Counts and abundance of macrozoobenthic organisms settled in artificial soft sediment at Brandal, Kongsfjorden, Spitsbergen

In the Arctic the currently observed rising air temperature results in more frequent calving of icebergs. The latter are derived from tidewater glaciers. Arctic macrozoobenthic soft-sediment communities are considerably disturbed by direct hits and sediment reallocation caused by iceberg scouring. With the aim to describe the primary succession of macrozoobenthic communities following these events, scientific divers installed 28 terracotta containers in the soft-sediment off Brandal (Kongsfjorden, Svalbard, Norway) at 20 m water depth in 2002. The containers were filled with a bentonite-sand-mixture resembling the natural sediment. Samples were taken annually between 2003 and 2007. A shift from pioneering species (e.g. Cumacea: Lamprops fuscatus) towards more specialized taxa, as well as from surface-detritivores towards subsurface-detritivores was observed. This is typical for an ecological succession following the facilitation and inhibition succession model. Similarity between experimental and non-manipulated communities from 2003 was significantly highest after three years of succession. In the following years similarity decreased, probably due to elevated temperatures, which prevented the fjord-system from freezing. Some organisms numerically important in the non-manipulated community (e.g., the polychaete Dipolydora quadrilobata) did not colonies the substrate during the experiment. This suggests that the community had not fully matured within the first three years. Later, the settlement was probably impeded by consequences of warming temperatures. This demonstrates the long-lasting effects of severe disturbances on Arctic macrozoobenthic communities. Furthermore, environmental changes, such as rising temperatures coupled with enhanced food availability due to an increasing frequency of ice-free days per year, may have a stronger effect on succession than exposure time.

国際公共財としての感染症対策

HIV/AIDS、SARS、鳥インフルエンザといった新興感染症、薬剤耐性を持った病原体の出現によって問題が深刻化している結核、マラリア等再興感染症への関心が世界で高まっている。感染症の予防や治療はそれを個人に施すことのプラスの効果が国境を超えてスピル・オーバーすることが多く、国際公共財としての性質を持っている。また、新薬・ワクチンの成分・製法に関する情報および、感染症の流行に関する情報は典型的な公共財であり、誰しもがフリー・ライドするインセンティブを持っている。したがって、これら公共財の過少供給の問題を解決するためには国際的な協調行動が必要である。 　世界の感染症対策は、感染がより大規模に広まっている発展途上国を中心としたものにならざるを得ない。現在これをリードしているのはアメリカであり、日本はWHOへの出資については存在感を示しているものの、それ以外の機関への出資や二国間協力の面において、少なくとも今現在においては貢献度が大きいと見られていない。また、新薬・ワクチン開発については日本の財政的な面での貢献は全く目立たない。 　国際的な感染症対策に関する日本の印象を高めるためには、沖縄感染症イニシアティブの際になされたような形で金銭的貢献度を再び高める、あるいは、国際的に必要と考えられているものの他国が協力を決めていない分野への貢献をいち早く宣言する、等の対応が考えられる。

Reliability analysis based on non-dimensional parameters

A reliability analysis method is proposed that starts with the identification of all variables involved. These are divided in three groups: (a) variables fixed by codes, as loads and strength project values, and their corresponding partial safety coefficients, (b) geometric variables defining the dimension of the main elements involved, (c) the cost variables, including the possible damages caused by failure, (d) the random variables as loads, strength, etc., and (e)the variables defining the statistical model, as the family of distribution and its corresponding parameters. Once the variables are known, the II-theorem is used to obtain a minimum equivalent set of non-dimensional variables, which is used to define the limit states. This allows a reduction in the number of variables involved and a better understanding of their coupling effects. Two minimum cost criteria are used for selecting the project dimensions. One is based on a bounded-probability of failure, and the other on a total cost, including the damages of the possible failure. Finally, the method is illustrated by means of an application.

Den Norske Nordhavs-expedition, 1876-1878.

