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The life-history theory suggests that parental experience of the environment is passed to offspring, which allows them to adapt to prevailing conditions. This idea is supported from the mother’s side, but to a much less extent from the father’s side. Here, we investigated the effect of immunising fathers on pre- and neonatal development and on immune and neuroendocrine phenotypes of their offspring in C57BL/6J mice. Nine days before mating, fathers were intraperitoneally injected with the immunogenic protein keyhole limpet hemocyanin (KLH). Females mated with immunised males had less pre-weaning mortality of newborns compared to those mated with control males. Although the antibody response to KLH was similar for the male offspring of control and immunised fathers, the mass indexes of their main immune organs and their androgen response differed significantly. The mass indexes of the thymus and spleen in adult male offspring of immunised fathers were higher compared with the control offspring. The plasma testosterone levels were significantly decreased after KLH administration in the male offspring of control but not of immunised fathers. This was correlated with changes in sperm average path and straight-line velocities. Finally, excitatory neurotransmitters prevailed over inhibitory ones in the amygdala of the progeny of immunised fathers, while in control offspring, the opposite occurred. This is indicative of complex behavioural changes in the offspring of immunised fathers, including sexual ones. Therefore, the paternal experience of foreign antigens modulates the immune and neuroendocrine systems of their progeny, suggesting possible survival and reproductive adaptations to parasitic pressure.

The latest vaccination campaign has actualized the potential impact of antigenic stimuli on reproductive functions. To address this, we mimicked vaccination’s effects by administering keyhole limpet hemocyanin (KLH ) to CD1 male mice and used their sperm for in vitro fertilization (IVF). Two-cell embryos after IVF with spermatozoa from control (C) or KLH-treated (Im) male mice were transferred to surrogate mothers mated with vasectomized control (C) or KLH-treated (Im) male mice, resulting in four experimental groups: C–C, Im–C, C–Im, and Im–Im. The pre-implantation losses were significantly lower in the Im–C group than in the C–Im group. At the same time, the resorption rates reduced markedly in the C–Im compared to the Im–C group. Embryo and placenta weights were significantly higher in the Im–Im group. Although the GM-CSF levels were lower in the amniotic fluid of the gestating surrogate mothers in the Im–Im group, they were strongly correlated with embryo mass. The number–size trade-off was only significant in the Im–Im group. This suggests a positive, cooperative effect of spermatozoa and seminal fluid from immune-primed males on embryo growth and the optimal distribution of surrogate mother maternal resources despite the negative impact of males’ antigenic challenge on the IVF success rate.

There is a canonical life-history trade-off between quantity and quality of offspring, but molecular determinants for this are unknown. Here, we show that knockout of tumor necrosis factor (TNF-KO) in mice switched a relation between the number and size of developing embryos from expectedly negative to unexpectedly positive. Depletion of TNFα imbalanced humoral and trophic maintenance of embryo growth during gestation with respect to the litter size. The levels of embryotrophic GM-CSF cytokine and placental efficiency attained positive correlations with the number and size of embryos in TNF-KO females. Thus, TNFα oversees mother’s resource allocations to balance embryo growth with the number of offspring. Consequently, this suggests an intricate link between the number-size trade-off and immunity given a pivotal role of TNFα in immune homeostasis.

Assisted reproductive technologies (ART) increasingly occupy the study of human reproduction. In addition, in developed countries they contribute to breeding of more than 50 % of cattle. In the management of collections of genetic lines of laboratory animals, these technologies are obligatory components of cryopreservation and rederivation. ART procedures include the development of early embryos outside the mother’s body and the high probability of incomplete synchronization of the physiological state of the surrogate mother and transplanted embryos. Since all this occurs at the stage of the highest susceptibility of embryos to epigenetic reprogramming, the full cycle of ART and its individual components can lead to stable phenotypic changes in the offspring. Their reality is confirmed by studies of the morphological and functional characteristics of sexually mature offspring of CD1 outbred mice, obtained using different variants of early embryo transplantation. Comparative studies of body mass and body composition, basal glucose level and response to glucose load (glucose-tolerance test – GTT) have been done on sexually mature males and females. Animals were separated in 4 groups according to the variant of embryo transplantation: group (control) – natural mating; group (2cl-bl) – incubation of 2-cell up to blastocysts; group (2cl-2cl) – removal and transplantation of the 2-cell embryo without incubation; group (Bl-bl) removal and transplantation of the blastocysts without incubation. All embryos were transplanted to recipient females of the same line. It was found that sexually mature offspring obtained with all variants of transplantations had a higher relative fat content and, correspondingly, lower lean mass compared to the control. This effect was more pronounced in females than in males. Unlike body compositions, embryo transplantations had a greater effect on basal glucose concentration and GTT in males than in females. In this case, the offspring of the 2cl-2cl and 2cl-bl groups were characterized by a higher tolerance to glucose load (GTT) compared with the control and the Bl-bl group. Stable deviations of body compositions and glucose homeostasis indices detected in experimental groups of progenies indicate the phenotypic significance of the embryo transplantations per se.

STUDY QUESTION Does the genotype of the surrogate mother modulate the body composition and immunity of her offspring? SUMMARY ANSWER C57BL/6J (B6) progenies carried by immunodeficient NOD SCID (NS) mothers had increased adaptive but decreased innate, immune responsiveness in comparison with the same genotype offspring carried by immunocompetent mothers, B6 and BALB/c (C); the B6 progenies carried by the same genotype mothers also showed higher body fat than the others. WHAT IS KNOWN ALREADY Differences in the major histocompatibility complex (MHC) genes between mother and foetus is considered as an important factor in prenatal embryo development, whereas the impact of such dissimilarity on the phenotype of the mature progeny is unclear. STUDY DESIGN, SIZE, DURATION Transplantation of two-cell mouse embryos into recipient females of the different MHC (H2) genotypes was used as an approach to simulate three variants of the immunogenic mother-foetus interaction: (i) bidirectional immunogenic dialogue between B6 (H2b haplotype) embryos and C (H2d haplotype) surrogate mother; (ii) one-way immunogenic interaction between B6 embryos and immunodeficient NS (H2g7 haplotype) surrogate mother and (iii) reduced immunogenetic dialogue between embryos and surrogate mother of the same H2b haplotype resulting in only a maternal response to HY antigens of male foetuses. Delivered by Caesarean section, pups were fostered by lactating B6 females and weighed after weaning (n = 171). Body mass and composition and innate and adaptive immunity were assessed in selected progeny groups at 9-11 weeks of age. PARTICIPANTS/MATERIALS, SETTING, METHODS The study was performed on the specific pathogen-free mouse, inbred strains C57BL/6J, NOD SCID and BALB/c. Plasma progesterone in pregnant females was measured by enzyme-linked immunosorbent assay (ELISA). Body composition was determined by magnetic resonance spectroscopy using a low-field NMR spectrometer (EchoMRI, USA). To assess peritoneal macrophage responses (innate immunity) to anthrax, lactate dehydrogenase (LDH) and interleukin-1 (IL-1β) were measured in a culture medium 24 h after the addition of both anthrax-lethal factor and anthrax-protective antigen. To assess adaptive immunity, 9-10 males in experimental groups were infected with Helicobacter hepaticus. Faeces collected 2 and 4 weeks after infection was used for quantitative assessment of the H. hepaticus DNA by real-time polymerase chain reaction. IgA, interferon (IFN-γ), tumour necrosis factor (TNFα), interleukin-17 (IL-17) and interleukin-10 (IL-10) in colon tissue and IgG in serum were determined in samples collected 4 weeks after gavage with H. hepaticus using ELISA. For statistical analyses, ANCOVA, post hoc least significant difference (LSD) test, Student's t-test, Spearman rank correlations and χ2 test were performed. P-value

