Measurement of the Positive Muon Anomalous Magnetic Moment to 0.20 ppm.

We present a new measurement of the positive muon magnetic anomaly, a_{µ}≡(g_{µ}-2)/2, from the Fermilab Muon g-2 Experiment using data collected in 2019 and 2020. We have analyzed more than 4 times the number of positrons from muon decay than in our previous result from 2018 data. The systematic error is reduced by more than a factor of 2 due to better running conditions, a more stable beam, and improved knowledge of the magnetic field weighted by the muon distribution, ω[over ˜]_{p}^{'}, and of the anomalous precession frequency corrected for beam dynamics effects, ω_{a}. From the ratio ω_{a}/ω[over ˜]_{p}^{'}, together with precisely determined external parameters, we determine a_{µ}=116 592 057(25)×10^{-11} (0.21 ppm). Combining this result with our previous result from the 2018 data, we obtain a_{µ}(FNAL)=116 592 055(24)×10^{-11} (0.20 ppm). The new experimental world average is a_{µ}(exp)=116 592 059(22)×10^{-11} (0.19 ppm), which represents a factor of 2 improvement in precision.

Measurement of the Positive Muon Anomalous Magnetic Moment to 0.46 ppm.

We present the first results of the Fermilab National Accelerator Laboratory (FNAL) Muon g-2 Experiment for the positive muon magnetic anomaly a_{µ}≡(g_{µ}-2)/2. The anomaly is determined from the precision measurements of two angular frequencies. Intensity variation of high-energy positrons from muon decays directly encodes the difference frequency ω_{a} between the spin-precession and cyclotron frequencies for polarized muons in a magnetic storage ring. The storage ring magnetic field is measured using nuclear magnetic resonance probes calibrated in terms of the equivalent proton spin precession frequency ω[over ˜]_{p}^{'} in a spherical water sample at 34.7 °C. The ratio ω_{a}/ω[over ˜]_{p}^{'}, together with known fundamental constants, determines a_{µ}(FNAL)=116 592 040(54)×10^{-11} (0.46 ppm). The result is 3.3 standard deviations greater than the standard model prediction and is in excellent agreement with the previous Brookhaven National Laboratory (BNL) E821 measurement. After combination with previous measurements of both µ^{+} and µ^{-}, the new experimental average of a_{µ}(Exp)=116 592 061(41)×10^{-11} (0.35 ppm) increases the tension between experiment and theory to 4.2 standard deviations.

[Cys-Flanked Cationic Peptides For Cell Delivery of the Herpes Simplex Virus Thymidine Kinase Gene for Suicide Gene Therapy of Uterine Leiomyoma].

Uterine leiomyoma (UL) is the most common benign tumor in women of reproductive age. Gene therapy using suicidal genes appears to be a promising approach for UL treatment. One of key factors for success of gene therapy is the right choice of genetic construct carrier. A promising group of non-viral carriers for cell delivery of expression vectors is cationic Cys-flanked peptides which form tight complexes with DNA due to electrostatic interactions and the presence of interpeptide disulfide bonds. The paper reports a comparative study of the physico-chemical, toxic, and transfectional properties of the DNA-peptide complexes obtained by matrix polymerization or oxidative polycondensation of Cys-flanked peptides using the chain growth terminator 2-amino ethanethiol. We have demonstrated the therapeutic effect of the delivery of the pPTK-1 plasmid carrying the herpes simplex virus type 1 (HSV-1) thymidine kinase gene into PANC-1, and HEK-293T cell culture as well as into primary UL cells. It has been shown that the carriers obtained by oxidative polycondensation transform primary UL cells more efficiently than those produced by matrix polymerization. Treatment with ganciclovir resulted in the death of up to 40% of UL cells transfected with the pPTK-1 plasmid. The perspectives of use of the polyR6 carrier produced by oxidative polycondensation as a tool for the development of modular peptide carriers for the purposes of UL gene therapy were discussed.

Effect of Peptide AEDG on Telomere Length and Mitotic Index of PHA-Stimulated Human Blood Lymphocytes.

