Stimulation of spermatogenesis by combined therapy with follicle-stimulating hormone and chorionic gonadotropin for azoospermia and infertility in cases of previous ineffective monotherapy with chorionic gonadotropin and antiestrogen

Often there is a need of application of the methods of treatment, directed on increase in quantity of spermatozoa in an ejaculate. In the research efficiency of the combined therapy by preparation follicle-stimulating hormone was estimated and a chorionic gonadotrophin in cases of the previous inefficiency monotherapy a chorionic gonadotrophin and an anti-estrogen. The efficiency of treatment concerning an oligoteratozoospermiya made 65 %. Positive changes of morphology of spermatozoa included improvement of condensation of a chromatin and decrease of the degrading forms. At the same time this treatment was safe and didn»t lead to development of side effects

ОПРЕДЕЛЕНИЕ СОСТАВА МИКРОВКЛЮЧЕНИЙ САМОРОДНОГО ЗОЛОТА В МАТРИЦЕ СУЛЬФИДНОГО МИНЕРАЛА ПРИ РЕНТГЕНОСПЕКТРАЛЬНОМ ЭЛЕКТРОННО-ЗОНДОВОМ МИКРОАНАЛИЗЕ

A special procedure was proposed to evaluate the gold content in gold-bearing particles found within the sulfide minerals. These particles’ dimensions were comparable or less than the x-ray radiation area during the electron probe microanalysis (EPMA). The procedure was based on the extrapolation of the linear trend dependence of the inclusion element content (or intensity of X-ray) from the content (or intensity) of the surrounding matrix elements in the sulfide mineral. It was justified with the attracting experimental data and computed dependences of x-ray radiation intensity obtained by the modeling of trajectories of electrons in the substance using the Monte-Carlo method. A simple 2-D version of the Monte-Carlo modeling was employed to evaluate the dependence of intensity of x-ray radiation excited by the electrons from the particle size in a homogenous matrix. The model was grounded upon the formula for the law of the Bethe electron stopping power and the Rutherford formula for the angle of elastic scattering of electron in colliding with the atom. The impact parameter in the Rutherford formula was calibrated to ensure the agreement of computed backscattering factor of electrons with the referenced literature data by Duncumb and Reed. The model was tested by comparing the computed data for the adsorption factor  the calculations by known Philibert’s formula for some pure elements, composite sulfide minerals and some sulfides. The proposed procedure was tested with a synthetic sample of sulfide mineral of pyrite with plated pure gold.  The measurements were performed by the electron probe microanalyzer JXA 8200 (JEOL, Japan). With the described above procedure it was feasible to evaluate the contents of gold and silver in the particles of gold-bearing inclusions with the dimensions less than 1 µm in arsenopyrite of the gold ore deposit.Keywords: X-ray electron probe microanalysis, gold inclusions, sulphide minerals, Monte Carlo simulation of electron trackDOI: http://dx.doi.org/10.15826/analitika.2017.21.3.006 V.V. Tatarinov1, 2, А.L. Finkelshtein1, 2, R.G. Kravtsova1, L.А. Pavlova1 1Vinogradov Institute of Geochemistry SB RAS, 1A, Favorsky St, Irkutsk 664033, Russian Federation2Irkutsk State University, 1, Karl Marx St, Irkutsk, 664033, Russian FederationПредложен способ оценки основного состава микровключений самородного золота (Au, Ag) в сульфидных минералах, размеры которых сопоставимы или меньше области генерации рентгеновского излучения при электронно-зондовом микроанализе. Способ основан на экстраполяции линейного тренда зависимости содержания (или интенсивности рентгеновского излучения) элемента включения в сравнении с содержанием (или интенсивностью излучения) элементов окружающей матрицы сульфидного минерала. Измерения проводили на электронно-зондовом микроанализаторе JXA 8200 (JEOL, Япония). Обоснование способа выполнено с привлечением экспериментальных данных и расчетных зависимостей интенсивности рентгеновского излучения элементов, полученных с помощью моделирования траекторий электронов в веществе методом Монте-Карло. Предложен простой двумерный вариант модели Монте-Карло для оценки зависимости интенсивности рентгеновского излучения, возбуждаемого электронами, от размера включений в однородной матрице. Модель была тестирована сравнением расчетных данных для фактора обратного рассеяния и фактора поглощения, применяемых для коррекции на матричные эффекты в программном обеспечении используемого нами электронно-зондового анализатора, для некоторых чистых элементов, составляющих сульфидные минералы, и некоторых сульфидных минералов. Экспериментальная проверка способа выполнена на образце минерала пирита с нанесенным слоем чистого золота. На примере изучения самородного золота в арсенопирите одного из золоторудных месторождений, показано, что предлагаемый способ позволяет оценивать содержание Au и Ag даже в его включениях, имеющих размер менее 1 мкм.Ключевые слова: рентгеноспектральный электронно-зондовый микроанализ, пробность золота, сульфидные минералы, Монте-Карло моделирование траекторий электроновDOI: http://dx.doi.org/10.15826/analitika.2017.21.3.00

