A voltage-gated proton-selective channel lacking the pore domain

Voltage changes across the cell membrane control the gating of many cation-selective ion channels. Conserved from bacteria to humans, the voltage-gated-ligand superfamily of ion channels are encoded as polypeptide chains of six transmembrane-spanning segments (S1-S6). S1-S4 functions as a self-contained voltage-sensing domain (VSD), in essence a positively charged lever that moves in response to voltage changes. The VSD 'ligand' transmits force via a linker to the S5-S6 pore domain 'receptor', thereby opening or closing the channel. The ascidian VSD protein Ci-VSP gates a phosphatase activity rather than a channel pore, indicating that VSDs function independently of ion channels. Here we describe a mammalian VSD protein (H(V)1) that lacks a discernible pore domain but is sufficient for expression of a voltage-sensitive proton-selective ion channel activity. H(v)1 currents are activated at depolarizing voltages, sensitive to the transmembrane pH gradient, H+-selective, and Zn2+-sensitive. Mutagenesis of H(v)1 identified three arginine residues in S4 that regulate channel gating and two histidine residues that are required for extracellular inhibition of H(v)1 by Zn2+. H(v)1 is expressed in immune tissues and manifests the characteristic properties of native proton conductances (G(vH+)). In phagocytic leukocytes, G(vH+) are required to support the oxidative burst that underlies microbial killing by the innate immune system. The data presented here identify H(v)1 as a long-sought voltage-gated H+ channel and establish H(v)1 as the founding member of a family of mammalian VSD proteins.     

Lunar activity from recent gas release

Samples of material returned from the Moon have established that widespread lunar volcanism ceased about 3.2 Gyr ago. Crater statistics and degradation models indicate that last-gasp eruptions of thin basalt flows continued until less than 1.0 Gyr ago, but the Moon is now considered to be unaffected by internal processes today, other than weak tidally driven moonquakes and young fault systems. It is therefore widely assumed that only impact craters have reshaped the lunar landscape over the past billion years. Here we report that patches of the lunar regolith in the Ina structure were recently removed. The preservation state of relief, the number of superimposed small craters, and the 'freshness' (spectral maturity) of the regolith together indicate that features within this structure must be as young as 10 Myr, and perhaps are still forming today. We propose that these features result from recent, episodic out-gassing from deep within the Moon. Such out-gassing probably contributed to the radiogenic gases detected during past lunar missions. Future monitoring (including Earth-based observations) should reveal the composition of the gas, yielding important clues to volatiles archived at great depth over the past 4-4.5 Gyr.     

Spider toxins activate the capsaicin receptor to produce inflammatory pain

Bites and stings from venomous creatures can produce pain and inflammation as part of their defensive strategy to ward off predators or competitors. Molecules accounting for lethal effects of venoms have been extensively characterized, but less is known about the mechanisms by which they produce pain. Venoms from spiders, snakes, cone snails or scorpions contain a pharmacopoeia of peptide toxins that block receptor or channel activation as a means of producing shock, paralysis or death. We examined whether these venoms also contain toxins that activate (rather than inhibit) excitatory channels on somatosensory neurons to produce a noxious sensation in mammals. Here we show that venom from a tarantula that is native to the West Indies contains three inhibitor cysteine knot (ICK) peptides that target the capsaicin receptor (TRPV1), an excitatory channel expressed by sensory neurons of the pain pathway. In contrast with the predominant role of ICK toxins as channel inhibitors, these previously unknown 'vanillotoxins' function as TRPV1 agonists, providing new tools for understanding mechanisms of TRP channel gating. Some vanillotoxins also inhibit voltage-gated potassium channels, supporting potential similarities between TRP and voltage-gated channel structures. TRP channels can now be included among the targets of peptide toxins, showing that animals, like plants (for example, chilli peppers), avert predators by activating TRP channels on sensory nerve fibres to elicit pain and inflammation.     

Episodic outgassing as the origin of atmospheric methane on Titan

Saturn's largest satellite, Titan, has a massive nitrogen atmosphere containing up to 5 per cent methane near its surface. Photochemistry in the stratosphere would remove the present-day atmospheric methane in a few tens of millions of years. Before the Cassini-Huygens mission arrived at Saturn, widespread liquid methane or mixed hydrocarbon seas hundreds of metres in thickness were proposed as reservoirs from which methane could be resupplied to the atmosphere over geologic time. Titan fly-by observations and ground-based observations rule out the presence of extensive bodies of liquid hydrocarbons at present, which means that methane must be derived from another source over Titan's history. Here we show that episodic outgassing of methane stored as clathrate hydrates within an icy shell above an ammonia-enriched water ocean is the most likely explanation for Titan's atmospheric methane. The other possible explanations all fail because they cannot explain the absence of surface liquid reservoirs and/or the low dissipative state of the interior. On the basis of our models, we predict that future fly-bys should reveal the existence of both a subsurface water ocean and a rocky core, and should detect more cryovolcanic edifices.     

