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 physical mechanism of calcium pump regulation in the heart.

The Ca-ATPase in the cardiac sarcoplasmic reticulum membrane is regulated by an amphipathic transmembrane protein, phospholamban. We have used time-resolved phosphorescence anisotropy to detect the microsecond rotational dynamics, and thereby the self-association, of the Ca-ATPase as a function of phospholamban phosphorylation and physiologically relevant calcium levels. The phosphorylation of phospholamban increases the rotational mobility of the Ca-ATPase in the sarcoplasmic reticulum bilayer, due to a decrease in large-scale protein association, with a [Ca2+] dependence parallel to that of enzyme activation. These results support a model in which phospholamban phosphorylation or calcium free the enzyme from a kinetically unfavorable associated state.     

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.     

A simple and rapid preparation of M13 sequencing templates for manual and automated dideoxy sequencing.

A simple and rapid procedure for the preparation of M13 single stranded DNA sequencing templates which does not involve phenol extractions and alcohol precipitations is described. Bacteriophages are precipitated from media supernatants with acetic acid and recovered on glass fiber filters. Subsequent dissociation of the phages and removal of contaminants is performed while the DNA is bound to the glass. Finally, the purified DNA is eluted in a small volume of low-salt buffer. The yield is higher than that obtained by standard methods. The simplified procedure takes less than 30 minutes and does not demand special skills or equipment; the sequence resolution is as good as that obtained by standard procedures both with the Klenow fragment and T7 DNA polymerase, with radioactive labelling as well as in automated sequencing with a fluorescent label.