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Search Results: 1 - 10 of 145 matches for " Dimitrije Krstic "
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Regulated Proteolytic Processing of Reelin through Interplay of Tissue Plasminogen Activator (tPA), ADAMTS-4, ADAMTS-5, and Their Modulators
Dimitrije Krstic, Myriam Rodriguez, Irene Knuesel
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0047793
Abstract: The extracellular signaling protein Reelin, indispensable for proper neuronal migration and cortical layering during development, is also expressed in the adult brain where it modulates synaptic functions. It has been shown that proteolytic processing of Reelin decreases its signaling activity and promotes Reelin aggregation in vitro, and that proteolytic processing is affected in various neurological disorders, including Alzheimer's disease (AD). However, neither the pathophysiological significance of dysregulated Reelin cleavage, nor the involved proteases and their modulators are known. Here we identified the serine protease tissue plasminogen activator (tPA) and two matrix metalloproteinases, ADAMTS-4 and ADAMTS-5, as Reelin cleaving enzymes. Moreover, we assessed the influence of several endogenous protease inhibitors, including tissue inhibitors of metalloproteinases (TIMPs), α-2-Macroglobulin, and multiple serpins, as well as matrix metalloproteinase 9 (MMP-9) on Reelin cleavage, and described their complex interplay in the regulation of this process. Finally, we could demonstrate that in the murine hippocampus, the expression levels and localization of Reelin proteases largely overlap with that of Reelin. While this pattern remained stable during normal aging, changes in their protein levels coincided with accelerated Reelin aggregation in a mouse model of AD.
Sensory Integration Regulating Male Courtship Behavior in Drosophila
Dimitrije Krstic, Werner Boll, Markus Noll
PLOS ONE , 2009, DOI: 10.1371/journal.pone.0004457
Abstract: The courtship behavior of Drosophila melanogaster serves as an excellent model system to study how complex innate behaviors are controlled by the nervous system. To understand how the underlying neural network controls this behavior, it is not sufficient to unravel its architecture, but also crucial to decipher its logic. By systematic analysis of how variations in sensory inputs alter the courtship behavior of a na?ve male in the single-choice courtship paradigm, we derive a model describing the logic of the network that integrates the various sensory stimuli and elicits this complex innate behavior. This approach and the model derived from it distinguish (i) between initiation and maintenance of courtship, (ii) between courtship in daylight and in the dark, where the male uses a scanning strategy to retrieve the decamping female, and (iii) between courtship towards receptive virgin females and mature males. The last distinction demonstrates that sexual orientation of the courting male, in the absence of discriminatory visual cues, depends on the integration of gustatory and behavioral feedback inputs, but not on olfactory signals from the courted animal. The model will complement studies on the connectivity and intrinsic properties of the neurons forming the circuitry that regulates male courtship behavior.
Influence of the White Locus on the Courtship Behavior of Drosophila Males
Dimitrije Krstic, Werner Boll, Markus Noll
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0077904
Abstract: Since its discovery by Morgan, the Drosophila white gene has become one of the most intensely studied genes and has been widely used as a genetic marker. Earlier reports that over- and misexpression of White protein in Drosophila males leads to male-male courtship implicated white in courtship control. While previous studies suggested that it is the mislocalization of White protein within cells that causes the courtship phenotype, we demonstrate here that also the lack of extra-retinal White can cause very similar behavioral changes. Moreover, we provide evidence that the lack of White function increases the sexual arousal of males in general, of which the enhanced male-male courtship might be an indirect effect. We further show that white mutant flies are not only optomotor blind but also dazzled by the over-flow of light in daylight. Implications of these findings for the proper interpretation of behavioral studies with white mutant flies are discussed.
