Local and global stability of equilibria for a class of chemical reaction networks

A class of chemical reaction networks is described with the property that each positive equilibrium is locally asymptotically stable relative to its stoichiometry class, an invariant subspace on which it lies. The reaction systems treated are characterized primarily by the existence of a certain factorization of their stoichiometric matrix and strong connectedness of an associated graph. Only very mild assumptions are made about the rates of reactions, and, in particular, mass action kinetics are not assumed. In many cases, local asymptotic stability can be extended to global asymptotic stability of each positive equilibrium relative to its stoichiometry class. The results are proved via the construction of Lyapunov functions whose existence follows from the fact that the reaction networks define monotone dynamical systems with increasing integrals

Проблема правової культури в історії філософсько-педагогічної думки

(uk) Стаття присвячена проблемі правової культури в історії філософсько-педагогічної думки

Heterosis effect in hybrid laying hens

The new original egg laying lines T, P and N selected at the Institute of Agriculture - Stara Zagora were used. Hybrid Т♂ × Р♀, Р♂ × Т♀ crosses were obtained and used for paternal line. Thereafter, the following breeding schedule of paternal and maternal lines was applied: Group I - (Р♂×Т♀)♂ ×N♀; group ІІ - (Т♂×Р♀)♂ ×N♀; group ІІІ - Т♂×N♀; and group ІV - Р♂×N♀. The production traits of original and hybrid birds were recorded: live weight at the age of 8 and 18 weeks, age of sexual maturity in days, 150 days egg production, average egg weight - at 2-week intervals until end of lay; livability, heterosis effect. The live weights of hybrids at 8 and 18 weeks of age were statistically significantly lower compared to original lines. The values of heterosis for this parameter were negative for all four hybrid combinations. The earliest beginning of egg lay occurred in (T♂×Р♀) ♂ ×N♀ (162.08 days of age) and Р♂×N♀ (163.11 days of age). The relative (%) heterosis for age of sexual maturity of studied hybrid combinations had moderate to low negative values. Average egg weights of hybrids were higher and the values of heterosis - positive for all four groups varying from 0.97% to 1.63%. The average 150 days egg production was lower in purebred lines compared to hybrids. The highest average 150 days egg production was determined in P♂×N♀ hybrids - 142 eggs. The heterosis effect for egg production in hybrids was significant

Effect of sex-linked dwarf gene on exterior appearance, productive performance and egg characteristics in a colored broiler dam line

The effect of sex-linked dwarf gene was investigated through comparison of dwarf hens with their full-sib normal sisters obtained by mating heterozygous males (DW/dw) to normal females (DW/_) from line F (used as maternal form for production of slow-growing colored chickens) with respect to the following traits: body weight, shank and keel length at 40 weeks of age, age of sexual maturity (at 50 % production), egg production, egg weight, feed intake, feed utilization, livability, fertility, hatchability and egg quality characteristics. The results demonstrated that the dw gene caused statistically significant reduction of body weight by 29.15 %, shank length by 20.17 %, keel length by 7 % and egg weight by 5.72 % (p<0.001). The hens with normal genotype attained sexual maturity 7 days earlier (p<0.001), but nevertheless, rate of lay was similar to that of mini forms. There were no considerable differences between both genetic groups with respect to livability percentage over the production cycle. Dwarf hens consumed by 23.38 % less feed (p<0.01) than normal sized hens and converted nutrients more efficiently by 12.69 % (p<0.05). The presence of dw gene in hen genotype increased the eggshell percentage, reduced egg yolk and albumen weights and had no effect on their quality. The positive effect of the sex-linked dwarf gene on economically important traits - feed intake and feed conversion, hatchability of eggs set, is a prerequisite for the development of more efficient broiler breeder hens for production of slow-growing chickens

