65 research outputs found
Selective activation of STAT5 unveils its role in stem cell self-renewal in normal and leukemic hematopoiesis
Although the concept of a leukemic stem cell system has recently been well accepted, its nature and the underlying molecular mechanisms remain obscure. Constitutive activation of signal transducers and activators of transcription 3 (STAT3) and STAT5 is frequently detected in various hematopoietic tumors. To evaluate their role in normal and leukemic stem cells, we took advantage of constitutively active STAT mutants to activate STAT signaling selectively in hematopoietic stem cells (HSCs). Activation of STAT5 in CD34–c-Kit+Sca-1+ lineage marker– (CD34–KSL) HSCs led to a drastic expansion of multipotential progenitors and promoted HSC self-renewal ex vivo. In sharp contrast, STAT3 was demonstrated to be dispensable for the HSC maintenance in vivo, and its activation facilitated lineage commitment of HSCs in vitro. In a mouse model of myeloproliferative disease (MPD), sustained STAT5 activation in CD34–KSL HSCs but not in CD34+KSL multipotential progenitors induced fatal MPD, indicating that the capacity of STAT5 to promote self-renewal of hematopoietic stem cells is crucial to MPD development. Our findings collectively establish a specific role for STAT5 in self-renewal of normal as well as leukemic stem cells
22449 Skeleton curve and increase of strength due to strain hardening of buckling restrained brace using steel mortar planks
研究報告書ページ(143)-(144
Production of doubly strange hypernuclei via {\Xi}- doorways in the 16O(K-, K+) reaction at 1.8 GeV/c
We examine theoretically production of doubly strange hypernuclei, 16 {\Xi}-C
and 16 {\Lambda}{\Lambda}C, in doublecharge exchange 16O(K-, K+) reactions
using a distorted-wave impulse approximation. The inclusive K+ spectrum at the
incident momentum pK- = 1.8 GeV/c and scattering angle {\theta}lab = 0^{\circ}
is estimated in a one-step mechanism, K-p \to K+{\Xi}- via {\Xi}- doorways
caused by a {\Xi}-p-{\Lambda}{\Lambda} coupling. The calculated spectrum in the
{\Xi}- bound region indicates that the integrated cross sections are on the
order of 7-12 nb/sr for significant 1- excited states with 14C(0+, 2+) \otimes
s{\Lambda}p{\Lambda} configurations in 16 {\Lambda}{\Lambda}C via the doorway
states of the spin-stretched 15N(1/2-, 3/2-) \otimes s{\Xi}- in 16 {\Xi}-C due
to a high momentum transfer q{\Xi}- \approx 400 MeV/c. The {\Xi}- admixture
probabilities of these states are on the order of 5-9%. However, populations of
the 0+ ground state with 14C(0+) \otimes s2{\Lambda} and the 2+ excited state
with 14C(2+) \otimes s2 {\Lambda} are very small. The sensitivity of the
spectrum on the {\Xi}N-{\Lambda}{\Lambda} coupling strength enables us to
extract the nature of {\Xi}N-{\Lambda}{\Lambda} dynamics in nuclei, and the
nuclear (K-, K+) reaction can extend our knowledge of the S = -2 world.Comment: 10 pages, 3 figure
Interlaboratory studies on in vitro test methods for estimating in vivo resorption of calcium phosphate ceramics
TGF-Β-FOXO signalling maintains leukaemia-initiating cells in chronic myeloid leukaemia
金沢大学がん研究所がん幹細胞研究センターChronic myeloid leukaemia (CML) is caused by a defined genetic abnormality that generates BCR-ABL, a constitutively active tyrosine kinase. It is widely believed that BCR-ABL activates Akt signalling that suppresses the forkhead O transcription factors (FOXO), supporting the proliferation or inhibiting the apoptosis of CML cells. Although the use of the tyrosine kinase inhibitor imatinib is a breakthrough for CML therapy, imatinib does not deplete the leukaemia-initiating cells (LICs) that drive the recurrence of CML. Here, using a syngeneic transplantation system and a CML-like myeloproliferative disease mouse model, we show that Foxo3a has an essential role in the maintenance of CML LICs. We find that cells with nuclear localization of Foxo3a and decreased Akt phosphorylation are enriched in the LIC population. Serial transplantation of LICs generated from Foxo3a+/+ and Foxo3a-/- mice shows that the ability of LICs to cause disease is significantly decreased by Foxo3a deficiency. Furthermore, we find that TGF-Β is a critical regulator of Akt activation in LICs and controls Foxo3a localization. A combination of TGF-Β inhibition, Foxo3a deficiency and imatinib treatment led to efficient depletion of CML in vivo. Furthermore, the treatment of human CML LICs with a TGF-Β inhibitor impaired their colony-forming ability in vitro. Our results demonstrate a critical role for the TGF-Β-FOXO pathway in the maintenance of LICs, and strengthen our understanding of the mechanisms that specifically maintain CML LICs in vivo. © 2010 Macmillan Publishers Limited. All rights reserved
Erratum: Synthesis of glycerolipids containing simple linear acyl chains or aromatic rings and evaluation of their Mincle signaling activity (Chem. Commun. (2019) 55 (711–714) DOI: 10.1039/C8CC07322H)
金沢大学医薬保健研究域薬学系The authors regret that the structures of brartemicin and compounds 6a and b presented in Fig. 2 of the article were incorrect. The correct structures are depicted below. In addition, explanations of the R’ groups have been added below each compound. (Figure Presented). This journal is © The Royal Society of Chemistr
Pillar[6]arene acts as a biosensor for quantitative detection of a vitamin metabolite in crude biological samples
ビタミン代謝物を迅速定量できる超分子バイオセンサーを開発. 京都大学プレスリリース. 2020-12-09.Metabolic syndrome is associated with obesity, hypertension, and dyslipidemia, and increased cardiovascular risk. Therefore, quick and accurate measurements of specific metabolites are critical for diagnosis; however, detection methods are limited. Here we describe the synthesis of pillar[n]arenes to target 1-methylnicotinamide (1-MNA), which is one metabolite of vitamin B3 (nicotinamide) produced by the cancer-associated nicotinamide N-methyltransferase (NNMT). We found that water-soluble pillar[5]arene (P5A) forms host–guest complexes with both 1-MNA and nicotinamide, and water-soluble pillar[6]arene (P6A) selectively binds to 1-MNA at the micromolar level. P6A can be used as a “turn-off sensor” by photoinduced electron transfer (detection limit is 4.38 × 10−6 M). In our cell-free reaction, P6A is used to quantitatively monitor the activity of NNMT. Moreover, studies using NNMT-deficient mice reveal that P6A exclusively binds to 1-MNA in crude urinary samples. Our findings demonstrate that P6A can be used as a biosensor to quantify 1-MNA in crude biological samples
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