Quo Vadis: Aberrations in the Development of Dendritic Cells in the Autoimmunity-Prone Non-Obese Diabetic Mouse

Immune system protects us from harmful microbes and tumor development. At the same time, the immune system makes sure that the unnecessary immune reaction against harmless foreign substances (known as antigens) or self-originating structures (self-antigens) either does not occur or is stopped before it induces irreparable damage to a healthy organ. Therefore, the immune system is able to make a distinction between the “dangerous” and the “harmless” irrespective of its origin. If a “dangerous” is encountered, defense mechanisms are activated that generate an inflammation. Elimination of the inflammation inducers leads to a deceleration of inflammation and a wound healing, which is actively regulated. The response against harmless antigens (either foreign or self) is also actively suppressed and is called tolerance. The mechanisms utilized for the controlled activation and inhibition of the inflammation and for the tolerance acquisition enable the balanced function of the immune system, called immune regulation. In some situations the immune regulation can be disturbed and the immune system starts to destroy healthy cells leading to an irreparable damage. This action of the immune system is called an autoimmune reaction and as a consequence an autoimmune disease develops. Such a process directed against b-cells in the islets of Langerhans in the pancreas leads to the autoimmune disease termed type 1 diabetes (also known as a sugar disease). Macrophages (Mf) and dendritic cells (DC) importantly contribute to the proper function of the immune system. These two cell types comprise a heterogeneous group of cells called mononuclear phagocytes, which differ in the phenotype, function or the origin. They are sentinels that reside in all organs and are the first that encounter the infectious agents, transformed cells, or some other harmful substances. As an immediate reaction, they activate the inborn immunity and start an inflammatory reaction that subsequently leads to the activation of other immune forces. Later, they also mediate the reduction of the inflammation and help the wound healing. In ad

FIFTY YEARS OF MICROPROCESSOR EVOLUTION: FROM SINGLE CPU TO MULTICORE AND MANYCORE SYSTEMS

Nowadays microprocessors are among the most complex electronic systems that man has ever designed. One small silicon chip can contain the complete processor, large memory and logic needed to connect it to the input-output devices. The performance of today's processors implemented on a single chip surpasses the performance of a room-sized supercomputer from just 50 years ago, which cost over $ 10 million [1]. Even the embedded processors found in everyday devices such as mobile phones are far more powerful than computer developers once imagined. The main components of a modern microprocessor are a number of general-purpose cores, a graphics processing unit, a shared cache, memory and input-output interface and a network on a chip to interconnect all these components [2]. The speed of the microprocessor is determined by its clock frequency and cannot exceed a certain limit. Namely, as the frequency increases, the power dissipation increases too, and consequently the amount of heating becomes critical. So, silicon manufacturers decided to design new processor architecture, called multicore processors [3]. With aim to increase performance and efficiency these multiple cores execute multiple instructions simultaneously. In this way, the amount of parallel computing or parallelism is increased [4]. In spite of mentioned advantages, numerous challenges must be addressed carefully when more cores and parallelism are used.This paper presents a review of microprocessor microarchitectures, discussing their generations over the past 50 years. Then, it describes the currently used implementations of the microarchitecture of modern microprocessors, pointing out the specifics of parallel computing in heterogeneous microprocessor systems. To use efficiently the possibility of multi-core technology, software applications must be multithreaded. The program execution must be distributed among the multi-core processors so they can operate simultaneously. To use multi-threading, it is imperative for programmer to understand the basic principles of parallel computing and parallel hardware. Finally, the paper provides details how to implement hardware parallelism in multicore systems

Bone marrow precursors of nonobese diabetic mice develop into defective macrophage-like dendritic cells in vitro

The NOD mouse spontaneously develops autoimmune diabetes. Dendritic cells (DC) play a crucial role in the autoimmune response. Previous studies have reported a defective DC generation in vitro from the NOD mouse bone marrow (BM), but a deviated development of myeloid precursors into non-DC in response to GM-CSF was not considered. In this study, we demonstrate several abnormalities during myeloid differentiation of NOD BM precursors using GM-CSF in vitro. 1) We found reduced proliferation and increased cell death in NOD cultures, which explain the previously reported low yield of DC progeny in NOD. Cell yield in NOR cultures was normal. 2) In a detailed analysis GM-CSF-stimulated cultures, we observed in both NOD and NOR mice an increased frequency of macrophages, identified as CD11c(+)/MHCII(-) cells with typical macrophage morphology, phenotype, and acid phosphatase activity. This points to a preferential maturation of BM precursors into macrophages in mice with the NOD background. 3) The few CD11c(+)/MHCII(high) cells that we obtained from NOD and NOR cultures, which resembled prototypic mature DC, appeared to be defective in stimulating allogeneic T cells. These DC had also strong acid phosphatase activity and elevated expression of monocyte/macrophage markers. In conclusion, in this study we describe a deviated development of myeloid BM precursors of NOD and NOR mice into macrophages and macrophage-like DC in vitro. Potentially, these anomalies contribute to the dysfunctional regulation of tolerance in NOD mice yet are insufficient to induce autoimmune diabetes because they occurred partly in NOR mice