Here, to study the relationship between anxiety levels with changes in the neurometabolic profile in the hippocampus and amygdala, an experimental predator stress model was reproduced in which Sprague-Dawley rats were exposed to cat urine for 10 minutes on a daily basis for 10 days. At the time of presentation of the stimulus, an online survey of behavioral reactions was conducted. Fear, aggressiveness, avoidance of stimulus and grooming were recorded. Fourteen days after the completion of the last stress exposure, the total level of anxiety was determined in the test of the“cross maze”. Using the method of in vivo NMR spectroscopy, the content of neurometabolites was determined in the hippocampus and in the amygdala. According to the peculiarities of behavioral reactions to a stressor, animals were retrospectively divided into two phenotypes. The first phenotype used a passive behavioral strategy, and the second phenotype was active. In animals of the first phenotype, the indicators of anxiety behavior remained at the control level. In animals of the second phenotype, a decrease in anxiety was observed. Animals of the second phenotype showed elevated levels of lactate in the hippocampus compared to animals of the first phenotype, and the lowest N-acetylaspartate levels significantly differed from those in the control and the first phenotype animals. In the amygdala, in animals of the second phenotype, the content of taurine is sharply reduced in comparison with those in the control and the animals of the first phenotype. Thus, the results obtained indicate a relationship of post-stress changes in anxiety, with the peculiarities of the behavioral reactions presented at the moment of the immediate action of the stressor. Among the hippocampal and amygdala neurometabolites, the most informative for the characterization of the anxiolytic action of the predator stress are identified.

Despite the advances in medicine, about 4 million children under the age of 6 months die annually around the world due to infection, which is 450 deaths per hour (UNISEF, 2009). The degree of development of the immune system of children born in time is determined by many factors, including the immunogenetic similarity or difference of mother and fetus organisms, which, in turn, is due to the genotypes of mating pairs, as well as the selection of surrogate mothers duringin vitrofertilization. From our review of the literature, it follows that immunogenetic interactions of mother and fetus organisms, which occur at all stages of pre- and postnatal development, have a signifcant effect on the resistance of offspring to infections and allergens. Before implantation, the mother’s immune responses are formed under the influence of semen fluid antigens, leukocytes and cytokines, as well as under the influence of the genes of the major histocompatibility complex, which are expressed in embryos at the stage of two cells. After implantation, transplacental transfer of immunoglobulins and immunocompetent cells becomes of immunomodulating importance. It is important to emphasize that, although substances with a high molecular weight usually do not pass through the placenta, this rule does not apply to immunoglobulin G (IgG), which, with a molecular weight of about 160 kDa, overcomes the transplacental barrier due to binding to the fetal Fc receptor. The level of IgG in newborns usually correlates with the level of maternal antibodies. During the period of natural feeding, the immune protection of newborns is provided by the mechanisms of innate immunity and the factors of humoral immunity of mothers. It has been shown that immunoglobulins from the milk of many animal species are transferred through the neonatal intestinal epithelium to the blood. Since breast milk contains large amounts of various immunoactive components, including proteins, cytokines, hormones, immunoglobulins, exosomes containing micro-RNA, and viable immune cells, the immunomodulating effects of breast milk persist even after elimination of maternal immunoglobulins from the blood of the offspring, up to maturation. Analysis of a large body of experimental data shows that the study of mechanisms of “motherfetus” and “mother-newborn” interactions are the basis of a knowledge base needed to fnd means of life-long directed modulation of the descendants’ immune status.

Finding novel biomarkers for human pathologies and predicting clinical outcomes for patients is challenging. This stems from the heterogeneous response of individuals to disease and is reflected in the inter-individual variability of gene expression responses that obscures differential gene expression analysis. Here, we developed an alternative approach that could be applied to dissect the disease-associated molecular changes. We define gene ensemble noise as a measure that represents a variance for a collection of genes encoding for either members of known biological pathways or subunits of annotated protein complexes and calculated within an individual. The gene ensemble noise allows for the holistic identification and interpretation of gene expression disbalance on the level of gene networks and systems. By comparing gene expression data from COVID-19, H1N1, and sepsis patients we identified common disturbances in a number of pathways and protein complexes relevant to the sepsis pathology. Among others, these include the mitochondrial respiratory chain complex I and peroxisomes. This suggests a Warburg effect and oxidative stress as common hallmarks of the immune host–pathogen response. Finally, we showed that gene ensemble noise could successfully be applied for the prediction of clinical outcome namely, the mortality of patients. Thus, we conclude that gene ensemble noise represents a promising approach for the investigation of molecular mechanisms of pathology through a prism of alterations in the coherent expression of gene circuits.

ATP-dependent chromatin remodelers control the accessibility of genomic DNA through nucleosome mobilization. However, the dynamics of genome exploration by remodelers, and the role of ATP hydrolysis in this process remain unclear. We used live-cell imaging ofDrosophilapolytene nuclei to monitor Brahma (BRM) remodeler interactions with its chromosomal targets. In parallel, we measured local chromatin condensation and its effect on BRM association. Surprisingly, only a small portion of BRM is bound to chromatin at any given time. BRM binds decondensed chromatin but is excluded from condensed chromatin, limiting its genomic search space. BRM-chromatin interactions are highly dynamic, whereas histone-exchange is limited and much slower. Intriguingly, loss of ATP hydrolysis enhanced chromatin retention and clustering of BRM, which was associated with reduced histone turnover. Thus, ATP hydrolysis couples nucleosome remodeling to remodeler release, driving a continuous transient probing of the genome.

Vavilovskii Zhurnal Genetiki i Selektsii = Vavilov Journal of Genetics and Breeding. 2019;23(5):582-587 (in Russian) Page 587, in Acknowledgements instead of The animals and behavioral testing are supported by the budget project (No. 0324-2019-0041). The MRI study is supported by the budget project (No. 0259-2019-0004). All studies are implemented using the equipment of Center for Genetic Resources of Laboratory Animals at ICG SB RAS, supported by the Ministry of Education and Science of Russia (Unique ID# of the project: RFMEFI62117X0015). should read The animals and behavioral testing are supported by the budget project (No. 0324-2019-0041). The MRI study is supported by the budget project (No. 0259-2019-0004). All studies are implemented using the equipment of Center for Genetic Resources of Laboratory Animals at ICG SB RAS, supported by the Ministry of Education and Science of Russia (Unique ID# of the project: RFMEFI62117X0015). The study was conducted within the basic part of the state task of the Ministry of Science and Higher Education of the Russian Federation (No. 17.7255.2017/8.9). The original article can be found under DOI 10.18699/VJ19.528.Вавиловский журнал генетики и селекции. 2019;23(5):582-587На странице 587 в разделе Благодарности вместо «Работа с животными и поведенческое тестирование выполнены в рамках бюджетного проекта № 0324-2019-0041. Томографические данные получены на средства бюджетного проекта № 0259-2019-0004. Исследование проведено с использованием оборудования ЦКП «Центр генетических ресурсов лабораторных животных» ФИЦ ИЦиГ СО РАН, поддержанного Минобрнауки России (уникальный идентификатор проекта RFMEFI62117X0015)».следует читать: «Работа с животными и поведенческое тестирование выполнены в рамках бюджетного проекта № 0324-2019-0041. Томографические данные получены на средства бюджетного проекта № 0259-2019-0004. Исследование проведено с использованием оборудования ЦКП «Центр генетических ресурсов лабораторных животных» ФИЦ ИЦиГ СО РАН, поддержанного Минобрнауки России (уникальный идентификатор проекта RFMEFI62117X0015). Исследование выполнено в рамках базовой части государственного задания Минобрнауки России (№ 17.7255.2017/8.9)».Оригинальная статья может быть найдена по DOI 10.18699/VJ19.528.

