Non-Lytic, Actin-Based Exit of Intracellular Parasites from C. elegans Intestinal Cells

The intestine is a common site for invasion by intracellular pathogens, but little is known about how pathogens restructure and exit intestinal cells in vivo. The natural microsporidian parasite N. parisii invades intestinal cells of the nematode C. elegans, progresses through its life cycle, and then exits cells in a transmissible spore form. Here we show that N. parisii causes rearrangements of host actin inside intestinal cells as part of a novel parasite exit strategy. First, we show that N. parisii infection causes ectopic localization of the normally apical-restricted actin to the basolateral side of intestinal cells, where it often forms network-like structures. Soon after this actin relocalization, we find that gaps appear in the terminal web, a conserved cytoskeletal structure that could present a barrier to exit. Reducing actin expression creates terminal web gaps in the absence of infection, suggesting that infection-induced actin relocalization triggers gap formation. We show that terminal web gaps form at a distinct stage of infection, precisely timed to precede spore exit, and that all contagious animals exhibit gaps. Interestingly, we find that while perturbations in actin can create these gaps, actin is not required for infection progression or spore formation, but actin is required for spore exit. Finally, we show that despite large numbers of spores exiting intestinal cells, this exit does not cause cell lysis. These results provide insight into parasite manipulation of the host cytoskeleton and non-lytic escape from intestinal cells in vivo

Epilepsy and intellectual disability linked protein Shrm4 interaction with GABA B Rs shapes inhibitory neurotransmission

Shrm4, a protein expressed only in polarized tissues, is encoded by the KIAA1202 gene, whose mutations have been linked to epilepsy and intellectual disability. However, a physiological role for Shrm4 in the brain is yet to be established. Here, we report that Shrm4 is localized to synapses where it regulates dendritic spine morphology and interacts with the C terminus of GABA B receptors (GABA B Rs) to control their cell surface expression and intracellular trafficking via a dynein-dependent mechanism. Knockdown of Shrm4 in rat severely impairs GABA B R activity causing increased anxiety-like behaviour and susceptibility to seizures. Moreover, Shrm4 influences hippocampal excitability by modulating tonic inhibition in dentate gyrus granule cells, in a process involving crosstalk between GABA B Rs and extrasynaptic \uce-subunit-containing GABA A Rs. Our data highlights a role for Shrm4 in synaptogenesis and in maintaining GABA B R-mediated inhibition, perturbation of which may be responsible for the involvement of Shrm4 in cognitive disorders and epilepsy

Iodine-125 brachytherapy for brain tumours - a review

Iodine-125 brachytherapy has been applied to brain tumours since 1979. Even though the physical and biological characteristics make these implants particularly attractive for minimal invasive treatment, the place for stereotactic brachytherapy is still poorly defined

Local culture, globalisation and policy outcomes: an example from long term care

It is argued that the impact of globalisation and global ideologies on social policy can depend on the ways that local cultures reinforce or combat global ideologies and pressures. The paper discusses the importance of local policy factors in shaping responses to globalisation, taking as an example the way in which global forces have affected outcomes for older people needing long term care in one marginalised province of a rich country. Local political, economic and sociocultural factors can reinforce global pressures for neo liberal policies and rising individualism and overwhelm the global ideologies of democracy and human rights (including gender rights and anti ageism) that might lead to better outcomes for older people and their caregivers. In the New Brunswick province of Canada, traditional cultural values can be seen as one factor allowing politicians to make suboptimal social policy choices

Effect of surface treatments of laboratory-fabricated composites on the microtensile bond strength to a luting resin cement Efeito dos tratamentos de superfície de resinas compostas de laboratório na resistência a microtração de um agente de fixação resinoso

