Neutron scattering study on spin correlations and fluctuations in the transition-metal-based magnetic quasicrystal Zn-Fe-Sc

Spin correlations and fluctuations in the 3d-transition-metal-based icosahedral quasicrystal Zn-Fe-Sc have been investigated by neutron scattering using polycrystalline samples. Magnetic diffuse scattering has been observed in the elastic experiment at low temperatures, indicating development of static short-range-spin correlations. In addition, the inelastic scattering experiment detects a $Q$-independent quasielastic signal ascribed to single-site relaxational spin fluctuations. Above the macroscopic freezing temperature $T_{\rm f} \simeq 7$ K, the spin relaxation rate shows Arrhenius-type behavior, indicating thermally activated relaxation process. In contrast, the relaxation rate remains finite even at the lowest temperature, suggesting a certain quantum origin for the spin fluctuations below $T_{\rm f}$.Comment: To be published in Phys. Rev.

Roles of 5-HT1A receptor in the expression of AMPA receptor and BDNF in developing mouse cortical neurons

The possible interactions between serotonergic and glutamatergic systems during neural development and under the pathogenesis of depression remain unclear. We now investigated roles of 5-HT1A receptor in the mRNA expression of AMPA receptor subunits (GluR1 and GluR2) and brain-derived neurotrophic factor (BDNF) using primary culture of cerebral cortex of mouse embryos. Neurons at embryonic day 18 were cultured for 3 days or 14 days and then treated with 5-HT1A receptor agonist (8-OH-DPAT) for 3 h or 24 h. In neurons cultured for 3 days, 8-OH-DPAT treatment for both 3 h and 24 h increased the mRNA levels of BDNF and GluR1, but not GluR2. In neurons cultured for 14 days, however, 8-OH-DPAT had no effects on these mRNA levels. Next, we examined in vivo roles of 5-HT1A receptor by administration of 8-OH-DPAT to newborn mice. Twenty-four hours after the oral administration of 8-OH-DPAT, the mRNA expression of BDNF was decreased in the frontal cortex, but had no effects on the mRNA expression of GluR1 and GluR2. Taken together, the present study suggests that 5-HT1A receptor activation modulates mRNA expression of AMPA receptor subunit and BDNF in cortical neurons, and the effects are different between in vitro and in vivo

Truncated serine/arginine-rich splicing factor 3 accelerates cell growth through up-regulating c-Jun expression

Serine/arginine-rich splicing factor 3 (SRSF3), a member of the SRSF family, plays a wide-ranging role in gene expression. The human SRSF3 gene generates a major mRNA isoform encoding a functional, full-length protein and a PTC-containing isoform (SRSF3-PTC). The latter is expected to be degraded through the nonsense-mediated mRNA decay system. However, it was reported that SRSF3-PTC mRNA was produced under stressful conditions and translated into a truncated SRSF3 protein (SRSF3-TR). To disclose unknown functions of SRSF3-TR, we established Flp-In-293 cells stably expressing SRSF3-TR. The SRSF3-TR-expressing cells increased mRNA and protein levels of positive regulators for G1 to S phase transition (cyclin D1, cyclin D3, CDC25A, and E2F1) and accelerated their growth. c-Jun is required for progression through the G1 phase, the mechanism by which involves transcriptional control of the cyclin D1 gene. We also found that the JUN promoter activity was significantly increased in the Flp-In-293 cells stably expressing SRSF3-TR, compared with mock-transfected control cells. The SRSF3-TR-expressing cells increased c-Jun and Sp-1 levels, which are important for the positive autoregulation and basal transcription of JUN, respectively. Our results suggest that stress-inducible SRSF3-TR may participate in the acceleration of cell growth through facilitating c-Jun-mediated G1 progression under stressful conditions

