Morphometric aspects of studying the features of remodeling of atrial structures at postresection portal hypertension

Introduction. Removal of the left and right lateral lobes of the liver in white rats leads to postresection portal hypertension, which is characterized by dilation and plethora of the hepatic portal vein, mesenteric veins, esophageal and gastric veins, veins of the anterior abdominal wall, splenomegaly, ascites and multiorgan failure. Objective of the research: to study the features of remodeling of the structures of the atria at postresection portal hypertension histostereometrically. Materials of the research and their discussion. The peculiarities of remodeling the structures of the atria were histostoreometrically studied in 65 adult white male rats, which were divided into 3 groups: the 1- consisted of 20 intact animals, the 2 – 30 rats with postresection portal hypertension, which was modeled by removal of the left and right lateral lobes of the liver, the 3 – 15 animals with postresection portal hypertension and multiorgan failure. One month after the start of the experiment, rats were euthanized by bloodletting under conditions of thiopental anesthesia. Histological micropreparations were used to determine the diameters of cardiomyocytes of the left and right atria, diameters of their nuclei, nuclear-cytoplasmic relations, relative volumes of cardiomyocytes, capillaries, stroma, stromal-cardiomyocyte, capillary-cardiomyocyte relations, relative volumes of damaged cardiomyocytes. Quantitative indicators were processed statistically. Results of the research and their discussion. Histostereometrically, it was found that postresection portal hypertrophy leads to hypertrophy of atrial cardiomyocytes, their nuclei, growth of stromal structures, relative volumes of damaged cardiomyocytes, disorders of tissue and cellular structural homeostasis. The revealed features of remodeling of the studied structures dominated in the left atrium at combination of postresection portal hypertension with multiorgan failure. Conclusions. Postresection portal hypertension leads to pronounced remodeling of the structures of the left and right atria, characterized by hypertrophy of cardiomyocytes, changes in their nuclear-cytoplasmic relations, an increase of the relative volume of stroma, damaged cardiomyocytes, pronounced disorders of tissue and cellular structural homeostasis. The revealed morphological changes dominated in the left atrium at combination of postresection portal hypertension with multiorgan failure.

Complement in structure and immune homeostasis in placenta

Aberrant complement activation can induce “thrombo-inflammation” attacks to host tissue. Beside kidney and blood vessel, the placenta is also susceptible to these attacks. Complement dysregulation is recently classified as one of the new mechanisms leading to pregnancy disorders. Studies have indicated that dampening complement activation can ameliorate pregnancy outcomes. During pregnancy, the mother’s immune system is finely domesticated to accept the semi-allogeneic fetal antigens. As an important part of the innate immune system, some interesting changes have also taken place in complement system during pregnancy. The complement proteins are highly expressed in placenta, and their split products are increased. They are tuned in maintain placental immunity and structural homeostasis. An abundance of evidence shew that complement protein deficiency lead to autoimmunity disease and pathological pregnancy marked by excessive inflammation. Although complement suppressing strategies have been proven effective in treating some pathological pregnancy in individual case studies. we should take the dual role of the complement into consideration that fully and completely inhibit of complement may not be a wise choice.

Individual kinetochore-fibers locally dissipate force to maintain robust mammalian spindle structure

At cell division, the mammalian kinetochore binds many spindle microtubules that make up the kinetochore-fiber. To segregate chromosomes, the kinetochore-fiber must be dynamic and generate and respond to force. Yet, how it remodels under force remains poorly understood. Kinetochore-fibers cannot be reconstituted in vitro, and exerting controlled forces in vivo remains challenging. Here, we use microneedles to pull on mammalian kinetochore-fibers and probe how sustained force regulates their dynamics and structure. We show that force lengthens kinetochore-fibers by persistently favoring plus-end polymerization, not by increasing polymerization rate. We demonstrate that force suppresses depolymerization at both plus and minus ends, rather than sliding microtubules within the kinetochore-fiber. Finally, we observe that kinetochore-fibers break but do not detach from kinetochores or poles. Together, this work suggests an engineering principle for spindle structural homeostasis: different physical mechanisms of local force dissipation by the k-fiber limit force transmission to preserve robust spindle structure. These findings may inform how other dynamic, force-generating cellular machines achieve mechanical robustness.

