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1. Stem cell-like transcriptional reprogramming mediates metastatic resistance to mTOR inhibition

Author

Mateo, F, Arenas, EJ, Aguilar, H, Serra-Musach, J, de Garibay, G Ruiz, Boni, J, Maicas, M, Du, S, Iorio, F, Herranz-Ors, C, Islam, A, Prado, X, Llorente, A, Petit, A, Vidal, A, Català, I, Soler, T, Venturas, G, Rojo-Sebastian, A, Serra, H, Cuadras, D, Blanco, I, Lozano, J, Canals, F, Sieuwerts, AM, de Weerd, V, Look, MP, Puertas, S, García, N, Perkins, AS, Bonifaci, N, Skowron, M, Gómez-Baldó, L, Hernández, V, Martínez-Aranda, A, Martínez-Iniesta, M, Serrat, X, Cerón, J, Brunet, J, Barretina, MP, Gil, M, Falo, C, Fernández, A, Morilla, I, Pernas, S, Plà, MJ, Andreu, X, Seguí, MA, Ballester, R, Castellà, E, Nellist, M, Morales, S, Valls, J, Velasco, A, Matias-Guiu, X, Figueras, A, Sánchez-Mut, JV, Sánchez-Céspedes, M, Cordero, A, Gómez-Miragaya, J, Palomero, L, Gómez, A, Gajewski, TF, Cohen, EEW, Jesiotr, M, Bodnar, L, Quintela-Fandino, M, López-Bigas, N, Valdés-Mas, R, Puente, XS, Viñals, F, Casanovas, O, Graupera, M, Hernández-Losa, J, Ramón y Cajal, S, García-Alonso, L, Saez-Rodriguez, J, Esteller, M, Sierra, A, Martín-Martín, N, Matheu, A, Carracedo, A, González-Suárez, E, Nanjundan, M, Cortés, J, Lázaro, C, Odero, MD, Martens, JWM, Moreno-Bueno, G, Barcellos-Hoff, MH, Villanueva, A, Gomis, RR, and Pujana, MA

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Cancer, Breast Cancer, Stem Cell Research, Adaptor Proteins, Signal Transducing, Adult, Aged, Breast Neoplasms, Carrier Proteins, Cell Proliferation, DNA-Binding Proteins, Female, Gene Expression Regulation, Neoplastic, Humans, Lung Neoplasms, MCF-7 Cells, MDS1 and EVI1 Complex Locus Protein, Microfilament Proteins, Middle Aged, Neoplasm Metastasis, Osteonectin, Proto-Oncogenes, Regulatory-Associated Protein of mTOR, SOX9 Transcription Factor, Signal Transduction, TOR Serine-Threonine Kinases, Transcription Factors, Xenograft Model Antitumor Assays, Clinical Sciences, Oncology & Carcinogenesis, Biochemistry and cell biology, Oncology and carcinogenesis
Abstract

Inhibitors of the mechanistic target of rapamycin (mTOR) are currently used to treat advanced metastatic breast cancer. However, whether an aggressive phenotype is sustained through adaptation or resistance to mTOR inhibition remains unknown. Here, complementary studies in human tumors, cancer models and cell lines reveal transcriptional reprogramming that supports metastasis in response to mTOR inhibition. This cancer feature is driven by EVI1 and SOX9. EVI1 functionally cooperates with and positively regulates SOX9, and promotes the transcriptional upregulation of key mTOR pathway components (REHB and RAPTOR) and of lung metastasis mediators (FSCN1 and SPARC). The expression of EVI1 and SOX9 is associated with stem cell-like and metastasis signatures, and their depletion impairs the metastatic potential of breast cancer cells. These results establish the mechanistic link between resistance to mTOR inhibition and cancer metastatic potential, thus enhancing our understanding of mTOR targeting failure.

