Murine models of colorectal cancer: the azoxymethane (AOM)/dextran sulfate sodium (DSS) model of colitis-associated cancer.

Background: Colorectal cancer (CRC) is the third most common cancer. It is a heterogeneous disease, including both hereditary and sporadic types of tumors. CRC results from complex interactions between various genetic and environmental factors. Inflammatory bowel disease is an important risk factor for developing CRC. Despite growing understanding of the CRC biology, preclinical models are still needed to investigate the etiology and pathogenesis of the disease, as well as to find new methods of treatment and prevention. Objectives: The purpose of this review is to describe existing murine models of CRC with a focus on the models of colitis-associated CRC. This manuscript could be relevant for experimental biologists and oncologists. Methodology: We checked PubMed and Google from 01/2018 to 05/2023 for reviews of CRC models. In addition, we searched PubMed from 01/2022 to 01/2023 for articles using the azoxymethane (AOM)/dextran sulfate sodium (DSS) CRC model. Results: Existing murine models of CRC include spontaneous, genetically engineered, transplantation, and chemically induced models. For the study of colitis-associated cancer (CAC), the AOM/DSS model is predominantly used. This model is very similar in histological and molecular characteristics to the human CAC, and is highly reproducible, inexpensive, and easy to use. Despite its popularity, the AOM/DSS model is not standardized, which makes it difficult to analyze and compare data from different studies. Conclusions: Each model demonstrates particular advantages and disadvantages, and allows to reproduce different subtypes or aspects of the pathogenesis of CRC.

Molecular and phenotypic distinctions of macrophages in tolerant and susceptible to hypoxia rats.

Individual hypoxia tolerance is a major influence on the course and outcome of infectious and inflammatory diseases. Macrophages, which play central roles in systemic inflammatory response and other immunity reactions, are subject to functional activation orchestrated by several transcription factors including hypoxia inducible factors (HIFs). HIF-1 expression levels and the lipopolysaccharide (LPS)-induced systemic inflammatory response severity have been shown to correlate with hypoxia tolerance. Molecular and functional features of macrophages, depending on the organisms resistance to hypoxia, can determine the severity of the course of infectious and inflammatory diseases, including the systemic inflammatory response. The purpose is the comparative molecular and functional characterization of non-activated and LPS-activated bone marrow-derived macrophages under normoxia in rats with different tolerance to oxygen deprivation. Hypoxia resistance was assessed by gasping time measurement in an 11,500 m altitude-equivalent hypobaric decompression chamber. Based on the outcome, the animals were assigned to three groups termed 'tolerant to hypoxia' (n = 12), 'normal', and 'susceptible to hypoxia' (n = 13). The 'normal' group was excluded from subsequent experiments. One month after hypoxia resistance test, the blood was collected from the tail vein to isolate monocytes. Non-activated and LPS-activated macrophage cultures were investigated by PCR, flow cytometry and Western blot methods. Gene expression patterns of non-activated cultured macrophages from tolerant and susceptible to hypoxia animals differed. We observed higher expression of VEGF and CD11b and lower expression of Tnfa, Il1b and Epas1 in non-activated cultures obtained from tolerant to hypoxia animals, whereas HIF-1α mRNA and protein expression levels were similar. LPS-activated macrophage cultures derived from susceptible to hypoxia animals expressed higher levels of Hif1a and CCR7 than the tolerant group; in addition, the activation was associated with increased content of HIF-1α in cell culture medium. The observed differences indicate a specific propensity toward pro-inflammatory macrophage polarization in susceptible to hypoxia rats.

Influence of Microplastics on Morphological Manifestations of Experimental Acute Colitis.

