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Kumai, T. et al. Optimization of peptide vaccines to induce robust antitumor CD4 T-cell responses. Cancer Immunol. Res. 5, 72–83 (2017). Department of Neurology with Institute of Translational Neurology, University of Münster, Münster, Germany Karlstaedt, A. et al. Oncometabolite d-2-hydroxyglutarate impairs α-ketoglutarate dehydrogenase and contractile function in rodent heart. Proc. Natl Acad. Sci. USA 113, 10436–10441 (2016). The QIAamp DNA Blood Mini kit (QIAGEN) was used to isolate genomic DNA from PBMCs of patients. A total of 100 µl DNA solution with a concentration of at least 20 ng µl −1 was submitted at room temperature for high-resolution HLA typing to DKMS, Germany. Briefly, at DKMS, long-range PCRs were performed, amplicons were fragmented and used for next-generation sequencing on an Illumina MiSeq device. The full HLA class I gene and exons 2–5 of HLA class II genes were analyzed using the NGSengine (GenDx) software. Depending on the resolution, typing results were delivered either as G-code or MAC/NMDP-code. MHC II immunohistochemistry

Partha, Mandal Pratim & Mandal, B. (2002-01-01). A Text Book of Homoeopathic Pharmacy. Kolkata, India: New Central Book Agency. p.46. ISBN 978-81-7381-009-1. PBMCs were expanded under exposure to mutant H3K27M (p14-40) peptide to enrich peptide-reactive T cell clones. Briefly, cells were thawed, transferred into X-Vivo20 (Lonza, BE04-380Q) medium supplemented with 2% AB serum (Sigma, H4522) and rested overnight as described above. On day 1, cell suspensions were adjusted to 1 × 10 6 cells ml −1 and half of the available volume was plated at 500 µl per well into a 24-well plate. All remaining cells were plated at the same density in a second 24-well plate. Individual wells were pulsed with either (1) 4 µg ml −1 H3-mut (p14-40), (2) 4 µg ml −1 H3-wt (p14-40) or (3) no peptide to control for unspecific expansion. Both plates were placed in a 37 °C CO 2 incubator. After 4 h, non-adherent cells of the plate that was not pulsed with peptide were plated on top of peptide-pulsed cells at a final concentration of 1 × 10 6 cells ml −1 and per well.Teclu burner – The lower part of its tube is conical, with a round screw nut below its base. The gap, set by the distance between the nut and the end of the tube, regulates the influx of the air in a way similar to the open slots of the Bunsen burner. The Teclu burner provides better mixing of air and fuel and can achieve higher flame temperatures than the Bunsen burner. [9] [10] Kolker, S. et al. NMDA receptor activation and respiratory chain complex V inhibition contribute to neurodegeneration in d-2-hydroxyglutaric aciduria. Eur. J. Neurosci. 16, 21–28 (2002). Pollard, P. J. et al. Accumulation of Krebs cycle intermediates and over-expression of HIF1α in tumours which result from germline FH and SDH mutations. Hum. Mol. Genet. 14, 2231–2239 (2005).

Young peacebuilders use social media platforms to develop viable counter-messages to extremists. These are more likely to be successful if grounded in local (sometimes high-risk) in-person activities or activism. a, b, l-Trp import and degradation dynamics in immune cell subsets exposed to R-2-HG. Intracellular LC–MS/MS measurements of l-Trp and l-Kyn in T cells and monocyte-derived macrophages exposed to 20 mM R-2-HG and varying doses of l-Trp. Top, linear regression of dose-dependent metabolite accumulation. Bottom, quantification of intracellular l-Trp and l-Kyn levels and the [ l-Kyn][ l-Trp] −1 ratio. s.e.m is shown as error bands (top) or bars (bottom). n = 3 independent healthy donors. s.e.m. is projected as error bands. Statistical significance was determined by one-way ANOVA in combination with Tukey’s test. c– e, Cell-free assay of IDO1, IDO2 and TDO2 enzymatic activities with increasing concentrations of synthetic R-2-HG. A nonlinear regression model (log (R-2-HG) versus response) is shown. Regression curves are representative of y = 0 + (0.16 − 0)(1 + 10 (log(EC50)− x)) −1 (EC 50, half-maximum effective concentration). Produced l-Kyn levels were measured by absorbance at 321 nm (A 321). Gray boxes indicate the concentration range of R-2-HG detected in patient glioma tissues 12. n = 2 independent measurements for IDO1, n = 4 independent measurements for IDO2, n = 4 independent measurements for TDO2. f, Expression of Tdo2 in different murine immune cell subsets. RNA-seq data were derived from ref. 27. T n, naive T cell; T eff, effector T cell; T em, effector memory T cell; T gd, γδ T cell; NK, natural killer cell (NK); Mo, monocyte; MG, microglia cell. g, Monocyte-derived macrophage–T cell 3H-dT proliferation assay. Monocyte-derived macrophages from n = 3 Tdo2 +/+ and n = 3 Tdo2 −/− mice were pretreated with 10 mM R-2-HG or vehicle; 10 ng ml −1 anti-IL-10 and anti-TGF-β antibodies (αIL-10/TGF-β) or an isotype (iso) control; 10 ng ml −1 anti-PD-L1 antibody or isotype control; or 10 mM l-Kyn or vehicle as indicated for 24 h and co-cultured with stimulated C57BL6/J T cells for 24 h. Statistical significance was determined by one-way ANOVA in combination with Tukey’s test. If not mentioned otherwise, all data are represented as mean ± s.e.m. Rho, M., Tang, H. & Ye, Y. FragGeneScan: predicting genes in short and error-prone reads. Nucleic Acids Res. 38, e191 (2010).Balss, J. et al. Enzymatic assay for quantitative analysis of (D)-2-hydroxyglutarate. Acta Neuropathol. 124, 883–891 (2012). Peacebuilding practitioners should systematize the use of social media technology for conflict stakeholder analysis, early warning, counter-messaging and the defence of democracy and human rights; Clinical status was assessed during patient visits by a clinical neuro-oncologist. MRI assessment, including diagnosis of PsPD, applied the iRANO criteria on standardized MRIs that were obtained at least every 3 months. As in the NOA16 study 20, PsPD was defined as an increase in the size of the tumor on T2-FLAIR MRI sequences and/or the new appearance or enlargement of contrast-enhancing lesions followed by stabilization or regression on follow-up MRI. Tumor sizes for Fig. 3a were determined by the product of maximal orthogonal diameters on T1-weighted contrast-enhanced MRI imaging and cerebral lesions were classified into measurable and non-measurable lesions based on iRANO criteria (cerebral lesion with both maximal orthogonal diameters >10 mm were classified as measurable). PBMC isolation