We studied the effect of peptide AEDG on telomere length and mitotic index of PHA-stimulated blood lymphocytes from young (18-22 years, N=5) and middle-aged (49-54 years, N=6) men. In the younger age group, no significant changes in the mitotic index were detected, while in the middle-aged group, a decrease in this parameter was found in one case. The relative length of telomeric regions of metaphase chromosomes was evaluated by in situ fluorescence hybridization with DNA probes specific to telomeres. After incubation with peptide AEDG, significant changes in the relative telomere length were found in 7 of 11 individuals (3 cases in the younger age group and 4 cases in the middle age group). Significant increase in telomere length after exposure to peptide AEDG was revealed in 5 cases, including two individuals of the younger age group (by 41 and 55%) and three individuals of the middle age group (by 156, 18, and 76%). In one individual of the younger age group and in one of the middle-age group, a significant decrease in telomere length (by 37 and 15%, respectively) was found. A tendency to normalization of telomere lengths was noted: this parameter increased in individuals with initially lower telomere length relative to the group mean value and decreased in individuals with initially longer telomeres compared to the mean length in the group.

Differential DNA Hydroxymethylation in Human Uterine Leiomyoma Cells Depending on the Phase of Menstrual Cycle and Presence of MED12 Gene Mutations.

Using immunofluorescence with specific antibodies, we analyzed DNA hydroxymethylation in uncultured cells from 25 human uterine leiomyomas considering the menstrual cycle phase during surgery and the presence of MED12 gene mutations. It was found that each tumor node had specific DNA hydroxymethylation level that did not depend on the presence of mutations in MED12 gene, but depended on the phase of menstrual cycle. The degree of DNA hydroxymethylation was significantly lower in cells of leiomyomas excised during the luteal phase compared to the follicular phase (p=0.0431). Hormonal status changing at various phases of menstrual cycle is a factor affecting DNA hydroxymethylation in leiomyoma cells.

Effect of Simulated Microgravity and Lunar Gravity on Human Inspiratory Muscle Function: 'Selena-T' 2015 Study.

As a part of the multi-disciplinary "SELENA-T"-2015 Bed Rest Study, we investigated the pattern of inspiratory muscles fatigue in 22 healthy male subjects during incremental exercise test to exhaustion before and after 21 days of hypokinesia evoked by bed rest. Hypokinesia consisted of head-down bed rest (HDBR) at a minus 6° angle, simulating microgravity present on orbiting spacecraft, in 10 subjects. The remaining 12 subjects spent the first 5 days of hypokinesia in HDBR position and the subsequent 16 days in head-up bed rest (HUBR) at a plus 9.6° angle, as a presumed analog of lunar gravity that is six times less than Earth's gravity. Maximal inspiratory pressure (MIP) and electromyograms (EMG) of the diaphragm (D), parasternal (PS), sternocleidomastoid (SCM), and scalene (S) muscles served as indices of inspiratory muscle function. Before both HDBR and HUBR, exercise decreased MIP and centroid frequency (fc) of EMG (D, PS, SCM, and S) power spectrum (p < 0.05). After 3 weeks of HDBR, but not HUBR, inspiratory muscles fatigue was more expressed compared with control (p < 0.05). We conclude that HDBR lowers inspiratory muscles resistance to fatigue during high-intensity exercise while HUBR has no such effect. These changes may limit maximal ventilation and may contribute to exercise intolerance observed after prolonged simulated microgravity. The physiological mechanisms of respiratory muscle dysfunction after HDBR consist primarily of postural effects, and are not due only to hypokinesia.

Functional Features of Microcirculation System and its Possibilities of Oxygen Transport in Children and Youths of Bryansk Region in Conditions of Radioecological Pressure.

The questions of influence of low radiation doses on microcirculation of blood in ontogeny of males from 7 to 27 years are presented in the article. Using the method of laser Doppler ultrasounds, optical oximetry and laser fluorescent diagnostics, we studied the blood perfusion level in the microcirculation system of 315 schoolchildren and students, considered the regulation mechanisms of microcirculation, the level of oxygen saturation of hemoglobin both in the circulation system and mixed blood, the index of oxygen utilization in tissues and the value of fluorescent use of oxygen. We received the information about the changes in the frequency of occurrence of different microcirculation types associated with the age and region of residence. In the case of higher radiation levels we marked a significant increase of individuals with the "extreme" microcirculation type (hypoemic and hyperemic) against the background of the decreased mesoemic type. A special feature of the metabolism process in children, teenagers, and youths is a decrease of the microcirculation density with an increase of the myogenic tone of metaarterioles and precapillary sphincters. The tone of arterioles grows with age. As a result of the limited blood volume, oxygen. is pulled compensatory from blood in larger amounts; it is shown from a significant decrease of the level of oxygen saturation in mixed blood. The strongest differences are shown for the hypoemic and hyperemic microcirculation type. Dwelling on the areas with radio-ecological pressure is accompanied by an increase in the fluorescent index of oxygen use. The level of the total oxygen use in these individuals is higher than in those living in radiation favorable areas.

