81 research outputs found

    Detection of hepatitis e virus (HEV) antibiodies in swine herds in Québec, Canada

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    Hepatitis E virus (HEV) has a zoonotic potential and pork products have been identified as possible human infection sources. Swine HEV infection in pigs have now been reported in pigs in many countries and generally occurs at about 2-3 months of age. Data from USA indicated that about 80-100% of pigs in commercial farms are infected. The objective of this study was to estimate prevalence of HEV in selected Canadian herds by serology using the PrioCHECK HEV Ab porcine-ELISA kit

    Single-probe serial position recall: evidence of modularity for olfactory, visual and auditory short-term memory

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    The present study examined and compared order memory for a list of sequentially presented odours, unfamiliar-faces and pure-tone. Employing single-probe serial position recall and following a correction for a response bias, qualitatively different serial position functions were observed across stimuli. Participants demonstrated an ability to perform absolute order memory judgments for odours. Furthermore, odours produced an absence of serial position effects, unfamiliar-faces produced both primacy and recency and pure-tones produced recency but not primacy. Such a finding is contrary to the proposal by Ward, Avons and Melling (2005) that the serial position function is task, rather than modality, dependent. In contrast, the observed functions support a modular conceptualisation of short-term memory (e.g. Andrade and Donaldson, 2007; Baddeley and Hitch, 1974), whereby separate modality-specific memorial systems operate. An alternative amodal interpretation is also discussed wherein serial position function disparities are accommodated via differences in the psychological distinctiveness of stimuli (Hay, Smyth, Hitch and Horton, 2007)

    Novel CCL21-Vault Nanocapsule Intratumoral Delivery Inhibits Lung Cancer Growth

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    Based on our preclinical findings, we are assessing the efficacy of intratumoral injection of dendritic cells (DC) transduced with an adenoviral vector expressing the secondary lymphoid chemokine (CCL21) gene (Ad-CCL21-DC) in a phase I trial in advanced non-small cell lung cancer (NSCLC). While this approach shows immune enhancement, the preparation of autologous DC for CCL21 genetic modification is cumbersome, expensive and time consuming. We are evaluating a non-DC based approach which utilizes vault nanoparticles for intratumoral CCL21 delivery to mediate antitumor activity in lung cancer.Here we describe that vault nanocapsule platform for CCL21 delivery elicits antitumor activity with inhibition of lung cancer growth. Vault nanocapsule packaged CCL21 (CCL21-vaults) demonstrated functional activity in chemotactic and antigen presenting activity assays. Recombinant vaults impacted chemotactic migration of T cells and this effect was predominantly CCL21 dependent as CCL21 neutralization abrogated the CCL21 mediated enhancement in chemotaxis. Intratumoral administration of CCL21-vaults in mice bearing lung cancer enhanced leukocytic infiltrates (CXCR3(+)T, CCR7(+)T, IFNγ(+)T lymphocytes, DEC205(+) DC), inhibited lung cancer tumor growth and reduced the frequencies of immune suppressive cells [myeloid derived suppressor cells (MDSC), T regulatory cells (Treg), IL-10 T cells]. CCL21-vaults induced systemic antitumor responses by augmenting splenic T cell lytic activity against parental tumor cells.This study demonstrates that the vault nanocapsule can efficiently deliver CCL21 to sustain antitumor activity and inhibit lung cancer growth. The vault nanocapsule can serve as an "off the shelf" approach to deliver antitumor cytokines to treat a broad range of malignancies

    Recruitment of the Major Vault Protein by InlK: A Listeria monocytogenes Strategy to Avoid Autophagy