The Southern Ocean biogeochemical divide

Modelling studies have demonstrated that the nutrient and carbon cycles in the Southern Ocean play a central role in setting the air-sea balance of CO(2) and global biological production. Box model studies first pointed out that an increase in nutrient utilization in the high latitudes results in a strong decrease in the atmospheric carbon dioxide partial pressure (pCO2). This early research led to two important ideas: high latitude regions are more important in determining atmospheric pCO2 than low latitudes, despite their much smaller area, and nutrient utilization and atmospheric pCO2 are tightly linked. Subsequent general circulation model simulations show that the Southern Ocean is the most important high latitude region in controlling pre-industrial atmospheric CO(2) because it serves as a lid to a larger volume of the deep ocean. Other studies point out the crucial role of the Southern Ocean in the uptake and storage of anthropogenic carbon dioxide and in controlling global biological production. Here we probe the system to determine whether certain regions of the Southern Ocean are more critical than others for air-sea CO(2) balance and the biological export production, by increasing surface nutrient drawdown in an ocean general circulation model. We demonstrate that atmospheric CO(2) and global biological export production are controlled by different regions of the Southern Ocean. The air-sea balance of carbon dioxide is controlled mainly by the biological pump and circulation in the Antarctic deep-water formation region, whereas global export production is controlled mainly by the biological pump and circulation in the Subantarctic intermediate and mode water formation region. The existence of this biogeochemical divide separating the Antarctic from the Subantarctic suggests that it may be possible for climate change or human intervention to modify one of these without greatly altering the other.     

两种蛋白酶在生皮脱毛上应用试验

无公害工业化生产要求制革企业放弃制革工艺中沿用的传统有害物质,采用新方法生产高质量皮革制品。介绍了中俄科研人员用两种不同的方法(涂布法、浸酶法)和两种不同的脱毛酶制剂进行的生皮脱毛试验。试验证明,用酶制剂脱毛效果良好,完全可以替代传统的硫化碱,同时能够改善制革工艺,削弱碱性物质对皮革表面的侵害,减少制革业对水源污染。     

Connexins and pannexins in the skeleton: gap junctions,hemichannels and more

Regulation of bone homeostasis depends on the concerted actions of bone-forming osteoblasts and bone-resorbing osteoclasts, controlled by osteocytes, cells derived from osteoblasts surrounded by bone matrix. The control of differentiation, viability and function of bone cells relies on the presence of connexins. Connexin43 regulates the expression of genes required for osteoblast and osteoclast differentiation directly or by changing the levels of osteocytic genes, and connexin45 may oppose connexin43 actions in osteoblastic cells. Connexin37 is required for osteoclast differentiation and its deletion results in increased bone mass. Less is known on the role of connexins in cartilage, ligaments and tendons. Connexin43, connexin45, connexin32, connexin46 and connexin29 are expressed in chondrocytes, while connexin43 and connexin32 are expressed in ligaments and tendons. Similarly, although the expression of pannexin1, pannexin2 and pannexin3 has been demonstrated in bone and cartilage cells, their function in these tissues is not fully understood.     

Imaging of oxygen and hypoxia in cell and tissue samples

Molecular oxygen (O₂) is a key player in cell mitochondrial function, redox balance and oxidative stress, normal tissue function and many common disease states. Various chemical, physical and biological methods have been proposed for measurement, real-time monitoring and imaging of O₂ concentration, state of decreased O₂ (hypoxia) and related parameters in cells and tissue. Here, we review the established and emerging optical microscopy techniques allowing to visualize O₂ levels in cells and tissue samples, mostly under in vitro and ex vivo, but also under in vivo settings. Particular examples include fluorescent hypoxia stains, fluorescent protein reporter systems, phosphorescent probes and nanosensors of different types. These techniques allow high-resolution mapping of O₂ gradients in live or post-mortem tissue, in 2D or 3D, qualitatively or quantitatively. They enable control and monitoring of oxygenation conditions and their correlation with other biomarkers of cell and tissue function. Comparison of these techniques and corresponding imaging setups, their analytical capabilities and typical applications are given.     

Forecasting and nowcasting emerging market GDP growth rates: The role of latent global economic policy uncertainty and macroeconomic data surprise factors

In this paper, we assess the predictive content of latent economic policy uncertainty and data surprise factors for forecasting and nowcasting gross domestic product (GDP) using factor-type econometric models. Our analysis focuses on five emerging market economies: Brazil, Indonesia, Mexico, South Africa, and Turkey; and we carry out a forecasting horse race in which predictions from various different models are compared. These models may (or may not) contain latent uncertainty and surprise factors constructed using both local and global economic datasets. The set of models that we examine in our experiments includes both simple benchmark linear econometric models as well as dynamic factor models that are estimated using a variety of frequentist and Bayesian data shrinkage methods based on the least absolute shrinkage operator (LASSO). We find that the inclusion of our new uncertainty and surprise factors leads to superior predictions of GDP growth, particularly when these latent factors are constructed using Bayesian variants of the LASSO. Overall, our findings point to the importance of spillover effects from global uncertainty and data surprises, when predicting GDP growth in emerging market economies.