Published
2017

6. A novel thermostable TP-84 capsule depolymerase: a method for rapid polyethyleneimine processing of a bacteriophage-expressed proteins

Author

Łubkowska Beata, Czajkowska Edyta, Stodolna Aleksandra, Sroczyński Michał, Zylicz-Stachula Agnieszka, Ireneusz Sobolewski, and Skowron M. Piotr

Subjects
Bioengineering, Applied Microbiology and Biotechnology, Biotechnology
Abstract

Background In spite of the fact that recombinant enzymes are preferably biotechnologically obtained using recombinant clones, the purification of proteins from native microorganisms, including those encoded by bacteriophages, continues. The native bacteriophage protein isolation is often troubled by large volumes of the infected bacterial cell lysates needed to be processed, which is highly undesired in scaled-up industrial processing. A well-known ammonium sulphate fractionation is often a method of choice during purification of the native bacteriophage protein. However, this method is time-consuming and cumbersome, and requires large amounts of the relatively expensive reagent. Thus, other effective and inexpensive methods of reversible protein precipitation are highly desirable. We have previously characterized thermophilic TP-84 bacteriophage, defined a new genus TP84virus within Siphoviridae family, conducted the TP-84 genome annotation and proteomic analysis. The longest Open Reading Frame (ORF) identified in the genome is TP84_26. We have previously annotated this ORF as a hydrolytic enzyme depolymerizing the thick polysaccharides host’s capsule. Results The TP84_26 ‘capsule depolymerase’ (depolymerase) is a large, 112 kDa protein, biosynthesized by the infected Geobacillus stearothermophilus 10 (G. stearothermophilus 10) cells. The TP84_26 protein biosynthesis was confirmed by three approaches: (i) purification of the protein of the expected size; (ii) mass spectrometry (LC–MS) analysis and (iii) detection of the enzymatic activity toward G. stearothermophilus polysaccharide capsules. Streptomycin-resistant mutant of the host was generated and microbiological aspects of both the TP-84 and G. stearothermophilus 10 were determined. A new variant of polyethyleneimine (PEI)-mediated purification method was developed, using the novel TP-84 depolymerase as a model. The enzyme was characterized. Three depolymerase forms were detected: soluble, unbound proteins in the bacteriophage/cells lysate and another integrated into the TP-84 virion. Conclusions The novel TP-84 depolymerase was purified and characterized. The enzyme exists in three forms. The soluble, unbound forms are probably responsible for the weakening of the capsules of the uninfected bacterial cells. The form integrated into virion particles may generate a local passage for the invading TP-84. The developed PEI purification method appears well suited for the scaled-up or industrial production of bacteriophage proteins.

Published
2023
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10. Entschlüsselung molekularer und (epi-)genetischer Mechanismen während der Differenzierung von Embryonalkarzinomen zu Dottersacktumoren

Author

Kotthoff, M, Wruck, W, Adjaye, JA, Nettersheim, D, Skowron, M, Bremmer, F, Fichtner, A, Schönberger, S, Calaminus, G, Vokuhl, C, Pfister, D, Heidenreich, A, Albers, P, Kotthoff, M, Wruck, W, Adjaye, JA, Nettersheim, D, Skowron, M, Bremmer, F, Fichtner, A, Schönberger, S, Calaminus, G, Vokuhl, C, Pfister, D, Heidenreich, A, and Albers, P

Published
2022

11. Die Untersuchungen zum Einfluss des Tumor-Mikromilieus auf Keimzelltumoren entschlüsseln neue bona fide Faktoren der Cisplatin-Resistenz

Author

Skowron, M, Eul, K, Ludwig, GF, Wakileh, G, Stephan, A, Söhngen, C, Bister, A, Raba, K, Petzsch, P, Poschmann, G, Stühler, K, Köhrer, K, Albers, P, Nettersheim, D, Skowron, M, Eul, K, Ludwig, GF, Wakileh, G, Stephan, A, Söhngen, C, Bister, A, Raba, K, Petzsch, P, Poschmann, G, Stühler, K, Köhrer, K, Albers, P, and Nettersheim, D

