Illusory vowels in Spanish-English sequential bilinguals: Evidence that accurate L2 perception is neither necessary nor sufficient for accurate L2 production

Spanish native speakers are known to pronounce onset /sC/ clusters in English with a prothetic vowel, as in esport for sport, due to their native language phonotactic constraints. We assessed whether accurate production of e.g. spi instead of espi was related to accurate perceptual discrimination of this contrast in second language (L2) speech of Spanish–English sequential bilinguals. A same–different discrimination task in stimulus pairs such as spi–espi assessed speech perception and a phonemic verbal fluency task elicited speech production. Logistic mixed model regressions revealed significant differences in accuracy between the bilinguals and the English monolinguals, although some bilinguals performed within the monolingual range. For the production task, but not for the perception task, bilinguals with more exposure to English and greater grammatical knowledge of English performed significantly more accurately than those with less exposure and lower grammatical knowledge. There was no significant correlation between production accuracy and perception accuracy. Through examining phonotactic constraints, these results expand a growing body of research into single sounds which suggests dissociations between L2 perception and production. In contrast to predictions made by L2 speech models, the findings indicate that accurate L2 perception is neither necessary nor sufficient for accurate L2 production, and instead are interpreted to indicate that the two capacities recruit different executive control mechanisms and are acquired – at least to a certain extent – independently in L2 acquisition.Peer Reviewe

Divergent Roles of Salmonella Pathogenicity Island 2 and Metabolic Traits during Interaction of S. enterica Serovar Typhimurium with Host Cells

The molecular mechanisms of virulence of the gastrointestinal pathogen Salmonella enterica are commonly studied using cell culture models of infection. In this work, we performed a direct comparison of the interaction of S. enterica serovar Typhimurium (S. Typhimurium) with the non-polarized epithelial cell line HeLa, the polarized cell lines CaCo2, T84 and MDCK, and macrophage-like RAW264.7 cells. The ability of S. Typhimurium wild-type and previously characterized auxotrophic mutant strains to enter host cells, survive and proliferate within mammalian cells and deploy the Salmonella Pathogenicity Island 2-encoded type III secretion system (SPI2-T3SS) was quantified. We found that the entry of S. Typhimurium into polarized cells was much more efficient than entry into non-polarized cells or phagocytic uptake. While SPI2-T3SS dependent intracellular proliferation was observed in HeLa and RAW cells, the intracellular replication in polarized cells was highly restricted and not affected by defective SPI2-T3SS. The contribution of aromatic amino acid metabolism and purine biosynthesis to intracellular proliferation was distinct in the various cell lines investigated. These observations indicate that the virulence phenotypes of S. Typhimurium are significantly affected by the cell culture model applied

The impact of incident vertebral and non-vertebral fractures on health related quality of life in postmenopausal women

BACKGROUND: Little empirical research has examined the multiple consequences of osteoporosis on quality of life. METHODS: Health related quality of life (HRQL) was examined in relationship to incident fractures in 2009 postmenopausal women 50 years and older who were seen in consultation at our tertiary care, university teaching hospital-affiliated office and who were registered in the Canadian Database of Osteoporosis and Osteopenia (CANDOO) patients. Patients were divided into three study groups according to incident fracture status: vertebral fractures, non-vertebral fractures and no fractures. Baseline assessments of anthropometric data, medical history, therapeutic drug use, and prevalent fracture status were obtained from all participants. The disease-targeted mini-Osteoporosis Quality of Life Questionnaire (mini-OQLQ) was used to measure HRQL. RESULTS: Multiple regression analyses revealed that subjects who had experienced an incident vertebral fracture had lower HRQL difference scores as compared with non-fractured participants in total score (-0.86; 95% confidence intervals (CI): -1.30, -0.43) and the symptoms (-0.76; 95% CI: -1.23, -0.30), physical functioning (-1.12; 95% CI: -1.57, -0.67), emotional functioning (-1.06; 95% CI: -1.44, -0.68), activities of daily living (-1.47; 95% CI: -1.97, -0.96), and leisure (-0.92; 95% CI: -1.37, -0.47) domains of the mini-OQLQ. Patients who experienced an incident non-vertebral fracture had lower HRQL difference scores as compared with non-fractured participants in total score (-0.47; 95% CI: -0.70, -0.25), and the symptoms (-0.25; 95% CI: -0.49, -0.01), physical functioning (-0.39; 95% CI: -0.65, -0.14), emotional functioning (-0.97; 95% CI: -1.20, -0.75) and the activities of daily living (-0.47; 95% CI: -0.73, -0.21) domains. CONCLUSION: Quality of life decreased in patients who sustained incident vertebral and non-vertebral fractures

Optimising care for patients with cognitive impairment and dementia following hip fracture

