Research articles

Secreted C-type lectins protect the intestinal epithelium from Gram-positive bacteria; this study shows that for the C-type lectin RegIIIα, bacterial killing occurs in a two-step process whereby the lectin first binds to bacterial peptidoglycans then oligomerizes on the bacterial membrane to form a permeabilizing pore.

This study shows that Bacillus subtilis switches from a solitary, motile lifestyle to a multicellular, sessile state in a random, memoryless fashion, but that the underlying gene network is buffered against its own stochastic variation to tightly time the reverse transition; thus bacteria keep track of time to force their progeny to cooperate during the earliest stage of multicellular growth.

Very little is known about how a G-protein-coupled receptor (GPCR) transitions from an inactive to an active state, but this study has solved the X-ray crystal structures of the human M2 muscarinic acetylcholine receptor bound to a high-affinity agonist in an active state and to a high-affinity agonist and a small-molecule allosteric modulator in an active state; the structures provide insights into the activation mechanism and allosteric modulation of muscarinic receptors.

Single-unit recordings and optogenetic manipulations in mice undergoing auditory fear conditioning show that fear expression is related to the phasic inhibition of prefrontal cortex (PFC) parvalbumin interneurons; inhibition disinhibits PFC projection neurons and synchronizes their firing, leading to fear expression.

Small molecules are developed that irreversibly bind to the common G12C mutant of K-Ras but not the wild-type protein; crystallographic studies reveal the formation of an allosteric pocket that is not apparent in previous Ras studies, and the small molecules shift the affinity of K-Ras to favour GDP over GTP.

An exactly solvable information-theoretical model of communications with a fully quantum electromagnetic field yields explicit expressions for all point-to-point capacities—the maximum possible rates of data transmission—of noisy quantum channels, with implications for quantum key distribution and fibre-optic communications.

Botulinum neurotoxin A (BoNT/A) is considered the most toxic substance known but is also used as a therapeutic drug for a growing number of diseases and conditions; researchers have now obtained a high-resolution crystal structure of the receptor-binding domain of the BoNT/A in complex with the luminal domain of synaptic vesicle protein 2C (SV2C), one of its receptors, allowing the identification of a peptide that can inhibit complex formation.

The crystal structure of the Lsm protein ring of the U6 small nuclear ribonucleoprotein (snRNP), with and without an RNA comprising the 3′ end of the U6 small nuclear RNA, is solved here; this structure provides insight into the function of U6 snRNP in precursor messenger RNA splicing.

The El Niño propagation asymmetry (in which sea surface temperature anomalies propagate eastwards during an extreme El Niño event) is shown to be caused by the variations in upper ocean currents in the equatorial Pacific Ocean; increased occurrences of the propagation asymmetry may be a manifestation of global greenhouse warming.

Two proteins are identified in yeast that regulate the timing of pre-ribosome export from the nucleus; Nug2 binds pre-60S particles until they are ready for export, at which time Nug2 is replaced by the export adaptor Nmd3, enabling the export machinery to recognise the pre-ribosome that is ready to be transferred to the cytoplasm.

Plant life-history traits, notably plant investments in growth versus reproduction, can explain the impact of nitrogen:phosphorus stoichiometry on plant species richness; compared with plants in nitrogen-limited communities, plants in phosphorus-limited communities (in which endangered plant species are more common) invest little in phosphorus-intense activity such as sexual reproduction and have conservative leaf traits.

Single magnetic atoms on non-magnetic surfaces have magnetic moments that are usually destabilized within a microsecond, too speedily to be useful, but here the magnetic moments of single holmium atoms on a highly conductive metallic substrate can reach lifetimes of the order of minutes.

The gut microbial metabolite butyrate is shown to induce the differentiation of colonic T regulatory cells in mice and to ameliorate the development of colitis; it also increases histone H3 acetylation at the Foxp3 promoter.

The O-glycosylation enzyme Galnt11 has an important role in heterotaxy, a disorder of left–right body patterning or laterality: Galnt11 modulates Notch signalling which alters cilia types at the embryonic left–right organizer, therefore determining laterality.

A dual-task computer game played by groups of different sizes is used to show that cultural evolution (the maintenance or improvement of cultural knowledge) strongly depends on population size; in larger groups of players, higher cultural complexity and cultural trait diversity are maintained, and improvements to existing cultural traits are more frequent.

Doppler-shifted X-ray emission lines from highly-ionized atoms, appearing together with radio emission from the relativistic jets of the black-hole candidate X-ray binary 4U 1630-47, indicate that the X-ray emission lines arise in a jet travelling at approximately two-thirds the speed of light and imply that the jet contains baryons.

Dormant bacterial persister cells evade antibiotic destruction and their survival gives rise to some chronic infections; this study reveals that persister cells can be eradicated with a compound activating the bacterial protease ClpP, providing an effective biofilm treatment in vitro and in mouse chronic infection models.

Chemical, isotopic and physical evidence indicate that some of the groundwater in the Chesapeake Bay crater is remnant Early Cretaceous North Atlantic sea water, probably 100–145 million years old, with an average salinity of about 70‰, which is twice that of modern sea water.

This work shows that the Themis protein has a critical role in positive and negative thymocyte selection by dampening responses to low-affinity ligands but without affecting responses to high-affinity ligands, thus enabling positive selection of weakly self-reactive thymocytes.

Two small-molecule disruptors of the glucokinase–glucokinase-regulatory-protein complex, AMG-1694 and AMG-3969, are identified that decrease blood glucose levels in various models of hyperglycaemic rodents.