Dragana Cvetković

A genetic study of idiopathic focal dystonias.

The inheritance of focal dystonias was investigated in 43 families containing 43 index cases with torticollis (n = 21), blepharospasm (n = 18) and writers cramp (n = 4). They generated a potential population of 235 first-degree relatives, and 168 out of 179 living first-degree relatives were examined. Ten relatives with dystonia were identified in ten families. Another two parents from two of the same group of ten families were affected according to the family history. The majority of the secondary cases (six patients, five siblings, and one child) were not aware of any dystonia. The tendency for affected relatives to have the same type of dystonia as index patients was observed only for torticollis. Overall, 23% of index patients had relatives with dystonia. Segregation analysis suggested the presence of an autosomal dominant gene or genes with reduced penetrante underlying focal dystonia.

Community structure of branchiopods (Anostraca, Notostraca and Conchostraca) in the Banat province in Yugoslavia

A survey of large branchiopods in the Banat provincein Yugoslavia revealed a particularly diverse fauna in the vicinity of the village Melenci, 100 km north of Belgrade. The temporary ponds here include 10 species of branchiopods, 5 anostracans, 2 notostracans and 3conchostracans (all belonging to the Spinicaudata group). This diversity represents 53% of the species known in Yugoslavia. Community structure, spatial distribution and seasonal dynamics of the species were analyzed over the period 1991–1995. More than one species was found in about 67% of ponds. The maximum number of coexisting species was 7.Anostracans were the most common as a group, while the notostracan Triops cancriformis and the conchostracan Leptestheria saetosa were the most frequent species. A high frequency of coexistence was established. Regarding community structure, two significantly different periods during the season were distinguished: the first, from the end of February to mid-April, and the second, from mid-April to the end of July. This extensive pool longevity may underlie the high diversity in this region.

Mobile agents and Java mobile agents toolkits

This paper gives an overview of what mobile agents are, what they should do, and how they can be implemented in Java. Why Java? The choice to concentrate on Java is evoked by many existing solutions in Java that handles architectural heterogeneity between communicating machines on the net. It seems to be the best available language for making mobile agents roam through the Internet for the time being.

Gene polymorphisms as markers of disease susceptibility.

Gene Polymorphisms as Markers of Disease Susceptibility The most widespread diseases of modern man have a polygenic basis, including genetic predisposition and factors in the external environment. Such is the case with cardiovascular disease, malignancy, diabetes and so on. It should be borne in mind that risk factors usually include disorders that are themselves multifactorial, which further indicates the complexity of pathophysiological mechanisms. In the investigation of genetic factors in polygenic diseases studies are underway to determine the association with specific gene polymorphisms. Genetic or DNA polymorphisms are differences in the hereditary basis which are normally found in human populations. The human genome consists of 3×109 nucleotide (base) pairs, and it is considered that, on average, every 1000th nucleotide is polymorphic, i.e. varies between two loci or two individuals. The most common type of gene polymorphisms is the single nucleotide polymorphism (SNP). Although gene polymorphisms are an expression of normal variations in the hereditary basis, their effect on the phenotype is interesting, especially the association with proneness to certain diseases. Association studies examine the incidence of certain genetic variants, i.e. genetic polymorphisms in a group of patients, and compare it with the data of a healthy population. The results are often contradictory, so the number of polymorphisms whose role as markers of genetic predisposition has been clearly confirmed is still small. In this paper we review literature data and present experiences from our laboratory in studying genetic polymorphisms as susceptibility factors for the occurrence of thrombophilia and atherosclerosis and its clinical manifestations. Genski Polimorfizmi kao Markeri Predispozicije za Oboljenja Najrasprostranjenije bolesti savremenog čoveka imaju poligensku tj. multifaktorsku osnovu, koja uključuje genetičke faktore predispozicije i činioce iz spoljne sredine. Takav je slučaj sa kardiovaskularnim bolestima, malignitetom, dijabetesom itd. Treba imati na umu da faktori rizika obično obuhvataju poremećaje koji su sami po sebi takođe multifaktorski, što dodatno ukazuje na kompleksnost patofizioloških mehanizama. U okviru istraživanja genetičkih činilaca kod poligenskih bolesti pristupa se studijama asocijacije sa određenim genskim polimorfizmima. Pod genskim, odnosno DNK polimorfizmom podrazumevaju se razlike u naslednoj osnovi koje se normalno sreću u humanim populacijama. Genom čoveka se sastoji od 3×109 nukleotidnih (baznih) parova a smatra se da je u proseku svaki 1000. nukleotid polimorfan, tj. da se razlikuje između dva lokusa ili dve osobe. Najčešći tip genskih polimorfizama su polimorfizmi pojedinačnih nukleotida (engl. single nucleotide polymorphism - SNP). Iako genski polimorfizmi predstavljaju izraz normalnih varijacija u naslednoj osnovi, zanimljiv je njihov uticaj na fenotip, a naročito je aktuelno povezivanje sa sklonošću ka određenim bolestima. U studijama asocijacije ispituje se učestalost pojedinih genskih varijanti, tj. genskih polimorfizama u grupi obolelih i upoređuje sa podacima u zdravoj populaciji. Rezultati su često protivrečni, pa je još uvek mali broj polimorfizama sa jasno potvrđenom ulogom genetičkog markera predispozicije. U radu iznosimo iskustva naše laboratorije u ispitivanju genskih polimorfizama kao faktora predispozicije za pojavu trombofilije i ateroskleroze i njenih kliničkih manifestacija.

Mobile Agents and Java Mobile Agents Toolkits

This paper gives an overview of what the mobile agents are, what they should do and how they can be implemented in Java. Why Java? The choice to concentrate on Java is evoked by many existing solutions in Java that handles architectural heterogeneity between communicating machines on the net. It seems to be the best available language for making mobile agents roaming through the Internet for the time being.

