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- da Cunha, E., et al.
(författare)
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Measurements of the Dust Properties in z similar or equal to 1-3 Submillimeter Galaxies with ALMA
- 2021
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 1538-4357 .- 0004-637X. ; 919:1
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Tidskriftsartikel (refereegranskat)abstract
- We present Atacama Large Millimeter/submillimeter Array (ALMA) 2 mm continuum observations of a complete and unbiased sample of 99 870 mu m selected submillimeter galaxies (SMGs) in the Extended Chandra Deep Field South (ALESS). Our observations of each SMG reach average sensitivities of 53 mu Jy beam(-1). We measure the flux densities for 70 sources, for which we obtain a typical 870 mu m-to-2 mm flux ratio of 14 +/- 5. We do not find a redshift dependence of this flux ratio, which would be expected if the dust emission properties of our SMGs were the same at all redshifts. By combining our ALMA measurements with existing Herschel/SPIRE observations, we construct a (biased) subset of 27 galaxies for which the cool dust emission is sufficiently well sampled to obtain precise constraints on their dust properties using simple isothermal models. Thanks to our new 2 mm observations, the dust emissivity index is well constrained and robust against different dust opacity assumptions. The median dust emissivity index of our SMGs is beta similar or equal to 1.9 +/- 0.4, consistent with the emissivity index of dust in the Milky Way and other local and high-redshift galaxies, as well as classical dust-grain model predictions. We also find a negative correlation between the dust temperature and beta, similar to low-redshift observational and theoretical studies. Our results indicate that beta similar or equal to 2 in high-redshift dusty star-forming galaxies, implying little evolution in dust-grain properties between our SMGs and local dusty galaxy samples, and suggesting that these high-mass and high-metallicity galaxies have dust reservoirs driven by grain growth in their interstellar medium.
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- Flinkman, Dani, et al.
(författare)
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Regulators of proteostasis are translationally repressed in fibroblasts from patients with sporadic and LRRK2-G2019S Parkinson's disease
- 2023
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Ingår i: Npj Parkinsons Disease. - : Springer Science and Business Media LLC. - 2373-8057. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- Deficits in protein synthesis are associated with Parkinson's disease (PD). However, it is not known which proteins are affected or if there are synthesis differences between patients with sporadic and Leucine-Rich Repeat Kinase 2 (LRRK2) G2019S PD, the most common monogenic form. Here we used bio-orthogonal non-canonical amino acid tagging for global analysis of newly translated proteins in fibroblasts from sporadic and LRKK2-G2019S patients. Quantitative proteomic analysis revealed that several nascent proteins were reduced in PD samples compared to healthy without any significant change in mRNA levels. Using targeted proteomics, we validated which of these proteins remained dysregulated at the static proteome level and found that regulators of endo-lysosomal sorting, mRNA processing and components of the translation machinery remained low. These proteins included autophagy-related protein 9A (ATG9A) and translational stability regulator YTH N6-ethyladenosine RNA binding protein 3 (YTHDF3). Notably, 77% of the affected proteins in sporadic patients were also repressed in LRRK2-G2019S patients (False discovery rate (FDR) < 0.05) in both sporadic and LRRK2-G2019S samples. This analysis of nascent proteomes from PD patient skin cells reveals that regulators of proteostasis are repressed in both sporadic and LRRK2-G2019S PD.
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- Kuisma, H, et al.
(författare)
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Parity associates with chromosomal damage in uterine leiomyomas
- 2021
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1, s. 5448-
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Tidskriftsartikel (refereegranskat)abstract
- Mechanical forces in a constrained cellular environment were recently established as a facilitator of chromosomal damage. Whether this could contribute to tumorigenesis is not known. Uterine leiomyomas are common neoplasms that display relatively few chromosomal aberrations. We hypothesized that if mechanical forces contribute to chromosomal damage, signs of this could be seen in uterine leiomyomas from parous women. We examined the karyotypes of 1946 tumors, and found a striking overrepresentation of chromosomal damage associated with parity. We then subjected myometrial cells to physiological forces similar to those encountered during pregnancy, and found this to cause DNA breaks and a DNA repair response. While mechanical forces acting in constrained cellular environments may thus contribute to neoplastic degeneration, and genesis of uterine leiomyoma, further studies are needed to prove possible causality of the observed association. No evidence for progression to malignancy was found.
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- Sahu, B, et al.
(författare)
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Sequence determinants of human gene regulatory elements
- 2022
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 54:3, s. 283-
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Tidskriftsartikel (refereegranskat)abstract
- DNA can determine where and when genes are expressed, but the full set of sequence determinants that control gene expression is unknown. Here, we measured the transcriptional activity of DNA sequences that represent an ~100 times larger sequence space than the human genome using massively parallel reporter assays (MPRAs). Machine learning models revealed that transcription factors (TFs) generally act in an additive manner with weak grammar and that most enhancers increase expression from a promoter by a mechanism that does not appear to involve specific TF–TF interactions. The enhancers themselves can be classified into three types: classical, closed chromatin and chromatin dependent. We also show that few TFs are strongly active in a cell, with most activities being similar between cell types. Individual TFs can have multiple gene regulatory activities, including chromatin opening and enhancing, promoting and determining transcription start site (TSS) activity, consistent with the view that the TF binding motif is the key atomic unit of gene expression.
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