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| 2. |
- Kawauchi, K., et al.
(författare)
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Validation and atmospheric exploration of the sub-Neptune TOI-2136b around a nearby M3 dwarf
- 2022
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 666
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Tidskriftsartikel (refereegranskat)abstract
- Context. The NASA space telescope TESS is currently in the extended mission of its all-sky search for new transiting planets. Of the thousands of candidates that TESS is expected to deliver, transiting planets orbiting nearby M dwarfs are particularly interesting targets since they provide a great opportunity to characterize their atmospheres by transmission spectroscopy. Aims. We aim to validate and characterize the new sub-Neptune-sized planet candidate TOI-2136.01 orbiting a nearby M dwarf (d = 33.36 +/- 0.02 pc, T-eff = 3373 +/- 108 K) with an orbital period of 7.852 days. Methods. We use TESS data, ground-based multicolor photometry, and radial velocity measurements with the InfraRed Doppler (IRD) instrument on the Subaru Telescope to validate the planetary nature of TOI-2136.01, and estimate the stellar and planetary parameters. We also conduct high-resolution transmission spectroscopy to search for helium in its atmosphere. Results. We confirm that TOI-2136.01 (now named TOI-2136b) is a bona fide planet with a planetary radius of R-p = 2.20 +/- 0.07 R-circle plus and a mass of M-p = 4.7(-2.6)(+3.1) M-circle plus. We also search for helium 10830 angstrom absorption lines and place an upper limit on the equivalent width of <7.8 m angstrom and on the absorption signal of <1.44% with 95% confidence. Conclusions. TOI-2136b is a sub-Neptune transiting a nearby and bright star (J = 10.8 mag), and is a potentially hycean planet, which is a new class of habitable planets with large oceans under a H-2-rich atmosphere, making it an excellent target for atmospheric studies to understand the formation, evolution, and habitability of the small planets.
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| 3. |
- Sliz, E., et al.
(författare)
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Evidence of a causal effect of genetic tendency to gain muscle mass on uterine leiomyomata
- 2023
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Uterine leiomyomata (UL) are the most common tumours of the female genital tract and the primary cause of surgical removal of the uterus. Genetic factors contribute to UL susceptibility. To add understanding to the heritable genetic risk factors, we conduct a genome-wide association study (GWAS) of UL in up to 426,558 European women from FinnGen and a previous UL meta-GWAS. In addition to the 50 known UL loci, we identify 22 loci that have not been associated with UL in prior studies. UL-associated loci harbour genes enriched for development, growth, and cellular senescence. Of particular interest are the smooth muscle cell differentiation and proliferation-regulating genes functioning on the myocardin-cyclin dependent kinase inhibitor 1A pathway. Our results further suggest that genetic predisposition to increased fat-free mass may be causally related to higher UL risk, underscoring the involvement of altered muscle tissue biology in UL pathophysiology. Overall, our findings add to the understanding of the genetic pathways underlying UL, which may aid in developing novel therapeutics.
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| 5. |
- Chen, CZ, et al.
(författare)
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Identification of Tumor Mutation Burden, Microsatellite Instability, and Somatic Copy Number Alteration Derived Nine Gene Signatures to Predict Clinical Outcomes in STAD
- 2022
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Ingår i: Frontiers in molecular biosciences. - : Frontiers Media SA. - 2296-889X. ; 9, s. 793403-
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Tidskriftsartikel (refereegranskat)abstract
- Genomic features, including tumor mutation burden (TMB), microsatellite instability (MSI), and somatic copy number alteration (SCNA), had been demonstrated to be involved with the tumor microenvironment (TME) and outcome of gastric cancer (GC). We obtained profiles of TMB, MSI, and SCNA by processing 405 GC data from The Cancer Genome Atlas (TCGA) and then conducted a comprehensive analysis though “iClusterPlus.” A total of two subgroups were generated, with distinguished prognosis, somatic mutation burden, copy number changes, and immune landscape. We revealed that Cluster1 was marked by a better prognosis, accompanied by higher TMB, MSIsensor score, TMEscore, and lower SCNA burden. Based on these clusters, we screened 196 differentially expressed genes (DEGs), which were subsequently projected into univariate Cox survival analysis. We constructed a 9-gene immune risk score (IRS) model using LASSO-penalized logistic regression. Moreover, the prognostic prediction of IRS was verified by receiver operating characteristic (ROC) curve analysis and nomogram plot. Another independent Gene Expression Omnibus (GEO) contained specimens from 109 GC patients was designed as an external validation. Our works suggested that the 9‐gene‐signature prediction model, which was derived from TMB, MSI, and SCNA, was a promising predictive tool for clinical outcomes in GC patients. This novel methodology may help clinicians uncover the underlying mechanisms and guide future treatment strategies.
