The Uchuu-UniverseMachine dataset: Galaxies in and around Clusters

We present the public data release of the Uchuu-UM galaxy catalogues by applying the UniverseMachine algorithm to assign galaxies to the dark matter halos in the Uchuu $N$-body cosmological simulation. It includes a variety of baryonic properties for all galaxies down to $\sim 5\times10^8 M_{\odot}$ with halos in a mass range of $10^{10}<M_{\rm halo}/M_{\odot}<5\times10^{15}$ up to redshift $z=10$. Uchuu-UM includes more than $10^{4}$ cluster-size halos in a volume of $8(h^{-1} {\rm Gpc})^3$, reproducing observed stellar mass functions across the redshift range of $z=0-7$, galaxy quenched fractions, and clustering statistics at low redshifts. Compared to the previous largest UM catalogue, the Uchuu-UM catalogue includes significantly more massive galaxies hosted by large-mass dark matter halos. Overall, the number density profile of galaxies in dark matter halos follows the dark matter profile, with the profile becoming steeper around the splashback radius and flattening at larger radii. The number density profile of galaxies tends to be steeper for larger stellar masses and depends on the color of galaxies, with red galaxies having steeper slopes at all radii than blue galaxies. The quenched fraction exhibits a strong dependence on the stellar mass and increases toward the inner regions of clusters. The publicly available Uchuu-UM galaxy catalogue presented here can serve to model ongoing and upcoming large galaxy surveys.Comment: 10 pages, 11 figures, accepted by MNRAS, public data available at http://www.skiesanduniverses.org

Formulation and constraints on decaying dark matter with finite mass daughter particles

Decaying dark matter cosmological models have been proposed to remedy the overproduction problem at small scales in the standard cold dark matter paradigm. We consider a decaying dark matter model in which one CDM mother particle decays into two daughter particles, with arbitrary masses. A complete set of Boltzmann equations of dark matter particles is derived which is necessary to calculate the evolutions of their energy densities and their density perturbations. By comparing the expansion history of the universe in this model and the free-streaming scale of daughter particles with astronomical observational data, we give constraints on the lifetime of the mother particle, $\Gamma^{-1}$, and the mass ratio between the daughter and the mother particles $m_{\rm D}/m_{\rm M}$. From the distance to the last scattering surface of the cosmic microwave background, we obtain $\Gamma^{-1}>$ 30 Gyr in the massless limit of daughter particles and, on the other hand, we obtain $m_{\rm D} >$ 0.97$m_{\rm M}$ in the limit $\Gamma^{-1}\to 0$. The free-streaming constraint tightens the bound on the mass ratio as $(\Gamma^{-1}/10^{-2}{\rm Gyr}) \lesssim ((1-m_{\rm D1}/m_{\rm M})/10^{-2})^{-3/2}$ for $\Gamma^{-1} < H^{-1}(z=3)$.Comment: 20 pages, 7 figure

Amplified EPOR/JAK2 Genes Define a Unique Subtype of Acute Erythroid Leukemia

ゲノム解析から急性赤白血病の変異プロファイルと治療標的を解明 --特定の遺伝子変異群の組み合わせと、特徴となる遺伝子の増幅が鍵--. 京都大学プレスリリース. 2022-08-05.Acute erythroid leukemia (AEL) is a unique subtype of acute myeloid leukemia characterized by prominent erythroid proliferation whose molecular basis is poorly understood. To elucidate the underlying mechanism of erythroid proliferation, we analyzed 121 AEL using whole-genome/exome and/or targeted-capture sequencing, together with transcriptome analysis of 21 AEL samples. Combining publicly available sequencing data, we found a high frequency of gains/amplifications involving EPOR/JAK2 in TP53-mutated cases, particularly those having >80% erythroblasts designated as pure erythroid leukemia (10/13). These cases were frequently accompanied by gains/amplifications of ERG/ETS2 and associated with a very poor prognosis, even compared with other TP53-mutated AEL. In addition to activation of the STAT5 pathway, a common feature across all AEL cases, these AEL cases exhibited enhanced cell proliferation and heme metabolism and often showed high sensitivity to ruxolitinib in vitro and in xenograft models, highlighting a potential role of JAK2 inhibition in therapeutics of AEL

Effect of Simultaneous Dual-Task Training on Regional Cerebral Blood Flow in Older Adults with Amnestic Mild Cognitive Impairment

東京都立大学Tokyo Metropolitan University博士（理学療法学）doctoral thesi

Generation and Characterization of Conditional Heparin-Binding EGF-Like Growth Factor Knockout Mice

