Genetic diversity of Oxytropis section Xerobia (Fabaceae) in one of the centres of speciation

Genetica - The genetic diversity and phylogenetic relationships of Oxytropis caespitosa, O. grandiflora, O. eriocarpa, O. mixotriche, O. nitens,...     

Glycan engineering reveals interrelated effects of terminal galactose and core fucose on antibody-dependent cell-mediated cytotoxicity

Antibody-dependent cell-mediated cytotoxicity (ADCC) has been identified as one of the potentially critical effector functions underlying the clinical efficacy of some therapeutic immunoglobin G1 (IgG1) antibodies. It has been well established that higher levels of afucosylated N-linked glycan structures on the Fc region enhance the IgG binding affinity to the FcγIIIa receptor and lead to increased ADCC activity. However, whether terminal galactosylation of an IgG1 impacts its ADCC activity is less understood. Here, we used a new strategy for glycan enrichment and remodeling to study the impact of terminal galactose on ADCC activity for therapeutic IgG1s. Our results indicate that the degree of influence of terminal galactose on in vitro ADCC activity depends on the presence or absence of the core fucose, which is typically linked to the first N-acetyl glucosamine residue of an N-linked glycosylation core structure. Specifically, terminal galactose on afucosylated IgG1 mAbs enhanced ADCC activity with impact coefficients (ADCC%/Gal%) more than 20, but had minimal influence on ADCC activity on fucosylated structures with impact coefficient in the range of 0.1–0.2. Knowledge gained here can be used to guide product and process development activities for biotherapeutic antibodies that require effector function for efficacy, and also highlight the complexity in modulating the immune response through N-linked glycosylation of antibodies.     

Structural characterization of the α-N-acetylglucosaminidase,a key enzyme in the pathogenesis of Sanfilippo syndrome B

Mucopolysaccharidosis III B (MPS III-B) is a rare lysosomal storage disorder caused by deficiencies in Alpha-N-acetylglucosaminidase (NAGLU) for which there is currently no cure, and present treatment is largely supportive. Understanding the structure of NAGLU may allow for identification of novel therapeutic targets for MPS III-B. Here we describe the first crystal structure of human NAGLU, determined to a resolution of 2.3?Å. The crystal structure reveals a novel homotrimeric configuration, maintained primarily by hydrophobic and electrostatic interactions via domain II of three contiguous domains from the N- to C-terminus. The active site cleft is located between domains II and III. Catalytic glutamate residues, E316 and E446, are located at the top of the (α/β)₈ barrel structure in domain II. We utilized the three-dimensional structure of NAGLU to map several MPS III-B mutations, and hypothesize their functional consequences. Revealing atomic level structural information about this critical lysosomal enzyme paves the way for the design of novel therapeutics to target the underlying causes of MPS III-B.     

Supplementary CaCl2 ameliorates wheat tolerance to NaCl

Nine-day-old seedlings of two wheat cultivars (Misr1 and Sakha93) were treated with NaCl at 75, 150 and 225 mM for 15 days with or without the presence of 10 mM CaCl₂. All concentrations of NaCl led to significant decreases in fresh and dry weights of only Sakha93; however, Misr1 seemed to be affected only at the highest concentration. Nonetheless, growth parameters of both cultivars under normal conditions were most likely similar. On the other hand, lipid peroxides (as MDA) and H₂O₂ were greatly accumulated particularly in Sakha93; significant increases were detected in Misr1 treated only at 225 mM. Also, all concentrations of NaCl decreased GSH content in Sakha93; nevertheless, there were no great differences among both cultivars under normal conditions. On the other hand, the activities of the enzymatic antioxidants, GR, GST, CAT and POD were unaffected in Misr1 by all concentrations but inhibited in Sakha93. AOX responded differently to NaCl, there were decreases in Misr1 by 75 and 225 mM and in Sakha93 by 75 and 150 mM. However, the application of CaCl₂ alleviated the impacts of NaCl; there was a retraction in growth reduction in Misr1 to reach most likely those of the control. In addition, the accumulated MDA and H₂O₂ were greatly counterbalanced. On the contrary, the decreased GSH contents seemed unrecovered in Sakha93 in spite of the alleviations in magnitudes. Moreover, there were recoveries in the activities of GR and POD in Sakha93; nevertheless, GST and CAT activities remained significantly inhibited. These findings suggest that Misr1 is a more tolerant cultivar to NaCl than Sakha93. Moreover, the results reveal that ROS scavenging is efficient and became more inducible in the less susceptible than in the more susceptible cultivar. The response of AOX appeared to coincide with antioxidants so that the damage which was inflicted by NaCl can be ameliorated by over-expression of antioxidants especially with the presence of CaCl₂.     

Microbiology research at the systems biology and bioinformatics - 2019 (SBB-2019) school

Background

The Uzon Caldera is one of the places on our planet with unique geological, ecological, and microbiological characteristics. Uzon oil is the youngest on Earth. Uzon oil has unique composition, with low proportion of heavy fractions and relatively high content of saturated hydrocarbons. Microbial communities of the «oil site» have a diverse composition and live at high temperatures (up to 97 °C), significant oscillations of Eh and pH, and high content of sulfur, sulfides, arsenic, antimony, and mercury in water and rocks.

Results

The study analyzed the composition, structure and unique genetics characteristics of the microbial communities of the oil site, analyzed the metabolic pathways in the communities. Metabolic pathways of hydrocarbon degradation by microorganisms have been found. The study found statistically significant relationships between geochemical parameters, taxonomic composition and the completeness of metabolic pathways. It was demonstrated that geochemical parameters determine the structure and metabolic potential of microbial communities.

Conclusions

There were statistically significant relationships between geochemical parameters, taxonomic composition, and the completeness of metabolic pathways. It was demonstrated that geochemical parameters define the structure and metabolic potential of microbial communities. Metabolic pathways of hydrocarbon oxidation was found to prevail in the studied communities, which corroborates the hypothesis on abiogenic synthesis of Uzon hydrothermal petroleum.