The Relation between Ion Temperature Anisotropy and Formation of Slow Shocks in Collisionless Magnetic Reconnection

We perform a two-dimensional simulation by using an electromagnetic hybrid code to study the formation of slow-mode shocks in collisionless magnetic reconnection in low beta plasmas, and we focus on the relation between the formation of slow shocks and the ion temperature anisotropy enhanced at the shock downstream region. It is known that as magnetic reconnection develops, the parallel temperature along the magnetic field becomes large in association with the anisotropic PSBL (plasma sheet boundary layer) ion beams, and this temperature anisotropy has a tendency to suppress the formation of slow shocks. Based on our simulation result, we found that the slow shock formation is suppressed due to the large temperature anisotropy near the X-type region, but the ion temperature anisotropy relaxes with increasing the distance from the magnetic neutral point. As a result, two pairs of current structures, which are the strong evidence of dissipation of magnetic field in slow shocks, are formed at the distance x > 115 ion inertial lengths from the neutral point.Comment: 28 pages, 8 figures, accepted for publication in JG

Epstein-Barr Virus-Associated γδ T-Cell Lymphoproliferative Disorder Associated With Hypomorphic IL2RG Mutation

Chronic active Epstein-Barr virus (EBV) infection (CAEBV) is an EBV-associated lymphoproliferative disease characterized by repeated or sustainable infectious mononucleosis (IM)-like symptoms. EBV is usually detected in B cells in patients who have IM or Burkitt's lymphoma and even in patients with X-linked lymphoproliferative syndrome, which is confirmed to have vulnerability to EBV infection. In contrast, EBV infects T cells (CD4+ T, CD8+ T, and γδT) or NK cells mono- or oligoclonally in CAEBV patients. It is known that the CAEBV phenotypes differ depending on which cells are infected with EBV. CAEBV is postulated to be associated with a genetic immunological abnormality, although its cause remains undefined. Here we describe a case of EBV-related γδT-cell proliferation with underlying hypomorphic IL2RG mutation. The immunological phenotype consisted of γδT-cell proliferation in the peripheral blood. A presence of EBV-infected B cells and γδT cells mimicked γδT-cell-type CAEBV. Although the patient had normal expression of CD132 (common γ chain), the phosphorylation of STAT was partially defective, indicating impaired activation of the downstream signal of the JAK/STAT pathway. Although the patient was not diagnosed as having CAEBV, this observation shows that CAEBV might be associated with immunological abnormality

Amelogenin binds to both heparan sulfate and bone morphogenetic protein 2 and pharmacologically suppresses the effect of noggin

Enamel matrix derivative (EMD) is widely considered useful to promote tissue regeneration during periodontal treatment. It has been reported that the main constituent of EMD is amelogenin and that the BMP-like and TGF-β-like activity of EMD promotes osteogenesis. However, it remains unclear whether those activities are dependent on amelogenin or another growth factor contained in EMD. We performed two-dimensional SDS-PAGE analysis of EMD, as well as Western blot analyses using anti-amelogenin, anti-BMP2/4, and anti-TGF-β1 antibodies, and amino acid sequencing. Our results revealed that a large number of splicing forms of amelogenin, BMP2/4, and other unknown molecules were involved in EMD, though TGF-β1 was not. In addition, we have evaluated intracellular signaling of ERK1/2 and Smad1/5/8, binding potential and alkaline phosphatase activity and have explored the potential regulatory relationship between amelogenin and BMP. Amelogenin bound to BMP2 as well as heparin/heparan sulfate. Thus, it was suggested that BMP2/4 carried over in EMD during processing promote binding activity and phosphorylate Smad1/5/8 in osteoblasts. On the other hand, amelogenin did not phosphorylate Smad1/5/8, but rather ERK1/2. Further, high-density amelogenin reduced the inhibition of alkaline phosphatase activity by noggin, though amelogenin did not have antagonistic properties against BMP. Together with the above findings, our findings suggest that the BMP2/4 contaminated during the purification process of EMD because of the avidity of amelogenin plays an important role in signaling pathway of calcification

Synthesis, structure-activity relationships, and mechanism of action of anti-HIV-1 lamellarin α 20-sulfate analogues.

Lamellarin α and six different types of lamellarin α 20-sulfate analogues were synthesized and their structure-activity relationships were investigated using a single round HIV-1 vector infection assay. All lamellarin sulfates having pentacyclic lamellarin core exhibited anti-HIV-1 activity at a 10μM concentration range regardless of the number and position of the sulfate group. On the other hand, non-sulfated lamellarin α and ring-opened lamellarin sulfate analogues did not affect HIV-1 vector infection in similar concentrations. The lamellarin sulfates utilized in this study did not exhibit unfavorable cytotoxic effect under the concentrations tested (IC(50)>100μM). Confocal laser scanning microscopic analysis indicated that hydrophilic lamellarin sulfates were hardly incorporated in the cell. HIV-1 Env-mediated cell-cell fusion was suppressed by lamellarin sulfates. These results suggested that lamellarin sulfates have a novel anti-HIV-1 activity besides the previously reported integrase activity inhibition, possibly at a viral entry step of HIV-1 replication

Materials in particulate form for tissue engineering. 1 Basic concepts

For biomedical applications, materials small in size are growing in importance. In an era where ‘nano’ is the new trend, micro- and nano-materials are in the forefront of developments. Materials in the particulate form aim to designate systems with a reduced size, such as micro- and nanoparticles. These systems can be produced starting from a diversity of materials, of which polymers are the most used. Similarly, a multitude of methods are used to produce particulate systems, and both materials and methods are critically reviewed here. Among the varied applications that materials in the particulate form can have, drug delivery systems are probably the most prominent, as these have been in the forefront of interest for biomedical applications. The basic concepts pertaining to drug delivery are summarized, and the role of polymers as drug delivery systems conclude this review

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