Nonsense-mediated mRNA decay in neuronal physiology and neurodegeneration

The processes of mRNA export from the nucleus and subsequent mRNA translation in the cytoplasm are of particular relevance in eukaryotic cells. In highly polarised cells such as neurons, finely-tuned molecular regulation of these processes serves to safeguard the spatiotemporal fidelity of gene expression. Nonsense-mediated mRNA decay (NMD) is a cytoplasmic translation-dependent quality control process that regulates gene expression in a wide range of scenarios in the nervous system, including neurodevelopment, learning, and memory formation. Moreover, NMD dysregulation has been implicated in a broad range of neurodevelopmental and neurodegenerative disorders. We discuss how NMD and related aspects of mRNA translation regulate key neuronal functions and, in particular, we focus on evidence implicating these processes in the molecular pathogenesis of neurodegeneration. Finally, we discuss the therapeutic potential and challenges of targeting mRNA translation and NMD across the spectrum of largely untreatable neurological diseases

Uloga motiva incesta u pripovijetci "Wälsungenblut" Thomasa Manna

In der vorliegenden Arbeit wird die Erzählung Wälsungenblut von Thomas Mann, dem bedeutendsten deutschen Erzähler in der ersten Hälfte des 20. Jahrhunderts, analysiert. Der Text dieser Erzählung entsteht zur Zeit des Wilhelminismus, wird aber fünfzehn Jahre danach zur Zeit der Weimarer Republik veröffentlicht. Dabei ist ein sehr intrigantes Merkmal dieser Erzählung ihr antisemitischer Zug, was dazu einlädt, sich die Frage zu stellen, ob hier Thomas Mann den um die Jahrhundertwende vorhandenen Antisemitismus bzw. Judenhass als Bestandteil des damaligen Zeitgeistes übernimmt oder unterwirft er diesen Hass in der Tiefenstruktur des Textes einer Kritik. Die Abschlussarbeit besteht aus fünf Kapiteln. Im einleitenden ersten Kapitel werden Thema, Absicht und Ziel der Arbeit vorgestellt. Diese liegen vor allem darin, die Funktion der Verwendung von Motiven wie Antisemitismus und Inzest zu erleuchten. Das zweite Kapitel enthält die wichtigsten Informationen über das Leben und Schaffen des Autors. Anschließend folgt das dritte Kapitel, das den Grundmerkmalen der Erzählung wie Entstehungsrahmen, Inhalt und Problematik gewidmet ist. Die Analyse des symbolischen Gehalts des Antisemitismus- und des Inzest-Motivs wird im vierten Kapitel vorgenommen, wo diesbezüglich festgestellt wird, dass der europäischen Gesellschaft um die Jahrhundertwende ein Dekadenzgefühl eigen ist, den dann Thomas Mann in seiner Erzählung kritisiert. Im fünften Kapitel wird abschließend auf eine zusammenfassende Weise die Schlussfolgerung der Arbeit hervorgehoben

Uloga motiva incesta u pripovijetci "Wälsungenblut" Thomasa Manna

In der vorliegenden Arbeit wird die Erzählung Wälsungenblut von Thomas Mann, dem bedeutendsten deutschen Erzähler in der ersten Hälfte des 20. Jahrhunderts, analysiert. Der Text dieser Erzählung entsteht zur Zeit des Wilhelminismus, wird aber fünfzehn Jahre danach zur Zeit der Weimarer Republik veröffentlicht. Dabei ist ein sehr intrigantes Merkmal dieser Erzählung ihr antisemitischer Zug, was dazu einlädt, sich die Frage zu stellen, ob hier Thomas Mann den um die Jahrhundertwende vorhandenen Antisemitismus bzw. Judenhass als Bestandteil des damaligen Zeitgeistes übernimmt oder unterwirft er diesen Hass in der Tiefenstruktur des Textes einer Kritik. Die Abschlussarbeit besteht aus fünf Kapiteln. Im einleitenden ersten Kapitel werden Thema, Absicht und Ziel der Arbeit vorgestellt. Diese liegen vor allem darin, die Funktion der Verwendung von Motiven wie Antisemitismus und Inzest zu erleuchten. Das zweite Kapitel enthält die wichtigsten Informationen über das Leben und Schaffen des Autors. Anschließend folgt das dritte Kapitel, das den Grundmerkmalen der Erzählung wie Entstehungsrahmen, Inhalt und Problematik gewidmet ist. Die Analyse des symbolischen Gehalts des Antisemitismus- und des Inzest-Motivs wird im vierten Kapitel vorgenommen, wo diesbezüglich festgestellt wird, dass der europäischen Gesellschaft um die Jahrhundertwende ein Dekadenzgefühl eigen ist, den dann Thomas Mann in seiner Erzählung kritisiert. Im fünften Kapitel wird abschließend auf eine zusammenfassende Weise die Schlussfolgerung der Arbeit hervorgehoben

