Late survival of Neanderthals at the southernmost extreme of Europe

The late survival of archaic hominin populations and their long contemporaneity with modern humans is now clear for southeast Asia. In Europe the extinction of the Neanderthals, firmly associated with Mousterian technology, has received much attention, and evidence of their survival after 35 kyr bp has recently been put in doubt. Here we present data, based on a high-resolution record of human occupation from Gorham's Cave, Gibraltar, that establish the survival of a population of Neanderthals to 28 kyr bp. These Neanderthals survived in the southernmost point of Europe, within a particular physiographic context, and are the last currently recorded anywhere. Our results show that the Neanderthals survived in isolated refuges well after the arrival of modern humans in Europe.     

Molecular machines: nanomotor rotates microscale objects

Nanomachines of the future will require molecular-scale motors that can perform work and collectively induce controlled motion of much larger objects. We have designed a synthetic, light-driven molecular motor that is embedded in a liquid-crystal film and can rotate objects placed on the film that exceed the size of the motor molecule by a factor of 10,000. The changes in shape of the motor during the rotary steps cause a remarkable rotational reorganization of the liquid-crystal film and its surface relief, which ultimately causes the rotation of submillimetre-sized particles on the film.     

Inhibition of climbing fibres is a signal for the extinction of conditioned eyelid responses

A fundamental tenet of cerebellar learning theories asserts that climbing fibre afferents from the inferior olive provide a teaching signal that promotes the gradual adaptation of movements. Data from several forms of motor learning provide support for this tenet. In pavlovian eyelid conditioning, for example, where a tone is repeatedly paired with a reinforcing unconditioned stimulus like periorbital stimulation, the unconditioned stimulus promotes acquisition of conditioned eyelid responses by activating climbing fibres. Climbing fibre activity elicited by an unconditioned stimulus is inhibited during the expression of conditioned responses-consistent with the inhibitory projection from the cerebellum to inferior olive. Here, we show that inhibition of climbing fibres serves as a teaching signal for extinction, where learning not to respond is signalled by presenting a tone without the unconditioned stimulus. We used reversible infusion of synaptic receptor antagonists to show that blocking inhibitory input to the climbing fibres prevents extinction of the conditioned response, whereas blocking excitatory input induces extinction. These results, combined with analysis of climbing fibre activity in a computer simulation of the cerebellar-olivary system, suggest that transient inhibition of climbing fibres below their background level is the signal that drives extinction.     

规范场、纽结与引力

20世纪物理学的两个最激动人心的发展是广义相对论与量子力学，后者最终形成了粒子相互作用的“标准模型”。广义相对论研究引力，而标准模型则研究剩下的自然力。不幸的是，这两种理论还没有整合成一个单一连贯的图像，还没有一个考虑到量子理论的引力有效理论。虽然量子化引力促使数学和物理学许多引人入胜的进展，但是在21世纪仍然面临着更大的挑战。     

Effect of initial microstructure on austenite formation kinetics in high-strength experimental microalloyed steels

Austenite formation kinetics in two high-strength experimental microalloyed steels with different initial microstructures compris-ing bainite–martensite and ferrite–martensite/austenite microconstituents was studied during continuous heating by dilatometric analysis. Austenite formation occurred in two steps:(1) carbide dissolution and precipitation and (2) transformation of residual ferrite to austenite. Di-latometric analysis was used to determine the critical temperatures of austenite formation and continuous heating transformation diagrams for heating rates ranging from 0.03°C×s?1 to 0.67°C×s?1. The austenite volume fraction was fitted using the Johnson–Mehl–Avrami–Kolmogorov equation to determine the kinetic parameters k and n as functions of the heating rate. Both n and k parameters increased with increasing heat-ing rate, which suggests an increase in the nucleation and growth rates of austenite. The activation energy of austenite formation was deter-mined by the Kissinger method. Two activation energies were associated with each of the two austenite formation steps. In the first step, the austenite growth rate was controlled by carbon diffusion from carbide dissolution and precipitation;in the second step, it was controlled by the dissolution of residual ferrite to austenite.     

A common haplotype of interferon regulatory factor 5 (IRF5) regulates splicing and expression and is associated with increased risk of systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by activation of the type I interferon (IFN) pathway. Here we convincingly replicate association of the IFN regulatory factor 5 (IRF5) rs2004640 T allele with SLE in four independent case-control cohorts (P = 4.4 x 10(-16)) and by family-based transmission disequilibrium test analysis (P = 0.0006). The rs2004640 T allele creates a 5' donor splice site in an alternate exon 1 of IRF5, allowing expression of several unique IRF5 isoforms. We also identify an independent cis-acting variant associated with elevated expression of IRF5 and linked to the exon 1B splice site. Haplotypes carrying the variant associated with elevated expression and lacking the exon 1B donor site do not confer risk of SLE. Thus, a common IRF5 haplotype driving elevated expression of multiple unique isoforms of IRF5 is an important genetic risk factor for SLE, establishing a causal role for type I IFN pathway genes in human autoimmunity.     

