PathVisio-MIM: PathVisio plugin for creating and editing Molecular Interaction Maps (MIMs)

MOTIVATION: A plugin for the Java-based PathVisio pathway editor has been developed to help users draw diagrams of bioregulatory networks according to the Molecular Interaction Map (MIM) notation. Together with the core PathVisio application, this plugin presents a simple to use and cross-platform application for the construction of complex MIM diagrams with the ability to annotate diagram elements with comments, literature references and links to external databases. This tool extends the capabilities of the PathVisio pathway editor by providing both MIM-specific glyphs and support for a MIM-specific markup language file format for exchange with other MIM-compatible tools and diagram validation. AVAILABILITY: The PathVisio-MIM plugin is freely available and works with versions of PathVisio 2.0.11 and later on Windows, Mac OS X and Linux. Information about MIM notation and the MIMML format is available at http://discover.nci.nih.gov/mim. The plugin, along with diagram examples, instructions and Java source code, may be downloaded at http://discover.nci.nih.gov/mim/mim_pathvisio.html.     

High gene flow in two thrips‐pollinated South‐East Asian pioneer trees: genetic diversity and population structure of Macaranga hypoleuca and M. beccariana (Euphorbiaceae)

As a result of intensive exploitation, disturbed forests now dominate large areas of lowland tropical rainforest in South‐East Asia. The genus Macaranga comprises some of the most important pioneer tree species of the region, among them M. beccariana and M. hypoleuca, two closely related obligate ant‐plants pollinated by thrips. We used nuclear and plastid DNA markers to address questions of genetic diversity and population structure. Twelve plastid haplotypes were detected among 281 samples, three of which were shared between the two study species. Hybrids between the two species appear to be rare. Overall, genetic diversity in both species was moderate to high, with low levels of population differentiation, consistent with other tropical pioneer trees. Genetic structure was generally more pronounced in plastid than in nuclear data, indicating that gene flow via pollen may be more efficient than via seeds. Thrips apparently also serve as efficient pollinators over long distances, perhaps through a combination of passive dispersal by wind and active search for inflorescences in the target area. Our results indicate that M. beccariana and M. hypoleuca populations from recently disturbed habitats do not yet suffer from reduced genetic diversity or increased inbreeding. © 2013 The Linnean Society of London, Botanical Journal of the Linnean Society, 2013, 173 , 606–621.     

Profile of resistance of human immunodeficiency virus to mannose-specific plant lectins

The mannose-specific plant lectins from the Amaryllidaceae family (e.g., Hippeastrum sp. hybrid and Galanthus nivalis) inhibit human immunodeficiency virus (HIV) infection of human lymphocytic cells in the higher nanogram per milliliter range and suppress syncytium formation between persistently HIV type 1 (HIV-1)-infected cells and uninfected CD4(+) T cells. These lectins inhibit virus entry. When exposed to escalating concentrations of G. nivalis and Hippeastrum sp. hybrid agglutinin, a variety of HIV-1(III(B)) strains were isolated after 20 to 40 subcultivations which showed a decreased sensitivity to the plant lectins. Several amino acid changes in the envelope glycoprotein gp120, but not in gp41, of the mutant virus isolates were observed. The vast majority of the amino acid changes occurred at the N glycosylation sites and at the S or T residues that are part of the N glycosylation motif. The degree of resistance to the plant lectins was invariably correlated with an increasing number of mutated glycosylation sites in gp120. The nature of these mutations was entirely different from that of mutations that are known to appear in HIV-1 gp120 under the pressure of other viral entry inhibitors such as dextran sulfate, bicyclams (i.e., AMD3100), and chicoric acid, which also explains the lack of cross-resistance of plant lectin-resistant viruses to any other HIV inhibitor including T-20 and the blue-green algae (cyanobacteria)-derived mannose-specific cyanovirin. The plant lectins represent a well-defined class of anti-HIV (microbicidal) drugs with a novel HIV drug resistance profile different from those of other existing anti-HIV drugs.     

An interaction map of endoplasmic reticulum chaperones and foldases

Chaperones and foldases in the endoplasmic reticulum (ER) ensure correct protein folding. Extensive protein-protein interaction maps have defined the organization and function of many cellular complexes, but ER complexes are under-represented. Consequently, chaperone and foldase networks in the ER are largely uncharacterized. Using complementary ER-specific methods, we have mapped interactions between ER-lumenal chaperones and foldases and describe their organization in multiprotein complexes. We identify new functional chaperone modules, including interactions between protein-disulfide isomerases and peptidyl-prolyl cis-trans-isomerases. We have examined in detail a novel ERp72-cyclophilin B complex that enhances the rate of folding of immunoglobulin G. Deletion analysis and NMR reveal a conserved surface of cyclophilin B that interacts with polyacidic stretches of ERp72 and GRp94. Mutagenesis within this highly charged surface region abrogates interactions with its chaperone partners and reveals a new mechanism of ER protein-protein interaction. This ability of cyclophilin B to interact with different partners using the same molecular surface suggests that ER-chaperone/foldase partnerships may switch depending on the needs of different substrates, illustrating the flexibility of multichaperone complexes of the ER folding machinery.     