Physiological and biochemical aspects of regeneration snake's head fritillary (Fritillaria meleargis L.) in vitro

Proučavana je in vitro regeneracijia košutice (Fritillaria meleagris), višegodišnje lukovičaste geofite. Indukcija morfogeneze in vitro košutice postignuta je u kulturi zrelih zigotskih embriona, segmenata lukovica kao i bazalnih delova listova in vitro formiranih lukovica. U kulturi zrelih zigotskih embriona regeneracija biljaka je postignuta procesom somatske embriogeneze i organogeneze u isto vreme i na istom eksplalntatu na hranljivoj podlozi bez regulatora rastenja ili hranljivoj podlozi obogaćenoj sa TDZ. U kulturi segmenata in vitro formiranih lukovica indukcija morfogeneze postignuta je na hranljivoj podlozi sa 2,4-D ili TDZ na svetlosti ili u mraku. Regeneracija biljaka je bila postignuta na obe hranljive podloge putem somatske embriogeneze i organogeneze, s tim da je regeneracija putem organogeneze bila uspešnija na hranljivoj podlozi obogaćenoj sa TDZ. U kulturi bazalnih delova listova indukovana je somatska embriogeneza na hranljivim podlogama sa 2,4-D, KIN ili 2,4-D i KIN. Anatomska istraživanja su pokazala da je somatska embriogeneza direktna, a somatski embrioni imaju višećelijsko poreklo i nastaju od epidermalnih i subepidermalnih slojeva ćelija bazalnih delova lista. Ispitan je uticaj niskih temperatura (15 i 4 °C), povećane koncentracije saharoze u hranljivoj podlozi kao i predtretman sa GA3 na rastenje, razviće i prevazilaženje dormancije in vitro formiranih lukovica košutice. Pokazano je da predhodno gajenje lukovica na sniženim temperaturama i hranljivoj podlozi sa 4,5 % saharoze pozitivno utiče na rastenje i umnožavanje lukovica. Pored toga, predtretman rastvorom GA3 pre izlaganja lukovica niskoj temperaturi (4 °C) dovodi do stimulacije umnožavanja i klijanja lukovica. Izlaganjem in vitro formiranih lukovica košutice niskoj temperaturi dolazi do promena u sadržaju šećera (saharoze, glukoze i fruktoze), fotosintetičkih pigmenata i poliola. Ispitana je aktivnost antioksidativnh enzima (SOD, CAT, GR i POX) tokom prevazilaženja dormancije lukovica gajenjem na niskoj temperaturi. Analize su pokazale da enzimi antioksidativnog stresa aktivno učestvuju u procesima prekidanja dormancije in vitro formiranih lukovica košutice, kao i aklimatizacije lukovica na ex vitro uslove. Enzimi antioksidativne zaštite su aktivni i tokom indukcije morfogeneze košutice u kulturi segmenata lukovica, a njihova aktivnost zavisi od sastava hranljive podloge i predtretmana kome su lukovice prethodno izložene. Zimogramskom detekcijom esteraza tokom indukcije morfogeneze in vitro u kulturi segmenata lukovica utvrđeno je prisustvo 6 izoformi i njihova aktivnost kao i zastupljenost pojedinih izoformi zavise takođe od predtretmana na kojima su lukovice predhodno gajene kao i od regulatora rastenja u hranljivoj podlozi. Praćena je promena sadržaja arabinogalaktanskih proteina (AGP) u eksplantatima tokom indukcije morfogeneze in vitro u kulturi bazalnih delova listova i segmenata lukovica na dve hranljive podloge obogaćene sa 2,4-D i KIN ili TDZ. Koncentracija AGP u eksplantatima se povećava već posle 7 dana gajenja bazalnih delova listova odnosno posle 21 dana gajenja segmenata lukovica na hranljivim podlogama sa regulatorima rastenja. Koncentracija AGP je veća u bazalnim segmentima lista