| 1. |
- Hop, Paul J., et al.
(författare)
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Genome-wide study of DNA methylation shows alterations in metabolic, inflammatory, and cholesterol pathways in ALS
- 2022
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Ingår i: Science Translational Medicine. - : American Association for the Advancement of Science. - 1946-6234 .- 1946-6242. ; 14:633
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Tidskriftsartikel (refereegranskat)abstract
- Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with an estimated heritability between 40 and 50%. DNA methylation patterns can serve as proxies of (past) exposures and disease progression, as well as providing a potential mechanism that mediates genetic or environmental risk. Here, we present a blood-based epigenome-wide association study meta-analysis in 9706 samples passing stringent quality control (6763 patients, 2943 controls). We identified a total of 45 differentially methylated positions (DMPs) annotated to 42 genes, which are enriched for pathways and traits related to metabolism, cholesterol biosynthesis, and immunity. We then tested 39 DNA methylation-based proxies of putative ALS risk factors and found that high-density lipoprotein cholesterol, body mass index, white blood cell proportions, and alcohol intake were independently associated with ALS. Integration of these results with our latest genome-wide association study showed that cholesterol biosynthesis was potentially causally related to ALS. Last, DNA methylation at several DMPs and blood cell proportion estimates derived from DNA methylation data were associated with survival rate in patients, suggesting that they might represent indicators of underlying disease processes potentially amenable to therapeutic interventions.
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| 2. |
- Bilous, A. V., et al.
(författare)
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Dual-frequency single-pulse study of PSR B0950+08
- 2022
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 658
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Tidskriftsartikel (refereegranskat)abstract
- PSR B0950+08 is a bright nonrecycled pulsar whose single-pulse fluence variability is reportedly large. Based on observations at two widely separated frequencies, 55 MHz (NenuFAR) and 1.4 GHz (Westerbork Synthesis Radio Telescope), we review the properties of these single pulses. We conclude that they are more similar to ordinary pulses of radio emission than to a special kind of short and bright giant pulses, observed from only a handful of pulsars. We argue that a temporal variation of the properties of the interstellar medium along the line of sight to this nearby pulsar, namely the fluctuating size of the decorrelation bandwidth of diffractive scintillation makes an important contribution to the observed single-pulse fluence variability. We further present interesting structures in the low-frequency single-pulse spectra that resemble the "sad trombones"seen in fast radio bursts (FRBs); although for PSR B0950+08 the upward frequency drift is also routinely present. We explain these spectral features with radius-to-frequency mapping, similar to the model developed by Wang et al. (2019, ApJ, 876, L15) for FRBs. Finally, we speculate that μs-scale fluence variability of the general pulsar population remains poorly known, and that its further study may bring important clues about the nature of FRBs.
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| 3. |
- Lemme, Max C., et al.
(författare)
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Nanoelectromechanical Sensors Based on Suspended 2D Materials
- 2020
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Ingår i: RESEARCH. - : AMER ASSOC ADVANCEMENT SCIENCE. - 2639-5274. ; 2020
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Forskningsöversikt (refereegranskat)abstract
- The unique properties and atomic thickness of two-dimensional (2D) materials enable smaller and better nanoelectromechanical sensors with novel functionalities. During the last decade, many studies have successfully shown the feasibility of using suspended membranes of 2D materials in pressure sensors, microphones, accelerometers, and mass and gas sensors. In this review, we explain the different sensing concepts and give an overview of the relevant material properties, fabrication routes, and device operation principles. Finally, we discuss sensor readout and integration methods and provide comparisons against the state of the art to show both the challenges and promises of 2D material-based nanoelectromechanical sensing.
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| 4. |
- Dufies, M, et al.
(författare)
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Plk1, upregulated by HIF-2, mediates metastasis and drug resistance of clear cell renal cell carcinoma
- 2021
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Ingår i: Communications biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 4:1, s. 166-
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Tidskriftsartikel (refereegranskat)abstract
- Polo-like kinase 1 (Plk1) expression is inversely correlated with survival advantages in many cancers. However, molecular mechanisms that underlie Plk1 expression are poorly understood. Here, we uncover a hypoxia-regulated mechanism of Plk1-mediated cancer metastasis and drug resistance. We demonstrated that a HIF-2-dependent regulatory pathway drives Plk1 expression in clear cell renal cell carcinoma (ccRCC). Mechanistically, HIF-2 transcriptionally targets the hypoxia response element of the Plk1 promoter. In ccRCC patients, high expression of Plk1 was correlated to poor disease-free survival and overall survival. Loss-of-function of Plk1 in vivo markedly attenuated ccRCC growth and metastasis. High Plk1 expression conferred a resistant phenotype of ccRCC to targeted therapeutics such as sunitinib, in vitro, in vivo, and in metastatic ccRCC patients. Importantly, high Plk1 expression was defined in a subpopulation of ccRCC patients that are refractory to current therapies. Hence, we propose a therapeutic paradigm for improving outcomes of ccRCC patients.
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