Can axion clumps be formed in a pre-inflationary scenario?

The QCD axion and an axion-like particle (ALP) are compelling candidates of dark matter. For the QCD axion, it is known that when the Peccei-Quinn (PQ) symmetry is spontaneously broken after inflation, the large initial fluctuation can lead to axion clump formation. On the other hand, when the symmetry is already broken during inflation, it has been believed that the axion clump formation does not occur due to the small amplitude of the initial axion fluctuation. We revisit this prevailing understanding, considering both the QCD axion and an ALP. We find that for the QCD axion, the clump formation does not occur even if we consider an extremely fine-tuned initial condition. Meanwhile, it turns out that for an ALP which allows a more general potential form, the clump formation can take place through the tachyonic instability or/and the resonance instability, considering a multiple cosine potential.Comment: 24 pages, 14 figure

Field-induced carrier delocalization in the strain-induced Mott insulating state of an organic superconductor

We report the influence of the field effect on the dc resistance and Hall coefficient in the strain-induced Mott insulating state of an organic superconductor $\kappa$-(BEDT-TTF)$_{2}$Cu[N(CN)$_{2}$]Br. Conductivity obeys the formula for activated transport $\sigma_{\Box} = \sigma_{0}\exp(-W/k_{B}T)$, where $\sigma_{0}$ is a constant and $W$ depends on the gate voltage. The gate voltage dependence of the Hall coefficient shows that, unlike in conventional FETs, the effective mobility of dense hole carriers ($\sim1.6\times 10^{14}$ cm$^{-2}$) is enhanced by a positive gate voltage. This implies that carrier doping involves delocalization of intrinsic carriers that were initially localized due to electron correlation.Comment: 5 pages, 3 figure

An α-synuclein decoy peptide prevents cytotoxic α-synuclein aggregation caused by fatty acid binding protein 3

α-synuclein (αSyn) is a protein known to form intracellular aggregates during the manifestation of Parkinson’s disease. Previously, it was shown that αSyn aggregation was strongly suppressed in the midbrain region of mice that did not possess the gene encoding the lipid transport protein fatty acid binding protein 3 (FABP3). An interaction between these two proteins was detected in vitro, suggesting that FABP3 may play a role in the aggregation and deposition of αSyn in neurons. In order to characterize the molecular mechanisms that underlie the interactions between FABP3 and αSyn that modulate the cellular accumulation of the latter, in this report, we used in vitro fluorescence assays combined with fluorescence microscopy, transmission electron microscopy, and quartz crystal microbalance assays to characterize in detail the process and consequences of FABP3-αSyn interaction. We demonstrated that binding of FABP3 to αSyn results in changes in the aggregation mechanism of the latter; specifically, a suppression of fibrillar forms of αSyn, and also the production of aggregates with an enhanced cytotoxicity toward mice neuro2A cells. Since this interaction involved the C-terminal sequence region of αSyn, we tested a peptide derived from this region of αSyn (αSynP130-140) as a decoy to prevent the FABP3-αSyn interaction. We observed that the peptide competitively inhibited binding of αSyn to FABP3 in vitro and in cultured cells. We propose that administration of αSynP130-140 might be used to prevent the accumulation of toxic FABP3-αSyn oligomers in cells, thereby preventing the progression of Parkinson’s disease

Sphingosine 1-phosphate has anti-apoptotic effect on liver sinusoidal endothelial cells and proliferative effect on hepatocytes in a paracrine manner in human