The purpose of this study was to evaluate the influence of different surface treatments on composite resin on the microtensile bond strength to a luting resin cement. Two laboratory composites for indirect restorations, Solidex and Targis, and a conventional composite, Filtek Z250, were tested. Forty-eight composite resin blocks (5.0 x 5.0 x 5.0mm) were incrementally manufactured, which were randomly divided into six groups, according to the surface treatments: 1- control, 600-grit SiC paper (C); 2- silane priming (SI); 3- sandblasting with 50 mm Al2O3 for 10s (SA); 4- etching with 10% hydrofluoric acid for 60 s (HF); 5- HF + SI; 6 - SA + SI. Composite blocks submitted to similar surface treatments were bonded together with the resin adhesive Single Bond and Rely X luting composite. A 500-g load was applied for 5 minutes and the samples were light-cured for 40s. The bonded blocks were serially sectioned into 3 slabs with 0.9mm of thickness perpendicularly to the bonded interface (n = 12). Slabs were trimmed to a dumbbell shape and tested in tension at 0.5mm/min. For all composites tested, the application of a silane primer after sandblasting provided the highest bond strength means.<br>O objetivo deste estudo foi avaliar a influência de diferentes tratamentos de superfície na resistência de união de resinas compostas a um agente de fixação resinoso. Dois compósitos de laboratório, Solidex e Targis, e um compósito convencional, Filtek Z250, foram testados. Quarenta e oito blocos de resina composta (5.0 x 5.0 x 5.0mm) foram confeccionados através da técnica incremental, para cada compósito testado, e foram aleatoriamente divididos em 6 grupos. Os blocos foram submetidos a seis tratamentos de superfície: 1 - Controle, Lixa 600-SiC (C); 2 - Silanização (SI); 3 - Jateamento com Al2O3 50µm por 10 segundos (SA); 4 - Condicionamento com ácido fluorídrico por 60 segundos (HF); 5 - HF + SI; 6 - SA + SI. Blocos submetidos ao mesmo tratamento foram unidos com o agente de fixação resinoso Rely X. Uma carga de 500g foi aplicada por 5 minutos e as amostras foram fotoativadas por 40 segundos. Os blocos unidos foram seccionados em fatias de 0.9mm de espessura perpendicularmente à interface de união (n = 12). Foram realizadas constrições limitando a interface de união a 1mm e as amostras foram levadas para o ensaio de tração. As maiores médias de união foram obtidas para as amostras submetidas à aplicação do silano após o jateamento com Al2O3

Tributes to McKenna

245 p. : ill., map ; 26 cm.Includes bibliographical references.Preface / Gina C. Gould and Susan K. Bell ; with contributions from James S. Mellett -- 1. Malcolm C. McKenna : a biography and bibliography / Susan K. Bell -- 2. The ankle structure of two pterodactyloid pterosaurs from the Santana Formation (Lower Cretaceous), Brazil / Alexander W.A. Kellner -- 3. Diversity of early Cretaceous mammals from Victoria, Australia / Thomas H. Rich and Patricia Vickers-Rich -- 4. The anterior dentition of the late Jurassic multituberculate Ctenacodon / George F. Engelmann -- 5. Marsupial mammals from the Albian-Cenomanian (early-late Cretaceous) boundary, Utah / Richard L. Cifelli -- 6. A polydolopine marsupial skull from the Cachapoal Valley, Andean main range, Chile / John J. Flynn and André R. Wyss -- 7. Phylogeny and divergence of basal Glires / Jin Meng -- 8. Adaptation and the origin of rodents / Leigh Van Valen -- 9. Assessing statistical techniques for detecting multispecies samples of heteromyids in the fossil record : a test using extant Dipodomys / Marc A. Carrasco -- 10. The edentulous skull of the North American pangolin, Patriomanis americanus / Robert J. Emry -- 11. Global climate and the evolution of large mammalian carnivores during the later Cenozoic in North America / Robert M. Hunt, Jr. -- 12. New felid material from the Ulaan Tologoi locality, Loh Formation (early Miocene) of Mongolia / Tom Rothwell -- 13. Humeri of Oligoscalops (Proscalopidae, Mammalia) from the Oligocene of Mongolia / Jonathan H. Geisler -- 14. The basicranial and posterior cranial anatomy of the families of the Toxodontia / Sherri L. Gabbert -- 15. Moropus merriami in the early Barstovian Lower Snake Creek fauna of Nebraska, with comments on biogeography of North American chalicotheres / Margery C. Coombs -- 16. A revised dental nomenclature for fossil horses / Robert L. Evander -- 17. Gigantism, dwarfism, and Cope's rule : "Nothing in evolution makes sense without a phylogeny" / Gina C. Gould and Bruce J. MacFadden -- 18. North American mammalian chronostratigraphy : the contributions of Malcolm C. McKenna / Donald R. Prothero