Phases Of Regression Research Articles

Research on Recent Progress in the Treatment of Thin Endometrium

The endometrium is an important part of the uterus. The human endometrium is a complex and dynamic tissue that goes through phases of growth and regression during any menstrual cycle. A thin endometrium might be relevant to a lower rate of implantation as well as a higher rate of miscarriage. Several treatments have been developed for thin endometrium, such as granulocyte colony-stimulating factor, stem cell therapy, acupuncture and physical therapy, among others. These approaches have been shown to have effects on the endometrium related to reducing the area of fibrosis, increasing the number of glands, promoting angiogenesis, increasing endometrial thickness, improving tissue structure, and increasing pregnancy rates. This review summarizes the key role of these treatments in repairing thin endometrium and improving clinical pregnancy rates.

Predictors of Human Milk Feeding and Direct Breastfeeding for Infants with Single Ventricle Congenital Heart Disease: Machine Learning Analysis of the National Pediatric Cardiology Quality Improvement Collaborative Registry

To identify factors that support or limit human milk (HM) feeding and direct breastfeeding (BF) for infants with single ventricle congenital heart disease at neonatal stage 1 palliation (S1P) discharge and at stage 2 palliation (S2P) (∼4-6months old). Analysis of the National Pediatric Cardiology Quality Improvement Collaborative (NPC-QIC) registry (2016-2021; 67 sites). Primary outcomes were any HM, exclusive HM, and any direct BF at S1P discharge and at S2P. The main analysis involved multiple phases of elastic net logistic regression on imputed data to identify important predictors. For 1944 infants, the strongest predictor domain areas included preoperative feeding, demographics/social determinants of health, feeding route, clinical course, and site. Significant findings included: preoperative BF was associated with any HM at S1P discharge (OR=2.02, 95% CI=1.74-3.44) and any BF at S2P (OR = 2.29, 95% CI = 1.38-3.80); private/self-insurance was associated with any HM at S1P discharge (OR = 1.91, 95% CI = 1.58-2.47); and Black/African-American infants had lower odds of any HM at S1P discharge (OR = 0.54, 95% CI = 0.38-0.65) and at S2P (0.57, 0.30-0.86). Adjusted odds of HM/BF practices varied among NPC-QIC sites. Preoperative feeding practices predict later HM and BF for infants with single ventricle congenital heart disease; therefore, family-centered interventions focused on HM/BF during the S1P preoperative time are needed. These interventions should include evidence-based strategies to address implicit bias and seek to minimize disparities related to social determinants of health. Future research is needed to identify supportive practices common to high-performing NPC-QIC sites.

Research on Recent Progress in the Treatment of Thin Endometrium

Objective: The endometrium is an important part of the uterus. The human endometrium is a complex and dynamic tissue that goes through phases of growth and regression during any menstrual cycle. In this review, we review the literature on thin endometrium and discuss recent therapeutic tools and recent progress of thin endometrium to inform clinicians on better treatment options.

Double mutation of claudin-1 and claudin-3 causes alopecia in infant mice.

Hair follicles (HFs) undergo cyclic phases of growth, regression, and rest in association with hair shafts to maintain the hair coat. Nonsense mutations in the tight junction protein claudin (CLDN)-1 cause hair loss in humans. Therefore, we evaluated the roles of CLDNs in hair retention. Among the 27 CLDN family members, CLDN1, CLDN3, CLDN4, CLDN6, and CLDN7 were expressed in the inner bulge layer, isthmus, and sebaceous gland of murine HFs. Hair phenotypes were observed in Cldn1 weaker knockdown and Cldn3-knockout (Cldn1Δ/Δ Cldn3-/- ) mice. Although hair growth was normal, Cldn1Δ/Δ Cldn3-/- mice showed striking hair loss in the first telogen. Simultaneous deficiencies in CLDN1 and CLDN3 caused abnormalities in telogen HFs, such as an aberrantly layered architecture of epithelial cell sheets in bulges with multiple cell layers, mislocalization of bulges adjacent to sebaceous glands, and dilated hair canals. Along with the telogen HF abnormalities, which shortened the hair retention period, there was an enhanced proliferation of the epithelium surrounding HFs in Cldn1Δ/Δ Cldn3-/- mice, causing accelerated hair regrowth in adults. Our findings suggested that CLDN1 and CLDN3 may regulate hair retention in infant mice by maintaining the appropriate layered architecture of HFs, a deficiency of which can lead to alopecia.

