Research articles

Electron microscopy has advanced to the stage where individual elements can be identified with atomic resolution. Here it is shown to be possible to get fine-structure spectroscopic information of individual light atoms such as those of carbon, and so also probe their chemical state. This capability is illustrated by investigating the edges of a graphene sample, where it is possible to discriminate between single-, double- and triple-coordinated carbon atoms.

Although loss of XLF, a classical non-homologous DNA end-joining (NHEJ) repair factor, shows strong effects in non-lymphoid cells, in lymphoid cells its absence has only modest effects on V(D)J recombination. This study now shows that in lymphoid cells, two other repair factors — ATM kinase and histone protein H2AX — have functional redundancy with XLF. Thus, mice deficient in both ATM and XLF have compromised conventional NHEJ, although alternative end-joining is retained. The results hint that the redundant function in end-joining that XLF has with both ATM and H2AX may have to do with an ATM role in chromatin accessibility.

Here, an indirect estimate for the magnetic field strength within the Earth's core from measurements of tidal dissipation is presented. Previously reported evidence of anomalous dissipation in the Earth's nutations can be explained with a core-averaged field of 2.5 mT, eliminating the need for high fluid viscosity or a stronger magnetic field at the inner-core boundary.

Hexagons can easily tile a flat surface, but not a curved one. Defects with topological charge (such as heptagons and pentagons) make it easier to tile curved surfaces, such as soccer balls. Here, a new type of defect is reported that accommodates curvature in the same way as fabric pleats. The appearance of such defects on the negatively curved surfaces of stretched colloidal crystals are observed. The results will facilitate the exploration of general theories of defects in curved spaces, the engineering of curved structures and novel methods for soft lithography and directed self-assembly.

Analysing single cells from human B-cell acute lymphoblastic leukaemias, this study maps the genetic heterogeneity of cells within a given tumour sample, the evolutionary path by which different subclones have emerged, and ongoing dynamic changes associated with relapse. Leukaemia-propagating cells that transplant the disease mirror the genetic variegation of the bulk tumours, providing insights into the heterogeneity of these functional subpopulations at the genetic level. This has implications for therapeutic approaches targeting the tumours and specifically leukaemia-propagating cells.

A crystal structure of the tandem PHD and bromodomain regions of the transcription and chromatin regulator TRIM24 reveals combinatorial recognition of dual marks on the histone H3 tail. TRIM24 is involved in activation of oestrogen-dependent genes and is aberrantly expressed in breast cancer.

Antigen receptor loci contain numerous gene segments that are recombined in response to antigen stimulation. The RAG endonuclease makes the double-strand breaks that initiate recombination. The ends of these breaks are hairpins that can only be cleaved by the Artemis nuclease. Here, it is shown that the specificity for Artemis is dictated by the histone protein H2AX, in cooperation with the repair protein MDC-1. In the absence of H2AX, another nuclease, CtIP, can open the ends but they are not joined efficiently; this leads to genomic instability.

How new phenotypes can be introduced during evolution without losses of fitness remains largely unexplained at the molecular level. By comparing the molecular details of a well known process — mating type determination — across a large diversity of yeast species, the network rewiring event of the intercalation of a new level of gene transcription control into an ancient regulatory circuit is shown, which allowed for the creation of a new phenotype — taking food availability into account when deciding to mate.

β-adrenergic receptor signalling in adipocytes stimulates energy expenditure via cAMP-dependent increases in lipolysis and fatty-acid oxidation, and this signalling mechanism is thought to be disrupted in obesity. Here, the cAMP-responsive CREB coactivator Crtc3 is shown to promote obesity in mice by attenuating β adrenergic receptor signalling in adipose tissue.

The dramatic loss of Arctic sea ice with climate change has led to the prediction of a tipping point beyond which ice loss is irreversible and polar bear habitat will be catastrophically lost. By contrast, this study shows a linear relationship between temperature and sea-ice coverage that overcomes the albedo effect that would cause a tipping point. As a result, reducing greenhouse gas emissions can have a positive effect on polar bear populations.

Identifying the genomic regulatory sequences, such as enhancers, that control early embryonic development remains a difficult challenge. Here, profiling of histone modifications and chromatin regulators in human embryonic stem cells (hESCs) reveals unique signatures that are used to identify over 2,000 putative enhancers. These enhancers are either active in the h ESCs or associated with early developmental genes.

The first X-ray crystal structure of a diterpene cyclase is reported — this enzyme, taxadiene synthase, catalyses the cyclization of an isoprenoid in the first committed step of the biosynthesis of the cancer chemotherapeutic drug Taxol. The C-terminal catalytic domain binds and activates the substrate in a manner seen in class I terpenoid cyclases, but the N-terminal domain and a third 'insertion' domain together adopt the fold of a class II terpenoid cyclase. It is proposed that this enzyme could be the ancestral progenitor of all terpenoid cyclases.

Studies have indicated an undefined role in DNA replication for CENP-B, a DNA binding protein associated with heterochromatin, centromeres and retrotransposon long terminal repeats (LTRs). Here it is shown that Sap1, which binds LTRs, promotes genomic instability when CENP-B activity is absent. CENP-B facilitates replication fork progression through LTRs in a way that protects against rearrangements.

Saturn's rings are more than 90–95% water ice, which implies that initially they were almost pure ice because they are continually polluted by rocky meteoroids. Saturn has only one large satellite, Titan, whereas Jupiter has four large satellites; additional large satellites probably existed originally but were lost as they spiralled into Saturn. Now, numerical simulations of the tidal removal of mass from a differentiated, Titan sized satellite as it migrates inward towards Saturn are reported. Planetary tidal forces preferentially strip material from the satellite's outer icy layers, while its rocky core remains intact and is lost to collision with the planet. The result is a pure ice ring.

Using a temporal series of growth factor manipulations to mimic embryonic intestinal development in culture, this study has successfully directed the differentiation of human pluripotent stem cells (both embryonic stem cells and induced pluripotent stem cells) into intestinal tissue. This approach may provide therapeutic benefit for disease studies.

The TET family of enzymes convert 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) in DNA. Mutations in the gene encoding TET2 are frequently observed in myeloid malignancies. Here it is shown that these disease-associated mutations compromise TET2 catalytic activity; bone marrow samples from patients with TET2 mutations have low levels of 5hmC in genomic DNA, and TET2 is required for normal haematopoietic differentiation. Measurement of genomic 5hmC levels may prove valuable as a diagnostic tool in myeloid cancers.

Observations of the 21-centimetre line of atomic hydrogen in the early Universe directly probe the history of the reionization of the gas between galaxies. If reionization happened rapidly, there will be a characteristic signature visible against the smooth foreground in an all-sky spectrum. Here, an all-sky average spectrum between 100 and 200 MHz is reported, corresponding to the redshift range 6 < z < 13 for the 21-centimetree line. The data exclude a rapid reionization timescale of Δz < 0.06 at the 95% confidence level.