SPECIATION FEATURES OF GOLD IN ORES AND MINERALS OF THE NATALKINSKOE DEPOSIT (NORTH-EAST RUSSIA)

The distribution and speciation features of gold in ores and minerals of the Natalkinskoe gold deposit (North-East Russia) are studied using light microscopy (LM), scanning electron microscopy with energy dispersive X-ray spectrometry (SEM-EDX), X-ray electron probe microanalysis (EPMA), "phase" chemical analysis with atomic absorption spectrometry (PCA-AAS) and atomic absorption spectrometry with analytical data selections for single crystals (AAS-ADSSC). The vein and streaky-vein ores are high-grade ores, whereas veinlet-disseminated ores are less rich and disseminated ores are poor in gold. Up to 85 % of the gold in the ores is in a free native state, associated with quartz and sulfide minerals. LM, SEM-EDX and EPMA reveal that the predominant gold grains are 0.01 to 2.00 mm in size and at a fineness of 720 to 900 ‰. The finely dispersed and submicron elemental gold particles (Au0) amounted to 20 % and are mainly enclosed into arsenopyrite and pyrite. According to PCA-AAS data, the highest Au concentrations (up to 1383 ppm) are recorded in arsenopyrite; lower contents are typical of pyrite (up to 158.2 ppm). In these sulfides, two non-mineral species of "invisible" Au are the structurally bound and surface-bound species recognized by AAS-ADSSC. The structural Au is included in the mineral structure. The surface-bounded Au prevails and is confined to nano-sized, non-autonomous phases (NAPs) on the sulfide surface. In common with "invisible" Au, the micro-sized particles of native gold are often observed on the surface and within the surface layers of sulfide crystals. This is consistent with the model of post-growth transformations of nano-sized NAPs, resulting in the formation of nano and micro-sized Au0 particles. It is expected that the major part of gold contained in arsenopyrite and pyrite as finely dispersed and submicron particles, as well as the surface-bound gold in NAPs, can be won with modified current schemes of gold concentration, which enhances the value of the gold ore mining

The Energy Level Shifts, Wave Functions and the Probability Current Distributions for the Bound Scalar and Spinor Particles Moving in a Uniform Magnetic Field

We discuss the equations for the bound one-active electron states based on the analytic solutions of the Schrodinger and Pauli equations for a uniform magnetic field and a single attractive $\delta({\bf r})$-potential. It is vary important that ground electron states in the magnetic field differ essentially from the analogous state of spin-0 particles, whose binding energy was intensively studied more than forty years ago. We show that binding energy equations for spin-1/2 particles can be obtained without using the language of boundary conditions in the $\delta$-potential model developed in pioneering works. We use the obtained equations to calculate the energy level displacements analytically and demonstrate nonlinear dependencies on field intensity. We show that the magnetic field indeed plays a stabilizing role in considered systems in a case of the weak intensity, but the opposite occurs in the case of strong intensity. These properties may be important for real quantum mechanical fermionic systems in two and three dimensions. We also analyze the exact solution of the Pauli equation for an electron moving in the potential field determined by the three-dimensional $\delta$-well in the presence of a strong magnetic field. We obtain asymptotic expressions for this solution for different values of the problem parameters. In addition, we consider electron probability currents and their dependence on the magnetic field. We show that including the spin in the framework of the nonrelativistic approach allows correctly taking the effect of the magnetic field on the electric current into account. The obtained dependencies of the current distribution, which is an experimentally observable quantity, can be manifested directly in scattering processes, for example.Comment: 31 pages, 10 figure

