25 research outputs found
Teacher Candidates’ Learning Gains: The Tale of Two Co-Teachers
Co-teaching during the student teaching experience has been given increased attention among researchers and teacher educators. Co-teaching facilitates an apprenticeship arrangement that encourages modeling of classroom practice for the candidate and provides a chance to implement directly what is being learned. This qualitative study explored teacher candidates’ learning gains using the co-teaching model for student teaching. Teacher candidates were able to see more clearly the dynamics of how a classroom works and the process by which teachers plan lessons, implement curriculum, and manage the many duties of a classroom teacher
Обоснование выбора электродвигателя и схемы его включения для системы точного поддержания скорости
Рассматривается применение в системах точного поддержания скорости различных синхронных электродвигателей. В результате сравнения рекомендовано применение в таких системах конденсаторного синхронного реактивного двигателя с трехфазными обмотками статора. Это позволяет упростить и удешевить систему точного электропривода и повысить ее надежность
Моделирование формирования структуры металломатричных композитов в процессе синтеза с оценкой эффективных свойств
Работа посвящена моделированию процесса кристаллизации композита с металлической матрицей и твердыми включениями с учетом условий синтеза (давление, скорость охлаждения), моделированию процесса формирования переходной зоны между частицами и матрицей и расчету эффективных свойств получаемых композитов.The work is devoted to modeling the crystallization process of metal matrix composite with solid inclusions, taking into account the synthesis conditions (pressure, cooling rate), to modeling the formation of the transition zone between particles and matrix, and calculating the effective properties of the resulting composites
Molecular mechanisms of the unconventional secretion of macrophage migration inhibitory factor (MIF)
Macrophage migration inhibitory factor is a pro-inflammatory cytokine that plays a pivotal role in the pathogenesis of inflammatory disease such as septic shock and rheumatoid arthritis. The release of MIF from inflammatory cells is a common feature in these diseases, and a correlation between the severity of disease and MIF production is observed. MIF is a leaderless protein that is secreted from cells by a specialized, non-classical export pathway, possibly involving the transporter ABCA1. The release of MIF nevertheless is tightly regulated with respect to its production in response to different inflammatory, proliferative, and activating stimuli. In recent studies it was demonstrated that the administration of neutralizing anti-MIF antibodies and small molecule MIF inhibitors is advantageous in inflammatory diseases. These approaches have in common that they all target MIF only after it is released from cells. A more effective approach in treating MIF-related diseases may be to target MIF before it is released from cells. The unconventional secretion pathway of MIF might permit to specifically block the release of MIF without compromising the general secretion mechanism of the cell. To date, little is known about the molecular mechanisms involved in the release of MIF. My thesis demonstrates that MIF associates with the novel MIF interaction partner p115, a Golgi-associated protein that takes part in the ER/Golgi secretion pathway. By confocal microscopy, I was able to demonstrate that MIF and p115 are associating in the cytoplasm; following activation, macrophages redistribute MIF to the plasma membrane together with a portion of p115. This finding agrees with results obtained from Western blot and ELISA analysis, demonstrating that upon LPS stimulation both MIF and p115 are co-secreted, accompanied by a corresponding decrease in intracellular protein concentration. Accordingly, I demonstrated that the depletion of p115 from monocytes/macrophages by RNAi results in an inhibition of MIF release after LPS stimulation. Intriguingly, the secretion of other pro-inflammatory cytokines, both conventionally released (TNF-alpha, IL-6) and unconventionally released (IL-1beta) was not affected by the partial depletion of p115. Similarly, the depletion of p115 in HeLa cells did not affect the conventional (FGF-4) or unconventional (FGF-2) secretion. This observation leads to the assumption that it is possible to specifically target the secretion of MIF without compromising the normal and necessary secretory mechanism of cells. It is important to note that the effect of p115 depletion on MIF secretion was not only observed