Maf and Mitf transcription factors regulate pancreatic endocrine cell differentiation and function

Diabetes - the imbalance in glucose homeostasis is partially caused by loss or dysfunction of pancreatic insulin producing β cells or development of insulin resistance. In Type 1 diabetes β cells are destroyed in the process of an autoimmune attack, whereas in Type 2 diabetes, islets produce insufficient amounts of insulin or the insulin cannot be used adequately. So far, the most promising therapy to treat Type 1 diabetes is pancreatic islet transplantation. However, this method cannot be used in a larger scale because of the severe scarcity of donors. Therefore, there is a great and urgent need to develop new methods and therapies. One of the potential sources of obtaining functional insulin cells are human embryonic stem cells (ESC) or inducible pluripotent stem cells (iPS). Hence, differentiating stem cells into functional β-cells requires a detailed understanding of pancreas development with the focus on molecular programs underlying β-cells formation and function. Pancreas development and differentiation of insulin and glucagon secreting cells is a complex process controlled by a variety of transcription factors. Two of these factors, MafA and MafB, have been shown to play a major role in the regulation of several genes critical to pancreas development and endocrine cell formation. MafB is essential for both α- and β-cell differentiation, as mice lacking MafB have fewer insulin+ and glucagon+ cells during pancreas development. In contrast, in mouse embryos lacking MafA, the development of β-cells is normal, but adult animals develop diabetes. In adult animals these two transcription factors have a distinct expression pattern, with MafB being expressed in α-cells, whereas MafA is exclusively found in β-cells. We have performed gene expression profiling of wild type and MafA/B mutant pancreata to identify genes important for β-cell maturation and function. In these microarray studies several known (insulin, glucagon, Glut2, PC2) but also novel genes were shown to be differentially expressed in MafB and MafA/MafB compound mutant embryos. Gene ontology analysis revealed that the differentially expressed genes were mainly associated with mature β-cell function. Our findings show that Neuronatin (Nnat), islet-specific zinc transporter (Slc30a8), islet-specific glucose-6-phosphatase catalytic subunit-2 protein (G6pc2) and Microphthalmia associated transcription factor (Mitf) are downregulated in embryonic and adult mutant pancreata. In contrast, the mRNA level of Retinol Binding Protein-4 (Rbp4) was upregulated in mutant tissue. Given the differences in spatio-temporal expression pattern of MafA and MafB in developing and adult pancreas, we propose that these two factors regulate islet β-cell formation and maturation in a unique and sequential manner. In MafA deficient models studied so far pancreas development is unaffected, most likely due to compensatory functions of MafB. Therefore, to be able to study the actual role of MafA in β-cell function we developed a β-cell-specific deletion of MafA. Our MafAΔβcell mutant animals lack expression of MafA and MafB in adult β-cells. In contrast to other MafA mutants, our animals have normal islet architecture, β-cells mass, β- to α-cell ratio, and MafB expression is restricted to α-cells. Thus we have created a system suitable for studying the true contribution of MafA to adult β-cell function. Our gene expression experiments have shown that in MafA and MafB mutant embryonic pancreata levels of Mitf expression are reduced comparing to levels found in wild type animals. We also show that Mitf loss of function mutation alters functionality of islet β-cell. In response to an intraperitoneal glucose challenge, but also during non-fasted conditions, Mitf mutant mice have lower blood glucose levels than wild type animals. Mutant islets secrete more insulin upon exposure to high glucose concentrations and Mitf mutant animals have higher circulating insulin levels in fasted conditions. Additionally, Mitf directly regulates the expression of genes regulating blood glucose levels and β-cell formation, which is significantly higher in Mitf mutant than in wild type animals. Thereby, we demonstrate that Mitf is an important factor in modulation of β-cell function

The musical practice of the Sandomierz Benedictine nuns during the eighteenth century

The congregation of the Benedictine nuns of Sandomierz, active between 1615 and 1903, belonged to wealthy magnatial foundations, which allowed the convent to foster cultural activities. Special emphasis was placed on musical performance of various types – the musical adornment of the liturgy. The ‘Glory of God’, as Benedictine nuns referred to it, constituted the essence of their congregational life. On weekdays, the celebration of the Liturgy of the Hours, Masses and – occasionally – other services in choir took six hours, and on numerous feast days of the liturgical year, when the Liturgy of the Hours was sung, not read, it required even more time. The higher the rank of the feast day, the greater was the effort to stress its importance by providing it with a proper musical setting, which led to the cultivation of musical practices of various kinds on special occasions. The musical repertory of the Sandomierz Benedictine nuns comprised plainchant without instrumental accompaniment, plainchant with organ accompaniment, polyphonic a cappella singing (referred to as ‘fi gure’), vocal-instrumental music (‘fractus’) and instrumental music. A picture of religious musical practice emerges primarily from extant musical sources, and also from a ‘choir agenda’ from 1749, a convent chronicle of the years 1762–1780, ‘treasury records’ from 1739– 1806 and convent registers. Eighteenth-century sources document the musical activity of twenty-four nuns of the Sandomierz convent, some of them considered to be ‘professional’ musicians and referred to as ‘singers and players’. The most interesting, but also most problematic, areas are vocal-instrumental practice and the likely consitution of the nuns’ music chapel. We fi nd information about nuns playing keyboard instruments, violin, viola da gamba, tromba marina and horn

Gniew i empatia a poziom zagrożenia wykluczeniem społecznym u młodzieży

The study sought to identify differences in empathy and expression of anger among youth with high and low risk of social exclusion. Youth at higher risk of social exclusion did not differ signiÞcantly in level of empa-thy from those less endangered. However, they scored higher on IRI scales: personal distress and fantasy (as measured by Mark Davis empathy questionnaire). Participants more threatened with social exclusion showed higher level of outward and lower level of inward anger than those less endangered

ANALYSIS OF STRENGTH AND FATIGUE PROPERTIES OF CONSTRU0CTION MATERIALS FOR MANUFACTURING THE PARTS OF SEMI-TRAILERS

The article presents the preliminary tests results of three high-strength steels, which are used in structural elements of semi-trailer's construction. Paper presents an analysis of tensile and fatigue test results of high-strength steels like Hardox 400, Hardox 450 and Strenx 700MC. The fatigue tests are in the range from 104 to 107 number of cycles of applied load with a frequency of 40 Hz. The Wöhler curve shows the results of the fatigue properties of these steels, which are used in the construction of vehicles. Fatigue fractures were subjected to fractographic analysis in order to determine the mechanism of fatigue crack propagation. Fractographic analysis confirmed no effect of inclusions on the test results

Postępy w diagnostyce obrazowej tętnic dogłowowych

Wobec ogromnego postępu w nieinwazyjnej i minimalnie inwazyjnej diagnostyce obrazowej tętnic dogłowowych zaistniała potrzeba zmiany istniejącego algorytmu diagnostycznego. Mimo że cyfrowa angiografia subtrakcyjna nadal pozostaje „złotym standardem”, to ze względu na swoją inwazyjność jest coraz rzadziej wykonywana w celach diagnostycznych i stała się ostatnim badaniem w algorytmie diagnostycznym. Obecnie pierwsze i podstawowe badanie to ultrasonografia w skali szarości oraz doplerowska. Badaniami uzupełniającymi są angiografia metodą tomografii komputerowej i angiografia rezonansu magnetycznego. Polski Przegląd Neurologiczny 2010; 6 (1): 17–2