Published
2022

12. Die molekulare und epigenetische Funktion des Signalmoleküls CD24 in Keimzelltumoren und dessen therapeutischer Angriff über Antikörper und NK-CAR-Zellen

Author

Skowron, M, Becker, T, Kurz, L, Jostes, S, Bremmer, F, Fronhoffs, F, Funke, K, Wakileh, G, Müller, M, Burmeister, A, Lenz, T, Stefanski, A, Stühler, K, Petzsch, P, Köhrer, K, Altevogt, P, Albers, P, Kristiansen, G, Schorle, H, Nettersheim, D, Skowron, M, Becker, T, Kurz, L, Jostes, S, Bremmer, F, Fronhoffs, F, Funke, K, Wakileh, G, Müller, M, Burmeister, A, Lenz, T, Stefanski, A, Stühler, K, Petzsch, P, Köhrer, K, Altevogt, P, Albers, P, Kristiansen, G, Schorle, H, and Nettersheim, D

Published
2022

14. Analysis of PMSM Short-Circuit Detection Systems Using Transfer Learning of Deep Convolutional Networks

Author

Skowron Maciej

Subjects
transfer learning, motor fault detection, inter-turn short circuits, convolutional neural network, field-circuit pmsm model, Electronics, TK7800-8360
Abstract

Modern permanent magnet synchronous motor (PMSM) diagnostic systems are now combined with advanced artificial intelligence techniques, such as deep neural networks. However, the design of such systems is mainly focussed on a selected type of damage or motor type with a limited range of rated parameters. The application of the idea of transfer learning (TL) allows the fully automatic extraction of universal fault symptoms, which can be used for various diagnostic tasks. In the research, the possibility of using the TL idea in the implementation of PMSM stator windings fault-detection systems was considered. The method is based on the characteristic symptoms of stator defects determined for another type of motor or mathematical model in the target diagnostic application of PMSM. This paper presents a comparison of PMSM motor inter-turn short circuit fault detection systems using TL of a deep convolutional network. Due to the use of direct phase current signal analysis by the convolutional neural network (CNN), it was possible to ensure high accuracy of fault detection with simultaneously short reaction time to occurring fault. The technique used was based on the use of a weight coefficient matrix of a pre-trained structure, the adaptation of which was carried out for different sources of diagnostic information.

Published
2024
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21. The application of chromatographic breath analysis in the search of volatile biomarkers of chronic kidney disease and coexisting type 2 diabetes mellitus

Author

Grabowska-Polanowska, Beata, Skowron, M., Miarka, Przemysław, Pietrzycka, Agata, and Śliwka, I.

Subjects
Adult, Male, Breath composition, Clinical Biochemistry, Methanethiol, Sulfides, 01 natural sciences, Biochemistry, Analytical Chemistry, Acetone, 03 medical and health sciences, chemistry.chemical_compound, Methylamines, 0302 clinical medicine, Hemiterpenes, Limit of Detection, Diabetes mellitus, Pentanes, medicine, Butadienes, Humans, Renal Insufficiency, Chronic, Volatile Organic Compounds, Chromatography, Chemistry, 010401 analytical chemistry, Case-control study, Type 2 Diabetes Mellitus, Exhalation, Reproducibility of Results, Cell Biology, General Medicine, Middle Aged, medicine.disease, 0104 chemical sciences, 030228 respiratory system, Breath gas analysis, Diabetes Mellitus, Type 2, Case-Control Studies, Female, Biomarkers, Kidney disease
Abstract

