Evaluation of myocardial damage in different types of rheumatoid arthritisduring disease-modifying antirheumatic drug or biological therapy (with infliximab)

Objective. To estimate the extent and pattern of myocardial damage in different types of rheumatoid arthritis (RA) during disease-modifying antirheumatic drug (DMARD) or biological therapy. Subjects and methods. Seventy-one patients with RA were examined; some of them received biological therapy with infliximab, while the others took DMARDs. A group of patients with incipient RA was also identified. B-type brain natriuretic peptide levels were estimated and electrocardiography, echocardiography (EchoCG), and cardiac magnetic resonance imaging (MRT) using the contrast medium Dotarem were conducted in all the patients. The follow-up totaled 6 months. A control examination was made at the moment of randomization and 6 months posttreatment. Results. Tn the bulk of patients, the level of B-type brain natriuretic peptide did not differ from the reference values, however, its lower level was observed in the incipient RA group, which was associated with the absence of cardiovascular diseases and with a younger age group. There were no negative EchoCG changes in myocardial viability values. Cardiac MRT demonstrated that the majority of patients had the similar changes that failed to affect myocardial kinetics and ejection fraction. These changes were not found in incipient RA patients without cardiovascular diseases. No improvement in myocardial viability was recorded in the patients receiving the biological therapy. Conclusion. Thus, cardiac MRT showed the similar changes that failed to affect myocardial kinetics and ejection fraction in patients with RA during both methotrexate and infliximab therapy

LysM Receptor-Like Kinase LYK9 of <i>Pisum Sativum</i> L. May Regulate Plant Responses to Chitooligosaccharides Differing in Structure

This study focused on the interactions of pea (Pisum sativum L.) plants with phytopathogenic and beneficial fungi. Here, we examined whether the lysin-motif (LysM) receptor-like kinase PsLYK9 is directly involved in the perception of long- and short-chain chitooligosaccharides (COs) released after hydrolysis of the cell walls of phytopathogenic fungi and identified in arbuscular mycorrhizal (AM) fungal exudates. The identification and analysis of pea mutants impaired in the lyk9 gene confirmed the involvement of PsLYK9 in symbiosis development with AM fungi. Additionally, PsLYK9 regulated the immune response and resistance to phytopathogenic fungi, suggesting its bifunctional role. The existence of co-receptors may provide explanations for the potential dual role of PsLYK9 in the regulation of interactions with pathogenic and AM fungi. Co-immunoprecipitation assay revealed that PsLYK9 and two proposed co-receptors, PsLYR4 and PsLYR3, can form complexes. Analysis of binding capacity showed that PsLYK9 and PsLYR4, synthesized as extracellular domains in insect cells, were able to bind the deacetylated (DA) oligomers CO5-DA–CO8-DA. Our results suggest that the receptor complex consisting of PsLYK9 and PsLYR4 can trigger a signal pathway that stimulates the immune response in peas. However, PsLYR3 seems not to be involved in the perception of CO4-5, as a possible co-receptor of PsLYK9

LysM Receptor-Like Kinase LYK9 of Pisum Sativum L. May Regulate Plant Responses to Chitooligosaccharides Differing in Structure

This study focused on the interactions of pea (Pisum sativum L.) plants with phytopathogenic and beneficial fungi. Here, we examined whether the lysin-motif (LysM) receptor-like kinase PsLYK9 is directly involved in the perception of long- and short-chain chitooligosaccharides (COs) released after hydrolysis of the cell walls of phytopathogenic fungi and identified in arbuscular mycorrhizal (AM) fungal exudates. The identification and analysis of pea mutants impaired in the lyk9 gene confirmed the involvement of PsLYK9 in symbiosis development with AM fungi. Additionally, PsLYK9 regulated the immune response and resistance to phytopathogenic fungi, suggesting its bifunctional role. The existence of co-receptors may provide explanations for the potential dual role of PsLYK9 in the regulation of interactions with pathogenic and AM fungi. Co-immunoprecipitation assay revealed that PsLYK9 and two proposed co-receptors, PsLYR4 and PsLYR3, can form complexes. Analysis of binding capacity showed that PsLYK9 and PsLYR4, synthesized as extracellular domains in insect cells, were able to bind the deacetylated (DA) oligomers CO5-DA&ndash;CO8-DA. Our results suggest that the receptor complex consisting of PsLYK9 and PsLYR4 can trigger a signal pathway that stimulates the immune response in peas. However, PsLYR3 seems not to be involved in the perception of CO4-5, as a possible co-receptor of PsLYK9

The role of heterotrimeric G proteins in the control of symbiosis development in legume plants

Heterotrimeric G proteins are involved in the regulation of signaling pathways in eukaryotes. Previously, the data about possible participation of heterotrimeric G proteins in the regulation of nodulation in legumes were obtained, however, specific proteins, their composition and role in this process remain poorly understood. In this work searching of the genes encoding the alpha, beta, and gamma subunits of heterotrimeric G proteins based on an analysis of the Pisum sativum L. genome was performed, as well as the dynamics of the gene expression encoding the particular subunits of G proteins in the process of symbiosis was studied. In addition, a significant effect of beta 1-subunit gene suppression by RNA interference on the nodulation process was revealed

Organic matter accumulation by alkaline-constructed soils in heavily metal-polluted area of Subarctic zone