A Method of Ground Simulation of Physiological Effects of Hypogravity on Humans.

A novel method of ground simulation in humans of physiological effects induced by the stay on the surface of celestial bodies with hypogravity was developed and successfully tested. This method is based on the change of gravity force angle, which decreases the gravitational component of the blood hydrostatic pressure characteristic of human vertical posture on the Earth and the load-weight onto the locomotor apparatus to the lower values expected at celestial bodies with hypogravity. The methodological requirements for ground simulation of the physiological effects of lunar gravity on human body are specified and substantiated by theoretical calculations. The experimental study revealed redistribution of liquid media in the human organism, functional changes in the cardiorespiratory system, and a decrease in the load-weight applied to the locomotor apparatus.

[The influence of fermented dairy whey on morphofunctional indices and physical training of sportsmen].

The aim of the study was to examine anthropometry, physical fitness, metabolism at the level of the microcirculation and adaptive processes of the organism as a whole under the inclusion of enzyme-hydrolyzed whey in the diet of 27 weightlifters 17-23 (21.7±2.7) years old, with the level of sports skills of 1 category of up to masters of sports. The body composition was determined by bioimpedance method, functioning of microcirculation system and oxygen transport were determined using the multifunction laser diagnostic complex. For analysis of heart rate variability we used complex "Varicard 2.51", physical fitness was assessed by generally accepted pedagogical tests. The products inclusion in the diet in the increasing dose of 0.5 to 1.5 g/kg of body weight within 21 days increases physical fitness. The growth of physical efficiency provided change of body composition with slight increase in muscle mass by 2% and decrease in fat component by 3.6% (p <0.05). Increasing muscle mass is the functional stimulus for the revitalization of the microcirculation system for the exchange of nutrients and energy. Under the consumption of serum the intensity of microcirculation increased by 131%, elevating dominance of active mechanisms of modulation of the flow over passive. As a result of intensive diffusion of oxygen from the blood into tissues, the saturation rate of mixed blood reduced by 7.7% and consumption of oxygen by cells of work tissues increased by 23.6%. Assimilation of nutrients and energy, adequate to physical exercises, improved functional capacity of the organism in general and extended its adaptive capacity, as evidenced by the increase of the balance of vegetative regulation of cardiac rhythm.

[Genetic and epigenetic news in gerontology].

The overview represents the recent most conspicuous findings in aging studies. It includes new data on the whole genome association studies (GWAS) in big cohort of centenaries, recently found mutation protecting from Alzheimer disease, discovery of hypothalamus as a command center of human aging, very important data on the negative effect of common antioxidants in the treatment of lung cancer as well as new data concerning antiaging and anticancer effects of common drugs such as rapamycine and metformin. Substantial part of the review is devoted to the epigenetic problems of senescence and feasible impact of basic epigenetic mechanisms (methylation of DNA and histone proteins, DNA heterochromatization) in regulation of gene expression, long-term genome reprogramming during early childhood, and transgeneration transmission of epigenetic traits. The necessity of transition from molecular studies of dormant human genome (anatomy of human genome) to genome in action (dynamic genome) and thus with special emphasis to epigenetic medicine is stressed.

[Frequency of some diseases and conditions in geriatric patients with coronary heart disease and various genotypes of transcription factor 7-like 2 protein].