Determination of the gold-containing micro particles composition in the sulfide mineral matrix using the electron probe microanalysis

A special procedure was proposed to evaluate the gold content in gold-bearing particles found within the sulfide minerals. These particles’ dimensions were comparable or less than the x-ray radiation area during the electron probe microanalysis (EPMA). The procedure was based on the extrapolation of the linear trend dependence of the inclusion element content (or intensity of X-ray) from the content (or intensity) of the surrounding matrix elements in the sulfide mineral. It was justified with the attracting experimental data and computed dependences of x-ray radiation intensity obtained by the modeling of trajectories of electrons in the substance using the Monte-Carlo method. A simple 2-D version of the Monte-Carlo modeling was employed to evaluate the dependence of intensity of x-ray radiation excited by the electrons from the particle size in a homogenous matrix. The model was grounded upon the formula for the law of the Bethe electron stopping power and the Rutherford formula for the angle of elastic scattering of electron in colliding with the atom. The impact parameter in the Rutherford formula was calibrated to ensure the agreement of computed backscattering factor of electrons with the referenced literature data by Duncumb and Reed. The model was tested by comparing the computed data for the adsorption factor the calculations by known Philibert’s formula for some pure elements, composite sulfide minerals and some sulfides. The proposed procedure was tested with a synthetic sample of sulfide mineral of pyrite with plated pure gold. The measurements were performed by the electron probe microanalyzer JXA 8200 (JEOL, Japan). With the described above procedure it was feasible to evaluate the contents of gold and silver in the particles of gold-bearing inclusions with the dimensions less than 1 μm in arsenopyrite of the gold ore deposit.Предложен способ оценки основного состава микровключений самородного золота (Au, Ag) в сульфидных минералах, размеры которых сопоставимы или меньше области генерации рентгеновского излучения при электронно-зондовом микроанализе. Способ основан на экстраполяции линейного тренда зависимости содержания (или интенсивности рентгеновского излучения) элемента включения в сравнении с содержанием (или интенсивностью излучения) элементов окружающей матрицы сульфидного минерала. Измерения проводили на электронно-зондовом микроанализаторе JXA 8200 (JEOL, Япония). Обоснование способа выполнено с привлечением экспериментальных данных и расчетных зависимостей интенсивности рентгеновского излучения элементов, полученных с помощью моделирования траекторий электронов в веществе методом Монте-Карло. Предложен простой двумерный вариант модели Монте-Карло для оценки зависимости интенсивности рентгеновского излучения, возбуждаемого электронами, от размера включений в однородной матрице. Модель была тестирована сравнением расчетных данных для фактора обратного рассеяния и фактора поглощения, применяемых для коррекции на матричные эффекты в программном обеспечении используемого нами электронно-зондового анализатора, для некоторых чистых элементов, составляющих сульфидные минералы, и некоторых сульфидных минералов. Экспериментальная проверка способа выполнена на образце минерала пирита с нанесенным слоем чистого золота. На примере изучения самородного золота в арсенопирите одного из золоторудных месторождений, показано, что предлагаемый способ позволяет оценивать содержание Au и Ag даже в его включениях, имеющих размер менее 1 мкм.The research was performed using the equipment of the joint use Isotope-Geochemical Research Center of IGC SB RAS center, and supported by The Russian Foundation for the Fundamental Research (projects № 17-05-00095)

Chronic Nicotine Modifies Skeletal Muscle Na,K-ATPase Activity through Its Interaction with the Nicotinic Acetylcholine Receptor and Phospholemman

