DNA repair is limiting for haematopoietic stem cells during ageing

Accumulation of DNA damage leading to adult stem cell exhaustion has been proposed to be a principal mechanism of ageing. Here we address this question by taking advantage of the highly specific role of DNA ligase IV in the repair of DNA double-strand breaks by non-homologous end-joining, and by the discovery of a unique mouse strain with a hypomorphic Lig4(Y288C) mutation. The Lig4(Y288C) mouse, identified by means of a mutagenesis screening programme, is a mouse model for human LIG4 syndrome, showing immunodeficiency and growth retardation. Diminished DNA double-strand break repair in the Lig4(Y288C) strain causes a progressive loss of haematopoietic stem cells and bone marrow cellularity during ageing, and severely impairs stem cell function in tissue culture and transplantation. The sensitivity of haematopoietic stem cells to non-homologous end-joining deficiency is therefore a key determinant of their ability to maintain themselves against physiological stress over time and to withstand culture and transplantation.     

Recent decline in the global land evapotranspiration trend due to limited moisture supply

More than half of the solar energy absorbed by land surfaces is currently used to evaporate water. Climate change is expected to intensify the hydrological cycle and to alter evapotranspiration, with implications for ecosystem services and feedback to regional and global climate. Evapotranspiration changes may already be under way, but direct observational constraints are lacking at the global scale. Until such evidence is available, changes in the water cycle on land?a key diagnostic criterion of the effects of climate change and variability?remain uncertain. Here we provide a data-driven estimate of global land evapotranspiration from 1982 to 2008, compiled using a global monitoring network, meteorological and remote-sensing observations, and a machine-learning algorithm. In addition, we have assessed evapotranspiration variations over the same time period using an ensemble of process-based land-surface models. Our results suggest that global annual evapotranspiration increased on average by 7.1?±?1.0?millimetres per year per decade from 1982 to 1997. After that, coincident with the last major El Ni?o event in 1998, the global evapotranspiration increase seems to have ceased until 2008. This change was driven primarily by moisture limitation in the Southern Hemisphere, particularly Africa and Australia. In these regions, microwave satellite observations indicate that soil moisture decreased from 1998 to 2008. Hence, increasing soil-moisture limitations on evapotranspiration largely explain the recent decline of the global land-evapotranspiration trend. Whether the changing behaviour of evapotranspiration is representative of natural climate variability or reflects a more permanent reorganization of the land water cycle is a key question for earth system science.     

High-resolution mapping of meiotic crossovers and non-crossovers in yeast

Meiotic recombination has a central role in the evolution of sexually reproducing organisms. The two recombination outcomes, crossover and non-crossover, increase genetic diversity, but have the potential to homogenize alleles by gene conversion. Whereas crossover rates vary considerably across the genome, non-crossovers and gene conversions have only been identified in a handful of loci. To examine recombination genome wide and at high spatial resolution, we generated maps of crossovers, crossover-associated gene conversion and non-crossover gene conversion using dense genetic marker data collected from all four products of fifty-six yeast (Saccharomyces cerevisiae) meioses. Our maps reveal differences in the distributions of crossovers and non-crossovers, showing more regions where either crossovers or non-crossovers are favoured than expected by chance. Furthermore, we detect evidence for interference between crossovers and non-crossovers, a phenomenon previously only known to occur between crossovers. Up to 1% of the genome of each meiotic product is subject to gene conversion in a single meiosis, with detectable bias towards GC nucleotides. To our knowledge the maps represent the first high-resolution, genome-wide characterization of the multiple outcomes of recombination in any organism. In addition, because non-crossover hotspots create holes of reduced linkage within haplotype blocks, our results stress the need to incorporate non-crossovers into genetic linkage analysis.     