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| 6. |
- Du, SH, et al.
(författare)
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Co-Inhibition of the Immunoproteasome Subunits LMP2 and LMP7 Ameliorates Immune Thrombocytopenia
- 2021
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Ingår i: Frontiers in immunology. - : Frontiers Media SA. - 1664-3224. ; 11, s. 603278-
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Tidskriftsartikel (refereegranskat)abstract
- The immunoproteasome, a special isoform of the 20S proteasome, is expressed when the cells receive an inflammatory signal. Immunoproteasome inhibition proved efficacy in the treatment of autoimmune diseases. However, the role of the immunoproteasome in the pathogenesis of immune thrombocytopenia (ITP) remains unknown. We found that the expression of the immunoproteasome catalytic subunit, large multifunctional protease 2 (LMP2), was significantly upregulated in peripheral blood mononuclear cells of active ITP patients compared to those of healthy controls. No significant differences in LMP7 expression were observed between patients and controls. ML604440, an specific LMP2 inhibitor, had no significant impact on the platelet count of ITP mice, while ONX-0914 (an inhibitor of both LMP2 and LMP7) increased the number of platelets. In vitro assays revealed that ONX-0914 decreased the expression of FcγRI in ITP mice and decreased that of FcγRIII in ITP patients, inhibited the activation of CD4+ T cells, and affected the differentiation of Th1 cells in patients with ITP. These results suggest that the inhibition of immunoproteasome is a potential therapeutic approach for ITP patients.
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| 8. |
- Teng, Dan, et al.
(författare)
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Mechanistic Studies on the Stereoselectivity of FFAR1 Modulators
- 2022
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Ingår i: Journal of Chemical Information and Modeling. - : American Chemical Society (ACS). - 1549-9596 .- 1549-960X. ; 62:15, s. 3664-3675
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Tidskriftsartikel (refereegranskat)abstract
- Free fatty acid receptor 1 (FFAR1) is a potential therapeutic target for the treatment of type 2 diabetes (T2D). It has been validated that agonists targeting FFAR1 can achieve the initial therapeutic endpoints of T2D, and the epimer agonists (R,S) AM-8596 can activate FFAR1 differently, with one acting as a partial agonist and the other as a full agonist. Up to now, the origin of the stereoselectivity of FFAR1 agonists remains elusive. In this work, we used molecular simulation methods to elucidate the mechanism of the stereoselectivity of the FFAR1 agonists (R)-AM-8596 and (S)-AM-8596. We found that the full agonist (R)-AM-8596 disrupts the residue interaction network around the receptor binding pocket and promotes the opening of the binding site for the G-protein, thereby resulting in the full activation of FFAR1. In contrast, the partial agonist (S)-AM-8596 forms stable electrostatic interactions with FFAR1, which stabilizes the residue network and hinders the conformational transition of the receptor. Our work thus clarifies the selectivity and underlying molecular activation mechanism of FFAR1 agonists.
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| 10. |
- Arheimer, Berit, et al.
(författare)
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The IAHS Science for Solutions decade, with Hydrology Engaging Local People IN a Global world (HELPING)
- 2024
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Ingår i: Hydrological Sciences Journal. - 0262-6667 .- 2150-3435.
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Tidskriftsartikel (refereegranskat)abstract
- The new scientific decade (2023-2032) of the International Association of Hydrological Sciences (IAHS) aims at searching for sustainable solutions to undesired water conditions - may it be too little, too much or too polluted. Many of the current issues originate from global change, while solutions to problems must embrace local understanding and context. The decade will explore the current water crises by searching for actionable knowledge within three themes: global and local interactions, sustainable solutions and innovative cross-cutting methods. We capitalise on previous IAHS Scientific Decades shaping a trilogy; from Hydrological Predictions (PUB) to Change and Interdisciplinarity (Panta Rhei) to Solutions (HELPING). The vision is to solve fundamental water-related environmental and societal problems by engaging with other disciplines and local stakeholders. The decade endorses mutual learning and co-creation to progress towards UN sustainable development goals. Hence, HELPING is a vehicle for putting science in action, driven by scientists working on local hydrology in coordination with local, regional, and global processes.
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