Influence of protein (human galectin-3) design on aspects of lectin activity

The concept of biomedical significance of the functional pairing between tissue lectins and their glycoconjugate counterreceptors has reached the mainstream of research on the flow of biological information. A major challenge now is to identify the principles of structure–activity relationships that underlie specificity of recognition and the ensuing post-binding processes. Toward this end, we focus on a distinct feature on the side of the lectin, i.e. its architecture to present the carbohydrate recognition domain (CRD). Working with a multifunctional human lectin, i.e. galectin-3, as model, its CRD is used in protein engineering to build variants with different modular assembly. Hereby, it becomes possible to compare activity features of the natural design, i.e. CRD attached to an N-terminal tail, with those of homo- and heterodimers and the tail-free protein. Thermodynamics of binding disaccharides proved full activity of all proteins at very similar affinity. The following glycan array testing revealed maintained preferential contact formation with N-acetyllactosamine oligomers and histo-blood group ABH epitopes irrespective of variant design. The study of carbohydrate-inhibitable binding of the test panel disclosed up to qualitative cell-type-dependent differences in sections of fixed murine epididymis and especially jejunum. By probing topological aspects of binding, the susceptibility to inhibition by a tetravalent glycocluster was markedly different for the wild-type vs the homodimeric variant proteins. The results teach the salient lesson that protein design matters: the type of CRD presentation can have a profound bearing on whether basically suited oligosaccharides, which for example tested positively in an array, will become binding partners in situ. When lectin-glycoconjugate aggregates (lattices) are formed, their structural organization will depend on this parameter. Further testing (ga)lectin variants will thus be instrumental (i) to define the full range of impact of altering protein assembly and (ii) to explain why certain types of design have been favored during the course of evolution, besides opening biomedical perspectives for potential applications of the novel galectin forms

Morphological variability of Colchicum laetum Steven (Colchidaceae) populations in the Lower Volga region and surrounding territories

Data on morphological variability of 13 populations of the species Colchicum laetum Steven, rare for the Russian Federation, in the territory of the Volgograd region, the Republic of Kalmykia and the Stavropol Territory are presented. A strong morphological variability of populations on the territory of the regions was noted both at the intra- and interpopulation level. Apparently, the heterogeneity of the environment in space, both signifi cant and local, is well felt by plants of populations that adapt to this heterogeneity in diff erent ways. However, the revealed change in the morphological parameters of C. laetum along the gradient of geographic coordinates indicates that, above all, weather and climatic factors determine the variability of morphological parameters in this species

Studying the Structural Significance of Galectin Design by Playing a Modular Puzzle: Homodimer Generation from Human Tandem-Repeat-Type (Heterodimeric) Galectin-8 by Domain Shuffling

Tissue lectins are emerging (patho) physiological effectors with broad significance. The capacity of adhesion/growth-regulatory galectins to form functional complexes with distinct cellular glycoconjugates is based on molecular selection of matching partners. Engineering of variants by changing the topological display of carbohydrate recognition domains (CRDs) provides tools to understand the inherent specificity of the functional pairing. We here illustrate its practical implementation in the case of human tandem-repeat-type galectin-8 (Gal-8). It is termed Gal-8 (NC) due to presence of two different CRDs at the N-and C-terminal positions. Gal-8N exhibits exceptionally high affinity for 3'-sialylated/sulfated beta-galactosides. This protein is turned into a new homodimer, i. e., Gal-8 (NN), by engineering. The product maintained activity for lactose-inhibitable binding of glycans and glycoproteins. Preferential association with 3'-sialylated/sulfated (and 6-sulfated) beta-galactosides was seen by glycan-array analysis when compared to the wild-type protein, which also strongly bound to ABH-type epitopes. Agglutination of erythrocytes documented functional bivalency. This result substantiates the potential for comparative functional studies between the variant and natural Gal-8 (NC)/Gal-8N

