| 1. |
- Marinucci, A., et al.
(author)
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Polarization constraints on the X-ray corona in Seyfert Galaxies : MCG-05-23-16
- 2022
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In: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 516:4, s. 5907-5913
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Journal article (peer-reviewed)abstract
- We report on the first observation of a radio-quiet active galactic nucleus (AGN) in polarized X-rays: the Seyfert 1.9 galaxy MCG-05-23-16. This source was pointed at with the Imaging X-ray Polarimetry Explorer (IXPE) starting on 2022 May 14 for a net observing time of 486 ks, simultaneously with XMM-Newton (58 ks) and NuSTAR (83 ks). A polarization degree Π smaller than 4.7 per cent (at the 99 per cent confidence level) is derived in the 2–8 keV energy range, where emission is dominated by the primary component ascribed to the hot corona. The broad-band spectrum, inferred from a simultaneous fit to the IXPE, NuSTAR, and XMM-Newton data, is well reproduced by a power law with photon index Γ = 1.85 ± 0.01 and a high-energy cutoff EC = 120 ± 15 keV. A comparison with Monte Carlo simulations shows that a lamp-post and a conical geometry of the corona are consistent with the observed upper limit, a slab geometry is allowed only if the inclination angle of the system is less than 50°.
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| 2. |
- Brasseur, Z., et al.
(author)
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Measurement report: Introduction to the HyICE-2018 campaign for measurements of ice-nucleating particles and instrument inter-comparison in the Hyytiala boreal forest
- 2022
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In: Atmospheric Chemistry and Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 22:8, s. 5117-5145
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Journal article (peer-reviewed)abstract
- The formation of ice particles in Earth's atmosphere strongly influences the dynamics and optical properties of clouds and their impacts on the climate system. Ice formation in clouds is often triggered heterogeneously by ice-nucleating particles (INPs) that represent a very low number of particles in the atmosphere. To date, many sources of INPs, such as mineral and soil dust, have been investigated and identified in the low and mid latitudes. Although less is known about the sources of ice nucleation at high latitudes, efforts have been made to identify the sources of INPs in the Arctic and boreal environments. In this study, we investigate the INP emission potential from high-latitude boreal forests in the mixed-phase cloud regime. We introduce the HyICE-2018 measurement campaign conducted in the boreal forest of Hyytiala, Finland, between February and June 2018. The campaign utilized the infrastructure of the Station for Measuring Ecosystem-Atmosphere Relations (SMEAR) II, with additional INP instruments, including the Portable Ice Nucleation Chamber I and II (PINC and PINCii), the SPectrometer for Ice Nuclei (SPIN), the Portable Ice Nucleation Experiment (PINE), the Ice Nucleation SpEctrometer of the Karlsruhe Institute of Technology (INSEKT) and the Microlitre Nucleation by Immersed Particle Instrument (mu L-NIPI), used to quantify the INP concentrations and sources in the boreal environment. In this contribution, we describe the measurement infrastructure and operating procedures during HyICE-2018, and we report results from specific time periods where INP instruments were run in parallel for inter-comparison purposes. Our results show that the suite of instruments deployed during HyICE-2018 reports consistent results and therefore lays the foundation for forthcoming results to be considered holistically. In addition, we compare measured INP concentrations to INP parameterizations, and we observe good agreement with the Tobo et al. (2013) parameterization developed from measurements conducted in a ponderosa pine forest ecosystem in Colorado, USA.
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| 3. |
- Li, Z. S., et al.
(author)
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Broadband X-ray spectra and timing of the accreting millisecond pulsar Swift J1756.9-2508 during its 2018 and 2019 outbursts
- 2021
-
In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 649
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Journal article (peer-reviewed)abstract
- The accreting millisecond X-ray pulsar Swift J1756.9-2508 launched into an outburst in April 2018 and June 2019 - 8.7 years after the previous period of activity. We investigated the temporal, timing, and spectral properties of these two outbursts using data from NICER, XMM-Newton, NuSTAR, INTEGRAL, Swift, and Insight-HXMT. The two outbursts exhibited similar broadband spectra and X-ray pulse profiles. For the first time, we report the detection of the pulsed emission up to similar to 100 keV that was observed by Insight-HXMT during the 2018 outburst. We also found the pulsation up to similar to 60 keV that was observed by NICER and NuSTAR during the 2019 outburst. We performed a coherent timing analysis combining the data from the two outbursts. The binary system is well described by a constant orbital period over a time span of similar to 12 years. The time-averaged broadband spectra are well fitted by the absorbed thermal Comptonization model COMPPS in a slab geometry with an electron temperature, kT(e)=40-50 keV, Thomson optical depth tau similar to 1.3, blackbody seed photon temperature kT(bb, seed)similar to 0.7-0.8 keV, and hydrogen column density of N-H similar to 4.2x10(22) cm(-2). We searched the available data for type-I (thermonuclear) X-ray bursts, but found none, which is unsurprising given the estimated low peak accretion rate (approximate to 0.05 of the Eddington rate) and generally low expected burst rates for hydrogen-poor fuel. Based on the history of four outbursts to date, we estimate the long-term average accretion rate at roughly 5x10(-12) M-circle dot yr(-1) for an assumed distance of 8 kpc. The expected mass transfer rate driven by gravitational radiation in the binary implies the source may be no closer than 4 kpc. Swift J1756.9-2508 is the third low mass X-ray binary exhibiting "double" outbursts, which are separated by much shorter intervals than what we typically see and are likely to result from interruption of the accretion flow from the disk onto the neutron star. Such behavior may have important implications for the disk instability model.