The ability to deliver particulated xenobiotics and therapeutic drugs directly from the nasal cavity to the central nervous system, bypassing the hemato-encephalic barrier, determines a high importance of investigation of factors influencing this process. It was shown that the bioavailability of solid particles is influenced by their size and surface charge. At the same time, the impact of a crystal structure (crystalline/amorphous) has been poorly investigated. In this study, using sexually mature male C57BL/6J mice, we analyzed the efficiency of the nose-to-brain transport of crystalline and amorphous manganese oxide nanoparticles. T1-weighted magnetic resonance imaging (MRI) was used to evaluate the accumulation of manganese nanoparticles in olfactory bulb (OB) and olfactory epithelium (OE). So, it has been established that amorphous particles have higher accumulation rate in OE and OB in comparison with crystalline particles after their intranasal administration. The unequal ability of amorphous and crystalline particles to overcome the mucosal layer covering the OE may be one of the possible reasons for the different nose-to-brain transport efficiency of particulated matter. Indeed, the introduction of mucolytic (dithiothreitol) 20 minutes prior to intranasal particle application did not influence the accumulation of amorphous particles in OE and OB, but enhanced the efficiency of crystalline nanoparticle entry. Data on the different intake of amorphous and crystalline nanoparticles from the nasal cavity to the brain, as well as the evidence for the key role of the mucosal layer in differentiating the penetrating power of these particles will be useful in developing approaches to assessing air pollution and optimizing the methods of inhalation therapy.

We analyzed the whole-genome experimental maps of nucleosomes in Drosophila melanogaster and classified genes by the expression level in S2 cells (RPKM value, reads per kilobase million) as well as the number of tissues in which a gene was expressed (breadth of expression, BoE). Chromatin in 5&prime, regions of genes we classified on four states according to the hidden Markov model (4HMM). Only the Aquamarine chromatin state we considered as Active, while the rest three states we defined as Non-Active. Surprisingly, about 20/40% of genes with 5&prime, regions mapped to Active/Non-Active chromatin possessed the minimal/at least modest RPKM and BoE. We found that regardless of RPKM/BoE the genes of Active chromatin possessed the regular nucleosome arrangement in 5&prime, regions, while genes of Non-Active chromatin did not show respective specificity. Only for genes of Active chromatin the RPKM/BoE positively correlates with the number of nucleosome sites upstream/around TSS and negatively with that downstream TSS. We propose that for genes of Active chromatin, regardless of RPKM value and BoE the nucleosome arrangement in 5&prime, regions potentiates transcription, while for genes of Non-Active chromatin, the transcription machinery does not require the substantial support from nucleosome arrangement to influence gene expression.

Finding novel biomarkers for human pathologies and predicting clinical outcomes for patients is rather challenging. This stems from the heterogenous response of individuals to disease which is also reflected in the inter-individual variability of gene expression responses. This in turn obscures differential gene expression analysis (DGE). In the midst of the COVID-19 pandemic, we wondered whether an alternative to DGE approaches could be applied to dissect the molecular nature of a host-response to infection exemplified here by an analysis of H1N1 influenza, community/hospital acquired pneumonia (CAP) and sepsis. To this end, we turned to the analysis of ensemble gene noise. Ensemble gene noise, as we defined it here, represents a variance within an individual for a collection of genes encoding for either members of known biological pathways or subunits of annotated protein complexes. From the law of total variance, ensemble gene noise depends on the stoichiometry of the ensemble genes’ expression and on their average noise (variance). Thus, rather than focusing on specific genes, ensemble gene noise allows for the holistic identification and interpretation of gene expression disbalance on the level of gene networks and systems. Comparing H1N1, CAP and sepsis patients we spotted common disturbances in a number of pathways/protein complexes relevant to the sepsis pathology which lead to an increase in the ensemble gene noise. Among others, these include mitochondrial respiratory chain complex I and peroxisomes which could be readily targeted for adjuvant treatment by methylene blue and 4-phenylbutyrate respectively. Finally, we showed that ensemble gene noise could be successfully applied for the prediction of clinical outcome, namely mortality, of CAP and sepsis patients. Thus, we conclude that ensemble gene noise represents a promising approach for the investigation of molecular mechanisms of a pathology through a prism of alterations in coherent expression of gene circuits.

The reproducibility of results obtained with rodent models depends on the genetic purity of the strain and the stability of the environment. However, another potential factor is changes in the gut microbiota due to the transmission of mother’s bacteria during embryo transfer. In this study, we demonstrate the transmission of the microbiota and immune cell blood phenotype to the offspring of 2 strains, C57BL/6JNskrc and BALB/cJNskrc, from surrogate dams of different genotypes. Interstrain embryo transfer resulted in a change in the number of Enterococcus spp. organisms, as shown by quantitative PCR analysis. The number of blood leukocytes was also affected, as estimated by flow cytometry. The number of blood leukocytes, including B cells and helper T cells, and the number of Enterococcus spp. organisms in male C57BL/6JNskrc offspring bornto BALB/cJNskrc surrogate dams became similar to those of male BALB/cJNskrc mice born to BALB/cJNskrc dams. Likewise, the same parameters of male BALB/cJNskrc mice born to C57BL/6JNskrc dams became similar to those of male C57BL/6JNskrc offspring. Researchers should be aware of the possible transmission of the dam’s microbiota and immune cell phenotypes to the experimental strains when planning embryo transfer experiments, because these factors could affect the experimental outcomes or the reproducibility of experimental results.

The effect of urine chemosignals of domestic male cats (Felis catus L.) on the stability of the bone marrow cell genome and corticosterone level in blood plasma of recipient mice (Mus musculus L.) is studied. It is demonstrated that a two-hour sniffing of volatile chemosignals leads to an increase in the frequency of bone marrow cells with damaged DNA, while 24 h exposure to chemosignals leads to an increase of chromosomal aberrations frequency in these cells. Thus, the effect of genomic instability induction in bone marrow cells of house mice by predator’s chemosignals is for the first time demonstrated in the work. At the same time, no increase in the corticosterone level is detected in the blood plasma either 30 or 60 min after the beginning of the exposure to the chemosignals of cat urine (CU). The physiological factors contributing to DNA damages accumulation in bone marrow cells, as well as the long-term consequences of the effect of these chemosignals on the genome stability, are discussed.

Deviations in brain metabolism are the result of longterm pathological processes, which finally are manifested as symptoms of Parkinson’s or Alzheimer’s diseases or multiple sclerosis and other neuropathologies, as for example diabetic neuropathy. A deficiency of available energy for brain cells under neurodegenerative diseases is either developed due to age-dependent underexpression of genes that encode glycolytic enzymes or induced due to the uncoupling of oxidation and phosphorylation that could be mediated by inflammatory cytokines. Since the activity of many enzymes is under the control of adenosine triphosphate (ATP) or cofactors, such as nicotinamide adenine dinucleotide (NADH) and nicotinamide adenine dinucleotide phosphate (NADPH), energy deficiency can cause metabolic changes in brain tissue. Some clinical studies using proton nuclear magnetic resonance spectroscopy (1H NMR spectroscopy) revealed metabolic changes in brain tissue in patients with neurodegenerative diseases. However, data from different authors are quite contradictory, probably because of the complex genesis of metabolic disorders. In the present study, we tested the hypothesis of multidirectional changes in metabolism under the impact of the oxidation and phosphorylation uncoupler 2,4-dinitrophenol (2,4-DNP) and under the impact of 2-deoxy-Dglucose (2-DG), blocking the access of glucose to the brain cells. 1H NMR spectroscopy showed that 2-DG leads to the predominance of excitatory (glutamine + glutamate) neurotransmitters over inhibitory ones (gamma-aminobutyric acid), and 2,4 DNP causes opposite effects. The biochemical mechanisms of the observed changes require a special study, but it can be noted that the ATP deficiency caused by inhibition of glycolysis and the ATP deficiency caused by the uncouplers are accompanied by differently directed changes in the intensity of the tricarboxylic acid cycle. These changes in the intensity of the Krebs cycle are correlated with differently directed changes in the balance of the exciting and inhibitory neurotransmitters. The obtained results show that 1H NMR spectroscopy can be an effective method of differentiated lifetime assessment of the available energy deficit caused by a general suppression of energy exchange in nerve cells or oxidation and phosphorylation uncoupling.

