34 research outputs found
Robustness of Baryon Acoustic Oscillations Measurements with Photometric Redshift Uncertainties
We investigate the robustness of baryon acoustic oscillations (BAO)
measurements with a photometric galaxy sample using mock galaxy catalogs with
various sizes of photometric redshift (photo-) uncertainties. We first
investigate the robustness of BAO measurements, assuming we have a perfect
knowledge of photo- uncertainties. We find that the BAO shift parameter
can be constrained in an unbiased manner for various sizes of
photometric redshift uncertainties at , , and as long as
the number density of galaxies is high. A sparse galaxy sample causes
additional noise in the covariance matrix calculation and it can bias the
constraint on . Next, we investigate the scenario where incorrect
photometric redshift uncertainties are assumed in the fitting model and find
that underestimating the photo- uncertainty leads to a degradation in the
constraining power on . In addition, we investigate BAO measurements
with a cross-correlation signal between a spec- sample and a photo-
sample. We find BAO constraints are unbiased and slightly tighter than the
auto-correlation signal of a photo- sample. We also quantify the
constraining power on assuming the LSST-like covariance and
find that the 95\% confidence level is -
corresponding to the photo- uncertainties of 1\% to 3\% respectively.
Finally, we examine whether the skewness in the photometric redshift can bias
the constraint on and confirm that the constraint on is
unbiased even if we use a fitting model assuming a Gaussian photo-
uncertainty.Comment: 10 pages, 11 figures, 3 table
Pharmacological HIF-1 activation upregulates extracellular vesicle production synergistically with adiponectin through transcriptional induction and protein stabilization of T-cadherin
Fujii K., Fujishima Y., Kita S., et al. Pharmacological HIF-1 activation upregulates extracellular vesicle production synergistically with adiponectin through transcriptional induction and protein stabilization of T-cadherin. Scientific Reports 14, 3620 (2024); https://doi.org/10.1038/s41598-024-51935-6.Pharmacological activation of hypoxia-inducible factor 1 (HIF-1), a hypoxia-responsive transcription factor, has attracted increasing attention due to its efficacy not only in renal anemia but also in various disease models. Our study demonstrated that a HIF-1 activator enhanced extracellular vesicle (EV) production from cultured endothelial cells synergistically with adiponectin, an adipocyte-derived factor, through both transcriptional induction and posttranscriptional stabilization of an adiponectin binding partner, T-cadherin. Increased EV levels were observed in wild-type mice but not in T-cadherin null mice after consecutive administration of roxadustat. Adiponectin- and T-cadherin-dependent increased EV production may be involved in the pleiotropic effects of HIF-1 activators
Soluble T-cadherin secretion from endothelial cells is regulated via insulin/PI3K/Akt signalling
Okita T., Kita S., Fukuda S., et al. Soluble T-cadherin secretion from endothelial cells is regulated via insulin/PI3K/Akt signalling. Biochemical and Biophysical Research Communications 732, 150403 (2024); https://doi.org/10.1016/j.bbrc.2024.150403.Aim and objective: Our recent report showed that soluble T-cadherin promotes pancreatic beta-cell proliferation. However, how and where the secretion of soluble T-cadherin is regulated remain unclear. Methods and results: Soluble T-cadherin levels significantly increased in leptin receptor-deficient db/db mice with hypoinsulinaemia or in wild-type mice treated with insulin receptor blockade by S961. Similar results were observed in human subjects; Diabetic ketoacidosis patients at the time of hospitalization had increased plasma soluble T-cadherin levels, which decreased after insulin infusion therapy. Patients with recurrent ovarian cancer who were administered a phosphatidylinositol-3 kinase (PI3K)-alpha inhibitor (a new anticancer drug) had increased plasma soluble T-cadherin and plasma C-peptide levels. Endothelial cell-specific T-cadherin knockout mice, but not skeletal muscle- or cardiac muscle-specific T-cadherin knockout mice, showed a 26 % reduction in plasma soluble T-cadherin levels and a significant increase in blood glucose levels in streptozocin-induced diabetes. The secretion of soluble T-cadherin from human endothelial cells was approximately 20 % decreased by insulin and this decrease was canceled by blockade of insulin receptor/Akt signalling, not Erk signalling. Conclusion: We conclude that insulin regulates soluble T-cadherin levels and soluble T-cadherin secretion from endothelial cells is positively regulated by insulin/insulin receptor/Akt signalling
Influence of substituent modifications on the binding of 2-amino-1,8-naphthyridines to cytosine opposite an AP site in DNA duplexes: thermodynamic characterization
