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1

Metabolic evolutionary roots of the macrophage immune response in amoeba-bacteria interactions: The conserved role of hypoxia-induced Factor and AMP kinase

100%
Dzik J. M.
Acta Biochimica Polonica
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2021
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tom 68
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nr 3
2

Molecules released by helminth parasites involved in host colonization

100%
Dzik J. M.
Acta Biochimica Polonica
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2006
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tom 53
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nr 1
Parasites are designed by evolution to invade the host and survive in its organism until they are ready to reproduce. Parasites release a variety of molecules that help them to penetrate the defensive barriers and avoid the immune attack of the host. In this respect, particularly interesting are enzymes and their inhibitors secreted by the parasites. Serine-, aspartic-, cysteine-, and metalloproteinases are involved in tissue invasion and extracellular protein digestion. Helminths secrete inhibitors of these enzymes (serpins, aspins, and cystatins) to inhibit proteinases, both of the host and their own. Proteinases and their inhibitors, as well as helminth homologues of cytokines and molecules containing phosphorylcholine, influence the immune response of the host biasing it towards the anti-inflammatory Th2 type. Nucleotide-metabolizing enzymes and cholinesterase are secreted by worms to reduce inflammation and expel the parasites from the gastrointestinal tract. An intracellular metazoan parasite, Trichinella spiralis, secretes, among others, protein kinases and phosphatases, endonucleases, and DNA-binding proteins, which are all thought to interfere with the host cellular signals for muscle cell differentiation. Secretion of antioxidant enzymes is believed to protect the parasite from reactive oxygen species which arise from the infection-stimulated host phagocytes. Aside from superoxide dismutase, catalase (rarely found in helminths), and glutathione peroxidase (selenium-independent, thus having a poor activity with H2O2), peroxiredoxins are probably the major H2O2-detoxifying enzymes in helminths. Secretion of antioxidant enzymes is stage-specific and there are examples of regulation of their expression by the concentration of reactive oxygen species surrounding the parasite. The majority of parasite-secreted molecules are commonly found in free-living organisms, thus parasites have only adapted them to use in their way of life.
3

Kernel electrical source imaging (kESI) method for reconstruction of sources of brain electric activity in realistic brain geometries

51%
Kowalska M., Dzik J. M., Chintaluri C., Wojcik D. K.
Acta Neurobiologiae Experimentalis
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2019
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tom 79
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nr Suppl.1
INTRODUCTION: Around 50 million people worldwide are affected by epilepsy. Despite efficiency and steady development of pharmacological treatments, every third patient suffers from intractable seizures. A surgical intervention may be the only solution in these cases. To identify the region for resection, neurosurgeons implant intracranial and subdural electrodes which are used to localize the epileptogenic zone from the measured potentials. AIM(S): Providing better tools for reliable reconstruction of sources of brain activity may lead to more precise localization of the seizure’s origin and better surgical outcomes. To reconstruct sources of brain activity, we use kernel approximation methods for the inverse problem (the reconstruction itself). We model the electric field generated by the neural activity (the forward problem) with finite element method (FEM). We use FEM as it enables the inclusion of realistic head anatomy and tissue properties in the model. METHOD(S): Here we present a method – kernel Electrical Source Imaging (kESI) – of reconstruction of the activity underlying the measured potentials. kESI allows us to use information from arbitrarily placed electrodes and may integrate patient-specific anatomical information which increases precision of localization of epileptogenic zone for a specific patient. RESULTS: The preliminary results are promising. The major advantage of kESI over previous work is that it accounts for spatial variations of brain conductivity and can take into account patient-specific brain and skull anatomy. CONCLUSIONS: Nevertheless, further work is necessary to bring this method to the level of clinical application. FINANCIAL SUPPORT: Project funded from the Polish National Science Centre’s OPUS grant (2015/17/B/ ST7/04123).
4
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Content available

Enzymatic activity and arginase gene expression in Arabidopsis plants infected with a cyst-forming nematode

51%
Rozanska E., Labudda M., Dzik J. M., Sobczak M.
BioTechnologia. Journal of Biotechnology Computational Biology and Bionanotechnology
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2013
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tom 94
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nr 3
5