Chromatographic studies on breath composition are aimed at finding volatile markers useful for medical diagnostics or in screening investigations. Studies leading to the development of screening breath tests are especially important for the diagnostics of chronic kidney disease (CKD) and type 2 diabetes mellitus (T2DM). The aim of the presented study was to confirm diagnostic usefulness of chosen volatile compounds detected in breath, which are suggested as potential biomarkers of renal dysfunction and diabetes. Breath analysis were carried out in three groups: 10 healthy volunteers, 10 patients with CKD and 10 patients with CKD and T2DM. All exhaled air samples were analyzed using gas chromatograph (Agilent 6890GC) coupled with mass spectrometer (5975MSD). Thermal desorption was applied as the enrichment method. TMA was detected only in CKD patients. Higher breath concentrations of methanethiol (MeSH) were observed in CKD patients with coexisting diabetes than in patients with renal dysfunction only or in the healthy group. There was a tendency of increasing MeSH concentration in breath with increasing total glutathione in plasma (r=0.53, p=0.0026). Also, a trend of increasing dimethylsulfide (DMS) levels detected in breath was noticed with an increase of hydrogen sulfide concentration in plasma (r=0.74; p=0.00001) as well as with aspartate aminotransferase (AST), (r=0.61; p=0.001). The presented results suggest the possibility of applying TMA, MeSH, and DMS detection in breath as diagnostic methods.

Published
2017

22. Stator winding fault diagnosis of induction motor operating under the field-oriented control with convolutional neural networks.

Author

SKOWRON, M., WOLKIEWICZ, M., and TARCHAŁA, G.

Subjects
*CONVOLUTIONAL neural networks, *FAULT diagnosis, *INDUCTION motors, *SIGNAL convolution, *STATORS, *FAST Fourier transforms
Abstract

In this paper deep neural networks are proposed to diagnose inter-turn short-circuits of induction motor stator windings operating under the Direct Field Oriented Control method. A convolutional neural network (CNN), trained with a Stochastic Gradient Descent with Momentum method is used. This kind of deep-trained neural network allows to significantly accelerate the diagnostic process compared to the traditional methods based on the Fast Fourier Transform as well as it does not require stationary operating conditions. To assess the effectiveness of the applied CNN-based detectors, the tests were carried out for variable load conditions and different values of the supply voltage frequency. Experimental results of the proposed induction motor fault detection system are presented and discussed. [ABSTRACT FROM AUTHOR]

Published
2020
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23. Application of deep learning neural networks for the diagnosis of electrical damage to the induction motor using the axial flux.

Author

SKOWRON, M.

Subjects
*INDUCTION machinery, *DEEP learning, *ELECTRIC circuits, *CONVOLUTIONAL neural networks, *FLUX (Energy), *INDUCTION motors
Abstract

In industrial drive systems, one of the widest group of machines are induction motors. During normal operation, these machines are exposed to various types of damages, resulting in high economic losses. Electrical circuits damages are more than half of all damages appearing in induction motors. In connection with the above, the task of early detection of machine defects becomes a priority in modern drive systems. The article presents the possibility of using deep neural networks to detect stator and rotor damages. The opportunity of detecting shorted turns and the broken rotor bars with the use of an axial flux signal is presented. [ABSTRACT FROM AUTHOR]

Published
2020
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28. Stem cell-like transcriptional reprogramming mediates metastatic resistance to mTOR inhibition