Comparative assessment of morphological mechanisms of maintaining structural liver homeostasis in the dynamics of exposure to coal-rock dust and sodium fluoride on the body

Introduction. The impact on the body of such factors of the production environment as coal-rock dust and fluorine compounds leads to certain shift s in strict indicators of homeostasis at the system level. Maintaining the relative constancy of the internal environment of the body is provided by the functional consistency of all organs and systems, the leading of which is the liver. Organ repair plays a crucial role in restoring the structure of genetic material and maintaining normal cell viability. When this mechanism is damaged, the compensatory capabilities of the organ are disrupted, homeostasis is disrupted at the cellular and organizational levels, and the development of the main pathological processes is noted.The aim of the study is to compare the morphological mechanisms of maintaining structural homeostasis of the liver in the dynamics of the impact on the body of coal-rock dust and sodium fluoride.Materials and methods. Experimental studies were conducted on adult white male laboratory rats. Features of morphological mechanisms for maintaining structural homeostasis of the liver in the dynamics of exposure to coal-rock dust and sodium fluoride were studied on experimental models of pneumoconiosis and fluoride intoxication. For histological examination in experimental animals, liver sampling was performed after 1, 3, 6, 9, 12 weeks of the experiment.Results. The specificity of morphological changes in the liver depending on the harmful production factor was revealed. It is shown that chronic exposure to coal-rock dust and sodium fluoride is characterized by the development of similar morphological changes in the liver and its vessels from the predominance of the initial compensatory-adaptive to pronounced violations of the stromal and parenchymal components. Long-term inhalation of coal-rock dust at 1–3 weeks of seeding triggers adaptive mechanisms in the liver in the form of increased functional activity of cells, formation of double-core hepatocytes, activation of immunocompetent cells and endotheliocytes, ensuring the preservation of the parenchyma and the general morphostructure of the organ until the 12th week of the experiment. Exposure to sodium fluoride leads to early disruption of liver compensatory mechanisms and the development of dystrophic changes in the parenchyma with the formation of necrosis foci as early as the 6th week of the experiment.Conclusions. The study of mechanisms for compensating the liver structure in conditions of long-term exposure to coal-rock dust and sodium fluoride, as well as processes that indicate their failure, and the timing of their occurrence, is of theoretical and practical importance for developing recommendations for the timely prevention and correction of pathological conditions developing in employees of the aluminum and coal industry.The authors declare no conflict of interests.

Individual kinetochore-fibers locally dissipate force to maintain robust mammalian spindle structure

At cell division, the mammalian kinetochore binds many spindle microtubules that make up the kinetochore-fiber. To segregate chromosomes, the kinetochore-fiber must be dynamic and generate and respond to force. Yet, how it remodels under force remains poorly understood. Kinetochore-fibers cannot be reconstituted in vitro, and exerting controlled forces in vivo remains challenging. Here, we use microneedles to pull on mammalian kinetochore-fibers and probe how sustained force regulates their dynamics and structure. We show that force lengthens kinetochore-fibers by persistently favoring plus-end polymerization, not by increasing polymerization rate. We demonstrate that force suppresses depolymerization at both plus- and minus-ends, rather than sliding microtubules within the kinetochore-fiber. Finally, we observe that kinetochore-fibers break but do not detach from kinetochores or poles. Together, this work suggests an engineering principle for spindle structural homeostasis: different physical mechanisms of local force dissipation by the k-fiber limit force transmission to preserve robust spindle structure. These findings may inform how other dynamic, force-generating cellular machines achieve mechanical robustness.

