| 1. |
- Yoshimatsu, Yasuhiro, et al.
(författare)
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Bone morphogenetic protein-9 inhibits lymphatic vessel formation via activin receptor-like kinase 1 during development and cancer progression
- 2013
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Ingår i: Proceedings of the National Academy of Sciences. - : Proceedings of the National Academy of Sciences. - 1091-6490 .- 0027-8424. ; 110:47, s. 18940-18945
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Tidskriftsartikel (refereegranskat)abstract
- Lymphatic vessels (LVs) play critical roles in the maintenance of fluid homeostasis and in pathological conditions, including cancer metastasis. Although mutations in ALK1, a member of the transforming growth factor (TGF)-beta/bone morphogenetic protein (BMP) receptor family, have been linked to hereditary hemorrhagic telangiectasia, a human vascular disease, the roles of activin receptor-like kinase 1(ALK-1) signals in LV formation largely remain to be elucidated. We show that ALK-1 signals inhibit LV formation, and LVs were enlarged in multiple organs in Alk1-depleted mice. These inhibitory effects of ALK-1 signaling were mediated by BMP-9, which decreased the number of cultured lymphatic endothelial cells. Bmp9-deficient mouse embryos consistently exhibited enlarged dermal LVs. BMP-9 also inhibited LV formation during inflammation and tumorigenesis. BMP-9 downregulated the expression of the transcription factor prospero-related homeobox 1, which is necessary to maintain lymphatic endothelial cell identity. Furthermore, silencing prospero-related homeobox 1 expression inhibited lymphatic endothelial cell proliferation. Our findings reveal a unique molecular basis for the physiological and pathological roles of BMP-9/ALK-1 signals in LV formation.
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| 2. |
- Ishiguro, Masateru, et al.
(författare)
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Polarimetric properties of the near-Sun asteroid (155140) 2005 UD in comparison with other asteroids and meteoritic samples
- 2022
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press. - 0035-8711 .- 1365-2966. ; 509:3, s. 4128-4142
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Tidskriftsartikel (refereegranskat)abstract
- The investigation of asteroids near the Sun is important for understanding the final evolutionary stage of primitive Solar system objects. A near-Sun asteroid (NSA), (155140) 2005 UD, has orbital elements similar to those of (3200) Phaethon (the target asteroid for the JAXA’s DESTINY+ mission). We conducted photometric and polarimetric observations of 2005 UD and found that this asteroid exhibits a polarization phase curve similar to that of Phaethon over a wide range of observed solar phase angles (α = 20–105°) but different from those of (101955) Bennu and (162173) Ryugu (asteroids composed of hydrated carbonaceous materials). At a low phase angle (α ≲ 30°), the polarimetric properties of these NSAs (2005 UD and Phaethon) are consistent with anhydrous carbonaceous chondrites, while the properties of Bennu are consistent with hydrous carbonaceous chondrites. We derived the geometric albedo, pV ∼ 0.1 (in the range of 0.088–0.109); mean V-band absolute magnitude, HV = 17.54 ± 0.02; synodic rotational period, Trot=5.2388±0.0022h (the two-peaked solution is assumed); and effective mean diameter, Deff=1.32±0.06km. At large phase angles (α ≳ 80°), the polarization phase curve are likely explained by the dominance of large grains and the paucity of small micron-sized grains. We conclude that the polarimetric similarity of these NSAs can be attributed to the intense solar heating of carbonaceous materials around their perihelia, where large anhydrous particles with small porosity could be produced by sintering.
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| 3. |
- Nakajima, Yoko, et al.
(författare)
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Clinical, biochemical and molecular analysis of 13 Japanese patients with beta-ureidopropionase deficiency demonstrates high prevalence of the c.977G > A (p.R326Q) mutation
- 2014
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Ingår i: Journal of Inherited Metabolic Disease. - : Wiley. - 0141-8955 .- 1573-2665. ; 37:5, s. 801-812
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Tidskriftsartikel (refereegranskat)abstract
- beta-ureidopropionase (beta UP) deficiency is an autosomal recessive disease characterized by N-carbamyl-beta-amino aciduria. To date, only 16 genetically confirmed patients with beta UP deficiency have been reported. Here, we report on the clinical, biochemical and molecular findings of 13 Japanese beta UP deficient patients. In this group of patients, three novel missense mutations (p.G31S, p.E271K, and p.I286T) and a recently described mutation (p.R326Q) were identified. The p.R326Q mutation was detected in all 13 patients with eight patients being homozygous for this mutation. Screening for the p.R326Q mutation in 110 Japanese individuals showed an allele frequency of 0.9 %. Transient expression of mutant beta UP enzymes in HEK293 cells showed that the p.E271K and p.R326Q mutations cause profound decreases in activity (a parts per thousand currency sign 1.3 %). Conversely, beta UP enzymes containing the p.G31S and p.I286T mutations possess residual activities of 50 and 70 %, respectively, suggesting we cannot exclude the presence of additional mutations in the non-coding region of the UPB1 gene. Analysis of a human beta UP homology model revealed that the effects of the mutations (p.G31S, p.E271K, and p.R326Q) on enzyme activity are most likely linked to improper oligomer assembly. Highly variable phenotypes ranging from neurological involvement (including convulsions and autism) to asymptomatic, were observed in diagnosed patients. High prevalence of p.R326Q in the normal Japanese population indicates that beta UP deficiency is not as rare as generally considered and screening for beta UP deficiency should be included in diagnosis of patients with unexplained neurological abnormalities.
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