Our previous finding that the muscle nicotinic acetylcholine receptor (nAChR) and the Na,K-ATPase interact as a regulatory complex to modulate Na,K-ATPase activity suggested that chronic, circulating nicotine may alter this interaction, with long-term changes in the membrane potential. To test this hypothesis, we chronically exposed rats to nicotine delivered orally for 21–31 days. Chronic nicotine produced a steady membrane depolarization of ∼3 mV in the diaphragm muscle, which resulted from a net change in electrogenic transport by the Na,K-ATPase α2 and α1 isoforms. Electrogenic transport by the α2 isoform increased (+1.8 mV) while the activity of the α1 isoform decreased (−4.4 mV). Protein expression of Na,K-ATPase α1 or α2 isoforms and the nAChR did not change; however, the content of α2 subunit in the plasma membrane decreased by 25%, indicating that its stimulated electrogenic transport is due to an increase in specific activity. The physical association between the nAChR, the Na,K-ATPase α1 or α2 subunits, and the regulatory subunit of the Na,K-ATPase, phospholemman (PLM), measured by co-immuno precipitation, was stable and unchanged. Chronic nicotine treatment activated PKCα/β2 and PKCδ and was accompanied by parallel increases in PLM phosphorylation at Ser63 and Ser68. Collectively, these results demonstrate that nicotine at chronic doses, acting through the nAChR-Na,K-ATPase complex, is able to modulate Na,K-ATPase activity in an isoform-specific manner and that the regulatory range includes both stimulation and inhibition of enzyme activity. Cholinergic modulation of Na,K-ATPase activity is achieved, in part, through activation of PKC and phosphorylation of PLM

ФОРМЫ НАХОЖДЕНИЯ ЗОЛОТА В РУДАХ И МИНЕРАЛАХ НАТАЛКИНСКОГО МЕСТОРОЖДЕНИЯ (СЕВЕРО-ВОСТОК РОССИИ)

The distribution and speciation features of gold in ores and minerals of the Natalkinskoe gold deposit (North-East Russia) are studied using light microscopy (LM), scanning electron microscopy with energy dispersive X-ray spectrometry (SEM-EDX), X-ray electron probe microanalysis (EPMA), "phase" chemical analysis with atomic absorption spectrometry (PCA-AAS) and atomic absorption spectrometry with analytical data selections for single crystals (AAS-ADSSC). The vein and streaky-vein ores are high-grade ores, whereas veinlet-disseminated ores are less rich and disseminated ores are poor in gold. Up to 85 % of the gold in the ores is in a free native state, associated with quartz and sulfide minerals. LM, SEM-EDX and EPMA reveal that the predominant gold grains are 0.01 to 2.00 mm in size and at a fineness of 720 to 900 ‰. The finely dispersed and submicron elemental gold particles (Au0) amounted to 20 % and are mainly enclosed into arsenopyrite and pyrite. According to PCA-AAS data, the highest Au concentrations (up to 1383 ppm) are recorded in arsenopyrite; lower contents are typical of pyrite (up to 158.2 ppm). In these sulfides, two non-mineral species of "invisible" Au are the structurally bound and surface-bound species recognized by AAS-ADSSC. The structural Au is included in the mineral structure. The surface-bounded Au prevails and is confined to nano-sized, non-autonomous phases (NAPs) on the sulfide surface. In common with "invisible" Au, the micro-sized particles of native gold are often observed on the surface and within the surface layers of sulfide crystals. This is consistent with the model of post-growth transformations of nano-sized NAPs, resulting in the formation of nano and micro-sized Au0 particles. It is expected that the major part of gold contained in arsenopyrite and pyrite as finely dispersed and submicron particles, as well as the surface-bound gold in NAPs, can be won with modified current schemes of gold concentration, which enhances the value of the gold ore mining.С помощью оптической микроскопии (ОМ), сканирующей электронной микроскопии с энергодисперсионной спектрометрией (СЭМ-ЭДС), рентгеноспектрального микроанализа (РСМА), фазового химического анализа на основе атомно-абсорбционной спектрометрии (ФХА-ААС) и метода статистических выборок аналитических данных для монокристаллов с применением ААС (СВАДМ-ААС) проведено изучение особенностей распределения и форм нахождения (ФН) Au в рудах и минералах Наталкинского золоторудного месторождения (северо-восток России). К наиболее «богатым» здесь относят жильные и прожилково-жильные руды, к менее «богатым» – прожилково-вкрапленные, к «бедным» – вкрапленные. До 80–85 % Au в руде находится в свободном самородном состоянии в ассоциации с кварцем и сульфидными минералами. По данным ОМ, СЭМ-ЭДС и РСМА преобладают золотины размером 0.01–2.00 мм и пробностью 720–900 ‰. До 15–20 % приходится на долю тонкодисперсных и субмикронных частиц элементного золота (Au0), большая часть которых заключена в арсенопирите и пирите. По данным ФХА-ААС самые высокие концентрации Au отмечены в арсенопирите (до 1383 г/т), менее высокие – в пирите (до 158.2 г/т). С помощью метода СВАДМ-ААС в этих сульфидах установлены две неминеральные ФН «невидимого» Au – структурная и поверхностно-связанная. Первая входит в структуру минералов, вторая, преобладающая, приурочена к наноразмерным неавтономным фазам (НФ) на их поверхности. Наряду с «невидимым» Au часто на поверхности и в поверхностном слое сульфидов развиты микровключения самородного Au, что согласуется с моделью постростовых преобразований наноразмерных НФ, приводящих к возникновению нано- и микрочастиц Au0. Предполагается, что большую часть золота, находящегося в сульфидах в виде тонкодисперсных и субмикронных частиц, а также поверхностно-связанного золота в НФ можно извлечь при доработке уже имеющихся схем обогащения, что повышает ценность добываемого сырья и значительно увеличивает перспективы месторождения

