Contribution of Activating Transcription Factor 3 to development of acinar-to-ductal cell metaplasia

Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancer death in North America. The highest risk factor for PDAC is recurrent pancreatitis. While the link between PDAC and pancreatitis is unknown, de-differentiation of acinar cells is common to both diseases. Our lab has shown that Activating Transcription Factor 3 (ATF3), a factor upregulated during pancreatic injury, contributes to the development of acinar-to-ductal cell metaplasia (ADM), a precursor phenotype of PDAC. The goal of this study was to identify how ATF3 contributes to ADM. I hypothesize that ATF3 regulates acinar gene expression promoting ADM. We observed decreased ADM development in Atf3-/- acinar cultures, along with expression changes in differentiation genes and ADM promoting pathways (EGFR) in vivo. Assessment following chronic injury indicated absence of ATF3 resulted in decreased tissue damage. These results suggest a novel mechanism where ATF3 promotes ADM through loss of the mature acinar cell phenotype

Activating Transcription Factor 3 Promotes Loss of the Acinar Cell Phenotype in Response to Cerulein-Induced Pancreatitis in Mice

Pancreatitis is a debilitating disease of the exocrine pancreas that, under chronic conditions, is a major susceptibility factor for pancreatic ductal adenocarcinoma (PDAC). Although down-regulation of genes that promote the mature acinar cell fate is required to reduce injury associated with pancreatitis, the factors that promote this repression are unknown. Activating transcription factor 3 (ATF3) is a key mediator of the unfolded protein response, a pathway rapidly activated during pancreatic insult. Using chromatin immunoprecipitation followed by next-generation sequencing, we show that ATF3 is bound to the transcriptional regulatory regions of \u3e30% of differentially expressed genes during the initiation of pancreatitis. Of importance, ATF3-dependent regulation of these genes was observed only upon induction of pancreatitis, with pathways involved in inflammation, acinar cell differentiation, and cell junctions being specifically targeted. Characterizing expression of transcription factors that affect acinar cell differentiation suggested that acinar cells lacking ATF3 maintain a mature cell phenotype during pancreatitis, a finding supported by maintenance of junctional proteins and polarity markers. As a result

Glycosylation of immunoglobulin G is regulated by a large network of genes pleiotropic with inflammatory diseases

Effector functions of immunoglobulin G (IgG) are regulated by the composition of a glycan moiety, thus affecting activity of the immune system. Aberrant glycosylation of IgG has been observed in many diseases, but little is understood about the underlying mechanisms. We performed a genome-wide association study of IgG N-glycosylation (N = 8090) and, using a data-driven network approach, suggested how associated loci form a functional network. We confirmed in vitro that knockdown of IKZF1 decreases the expression of fucosyltransferase FUT8, resulting in increased levels of fucosylated glycans, and suggest that RUNX1 and RUNX3, together with SMARCB1, regulate expression of glycosyltransferase MGAT3. We also show that variants affecting the expression of genes involved in the regulation of glycoenzymes colocalize with variants affecting risk for inflammatory diseases. This study provides new evidence that variation in key transcription factors coupled with regulatory variation in glycogenes modifies IgG glycosylation and has influence on inflammatory diseases

Croatian educational politics in the context of European Union: analysis of the indicators of educational politics

Diplomski rad bavi se razvojem obrazovne politike u Republici Hrvatskoj s naglaskom na razdoblje od pristupanja Hrvatske Europskoj uniji do danas. Cilj rada je opisati i analizirati pokazatelje obrazovne politike kako bi se dokazalo da Hrvatska, u odnosu na druge zemlje Europske unije, prilično zaostaje u području obrazovne politike s obzirom na pokazatelje razvijenosti obrazovanja. Za testiranje hipoteze napravljena je analiza pokazatelja stanja obrazovanja u Republici Hrvatskoj i skupi 28 država članica Europske unije. Analizom službenih podataka potvrđeno je da Hrvatska, u odnosu na druge zemlje Europske unije, zaostaje u području obrazovne politike s obzirom na pokazatelje razvijenosti obrazovanja. Rad započinje teorijskim dijelom koji se proteže na 31 stranicu, dok je analiza podataka napisana na 21 stranicu i potkrijepljena s 12 grafikona.Graduate work deals with the development of educational policy in the Republic of Croatia, with an emphasis on the period of Croatian accession to the European Union to date. The aim is to describe and analyze the indicators of educational policy in order to prove that Croatia, as compared to other countries in the European Union, straggle in the field of education policy considering indicators of development in education. To test the hypothesis, indicators of development in education in the Republic of Croatia and 28 EU member states were analyzed. The analysis of official data confirmed that Croatia, as compared to other EU countries, lag behind in the field of education policy considering indicators of development in education. The graduate work starts with the theoretical part which extends to 31 pages, while the analysis of the data is written on 21 pages and supported by 12 charts

