Articles in 2014

This study reports the correction of pulmonary alveolar proteinosis (PAP) in Csf2rb^–/– mice by a single transfer of either wild-type or gene-corrected macrophages directly to the lungs — the transplanted macrophages persisted for at least 1 year; this transplantation strategy obviated the need for myeloablation and immunosuppression and should be a feasible therapy for humans with hereditary PAP.

The monarch butterfly, well known for its spectacular annual migration across North America, is shown by genome sequencing of monarchs from around the world to have been ancestrally migratory and to have dispersed out of North America to occupy its current broad distribution; the authors also discovered signatures of selection associated with migration within loci implicated in flight muscle function, leading to greater flight efficiency.

This study determines the structure of a branched lariat RNA, providing insights into rearrangement of the intron between the two steps of RNA splicing.

This study reprograms fibroblasts from thanatophoric dysplasia type I (TD1) and achondroplasia (ACH) patients into induced pluripotent stem cells (iPSCs), finding that chondrogenic differentiation results in the formation of degraded cartilage; statin treatment led to significant recovery of bone growth in a mouse model of ACH.

Non-caloric artificial sweeteners (NAS), widely used food additives considered to be safe and beneficial alternatives to sugars, are shown here to lead to the development of glucose intolerance through compositional and functional changes in the gut microbiota of mice, and the deleterious metabolic effects are transferred to germ-free mice by faecal transplant; NAS-induced dysbiosis and glucose intolerance are also demonstrated in healthy human subjects.

A catalytic process is reported that begins with a highly selective copper–boron addition to a monosubstituted allene, and in which the resulting boron-substituted organocopper intermediate then participates in a chemoselective, site-selective and enantioselective allylic substitution; this approach is used in the enantioselective synthesis of gram quantities of two natural products.

Asian monsoons were strongly active 40 million years ago and were enhanced by high atmospheric CO₂ content. They were significantly weakened when CO₂ levels decreased 34 million years ago and then reinitiated several million years later.

Three new euharamiyidan species from the Jurassic period of China are described, cementing the alliance with multituberculates and showing that the initial divergence between groups of extant mammals—monotremes on the one side, marsupials and placentals on the other—goes back to the Triassic period.

The iterative, reagent-controlled homologation of a boronic ester is used to create an ‘assembly line’ capable of synthesizing organic molecules that contain ten contiguous, stereochemically defined methyl groups and which have different shapes depending on the stereochemistry of those groups.

The genome of the gibbon, a tree-dwelling ape from Asia positioned between Old World monkeys and the great apes, is presented, providing insights into the evolutionary history of gibbon species and their accelerated karyotypes, as well as evidence for selection of genes such as those for forelimb development and connective tissue that may be important for locomotion through trees.

Whereas previous structural investigation of ribosome inhibitors has been done using the prokaryotic ribosome, this work presents X-ray crystal structures of the yeast ribosome in complex with 16 inhibitors including eukaryotic-specific inhibitors; the inhibitors all bind the mRNA or tRNA binding sites, larger molecules appear to target specifically the first elongation cycle.

Complex I is the first enzyme of the mitochondrial electron transport chain and it is essential for oxidative phosphorylation in mammalian mitochondria; here the electron cryo-microscopy structure of complex I from bovine heart mitochondria is reported, advancing knowledge of its structure in mammals.

Genomes and transcriptomes of five distinct lineages of African cichlids, a textbook example of adaptive radiation, have been sequenced and analysed to reveal that many types of molecular changes contributed to rapid evolution, and that standing variation accumulated during periods of relaxed selection may have primed subsequent diversification.

A new treatment, containing an optimized cocktail of three monoclonal antibodies against Ebola virus, provided full protection and disease reversal in rhesus monkeys when given under conditions in which controls succumbed by day 8; this new therapy may be a good candidate for treating Ebola virus infection in human patients.

The most primitive extant bony fish, Polypterus, exhibits adaptive plasticity for life on land when raised on land rather than in water, suggesting that environmentally induced phenotypic plasticity might have facilitated the macroevolutionary transition to life on land.

Chromatin immunoprecipitation followed by sequencing across multiple stages of Caenorhabditis elegans development reveals the genomic distribution of binding sites for 92 transcription factors and regulatory proteins, and integration of these and cellular-resolution expression data produce a spatiotemporally resolved metazoan transcription factor binding map allowing exploration into the properties of developmental regulatory circuits.

Here auditory cortex excitatory neurons are shown to decrease their activity during locomotion, grooming and vocalization, and this decrease was paralleled by increased activity in inhibitory interneurons; these findings provide a circuit basis for how self-motion and external sensory signals can be integrated to potentially facilitate hearing.

Spectral observations of the low-energy neutrinos produced by proton–proton fusion in the Sun demonstrate that about 99 per cent of the Sun’s power is generated by this process.

The mammalian aryl hydrocarbon receptor (known to sense environmental pollutants) is shown to also have a role as a pattern recognition receptor in sensing bacterial virulence factors, resulting in an antibacterial response and activation of innate and natural defences.

Caspase-4 and caspase-11 are shown to be the direct sensors for cytoplasmic lipopolysaccharide in humans and mice, respectively, mediating inflammatory cell death in intracellular bacterial infection.