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| 4. |
- Sepponen, K., et al.
(author)
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Steroidogenic factor 1 (NR5A1) induces multiple transcriptional changes during differentiation of human gonadal-like cells
- 2022
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In: Differentiation. - : Elsevier BV. - 0301-4681. ; 128:Nov-Dec, s. 83-100
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Journal article (peer-reviewed)abstract
- Nuclear receptor subfamily 5 group A member 1 (NR5A1) encodes steroidogenic factor 1 (SF1), a key regulatory factor that determines gonadal development and coordinates endocrine functions. Here, we have established a stem cell-based model of human gonadal development and applied it to evaluate the effects of NR5A1 during the transition from bipotential gonad to testicular cells. We combined directed differentiation of human induced pluripotent stem cells (46,XY) with activation of endogenous NR5A1 expression by conditionally-inducible CRISPR activation. The resulting male gonadal-like cells expressed several Sertoli cell transcripts, secreted anti-Müllerian hormone and responded to follicle-stimulating hormone by producing sex steroid intermediates. These characteristics were not induced without NR5A1 activation. A total of 2691 differentially expressed genetic elements, including both coding and non-coding RNAs, were detected immediately following activation of NR5A1 expression. Of those, we identified novel gonad-related putative NR5A1 targets, such as SCARA5, which we validated also by immunocytochemistry. In addition, NR5A1 activation was associated with dynamic expression of multiple gonad- and infertility-related differentially expressed genes. In conclusion, by combining targeted differentiation and endogenous activation of NR5A1 we have for the first time, been able to examine in detail the effects of NR5A1 in early human gonadal cells. The model and results obtained provide a useful resource for future investigations exploring the causative reasons for gonadal dysgenesis and infertility in humans. © 2022 The Authors
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| 5. |
- El Kharraz, S., et al.
(author)
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The androgen receptor depends on ligand-binding domain dimerization for transcriptional activation
- 2021
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In: Embo Reports. - : EMBO. - 1469-221X .- 1469-3178. ; 22:12
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Journal article (peer-reviewed)abstract
- Whereas dimerization of the DNA-binding domain of the androgen receptor (AR) plays an evident role in recognizing bipartite response elements, the contribution of the dimerization of the ligand-binding domain (LBD) to the correct functioning of the AR remains unclear. Here, we describe a mouse model with disrupted dimerization of the AR LBD (AR(Lmon/Y)). The disruptive effect of the mutation is demonstrated by the feminized phenotype, absence of male accessory sex glands, and strongly affected spermatogenesis, despite high circulating levels of testosterone. Testosterone replacement studies in orchidectomized mice demonstrate that androgen-regulated transcriptomes in AR(Lmon/Y) mice are completely lost. The mutated AR still translocates to the nucleus and binds chromatin, but does not bind to specific AR binding sites. In vitro studies reveal that the mutation in the LBD dimer interface also affects other AR functions such as DNA binding, ligand binding, and co-regulator binding. In conclusion, LBD dimerization is crucial for the development of AR-dependent tissues through its role in transcriptional regulation in vivo. Our findings identify AR LBD dimerization as a possible target for AR inhibition.
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| 6. |
- Patyra, K., et al.