Really reproducible behavioural paper

45%
Dzik J. M., Puscian A., Harda Z., Radwanska K., Leski S.
Acta Neurobiologiae Experimentalis
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2017
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tom 77
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nr Suppl.1
INTRODUCTION: The reproducibility of behavioural tests has been improved by the introduction of a number of automated experimental systems. One of such systems is IntelliCage™, which allows for sophisticated experimental designs. Despite the improved reproducibility of experiments, reported results may be rendered irreproducible due to errors introduced by manual data analysis and not standardized reporting of analysis methods. The efficiency of manual analysis is also an issue. AIM(S): Our aim was to facilitate development of automated workflows for reproducible analysis of data yielded by the IntelliCage™ system. METHOD(S): We developed an open source Python library (PyMICE – RRID:nlx_158570) providing IntelliCage™ data as collection of data structures. We have described the library and presented some examples of its use in a paper. According to the literate programming paradigm, the paper was composed of Python and LaTeX snippets. Pweave tool has been used to weave the paper. RESULTS: All analyses contained in our paper “PyMICE – a Python library for analysis of IntelliCage data” (accepted by Behavior Research Methods) are fully reproducible. The source code of the paper (https://github.com/Neuroinflab/PyMICE_SM) does not contain any plots. Instead, they may be easily reproduced by the reader. Also, the correctness of performed analyses may be easily verified. CONCLUSIONS: We propose PyMICE as a common platform for implementing and sharing automated analysis workflows for IntelliCage™ data. The library is a user-friendly tool for analysis of behavioural data in an automated workflow. Such workflow is an unambiguous, formal specification of the performed analysis. The analysis itself may be easily reproduced by simply reapplying the workflow to the same data. Such workflow may be used to perform exactly the same analysis for multiple datasets, e.g. when the same protocol is applied to multiple groups of animals. This is a very common case, as most of experiments have at least one experimental and one control group. FINANCIAL SUPPORT: JD, KR and SŁ supported by a Symfonia NCN grant UMO-2013/08/W/NZ4/00691. AP supported by a grant from Switzerland through the Swiss Contribution to the enlarged European Union (PSPB-210/2010 to Ewelina Knapska and Hans-Peter Lipp). KR and ZH supported by an FNP grant POMOST/2011-4/7 to KR.
6
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Content available

Activity of cuticle-degrading enzymes from entomopathogenic fungus Conidiobolus coronatus

45%
Czygier M., Samborski J., Dzik J. M., Walajtys-Rode E., Bogus M.
Wiadomości Parazytologiczne
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1998
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tom 44
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nr 3
7

Kernel current source density revisited

39%
Chintaluri C., Kowalska M., Czerwinski M. B., Sredniawa W., Jedrzejewska-Szmek J., Dzik J. M., Wojcik D. K.
Acta Neurobiologiae Experimentalis
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2019
|
tom 79
|
nr Suppl.1
INTRODUCTION: Extracellular recordings reflect transmembrane currents of neural and glial cells and thus have long been the foundation of measurements of neural activity. Recorded potential reflects activity of the underlying neural network and is directly related to the distribution of current sources along the active cells (current source density, CSD). The long‑range of the electric field leads to significant correlations between recordings at distant sites, which complicates the analysis. However, data interpretation can be facilitated by reconstruction of current sources. AIM(S): Facilitate reconstruction of sources of brain activity with open software. METHOD(S): The Kernel Current Source Density method (KCSD) is a general non-parametric framework for CSD estimation based on kernel techniques, which are widely used in machine‑learning. KCSD allows for current source estimation from potentials recorded by arbitrarily distributed electrodes. Overfitting is prevented by constraining complexity of the inferred CSD model. RESULTS: Here, we revisit KCSD to present a new, open-source implementation in the form of a package, which includes new functionality and several additional tools for kCSD analysis and for validation of the results of analysis accompanied by extensive tutorials implemented in Jupyter notebook. Specifically, we have added 1) analysis of spectral properties of the method; 2) error map generation for assessment of reconstruction accuracy; and 3) L‑curve, a method for estimation of optimum reconstruction parameters. The new implementation allows for CSD reconstruction from potentials measured by 1D, 2D, and 3D experimental setups for a) sources distributed in the entire tissue, b) in a slice, or c) in a single cell with known morphology, provided that the potential is generated by that cell. CONCLUSIONS: New Python implementation of kCSD facilitates CSD analysis and allows for estimation of errors. The toolbox and tutorials are available at https:// github.com/Neuroinflab/kCSD‑python.
8

Sulfamide antifolates inhibiting thymidylate synthase: synthesis, enzyme inhibition and cytotoxicity

