TGFBR1 Intralocus Epistatic Interaction as a Risk Factor for Colorectal Cancer

In colorectal cancer (CRC), an inherited susceptibility risk affects about 35% of patients, whereas high-penetrance germline mutations account for <6% of cases. A considerable proportion of sporadic tumors could be explained by the coinheritance of multiple low-penetrance variants, some of which are common. We assessed the susceptibility to CRC conferred by genetic variants at the TGFBR1 locus. We analyzed 14 polymorphisms and the allele-specific expression (ASE) of TGFBR1 in 1025 individuals from the Spanish population. A case-control study was undertaken with 504 controls and 521 patients with sporadic CRC. Fourteen polymorphisms located at the TGFBR1 locus were genotyped with the iPLEX Gold (MassARRAY-Sequenom) technology. Descriptive analyses of the polymorphisms and haplotypes and association studies were performed with the SNPator workpackage. No relevant associations were detected between individual polymorphisms or haplotypes and the risk of CRC. The TGFBR1*9A/6A polymorphism was used for the ASE analysis. Heterozygous individuals were analyzed for ASE by fragment analysis using cDNA from normal tissue. The relative level of allelic expression was extrapolated from a standard curve. The cutoff value was calculated with Youden's index. ASE was found in 25.4% of patients and 16.4% of controls. Considering both bimodal and continuous types of distribution, no significant differences between the ASE values of patients and controls were identified. Interestingly, a combined analysis of the polymorphisms and ASE for the association with CRC occurrence revealed that ASE-positive individuals carrying one of the most common haplotypes (H2: 20.7%) showed remarkable susceptibility to CRC (RR: 5.25; 95% CI: 2.547–5.250; p<0.001) with a synergy factor of 3.7. In our study, 54.1% of sporadic CRC cases were attributable to the coinheritance of the H2 haplotype and TGFBR1 ASE. These results support the hypothesis that the allelic architecture of cancer genes, rather than individual polymorphisms, more accurately defines the CRC risk

Innovation and entrepreneurship as strategies for success among Cuban-based firms in the late years of the transatlantic slave trade

This article examines how Cuban-based firms and entrepreneurs circumvented ever- increasing risks in the illegal slave trade. The article sheds light to this question by analyzing new qualitative information of 65 Cuban-based firms against the Slavevoyages database. Our findings indicate that Cuban-based firms were entrepreneurial as they exploited the opportunities arising from the volatility of the slave trade by: (a) internalizing networks of agents which allowed the rapid diffusion of information, (b) diversifying trading goods and expanding the number of partnerships to reduce transaction costs and risk, and (c) adopting technological innovations that modified the design and use of vessels

Etude de nanoantennes optiques (application aux diffusions Raman exaltées de surface et par pointe)

L'objectif de cette thèse est l'étude de nanostructures d'or ayant un rapport de forme important (nanofils, pointes ), assimilables à des nanoantennes optiques. Ainsi, j'ai tout d'abord étudié la diffusion Raman exaltée de surface (SERS) de réseaux de nanofils d'or de forme et de taille contrôlées produits par lithographie électronique. Je me suis notamment intéressé à l'influence des plasmons de surface localisés sur l'efficacité SERS de ces nanofils. Nous avons ainsi observé les plasmons de surface d ordre supérieur jusqu'à 7. Nous avons alors relié l'exaltation SERS à la position de la résonance plasmon et déterminé l'efficacité des ordres supérieurs. Nous avons également mis en évidence que le maximum d'exaltation est obtenu pour une résonance plasmon proche de la longueur d'onde de diffusion Raman et ceci pour deux excitations laser différentes. Ensuite, j ai monté une expérience de Raman en champ proche (ou TERS) et développé une technique reproductible de fabrication de pointes en or. Puis, j ai effectué une étude quantitative des propriétés de dépolarisation des pointes métalliques utilisées en a-SNOM et en TERS. Nos résultats montrent des facteurs de dépolarisation entre 5 et 30% qui varient en fonction de la polarisation de la lumière incidente et de la forme de la pointe. Les conséquences importantes de ce phénomène de dépolarisation ont été mises en évidence dans des expériences TERS sur du Silicium cristallin; On montre que la dépolarisation doit être prise en compte pour une estimation correcte de l'exaltation induite par la pointeDuring my thesis, various subjects of research were tackled. I started by making nanofabrication of Raman active surface for enhancement -SERS- (gold nanowires arrays) by e-beam lithography. Then, I carried out a study about SERS efficiency according to the position of plasmon resonance (controlled by nanowires dimensions) for various wavelengths in the visible range. All the studies give a similar conclusion: to obtain a Raman enhanced maximum, the plasmon resonance have to be closed to the Raman wavelength. For the second part of my PhD thesis, I have worked on gold nano-tips fabrication and the implementation of a tip-enhanced Raman scattering set-up (TERS). Thus, I have developed a new process, based on an electrochemical at-tack, to produce reproducible gold tips for apertureless scanning near-field microscopy (SNOM) and TERS experiments. I have done a study about the depolarization properties of gold nano-tips. Our results show depolarization factor between 5 and 30 % that depends on the shape, the roughness and the material of the tip used and the excitation polarization state. Important consequences of this depolarization effect were underline in TERS experiments on Silicon crystal. It was bringing to light the importance to consider weight of the depolarization factor in the enhancement Raman during polarization TERS experimentsTROYES-SCD-UTT (103872102) / SudocSudocFranceF