North American Midcontinent Pennsylvanian cyclothems and their implications

Abstract Cyclothems are stratigraphic sequences deposited during glacial-eustatic transgressive–regressive inundations of land. Major cyclothems are most complete on lower shelves and become separated by exposure surfaces higher on the shelf. Minor cyclothems extend only onto lower shelves or are parasequences reflecting a reversal of sea level during general phases of transgression or regression. In Midcontinent North America, highstand condensed intervals of major cyclothems are conodont-rich black shales correlated eastwards into the Illinois and Appalachian basins. The number of cyclothems decreased by loss of lesser cyclothems across these basins, signifying an eastwards increase in their depositional elevations. Generalized palaeogeographical maps show that facies successions developed across these basins during a single major interglacial transgression and regression. The control of glacial eustasy by the interaction of Earth's orbital parameters, along with radiometric dating, allows subdivision of the cyclothem succession into c. 400 kyr groupings, which reflect the longest eccentricity cycle and facilitates global correlation. Delineation of the basinward extents of regression from the disappearance of exposure surfaces elucidates the history of basin-margin development. Major cyclothems that underwent reversals of general sea-level trend display ‘splays’ of lesser cycles onto the higher shelf. Geochemical cycles ‘nested’ within deepest-water shales on low shelves appear as thin nearshore facies between exposure surfaces at their high-shelf shorelines.

The megathermal ant genus Gesomyrmex (Formicidae: Formicinae), palaeoindicator of wide latitudinal biome homogeneity during the PETM

AbstractThe Palaeocene–Eocene Thermal Maximum (PETM) is one of the most important Cenozoic climatic events shaping modern biodiversity, yet reconstructions of its palaeobiomes remain controversial. Here we describe Gesomyrmex gallicus sp. nov., a new, extinct species of the ant genus Gesomyrmex Mayr, 1868, based on minor and major workers preserved in the early Eocene amber of Oise, France. Although there are only seven known extant species in the genus, all confined to warm and humid forests of SE Asia, the fossil record of Gesomyrmex indicates that the genus once radiated across Eurasia. The new species therefore provides direct evidence that this radiation likely co-occurred with the PETM. This observation constrains palaeoclimatic reconstructions of the Early Eocene by requiring the presence of an extensive, homogeneous and interconnected rainforest-like biome across palaeo-Eurasia, a scenario otherwise corroborated by pollen assemblages. The phases of regression of warm and humid forests and the widening of dry biomes probably occurred later during the Eocene, in between hyperthermals, and were probably less extensive than some computer models predicted.

Ovarian Follicular Dynamics and Its Functional Significance in Relation with Follicle Deviation, Vaginal Cytology, and Hormone Profiles in Llamas (Lama glama).

The reproductive physiology in camelid species has its particularities. The present study aimed to characterize the ovarian follicular dynamics and its functional significance in relation to follicular deviation, vaginal cytological characteristics, and sexual hormone profiles in llamas as the first report in South American camelids. Non-pregnant, multiparous llamas (Lama glama; n = 10; age: 48−72 mo.; BCS: 2.5−3.0) were enrolled in the study. The ultrasonographic assessment was carried out transvaginally and follicular ablation was performed (day 0) when follicles were larger than 7 mm. The follicle number and diameter were scored daily throughout the process for a proper evaluation of the deviated follicles and to monitor the presence of new follicle pools (1.5 to 2.5 mm diameter). Vaginal cytological evaluation (parabasal, intermediate, and superficial cells) was performed every other day until day 6. Endocrine profiles (17β estradiol, anti-Mullerian hormone, testosterone, and progesterone) during pre- and post-follicular deviation were determined by using the ELISA assay. Differential follicular dynamics both in the presence of a single dominant follicle (DF) and in codominance during the follicular deviation process were detected in llamas (p < 0.05). The percentage of superficial cells was the most related to the follicular wave phase. However, the percentage of parabasal, intermediate, and superficial cells was not related to the phases of follicular growth, dominance, and regression (p > 0.05). Differential patterns among the different hormone concentration levels regarding the 17β estradiol, anti-Mullerian hormone, progesterone, and testosterone during follicular deviation were observed, with the latter being significantly different along the deviation process (p < 0.05). In conclusion, the use of vaginal cytology assessment would not be sufficient to determine the follicular phases in llamas. Therefore, complementary analyses, such as ultrasonography and endocrine assessment, are strongly recommended to determine follicular dynamics during the follicular deviation.

