A subset of nuclear receptors (NRs) function as permissive heterodimers with retinoid X receptor (RXR), defined by transcriptional activation in response to binding RXR agonist ligands. Permissive NR-RXR activation operates via a classical pharmacological mechanism, where binding of an RXR agonist increases coactivator recruitment to the heterodimer. However, we previously demonstrated that transcriptional activation of permissive Nurr1-RXRα (NR4A2-NR2B1) heterodimers by an RXR ligand set, which included pharmacological RXR agonists and selective Nurr1-RXRα agonists that function as antagonists of RXRα homodimers, occurs via a non-classical mechanism: ligand-binding domain (LBD) heterodimer dissociation (Yu et al., 2023). Here, we extend mechanistic ligand profiling of the same RXR ligand set to Nur77-RXRγ (NR4A1-NR2B3), which is evolutionarily related to Nurr1-RXRα. Biochemical and NMR protein-protein interaction profiling along with cellular transcription studies indicate that the RXR ligand set, which lacks selective Nur77-RXRγ agonists, may influence Nur77-RXRγ transcriptional activation through both classical pharmacological activation and LBD heterodimer dissociation. However, upon reanalyzing our previously published data for Nurr1-RXRα, we found that the inclusion of selective Nurr1-RXRα agonists was essential for elucidating the LBD heterodimer dissociation mechanism. Our findings underscore the need for a more functionally diverse RXR ligand set to explore Nur77-RXRγ activation and unify LBD heterodimer dissociation as a potential targeting mechanism for NR4A-RXR heterodimers in neurodegenerative and inflammatory diseases.

• Book : ()
• Pub. Date : 2025
• Page :
• Keyword :

Abstract We present a study of giant molecular cloud (GMC) properties in the Andromeda galaxy (M31) using CO(3-2) data from the James Clerk Maxwell Telescope (JCMT) in selected regions across the disc and in the nuclear ring, and comparing them with CO(1-0) observations from the IRAM 30m telescope in the same regions. We find that GMCs in the centre of M31 generally exhibit larger velocity dispersions (σ) and sizes (R) compared to those in the disc, while their average surface density (Σ) and turbulent pressure (Pturb) are lower. This low turbulent pressure in the central region is primarily due to the low density of molecular gas. The estimated GMC properties depend on the choice of CO transitions. Compared to CO(1-0), CO(3-2) exhibits smaller velocity dispersion and equivalent radius but higher surface density. These differences highlight the distinct physical conditions probed by different molecular gas tracers. We estimate the virial parameter αvir∝σ2R/Σ and find that most molecular clouds exhibit high values (αvir ∼ 4 − 6) for both CO transitions, indicating that they are unbound. Furthermore, clouds in the nuclear ring display even larger αvir values of ≲ 100, suggesting that they may be highly dynamic, short-lived structures, although they could potentially achieve equilibrium under the external pressure exerted by the surrounding interstellar medium.

• Book : ()
• Pub. Date : 2025
• Page :
• Keyword :

AbstractPurposeThe response of various detectors in small fields from a variety of treatment machines has been studied and is summarized in IAEA TRS‐483. However, data for the novel RefleXion system remains largely unexplored. This study measured the output correction factors of multiple detectors in small fields for a clinical RefleXion unit.MethodsThe RefleXion machine consists of a binary multi‐leaf collimator and two pairs of Y‐jaws with clinical openings of 1 and 2 cm. The reference dosimetry is applied to the 10 × 2 cm2 clinical‐reference field, and the output factors of different fields are presented relative to the clinical‐reference field. The responses of detectors Edge, Razor, Micro‐Diamond, A14SL, CC01 and CC03 in rectangular fields from 1.25 × 1 to 20 × 2 cm2 on the RefleXion unit was studied at a depth of 10 cm in an IBA Blue‐Phantom‐Helix with a 85 cm source‐to‐surface distance. Gafchromic EBT4 film data in a solid‐water phantom were used as the reference to obtain correction factors for the detectors.ResultsIn the fields of the 2 cm jaw, all 6 detectors showed similar responses to the film reference within around 0.5% except at the first field width (1.25 cm), where the Edge and Micro‐Diamond exhibited over‐response and the CC13 showed the volume effect of ion chambers. In the fields of the 1 cm jaw, the Edge and Micro‐Diamond had responses close to the film and the same over‐response at small field‐widths. Significant deviations of the CC13 (∼4%) and the A14SL (∼2.5%) from the film were present over the whole range of field widths.ConclusionsThe small field output correction factors of 6 kinds of detectors were determined for a RefleXion system, conforming to the formalism in TRS‐483. All detectors except CC13 fulfil the 5% correction limit recommended by the TRS‐483 for output factor measurement.