Microplastic pollution poses a threat to human health. It is possible that the increase in the incidence of inflammatory bowel disease is associated with exposure to microplastics. We investigated the effect of the consumption of polystyrene microparticles with a diameter of 5 µm at a dose of 2.3 mg/kg/day for 6 weeks on morphological changes in the colons of healthy male C57BL/6 mice and of mice with acute colitis induced by a 1% dextran sulfate sodium solution (DSS). In healthy mice, microplastics caused an increase in the number of endocrine cells, an increase in the content of highly sulfated mucins in goblet cells, an increase in the number of cells in the lamina propria, and a decrease in the volume fraction of macrophages. Microplastic consumption caused more severe acute colitis, which is characterized by a greater prevalence of ulcers and inflammation and a decrease in the content of neutral mucins in goblet cells.

Role of MicroRNAs in Regulation of Cellular Response to Hypoxia.

Hypoxia causes changes in transcription of the genes that contribute to adaptation of the cells to low levels of oxygen. The main mechanism regulating cellular response to hypoxia is activation of hypoxia-inducible transcription factors (HIF), which include several isoforms and control expression of more than a thousand genes. HIF activity is regulated at various levels, including by small non-coding RNA molecules called microRNAs (miRNAs). miRNAs regulate cellular response to hypoxia by influencing activation of HIF, its degradation, and translation of HIF-dependent proteins. At the same time, HIFs also affect miRNAs biogenesis. Data on the relationship of a particular HIF isoform with miRNAs are contradictory, since studies have been performed using different cell lines, various types of experimental animals and clinical material, as well as at different oxygen concentrations and durations of hypoxic exposure. In addition, HIF expression may be affected by the initial resistance of organisms to lack of oxygen, which has not been taken into account in the studies. This review analyzes the data on the effect of hypoxia on biogenesis and functioning of miRNAs, as well as on the effect of miRNAs on mRNAs of the genes involved in adaptation to oxygen deficiency. Understanding the mechanisms of relationship between HIF, hypoxia, and miRNA is necessary to develop new approaches to personalized therapy for diseases accompanied by oxygen deficiency.

Structure, Optical Properties and Physicochemical Features of LiNbO3:Mg,B Crystals Grown in a Single Technological Cycle: An Optical Material for Converting Laser Radiation.

Two series of LiNbO3:Mg:B crystals have been grown and studied. Two doping methods-have been used. The crystals-have been co-doped with Mg and a non-metallic dopant, B. The physicochemical features of the growth-have been considered for LiNbO3:Mg:B crystals obtained from a boron-doped melt. The charge-has been prepared using different technologies: homogeneous (HG) and solid-phase (SP) doping. The same two methods have been used to grow single-doped LiNbO3:Mg crystals. A control near-stoichiometric (NSLN) crystal-has been grown via the HTTSSG (high-temperature top-seeded solution growth) method from a congruent melt (Li/Nb ≈ 0.946) with 5.5 wt% K2O. The characteristics of the LiNbO3:Mg:B crystals-have been compared with those of the LiNbO3:Mg and NSLN crystals. Physicochemical and structural reasons have been established for the differences in the distribution coefficients of magnesium (KD) during the growth of the HG- and SP-doped LiNbO3:B:Mg and LiNbO3:Mg crystals. The optical characteristics of the LiNbO3:B:Mg crystals-have been studied via optical spectroscopy, laser conoscopy and photoinduced light scattering (PILS). The influence of boron on the microstructure, compositional and optical uniformities and optical damage resistance of the LiNbO3:Mg:B crystals-has been estimated. Optimal technological approaches to growing optically uniform LiNbO3:B:Mg crystals have been determined. LiNbO3:Mg:B crystals have been shown to have a significant advantage over the commercially used LiNbO3:Mg crystals since large LiNbO3:Mg:B crystals can be grown without stripes. Such stripes usually appear perpendicular to the growth axis. In addition, the photorefractive effect is suppressed in LiNbO3:Mg:B crystals at lower magnesium concentrations ([Mg] ≈ 2.5 mol%) than in LiNbO3:Mg ([Mg] ≈ 5.5 mol%).

Chamber Protection of Zinc with Ethylhexanoic Acid.

