Liver-Targeting of Interferon-Alpha with Tissue-Specific Domain Antibodies

PMCID: PMC3581439This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

A qualitative study into the perceived barriers of accessing healthcare among a vulnerable population involved with a community centre in Romania

(1) Interview guide for family members, and (2) Interview guide for staff members. (DOCX 103 kb

The neural correlates of referential communication : taking advantage of sparse-sampling fMRI to study verbal communication with a real interaction partner

This paper introduces an innovative functional magnetic resonance imaging (fMRI) protocol to study real verbal interactions while limiting the impact of speech-related movement artefacts. This protocol is based on a sparse sampling acquisition technique and allowed participants to complete a referential communication task with a real interaction partner. During verbal interactions, speakers adjust their verbal productions depending on their interlocutors' knowledge of the referents being mentioned. These adjustments have been linked to theory of mind (ToM), the ability to infer other's mental states. We thus sought to determine if the brain regions supporting ToM would also be activated during a referential communication task in which participants have to present movie characters that vary in their likelihood of being known by their interlocutor. This pilot study establishes that the sparse sampling strategy is a viable option to study the neural correlates of referential communication while minimizing movement artefacts. In addition, the brain regions supporting ToM were recruited during the task, though specifically for the conditions where participants could adjust their verbal productions to the interlocutor's likely knowledge of the referent. This study therefore demonstrates the feasibility and relevance of a sparse-sampling approach to study verbal interactions with fMRI, including referential communication

Descriptive epidemiology of cleft lip and cleft palate in Western Australia

BACKGROUND: Most national and provincial commissions on healthcare services in Canada over the past decade have recommended that primary care services be strengthened in order to guarantee each citizen access to a family physician. Despite these recommendations, finding a family physician continues to be problematic. The issue of enrollment with a family physician is worrying in Canada, where nearly 21% of the country's population reported not having a family physician in the last Commonwealth Fund survey.To respond to this important need, centralized waiting lists have been implemented in four Canadian provinces to help 'orphan,' or unaffiliated, patients find a family physician. These organizational mechanisms are intended to better coordinate the demand for and supply of family physicians. The objectives of this study are: to assess the effects of centralized waiting lists for orphan patients (GACOs) implemented in the province of Quebec and to explain the variation among their effects by analyzing factors influencing implementation process. METHODS: This study is based on two complementary and sequential research strategies. The first (objective 1) is a quantitative longitudinal design to assess the effects of all the GACOs (n = 93) in Quebec using clinical-administrative data. The second (objective 2) involves using four case studies to explain variations in effects through in-depth analysis of the various factors contributing to the observed effects. The primary source of data will be key actors involved in the GACOs. We expect to conduct around 40 semi-structured interviews. DISCUSSION: This will be the first study in Canada to evaluate the implementation of this innovation. It will provide an exhaustive picture of the effects of GACO implementation in Quebec and to assess their potential for generalization elsewhere in Canada. At the theoretical level, this study will produce new knowledge on the factors having the greatest influence on the implementation of primary care innovations in professional environments

P113 is a merozoite surface protein that binds the N terminus of Plasmodium falciparum RH5.

Invasion of erythrocytes by Plasmodium falciparum merozoites is necessary for malaria pathogenesis and is therefore a primary target for vaccine development. RH5 is a leading subunit vaccine candidate because anti-RH5 antibodies inhibit parasite growth and the interaction with its erythrocyte receptor basigin is essential for invasion. RH5 is secreted, complexes with other parasite proteins including CyRPA and RIPR, and contains a conserved N-terminal region (RH5Nt) of unknown function that is cleaved from the native protein. Here, we identify P113 as a merozoite surface protein that directly interacts with RH5Nt. Using recombinant proteins and a sensitive protein interaction assay, we establish the binding interdependencies of all the other known RH5 complex components and conclude that the RH5Nt-P113 interaction provides a releasable mechanism for anchoring RH5 to the merozoite surface. We exploit these findings to design a chemically synthesized peptide corresponding to RH5Nt, which could contribute to a cost-effective malaria vaccine

The Effect of a DNA Repair Gene on Cellular Invasiveness: Xrcc3 Over-Expression in Breast Cancer Cells

Over-expression of DNA repair genes has been associated with resistance to radiation and DNA-damage induced by chemotherapeutic agents such as cisplatin. More recently, based on the analysis of genome expression profiling, it was proposed that over-expression of DNA repair genes enhances the invasive behaviour of tumour cells. In this study we present experimental evidence utilizing functional assays to test this hypothesis. We assessed the effect of the DNA repair proteins known as X-ray complementing protein 3 (XRCC3) and RAD51, to the invasive behavior of the MCF-7 luminal epithelial-like and BT20 basal-like triple negative human breast cancer cell lines. We report that stable or transient over-expression of XRCC3 but not RAD51 increased invasiveness in both cell lines in vitro. Moreover, XRCC3 over-expressing MCF-7 cells also showed a higher tumorigenesis in vivo and this phenotype was associated with increased activity of the metalloproteinase MMP-9 and the expression of known modulators of cell-cell adhesion and metastasis such as CD44, ID-1, DDR1 and TFF1. Our results suggest that in addition to its' role in facilitating repair of DNA damage, XRCC3 affects invasiveness of breast cancer cell lines and the expression of genes associated with cell adhesion and invasion