–endothelial transition and acquire an endothelial-cell like fate, a process mediated, in part, by a p53-dependent mechanism — use of a small molecule activator of p53 increases mesenchymal–endothelial transition, leading to reduced scarring and better preservation of heart function.

Ultrastructural analysis of synaptic vesicle recycling reveals that clathrin is not required for the initial rapid step of vesicle recycling by ultrafast endocytosis at the plasma membrane and instead clathrin acts later at an endosome to regenerate synaptic vesicles; however, when ultrafast endocytosis does not occur (for example, in experiments at room temperature rather than physiological temperature), clathrin-mediated endocytosis does happen at the plasma membrane.

A crystal structure of the human immunodeficiency virus Env trimer, used by the virus to infect cells, is determined here; the new structure, which shows the pre-fusion form of Env, increases our understanding of the fusion mechanism and of how the conformation of Env allows the virus to evade the immune response.

On the basis of transplantation experiments it is generally believed that a very small number of haematopoietic stem cells maintain multi-lineage haematopoiesis by stably producing a hierarchy of short-lived progenitor cells; here a new transposon-based labelling technique shows that this might not be the case during non-transplant haematopoiesis, but rather that a large number of long-lived progenitors are the main drivers of steady-state haematopoiesis during most of adulthood.

Previous work has shown that human skin is home to a rich and varied microbiota; here a metagenomic approach for samples from physiologically diverse body sites illuminates that the skin microbiota, including bacterial, fungal and viral members, is shaped by the local biogeography and yet marked by strong individuality.