gajenim na hranljivoj podlozi sa 2,4-D i KIN nego na hranljivoj podlozi sa TDZ. Analizom profila AGP dobijenog ukrštenom elektroforezom pokazano je prisustvo samo jednog tipa AGP tokom indukcije morfogeneze in vitro.We have investigated in vitro regeneration of snake’head fritillary (Fritillaria meleagris L.), a perennial bulbous geophyte. The induction of morphogenesis in vitro of snake’head fritillary was achieved in mature zygotic embryo culture, scale segment and leaf base culture of in vitro formed bulbs. Plant regeneration via somatic embryogenesis and organogenesis was obtained in mature zygotic embryo culture on a growth regulator-free medium or on medium supplemented with TDZ. The induction of morphogenesis in vitro was achieved in scale segment culture of the in vitro formed bulbs on media supplemented with 2,4-D or TDZ, grown either on light or in darkness, with more efficient regeneration on media supplementned with TDZ. Somatic embryogenesis was induced in leaf base culture of the in vitro formed plants on media with 2,4-D, KIN or 2,4-D and KIN. Anatomical studies revealed that the somatic embryogenesis was direct, with somatic embryos of multicellular origin formed from epidermal and subepidermal leaf base cells . The effect of low temperature (4 and 15 °C), higher concentration of sucrose in the nutritional media and GA3 pretreatment on growth, differentiation and dormancy breaking of the in vitro formed bulbs was investigated. It was shown that pre-cultivation of the in vitro regenerated bulbs at lower temperatures and higher concentration of sucrose in the nutrition media (4,5 %) have stimulatory effect on growth and multiplication of the bulbs. Also, GA3 pretretment followed by cultivation at low temperature (4 °C) had a stimulatory effect on multiplication and germination of the bulbs. Cultivation at low temperature breaks dormancy of the bulbs and causees changes in the sugar content (sucrose, glucose and fructose), photosinthetic pigments and poliols. Activity of antioxidative enzymes (SOD, CAT, GR i POX) during dormancy breaking was investigated. It was shown that these enyzmes are actively involved in dormancy breaking of the in vitro formed bulbs, and in the process of acclimatization of the bulbs to ex vitro conditions. Antioxidative enzymes were active during the induction of morphogenesis in vitro in bulb segment culture and their activity depended on the nutritional media and the pretreatment to which the bulbs were exposed. During morphogenesis in vitro in the scale segment culture of snake’s head fritillary, up to 6 esterase isoforms have been detected, depending on the pretreatment and media composition. The content of arabinogalactan proteins (AGPs) in explants during the induction of morphogenesis in vitro in leaf base and scale segment cultures at media supplemented either with 2,4-D and KIN or with TDZ was determined. Concentration of AGPs increased after seven days of cultivation of explants on media with growth regulators in the leaf base culture and 21 days in the scale segment culture. In the leaf base culture, concentration of AGPs in explants was higher on a medium with 2,4-D and KIN than on a medium with TDZ. The AGP profile obtained by crossed electroforesis reveiled the presence of one AGP type during induction of morphogenesis in vitro of F. meleagris