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Engineering the largest RNA virus genome as an infectious bacterial artificial chromosome

The construction of cDNA clones encoding large-size RNA molecules of biological interest, like coronavirus genomes, which are among the largest mature RNA molecules known to biology, has been hampered by the instability of those cDNAs in bacteria. Herein, we show that the application of two strategies, cloning of the cDNAs into a bacterial artificial chromosome and nuclear expression of RNAs that are typically produced within the cytoplasm, is useful for the engineering of large RNA molecules. A cDNA encoding an infectious coronavirus RNA genome has been cloned as a bacterial artificial chromosome. The rescued coronavirus conserved all of the genetic markers introduced throughout the sequence and showed a standard mRNA pattern and the antigenic characteristics expected for the synthetic virus. The cDNA was transcribed within the nucleus, and the RNA translocated to the cytoplasm. Interestingly, the recovered virus had essentially the same sequence as the original one, and no splicing was observed. The cDNA was derived from an attenuated isolate that replicates exclusively in the respiratory tract of swine. During the engineering of the infectious cDNA, the spike gene of the virus was replaced by the spike gene of an enteric isolate. The synthetic virus replicated abundantly in the enteric tract and was fully virulent, demonstrating that the tropism and virulence of the recovered coronavirus can be modified. This demonstration opens up the possibility of employing this infectious cDNA as a vector for vaccine development in human, porcine, canine, and feline species susceptible to group 1 coronaviruses.

Crystal structure of the SarR protein from Staphylococcus aureus

The expression of virulence determinants in Staphylococcus aureus is controlled by global regulatory loci (e.g., sarA and agr). The sar (Staphylococcus accessory regulator) locus is composed of three overlapping transcripts (sarA P1, P3, and P2, transcripts initiated from the P1, P3, and P2 promoters, respectively), all encoding the 124-aa SarA protein. The level of SarA, the major regulatory protein, is partially controlled by the differential activation of the sarA promoters. We previously partially purified a 13.6-kDa protein, designated SarR, that binds to the sarA promoter region to down-modulate sarA transcription from the P1 promoter and subsequently SarA expression. SarR shares sequence similarity to SarA, and another SarA homolog, SarS. Here we report the 2.3 Å-resolution x-ray crystal structure of the dimeric SarR-MBP (maltose binding protein) fusion protein. The structure reveals that the SarR protein not only has a classic helix–turn–helix module for DNA binding at the major grooves, but also has an additional loop region involved in DNA recognition at the minor grooves. This interaction mode could represent a new functional class of the “winged helix” family. The dimeric SarR structure could accommodate an unusually long stretch of ≈27 nucleotides with two or four bending points along the course, which could lead to the bending of DNA by 90° or more, similar to that seen in the catabolite activator protein (CAP)–DNA complex. The structure also demonstrates the molecular basis for the stable dimerization of the SarR monomers and possible motifs for interaction with other proteins.

Structure-activity relationships derived by machine learning: the use of atoms and their bond connectivities to predict mutagenicity by inductive logic programming.

We present a general approach to forming structure-activity relationships (SARs). This approach is based on representing chemical structure by atoms and their bond connectivities in combination with the inductive logic programming (ILP) algorithm PROGOL. Existing SAR methods describe chemical structure by using attributes which are general properties of an object. It is not possible to map chemical structure directly to attribute-based descriptions, as such descriptions have no internal organization. A more natural and general way to describe chemical structure is to use a relational description, where the internal construction of the description maps that of the object described. Our atom and bond connectivities representation is a relational description. ILP algorithms can form SARs with relational descriptions. We have tested the relational approach by investigating the SARs of 230 aromatic and heteroaromatic nitro compounds. These compounds had been split previously into two subsets, 188 compounds that were amenable to regression and 42 that were not. For the 188 compounds, a SAR was found that was as accurate as the best statistical or neural network-generated SARs. The PROGOL SAR has the advantages that it did not need the use of any indicator variables handcrafted by an expert, and the generated rules were easily comprehensible. For the 42 compounds, PROGOL formed a SAR that was significantly (P < 0.025) more accurate than linear regression, quadratic regression, and back-propagation. This SAR is based on an automatically generated structural alert for mutagenicity.

A pregnancy-specific glycoprotein is expressed in the brain and serves as a receptor for mouse hepatitis virus.

Mouse hepatitis virus (MHV), a murine coronavirus known to cause encephalitis and demyelination, uses murine homologues of carcinoembryonic antigens as receptors. However, the expression of these receptors is extremely low in the brain. By low-stringency screening of a mouse brain cDNA library, we have identified a member of the pregnancy-specific glycoprotein (PSG) subgroup of the carcinoembryonic antigen gene family. Unlike other PSG that are expressed in the placenta, it is expressed predominantly in the brain. Transfection of the cDNA into COS-7 cells, which lack a functional MHV receptor, conferred susceptibility to infection by some MHV strains, including A59, MHV-2, and MHV-3, but not JHM. Thus, this is a virus strain-specific receptor. The detection of multiple receptors for MHV suggests the flexibility of this virus in receptor utilization. The identification of this virus in receptor utilization. The identification of a PSG predominantly expressed in the brain also expands the potential functions of these molecules.