Background: Steroidogenic factor 1 (SF-1) is a key determinant of endocrine development and function of adrenal cortex. SF-1 overexpression and gene amplification were previously demonstrated in a ...small group of pediatric adrenocortical tumors.
Objective: Our objective was to determine the frequency of SF-1 protein expression and gene amplification in a large cohort of pediatric and adult adrenocortical tumors.
Patients: SF-1 protein expression was assessed in a cohort of 103 adrenocortical tumors from 36 children and 67 adults, whereas gene amplification was studied in 38 adrenocortical tumors (17 from children).
Methods: Tissue microarray, multiplex ligation-dependent probe amplification, and quantitative real-time PCR were used.
Results: A strong nuclear SF-1 expression was detected by tissue microarray in 56% (20 of 36) and 19% (13 of 67) of the pediatric and adult adrenocortical tumors, respectively (P = 0.0004). Increased SF-1 copy number was identified in 47% (eight of 17) and 10% (two of 21) of the pediatric and adult adrenocortical tumors, respectively (P = 0.02). All adrenocortical tumors with SF-1 gene amplification showed a strong SF-1 staining, whereas most of the tumors (61%) without SF-1 amplification displayed a weak or negative staining (P = 0.0008). Interestingly, a strong SF-1 staining was identified in five (29%) pediatric adrenocortical tumors without SF-1 amplification. The frequency of SF-1 overexpression and gene amplification was similar in adrenocortical adenomas and carcinomas.
Conclusion: We demonstrated a higher frequency of SF-1 overexpression and gene amplification in pediatric than in adult adrenocortical tumors, suggesting an important role of SF-1 in pediatric adrenocortical tumorigenesis.
Steroidogenic factor 1 (SF-1) overexpression and gene amplification are more frequent in pediatric than in adult adrenocortical tumors, suggesting an important role of SF-1 in pediatric adrenocortical tumorigenesis.
Abstract A large energy-dependent X-ray polarization degree is detected by the Imaging X-ray Polarimetry Explorer (IXPE) in the high-soft emission state of the black hole X-ray binary 4U 1630–47. The ...highly significant detection (at ≈50 σ confidence level) of an unexpectedly high polarization, rising from ∼6% at 2 keV to ∼10% at 8 keV, cannot be easily reconciled with standard models of thin accretion disks. In this work, we compare the predictions of different theoretical models with the IXPE data and conclude that the observed polarization properties are compatible with a scenario in which matter accretes onto the black hole through a thin disk covered by a partially ionized atmosphere flowing away at mildly relativistic velocities.
Abstract We present the first X-ray polarimetric study of the dipping accreting neutron star 4U 1624−49 with the Imaging X-ray Polarimetry Explorer. We report a detection of polarization in the ...nondip time intervals with a confidence level of 99.99%. We find an average polarization degree (PD) of 3.1% ± 0.7% and a polarization angle of 81° ± 6° east of north in the 2–8 keV band. We report an upper limit on the PD of 22% during the X-ray dips with 95% confidence. The PD increases with energy, reaching from 3.0% ± 0.9% in the 4–6 keV band to 6% ± 2% in the 6–8 keV band. This indicates the polarization likely arises from Comptonization. The high PD observed is unlikely to be produced by Comptonization in the boundary layer or spreading layer alone. It can be produced by the addition of an extended geometrically thin slab corona covering part of the accretion disk, as assumed in previous models of dippers, and/or a reflection component from the accretion disk.
ABSTRACT
We report on IXPE, NICER, and XMM–Newton observations of the magnetar 1E 2259+586. We find that the source is significantly polarized at about or above 20 per cent for all phases except for ...the secondary peak where it is more weakly polarized. The polarization degree is strongest during the primary minimum which is also the phase where an absorption feature has been identified previously. The polarization angle of the photons are consistent with a rotating vector model with a mode switch between the primary minimum and the rest of the rotation of the neutron star. We propose a scenario in which the emission at the source is weakly polarized (as in a condensed surface) and, as the radiation passes through a plasma arch, resonant cyclotron scattering off of protons produces the observed polarized radiation. This confirms the magnetar nature of the source with a surface field greater than about 1015 G.
