Frequency of galactose-1-phosphate uridyl transferase gene mutations in healthy population of Croatia

Galactosemia is a human disease caused by deficient activity of each one of the three enzymes involved in galactose metabolism, galactokinase (GALK), galactose-1-phosphate uridyl transferase (GALT) and UDP-galactose-4-epimerase (GALE). Absence or deficiency of GALT activity results in classical galactosemia. This disorder exhibits allelic heterogeneity in different populations and ethnic groups. The aim of this study was to search for galactosemia mutations Q188R, N314D, and K285N in healthy population of Croatia. DNA samples from 221 subjects were analyzed by the polymerase chain reaction, followed by digestion with restriction endonucleases (PCR-RFLP procedure). Allele frequencies for Q188R, N314D, and K285N were found to be 0.2 %, 7.5 % and 0 %, respectively, and correlate well with those published for most other healthy Caucasian populations

Ultrasound assessment of age-related arterial wall changes

Koronarna bolest srca (KBS) i moždani udar (MU) su vodeći uzroci smrti u svijetu. Uspješno prepoznavanje pacijenata s povišenim rizikom za obolijevanje od kardiovaskularnih bolesti (KVB) omogućava poduzimanje mjera primarne prevencije. Međutim, metode procjene rizika zasnivane na tradicionalnim čimbenicima rizika (npr. Framinghamska ljestvica, SCORE) nisu se pokazale dovoljno pouzdanima u otkrivanju najčešćeg uzroka KVB – ateroskleroze. Starenje je jedan od značajnijih ireverzibilnih rizičnih čimbenika za razvoj KVB. Dovodi do postupne promjene strukture i funkcije krvnih žila koja počinje rano u životu. Većina složenih podležećih degenerativnih mehanizama se isprepliće s mehanizmima koji dovode do ateroskleroze. Ukupna debljina intime i medije stijenke karotidnih arterija (eng. cIMT=carotid intima-media thickness) mjerena ultrazvukom u B-načinu rada je pouzdana, neinvazivna i relativno jeftina metoda otkrivanja subkliničke ateroskleroze koja se može ponavljati bez nuspojava za pacijenta. Epidemiološka istraživanja su pokazala značajnu i neovisnu korelaciju cIMT s kardiovaskularnim incidentima. Usprkos tome, još uvijek je upitno poboljšanje stratifikacije rizika ubrajanjem cIMT među tradicionalne rizične čimbenike za KVB. Na temelju dobno- i spolno- specifične percentilne vrijednosti cIMT, kronološka dob se može preračunati u tzv. vaskularnu dob, koncept koji označava težinu aterosklerotske bolesti. Kontrola čimbenika rizika za KVB mogla bi dovesti do usporavanja razvoja ranih aterosklerotskih promjena. Pretilost je značajni i neovisni čimbenik rizika za KVB te je povezana s višom vrijednosti i ubrzanom progresijom cIMT. Stoga smo na skupini pretilih osoba ispitali hipotezu da smanjenje tjelesne mase (TM) reducira cIMT u pretilih osoba. Istraživanje je pratilo 19 pretilih ispitanika, sudionika programa za smanjenje TM pod liječničkim nadzorom. Nakon 6 mjeseci ispitanici su podijeljeni u tri skupine prema uspješnosti gubitka TM. Rezultati istraživanja nisu pokazali statistički značajnu razliku smanjenja cIMT između skupina.Coronary heart disease and stroke are the leading causes of death in the world. Primary prevention measures can reduce the risk of cardiovascular disease after a patient has been accurately assessed. However, risk assessment methods based on traditional risk factors (i.e. Framingham risk score, SCORE) fail to directly reveal the presence of the most common cause of cardiovascular disease – atherosclerosis. Ageing is considered a major and irreversible risk factor for cardiovascular disease. Age-related gradual changes of vascular structure and function start early in life. Most of the complex mechanisms that lead to degenerative changes in the arterial wall are common with those mediating atherosclerosis. B-mode ultrasound measurement of carotid intima-media thickness (cIMT) is a reproducible, noninvasive and relatively low-cost method of determining the presence of subclinical atherosclerosis without any known adverse effects. Epidemiological studies have shown that cIMT is significantly and independently correlated with future cardiovascular events. Nevertheless, the usefulness of adding cIMT to the traditional risk factors is still questionable as risk stratification improvement is limited. On the basis of the estimated age- and sex- specific percentile of cIMT, patients' chronological age can be adjusted for their atherosclerotic burden, a concept that is called vascular age. Reducing risk factors for cardiovascular disease could lead to slower progression of early atherosclerotic changes. Obesity is a significant and independent risk factor for cardiovascular disease and it is related to the increased value and faster progression of cIMT. The objective of this paper is to investigate whether weight loss reduces cIMT in obese subjects. The study followed 19 obese subjects which participated in weight reduction program under medical supervision. At six-month follow-up subjects were divided into three groups based on the extent of weight loss. However, results did not find statistically significant differences between groups