Dynamic alterations in PD-1/PD-L1 expression level and immune cell profiles based on radiation response status in mouse tumor model.

Based on the immunologic effects of anti-cancer treatment and their therapeutic implications, we evaluated radiotherapy (RT)-induced dynamic alterations in programmed death-1 (PD-1)/PD ligand-1 (PD-L1) expression profiles. Local RT with 2 Gy × 5 or 7.5 Gy × 1 was administered to the CT26 mouse model. Thereafter, tumors were resected and evaluated at the following predefined timepoints according to radiation response status: baseline, early (immediately after RT), middle (beginning of tumor shrinkage), late (stable status with RT effect), and progression (tumor regrowth). PD-1/PD-L1 activity and related immune cell profiles were quantitatively assessed. RT upregulated PD-L1 expression in tumor cells from the middle to late phase; however, the levels subsequently decreased to levels comparable to baseline in the progression phase. RT with 2 Gy × 5 induced a higher frequency of PD-L1+ myeloid-derived suppressor cells, with a lesser degree of tumor regression, compared to 7.5 Gy. The proportion of PD-1+ and interferon (IFN)-γ+CD8α T cells continued to increase. The frequency of splenic PD-1+CD8+ T cells was markedly elevated, and was sustained longer with 2 Gy × 5. Based on the transcriptomic data, RT stimulated the transcription of immune-related genes, leading to sequentially altered patterns. The dynamic alterations in PD-1/PD-L1 expression level were observed according to the time phases of tumor regression. This study suggests the influence of tumor cell killing and radiation dosing strategy on the tumor immune microenvironment.

An integrative analysis of the lncRNA-miRNA-mRNA competitive endogenous RNA network reveals potential mechanisms in the murine hair follicle cycle.

Alopecia is a common progressive disorder associated with abnormalities of the hair follicle cycle. Hair follicles undergo cyclic phases of hair growth (anagen), regression (catagen), and rest (telogen), which are precisely regulated by various mechanisms. However, the specific mechanism associated with hair follicle cycling, which includes noncoding RNAs and regulation of competitive endogenous RNA (ceRNA) network, is still unclear. We obtained data from publicly available databases and performed real-time quantitative polymerase chain reaction validations. These analyses revealed an increase in the expression of miRNAs and a decrease in the expression of target mRNAs and lncRNAs from the anagen to telogen phase of the murine hair follicle cycle. Subsequently, we constructed the ceRNA networks and investigated their functions using enrichment analysis. Furthermore, the androgenetic alopecia (AGA) microarray data analysis revealed that several novel alopecia-related genes were identified in the ceRNA networks. Lastly, GSPT1 expression was detected using immunohistochemistry. Our analysis revealed 11 miRNAs (miR-148a-3p, miR-146a-5p, miR-200a-3p, miR-30e-5p, miR-30a-5p, miR-27a-3p, miR-143-3p, miR-27b-3p, miR-126a-3p, miR-378a-3p, and miR-22-3p), 9 target mRNAs (Atp6v1a, Cdkn1a, Gadd45a, Gspt1, Mafb, Mitf, Notch1, Plk2, and Slc7a5), and 2 target lncRNAs (Neat1 and Tug1) were differentially expressed in hair follicle cycling. The ceRNA networks were made of 12 interactive miRNA-mRNA pairs and 13 miRNA-lncRNA pairs. The functional enrichment analysis revealed the enrichment of hair growth-related signaling pathways. Additionally, GSPT1 was downregulated in androgenetic alopecia patients, possibly associated with alopecia progression. The ceRNA network identified by our analysis could be involved in regulating the hair follicle cycle.

Cell-mediated immunity and expression of MHC class I and class II molecules in dogs naturally infected by canine transmissible venereal tumor: Is there complete spontaneous regression outside the experimental CTVT?

