Functional Clustering of Immunoglobulin Superfamily Proteins with Protein–Protein Interaction Information Calibrated Hidden Markov Model Sequence Profiles

Secreted and cell-surface-localized members of the immunoglobulin superfamily (IgSF) play central roles in regulating adaptive and innate immune responses and are prime targets for the development of protein-based therapeutics. An essential activity of the ectodomains of these proteins is the specific recognition of cognate ligands, which are often other members of the IgSF. In this work, we provide functional insight for this important class of proteins through the development of a clustering algorithm that groups together extracellular domains of the IgSF with similar binding preferences. Information from hidden Markov model-based sequence profiles and domain architecture is calibrated against manually curated protein interaction data to define functional families of IgSF proteins. The method is able to assign 82% of the 477 extracellular IgSF protein to a functional family, while the rest are either single proteins with unique function or proteins that could not be assigned with the current technology. The functional clustering of IgSF proteins generates hypotheses regarding the identification of new cognate receptor–ligand pairs and reduces the pool of possible interacting partners to a manageable level for experimental validation.     

Prevalence of human T‐lymphotropic virus type 1 carriers among pregnant women in Hokkaido,Japan

As there is a risk of MTCT of HTLV‐1, the HSGP HTLV‐1 MTCT was organized in 2011. To determine how many pregnant women are infected with HTLV‐1 in Hokkaido, which is the northernmost and the second largest island in Japan with a population of 5 467 000 and 39 392 newborns in 2011, the HSGP HTLV‐1 MTCT asked all facilities that may care for pregnant women in Hokkaido in July 2013 to provide information on the number of pregnant women who underwent screening for anti‐HTLV‐1 antibody using particle agglutination or chemiluminescent enzyme immunoassay, and the numbers of those with positive, equivocal, and negative test results in the screening and confirmation tests using western blotting or PCR methods in 2012, respectively. A total of 111 facilities participated in this study and provided information on 33 617 pregnant women who underwent screening in 2012, corresponding to approximately 85% of all pregnant women who gave birth in Hokkaido in 2012. Of 81 candidates for a confirmation test because of positive (n = 77) or equivocal (n = 4) results on screening, 63 (78%) underwent the confirmation test and, finally, 34 (0.1%) and 33 563 (99.8%) women were judged to be HTLV‐1 carriers and non‐carriers, respectively. It was concluded that the prevalence rate of HTLV‐1 carriers was low, one per 1000 pregnant women in Hokkaido. Approximately 40 infants are born yearly to mothers infected with HTLV‐1 in Hokkaido.     

Within‐lake distribution patterns of fish assemblages: the relative roles of spatial,temporal and random environmental factors in assessing fish assemblages using gillnets in a large and shallow temperate lake

In this study, the relative role of spatio‐temporal factors and associated environmental variables (water transparency and temperature) were quantified in relation to gillnet samples of fishes in a large and shallow lake (Lake Balaton, Hungary). Most of the variance (56·1%) in the relative abundance data (%) was related to the vertical segregation of fishes. This gradient substantially affected the catch per unit effort (CPUE) by number of the dominant species, the surface‐oriented bleak Alburnus alburnus and the benthic common bream Abramis brama. It also influenced total CPUE, mean fish mass and species richness and diversity. At the lake level, horizontal habitat heterogeneity (i.e. littoral v. offshore) accounted for only 8·3% of the total variance in relative abundance data, but was important in structuring the CPUE of the ruffe Gymnocephalus cernua and the pikeperch Sander lucioperca. The longitudinal environmental gradient (i.e. lake basin), year and season of sampling, water transparency and temperature had significant effects on relative abundance only at the habitat level, but were also important components of variability of CPUE in some species at the lake level. As sampling schemes need to consider the main gradients in fish assemblage distributions, the use of surface and pelagic gillnets should be more intensively incorporated in the study and monitoring of fish assemblages in shallow lakes and lake habitats.     

Adaptations of tropical marine microphytobenthic assemblages along a gradient of light and nutrient availability in Suva Lagoon,Fiji

How are microphytobenthic biofilms adapted to the high incident irradiances and temperatures, low inorganic nutrient concentrations and high desiccation stresses on intertidal flats present in tropical environments? This study investigated biofilms subject to different environmental conditions in a range of tropical sites in Suva lagoon, Fiji. PAM fluorescence was used to measure photophysiological responses to the light climate. Biofilm colloidal carbohydrate, extracellular polymeric substances (EPS) and low molecular weight (MW) carbohydrate concentrations and diel carbohydrate production patterns were measured. Average biomass (Chl a) ranged from 15 to 36?mg?m^?2, and was highest in seagrass bed sediments, but biomass was not correlated with water column or sediment porewater nutrient concentrations. Biofilm photophysiology differed significantly along a combined gradient of light and nutrient availability, with F _v/F _m, relative ETR_max and E _k of biofilms highest in mangrove and intertidal main island sites and lowest in subtidal coral reef flats. Subtidal biofilms showed photoinhibition at irradiances > 1000?µmol?m^?2. Significant correlations between Chl a and colloidal carbohydrate concentrations were present (except on intertidal sandflats), and tropical biofilms had higher ratios of colloidal carbohydrate and EPS to Chl a than temperate estuarine biofilms, probably due to a combination of high irradiance and low nutrient availability leading to the production of excess photoassimilates. The percentage of EPS present in the colloidal fraction was highest in coral sand biofilms (42%), which had the lowest nutrient concentrations, compared with other sites (25–32%). Intertidal biofilms predominantly consisted of large motile taxa and showed strong rhythms of vertical migration. During tidal emersion, high sediment temperatures (41?°C), irradiance (>2300?µmol?m^?2?s^?1) and salinity (49‰) stimulated downward migration. In silty sediments, migration resulted in a reduction in photosynthetic activity during the midday period but, in sands with high light penetration (to a depth of > 1700?µm), high production rates of EPS (18.2?µg carbo. µg Chl a^?1 h^?1) and low MW carbohydrate exudates (40.2?µg carbo. µg Chl a^?1 h^?1) occurred. Vertical migration, high E _k and high rates of photoassimilate dumping are all adaptations to living in the tropical intertidal zone. Seagrass and reef flat biofilms consisted of a diverse non-migratory flora of motile and non-motile taxa that were not subject to such extreme temperature and irradiance conditions. Low values of photosynthetic parameters and high colloidal and EPS content indicated that these biofilms were nutrient-limited.     

