Past and future of a regional railway network in Mezohegyes (Hungary) area

The role of railway network in the internal passenger and heavy traffic is continuously decreasing. Regarding the number of passengers, proportion of the railway out of the internal passenger transport was more than 20% less in 2000. The railway passenger transportation suffered a setback in shorter distances in the last decades. In case of railway transportation of goods both the carriage distance and the quantity of goods have decreased. Content of the load has changed, too. Comparing to the previous one, quantity of the transported building materials, metal waste, ores and coal etc. lessened. In contrast with it proportion of agricultural products, machines has increased. It is worth examining the changes in connection with the passenger and heavy traffic in the last few years not only in country level but in the level of several settlements, as well. In settlements’ life a transportation route of the infrastructural sphere plays an important role. In this essay it is aiming to examine the changes in railway traffic of town Mezohegyes, a settlement on the Southern part of the Hungarian Plain, between 1990 and 2006. Research work of this kind has been carried out about town Mezohegyes earlier

Motor neuron apoptosis and neuromuscular junction perturbation are prominent features in a Drosophila model of Fus-mediated ALS

<p>Abstract</p> <p>Backgound</p> <p>Amyotrophic lateral sclerosis (ALS) is progressive neurodegenerative disease characterized by the loss of motor function. Several ALS genes have been identified as their mutations can lead to familial ALS, including the recently reported RNA-binding protein fused in sarcoma (Fus). However, it is not clear how mutations of Fus lead to motor neuron degeneration in ALS. In this study, we present a <it>Drosophila </it>model to examine the toxicity of Fus, its <it>Drosophila </it>orthologue Cabeza (Caz), and the ALS-related Fus mutants.</p> <p>Results</p> <p>Our results show that the expression of wild-type Fus/Caz or FusR521G induced progressive toxicity in multiple tissues of the transgenic flies in a dose- and age-dependent manner. The expression of Fus, Caz, or FusR521G in motor neurons significantly impaired the locomotive ability of fly larvae and adults. The presynaptic structures in neuromuscular junctions were disrupted and motor neurons in the ventral nerve cord (VNC) were disorganized and underwent apoptosis. Surprisingly, the interruption of Fus nuclear localization by either deleting its nuclear localization sequence (NLS) or adding a nuclear export signal (NES) blocked Fus toxicity. Moreover, we discovered that the loss of <it>caz </it>in <it>Drosophila </it>led to severe growth defects in the eyes and VNCs, caused locomotive disability and NMJ disruption, but did not induce apoptotic cell death.</p> <p>Conclusions</p> <p>These data demonstrate that the overexpression of Fus/Caz causes <it>in vivo </it>toxicity by disrupting neuromuscular junctions (NMJs) and inducing apoptosis in motor neurons. In addition, the nuclear localization of Fus is essential for Fus to induce toxicity. Our findings also suggest that Fus overexpression and gene deletion can cause similar degenerative phenotypes but the underlying mechanisms are likely different.</p

Motor neuron apoptosis and neuromuscular junction perturbation are prominent features in a \u3cem\u3eDrosophila\u3c/em\u3e model of Fus-mediated ALS

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is progressive neurodegenerative disease characterized by the loss of motor function. Several ALS genes have been identified as their mutations can lead to familial ALS, including the recently reported RNA-binding protein fused in sarcoma (Fus). However, it is not clear how mutations of Fus lead to motor neuron degeneration in ALS. In this study, we present a Drosophila model to examine the toxicity of Fus, its Drosophila orthologue Cabeza (Caz), and the ALS-related Fus mutants. RESULTS: Our results show that the expression of wild-type Fus/Caz or FusR521G induced progressive toxicity in multiple tissues of the transgenic flies in a dose- and age-dependent manner. The expression of Fus, Caz, or FusR521G in motor neurons significantly impaired the locomotive ability of fly larvae and adults. The presynaptic structures in neuromuscular junctions were disrupted and motor neurons in the ventral nerve cord (VNC) were disorganized and underwent apoptosis. Surprisingly, the interruption of Fus nuclear localization by either deleting its nuclear localization sequence (NLS) or adding a nuclear export signal (NES) blocked Fus toxicity. Moreover, we discovered that the loss of caz in Drosophila led to severe growth defects in the eyes and VNCs, caused locomotive disability and NMJ disruption, but did not induce apoptotic cell death. CONCLUSIONS: These data demonstrate that the overexpression of Fus/Caz causes in vivo toxicity by disrupting neuromuscular junctions (NMJs) and inducing apoptosis in motor neurons. In addition, the nuclear localization of Fus is essential for Fus to induce toxicity. Our findings also suggest that Fus overexpression and gene deletion can cause similar degenerative phenotypes but the underlying mechanisms are likely different

Small aircraft infrared radiation measurements supporting the engine airframe aero-thermal integration

© 2018 Budapest University of Technology and Economics. All rights reserved. The large, EU Supported ESPOSA (Efficient Systems and propulsion for Small Aircraft) project has developed new small gas turbines for small aircraft. One of the important tasks was the engine - airframe aero-thermal radiation integration that included task of minimizing the infrared radiation of the small aircraft, too. This paper discusses the factors influencing on the aircraft infrared radiation, its possible simulation and measurements and introduces the results of small aircraft infrared radiation measurements. The temperature of aircraft hot parts heated by engines were determined for validation of methodology developed and applied to engine - aircraft thermal integration

Clinical and Experimental Studies of a Novel P525R FUS Mutation in Amyotrophic Lateral Sclerosis