The representation of values in Franz Grillparzer‘s „Der arme Spielmann“ and Annette von Droste-Hülshoff‘s „Die Judenbuche“

Diese Abschlussarbeit beschäftigt sich mit der Vorstellung von Werten in Franz Grillparzers Novelle „Der arme Spielmann“ und Annette von Droste-Hülshoffs Novelle „Die Judenbuche“. Das Ziel dieser Abschlussarbeit ist zu erklären, was Werte eigentlich sind und wie sie sich unterscheiden, und zu zeigen, dass Menschen oft verschiedene Werte im Leben haben und verfolgen. Auf den Beispielen der zwei Hauptfiguren der Novellen wird gezeigt, wie unterschiedliche Erfahrungen und Erlebnisse im Leben dazu führen können, dass man bestimmte Werte verfolgt, während ein anderer Mensch, der nicht dieselben Erfahrungen und Erlebnisse hat, andere Werte schätzen wird. Untersuchungen andere Autoren werden auch beschrieben werden und nach der Analyse der Wertevorstellungen in den beiden Werken, werden die Hauptfiguren vergleicht, und mit den Stimmen, in denen sie geschrieben sind (Frauen- und Männerstimme) analysiert und verbunden.Ovaj završni rad se bavi načinom prikaza vrijednosti u noveli „Der arme Spielmann“ Franza Grillparzera i noveli „Die Judenbuche“ Annette von Droste-Hülshoff. Cilj ovog završnog rada je objasniti što su uopće vrijednosti i kako se one međusobno razlikuju, i pokazati da ljudi često imaju različite vrijednosti kojima teže. Na primjeru dvaju glavnih likova novela je pokazano, kako različita saznanja i iskustva u životu mogu dovesti do toga da jedan čovjek teži jednim vrijednostima, dok drugi čovjek s drugačijim saznanjima i iskustvima teži drugim vrijednostima. Istraživanja drugih autora će također biti opisana, a nakon analize načina prikaza vrijednosti u oba djela, će glavni likovi biti uspoređeni, i analizirani i povezani sa glasovima, u kojima su pisani (ženski i muški glas).This thesis deals with the ways in which values are represented in Franz Grillparzer‘s novella “Der arme Spielmann“ and Annette von Droste-Hülshoff’s novella “Die Judenbuche“. The aim of this thesis is to explain what values are and to explain how they are different from one another, and to show that people have different values in life which they follow. The ways in which different experiences and different types of knowledge influence the choice of values which a person follows, while another person with different experiences and knowledge follows other values, are shown, based on the lives of the two main characters of the books. The analyses of other authors are also described, and, after the representations of values in the two books, the two main characters are compared, while being connected and analysed with the voices in which they are written (women and man voice)