Robust Stoichiometry of FliW-CsrA Governs Flagellin Homeostasis and Cytoplasmic Organization inBacillus subtilis

ABSTRACTFlagellin (Hag) is one of the most abundant proteins inBacillus subtilis. Here we show that each flagellar filament is assembled from ∼12,000 Hag monomers and that there is a cytoplasmic pool of Hag that is restricted to 5% of the total. Hag is thought to be restricted at the level of translation by a partner-switching mechanism involving FliW and the homodimeric RNA-binding protein CsrA (CsrAdimer). We further show that the mechanism of translation inhibition is hypersensitive due to a 1:1 ratio of Hag to FliW, a 1:1 inhibitory ratio of FliW to CsrAdimer, and a nearly 1:1 ratio of CsrAdimertohagtranscripts. Equimolarity of all components couples single-molecule detection of Hag export to compensatory translation and causes cytoplasmic Hag concentrations to oscillate around the level of FliW. We found that stoichiometry is ensured by genetic architecture, translational coupling, and the ability of CsrAdimerto restricthagtranscript accumulation. We further show that homeostasis prevents Hag hyperaccumulation that would otherwise cause severe defects in intracellular architecture, perhaps due to increased molecular crowding. We note that FliW-CsrA-mediated structural homeostasis has similarities to that seen with some toxin-antitoxin systems.IMPORTANCEThe intracellular concentration of flagellar filament protein Hag is restricted by the Hag-FliW-CsrA system inB. subtilis. Here we show that the Hag-FliW-CsrAdimersystem functions at nearly 1:1:1 stoichiometry and that the system is both robust with respect to perturbation and hypersensitive to the Hag intracellular concentration. Moreover, restriction of cytoplasmic Hag levels is important for maintaining proper intracellular architecture, as artificial Hag hyperaccumulation led to generalized spatial defects and a high frequency of minicell production. The Hag-FliW-CsrA system is conserved in the deeper branches of bacterial phylogeny, and we note that the Hag-FliW-CsrA “homeostasis module” resembles a toxin-antitoxin system where, by analogy, CsrA is the “toxin,” FliW is the “antitoxin,” and Hag is the target.

The influence of the ratio of liver cells and bone marrow in the implantable cell-engineering structures of the liver on the recovery efficiency of functional and morphological parameters in chronic liver failure

Aim: to determinate the most effective liver cells and multipotent mesenchymal stromal cells of bone marrow (MMSC BM) ratio into implantable cell engineering constructions (CECs) used for chronic liver failure (CLF) correcting.Materials and methods. For creating liver CECs it was used a biopolymer implant – a composition of a heterogeneous collagen-containing gel (BMCG) (Sphero®GEL trademark) containing viable liver cells and MMSC BM in the following ratios – 1 : 1; 5 : 1 and 10 : 1 respectively. CECs with different ratios of liver cells and MMSC BM were implanted into liver of rats in which chronic liver failure (CLF), was modeled by using CCl4. The effectiveness of the regulatory effects of CECs (with different cell ratios) on regenerative processes in livers were assessed by using biochemical, morphological and morphometric methods at different periods after their implantation.Results. Corrective effect of CECs with different cell composition on biochemical and morphological parameters of livers at chronic liver failure was established. During studying the liver CECs with various cell ratios of liver cells and MMSC BM (1 : 1; 5 : 1 and 10 : 1 respectively), it was found that the most optimal ratio of cells into the CECs is 5 : 1, because at this ratio of cells, there were a more distinct normalization of the morphological and functional liver parameters within 365 days after modeling CLF and maintenance of the structural homeostasis into the CECs. Themselves, which allows predicting their long-term regulatory effect on the liver tissue in CLF and maintaining its normal structural and functional state.Conclusion. The effective correction of chronic liver failure can be carried out by using the implanted liver CECs, in which donor liver cells and MMSC BM where presented in ratios – 1 : 1; 5 : 1 and 10 : 1. But analysis of prolonged correction of liver morphological and functional parameters at CECs using it was allow to recommend the preferences using of CECs with ratio 5 : 1, because prolonged preservation of structural homeostasis into these CECs makes possible to prognosticate their prolonged regulatory action on the liver tissue at CLF, especially for recipients on a waiting list for liver transplantation.