the gatto study a phase i of the anti egfr tomuzotuximab to in combination with the anti muc1 gatipotuzumab gat in patients with egfr positive solid tumors

n/

Down-regulation of the myo-inositol oxygenase gene family has no effect on cell wall composition in Arabidopsis

The enzyme myo-inositol oxygenase (MIOX; E.C. 1.13.99.1) catalyzes the ring-opening four-electron oxidation of myo-inositol into glucuronic acid, which is subsequently activated to UDP-glucuronic acid (UDP-GlcA) and serves as a precursor for plant cell wall polysaccharides. Starting from single T-DNA insertion lines in different MIOX-genes a quadruple knockdown (miox1/2/4/5-mutant) was obtained by crossing, which exhibits greater than 90% down-regulation of all four functional MIOX genes. Miox1/2/4/5-mutant shows no visible phenotype and produces viable pollen. The alternative pathway to UDP-glucuronic acid via UDP-glucose is upregulated in the miox1/2/4/5-mutant as a compensatory mechanism. Miox1/2/4/5-mutant is impaired in the utilization of myo-inositol for seedling growth. The incorporation of myo-inositol derived sugars into cell walls is strongly (>90%) inhibited. Instead, myo-inositol and metabolites produced from myo-inositol such as galactinol accumulate in the miox1/2/4/5-mutant. The increase in galactinol and raffinose family oligosaccharides does not enhance stress tolerance. The ascorbic acid levels are the same in mutant and wild type plants

Identifying core features of adaptive metabolic mechanisms for chronic heat stress attenuation contributing to systems robustness

The contribution of metabolism to heat stress may play a significant role in defining robustness and recovery of systems; either by providing the energy and metabolites required for cellular homeostasis, or through the generation of protective osmolytes. However, the mechanisms by which heat stress attenuation could be adapted through metabolic processes as a stabilizing strategy against thermal stress are still largely unclear. We address this issue through metabolomic and transcriptomic profiles for populations along a thermal cline where two seagrass species, Zostera marina and Zostera noltii, were found in close proximity. Significant changes captured by these profile comparisons could be detected, with a larger response magnitude observed in northern populations to heat stress. Sucrose, fructose, and myo-inositol were identified to be the most responsive of the 29 analyzed organic metabolites. Many key enzymes in the Calvin cycle, glycolysis and pentose phosphate pathways also showed significant differential expression. The reported comparison suggests that adaptive mechanisms are involved through metabolic pathways to dampen the impacts of heat stress, and interactions between the metabolome and proteome should be further investigated in systems biology to understand robust design features against abiotic stress

Cloning and endogenous expression of a Eucalyptus grandis UDP-glucose dehydrogenase cDNA

UDP-glucose dehydrogenase (UGDH) catalyzes the oxidation of UDP-glucose (UDP-Glc) to UDP-glucuronate (UDP-GlcA), a key sugar nucleotide involved in the biosynthesis of plant cell wall polysaccharides. A full-length cDNA fragment coding for UGDH was cloned from the cambial region of 6-month-old E. grandis saplings by RT-PCR. The 1443-bp-ORF encodes a protein of 480 amino acids with a predicted molecular weight of 53 kDa. The recombinant protein expressed in Escherichia coli catalyzed the conversion of UDP-Glc to UDP-GlcA, confirming that the cloned cDNA encodes UGDH. The deduced amino acid sequence of the cDNA showed a high degree of identity with UGDH from several plant species. The Southern blot assay indicated that more than one copy of UGDH is present in Eucalyptus. These results were also confirmed by the proteomic analysis of the cambial region of 3- and 22-year-old E. grandis trees by 2-DE and LC-MS/MS, showing that at least two isoforms are present. The cloned gene is mainly expressed in roots, stem and bark of 6-month-old saplings, with a lower expression in leaves. High expression levels were also observed in the cambial region of 3- and 22-year-old trees. The results described in this paper provide a further view of the hemicellulose biosynthesis during wood formation in E. grandis