Chamber protection is a promising and quickly developing method of vapor-phase protection of metals against atmospheric corrosion by inhibitors. It was shown that chamber treatment with 2-ethylhexanoic acid (EHA) efficiently inhibits the initiation of zinc corrosion. The optimum conditions (temperature and duration) of zinc treatment with vapors of this compound were determined. If these conditions are met, adsorption films of EHA with thicknesses up to 100 nm are formed on the metal surface. It was found that their protective properties increase during the first day as zinc is exposed to air after chamber treatment. The anticorrosive action of adsorption films is due both to the surface being shielded from the corrosive environment and to the inhibition of corrosion processes on the active surface of the metal. Corrosion inhibition was caused by the ability of EHA to convert zinc to the passive state and inhibit its local anionic depassivation.

Growing, Structure and Optical Properties of LiNbO3:B Crystals, a Material for Laser Radiation Transformation.

Physical and chemical properties have been studied in lithium niobate (LiNbO3, LN) crystals grown by Czochralski from a boron doped melt. Optical uniformity and optical damage resistance of LiNbO3:B crystals have been compared with control crystals of nominally pure congruent (CLN) and near-stoichiometric (NSLN K2O) composition. LiNbO3:B crystals structure has been studied. Studied LiNbO3:B crystals have been grown from differently synthesized charges. The charges have been synthesized from a mixture Nb2O5:B-Li2CO3 using homogeneously doped Nb2O5:B precursor (sample 1, (B) = 0.0034 wt% in the charge) and by a direct solid phase synthesis from Nb2O5-Li2CO3-H3BO3 mixture (sample 2, (B) = 0.0079 wt% in the charge). Only traces of boron (10-5-10-4 wt%) have been detected in the samples. We have established that concentration of anti-site defects NbLi is lower in both LiNbO3:B than in CLN crystals. XRD analysis has confirmed that B3+ cations localize in faces of tetrahedral voids O4 of LN structure. The voids act as buffers at the anion sublattice distortion. Sample 1 has been shown to have a structure closer to NSLN K2O crystal than sample 2. We have also shown that the chemical purity of LN crystal increases compared to the melt purity because boron creates strong compounds with impurities in the melt system Li2O-Nb2O5-B2O3. Metals impurities thus stay in the melt and do not transfer to the crystal.

Genetic characteristics and treatment outcome in infants with KMT2A germline B-cell precursor acute lymphoblastic leukemia: Results of MLL-Baby protocol.

The aim of this study was to present the diagnostic and outcome characteristics of infants with germline status of KMT2A gene (KMT2A-g) B-cell precursor acute lymphoblastic leukemia (BCP-ALL) treated consistently according to the MLL-Baby protocol, a moderate-intensity protocol. Of the 139 patients enrolled in the MLL-Baby study, 100 (71.9%) carried different types of rearranged KMT2A (KMT2A-r), while the remaining 39 infants (28.1%) had KMT2A-g. KMT2A-g patients were generally older (77% older than 6 months), less likely to have a very high white blood cell count (greater than 100 × 109 /L), less likely to be central nervous system (CNS)-positive, and more likely to be CD10-positive. The 6-year event-free survival and overall survival rates for all 39 patients were 0.74 (standard error [SE] 0.07) and 0.80 (SE 0.07), respectively. Relapse was the most common adverse event (n = 5), with a cumulative incidence of relapse (CIR) of 0.13 (SE 0.06), while the incidence of a second malignancy (n = 1) and death in remission (n = 3) was 0.03 (SE 0.04) and 0.08 (SE 0.04), respectively. None of the initial parameters, including genetics and the presence of recently described fusions of NUTM1 and PAX5 genes, was able to distinguish patients with different outcomes. Only rapidity of response, measured as minimal residual disease (MRD) by flow cytometry, showed a statistically significant impact. Moderate-intensity therapy, as used in the MLL-Baby protocol in infants with KMT2A-g BCP-ALL, yields results comparable to other infant studies. Patients with a slow multicolor flow cytometry (MFC)-MRD response should be subjected to advanced therapies, such as targeted or immunotherapies.