Developmental stages of myeloid dendritic cells in mouse bone marrow

The lineage relationship of dendritic cells (DC) with other hematopoietic cell types has been studied extensively, resulting in the identification of different bone marrow (BM) progenitors that give rise to distinct DC types. However, the identity of the different maturation stages of DC precursors in the BM remains unclear. In this study we define the in vivo developmental steps of the myeloid DC lineage in mouse BM. To this end, BM cells were separated according to their expression of CD31 (ER-MP12), Ly-6C (ER-MP20) and ER-MP58 antigens, and stimulated to develop into myeloid DC, using granulocyte macrophage colony stimulating factor as a specific growth factor. DC developed from three BM subpopulations: ER-MP12(hi)/20(-) (early blast cells), ER-MP12(+)/20(+) (myeloid blasts) and ER-MP12(-)/20(hi) (monocytes). The kinetic and phenotypic features of DC developing in vitro indicate that the three populations represent successive maturation stages of myeloid DC precursors. Within the earliest ER-MP12(hi)/20(-) population, DC precursors exclusively occurred in the myeloid-restricted ER-MP58(hi) subset. By using switch cultures, we show that these BM precursor subpopulations, when stimulated to develop into macrophages using macrophage colony stimulating factor, retain the ability to develop into myeloid DC until advanced stages of maturation. Together, these findings support a common ER-MP12/20-defined differentiation pathway for both macrophages and myeloid DC throughout their BM development

Forenzički aspekti postmortalne analize transferina s nedostatkom ugljenih hidrata kao markera zloupotrebe alkohola

Introduction Carbohydrate-deficient transferrin (CDT) has been suggested as one of alcohol abuse indicators having produced good results in forensic medicine for years. Objective The aim of the study was to identify correlation between present methodology of alcohol abuse diagnosis at autopsy (macroscopic and microscopic findings) and CDT examination using the method of isoelectrofocusing (IEF) in polyacrylamide gel electrophoresis (PAGE). We also analyzed if the time interval between the moment of death and blood sample collection influences CDT findings. Methods The method used for CDT analysis was IEF-PAGE. Sera of 49 males and 11 females aged 14-87 years, average age 46.85 +/- 18.53, were used in this study. Control group consisted of five patients who died after medical treatment that lasted longer than 15 days, and five patients who started Disulfiram therapy in controlled hospital environment. Results The results obtained in CDT examination in dead bodies' sera showed sensitivity 59% and specificity 71%. A high incidence of falsely positive CDT result was noticed in liver failure and cirrhosis of non-alcoholic origin. CDT analysis is also possible to be done in samples collected postmortem up to 76 hours. Conclusion In forensic medicine, the method of CDT determination is reliable for the diagnosis of alcohol abuse.Uvod. Poslednjih godina transferin s nedostatkom ugljenih hidrata (engl. carbohydrate-deficient transferrin - CDT) jedan je od markera zloupotrebe alkohola koji je pokazao najbolje rezultate u sudskoj medicini. Cilj rada. Cilj studije je bio da se odredi korelacija između aktuelne metodologije dijagnoze zloupotrebe alkohola na postmortalnom materijalu (makroskopski i mikroskopski nalaz) i određivanja CDT korišćenjem metode isoelektrofokusiranja (engl. isoelectric focusing - IEF) u poliakrilamidnom gelu (engl. polyacrylamide gel electrophoresis - PAGE). Utvrđivano je da li interval između vremena smrti i uzimanja uzoraka za CDT analizu utiče na nalaz CDT. Metode rada. Za analizu CDT korišćena je metoda IEF-PAGE. Za studiju su analizirani serumi 49 muškaraca i 11 žena prosečne starosti od 46,85±18,53 godina (raspon 14-87 godina). Kontrolnu grupu činilo je pet pacijenata koji su umrli nakon bolničkog lečenja koje je trajalo duže od 15 dana i pet pacijenata kod kojih je u kontrolisanim bolničkim uslovima počelo lečenje disulfiramom. Rezultati. Dobijeni rezultati pokazuju da ova metoda analize CDT na postmortalnom materijalu ima senzitivnost od 59% i specifičnost od 71%. Visoka učestalost lažno pozitivnih rezultata utvrđena je kod oboljenja jetre i ci- roze nealkoholnog porekla. Analizu CDT je moguće raditi i iz uzoraka uzetih do 76 sati nakon smrti. Zaključak. U sudskomedicinskoj praksi ova metoda analize CDT može se koristiti za dijagnostikovanje hronične zloupotrebe alkohola

