Mayday - integrative analytics for expression data

Background  

DNA Microarrays have become the standard method for large scale analyses of gene expression and epigenomics. The increasing complexity and inherent noisiness of the generated data makes visual data exploration ever more important. Fast deployment of new methods as well as a combination of predefined, easy to apply methods with programmer's access to the data are important requirements for any analysis framework. Mayday is an open source platform with emphasis on visual data exploration and analysis. Many built-in methods for clustering, machine learning and classification are provided for dissecting complex datasets. Plugins can easily be written to extend Mayday's functionality in a large number of ways. As Java program, Mayday is platform-independent and can be used as Java WebStart application without any installation. Mayday can import data from several file formats, database connectivity is included for efficient data organization. Numerous interactive visualization tools, including box plots, profile plots, principal component plots and a heatmap are available, can be enhanced with metadata and exported as publication quality vector files.     

The Hemagglutinin of Bat-Associated Influenza Viruses Is Activated by TMPRSS2 for pH-Dependent Entry into Bat but Not Human Cells

New World bats have recently been discovered to harbor influenza A virus (FLUAV)-related viruses, termed bat-associated influenza A-like viruses (batFLUAV). The internal proteins of batFLUAV are functional in mammalian cells. In contrast, no biological functionality could be demonstrated for the surface proteins, hemagglutinin (HA)-like (HAL) and neuraminidase (NA)-like (NAL), and these proteins need to be replaced by their human counterparts to allow spread of batFLUAV in human cells. Here, we employed rhabdoviral vectors to study the role of HAL and NAL in viral entry. Vectors pseudotyped with batFLUAV-HAL and -NAL were able to enter bat cells but not cells from other mammalian species. Host cell entry was mediated by HAL and was dependent on prior proteolytic activation of HAL and endosomal low pH. In contrast, sialic acids were dispensable for HAL-driven entry. Finally, the type II transmembrane serine protease TMPRSS2 was able to activate HAL for cell entry indicating that batFLUAV can utilize human proteases for HAL activation. Collectively, these results identify viral and cellular factors governing host cell entry driven by batFLUAV surface proteins. They suggest that the absence of a functional receptor precludes entry of batFLUAV into human cells while other prerequisites for entry, HAL activation and protonation, are met in target cells of human origin.     

Climate‐driven rampant speciation of the Cape flora

Aim To test whether the radiation of the extremely rich Cape flora is correlated with marine‐driven climate change. Location Middle to Late Miocene in the south‐east Atlantic and the Benguela Upwelling System (BUS) off the west coast of South Africa. Methods We studied the palynology of the thoroughly dated Middle to Late Miocene sediments of Ocean Drilling Program (ODP) Site 1085 retrieved from the Atlantic off the mouth of the Orange River. Both marine upwelling and terrestrial input are recorded at this site, which allows a direct correlation between changes in the terrestrial flora and the marine BUS in the south‐east Atlantic. Results Pollen types from plants of tropical affinity disappeared, and those from the Cape flora gradually increased, between 10 and 6 Ma. Our data corroborate the inferred dating of the diversification in Aizoaceae c. 8 Ma. Main conclusions Inferred vegetation changes for the Late Miocene south‐western African coast are the disappearance of Podocarpus‐dominated Afromontane forests, and a change in the vegetation of the coastal plain from tropical grassland and thicket to semi‐arid succulent vegetation. These changes are indicative of an increased summer drought, and are in step with the development of the southern BUS. They pre‐date the Pliocene uplift of the East African escarpment, suggesting that this did not play a role in stimulating vegetation change. Some Fynbos elements were present throughout the recorded period (from 11 Ma), suggesting that at least some elements of this vegetation were already in place during the onset of the BUS. This is consistent with a marine‐driven climate change in south‐western Africa triggering substantial radiation in the terrestrial flora, especially in the Aizoaceae.     

Morphological and histological changes of dermal scales during the fish‐to‐tetrapod transition