Systemic immune challenges trigger and drive Alzheimer-like neuropathology in mice
Dimitrije Krstic, Amrita Madhusudan, Jana Doehner, Prisca Vogel, Tina Notter, Claudine Imhof, Abigail Manalastas, Martina Hilfiker, Sandra Pfister, Cornelia Schwerdel, Carsten Riether, Urs Meyer, Irene Knuesel
Journal of Neuroinflammation , 2012, DOI: 10.1186/1742-2094-9-151
Abstract: The viral mimic, polyriboinosinic-polyribocytidilic acid (PolyI:C) was used to stimulate the immune system of experimental animals. Wild-type (WT) and transgenic mice were exposed to this cytokine inducer prenatally (gestation day (GD)17) and/or in adulthood. Behavioral, immunological, immunohistochemical, and biochemical analyses of AD-associated neuropathologic changes were performed during aging.We found that a systemic immune challenge during late gestation predisposes WT mice to develop AD-like neuropathology during the course of aging. They display chronic elevation of inflammatory cytokines, an increase in the levels of hippocampal amyloid precursor protein (APP) and its proteolytic fragments, altered Tau phosphorylation, and mis-sorting to somatodendritic compartments, and significant impairments in working memory in old age. If this prenatal infection is followed by a second immune challenge in adulthood, the phenotype is strongly exacerbated, and mimics AD-like neuropathologic changes. These include deposition of APP and its proteolytic fragments, along with Tau aggregation, microglia activation and reactive gliosis. Whereas Aβ peptides were not significantly enriched in extracellular deposits of double immune-challenged WT mice at 15 months, they dramatically increased in age-matched immune-challenged transgenic AD mice, precisely around the inflammation-induced accumulations of APP and its proteolytic fragments, in striking similarity to the post-mortem findings in human patients with AD.Chronic inflammatory conditions induce age-associated development of an AD-like phenotype in WT mice, including the induction of APP accumulations, which represent a seed for deposition of aggregation-prone peptides. The PolyI:C mouse model therefore provides a unique tool to investigate the molecular mechanisms underlying the earliest pathophysiological changes preceding fibrillary Aβ plaque deposition and neurofibrillary tangle formations in a physiological context of
Bijections Between Multiparking Functions, Dirichlet Configurations, and Descending R-Traversals
Dimitrije Kostic
Mathematics , 2006,
Abstract: There are several combinatorial objects that are known to be in bijection to the spanning trees of a graph G. These objects include G-parking functions, critical configurations of G, and descending traversals of G. In this paper, we extend the bijections to generalizations of all three objects.
Dragan Krstic,Jelena Krstic,Slavko Krstic,Dragana Mitic-Kocic
Acta Facultatis Medicae Naissensis , 2006,
Abstract: The aim of the paper was to investigate the impact of stress on incidence of major miscarriages during the bombing of the FR of Yugoslavia. The data have been collected retrospectively from the official fetal death records of the Leskovac District Health Center and processed using x2 test. The Leskovac Health Center is the only hospital providing medical services to 250,000 residents of the Jablanica District in the South of Serbia.. The study includes 81 cases of spontaneous miscarriage after the 12th week, and with fetus weight under 1,000 grams, in the period between March 24 – June 9 of the year before, during and the year after air attacks in 1999. Data on miscarriages in the embryonic period are not included in the survey since there are no reliable sources in our databases. A significant increase in the incidence of spontaneous miscarriages after the 12th week of gestation is registered in the period of bombardment compared to the same period the year before. A significant increase in the incidence in the year after the bombardment would be more in accord with the results obtained from the Gulf War published in America and Kuwait. In that respect, there are only indications in our study proving that direct consequences of stress on pregnancy are considerable. The mechanism of stress considerably increased the incidence of spontaneous miscarriages but only during the bombardment.
Dragan Krstic,Jelena Krstic,Slavko Krstic,Dragana Mitic - Kocic
Acta Facultatis Medicae Naissensis , 2006,
Abstract: The aim of the study was to prove that during the three-month-long bombing of FR of Yugoslavia the pregnancy period was shorter and the incidence of prematurity was not increased. Retrospective studies were based on the data obtained from medical histories of the newly born in the Neonatal Department of the Hospital of the Health Centre in Leskovac. The hospital includes a maternity department with 2300 deliveries annually per 250.000 residents of the Jablanica District which was bombed for 78 days. The study involves 1448 newly born babies born in the period from March 24 till June 9, a year before, during, and a year after the bombing in 1999. On the whole, the results show that the perinatal outcome was better during the bombing with significantly fewer post-dated deliveries. Such, at first glance, paradoxical results remind us of the times when life was harder and deliveries easier. Stress shortens the length of pregnancy but synchronizes development of the embryo with an earlier delivery, so that it does not increase the incidence of prematurity.