Comparison of minimal residual disease measurement by multicolour flow cytometry and PCR for fusion gene transcripts in infants with acute lymphoblastic leukaemia with KMT2A gene rearrangements.

This study aimed to evaluate the concordance between minimal residual disease (MRD) results obtained by multicolour flow cytometry (MFC) and polymerase chain reaction for fusion gene transcripts (FGTs) in infants with acute lymphoblastic leukaemia (ALL) associated with rearrangement of the KMT2A gene (KMT2A-r). A total of 942 bone marrow (BM) samples from 123 infants were studied for MFC-MRD and FGT-MRD. In total, 383 samples (40.7%) were concordantly MRD-negative. MRD was detected by the two methods in 441 cases (46.8%); 99 samples (10.5%) were only FGT-MRD-positive and 19 (2.0%) were only MFC-MRD-positive. A final concordance rate of 87.4% was established. Most discordance occurred if residual leukaemia was present at levels close to the sensitivity limits. Neither the type of KMT2A fusion nor a new type of treatment hampering MFC methodology had an influence on the concordance rate. The prognostic value of MFC-MRD and FGT-MRD differed. MFC-MRD was able to identify a rapid response at early time-points, whereas FGT-MRD was a reliable relapse predictor at later treatment stages. Additionally, the most precise risk definition was obtained when combining the two methods. Because of the high comparability in results, these two rather simple and inexpensive approaches could be good options of high clinical value.

Freestanding high-aspect-ratio gold masks for low-energy, phase-based x-ray microscopy.

High-resolution, x-ray phase contrast microscopy, a key technique with promising potential in biomedical imaging and diagnostics, is based on narrow-slit high-aspect-ratio gold gratings. We present the development, fabrication details, and experimental testing of the freestanding 10µm thick gold membrane masks with an array of 0.9-1.5µm void slit apertures for a novel low-energy x-ray microscope. The overall mask size is 4 mm × 4 mm, with a grating pitch of 7.5µm, 6.0-6.6µm wide gold bars are supported by 3µm wide crosslinks at 400µm intervals. The fabrication process is based on gold electroplating into a silicon mold coated with various thin films to form a voltage barrier, plating base, and sacrificial layer, followed by the mold removal to obtain the freestanding gold membrane with void slit apertures. We discuss key aspects for the materials and processes, including gold structures homogeneity, residual stresses, and prevention of collapsing of the grid elements. We further demonstrate the possibility to obtain high-resolution, high contrast 2D images of biological samples using an incoherent, rotating anode x-ray tube.

The Role of Hypoxia-Inducible Factor in the Mechanisms of Aging.

Aging is accompanied by a reduction in the oxygen delivery to all organs and tissues and decrease in the oxygen partial pressure in them, resulting in the development of hypoxia. The lack of oxygen activates cell signaling pathway mediated by the hypoxia-inducible transcription factor (HIF), which exists in three isoforms - HIF-1, HIF-2, and HIF-3. HIF regulates expression of several thousand genes and is a potential target for the development of new drugs for the treatment of many diseases, including those associated with age. Human organism and organisms of laboratory animals differ in their tolerance to hypoxia and expression of HIF and HIF-dependent genes, which may contribute to the development of inflammatory, tumor, and cardiovascular diseases. Currently, the data on changes in the HIF expression with age are contradictory, which is mostly due to the fact that such studies are conducted in different age groups, cell types, and model organisms, as well as under different hypoxic conditions and mainly in vitro. Furthermore, the observed discrepancies can be due to the individual tolerance of the studied organisms to hypoxia, which is typically not taken into account. Therefore, the purpose of this review was to analyze the published data on the connection between the mechanisms of aging, basal tolerance to hypoxia, and changes in the level of HIF expression with age. Here, we summarized the data on the age-related changes in the hypoxia tolerance, HIF expression and the role of HIF in aging, which is associated with its involvement in the molecular pathways mediated by insulin and IGF-1 (IIS), sirtuins (SIRTs), and mTOR. HIF-1 interacts with many components of the IIS pathway, in particular with FOXO, the activation of which reduces production of reactive oxygen species (ROS) and increases hypoxia tolerance. Under hypoxic conditions, FOXO is activated via both HIF-dependent and HIF-independent pathways, which contributes to a decrease in the ROS levels. The activity of HIF-1 is regulated by all members of the sirtuin family, except SIRT5, while the mechanisms of SIRT interaction with HIF-2 and HIF-3 are poorly understood. The connection between HIF and mTOR and its inhibitor, AMPK, has been identified, but its exact mechanism has yet to be studied. Understanding the role of HIF and hypoxia in aging and pathogenesis of age-associated diseases is essential for the development of new approaches to the personalized therapy of these diseases, and requires further research.

