High protonic potential actuates a mechanism of production of reactive oxygen species in mitochondria

AbstractFormation of H2O2 has been studied in rat heart mitochondria, pretreated with H2O2 and aminotriazole to lower their antioxidant capacity. It is shown that the rate of H2O2 formation by mitochondria oxidizing 6 mM succinate is inhibited by a protonophorous uncoupler, ADP and phosphate, malonate, rotenone and myxothiazol, and is stimulated by antimycin A. The effect of ADP is abolished by carboxyatractylate and oligomycin. Addition of uncoupler after rotenone induces further inhibition of H2O2 production. Inhibition of H2O2 formation by uncoupler, malonate and ADP+Pi is shown to be proportional to the ΔΨ decrease by these compounds. A threshold ΔΨ value is found, above which a very strong increase in H2O2 production takes place. This threshold slightly exceeds the state 3 ΔΨ level. The data obtained are in line with the concept [Skulachev, V.P., Q. Rev. Biophys. 29 (1996), 169–202] that a high proton motive force in state 4 is potentially dangerous for the cell due to an increase in the probability of superoxide formation

Evaluation of the shear strength of rocks by cracks based on the results of testing samples with spherical indentors

Experimental data on the relationship of the residual shear strength of rocks in closed cracks with the functional characteristics of intact rocks – the tensile and compressive components of adhesion, the roughness of the crack surfaces, and the level of normal stresses are presented. A unified integrated approach determines the shear strength of intact and destroyed rocks, the residual shear strength of closed rough cracks has been developed. The approach provides for the selection of stress intervals corresponding to different types of fracture, for each of which a strength criterion is proposed, expressed in terms of functional characteristics of intact rock. An express method for estimating the residual shear strength of rocks by cracks with a rough surface has been developed, in which an improved method of loading samples with spherical indentors is used as a basic test method. The express method implements the transition from the data of mechanical tests of samples with spherical indentors to the shear strength indicators for cracks in the rock mass, taking into account the level of normal stresses and the roughness of the crack surfaces measured in field conditions. In this case the roughness scale developed by Barton is used. The express method is informative and available in the fieldwork

Quasiparticle states of the Hubbard model near the Fermi level

The spectra of the t-U and t-t'-U Hubbard models are investigated in the one-loop approximation for different values of the electron filling. It is shown that the four-band structure which is inherent in the case of half-filling and low temperatures persists also for some excess or deficiency of electrons. Besides, with some departure from half-filling an additional narrow band of quasiparticle states arises near the Fermi level. The dispersion of the band, its bandwidth and the variation with filling are close to those of the spin-polaron band of the t-J model. For moderate doping spectral intensities in the new band and in one of the inner bands of the four-band structure decrease as the Fermi level is approached which leads to the appearance of a pseudogap in the spectrum.Comment: 8 pages, 7 figure

Fluctuating charge density waves in the Hubbard model

The charge susceptibility of the two-dimensional repulsive Hubbard model is investigated using the diagram technique developed for the case of strong correlations. In this technique, a power series in the hopping constant is used. It is shown that once the Fermi level crosses one of the Hubbard subbands a sharp peak appears in the momentum dependence of the static susceptibility. With further departure from half-filling the peak transforms to a ridge around the $\Gamma$ point. In the considered range 0\leq|1-\bar{n}|\alt 0.2 of the electron filling $\bar{n}$ the static susceptibility is finite which points to the absence of the long-range charge ordering. However, for $|1-\bar{n}|\approx 0.12$ the susceptibility maxima are located halfway between the center and the boundaries of the Brillouin zone. In this case an interaction of carriers with tetragonal distortions can stabilize the charge density wave with the wavelength of four lattice spacings, as observed experimentally in the low-temperature tetragonal phase of lanthanum cuprates. In the range of parameters inherent in cuprate perovskites the character of the susceptibility evolution with $\bar{n}$ depends only weakly on the ratio of the nearest-neighbor hopping constant to the Hubbard repulsion and on details of the initial band structure. The location of the susceptibility maxima in the Brillouin zone is mainly determined by the value of $\bar{n}$.Comment: 8 pages, 4 figure

Thermoregulatory uncoupling in heart muscle mitochondria: involvement of the ATP/ADP antiporter and uncoupling protein