Adrenocortical carcinoma (ACC) is a rare cancer in which tissue-specific differentiation is paradoxically associated with dismal outcomes. The differentiated ACC subtype CIMP-high is prevalent, ...incurable, and routinely fatal. CIMP-high ACC possess abnormal DNA methylation and frequent β-catenin-activating mutations. Here, we demonstrated that ACC differentiation is maintained by a balance between nuclear, tissue-specific β-catenin-containing complexes, and the epigenome. On chromatin, β-catenin bound master adrenal transcription factor SF1 and hijacked the adrenocortical super-enhancer landscape to maintain differentiation in CIMP-high ACC; off chromatin, β-catenin bound histone methyltransferase EZH2. SF1/β-catenin and EZH2/β-catenin complexes present in normal adrenals persisted through all phases of ACC evolution. Pharmacologic EZH2 inhibition in CIMP-high ACC expelled SF1/β-catenin from chromatin and favored EZH2/β-catenin assembly, erasing differentiation and restraining cancer growth in vitro and in vivo. These studies illustrate how tissue-specific programs shape oncogene selection, surreptitiously encoding targetable therapeutic vulnerabilities.
Oncogenic β-catenin can use tissue-specific partners to regulate cellular differentiation programs that can be reversed by epigenetic therapies, identifying epigenetic control of differentiation as a viable target for β-catenin-driven cancers.
Abstract We report on X-ray polarization measurements of the extragalactic Crab-like PSR B0540-69 and its Pulsar Wind Nebula (PWN) in the Large Magellanic Cloud, using a ∼850 ks Imaging X-ray ...Polarimetry Explorer (IXPE) exposure. The PWN is unresolved by IXPE. No statistically significant polarization is detected for the image-averaged data, giving a 99% confidence polarization upper limit (MDP 99 ) of 5.3% in the 2–8 keV energy range. However, a phase-resolved analysis detects polarization for both the nebula and pulsar in the 4–6 keV energy range. For the PWN defined as the off-pulse phases, the polarization degree (PD) of (24.5 ± 5.3)% and polarization angle (PA) of (78.1 ± 6.2)° is detected at 4.6 σ significance level, consistent with the PA observed in the optical band. In a single on-pulse window, a hint of polarization is measured at 3.8 σ with PD of (50.0 ± 13.1)% and PA of (6.2 ± 7.4)°. A “simultaneous” PSR/PWN analysis finds two bins at the edges of the pulse exceeding 3 σ PD significance, with PD of (68 ± 20)% and (62 ± 20)%; intervening bins at 2–3 σ significance have lower PD, hinting at additional polarization structure.
Abstract We present the first X-ray spectropolarimetric results for Cygnus X-1 in its soft state from a campaign of five IXPE observations conducted during 2023 May–June. Companion multiwavelength ...data during the campaign are likewise shown. The 2–8 keV X-rays exhibit a net polarization degree PD = 1.99% ± 0.13% (68% confidence). The polarization signal is found to increase with energy across the Imaging X-ray Polarimetry Explorer’s (IXPE) 2–8 keV bandpass. The polarized X-rays exhibit an energy-independent polarization angle of PA = −25.°7 ± 1.°8 east of north (68% confidence). This is consistent with being aligned to Cyg X-1’s au-scale compact radio jet and its parsec-scale radio lobes. In comparison to earlier hard-state observations, the soft state exhibits a factor of 2 lower polarization degree but a similar trend with energy and a similar (also energy-independent) position angle. When scaling by the natural unit of the disk temperature, we find the appearance of a consistent trend line in the polarization degree between the soft and hard states. Our favored polarimetric model indicates that Cyg X-1’s spin is likely high ( a * ≳ 0.96). The substantial X-ray polarization in Cyg X-1's soft state is most readily explained as resulting from a large portion of X-rays emitted from the disk returning and reflecting off the disk surface, generating a high polarization degree and a polarization direction parallel to the black hole spin axis and radio jet. In IXPE’s bandpass, the polarization signal is dominated by the returning reflection emission. This constitutes polarimetric evidence for strong gravitational lensing of X-rays close to the black hole.