Pajor, A. M. & Randolph, K. M. Inhibition of the Na+/dicarboxylate cotransporter by anthranilic acid derivatives. Mol. Pharmacol. 72, 1330–1336 (2007).

Selected publications

Kaelin, W. G.Jr. Cancer and altered metabolism: potential importance of hypoxia-inducible factor and 2-oxoglutarate-dependent dioxygenases. Cold Spring Harb. Symp. Quant. Biol. 76, 335–345 (2011). BUNCE n. British -- money or profit. A word dating from the 19th century and almost obsolete by the 1960s, except among street traders and the London underworld. In the late 1980s the word was revived by middle-class users such as alternative comedians in search of colourful synonyms in a climate of financial excesses. Bunce may originally have been a corruption of 'bonus.'" "The Dictionary of Contemporary Slang" by Tony Thorne (Pantheon Books, New York, 1990). Platten, M. et al. A vaccine targeting mutant IDH1 in newly diagnosed glioma. Nature 592, 463–468 (2021).

A Bunsen burner is also used in microbiology laboratories to sterilise pieces of equipment [7] and to produce an updraft that forces airborne contaminants away from the working area. [8] Variants Patients received H3K27M-vac between August 2017 and November 2022 at the University Hospitals of Heidelberg and Mannheim. Treatment was approved by the institutional review board and ethics committee. All patients provided written signed informed consent according to CARE guidelines and in compliance with the Declaration of Helsinki principles. Patients received no compensation for participation in this compassionate use program. Only adult patients of all sexes and genders with unequivocal disease progression of histologically confirmed H3K27M + DMG were offered to receive treatment with H3K27M-vac. Sex was determined based on self-report. Concomitant anti-PD-1 therapy was allowed depending on the treating physician’s discretion. As anti-PD-1 therapy is not approved for the treatment of DMG in Germany, the exact anti-PD-1 drug was dependent on availability. K27M substitution was determined by immunohistochemistry, hence allowing no differentiation between mutations in H3F3A and HIST2H1B/C. Exclusion criteria included concomitant treatment with dexamethasone (or equivalent) >4 mg d −1, Karnofsky performance index (KPI) < 70 and age <18 years. All patients had received radiotherapy in combination with chemotherapy with TMZ before the start of therapy. Radiation doses and the number of chemotherapy cycles at a dose of 200 mg m −2 are specified for each patient in Extended Data Table 1. Treatment consisted of vaccinations with H3K27M-vac in weeks 0, 2, 4, 6, 10, 14, 18 and 22, but was stopped in case of PD. After week 22, patients with stable disease were offered to continue vaccinations every three months until PD. MRI assessment was conducted every 12 ± 2 weeks. Patients were assessed for AEs by CTCAE v.5.0 on every visit for vaccination and every 12 weeks thereafter. According to good clinical practice, an AE was defined as any untoward medical occurrence during treatment with H3K27M-vac irrespective of causal relationship. AEs were judged to be treatment-related if the relationship to treatment was ‘possible’, ‘probable’ or ‘definite’. Disease progression and events which are unequivocally related to disease progression regardless of their outcome were not considered AEs. One brief partial seizure and one brief generalized seizure were not associated with disease progression, but were judged to be disease related in analogy to most clinical trials in neuro-oncology. All remaining AEs that were considered disease related occurred less than a week before MRI that showed PD. Regimen-limiting toxicity was defined as an occurrence of any treatment-related AE >grade 2 during the treatment phase. H3K27M-vac treatment Tech companies should redesign their social media tools to prevent them from being employed for harmful political ends and from favouring conflict over consensus; and Piontek, J. et al. Acidification increases microbial polysaccharide degradation in the ocean. Biogeosciences 7, 1615–1624 (2010). Bunse, L. et al. Suppression of antitumor T cell immunity by the oncometabolite (R)-2-hydroxyglutarate. Nat. Med. 24, 1192–1203 (2018).Tagliabue, A., Bopp, L. & Gehlen, M. The response of marine carbon and nutrient cycles to ocean acidification: large uncertainties related to phytoplankton physiological assumptions. Glob. Biogeochem. Cycles 25, GB3017 (2011). Mullen, A. R. & DeBerardinis, R. J. Genetically-defined metabolic reprogramming in cancer. Trends Endocrinol. Metab. 23, 552–559 (2012). Niklas Grassl, Lukas Bunse, Iris Mildenberger, Kristine Jähne, Edward W. Green, Philipp Eisele, Michael Platten & Katharina Sahm

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