YIELD AND QUALITY OF MÜLLER-THURGAU CLONE GM11 OF NIS GRAPE GROWING REGION

This paper presents the results of research variety Müller-Thurgau, clone 11 Gm, in order to determine quality indicators and the possibility of expansion in the vineyards of Southern Serbia. In terms of Nis grape growing region of the test are the most important agro technological and economic characteristics of the clone 11 Gm compared to the standard variety Müller-Thurgau. The test clone exhibited significant differences in yield and quality of grapes

Razrada metoda za dokazivanje Pseudomonas savastanoi pv. phaseolicola na semenu pasulja

Pseudomonas savastanoi pv. phaseolicola detection on artificially inoculated bean seeds was investigated. The method of the International Seed Federation – ISF (2006) was used. It includes bacteria extraction from seeds, isolation on semiselective media and checking the pathogenicity of investigated isolates. For verification of results, quick new methods of investigation were used (ELISA test and PCR). The results show that semiselective media MT (Milk Tween Agar) and MSP (Modified Sucrose Peptone Agar) can be appropriate for isolation of this bacterium. Pathogenicity of the investigated isolates was confirmed on cotyledon leaves of bean. ELISA test and PCR confirmed that all investigated isolates and reisolates belong to the bacterium P. s. pv. phaseolicola.U radu je ispitivana mogućnost utvrđivanja prisustva bakterije Pseudomonas savastanoi pv. phaseolicola sa veštački inokulisanog semena pasulja. Korišćena je metoda International Seed Federation (ISF), koja uključuje ekstrakciju bakterija iz semena, izolaciju na poluselektivne podloge i proveru patogenosti dobijenih izolata. U cilju potvrde rezultata korišćene su brze savremene metode identifikacije (ELISA test i PCR). Rezultati dobijeni tokom rada pokazuju da su poluselektivne podloge MT (Milk Tween Agar) i MSP (Modified Sucrose Peptone Agar) pogodne za izolaciju ove bakterije. Patogenost odabranih izolata dokazana je na kotiledonim listovima pasulja. Primenom ELISA testova i PCR, potvrđeno je da svi ispitivani izolati i reizolati pripadaju bakteriji P. s. pv. phaseolicola

Razrada metoda za dokazivanje Xanthomonas axonopodis pv. phaseoli na semenu pasulja

Xanthomonas axonopodis pv. phaseoli detection on artificially inoculated bean seeds was investigated. The method of the International Seed Federation – ISF (2006) was used. It included bacteria extraction from seeds and isolation on semiselective media with pathogenicity test of the investigated isolates. ELISA and PCR were used for verification of results. The results showed that the semiselective media MT (Milk Tween Agar) and XCP1 (Xanthomonas campestris pv. phaseoli Agar) were very suitable for isolation of X. a. pv. phaseoli. Pathogenicity was confirmed on young bean plants. ELISA test and PCR confirmed that all investigated isolates and reisolates belong to the bacterium X. a. pv. phaseoli.U radu je ispitivana mogućnost utvrđivanja prisustva bakterije Xanthomonas axonopodis pv. phaseoli na veštački inokulisanom semenu pasulja. Ispitivanja su vršena po metodi International Seed Federation (ISF), ekstrakcijom bakterija iz semena i izolacijom na poluselektivne podloge uz proveru patogenosti dobijenih izolata. Za potvrdu dobijenih rezultata korišćen je ELISA test i PCR. Prema dobijenim rezultatima ova bakterija se može uspešno izolovati na poluselektivne podloge MT (Milk Tween Agar) i XCP1 (Xanthomonas campestris pv. phaseoli Agar). Patogenost je dokazana na mladim biljčicama pasulja. ELISA testovi i PCR su potvrdili da svi ispitivani izolati i reizolati pripadaju bakteriji X. a. pv. phaseoli

Comparison of Essential Metals in Different Pork Meat Cuts from the Serbian Market

AbstractPork consumption in Serbia accounts for a large share of total meat consumption. Pork is valuable sources of nutrients. We analyzed metal content in three different cuts of pork collected from the Serbian market during 2014. Analyses of the following isotopes: zinc (66Zn), copper (63Cu) and iron (57Fe) were performed by ICP-MS. Our data show that Zn, Cu and Fe were present in significantly different levels in hind leg, loin and shoulder, and that shoulder meat was richest in the analyzed metals. The differing mineral status of different pork cuts implies differences in their nutritional benefits for the human diet