New data on isotopic composition of Jurassic-Early Cretaceous cephalopods

The aim of this paper is to reconstruct the Jurassic-Early Cretaceous climatic conditions using new isotopic data. Paleobotanical data indicate that a cooling occurred gradually just after Late Triassic, and a temperature minimum was reached in the Pliensbachian. This was followed by a climatic optimum in the early Toarcian, cooling in the late Toarcian and a second climatic optimum in the Oxfordian. Published isotopic thermometry data and our new results on isotopic composition of some Jurassic invertebrate shells from the Russian Platform, Poland, Germany and England generally confirm this pattern, and also indicate a third climatic optimum in the Middle Callovian. Middle-Late Mesozoic adult belemnites apparently lived during their spawning phase, in shallow waters similar to extant Nautilus. However, at least juvenile belemnoids, unlike ammonoids, engaged in significant short-term vertical migrations in the water column, reaching colder waters of the upper bathyal zone.     

随机场估计

本书给出随机场估计的解析理论，这种估计按照估计误差的方差的极小性判据是最优的，是经典的Wiener理论的一般化，其中不假定场的Gauss或Markov性质，整个理论在协方差框架建立，以估计理论中新的一类基本的多维积分方程的解析研究为基础。本书作者是这个理论的创始者。[第一段]     

A heteromeric Texas coral snake toxin targets acid-sensing ion channels to produce pain

Natural products that elicit discomfort or pain represent invaluable tools for probing molecular mechanisms underlying pain sensation. Plant-derived irritants have predominated in this regard, but animal venoms have also evolved to avert predators by targeting neurons and receptors whose activation produces noxious sensations. As such, venoms provide a rich and varied source of small molecule and protein pharmacophores that can be exploited to characterize and manipulate key components of the pain-signalling pathway. With this in mind, here we perform an unbiased in vitro screen to identify snake venoms capable of activating somatosensory neurons. Venom from the Texas coral snake (Micrurus tener tener), whose bite produces intense and unremitting pain, excites a large cohort of sensory neurons. The purified active species (MitTx) consists of a heteromeric complex between Kunitz- and phospholipase-A2-like proteins that together function as a potent, persistent and selective agonist for acid-sensing ion channels (ASICs), showing equal or greater efficacy compared with acidic pH. MitTx is highly selective for the ASIC1 subtype at neutral pH; under more acidic conditions (pH < 6.5), MitTx massively potentiates (>100-fold) proton-evoked activation of ASIC2a channels. These observations raise the possibility that ASIC channels function as coincidence detectors for extracellular protons and other, as yet unidentified, endogenous factors. Purified MitTx elicits robust pain-related behaviour in mice by activation of ASIC1 channels on capsaicin-sensitive nerve fibres. These findings reveal a mechanism whereby snake venoms produce pain, and highlight an unexpected contribution of ASIC1 channels to nociception.     

The genome sequence of Atlantic cod reveals a unique immune system

Atlantic cod (Gadus morhua) is a large, cold-adapted teleost that sustains long-standing commercial fisheries and incipient aquaculture. Here we present the genome sequence of Atlantic cod, showing evidence for complex thermal adaptations in its haemoglobin gene cluster and an unusual immune architecture compared to other sequenced vertebrates. The genome assembly was obtained exclusively by 454 sequencing of shotgun and paired-end libraries, and automated annotation identified 22,154 genes. The major histocompatibility complex (MHC)?II is a conserved feature of the adaptive immune system of jawed vertebrates, but we show that Atlantic cod has lost the genes for MHC?II, CD4 and invariant chain (Ii) that are essential for the function of this pathway. Nevertheless, Atlantic cod is not exceptionally susceptible to disease under natural conditions. We find a highly expanded number of MHC?I genes and a unique composition of its Toll-like receptor (TLR) families. This indicates how the Atlantic cod immune system has evolved compensatory mechanisms in both adaptive and innate immunity in the absence of MHC?II. These observations affect fundamental assumptions about the evolution of the adaptive immune system and its components in vertebrates.     

