NMRium: Teaching nuclear magnetic resonance spectra interpretation in an online platform.

NMRium is the first web-based software that allows displaying, processing, interpretation, and teaching of 1D and 2D NMR data in a user-friendly interface. It can import the most common data formats (e.g., JCAMP-DX, Bruker, Varian, and Jeol). While the scope for the use of NMRium encompasses a variety of applications such as being a component in data repositories or electronic lab notebooks (ELN), performing structure elucidation or preparing raw spectral data for publication, it also excels in enhancing teaching of NMR interpretation. In this paper, we present some current possibilities of this new tool. Several series of exercises are already provided on https://www.nmrium.org/teaching.

A cancer-unique glycan: de-N-acetyl polysialic acid (dPSA) linked to cell surface nucleolin depends on re-expression of the fetal polysialyltransferase ST8SIA2 gene.

BACKGROUND: Polysialic acid (polySia) modifies six cell surface proteins in humans mainly during fetal development and some blood cells in adults. Two genes in humans, ST8SIA2 and ST8SIA4, code for polysialyltransferases that synthesize polySia. ST8SIA2 is highly expressed during fetal development and in cancer but not in adult normal human cells. ST8SIA4 is expressed in fetal and adult brain, spleen, thymus, and peripheral blood leukocytes and in cancer. We identified a derivative of polySia containing de-N-acetyl neuraminic acid residues (dPSA), which is expressed on the cell surface of human cancer cell lines and tumors but not normal cells. METHODS: dPSA-modified proteins in several human cancer cell lines and normal blood cells were identified using co-immunoprecipitation with anti-dPSA antibodies, mass spectroscopy and Western blot. RNAi and CRISPR were used to knockdown and knockout, respectively, the polysialyltransferase genes in human melanoma SK-MEL-28 and neuroblastoma CHP-134 cell lines, respectively, to determine the effect on production of cell surface dPSA measured by flow cytometry and fluorescence microscopy. RESULTS: We found that dPSA is linked to or associated with nucleolin, a nuclear protein reported to be on the cell surface of cancer but not normal cells. Knocking down expression of ST8SIA2 with RNAi or knocking out each gene individually and in combination using CRISPR showed that cell surface dPSA depended on expression of ST8SIA2. CONCLUSIONS: The presence of dPSA specifically in a broad range of human cancers but not human adult normal cells offers novel possibilities for diagnosis, prevention and treatment targeting the dPSA antigen that appears to be cancer-specific, consistent across not only human cancers but also species, and may be an unrecognized mechanism of immune shielding.

Teaching NMR spectra analysis with nmr.cheminfo.org.

Teaching spectra analysis and structure elucidation requires students to get trained on real problems. This involves solving exercises of increasing complexity and when necessary using computational tools. Although desktop software packages exist for this purpose, nmr.cheminfo.org platform offers students an online alternative. It provides a set of exercises and tools to help solving them. Only a small number of exercises are currently available, but contributors are invited to submit new ones and suggest new types of problems.

The C6H6 NMR repository: An integral solution to control the flow of your data from the magnet to the public.

NMR is a mature technique that is well established and adopted in a wide range of research facilities from laboratories to hospitals. This accounts for large amounts of valuable experimental data that may be readily exported into a standard and open format. Yet the publication of these data faces an important issue: Raw data are not made available; instead, the information is slimed down into a string of characters (the list of peaks). Although historical limitations of technology explain this practice, it is not acceptable in the era of Internet. The idea of modernizing the strategy for sharing NMR data is not new, and some repositories exist, but sharing raw data is still not an established practice. Here, we present a powerful toolbox built on recent technologies that runs inside the browser and provides a means to store, share, analyse, and interact with original NMR data. Stored spectra can be streamlined into the publication pipeline, to improve the revision process for instance. The set of tools is still basic but is intended to be extended. The project is open source under the Massachusetts Institute of Technology (MIT) licence.

GHEP-ISFG collaborative simulated exercise for DVI/MPI: Lessons learned about large-scale profile database comparisons.

The GHEP-ISFG Working Group has recognized the importance of assisting DNA laboratories to gain expertise in handling DVI or missing persons identification (MPI) projects which involve the need for large-scale genetic profile comparisons. Eleven laboratories participated in a DNA matching exercise to identify victims from a hypothetical conflict with 193 missing persons. The post mortem database was comprised of 87 skeletal remain profiles from a secondary mass grave displaying a minimal number of 58 individuals with evidence of commingling. The reference database was represented by 286 family reference profiles with diverse pedigrees. The goal of the exercise was to correctly discover re-associations and family matches. The results of direct matching for commingled remains re-associations were correct and fully concordant among all laboratories. However, the kinship analysis for missing persons identifications showed variable results among the participants. There was a group of laboratories with correct, concordant results but nearly half of the others showed discrepant results exhibiting likelihood ratio differences of several degrees of magnitude in some cases. Three main errors were detected: (a) some laboratories did not use the complete reference family genetic data to report the match with the remains, (b) the identity and/or non-identity hypotheses were sometimes wrongly expressed in the likelihood ratio calculations, and (c) many laboratories did not properly evaluate the prior odds for the event. The results suggest that large-scale profile comparisons for DVI or MPI is a challenge for forensic genetics laboratories and the statistical treatment of DNA matching and the Bayesian framework should be better standardized among laboratories.

Ehlers-Danlos Syndrome Type VIIC: A Mexican Case Report.

Ehlers-Danlos syndrome (EDS) is a heterogeneous group of heritable connective tissue disorders whose primary clinical features include soft and extensible skin, articular hypermobility and tissue fragility. EDS type VIIC or 'human dermatosparaxis' is an autosomal recessive disease characterized by severe skin fragility and sagging redundant skin (major criteria) with a soft, doughy texture, easy bruising, premature rupture of fetal membranes and large hernias (minor criteria). Dermatosparaxis (meaning 'tearing of skin'), which has been described in several non-human species, is a disorder of the connective tissue resulting from a deficiency of the enzyme that cleaves the registration peptide off the N-terminal end of collagen after it has been secreted from fibroblasts. We describe a Mexican case from consanguineous parents with all the phenotypical characteristics previously described, plus skeletal abnormalities.