XPF nuclease-dependent telomere loss and increased DNA damage in mice overexpressing TRF2 result in premature aging and cancer

TRF2 is a telomere-binding protein that has a role in telomere protection. We generated mice that overexpress TRF2 in the skin. These mice had a severe phenotype in the skin in response to light, consisting of premature skin deterioration, hyperpigmentation and increased skin cancer, which resembles the human syndrome xeroderma pigmentosum. Keratinocytes from these mice were hypersensitive to ultraviolet irradiation and DNA crosslinking agents. The skin cells of these mice had marked telomere shortening, loss of the telomeric G-strand overhang and increased chromosomal instability. Telomere loss in these mice was mediated by XPF, a structure-specific nuclease involved in ultraviolet-induced damage repair and mutated in individuals with xeroderma pigmentosum. These findings suggest that TRF2 provides a crucial link between telomere function and ultraviolet-induced damage repair, whose alteration underlies genomic instability, cancer and aging. Finally, we show that a number of human skin tumors have increased expression of TRF2, further highlighting a role for TRF2 in skin cancer.     

Ipr1 gene mediates innate immunity to tuberculosis

An estimated eight million people are infected each year with the pathogen Mycobacterium tuberculosis, and more than two million die annually. Yet only about 10% of those infected develop tuberculosis. Genetic variation within host populations is known to be significant in humans and animals, but the nature of genetic control of host resistance to tuberculosis remains poorly understood. Previously we mapped a new genetic locus on mouse chromosome 1, designated sst1 (for supersusceptibility to tuberculosis 1). Here we show that this locus mediates innate immunity in sst1 congenic mouse strains and identify a candidate gene, Intracellular pathogen resistance 1 (Ipr1), within the sst1 locus. The Ipr1 gene is upregulated in the sst1 resistant macrophages after activation and infection, but it is not expressed in the sst1 susceptible macrophages. Expression of the Ipr1 transgene in the sst1 susceptible macrophages limits the multiplication not only of M. tuberculosis but also of Listeria monocytogenes and switches a cell death pathway of the infected macrophages from necrosis to apoptosis. Our data indicate that the Ipr1 gene product might have a previously undocumented function in integrating signals generated by intracellular pathogens with mechanisms controlling innate immunity, cell death and pathogenesis.     

Sodium channel mutation leading to saxitoxin resistance in clams increases risk of PSP

Bivalve molluscs, the primary vectors of paralytic shellfish poisoning (PSP) in humans, show marked inter-species variation in their capacity to accumulate PSP toxins (PSTs) which has a neural basis. PSTs cause human fatalities by blocking sodium conductance in nerve fibres. Here we identify a molecular basis for inter-population variation in PSP resistance within a species, consistent with genetic adaptation to PSTs. Softshell clams (Mya arenaria) from areas exposed to 'red tides' are more resistant to PSTs, as demonstrated by whole-nerve assays, and accumulate toxins at greater rates than sensitive clams from unexposed areas. PSTs lead to selective mortality of sensitive clams. Resistance is caused by natural mutation of a single amino acid residue, which causes a 1,000-fold decrease in affinity at the saxitoxin-binding site in the sodium channel pore of resistant, but not sensitive, clams. Thus PSTs might act as potent natural selection agents, leading to greater toxin resistance in clam populations and increased risk of PSP in humans. Furthermore, global expansion of PSP to previously unaffected coastal areas might result in long-term changes to communities and ecosystems.     

Phyllosilicates on Mars and implications for early martian climate

The recent identification of large deposits of sulphates by remote sensing and in situ observations has been considered evidence of the past presence of liquid water on Mars. Here we report the unambiguous detection of diverse phyllosilicates, a family of aqueous alteration products, on the basis of observations by the OMEGA imaging spectrometer on board the Mars Express spacecraft. These minerals are mainly associated with Noachian outcrops, which is consistent with an early active hydrological system, sustaining the long-term contact of igneous minerals with liquid water. We infer that the two main families of hydrated alteration products detected-phyllosilicates and sulphates--result from different formation processes. These occurred during two distinct climatic episodes: an early Noachian Mars, resulting in the formation of hydrated silicates, followed by a more acidic environment, in which sulphates formed.     

