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1.
SNAP-25b-deficiency increases insulin secretion and changes spatiotemporal profile of $Ca^{2+}$ oscillations in $\beta$ cell networks
Teresa Daraio, Lidija Križančić Bombek, Marko Gosak, Ismael Valladolid-Acebes, Maša Skelin, Essam Refai, Per-Olof Berggren, Kerstin Brismar, Marjan Rupnik, Christina Bark, 2017, original scientific article

Abstract: SNAP-25 is a protein of the core SNARE complex mediating stimulus-dependent release of insulin from pancreatic $\beta$ cells. The protein exists as two alternatively spliced isoforms, SNAP-25a and SNAP-25b, differing in 9 out of 206 amino acids, yet their specific roles in pancreatic $\beta$ cells remain unclear. We explored the effect of SNAP-25b-deficiency on glucose-stimulated insulin release in islets and found increased secretion both in vivo and in vitro. However, slow photo-release of caged $Ca^{2+}$ in $\beta$ cells within pancreatic slices showed no significant differences in $Ca^{2+}$-sensitivity, amplitude or rate of exocytosis between SNAP-25b-deficient and wild-type littermates. Therefore, we next investigated if $Ca^{2+}$ handling was affected in glucose-stimulated [beta] cells using intracellular $Ca^{2+}$-imaging and found premature activation and delayed termination of [$Ca^{2+}$] i elevations. These findings were accompanied by less synchronized $Ca^{2+}$-oscillations and hence more segregated functional $\beta$ cell networks in SNAP-25b-deficient mice. Islet gross morphology and architecture were maintained in mutant mice, although sex specific compensatory changes were observed. Thus, our study proposes that SNAP-25b in pancreatic [beta] cells, except for participating in the core SNARE complex, is necessary for accurate regulation of $Ca^{2+}$-dynamics.
Keywords: insulin secretion, pre-diabetes
Published: 23.08.2017; Views: 27; Downloads: 0
.pdf Full text (3,80 MB)

2.
High resolution melting curve analysis for high-throughput SNP genotyping in IL23R gene and association of IL23R with Slovenian inflammatory bowel diseases patients
Mitja Mitrovič, Uroš Potočnik, 2010, original scientific article

Abstract: Single nucleotide polymorphism (SNP) analysis is important tool in the studies of genetic factors associated with complex diseases and with genetically influenced response to drug therapy (pharmacogenetics). Recently, a new generation of generic dsDNA binding dyes (LCGreen$^{TM}$) contributed to the development of fast and low-cost method for SNP detection and/or genotyping based on high resolution melting (HRM) analysis. The aim of our study was to develop HRM assay for IL23R gene (rs7517847) and to perform association study in Slovenian inflammatory bowel diseases (IBD) patients. We genotyped 345 Slovenian healthy controls and 295 IBD patients including 159 with Crohn's disease (CD) and 136 with ulcerative colitis (UC) for rs7517847 polymorphism in IL23R gene using standard RFLP and optimized HRM methods. In this study, we showed, that HRM is a simple, fast and reliable method for genotyping of clinical samples where homozygotes (GG and TT) were determined by Tm calling method and difference between homozygotes and heterozygotes was determined by different melting curve shape using gene scanning method. With combination of results from Tm calling and gene scanning methods, we achieved 98,6% concordance between PCR-RFLP and PCRHRM results, based on the analysis of 640 samples. We found statistically significant association of IL23R polymorphism with Slovenian Crohn's disease patients when comparing genotype and allele frequencies between CD patients and controls. Allele frequency of minor allele G was 0,46 in controls and was reduced to 0,33 in CD patients (p < 0,001, OR = 0,588). The frequency of T/T genotype carriers was higher in CD patients (50,3%) than in controls (26,7%, p = 0,002, OR = 2,558). We found weak association between IL23R polymorphism and Slovenian UC patients. Carriers of T/T genotype have higher risk for UC (p = 0,035, OR = 1,599). These results suggest IL23R plays important role in CD and UC development in Slovenian patients.
Keywords: SNP genotyping, high resolution melting, DNA dyes, inflammatory bowel diseases, LC Green Plus
Published: 18.08.2017; Views: 84; Downloads: 0
.pdf Full text (232,19 KB)

3.
Domestic violence and abuse in intimate relationship from public health perspective
Zlatka Rakovec-Felser, 2014, review article