39%
Pawelczak K., Makowski M., Kempny M., Dzik J. M., Golos B., Rode W., Rzeszotarska B.
Acta Biochimica Polonica
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2002
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tom 49
|
nr 2
Synthesis and biological evaluation are described of seven new analogues (3-9) of two potent thymidylate synthase inhibitors, 10-propargyl-5,8-dideazafolate (1) and its 2-methyl-2-deamino congener ICI 198583 (2). While the new compunds 3 and 4 were analogues of 1 and 2, respectively, containing a p-aminobenzenesulfonyl residue in place of the p-aminobenzoic acid residue, the remaining 5 new compounds were ana­logues of 4 with the L-glutamic acid residue replaced by glycine (5), L-valine (6), L-alanine (7), L-phenylglycine (8) or L-norvaline (9). The new analogues were tested as inhibitors of thymidylate synthases isolated from tumour (Ehrlich carcinoma), para­site (Hymenolepis diminuta) and normal tissue (regenerating rat liver) and found to be weaker inhibitors than the parent 10-propargyl-5,8-dideazafolic acid. Selected new analogues, tested as inhibitors of growth of mouse leukemia L 5178Y cells, were less potent than the parent 10-propargyl-5,8-dideazafolic acid. Substitution of the glutamyl residue in compound 4 with L-norvaline (9) resulted in only a 5-fold stronger thymidylate synthase inhibitor, but a 40-fold weaker cell growth inhibitor.
9

Effect of cyclosporin A on immunological response in lungs of guinea pigs infected with Trichinella spiralis

39%
Dzik J. M., Zielinski Z., Golos B., Jagielska E., Wranicz M., Walajtys-Rode E.
Acta Biochimica Polonica
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2002
|
tom 49
|
nr 1
The effects of cyclosporin A (CsA), a potent immunosuppressive drug with anti­parasitic activity, on the innate immunological response in guinea pig lungs during an early period (6th and 14th days) after T. spiralis infection were studied. CsA treat­ment of T. spiralis-infected guinea pigs caused a significant attenuation of immuno- logical response in lungs by decreasing lymphocyte infiltration into pulmonary alveo­lar space, inhibiting alveolar macrophage superoxide anion production and lowering both the production of NO metabolites measured in bronchoalveolar lavage fluid and expression of the iNOS protein in lung homogenates, allowing us to speculate that the T. spiralis-dependent immunological response is dependent on lymphocyte T func­tion. Interestingly, CsA itself had a pro-inflammatory effect, promoting leucocyte ac­cumulation and macrophage superoxide production in guinea pig lungs. This observa­tion may have a relevance to the situation in patients undergoing CsA therapy. Macrophage expression of the iNOS protein, evaluated by immunoblotting was not in­fluenced by treatment of animals with CsA or anti-TGF-antibody, indicating different regulation of the guinea pig and murine enzymes.
10

Synthesis and biological activity of Na-[4-[N-[[3,4-dihydro-2-methyl-4-oxo-6-quinazolinyl]methyl]-N-propargylamino]phenylacetyl]-L-glutamic acid

33%
Kusakiewicz-Dawid A., Bugaj M., Dzik J. M., Golos B., Winska P., Pawelczak K., Rzeszotarska B., Rode W.
Acta Biochimica Polonica
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2002
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tom 49
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nr 1
2-Deamino-2-methyl-N10-propargyl-5,8-dideazafolic acid (ICI 198583) is a potent in­hibitor of thymidylate synthase. Its analogue, Nα-[4-[N-[(3,4-dihydro 2-methyl-4 -oxo- 6-quinazolinyl)methyl]-N-propargylamino]phenylacetyl]-L-glutamic acid, containing p-aminophenylacetic acid residue substituting p-aminobenzoic acid residue, was syn­thesized. The new analogue exhibited a moderately potent thymidylate synthase inhi­bition, of linear mixed type vs. the cofactor, N5,10 -methylenetetrahydrofolate. The K value of 0.34 uM, determined with a purified recombinant rat hepatoma enzyme, was about 30-fold higher than that reported for inhibition of thymidylate synthase from mouse leukemia L1210 cells by ICI 198583 (Hughes et al., 1990, J. Med. Chem. 33, 3060). Growth of mouse leukemia L5178Y cells was inhibited by the analogue (IC50 = 1.26 mM) 180-fold weaker than by ICI 198583 (IC50 = 6.9 uM).
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