The global shift in demographics towards aging populations is leading to a commensurate increase in age-related disease and frailty. It is essential to optimise health services to meet current needs and prepare for anticipated future demands. This paper explores issues impacting on people living with cognitive impairment and/or dementia who experience a hip fracture and are cared for in acute settings. This is important given the high mortality and morbidity associated with this population. Given the current insufficiency of clear evidence on optimum rehabilitation of this patient group, this paper explored three key themes namely: recognition of cognitive impairment, response by way of training and education of staff to optimise care for this patient group and review of the importance of outcomes measures. Whilst there is currently insufficient evidence to draw conclusions about the optimal ways of caring for patients living with dementia following hip fracture, this paper concludes that future research should improve understanding of healthcare staff education to improve the outcomes for this important group of patients

Differential Epigenetic Compatibility of qnr Antibiotic Resistance Determinants with the Chromosome of Escherichia coli

Environmental bacteria harbor a plethora of genes that, upon their horizontal transfer to new hosts, may confer resistance to antibiotics, although the number of such determinants actually acquired by pathogenic bacteria is very low. The founder effect, fitness costs and ecological connectivity all influence the chances of resistance transfer being successful. We examined the importance of these bottlenecks using the family of quinolone resistance determinants Qnr. The results indicate the epigenetic compatibility of a determinant with the host genome to be of great importance in the acquisition and spread of resistance. A plasmid carrying the widely distributed QnrA determinant was stable in Escherichia coli, whereas the SmQnr determinant was unstable despite both proteins having very similar tertiary structures. This indicates that the fitness costs associated with the acquisition of antibiotic resistance may not derive from a non-specific metabolic burden, but from the acquired gene causing specific changes in bacterial metabolic and regulatory networks. The observed stabilization of the plasmid encoding SmQnr by chromosomal mutations, including a mutant lacking the global regulator H-NS, reinforces this idea. Since quinolones are synthetic antibiotics, and since the origin of QnrA is the environmental bacterium Shewanella algae, the role of QnrA in this organism is unlikely to be that of conferring resistance. Its evolution toward this may have occurred through mutations or because of an environmental change (exaptation). The present results indicate that the chromosomally encoded Qnr determinants of S. algae can confer quinolone resistance upon their transfer to E. coli without the need of any further mutation. These results suggest that exaptation is important in the evolution of antibiotic resistance

Gene Targeting Implicates Cdc42 GTPase in GPVI and Non-GPVI Mediated Platelet Filopodia Formation, Secretion and Aggregation

Background: Cdc42 and Rac1, members of the Rho family of small GTPases, play critical roles in actin cytoskeleton regulation. We have shown previously that Rac1 is involved in regulation of platelet secretion and aggregation. However, the role of Cdc42 in platelet activation remains controversial. This study was undertaken to better understand the role of Cdc42 in platelet activation. Methodology/Principal Findings: We utilized the Mx-cre;Cdc42 lox/lox inducible mice with transient Cdc42 deletion to investigate the involvement of Cdc42 in platelet function. The Cdc42-deficient mice exhibited a significantly reduced platelet count than the matching Cdc42 +/+ mice. Platelets isolated from Cdc42 2/2, as compared to Cdc42 +/+, mice exhibited (a) diminished phosphorylation of PAK1/2, an effector molecule of Cdc42, (b) inhibition of filopodia formation on immobilized CRP or fibrinogen, (c) inhibition of CRP- or thrombin-induced secretion of ATP and release of P-selectin, (d) inhibition of CRP, collagen or thrombin induced platelet aggregation, and (e) minimal phosphorylation of Akt upon stimulation with CRP or thrombin. The bleeding times were significantly prolonged in Cdc42 2/2 mice compared with Cdc42 +/+ mice. Conclusion/Significance: Our data demonstrate that Cdc42 is required for platelet filopodia formation, secretion an

Extracellular Heat Shock Protein (Hsp)70 and Hsp90α Assist in Matrix Metalloproteinase-2 Activation and Breast Cancer Cell Migration and Invasion