The canine transmissible venereal tumor (CTVT) is a transplantable cancer with the ability evade the immune system, despite strict immune surveillance of the host; in this context, the relationship between inflammatory infiltrate and CTVT prognosis is not entirely understood. Natural canine transmissible venereal tumors of 22 dogs were evaluated for tumor/host interaction through clinical and epidemiological data, cyto-histopathological and cytogenetic findings and, mainly, cell-mediated immune response. We performed analysis on dogs with naturally acquired disease to provide information from the study of CTVT biology in its natural course, as the clinical evolution of the natural tumor in the host is not yet as well known as in the laboratory. Populations for T cell labeling (CD3+ CD4+ CD8+), B cells, NK cells, and macrophages were analyzed by flow cytometry in blood and tumor samples and expressions of MHC class I and class II molecules were quantified by immunohistochemistry and compared mainly between the phases of progression and regression in the natural CTVT. Dogs were also treated with vincristine sulfate and evaluated for chemotherapeutic response. Chemotherapy was effective in 88% of cases and there was no recurrence of the disease 12 months after the cure. Tumor cells displayed a numerical chromosomal variation between 54 and 72, not correlating with the host genotype. Although a greater expression of MHC molecules [18.6 ± 5.8% class I (P < 0.004) and 38.5 ± 6.5% class II (P < 0.003)] was observed in the regression phase, no significant effect was observed between the clinical phase of the tumor and cellular immune response in the analysis by flow cytometry (P > 0.05). We also found no correlation between cytological subtype of the tumor (plasmacytoid, lymphocytoid and mixed) and cellular immune response, suggesting that there is no difference in tumor immunogenicity. Here, we found no immunological evidence to support the theory of the immune-induced complete spontaneous regression in CTVT.

Transformation of Trolleybus Transport in Poland. Does In-Motion Charging (Technology) Matter?

Transport in cities is one of the most important sources of emissions. Electromobility is an essential element in the catalogue of activities of local authorities aimed at combating climate change. Over the years trolleybus transport has been characterised by both phases of development and regression and is still an essential component of zero-emission urban transport in about 300 cities worldwide. The development of electricity storage technology, especially in the form of a battery, has opened up new prospects for this mode of transport. A trolleybus equipped with a battery (in-motion charging technology) gains unique characteristics for operation independent of the catenary. This study presents the approach for assessing the development of in-motion charging for trolleybuses in all Polish cities operating this means of transport. A set of KPIs has therefore, been set and analysed. The analysis covers a comparison between 2014 and 2019, aimed at showing the development of technological innovations in this field. The results clearly show that in-motion charging technology leads to the development of trolleybus transport, although this development has mainly a qualitative dimension. A key factor determining the development of trolleybus transport using in-motion charging technology is progress in the development of traction batteries.

Dynamic Usage-based Principles in the Development of L2 Finnish Evaluative Constructions

AbstractThis study investigates the formal verbalizations of evaluation used by four beginning L2 learners of Finnish from a dynamic usage-based perspective. Longitudinal data collected weekly were used to investigate what kind of constructions learners use to express evaluation and how these interact and develop over time. The results show that when a new construction is acquired in the L2, another related construction might regress. The results also point to increased variability in the construction during a phase of rapid development and reduced variability in the phases of regression or slower progress. These findings add to our understanding of a developing L2 as a system in which changes in one aspect have the potential to bring about changes in interconnected aspects. The variability patterns found in the learners’ developmental trajectories add to the growing body of research that proposes variability as meaningful in the learning process.

The Molecular Anatomy of Mouse Skin during Hair Growth and Rest.

Skin homeostasis is orchestrated by dozens of cell types that together direct stem cell renewal, lineage commitment, and differentiation. Here, we use single-cell RNA sequencing and single-molecule RNA FISH to provide a systematic molecular atlas of full-thickness skin, determining gene expression profiles and spatial locations that define 56 cell types and states during hair growth and rest. These findings reveal how the outer root sheath (ORS) and inner hair follicle layers coordinate hair production. We found that the ORS is composed of two intermingling but transcriptionally distinct cell types with differing capacities for interactions with stromal cell types. Inner layer cells branch from transcriptionally uncommitted progenitors, and each lineage differentiation passes through an intermediate state. We also provide an online tool to explore this comprehensive skin cell atlas, including epithelial and stromal cells such as fibroblasts, vascular, and immune cells, to spur further discoveries in skin biology.

Immune cell regulation of the hair cycle.

