The tungsten isotopic composition of the Earth's mantle before the terminal bombardment

Many precious, 'iron-loving' metals, such as gold, are surprisingly abundant in the accessible parts of the Earth, given the efficiency with which core formation should have removed them to the planet's deep interior. One explanation of their over-abundance is a 'late veneer'--a flux of meteorites added to the Earth after core formation as a 'terminal' bombardment that culminated in the cratering of the Moon. Some 3.8 billion-year-old rocks from Isua, Greenland, are derived from sources that retain an isotopic memory of events pre-dating this cataclysmic meteorite shower. These Isua samples thus provide a window on the composition of the Earth before such a late veneer and allow a direct test of its importance in modifying the composition of the planet. Using high-precision (less than 6 parts per million, 2 standard deviations) tungsten isotope analyses of these rocks, here we show that they have a isotopic tungsten ratio (182)W/(184)W that is significantly higher (about 13 parts per million) than modern terrestrial samples. This finding is in good agreement with the expected influence of a late veneer. We also show that alternative interpretations, such as partial remixing of a deep-mantle reservoir formed in the Hadean eon (more than four billion years ago) or core-mantle interaction, do not explain the W isotope data well. The decrease in mantle (182)W/(184)W occurs during the Archean eon (about four to three billion years ago), potentially on the same timescale as a notable decrease in (142)Nd/(144)Nd (refs 3 and 6). We speculate that both observations can be explained if late meteorite bombardment triggered the onset of the current style of mantle convection.     

T-cell recognition of chemicals, protein allergens and drugs: towards the development of in vitro assays

Chemicals can elicit T-cell-mediated diseases such as allergic contact dermatitis and adverse drug reactions. Therefore, testing of chemicals, drugs and protein allergens for hazard identification and risk assessment is essential in regulatory toxicology. The seventh amendment of the EU Cosmetics Directive now prohibits the testing of cosmetic ingredients in mice, guinea pigs and other animal species to assess their sensitizing potential. In addition, the EU Chemicals Directive REACh requires the retesting of more than 30,000 chemicals for different toxicological endpoints, including sensitization, requiring vast numbers of animals. Therefore, alternative methods are urgently needed to eventually replace animal testing. Here, we summarize the outcome of an expert meeting in Rome on 7 November 2009 on the development of T-cell-based in vitro assays as tools in immunotoxicology to identify hazardous chemicals and drugs. In addition, we provide an overview of the development of the field over the last two decades.     

UCP2 mediates ghrelin's action on NPY/AgRP neurons by lowering free radicals

The gut-derived hormone ghrelin exerts its effect on the brain by regulating neuronal activity. Ghrelin-induced feeding behaviour is controlled by arcuate nucleus neurons that co-express neuropeptide Y and agouti-related protein (NPY/AgRP neurons). However, the intracellular mechanisms triggered by ghrelin to alter NPY/AgRP neuronal activity are poorly understood. Here we show that ghrelin initiates robust changes in hypothalamic mitochondrial respiration in mice that are dependent on uncoupling protein 2 (UCP2). Activation of this mitochondrial mechanism is critical for ghrelin-induced mitochondrial proliferation and electric activation of NPY/AgRP neurons, for ghrelin-triggered synaptic plasticity of pro-opiomelanocortin-expressing neurons, and for ghrelin-induced food intake. The UCP2-dependent action of ghrelin on NPY/AgRP neurons is driven by a hypothalamic fatty acid oxidation pathway involving AMPK, CPT1 and free radicals that are scavenged by UCP2. These results reveal a signalling modality connecting mitochondria-mediated effects of G-protein-coupled receptors on neuronal function and associated behaviour.     

Ecologically implausible carbon response?

Magnani et al. present a very strong correlation between mean lifetime net ecosystem production (NEP, defined as the net rate of carbon (C) accumulation in ecosystems) and wet nitrogen (N) deposition. For their data in the range 4.9-9.8 kg N ha(-1) yr(-1), on which the correlation largely depends, the response is approximately 725 kg C per kg N in wet deposition. According to the authors, the maximum N wet deposition level of 9.8 kg N ha(-1) yr(-1) is equivalent to a total deposition of 15 kg N ha(-1 )yr(-1), implying a net sequestration near 470 kg C per kg N of total deposition. We question the ecological plausibility of the relationship and show, from a multi-factor analysis of European forest measurements, how interactions with site productivity and environment imply a much smaller NEP response to N deposition.     

Palindromic assembly of the giant muscle protein titin in the sarcomeric Z-disk

The Z-disk of striated and cardiac muscle sarcomeres is one of the most densely packed cellular structures in eukaryotic cells. It provides the architectural framework for assembling and anchoring the largest known muscle filament systems by an extensive network of protein-protein interactions, requiring an extraordinary level of mechanical stability. Here we show, using X-ray crystallography, how the amino terminus of the longest filament component, the giant muscle protein titin, is assembled into an antiparallel (2:1) sandwich complex by the Z-disk ligand telethonin. The pseudosymmetric structure of telethonin mediates a unique palindromic arrangement of two titin filaments, a type of molecular assembly previously found only in protein-DNA complexes. We have confirmed its unique architecture in vivo by protein complementation assays, and in vitro by experiments using fluorescence resonance energy transfer. The model proposed may provide a molecular paradigm of how major sarcomeric filaments are crosslinked, anchored and aligned within complex cytoskeletal networks.     

Social Choice Meets Graph Drawing： How to Get Subexponential Time Algorithms for Ranking and Drawing Problems

We analyze a common feature of p-Kemeny AGGregation(p-KAGG) and p-One-Sided Crossing Minimization(p-OSCM) to provide new insights and findings of interest to both the graph drawing community and the social choice community. We obtain parameterized subexponential-time algorithms for p-KAGG—a problem in social choice theory—and for p-OSCM—a problem in graph drawing. These algorithms run in time O.2O.pk logk//,where k is the parameter, and significantly improve the previous best algorithms with running times O.1.403k/and O.1.4656k/, respectively. We also study natural above-guarantee versions of these problems and show them to be fixed parameter tractable. In fact, we show that the above-guarantee versions of these problems are equivalent to a weighted variant of p-directed feedback arc set. Our results for the above-guarantee version of p-KAGG reveal an interesting contrast. We show that when the number of votes in the input to p-KAGG is odd the above guarantee version can still be solved in time O.2O.pk logk//, while if it is even then the problem cannot have a subexponential time algorithm unless the exponential time hypothesis fails(equivalently, unless FPT D M[1]).