Research articles

The de novo generation of benzynes—through a hexadehydro-Diels–Alder reaction—followed by their in situ elaboration is reported; the reaction is metal-free and reagent-free, and reveals new modes of intrinsic benzyne reactivity.

The activity of somatostatin-expressing inhibitory neurons (SOMs) in the superficial layers of the mouse visual cortex increases with stimulation of the receptive-field surround, thereby contributing to the surround suppression of pyramidal cells.

The structure of the major histocompatibility complex (MHC)-class-I-like molecule MR1 in complex with a vitamin B9 derivative is determined; metabolites of vitamin B2 are shown to activate MR1-restricted mucosal-associated invariant T cells, implicating them in microbial immunosurveillance.

The X-ray crystal structure of a rat neurotensin receptor in complex with the C-terminal portion of neurotensin is presented; this is the first structure of a member of the β group of class A G-protein-coupled receptors.

Transient overexpression of the transcription factors NKX2-1 and PAX8 in a murine cell model is shown to direct the differentiation of embryonic stem cells towards a thyroid follicular cell lineage; the resulting three-dimensional thyroid follicles created by subsequent thyrotropin treatment show hallmarks of thyroid function in vitro and rescue thyroid function in vivo when transplanted into athyroid mice, adding to our understanding of the molecular mechanisms underlying thyroid development.

In live neonatal mice, waves of spontaneous retinal activity are present and can propagate patterned information capable of guiding activity-dependent development of complex intra- and inter-hemispheric circuits throughout the visual system before the onset of vision (before eye opening).

This study develops an NMR-based approach that can capture previously inaccessible, highly transient, low-populated ‘excited states’ in RNA; the localized rearrangements in base-pairing giving rise to these states are found to affect function by changing the exposure of residues required for a specific biological process.

Whole-genome sequences of wild rice and cultivated rice varieties are used to produce a map of rice genome variation, and show that rice was probably first domesticated in southern China.

The expression of fibroblast growth factor in aged muscle fibre, the muscle stem cell niche, is shown to cause satellite cells to lose the capacity for self-renewal, and is thus an age-dependent change that directly influences stem cell quiescence and function.

The authors have developed a new method, metagenome-wide association study (MGWAS), to compare the combined genetic content of the faecal microbiota of healthy people versus patients with type 2 diabetes; they identify multiple microbial species and metabolic pathways that are associated with either cohort and show that some of these may be used as biomarkers.

The X-ray crystal structure of the transporter-binding protein complex BtuCD–F, involved in the uptake of vitamin B₁₂ across the inner membrane of Escherichia coli, is determined in an ATP analogue-bound state; the membrane-spanning BtuC subunits adopt a previously unseen conformation in which the central translocation pathway is sealed by an additional gate, and membrane transport is seen to occur through an unexpected peristaltic transport mechanism, distinct from what has been observed for other ABC transporters.

The Cancer Genome Atlas Network describe their multifaceted analyses of primary breast cancers, shedding light on breast cancer heterogeneity; although only three genes (TP53, PIK3CA and GATA3) are mutated at a frequency greater than 10% across all breast cancers, numerous subtype-associated and novel mutations were identified.

Laser microdissection and microarrays are used to assess 900 precise subdivisions of the brains from three healthy men with 60,000 gene expression probes; the resulting atlas allows comparisons between humans and other animals, and will facilitate studies of human neurological and psychiatric diseases.

The sequencing and assembly of the highly polymorphic oyster genome through a combination of short reads and fosmid pooling, complemented with extensive transcriptome analysis of development and stress response and proteome analysis of the shell, provides new insight into oyster biology and adaptation to a highly changeable environment.

The roles of BATF transcription factors in dendritic cell differentiation are studied, providing evidence for molecular compensation by related family members; compensation is based on the interaction of the BATF leucine zipper domains with IRF factors to mediate cooperative gene activation.

By combining full-genome sequencing and ‘evolutionary replay’ experiments to dissect the origin of aerobic citrate use in an experimental Escherichia coli population over 40,000 generations and 2 decades, the authors unveil a 3-step process in which potentiation makes a trait possible, actualization makes the trait manifest and refinement makes it effective.

Magnetic quasiparticles in a doped quantum magnet are shown to be well suited for realizing and exploring the ‘glassy’ states that are predicted to emerge for interacting bosons in the presence of disorder.

A novel neutralizing antibody from a healthy HIV-1-infected donor that is specific for the membrane proximal region of gp41 is reported; the antibody has high potency and breadth, is not autoreactive and does not bind phospholipids.

The crystal structure of an influenza antibody that recognizes a small, conserved site in the variable receptor-binding domain of HA is described; this antibody shows broad neutralization across multiple subtypes of influenza A virus through an antibody–antigen interaction dominated by a single heavy-chain complementarity-determining region 3 loop.

Heat stroke triggers necrotic cell death and neurodegeneration in Caenorhabditis elegans, but hormetic preconditioning at a mildly elevated temperature strongly protects C. elegans from necrosis induced by several insults, including heat, and shields mammalian neurons from heat cytotoxicity, suggesting that this protective mechanism is conserved.