Research articles

A draft map of the human proteome is presented here, accounting for over 80% of the annotated protein-coding genes in humans; some novel protein-coding regions, including translated pseudogenes, non-coding RNAs and upstream open reading frames, are identified.

The feasibility of targeted genome editing in human haematopoietic stem cells is demonstrated; the study overcomes previously existing barriers by tailoring delivery platforms and culture conditions.

Loss-of-function mutations in the human CTP synthase 1 gene cause an immunodeficiency disease with impaired T cell proliferation after antigen stimulation, revealing a potential new target for immunosuppressive drugs.

A new mechanism by which acute myeloid leukaemia patients become resistant to Ara-C and a newer treatment, ribavirin, is uncovered; these drugs can be glucuronidated and thereby inactivated by members of the UDP glucuronosyltransferase family of enzymes activated through GLI1 signalling.

The ubiquitin ligase RLIM is known to activate the long non-coding RNA Xist, which is crucial for X-chromosome inactivation in female mice; however, unlike imprinted X-chromosome inactivation that requires RLIM for Xist expression, evidence is now provided that during random X-chromosome inactivation Xist expression is regulated by an RLIM-independent pathway in vivo.

Two species may be fully reproductively isolated at the point they meet, but be connected by continuous gene flow by a longer route around the back of a geographical barrier; such a ring species complex exists for the greenish warbler, and genomics shows that there have been several historical breaks in gene flow along the continuum, as well as some introgression between the end forms.

The molecular relationship between synaptic dysfunction and psychiatric disorders was investigated using a mouse model system; presynaptically localized Cntnap4 is required for the output of two disease-relevant neuronal subpopulations (cortical parvalbumin-positive GABAergic cells and midbrain dopaminergic neurons) and Cntnap4 mutants show behavioural abnormalities which can be pharmacologically reversed.

A computational method is reported that can be used to design protein nanomaterials in which two distinct subunits co-assemble into a specific architecture; five 24-subunit cage-like protein nanomaterials are designed, and experiments show that their structures are in close agreement with the computational design models.

Using a phylogenetic approach, the protein archease is identified as being a subunit of the human transfer RNA splicing ligase, and found to be necessary for full ligase activity, in cooperation with DDX1.

A mouse study reveals that the stem cell quiescent state is composed of two distinct phases, G₀ and G_Alert; stem cells reversibly transition between these two phases in response to systemic environmental stimuli acting through the mTORC1 pathway.

Formation of an active cyclin D1–Cdk4 complex suppresses glucose metabolism independently of cell division.

Conventional quantum cryptography relies on monitoring signal disturbance to make sure that information leakage is negligible; here a new quantum method of achieving security is described, in which little information is leaked to the eavesdropper regardless of the signal disturbance.

The draft genome of the ctenophore Pleurobrachia bachei (Pacific sea gooseberry) is presented, together with ten other ctenophore transcriptomes — these genomes have a very different neurogenic, immune and developmental gene content when compared with other animal genomes, and it is proposed that ctenophore neural systems, and possibly muscle specification, evolved independently from those in other animals.

The discovery of a selective, physiologically active inhibitor of insulin-degrading enzyme (IDE) illuminates the therapeutic potential of IDE inhibitors for the treatment of diabetes and reveals that IDE regulates in vivo glucagon and amylin, in addition to insulin.

Metformin treatment of rats at physiologically relevant doses inhibits the redox shuttle enzyme mitochondrial glycerophosphate dehydrogenase.

The unusually large land carbon sink reported in 2011 can mostly be attributed to semi-arid vegetation growth in the Southern Hemisphere following increased rainfall and long-term greening trends.

The detection of strong emission lines in an early-time spectrum of type IIb supernova SN 2013cu reveals Wolf–Rayet-like wind signatures, suggesting that the supernova’s progenitor may have been a Wolf–Rayet star with a wind dominated by helium and nitrogen, with traces of hydrogen.

SMYD3 is a methyltransferase overexpressed in several human tumours; here methylation of the MAP3K2 kinase by SMYD3 is shown to be critical for Ras-induced tumour development in mouse models and human tumour cells, showing an unexpected role for methylation in a kinase signalling pathway and revealing a candidate therapeutic target.

Information integration in the nucleus accumbens is commandeered by cocaine at discrete synapses to allow relapse.

Functional metagenomic selections for resistance to 18 antibiotics in 18 different soils reveal that bacterial community composition is the primary determinant of soil antibiotic resistance gene content.