AbstractPossible involvement of the ATP/ADP antiporter and uncoupling protein (UCP) in thermoregulatory uncoupling of oxidative phosphorylation in heart muscle has been studied. To this end, effects of carboxyatractylate (cAtr) and GDP, specific inhibitors of the antiporter and UCP, on the membrane potential of the oligomycin-treated mitochondria from cold-exposed (6°C, 48 h) and control rats have been measured. It is found that cAtr increases the membrane potential level in both cold-exposed and non-exposed groups, the effect being strongly enhanced by cooling. As for GDP, it is effective only in mitochondria from the cold-exposed rats. In these mitochondria, the coupling effect of GDP is smaller than that of cAtr. CDP, which does not interact with UCP, is without any influence on membrane potential. The cold exposure is found to increase the uncoupling efficiency of added natural (palmitate) or artificial (SF6847) uncouplers, the increase being cAtr- and GDP-sensitive in the case of palmitate. The fatty acid-free bovine serum albumin enhances ΔΨ in both cold-exposed and control groups, the effect being much larger in the former case. It is concluded that in heart muscle mitochondria the ATP/ADP antiporter is responsible for the `mild uncoupling' under normal conditions and for major portion of the thermoregulatory uncoupling in the cold whereas the rest of thermoregulatory uncoupling is served by UCP (presumably by UCP2 since the UCP2 mRNA level is shown to strongly increase in rat heart muscle under the cold exposure conditions used)

Imaging spontaneous currents in superconducting arrays of pi-junctions

Superconductors separated by a thin tunneling barrier exhibit the Josephson effect that allows charge transport at zero voltage, typically with no phase shift between the superconductors in the lowest energy state. Recently, Josephson junctions with ground state phase shifts of pi proposed by theory three decades ago have been demonstrated. In superconducting loops, pi-junctions cause spontaneous circulation of persistent currents in zero magnetic field, analogous to spin-1/2 systems. Here we image the spontaneous zero-field currents in superconducting networks of temperature-controlled pi-junctions with weakly ferromagnetic barriers using a scanning SQUID microscope. We find an onset of spontaneous supercurrents at the 0-pi transition temperature of the junctions Tpi = 3 K. We image the currents in non-uniformly frustrated arrays consisting of cells with even and odd numbers of pi-junctions. Such arrays are attractive model systems for studying the exotic phases of the 2D XY-model and achieving scalable adiabatic quantum computers.Comment: Pre-referee version. Accepted to Nature Physic