The concept and importance of medical law
Jakovljevi? Branislava,Segedi Dimitrije
Medicinski Pregled , 2006, DOI: 10.2298/mpns0604135j
Abstract: Introduction. Medical law is a scientific discipline which has not been affirmed in our country, but at law schools in many developed countries it has gained the status of a separate scientific discipline and today it is studied with multidisciplinary cooperation of Schools of Medicine, Schools of Dentistry and Schools of Pharmacy. Generally speaking, medical law concerns the rights and duties of the medical profession. Ethics and legal questions of medical law. The progress of scientific research and of new technology used in diagnostics and treatment, opens new fields in terms of responsibility. Most European countries have legal institutions in the field of health care. These include laws and legal acts, as well as codification of professional norms. Law concerning physicians. Apart from the national law, there is also an international law concerning physisians. The World Health Organization and the World Association of Medical Doctors brought the following declarations: Declaration on Promotion of Patients' Rights, the Revised Lisbon Declaration on Patients' Rights, the Revised Helsinki Declaration on Biomedical Research Involving Human Subjects and the Council of Europe's Convention on Human Rights and Biomedicine. Conclusion. There is no national order of physicians in Serbia and Montenegro, because chambers of physisians with legal authority and mandatory membership have not been formed. The foundation of Chambers of Physicians of Vojvodina and Montenegro is the first step to goal achieving. .
Vertex routing models
Dimitrije Markovic,Claudius Gros
Physics , 2009, DOI: 10.1088/1367-2630/11/7/073002
Abstract: A class of models describing the flow of information within networks via routing processes is proposed and investigated, concentrating on the effects of memory traces on the global properties. The long-term flow of information is governed by cyclic attractors, allowing to define a measure for the information centrality of a vertex given by the number of attractors passing through this vertex. We find the number of vertices having a non-zero information centrality to be extensive/sub-extensive for models with/without a memory trace in the thermodynamic limit. We evaluate the distribution of the number of cycles, of the cycle length and of the maximal basins of attraction, finding a complete scaling collapse in the thermodynamic limit for the latter. Possible implications of our results on the information flow in social networks are discussed.
Power laws and Self-Organized Criticality in Theory and Nature
Dimitrije Markovic,Claudius Gros
Physics , 2013, DOI: 10.1016/j.physrep.2013.11.002
Abstract: Power laws and distributions with heavy tails are common features of many experimentally studied complex systems, like the distribution of the sizes of earthquakes and solar flares, or the duration of neuronal avalanches in the brain. Previously, researchers surmised that a single general concept may act as a unifying underlying generative mechanism, with the theory of self organized criticality being a weighty contender. Consequently, a substantial amount of effort has gone into developing new and extended models and, hitherto, three classes of models have emerged. The first line of models is based on a separation between the time scales of drive and dissipation, and includes the original sandpile model and its extensions, like the dissipative earthquake model. Within this approach the steady state is close to criticality in terms of an absorbing phase transition. The second line of models is based on external drives and internal dynamics competing on similar time scales and includes the coherent noise model, which has a non-critical steady state characterized by heavy-tailed distributions. The third line of models proposes a non-critical self-organizing state, being guided by an optimization principle, such as the concept of highly optimized tolerance. We present a comparative overview regarding distinct modeling approaches together with a discussion of their potential relevance as underlying generative models for real-world phenomena. The complexity of physical and biological scaling phenomena has been found to transcend the explanatory power of individual paradigmal concepts. The interaction between theoretical development and experimental observations has been very fruitful, leading to a series of novel concepts and insights.
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