Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has emerged as a global pandemic that upended existing protocols and practices, ...including those for allogeneic hematopoietic stem cell transplantation (HCT). Here, we describe the successful clinical course and multiple key interventions administered to an acute lymphoblastic leukemia patient, who tested SARS-CoV-2 positive by reverse transcriptase polymerase chain reaction on day −1 of matched unrelated donor (SARS-CoV-2 immunoglobulin G negative) T-cell-replete HCT. This experience allowed for implementing a virologic and immunomonitoring panel to characterize the impact of SARS-CoV-2 on the recipient's nascent humoral and cellular immune response. The finding of robust, functional, and persistent levels of SARS-CoV-2-specific T cells, starting early after transplant was unexpected, and in combination with the clinical strategy, may have contributed to the favorable outcome. Additionally, it is plausible that preexisting cross-reactive endemic coronavirus immunity in the allogeneic graft reduced recipient susceptibility to COVID-19 disease. This case supports the critical role that T-cell responses may play in mitigating SARS-CoV-2 infection, even in the context of transplant immunosuppression, in which reconstitution of humoral response is commonly delayed. Interventional approaches to transfer SARS-CoV-2-specific cellular immunity such as HCT donor vaccination and adaptive cellular therapy could be of benefit.
•We describe the clinical strategy implemented for successful treatment and outcome of pre-engraftment SARS-CoV2 infection in HCT recipient.•Robust levels of SARS-CoV-2-specific and functional T cells rapidly expanded early post-HCT and may have contributed to viral clearance.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Abstract
Glycogen and starch are the main storage polysaccharides, acting as a source of carbon and energy when necessary. Interconversion of glucose-1-phosphate and glucose-6-phosphate by ...phosphoglucomutases connects the metabolism of these polysaccharides with central carbon metabolism. However, knowledge about how this connection affects the ability of cells to cope with environmental stresses is still scarce. The cyanobacterium Synechocystis sp. PCC 6803 has two enzymes with phosphoglucomutase activity, PGM (phosphoglucomutase) and PMM/PGM (phosphomannomutase/phosphoglucomutase). In this work, we generated a null mutant of PGM (∆PGM) that exhibits very reduced phosphoglucomutase activity (1% of wild type activity). Although this mutant accumulates moderate amounts of glycogen, its phenotype resembles that of glycogen-less mutants, including high light sensitivity and altered response to nitrogen deprivation. Using an on/off arsenite promoter, we demonstrate that PMM/PGM is essential for growth and responsible for the remaining phosphoglucomutase activity in the ∆PGM strain. Furthermore, overexpression of PMM/PGM in the ∆PGM strain is enough to revoke the phenotype of this mutant. These results emphasize the importance of an adequate flux between glycogen and central carbon metabolism to maintain cellular fitness and indicate that although PGM is the main phosphoglucomutase activity, the phosphoglucomutase activity of PMM/PGM can substitute it when expressed in sufficient amounts.
Synechocystis has two enzymes with phosphoglucomutase activity: PGM and PMM/PGM. PGM is responsible for most of the phosphoglucomutase activity, but PMM/PGM is sufficient to sustain glycogen metabolism and its overexpression overrides the stress sensitivity phenotype of a PGM-null mutant.
The aim of this study was to benchmark the accuracy of the VIrtual Phantom Epid dose Reconstruction (VIPER) software for pre‐treatment dosimetric verification of multiple‐target stereotactic ...radiosurgery (SRS). VIPER is an EPID‐based method to reconstruct a 3D dose distribution in a virtual phantom from in‐air portal images. Validation of the VIPER dose calculation was assessed using several MLC‐defined fields for a 6 MV photon beam. Central axis percent depth doses (PDDs) and output factors were measured with an ionization chamber in a water tank, while dose planes at a depth of 10 cm in a solid flat phantom were acquired with radiochromic films. The accuracy of VIPER for multiple‐target SRS plan verification was benchmarked against Monte Carlo simulations. Eighteen multiple‐target SRS plans designed with the Eclipse treatment planning system were mapped to a cylindrical water phantom. For each plan, the 3D dose distribution reconstructed by VIPER within the phantom was compared with the Monte Carlo simulation, using a 3D gamma analysis. Dose differences (VIPER vs. measurements) generally within 2% were found for the MLC‐defined fields, while film dosimetry revealed gamma passing rates (GPRs) ≥95% for a 3%/1 mm criteria. For the 18 multiple‐target SRS plans, average 3D GPRs greater than 93% and 98% for the 3%/2 mm and 5%/2 mm criteria, respectively. Our results validate the use of VIPER as a dosimetric verification tool for pre‐treatment QA of single‐isocenter multiple‐target SRS plans. The method requires no setup time on the linac and results in an accurate 3D characterization of the delivered dose.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
•Polysaccharidic coatings improve postharvest quality of zucchini fruit.•Dextrin enhances antioxidant defence diminishing chilling injury during storage.•Additives olive oil and oleuropein increase ...the ascorbate and phenolics content.•Dextrin-based coatings improve the nutraceutical properties of zucchini fruit.