Результаты трехлетней вакцинации детей против пневмококковой инфекции в России

Background. After inclusion of pneumococcal vaccination in the National Vaccination Schedule, it is very important to evaluate the efficacy of routine immunisation of the child population for more than 3 years. The obtained results provide opportunity to analyse the problems in achieving the goal, determine their causes, and suggest the ways of overcoming. Our aim was to study the results of a three-year period of pneumococcal vaccination of children. Methods. The quality of immunoprophylaxis of pneumococcal infection in the territory of the Russian Federation were assessed by analysing the coverage of vaccination and timeliness of its conduct after the inclusion of pneumococcal vaccine in the National Vaccination Schedule. The actual epidemiological efficacy of pneumococcal vaccination was assessed based on morbidity and mortality due to community-acquired pneumonia, incidence of acute otitis media among children. By questioning parents (n = 352) who applied to the Federal State Autonomous Institution of the Russian Federation Ministry of Health ‘National Medical Research Centre for Children’s Health, the timeliness of pneumococcal vaccination for infants was established. Results. In most regions, a high level of pneumococcal vaccination coverage was reached (87% of children). Despite the fact that the majority of children (73%) were vaccinated untimely. In particular, the results of a questionnaire survey conducted in the Moscow vaccination centre indicate insufficient awareness of parents for the need to vaccinate infants against pneumococcal infection by primary care professionals and, as a consequence, a low level of timely initiated vaccine introduction (40.1%). The introduction of routine prophylactic pneumococcal vaccination in Russia resulted in a 35% reduction in the death rate of children from community-acquired pneumonia, led to a decrease in the incidence of acute otitis media. Conclusion. The introduction of routine prophylactic vaccination of children against Streptococcus pneumoniae helps to reduce morbidity and mortality from pneumococcal infections. The surveillance system for community-acquired pneumonia requires further improvement. It is advisable to conduct an additional analysis on the reasons for refusals and medical exemptions to vaccination. It is important to increase the professional level of paediatricians in prophylactic vaccination.Обоснование. После включения в Национальный календарь профилактических прививок вакцинации против пневмококковой инфекции очень важно оценить эффективность проводимой более 3 лет рутинной иммунизации детского населения. Полученные результаты позволят проанализировать проблемы в достижении цели, установить их причины и предложить пути преодоления. Цель исследования — изучить результаты трехлетнего периода вакцинации детей против пневмококковой инфекции. Методы. Проведена оценка качества иммунопрофилактики пневмококковой инфекции на территории Российской Федерации путем анализа охвата прививками, своевременности их проведения после включения пневмококковой вакцины в Национальный календарь профилактических прививок. Выполнена оценка фактической эпидемиологической эффективности вакцинации против пневмококковой инфекции на основании заболеваемости и смертности внебольничными пневмониями, заболеваемости острым средним отитом среди детского населения. Путем анкетирования родителей (n=352), обратившихся в ФГАУ «НМИЦ здоровья детей» Минздрава России, установлена своевременность вакцинации младенцев против пневмококковой инфекции. Результаты. В большинстве регионов достигнут высокий уровень охвата детей прививкой против пневмококковой инфекции (87%). При этом большинство детей (73%) были вакцинированы несвоевременно. В частности, результаты анкетирования, проведенного в центре вакцинации г. Москвы, указывают на недостаточную информированность родителей о необходимости вакцинации младенцев против пневмококковой инфекции специалистами первичного звена и, как следствие, низкий уровень своевременного начала введения вакцины (40,1%). Внедрение плановой вакцинопрофилактики против пневмококковой инфекции в России позволило на 35% снизить смертность детей от внебольничных пневмоний, привело к уменьшению заболеваемости острыми средними отитами. Заключение. Внедрение плановой вакцинопрофилактики детей против Streptococcus pneumoniae способствует снижению заболеваемости и смертности от пневмококковых инфекций. Система эпиднадзора за внебольничными пневмониями требует дальнейшего совершенствования. Целесообразно проведение дополнительного анализа причин отказов и медицинских отводов от вакцинации; важное значение имеет повышение профессионального уровня врачей-педиатров по вопросам вакцинопрофилактики.КОНФЛИКТ ИНТЕРЕСОВЛ.С. Намазова-Баранова — получение исследовательских грантов от фармацевтических компаний Пьер Фабр, Genzyme Europe B. V., ООО «Астра зенека Фармасьютикалз», Gilead / PRA «Фармасьютикал Рисерч Ассошиэйтс СиАйЭс», Teva Branded Pharma ceuti cal products R&D, Inc / ООО «ППД Девелопмент (Смоленск)», «Сталлержен С. А.» / «Квинтайлс ГезмбХ» (Австрия).М.В. Федосеенко — получение гонораров от компаний Pfizer, Sanofi Pasteur, MSD за чтение лекций.Остальные авторы статьи подтвердили отсутствие конфликта интересов, о котором необходимо сообщить

Estimating global injuries morbidity and mortality : methods and data used in the Global Burden of Disease 2017 study

Background: While there is a long history of measuring death and disability from injuries, modern research methods must account for the wide spectrum of disability that can occur in an injury, and must provide estimates with sufficient demographic, geographical and temporal detail to be useful for policy makers. The Global Burden of Disease (GBD) 2017 study used methods to provide highly detailed estimates of global injury burden that meet these criteria. Methods: In this study, we report and discuss the methods used in GBD 2017 for injury morbidity and mortality burden estimation. In summary, these methods included estimating cause-specific mortality for every cause of injury, and then estimating incidence for every cause of injury. Non-fatal disability for each cause is then calculated based on the probabilities of suffering from different types of bodily injury experienced. Results: GBD 2017 produced morbidity and mortality estimates for 38 causes of injury. Estimates were produced in terms of incidence, prevalence, years lived with disability, cause-specific mortality, years of life lost and disability-adjusted life-years for a 28-year period for 22 age groups, 195 countries and both sexes. Conclusions: GBD 2017 demonstrated a complex and sophisticated series of analytical steps using the largest known database of morbidity and mortality data on injuries. GBD 2017 results should be used to help inform injury prevention policy making and resource allocation. We also identify important avenues for improving injury burden estimation in the future

Global age-sex-specific fertility, mortality, healthy life expectancy (HALE), and population estimates in 204 countries and territories, 1950-2019 : a comprehensive demographic analysis for the Global Burden of Disease Study 2019