Evaluation of a combined glycomics and glycoproteomics approach for studying the major glycoproteins present in biofluids: Application to cerebrospinal fluid

International audienceRationale Glycosylation is one of the most complex types of post‐translational modifications of proteins. The alteration of glycans bound to proteins from cerebrospinal fluid (CSF) in relation to disorders of the central nervous system is a highly relevant subject, but only few studies have focused on the glycosylation of CSF proteins. Methods Reproducible profiles of CSF N‐glycans were first obtained by matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry after permethylation. Tryptic glycopeptides from CSF proteins were also enriched by hydrophilic interaction, and the resulting extracts divided into two equal aliquots. A first aliquot was enzymatically deglycosylated and analyzed by nano‐liquid chromatography/tandem mass spectrometry while the second one, containing intact enriched glycopeptides, was directly analyzed. Site‐specific data were obtained by combining the data from these three experiments. Results We describe the development of a versatile approach for obtaining site‐specific information on the N‐glycosylation of CSF glycoproteins. Under these conditions, 124 N‐glycopeptides representing 55 N‐glycosites from 36 glycoproteins were tentatively identified. Special emphasis was placed on the analysis of glycoproteins/glycopeptides bearing 'brain‐type' N‐glycans, representing potential biologically relevant structures in the field of neurodegenerative disorders. Using our workflow, only a few proteins were shown to carry such particular glycan motifs. Conclusions We developed an approach combining N‐glycomics and N‐glycoproteomics and underline its usefulness to study the site‐specific glycosylation of major human CSF proteins. The final rather long‐term objective is to combine these data with those from other omics approaches to delve deeper into the understanding of particular neurological disorders. Copyright © 2015 John Wiley & Sons, Ltd

Fast and reliable fabrication of gold tips with sub-50 nm radius of curvature for tip-enhanced Raman spectroscopy

International audienceWe have developed a new electrochemical etching procedure to fabricate gold tips with sub-50 nmapical radius of curvature with a production yield of 80% and production time lower than 5 min.The technique is based on a two-step self-terminating process in which a gold wire is first quickly(<1 min) pre-etched in an hydrochloric acid (HCl)/ethanol solution at high voltage (10 VDC), and thenslowly (2–4 min) etched at lower voltages (<2.5 VDC). The first step occurs under intense bubblingconditions and allows us to thin rapidly the wire. This reduces the time required by subsequent lowvoltageprocess during which the tips are formed at the liquid/air interface. A statistical analysis ofthe surface morphology has been carried out on a set of 60 tips by scanning electron microscopy. Theresults show that the surface roughness and the sharpness of the final tip are critically influenced bythe intrinsic granularity of the gold wires. Moreover, there is a correlation between the tip qualityand the time elapse required to complete the low-voltage etching step. Tips featuring smooth surfacesand radii of curvature <50 nm are produced whenever the etching times are lower than 250 s, whileetching times larger than 300 s typically yield rough, blunt tips. Such a correlation can be used asa screening criterion to select sharp tips during production with an 80% yield. The high quality ofthe gold tips produced with such method is confirmed by the electromagnetic field enhancementmeasured both in tip-enhanced Raman scattering and surface-enhanced Raman scattering on the tipapex experiments

Light depolarization induced by metallic tips in apertureless near-field optical microscopy and tip-enhanced raman spectroscopy

1 - ArticleWe have investigated the depolarization effects of light scattered by sharp tips used for apertureless near-field optical microscopy. Dielectric and metal coated tips have been investigated and depolarization factors between 5 and 30% have been measured, changing as a function of the incident light polarization and of the tip shape. The experimental results are in good agreement with theoretical calculations performed by the finite element method, giving a near-field depolarization factor close to 10%. The effect of depolarization has been investigated in polarized tip-enhanced Raman spectroscopy (TERS) experiments; the depolarization gives rise to forbidden Raman modes in Si crystals

Resonances of individual lithographic gold nanowires in the infrared

1 - ArticleWith infrared spectroscopic microscopy using synchrotron radiation, we systematically studied resonant light scattering from electron-beam lithographically produced gold nanowires (nanostripes) with diameters in the 100 nm range and with various lengths below 1 to about 2.5 mu m. Similar to electrochemically grown cylindrical wires of high crystalline quality, clear antennalike plasmon resonances were observed for these stripelike and less-perfect wires. The resonance wavelength shifts with length as theoretically predicted for cylindrical gold antennas in the optical range. Surprisingly, also the extinction cross section of the nanostripes is equal to that measured for highly crystalline cylinders