Although the mechanism of Aβ action in the pathogenesis of Alzheimer’s disease (AD) has remained elusive, it is known to increase the expression of the antagonist of canonical wnt signalling, Dickkopf-1 (Dkk1), whereas the silencing of Dkk1 blocks Aβ neurotoxicity. We asked if clusterin, known to be regulated by wnt, is part of an Aβ/Dkk1 neurotoxic pathway. Knockdown of clusterin in primary neurons reduced Aβ toxicity and DKK1 upregulation and, conversely, Aβ increased intracellular clusterin and decreased clusterin protein secretion, resulting in the p53-dependent induction of DKK1. To further elucidate how the clusterin-dependent induction of Dkk1 by Aβ mediates neurotoxicity, we measured the effects of Aβ and Dkk1 protein on whole-genome expression in primary neurons, finding a common pathway suggestive of activation of wnt–planar cell polarity (PCP)–c-Jun N-terminal kinase (JNK) signalling leading to the induction of genes including EGR1 (early growth response-1), NAB2 (Ngfi-A-binding protein-2) and KLF10 (Krüppel-like factor-10) that, when individually silenced, protected against Aβ neurotoxicity and/or tau phosphorylation. Neuronal overexpression of Dkk1 in transgenic mice mimicked this Aβ-induced pathway and resulted in age-dependent increases in tau phosphorylation in hippocampus and cognitive impairment. Furthermore, we show that this Dkk1/wnt–PCP–JNK pathway is active in an Aβ-based mouse model of AD and in AD brain, but not in a tau-based mouse model or in frontotemporal dementia brain. Thus, we have identified a pathway whereby Aβ induces a clusterin/p53/Dkk1/wnt–PCP–JNK pathway, which drives the upregulation of several genes that mediate the development of AD-like neuropathologies, thereby providing new mechanistic insights into the action of Aβ in neurodegenerative diseases.

Large scale genetic association meta-analyses showed that neurocan (NCAN) gene polymorphism rs1064395 is susceptibility locus for bipolar disorder. These studies also included patients with bipolar disorder originated from Bosnia and Herzegovina. Followed by theory of shared genetic elements between bipolar disorder and schizophrenia susceptibility, other studies explored several genetic factors with schizophrenia vulnerability as well. In this work, authors investigated the association between previously confirmed bipolar disorder genetic risk factor- neurocan with schizophrenia in a population sample of Bosnia and Herzegovina. Ethical aspects of this research were assessed by Ethics Committee of Clinical Center University of Sarajevo. Blood samples for DNA extraction were taken from the total of 86 patients and healthy individuals who previously signed informed consent. Genotyping for rs 1064395 was done using direct sequencing method. A case-control analysis of common genetic polymorphism within neurocan gene and schizophrenia status in a consecutively sampled patient cohort have been done using Fisher-exact test with odds-ratio calculation. No statistically significant allele and genotype association with disease status was found (p>0.05). Our finding supports the fact that large-scale genetic association studies approach need to be employed when detecting the variants with small additive effect in phenotypes with complex ethiology.

The major purpose of this paper is to present a way of solving problems through so-called visual planning and programming using object-oriented concepts. This paper describes the process of UML modeling for solving the traveling salesman problem using one of the metaheuristic-genetic algorithms. The analysis and problem solving in this way has many advantages just because it provides a clear definition of requirements and specific plan that we will later use to create specific applications. This is a good way to resolve because the UML describes the source code, models help to visualize the system as it is or what it should be and allow you to determine the structure and behavior of the system. Static and dynamic diagrams implemented in developing tools for modeling, as well as a description of specific applications and testing are mentioned. With this approach we describe modeling tool that can be used in the development of specific solutions and a way of establishing explicit links between concepts and execution code.

To evaluate cytotoxicity of experimental conventional and resin modified glass-ionomer cements on UMR-106 osteoblast cell cultures and cell cultures of NIH(3)T(3) mouse fibroblasts specimens were prepared for every experimental material and divided into: group 1.Conventional glass-ionomer cements: GC Fuji IX GP Fast, GC Fuji Triage and Ketac Silver; group 2. Resin modified glass-ionomer cements: GC Fuji II LC, GC Fuji Plus and Vitrebond; group 3. Positive control was presented by specimens of composite Vit-l-ecence® and negative control-group 4. was presented by α-minimum essential medium for UMR-106 - osteoblast-like cells and Dulbecco's Modified Eagle's Medium for NIH(3)T(3) mouse fibroblast cells. Both cell cultures were exposed to 10% of eluate of each single specimen of each experimental material. Experimental dishes were incubated for 24 h. Cell metabolism was evaluated using methyltetrazolium assay. Kruskal-Wallis test and Tukey-Kramer post hoc test for the materials evaluated on NIH(3)T(3) mouse fibroblast cells, as well as UMR-106 osteoblast-like cells showed significantly more cytotoxicity of RMGICs, predominantly Vitrebond to both GICs and composite- Vit-l-ecence®.The lowest influence on cell's metabolism on UMR-106 osteoblas-like cells was shown by Ketac Silver and the lowest influence on cell's metabolism on NIH(3)T(3) mouse fibroblast cells was shown by Fuji IX GP Fast. Statistical evaluation of sensitivity of cell lines UMR-106 osteoblast-like cells and NIH(3)T(3) mouse fibroblast cells, using Mann-Whitney test, showed that NIH(3)T(3) mouse fibroblast cells were more sensitive for the evaluation of cytotoxicity of dental materials.

2012 A study of caddisfl y biodiversity and its application for use as indicator species to assess the ecological integrity of aquatic environments was conducted in the area of the Listica River, Bosnia and Herzegovina. A portable UV light- trap was used to collect caddisfl ies at two sites: the spring of Listica - Bilo Vrilo and the middle reach of this river in a karstic depression - Mostarsko Blato. From March 2003 to March 2004 a total of 4334 individuals, representing 34 species, were caught. There were signifi cant differences in species composition and abundance between sampling sites. The fl ight periods are shown for all recorded species and studied in detail for twelve abundant species. The species inventories were used for analysing the longitudinal classifi cation of the sampling sites, composition of functional feeding guilds and the saprobic indices. Caddisfl ies, Listica River, Bosnia and Herzegovina, ecological integrity S. STANIC-KOSTROMAN, M. KUCINIC, A. KOLOBARA, D. SKOBIC, L. KNEZOVIC i P. DURBESIC: Odrasli tulari (Insecta: Trichoptera) kao pokazatelji ekoloskog statusa rijeke Listice, Bosna i Hercegovina. Entomol. Croat. 2012. Vol. 16. Num. 1-4: 21-35. Istraživana je bioraznolikost tulara rijeke Listice te primjena njihovih zajednica u procjeni ekoloskog statusa vodenih ekosustava. Odrasle jedinke uzorkovane su na dvjema postajama, tj na izvoru rijeke Bilo vrilo i sredisnjem dijelu toka Listice, u krskom polju Mostarskom blatu. Materijal je prikupljan godinu dana (ožujak 2003. - ožujak 2004.) metodom lova pomocu UV lampe. Istraživanjima su zabilježene 34 vrste s 4334 uzorkovanih jedinki. Utvrđene