Real-time Digital Imaging of Leukocyte-endothelial Interaction in Ischemia-reperfusion Injury (IRI) of the Rat Cremaster Muscle

Ischemia-reperfusion injury (IRI) has been implicated in a large array of pathological conditions such as cerebral stroke, myocardial infarction, intestinal ischemia as well as following transplant and cardiovascular surgery.¹ Reperfusion of previously ischemic tissue, while essential for the prevention of irreversible tissue injury, elicits excessive inflammation of the affected tissue. Adjacent to the production of reactive oxygen species, activation of the complement system and increased microvascular permeability, the activation of leukocytes is one of the principle actors in the pathological cascade of inflammatory tissue damage during reperfusion.^{2, 3} Leukocyte activation is a multistep process consisting of rolling, firm adhesion and transmigration and is mediated by a complex interaction between adhesion molecules in response to chemoattractants such as complement factors, chemokines, or platelet-activating factor.⁴While leukocyte rolling in postcapillary venules is predominantly mediated by the interaction of selectins⁵ with their counter ligands, firm adhesion of leukocytes to the endothelium is selectin-controlled via binding to intercellular adhesion molecules (ICAM) and vascular cellular adhesion molecules (VCAM).^{6, 7}Gold standard for the in vivo observation of leukocyte-endothelial interaction is the technique of intravital microscopy, first described in 1968.⁸Though various models of IRI (ischemia-reperfusion injury) have been described for various organs, ^9-12 only few are suitable for direct visualization of leukocyte recruitment in the microvascular bed on a high level of image quality.⁸We here promote the digital intravital epifluorescence microscopy of the postcapillary venule in the cremasteric microcirculation of the rat ¹³ as a convenient method to qualitatively and quantitatively analyze leukocyte recruitment for IRI-research in striated muscle tissue and provide a detailed manual for accomplishing the technique. We further illustrate common pitfalls and provide useful tips which should enable the reader to truly appreciate, and safely perform the method.In a step by step protocol we depict how to get started with respiration controlled anesthesia under sufficient monitoring to keep the animal firmly anesthetized for longer periods of time. We then describe the cremasteric preparation as a thin flat sheet for outstanding optical resolution and provide a protocol for leukocyte imaging in IRI that has been well established in our laboratories.Download video file.^{(88M, mov)}     

The Evolution of Resistance to Simian Immunodeficiency Virus (SIV): A Review

Examining how pathogens cross species boundaries, spread within species, and persist within their hosts is an essential part of understanding the factors that underpin the evolution of virulence and host resistance. Here, we review current knowledge about the genetic diversity, molecular epidemiology, prevalence, and pathogenicity of simian immunodeficiency viruses (SIVs). SIVs have crossed species boundaries from simian hosts to humans on at least 12 separate occasions, one of which led to the global HIV–AIDS crisis. Though SIVs infect a wide range of primates, scientists have only recently begun to describe the natural history of SIV infection in their natural hosts. Several new studies reveal how both viral and host factors are responsible for the transmission to, and adaptation in, new hosts. These studies also suggest that the spread of the virus may be affected by host-specific traits, including social structure, mating system and demographic history. These studies challenge the traditional view that SIV is relatively benign in its natural host, and instead suggest that a highly dynamic relationship exists between SIV and its simian hosts.     

Entwicklungsgeschichtliche und cytologische Untersuchungen am Balkentapetum von Gentiana cruciata L. und Impatiens glandulifera Royle

Zusammenfassung Die Entstehung des Balkentapetums beiGentiana cruciata undImpatiens glandulifera wird beschrieben und in Beziehung zu den übrigen Tapetumtypen gesetzt. BeiGentiana verläuft die Wandschichtenbildung meist zentripetal, oft (in 30% aller untersuchten Fälle) auch zentrifugal. Die Entstehung der Zwischenschichten schreitet an der Loculus-Innenseite von einem Placentoid aus peripher fort. BeiImpatiens entstehen das Endothecium und die beiden Zwischenschichten stets in zentrifugaler Folge. Das Tapetum ist bei beiden untersuchten Arten sporogenen Ursprungs und wird in Form einer peripheren Lage und von 1–2 Zellen breiten Balken gebildet, die den Loculus in unterschiedlich große Kammern aufteilen. Pollenmutter- und Tapetumzellen unterscheiden sich cytologisch und karyologisch (Kern- und Nucleolusvolumina und Chromozentrengröße). Kurz vor oder zu Beginn der Meiosis beginnen bei beiden Arten die karyologischen Veränderungen im Tapetum: seine Zellen werden beiGentiana durch Endomitose tetraploid, beiImpatiens durch freie Kernteilung zweikernig. Entgegen früheren Literaturangaben bleiben sie bis zur Degeneration zellig. Beide Arten besitzen also ein celluläres Sekretionstapetum. — Der Nachweis der Endomitose im Tapetum vonGentiana cruciata erfolgte durch Strukturanalyse der Kerne (Endo-Inter- und Endo-Prophase) und den Nachweis der periodischen Wiederkehr dieser Strukturen in verschiedenen Kern-Größenklassen.Mit 14 TextabbildungenHerrn Prof. Dr.P. Claussen zum 80. Geburtstag gewidmet.