Metabolic Profiling of Genetically Modified Potato Periderm Tissues

Potato tubers are protected from dehydration and pathogens by a covering peel (periderm) impregnated with suberin, a complex cross-linked biopolymer that contains both polyaliphatic and lignin-like aromatic domains. Current models describing the macromolecular structure of suberin assume that ferulic acid cross-links both domains as it may form carboxyl ester bonds with aliphatic monomers and non-ester radical-coupled bonds with phenolics. Ferulic acid also links by ester bonds to glycans and acts in cross-linking polysaccharides and lignin. Fatty alcohol/ω-hydroxyacid hydroxycinnamoyl transferase (FHT) is a BADH acyltransferase responsible for the synthesis of akyl-ferulates that is necessary for suberin biosynthesis. Periderm from FHT-RNAi tubers showed a significant decrease in suberin ferulate esters and an increase in soluble phenolic breakdown products. This periderm also showed changes in texture and water permeability but, surprisingly, the suberin lamellar structure was not altered. The CYP86A gene is a strong candidate for aliphatic suberin biosynthesis. CYP86A33-RNAi potato periderm had a striking loss of suberin lamellar structure and diminished w-hydroxyacids and a,w-diacids. To obtain a more comprehensive molecular view of the consequences of gene silencing on potato periderm composition, metabolite profiling was conducted on soluble polar and nonv polar extracts from native and wound periderms of wild-type (WT) and FHT-RNAi silenced potato samples using liquid-chromatography mass-spectrometry (LC-MS), gas-chromatography mass-spectrometry (GC-MS) and 1H nuclear magnetic resonance spectroscopy (NMR). The solid interface was analyzed by solid-state NMR. FHT deficiency induced significant changes in the metabolite pool of both polar and non-polar extracts from native periderms. In particular, FHT silencing induced accumulation of phenolic amides such as caffeoylputrescine, feruloylputrescine, feruloyltyramine, and amide dimers in the polar extracts and long-chain saturated fatty acids (C22, C23, C24, C27), long-chain primary alcohols (C22, C26, C27, C28, C29), methyl esters (C17:0, C19:2) and 1-monohexadecanoyl glycerol in the non-polar extracts. Phenolic acids, glycoalkaloids, alkanes (C21, C23, C25, C27, C29) and fatty acids (C16:0, C18:0, C18:2) were down-regulated in FHT-RNAi native periderms. For the solid interfacial residue, the FHT-RNAi variety displayed higher arene-to-(CH2)n and oxygenated alkoxy-to-(CH2)n ratios compared to WT. In contrast to the native tissues, the WT and FHT-RNAi-silenced tissue extracts and solid interfacial residues from developing wound periderms each exhibited similar compositional progressions with time; their initially distinct metabolic profiles became overlapped and underwent a striking convergence. An analogous analysis was conducted on CYP86A33-RNAi native periderm. In CYP86A33 silenced native potato periderms, glycoalkaloids were highly abundant in polar extracts while polyamides were down-regulated compared with WT. Non-polar extracts are to be analyzed with GC-MS and LC-MS

Evaluation of Arctic sea ice simulation of CMIP6 models from China

Nine coupled climate models from China participating in the Coupled Model Intercomparison Project Phase 6 (CMIP6) were evaluated in terms of their capability in ensemble historical Arctic sea ice simulation in the context of 56 CMIP6 models. We evaluated these nine models using satellite observations from 1980 to 2014. This evaluation was conducted comprehensively using 12 metrics covering different aspects of the seasonal cycle and long-term trend of sea ice extent (SIE) and sea ice concentration (SIC). The nine Chinese models tended to overestimate SIE, especially in March, and underestimate its long-term decline trend. There was less spread in model skill in reproducing the spatial pattern of March SIC than in reproducing the spatial pattern of September SIC. The error of March SIC simulation was distributed at the margins of sea ice cover, such as in the Nordic Seas, the Barents Sea, the Labrador Sea, the Bering Sea, and the Sea of Okhotsk. However, the error of September SIC was distributed both at the margins of sea ice cover and in the central part of the Arctic Basin. Five of these nine models had capabilities comparable with the majority of the CMIP6 models in reproducing the seasonal cycle and long-term trend of Arctic sea ice

Low Cost Industrial Production of Coagulation Factor IX Bioencapsulated in Lettuce Cells for Oral Tolerance Induction in Hemophilia B

Antibodies (inhibitors) developed by hemophilia B patients against coagulation factor IX (FIX) are challenging to eliminate because of anaphylaxis or nephrotic syndrome after continued infusion. To address this urgent unmet medical need, FIX fused with a transmucosal carrier (CTB) was produced in a commercial lettuce (Simpson Elite) cultivar using species specific chloroplast vectors regulated by endogenous psbA sequences. CTB-FIX (~1mg/g) in lyophilized cells was stable with proper folding, disulfide bonds and pentamer assembly when stored ~2 years at ambient temperature. Feeding lettuce cells to hemophilia B mice delivered CTB-FIX efficiently to the gut immune system, induced LAP+ regulatory T cells and suppressed inhibitor/IgE formation and anaphylaxis against FIX. Lyophilized cells enabled 10-fold dose escalation studies and successful induction of oral tolerance was observed in all tested doses. Induction of tolerance in such a broad dose range should enable oral delivery to patients of different age groups and diverse genetic background. Using Fraunhofer cGMP hydroponic system, ~870 kg fresh or 43.5 kg dry weight can be harvested per 1000 ft2 per annum yielding 24,000–36,000 doses for 20-kg pediatric patients, enabling first commercial development of an oral drug, addressing prohibitively expensive purification, cold storage/transportation and short shelf life of current protein drugs

Circulating tumor DNA determining hyperprogressive disease after CAR-T therapy alarms in DLBCL: a case report and literature review

Chimeric antigen receptor T-cell therapy (CAR-T) has been widely applied in the clinical practice of relapse/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) due to its promising effects. Hyperprogressive disease (HPD) has gained attention for rapid tumor progression and has become a therapeutic and prognostic challenge. Here, we present a patient who had suffered from several recurrences previously and controlled well with a very small tumor lesion left was infused with CD19/CD22 bispecific CAR-T, with no immune effector cell-associated neurotoxicity syndrome, or cytokine release syndrome observed. However, rapid deterioration, subsequent imaging examination, circulating tumor DNA, and serum biomarkers detection identified HPD. The patient did not respond to salvage treatment and died 40 days after infusion. To our knowledge, only one case of HPD in DLBCL after CAR-T therapy has been reported. This fatal case alarmed the risk of HPD and the ctDNA profile monitoring we used was performed as a non-invasive method to diagnose HPD, providing far-reaching practical instruction for CAR-T therapy

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements

26th Annual Computational Neuroscience Meeting (CNS*2017): Part 3 - Meeting Abstracts - Antwerp, Belgium. 15–20 July 2017

This work was produced as part of the activities of FAPESP Research,\ud Disseminations and Innovation Center for Neuromathematics (grant\ud 2013/07699-0, S. Paulo Research Foundation). NLK is supported by a\ud FAPESP postdoctoral fellowship (grant 2016/03855-5). ACR is partially\ud supported by a CNPq fellowship (grant 306251/2014-0)