Contactins (Cntn1-6) are a family of neuronal membrane proteins expressed in the brain. They are required for establishing cell-to-cell contacts between neurons and for the growth and maturation of the axons. In humans, structural genomic variations in the Contactin genes are implicated in neurodevelopmental disorders. In addition, population genetic studies associate Contactins loci with obesity and hypertension. Cntn5 knockout mice were first described in 2003, but showed no gross physiological or behavioral abnormalities (just minor auditory defects). We report a novel Cntn5 knockout mouse line generated by a random transgene integration as an outcome of pronuclear microinjection. Investigation of the transgene integration site revealed that the 6Kbp transgene construct coding for the human granulocyte-macrophage colony-stimulating factor (hGMCSF) replaced 170 Kbp of the Cntn5 gene, including four exons. Reverse transcription PCR analysis of the Cntn5 transcripts in the wild-type and transgenic mouse lines showed that splicing of the transgene leads to a set of chimeric hGMCSF-Cntn5 transcript variants, none of which encode functional Cntn5 protein due to introduction of stop codons. Although Cntn5 knockout animals displayed no abnormalities in behavior, we noted that they were leaner, with less body mass and fat percentage than wild-type animals. Their cardiovascular parameters (heart rate, blood pressure and blood flow speed) were elevated compared to controls. These findings link Cntn5 deficiency to obesity and hypertension.

The transgenesis technologies are actively used in different fields of biological studies. The most actively used method to obtain transgenic animals by DNA injection in the zygote pronucleus can be accompanied by the violation of the genes’ function instead of integrating the transgenic construction. In this work, the morphophysiological effects of integrating the transgenic construction providing the production of the human granulocyte–macrophage colony-stimulating factor in the milk of the mouse line (GM9) (the insertion of the construction in the intron of the contactin 5 (Cntn5) gene) were described. It was demonstrated that the insertion of the construction did not result in the Cntn5 knockout. However, the gene transcription in the heart and kidneys of transgenic animals changes compared with wild-type animals, and the spectrum of transcripts also changes, indicating a violation in the Cntn5 gene splicing regulation. It is known from the published data that the Cntn5 polymorphisms are associated with an addiction to obesity and a predisposition to arterial hypertension. We studied the main parameters of the fat metabolism and cardiovascular activity in mice homozygous for the transgene insertion in the Cntn5 gene, heterozygous animals, and wild-type animals. The phenotyping carried out demonstrates that homozygous mice have a smaller body weight than wild-type individuals. And the weight difference between genotypes is determined more by significantly lower fat accumulation than by the lag of mutants in the development of the skeleton and muscles constituting the lean mass. Statistically significant differences in the parameters characterizing the intensity of the blood circulation were found in the studied lines. Homozygous mice exceed wild-type individuals by their arterial pressure values, heart rate, and blood flow rate in the tail vessels. It should be noted that heterozygous individuals have intermediate values between mutants and wild-type according to all the measured morphofunctional parameters.

The spectrum of the metabolites in the dorsal region of the hippocampus and striatum was studied using the method of 1H magnetic resonance spectroscopy at experimental modeling of the posttraumatic stress disorder syndrome (PTSD) in rats. PTSD was reproduced by exposure of the cat cue to rats daily along 10 day by 10 minutes at once. The anxiety level of animals was estimated 12 days later after the end of the experimental series of stress. Based on the anxiety index, the rats were divided into 3 phenotypes. The animals with an anxiety index > 0.8 (group 1) had lower plasma corticosterone compared with rats form the control group. In animals with an anxiety index in the range 0.7–0.8 (group 2), an elevated corticosterone level was noted. The rats with an anxiety index < 0.7 (group 3) had a lower plasma corticosterone level compared with animals from the control group. Rats of group 2 were characterized by an increased level of GABA in the hippocampus compared with controls. In the remaining groups, the percentages of GABA in the hippocampus and striatum did not differ significantly from the control. The distribution of NAA differed form that of GABA. The highest level of NAA was found in the striatum for rats from group 1, whereas NAA in animals form groups 1 or 3 did not differ from the control. The NAA level in the hippocampus was similar between all groups, including the control. The results obtained indicate that multiple exposures to psychological stress associated with the sense of proximity of a natural enemy in some animals cause an anxiolytic reaction. These animals are characterized by a stable corticosterone level and a stable level of neurometabolites in the studied structures of the brain. For rats with the highest level of anxiety, a lowered level of corticosterone with a constant level of neurometabolites in the hippocampus and striatum is characteristic. And only in rats with an intermediate level of anxiety, synchronization was observed between the increase in plasma corticosterone and the increase in hippocampal GABA content. The results obtained are in good agreement with the ideas of the protective action of glucocorticoids under PTSD manifested in restraining violations of the psycho-physiological status. The mate rials allow the neurobiological mechanisms of the protective action of glucocorticoids to be detailed.

The immune response to immunogenic stimuli depends on various factors such as the cytokine context, way of entry, and immune status of the organism. In mice, the entry of the female’s chemosignals into the male organism via the respiratory system activates the mucosal immune response, which leads to the development of enhanced resistance to infections and is of adaptive value. However, the activation of mucosal immunity depends on the genetic predispositions of the immune response. BALB/c and C57BL/6 are prototypically Th2-and Th1-type mouse strains, respectively; therefore, they can serve as the perfect model organisms for studying the activation mechanism of the lungs’ mucosal immune activation in response to the female’s chemosignals. The respiratory tract’s mucosal immune response to intranasal application of LPS, urea solution, saline solution, and female urine used as a chemosignal was investigated in the BALB/c and C57BL/6 male mice. Application of both female urine and LPS increased the total white blood cell count and protein concentration in the bronchoalveolar lavage fluid (BLF) in BALB/c male mice but not in C57BL/6 male mice, suggesting an important role of the Th2 pathway in the lungs’ mucosal immune response. At the same time, urine application provoked a significantly lower plasma corticosterone elevation than LPS. Thus, the sexual signals associated with infection risks provide genotype-dependent mobilization of the innate immunity without significant activation of physiological stress mechanisms.

Cholera remains a topical infection in the world, which determines the high risk of importation of the pathogen on the territory of the Russian Federation. MLVA-typing of 135 strains at 5 tandem repeats loci was carried outin order to study the clonal-population structure of the isolated from 1973 to 2016 on the Transbaikal territory V. cholerae. Analysis of the distribution patterns showed that the primary emergence of strains with new atypical for the territory genotypes in 1970s, 1980s, 1990s, occurred in sewage waters with the subsequent detection of the given genotypes generally in Ingoda river and Kenon lake. The strains firstly isolated from Borzya river and Haranor lake and found out at various times in Ingoda river and Kenon lake, Chita, Argun rivers, Haranor lake and Borzya river have been dominating since 2005 in Transbaikal territory. Finding groups of isolates with identical or similar MLVA-profile appeared in cluster complexes evidence of their long-term preservation in specific ecological niches, strains’ allelic profiles undergo minor transformation on the most variable loci in the process of adaptation. Identification of V. cholerae El Tor that variable tandem repeat loci structure materially differs from those of the dominant clones may serve as proof of their invasive origin.