Superoxide dismutase and lipid hydroperoxides in blood and endometrial tissue of patients with benign, hyperplastic and malignant endometrium

Epidemiological and experimental data point to involvement of oxygen derived radicals in the pathogenesis of gynecological disorders, as well as in cancer development. The objective of the present study was to examine changes in activities and levels of copper/zinc superoxide dismutase (CuZnSOD) and lipid hydroperoxides (LOOH) in blood and endometrial tissue of patients diagnosed with uterine myoma, endometrial polypus, hyperplasia simplex, hyperplasia complex and adenocarcinoma endometrii. The results of our study have shown decreased SOD activities and unchanged SOD protein level in blood of all examined patients in comparison to healthy subjects. Decrease of both SOD activity and level was found in endometrium of patients with hyperplasia simplex, hyperplasia complex and adenocarcinoma in comparison to women with polypus or myoma. LOOH level was elevated in both tissues of patients with hyperplasia or adenocarcinoma in comparison to healthy subjects or patients with benign diagnosis. Our findings suggest that the decrease in SOD activity and level, as well as the increase in LOOH level, in patients with gynecological disorders, render these patients more susceptible to oxidative damage caused by reactive oxygen species (ROS). An imbalance in ROS formation and SOD level may be important in the pathogenesis and/or perpetuation of tissue damage in gynecological patients. Since evidence suggests that SOD may be a therapy target for cancer treatment, our findings provide a basis for further research and options for clinical applications.

Phenotype of non-c.907_909delGAG mutations in TOR1A: DYT1 dystonia revisited.

BACKGROUND In addition to the most frequent TOR1A/DYT1 mutation (c.907_909delGAG), a growing number of TOR1A sequence variants are found in dystonia patients. For most, functional characterization has demonstrated pathogenicity at different levels, implying that TOR1A genetic testing should not be limited to screening for c.907_909delGAG. METHODS We tested 461 Serbian patients with isolated or combined dystonia for changes in the TOR1A gene and performed a systematic literature review of the clinical characteristics of patients carrying TOR1A mutations other than c.907_909delGAG. RESULTS One likely pathogenic TOR1A mutation (c.385G>A, p.Val129Ile) was detected in an adult-onset cervical dystonia patient. This change is in proximity to the previously reported p.Glu121Lys mutation and predicted to decrease the stability of TOR1A-encoded protein TorsinA. CONCLUSIONS Our patient and three other reported carriers of non-c.907_909delGAG-mutations within the first three exons of TOR1A showed similar phenotypes of adult-onset focal or segmental cervical dystonia. This observation raises the possibility of genotype-phenotype correlations in DYT1 and indicates that the clinical spectrum of this type of dystonia might be broader then previous classic descriptions.

Genetic search based on multiple mutations

Because of the fast growth in the quantity and variety of Web sites, quickly and efficiently retrieving information on the Internet is becoming increasingly difficult. Searches often result in a huge number of documents, many of which are completely unrelated to what the users are looking for. The paper considers how genetic search algorithms enable intelligent and efficient Internet searches. They are especially useful when the search space is relatively large.

The modulatory effect of estradiol benzoate on superoxide dismutase activity in the developing rat brain

The sensitivity of copper,zinc (CuZn)- and manganese (Mn)-superoxide dismutase (SOD) to exogenous estradiol benzoate (EB) was investigated in Wistar rats during postnatal brain development. Enzyme activities were measured in samples prepared from brains of rats of both sexes and various ages between 0 and 75 days, treated sc with 0.5 micro g EB/100 g body weight in 0.1 ml olive oil/100 g body weight, 48 and 24 h before sacrifice. In females, EB treatment stimulated MnSOD activity on days 0 (66.1%), 8 (72.7%) and 15 (81.7%). In males, the stimulatory effect of EB on MnSOD activity on day 0 (113.6%) disappeared on day 8 and on days 15 and 45 it became inhibitory (40.3 and 30.5%, respectively). EB had no effect on the other age groups. The stimulatory effect of EB on CuZnSOD activity in newborn females (51.8%) changed to an inhibitory effect on day 8 (38.4%) and disappeared by day 45 when inhibition was detected again (48.7%). In males, the inhibitory effect on this enzyme was observed on days 0 (45.0%) and 15 (28.9%), and then disappeared until day 60 when a stimulatory effect was observed (38.4%). EB treatment had no effect on the other age groups. The sensitivity of MnSOD to estradiol differed significantly between sexes during the neonatal and prepubertal period, whereas it followed a similar pattern thereafter. The sensitivity of CuZnSOD to estradiol differed significantly between sexes during most of the study period. Regression analysis showed that the sensitivity of MnSOD to this estrogen tended to decrease similarly in both sexes, whereas the sensitivity of CuZnSOD showed a significantly different opposite tendency in female and male rats. These are the first reports indicating hormonal modulation of antioxidant enzyme activities related to the developmental process.

Architecture of the mobile environment for intelligent genetic search and proxy caching

As the number of documents and servers on the Internet grows with enormous speed, it becomes necessary to design efficient algorithms and tools for searching and retrieval of documents. Also, the number of accesses to servers on the Internet is constantly growing. Congestion of servers and links can be alleviated using proxy caches. Latency on the Web can be reduced using prefetching and caching. Efficient searching of documents can be done with an improved genetic algorithm that exploits the principles of temporal and spatial locality. Mobile agents can be used to optimize network traffic for distributed applications. This paper describes several existing solutions to the problem and discusses the implementation of a Java distributed object application for experimenting with genetic search and proxy caching algorithms for the Internet.