Author

Mateo, F. (F.), Arenas, E.J. (E. J.), Aguilar, H. (Helena), Serra-Musach, J. (Jordi), De Garibay, G.R. (G. Ruiz), Boni, J. (J.), Maicas, M. (M.), Du, S. (S.), Iorio, F. (F.), Herranz-Ors, C. (C.), Islam, A. (A.), Prado, X. (X.), Llorente, A. (A.), Petit, A. (Anna), Vidal, A. (A.), Català, I. (Isabel), Soler, T. (T.), Venturas, G. (G.), Rojo-Sebastian, A. (A.), Serra, H. (H.), Cuadras, D. (Daniel), Blanco, I. (I.), Lozano, J. (J.), Canals, F. (F.), Sieuwerts, A.M. (Anieta), Weerd, V. (Vanja) de, Look, M.P. (Maxime), Puertas, S. (S.), García, N. (Nadia), Perkins, A.S. (A. S.), Bonifaci, N. (Núria), Skowron, M. (Margaretha), Gómez-Baldó, L. (Laia), Hernández, V. (V.), Martínez-Aranda, A. (A.), Martínez-Iniesta, M. (M.), Serrat, X. (X.), Cerón, J. (Julián), Brunet, J. (Joan), Barretina, M.P. (M. P.), Gil, M. (Miguel), Falo, C. (C.), Fernández, A. (A.), Morilla, I. (I.), Pernas, S. (S.), Plà, M.J. (M. J.), Andreu, X. (X.), Seguí, M.A. (M. A.), Ballester, R. (R.), Castellà, E. (E.), Nellist, M.D. (Mark), Morales, S. (S.), Valls, J. (J.), Velasco, A. (A.), Matias-Guiu, X. (Xavier), Figueras, J., Sánchez-Mut, J.V. (J. V.), Sánchez-Céspedes, M. (M.), Cordero, A. (A.), Gómez-Miragaya, J. (J.), Palomero, L. (L.), Gómez, A. (A.), Gajewski, T.F. (T. F.), Cohen, E.E.W. (E. E.W.), Jesiotr, M. (M.), Bodnar, L. (L.), Quintela-Fandino, M. (M.), López-Bigas, N. (Núria), Valdés-Mas, R. (Rafael), Puente, X.S. (Xose), Viñals, F. (F.), Casanovas, O. (O.), Graupera, M. (M.), Hernandez-Losa, J. (Javier), Ramóny Cajal, S. (S.), García-Alonso, L. (L.), Saez-Rodriguez, J. (J.), Esteller, M. (Manel), Sierra, A. (A.), Martín-Martín, N. (N.), Matheu, A. (A.), Carracedo, A. (A.), González-Suárez, E. (E.), Nanjundan, M. (M.), Cortés, J. (J.), Lázaro, C. (C.), Odero, M.D. (Maria), Martens, J.W.M. (John), Moreno-Bueno, G. (G.), Barcellos-Hoff, M.H., Villanueva, A. (Alberto), Gomis, R.R. (R. R.), Pujana, M.A. (M. A.), Mateo, F. (F.), Arenas, E.J. (E. J.), Aguilar, H. (Helena), Serra-Musach, J. (Jordi), De Garibay, G.R. (G. Ruiz), Boni, J. (J.), Maicas, M. (M.), Du, S. (S.), Iorio, F. (F.), Herranz-Ors, C. (C.), Islam, A. (A.), Prado, X. (X.), Llorente, A. (A.), Petit, A. (Anna), Vidal, A. (A.), Català, I. (Isabel), Soler, T. (T.), Venturas, G. (G.), Rojo-Sebastian, A. (A.), Serra, H. (H.), Cuadras, D. (Daniel), Blanco, I. (I.), Lozano, J. (J.), Canals, F. (F.), Sieuwerts, A.M. (Anieta), Weerd, V. (Vanja) de, Look, M.P. (Maxime), Puertas, S. (S.), García, N. (Nadia), Perkins, A.S. (A. S.), Bonifaci, N. (Núria), Skowron, M. (Margaretha), Gómez-Baldó, L. (Laia), Hernández, V. (V.), Martínez-Aranda, A. (A.), Martínez-Iniesta, M. (M.), Serrat, X. (X.), Cerón, J. (Julián), Brunet, J. (Joan), Barretina, M.P. (M. P.), Gil, M. (Miguel), Falo, C. (C.), Fernández, A. (A.), Morilla, I. (I.), Pernas, S. (S.), Plà, M.J. (M. J.), Andreu, X. (X.), Seguí, M.A. (M. A.), Ballester, R. (R.), Castellà, E. (E.), Nellist, M.D. (Mark), Morales, S. (S.), Valls, J. (J.), Velasco, A. (A.), Matias-Guiu, X. (Xavier), Figueras, J., Sánchez-Mut, J.V. (J. V.), Sánchez-Céspedes, M. (M.), Cordero, A. (A.), Gómez-Miragaya, J. (J.), Palomero, L. (L.), Gómez, A. (A.), Gajewski, T.F. (T. F.), Cohen, E.E.W. (E. E.W.), Jesiotr, M. (M.), Bodnar, L. (L.), Quintela-Fandino, M. (M.), López-Bigas, N. (Núria), Valdés-Mas, R. (Rafael), Puente, X.S. (Xose), Viñals, F. (F.), Casanovas, O. (O.), Graupera, M. (M.), Hernandez-Losa, J. (Javier), Ramóny Cajal, S. (S.), García-Alonso, L. (L.), Saez-Rodriguez, J. (J.), Esteller, M. (Manel), Sierra, A. (A.), Martín-Martín, N. (N.), Matheu, A. (A.), Carracedo, A. (A.), González-Suárez, E. (E.), Nanjundan, M. (M.), Cortés, J. (J.), Lázaro, C. (C.), Odero, M.D. (Maria), Martens, J.W.M. (John), Moreno-Bueno, G. (G.), Barcellos-Hoff, M.H., Villanueva, A. (Alberto), Gomis, R.R. (R. R.), and Pujana, M.A. (M. A.)

