Female Scent Signals Enhances Male Resistance to Influenza

Scent of receptive females as signal to reproduction stimulate male mice to olfactory search of a potential breeding partner^1, 2^. This searching behavior is coupled with infection risk due to bacterial contamination of the fecal and urine scent marks^4^. The theoretical consideration of host evolution under inevitable parasitic pressures, including helminthes, bacteria, virus etc., predicts adaptations that help protect against parasites associated with breeding^7^. In this study, we propose that acceptation of female signals by male mice leads to adaptive redistribution of immune defense directed to protection against respiratory infection risks. Our results reveal migration of macrophages and neutrophils to upper airways upon exposure to female odor stimulus resulting in increased resistance to influenza virus in male mice. Contrary to widely accepted immunosuppressive function of female sexual signals, our data provide the first demonstration of the adaptive immunological response to female odor stimulus through induction of nonspecific immune response in upper airways

Results and interpretation of measurements of the light flux in the near-surface layer of the Venusian atmosphere

The characteristics of the field of radiation in the near surface layer of the atmosphere and on the surface of Venus are reported. Optical measurements made during the landing of the descent vehicles are described. The relief of the surface and the amount of dust on it are examined. The spectral relationship of the albedo of the soil and the light flux incident on the surface is discussed

Spectrophotometric experiment on the Verera-11 and Venera-12 descent vehicles: Some results of the analysis of the spectrum of the daytime sky of Venus

The spectra of the daytime sky of Venus were recorded on the Venera-11 and Venera-12 descent vehicles at various altitudes above the planet's surface, within the interval of 4500 to 12,000 Angstroms. The angular distribution of the brightness of the scattered radiation was recorded and the ratio of water and carbon dioxide were studied, with respect to the cloud cover boundaries

Impact of glycolysis inhibitor (2-DG) and oxidation and phosphorylation uncoupler (2,4-DNP) on brain metabolites

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

Female Scent Signals Enhance the Resistance of Male Mice to Influenza

Background: The scent from receptive female mice functions as a signal, which stimulates male mice to search for potential mating partners. This searching behavior is coupled with infection risk due to sniffing both scent marks as well as nasal and anogenital areas of females, which harbor bacteria and viruses. Consideration of host evolution under unavoidable parasitic pressures, including helminthes, bacteria, viruses, etc., predicts adaptations that help protect hosts against the parasites associated with mating. Methods and Findings: We propose that the perception of female signals by BALB/c male mice leads to adaptive redistribution of the immune defense directed to protection against respiratory infection risks. Our results demonstrate migration of macrophages and neutrophils to the upper airways upon exposure to female odor stimuli, which results in an increased resistance of the males to experimental influenza virus infection. This moderate leukocyte intervention had no negative effect on the aerobic performance in male mice. Conclusions: Our data provide the first demonstration of the adaptive immunological response to female odor stimul

Generation of donor organs in chimeric animals via blastocyst complementation

The lack of organs for transplantation is an important problem in medicine today. The growth of organs in chimeric animals may be the solution of this. The proposed technology is the interspecific blastocyst complementation method in combination with genomic editing for obtaining “free niches” and pluripotent stem cell production methods. The CRISPR/Cas9 method allows the so-called “free niches” to be obtained for blastocyst complementation. The technologies of producing induced pluripotent stem cells give us the opportunity to obtain human donor cells capable of populating a “free niche”. Taken together, these technologies allow interspecific blastocyst complementation between humans and other animals, which makes it possible in the future to grow human organs for transplantations inside chimeric animals. However, in practice, in order to achieve successful interspecific blastocyst complementation, it is necessary to solve a number of problems: to improve methods for producing “chimeric competent” cells, to overcome specific interspecific barriers, to select compatible cell developmental stages for injection and the corresponding developmental stage of the host embryo, to prevent apoptosis of donor cells and to achieve effective proliferation of the human donor cells in the host animal. Also, it is very important to analyze the ethical aspects related to developing technologies of chimeric organisms with the participation of human cells. Today, many researchers are trying to solve these problems and also to establish new approaches in the creation of interspecific chimeric organisms in order to grow human organs for transplantation. In the present review we described the historical stages of the development of the blastocyst complementation method, examined in detail the technologies that underlie modern blastocyst complementation, and analyzed current progress that gives us the possibility to grow human organs in chimeric animals. We also considered the barriers and issues preventing the successful implementation of interspecific blastocyst complementation in practice, and discussed the further development of this method

Effects of female sexual chemosignals on mucosal immunity in BALB/c and C57BL/6 male mice

The immune response to immunogenic stimuli depends on various factors like cytokine context, way of entry, and immune status of the organism. In mice, female chemosignal entry into the male organism via the respiratory system causes activation of 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 perfect model organisms for studying mechanism of lung mucosal immune activation in response to female chemosignals. Respiratory tract mucosal immune response to intranasal application of LPS, urea solution, saline and female urine used as a chemosignal was investigated in BALB/c and C57BL/6 male mice. Application of both female urine and LPS increased total white blood cell count and protein concentration in bronchoalveolar lavage fluid in BALB/c, but not in C57BL/6 male mice, suggesting an important role of Th2 pathway in lung mucosal immune response. At the same time, urine application provoked a significantly lower plasma corticosterone elevation than LPS. Thus, sexual signals associated with infection risks provide genotype-dependent mobilization of innate immunity without significant activation of physiological stress mechanisms

Olfactory transport efficiency of the manganese oxide nanoparticles (II) after their single or multiple intranasal administrations

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

Olfactory transport efficiency of the amorphous and crystalline manganese oxide nanoparticles

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

Brain metabolites in ISIAH and Wistar rats

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