Articles in 2013

Replacement of the wingless (wg) gene in Drosophila with one that expresses a membrane-tethered form of Wg results in viable flies with normally patterned appendages of nearly the right size; early wg transcription and memory of signalling ensure continued target-gene expression in the absence of Wg release, even though the spread of Wg could boost cell proliferation.

Cryo-electron microscopy combined with chemical crosslinking and mass spectrometry is used to determine the structure of the large subunit of the mammalian mitoribosome; this structure provides detailed structural insight, particularly of the molecular architecture of the polypeptide exit site, which has been structurally remodelled during evolution, presumably to help facilitate the membrane insertion of the highly hydrophobic proteins encoded by the mitochondrial genome.

Quiescent CD4 T cells in lymphoid tissues are shown to die after HIV-1 infection by caspase-1-mediated pyroptosis, a highly inflammatory form of programmed cell death; caspase 1 inhibitors, which are safe for human use, can rescue the cell death in vitro raising the possibility of new therapeutics targeting the host instead of the virus.

The analysis of multiple SIV vaccine regimens in macaques leads to the identification of a key two-amino-acid signature that confers resistance to neutralizing antibodies; a similar mechanism of immune escape is shown to operate in HIV and may explain the limited efficacy seen in HIV vaccine trials.

A molecular marker is required to monitor artemisinin-resistant Plasmodium falciparum parasites in southeast Asia; here mutations in K13-propeller are associated with artemisinin resistance in vitro and in vivo and also cluster in Cambodian provinces where resistance is prevalent.

A complete genome sequence is presented of a female Neanderthal from Siberia, providing information about interbreeding between close relatives and uncovering gene flow events among Neanderthals, Denisovans and early modern humans, as well as establishing substitutions that became fixed in modern humans after their separation from the ancestors of Neanderthals and Denisovans.

Rare copy-number variants (CNVs) conferring risk of schizophrenia or autism affect fecundity of carriers in Iceland, and carriers of these CNVs who do not suffer disease or have not been diagnosed with intellectual disability show phenotypes in brain structure and cognitive abilities between those of non-carrier controls and patients with schizophrenia.

Strigolactones (SLs), key regulators of plant growth, are believed to mediate their responses through a proposed receptor (D14) that interacts with an F-box protein (D3) to form a D14–SCF^D3 protein complex; here the perception of SLs by the D14–SCF^D3 complex and the control of gene expression are linked by the finding that DWARF 53, a repressor protein of SL signalling, interacts with the D14–SCF^D3 complex and is ubiquitinated and degraded in a SL-dependent manner.

Strigolactones (SLs), key regulators of plant growth, are believed to mediate their responses through a proposed receptor (D14) that interacts with an F-box protein (D3) to form a D14–SCF^D3 protein complex; here the perception of SLs by the D14–SCF^D3 complex and the control of gene expression are linked by the finding that DWARF 53, a repressor protein of SL function, interacts with the D14–SCF^D3 complex and is ubiquitinated and degraded in a SL-dependent manner.

The idea that magnetic particles suspended in a liquid crystal might spontaneously orient into a ferromagnetic state has hitherto not been confirmed experimentally, but such a state has now been realized using nanometre-sized ferromagnetic platelets in a nematic liquid crystal.

Examination of demographic age trajectories for species from a wide range of taxonomic groups shows that these species have very diverse life-history patterns; mortality and reproduction vary greatly with age for both long- and short-lived species, and the relationships between ageing, mortality and reproduction are clearly complex.

Sustained neurotransmission requires recycling of synaptic vesicles, but the proposed mechanisms have been controversial; here a ‘flash-and-freeze’ method for electron microscopy reveals a new ultrafast form of endocytosis that is actin- and dynamin-dependent and occurs within 100 milliseconds of stimulation.

Using a peptide toxin and small vanilloid agonists as pharmacological probes, high-resolution electron cryo-microscopy structures of rat TRPV1–ligand complexes are solved; these structures highlight conformational differences between TRP and voltage-gated ion channels in their active states, and suggest a dual gating mechanism that may account for the ability of members of the TRP channel superfamily to integrate diverse physiological signals.

Crystallographic structural analysis of bound states of the GBR1 and GBR2 subunits of human GABA_B receptor shows that both subunits adopt an open conformation at rest — represented by the apo and antagonist-bound structures — and that only GBR1 closes in the activated state — represented by the agonist-bound structure.

A high-resolution electron cryo-microscopy structure of the rat transient receptor potential (TRP) channel TRPV1 in its ‘closed’ state is presented; the overall structure of this ion channel is found to share some common features with voltage-gated ion channels, although several unique, TRP-specific features are also characterized.

Many DNA processes require chromosomes to be held together by a ring-shaped complex called cohesin, but despite the importance of this protein, its interaction with DNA has not been reproduced in vitro; here, using purified yeast proteins, cohesin loading is successfully recapitulated, offering mechanistic insight into how the loader complex mediates topological cohesin binding.

The lipid kinase phosphatidylinositol-4-OH kinase (PI(4)K) is identified as a target of the imidazopyrazines, a new antimalarial compound class that can inhibit several Plasmodium species at each stage of the parasite life cycle; the imidazopyrazines exert their inhibitory action by interacting with the ATP-binding pocket of PI(4)K.

X-ray crystal structures of a voltage-gated Na⁺channel mutated to be highly Ca²⁺selective provide a framework for understanding the mechanisms of ion selectivity and conductance in vertebrate voltage-gated Ca²⁺channels.

This study describes comprehensive synaptic engulfment by astrocytes, mediating synapse elimination in an activity-dependent manner; this elimination process involves the MEGF10 and MERTK phagocytic pathways and persists into adulthood, with mutant mice that lack these pathways in astrocytes exhibiting a failure to refine retinogeniculate connections during development.

An analysis of regional variations in global inland water surface area, dissolved CO₂ and gas transfer velocity yields a global CO₂ evasion rate of 2.1 × 10¹⁵ grams of carbon per year, which is higher than previous estimates owing to a larger contribution from streams and rivers.