(author)
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Congenital Hypothyroidism and Hyperthyroidism Alters Adrenal Gene Expression, Development, and Function
- 2022
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In: Thyroid. - : Mary Ann Liebert Inc. - 1050-7256 .- 1557-9077. ; 32:4, s. 459-471
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Journal article (peer-reviewed)abstract
- Background: The human adrenal cortex undergoes several rapid remodeling steps during its lifetime. In rodents, similar remodeling occurs postnatally in the "X-zone" layer through unknown mechanisms. Furthermore, little is known regarding the impact of thyroid hormone (TH) on adrenal glands in humans.Methods: To investigate the impact of TH on adrenal pathophysiology, we created two genetic murine models mimicking human nonautoimmune hypothyroidism and hyperthyroidism. Moreover, we analyzed serum thyrotropin (TSH) and steroid hormone concentrations in patients diagnosed with congenital hypothyroidism and premature adrenarche (PA).Results: We found that TH receptor beta-mediated hypertrophy of the X-zone significantly elevated the adrenal weights of hyperthyroid women. In the hypothyroid model, the X-zone was poorly developed in both sexes. Moreover, large reciprocal changes in the expression levels of genes that regulate adrenal cortical function were observed with both models. Unexpectedly, up- and downregulation of several genes involved in catecholamine synthesis were detected in the adrenal glands of the hypothyroid and hyperthyroid models, respectively. Furthermore, TSH and adrenal steroid concentrations correlated positively in pediatric patients with congenital hypothyroidism and PA.Conclusions: Our results revealed that congenital hypothyroidism and hyperthyroidism functionally affect adrenal gland development and related steroidogenic activity, as well as the adrenal medulla.
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| 7. |
- Colldén, Hannah, et al.
(author)
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Dehydroepiandrosterone Supplementation Results in Varying Tissue-specific Levels of Dihydrotestosterone in Male Mice
- 2022
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In: Endocrinology. - : The Endocrine Society. - 0013-7227 .- 1945-7170. ; 163:12
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Journal article (peer-reviewed)abstract
- Dehydroepiandrosterone (DHEA), an adrenal androgen precursor, can be metabolized in target tissues into active sex steroids. It has been proposed that DHEA supplementation might result in restoration of physiological local sex steroid levels, but knowledge on the effect of DHEA treatment on local sex steroid levels in multiple tissues is lacking. To determine the effects of DHEA on tissue-specific levels of sex steroids, we treated orchiectomized (ORX) male mice with DHEA for 3 weeks and compared them with vehicle-treated ORX mice and gonadal intact mice. Intra-tissue levels of sex steroids were analyzed in reproductive organs (seminal vesicles, prostate, m. levator ani), major body compartments (white adipose tissue, skeletal muscle, and brain), adrenals, liver, and serum using a sensitive and validated gas chromatography-mass spectrometry method. DHEA treatment restored levels of both testosterone (T) and dihydrotestosterone (DHT) to approximately physiological levels in male reproductive organs. In contrast, this treatment did not increase DHT levels in skeletal muscle or brain. In the liver, DHEA treatment substantially increased levels of T (at least 4-fold) and DHT (+536%, P < 0.01) compared with vehicle-treated ORX mice. In conclusion, we provide a comprehensive map of the effect of DHEA treatment on intra-tissue sex steroid levels in ORX mice with a restoration of physiological levels of androgens in male reproductive organs while DHT levels were not restored in the skeletal muscle or brain. This, and the unexpected supraphysiological androgen levels in the liver, may be a cause for concern considering the uncontrolled use of DHEA.
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| 8. |
- Kuiper, L., et al.
(author)
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High-energy characteristics of the accretion-powered millisecond pulsar IGR J17591-2342 during its 2018 outburst : XMM-Newton, NICER, NuSTAR, and INTEGRAL view of the 0.3-300 keV X-ray band
- 2020
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In: Astronomy and Astrophysics. - : EDP SCIENCES S A. - 0004-6361 .- 1432-0746. ; 641
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Journal article (peer-reviewed)abstract
- IGR J17591-2342 is an accreting millisecond X-ray pulsar, discovered with INTEGRAL, which went into outburst around July 21, 2018. To better understand the physics acting in these systems during the outburst episode, we performed detailed temporal-, timing-, and spectral analyses across the 0.3-300 keV band using data from NICER, XMM-Newton, NuSTAR, and INTEGRAL. The hard X-ray 20-60 keV outburst profile covering similar to 85 days is composed of four flares. Over the course of the maximum of the last flare, we discovered a type-I thermonuclear burst in INTEGRAL JEM-X data, posing constraints on the source distance. We derived a distance of 7.6 +/- 0.7 kpc, adopting Eddington-limited photospheric radius expansion and assuming anisotropic emission. In the timing analysis, using all NICER 1-10 keV monitoring data, we observed a rather complex set of behaviours starting with a spin-up period (MJD 58345-58364), followed by a frequency drop (MJD 58364-58370), an episode of constant frequency (MJD 58370-58383), concluded by irregular behaviour till the end of the outburst. The 1-50 keV phase distributions of the pulsed emission, detected up to similar to 120 keV using INTEGRAL ISGRI data, was decomposed in three Fourier harmonics showing that the pulsed fraction of the fundamental increases from similar to 10% to similar to 17% going from similar to 1.5 to similar to 4 keV, while the harder photons arrive earlier than the soft photons for energies less than or similar to 10 keV. The total emission spectrum of IGR J17591-2342 across the 0.3-150 keV band could adequately be fitted in terms of an absorbed COMPPS model yielding as best fit parameters a column density of N-H=(2.09 +/- 0.05) x 10(22) cm(-2), a blackbody seed photon temperature kT(bb, seed) of 0.64 +/- 0.02 keV, electron temperature kT(e)=38.8 +/- 1.2 keV and Thomson optical depth tau (T)=1.59 +/- 0.04. The fit normalisation results in an emission area radius of 11.3 +/- 0.5 km adopting a distance of 7.6 kpc. Finally, the results are discussed within the framework of accretion physics- and X-ray thermonuclear burst theory.