Building a mechanistic mathematical model of hepatitis C virus entry

The mechanism by which hepatitis C virus (HCV) gains entry into cells is a complex one, involving a broad range of host proteins. Entry is a critical phase of the viral lifecycle, and a potential target for therapeutic or vaccine-mediated intervention. However, the mechanics of HCV entry remain poorly understood. Here we describe a novel computational model of viral entry, encompassing the relationship between HCV and the key host receptors CD81 and SR-B1. We conduct experiments to thoroughly quantify the influence of an increase or decrease in receptor availability upon the extent of viral entry. We use these data to build and parameterise a mathematical model, which we then validate by further experiments. Our results are consistent with sequential HCV-receptor interactions, whereby initial interaction between the HCV E2 glycoprotein and SR-B1 facilitates the accumulation CD81 receptors, leading to viral entry. However, we also demonstrate that a small minority of virus can achieve entry in the absence of SR-B1. Our model estimates the impact of the different obstacles that viruses must surmount to achieve entry; among virus particles attaching to the cell surface, around one third of viruses accumulate sufficient CD81 receptors, of which 4-8% then complete the subsequent steps to achieve productive infection. Furthermore, we make estimates of receptor stoichiometry; in excess of 10 receptors are likely to be required to achieve viral entry. Our model provides a tool to investigate the entry characteristics of HCV variants and outlines a framework for future quantitative studies of the multi-receptor dynamics of HCV entry

Golexanolone improves fatigue, motor incoordination and gait and memory in rats with bile duct ligation

\ua9 2023 The Authors. Liver International published by John Wiley &amp; Sons Ltd.Background and Aims: Many patients with the chronic cholestatic liver disease primary biliary cholangitis (PBC) show fatigue and cognitive impairment that reduces their quality of life. Likewise, rats with bile duct ligation (BDL) are a model of cholestatic liver disease. Current PBC treatments do not improve symptomatic alterations such as fatigue or cognitive impairment and new, more effective treatments are therefore required. Golexanolone reduces the potentiation of GABAA receptors activation by neurosteroids. Golexanolone reduces peripheral inflammation and neuroinflammation and improves cognitive and motor function in rats with chronic hyperammonemia. The aims of the present study were to assess if golexanolone treatment improves fatigue and cognitive and motor function in cholestatic BDL rats and if this is associated with improvement of peripheral inflammation, neuroinflammation, and GABAergic neurotransmission in the cerebellum. Methods: Rats were subjected to bile duct ligation. One week after surgery, oral golexanolone was administered daily to BDL and sham-operated controls. Fatigue was analysed in the treadmill, motor coordination in the motorater, locomotor gait in the Catwalk, and short-term memory in the Y-maze. We also analysed peripheral inflammation, neuroinflammation, and GABAergic neurotransmission markers by immunohistochemistry and Western blot. Results: BDL induces fatigue, impairs memory and motor coordination, and alters locomotor gait in cholestatic rats. Golexanolone improves these alterations, and this was associated with improvement of peripheral inflammation, neuroinflammation, and GABAergic neurotransmission in the cerebellum. Conclusion: Golexanolone may have beneficial effects to treat fatigue, and motor and cognitive impairment in patients with the chronic cholestatic liver disease PBC

Thermal- and Oxidative Stress Causes Enhanced Release of NKG2D Ligand-Bearing Immunosuppressive Exosomes in Leukemia/Lymphoma T and B Cells

Immune evasion from NK surveillance related to inadequate NK-cell function has been suggested as an explanation of the high incidence of relapse and fatal outcome of many blood malignancies. In this report we have used Jurkat and Raji cell lines as a model for studies of the NKG2D receptor-ligand system in T-and B cell leukemia/lymphoma. Using real-time quantitative RT-PCR and immunoflow cytometry we show that Jurkat and Raji cells constitutively express mRNA and protein for the stress-inducible NKG2D ligands MICA/B and ULBP1 and 2, and up-regulate the expression in a cell-line specific and stress-specific manner. Furthermore, we revealed by electron microscopy, immunoflow cytometry and western blot that these ligands were expressed and secreted on exosomes, nanometer-sized microvesicles of endosomal origin. Acting as a decoy, the NKG2D ligand-bearing exosomes downregulate the in vitro NKG2D receptor-mediated cytotoxicity and thus impair NK-cell function. Interestingly, thermal and oxidative stress enhanced the exosome secretion generating more soluble NKG2D ligands that aggravated the impairment of the cytotoxic response. Taken together, our results might partly explain the clinically observed NK-cell dysfunction in patients suffering from leukemia/lymphoma. The adverse effect of thermal and oxidative stress, enhancing the release of immunosuppressive exosomes, should be considered when cytostatic and hyperthermal anti-cancer therapies are designed