Recently, neurotrophic factors and cytokines have been shown to be associated in psychiatric disorders, such as schizophrenia, bipolar disorder, and depression. Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is a member of the EGF family, serves as a neurotrophic molecular and plays a significant role in the brain. We generated mice in which HB-EGF activity is disrupted specifically in the ventral forebrain. These knockout mice showed (a) behavioral abnormalities similar to those described in psychiatric disorders, which were ameliorated by typical or atypical antipsychotics, (b) altered dopamine and serotonin levels in the brain, (c) decreases in spine density in neurons of the prefrontal cortex, (d) reductions in the protein levels of the NR1 subunit of the N-methyl-D-aspartate (NMDA) receptor and post-synaptic protein-95 (PSD-95), (e) decreases in the EGF receptor, and in the calcium/calmodulin-dependent protein kinase II (CaMK II) signal cascade. These results suggest the alterations affecting HB-EGF signaling could comprise a contributing factor in psychiatric disorder

Post-intervention Status in Patients With Refractory Myasthenia Gravis Treated With Eculizumab During REGAIN and Its Open-Label Extension

OBJECTIVE: To evaluate whether eculizumab helps patients with anti-acetylcholine receptor-positive (AChR+) refractory generalized myasthenia gravis (gMG) achieve the Myasthenia Gravis Foundation of America (MGFA) post-intervention status of minimal manifestations (MM), we assessed patients' status throughout REGAIN (Safety and Efficacy of Eculizumab in AChR+ Refractory Generalized Myasthenia Gravis) and its open-label extension. METHODS: Patients who completed the REGAIN randomized controlled trial and continued into the open-label extension were included in this tertiary endpoint analysis. Patients were assessed for the MGFA post-intervention status of improved, unchanged, worse, MM, and pharmacologic remission at defined time points during REGAIN and through week 130 of the open-label study. RESULTS: A total of 117 patients completed REGAIN and continued into the open-label study (eculizumab/eculizumab: 56; placebo/eculizumab: 61). At week 26 of REGAIN, more eculizumab-treated patients than placebo-treated patients achieved a status of improved (60.7% vs 41.7%) or MM (25.0% vs 13.3%; common OR: 2.3; 95% CI: 1.1-4.5). After 130 weeks of eculizumab treatment, 88.0% of patients achieved improved status and 57.3% of patients achieved MM status. The safety profile of eculizumab was consistent with its known profile and no new safety signals were detected. CONCLUSION: Eculizumab led to rapid and sustained achievement of MM in patients with AChR+ refractory gMG. These findings support the use of eculizumab in this previously difficult-to-treat patient population. CLINICALTRIALSGOV IDENTIFIER: REGAIN, NCT01997229; REGAIN open-label extension, NCT02301624. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that, after 26 weeks of eculizumab treatment, 25.0% of adults with AChR+ refractory gMG achieved MM, compared with 13.3% who received placebo

Minimal Symptom Expression' in Patients With Acetylcholine Receptor Antibody-Positive Refractory Generalized Myasthenia Gravis Treated With Eculizumab

The efficacy and tolerability of eculizumab were assessed in REGAIN, a 26-week, phase 3, randomized, double-blind, placebo-controlled study in anti-acetylcholine receptor antibody-positive (AChR+) refractory generalized myasthenia gravis (gMG), and its open-label extension

Novel Pathway of Salicylate Degradation by Streptomyces sp. Strain WA46

A novel salicylate-degrading Streptomyces sp., strain WA46, was identified by UV fluorescence on solid minimal medium containing salicylate; trace amounts of gentisate were detected by high-pressure liquid chromatography when strain WA46 was grown with salicylate. PCR amplification of WA46 DNA with degenerate primers for gentisate 1,2-dioxygenase (GDO) genes produced an amplicon of the expected size. Sequential PCR with nested GDO primers was then used to identify a salicylate degradation gene cluster in a plasmid library of WA46 chromosomal DNA. The nucleotide sequence of a 13.5-kb insert in recombinant plasmid pWD1 (which was sufficient for the complete degradation of salicylate) showed that nine putative open reading frames (ORFs) (sdgABCDEFGHR) were involved. Plasmid pWD1 derivatives disrupted in each putative gene were transformed into Streptomyces lividans TK64. Disruption of either sdgA or sdgC blocked salicylate degradation; constructs lacking sdgD accumulated gentisate. Cell extracts from Escherichia coli DH5α transformants harboring pUC19 that expressed each of the sdg ORFs showed that conversions of salicylate to salicylyl-coenzyme A (CoA) and salicylyl-CoA to gentisyl-CoA required SdgA and SdgC, respectively. SdgA required CoA and ATP as cofactors, while NADH was required for SdgC activity; SdgC was identified as salicylyl-CoA 5-hydroxylase. Gentisyl-CoA underwent spontaneous cleavage to gentisate and CoA. SdgA behaved as a salicylyl-CoA ligase despite showing amino acid sequence similarity to an AMP-ligase. SdgD was identified as a GDO. These results suggest that Streptomyces sp. strain WA46 degrades salicylate by a novel pathway via a CoA derivative. Two-dimensional polyacrylamide gel electrophoresis and reverse transcriptase-PCR studies indicated that salicylate induced expression of the sdg cluster