Abstract: In this article we pay attention to the violence which, due to the fear of social stigma, could be hidden from the public eye for a long time but could have serious health consequences for the individual, family, and society-physical and psychological forms of domestic violence and abuse in male-female intimate relationship. Besides its nature and extent data in general population, we review also the surveys data about its theoretical basis, its risk factors and possible effects on mental and physical health, not only on in conflicts involved partners, but also on family as a whole, and especially on the children that growing up in such a problematic domestic circumstances.
Keywords: domestic violence, perpetrator, victim, gender differences
Published: 08.08.2017; Views: 31; Downloads: 0
.pdf Full text (674,83 KB)

4.
Clostridium difficile ribotypes in humans and animals in Brazil
Rodrigo Otávio Silveira Silva, Maja Rupnik, Amanda Nádia Diniz, Eduardo Garcia Vilela, Francisco Carlos Faria Lobato, 2015, original scientific article

Abstract: Clostridium difficile is an emerging enteropathogen responsible for pseudomembranous colitis in humans and diarrhoea in several domestic and wild animal species. Despite its known importance, there are few studies aboutC. difficile polymerase chain reaction (PCR) ribotypes in Brazil and the actual knowledge is restricted to studies on human isolates. The aim of the study was therefore to compare C. difficileribotypes isolated from humans and animals in Brazil. Seventy-six C. difficile strains isolated from humans (n = 25), dogs (n = 23), piglets (n = 12), foals (n = 7), calves (n = 7), one cat, and one manned wolf were distributed into 24 different PCR ribotypes. Among toxigenic strains, PCR ribotypes 014/020 and 106 were the most common, accounting for 14 (18.4%) and eight (10.5%) samples, respectively. Fourteen different PCR ribotypes were detected among human isolates, nine of them have also been identified in at least one animal species. PCR ribotype 027 was not detected, whereas 078 were found only in foals. This data suggests a high diversity of PCR ribotypes in humans and animals in Brazil and support the discussion of C. difficile as a zoonotic pathogen.
Keywords: Clostridium difficile, pseudomembranous colitis, zoonosis
Published: 07.08.2017; Views: 50; Downloads: 1
.pdf Full text (185,91 KB)

5.
Hypodontia prevalence and pattern in women with epithelial ovarian cancer
Anita Fekonja, Andrej Čretnik, Iztok Takač, 2014, original scientific article

Abstract: Objective: To analyze the possible association between hypodontia and epithelial ovarian cancer (EOC), with the special interest in hypodontia pattern. Materials and Methods: One hundred twenty women with EOC treated at the Department of Gynecologic and Breast Oncology at the University Clinical Centre and 120 gynecologically healthy women of the same average age were reviewed for the presence and pattern of hypodontia. Collected data were analyzed for frequency, tooth type, location per jaw and side, number of missing teeth per person, and family history of hypodontia. Results: The results of the study showed prevalence of hypodontia in 19.2% of women with EOC and in 6.7% of women in the control group (P = .004). The most frequently missing teeth for women with EOC and women in the control group were maxillary second premolars and maxillary lateral incisors, respectively. Unilateral occurrence of hypodontia was more common than bilateral occurrence in women with EOC (P = .034). Of women with EOC and hypodontia, 21.7% reported a positive family history of hypodontia compared with no report in the control group of women with hypodontia (P = .150). Conclusions: The results statistically support possible association between EOC and hypodontia. Because hypdontia can be recognized early in life, this finding could possibly help in earlier detection of EOC, resulting in better prognosis and treatment in earlier stages of the disease. Earlier EOC diagnosis and treatment could save many lives.
Keywords: hypodontia, tooth agenesis, ovarian cancer, neoplasms
Published: 07.08.2017; Views: 38; Downloads: 0
.pdf Full text (64,81 KB)

6.
Defining rural, remote and isolated practices
Rok Petrovčič, 2016, review article

Abstract: There is no single definition of rural practice available. Definitions vary from one country to another, as countries differ in geography and have different health care systems with varying organizational specificities, even within the same country. In spite of increased urbanization and the specific health-related problems it brings with it, a large proportion of the world population still dwells in rural, remote, and isolated areas. In fact, there are many countries in the world with extensive rural areas. Rural areas are unique in organization, demographics, and infrastructure, and so are the specific health-related problems of people living in them. Healthcare in such areas is generally provided by general practitioners or by physicians specialized in family medicine. One of the basic challenges in rural health is defining which areas are rural and finding the characteristics that define “rural”. There are several criteria and combinations of criteria that can be used to define rural areas. Their use mostly depends on the purpose for which the definition is used, and can thus vary from application to application. This paper addresses issues in rural family practice and criteria that may be used to define such practices. It also presents the use of criteria for defining rural practices in a small European country, on the example of Slovenia.
Keywords: Slovenia, rural health, rural population, family practice
Published: 07.08.2017; Views: 31; Downloads: 0
.pdf Full text (174,94 KB)