Background. Long coevolution of prey and predator species of mammals creates specific mechanisms of their interaction, e. g. preys innate behavior aversive to the predator odor. However, little is known about genetic responses in the prey organism. We assessed genome instability of the bone marrow cells in mice affected by the cats odor influence, and proposed pathway of such action. Materials and methods. CBA mouse males were exposed to volatiles from adult cat urine for 2 or 24 hours. To estimate the genetic effect, ana-telophase method of chromosome aberration analysis and comet assay were used. The level of corticosterone was also measured after the exposure for 30 or 60 minutes. Results. The exposure to cats urine volatiles for 2 hours induced damage of DNA in bone marrow cells of the mouse males as was shown by the DNA comet analysis. The exposure for 24 hours elevated the frequency of chromosome aberrations in mitotically dividing cells at ana-telophase stage. No significant changes were found in the level of corticosterone in the peripheral blood. Conclusion. We have shown that volatile chemosignals from predators urine induce genomic instability in bone marrow cells of a prey. The hormonal pathway of such influence is still unknown. Intraorganismic paths leading to genome damage are discussed as well as far consequences of discovered effects.

Long-lived systems are expected to be stable, i. e. resistant to either external influences, or internal failures. Robustness of biological systems can be defined as a reciprocal value to their phenotypic plasticity expressed through a coefficient of variation (C.V.) for positively distributed phenotypic traits. Considering lifespan as phenotype, which integrates all functions of an organism, we showed that its phenotypic robustness correlates positively with life expectancy. We assessed lifespan parameters for a selection of inbred Drosophila melanogaster strains from Drosophila Genetic Reference Panel (DGRP) reared at 29 ºС. The robustness of lifespan phenotype (C.V.–1) correlated positively with estimated life expectancy for these strains. The same relation also holds for the lifespan of all DGRP strains reared at 25 ºС. Also, in agreement with previous observations, upon temperature change (decrease or increase) the survival curves scaled in time (stretched or shrunk respectively). In other words, the average lifespan decreased for flies reared at elevated temperature, but so did the standard deviation, and thus the coefficients of variation remained in the same range. From this we conclude that coefficients of variation correlate with life expectancies and account for the robustness of lifespan phenotype irrespective of accelerated aging caused by temperature.

In experiments with reusable inhalation of nano-sized metal oxide particles, it has been shown that there is no significant relationship between the number of presentations and the metal concentration in the olfactory bulb. This fact raises the question of a possible decrease in the efficiency of particulate capturing by the olfactory epithelium after their repeated application into the nasal cavity. In this study, we compared the effectiveness of nasal transport of paramagnetic nanoparticles after their single and multiple intranasal administration and evaluated their effects on the morphological and functional characteristics of the olfactory system. Based on the data, the accumulation of MnO-NPs in the olfactory bulb of mice was reduced after repeated intranasal application. In addition, the decrease in the efficiency of olfactory transport observed after repeated administration of MnO-NPs was partially restored by intranasal application of mucolytic (0.01 M N-acetyl-L-cysteine). In this case, the concentration of particles in the olfactory bulb was proportional to the volume of the structure, which in particular depends on the number of synaptic contacts between the mitral cell of the olfactory bulb (OB) and olfactory epithelium (OE). It should be noted that multiple intranasal injections of MnO-NPs reduce mouse OE thickness. Thus, repeated intranasal introduction of MnO-NPs reduces the efficiency of nanoparticle olfactory transport from the nasal cavity to the brain, which is combined with the increase in the viscosity of the mucosal layer and the reduction in the number of synaptic contacts between OB and OE. These results indicate the presence of the natural mechanisms of protection against the penetration of pathogens and xenobiotics into the olfactory epithelium; they also allow us to formulate practical recommendations on intranasal drugs delivery.

Transcriptome sequencing is a powerful technique to study molecular changes that underlie the differences in physiological conditions and disease progression. A typical question that is posed in such studies is finding genes with significant changes between sample groups. In this respect expression variability is regarded as a nuisance factor that is primarily of technical origin and complicates the data analysis. However, it is becoming apparent that the biological variation in gene expression might be an important molecular phenotype that can affect physiological parameters. In this review we explore the recent literature on technical and biological variability in gene expression, sources of expression variability, (epi-)genetic hallmarks, and evolutionary constraints in genes with robust and variable gene expression. We provide an overview of recent findings on effects of external cues, such as diet and aging, on expression variability and on other biological phenomena that can be linked to it. We discuss metrics and tools that were developed for quantification of expression variability and highlight the importance of future studies in this direction. To assist the adoption of expression variability analysis, we also provide a detailed description and computer code, which can easily be utilized by other researchers. We also provide a reanalysis of recently published data to highlight the value of the analysis method.

Nanoparticles are capable of penetrating cells, but little is known about the way they interact with intracellular proteome. Here we show that inorganic nanoparticles associate with low-complexity, intrinsically disordered proteins from HeLa cytosolic protein extracts in nondenaturing in vitro nanoparticle pull-down assays. Intrinsic protein disorder associates with structural mobility, suggesting that side-chain flexibility plays an important role in the driving of a protein to nanoparticle absorption. Disordered protein domains are often found in a diverse group of RNA-binding proteins. Consequently, the nanoparticle-associated proteomes were enriched in subunits of RNA-processing protein complexes. In turn, this indicates that within a cell, nanoparticles might interfere with protein synthesis triggering a range of cellular responses.

In experiments in which nano-sized metal oxide particles are multiply administered through inhalation, the absence of a material correlation between the number of they are administered and the metal concentration in olfactory bulbs (OBs) is demonstrated. This circumstance raises the question about a possible decrease in the efficiency of the capture of solid particles by the olfactory epithelium when they are repeatedly introduced in the nasal cavity. In this work, the efficiency of the nasal transport of magneto-contrasting nanoparticles during single and multiple intranasal administration is compared and their effect on the morphofunctional characteristics of the olfactory system is estimated. According to the data obtained, the accumulation of MnO-NP in the OBs of mice decreases during their repeated intranasal application. In addition, the decrease in the efficiency of the olfactory transport (observed during the multiple introduction of MnONP) partially recovers during the intranasal application of a mucolytic agent (0.01 M N-acetyl-L-cysteine). Moreover, the concentration of particles in OBs was proportional to the volume of this structure, which particularly depends on the number of synaptic contacts between the OBs and the olfactory epithelium. It should be noted that the olfactory epithelium’s thickness decreases during the multiple introduction of MnO-NP in mice. Thus, the efficiency of the olfactory transport of nanoparticles from the nasal cavity to the brain decreases during the multiple intranasal introduction of MnO-NP; this is combined with an increase in the mucosal layer’s viscosity and a decrease in the number of synaptic contacts between the OBs and the olfactory epithelium. The results obtained indicate the presence of the natural protection mechanisms of the olfactory epithelium against the penetration of pathogens and xenobiotics and allows us to formulate specific practical recommendations concerning the intranasal application of medications.

This review shows that the interpenetration of population ecology and animal physiology positively affects the both scientific directions that are important fields of modern zoology. Due to progress in the development of telemetry and non-invasive methods to assess the animal state, as well as of moleculargenetic methods that permit to distinguish the markers reflecting the individual history of an individual, the possibilities of studying responses of an organism to environmental impacts have been greatly expanded. The combined use of traditional ecological and modern physiological, immunological, and molecular-genetic methods promotes to reveal mechanisms responsible for the stable existence of population in the dynamic environment. In addition, the analysis of the contribution of physiological and immunological processes to the formation of adaptations on the population level is a requirement to understand their adaptive importance, which is not always evident when considering a problem at the organism-centric level.