Pregled bolesti u djece turista za vrijeme posjeta Splitsko-dalmatinskoj županiji

The aim was to determine morbidity of foreign children during their tourist visit to Split-Dalmatia County, Croatia. The study included medical documentation of 233 foreign children tourists aged under 18 years, hospitalized at Clinical Department of Pediatrics, Split University Hospital Center in the period from January 2007 to December 2013. Demographic data were statistically analyzed. Of 233 children tourists hospitalized at our department, 134 (57.5%) were boys. Most of the children tourists (51.1%) were aged 0-5 years. According to nationality, they were from 30 countries from all over the world, but mostly from Europe (97.9%). The highest number of children tourists were from Germany (14.2%). The highest percentage of children tourists (92.7%) were hospitalized during summer months. The mean length of hospital stay was 4.4±3.3 days. According to the reason for hospitalization, children tourists were mostly admitted to our hospital for nervous system symptoms (32.6%); 43.4% of these had febrile seizures and 39.5% epilepsy. The nervous system symptoms were followed by injury and poisoning (14.6%), respiratory symptoms (14.1%), submersion and heat injuries (9.9%), and digestive symptoms (9.4%). In conclusion, we describe foreign pediatric population hospitalized in the Split University Hospital Center during their vacation in the Split-Dalmatia County, Croatia. The largest number of children tourists were from Germany and the nervous system symptoms were the most common reason for hospitalization. Therefore, we suggest cooperation between the Croatian health care system and Croatian National Tourist Board for developing prevention strategies regarding morbidity in pediatric tourist population. In particular, prevention and fi rst line therapy for cerebral seizures should be broadly available, such as in hotels, apartments, and even on beaches.Cilj je odrediti morbiditet u strane djece za vrijeme turističkog posjeta Splitsko-dalmatinskoj županiji, Hrvatska. U istraživanje je uključena medicinska dokumentacija 233-je strane djece turista u dobi do 18 godina, hospitalizirane na Klinici za dječje bolesti KBC Split u razdoblju od siječnja 2007. do prosinca 2013. godine. Demografski podatci su statistički analizirani. Od ukupno 233-je djece turista hospitalizirane na našem odjelu njih 134 (57,5%) bili su dječaci. Većina djece turista (51,1%) bila je u dobnoj skupini od 0-5 godina. Prema nacionalnosti bila su iz ukupno 30 zemalja diljem svijeta, ali većinom iz Europe (97,9%). Najveći broj djece turista bio je iz Njemačke (14,2%). Najviši postotak djece turista (92,7%) bio je hospitaliziran ljeti. Hospitalizacija je prosječno trajala 4,4±3,3 dana. Najčešći razlozi hospitalizacije djece turista bili su neurološki simptomi (32,6%), od toga je 43,4% imalo febrilne konvulzije i 39,5% epilepsiju. Zatim su slijedile ozljede i trovanja (14,6%), od toga su ozljede bile prisutne u 61,8% slučajeva, a trovanja u 38,2%. Blesti dišnog sustava (14,2%) treće su po učestalosti, većina bolesnika imala je upalu donjih (42,4%) ili gornjih (36,4%) dišnih puteva. Potom slijede utapanja i ozljede toplinom (9,9%) te bolesti probavnog sustava (9,4%). Zaključno, opisali smo stranu pedijatrijsku populaciju hospitaliziranu u KBC-u Split za vrijeme turističkog posjeta Splitsko-dalmatinskoj županiji. Najveći broj djece turista bio je iz Njemačke i najčešći razlog hospitalizacije bili su neurološki simptomi. Stoga predlažemo suradnju između Ministarstva zdravlja i Hrvatske turističke zajednice radi razvoja strategije za prevenciju bolesti, uzimajući u obzir morbiditet u djece turista. Posebice treba naglasiti prevenciju cerebralnih napadaja te činjenicu da bi prvolinijska terapija trebala biti široko dostupna, primjerice u hotelima i apartmanima, pa i na plažama

Textbooks of the First Physicists Trained at the University of Zagreb

Analizom studijske literature studenata Mudroslovnog fakulteta u Zagrebu koji su se u razdoblju 1886. – 1907. prijavili za polaganje stručnog ispita iz fizike pred Kraljevskim povjerenstvom za ispitivanje kandidata gimnazijskoga i realačkoga učiteljstva identificirane su klase korištenih udžbenika fizike i najčešće korišteni predstavnici tih klasa te je konstruiran reprezentativni skup udžbenika fizike zagrebačkih studenata fizike s kraja 19. i početka 20. stoljeća.Physicists have been trained at the University of Zagreb since 1876, but today not much is known about the content of the training at the turn of the nineteenth and the twentieth century. In this paper an attempt is made to partially fill this gap through the identification of the main physics textbooks used at the Faculty of Arts in Zagreb until 1907. For this purpose the files of the students of the Faculty who took the teacher licensing examination in physics before the Royal Commission for the Examination of Candidates for Secondary School Teachers in Zagreb until 1907 have been searched. Textbooks are listed in 23 lists of study literature (53% of examinees) dated from 1886 to 1907. They are analysed and classified (books for the general public, secondary school textbooks, handbooks for practical exercises, preparatory textbooks, advanced textbooks for non-physicists, advanced textbooks for physicists, textbooks of theoretical physics) and the most frequent representatives of these classes are identified. The average scope and structure of the literature used has been determined by means of statistical analysis. Finally, on the basis of the collected data, a representative set of physics textbooks of students of physics at the University of Zagreb at the end of the nineteenth and the beginning of the twentieth century has been constructed: this matches the standard physics literature of these students in terms of its scope, structure, and content

Superoxide dismutase activity and isoenzyme profiles in bulbs of snake's head fritillary in response to cold treatment

The activities and isoenzyme profiles of superoxide dismutase (SOD) in in vitro Fritillaria meleagris bulbs in response to cold treatment (4°C) were investigated. Differences in SOD activity and isoenzyme profiles in bulbs under standard growth conditions, six weeks chilling, as well as seven days after the completion of cold treatment are presented. SOD activity initially decreased but then rapidly increased seven days after cold treatment. Four isoforms of SOD are active under standard and chilling conditions, while three isoforms are presented 7 days after cold treatment. Native gel electrophoresis indicated the presence of mitochondrial and chloroplast localized SODs.