Calling Behavior and Morphology of the Stridulatory Apparatus in Neotropical Grasshoppers (Aleuas Stål; Orthoptera)

The sound production and sound producing apparatus of two species of grasshoppers, A. lineatus Stål, 1878 and A. vitticollis Stål, 1878 (Orthoptera, Acrididae, Copiocerinae) have been studied. For both species oscillograms and other physical data on sounds are presented for the first time. The sound producing behavior is described and the stridulation apparatus mechanism is illustrated. In the case of A. vitticollis these data are the first known on its sound production and general acoustic behavior.     

The flagellar filament structure of the extreme acidothermophile Sulfolobus shibatae B12 suggests that archaeabacterial flagella have a unique and common symmetry and design

Archaea, constituting a third domain of life between Eubacteria and Eukarya, characteristically inhabit extreme environments. They swim by rotating flagellar filaments that are phenomenologically and functionally similar to those of eubacteria. However, biochemical, genetic and structural evidence has pointed to significant differences but even greater similarity to eubacterial type IV pili. Here we determined the three-dimensional symmetry and structure of the flagellar filament of the acidothermophilic archaeabacterium Sulfolobus shibatae B12 using transmission electron microscopy (TEM) and scanning transmission electron microscopy (STEM). Processing of the cryo-negatively stained filaments included analysis of their helical symmetry and subsequent single particle reconstruction. Two filament subunit packing arrangements were identified: one has helical symmetry, similar to that of the extreme halophile Halobacterium salinarum, with ten subunits per 5.3 nm repeat and the other has helically arranged stacked disks with C₃ symmetry and 12 subunits per repeat. The two structures are related by a slight twist. The S. shibatae filament has a larger diameter compared to that of H. salinarum, at the opposite end of the archaeabacterial phylogenetic spectrum, but the basic three-start symmetry and the size and arrangement of the core domain are conserved and the filament lacks a central channel. This similarity suggests a unique and common underlying symmetry for archaeabacterial flagellar filaments.     

Improving fold recognition without folds

The most reliable way to align two proteins of unknown structure is through sequence-profile and profile-profile alignment methods. If the structure for one of the two is known, fold recognition methods outperform purely sequence-based alignments. Here, we introduced a novel method that aligns generalised sequence and predicted structure profiles. Using predicted 1D structure (secondary structure and solvent accessibility) significantly improved over sequence-only methods, both in terms of correctly recognising pairs of proteins with different sequences and similar structures and in terms of correctly aligning the pairs. The scores obtained by our generalised scoring matrix followed an extreme value distribution; this yielded accurate estimates of the statistical significance of our alignments. We found that mistakes in 1D structure predictions correlated between proteins from different sequence-structure families. The impact of this surprising result was that our method succeeded in significantly out-performing sequence-only methods even without explicitly using structural information from any of the two. Since AGAPE also outperformed established methods that rely on 3D information, we made it available through. If we solved the problem of CPU-time required to apply AGAPE on millions of proteins, our results could also impact everyday database searches.     

利用生物效应比评价利咽丹质量的方法研究

目的:测定利咽丹(Liyan Dan,LYD)及其药效组分(active components alignment,ACA)抗Ⅰ型单纯疱疹病毒(HSV-Ⅰ)的生物效应比,探讨使用药效组分标准生物效价表述中药质量的新鉴定方法。方法:用MTT染色法检测对HSV-Ⅰ所致细胞病变(cytopathogenoc effect,CPE)的抑制作用,用HPLC和UV法检测药效组分。用利咽丹及其药效组分对感染HSV-Ⅰ的细胞保护率(protective percent,PP)计算其生物效应比(biologlical effect ratio,BER)。BERS=PPS／PPACA(药物对细胞的保护率／药效组分对细胞的保护率;药物浓度2-x mg/mL)。结果:利咽丹有抑制HSV-Ⅰ所致CPE的活性,其生物效应比为1．16。结论:中药及其药效组分的生物效应比可以反映和揭示其品质的内涵,该指标可以客观地表述中药疗效的本质。本研究提出了中药品质研究的新思路和方法,引入了生物效应比和药效组分的新概念。中药药效组分生物效应质量鉴定方法如下:第一,建立药效组分标准生物效应作为效应标准;第二,按照药效组分生物效应标准的检测方法测定供试品;第三,按照公式计算生物效应比(BERS=PPS／PPACA)。中药药效组分质量评价生物效应比标准:1≥BERS≥0．9时,为合格药品;BERS>1时为优质药品;BERS<0．9时为不合格药品。此质量评价方法比仅依靠一种或两种化学成分含量来评价质量要更科学。