Croatian educational politics in the context of European Union: analysis of the indicators of educational politics

Diplomski rad bavi se razvojem obrazovne politike u Republici Hrvatskoj s naglaskom na razdoblje od pristupanja Hrvatske Europskoj uniji do danas. Cilj rada je opisati i analizirati pokazatelje obrazovne politike kako bi se dokazalo da Hrvatska, u odnosu na druge zemlje Europske unije, prilično zaostaje u području obrazovne politike s obzirom na pokazatelje razvijenosti obrazovanja. Za testiranje hipoteze napravljena je analiza pokazatelja stanja obrazovanja u Republici Hrvatskoj i skupi 28 država članica Europske unije. Analizom službenih podataka potvrđeno je da Hrvatska, u odnosu na druge zemlje Europske unije, zaostaje u području obrazovne politike s obzirom na pokazatelje razvijenosti obrazovanja. Rad započinje teorijskim dijelom koji se proteže na 31 stranicu, dok je analiza podataka napisana na 21 stranicu i potkrijepljena s 12 grafikona.Graduate work deals with the development of educational policy in the Republic of Croatia, with an emphasis on the period of Croatian accession to the European Union to date. The aim is to describe and analyze the indicators of educational policy in order to prove that Croatia, as compared to other countries in the European Union, straggle in the field of education policy considering indicators of development in education. To test the hypothesis, indicators of development in education in the Republic of Croatia and 28 EU member states were analyzed. The analysis of official data confirmed that Croatia, as compared to other EU countries, lag behind in the field of education policy considering indicators of development in education. The graduate work starts with the theoretical part which extends to 31 pages, while the analysis of the data is written on 21 pages and supported by 12 charts

Croatian educational politics in the context of European Union: analysis of the indicators of educational politics

Diplomski rad bavi se razvojem obrazovne politike u Republici Hrvatskoj s naglaskom na razdoblje od pristupanja Hrvatske Europskoj uniji do danas. Cilj rada je opisati i analizirati pokazatelje obrazovne politike kako bi se dokazalo da Hrvatska, u odnosu na druge zemlje Europske unije, prilično zaostaje u području obrazovne politike s obzirom na pokazatelje razvijenosti obrazovanja. Za testiranje hipoteze napravljena je analiza pokazatelja stanja obrazovanja u Republici Hrvatskoj i skupi 28 država članica Europske unije. Analizom službenih podataka potvrđeno je da Hrvatska, u odnosu na druge zemlje Europske unije, zaostaje u području obrazovne politike s obzirom na pokazatelje razvijenosti obrazovanja. Rad započinje teorijskim dijelom koji se proteže na 31 stranicu, dok je analiza podataka napisana na 21 stranicu i potkrijepljena s 12 grafikona.Graduate work deals with the development of educational policy in the Republic of Croatia, with an emphasis on the period of Croatian accession to the European Union to date. The aim is to describe and analyze the indicators of educational policy in order to prove that Croatia, as compared to other countries in the European Union, straggle in the field of education policy considering indicators of development in education. To test the hypothesis, indicators of development in education in the Republic of Croatia and 28 EU member states were analyzed. The analysis of official data confirmed that Croatia, as compared to other EU countries, lag behind in the field of education policy considering indicators of development in education. The graduate work starts with the theoretical part which extends to 31 pages, while the analysis of the data is written on 21 pages and supported by 12 charts