Biomimetic self-templating supramolecular structures

In nature, helical macromolecules such as collagen, chitin and cellulose are critical to the morphogenesis and functionality of various hierarchically structured materials. During tissue formation, these chiral macromolecules are secreted and undergo self-templating assembly, a process whereby multiple kinetic factors influence the assembly of the incoming building blocks to produce non-equilibrium structures. A single macromolecule can form diverse functional structures when self-templated under different conditions. Collagen type I, for instance, forms transparent corneal tissues from orthogonally aligned nematic fibres, distinctively coloured skin tissues from cholesteric phase fibre bundles, and mineralized tissues from hierarchically organized fibres. Nature's self-templated materials surpass the functional and structural complexity achievable by current top-down and bottom-up fabrication methods. However, self-templating has not been thoroughly explored for engineering synthetic materials. Here we demonstrate the biomimetic, self-templating assembly of chiral colloidal particles (M13 phage) into functional materials. A single-step process produces long-range-ordered, supramolecular films showing multiple levels of hierarchical organization and helical twist. Three distinct supramolecular structures are created by this approach: nematic orthogonal twists, cholesteric helical ribbons and smectic helicolidal nanofilaments. Both chiral liquid crystalline phase transitions and competing interfacial forces at the interface are found to be critical factors in determining the morphology of the templated structures during assembly. The resulting materials show distinctive optical and photonic properties, functioning as chiral reflector/filters and structural colour matrices. In addition, M13 phages with genetically incorporated bioactive peptide ligands direct both soft and hard tissue growth in a hierarchically organized manner. Our assembly approach provides insight into the complexities of hierarchical assembly in nature and could be expanded to other chiral molecules to engineer sophisticated functional helical-twisted structures.     

Atom-resolved imaging of ordered defect superstructures at individual grain boundaries

The ability to resolve spatially and identify chemically atoms in defects would greatly advance our understanding of the correlation between structure and property in materials. This is particularly important in polycrystalline materials, in which the grain boundaries have profound implications for the properties and applications of the final material. However, such atomic resolution is still extremely difficult to achieve, partly because grain boundaries are effective sinks for atomic defects and impurities, which may drive structural transformation of grain boundaries and consequently modify material properties. Regardless of the origin of these sinks, the interplay between defects and grain boundaries complicates our efforts to pinpoint the exact sites and chemistries of the entities present in the defective regions, thereby limiting our understanding of how specific defects mediate property changes. Here we show that the combination of advanced electron microscopy, spectroscopy and first-principles calculations can provide three-dimensional images of complex, multicomponent grain boundaries with both atomic resolution and chemical sensitivity. The high resolution of these techniques allows us to demonstrate that even for magnesium oxide, which has a simple rock-salt structure, grain boundaries can accommodate complex ordered defect superstructures that induce significant electron trapping in the bandgap of the oxide. These results offer insights into interactions between defects and grain boundaries in ceramics and demonstrate that atomic-scale analysis of complex multicomponent structures in materials is now becoming possible.     

Aberrant lipid metabolism disrupts calcium homeostasis causing liver endoplasmic reticulum stress in obesity

The endoplasmic reticulum (ER) is the main site of protein and lipid synthesis, membrane biogenesis, xenobiotic detoxification and cellular calcium storage, and perturbation of ER homeostasis leads to stress and the activation of the unfolded protein response. Chronic activation of ER stress has been shown to have an important role in the development of insulin resistance and diabetes in obesity. However, the mechanisms that lead to chronic ER stress in a metabolic context in general, and in obesity in particular, are not understood. Here we comparatively examined the proteomic and lipidomic landscape of hepatic ER purified from lean and obese mice to explore the mechanisms of chronic ER stress in obesity. We found suppression of protein but stimulation of lipid synthesis in the obese ER without significant alterations in chaperone content. Alterations in ER fatty acid and lipid composition result in the inhibition of sarco/endoplasmic reticulum calcium ATPase (SERCA) activity and ER stress. Correcting the obesity-induced alteration of ER phospholipid composition or hepatic Serca overexpression in vivo both reduced chronic ER stress and improved glucose homeostasis. Hence, we established that abnormal lipid and calcium metabolism are important contributors to hepatic ER stress in obesity.     

Improved molecular replacement by density- and energy-guided protein structure optimization

Molecular replacement procedures, which search for placements of a starting model within the crystallographic unit cell that best account for the measured diffraction amplitudes, followed by automatic chain tracing methods, have allowed the rapid solution of large numbers of protein crystal structures. Despite extensive work, molecular replacement or the subsequent rebuilding usually fail with more divergent starting models based on remote homologues with less than 30% sequence identity. Here we show that this limitation can be substantially reduced by combining algorithms for protein structure modelling with those developed for crystallographic structure determination. An approach integrating Rosetta structure modelling with Autobuild chain tracing yielded high-resolution structures for 8 of 13 X-ray diffraction data sets that could not be solved in the laboratories of expert crystallographers and that remained unsolved after application of an extensive array of alternative approaches. We estimate that the new method should allow rapid structure determination without experimental phase information for over half the cases where current methods fail, given diffraction data sets of better than 3.2?? resolution, four or fewer copies in the asymmetric unit, and the availability of structures of homologous proteins with >20% sequence identity.