Background: Accurate and up-to-date assessment of demographic metrics is crucial for understanding a wide range of social, economic, and public health issues that affect populations worldwide. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 produced updated and comprehensive demographic assessments of the key indicators of fertility, mortality, migration, and population for 204 countries and territories and selected subnational locations from 1950 to 2019. Methods: 8078 country-years of vital registration and sample registration data, 938 surveys, 349 censuses, and 238 other sources were identified and used to estimate age-specific fertility. Spatiotemporal Gaussian process regression (ST-GPR) was used to generate age-specific fertility rates for 5-year age groups between ages 15 and 49 years. With extensions to age groups 10–14 and 50–54 years, the total fertility rate (TFR) was then aggregated using the estimated age-specific fertility between ages 10 and 54 years. 7417 sources were used for under-5 mortality estimation and 7355 for adult mortality. ST-GPR was used to synthesise data sources after correction for known biases. Adult mortality was measured as the probability of death between ages 15 and 60 years based on vital registration, sample registration, and sibling histories, and was also estimated using ST-GPR. HIV-free life tables were then estimated using estimates of under-5 and adult mortality rates using a relational model life table system created for GBD, which closely tracks observed age-specific mortality rates from complete vital registration when available. Independent estimates of HIV-specific mortality generated by an epidemiological analysis of HIV prevalence surveys and antenatal clinic serosurveillance and other sources were incorporated into the estimates in countries with large epidemics. Annual and single-year age estimates of net migration and population for each country and territory were generated using a Bayesian hierarchical cohort component model that analysed estimated age-specific fertility and mortality rates along with 1250 censuses and 747 population registry years. We classified location-years into seven categories on the basis of the natural rate of increase in population (calculated by subtracting the crude death rate from the crude birth rate) and the net migration rate. We computed healthy life expectancy (HALE) using years lived with disability (YLDs) per capita, life tables, and standard demographic methods. Uncertainty was propagated throughout the demographic estimation process, including fertility, mortality, and population, with 1000 draw-level estimates produced for each metric. Findings: The global TFR decreased from 2·72 (95% uncertainty interval [UI] 2·66–2·79) in 2000 to 2·31 (2·17–2·46) in 2019. Global annual livebirths increased from 134·5 million (131·5–137·8) in 2000 to a peak of 139·6 million (133·0–146·9) in 2016. Global livebirths then declined to 135·3 million (127·2–144·1) in 2019. Of the 204 countries and territories included in this study, in 2019, 102 had a TFR lower than 2·1, which is considered a good approximation of replacement-level fertility. All countries in sub-Saharan Africa had TFRs above replacement level in 2019 and accounted for 27·1% (95% UI 26·4–27·8) of global livebirths. Global life expectancy at birth increased from 67·2 years (95% UI 66·8–67·6) in 2000 to 73·5 years (72·8–74·3) in 2019. The total number of deaths increased from 50·7 million (49·5–51·9) in 2000 to 56·5 million (53·7–59·2) in 2019. Under-5 deaths declined from 9·6 million (9·1–10·3) in 2000 to 5·0 million (4·3–6·0) in 2019. Global population increased by 25·7%, from 6·2 billion (6·0–6·3) in 2000 to 7·7 billion (7·5–8·0) in 2019. In 2019, 34 countries had negative natural rates of increase; in 17 of these, the population declined because immigration was not sufficient to counteract the negative rate of decline. Globally, HALE increased from 58·6 years (56·1–60·8) in 2000 to 63·5 years (60·8–66·1) in 2019. HALE increased in 202 of 204 countries and territories between 2000 and 2019

Estimating global injuries morbidity and mortality : methods and data used in the Global Burden of Disease 2017 study

Background While there is a long history of measuring death and disability from injuries, modern research methods must account for the wide spectrum of disability that can occur in an injury, and must provide estimates with sufficient demographic, geographical and temporal detail to be useful for policy makers. The Global Burden of Disease (GBD) 2017 study used methods to provide highly detailed estimates of global injury burden that meet these criteria. Methods In this study, we report and discuss the methods used in GBD 2017 for injury morbidity and mortality burden estimation. In summary, these methods included estimating cause-specific mortality for every cause of injury, and then estimating incidence for every cause of injury. Non-fatal disability for each cause is then calculated based on the probabilities of suffering from different types of bodily injury experienced. Results GBD 2017 produced morbidity and mortality estimates for 38 causes of injury. Estimates were produced in terms of incidence, prevalence, years lived with disability, cause-specific mortality, years of life lost and disability-adjusted life-years for a 28-year period for 22 age groups, 195 countries and both sexes. Conclusions GBD 2017 demonstrated a complex and sophisticated series of analytical steps using the largest known database of morbidity and mortality data on injuries. GBD 2017 results should be used to help inform injury prevention policy making and resource allocation. We also identify important avenues for improving injury burden estimation in the future.Peer reviewe