after LPS stimulation, but also after bacterial infection with Chlamydia trachomatis. Notably, the prototypic small molecule MIF inhibitor, 4-iodo-6-phenylpyrimidine, inhibits MIF secretion by targeting the interaction between MIF and p115. My data reveal p115 to be a critical intermediary component in the regulated secretion of MIF from monocytes/macrophages. After the discovery of GRASP65 in the unconventional secretion of acyl-CoA binding protein in Dictyostelium, p115 is the second protein of the Golgi complex attributed with a dual function in secretion. On one hand p115 is involved in the classical secretion pathway tethering vesicles arriving from the ER to the Golgi, and on the other hand it is involved in the unconventional secretion of MIF. The discovery that 4-IPP specifically blocks the secretion of MIF by interfering with MIF’s interaction with p115 gives hope in the search of a potent approach in treating MIF-related diseases by blocking its release from cells. It seems feasible to perform a screening of MIF inhibitors that specifically target MIF’s ability to interact with p115 and block its release from cells. In addition, in my thesis I report on the initial characterization of the structural homolog of MIF, D-dopachrome tautomerase (DDT). After the successful purification of recombinant, native murine DDT, a specific anti-DDT antibody was produced and utilized for the establishment of a DDT-specific ELISA. It was shown that DDT is released from macrophages in response to LPS in a pattern similar to that of MIF. Furthermore, it was shown that the deletion of the mif gene has no effect on the production of DDT. The precise biological function of DDT remains unclear and the detailed characterization of the secretion pathway of DDT was beyond the scope of this thesis, but the comparable release patterns of MIF and DDT suggest related functions of the two proteins
Molecular mechanisms of the unconventional secretion of macrophage migration inhibitory factor (MIF)
Macrophage migration inhibitory factor is a pro-inflammatory cytokine that plays a pivotal role in the pathogenesis of inflammatory disease such as septic shock and rheumatoid arthritis. The release of MIF from inflammatory cells is a common feature in these diseases, and a correlation between the severity of disease and MIF production is observed. MIF is a leaderless protein that is secreted from cells by a specialized, non-classical export pathway, possibly involving the transporter ABCA1. The release of MIF nevertheless is tightly regulated with respect to its production in response to different inflammatory, proliferative, and activating stimuli. In recent studies it was demonstrated that the administration of neutralizing anti-MIF antibodies and small molecule MIF inhibitors is advantageous in inflammatory diseases. These approaches have in common that they all target MIF only after it is released from cells. A more effective approach in treating MIF-related diseases may be to target MIF before it is released from cells. The unconventional secretion pathway of MIF might permit to specifically block the release of MIF without compromising the general secretion mechanism of the cell. To date, little is known about the molecular mechanisms involved in the release of MIF. My thesis demonstrates that MIF associates with the novel MIF interaction partner p115, a Golgi-associated protein that takes part in the ER/Golgi secretion pathway. By confocal microscopy, I was able to demonstrate that MIF and p115 are associating in the cytoplasm; following activation, macrophages redistribute MIF to the plasma membrane together with a portion of p115. This finding agrees with results obtained from Western blot and ELISA analysis, demonstrating that upon LPS stimulation both MIF and p115 are co-secreted, accompanied by a corresponding decrease in intracellular protein concentration. Accordingly, I demonstrated that the depletion of p115 from monocytes/macrophages by RNAi results in an inhibition of MIF release after LPS stimulation. Intriguingly, the secretion of other pro-inflammatory cytokines, both conventionally released (TNF-alpha, IL-6) and unconventionally released (IL-1beta) was not affected by the partial depletion of p115. Similarly, the depletion of p115 in HeLa cells did not affect the conventional (FGF-4) or unconventional (FGF-2) secretion. This observation leads to the assumption that it is possible to specifically target the secretion of MIF without compromising the normal and necessary secretory mechanism of cells. It is important to note that the effect of p115 depletion on MIF secretion was not only observed after