Large-scale gene-centric analysis identifies novel variants for coronary artery disease

Coronary artery disease (CAD) has a significant genetic contribution that is incompletely characterized. To complement genome-wide association (GWA) studies, we conducted a large and systematic candidate gene study of CAD susceptibility, including analysis of many uncommon and functional variants. We examined 49,094 genetic variants in ∼2,100 genes of cardiovascular relevance, using a customised gene array in 15,596 CAD cases and 34,992 controls (11,202 cases and 30,733 controls of European descent; 4,394 cases and 4,259 controls of South Asian origin). We attempted to replicate putative novel associations in an additional 17,121 CAD cases and 40,473 controls. Potential mechanisms through which the novel variants could affect CAD risk were explored through association tests with vascular risk factors and gene expression. We confirmed associations of several previously known CAD susceptibility loci (eg, 9p21.3:p<10−33; LPA:p<10−19; 1p13.3:p<10−17) as well as three recently discovered loci (COL4A1/COL4A2, ZC3HC1, CYP17A1:p<5×10−7). However, we found essentially null results for most previously suggested CAD candidate genes. In our replication study of 24 promising common variants, we identified novel associations of variants in or near LIPA, IL5, TRIB1, and ABCG5/ABCG8, with per-allele odds ratios for CAD risk with each of the novel variants ranging from 1.06–1.09. Associations with variants at LIPA, TRIB1, and ABCG5/ABCG8 were supported by gene expression data or effects on lipid levels. Apart from the previously reported variants in LPA, none of the other ∼4,500 low frequency and functional variants showed a strong effect. Associations in South Asians did not differ appreciably from those in Europeans, except for 9p21.3 (per-allele odds ratio: 1.14 versus 1.27 respectively; P for heterogeneity = 0.003). This large-scale gene-centric analysis has identified several novel genes for CAD that relate to diverse biochemical and cellular functions and clarified the literature with regard to many previously suggested genes

Beyond Co-optation: Revisiting the Transformative Function of "Workers’ Self-Directed Enterprises"

This is the author accepted manuscript. The final version is available from Taylor & Francis (Routledge) via the DOI in this record.No abstrac

Implications of C1q/TNF-related protein superfamily in patients with coronary artery disease.

The C1q complement/TNF-related protein superfamily (CTRPs) displays differential effects on the regulation of metabolic homeostasis, governing cardiovascular function. However, whether and how they may serve as predictor/pro-diagnosis factors for assessing the risks of coronary artery disease (CAD) remains controversial. Therefore, we performed a clinical study to elaborate on the implication of CTRPs (CTRP1, CTRP5, CTRP7, and CTRP15) in CAD. CTRP1 were significantly increased, whereas CTRP7 and CTRP15 levels were decreased in CAD patients compared to the non-CAD group. Significant differences in CTRP1 levels were discovered between the single- and triple-vascular-vessel lesion groups. ROC analysis revealed that CTRP7 and CTRP15 may serve as CAD markers, while CTRP1 may serve as a marker for the single-vessel lesion of CAD. CTRP1 and CTRP5 can serve as markers for the triple-vessel lesion. CTRP1 may serve as an independent risk predictor for triple-vessel lesion, whereas CTRP15 alteration may serve for a single-vessel lesion of CAD. CTRP1 may serve as a novel superior biomarker for diagnosis of severity of vessel-lesion of CAD patients. CTRP7, CTRP15 may serve as more suitable biomarker for the diagnosis of CAD patients, whereas CTRP5 may serve as an independent predictor for CAD. These findings suggest CTRPs may be the superior predictive factors for the vascular lesion of CAD and represent novel therapeutic targets against CAD

T-cadherin deficiency increases vascular vulnerability in T2DM through impaired NO bioactivity.

BACKGROUND: Endothelial dysfunction plays a critical role in the development of type 2 diabetes (T2DM). T-cadherin (T-cad) has gained recognition as a regulator of endothelial cell (EC) function. The present study examined whether T-cad deficiency increases vascular vulnerability in T2DM. METHODS: Vascular segments were isolated from WT or T-cad knockout mice. Endothelial function, total NO accumulation, and the expression of T-cad related proteins were determined. RESULTS: Ach and acidified NaNO2 induced similar vasorelaxation in WT groups. T-cad KO mice exhibited normal response to acidified NaNO2, but manifested markedly reduced response to Ach. NO accumulation was also decreased in T-cad KO group. T-cad expression was reduced in WT mice fed 8 weeks of high fat diet (HFD). Furthermore, exacerbated reduction of vasorelaxation was observed in T-cad KO mice fed 8 weeks of HFD. CONCLUSIONS: In the current study, we provide the first in vivo evidence that T-cadherin deficiency causes endothelial dysfunction in T2DM vascular segments, suggesting the involvement of T-cad deficiency in T2DM pathogenesis