Alzheimer's Disease and Inflammaging.

Alzheimer's disease is one of the most common age-related neurodegenerative disorders. The main theory of Alzheimer's disease progress is the amyloid-ß cascade hypothesis. However, the initial mechanisms of insoluble forms of amyloid-ß formation and hyperphosphorylated tau protein in neurons remain unclear. One of the factors, which might play a key role in senile plaques and tau fibrils generation due to Alzheimer's disease, is inflammaging, i.e., systemic chronic low-grade age-related inflammation. The activation of the proinflammatory cell phenotype is observed during aging, which might be one of the pivotal mechanisms for the development of chronic inflammatory diseases, e.g., atherosclerosis, metabolic syndrome, type 2 diabetes mellitus, and Alzheimer's disease. This review discusses the role of the inflammatory processes in developing neurodegeneration, activated during physiological aging and due to various diseases such as atherosclerosis, obesity, type 2 diabetes mellitus, and depressive disorders.

Harmful effects of the microplastic pollution on animal health: a literature review.

Background: The environmental pollution by microplastics is a global problem arising from the extensive production and use of plastics. Small particles of different plastics, measured less than 5 mm in diameter, are found in water, air, soil, and various living organisms around the globe. Humans constantly inhale and ingest these particles. The associated health risks raise major concerns and require dedicated evaluation. Objectives: In this review we systematize and summarize the effects of microplastics on the health of different animals. The article would be of interest to ecologists, experimental biologists, environmental physicians, and all those concerned with anthropogenic environmental changes. Methodology: We searched PubMed and Scopus from the period of 01/2010 to 09/2021 for peer-reviewed scientific publications focused on (1) environmental pollution with microplastics; (2) uptake of microplastics by humans; and (3) the impact of microplastics on animal health. Results: The number of published studies considering the effects of microplastic particles on aquatic organisms is considerable. In aquatic invertebrates, microplastics cause a decline in feeding behavior and fertility, slow down larval growth and development, increase oxygen consumption, and stimulate the production of reactive oxygen species. In fish, the microplastics may cause structural damage to the intestine, liver, gills, and brain, while affecting metabolic balance, behavior, and fertility; the degree of these harmful effects depends on the particle sizes and doses, as well as the exposure parameters. The corresponding data for terrestrial mammals are less abundant: only 30 papers found in PubMed and Scopus deal with the effects of microplastics in laboratory mice and rats; remarkably, about half of these papers were published in 2021, indicating the growing interest of the scientific community in this issue. The studies demonstrate that in mice and rats microplastics may also cause biochemical and structural damage with noticeable dysfunctions of the intestine, liver, and excretory and reproductive systems. Conclusions: Microplastics pollute the seas and negatively affect the health of aquatic organisms. The data obtained in laboratory mice and rats suggest a profound negative influence of microplastics on human health. However, given significant variation in plastic types, particle sizes, doses, models, and modes of administration, the available experimental data are still fragmentary and controversial.

Incidence and prognostic value of central nervous system involvement in infants with B-cell precursor acute lymphoblastic leukemia treated according to the MLL-Baby protocol.