THE NITROGEN RATIONAL APPLICATION IN THE PLANT PRODUCTION WITH THE AIM TO MAINTAIN SUSTAINABILITY OF THE AGRO-ECO-SYSTEM

Nitrogen is one of the most important nutrient elements used all over the world with the aim of increasing and sustainability of the production of the agricultural crops. During the 'Green Revolution', nitrogen fertilisers contributed to the increase and maintenance of crop yields under different agroecosystems. Nitrogen was a key of economic variability of the agricultural production worldwide, and in this way, it was globally a key of food. On the other hand, anthropogenic influences (fossil fuel combustion) contributed to a greater release of gases, such as carbon dioxide and nitrogen oxides, resulting in global warming of our planet. The application of organic and mineral nitrogen fertilisers can cause losses of nitrogen in gaseous states, as well as, nitrite leaching. Therefore, nitrite contamination of drinking water is already a serious problem in many parts of the world. New technologies in the application of nitrogen fertilisers and crop growing, such as: a precise technique of the plant production, quick tests (in situ) for analysing concentrations of nitrite nitrogen in the plant tissues, rapid tests for chlorophyll determination, the use of computer models of simulation for the improvement of production planning and organising - can affect the increase of the average efficiency in the nitrogen utilisation under different agroecosystems by more than 50%. This paper presents the modes and possibilities of the rational application of nitrogen fertilisers in the seed maize production, which is specific in many of its parameters, as a necessary procedure to maintain a safe agroecosystem

THE NITROGEN RATIONAL APPLICATION IN THE PLANT PRODUCTION WITH THE AIM TO MAINTAIN SUSTAINABILITY OF THE AGRO-ECO-SYSTEM

Nitrogen is one of the most important nutrient elements used all over the world with the aim of increasing and sustainability of the production of the agricultural crops. During the 'Green Revolution', nitrogen fertilisers contributed to the increase and maintenance of crop yields under different agroecosystems. Nitrogen was a key of economic variability of the agricultural production worldwide, and in this way, it was globally a key of food. On the other hand, anthropogenic influences (fossil fuel combustion) contributed to a greater release of gases, such as carbon dioxide and nitrogen oxides, resulting in global warming of our planet. The application of organic and mineral nitrogen fertilisers can cause losses of nitrogen in gaseous states, as well as, nitrite leaching. Therefore, nitrite contamination of drinking water is already a serious problem in many parts of the world. New technologies in the application of nitrogen fertilisers and crop growing, such as: a precise technique of the plant production, quick tests (in situ) for analysing concentrations of nitrite nitrogen in the plant tissues, rapid tests for chlorophyll determination, the use of computer models of simulation for the improvement of production planning and organising - can affect the increase of the average efficiency in the nitrogen utilisation under different agroecosystems by more than 50%. This paper presents the modes and possibilities of the rational application of nitrogen fertilisers in the seed maize production, which is specific in many of its parameters, as a necessary procedure to maintain a safe agroecosystem

Three-dimensional quantification of facial symmetry in adolescents using laser surface scanning

Laser scanning is a non-invasive method for three-dimensional assessment of facial morphology and symmetry. The aim of this study was to quantify facial symmetry in healthy adolescents and explore if there is any gender difference. Facial scans of 270 subjects, 123 males and 147 females (aged 15.3 ± 0.1 years, range 14.6–15.6), were randomly selected from the Avon Longitudinal Study of Parents and Children. Facial scans were processed and analysed using in-house developed subroutines for commercial software. The surface matching between the original face and its mirror image was measured for the whole face, upper, middle, and lower facial thirds. In addition, 3 angular and 14 linear parameters were measured. The percentage of symmetry of the whole face was significantly lower in males (53.49 ± 10.73 per cent) than in females (58.50 ± 10.27 per cent; P 0.05). Average values of linear parameters were less than 1 mm and did not differ significantly between genders (P > 0.05). One angular parameter showed slight lip line asymmetry in both genders. Faces of male 15-year-old adolescents were less symmetric than those of females, but the difference in the amount of symmetry, albeit statistically significant, may not be clinically relevant. Upper, middle, and lower thirds of the face did not differ in the amount of three-dimensional symmetry. Angular and linear parameters of facial symmetry did not show any gender difference