Olfactory perception plays the key role in the interaction of animals with biotic factors of the species- specific econiche. Identification of odorants informs nocturnal animals about social environment, presence of predators, or infected food. Olfactory efficiency depends on physiological conditions; in particular, odor sensitiveity can be changed by infection. This work considers use of fMRI in the study of the influence of innate immunity activation on the neuronal response during perception and differentiation of socially significant (2,5-dimethylpyrazine, 2-heptanon) and socially insignificant (1-hexanol and isoprene) olfactory stimuli by CD-1 mice. We stimulated innate immunity by intraperitoneal injection of bacterial lipopolysaccharide (LPS) in a dose of 500 μg/kg three hours before tomography. Urethane anesthesia was used during the MRI trail. Odor was stimulated with a lab-made metering unit for supplying standard doses of volatile organic compounds. The supply of olfactory stimuli induced the activation of neurons in the primary perceptual center and the centers of secondary processing of olfactory information. The olfactory stimulus type affected the neuronal response rate in an olfactory bulb but did not affect the response parameters in the other brain regions studied. This increase in neuronal activity is likely to be of adaptive significance as a mechanism supporting an increase in olfactory sensitivity, which plays the key role in the identification of potential infection sources.

Hypertension is one of the most common human diseases, which leads to serious disturbances, such as myocardial infarction and stroke. A decrease in the neuron viability in different parts of the brain in humans with hypertension has been shown by nuclear magnetic resonance spectroscopy (NMRS). Translation of NMRS tools to the clinical practice requires the accumulation of empirical data on neurometabolic changes in a strictly controlled experiment. It is particularly interesting to compare the metabolic parameters of laboratory animals with the normal and high blood pressure maintained under standard conditions on the same diet. In this study, we examined the cortex and hypothalamus metabolites of ISIAH and Wistar male rats at the age of 8–9 weeks. The cortex and hypothalamus metabolites were measured in animals under isoflurane anesthesia using proton magnetic resonance spectroscopy (1Н MRS). Processing the primary data using the Partial Least Squares Discriminant Analysis (PLS-DA) allowed us to identify the main discriminating axis (Y1) and its variations, which showed the predominance of the excitatory neurometabolites (glutamine and glutamate) over the inhibitory ones (GABA and glycine). In the cortex, the Y1 axis values were lower in ISIAH rats than in Wistar rats. This indicates a decrease in the cortical excitability in hypertensive animals. In contrast, in the hypothalamus, the Y1 axis values were higher in ISIAH rats than in Wistar rats, and the predominance of the excitatory neurometabolites was positively correlated to the level of the mean blood pressure, which agrees well with the idea of caudal hypothalamic activation in hypertensive animal models.

Restricted mobility and spatial isolation of social units in gregarious subterranean mammals ensure good defence mechanisms against parasites, which in turn allows for a reduction of immunity components. In contrast, a parasite invasion may cause an increased adaptive immune response. Therefore, it can be expected that spatial and temporal distribution of parasites within a population will correlate with the local variability in the host's immunocompetence. To test this hypothesis, the intra-population variability of a whipworm infestation and the humoral immune response to non-replicated antigens in mole voles (Ellobius talpinus Pall.), social subterranean rodents, was estimated. Whipworm prevalence in mole voles increased from spring to autumn, and this tendency was more pronounced in settlements living in natural meadows compared to settlements in man-made meadows. However, humoral immune response was lowest in animals from natural meadows trapped in autumn. Since whipworm infestation does not directly affect the immunity of mole voles, the reciprocal tendencies in seasonal dynamics and spatial distribution of whipworm abundance and host immunocompetence may be explained by local deterioration of habitat conditions, which increases the probability of an infestation.

Nucleosomal DNA is thought to be generally inaccessible to DNA-binding factors, such as micrococcal nuclease (MNase). Here, we digest Drosophila chromatin with high and low concentrations of MNase to reveal two distinct nucleosome types: MNase-sensitive and MNase-resistant. MNase-resistant nucleosomes assemble on sequences depleted of A/T and enriched in G/C-containing dinucleotides, whereas MNase-sensitive nucleosomes form on A/Trich sequences found at transcription start and termination sites, enhancers and DNase I hypersensitive sites. Estimates of nucleosome formation energies indicate that MNase-sensitive nucleosomes tend to be less stable than MNase-resistant ones. Strikingly, a decrease in cell growth temperature of about 10 degrees C makes MNase-sensitive nucleosomes less accessible, suggesting that observed variations in MNase sensitivity are related to either thermal fluctuations of chromatin fibers or the activity of enzymatic machinery. In the vicinity of active genes and DNase I hypersensitive sites nucleosomes are organized into periodic arrays, likely due to 'phasing' off potential barriers formed by DNA-bound factors or by nucleosomes anchored to their positions through external interactions. The latter idea is substantiated by our biophysical model of nucleosome positioning and energetics, which predicts that nucleosomes immediately downstream of transcription start sites are anchored and recapitulates nucleosome phasing at active genes significantly better than sequence-dependent models.

Background We report the first case of composite lymphoma consisting of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), follicular lymphoma (FL) and high-grade B-cell lymphoma with MYC and BCL2 rearrangements within the same needle biopsy in which a clonal relationship between the FL and high-grade B-cell lymphoma components was demonstrated by molecular cytogenetics. Case presentation An 85-year-old man presented with masses in his neck and right groin. Cutting needle biopsy of the inguinal mass revealed the three lymphoma types which were morphologically, immunophenotypically and topographically distinct. Fluorescence in situ hybridization (FISH) identified an IGH-BCL2 rearrangement in both the FL and high-grade B-cell components while a MYC rearrangement was detected in the high-grade B-cell component alone. Conclusions Our findings suggest that the high-grade lymphoma with MYC and BCL2 translocations evolved through transformation of the FL by a process that entailed acquisition of the MYC translocation. No clonal relationship between the FL and CLL/SLL components was evident since the IGH-BCL2 rearrangement was present in in the former but not the latter. This unique case of co-localized FL, CLL/SLL, and high-grade B-cell lymphoma contributes to our understanding of the clonal relationships that may exist between the components of composite lymphomas.

Zonal organization of the olfactory system is determined not only by peculiarities of the expression of olfactory receptor genes but also by the geometry of nasal passage, where receptors to the most muco-soluble compounds are concentrated in the area with the maximal rate of air flow (dorsal part), while receptors to less volatile compounds are concentrated in ventral part of the nose. An increase in the flow rate in certain areas of nasal cavity, on the one hand, allows acceleration of the perception of odor stimuli by olfactory receptors and, on the other hand, increases the risk of the effect of different pathogens (contained in the air) on this area due to the larger intensity of their precipitation. In this study, we demonstrated by means of manganese- enhanced magnetic resonance imaging (MRI) that a more intensive capture of insoluble particles occurs in ventral part of mouse olfactory epithelium than in dorsal part during intranasal introduction of the colloid solution of manganese oxide nanoparticles (MON, Mn3O4). The joint introduction of MON and specific blockers of cellular transport and endocytosis demonstrated that the particles are captured from the nasal cavity by means of endocytosis and are transported in olfactory bulb cells by means of intracellular transport. The clathrin-dependent type of endocytosis mainly contributes to the capture of MON in the dorsal part of the olfactory epithelium (as opposed to ventral). Thus, it was established that two functional regions of mouse olfactory epithelium differing in the intensities of precipitation of submicron aerosols demonstrate different intensities of the capture of insoluble particles from the nasal cavity and have differences in the mechanisms of their endocytosis. Consequently, the structural and functional organization of mouse nasal cavity completely meets the principle of adaptive congruence, which limits infectious and toxic effects of nanoaerosols on the olfactory epithelium cells and the brain.