The Teaching of Visual Literacy in Initial English Language Teacher Education

The pressure on teacher education to prepare student teachers to bridge the gap between the traditional literacy and multiliteracies/multimodality has intensified in the last years. Student teachers need to acquire richer and more complex learning experiences, they need to be aware that language is not the only or, sometimes, the predominant mode of communication (Early, Kendrick & Potts, 2015). Thus, this study attempts to integrate the teaching of visual literacy within an Initial English Language Teacher Education (IELTE) programme to help expand student teachers communicative potential in the foreign language classroom. Currently, student teachers ́ literacy instruction favors the interpretation of the verbal mode; however, to promote literacy skills in this century, literacy programmes should promote the reading and the understanding of meaning making signs of both the verbal and visual mode and their relationship with the structural components of a narrative text (Painter, 2012). In the Argentinian context, there are studies that explore the teaching of visual literacy to student teachers ́ but none of the works focuses on the teaching of visual literacy within an IELTE programme. This study will explore how the explicit teaching of visual literacy can enhance student-teachers ́ communication skills in the second language. This case study involves twelve student teachers from the third year of an IELTE programme, a teacher observer and the researcher herself. To triangulate data, different data collecting tools were employed: a) pretest and posttest; b) classroom observation; c) document analysis, and d) interviews to students. The analysis of the data was of an interpretative nature supported by statistical data. Research findings, pedagogical implications and suggestions for further research are presented in the last chapters.Fil: Cad, Ana Cecilia. Universidad Nacional de Córdoba. Facultad de Lenguas; Argentina

Inter-observer agreement of the Coronary Artery Disease Reporting and Data System (CAD-RADS^{TM}) in patients with stable chest pain

Purpose: To assess inter-observer variability of the Coronary Artery Disease - Reporting and Data System (CAD-RADS) for classifying the degree of coronary artery stenosis in patients with stable chest pain. Material and methods: A prospective study was conducted upon 96 patients with coronary artery disease, who underwent coronary computed tomography angiography (CTA). The images were classified using the CAD-RAD system according to the degree of stenosis, the presence of a modifier: graft (G), stent (S), vulnerable plaque (V), or non-diagnostic (n) and the associated coronary anomalies, and non-coronary cardiac and extra-cardiac findings. Image analysis was performed by two reviewers. Inter-observer agreement was assessed. Results: There was excellent inter-observer agreement for CAD-RADS (k = 0.862), at 88.5%. There was excellent agreement for CAD-RADS 0 (k = 1.0), CAD-RADS 1 (k = 0.92), CAD-RADS 3 (k = 0.808), CAD-RADS 4 (k = 0.826), and CAD-RADS 5 (k = 0.833) and good agreement for CAD-RADS 2 (k = 0.76). There was excellent agreement for modifier G (k = 1.0) and modifier S (k = 1.0), good agreement for modifier N (k = 0.79), and moderate agreement for modifier V (k = 0.59). There was excellent agreement for associated coronary artery anomalies (k = 0.845), non-coronary cardiac findings (k = 0.857), and extra-cardiac findings (k = 0.81). Conclusions: There is inter-observer agreement of CAD-RADS in categorising the degree of coronary arteries stenosis, and the modifier of the system and associated cardiac and extra-cardiac findings

Data transfer between Cad system and RP system: a report

Rapid Prototyping (RP) is a technology that transform a design generated in Computer Aided Design (CAD) to a 3D model parts. CAD models are usually done on a CAD system and then transported into the RP system. A good interface between the CAD and the RP system is one of the key factors of producing a good quality prototype. This paper reports on the results of an experimentation carried out to identify the problems in transferring data between a CAD system (UNIGRAPHICS) and an RP system (QUICKSLICE). Based on the experimentation’s results and analysis, a basic guideline is proposed for a safer data transfer between the CAD system (UNIGRAPHICS) and an RP system (QUICKSLICE)

Caldesmon regulates actin dynamics to influence cranial neural crest migration in Xenopus

Caldesmon (CaD) is an important actin modulator that associates with actin filaments to regulate cell morphology and motility. Although extensively studied in cultured cells, there is little functional information regarding the role of CaD in migrating cells in vivo. Here we show that nonmuscle CaD is highly expressed in both premigratory and migrating cranial neural crest cells of Xenopus embryos. Depletion of CaD with antisense morpholino oligonucleotides causes cranial neural crest cells to migrate a significantly shorter distance, prevents their segregation into distinct migratory streams, and later results in severe defects in cartilage formation. Demonstrating specificity, these effects are rescued by adding back exogenous CaD. Interestingly, CaD proteins with mutations in the Ca^(2+)-calmodulin–binding sites or ErK/Cdk1 phosphorylation sites fail to rescue the knockdown phenotypes, whereas mutation of the PAK phosphorylation site is able to rescue them. Analysis of neural crest explants reveals that CaD is required for the dynamic arrangements of actin and, thus, for cell shape changes and process formation. Taken together, these results suggest that the actin-modulating activity of CaD may underlie its critical function and is regulated by distinct signaling pathways during normal neural crest migration