Can L2 sentence processing strategies be native-like? Evidence from English speakers’ L2 processing of Chinese base-generated-topic sentences

This article reports on an empirical study examining English speakers’ L2 processing of Chinese base-generated-topic (BGT) sentences. Forty-four highly proficient English-speaking L2 learners of Chinese and 23 native Chinese speakers were involved in the study. Results of a self-paced reading task reveal that both native Chinese speakers’ and L2 Chinese learners’ processing of Chinese BGT sentences is syntactically induced in a top-down manner. English speakers are sensitive to and are able to make use of syntactic cues as well as semantic information in their processing of Chinese BGT sentences. The study provides disconfirming evidence against the Shallow Structure Hypothesis (Clahsen and Felser, 2006a,b), which predicts that unlike native speakers, L2 learners do not rely on structure-based processing strategies when solving ambiguities in L2 sentence processing

Asthma susceptibility variants are more strongly associated with clinically similar subgroups

<p><i>Objective</i>: Genome-wide association studies (GWAS) identified single nucleotide polymorphisms (SNPs) reproducibly associated with asthma. This study evaluated whether GWAS-nominated SNPs are more strongly associated with asthma patients sharing the same clinical characteristics in order to refine the role of recently identified genes. <i>Methods</i>: Analyses were performed in unrelated French Canadian subjects (566 cases and 416 controls) with data collected on lung function, blood cell counts, atopy, disease history and medication. Previously defined asthma subgroups were used for analysis: 1) older patients with low atopy and low lung function, 2) high atopy, 3) young non-smoking women and 4) high smoking history. Allele frequencies of 68 GWAS-nominated SNPs were compared between controls and cases or controls and subgroups of cases defined by cluster analysis. <i>Results</i>: Twelve GWAS-nominated SNPs demonstrated evidence of replication (<i>p</i> value < 0.05) for association with asthma. In phenotypically similar asthma patients, rs10197862, located in <i>IL1RL1/IL18R1</i>, was the most strongly associated SNP with the high atopy subgroup (<i>p</i> = 0.0009). SNPs located at the <i>IL33</i> and the <i>STARD3</i>/<i>PGAP3</i> loci were also associated with the high atopy subgroup. Two SNPs, rs1544791 (<i>PDE4D</i>) and rs3806932 (<i>TSLP</i>), were more strongly associated with the high smoking history subgroup than with asthma or any other subgroups. All 10 SNPs that replicated for asthma <i>per se</i> and within subgroups had lower <i>p</i> values in subgroups. Moreover, 12 SNPs were only replicated in a subgroup. <i>Conclusion</i>: This study shows that the majority of GWAS-nominated SNPs are more strongly associated with homogeneous subgroups of asthma than broadly defined asthma.</p

Intraindividual variability in serum alpha-1 antitrypsin levels

Background: Measuring alpha-1 antitrypsin (AAT) serum levels is often the first step when investigating for alpha-1 antitrypsin deficiency (AATD). The purpose of this study was to determine the test-retest reproducibility of AAT serum levels and to determine if between-measurements variability was associated with acute phase markers of inflammation. Methods: We retrospectively analyzed a sample of 255 patients from a community respirology practice with chronic obstructive pulmonary disease (COPD) in whom AAT serum levels were measured twice, on separate visits. White blood cell count and fibrinogen were also measured at the time of the second blood sampling as markers of acute phase inflammation. Intraclass correlation coefficient (ICC), Pearson correlation coefficient, and Bland-Altman analysis were used to document test-retest reproducibility. Regression analyses were used to identify potential correlates of test-retest AAT level differences. Results: Although the 2 AAT serum levels were significantly correlated, the between-measurement agreement was weak (ICC of 0.38 [95% confidence interval (CI), 0.27 to 0.48]; Pearson correlation coefficient of 0.34 [95% CI, 0.23 to 0.44]) and Bland-Altman analysis revealed wide 95% limits of agreement. Considering that an AAT serum level below 1.13g/L should trigger further investigations to confirm the AAT status, discrepancies between the test-retest AAT levels resulted in reconsidering requirement for further investigation in 22% of patients. A significant correlation between the fibrinogen value and the second AAT level was found (r=0.21, p=0.004 [n=173]). Conclusions: Serum AAT levels showed weak intra-individual reproducibility which could lead to AATD status misclassification and potentially a missed diagnosis of AATD.</p

Expression of SCL20A1 in human calcific aortic valve disease.

