| 1. |
- Delrez, Laetitia, et al.
(author)
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Transit detection of the long-period volatile-rich super-Earth nu(2) Lupi d with CHEOPS
- 2021
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In: Nature Astronomy. - : Springer Science and Business Media LLC. - 2397-3366. ; :5, s. 775-787
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Journal article (peer-reviewed)abstract
- Exoplanets transiting bright nearby stars are key objects for advancing our knowledge of planetary formation and evolution. The wealth of photons from the host star gives detailed access to the atmospheric, interior and orbital properties of the planetary companions. nu(2) Lupi (HD 136352) is a naked-eye (V = 5.78) Sun-like star that was discovered to host three low-mass planets with orbital periods of 11.6, 27.6 and 107.6 d via radial-velocity monitoring(1). The two inner planets (b and c) were recently found to transit(2), prompting a photometric follow-up by the brand new Characterising Exoplanets Satellite (CHEOPS). Here, we report that the outer planet d is also transiting, and measure its radius and mass to be 2.56 +/- 0.09 R-circle plus and 8.82 +/- 0.94 M-circle plus, respectively. With its bright Sun-like star, long period and mild irradiation (similar to 5.7 times the irradiation of Earth), nu(2) Lupi d unlocks a completely new region in the parameter space of exoplanets amenable to detailed characterization. We refine the properties of all three planets: planet b probably has a rocky mostly dry composition, while planets c and d seem to have retained small hydrogen-helium envelopes and a possibly large water fraction. This diversity of planetary compositions makes the nu(2) Lupi system an excellent laboratory for testing formation and evolution models of low-mass planets.
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| 2. |
- Gógl, Gergö, et al.
(author)
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Structural basis of Ribosomal S6 Kinase 1 (RSK1) inhibition by S100B Protein: modulation of the Extracellular Signal-regulated Kinase (ERK) signaling cascade in a calcium-dependent way.
- 2016
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In: The Journal of biological chemistry. - 1083-351X. ; 291:1, s. 11-27
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Journal article (peer-reviewed)abstract
- Mitogen-activated protein kinases (MAPK) promote MAPK activated protein kinase (MAPKAPK) activation. In the MAPK pathway responsible to cell growth, ERK2 initiates the first phosphorylation event on RSK1, which is inhibited by calcium-binding S100 proteins in malignant melanomas. Here we present a detailed in vitro biochemical and structural characterization of the S100B-RSK1 interaction. The calcium-dependent binding of S100B to the calcium/calmodulin dependent protein kinase (CaMK)-type domain of RSK1 is reminiscent to the better known binding of calmodulin to CaMKII. Although S100B-RSK1 and the calmodulin-CAMKII system are clearly distinct functionally, they demonstrate how unrelated intracellular Ca(2+) binding proteins could influence the activity of CaMK domain containing protein kinases. Our crystallographic, small angle X-ray scattering (SAXS) and NMR analysis revealed that S100B forms a ″fuzzy″ complex with RSK1 peptide ligands. Based on fast-kinetics experiments we conclude that the binding involves both conformation selection and induced fit steps. Knowledge of the structural basis of this interaction could facilitate therapeutic targeting of melanomas.
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| 3. |
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| 4. |
- Maróti, Zoltán, et al.
(author)
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The genetic origin of Huns, Avars, and conquering Hungarians
- 2022
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In: Current Biology. - : Elsevier BV. - 0960-9822 .- 1879-0445. ; 32:13, s. 2858-2870, 2858–2870.e1–e7
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Journal article (peer-reviewed)abstract
- Huns, Avars, and conquering Hungarians were migration-period nomadic tribal confederations that arrived in three successive waves in the Carpathian Basin between the 5th and 9th centuries. Based on the historical data, each of these groups are thought to have arrived from Asia, although their exact origin and relation to other ancient and modern populations have been debated. Recently, hundreds of ancient genomes were analyzed from Central Asia, Mongolia, and China, from which we aimed to identify putative source populations for the above-mentioned groups. In this study, we have sequenced 9 Hun, 143 Avar, and 113 Hungarian conquest period samples and identified three core populations, representing immigrants from each period with no recent European ancestry. Our results reveal that this “immigrant core” of both Huns and Avars likely originated in present day Mongolia, and their origin can be traced back to Xiongnus (Asian Huns), as suggested by several historians. On the other hand, the “immigrant core” of the conquering Hungarians derived from an earlier admixture of Mansis, early Sarmatians, and descendants of late Xiongnus. We have also shown that a common “proto-Ugric” gene pool appeared in the Bronze Age from the admixture of Mezhovskaya and Nganasan people, supporting genetic and linguistic data. In addition, we detected shared Hun-related ancestry in numerous Avar and Hungarian conquest period genetic outliers, indicating a genetic link between these successive nomadic groups. Aside from the immigrant core groups, we identified that the majority of the individuals from each period were local residents harboring “native European” ancestry.
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| 5. |
- Mates, L, et al.