Sustainable Agricultural Development in the Coal Mining Region: Specific Characteristics and Conditions (a Case Study in the Kemerovo Region)

Agricultural development is an essential condition for the balanced socio-economic development of any region. The level of development in the agricultural sector impacts food security of the population in the given region, while the quality of agricultural output and the price level affects the standard and the quality of living of the population. The link between the level of agricultural development and socio-economic development of rural areas is important. On the one hand, well-developed agriculture preserves rural areas, contributes to job creation in rural areas and helps develop social rural infrastructure. On the other hand, human capacity of agriculture depends on the socio-economic development of rural areas. There are significant variations in agriculture among different regions. Industrial regions often have unfavourable conditions and factors for agricultural development, which is especially evident in mining areas with a specific demographic situation, unfavourable environmental conditions, low interest of business in the development of agriculture. This article uses a case study of the Kemerovo region–Kuzbass to analyze the peculiarities of agricultural development in the coal mining area. The article gives the basic indicators characterizing agricultural development, assesses the adverse limiting factors for agricultural development, assesses the implementation of agricultural functions in the industrial region and highlights the main prospects for agricultural development in the Kemerovo region–Kuzbass

Formation of competitive AIC in conditions of mining region sustainable development (on the example of Kuzbass)

This article considers the particular features of the development of the agro-industrial complex (AIC) in the conditions of mining regions. The Kuzbass (Kemerovo region) has been chosen as the object of analysis. A conceptual approach to the food security of the industrial region is presented, in the framework of which the main goals and objectives, principles and directions of development of the agricultural sector of industrial regions are shown. The article systematizes the results of previous studies of the authors related to the conditions and development factors of the AIC of the Kemerovo region. It has been established that the Kemerovo region as an industrial region is characterized by specific features of the AIC development which have evolved under the influence of climate, the available natural resources and the results of local economic activity. The current state of the Kuzbass agro-industry suggests that the region cannot ensure high competitiveness in the main types of agricultural products and their processed products. In the current economic conditions, introduction of deep processing of agricultural products on an innovative basis, production of functional products, integration and cooperation of producers, and improvement of production technologies may become the promising areas for the development of the agro-industrial complex of the Kemerovo region. The development of these areas will make it possible to produce agricultural products and food products with higher added value, and therefore, to increase the competitiveness of the agricultural sector in the region

Standard vs. Calorie-Dense Immune Nutrition in Haemodynamically Compromised Cardiac Patients: A Prospective Randomized Controlled Pilot Study

Background. The aim of study was to test the hypothesis that early enteral nutrition (EN) with calorie-dense and protein rich enteral formula improves enteral energy and protein delivery in critically ill cardiac patients. Methods. Prospective randomized pilot study of 40 ventilated adult patients undergoing elective cardiac surgery with use of cardiopulmonary bypass receiving inotropic support postoperatively. Patients were to receive either standard isocaloric (1000 Kcal/L and 38 g/L protein) early EN (n = 20) or calorie-dense and protein-rich (1300 Kcal/L and 66.7 g/L protein) early EN (n = 20). Results. The mean time to EN initiation was 27 ± 11 h. Early EN with the calorie-dense formula provided significantly more energy and protein enteral delivery on the 2nd, (p < 0.0001), 5th (p = 0.036), and 7th days (p = 0.024), and was associated with higher levels of prealbumin concentration on the 14th day (0.13 ± 0.01 g/L and 0.21 ± 0.1 g/L; p = 0.04) and significantly increased levels of transferrin on the 3rd, 5th, and 7th day (p < 0.05) after surgery. Conclusion. Present findings support hypothesis that early EN using a calorie-dense and protein rich formula leads to better enteral energy and protein delivery and higher levels of short-lived serum proteins

On the Bounds for a Two-Dimensional Birth-Death Process with Catastrophes

The model of a two-dimensional birth-death process with possible catastrophes is studied. The upper bounds on the rate of convergence in some weighted norms and the corresponding perturbation bounds are obtained. In addition, we consider the detailed description of two examples with 1-periodic intensities and various types of death (service) rates. The bounds on the rate of convergence and the behavior of the corresponding mathematical expectations are obtained for each example