AIM: The aim of the study was to evaluate the incidence and prognostic impact of central nervous system (CNS) involvement in infants with B-cell precursor acute lymphoblastic leukemia (BCP-ALL), as well as its relation with minimal residual disease (MRD) data. METHODS: A total of 139 consecutive infants with BCP-ALL from the MLL-Baby trial were studied. Cerebrospinal fluid (CSF) samples were investigated by microscopy of cytospin slides. MRD was evaluated according to the protocol schedule by flow cytometry and PCR for fusion gene transcripts (FGT). RESULTS: Involvement of the CNS at any level was found in 50 infants (36.0%). The incidence of CNS involvement was higher in patients with KMT2A gene rearrangements (44.0% for KMT2A-r vs. 15.4% for KMT2A-g, p = .003). The outcome of CNS-positive infants was significantly worse than that of CNS-negative infants, although this prognostic impact was limited to the KMT2A-r group (event-free survival 0.21 for CNS-positive vs. 0.48 for CNS-negative infants, p = .044). CNS-positive infants could not be treated successfully by conventional chemotherapy alone, irrespective of the rapidity of MRD response. In contrast, the combination of initial CNS negativity and FGT-MRD negativity identified a group comprising up to one-third of infants with KMT2A-r ALL who can be treated with chemotherapy and achieve very good outcomes (disease-free survival above 95%), and remaining patients should be allocated to receive other types of treatment. CONCLUSION: We can conclude that this combination of initial CNS involvement and MRD data can significantly improve risk-group allocation in future clinical trials enrolling infants with ALL.

Description of Oromurcia magadanensis sp. nov. (Acari, Oribatida, Ceratozetidae) from Russia, with remarks on biogeography of the genus Oromurcia Thor, 1930.

Species of the genus Oromurcia Thor, 1930 (Oribatida, Ceratozetidae) mainly have an arctic or alpine distribution in the Western Palaearctic region and Greenland. We describe a new species of Oromurcia from Northeast Asia (Magadan Region, Russia) based on adult and juvenile instars. Numerous populations of Oromurcia magadanensis sp. nov. were found under arctic-alpine plants in a narrow stream gully with large snow accumulation on the Ola Plateau (1023 m a.s.l.). Adults of Oromurcia magadanensis sp. nov. differ from those of Oromurcia bicuspidata and O. sudetica by their smaller size, the presence of clavate, distally broadly rounded bothridial seta, tutorium with several teeth distally, and the absence of striations on the lamella. Juvenile instars of the new species differ from those of O. bicuspidata and O. sudetica by the presence of medium-sized gastronotic setae in the larva, and long lateral and posterior gastronotic setae in nymphs. We compare adult and juveniles of Oromurcia magadanensis sp. nov. with those of other members of the ceratozetid subfamily Trichoribatinae Shaldybina, 1966 from arctic or alpine regions, for which ontogeny is known, and provide revised diagnoses for adult and juvenile members of Trichoribatinae. All Oromurcia species are associated with cold wet places (periglacial habitats, bogs and fens, alpine meadows, snowbeds, and, less frequently, montane coniferous forests) in Eastern and Western Palaearctic, but they are absent from High Arctic and Siberian regions that are ultra-cold in winter. This spatial disjunction argues for a former Trans-Palaearctic range that was possibly subdivided by reсurrent cryo-arid Pleistocene episodes.

HIF-Dependent Mechanisms of Relationship between Hypoxia Tolerance and Tumor Development.