DNA metabarcoding of benthic algae and associated eukaryotes from Lake Baikal in the face of rapid environmental changes

Here we report new data describing the biodiversity of phytobenthic communities based on DNA-metabarcoding using the 18S rDNA marker and the Illumina MiSeq system. The study was initiated due to the blooming of filamentous algae (mainly of the genus Spirogyra) and cyanobacteria in the coastal zone of Lake Baikal under climate change and anthropogenic impact. The composition and taxonomic diversity of algae and other organisms associated with them on different sites of Lake Baikal (near Bolshoi Ushkaniy Island, in Listvennichny Bay) and in the Kaya (within the city of Irkutsk, located in the same drainage basin as Lake Baikal) were determined using DNAmetabarcoding. About 15 thousand reads of the 18S rRNA marker were obtained by applying NGS (next-generation sequencing). The species of algae dominating in the number of reads, as well as the difficult-to-identify taxa (Stramenopiles, Alveolata, Euglenozoa, Chromista, Rhizaria, Amoebozoa, etc.), which play an important role in the functioning and formation of the structure of algal communities, were revealed. The Shannon index of the communities studied ranges from 1.56 to 2.72. The advantages and weaknesses of using DNA-metabarcoding based on the 18S rRNA gene fragment for studying the structure of algal communities are shown. The advantage of this method is the possibility to more fully determine the diversity of eukaryotes taxa, which are difficult to identify by morphology, without involving a large number of specialists, while the disadvantage of the method is the distortion that may occur during the PCR. Here, ways of solving this problem are proposed. The results of the study show that the analysis of the minor component of the eukaryotic community in samples (organisms with low biomass) consisting of a mixture of multicellular and unicellular organisms requires a read-depths of at least 100,000 sequences per sample. In general, the DNA-metabarcoding method is recommended for studying the structure of algal communities and eukaryotes associated with them

Syncytiotrophoblast extracellular vesicles from pre-eclampsia placentas differentially affect platelet function

Pre-eclampsia (PE) complicates around 3% of all pregnancies and is one of the most common causes of maternal mortality worldwide. The pathophysiology of PE remains unclear however its underlying cause originates from the placenta and manifests as raised blood pressure, proteinuria, vascular or systemic inflammation and hypercoagulation in the mother. Women who develop PE are also at significantly higher risk of subsequently developing cardiovascular (CV) disease. In PE, the failing endoplasmic reticulum, oxidative and inflammatory stressed syncytiotrophoblast layer of the placenta sheds increased numbers of syncytiotrophoblast extracellular vesicles (STBEV) into the maternal circulation. Platelet reactivity, size and concentration are also known to be altered in some women who develop PE, although the underlying reasons for this have not been determined. In this study we show that STBEV from disease free placenta isolated ex vivo by dual placental perfusion associate rapidly with platelets. We provide evidence that STBEV isolated from normal placentas cause platelet activation and that this is increased with STBEV from PE pregnancies. Furthermore, treatment of platelets with aspirin, currently prescribed for women at high risk of PE to reduce platelet aggregation, also inhibits STBEV-induced reversible aggregation of washed platelets. Increased platelet reactivity as a result of exposure to PE placenta derived STBEVs correlates with increased thrombotic risk associated with PE. These observations establish a possible direct link between the clotting disturbances of PE and dysfunction of the placenta, as well as the known increased risk of thromboembolism associated with this condition