Here, we report on a significant effect of substitutions on the binding affinity of a series of 2-amino-1,8-naphthyridines, i.e., 2-amino-1,8-naphthyridine (AND), 2-amino-7-methyl-1,8-naphthyridine (AMND), 2-amino-5,7-dimethyl-1,8-naphthyridine (ADMND) and 2-amino-5,6,7-trimethyl-1,8-naphthyridine (ATMND), all of which can bind to cytosine opposite an AP site in DNA duplexes. Fluorescence titration experiments show that the binding affinity for cytosine is effectively enhanced by the introduction of methyl groups to the naphthyridine ring, and the 1:1 binding constant (106 M−1) follows in the order of AND (0.30) < AMND (2.7) < ADMND (6.1) < ATMND (19) in solutions containing 110 mM Na+ (pH 7.0, at 20°C). The thermodynamic parameters obtained by isothermal titration calorimetry experiments indicate that the introduction of methyl groups effectively reduces the loss of binding entropy, which is indeed responsible for the increase in the binding affinity. The heat capacity change (ΔCp), as determined from temperature dependence of the binding enthalpy, is found to be significantly different between AND (−161 cal/mol K) and ATMND (−217 cal/mol K). The hydrophobic contribution appears to be a key force to explain the observed effect of substitutions on the binding affinity when the observed binding free energy (ΔGobs) is dissected into its component terms
Genetic polymorphism of pleiotrophin is associated with pain experience in Japanese adults Case-control study
Genetic factors play a role in individual differences in pain experience. Here, we performed a genome-wide association study (GWAS) to identify novel loci regulating pain processing. We conducted a 2-stage GWAS and the candidate single-nucleotide polymorphisms (SNPs) association study on pain experience using an exploratory cohort of patients with cancer pain. The confirmatory cohort comprised of participants from the general population with and without habitual use of analgesic medication. In the exploratory cohort, we evaluated pain intensity using a numerical rating scale, recorded daily opioid dosages, and calculated pain reduction rate. In the confirmatory cohort, pain experience was defined as habitual nonsteroidal anti-inflammatory drug usage. Using linear regression models, we identified candidate SNP in the exploratory samples, and tested the association between phenotype and experienced pain in the confirmatory samples. We found 1 novel SNP (rs11764598)—located on the gene encoding for pleiotrophin on chromosome 7—that passed the genome-wide suggestive significance at 20% false discovery rate (FDR) correction in the exploratory samples of patients with cancer pain (P = 1.31 × 10-7, FDR = 0.101). We confirmed its significant association with daily analgesic usage in the confirmatory cohort (P = .028), although the minor allele affected pain experience in an opposite manner. We identified a novel genetic variant associated with pain experience. Further studies are required to validate the role of pleiotrophin in pain processing
The Japanese space gravitational wave antenna; DECIGO
DECi-hertz Interferometer Gravitational wave Observatory (DECIGO) is the future
Japanese space gravitational wave antenna. DECIGO is expected to open a new window of
observation for gravitational wave astronomy especially between 0.1 Hz and 10 Hz, revealing
various mysteries of the universe such as dark energy, formation mechanism of supermassive
black holes, and inflation of the universe. The pre-conceptual design of DECIGO consists of
three drag-free spacecraft, whose relative displacements are measured by a differential Fabry–
Perot Michelson interferometer. We plan to launch two missions, DECIGO pathfinder and pre-
DECIGO first and finally DECIGO in 2024
DECIGO pathfinder
DECIGO pathfinder (DPF) is a milestone satellite mission for DECIGO (DECi-hertz Interferometer Gravitational wave Observatory) which is a future space gravitational wave antenna. DECIGO is expected to provide us fruitful insights into the universe, in particular about dark energy, a formation mechanism of supermassive black holes, and the inflation of the universe. Since DECIGO will be an extremely large mission which will formed by three drag-free spacecraft with 1000m separation, it is significant to gain the technical feasibility of DECIGO before its planned launch in 2024. Thus, we are planning to launch two milestone missions: DPF and pre-DECIGO. The conceptual design and current status of the first milestone mission, DPF, are reviewed in this article
Time-resolved serial femtosecond crystallography reveals early structural changes in channelrhodopsin
X線自由電子レーザーを用いて、光照射によるチャネルロドプシンの構造変化の過程を捉えることに成功. 京都大学プレスリリース. 2021-03-26.Channelrhodopsins (ChRs) are microbial light-gated ion channels utilized in optogenetics to control neural activity with light . Light absorption causes retinal chromophore isomerization and subsequent protein conformational changes visualized as optically distinguished intermediates, coupled with channel opening and closing. However, the detailed molecular events underlying channel gating remain unknown. We performed time-resolved serial femtosecond crystallographic analyses of ChR by using an X-ray free electron laser, which revealed conformational changes following photoactivation. The isomerized retinal adopts a twisted conformation and shifts toward the putative internal proton donor residues, consequently inducing an outward shift of TM3, as well as a local deformation in TM7. These early conformational changes in the pore-forming helices should be the triggers that lead to opening of the ion conducting pore