Purpose: The research aimed to investigate properties and functions of soils constructed from alkaline mining wastes of different origin to remediate the industrial barren resulted from long-term emissions of the copper-nickel factory in the Subarctic region (Kola Peninsula, Russia). Conventional indicators of the remediation effectiveness (pH and metal content in geochemical fractions) were related to the indicators of soil functions such as biomass production, accumulation of organic carbon, microbial activity, and soil respiration. Materials and methods: The experimental area included two sites with polluted and degraded Podzol and Histosol soils located in 1.5 and 0.7 km from the nonferrous (Cu-Ni) smelter, respectively. At the sites, artificial soil constructions were made from mining wastes or quarry sand covered by the vermiculite layer with lawn grasses planted on top. Plant biomass was collected every year starting from the experiment set-up. In 5 to 8 years, soil samples were collected on the layer basis, and chemical, biological, and morphological properties were analyzed. Sequential fractionation of metals was conducted using a modified Tessier’s scheme. The microbial biomass and its respiration activity were determined. Micromorphological studies were conducted using an optical microscope. Soil respiration was measured on-site by IRGA with simultaneous observations of soil moisture and temperature. Results: The plant growth and residues' deposition at both experimental sites triggered carbon accumulation and resulted in 2–3 times higher content of organic carbon in the upper constructed soil layer compared to the initial content in mining wastes. Carbon accumulation was a key driver for the development of soil microbial communities and had a positive effect on the metal immobilization. This effect was strengthened by high pH inherited from the alkaline wastes and resulted in the performance of constructed soils as geochemical barriers. In their upper layers, where the root biomass was the highest, about 30–60% of Cu and Ni were bound by organic matter. In the underlying polluted soil, the most toxic water-soluble metal fraction was completely neutralized; and the metal concentrations in exchangeable fraction decreased by a factor of four improving the habitat conditions of the microbiome. Organic matter accumulation by clay material with the formation of organo-mineral films was found in the vermiculite-lizardite variant. Conclusion: Soil constructions made from alkaline mining wastes in the Subarctic supported the development of plant and microbial communities, organic matter accumulation, and metal immobilization. This technology allows protecting the environment from further pollution under the continuous emissions of the copper-nickel factory

Urbanization affects soil microbiome profile distribution in the russian arctic region

Urbanization in the Arctic results in considerable and still poorly known environmental consequences. The effect of urbanization on soil microbiome—an ecosystem component highly sensi-tive to anthropogenic disturbance—remains overlooked for the Arctic region. The research compared chemical and microbial properties of the natural Podzol soils and urban soils of Murmansk—the largest Arctic city. Particular attention was given to the profile distribution, which is almost com-pletely ignored by most microbial studies. Soil microbiome was investigated by the quantitative indicators based on fluorescence microscopy (microbial biomass) and PCR real-time methods (amount of rRNA genes copies of archaea, bacteria, and fungi). The principal changes in urban soils’ properties compared to the natural references included a shift in pH and an increase in C and nutrients’ contents, especially remarkable for the subsoil. The numbers of rRNA genes copies of archaea, bacteria, and fungi in urban topsoils (106 –1010, 109 –1010, and 107 –109, respectively) were lower than in Podzol; however, the opposite pattern was shown for the subsoil. Similarly, the total microbial biomass in urban topsoils (0.55–0.75 mg g−1 ) was lower compared to the 1.02 mg g−1 in Podzols, while urban subsoil microbial biomass was 2–2.5 times higher than in the natural conditions. Both for urban and natural soils and throughout the profiles, fungi were dominated by mycelium forms; however, the ratios of mycelium–spores were lower, and the amount of thin mycelium was higher in urban soils than in natural Podzols. Urbanization in the Arctic altered soil morphological and chemical properties and created a new niche for microbial development in urban subsoils; its contribution to biodiversity and nutrient cycling promises to become increasingly important under projected climate change

DR5-Selective TRAIL Variant DR5-B Functionalized with Tumor-Penetrating iRGD Peptide for Enhanced Antitumor Activity against Glioblastoma

TRAIL (TNF-related apoptosis-inducing ligand) and its derivatives are potentials for anticancer therapy due to the selective induction of apoptosis in tumor cells upon binding to death receptors DR4 or DR5. Previously, we generated a DR5-selective TRAIL mutant variant DR5-B overcoming receptor-dependent resistance of tumor cells to TRAIL. In the current study, we improved the antitumor activity of DR5-B by fusion with a tumor-homing iRGD peptide, which is known to enhance the drug penetration into tumor tissues. The obtained bispecific fusion protein DR5-B-iRGD exhibited dual affinity for DR5 and integrin αvβ3 receptors. DR5-B-iRGD penetrated into U-87 tumor spheroids faster than DR5-B and demonstrated an enhanced antitumor effect in human glioblastoma cell lines T98G and U-87, as well as in primary patient-derived glioblastoma neurospheres in vitro. Additionally, DR5-B-iRGD was highly effective in a xenograft mouse model of the U-87 human glioblastoma cell line in vivo. We suggest that DR5-B-iRGD may become a promising candidate for targeted therapy for glioblastoma

Mirror proteorhodopsins

Abstract Proteorhodopsins (PRs), bacterial light-driven outward proton pumps comprise the first discovered and largest family of rhodopsins, they play a significant role in life on the Earth. A big remaining mystery was that up-to-date there was no described bacterial rhodopsins pumping protons at acidic pH despite the fact that bacteria live in different pH environment. Here we describe conceptually new bacterial rhodopsins which are operating as outward proton pumps at acidic pH. A comprehensive function-structure study of a representative of a new clade of proton pumping rhodopsins which we name “mirror proteorhodopsins”, from Sphingomonas paucimobilis (SpaR) shows cavity/gate architecture of the proton translocation pathway rather resembling channelrhodopsins than the known rhodopsin proton pumps. Another unique property of mirror proteorhodopsins is that proton pumping is inhibited by a millimolar concentration of zinc. We also show that mirror proteorhodopsins are extensively represented in opportunistic multidrug resistant human pathogens, plant growth-promoting and zinc solubilizing bacteria. They may be of optogenetic interest