First trimester thyroid function in pregnant women residing in Saint Petersburg (Russia): reference values and risk of gestational diabetes

Background. Subclinical hypothyroidism during pregnancy and gestational diabetes mellitus (GDM) is known to be associated with maternal and child morbidity. The concept of subclinical dysfunction of the thyroid gland in pregnant women depends on the population-specific and trimester-specific reference values so fixed universal cutoff concentrations for thyroid-stimulating hormone (TSH) that were recommended earlier now are put under the question. Population-specific and trimester-specific reference values have not been defined for pregnant women residing in Saint Petersburg. The data concerning the association of maternal thyroid status with GDM development are controversial. Aims. The aim of the study was to determine the reference values of TSH and free thyroxin (fT4) in the first trimester of pregnancy in women living in St. Petersburg, and to assess the relationship between thyroid status and the risk of subsequent development of GDM. Materials and methods. The levels of TSH, fT4 and thyroid peroxidase antibodies (TPO-Ab) were analyzed in 503 pregnant women before the 14th week of gestation. The women underwent oral glucose tolerance test (OGTT) at 2428 weeks to find out those with GDM. The association between thyroid function, thyroid autoimmunity and the risk of GDM we estimated. Results. The reference values for TSH were 0.07 4.40 mU /L, and for fT4 11.7 20.3 pmol/L. The prevalence of subclinical hypothyroidism in the 503 pregnant women was 16.9% according to the diagnostic criteria of TSH 2.5 mIU / L and 3.8% using our calculated reference interval. Hypothyroxinemia was registered in 5,3% using reference values recommended by diagnostic tests manufacturer and in 2,8% according to our calculated reference interval for fT4. GDM was diagnosed in 23% of women. Logistic regression analysis showed associations of hypothyroxinemia and TPO-Ab-positivity with the increased risk of GDM that remained significant after adjustments on age and body mass index (BMI) [adjusted OR (95% CI) = 7.39 (1.2742.93) for hypothyroxinemia, p=0.026; and adjusted OR (95% CI) = 2.02 (1.014.04) for TPO-Ab-positivity, p=0.047). Conclusions. Reference intervals for first trimester TSH and fT4 have been established for pregnant women living in St. Petersburg. Hypothyroxinemia and TPO-Ab-positivity were associated with the increased risk of GDM

Structural Characterization of Rat Galectin-5, an N-Tailed Monomeric Proto-Type-like Galectin

Galectins are multi-purpose effectors acting via interactions with distinct counterreceptors based on protein-glycan/protein recognition. These processes are emerging to involve several regions on the protein so that the availability of a detailed structural characterization of a full-length galectin is essential. We report here the first crystallographic information on the N-terminal extension of the carbohydrate recognition domain of rat galectin-5, which is precisely described as an N-tailed proto-type-like galectin. In the ligand-free protein, the three amino-acid stretch from Ser2 to Ser5 is revealed to form an extra β-strand (F0), and the residues from Thr6 to Asn12 are part of a loop protruding from strands S1 and F0. In the ligand-bound structure, amino acids Ser2–Tyr10 switch position and are aligned to the edge of the β-sandwich. Interestingly, the signal profile in our glycan array screening shows the sugar-binding site to preferentially accommodate the histo-blood-group B (type 2) tetrasaccharide and N-acetyllactosamine-based di- and oligomers. The crystal structures revealed the characteristically preformed structural organization around the central Trp77 of the CRD with involvement of the sequence signature’s amino acids in binding. Ligand binding was also characterized calorimetrically. The presented data shows that the N-terminal extension can adopt an ordered structure and shapes the hypothesis that a ligand-induced shift in the equilibrium between flexible and ordered conformers potentially acts as a molecular switch, enabling new contacts in this region