Genetic Predisposition to the Mortality in Septic Shock Patients: From GWAS to the Identification of a Regulatory Variant Modulating the Activity of a CISH Enhancer

The high mortality rate in septic shock patients is likely due to environmental and genetic factors, which influence the host response to infection. Two genome-wide association studies (GWAS) on 832 septic shock patients were performed. We used integrative bioinformatic approaches to annotate and prioritize the sepsis-associated single nucleotide polymorphisms (SNPs). An association of 139 SNPs with death based on a false discovery rate of 5% was detected. The most significant SNPs were within the CISH gene involved in cytokine regulation. Among the 139 SNPs associated with death and the 1311 SNPs in strong linkage disequilibrium with them, we investigated 1439 SNPs within non-coding regions to identify regulatory variants. The highest integrative weighted score (IW-score) was obtained for rs143356980, indicating that this SNP is a robust regulatory candidate. The rs143356980 region is located in a non-coding region close to the CISH gene. A CRISPR-Cas9-mediated deletion of this region and specific luciferase assays in K562 cells showed that rs143356980 modulates the enhancer activity in K562 cells. These analyses allowed us to identify several genes associated with death in patients with septic shock. They suggest that genetic variations in key genes, such as CISH, perturb relevant pathways, increasing the risk of death in sepsis patients.     

Toward a wire medium endoscope for MRI imaging

This paper shows, numerically and experimentally, that imaging is realizable with a strongly curved wire medium. In a first part, simulation results obtained for various curvatures are presented and sub-wavelength imaging on a wide bandwidth is demonstrated. It is also shown that the collimation phenomenon remains very effective for structures having a cross-section corresponding to about a hundredth of the wavelength. In a second part, experimental results are shown for transmission of a medical image through a 63° curved wire medium in which the receiving antenna has been inserted.     

Glycation of bovine β-Lactoglobulin: effect on the protein structure

Summary Since temperature and water activity are among the most important parameters that affect the Maillard reaction, the glycation sites in pure, native bovine β-lactoglobulin were determined after a mild heat treatment (60 °C) in an aqueous solution and after a treatment under a restricted water environment (50 °C, 65% relative humidity). In both systems, the results obtained underlined the structural heterogeneity of β-lactoglobulin (β-LG) glycoforms with respect to the number of lactose residues linked per protein molecule and to the binding sites involved. Subsequently, the effect of the glycation conditions on both the association behaviour and the conformational changes of the glycated β-LG were characterised by proteolytic susceptibility, binding of the fluorescent probe 8-anilino-1-naphtalene-sulfonic acid, SDS-PAGE and size exclusion chromatography. The results showed that dry-way glycation did not significantly alter the native-like behaviour of the protein while the treatment in solution led to important structural changes. These changes resulted in a specific denatured β-LG monomer, which covalently associated via the free thiol group. The homodimers thus formed and the expanded monomers underwent subsequent aggregation to form high molecular weight species, via non–covalent interactions. The use of monoclonal antibodies with defined epitopes, raised against native β-LG, confirmed that the protein conformation was much more modified when glycation was performed in a solution while the structural changes induced during dry-way treatment were limited to the AB loop region of the protein.     

Analysis of arabic gum: Study of degradation and water desorption processes

Arabic gum is very much used in the agroalimentary industry, mainly as an emulsifier. It is a natural origin polysaccharide and therefore subject to more or less important variabilities of its properties. This work deals with two similar polysaccharides exuded by Acacia senegal of different history and an Acacia seyal sample. To characterize these samples, wide angle X-ray scattering (WAXS) and thermogravimetric analysis in dynamic and isothermal mode are used.The initial structure checked by X-ray diffraction allows to affirm that samples are equivalent in their crystalline structure. The activation energy used to characterize the main degradation process is the same for A. senegal samples, but higher for the A. seyal gum sample. Differences are furthermore observed for the kinetics of water desorption. We conclude that the samples from the same type of gum (A. senegal) are very similar and that A. seyal exudates can be detected by this technique. The water desorption of the two exudates is different.     

Kinetic modeling of an unsaturated polyester resin using two complementary techniques: Near infrared spectroscopy and heat flux sensors

This article concerns the characterization of the polymerization kinetics of an unsaturated polyester resin containing a large excess of styrene. For this type of resin, DSC measurements happen to not be satisfactory. Two complementary techniques were then used: an in situ near infrared spectroscopy and a PVT mold equipped with heat flux sensors. This article describes these two experimental devices and the methods used to obtain the experimental data. By monitoring the evolutions of unsaturated polyester and styrene conversions with near infrared spectroscopy, it was possible to identify two different chemical mechanisms occurring during the resin cure responsible for the measured two‐peaks thermograms. Their relative importance was quantified. A kinetic model representative of these two coupled reactions was established and its parameters evaluated from the thermal analysis. This model was able to predict the kinetic behavior of the resin outside of the domain of study, even at high temperature, where the second peak of the thermogram vanishes while the final conversion decreases. This model was also able to simulate the resin cure during experiments with an imposed heating rate. POLYM. ENG. SCI. 45:846–856, 2005. © 2005 Society of Plastics Engineers     

A Novel Cross‐linked Poly(vinyl alcohol) (PVA) for Vascular Grafts

Poly(vinyl alcohol) (PVA) is a water‐soluble synthetic polymer with excellent film‐forming, emulsifying, and adhesive properties. The aim of this study is to design a simple process for PVA cross‐linking with sodium trimetaphosphate to form membrane devices suitable for biomedical applications. This procedure requires no organic solvent, nor melting process to obtain films with high mechanical strength. Fabrication of a small diameter tube from a PVA film is easy with a single wrapping step around a Teflon rod. Dynamic mechanical analysis demonstrated that, upon removal of the applied stress, the PVA film with a Young's modulus of 2 × 10⁵ kPa returns to its original size and shape. The wall thickness of PVA tubes is 344 ± 13 µm (n = 12), which is close to the wall thickness of a human artery (350–710 µm). Suture retention of a PVA tube is excellent (140 ± 11 g), close to that of human vessels. The burst pressure of PVA tubes is found to be 507 ± 25 mm Hg, more than three times higher than the human healthy systolic arterial pressure. Under arterial pressure, there was no leakage even after needle puncture, contrary to clinical vascular expanded polytetrafluoroethylene prostheses. Finally, PVA tubes of 2 mm in diameter are used to replace a segment of an infrarenal aorta in rats. For at least one week, no mechanical nor thrombotic complications are noticed even in the absence of anticoagulant or antiplatelet treatment. Graft patency is also evidenced with non‐invasive imaging techniques. As a conclusion, this novel cross‐linking method confers to poly(vinyl alcohol) particular mechanical properties such as compliance, elasticity and resistance to mechanical stress, compatible with the circulatory blood flow.