Common variants on chromosomes 2q35 and 16q12 confer susceptibility to estrogen receptor-positive breast cancer

Familial clustering studies indicate that breast cancer risk has a substantial genetic component. To identify new breast cancer risk variants, we genotyped approximately 300,000 SNPs in 1,600 Icelandic individuals with breast cancer and 11,563 controls using the Illumina Hap300 platform. We then tested selected SNPs in five replication sample sets. Overall, we studied 4,554 affected individuals and 17,577 controls. Two SNPs consistently associated with breast cancer: approximately 25% of individuals of European descent are homozygous for allele A of rs13387042 on chromosome 2q35 and have an estimated 1.44-fold greater risk than noncarriers, and for allele T of rs3803662 on 16q12, about 7% are homozygous and have a 1.64-fold greater risk. Risk from both alleles was confined to estrogen receptor-positive tumors. At present, no genes have been identified in the linkage disequilibrium block containing rs13387042. rs3803662 is near the 5' end of TNRC9 , a high mobility group chromatin-associated protein whose expression is implicated in breast cancer metastasis to bone.     

Discovery of a magma chamber and faults beneath a Mid-Atlantic Ridge hydrothermal field

Crust at slow-spreading ridges is formed by a combination of magmatic and tectonic processes, with magmatic accretion possibly involving short-lived crustal magma chambers. The reflections of seismic waves from crustal magma chambers have been observed beneath intermediate and fast-spreading centres, but it has been difficult to image such magma chambers beneath slow-spreading centres, owing to rough seafloor topography and associated seafloor scattering. In the absence of any images of magma chambers or of subsurface near-axis faults, it has been difficult to characterize the interplay of magmatic and tectonic processes in crustal accretion and hydrothermal circulation at slow-spreading ridges. Here we report the presence of a crustal magma chamber beneath the slow-spreading Lucky Strike segment of the Mid-Atlantic Ridge. The reflection from the top of the magma chamber, centred beneath the Lucky Strike volcano and hydrothermal field, is approximately 3 km beneath the sea floor, 3-4 km wide and extends up to 7 km along-axis. We suggest that this magma chamber provides the heat for the active hydrothermal vent field above it. We also observe axial valley bounding faults that seem to penetrate down to the magma chamber depth as well as a set of inward-dipping faults cutting through the volcanic edifice, suggesting continuous interactions between tectonic and magmatic processes.     

Widespread active detachment faulting and core complex formation near 13 degrees N on the Mid-Atlantic Ridge

Oceanic core complexes are massifs in which lower-crustal and upper-mantle rocks are exposed at the sea floor. They form at mid-ocean ridges through slip on detachment faults rooted below the spreading axis. To date, most studies of core complexes have been based on isolated inactive massifs that have spread away from ridge axes. Here we present a survey of the Mid-Atlantic Ridge near 13 degrees N containing a segment in which a number of linked detachment faults extend for 75 km along one flank of the spreading axis. The detachment faults are apparently all currently active and at various stages of development. A field of extinct core complexes extends away from the axis for at least 100 km. Our observations reveal the topographic characteristics of actively forming core complexes and their evolution from initiation within the axial valley floor to maturity and eventual inactivity. Within the surrounding region there is a strong correlation between detachment fault morphology at the ridge axis and high rates of hydroacoustically recorded earthquake seismicity. Preliminary examination of seismicity and seafloor morphology farther north along the Mid-Atlantic Ridge suggests that active detachment faulting is occurring in many segments and that detachment faulting is more important in the generation of ocean crust at this slow-spreading ridge than previously suspected.     

Visualizing molecular juggling within a B12-dependent methyltransferase complex

Derivatives of vitamin B(12) are used in methyl group transfer in biological processes as diverse as methionine synthesis in humans and CO(2) fixation in acetogenic bacteria. This seemingly straightforward reaction requires large, multimodular enzyme complexes that adopt multiple conformations to alternately activate, protect and perform catalysis on the reactive B(12) cofactor. Crystal structures determined thus far have provided structural information for only fragments of these complexes, inspiring speculation about the overall protein assembly and conformational movements inherent to activity. Here we present X-ray crystal structures of a complete 220?kDa complex that contains all enzymes responsible for B(12)-dependent methyl transfer, namely the corrinoid iron-sulphur protein and its methyltransferase from the model acetogen Moorella thermoacetica. These structures provide the first three-dimensional depiction of all protein modules required for the activation, protection and catalytic steps of B(12)-dependent methyl transfer. In addition, the structures capture B(12) at multiple locations between its 'resting' and catalytic positions, allowing visualization of the dramatic protein rearrangements that enable methyl transfer and identification of the trajectory for B(12) movement within the large enzyme scaffold. The structures are also presented alongside in crystallo spectroscopic data, which confirm enzymatic activity within crystals and demonstrate the largest known conformational movements of proteins in a crystalline state. Taken together, this work provides a model for the molecular juggling that accompanies turnover and helps explain why such an elaborate protein framework is required for such a simple, yet biologically essential reaction.