In 2009-2010, 98 patients diagnosed with the coronary heart disease, but without the expressed metabolic violations, decompensated conditions and diseases were surveyed. Patients of 60-90 years were divided by age into two groups: younger than 75 years--47 people; 75 years and older--51; there were 41 women and 57 men; the ratio between women and men was 1:1.4; average age was 76.0 ± 1.3 years. The average age of women was 76.0 ± 1.8 years, men--76.1 ± 2,0 years. 96.0 ± 2.0% of geriatric patients with CHD complained of steno-cardiac pains in pre-cardiac area; the excess mass of a body was observed in 43.4 ± 5.0% of geriatric patients with CHD, acute myocardial infarction in the anamnesis was noted in 52.5 ± 6.9% (n = 52); hypertensive illness had 98.0 ± 1.4% (n = 97). Patients had the favorable average levels of lipoproteins of high density (not lower than 1 mmol/l). A significant number (79.2 ± 5.6%) of patients had hemodynamically significant narrowing of coronary vessels (75% and more), while the area of myocardial hypokinesia was observed in 41.2 ± 6.9% of patients, sharp violation of brain blood circulation was noted in 14.1 ± 9.8%. Wild type homozygous genotype of TCF7L2 gene was detected significantly more often (77.6 ± 4.7%) in patients of advanced and senile age with CHD, regardless of age group, exis-tence of accompanying diseases and conditions, such as previous myocardial damage, acute disorders of cerebral circulation and fatty degeneration of the liver. However allele of risk T (totally C/Tand T/T) of TCF7L2 gene came to light in 22.4 ± 9.1% of geriatric patients with CHD, that contributes to development of a metabolic syndrome in such patients and reduces term of their life.

[Genotype and allele frequencies of UCP and PPAR gene families in residents of besieged Leningrad and in the control group].

Genotype and allele frequencies of uncoupling proteins 2 and 3 genes (UCP2 and UCP3) and peroxisome proliferator-activated receptors genes (PPARA, PPARD and PPARG) were studied in 206 residents of the siege and in 139 individuals of more than 69 years old (control group). Studied polymorphisms included UCP2 (Ala55Val), UCP3 (C-55T), PPARA (G/C), PPARD (+294T/C), and PPARG (Pro12Ala). The G allele and the G/G genotype (PPARA) were overrepresented in the group of survivors and C/C (UCP3) genotype prevailed in the women of besieged Leningrad compared to relevant control groups of the persons of the same age who did not suffered hungry disaster. Feasible protective effects of PPARA gene allele G and C allele of UCP2 genes are briefly discussed.

[Association of matrix metalloproteinases' polymorphisms of MMP3 and MMP9 with development of genital endometriosis].

We present a comparative analysis of the allelic polymorphism of the matrix metalloproteinase (MMP) gene family, including MMP3 (rs3025058), MMP7 (rs11568818), MMP9 (rs17576, rs2250889), MMP12 (rs2276109), and MMP13 (rs2252070), in patients with external genital endometriosis (EGE) and in a control group of healthy women proven to be free of disease by laparoscopic inspection. We found significant differences in the incidence of particular MMP3 and MMP9 alleles, which substantiate the role of matrix metalloproteinases in EGE pathogenesis. We used the Multifactor Dimensionality Reduction (MDR) analysis to show that 14 allelic combinations of the MMP containing MMP3 (rs3025058) x MMP7 (rs11568818) x MMP9 (rs17576) alleles showed a statistically significant association with an increased risk of EGE, while 10 other combinations correlated with a reduced risk of the disease. MDR analysis produced two statistically significant models for MMP allelic combinations involved in EGE progression, both with 100% penetrance and 83% and 78% accuracy.

[Theoretical study of hydrophobicity and hydrophilicity of uracil and its dimers].

The influence of hydrophilic and hydrophobic properties of the uracil elementary nucleic acids bases on its solubility and structure in aqueous solution was studied. Complexes of uracil with water molecules (from 1 to 14) were then calculated. The geometrical parameters of the hydrogen bridge of uracil and the changes in the frequency of valence vibrations of the bonds participating directly in hydrogen bond formation were calculated. It is shown that for the hydrogen bonds O(w)...HN(1) and O(w)...HN3 the hydrogen atom can tear, it may lead to tautomeric transformation of uracil. The results obtained having calculated the structure of uracil dimers, formed with the hydrogen bonds, in an isolated state and water solution, energy, dipole moments and the hydrogen bridge parameters made it possible to explain low solubility of uracil in water at room temperature. It is shown that water molecules with increase in their number are located mainly at one side of the plane of a pyrimidine uracil ring, that leads to the formation of stacking. Of two possible variants of stacking formation, the most profitable grouping is when a dipole moment of the formed dimer is equal to zero (anti-parallel stacking).

[Murine peritoneal neutrophil activation upon tungsten nanoparticles exposure in vivo].