7.
Low-dose gemcitabine in long infusion
Matjaž Zwitter, 2012, short scientific article

Keywords: lung cancer, gemcitabine
Published: 04.08.2017; Views: 76; Downloads: 1
.pdf Full text (293,79 KB)

8.
Independent clinical research may alleviate disparities in cancer treatment
Matjaž Zwitter, 2016, original scientific article

Abstract: Disparities in cancer care are a reality of the modern world. Unfortunately, current clinical research is in the hands of for-profit pharmaceutical companies and of researchers from the developed world. Problems specific to cancer care in developing countries and among deprivileged populations are ignored. Independent clinical research can offer new valuable knowledge and identify affordable and cost-effective treatments. As such, research not depending on commercial sponsors should become one of the important avenues to alleviate the problem of cancer disparities.
Keywords: clinical research, disparities in cancer care, cost-effective treatment
Published: 04.08.2017; Views: 70; Downloads: 0
.pdf Full text (472,46 KB)

9.
Exploring ComQXPA quorum-sensing diversity and biocontrol potential of Bacillus spp. isolates from tomato rhizoplane
Anna Oslizlo, Polonca Štefanič, Sabina Vatovec, Sara Beigot Glaser, Maja Rupnik, Ines Mandić-Mulec, 2015, original scientific article

Abstract: Bacillus subtilis is a widespread and diverse bacterium t exhibits a remarkable intraspecific diversity of the ComQXPA quorum-sensing (QS) system. This manifests in the existence of distinct communication groups (pherotypes) that can efficiently communicate within a group, but not between groups. Similar QS diversity was also found in other bacterial species, and its ecological and evolutionary meaning is still being explored. Here we further address the ComQXPA QS diversity among isolates from the tomato rhizoplane, a natural habitat of B. subtilis, where these bacteria likely exist in their vegetative form. Because this QS system regulates production of anti-pathogenic and biofilm-inducing substances such as surfactins, knowledge on cell–cell communication of this bacterium within rhizoplane is also important from the biocontrol perspective. We confirm the presence of pherotype diversity within B. subtilis strains isolated from a rhizoplane of a single plant. We also show that B. subtilis rhizoplane isolates show a remarkable diversity of surfactin production and potential plant growth promoting traits. Finally, we discover that effects of surfactin deletion on biofilm formation can be strain specific and unexpected in the light of current knowledge on its role it this process.
Keywords: Bacillus subtilis, quorum sensing, cellular communication, rhizosphere
Published: 04.08.2017; Views: 56; Downloads: 1
.pdf Full text (944,16 KB)

10.
Comparative genome-wide analysis of small RNAs of major Gram-positive pathogens
Mobarak Mraheil, André Billion, Carsten Kuenne, Jordan Pischimarov, Bernd Kreikemayer, Sussane Engelmann, Axel Hartke, Jean-Christophe Giard, Maja Rupnik, Sonja Vorwerk, Markus Beier, Julia Retey, Thomas Hartsch, Anette Jacob, Franz Cemič, Jürgen Hemberger, Trinad Chakraborty, Torsten Hain, 2010, review article

Abstract: In the recent years, the number of drug- and multi-drug-resistant microbial strains has increased rapidly. Therefore, the need to identify innovative approaches for development of novel anti-infectives and new therapeutic targets is of high priority in global health care. The detection of small RNAs (sRNAs) in bacteria has attracted considerable attention as an emerging class of new gene expression regulators. Several experimental technologies to predict sRNA have been established for the Gram-negative model organism Escherichia coli. In many respects, sRNA screens in this model system have set a blueprint for the global and functional identification of sRNAs for Gram-positive microbes, but the functional role of sRNAs in colonization and pathogenicity for Listeria monocytogenes, Staphylococcus aureus, Streptococcuspyogenes, Enterococcus faecalis and Clostridium difficile is almost completely unknown. Here, we report the current knowledge about the sRNAs of these socioeconomically relevant Gram-positive pathogens, overview the state-of-the-art high-throughput sRNA screening methods and summarize bioinformatics approaches for genome-wide sRNA identification and target prediction. Finally, we discuss the use of modified peptide nucleic acids (PNAs) as a novel tool to inactivate potential sRNA and their applications in rapid and specific detection of pathogenic bacteria.
Keywords: anti-infectiveness, peptide nucleic acids, sRNA
Published: 04.08.2017; Views: 53; Downloads: 0
.pdf Full text (698,61 KB)

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