Perturbations in host energetics are considered to be an essential pathway for parasite impact on host fitness. However, direct estimations of parasite-induced variations in basal metabolic rates of vertebrate hosts have so far provided contradictory results. The energy requirements of immunity and other vital functions may be compromised in energy-demanding conditions in comparison to comfortable conditions; therefore, in our study performed on the wild red-backed vole, Myodes rutilus, we compared the values of indices that reflect metabolic and thermoregulatory responses to acute cooling in individuals that had been naturally infected by gut helminths or Ixodes persulcatus taiga ticks to individuals with no signs of infestation. To consider the possible effects of an acquired immune response on host energetics, we also injected some of the tested individuals with sheep red blood cells (SRBC). Red-backed voles infected by the nematode Heligmosomum mixtum injected with SRBC showed significantly lower cold-induced maximum oxygen consumption than the saline control. Additionally, individuals infected with H. mixtum showed significantly lower oxygen consumption during the final minute of the 15-min acute cooling period and a significantly greater decline in body temperature than individuals free from helminths. In individuals concurrently infected by H. mixtum and the cestodes Arostrilepis horrida, these indices did not differ from helminth-free individuals. The number of ticks simultaneously parasitizing the voles at the moment of capture correlated positively with their SMR. Our results suggest that even natural parasites produce deleterious effects on host aerobic capacity and thermoregulatory abilities, although the effects of different parasites might not be additive.

SummaryDuring spermatogenesis, the paternal genome is repackaged into a non-nucleosomal, highly compacted chromatin structure. Bioinformatic analysis revealed that Drosophila sperm chromatin proteins are characterized by a motif related to the high-mobility group (HMG) box, which we termed male-specific transcript (MST)-HMG box. MST77F is a MST-HMG-box protein that forms an essential component of sperm chromatin. The deposition of MST77F onto the paternal genome requires the chaperone function of tNAP, a testis-specific NAP protein. MST77F, in turn, enables the stable incorporation of MST35Ba and MST35Bb into sperm chromatin. Following MST-HMG-box protein deposition, the ATP-dependent chromatin remodeler ISWI mediates the appropriate organization of sperm chromatin. Conversely, at fertilization, maternal ISWI targets the paternal genome and drives its repackaging into de-condensed nucleosomal chromatin. Failure of this transition in ISWI mutant embryos is followed by mitotic defects, aneuploidy, and haploid embryonic divisions. Thus, ISWI enables bi-directional transitions between two fundamentally different forms of chromatin.

The aim of the present study was to examine how administration of a compound of 1,3,4- thiadiazine class 2-morpholino-5-phenyl-6H-1,3,4-thiadiazine, hydrobromide (L-17) with hypothermia inducing properties affects the brain metabolism. The mechanism by which L-17 induces hypothermia is unknown; it may involve hypothalamic central thermoregulation as well as act via inhibition of energy metabolism. We tested the hypothesis that L-17 may induce hypothermia by directly inhibiting energy metabolism. The study in vivo was carried out on Sprague-Dawley adult rats. Two doses of L-17 were administered (190 mg/kg and 760 mg/kg). Brain metabolites were analyzed in control and treated groups using magnetic resonance spectroscopy, along with blood flow rate measurements in carotid arteries and body temperature measurements. Further in vitro studies on primary cultures from rat hippocampus were carried out to perform a mitochondria function test of L-17 pre-incubation (100 μM, 30 min). Analysis of brain metabolites showed no significant changes in 190 mg/kg treated group along with a significant reduction in body temperature by 1.5°C. However, administration of L-17 in higher dose 760 mg/kg provoked changes in brain metabolites indicative of neurotoxicity as well as reduction in carotid arteries flow rate. In addition, a balance change of excitatory and inhibitory neurotransmitters was observed. The L-17 pre-incubation with cell primary cultures from rat brain showed no significant changes in mitochondrial function. The results obtained in the study indicate that acute administration of L-17 190 mg/kg in rats induces mild hypothermia with no adverse effects onto brain metabolism.

Inhalation of air-dispersed sub-micrometre and nano-sized particles presents a risk factor for animal and human health. Here, we show that nasal aerodynamics plays a pivotal role in the protection of the subterranean mole vole Ellobius talpinus from an increased exposure to nano-aerosols. Quantitative simulation of particle flow has shown that their deposition on the total surface of the nasal cavity is higher in the mole vole than in a terrestrial rodent Mus musculus (mouse), but lower on the olfactory epithelium. In agreement with simulation results, we found a reduced accumulation of manganese in olfactory bulbs of mole voles in comparison with mice after the inhalation of nano-sized MnCl2 aerosols. We ruled out the possibility that this reduction is owing to a lower transportation from epithelium to brain in the mole vole as intranasal instillations of MnCl2 solution and hydrated nanoparticles of manganese oxide MnO · (H2O)x revealed similar uptake rates for both species. Together, we conclude that nasal geometry contributes to the protection of brain and lung from accumulation of air-dispersed particles in mole voles.

Cestodes found in water voles (Arvicola terrestris L., 1758) trapped over six breeding seasons in the same local habitats included the following species: Arvicolepis transfuga (Spassky et Merkuscheva 1967), Paranoplacepala blanchardi (Moniez 1891), P. omphalodes (Hermann 1783), Parandria feodorovi (Gulyaev et Chetchulin 1996), Aprostatandrya dentate (Galli-Valerio 1905), and Arostrilepis microtis (Gulyaev et Chetchulin 2005). The dependence of cestode maturation on interannual variation in the food supply, territorial status, and morphofunctional characters of the hosts was analyzed in the two most abundant species, A. transfuga and P. feodorovi. The results showed that differences in host sex and food supply had no significant effect on cestode maturation. Judging from the proportion of gravid helminths of either species, the rate of their maturation was higher in nonresident than in resident voles. This proportion negatively correlated with body weight of male or female voles. It also negatively correlated with male fecal testosterone level, whereas correlations with fecal protein and progesterone levels were positive. The observed relationships do not explain why the occurrence frequency of gravid cestodes was higher in nonresident water voles, because they either did not differ from residents in parameters relevant to cestode maturation (body weight, fecal protein and testosterone levels) or the difference was opposite in direction (fecal progesterone was higher in resident voles). Nevertheless, an increase in the proportion of gravid cestodes in nonresident water voles may provide for more effective dispersal of these parasites.

In a majority of mammals, male infants have heavier body mass and grow faster than female infants. Accordingly, male offspring nursing requires a much greater maternal energy contribution to lactation. It is possible that the maternal-fetal immunoendocrine dialog plays an important role in female preparation for lactation during pregnancy. Immune system genes are an integral part of gene regulatory networks in lactation and tumor necrosis factor alpha (TNF) is a proinflammatory cytokine that also plays an important role in normal mammary gland development. The aim of this study was to evaluate the influence of the sex of calf and/or the -824A/G polymorphism in the promoter region of TNF gene on milk performance traits in Black Pied cattle over the course of lactation. We also studied the allele frequency differences of -824A/G variants across several cattle breeds, which were bred in different climatic conditions. The G allele frequency decreased gradually over the course of lactation events in the Black Pied dairy cattle because of a higher culling rate of cows with the G/G genotype (p

According to -the automatic tracing of the movement of ticks in a Petri dish, motivational variability of the spontaneous activity and behavioral response of the taiga tick to olfactory stimuli was analyzed. In the studied sample, two groups of ticks that differ in the movement trajectory in the absence of stimulus were isolated, including ticks that mainly moved on the edge of the dish at maximum accessible height (group 1) and ticks that mainly moved at the bottom and wall of the dish (group 2). It was registered that ticks of group 1 (as opposed to ticks of group 2) demonstrated a pronounced behavioral response to olfactory stimuli (human synthetic pheromones and ammonia) and negative geotaxis. It was established that belonging to these groups depended On the time of day when the testing was performed and did not depend on the physiological age and infectious status.

Infections with Helicobacter spp. are known to have serious effects on rodent health, especially in immunocompromised animals. In this study three approaches were used to eradicate Helicobacter spp. infection in mice with a deficiency in intestinal proteoglycan (mucin2), namely triple oral antibiotic therapy (amoxicillin, clarithromycin and metronidazole), cross-fostering of neonatal pups by surrogate mothers negative for Helicobacter spp., and in vitro fertilization (IVF) with embryo transfer into Helicobacter-free mothers. However, triple antibiotic therapy in mice with mucin2 deficiency was not effective and had negative effects on reproductive performance, and high susceptibility of mucin2-deficient mice to Helicobacter spp. during the first 12 h after birth rendered cross-fostering impossible. Only IVF with embryo transfer was effective in eradicating Helicobacter infection from transgenic mice with mucin2 deficiency.