Genomic DNA from 18 patients with combined pituitary hormone deficiency was screened for 2-bp deletion (A301,G302) in PROP1 gene by BcgI restriction endonuclease analysis of PCR-amplified exon 2 gene ...fragments. Two unrelated female patients were homozygous for this 2-bp deletion. Patient 1 presented at 8.8 yr with severe short stature (-2.9 SD score), slightly enlarged sella turcica at x-rays, and diffusely enlarged pituitary gland (height, 8 mm vs. 4.5 +/- 0.6 mm in matched controls) with hyperintense enhanced signal at T1 weighted image at coronal and sagittal views at magnetic resonance imaging (MRI). MRI repeated at age 15 yr revealed a marked reduction of pituitary height (2 mm vs. 5.3 +/- 0.8 mm in matched controls). Patient 2 presented at 27 yr with short stature (-5.5 SD score) without pubertal development, normal sella turcica, and a pituitary gland of reduced size (height, 5 mm vs. 6.1 +/- 0.3 mm in matched controls) of normal intensity at MRI. Both patients had normal pituitary stalk and normally located neurohypophysis. Hormonal features were characterized by GH, TSH, PRL, LH, and FSH deficiencies. Patient 1 had normal cortisol secretion at 8.8 yr, and at 16.6 yr had developed partial cortisol deficiency, whereas patient 2 maintained normal cortisol secretion at 28.4 yr. We conclude that 1) a large sella turcica and an enlarged pituitary anterior lobe with hyperintense enhanced signal at T1 at MRI can be suggestive of PROP1 deficiency; 2) pituitary morphology can change during follow-up of patients with PROP1 gene mutation; and 3) hormonal deficiencies could include the adrenal axis.
Abstract
The Imaging X-ray Polarimetry Explorer (IXPE) observed the black hole X-ray binary 4U 1630–47 in the steep power-law (or very high) state. The observations reveal a linear polarization ...degree of the 2–8 keV X-rays of 6.8% ± 0.2% at a position angle of 21.°3 ± 0.°9 east of north (all errors at 1
σ
confidence level). Whereas the polarization degree increases with energy, the polarization angle stays constant within the accuracy of our measurements. We compare the polarization of the source in the steep power-law state with the previous IXPE measurement of the source in the high soft state. We find that, even though the source flux and spectral shape are significantly different between the high soft state and the steep power-law state, their polarization signatures are similar. Assuming that the polarization of both the thermal and power-law emission components are constant over time, we estimate the power-law component polarization to be 6.8%–7.0% and note that the polarization angle of the thermal and power-law components must be approximately aligned. We discuss the implications for the origin of the power-law component and the properties of the emitting plasma.
Abstract
We describe IXPE polarization observations of the pulsar wind nebula (PWN) MSH 15−5
2
, the “Cosmic Hand.” We find X-ray polarization across the PWN, with
B
-field vectors generally aligned ...with filamentary X-ray structures. High-significance polarization is seen in arcs surrounding the pulsar and toward the end of the “jet,” with polarization degree PD > 70%, thus approaching the maximum allowed synchrotron value. In contrast, the base of the jet has lower polarization, indicating a complex magnetic field at significant angle to the jet axis. We also detect significant polarization from PSR B1509−58 itself. Although only the central pulse phase bin of the pulse has high individual significance, flanking bins provide lower-significance detections and, in conjunction with the X-ray image and radio polarization, can be used to constrain rotating vector model solutions for the pulsar geometry.
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