<p><b>A</b>. In human calcific aortic valve disease (CAVD) tissues, expression of SLC20A1 was increased, both in tricuspid and bicuspid aortic valves, when compared to control non-mineralized aortic valves. <b>B, C and D</b>. Immunostaining for SLC20A1 revealed faint expression in control aortic valves (B), whereas in CAVD tissues we observed a strong immunostaining in areas of tissue remodelling in the vicinity of calcific nodules (C) (100×) (in panel D magnification 200× of inset in C). * p<0.005 compared to control (Ctn).</p

Pi transporters in human valve interstitial cells (VICs).

<p><b>A</b>. In isolated VICs, only transcripts of SLC20A1 and SL20A2 were expressed. <b>B.</b> Following exposure to Pi, VICs have increased expression of SLC20A1 and SLC20A2 transcripts by several folds, with the highest magnitude for SLC20A1 (results expressed in function of SLC20A2 as the referent) (SLC20A1 increased by 5.3-folds when compared to SLC20A2) <b>C</b>. Treatment with PFA, a Pi transporter inhibitor, blocked the rise of SLC20A1 and SLC20A2 transcripts induced by the mineralizing medium (Pi). <b>D</b>. PFA prevented the mineralization of VIC cultures induced by Pi. <b>E</b>. PFA prevented the Pi-induced rise of osteopontin, osteonectin, osteocalcin, Runx2 and alkaline phosphatase transcripts. <b>F and G</b>. In isolated VICs, siRNA-mediated knockdown of SLC20A1 (F) resulted in a decreased Pi-induced mineralization (G). When compared with the knockdown of SLC20A2, the siRNA against SLC20A1 provided a greater reduction of mineralization of VIC cultures (G). (For in vitro experiments n = 3); PFA: Phosphonoformic acid; * p<0.0001 compared to negative control (Ctn); # p<0.005 compared to mineralizing medium (PO₄).</p

Pi induces apoptosis of valve interstitial cells through the mitochondrial pathway.

<p><b>A</b>. The percentage of apoptotic cells, measured by TUNEL assay, increased significantly during VIC mineralization, whereas treatment with PFA blocked this response. <b>B</b>. The mitochondrial membrane potential (ΔΨm) decreased following treatment with Pi, but addition of PFA protected the ΔΨm. <b>C.</b> Epifluorescence images of VICs with the MitoPT TRME fluorescent dye in different conditions. In control cells, the mitochondrial uptake of MitoPT TRME gives a clear and distinct fluorescent pattern, indicating a normal ΔΨm. Following treatment with Pi, however, the fluorescent pattern is diffuse and accompanied by an abnormal mitochondrial morphology indicating a loss in the ΔΨm. The addition of PFA prevented Pi-mediated loss in the ΔΨm. <b>D.</b> This protection with PFA was also confirmed with an immunofluorescence assay measuring cytochrome <i>c</i> release in VICs under mineralizing condition. <b>E</b>. Cyclosporin A which is an inhibitor of MTP, prevented Pi-mediated apoptosis of VIC cultures as detected with TUNEL assay. <b>F.</b> The effect of cyclosporine A on Pi-mediated apoptosis was confirmed by the APOPercentage assay, which relies on changes in membrane asymmetry during apoptosis. <b>G</b>. Cyclosporin A prevented Pi-induced mineralization of VIC cultures. (For in vitro experiments n = 3); PFA: Phosphonoformic acid; MTP: mitochondrial permeability transition pore; * p<0.0001 compared to negative control (Ctn); # p<0.0001 compared to mineralizing medium (PO₄).</p

Akt-1 a regulator of Pi-induced mineralization.