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| 9. |
- Colldén, Hannah, et al.
(author)
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Comprehensive Sex Steroid Profiling in Multiple Tissues Reveals Novel Insights in Sex Steroid Distribution in Male Mice
- 2022
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In: Endocrinology. - : The Endocrine Society. - 0013-7227 .- 1945-7170. ; 163:3
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Journal article (peer-reviewed)abstract
- A comprehensive atlas of sex steroid distribution in multiple tissues is currently lacking, and how circulating and tissue sex steroid levels correlate remains unknown. Here, we adapted and validated a gas chromatography tandem mass spectrometry method for simultaneous measurement of testosterone (T), dihydrotestosterone (DHT), androstenedione, progesterone (Prog), estradiol, and estrone in mouse tissues. We then mapped the sex steroid pattern in 10 different endocrine, reproductive, and major body compartment tissues and serum of gonadal intact and orchiectomized (ORX) male mice. In gonadal intact males, high levels of DHT were observed in reproductive tissues, but also in white adipose tissue (WAT). A major part of the total body reservoir of androgens (T and DHT) and Prog was found in WAT. Serum levels of androgens and Prog were strongly correlated with corresponding levels in the brain while only modestly correlated with corresponding levels in WAT. After orchiectomy, the levels of the active androgens T and DHT decreased markedly while Prog levels in male reproductive tissues increased slightly. In ORX mice, Prog was by far the most abundant sex steroid, and, again, WAT constituted the major reservoir of Prog in the body. In conclusion, we present a comprehensive atlas of tissue and serum concentrations of sex hormones in male mice, revealing novel insights in sex steroid distribution. Brain sex steroid levels are well reflected by serum levels and WAT constitutes a large reservoir of sex steroids in male mice. In addition, Prog is the most abundant sex hormone in ORX mice.
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| 10. |
- Heinosalo, T., et al.
(author)
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Overexpression of Human Estrogen Biosynthetic Enzyme Hydroxysteroid (17beta) Dehydrogenase Type 1 Induces Adenomyosis-like Phenotype in Transgenic Mice
- 2022
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In: International Journal of Molecular Sciences. - : MDPI AG. - 1422-0067. ; 23:9
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Journal article (peer-reviewed)abstract
- Hydroxysteroid (17beta) dehydrogenase type 1 (HSD17B1) is an enzyme that converts estrone to estradiol, while adenomyosis is an estrogen-dependent disease with poorly understood pathophysiology. In the present study, we show that mice universally over-expressing human estrogen biosynthetic enzyme HSD17B1 (HSD17B1TG mice) present with adenomyosis phenotype, characterized by histological and molecular evaluation. The first adenomyotic changes with endometrial glands partially or fully infiltrated into the myometrium appeared at the age of 5.5 months in HSD17B1TG females and became more prominent with increasing age. Preceding the phenotype, increased myometrial smooth muscle actin positivity and increased amount of glandular myofibroblast cells were observed in HSD17B1TG uteri. This was accompanied by transcriptomic upregulation of inflammatory and estrogen signaling pathways. Further, the genes upregulated in the HSD17B1TG uterus were enriched with genes previously observed to be induced in the human adenomyotic uterus, including several genes of the NFKB pathway. A 6-week-long HSD17B1 inhibitor treatment reduced the occurrence of the adenomyotic changes by 5-fold, whereas no effect was observed in the vehicle-treated HSD17B1TG mice, suggesting that estrogen is the main upstream regulator of adenomyosis-induced uterine signaling pathways. HSD17B1 is considered as a promising drug target to inhibit estrogen-dependent growth of endometrial disorders. The present data indicate that HSD17B1 over-expression in TG mice results in adenomyotic changes reversed by HSD17B1 inhibitor treatment and HSD17B1 is, thus, a potential novel drug target for adenomyosis.
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