• Book : ()
• Pub. Date : 2025
• Page :
• Keyword :

The mitochondrial proteome arises from dual genetic origin. Nuclear-encoded proteins need to be transported across or inserted into two distinguished membranes, and the TOM complex represents the main translocase in the outer mitochondrial membrane. Its composition and regulations have been extensively investigated within yeast cells. However, we have little knowledge of the TOM complex composition within human cells. Here, we have defined the TOM interactome in a comprehensive manner using biochemical approaches to isolate the TOM complex in combination with quantitative mass spectrometry analyses. Within these studies, we defined the pleiotropic nature of the human TOM complex, including new interactors, such as TRABD. Our studies provide a framework to understand the various biogenesis pathways that merge at the TOM complex within human cells.

• Book : ()
• Pub. Date : 2025
• Page :
• Keyword :

AbstractReactive oxygen species (ROS) of hosts are widely involved in intracellular signaling and against pathogens. Viruses manipulate ROS homeostasis of hosts as a strategy to evade ROS‐mediated negative effects of their infection, but the mechanisms remain unclear. The economically important aquaculture shrimp, Litopenaeus vannamei, is selected to investigate the molecular mechanism of how white spot syndrome virus (WSSV) regulates ROS dynamics and enhances viral replication. WSSV protein wsv220 binds to the repressor of shrimp nuclear factor erythroid 2‐related factor 2 (LvNrf2), called Kelch‐like ECH‐associated protein 1 (LvKeap1), disrupting LvNrf2/LvKeap1 complex and facilitating LvNrf2 nuclear translocation. This activation of LvNrf2 causes up‐regulation of antioxidant genes, including glucose‐6‐phosphate dehydrogenase (LvG6PDH), which increases nicotinamide adenine dinucleotide phosphate (NADPH) and glutathione (GSH) production, effectively eliminating excessive ROS. Moreover, WSSV exploits LvNrf2 to establish a positive feedback loop by up‐regulating viral immediate early gene wsv051, which further enhances wsv220 expression. Knockdown of LvNrf2 or LvG6PDH reduces WSSV replication and increases host ROS levels. Therefore, WSSV hijacks LvNrf2 pathway to maintain ROS homeostasis and establishes a positive feedback loop to facilitate WSSV replication. These findings reveal a novel molecular mechanism of viral manipulation of host ROS dynamics and suggest potential antiviral strategies targeting LvNrf2 pathway.

• Book : ()
• Pub. Date : 2025
• Page :
• Keyword :