Two examples of tungsten carbide nanoparticles (d = 15 nm, 50 nm) and tungsten carbide nanoparticles with 8% cobalt (d = 50 nm) have been found to induce the neutrophil activation 3 h and 36 h after intraperitoneal administration in the doses 0.005; 0.025; 0.05; 0.25; 0.5; 1; 2.5 and 5 microgram per 1 gram body weight to FVB mice. Neutrophil activation was calculated based on the CD11b and S100 antigen expression. Effect of nanoparticles is bimodal for all tested examples.

[Structural-functional characteristics of cervical vessels in hypertensive patients under changed atmospheric pressure].

The ultrasonic location technique was used to measure intima-media thickness (IMT), as well as internal systolic diameter of and linear blood velocity in the cervical arteries in people with initial hypertension. Correlation analysis elicited a temporal contingency between these parameters and daily average values of atmospheric pressure. Thus, common carotid artery IMT tended to increase on high-pressure days. Besides, diameters of the common and internal carotid arteries, and vertebral artery were narrowed and, consequently, linear blood velocity in these vessels increased. This relationship is more evident in men than women and in elderly subjects than young. These results are suggestive of a vasoconstrictive action of high atmospheric pressure on these arteries. The relationship is not universal, as it is nonlinear for diameter of the internal carotid artery and inverse for the external one. This implies different sensitivity of arteries to the factor under study and possible blood redistribution in the arterial basin depending on external pressure. The relationship was observed equally on the day of investigation and previous days, which points to its temporal stability.

Effect of a helium and oxygen mixture on physiological parameters of rats with cerebral arterial air embolism.

Introduction: Cerebral arterial air embolism (CAE) is a serious and potentially dangerous condition that can interrupt the blood supply to the brain and cause stroke. One of the promising gas mixtures for emergency treatment of air embolism is an oxygen-helium mixture. Methods: We modeled CAE in awake rats by injecting air into the common carotid artery. Immediately after CAE, animals were either untreated or underwent hyperbaria, oxygen inhalation, heated air inhalation, or helium-oxygen mixture inhalation. Body temperature, locomotor activity, respiratory and cardiovascular parameters were monitored in the animals before CAE modeling, and 3 and 24 h after CAE modeling. Results: After 3 hours of CAE modeling in awake rats, depression of the nervous, cardiovascular and respiratory systems, as well as decreased body temperature were observed. 24 h after CAE modeling multifocal cerebral ischemia was observed. Normobaric helium-oxygen mixture inhalation, on par with hyperbaric treatment, restored body temperature, locomotor activity, respiratory volume, respiratory rate, and blood pressure 3 hours after CAE, and prevented the formation of ischemic brain damage lesions 24 h after CAE. Discussion: Thus, inhalation of a heated oxygen-helium gas mixture (O2 30% and He 70%) immediately after CAE improves the physiological condition of the animals and prevents the foci of ischemic brain damage formation.

Intersystem relationships of respiration and hemodynamics in the initial period of postural effects.

We studied the dependence of parameters of lung volumes and the elastic properties of the lungs on changes in the central hemodynamics occurring in the initial period of passive postural changes in cats. It was found that transition from the horizontal to head-up and head-down tilting was accompanied by opposite hemodynamic changes in the cranial and caudal parts of the body. Changes in lung compliance and functional residual capacity of the lungs were opposite and linearly depended on the intensity of hemodynamic shifts, which indicates passive character of the primary disorders primarily determined by a physical factor, gravity-dependent redistribution of body fluids.

Influence of space flight factors on the ultrastructure of rat diaphragm muscle.

Analysis of ultrastructural changes in diaphragm muscle and synaptic apparatus after 7- and 14-day biosatellite spaceflight showed destructive and atrophic changes that developed starting from in the early terms of exposure. Structural alterations of different severity were revealed in all elements of the muscle (muscle fibers, neuromuscular junctions, intramuscular nerves, and blood vessels) and were paralleled by activation of regeneration processes.

Effect of long-term simulated weightlessness on surfactant and water balance in mouse lungs.

Weightlessness produces adaptive and maladaptive changes in the respiratory system. We assessed the effects of 30-day antiorthostatic hanging as a model of microgravity on the water balance in the lungs and surface activity and phospholipid composition of pulmonary surfactant in C57Bl/6 mice. Long-term antiorthostatic hanging increased water content in the lungs and reduced surface-active properties of the surfactant. This was accompanied by an increase in the content of alveolar phospholipids and changes in their fractional composition (increase in the relative content of lysophosphatidylcholine and phosphatidylethanolamine).