Breast cancer is second only to lung cancer in cancer-related deaths in women, and the majority of these deaths are caused by metastases. Obtaining a better understanding of migration and invasion, two early steps in metastasis, is critical for the development of treatments that inhibit breast cancer metastasis. In a functional proteomic screen for proteins required for invasion, extracellular heat shock protein 90 alpha (Hsp90α) was identified and shown to activate matrix metalloproteinase 2 (MMP-2). The mechanism of MMP-2 activation by Hsp90α is unknown. Intracellular Hsp90α commonly functions with a complex of co-chaperones, leading to our hypothesis that Hsp90α functions similarly outside of the cell. In this study, we show that a complex of co-chaperones outside of breast cancer cells assists Hsp90α mediated activation of MMP-2. We demonstrate that the co-chaperones Hsp70, Hop, Hsp40, and p23 are present outside of breast cancer cells and co-immunoprecipitate with Hsp90α in vitro and in breast cancer conditioned media. These co-chaperones also increase the association of Hsp90α and MMP-2 in vitro. This co-chaperone complex enhances Hsp90α-mediated activation of MMP-2 in vitro, while inhibition of Hsp70 in conditioned media reduces this activation and decreases cancer cell migration and invasion. Together, these findings support a model in which MMP-2 activation by an extracellular co-chaperone complex mediated by Hsp90α increases breast cancer cell migration and invasion. Our studies provide insight into a novel pathway for MMP-2 activation and suggest Hsp70 as an additional extracellular target for anti-metastatic drug development

Internal fixation treatments for intertrochanteric fracture: A systematic review and meta-Analysis of randomized evidence

The relative effects of internal fixation strategies for intertrochanteric fracture after operation remain uncertain. We conducted a systematic review and meta-Analysis of randomized controlled trials (RCTs) to address this important issue. We searched PubMed, EMBASE and CENTRAL for RCTs that compared different internal fixation implants in patients with intertrochanteric fracture at 6-month follow-up or longer. We ultimately included 43 trials enrolling 6911 patients; most trials were small in sample sizes and events. Their risk of bias was generally unclear due to insufficient reporting. Because of these, no statistically significant differences were present from most of the comparisons across all the outcomes, and no definitive conclusions can be made. However, a number of trials compared two commonly used internal fixation strategies, gamma nail (GN) and sliding hip screw (SHS). There is good evidence suggesting that, compared to SHS, GN may increase the risk of cut out (OR = 1.87, 95% CI, 1.08 to 3.21), re-operation (OR = 1.61, 95% CI, 1.02 to 2.53), intra-operative (OR = 3.14, 95% CI, 1.34 to 7.35) and later fractures (OR = 3.67, 95% CI, 1.37 to 9.83). Future randomized trials or observational studies that are carefully designed and conducted are warranted to establish the effects of alternative internal fixation strategies for intertrochanteric fracture

Circadian Rhythm and Cartilage Extracellular Matrix Genes in Osseointegration: A Genome-Wide Screening of Implant Failure by Vitamin D Deficiency

Successful dental and orthopedic implants require the establishment of an intimate association with bone tissue; however, the mechanistic explanation of how biological systems accomplish osseointegration is still incomplete. We sought to identify critical gene networks involved in osseointegration by exploring the implant failure model under vitamin D deficiency.Adult male Sprague-Dawley rats were exposed to control or vitamin D-deficient diet prior to the osteotomy surgery in the femur bone and the placement of T-shaped Ti4Al6V implant. Two weeks after the osteotomy and implant placement, tissue formed at the osteotomy site or in the hollow chamber of T-shaped implant was harvested and total RNA was evaluated by whole genome microarray analyses.Two-way ANOVA of microarray data identified 103 genes that were significantly (>2 fold) modulated by the implant placement and vitamin D deficiency. Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses assigned the highest z-score to the circadian rhythm pathway including neuronal PAS domain 2 (NPAS2), and period homolog 2 (Per2). NPAS2 and Aryl hydrocarbon receptor nuclear translocator-like (ARNTL/Bmal 1) were upregulated around implant and diminished by vitamin D deficiency, whereas the expression pattern of Per2 was complementary. Hierarchical cluster analysis further revealed that NPAS2 was in a group predominantly composed of cartilage extracellular matrix (ECM) genes. Whereas the expression of bone ECM genes around implant was not significantly affected by vitamin D deficiency, cartilage ECM genes were modulated by the presence of the implant and vitamin D status. In a proof-of-concept in vitro study, the expression of cartilage type II and X collagens was found upregulated when mouse mesenchymal stem cells were cultured on implant disk with 1,25D supplementation.This study suggests that the circadian rhythm system and cartilage extracellular matrix may be involved in the establishment of osseointegration under vitamin D regulation

Survival in amoeba: a major selection pressure on the presence of bacterial copper and zinc resistance determinants?: identification of a "copper pathogenicity island"

The presence of metal resistance determinants in bacteria usually is attributed to geological or anthropogenic metal contamination in different environments or associated with the use of antimicrobial metals in human healthcare or in agriculture. While this is certainly true, we hypothesize that protozoan predation and macrophage killing are also responsible for selection of copper/zinc resistance genes in bacteria. In this review, we outline evidence supporting this hypothesis, as well as highlight the correlation between metal resistance and pathogenicity in bacteria. In addition, we introduce and characterize the "copper pathogenicity island" identified in Escherichia coli and Salmonella strains isolated from copper- and zinc-fed Danish pigs