The C. elegans genome sequencing project: a beginning.

The long-term goal of this project is the elucidation of the complete sequence of the Caenorhabditis elegans genome. During the first year methods have been developed and a strategy implemented that is amenable to large-scale sequencing. The three cosmids sequenced in this initial phase are surprisingly rich in genes, many of which have mammalian homologues.     

Prioritizing global conservation efforts

One of the most pressing issues facing the global conservation community is how to distribute limited resources between regions identified as priorities for biodiversity conservation. Approaches such as biodiversity hotspots, endemic bird areas and ecoregions are used by international organizations to prioritize conservation efforts globally. Although identifying priority regions is an important first step in solving this problem, it does not indicate how limited resources should be allocated between regions. Here we formulate how to allocate optimally conservation resources between regions identified as priorities for conservation--the 'conservation resource allocation problem'. Stochastic dynamic programming is used to find the optimal schedule of resource allocation for small problems but is intractable for large problems owing to the "curse of dimensionality". We identify two easy-to-use and easy-to-interpret heuristics that closely approximate the optimal solution. We also show the importance of both correctly formulating the problem and using information on how investment returns change through time. Our conservation resource allocation approach can be applied at any spatial scale. We demonstrate the approach with an example of optimal resource allocation among five priority regions in Wallacea and Sundaland, the transition zone between Asia and Australasia.     

Crystallographic studies on the activity of glycogen phosphorylase b

High resolution studies on the crystal structure of glycogen phosphorylase b have identified the catalytic site to which the substrate glucose-1-phosphate binds strongly with some local conformational changes. The site is situated 8 A (phosphate-to-phosphate distance) from pyridoxal phosphate, an essential cofactor of all glycogen phosphorylases. The catalytic site is 33 A from the site in the N-terminal portion of the molecule to which adenine nucleotides bind. In contrast to phosphorylase a (the active form of the enzyme which is phosphorylated at Ser 14), the positions of the first 19 residues of phosphorylase b are not well defined.     

高斯杂波中距离扩展目标的模糊CFAR检测

为提高高分辨雷达的检测性能,提出了一种高斯杂波背景下距离扩展目标的模糊检测方法。该方法采用模糊恒虚警率(constant false alarm rate, CFAR)检测器代替传统的二进制CFAR检测器,将距离单元值转换成映射到虚警空间的模糊隶属函数值,然后采用模糊积累准则进行积累,得到检测统计量。研究了模糊代数积、模糊代数和两种积累准则,推导出这两种方法虚警概率的数学解析式。仿真结果表明,高斯杂波背景下模糊代数积积累较双门限二进制积累可获得近2 dB的性能改善。同时,模糊检测方法只采用单个检测门限,具有易于调节的优点。     

Polyreactivity increases the apparent affinity of anti-HIV antibodies by heteroligation

During immune responses, antibodies are selected for their ability to bind to foreign antigens with high affinity, in part by their ability to undergo homotypic bivalent binding. However, this type of binding is not always possible. For example, the small number of gp140 glycoprotein spikes displayed on the surface of the human immunodeficiency virus (HIV) disfavours homotypic bivalent antibody binding. Here we show that during the human antibody response to HIV, somatic mutations that increase antibody affinity also increase breadth and neutralizing potency. Surprisingly, the responding naive and memory B cells produce polyreactive antibodies, which are capable of bivalent heteroligation between one high-affinity anti-HIV-gp140 combining site and a second low-affinity site on another molecular structure on HIV. Although cross-reactivity to self-antigens or polyreactivity is strongly selected against during B-cell development, it is a common serologic feature of certain infections in humans, including HIV, Epstein-Barr virus and hepatitis C virus. Seventy-five per cent of the 134 monoclonal anti-HIV-gp140 antibodies cloned from six patients with high titres of neutralizing antibodies are polyreactive. Despite the low affinity of the polyreactive combining site, heteroligation demonstrably increases the apparent affinity of polyreactive antibodies to HIV.     

Lateral presynaptic inhibition mediates gain control in an olfactory circuit

Olfactory signals are transduced by a large family of odorant receptor proteins, each of which corresponds to a unique glomerulus in the first olfactory relay of the brain. Crosstalk between glomeruli has been proposed to be important in olfactory processing, but it is not clear how these interactions shape the odour responses of second-order neurons. In the Drosophila antennal lobe (a region analogous to the vertebrate olfactory bulb), we selectively removed most interglomerular input to genetically identified second-order olfactory neurons. Here we show that this broadens the odour tuning of these neurons, implying that interglomerular inhibition dominates over interglomerular excitation. The strength of this inhibitory signal scales with total feedforward input to the entire antennal lobe, and has similar tuning in different glomeruli. A substantial portion of this interglomerular inhibition acts at a presynaptic locus, and our results imply that this is mediated by both ionotropic and metabotropic receptors on the same nerve terminal.     

Eocene/Oligocene ocean de-acidification linked to Antarctic glaciation by sea-level fall

One of the most dramatic perturbations to the Earth system during the past 100 million years was the rapid onset of Antarctic glaciation near the Eocene/Oligocene epoch boundary (approximately 34 million years ago). This climate transition was accompanied by a deepening of the calcite compensation depth--the ocean depth at which the rate of calcium carbonate input from surface waters equals the rate of dissolution. Changes in the global carbon cycle, rather than changes in continental configuration, have recently been proposed as the most likely root cause of Antarctic glaciation, but the mechanism linking glaciation to the deepening of calcite compensation depth remains unclear. Here we use a global biogeochemical box model to test competing hypotheses put forward to explain the Eocene/Oligocene transition. We find that, of the candidate hypotheses, only shelf to deep sea carbonate partitioning is capable of explaining the observed changes in both carbon isotope composition and calcium carbonate accumulation at the sea floor. In our simulations, glacioeustatic sea-level fall associated with the growth of Antarctic ice sheets permanently reduces global calcium carbonate accumulation on the continental shelves, leading to an increase in pelagic burial via permanent deepening of the calcite compensation depth. At the same time, fresh limestones are exposed to erosion, thus temporarily increasing global river inputs of dissolved carbonate and increasing seawater delta13C. Our work sheds new light on the mechanisms linking glaciation and ocean acidity change across arguably the most important climate transition of the Cenozoic era.