Objective: To describe the clinical features of a novel fused in sarcoma (FUS) mutation in a young adult female amyotrophic lateral sclerosis (ALS) patient with rapid progression of weakness and to experimentally validate the consequences of the P525R mutation in cellular neuronal models. Methods: We conducted sequencing of genomic DNA from the index patient and her family members. Immunocytochemistry was performed in various cellular models to determine whether the newly identified P525R mutant FUS protein accumulated in cytoplasmic inclusions. Clinical features of the index patient were compared with 19 other patients with ALS carrying the P525L mutation in the same amino acid position. Results: A novel mutation c.1574C\u3eG (p.525P\u3eR) in the in the FUS gene was identified in the index patient. The clinical symptoms are similar to those in familial ALS patients with the P525L mutation at the same position. The P525R mutant FUS protein showed cytoplasmic localization and formed large stress granule–like cytoplasmic inclusions in multiple cellular models. Conclusions: The clinical features of the patient and the cytoplasmic inclusions of the P525R mutant FUS protein strengthen the notion that mutations at position 525 of the FUS protein result in a coherent phenotype characterized by juvenile or young adult onset, rapid progression, variable positive family history, and female preponderance

FUsed in Sarcoma is a Novel Regulator of Manganese Superoxide Dismutase Gene Transcription

AIMS: FUsed in sarcoma (FUS) is a multifunctional DNA/RNA-binding protein that possesses diverse roles, such as RNA splicing, RNA transport, DNA repair, translation, and transcription. The network of enzymes and processes regulated by FUS is far from being fully described. In this study, we have focused on the mechanisms of FUS-regulated manganese superoxide dismutase (MnSOD) gene transcription. RESULTS: Here we demonstrate that FUS is a component of the transcription complex that regulates the expression of MnSOD. Overexpression of FUS increased MnSOD expression in a dose-dependent manner and knockdown of FUS by siRNA led to the inhibition of MnSOD gene transcription. Reporter analyses, chromatin immunoprecipitation assay, electrophoretic mobility shift assay, affinity chromatography, and surface plasmon resonance analyses revealed the far upstream region of MnSOD promoter as an important target of FUS-mediated MnSOD transcription and confirmed that FUS binds to the MnSOD promoter and interacts with specificity protein 1 (Sp1). Importantly, overexpression of familial amyotropic lateral sclerosis (fALS)-linked R521G mutant FUS resulted in a significantly reduced level of MnSOD expression and activity, which is consistent with the decline in MnSOD activity observed in fibroblasts from fALS patients with the R521G mutation. R521G-mutant FUS abrogates MnSOD promoter-binding activity and interaction with Sp1. INNOVATION AND CONCLUSION: This study identifies FUS as playing a critical role in MnSOD gene transcription and reveals a previously unrecognized relationship between MnSOD and mutant FUS in fALS

The Double-peaked Radio Light Curve of Supernova PTF11qcj

We present continued radio and X-ray follow-up observations of PTF11qcj, a highly energetic broad-lined Type Ic supernova (SN), with a radio peak luminosity comparable to that of the γ-ray burst (GRB) associated SN 1998bw. The latest radio observations, carried out with the Karl G. Jansky Very Large Array, extend up to ~5 yr after the PTF11qcj optical discovery. The radio light curve shows a double-peak profile, possibly associated with density variations in the circumstellar medium (CSM), or with the presence of an off-axis GRB jet. Optical spectra of PTF11qcj taken during both peaks of the radio light curve do not show the broad Hα features typically expected from H-rich circumstellar interaction. Modeling of the second radio peak within the CSM-interaction scenario requires a flatter density profile and an enhanced progenitor mass-loss rate compared to those required to model the first peak. Our radio data alone cannot rule out the alternative scenario of an off-axis GRB powering the second radio peak, but the derived GRB parameters are somewhat unusual compared to typical values found for cosmological long GRBs. On the other hand, Chandra X-ray observations carried out during the second radio peak are compatible with the off-axis GRB hypothesis, within the large measurement errors. We conclude that VLBI measurements of the PTF11qcj radio ejecta are needed to unambiguously confirm or rule out the off-axis GRB jet scenario

Tumor Suppressor Spred2 Interaction with LC3 Promotes Autophagosome Maturation and Induces Autophagy-Dependent Cell Death

The tumor suppressor Spred2 (Sprouty-related EVH1 domain-2) induces cell death in a variety of cancers. However, the underlying mechanism remains to be elucidated. Here we show that Spred2 induces caspase-independent but autophagy-dependent cell death in human cervical carcinoma HeLa and lung cancer A549 cells. We demonstrate that ectopic Spred2 increased both the conversion of microtubule-associated protein 1 light chain 3 (LC3), GFP-LC3 puncta formation and p62/SQSTM1 degradation in A549 and HeLa cells. Conversely, knockdown of Spred2 in tumor cells inhibited upregulation of autophagosome maturation induced by the autophagy inducer Rapamycin, which could be reversed by the rescue Spred2. These data suggest that Spred2 promotes autophagy in tumor cells. Mechanistically, Spred2 co-localized and interacted with LC3 via the LC3-interacting region (LIR) motifs in its SPR domain. Mutations in the LIR motifs or deletion of the SPR domain impaired Spred2-mediated autophagosome maturation and tumor cell death, indicating that functional LIR is required for Spred2 to trigger tumor cell death. Additionally, Spred2 interacted and co-localized with p62/SQSTM1 through its SPR domain. Furthermore, the co-localization of Spred2, p62 and LAMP2 in HeLa cells indicates that p62 may be involved in Spred2-mediated autophagosome maturation. Inhibition of autophagy using the lysosomal inhibitor chloroquine, reduced Spred2-mediated HeLa cell death. Silencing the expression of autophagy-related genes ATG5, LC3 or p62 in HeLa and A549 cells gave similar results, suggesting that autophagy is required for Spred2-induced tumor cell death. Collectively, these data indicate that Spred2 induces tumor cell death in an autophagy-dependent manner