LPS stimulation, but also after bacterial infection with Chlamydia trachomatis. Notably, the prototypic small molecule MIF inhibitor, 4-iodo-6-phenylpyrimidine, inhibits MIF secretion by targeting the interaction between MIF and p115. My data reveal p115 to be a critical intermediary component in the regulated secretion of MIF from monocytes/macrophages. After the discovery of GRASP65 in the unconventional secretion of acyl-CoA binding protein in Dictyostelium, p115 is the second protein of the Golgi complex attributed with a dual function in secretion. On one hand p115 is involved in the classical secretion pathway tethering vesicles arriving from the ER to the Golgi, and on the other hand it is involved in the unconventional secretion of MIF. The discovery that 4-IPP specifically blocks the secretion of MIF by interfering with MIF’s interaction with p115 gives hope in the search of a potent approach in treating MIF-related diseases by blocking its release from cells. It seems feasible to perform a screening of MIF inhibitors that specifically target MIF’s ability to interact with p115 and block its release from cells. In addition, in my thesis I report on the initial characterization of the structural homolog of MIF, D-dopachrome tautomerase (DDT). After the successful purification of recombinant, native murine DDT, a specific anti-DDT antibody was produced and utilized for the establishment of a DDT-specific ELISA. It was shown that DDT is released from macrophages in response to LPS in a pattern similar to that of MIF. Furthermore, it was shown that the deletion of the mif gene has no effect on the production of DDT. The precise biological function of DDT remains unclear and the detailed characterization of the secretion pathway of DDT was beyond the scope of this thesis, but the comparable release patterns of MIF and DDT suggest related functions of the two proteins
Role for Reduced MIF Secretion in Attenuated AMPK Activation and Ischemic Recovery in the Senescent Heart
Role for Reduced MIF Secretion in Attenuated AMPK Activation and Ischemic Recovery in the Senescent Heart
Glucocorticoid-induced MIF expression by human CEM T cells.
Macrophage migration inhibitory factor (MIF) is an upstream activator of the immune response that counter-regulates the immunosuppressive effects of glucocorticoids. While MIF is released by cells in response to diverse microbial and invasive stimuli, evidence that glucocorticoids in low concentrations also induce MIF secretion suggests an additional regulatory relationship between these mediators. We investigated the expression of MIF from the human CEM T cell line, which exists in two well-characterized, glucocorticoid-sensitive (CEM-C7) and glucocorticoid-resistant (CEM-C1) variant clones. Dexamethasone in low concentrations induced MIF secretion from CEM-C7 but not CEM-C1 T cells by a bell-shaped dose response that was similar to that reported previously for the release of MIF by monocytes/macrophages. Glucocorticoid stimulation of CEM-C7 T cells was accompanied by an MIF transcriptional response, which by promoter analysis was found to involve the GRE and ATF/CRE transcription factor binding sites. These data support a glucocorticoid-mediated MIF secretion response by T cells that may contribute to the regulation of the adaptive immune response
Chemical elements in soils and surface waters of the Ukok plateau (South-Eastern Altai)
Актуальность исследования обусловлена слабой изученностью химического состава почв и поверхностных вод плоскогорья Укок, являющегося объектом всемирного наследия ЮНЕСКО. Цель: изучить уровни содержания химических элементов в почвах и поверхностных водах центральной, южной и юго-восточной части плоскогорья Укок и дать эколого-биогеохимическую оценку этой малоизученной территории. Объекты: основные типы почв (криоаридные и горные лугово-степные, горные луговые, горные тундровые) и поверхностные воды (реки Жумалы, Калгуты, Аргамжи, Ак-Алаха, Тархата и озеро Укок) плоскогорья Укок (Республика Алтай, Российская Федерация). Методы. Содержание металлов в почвах определено методом эмиссионного спектрального анализа в Институте геологии и минералогии СО РАН, общее содержание микроэлементов в природных водах – в химико-аналитическом центре ИВЭП СО РАН спектрометрическим методом с использованием электротермической атомизации. Результаты. Представлен химический состав различных типов почв и поверхностных вод высокогорного плоскогорья Укок. Уровни содержания химических элементов в почвах плоскогорья не превышают их кларков в почвенном покрове и соответствуют их концентрациям в горно-тундровых почвах Алтая. Исключением являются почвы и