Search Results (4)

Three murine glioma cell lines (GL261, CT2A, and ALTS1C1) were modified to downregulate the expression of the murine LDH-A gene using shRNA, and compared to shRNA scrambled control (NC) cell lines. Differences in the expression of LDH-A and LDH-B mRNA, protein and enzymatic activity, as well as their LDH isoenzyme profiles, were observed in the six cell lines, and confirmed successful LDH-A KD. LDH-A KD (knock-down) resulted in metabolic changes in cells with a reduction in glycolysis (GlycoPER) and an increase in basal respiratory rate (mitoOCR). GL261 cells had a more limited ATP production capacity compared to CT2A and ALTS1C1 cells. An analysis of mRNA expression data indicated that: (i) GL261 LDH-A KD cells may have an improved ability to metabolize lactate into the TCA cycle; and (ii) that GL261 LDH-A KD cells can upregulate lipid metabolism/fatty acid oxidation pathways, whereas the other glioma cell lines do not have this capacity. These two observations suggest that GL261 LDH-A KD cells can develop/activate alternative metabolic pathways for enhanced survival in a nutrient-limited environment, and that specific nutrient limitations have a variable impact on tumor cell metabolism and proliferation. The phenotypic effects of LDH-A KD were compared to those in control (NC) cells and tumors. LDH-A KD prolonged the doubling time of GL261 cells in culture and prevented the formation of subcutaneous flank tumors in immune-competent C57BL/6 mice, whereas GL261 NC tumors had a prolonged growth delay in C57BL/6 mice. In nude mice, both LDH-A KD and NC GL261 tumors grew rapidly (more rapidly than GL261 NC tumors in C57BL/6 mice), demonstrating the impact of an intact immune system on GL261 tumor growth. No differences between NC and KD cell proliferation (in vitro) or tumor growth in C57BL/6 mice (doubling time) were observed for CT2A and ALTS1C1 cells and tumors, despite the small changes to their LDH isoenzyme profiles. These results suggest that GL261 glioma cells (but not CT2A and ALTS1C1 cells) are pre-programmed to have the capacity for activating different metabolic pathways with higher TCA cycle activity, and that this capacity is enhanced by LDH-A depletion. We observed that the combined impact of LDH-A depletion and the immune system had a significant impact on the growth of subcutaneous-located GL261 tumors. Full article

The level of ambiguity in describing glycan structure has significantly increased with the upsurge of large-scale glycomics and glycoproteomics experiments. Consequently, an ontology-based model appears as an appropriate solution for navigating these data. However, navigation is not sufficient and the model should also enable advanced search and comparison. A new ontology with a tree logical structure is introduced to represent glycan structures irrespective of the precision of molecular details. The model heavily relies on the GlycoCT encoding of glycan structures. Its implementation in the GlySTreeM knowledge base was validated with GlyConnect data and benchmarked with the Glycowork library. GlySTreeM is shown to be fast, consistent, reliable and more flexible than existing solutions for matching parts of or whole glycan structures. The model is also well suited for painless future expansion. Full article

In life science fields, database integration is progressing and contributing to collaboration between different research fields, including the glycosciences. The integration of glycan databases has greatly progressed collaboration worldwide with the development of the international glycan structure repository, GlyTouCan. This trend has increased the need for a tool by which researchers in various fields can easily search glycan structures from integrated databases. We have developed a web-based glycan structure search tool, SugarDrawer, which supports the depiction of glycans including ambiguity, such as glycan fragments which contain underdetermined linkages, and a database search for glycans drawn on the canvas. This tool provides an easy editing feature for various glycan structures in just a few steps using template structures and pop-up windows which allow users to select specific information for each structure element. This tool has a unique feature for selecting possible attachment sites, which is defined in the Symbol Nomenclature for Glycans (SNFG). In addition, this tool can input and output glycans in WURCS and GlycoCT formats, which are the most commonly-used text formats for glycan structures. Full article

SugarSketcher is an intuitive and fast JavaScript interface module for online drawing of glycan structures in the popular Symbol Nomenclature for Glycans (SNFG) notation and exporting them to various commonly used formats encoding carbohydrate sequences (e.g., GlycoCT) or quality images (e.g., svg). It does not require a backend server or any specific browser plugins and can be integrated in any web glycoinformatics project. SugarSketcher allows drawing glycans both for glycobiologists and non-expert users. The “quick mode” allows a newcomer to build up a glycan structure having only a limited knowledge in carbohydrate chemistry. The “normal mode” integrates advanced options which enable glycobiologists to tailor complex carbohydrate structures. The source code is freely available on GitHub and glycoinformaticians are encouraged to participate in the development process while users are invited to test a prototype available on the ExPASY web-site and send feedback. Full article