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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.
This review lists Agama smithii Boulenger 1896 as a synonym of Agama agama (Linnaeus 1758), Agama trachypleura Peters 1982 as a synonym of Acanthocercus phillipsii (Boulenger 1895) and describes for the first time Acanthocercus guentherpetersi n. sp. Without more convincing evidence, Chamaeleon ruspolii Boettger 1893 cannot be accepted as specifically distinct from Chamaeleo dilepis Leach 1819, nor Chamaeleo calcaricarens Böhme 1985 from C. africanus Laurenti 1768. Consequently, 101 species of lizard are currently recognised in Ethiopia, of which some 40% appear to be denizens of the Somali-arid zone. This significant proportion is attributable in part to the importance of the Horn of Africa as a centre for reptilian diversification and endemicity, in part to the fact that this lowland fauna was rather extensively sampled during the 1930s, but also to the conspicuous neglect of lizards in other regions of the country. Mountain and forested habitats are widespread in Ethiopia, so it seems extraordinary to record only five saurian species which are believed to be endemic in such environments. The inference that there are many more still to be discovered has important implications for conservation, because montane forest is known to be among the most threatened of Ethiopian biomes and there is clearly an urgent need for its herpetofauna to be more thoroughly researched and documented.
The present paper contains descriptions of 4 new genera and 62 new species of South African Spiders contained in the Collection of the South African Museum. With the exception of 3 new species of Prodidomidae, all of them belong to the groups Mygalomorphae (Migidce, 1 n. sp.; Ctenizidae, 1 n. gen. and 5 n. spp.; Barychelidae, 2 n. spp.), Cribellatae (Uloboridae, 1 n. gen. and 3 n. spp.; Dictynirlce, 4 n. spp.; Eresidae, 6 n. spp.) , and Ecribellatae Haplogynae (Sicariidae, 19 n. spp.; Dysderidae, 1 n. geu. and 11 n. spp.; Caponiidae, 1 n. gen. and 8 n. spp.).
It has been the goal of this review to describe the functional interrelations between Deiters' vestibular nucleus and numerous brain structures. Emphasis is placed on dynamic and integrative properties of linkages between the neurons of Deiters' nucleus and many other brain structures in order to begin considering the capabilities of the loops in the light of motor control and coordination of movement. The problem of somatotopy within the loops is also considered. Putting this information together, the possible roles of Deiters' nucleus in the control of movements are described. It is suggested that Deiters' nucleus in co-operation with cerebral cortex, cerebellum, subcortical and brainstem structures are responsible for the integration and realization of different movements.
This stndy is based largely upon collections from the Danish Noona Dan Expedition to the southern Philippines and the Bismarck Islands (Pelersen, 1966), supplemented with collections from the B. P. Bishop Museum, British Museum (Natural History), U. S. National Museum, California Academy of Science, Zoologisches Museum der Humboldt Universität zu Berlin, and the Chicago Natural History Museum. I greatly appreciate having had the privilege of studying these valuable collections. ...
Background: The treatment of high-risk neuroblastoma patients consists of multimodal induction therapy to achieve remission followed by consolidation therapy to prevent relapses. However, the type of consolidation therapy is still discussed controversial. We applied metronomic chemotherapy in the prospective NB90 trial and monoclonal anti-GD2-antibody (MAB) ch14.18 in the NB97 trial. Here, we present the long term outcome data of the patient cohort. Methods: A total of 334 stage 4 neuroblastoma patients one year or older were included. All patients successfully completed the induction therapy. In the NB90 trial, 99 patients received at least one cycle of the oral maintenance chemotherapy (NB90 MT, 12 alternating cycles of oral melphalan/etoposide and vincristine/cyclophosphamide). In the NB97 trial, 166 patients commenced the MAB ch14.18 consolidation therapy (six cycles over 12 months). Patients who received no maintenance therapy according to the NB90 protocol or by refusal in NB97 (n = 69) served as controls. Results: The median observation time was 11.11 years. The nine-year event-free survival rates were 41 ± 4%, 31 ± 5%, and 32 ± 6% for MAB ch14.18, NB90 MT, and no consolidation, respectively (p = 0.098). In contrast to earlier reports, MAB ch14.18 treatment improved the long-term outcome compared to no additional therapy (p = 0.038). The overall survival was better in the MAB ch14.18-treated group (9-y-OS 46 ± 4%) compared to NB90 MT (34 ± 5%, p = 0.026) and to no consolidation (35 ± 6%, p = 0.019). Multivariable Cox regression analysis revealed ch14.18 consolidation to improve outcome compared to no consolidation, however, no difference between NB90 MT and MAB ch14.18-treated patients was found. Conclusions: Follow-up analysis of the patient cohort indicated that immunotherapy with MAB ch14.18 may prevent late relapses. Finally, metronomic oral maintenance chemotherapy also appeared effective.
A review of biological control efforts against Diptera of medical and veterinary importance includes pertinent literature of major dipterous taxonomic groups where some success has been achieved or where work is currently being conducted on species breeding in aquatic (e.g., mosquitoes, blackflies, tabanids) and terrestrial habitats (muscids, tsetse, etc.). Most effort has been directed against aquatic Diptera because of the human and animal disease agents they transmit. Research has established that the natural enemy component frequently is responsible for significant population reduction and indispensable to integrated control which seeks to maintain populations below annoyance or disease transmission levels. The manipulation of natural enemies through introduction and/or augmentation has in some cases provided satisfactory control, and sustained releases of natural enemies over several years may overcome the relative high cost of massive release rates. Ultimately, to guarantee the existence and maximum expression of resident natural enemies has become almost universally accepted, and challenging, to sound control practices. Indeed, chemical industry recognizing this, has sought to manufacture products such as Bacillus toxins, juvenile hormones, and baits that are minimally disruptive to existing natural controls. Although such easily applied products have been widely adopted, their cost continues to become prohibitive with developing resistance, as was observed earlier with many organophosphate and chlorinated hydrocarbon insecticides. Further advancements in the control ofthese Diptera should continue to embrace a sound appreciation for the natural control component and nurture ways to allow its maximum expression. Keyword Index: Biological Control, Diptera, Medical, Veterinary.