Filtern
Dokumenttyp
Sprache
- Englisch (6) (entfernen)
Volltext vorhanden
- ja (6)
Gehört zur Bibliographie
- nein (6)
Schlagworte
- Odonata (2)
- distribution (2)
- dragonflies (2)
- Cape Verde (1)
- Cape Verde Islands (1)
- Genetics research (1)
- Immunological techniques (1)
- Mutations (1)
- Myeloproliferative disease (1)
- Translational research (1)
Institut
- Medizin (2)
- Extern (1)
- Georg-Speyer-Haus (1)
The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles (“MISEV”) guidelines for the field in 2014. We now update these “MISEV2014” guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities. Finally, a checklist is provided with summaries of key points.
Necroptosis contributes to the pathophysiology of several inflammatory, infectious and degenerative disorders. TNF-induced necroptosis involves activation of the receptor-interacting protein kinases 1 and 3 (RIPK1/3) in a necrosome complex, eventually leading to the phosphorylation and relocation of mixed lineage kinase domain like protein (MLKL). Using a high-content screening of small compounds and FDA-approved drug libraries, we identified the anti-cancer drug Sorafenib tosylate as a potent inhibitor of TNF-dependent necroptosis. Interestingly, Sorafenib has a dual activity spectrum depending on its concentration. In murine and human cell lines it induces cell death, while at lower concentrations it inhibits necroptosis, without affecting NF-κB activation. Pull down experiments with biotinylated Sorafenib show that it binds independently RIPK1, RIPK3 and MLKL. Moreover, it inhibits RIPK1 and RIPK3 kinase activity. In vivo Sorafenib protects against TNF-induced systemic inflammatory response syndrome (SIRS) and renal ischemia–reperfusion injury (IRI). Altogether, we show that Sorafenib can, next to the reported Braf/Mek/Erk and VEGFR pathways, also target the necroptotic pathway and that it can protect in an acute inflammatory RIPK1/3-mediated pathology.
Recent advances in the diagnostic of myeloproliferative neoplasms (MPNs) discovered CALRETICULIN (CALR) mutations as a major driver in these disorders. In contrast to JAK2 mutations being mainly associated with polycythaemia vera, CALR mutations are only associated with primary myelofibrosis (PMF) and essential thrombocythaemia (ET). CALR mutations are present in the majority of PMF and ET patients lacking JAK2 and MPL mutations. As these CALR mutations are absent from reactive bone marrow (BM) lesions their presence indicates ET or PMF. So far these mutations are detectable only by molecular assays. Their molecular detection is cumbersome because of the great CALR mutation heterogeneity. Therefore, the availability of a simple assay would be of great help. All CALR mutations reported lead to a frameshift generating a new 36 amino-acid C-terminus. We generated a monoclonal antibody (CAL2) to this C-neoterminus by immunizing mice with a representative peptide and compared its performance with Sanger sequencing data in 173 MPNs and other BM diseases. There was a 100% correlation between the molecular and the CAL2 immunohistochemical (IHC) assays. Thus, the detection of CALR mutations by the CAL2 IHC is a specific, sensitive, rapid, simple and low-cost method.
Dragonflies from the Cape Verde Islands, collected between 1960 and 1989 and kept in institutes in Portugal and Cape Verde, were studied. The Cape Verde collection at the Centro de Zoologia, Instituto de Investigação Científica Tropical, Lisbon, Portugal, includes eight species of dragonflies represented by 279 specimens collected in 1960-61 and 1969-72. The entomological collection at the Instituto Nacional de Investigação e Desenvolvimento Agrário (INIDA), São Jorge dos Orgãos, Republic of Cape Verde, includes four odonate species, represented by 27 specimens, collected in the years 1987 and 1989. Anax tristis Hagen and A. rutherfordi McLachlan, single male specimens of which were collected in Santo Antão, 27 October 1972, are new taxa for the archipelago. Both are tropical migrants of which the nearest known occurrence in continental Africa is more than 1,000 and 1,500 km, respectively, from the Cape Verde Islands. The two collections contain several specimens from new localities within the archipelago, particularly from the islands of Maio and Fogo. Current knowledge of flight season and island distribution are summarized and updated.
Background: The interferon-inducible immunity-related GTPases (IRG proteins/p47 GTPases) are a distinctive family of GTPases that function as powerful cell-autonomous resistance factors. The IRG protein, Irga6 (IIGP1), participates in the disruption of the vacuolar membrane surrounding the intracellular parasite, Toxoplasma gondii, through which it communicates with its cellular hosts. Some aspects of the protein's behaviour have suggested a dynamin-like molecular mode of action, in that the energy released by GTP hydrolysis is transduced into mechanical work that results in deformation and ultimately rupture of the vacuolar membrane. Results: Irga6 forms GTP-dependent oligomers in vitro and thereby activates hydrolysis of the GTP substrate. In this study we define the catalytic G-domain interface by mutagenesis and present a structural model, of how GTP hydrolysis is activated in Irga6 complexes, based on the substrate-twinning reaction mechanism of the signal recognition particle (SRP) and its receptor (SRalpha). In conformity with this model, we show that the bound nucleotide is part of the catalytic interface and that the 3'hydroxyl of the GTP ribose bound to each subunit is essential for trans-activation of hydrolysis of the GTP bound to the other subunit. We show that both positive and negative regulatory interactions between IRG proteins occur via the catalytic interface. Furthermore, mutations that disrupt the catalytic interface also prevent Irga6 from accumulating on the parasitophorous vacuole membrane of T. gondii, showing that GTP-dependent Irga6 activation is an essential component of the resistance mechanism. Conclusions: The catalytic interface of Irga6 defined in the present experiments can probably be used as a paradigm for the nucleotide-dependent interactions of all members of the large family of IRG GTPases, both activating and regulatory. Understanding the activation mechanism of Irga6 will help to explain the mechanism by which IRG proteins exercise their resistance function. We find no support from sequence or G-domain structure for the idea that IRG proteins and the SRP GTPases have a common phylogenetic origin. It therefore seems probable, if surprising, that the substrate-assisted catalytic mechanism has been independently evolved in the two protein families.
Dragonflies (Insecta, Odonata) of São Vicente, Cape Verde Islands : 10 species on a desert island
(2010)
The island of São Vicente, Cape Verde Islands, has no natural and permanent surface fresh water habitats. Surprisingly, with records of 10 species of dragonflies, the island is the most species-rich in the archipelago so far (cf. Aistleitner et al. 2008, this study). Knowledge of Odonata from São Vicente is based on a small number of reports, mostly including single records only (Calvert 1893, Kirby 1897, Lobin 1982, Aistleitner et al. 2008). During a visit to the island in August 2009, AM recorded four species as single adults. Two species were recorded on 26 August 2009, after two days of heavy rainfall which caused extensive temporary waterflows and pools in the main courses of river beds, on the plains, as well as on roads and sports grounds in and around the town of Mindelo.