Trend of Body Mass Index Movement of Primary School Students Over a 15 - Year Period

Cilj je ovoga rada bio opisati trend kretanja medijana indeksa tjelesne mase učenika od petih do osmih razreda jedne osnovne škole u Zagrebu u razdoblju od 1999. do 2014. godine. Uzorak ispitanika čine učenici (N=3.567; 1.652 učenice i 1.915 učenika) od petih do osmih razreda osnovnih škola u gradu Zagrebu, kronološke dobi od 12 do 15 godina. Na temelju prikupljenih podataka mase i visine tijela na početku školske godine izračunat je indeks tjelesne mase. Ova metoda koristi se kao pokazatelj stupnja uhranjenosti osobe. Za prikaz kretanja indeksa tjelesne mase korištena je regresijska analiza. Podaci pokazuju da je u većine razreda uočljiv rastući trend indeksa tjelesne mase, ali je statistički značajan samo kod učenika šestih i sedmih razreda. Kod učenika šestih razreda regresijska analiza pokazuje statistički značajan (p=0.019) trend porasta medijana indeksa tjelesne mase tijekom promatranoga razdoblja u iznosu od 0.08 kg/m2 godišnje. Kod učenika sedmih razreda utvrđen je statistički značajan (p=0.004) trend porasta medijana indeksa tjelesne mase u iznosu od 0.14 kg/m2 godišnje.The aim of this study was to describe the trend of median body mass index (BMI) in students from the fifth to the eighth grade in a primary school in Zagreb in the period from 1999 to 2014. The sample consisted of students (N=3.567; 1.652 female and 1.915 male students) from the fifth to the eighth grade of primary school in the city of Zagreb, chronological age of 12 to 15 years. BMI was defined at the beginning of the school year on the basis of the collected data on body mass and body height of the students. This method was used as an indicator of their nutritional status. Regression analysis was used in order to review the trend of BMI. The results have shown that among the majority of the classes an increase in BMI was visible, but it was statistically significant only in the male students of the sixth and seventh grade. The regression analysis of the sixth graders showed a statistically significant (p=0.019) increase of the median of BMI (0.08 kg/m² per year) during the period of research. As for the seventh graders, there was a statistically significant (p=0.004) increase in the median of BMI (0.14 kg/m²) per year

Trend of Body Mass Index Movement of Primary School Students Over a 15 - Year Period

Cilj je ovoga rada bio opisati trend kretanja medijana indeksa tjelesne mase učenika od petih do osmih razreda jedne osnovne škole u Zagrebu u razdoblju od 1999. do 2014. godine. Uzorak ispitanika čine učenici (N=3.567; 1.652 učenice i 1.915 učenika) od petih do osmih razreda osnovnih škola u gradu Zagrebu, kronološke dobi od 12 do 15 godina. Na temelju prikupljenih podataka mase i visine tijela na početku školske godine izračunat je indeks tjelesne mase. Ova metoda koristi se kao pokazatelj stupnja uhranjenosti osobe. Za prikaz kretanja indeksa tjelesne mase korištena je regresijska analiza. Podaci pokazuju da je u većine razreda uočljiv rastući trend indeksa tjelesne mase, ali je statistički značajan samo kod učenika šestih i sedmih razreda. Kod učenika šestih razreda regresijska analiza pokazuje statistički značajan (p=0.019) trend porasta medijana indeksa tjelesne mase tijekom promatranoga razdoblja u iznosu od 0.08 kg/m2 godišnje. Kod učenika sedmih razreda utvrđen je statistički značajan (p=0.004) trend porasta medijana indeksa tjelesne mase u iznosu od 0.14 kg/m2 godišnje.The aim of this study was to describe the trend of median body mass index (BMI) in students from the fifth to the eighth grade in a primary school in Zagreb in the period from 1999 to 2014. The sample consisted of students (N=3.567; 1.652 female and 1.915 male students) from the fifth to the eighth grade of primary school in the city of Zagreb, chronological age of 12 to 15 years. BMI was defined at the beginning of the school year on the basis of the collected data on body mass and body height of the students. This method was used as an indicator of their nutritional status. Regression analysis was used in order to review the trend of BMI. The results have shown that among the majority of the classes an increase in BMI was visible, but it was statistically significant only in the male students of the sixth and seventh grade. The regression analysis of the sixth graders showed a statistically significant (p=0.019) increase of the median of BMI (0.08 kg/m² per year) during the period of research. As for the seventh graders, there was a statistically significant (p=0.004) increase in the median of BMI (0.14 kg/m²) per year