Witzmann F. (2011). Morphological and histological changes of dermal scales during the fish‐to‐tetrapod transition. —Acta Zoologica (Stockholm) 92 : 281–302. The gastral scales of limbed tetrapodomorphs evolved from the ‘elpistostegid’‐type of scale by an enlargement and differentiation of the articulation facets and a shortening and broadening of the keel. These changes caused a tighter connection between gastral scales within a scale row and a greater overlap between the rows. Dorsal round scales of limbed tetrapodomorphs developed from a gastral scale‐type by an alteration of the ontogenetic pathway. The posterolateral direction of scale rows in ‘elpistostegids’ was retained in the gastral scalation of most limbed tetrapodomorphs, whereas the arrangement of round dorsal scales is modified to a transverse orientation. Both gastral and dorsal scales of limbed tetrapodomorphs consist solely of parallel‐fibred bone with circumferential growth marks. The proportionally larger overlap surfaces of gastral scales and their mode of articulation in the ventral midline indicate that the body of limbed tetrapodomorphs might have been more flexible than that of their finned relatives. The alteration of dermal scales was one of the most rapid morphological changes during the fish‐to‐tetrapod transition. Once established, gastral and dorsal scales were retained as a conservative character in different lineages of basal tetrapods, in both the amphibian and the amniote lineages.     

Measuring ligament elasticity of the knee joint--elasticity measuring strip and its alternatives]

Those techniques for measuring ligament tension at the knee joint that are most commonly cited and easiest to carry out are discussed. These include four techniques based on the use of strain gauges. Apart from the Omega transducer and the buckle transducer, there is also the tendon force transducer, and the application of strain gauges to the bony ligament insertion sites. Other indirect measuring methods considered are the mercury strain transducer and the Hall effect transducer. The parameter measured with all of these methods is fluctuating current or voltage, which is then correlated with ligament tension. Three direct measurements are also discussed: the separation distances of marked fibres of the ligaments, replacement of fibres by threads, and a load cell/bone plug construction. The measured value is equated with the effective change in ligament length.     

Fine structural recognition specificities of IgE antibodies distinguishing amoxicilloyl and amoxicillanyl determinants in allergic subjects.

IgE antibodies in the sera of subjects allergic to beta-lactam antibiotics detect a spectrum of specificities ranging from side-chain groups to an entire penicillin or cephalosporin molecule. In addition to such structural heterogeneity of allergenic determinants, IgE antibodies in the sera of different allergic subjects show heterogeneous recognition responses. Detailed immunochemical studies were carried out on the sera of penicillin-allergic subjects that showed selective and unexpected reactions with the frequently prescribed penicillin, amoxicillin. Antibodies from one subject reacted only with the amoxicilloyl determinant while IgE from another subject showed multiple reactivity with penicilloyl and penicillanyl determinants of different penicillins but not with the amoxicilloyl determinant. Quantitative hapten inhibition studies revealed that the combining sites of the former antibodies were complementary to amoxicillin in a form that permits binding to the hydroxyaminobenzyl side-chain and the thiazolidine ring carboxyl. These conditions are satisfied with the drug in the '-oyl' but not in the '-anyl' form which involves linkage through the 2-carboxyl of the thiazolidine ring. With the second serum, adsorption studies showed that the wide-ranging reactivity of IgE was due to a single population of antibodies that detected a common specificity on the different penicillins. Combining site studies revealed clear recognition of the benzyl portion of the side-chain of benzylpenicilloyl, benzylpenicillanyl, ampicilloyl, ampicillanyl and amoxicillanyl determinants when free antibody access to the side-chain was possible but little or no recognition of the ring hydroxyl of amoxicillin. Such uninhibited access may not occur, however, when amoxicillin is conjugated in the '-oyl' form since opening the beta-lactam ring allows increased flexibility and rotation of the molecule and the possibility of close association of the hydroxyaminobenzyl side-chain of amoxicillin with the linked peptide carrier. In such close steric association, H-bonding involving the ring hydroxyl and amino acids of the carrier may prevent antibody access to the side-chain region of the amoxicilloyl determinant.     

TGA cysteine codons and intron sequences in conserved and nonconserved positions are found in macronuclear RNA polymerase genes of Euplotes octocarinatus.

The gene sequences of the second largest subunits of RNA polymerases I and II of Euplotes octocarinatus, RPA2 and RPB2, were determined and compared to the respective known sequences of Saccharomyces cerevisiae. The similarity of the derived polypeptide sequences permitted their assignment to the respective polymerases and allowed the comparison of the zinc binding regions. In frame TGA codons were detected, which are likely to encode conserved cysteinyl residues in the putative zinc-finger region of the RPA2 gene. They were also found in other positions in both the RPA2 and RPB2 genes. The RPB2 gene contains a 30 bp intron close to the 5'-end of its coding region. The 5'-ends of the coding regions of all three genes encoding the largest subunits of the three different polymerases were also analyzed. The zinc finger structures again show the use of TGA codons for conserved cysteinyl residues in two of the genes. An N-terminal intron is located in the RPB1 gene at a conserved position as compared to the respective genes of several other eucarya.