Research articles

Age-associated changes in stem cell supportive niche cells are shown to deregulate normal haematopoiesis by causing haematopoietic stem cell dysfunction. Age-dependent defects in niche cells are systemically regulated and can be reversed by exposure to a young circulation or by neutralization of the conserved longevity regulator, insulin-like growth factor-1, in the marrow microenvironment.

The γ-carboxylation of many blood coagulation factors relies on the generation of vitamin K hydroquinone by the enzyme vitamin K epoxide reductase (VKOR), of which the anticoagulant warfarin is an inhibitor. Here, the X-ray crystal structure of a bacterial homologue of VKOR is presented; the results have implications for the mechanism of action of mammalian VKOR and explain how mutations can cause warfarin resistance.

Anthropogenic global warming is likely to be amplified by positive feedback from the global carbon cycle; however, the magnitude of the climate sensitivity of the global carbon cycle, and thus of its positive feedback strength, is under debate. By combining a probabilistic approach with an ensemble of proxy-based temperature reconstructions and pre-industrial CO₂ data from three ice cores, this climate sensitivity is now shown to be much smaller than previously thought.

Although humans have engaged in long-distance running either barefoot or with minimal footwear for most of human evolutionary history, the modern running shoe was not invented until the 1970s. Here, runners who habitually run in sports shoes are shown to run differently to those who habitually run barefoot, with the latter often landing on the fore-foot rather than the rear-foot. This strike pattern may have evolved to protect from some of the impact-related injuries now experienced by runners.

Mouse and human fibroblasts can be reprogrammed to a pluripotent state with a combination of four transcription factors. Here, mature differentiated cells are directed, via a combination of a few transcription factors (distinct from those described for generating iPS cells), to form functional neurons in vitro, without having to revert the fibroblasts to an embryonic state.

Echolocation is usually associated with bats. Many echolocating bats produce signals in the larynx, but a few species produce tongue clicks. Here, studies show that in all bats that use larynx-generated clicks, the stylohyal bone is connected to the tympanic bone. Study of the stylohyal and tympanic bones of a primitive fossil bat indicates that this species may have been able to echolocate, despite previous evidence to the contrary, raising the question of when and how echolocation evolved in bats.

Animals use the Earth's magnetic field for orientation but the biophysical basis of this is unclear. The light-dependent magnetic sense of Drosophila melanogaster was recently shown to be mediated by the cryptochrome (Cry) photoreceptor; here, using a transgenic approach, the type 1 and 2 Cry of the monarch butterfly are shown to both function in the magnetoreception system of Drosophila, and probably use an unconventional photochemical mechanism.

The extent of epigenetic reprogramming in mammalian primordial germ cells (PGCs) and in early embryos, and its molecular mechanisms, are poorly understood. DNA methylation profiling in PGCs now reveals a genome–wide erasure of methylation, with female PGCs being less methylated than male ones. A deficiency of the cytidine deaminase AID interferes with the genome–wide erasure of DNA methylation, indicating that AID has a critical function in epigenetic reprogramming.

High concentrations of ozone in the troposphere are toxic and act as a greenhouse gas. Anthropogenic emissions of ozone precursors have caused widespread increases in ozone concentrations since the late 1800s, with the fastest-growing ozone precursor emissions currently coming out of east Asia. Much of the springtime east Asian pollution is exported towards western North America; a strong increase in springtime ozone mixing ratios is now found in the free troposphere over this region.

A defining focus of synthetic biology is the engineering of genetic circuits with predictive functionality in living cells. Here, a decade after the first synthesized genetic toggle switch and oscillator, an engineered gene network with global intercellular coupling is designed that is capable of generating synchronized oscillations in a growing population of cells.

Although cyclin D1 is frequently overexpressed in human cancers, the full range of its functions in normal development and oncogenesis is unclear. Here, tagged cyclin D1 knock-in mouse strains are developed to allow a search for cyclin D1-binding proteins in different mouse organs using high-throughput mass spectrometry. The results show that, in addition to its established cell cycle roles, cyclin D1 has an in vivo transcriptional function in mouse development.

Although deformation twinning in crystals controls the mechanical behaviour of many materials, its size-dependence has not been explored. Using micro-compression and in situ nano-compression experiments, the stress required for deformation twinning is now found to increase drastically with decreasing sample size of a titanium alloy single crystal, until the sample size is reduced to one micrometre; below this point, deformation twinning is replaced by dislocation plasticity.

If robustness is the opposite of evolvability, we might expect that a robust population would have difficulty adapting to environmental change; however, some studies have suggested that genetic robustness facilitates adaptation. Here, using a general population genetics model, mutational robustness is found to either impede or facilitate adaptation depending on the population size, the mutation rate and the structure of the fitness landscape.

Antimicrobial peptides (AMPs) are an important class of immune effector molecules which fight pathogen infections. AMP induction in Drosophila is regulated through the activation of the Toll and immune deficiency pathways; it is now shown that AMP activation can be achieved independently of these pathways by the transcription factor FOXO. In non-infected animals, AMP genes are activated in response to nuclear FOXO activity when induced by starvation.

Telescopic measurements of asteroids' colours rarely match laboratory reflectance spectra of meteorites owing to a 'space weathering' process that rapidly reddens asteroid surfaces. 'Unweathered' asteroids, however, with spectra matching ordinary chondrite meteorites, are seen only among small bodies with orbits that cross inside the orbits of Mars and Earth. Such unweathered asteroids are now shown to have experienced orbital intersections closer than the Earth–Moon distance within the past half-million years.

In the search to reduce our dependency on fossil-fuel energy, new plastic materials that are less dependent on petroleum are being developed, with water-based gels — hydrogels — representing one possible solution. Here, a mixture of water, 3% clay and a tiny amount of a special organic binder is shown to form a transparent hydrogel that can be moulded into shape-persistent, free-standing objects and that rapidly and completely self-heals when damaged.

Group II chaperonins are present in eukaryotes and archaea and are essential mediators of cellular protein folding. This process is critically dependent on the closure of a built-in lid, which is triggered by ATP hydrolysis, but the structural rearrangements and molecular events leading to lid closure are unknown. Using cryo-electron microscopy, the structures of an archaeal group II chaperonin in the open and closed states are now reported, providing details of this mechanism.

The amino acid antiporter AdiC is important for the survival of enteric bacteria such as Escherichia coli in extremely acid environments. Although the structure of substrate-free AdiC is known, how the substrate (arginine or agmatine) is recognized and transported by AdiC remains unclear. The crystal structure of an E. coli AdiC variant bound to arginine is now reported and analysed.