Abstract

Inhibitors of the mechanistic target of rapamycin (mTOR) are currently used to treat advanced metastatic breast cancer. However, whether an aggressive phenotype is sustained through adaptation or resistance to mTOR inhibition remains unknown. Here, complementary studies in human tumors, cancer models and cell lines reveal transcriptional reprogramming that supports metastasis in response to mTOR inhibition. This cancer feature is driven by EVI1 and SOX9. EVI1 functionally cooperates with and positively regulates SOX9, and promotes the transcriptional upregulation of key mTOR pathway components (REHB and RAPTOR) and of lung metastasis mediators (FSCN1 and SPARC). The expression of EVI1 and SOX9 is associated with stem cell-like and metastasis signatures, and their depletion impairs the metastatic potential of breast cancer cells. These results establish the mechanistic link between resistance to mTOR inhibition and cancer metastatic potential, thus enhancing our understanding of mTOR targeting failure.

Published
2017
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32. Lifetime increase method of cutting ability of grinding wheels in the process of magnesium alloy grinding.

Author

Dębkowski, R., Gołąbczak, M., Skowron, M., and Urbaniak, M.

Subjects
GRINDING wheels, GEOMETRIC surfaces, MILLING (Metalwork), SURFACE structure, MAGNESIUM alloys
Abstract

Copyright of Materialwissenschaft und Werkstoffechnik is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Published
2019
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33. Tubers from patients with tuberous sclerosis complex are characterized by changes in microtubule biology through ROCK2 signalling

Author

Ferrer, I, Mohan, P, Chen, H, Castellsague, J, Gomez-Baldo, L, Carmona, M, Garcia, N, Aguilar, H, Jiang, JH, Skowron, M, Nellist, Mark, Ampuero, I, Russi, A, Lazaro, C (Conxi), Maxwell, CA, Pujana, MA, and Clinical Genetics

Subjects
congenital, hereditary, and neonatal diseases and abnormalities, food and beverages
Abstract

Most patients with tuberous sclerosis complex (TSC) develop cortical tubers that cause severe neurological disabilities. It has been suggested that defects in neuronal differentiation and/or migration underlie the appearance of tubers. However, the precise molecular alterations remain largely unknown. Here, by combining cytological and immunohistochemical analyses of tubers from nine TSC patients (four of them diagnosed with TSC2 germline mutations), we show that alteration of microtubule biology through ROCK2 signalling contributes to TSC neuropathology. All tubers showed a larger number of binucleated neurons than expected relative to control cortex. An excess of normal and altered cytokinetic figures was also commonly observed. Analysis of centrosomal markers suggested increased microtubule nucleation capacity, which was supported by the analysis of an expression dataset from cortical tubers and control cortex, and subsequently linked to under-expression of Rho-associated coiled-coil containing kinase 2 (ROCK2). Thus, augmented microtubule nucleation capacity was observed in mouse embryonic fibroblasts and human fibroblasts deficient in the Tsc2/TSC2 gene product, tuberin. Consistent with ROCK2 under-expression, microtubule acetylation was found to be increased with tuberin deficiency; this alteration was abrogated by rapamycin treatment and mimicked by HDAC6 inhibition. Together, the results of this study support the hypothesis that loss of TSC2 expression can alter microtubule organization and dynamics, which, in turn, deregulate cell division and potentially impair neuronal differentiation. Copyright (c) 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd

Published
2014

34. Stem cell-like transcriptional reprogramming mediates metastatic resistance to mTOR inhibition

Author

Mateo, F, primary, Arenas, E J, additional, Aguilar, H, additional, Serra-Musach, J, additional, de Garibay, G Ruiz, additional, Boni, J, additional, Maicas, M, additional, Du, S, additional, Iorio, F, additional, Herranz-Ors, C, additional, Islam, A, additional, Prado, X, additional, Llorente, A, additional, Petit, A, additional, Vidal, A, additional, Català, I, additional, Soler, T, additional, Venturas, G, additional, Rojo-Sebastian, A, additional, Serra, H, additional, Cuadras, D, additional, Blanco, I, additional, Lozano, J, additional, Canals, F, additional, Sieuwerts, A M, additional, de Weerd, V, additional, Look, M P, additional, Puertas, S, additional, García, N, additional, Perkins, A S, additional, Bonifaci, N, additional, Skowron, M, additional, Gómez-Baldó, L, additional, Hernández, V, additional, Martínez-Aranda, A, additional, Martínez-Iniesta, M, additional, Serrat, X, additional, Cerón, J, additional, Brunet, J, additional, Barretina, M P, additional, Gil, M, additional, Falo, C, additional, Fernández, A, additional, Morilla, I, additional, Pernas, S, additional, Plà, M J, additional, Andreu, X, additional, Seguí, M A, additional, Ballester, R, additional, Castellà, E, additional, Nellist, M, additional, Morales, S, additional, Valls, J, additional, Velasco, A, additional, Matias-Guiu, X, additional, Figueras, A, additional, Sánchez-Mut, J V, additional, Sánchez-Céspedes, M, additional, Cordero, A, additional, Gómez-Miragaya, J, additional, Palomero, L, additional, Gómez, A, additional, Gajewski, T F, additional, Cohen, E E W, additional, Jesiotr, M, additional, Bodnar, L, additional, Quintela-Fandino, M, additional, López-Bigas, N, additional, Valdés-Mas, R, additional, Puente, X S, additional, Viñals, F, additional, Casanovas, O, additional, Graupera, M, additional, Hernández-Losa, J, additional, Ramón y Cajal, S, additional, García-Alonso, L, additional, Saez-Rodriguez, J, additional, Esteller, M, additional, Sierra, A, additional, Martín-Martín, N, additional, Matheu, A, additional, Carracedo, A, additional, González-Suárez, E, additional, Nanjundan, M, additional, Cortés, J, additional, Lázaro, C, additional, Odero, M D, additional, Martens, J W M, additional, Moreno-Bueno, G, additional, Barcellos-Hoff, M H, additional, Villanueva, A, additional, Gomis, R R, additional, and Pujana, M A, additional

Published
2016
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37. Tubers from patients with tuberous sclerosis complex are characterized by changes in microtubule biology through ROCK2 signalling