Truncated SRSF3 regulates IL-8 production

Serine/arginine-rich splicing factor 3 (SRSF3) is a member of the SR protein family and plays wide-ranging roles in gene expression. The human SRSF3 gene generates two alternative splice transcripts, a major mRNA isoform (SRSF3-FL) encoding functional full-length protein and a premature termination codon (PTC)-containing isoform (SRSF3-PTC). The latter is degraded through nonsense-mediated mRNA decay (NMD). Treatment of a human colon cancer cell line (HCT116) with 100 μM sodium arsenite increased SRSF3-PTC mRNA levels without changing SRSF3-FL mRNA levels. A chemiluminescence-based NMD reporter assay system demonstrated that arsenite treatment inhibited NMD activity and increased SRSF3-PTC mRNA levels in the cytoplasm, facilitating translation of a truncated SRSF3 protein (SRSF3-TR) from SRSF3-PTC mRNA. SRSF3-TR lacked two-thirds of Arg/Ser-rich (RS) domain whose phosphorylation state is known to be crucial for subcellular distribution. SRSF3-FL was localized in the nucleus, while overexpressed SRSF3-TR was diffusely distributed in the cytoplasm and the nucleus. A part of SRSF3-TR was also associated with stress granules in the cytoplasm. Interestingly, treatment of HCT116 cells with a small interference RNA specifically targeting SRSF3-PTC mRNA significantly attenuated arsenite-stimulated induction of c-JUN protein, its binding activity to the AP-1 binding site (-126 to 120 bp) in the interleukin (IL)-8 gene promoter, and AP-1 promoter activity, resulting in significant reduction of arsenite-stimulated IL-8 production. Our results suggest that SRSF3-TR may function as a positive regulator of oxidative stress-initiated inflammatory responses in colon cancer cells

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

The effect of monovalent anion species on the aggregation and charging of allophane clay nanoparticles

Allophane is a kind of clay mineral which has amorphous hollow spherical structure. To clarify the dispersion, aggregation and charging behaviour of allophane in the presence of various monovalent anions, F−, Cl−, Br−, I−, BrO3−, IO3−, and SCN−, the stability ratio and electrophoretic mobility of allophane were investigated. The stability ratio was obtained from the temporal change in the average hydrodynamic diameter of allophane measured by dynamic light scattering. The charging behaviour was evaluated from the measurement of electrophoretic mobility (EPM) of allophane. These experiments were performed as a function of electrolyte concentration at pH 5, where the net charge of allophane is positive. The experimental results demonstrated that the stability ratio decreased with increasing the salt concentration and finally it became unity independent of the salt concentration. Consequently, we observed slow aggregation regime, fast aggregation regime, and critical coagulation concentration (CCC). Therefore, the stability ratio follow the classical theory of Derjaguin, Landau, Verwey, Overbeek (DLVO) at least qualitatively. However, the CCC of allophane showed difference for each anion species; the CCC followed the order F− < IO3− < Cl− < SCN− < BrO3− < Br− < I−. We also confirmed the difference in EPM among anion species; the reduction of EPM magnitude was significant for well-hydrated ions. We presume that the CCC and EPM of allophane depend on the affinity of anions to the allophane surface characterized by the degree of hydration of each ion. That is, well-hydrated anions can adsorb to the hydrophilic surface of allophane and effectively decrease the positive charge of allophane. Besides this, the fluoride ion induced much lower CCC and charge reversal. These results are due to the strong affinity of fluoride ion for the allophane surface. Meanwhile the dependence of CCC on the zeta potential followed the DLVO prediction. Although the zeta potential of allophane is affected by anion species, the CCC behaviors can be understood by the DLVO theory through the evaluation of zeta potential of allophane. This means that the measurement of stability ratio and electrophoretic mobility accompanied with the DLVO theory are valuable tools for the understanding of the aggregation-dispersion of charge-stabilized natural clays

Synthesis of Carbazole-Based Selenaporphyrin <i>via</i> Annulation

Cu(I)-mediated alkoxylation of doubly 1,3-butadiyne-bridged carbazole dimer <b>1</b>, followed by acid-catalyzed cyclization, provided furan-bridged carbazole dimer <b>3</b>, while annulation reaction of <b>1</b> with selenium in the presence of hydrazine monohydrate provided selenophene-bridged carbazole dimer <b>5a</b>. Oxidation of isophlorin <b>5a</b> afforded carbazole-based selenaporphyrin <b>5b</b>, which possessed distinct aromaticity and produced intensified and red-shifted absorption bands in the near-IR region

Effective π‑Extension of Carbazole-Based Thiaporphyrins by Peripheral Phenylethynyl Substituents

Several tetrakis(phenylethynyl)- and (phenylethynylphenylethynyl)-substituted carbazole-based thiaporphyrins were synthesized. These π-extended porphyrins display remarkably intensified and red-shifted absorption bands in the NIR region up to 1126 nm due to perturbation by the phenylethynyl substituents