Changes in cell wall composition due to a pectin biosynthesis enzyme GAUT10 impact root growth.

Arabidopsis (Arabidopsis thaliana) root development is regulated by multiple dynamic growth cues that require central metabolism pathways such as ß-oxidation and auxin. Loss of the pectin biosynthesizing enzyme GALACTURONOSYLTRANSFERASE 10 (GAUT10) leads to a short-root phenotype under sucrose-limited conditions. The present study focused on determining the specific contributions of GAUT10 to pectin composition in primary roots and the underlying defects associated with gaut10 roots. Using live-cell microscopy, we determined reduced root growth in gaut10 is due to a reduction in both root apical meristem size and epidermal cell elongation. In addition, GAUT10 was required for normal pectin and hemicellulose composition in primary Arabidopsis roots. Specifically, loss of GAUT10 led to a reduction in galacturonic acid and xylose in root cell walls and altered the presence of rhamnogalacturonan-I (RG-I) and homogalacturonan (HG) polymers in the root. Transcriptomic analysis of gaut10 roots compared to wild type uncovered hundreds of genes differentially expressed in the mutant, including genes related to auxin metabolism and peroxisome function. Consistent with these results, both auxin signaling and metabolism were modified in gaut10 roots. The sucrose-dependent short-root phenotype in gaut10 was linked to ß-oxidation based on hypersensitivity to indole-3-butyric acid (IBA) and an epistatic interaction with TRANSPORTER OF IBA1 (TOB1). Altogether, these data support a growing body of evidence suggesting that pectin composition may influence auxin pathways and peroxisome activity.

Dextran Microparticulate Inhalable Dry Powder for the Treatment of Cystic Fibrosis and Mucopolysaccharidosis.

BACKGROUND: Cystic Fibrosis (CF) is a genetic disease which affects the patient's lungs, pancreas, liver, kidney and intestine and lacks sulfatase enzyme, leading to mucopolysaccharidosis. Colistin sulfate acts by interacting with phospholipids of bacterial cell membranes. Sulfatase enzyme reduces the high levels of sulfated glycosaminoglycans and glycolipids by the hydrolysis of sulfate esters in lysosome. OBJECTIVE: The aim of the present investigation was to prepare and evaluate dextran microparticulate inhalable dry powder for the efficient targeting of colistin sulfate at affected area of lung without causing the side effects in the treatment of CF and mucopolysaccharidosis. METHODS: Microparticulate dry powder was prepared by the lyophilization method and evaluated for particle size, % yield, % drug content, solid state characterization, in-vitro lung deposition study, and in-vitro drug release study. RESULTS: Particle size, % yield and % drug content were found to be 4.03 ± 0.196 µm, 94.02 % and 99.45 ± 0.015% respectively. Bulk density, tapped density, hausner's ratio, carr's index and angle of repose of optimized batch were found to be 0.216 ± 0.025 g/cm3, 0.236 ± 0.035 g/cm3, 1.09 ± 0.026, 8.47 ± 0.025 % and 26.10 ± 0.029˚ respectively. A fine particle fraction, fine particle dose, mass median aerodynamic diameter, geometric standard deviation and emitted dose were found to be 66.78%, 16.45 mg, 4.89 µm, 1.32 and 246.33 mg respectively. The % CDR of optimized batch was found to be 96.12 ± 0.049 % at 24 h. CONCLUSION: Based on the obtained results, we conclude that dextran microparticulate inhalable dry powder might be suitable carrier for the delivery of colistin sulfate and sulfatase in combination via pulmonary route for the treatment of cystic fibrosis and mucopolysaccharidosis.