The ability to manipulate the mammalian hair cycle will lead to novel therapies and strategies to combat all forms of alopecia. Thus, in addition to the epithelial-mesenchymal interactions in the hair follicle, niche and microenvironmental signals that accompany the phases of growth, regression and rest need to be scrutinized. Immune cells are well described in skin homeostasis and wound healing and have recently been shown to play an important role in the mammalian hair cycle. In this review, we will summarize our current knowledge of the role of immune cells in hair cycle control and discuss their relevance to human hair cycling disorders. Increased attention to this aspect of the hair cycle will provide new avenues to manipulate hair regeneration in humans and provide better insight into developing better ex vivo models of hair growth.

Mid Holocene Sea-Level Changes in and around Dhaka City, Bangladesh

Bengal basin, the largest fluvio-deltaic sedimentary system on Earth, is located in Bangladesh and three eastern states of India. Sediment accumulates in the basin from the Ganges, Brahmaputra, and Meghna (GBM) river systems and is dispersed into the Bay of Bengal, forming the largest submarine fan in the world. The present-day geomorphology is dominated by the extensive Holocene GBM floodplain and delta. The initiation of the modern GBM delta at the onset of the Pleistocene glacial maximum and its evolution to the present configuration are intricately related to Holocene fluvio-dynamic processes, eustatic sea-level changes, and tectonic movements. Quaternary System in Bengal basin has varieties of depositional environment. Sediment characteristics of different geomorphic units are different. Late Quaternary monsoon climatic episodes played the vital role in creating the present morphology of the Madhupur surfaces. During the Holocene, the central part of the basin experienced cyclic transgression and regression phase in several times. This was the evidence by mangrove pollens. The presence of mangrove pollen specially Phoenix paludosa, Avicennia sp, Phoenix sylvestris, Prosopis grandis, Sonneratiopollis sp found in Chatbari, Dubadia and Mirertek area of Dhaka city along with radiocarbon dating indicated that marine influence occurred during Mid Holocene time. Two phases of transgression and regression have been recorded during mid Holocene time. First transgression was noticed around 6500 cal BP and then a subsequent regression of the bay had been observed around 5500-3500 cal BP. This was again followed by another transgression episode around 3500-1500 cal BP. and then a regression during between 1500 cal BP onwards.

Multiple roles of hypoxia in bovine corpus luteum.

There has been increasing interest in the role of hypoxia in the microenvironment of organs, because of the discovery of hypoxia-inducible factor-1 (HIF1), which acts as a transcription factor for many genes activated specifically under hypoxic conditions. The ovary changes day by day during the estrous cycle as it goes through phases of follicular growth, ovulation, and formation and regression of the corpus luteum (CL). These phenomena are regulated by hypothalamic and pituitary hormones, sex steroids, peptides and cytokines, as well as oxygen conditions. Hypoxia strongly induces angiogenesis via transcription of a potent angiogenic factor, vascular endothelial growth factor (VEGF), that is regulated by HIF1. A CL forms with a rapid increase of angiogenesis that is mainly induced by HIF1-VEGF signaling. Hypoxia also contributes to luteolysis by down-regulating progesterone synthesis and by up-regulating apoptosis of luteal cells. This review focuses on recent studies on the roles of hypoxia- and HIF1-regulated genes in the regulation of bovine CL function.

A Role for Angiogenesis in Canine Cutaneous Histiocytoma Regression: Insights into an Old Clinical Enigma.

Canine Cutaneous Histiocytoma (CCH) is a Langerhans' cells benign tumour that undergoes spontaneous regression. The aim of the present study was to investigate the role of angiogenesis, a key step for tumour development, in CCH regression. 50 CCH samples were classified into 4 histological groups according to a regression scale, and evaluated for expression of vascular endothelial factor-A (VEGF-A) and its receptor VEGFR-2 as well as microvessel density (MVD). Tumours during early stages of the regressive process had a lower MVD compared to later stages, while CCH tumoural cells showed a limited production of VEGF, but higher levels of VEGFR-2. On the contrary, tumours in advanced phases of regression showed a higher number of neovessels, probably associated with the inflammatory state and the healing process. Our results suggest that angiogenesis may be compromised at early stages of histiocytoma development and this may be a determinant of regression in this tumour.

Developmental Stage-Specific Distribution of Macrophages in Mouse Mammary Gland.

