Identification of a cyclin B1-derived CTL epitope eliciting spontaneous responses in both cancer patients and healthy donors

With the aim to identify cyclin B1-derived peptides with high affinity for HLA-A2, we used three in silico prediction algorithms to screen the protein sequence for possible HLA-A2 binders. One peptide scored highest in all three algorithms, and the high HLA-A2-binding affinity of this peptide was verified in an HLA stabilization assay. By stimulation with peptide-loaded dendritic cells a CTL clone was established, which was able to kill two breast cancer cell lines in an HLA-A2-dependent and peptide-specific manner, demonstrating presentation of the peptide on the surface of cancer cells. Furthermore, blood from cancer patients and healthy donors was screened for spontaneous T-cell reactivity against the peptide in IFN-γ ELISPOT assays. Patients with breast cancer, malignant melanoma, or renal cell carcinoma hosted powerful and high-frequency T-cell responses against the peptide. In addition, when blood from healthy donors was tested, similar responses were observed. Ultimately, serum from cancer patients and healthy donors was analyzed for anti-cyclin B1 antibodies. Humoral responses against cyclin B1 were frequently detected in both cancer patients and healthy donors. In conclusion, a high-affinity cyclin B1-derived HLA-A2-restricted CTL epitope was identified, which was presented on the cell surface of cancer cells, and elicited spontaneous T-cell responses in cancer patients and healthy donors

Giant tunnel-electron injection in nitrogen-doped graphene

International audienceScanning tunneling microscopy experiments have been performed to measure the local electron injection in nitrogen-doped graphene on SiC(000¯1) and were successfully compared to ab initio calculations. In graphene, a gaplike feature is measured around the Fermi level due to a phonon-mediated tunneling channel. At nitrogen sites, this feature vanishes due to an increase of the elastic channel that is allowed because of symmetry breaking induced by the nitrogen atoms. A large conductance enhancement by a factor of up to 500 was measured at the Fermi level by comparing local spectroscopy at nitrogen sites and at carbon sites. Nitrogen doping can therefore be proposed as a way to improve tunnel-electron injection in graphene

MethCORR Modelling of Methylomes From Formalin-Fixed Paraffin-Embedded Tissue Enables Characterization and Prognostication of Colorectal Cancer

Transcriptional characterization and classification has potential to resolve the inter-tumor heterogeneity of colorectal cancer and improve patient management. Yet, robust transcriptional profiling is difficult using formalin-fixed, paraffin-embedded (FFPE) samples, which complicates testing in clinical and archival material. We present MethCORR, an approach that allows uniform molecular characterization and classification of fresh-frozen and FFPE samples. MethCORR identifies genome-wide correlations between RNA expression and DNA methylation in fresh-frozen samples. This information is used to infer gene expression information in FFPE samples from their methylation profiles. MethCORR is here applied to methylation profiles from 877 fresh-frozen/FFPE samples and comparative analysis identifies the same two subtypes in four independent cohorts. Furthermore, subtype-specific prognostic biomarkers that better predicts relapse-free survival (HR = 2.66, 95%CI [1.67-4.22], P value < 0.001 (log-rank test)) than UICC tumor, node, metastasis (TNM) staging and microsatellite instability status are identified and validated using DNA methylation-specific PCR. The MethCORR approach is general, and may be similarly successful for other cancer types

Aldebaran b's temperate past uncovered in planet search data

The nearby red giant Aldebaran is known to host a gas giant planetary companion from decades of ground-based spectroscopic radial velocity measurements. Using Gaussian Process-based Continuous Auto-Regressive Moving Average (CARMA) models, we show that these historic data also contain evidence of acoustic oscillations in the star itself, and verify this result with further dedicated ground-based spectroscopy and space-based photometry with the Kepler Space Telescope. From the frequency of these oscillations we determine the mass of Aldebaran to be $1.16 \pm 0.07 \, M_\odot$, and note that this implies its planet will have been subject to insolation comparable to the Earth for some of the star's main sequence lifetime. Our approach to sparse, irregularly sampled time series astronomical observations has the potential to unlock asteroseismic measurements for thousands of stars in archival data, and push to lower-mass planets around red giant stars.Comment: 24 pages, 7 figures (including appendices); submitted to ApJL; paper text, figures, data, and code at https://github.com/farr/Aldebara

Characterization of the LM5 pectic galactan epitope with synthetic analogues of β-1,4-d-galactotetraose

Plant cell wall glycans are important polymers that are crucial to plant development and serve as an important source of sustainable biomass. The study of polysaccharides in the plant cell wall relies heavily on monoclonal antibodies for localization and visualization of glycans, using e.g. Immunofluorescent microscopy. Here, we describe the detailed epitope mapping of the mab LM5 that is shown to bind to a minimum of three sugar residues at the non-reducing end of linear beta-1,4-linked galactan. The study uses de novo synthetic analogs of galactans combined with carbohydrate microarray and competitive inhibition ELISA for analysis of antibody-carbohydrate interactions