почвообразующие породы над Калгутинским W-Mo-V-Cu месторождением, где отмечается аномально высокое содержание вольфрама – до 30–60 мг/кг. С ореолами рассеяния и воздействием отвалов штольни и хвостохранилища обогатительной фабрики этого месторождения мы связываем повышенное содержание Cu в водах реки Калгуты – 16 мкг/дм3 и в почвах бассейна. Почвы плоскогорья отличаются невысоким валовым содержанием P и Са, но обогащены калием - его содержание превышает 2 % в большинстве образцов. Концентрация фосфора в почвах плоскогорья Укок возрастает с запада на восток, от выровненной (центральной) части к горным окаймлениям, что обусловлено фосфоритоносностью коренных пород Алтае-Саянской горной страны. Низкие значения элювиально-аккумулятивных коэффициентов большинства металлов в изученных почвах плоскогорья могут служить показателем отсутствия на данный момент здесь выраженного антропогенного загрязнения. Содержание большинства элементов в почвах увеличивается c глубиной. В горно-тундровых торфянистых почвах под ерником обнаружена биогенная аккумуляция Mn. Для степных почв отмечено некоторое накопление в поверхностных горизонтах Zn, Cr, V и Ni. Наиболее равномерным распределением отличается Pb и Zn. Исходная неоднородность моренных и озерно-ледниковых отложений определяет разнообразие внутрипрофильного распределения металлов в почвах, на них сформированных. Не выявлено четкой зависимости содержания большинства макро- и микроэлементов в поверхностных водах от уровня их концентраций в почвах. Тем не менее отмечено повышение интенсивность водной миграции железа в заболоченных ландшафтах Бертекской части бассейна реки Ак-Алаха, в водах которой обнаружено его наиболее высокое содержание.The relevance of the research is in the poorly studied chemical composition of soils and surface waters of the Ukok plateau - the UNESCO world heritage site. The aim of the research is to study chemical elements content level in soils and surface waters of the central, southern and south-eastern parts of the Ukok plateau, to give an ecological and biogeochemical assessment of this little-studied area. Objects: main soil types (Mollic Leptosols Eutric, Umbric Leptosols Dystric, Lithic Leptosols Brunic) and surface water (rivers Zhumaly, Kalguty, Argamzhi, Ak-Alakh, Tarkhat and lake Ukok) of the plateau Ukok (Altai Republic, Russian Federation). Methods. Metal content in soils was determined by the approximate-quantitative emission spectral analysis at the Institute of Geochemistry and Mineralogy of SB RAS, while the content of trace elements in natural waters was defined by means of the atomic absorption spectrometry using electrothermal atomization at the Chemical Analytical Center of IWEP SB RAS. Results. The paper presents the results of studying chemical composition of different types of soils and surface waters of the high-mountain plateau Ukok. The concentrations of chemical elements in soils of the plateau do not exceed their Clarks in the soil cover and correspond to those in the mountain-tundra soils of Altai, except for the soils and parent rocks above the Kalguty W-Mo-V-Cu deposit distinguished by the abnormally high content of tungsten (up to 30-60 mg/kg). The increased content of Cu in the waters of the river Kalguty (16 µg/dm3 ) and the soils of the basin is related to the halos and the influence of pilings and tailings of the concentration plant. The plateau soils are characterized by low gross content of P and Ca needed for plants, but enriched with potassium, the content of which exceeds 2 % in more than half of the samples. In soils of the Ukok plateau, P content increases from west to east, from true surface (central) part to the edging mountains that is due to phosphor presence in indigenous rocks of the Altai-Sayan mountain country. At present, low eluvial-accumulative ratios of metals in the studied soils of the plateau are evidence of the lack of pronounced anthropogenic pollution. The content of most elements in soils increases with depth. In mountain-tundra peat soils, the biogenic accumulation of Mn was found under dwarf birches. For steppe soils, some accumulation of Zn, Cr, V and Ni was observed in surface horizons. Pb and Zn had the most uniform distribution. The initial heterogeneity of moraine and lake-glacial deposits determines the diversity of intra-profile distribution of metals in the formed soils. Clear dependence of most macro-and microelements content in surface waters on their concentrations in soils was not established. Nevertheless, there was an increase in the intensity of water migration of iron in wetlands of the Bertek part of the Ak-Alakh river basin, where its content was the highest