In situ measurements of the physical characteristics of Titan's environment

On the basis of previous ground-based and fly-by information, we knew that Titan's atmosphere was mainly nitrogen, with some methane, but its temperature and pressure profiles were poorly constrained because of uncertainties in the detailed composition. The extent of atmospheric electricity ('lightning') was also hitherto unknown. Here we report the temperature and density profiles, as determined by the Huygens Atmospheric Structure Instrument (HASI), from an altitude of 1,400 km down to the surface. In the upper part of the atmosphere, the temperature and density were both higher than expected. There is a lower ionospheric layer between 140 km and 40 km, with electrical conductivity peaking near 60 km. We may also have seen the signature of lightning. At the surface, the temperature was 93.65 +/- 0.25 K, and the pressure was 1,467 +/- 1 hPa.     

Forensics: age written in teeth by nuclear tests

Establishing the age at death of individuals is an important step in their identification and can be done with high precision up to adolescence by analysis of dentition, but it is more difficult in adults. Here we show that the amount of radiocarbon present in tooth enamel as a result of nuclear bomb testing during 1955-63 is a remarkably accurate indicator of when a person was born. Age is determined to within 1.6 years, whereas the commonly used morphological evaluation of skeletal remains and tooth wear is sensitive to within 5-10 years in adults.     

Self-similarity of complex networks

Complex networks have been studied extensively owing to their relevance to many real systems such as the world-wide web, the Internet, energy landscapes and biological and social networks. A large number of real networks are referred to as 'scale-free' because they show a power-law distribution of the number of links per node. However, it is widely believed that complex networks are not invariant or self-similar under a length-scale transformation. This conclusion originates from the 'small-world' property of these networks, which implies that the number of nodes increases exponentially with the 'diameter' of the network, rather than the power-law relation expected for a self-similar structure. Here we analyse a variety of real complex networks and find that, on the contrary, they consist of self-repeating patterns on all length scales. This result is achieved by the application of a renormalization procedure that coarse-grains the system into boxes containing nodes within a given 'size'. We identify a power-law relation between the number of boxes needed to cover the network and the size of the box, defining a finite self-similar exponent. These fundamental properties help to explain the scale-free nature of complex networks and suggest a common self-organization dynamics.     

A short gamma-ray burst apparently associated with an elliptical galaxy at redshift z = 0.225

Gamma-ray bursts (GRBs) come in two classes: long (> 2 s), soft-spectrum bursts and short, hard events. Most progress has been made on understanding the long GRBs, which are typically observed at high redshift (z approximately 1) and found in subluminous star-forming host galaxies. They are likely to be produced in core-collapse explosions of massive stars. In contrast, no short GRB had been accurately (< 10') and rapidly (minutes) located. Here we report the detection of the X-ray afterglow from--and the localization of--the short burst GRB 050509B. Its position on the sky is near a luminous, non-star-forming elliptical galaxy at a redshift of 0.225, which is the location one would expect if the origin of this GRB is through the merger of neutron-star or black-hole binaries. The X-ray afterglow was weak and faded below the detection limit within a few hours; no optical afterglow was detected to stringent limits, explaining the past difficulty in localizing short GRBs.     

Europe-wide reduction in primary productivity caused by the heat and drought in 2003

Future climate warming is expected to enhance plant growth in temperate ecosystems and to increase carbon sequestration. But although severe regional heatwaves may become more frequent in a changing climate, their impact on terrestrial carbon cycling is unclear. Here we report measurements of ecosystem carbon dioxide fluxes, remotely sensed radiation absorbed by plants, and country-level crop yields taken during the European heatwave in 2003. We use a terrestrial biosphere simulation model to assess continental-scale changes in primary productivity during 2003, and their consequences for the net carbon balance. We estimate a 30 per cent reduction in gross primary productivity over Europe, which resulted in a strong anomalous net source of carbon dioxide (0.5 Pg C yr(-1)) to the atmosphere and reversed the effect of four years of net ecosystem carbon sequestration. Our results suggest that productivity reduction in eastern and western Europe can be explained by rainfall deficit and extreme summer heat, respectively. We also find that ecosystem respiration decreased together with gross primary productivity, rather than accelerating with the temperature rise. Model results, corroborated by historical records of crop yields, suggest that such a reduction in Europe's primary productivity is unprecedented during the last century. An increase in future drought events could turn temperate ecosystems into carbon sources, contributing to positive carbon-climate feedbacks already anticipated in the tropics and at high latitudes.