Mammary gland development begins in the embryo and continues throughout the reproductive life of female mammals. Tissue macrophages (Mϕs), dependent on signals from the Mϕ colony stimulating factor 1 receptor (CSF1R), have been shown to regulate the generation, regression and regeneration of this organ, which is central for mammalian offspring survival. However, the distribution of Mϕs in the pre- and post-natal mammary gland, as it undergoes distinct phases of development and regression, is unknown or has been inferred from immunostaining of thin tissue sections. Here, we used optical tissue clearing and 3-dimensional imaging of mammary tissue obtained from Csf1r-EGFP mice. Whilst tissue Mϕs were observed at all developmental phases, their abundance, morphology, localization and association with luminal and basal epithelial cells exhibited stage-specific differences. Furthermore, sexual dimorphism was observed at E14.5, when the male mammary bud is severed from the overlying epidermis. These findings provide new insights into the localization and possible functions of heterogeneous tissue Mϕ populations in mammogenesis.

Nanoparticle Conjugation of Human Papillomavirus 16 E7-long Peptides Enhances Therapeutic Vaccine Efficacy against Solid Tumors in Mice.

Treatment of patients bearing human papillomavirus (HPV)-related cancers with synthetic long-peptide (SLP) therapeutic vaccines has shown promising results in clinical trials against premalignant lesions, whereas responses against later stage carcinomas have remained elusive. We show that conjugation of a well-documented HPV-E7 SLP to ultra-small polymeric nanoparticles (NP) enhances the antitumor efficacy of therapeutic vaccination in different mouse models of HPV+ cancers. Immunization of TC-1 tumor-bearing mice with a single dose of NP-conjugated E7LP (NP-E7LP) generated a larger pool of E7-specific CD8+ T cells with increased effector functions than unconjugated free E7LP. At the tumor site, NP-E7LP prompted a robust infiltration of CD8+ T cells that was not accompanied by concomitant accumulation of regulatory T cells (Tregs), resulting in a higher CD8+ T-cell to Treg ratio. Consequently, the amplified immune response elicited by the NP-E7LP formulation led to increased regression of large, well-established tumors, resulting in a significant percentage of complete responses that were not achievable by immunizing with the non-NP-conjugated long-peptide. The partial responses were characterized by distinct phases of regression, stable disease, and relapse to progressive growth, establishing a platform to investigate adaptive resistance mechanisms. The efficacy of NP-E7LP could be further improved by therapeutic activation of the costimulatory receptor 4-1BB. This NP-E7LP formulation illustrates a "solid-phase" antigen delivery strategy that is more effective than a conventional free-peptide ("liquid") vaccine, further highlighting the potential of using such formulations for therapeutic vaccination against solid tumors. Cancer Immunol Res; 6(11); 1301-13. ©2018 AACR.

Physical modeling experiments to study periodic activation of faults in seismic zones

Our study aimed to find a mechanism that controls preparation and subsequent full seismic activation of large faults that may act as sources of strong earthquakes. A large fault was physically modeled to investigate the dynamics of its deformation. The experiments were conducted on elastoviscoplastic and elastic models of the lithosphere. A digital camera was used to capture images in the course of the modeling experiments. The digital image correlation method (DIC) detected the moments of impulse activation and displacements along the entire fault or its major segment. Between the activation moments, the fault structure consists of segments, including active ones. Activation is directional and involves a few large segments of the fault, then numerous small ruptures, and the latter are gradually degenerating. The long-term deformation dynamics of the fault is represented by a regular sequence of its full activations. In most cases, each moment of activation correlates with a minimum dip angle of the repeatability curve (β) and a maximum value of information entropy (Si). We analysed in detail the deformation dynamics of the fault and in its wings between two full activation that occurred in a regular pattern, including the phases of regression and progression of the deformation process. The analysis revealed two similar scenarios in the evolution of the active segments and plastic micro slip faults within the active segments. In some intervals of time, deformation takes place considerably differently on the segments and the plastic micro slip faults. Such differences suggest that in the studies attempting to statistically predict and assess a large and potentially seismically hazardous fault zone, this zone should be considered spatially subdivided into a central narrow subzone (including the main fault plane) and two wide subzones framing the fault wings. According to our physical modeling results, the central subzone can be up to10 km wide, and the total width of all the subzones can amount to100 km or more. This study contributes to the development of the concepts of geodynamics of large faults in the seismic zones of the lithosphere and investigates one of the possible mechanisms preparing strong earthquakes in the seismic zones.