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.     

Estimating survival of the shortfin mako Isurus oxyrinchus (Rafinesque) in the north-west Atlantic from tag-recapture data

Survival was estimated for shortfin mako Isurus oxyrinchus in the north-west Atlantic from tag-recapture data. The data used in this study were collected by the National Marine Fisheries Service Cooperative Shark Tagging Programme from 1962 to 2003. In total, 6309 shortfin mako sharks were tagged, of which 730 were recaptured. The high recapture rate of 11·6% for this species provided adequate recapture data to carry out survival analyses. Estimates of survival were generated with the computer software MARK, which provided a means for estimating parameters from tagged animals when they were recaptured. The results of several models are presented with various combinations of constant and time-specific survival and recovery rates. A parametric bootstrap and the median variance inflation factor ( ) approach were used to test the fit of the general model to the data. The estimated indicated a very good model fit. The models with time invariant survival rate had the most support from the data and no group or time period effects were found. Recovery rate ( f ) appeared to increase from 0·043 in the early years to 0·056 in the later years. The nominal survival rate of 0·59 year⁻¹ was adjusted with an estimated tag-shedding rate of 0·26 year⁻¹ to generate a final corrected annual survival estimate of 0·79 with a 95% CI of 0·71–0·87.     

Tumor-specific idiotype vaccines. III. Induction of T helper cells by anti-idiotype and tumor cells

In a previous report, we have demonstrated the induction of tumor-specific immunity by monoclonal anti-idiotype antibodies generated against a monoclonal anti-tumor antibody, 11C1, that also cross-reacts with mouse mammary tumor virus envelope glycoprotein gp52. Also, we showed that whereas one anti-idiotype antibody, 2F10, could induce protective immunity, another anti-idiotype antibody, 3A4, induced nonprotective immunity. Here we demonstrated the existence of T helper cells which recognize anti-idiotypes that exert differential controls on tumor growth. The qualitative nature of idiotype recognizing T cells generated in response to 2F10, 3A4, irradiated tumor, and progressively growing tumor was compared. The reactivity pattern of idiotype recognizing T cells obtained from 2F10 and irradiated tumor immunized mice were similar in nature in the sense that Lyt-2- T cells obtained from these immunized mice responded to both 2F10 and 3A4 as antigen, although T cells from tumor immunized mice responded better to 3A4 antigen. On the other hand, the idiotype-recognizing T cells obtained from 3A4-immunized mice showed a similar reactivity pattern to T cells isolated from mice during the early phase of tumor growth (within day 4 to 5 after the inoculation of 10(4) live tumor cells). Lyt-2- T cells isolated from mice immunized with 3A4 or during the early phase of tumor growth responded only to 3A4 antigen. The inability of Lyt-2- T cells, isolated from 4- to 5-day-old tumor in mice, to cooperate with 2F10-TNP is not due to the absence of 2F10 idiotype recognizing T cells as 2F10 id recognizing T cells are present when examined at the precursor level. These data on the idiotype specificity of T helper cells show a correlation with the presence of anti-tumor immunity. This information will help in the design and application of idiotype vaccine in tumor immunotherapy.     

Analysis of the idiotypic network in tumor immunity

Herein we have analyzed the expression of idiotopes associated with a monoclonal anti-tumor-associated antigen (TAA) antibody in DBA/2 mice which have progressively growing tumors or resist tumor growth. A panel of eight monoclonal antiidiotypic antibodies raised against a monoclonal antibody which reacts with a mouse mammary tumor virus cross-reactive qp52 envelope protein (TAA) of the L1210/GZL lymphoma was used to measure the expression of idiotopes in sera from different treatment groups. Significant correlations between the expression of certain idiotopes and the growth of the tumor or the establishment of anti-tumor immunity are seen. 1) Idiotypes detected by anti-idiotype D11 are high in anti-idiotype immunized progressor or tumor-susceptible mice and low or absent in regressor mice, i.e., the mice immunized with the protective 2F10 anti-idiotype; 2) the 3A4-detected idiotypes are less frequent or absent in irradiated tumor-immunized regressor mice than in untreated mice challenged with live tumor or progressor mice; 3) no difference in the anti-TAA titers is seen in mice in which the tumor growth is inhibited and in mice in which the tumor grows; 4) no difference in 11C1 idiotype + anti-TAA titer was observed between regressor and progressor mice; and 5) mice with normal or accelerated tumor growth have higher titers of idiotypes detected by a polyclonal anti-idiotype. These findings provide evidence for a regulatory idiotype network induced by the growing L1210/GZL tumor or by anti-idiotypic immunization. The titer of anti-TAA antibody does not correlate with the biology of tumor growth, but certain idiotopes correlate with either progressive or regressive tumor behavior. Therefore, the target of the idiotype regulation is likely to be anti-tumor T effector cells. Effective idiotype therapy of tumors must deal with the complexity of idiotype regulation induced by the tumor itself and is unlikely to be successful if anti-idiotypes are used only as internal mimicry of a TAA.     

Enhanced tumor susceptibility of immunocompetent mice infected with lymphocytic choriomeningitis virus

Summary Mice infected i.v. with high doses of lymphocytic choriomeningitis virus (LCMV; 10⁵–10⁶ plaqueforming units) 8–10 days prior to challenge with the methylcholanthrene-induced fibrosarcoma tumor cell line MC57G or the melanoma cell line B16 tumor cells showed an enhanced tumor susceptibility with respect to both growth kinetics of the tumor and the minimal dose necessary for tumor take. After transient initial growth, MC57G tumor cells were all rejected by uninfected C57BL/6 mice by day 14. Mice preinfected i.v. with LCMV 3 weeks before or at the time of tumor challenge, but not those infected 2 months before or 7 days after, showed increasing tumor growth, the tumor take being 100% for 10⁶, 50% for 10⁵ and 37% for 10⁴ MC57G tumor cells injected into the footpad compared with resistance to 10⁶ cells in normal mice. B16 melanoma cells also grew more rapidly in LCMV-preinfected mice and by day 40 tumors were established with about 100 times fewer cells, i.e. about 10³ compared with 3×10⁴–3×10⁵ for uninfected mice. Analysis of the growth of tumor cells in normal and in LCMV-carrier mice revealed that the latter mice were not more susceptible to LCMV-infected than to uninfected MC57G. Since LCMV-carrier mice fail to mount LCMV-specific T cell responses, these results suggest that anti-LCMV-specific T cells may be responsible for acquired immunodeficiency hampering immune surveillance against the tumors studied.Supported by grants from the Swiss National Science Foundation 3.259–0.87 and the Kanton of Zürich