25 research outputs found

    Elektron-elektron kölcsönhatás szilárdtestekben - DFG - IRTG = Electron- Electron Interactions in Solids - DFG - IRTG

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    A kutatási támogatást a Budapest-Marburg nemzetközi doktori iskola két magyar PhD hallgatójának ösztöndíjára fordítottuk. A hallgatók személye a futamidő alatt tanévenként változott, így a beszámolásköteles tevékenység a doktori iskola több témáját is érinti. A ''Nemkonvencionális sűrűséghullámok'' című kutatási irány keretén belül elméleti eredményeinket kísérletekkel összevetve meggyőzően demonstráltuk számos anyag (pl. egyes magashőmérsékletű szupravezetők) esetében, hogy anomális viselkedésük (pszeudogap, termomágneses transzport) hátterében a fázisdiagrammjuk egyes tartományaiban megjelenő nemkonvencionális kondenzátum áll. A ""Kvantum fázisátalakulások erősen korrelált rendszerekben"" című kutatási program keretében kidolgoztuk a trion-szuperfolyadék fázisátmenet elméletét, mely a csapdázott alkáli atomok mellett releváns lehet a hadron-színszupravezető átmenet értelmezése során is. Az ''Elektron spin rezonancia szilárdtestekben'' című témakörben megállapítottuk egy erősen aluldópolt magashőmérsékletű szupravezető ötvözetről, hogy antiferromágneses fázisában a lyuk koncentráció térben inhomogén, és a polarizáció négyforgású szimmetriával rendelkezik. Végezetül a ""Mágneses momentumok frusztrált rácsokon"" című témakörben megvizsgáltuk egy kooperatív paramágnes alacsony energiás modelljét, és meghatároztuk a rendszer fázisdiagrammját, mely rendezett és rendezetlen tartományokkal is rendelkezik. | The grant support was used to finance the fellowships of two hungarian PhD students of the Budapest-Marburg international graduate school. During the grant period the persons supported by the fellowships changed from schoolyear to schoolyear, therefore the present report touches upon several projects of the graduate school. While working on the project ''Unconventional density waves'', we compared our theoretical results with experiments, and convincingly demonstrated that a number of materials (e.g. certain high temperature superconductors) owe their anomalous behavior (pseudogap, thermomagnetic transport) to unconventional condensates in regions of their phase diagrams. Work on the project ""Quantum phase transitions in strongly correlated systems"" led to the theory of the trion-superfluid phase transition, which is relevant not only to the understanding of trapped alkali atoms, but to the hadron-colorsuperconductor transition as well. Within the framework of the project ''Electron spin resonance in solids'' we have investigated a strongly underdoped high temperature superconductor compound, and determined that in its antiferromagnetic phase the hole concentration is inhomogeneous, and that the polarization has fourfold symmetry. Finally, in the project ""Magnetic moments on frustrated lattices"" we investigated the low energy model of a cooperative paramagnet, and determined the phase diagram of the system, containing both ordered and disordered regions

    Cigarette Smoke-Induced Pulmonary Inflammation Becomes Systemic by Circulating Extracellular Vesicles Containing Wnt5a and Inflammatory Cytokines

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    Chronic obstructive pulmonary disease (COPD) is a devastating, irreversible pathology affecting millions of people worldwide. Clinical studies show that currently available therapies are insufficient, have no or little effect on elevated comorbidities and on systemic inflammation. To develop alternative therapeutic options, a better understanding of the molecular background of COPD is essential. In the present study, we show that non-canonical and pro-inflammatory Wnt5a is up-regulated by cigarette smoking with parallel up-regulation of pro-inflammatory cytokines in both mouse and human model systems. Wnt5a is not only a pro-inflammatory Wnt ligand but can also inhibit the anti-inflammatory peroxisome proliferator-activated receptor gamma transcription and affect M1/M2 macrophage polarization. Both Wnt5a and pro-inflammatory cytokines can be transported in lipid bilayer sealed extracellular vesicles that reach and deliver their contents to every organ measured in the blood of COPD patients, therefore, demonstrating a potential mechanism for the systemic nature of this crippling disease

    Ligation of TLR Homologue CD180 of B Cells Activates the PI3K/Akt/mTOR Pathway in Systemic Sclerosis and Induces a Pathological Shift in the Expression of BAFF Receptors

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    The phosphatidylinositol-3-kinase (PI3K)/Akt and the mammalian target of rapamycin (mTOR) pathways are known to play a key role in B-cell activation and fibrosis in systemic sclerosis (SSc). Receptors of B-cell activator factor (BAFF) utilize these pathways, which can be influenced by Toll-like receptors (TLRs), as TLRs can alter the expression of BAFF-binding receptors. Our results show that B-cell stimulation via TLR homologue CD180 phosphorylates Akt in diffuse cutaneous SSc (dcSSc) to a lower extent than in healthy controls (HCs). We found basal downregulated BAFF receptor (BAFF-R) and enhanced transmembrane activator and calcium-modulator and cyclophilin ligand interactor (TACI) expression in dcSSc B cells, which might enhance the formation of autoantibody-secreting plasma cells. Moreover, this pathological shift was observed in naive B cells, emphasizing the importance of their increase in SSc. Additionally, we measured higher serum levels of autoantibodies to BAFF in dcSSc patients, suggesting that an imbalance in the complex system of BAFF/anti-BAFF autoantibodies/BAFF-binding receptors may contribute to the development of SSc. Anti-CD180 antibody treatment had opposite effects on the expression of BAFF-R and TACI in HC B cells, resulting in similar levels as observed in SSc B cells without stimulation, which argues against the usefulness of such therapy in SSc

    COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

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    Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P < 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

    WNT signaling – lung cancer is no exception

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    Abstract Since the initial discovery of the oncogenic activity of WNT ligands our understanding of the complex roles for WNT signaling pathways in lung cancers has increased substantially. In the current review, the various effects of activation and inhibition of the WNT signaling pathways are summarized in the context of lung carcinogenesis. Recent evidence regarding WNT ligand transport mechanisms, the role of WNT signaling in lung cancer angiogenesis and drug transporter regulation and the importance of microRNA and posttranscriptional regulation of WNT signaling are also reviewed

    Cell death and survival following manual and femtosecond laser-assisted capsulotomy in age-related cataract

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    AIM: To study molecular and morphological changes in lens epithelial cells following femtosecond laser-assisted and manually performed continuous curvilinear capsulotomy (CCC) in order to get information about these methods regarding their potential role in the induction of development of secondary cataract. METHODS: Anterior lens capsules (ALC) were removed from 40 patients with age-related cataract by manual CCC and by femtosecond laser-assisted capsulotomy (FLAC). Samples removed by manual CCC were assorted in group 1, FLAC samples were classified in group 2. Morphology of lens epithelial cells was examined with light and electron microscopes. Following capsulotomy, expressions of p53, Bcl-2 and cyclin D1 genes were analyzed with reverse transcriptase polymerase chain reaction. Immunohistochemistry was used to detect the pro-apoptotic p53 in the epithelial cells. RESULTS: Light and electron microscopic examination showed that ALC of group 1 contained more degenerating cells following manual CCC than after FLAC. The expression level of p53 was higher after manual than laser-assisted surgery. Immunocytochemistry indicated significantly higher number of cells containing p53 protein in the manual CCC group than following FLAC. Bcl-2 and cyclin D1 gene expression levels were slightly lower following manual CCC than after FLAC, but the difference was not significant. CONCLUSION: Manually removed ALC shows slightly, but not significantly larger damage due to the mechanical stretching and pulling of the capsule than those removed using FLAC

    Down-Regulation of Canonical and Up-Regulation of Non-Canonical Wnt Signalling in the Carcinogenic Process of Squamous Cell Lung Carcinoma

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    <div><p>The majority of lung cancers (LC) belong to the non-small cell lung carcinoma (NSCLC) type. The two main NSCLC sub-types, namely adenocarcinoma (AC) and squamous cell carcinoma (SCC), respond differently to therapy. Whereas the link between cigarette smoke and lung cancer risk is well established, the relevance of non-canonical Wnt pathway up-regulation detected in SCC remains poorly understood. The present study was undertaken to investigate further the molecular events in canonical and non-canonical Wnt signalling during SCC development. A total of 20 SCC and AC samples with matched non-cancerous controls were obtained after surgery. TaqMan array analysis confirmed up-regulation of non-canonical Wnt5a and Wnt11 and identified down-regulation of canonical Wnt signalling in SCC samples. The molecular changes were tested in primary small airway epithelial cells (SAEC) and various lung cancer cell lines (e.g. A549, H157, etc). Our studies identified Wnt11 and Wnt5a as regulators of cadherin expression and potentiated relocation of β-catenin to the nucleus as an important step in decreased cellular adhesion. The presented data identifies additional details in the regulation of SCC that can aid identification of therapeutic drug targets in the future.</p> </div

    Level of Wnt signalling molecules in AC and SCC.

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    <p>Pooled cDNA of 12 AC, 8 SSC samples were targeted to gene expression analysis using a commercially available Taqman array. Four housekeeping genes were used (18S, GAPDH, HPRT1, GUSB). <b>A:</b> Expression profile of AC. Pooled cDNA of autologous normal tissue samples of the same AC patients served as reference. Note the increased level of the canonical Wnt-7b, and the receptor Fzd-3. (For the list of all gene expression changes see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0057393#pone.0057393.s004" target="_blank">Table S1</a>). <b>B:</b> Gene expression levels of SCC. Pooled cDNA of autologous normal tissue samples of the same SCC patients served as reference. Note the upregulation of the non-canonical Wnt5a and the canonical pathway inhibitor Dkk-1, along with increased level of Fzd-10 gene expression. (For the list of all gene expression changes see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0057393#pone.0057393.s005" target="_blank">Table S2</a>). <b>C:</b> Gene expression of SCC compared to AC. Note the increased level of non-canonical Wnts (Wnt5a and Wnt11), several receptors (Fzd-7, -9, -10), a canonical pathway inhibitor (Dkk-1) and an inhibitory receptor (Krm2). (For the list of all gene expression changes see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0057393#pone.0057393.s006" target="_blank">Table S3</a>). <b>D and E:</b> Immunohistochemical staining of primary control (Panel D) and AC (Panel E) tissues for Wnt11. Note the higher Wnt11 expression in the tumours emphasizing the relative nature of the initially identified differences at mRNA level. Images shown are representatives of three independent stainings. <b>F:</b> Wnt11 gene transcription was also measured in an AC (A549) and an SCC (H157) cancer cell line. Note the higher Wnt11 levels in the observed cancer cell lines compared to the normal, non-cancerous pulmonary epithelium (SAEC). The AC cell line showed a more pronounced increase in Wnt11 expression than the SCC cell line. (The results are representative of three independent experiments where the non-cancerous control (SAEC) was derived from three individual donors of different ages).</p
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