Oxygen deficiency is one of the key pathogenetic factors determining development and severity of many diseases, including inflammatory, infectious diseases, and cancer. Lack of oxygen activates the signaling pathway of the hypoxia-inducible transcription factor HIF in cells that has three isoforms, HIF-1, HIF-2, HIF-3, regulating expression of several thousand genes. Throughout tumor progression, HIF activation stimulates angiogenesis, promotes changes in cell metabolism, adhesion, invasiveness, and ability to metastasize. HIF isoforms can play opposite roles in the development of inflammatory and neoplastic processes. Humans and laboratory animals differ both in tolerance to hypoxia and in the levels of expression of HIF and HIF-dependent genes, which may lead to predisposition to the development of certain oncological disorders. In particular, the ratio of different histogenetic types of tumors may vary among people living in the mountains and at the sea level. However, despite the key role of hypoxia at almost all stages of tumor development, basal tolerance to oxygen deficiency is not considered as a factor of predisposition to the tumor growth initiation. In literature, there are many works characterizing the level of local hypoxia in various tumors, and suggesting fundamental approaches to its mitigation by HIF inhibition. HIF inhibitors, as a rule, have a systemic effect on the organism, however, basal tolerance of an organism to hypoxia as well as the level of HIF expression are not taken into account in the process of their use. The review summarizes the literature data on different HIF isoforms and their role in tumor progression, with extrapolation to organisms with high and low tolerance to hypoxia, as well as on the prevalence of various types of tumors in the populations living at high altitudes.

Age-related differences in hypoxia-associated genes and cytokine profile in male Wistar rats.

Hypoxia tolerance of the organism depends on many factors, including age. High newborn organisms tolerance and high level of oxidative stress throughout aging were demonstrated by many studies. However, there is lack of investigations reflecting the expression of key hypoxia-inducible factor HIF in different age organisms in correlation to levels of pro-inflammatory and anti-inflammatory cytokines. Liver is a sensitive to hypoxia organ, and is an important organ in providing an acute reaction to infections - it synthesizes acute inflammation phase proteins, in particular, C-reactive protein. The aim of study was to determine relationship between age-related tolerance to hypoxia and HIF-1 and PHD2 (prolyl hydroxylase domain protein) expression levels in the liver and the production of cytokines in the spleen in newborn, prepubertal and adult Wistar rats. Newborn rats are characterized by high mRNA Hif-1α expression level in the liver, accompanied by a low content of HIF-1 protein and high level of PHD2. The growth in HIF-1α protein level throughout age is accompanied by the growth of pro-inflammatory cytokines level. Prepubertal animals are the least hypoxia resistant and their HIF-1α mRNA expression level was higher than in adult animals. The PHD2 activity in prepubertal animals was significantly reduced in comparison to newborn rats, and the HIF-1α protein level did not change. Further studies require the identification of additional mechanisms, determining the regulation of the HIF-1α level in prepubertal animals.

Distribution, habitats, and redescription of the rare mite species emIphidonopsis/em emsculptus/em Gwiazdowicz, 2004 (Mesostigmata: Ascidae).

Iphidonopsis sculptus Gwiazdowicz, 2004, is currently known only from the type locality in eastern Poland and a record in southwestern Finland (Huhta, 2016). Here, we record this species from twelve localities elsewhere (Europe, Siberia, Far East of Russia, Canada) indicating its broadly Holarctic geographical range. Another genus member, Iphidonopsis magnanalis (Ma Yin, 1999), is known only from China. About half of Iphidonopsis sculptus records are associated with litter of coniferous or mixed forests, but the others, including samples with juveniles (deutonymphs), were found in bracket fungi or under tree bark. The finding of two adult females on a bark beetle, Dryocoetes affaber (Mannerheim) (Coleoptera: Curculionidae: Scolytinae), suggests a phoretic association, though members of the closely related genus Zerconopsis Hull, 1918 as well as of all of the subfamily Arctoseiinae are known only from phoretic dispersal by nematoceran dipterans. The morphology of adults and an immature instar (deutonymph) of I. sculptus is redescribed and newly described, respectively, and illustrated in detail. A subdivision of the subfamily Arctoseiinae Evans, 1963 into three tribes is proposed-Arctoseiini Evans, 1963 (including Arctoseius Thor, 1930 and Iphidozercon Berlese, 1903), Zerconopsini tribe n. (Zerconopsis Hull, 1918; Xenoseius Lindquist Evans, 1965; and Iphidonopsis Gwiazdowicz, 2004), and Maxiniini tribe n. (Maxinia Lindquist Makarova, 2012).