<p>Transfection of VICs with a pCMVAkt-1 resulted in higher expression of Akt-1 transcripts. <b>B</b>. The transfection of Akt-1 (pCMVAkt-1) prevented Pi-induced apoptosis of VICs (measured with the TUNEL assay). <b>C</b>. Transfection of Akt-1 reduced significantly Pi-induced mineralization of VIC cultures. <b>D.</b> Inhibition of PI3K, a kinase acting upstream of Akt, with Ly294002 increased mineralization of VIC cultures by several-folds. <b>E and F.</b> Similarly, the knockdown of Akt-1 (F) resulted in higher mineralization of VIC cultures (E). (For in vitro experiments n = 3); pCMV empty is the control (ctn) in panels A–C * p<0.0001 compared to negative control (Ctn); # p<0.0001 compared to mineralizing medium (PO₄).</p

Clinical characteristics of patients used for SLC20A1 and Akt-1 quantitative real-time PCR analysis.

<p>CAVD: calcific aortic valve disease; BMI: body mass index; LDL: Low-density lipoprotein; HDL: High-density lipoprotein; TG: Triglycerides; BAV: Bicuspid Aortic Valves.</p

Pi-mediated regulation of Akt levels.

<p><b>A.</b> In isolated VICs Akt-1 and Akt-2 were expressed. <b>B</b>. The levels of Akt-1 transcript were reduced significantly in CAVD tissues (n = 50) when compared to control non-mineralized aortic valves (n = 28). <b>C and D.</b> In isolated VICs, the levels of Akt-1 transcript were lowered following exposure to Pi, whereas PFA (C) and siRNA targeting SLC20A1 (D) prevented this response. <b>E and F</b>. Both Akt (E) and pAkt (F) protein levels were reduced by Pi treatment of VICs, whereas in the presence of PFA, levels were maintained. (For in vitro experiments n = 3); PFA: Phosphonoformic acid; CAVD: Calcific Aortic Valve Disease; * p<0.0001 compared to negative control (Ctn); # p<0.005 compared to mineralizing medium (PO₄).</p

Influences of Gestational Obesity on Associations between Genotypes and Gene Expression Levels in Offspring following Maternal Gastrointestinal Bypass Surgery for Obesity

<div><p>Maternal obesity and excess gestational weight gain with compromised metabolic fitness predispose offspring to lifelong obesity and its comorbidities. We demonstrated that compared to offspring born before maternal gastrointestinal bypass surgery (BMS) those born after (AMS) were less obese, with less cardiometabolic risk reflected in the expression and methylation of diabetes, immune and inflammatory pathway genes. Here we examine relationships between gestational obesity and offspring gene variations on expression levels.</p><p>Methods</p><p>Whole-genome genotyping and gene expression analyses in blood of 22 BMS and 23 AMS offspring from 19 mothers were conducted using Illumina HumanOmni-5-Quad and HumanHT-12 v4 Expression BeadChips, respectively. Using PLINK we analyzed interactions between offspring gene variations and maternal surgical status on offspring gene expression levels. Altered biological functions and pathways were identified and visualized using DAVID and Ingenuity Pathway Analysis.</p><p>Results</p><p>Significant interactions (p ≤ 1.22x10^-12) were found for 525 among the 16,060 expressed transcripts: 1.9% of tested SNPs were involved. Gene function and pathway analysis demonstrated enrichment of transcription and of cellular metabolism functions and overrepresentation of cellular stress and signaling, immune response, inflammation, growth, proliferation and development pathways.</p><p>Conclusion</p><p>We suggest that impaired maternal gestational metabolic fitness interacts with offspring gene variations modulating gene expression levels, providing potential mechanisms explaining improved cardiometabolic risk profiles of AMS offspring related to ameliorated maternal lipid and carbohydrate metabolism.</p></div