AimSphingosine 1-phosphate (S1P) is a bioactive sphingolipid metabolite released from erythrocytes and platelets, and is a potent stimulus for endothelial cell proliferation. However, the role of S1P on human liver sinusoidal endothelial cells (LSEC) remains unclear. The proliferation and inhibition of apoptosis in LSEC are involved in the promotion of liver regeneration and the suppression of liver injury after liver resection and transplantation. The aim of this study is to investigate the role of S1P on human LSEC and the interaction between S1P and LSEC in hepatocyte proliferation in vitro.MethodsImmortalized human LSEC were used. LSEC were cultured with S1P, and the cell proliferation, anti-apoptosis, signal transductions and production of cytokines and growth factors were subsequently examined. To investigate the interaction between S1P and LSEC in hepatocyte proliferation, primary human hepatocytes were cultured with the supernatants of LSEC with and without S1P. DNA synthesis and signal transductions in hepatocytes were examined.ResultsS1P induced LSEC proliferation through activation of Akt and extracellular signal-related kinase pathways and suppressed LSEC apoptosis by affecting the expression levels of Bcl-2, Bax and cleaved caspase-3. S1P promoted interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF) production in LSEC. The supernatants of LSEC cultured with S1P enhanced hepatocyte DNA synthesis more strongly than the supernatants of LSEC cultured without S1P through activation of the signal transducer and activator of transcription-3 pathway.ConclusionS1P has proliferative and anti-apoptotic effects and promotes the production of IL-6 and VEGF in human LSEC, thereby promoting hepatocyte proliferation

Augmentation of Neovascularizaiton in Hindlimb Ischemia by Combined Transplantation of Human Embryonic Stem Cells-Derived Endothelial and Mural Cells

BACKGROUND: We demonstrated that mouse embryonic stem (ES) cells-derived vascular endothelial growth factor receptor-2 (VEGF-R2) positive cells could differentiate into both endothelial cells (EC) and mural cells (MC), and termed them as vascular progenitor cells (VPC). Recently, we have established a method to expand monkey and human ES cells-derived VPC with the proper differentiation stage in a large quantity. Here we investigated the therapeutic potential of human VPC-derived EC and MC for vascular regeneration. METHODS AND RESULTS: After the expansion of human VPC-derived vascular cells, we transplanted these cells to nude mice with hindlimb ischemia. The blood flow recovery and capillary density in ischemic hindlimbs were significantly improved in human VPC-derived EC-transplanted mice, compared to human peripheral and umbilical cord blood-derived endothelial progenitor cells (pEPC and uEPC) transplanted mice. The combined transplantation of human VPC-derived EC and MC synergistically improved blood flow of ischemic hindlimbs remarkably, compared to the single cell transplantations. Transplanted VPC-derived vascular cells were effectively incorporated into host circulating vessels as EC and MC to maintain long-term vascular integrity. CONCLUSIONS: Our findings suggest that the combined transplantation of human ES cells-derived EC and MC can be used as a new promising strategy for therapeutic vascular regeneration in patients with tissue ischemia

The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force

「コロナ制圧タスクフォース」COVID-19患者由来の血液細胞における遺伝子発現の網羅的解析 --重症度に応じた遺伝子発現の変化には、ヒトゲノム配列の個人差が影響する--. 京都大学プレスリリース. 2022-08-23.Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target

Efficient self-resonance instability from axions

Fukunaga H, Kitajima N, Urakawa Y. Efficient self-resonance instability from axions. JOURNAL OF COSMOLOGY AND ASTROPARTICLE PHYSICS. 2019;2019(6): 55.It was recently shown that a coherent oscillation of an axion can cause an efficient parametric resonance, leading to a prominent emission of the gravitational waves (GWs). In this paper, conducting the Floquet analysis, we investigate the parametric resonance instability, which potentially triggers the emission of the GWs from axions. Such a resonance instability takes place, when the time evolution of the background field significantly deviates from the harmonic oscillation. Therefore, the resonance instability cannot be described by the Mathieu equation, whose stability/instability chart is well known. In this paper, introducing an explicitly calculable parameter (q) over tilde ,which can be used to classify different types of the parametric resonance described by the general Hill's equation, we investigate the stability/instability chart for the general Hill's equation. This can also apply to the case where the background oscillation is anharmonic. We show that the flapping resonance instability, which takes place for (q ) over tilde = O(1), typically leads to the most significant growth of the inhomogeneous modes among the self-resonance instability. We also investigate whether the flapping resonance takes place for the cosine potential or not