Author

Ferrer, I. (Isidro), Mohan, P. (Pooja), Chen, H. (Helen), Castellsagué, J. (Joan), Gómez-Baldó, L. (Laia), Carmona, M. (Marga), García, N. (Nadia), Aguilar, H. (Helena), Jiang, J. (John), Skowron, M. (Margaretha), Nellist, M.D. (Mark), Ampuero, I. (Israel), Russi, A. (Antonio), Lázaro, C. (Conxi), Maxwell, C.A. (Christopher), Pujana, M.A. (Miguel), Ferrer, I. (Isidro), Mohan, P. (Pooja), Chen, H. (Helen), Castellsagué, J. (Joan), Gómez-Baldó, L. (Laia), Carmona, M. (Marga), García, N. (Nadia), Aguilar, H. (Helena), Jiang, J. (John), Skowron, M. (Margaretha), Nellist, M.D. (Mark), Ampuero, I. (Israel), Russi, A. (Antonio), Lázaro, C. (Conxi), Maxwell, C.A. (Christopher), and Pujana, M.A. (Miguel)

Abstract

Most patients with tuberous sclerosis complex (TSC) develop cortical tubers that cause severe neurological disabilities. It has been suggested that defects in neuronal differentiation and/or migration underlie the appearance of tubers. However, the precise molecular alterations remain largely unknown. Here, by combining cytological and immunohistochemical analyses of tubers from nine TSC patients (four of them diagnosed with TSC2 germline mutations), we show that alteration of microtubule biology through ROCK2 signalling contributes to TSC neuropathology. All tubers showed a larger number of binucleated neurons than expected relative to control cortex. An excess of normal and altered cytokinetic figures was also commonly observed. Analysis of centrosomal markers suggested increased microtubule nucleation capacity, which was supported by the analysis of an expression dataset from cortical tubers and control cortex, and subsequently linked to under-expression of Rho-associated coiled-coil containing kinase 2 (ROCK2). Thus, augmented microtubule nucleation capacity was observed in mouse embryonic fibroblasts and human fibroblasts deficient in the Tsc2/TSC2 gene product, tuberin. Consistent with ROCK2 under-expression, microtubule acetylation was found to be increased with tuberin deficiency; this alteration was abrogated by rapamycin treatment and mimicked by HDAC6 inhibition. Together, the results of this study support the hypothesis that loss of TSC2 expression can alter microtubule organization and dynamics, which, in turn, deregulate cell division and potentially impair neuronal differentiation. Copyright

Published
2014
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49. Antioxidant enzyme activities in rabbits under oxidative stress induced by high fat diet

Author

Skowron Marta, Zalejska-Fiolka Jolanta, Błaszczyk Urszula, Chwalińska Ewa, Owczarek Aleksander, and Birkner Ewa

Subjects
rabbit, oil, antioxidant enzymes, mda, oxidative stress, Veterinary medicine, SF600-1100
Abstract

The aim of this study was to investigate whether the type and form of oil (raw/non-oxidised (N) or post-frying/oxidised (O)) consumed in high-fat diets affect the oxidative status of an organism, as observed by malondialdehyde (MDA) concentration as an oxidative factor and antioxidant enzyme activity.

Published
2018
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50. The Influence of Diesel Oil Improvers on Indices of Atomisation and Combustion in High-Efficiency Engines

Author

Pielecha Ireneusz, Pielecha Jacek, Skowron Maciej, and Mazanek Aleksander

Subjects
diesel oil, diesel engine, improvers, fuel injection, fuel combustion, Naval architecture. Shipbuilding. Marine engineering, VM1-989
Abstract

The process of fuel combustion in a diesel engine is determined by factors existing during liquid fuel injection and atomisation. The physicochemical properties of the fuel to a large extent decide upon the quality of this phase of cylinder fuelling. So it is important to ensure appropriate properties of a fuel affecting its atomisation and, as a result, combustion. The paper deals with the topic of diesel oil improvers and the analysis of their influence on atomisation and combustion indices. In the studies base diesel oil and a diesel fuel improved by a package of additives, were used. The process of conventional and improved fuel injection was analysed by using optical examinations. The amount of released heat was evaluated during the studies carried out on combustion. Significant aspects of the applied improvers in relation to fuel injection and its combustion have been indicated.

Published
2017
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