The silent information regulator 1 (Sirt1) has been shown to have negative effects on the Notch pathway in several contexts. We bring evidence that Sirt1 has a positive effect on Notch activation in Drosophila, in the context of sensory organ precursor specification and during wing development. The phenotype of Sirt1 mutant resembles weak Notch loss-of-function phenotypes, and genetic interactions of Sirt1 with the components of the Notch pathway also suggest a positive role for Sirt1 in Notch signalling. Sirt1 is necessary for the efficient activation of enhancer of split [E(spl)] genes by Notch in S2N cells. Additionally, the Notch-dependent response of several E(spl) genes is sensitive to metabolic stress caused by 2-deoxy-d-glucose treatment, in a Sirt1-dependent manner. We found Sirt1 associated with several proteins involved in Notch repression as well as activation, including the cofactor exchange factor Ebi (TBL1), the RLAF/LAF histone chaperone complex and the Tip60 acetylation complex. Moreover, Sirt1 participates in the deacetylation of the CSL transcription factor Suppressor of Hairless. The role of Sirt1 in Notch signalling is, therefore, more complex than previously recognized, and its diverse effects may be explained by a plethora of Sirt1 substrates involved in the regulation of Notch signalling.

The modification of pre- and postnatal development conferred by immunogenic stimulation of mothers provides a population-level adaptation mechanism for non-genetic transfer of maternal experiences to progeny. However little is known about the transmission of paternal immune experiences to offspring. Here, we show that immune priming of males 3–9 days before mating affects the growth and humoral environment of developing embryos of outbred (ICR) and inbred (C57BL and BALB/c) mice. Antigenic stimulation of fathers caused a significant increase in embryonic bodyweight as measured on Day 16 of pregnancy and altered other gestation parameters, such as feto–placental ratio. Pregnant females mated with immunised males were also characterised by changes in humoral conditions as shown by measurements of blood and amniotic progesterone, testosterone and granulocyte–macrophage colony-stimulating factor (GM-CSF) cytokine concentrations. These results emphasise the role of paternal effects of immune priming on the in utero environment and fetal growth.

Diversity of viruses, bacteria, microscopic fungi, and endo- and ectoparasites is an inevitable environmental factor that influences the host reproduction and that is determined not only by negative effects of infectious diseases but also by activation of protective mechanisms, which provide a confrontation to the pressure of parasites. In the present work, hemocyanin was injected into males of the ICR outbred line in order to study reproductive consequences of antigenic stimulation of males. Intact females were added to control and antigen-stimulated males at the initial stage of antibody formation. During 6 days of combined keeping, a significantly greater amount of ovulated egg cells and living embryos were registered in the females added to males that were injected with hemocyanin compared with that theoretically expected for equal reproductive yield. Females covered by antigen-stimulated males bred larger embryos compared with those in the control. Indices of female fertility depended on prevalence of cellular (Th1) or humoral (Th2) immune responses in antigen-stimulated males. Shift of Th1/Th2 balance resulted in higher preimplantation embryonic losses in females covered by males with a prevalence of cellular immune response; however, they bred larger embryos. Thus, it was established that activation of the immune system in males does not influence their reproductive abilities. This allows us, on the one hand, to explain the contribution of protective reactions of the organism in the increase in fertility of the mammals that inhabit territories with high specific abundance of parasites; on the other hand, it demonstrates new ways of the management of the reproduction of animals bred under human control.

In a population of red-backed voles (Myodes rutilus) that live in optimal habitats (mountain taiga of North-Eastern Altai) in the years of peak density we have observed total suppression of sexual maturation of young animals which is known to be the main mechanism of density regulation. Increase of voles' local density is accompanied by the increase of glucocorticoids in blood of mature and immature individuals of both sexes that argues for the important role of hypothalamic-pituitary-adrenal axis in density dependent regulation. Another population of red-backed voles from south-west Siberia that live in suboptimal habitats (Novosibirsk city vicinity), had significantly lower density. Here, the dynamics of demographic traits and endocrine status of the individuals did not correlate with interannual fluctuations of abundance and density. Even though, the possibility that in suboptimal conditions local density occasionally reaches the values sufficient for the induction of self-regulation cannot be excluded.

The physiologic mechanisms of stress have multiple effects on the adaptive capacity of an individual. Thus, the analysis of factors that determine the level of stress in animals in a changing environment acquires considerable ecologic and evolutionary significance. The results of long-term studies performed at the site of an irrigation canal, which is annually populated by water voles, are described in this paper. A high level of stress in male water voles has been found when the resources (food and mates) are scarce. The activation of adrenocortical function under the conditions of insufficient resources occurs due to the intensification of the intraspecific competition, which takes place after a decrease in both the food supply and the ratio of females in the local population. The effects of these factors are mediated by changes in spatial and ethologic structure of a studied population appearing as an increasing overlap of individual areas. The food supply and insufficient number of females affect the levels of glucocorticoids differently in resident and nonresident males. Our results suggest that social interactions act as actual stress factors in water voles, even if a considerable decrease occurs in water vole populations, which takes place in North Baraba due to the reduction of watering in the area and the decrease in territories suitable for summer habitation.

Cells need to coordinate gene expression and metabolic state. Inosine monophosphate dehydrogenase (IMPDH) controls the guanine nucleotide pool and, thereby, cell proliferation. We found that Drosophila IMPDH is also a DNA-binding transcriptional repressor. IMPDH attenuates expression of histone genes and E2f, a key driver of cell proliferation. Nuclear IMPDH accumulates during the G2 phase of the cell cycle or following replicative or oxidative stress. Thus, IMPDH can couple the expression of histones and E2F to cellular state. Genome-wide profiling and in vitro binding assays established that IMPDH binds sequence specifically to single-stranded, CT-rich DNA elements. Surprisingly, this DNA-binding function is conserved in E. cOli IMPDH. The catalytic function of IMPDH is not required for DNA binding. Yet substitutions that correspond to human retinits pigmentosa mutations disrupt IMPDH binding to CT-rich, singlle-stranded DNA elements. By doubling as nucleotide biosynthetic enzyme or transcription factor, IMPDH can either enable or restrict cell proliferation.

The nucleosome is the fundamental repeating unit of eukaryotic chromatin. Here, we assessed the interplay between DNA sequence and ATP-dependent chromatin-remodeling factors (remodelers) in the nucleosomal organization of a eukaryotic genome. We compared the genome-wide distribution of Drosophila NURD, (P)BAP, INO80, and ISWI, representing the four major remodeler families. Each remodeler has a unique set of genomic targets and generates distinct chromatin signatures. Remodeler loci have characteristic DNA sequence features, predicted to influence nucleosome formation. Strikingly, remodelers counteract DNA sequence-driven nucleosome distribution in two distinct ways. NURD, (P)BAP, and INO80 increase histone density at their target sequences, which intrinsically disfavor positioned nucleosome formation. In contrast, ISWI promotes open chromatin at sites that are propitious for precise nucleosome placement. Remodelers influence nucleosome organization genome-wide, reflecting their high genomic density and the propagation of nucleosome redistribution beyond remodeler binding sites. In transcriptionally silent early embryos, nucleosome organization correlates with intrinsic histone-DNA sequence preferences. Following differential expression of the genome, however, this relationship diminishes and eventually disappears. We conclude that the cellular nucleosome landscape is the result of the balance between DNA sequence-driven nucleosome placement and active nucleosome repositioning by remodelers and the transcription machinery.