The degradation of p53 and its major E3 ligase Mdm2 is differentially dependent on the proteasomal ubiquitin receptor S5a.

p53 and its major E3 ligase Mdm2 are both ubiquitinated and targeted to the proteasome for degradation. Despite the importance of this in regulating the p53 pathway, little is known about the mechanisms of proteasomal recognition of ubiquitinated p53 and Mdm2. In this study, we show that knockdown of the proteasomal ubiquitin receptor S5a/PSMD4/Rpn10 inhibits p53 protein degradation and results in the accumulation of ubiquitinated p53. Overexpression of a dominant-negative deletion of S5a lacking its ubiquitin-interacting motifs (UIM)s, but which can be incorporated into the proteasome, also causes the stabilization of p53. Furthermore, small-interferring RNA (siRNA) rescue experiments confirm that the UIMs of S5a are required for the maintenance of low p53 levels. These observations indicate that S5a participates in the recognition of ubiquitinated p53 by the proteasome. In contrast, targeting S5a has no effect on the rate of degradation of Mdm2, indicating that proteasomal recognition of Mdm2 can be mediated by an S5a-independent pathway. S5a knockdown results in an increase in the transcriptional activity of p53. The selective stabilization of p53 and not Mdm2 provides a mechanism for p53 activation. Depletion of S5a causes a p53-dependent decrease in cell proliferation, demonstrating that p53 can have a dominant role in the response to targeting S5a. This study provides evidence for alternative pathways of proteasomal recognition of p53 and Mdm2. Differences in recognition by the proteasome could provide a means to modulate the relative stability of p53 and Mdm2 in response to cellular signals. In addition, they could be exploited for p53-activating therapies. This work shows that the degradation of proteins by the proteasome can be selectively dependent on S5a in human cells, and that this selectivity can extend to an E3 ubiquitin ligase and its substrate

Правила проведения исследований биоаналоговых лекарственных средств (биоаналогов)

В настоящих Правилах изложены основные принципы нормативного регулирования доклинического и клинического изучения биоаналоговых лекарственных средств (далее — биоаналогов), в отношении которых заявлено, что они аналогичны инновационным биологическим лекарственным препаратам