CDK targets Sae2 to control DNA-end resection and homologous recombination

DNA double-strand breaks (DSBs) are repaired by two principal mechanisms: non-homologous end-joining (NHEJ) and homologous recombination (HR). HR is the most accurate DSB repair mechanism but is generally restricted to the S and G2 phases of the cell cycle, when DNA has been replicated and a sister chromatid is available as a repair template. By contrast, NHEJ operates throughout the cell cycle but assumes most importance in G1 (refs 4, 6). The choice between repair pathways is governed by cyclin-dependent protein kinases (CDKs), with a major site of control being at the level of DSB resection, an event that is necessary for HR but not NHEJ, and which takes place most effectively in S and G2 (refs 2, 5). Here we establish that cell-cycle control of DSB resection in Saccharomyces cerevisiae results from the phosphorylation by CDK of an evolutionarily conserved motif in the Sae2 protein. We show that mutating Ser 267 of Sae2 to a non-phosphorylatable residue causes phenotypes comparable to those of a sae2Delta null mutant, including hypersensitivity to camptothecin, defective sporulation, reduced hairpin-induced recombination, severely impaired DNA-end processing and faulty assembly and disassembly of HR factors. Furthermore, a Sae2 mutation that mimics constitutive Ser 267 phosphorylation complements these phenotypes and overcomes the necessity of CDK activity for DSB resection. The Sae2 mutations also cause cell-cycle-stage specific hypersensitivity to DNA damage and affect the balance between HR and NHEJ. These findings therefore provide a mechanistic basis for cell-cycle control of DSB repair and highlight the importance of regulating DSB resection.     

Theta-paced flickering between place-cell maps in the hippocampus

The ability to recall discrete memories is thought to depend on the formation of attractor states in recurrent neural networks. In such networks, representations can be reactivated reliably from subsets of the cues that were present when the memory was encoded, at the same time as interference from competing representations is minimized. Theoretical studies have pointed to the recurrent CA3 system of the hippocampus as a possible attractor network. Consistent with predictions from these studies, experiments have shown that place representations in CA3 and downstream CA1 tolerate small changes in the configuration of the environment but switch to uncorrelated representations when dissimilarities become larger. However, the kinetics supporting such network transitions, at the subsecond timescale, is poorly understood. Here we show in rats that instantaneous transformation of the spatial context does not change the hippocampal representation all at once but is followed by temporary bistability in the discharge activity of CA3 ensembles. Rather than sliding through a continuum of intermediate activity states, the CA3 network undergoes a short period of competitive flickering between preformed representations of the past and present environment before settling on the latter. Network flickers are extremely fast, often with complete replacement of the active ensemble from one theta cycle to the next. Within individual cycles, segregation is stronger towards the end, when firing starts to decline, pointing to the theta cycle as a temporal unit for expression of attractor states in the hippocampus. Repetition of pattern-completion processes across successive theta cycles may facilitate error correction and enhance discriminative power in the presence of weak and ambiguous input cues.     

Dynamical Criticality: Overview and Open Questions

Systems that exhibit complex behaviours are often found in a particular dynamical condition, poised between order and disorder. This observation is at the core of the so-called criticality hypothesis, which states that systems in a dynamical regime between order and disorder attain the highest level of computational capabilities and achieve an optimal trade-off between robustness and flexibility. Recent results in cellular and evolutionary biology, neuroscience and computer science have revitalised the interest in the criticality hypothesis, emphasising its role as a viable candidate general law in adaptive complex systems. This paper provides an overview of the works on dynamical criticality that are — To the best of our knowledge — Particularly relevant for the criticality hypothesis. The authors review the main contributions concerning dynamics and information processing at the edge of chaos, and illustrate the main achievements in the study of critical dynamics in biological systems.Finally, the authors discuss open questions and propose an agenda for future work.     

Demonstration of temporal cloaking

Recent research has uncovered a remarkable ability to manipulate and control electromagnetic fields to produce effects such as perfect imaging and spatial cloaking. To achieve spatial cloaking, the index of refraction is manipulated to flow light from a probe around an object in such a way that a 'hole' in space is created, and the object remains hidden. Alternatively, it may be desirable to cloak the occurrence of an event over a finite time period, and the idea of temporal cloaking has been proposed in which the dispersion of the material is manipulated in time, producing a 'time hole' in the probe beam to hide the occurrence of the event from the observer. This approach is based on accelerating the front part of a probe light beam and slowing down its rear part to create a well controlled temporal gap--inside which an event occurs--such that the probe beam is not modified in any way by the event. The probe beam is then restored to its original form by the reverse manipulation of the dispersion. Here we present an experimental demonstration of temporal cloaking in an optical fibre-based system by applying concepts from the space-time duality between diffraction and dispersive broadening. We characterize the performance of our temporal cloak by detecting the spectral modification of a probe beam due to an optical interaction and show that the amplitude of the event (at the picosecond timescale) is reduced by more than an order of magnitude when the cloak is turned on. These results are a significant step towards the development of full spatio-temporal cloaking.     