Background: Cutaneous lymphomas represent the second most common extra-nodal non-Hodgkin lymphoma. Mycosis fungoides (MF) is the most common primary cutaneous lymphoma. In this study, we aim to estimate the prevalence of cutaneous lymphomas and to differentiate early MF from reactive cutaneous lymphoid hyperplasia (CLH) of the skin. Materials and Methods: We retrospectively studied all biopsy and resection specimens with a high index of clinical and histomorphological suspicion for cutaneous lymphoma for 10 years. We classified all the cases according to the World Health Organisation’s (WHO) 2022 classification of haematopoietic and lymphoid neoplasms. Statistical analyses were carried out using the software SPSS Statistics v23.0. Results: Out of 33 lymphoma cases, MF was the most common, followed by subcutaneous panniculitis-like T-cell lymphoma (SPLTCL). There were 13 males (39.3%) and 20 females (60.7%). Patches were the most common skin lesion, accounting for 78.7% of the cases, and presented as multiple lesions (81.8%), with the majority affecting the extremities (33.3%). Epidermotropism and basal tagging of lymphocytes, dermal fibrosis, and convoluted nuclear membranes were significant in early MF. Spongiosis correlated negatively with MF. T-cell receptor rearrangements were observed in 12 cases of MF. Conclusion: MF, the most common cutaneous lymphoma, is increasingly common in younger people. Histological variables such as epidermotropism, basal tagging of lymphocytes, convoluted nuclear membranes, and dermal fibrosis, along with clonal T-cell receptor rearrangements, aid in correct diagnosis and early therapeutic decision-making.

• Book : ()
• Pub. Date : 2025
• Page :
• Keyword :

• Book : ()
• Pub. Date : 2025
• Page : pp.100745-100745
• Keyword :

Abstract Primary activity standardization of the radionuclide iodine-123 using 4π(X,e)(LS)-γ coincidence counting is presented in this paper. The activity concentration of an aqueous solution was determined by the efficiency extrapolation technique using neutral density filters. The measurements were realized using a digitizer-based data acquisition system. The coincidence analysis of the collected list-mode data was performed offline using a custom-developed computer code. The results were used to participate in an international comparison under the auspices of the International Bureau of Weights and Measures (BIPM) via the International Reference System (SIR) as well as the Transfer Instrument of the International Reference System (SIRTI).

• Book : ()
• Pub. Date : 2025
• Page :
• Keyword :

AbstractSolar radiation modification (SRM) reflects sunlight back into space and could rapidly cool Earth, potentially reducing the harms of dangerous climate change. Current international law fails to directly and comprehensively address the transboundary, regional and global governance challenges that SRM presents. Various ideas for governance have emerged, drawing on multiple areas of existing law. This article offers a critical review of the existing space law literature and analyses its applicability to SRM governance. First, space law would ‘directly’ apply to space‐based SRM proposals such as a large satellite sunshade. Second, this paper argues that space law could ‘indirectly’ contribute to SRM governance, in that space activities and their governance can provide useful insights for future SRM governance. This article pushes for a deeper investigation of space law to inform future SRM governance.

• Book : ()
• Pub. Date : 2025
• Page :
• Keyword :

Variations in solar energy when it reaches the Earth impact the production of photovoltaic (PV) solar plants and, in turn, the dynamics of clean energy expansion. This incentivizes the objective of experimentally forecasting solar energy by parametric models, the results of which are then refined by machine learning methods (MLMs). To estimate solar energy, parametric models consider all atmospheric, climatic, geographic, and spatiotemporal factors that influence decreases in solar energy. In this study, data on ozone, evenly mixed gases, water vapor, aerosols, and solar radiation were gathered throughout the year in the mid-north area of Mozambique. The results show that the calculated solar energy was close to the theoretical solar energy under a clear sky. When paired with MLMs, the clear-sky index had a correlational order of 0.98, with most full-sun days having intermediate and clear-sky types. This suggests the potential of this area for PV use, with high correlation and regression coefficients in the range of 0.86 and 0.89 and a measurement error in the range of 0.25. We conclude that evenly mixed gases and the ozone layer have considerable influence on transmittance. However, the parametrically forecasted solar energy is close to the energy forecasted by the theoretical model. By adjusting the local characteristics, the model can be used in diverse contexts to increase PV plants’ electrical power output efficiency.

• Book : 10(3)
• Pub. Date : 2025
• Page : pp.37-37
• Keyword :