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    L. monocytogenes is a facultative intracellular bacterium responsible for listeriosis. It is able to invade, survive and replicate in phagocytic and non-phagocytic cells. The infectious process at the cellular level has been extensively studied and many virulence factors have been identified. Yet, the role of InlK, a member of the internalin family specific to L. monocytogenes, remains unknown. Here, we first show using deletion analysis and in vivo infection, that InlK is a bona fide virulence factor, poorly expressed in vitro and well expressed in vivo, and that it is anchored to the bacterial surface by sortase A. We then demonstrate by a yeast two hybrid screen using InlK as a bait, validated by pulldown experiments and immunofluorescence analysis that intracytosolic bacteria via an interaction with the protein InlK interact with the Major Vault Protein (MVP), the main component of cytoplasmic ribonucleoproteic particules named vaults. Although vaults have been implicated in several cellular processes, their role has remained elusive. Our analysis demonstrates that MVP recruitment disguises intracytosolic bacteria from autophagic recognition, leading to an increased survival rate of InlK over-expressing bacteria compared to InlK− bacteria. Together these results reveal that MVP is hijacked by L. monocytogenes in order to counteract the autophagy process, a finding that could have major implications in deciphering the cellular role of vault particles

    Mutations in Eml1 lead to ectopic progenitors and neuronal heterotopia in mouse and human.

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    Neuronal migration disorders such as lissencephaly and subcortical band heterotopia are associated with epilepsy and intellectual disability. DCX, PAFAH1B1 and TUBA1A are mutated in these disorders; however, corresponding mouse mutants do not show heterotopic neurons in the neocortex. In contrast, spontaneously arisen HeCo mice display this phenotype, and our study revealed that misplaced apical progenitors contribute to heterotopia formation. While HeCo neurons migrated at the same speed as wild type, abnormally distributed dividing progenitors were found throughout the cortical wall from embryonic day 13. We identified Eml1, encoding a microtubule-associated protein, as the gene mutated in HeCo mice. Full-length transcripts were lacking as a result of a retrotransposon insertion in an intron. Eml1 knockdown mimicked the HeCo progenitor phenotype and reexpression rescued it. We further found EML1 to be mutated in ribbon-like heterotopia in humans. Our data link abnormal spindle orientations, ectopic progenitors and severe heterotopia in mouse and human

    Xenopus Meiotic Microtubule-Associated Interactome

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    In metazoan oocytes the assembly of a microtubule-based spindle depends on the activity of a large number of accessory non-tubulin proteins, many of which remain unknown. In this work we isolated the microtubule-bound proteins from Xenopus eggs. Using mass spectrometry we identified 318 proteins, only 43 of which are known to bind microtubules. To integrate our results, we compiled for the first time a network of the meiotic microtubule-related interactome. The map reveals numerous interactions between spindle microtubules and the newly identified non-tubulin spindle components and highlights proteins absent from the mitotic spindle proteome. To validate newly identified spindle components, we expressed as GFP-fusions nine proteins identified by us and for first time demonstrated that Mgc68500, Loc398535, Nif3l1bp1/THOC7, LSM14A/RAP55A, TSGA14/CEP41, Mgc80361 and Mgc81475 are associated with spindles in egg extracts or in somatic cells. Furthermore, we showed that transfection of HeLa cells with siRNAs, corresponding to the human orthologue of Mgc81475 dramatically perturbs spindle formation in HeLa cells. These results show that our approach to the identification of the Xenopus microtubule-associated proteome yielded bona fide factors with a role in spindle assembly

    Detection of hepatitis e virus (HEV) antibiodies in swine herds in Québec, Canada

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    Hepatitis E virus (HEV) has a zoonotic potential and pork products have been identified as possible human infection sources. Swine HEV infection in pigs have now been reported in pigs in many countries and generally occurs at about 2-3 months of age. Data from USA indicated that about 80-100% of pigs in commercial farms are infected. The objective of this study was to estimate prevalence of HEV in selected Canadian herds by serology using the PrioCHECK HEV Ab porcine-ELISA kit.</p

    Abolishing the word-length effect

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    The authors report 2 experiments that compare the recall of long and short words in pure and mixed lists. In pure lists, long words were much more poorly remembered than short words. In mixed lists, this word-length effect was abolished and both the long and short words were recalled as well as short words in pure lists. These findings contradict current models that seek to explain the word-length effect in terms of item-based effects such as difficulty in assembling items, or in terms of list-based accounts of rehearsal speed. An alternative explanation, drawing on ideas of item complexity and item distinctiveness, is proposed
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