How can cloud computing be profitable and justified

U ovom završnom radu obrađena je tema računalstva u oblaku, odnosno koliko je samo računalstvo u oblaku isplativo i opravdano. Na početku je opisan nastanak računalstva u oblaku i njegove najčešće definicije. Obrađene su arhitekture i razvoj računalstva u oblaku, poznate aplikacije koje koriste računalstvo u oblaku i platforme za skladištenje podataka. Na samom kraju, navedene su najbitnije prednosti i nedostaci upotrebe računalstva u oblaku te sigurnosni aspekti.In this final work was processed topic of cloud computing, apropos how is cloud computing profitabile and justified. An the begining it is described how cloud computing is started and it’s moust common definition. It mentions architecture and a variety of computing in the cloud, popular aplications which use cloud computing and platforms for storing dana. At the ond of final work are listed the usully advantages and disadvantages of using cloud computing, and security aspects

Molecular Characterization Of Purβ: A Purine-Rich Single-Stranded Dna-Binding Repressor Of Myofibroblast Differentiation

The trans-differentiation of injury-activated fibroblasts to myofibroblasts is a process that provides contractile strength for wound closure. Persistent myofibroblast differentiation, however, is associated with fibrotic pathologies such as organ fibrosis, vascular remodeling, and atherosclerotic plaque formation. Myofibroblasts acquire a contractile phenotype with biochemical properties characteristic of both smooth muscle cells and stromal fibroblasts. The cyto-contractile protein, smooth muscle α-actin (SMαA) is a biomarker of myofibroblast differentiation. Expression of the SMαA gene, ACTA2, is regulated by cis-acting elements and transcription factors that activate or repress the ACTA2 promoter. Purine-rich element binding proteins A (Purα) and B (Purβ) are sequence-specific, single-stranded DNA (ssDNA)/RNA-binding proteins that act as transcriptional repressors of ACTA2 expression. Both Pur proteins interact with the purine-rich strand of a cryptic muscle-CAT (MCAT) enhancer motif in 5\u27-flanking region of the ACTA2 promoter. Despite significant sequence homology with Purα, Purβ was identified as the dominant repressor of ACTA2 expression in mouse embryonic fibroblasts and vascular smooth muscle cells by virtue of gain-of function and loss-of-function analyses in cultured cells. Biophysical studies indicated that Purβ reversibly self-associates in solution to form a homodimer. Quantitative DNA-binding assays revealed that Purβ interacts with the purine-rich strand of the ACTA2 MCAT motif via a cooperative, multisite binding mechanism to form a high-affinity 2:1 Purβ-ssDNA complex. In this dissertation, a combination of computational, biochemical, and cell-based approaches were employed to elucidate the molecular basis of Purβ repressor interaction with the ACTA2 gene. Limited proteolysis of recombinant mouse Purβ in the presence and absence of the purine-rich strand of the ACTA2 MCAT element led to the identification of a core ssDNA-binding region that retains the ability to dimerize in solution. Knockdown of endogenous Purβ in mouse embryonic fibroblasts via RNA interference induced SMαA expression and conversion to a myofibroblast-like phenotype. To map the specific structural domains in the core region of Purβ that account for its unique ACTA2 repressor and ssDNA-binding functions, computational homology models of the Purβ monomer and dimer were generated based on the x-ray crystal structure of an intramolecular subdomain of Drosophila melanogaster Purα. Empirical biochemical and cell-based analyses of rationally-designed Purβ truncation proteins revealed that the assembled Purβ homodimer is composed of three separate purine-rich ssDNA-binding subdomains. Evaluation of the effects of anionic detergent and high-salt on the binding of Purβ to ssDNA implicated the involvement of hydrophobic and electrostatic interactions in mediating high-affinity nucleoprotein complex formation. This inference was validated by site-directed mutagenesis experiments, which identified several basic amino acid residues required for the ACTA2 repressor activity of Purβ. Collectively, the findings described herein establish the structural and chemical basis for the cooperative interaction of Purβ with the ACTA2 MCAT enhancer and for Purβ-dependent suppression of myofibroblast differentiation