Reconciling the temperature dependence of respiration across timescales and ecosystem types

Ecosystem respiration is the biotic conversion of organic carbon to carbon dioxide by all of the organisms in an ecosystem, including both consumers and primary producers. Respiration exhibits an exponential temperature dependence at the subcellular and individual levels, but at the ecosystem level respiration can be modified by many variables including community abundance and biomass, which vary substantially among ecosystems. Despite its importance for predicting the responses of the biosphere to climate change, it is as yet unknown whether the temperature dependence of ecosystem respiration varies systematically between aquatic and terrestrial environments. Here we use the largest database of respiratory measurements yet compiled to show that the sensitivity of ecosystem respiration to seasonal changes in temperature is remarkably similar for diverse environments encompassing lakes, rivers, estuaries, the open ocean and forested and non-forested terrestrial ecosystems, with an average activation energy similar to that of the respiratory complex (approximately 0.65?electronvolts (eV)). By contrast, annual ecosystem respiration shows a substantially greater temperature dependence across aquatic (approximately 0.65?eV) versus terrestrial ecosystems (approximately 0.32?eV) that span broad geographic gradients in temperature. Using a model derived from metabolic theory, these findings can be reconciled by similarities in the biochemical kinetics of metabolism at the subcellular level, and fundamental differences in the importance of other variables besides temperature—such as primary productivity and allochthonous carbon inputs—on the structure of aquatic and terrestrial biota at the community level.     

Iron meteorites as remnants of planetesimals formed in the terrestrial planet region

Iron meteorites are core fragments from differentiated and subsequently disrupted planetesimals. The parent bodies are usually assumed to have formed in the main asteroid belt, which is the source of most meteorites. Observational evidence, however, does not indicate that differentiated bodies or their fragments were ever common there. This view is also difficult to reconcile with the fact that the parent bodies of iron meteorites were as small as 20 km in diameter and that they formed 1-2 Myr earlier than the parent bodies of the ordinary chondrites. Here we show that the iron-meteorite parent bodies most probably formed in the terrestrial planet region. Fast accretion times there allowed small planetesimals to melt early in Solar System history by the decay of short-lived radionuclides (such as 26Al, 60Fe). The protoplanets emerging from this population not only induced collisional evolution among the remaining planetesimals but also scattered some of the survivors into the main belt, where they stayed for billions of years before escaping via a combination of collisions, Yarkovsky thermal forces, and resonances. We predict that some asteroids are main-belt interlopers (such as (4) Vesta). A select few may even be remnants of the long-lost precursor material that formed the Earth.     

Terahertz semiconductor-heterostructure laser

Semiconductor devices have become indispensable for generating electromagnetic radiation in everyday applications. Visible and infrared diode lasers are at the core of information technology, and at the other end of the spectrum, microwave and radio-frequency emitters enable wireless communications. But the terahertz region (1-10 THz; 1 THz = 10(12) Hz) between these ranges has remained largely underdeveloped, despite the identification of various possible applications--for example, chemical detection, astronomy and medical imaging. Progress in this area has been hampered by the lack of compact, low-consumption, solid-state terahertz sources. Here we report a monolithic terahertz injection laser that is based on interminiband transitions in the conduction band of a semiconductor (GaAs/AlGaAs) heterostructure. The prototype demonstrated emits a single mode at 4.4 THz, and already shows high output powers of more than 2 mW with low threshold current densities of about a few hundred A cm(-2) up to 50 K. These results are very promising for extending the present laser concept to continuous-wave and high-temperature operation, which would lead to implementation in practical photonic systems.