High-Mannose N-Glycans as Malignant Progression Markers in Early-Stage Colorectal Cancer

Simple Summary The detection of colorectal cancer (CRC) at an early stage is increasing due to the implementation of screening programs. Local excision of early CRC is potentially curative, however the identification of early lesions at high risk of regional metastases remains challenging, and greatly influencing therapy decision making. Variations in sugar molecules has been associated with development and progression in various cancer types including CRC. Therefore, we examined these sugar signatures, so-called N-glycans, in different stages of progression of CRC starting from epithelium to pre-cancerous and cancerous tissue. We report that the sugar signatures clearly differentiate each step of CRC progression, especially between pre-cancerous and cancerous tissue. We also observed some of the glycosylation signatures of the cancerous areas to be spreading into the tumor microenvironment. The increase incidence of early colorectal cancer (T1 CRC) last years is mainly due to the introduction of population-based screening for CRC. T1 CRC staging based on histological criteria remains challenging and there is high variability among pathologists in the scoring of these criteria. It is crucial to unravel the biology behind the progression of adenoma into T1 CRC. Glycomic studies have reported extensively on alterations of the N-glycomic pattern in CRC; therefore, investigating these alterations may reveal new insights into the development of T1 CRC. We used matrix-assisted laser desorption ionization (MALDI) mass spectrometry imaging (MSI) to spatially profile the N-glycan species in a cohort of pT1 CRC using archival formalin-fixed and paraffin-embedded (FFPE) material. To generate structural information on the observed N-glycans, CE-ESI-MS/MS was used in conjunction with MALDI-MSI. Relative intensities and glycosylation traits were calculated based on a panel of 58 N-glycans. Our analysis showed pronounced differences between normal epithelium, dysplastic, and carcinoma regions. High-mannose-type N-glycans were higher in the dysplastic region than in carcinoma, which correlates to increased proliferation of the cells. We observed changes in the cancer invasive front, including higher expression of alpha 2,3-linked sialic acids which followed the glycosylation pattern of the carcinoma region.Cellular mechanisms in basic and clinical gastroenterology and hepatolog

N-glycomic signature of stage II colorectal cancer and its association with the tumor microenvironment

The choice for adjuvant chemotherapy in stage II colorectal cancer is controversial as many patients are cured by surgery alone and it is difficult to identify patients with high risk of recurrence of the disease. There is a need for better stratification of this group of patients. Mass spectrometry imaging could identify patients at risk. We report here the N-glycosylation signatures of the different cell populations in a group of stage II colorectal cancer tissue samples. The cancer cells, compared with normal epithelial cells, have increased levels of sialylation and high-mannose glycans, as well as decreased levels of fucosylation and highly branched N-glycans. When looking at the interface between cancer and its microenvironment, it seems that the cancer N-glycosylation signature spreads into the surrounding stroma at the invasive front of the tumor. This finding was more outspoken in patients with a worse outcome within this sample group.Surgical oncolog

Non-linear model reduction for the Navier–Stokes equations using residual DEIM method

This article presents a new reduced order model based upon proper orthogonal decomposition (POD) for solving the Navier–Stokes equations. The novelty of the method lies in its treatment of the equation's non-linear operator, for which a new method is proposed that provides accurate simulations within an efficient framework. The method itself is a hybrid of two existing approaches, namely the quadratic expansion method and the Discrete Empirical Interpolation Method (DEIM), that have already been developed to treat non-linear operators within reduced order models. The method proposed applies the quadratic expansion to provide a first approximation of the non-linear operator, and DEIM is then used as a corrector to improve its representation. In addition to the treatment of the non-linear operator the POD model is stabilized using a Petrov–Galerkin method. This adds artificial dissipation to the solution of the reduced order model which is necessary to avoid spurious oscillations and unstable solutions.A demonstration of the capabilities of this new approach is provided by solving the incompressible Navier–Stokes equations for simulating a flow past a cylinder and gyre problems. Comparisons are made with other treatments of non-linear operators, and these show the new method to provide significant improvements in the solution's accuracy

The Complete Genome of Propionibacterium freudenreichii CIRM-BIA1T, a Hardy Actinobacterium with Food and Probiotic Applications

Background: Propionibacterium freudenreichii is essential as a ripening culture in Swiss-type cheeses and is also considered for its probiotic use [1]. This species exhibits slow growth, low nutritional requirements, and hardiness in many habitats. It belongs to the taxonomic group of dairy propionibacteria, in contrast to the cutaneous species P. acnes. The genome of the type strain, P. freudenreichii subsp. shermanii CIRM-BIA1 (CIP 103027T), was sequenced with an 11-fold coverage. Methodology/Principal Findings: The circular chromosome of 2.7 Mb of the CIRM-BIA1 strain has a GC-content of 67% and contains 22 different insertion sequences (3.5% of the genome in base pairs). Using a proteomic approach, 490 of the 2439 predicted proteins were confirmed. The annotation revealed the genetic basis for the hardiness of P. freudenreichii, as the bacterium possesses a complete enzymatic arsenal for de novo biosynthesis of aminoacids and vitamins (except panthotenate and biotin) as well as sequences involved in metabolism of various carbon sources, immunity against phages, duplicated chaperone genes and, interestingly, genes involved in the management of polyphosphate, glycogen and trehalose storage. The complete biosynthesis pathway for a bifidogenic compound is described, as well as a high number of surface proteins involved in interactions with the host and present in other probiotic bacteria. By comparative genomics, no pathogenicity factors found in P. acnes or in other pathogenic microbial species were identified in P. freudenreichii, which is consistent with the Generally Recognized As Safe and Qualified Presumption of Safety status of P. freudenreichii. Various pathways for formation of cheese flavor compounds were identified: the Wood-Werkman cycle for propionic acid formation, amino acid degradation pathways resulting in the formation of volatile branched chain fatty acids, and esterases involved in the formation of free fatty acids and esters. Conclusions/Significance: With the exception of its ability to degrade lactose, P. freudenreichii seems poorly adapted to dairy niches. This genome annotation opens up new prospects for the understanding of the P. freudenreichii probiotic activity

Utilisation de la flore lactique naturelle du poisson pour inhiber le développement de Listeria monocytogenes au cours de la conservation à 4øC du saumon fumé à froid emballé sous vide

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Electromagnetic Modeling in Near-Field Scanning Microwave Microscopy Highlighting Limitations in Spatial and Electrical Resolutions

International audienceNear-field scanning microwave microscopy (NSMM) is a scanning probe microscopy (SPM) technique that measures the local interaction of evanescent microwaves with a sample using a sharp tip probe. The traceability in NSMM is still challenging as the distribution of the electrical fields is affected by several parameters. In this effort, finite element method (FEM) based electromagnetic modeling methods are used to study the effects of the wavelength of operation and the humidity on the spatial and electrical resolutions respectively. From the simulated data, it is demonstrated that the lateral resolution is improved with increasing the frequency of operation. Furthermore, the existence and influence of a water meniscus is highlighted by fine comparison between simulated and measured data. To face these issues, an alternative near-field scanning millimeter-wave microscopy working in a controlled environment is proposed. Keywords-near-field scanning microwave microscopy (NSMM); finite element method (FEM); electromagnetic modeling; vector network analyzer (VNA); scanning electron microscope (SEM)