(author)
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Comparative analysis of the mouse and human genes (Matn2 and MATN2) for matrilin-2, a filament-forming protein widely distributed in extracellular matrices
- 2002
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In: Matrix Biology. - 1569-1802. ; 21:2, s. 163-174
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Journal article (peer-reviewed)abstract
- We previously identified matrilin-2 (MATN2), the largest member of the novel family of matrilins. These filament-forming adapter proteins expressed in a distinct, but partially overlapping, pattern in all tissues were implicated in the organization of the extracellular matrix. Matrilin-2 functions in a great variety of tissues. Here, we present the genomic organization of the highly conserved mouse and human MATN2 loci, which cover > 100 kb and 167.167 kb genomic regions, respectively, and are composed of 19 exons. RT-PCR analysis revealed that alternative transcripts with identical protein coding regions are transcribed from two promoters in both species. The upstream, housekeeping type promoter is functional in all tissues and cell types tested. The activity of the downstream, TATA-like promoter preceded with putative motifs for the homeobox transcription factor PRRX2 is restricted to embryonic fibroblasts and certain cell lines. The oligomerization module is split by an U12-type AT-AC intron found in conserved position in all four matrilin genes. We assigned Matn2 to mouse chromosome 15, linked to Trhr and Sntb1 in a region synthenic to human chromosome 8q22-24.
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| 6. |
- Pilz, Patrick M., et al.
(author)
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Remote ischemic perconditioning attenuates adverse cardiac remodeling and preserves left ventricular function in a rat model of reperfused myocardial infarction
- 2019
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In: International Journal of Cardiology. - : Elsevier BV. - 0167-5273. ; 285, s. 72-79
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Journal article (peer-reviewed)abstract
- Aims: Remote ischemic conditioning (RIC) is considered a potential clinical approach to reduce myocardial infarct size and ameliorate adverse post-infarct left ventricular (LV) remodeling, however the mechanisms are unknown. The aim was to clarify the impact of RIC on Neuregulin-1 (NRG-1)/ErbBs expression, inflammation and LV hemodynamic function. Methods and results: Male Sprague-Dawley rats were subjected to 30 min occlusion of the left coronary artery (LCA) followed by 2 weeks of reperfusion and separated into three groups: (1) sham operated (without LCA occlusion); (2) Myocardial ischemia/reperfusion (MIR) and (3) remote ischemic perconditioning group (MIR + RIPerc). Cardiac structural and functional changes were evaluated by echocardiography and on the isolated working heart system. The level of H3K4me3 at the NRG-1 promoter, and both plasma and LV tissue levels of NRG-1 were assessed. The expression of pro-inflammatory cytokines, ECM components and ErbB receptors were assessed by RT-qPCR. MIR resulted in a significant decrease in LV function and enlargement of LV chamber. This was accompanied with a decrease in the level of H3K4me3 at the NRG-1 promoter. Consequently NRG-1 protein levels were reduced in the infarcted myocardium. Subsequently, an upregulated influx of CD68+ macrophages, high expression of MMP-2 and -9 as well as an increase of IL-1β TLR-4, TNF-α TNC expression were observed. In contrast, RIPerc significantly decreased inflammation and improved LV function in association with the enhancement of NRG-1 levels and ErbB3 expression. Conclusions: These findings may reveal a novel anti-remodeling and anti-inflammatory effect of RIPerc, involving activation of NRG-1/ErbB3 signaling.
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| 7. |
- Szeitz, Beáta, et al.
(author)
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In-depth proteomic analysis reveals unique subtype-specific signatures in human small-cell lung cancer
- 2022
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In: Clinical and Translational Medicine. - : Wiley. - 2001-1326. ; 12:9, s. 1060-1060
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Journal article (peer-reviewed)abstract
- BACKGROUND: Small-cell lung cancer (SCLC) molecular subtypes have been primarily characterized based on the expression pattern of the following key transcription regulators: ASCL1 (SCLC-A), NEUROD1 (SCLC-N), POU2F3 (SCLC-P) and YAP1 (SCLC-Y). Here, we investigated the proteomic landscape of these molecular subsets with the aim to identify novel subtype-specific proteins of diagnostic and therapeutic relevance.METHODS: Pellets and cell media of 26 human SCLC cell lines were subjected to label-free shotgun proteomics for large-scale protein identification and quantitation, followed by in-depth bioinformatic analyses. Proteomic data were correlated with the cell lines' phenotypic characteristics and with public transcriptomic data of SCLC cell lines and tissues.RESULTS: Our quantitative proteomic data highlighted that four molecular subtypes are clearly distinguishable at the protein level. The cell lines exhibited diverse neuroendocrine and epithelial-mesenchymal characteristics that varied by subtype. A total of 367 proteins were identified in the cell pellet and 34 in the culture media that showed significant up- or downregulation in one subtype, including known druggable proteins and potential blood-based markers. Pathway enrichment analysis and parallel investigation of transcriptomics from SCLC cell lines outlined unique signatures for each subtype, such as upregulated oxidative phosphorylation in SCLC-A, DNA replication in SCLC-N, neurotrophin signalling in SCLC-P and epithelial-mesenchymal transition in SCLC-Y. Importantly, we identified the YAP1-driven subtype as the most distinct SCLC subgroup. Using sparse partial least squares discriminant analysis, we identified proteins that clearly distinguish four SCLC subtypes based on their expression pattern, including potential diagnostic markers for SCLC-Y (e.g. GPX8, PKD2 and UFO).CONCLUSIONS: We report for the first time, the protein expression differences among SCLC subtypes. By shedding light on potential subtype-specific therapeutic vulnerabilities and diagnostic biomarkers, our results may contribute to a better understanding of SCLC biology and the development of novel therapies.
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