The use of edible coatings has surged as a response to the ever-increasing demand for ecologically-friendly methods for maintaining fruit quality during storage. This study analyses the application of different polysaccharide-based coatings, carboxymethylcellulose, chitosan, dextrin and starch, and the use of a plasticizer agent, glycerol, with dextrin shown to be the most effective in maintaining the postharvest quality of zucchini fruit during cold storage. Subsequently, to improve these results, the nutraceutical additives oleuropein and olive oil, were tested in combination with dextrin. Results showed that dextrin coatings reduced weight loss, chilling injury, and oxidative stress in zucchini fruit at low temperature, maintaining fruit quality. The natural additives obtained from the olive tree showed a higher induction of antioxidant enzymes as well as a greater accumulation of ascorbate and total phenolics, with the dextrin coating with olive oil being even more effective in maintaining the chilling injury low until the end of storage, associated to phenolic metabolism. This type of preservation could be implemented for extending postharvest life and enhancing the overall quality of zucchini fruit.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
...maintenance of the glutamate extracellular concentration involves tight control of its release and uptake. ...the cystine/glutamate exchanger, also known as system x−c xc− , exports glutamate in ...exchange for cystine (Jabaudon et al., 1999; Warr et al., 1999; Featherstone and Shippy, 2008). Abnormalities in uptake and motor function were alleviated via over-expression of a C-terminal truncated EAAT2 protein (Hirschberg et al.). Because most of the glutamate clearance (80–90%) is mediated by astrocytic EAAT2/GLT-1, the function of GLT-1 in other cell types has remained largely unexplored. ...the Robinson group used pharmacological inhibition of EAAT function to demonstrate their importance to arteriole patency (Jackson et al.), highlighting another important function of EAATs, which is to act as a bridge between local neuronal activity and increases in blood flow.
This paper describes the design, fabrication, simulation, and experimental results of an improved miniaturized two-axis sun sensor for industrial applications, created by adapting a technology used ...previously in satellite applications. The sensor for each axis is composed of six photodiodes integrated in a crystalline-silicon substrate and a layer of cover glass, which is used to protect the silicon and to hold the windows. The high precision is obtained by the subdivision of the field of view, which is ±60°, with a resolution of 0.1°. Each region is controlled by an independent high-precision solar sensor. The sensor can be used for sun-tracking applications in a photovoltaic system, heliostat concentration plants, and lighting applications.
Background and aimsDespite a recent new classification, a stable phylogeny for the cycads has been elusive, particularly regarding resolution of Bowenia, Stangeria and Dioon. In this study, five ...single-copy nuclear genes (SCNGs) are applied to the phylogeny of the order Cycadales. The specific aim is to evaluate several gene tree–species tree reconciliation approaches for developing an accurate phylogeny of the order, to contrast them with concatenated parsimony analysis and to resolve the erstwhile problematic phylogenetic position of these three genera.MethodsDNA sequences of five SCNGs were obtained for 20 cycad species representing all ten genera of Cycadales. These were analysed with parsimony, maximum likelihood (ML) and three Bayesian methods of gene tree–species tree reconciliation, using Cycas as the outgroup. A calibrated date estimation was developed with Bayesian methods, and biogeographic analysis was also conducted.Key ResultsConcatenated parsimony, ML and three species tree inference methods resolve exactly the same tree topology with high support at most nodes. Dioon and Bowenia are the first and second branches of Cycadales after Cycas, respectively, followed by an encephalartoid clade (Macrozamia–Lepidozamia–Encephalartos), which is sister to a zamioid clade, of which Ceratozamia is the first branch, and in which Stangeria is sister to Microcycas and Zamia.ConclusionsA single, well-supported phylogenetic hypothesis of the generic relationships of the Cycadales is presented. However, massive extinction events inferred from the fossil record that eliminated broader ancestral distributions within Zamiaceae compromise accurate optimization of ancestral biogeographical areas for that hypothesis. While major lineages of Cycadales are ancient, crown ages of all modern genera are no older than 12 million years, supporting a recent hypothesis of mostly Miocene radiations. This phylogeny can contribute to an accurate infrafamilial classification of Zamiaceae.
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BFBNIB, IZUM, KILJ, NMLJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Lack of glycogen synthases results in the lethal accumulation of their substrate, ADP-glucose, but providing an alternative metabolic sink restores cell viability and the nutrient deprivation ...response.
Abstract
Cyanobacteria are widely distributed photosynthetic organisms. During the day they store carbon, mainly as glycogen, to provide the energy and carbon source they require for maintenance during the night. Here, we generate a mutant strain of the freshwater cyanobacterium Synechocystis sp. PCC 6803 lacking both glycogen synthases. This mutant has a lethal phenotype due to massive accumulation of ADP-glucose, the substrate of glycogen synthases. This accumulation leads to alterations in its photosynthetic capacity and a dramatic decrease in the adenylate energy charge of the cell to values as low as 0.1. Lack of ADP-glucose pyrophosphorylase, the enzyme responsible for ADP-glucose synthesis, or reintroduction of any of the glycogen synthases abolishes the lethal phenotype. Viability of the glycogen synthase mutant is also fully recovered in NaCl-supplemented medium, which redirects the surplus of ADP-glucose to synthesize the osmolite glucosylglycerol. This alternative metabolic sink also suppresses phenotypes associated with the defective response to nitrogen deprivation characteristic of glycogen-less mutants, restoring the capacity to degrade phycobiliproteins. Thus, our system is an excellent example of how inadequate management of the adenine nucleotide pools results in a lethal phenotype, and the influence of metabolic carbon flux in cell viability and fitness.
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