Third Stable Branch and Tristability of Nuclear Spin Polarization in Single Quantum Dot System

Semiconductor quantum dots provide a spin-coupled system of an electron and nuclei via enhanced hyperfine interaction. We showed that the nuclear spin polarization in single quantum dots can have three stable branches under a longitudinal magnetic field. The states were accompanied by hysteresis loops around the boundaries of each branch with a change in the excitation condition. To explain these findings, we incorporated the electron spin relaxation caused by the nuclear spin fluctuation into the previously-studied dynamic nuclear spin polarization mechanism. The model reproduces the new features of nuclear spin polarization and the associated strong reduction in the observed electron spin polarization, and can refer to the tristability of nuclear spin polarization.Comment: 5 pages, 3 figure

Metabolomic characterization of monoclonal antibody-producing Chinese hamster lung (CHL)-YN cells in glucose-controlled serum-free fed-batch operation

Sukwattananipaat P., Kuroda H., Yamano-Adachi N., et al. Metabolomic characterization of monoclonal antibody-producing Chinese hamster lung (CHL)-YN cells in glucose-controlled serum-free fed-batch operation. Biotechnology and Bioengineering, (2024); https://doi.org/10.1002/bit.28777.The fast-growing Chinese hamster lung (CHL)-YN cell line was recently developed for monoclonal antibody production. In this study, we applied a serum-free fed-batch cultivation process to immunoglobulin (Ig)G1-producing CHL-YN cells, which were then used to design a dynamic glucose supply system to stabilize the extracellular glucose concentration based on glucose consumption. Glucose consumption of the cultures rapidly oscillated following three phases of glutamine metabolism: consumption, production, and re-consumption. Use of the dynamic glucose supply prolonged the viability of the CHL-YN-IgG1 cell cultures and increased IgG1 production. Liquid chromatography with tandem mass spectrometry-based target metabolomics analysis of the extracellular metabolites during the first glutamine shift was conducted to search for depleted compounds. The results suggest that the levels of four amino acids, namely arginine, aspartate, methionine, and serine, were sharply decreased in CHL-YN cells during glutamine production. Supporting evidence from metabolic and gene expression analyses also suggest that CHL-YN cells acquired ornithine- and cystathionine-production abilities that differed from those in Chinese hamster ovary-K1 cells, potentially leading to proline and cysteine biosynthesis

Modulation of vif-mRNA by HIV-1-SA1D2prox

Genomic RNA of HIV-1 contains localized structures critical for viral replication. Its structural analysis has demonstrated a stem-loop structure, SLSA1, in a nearby region of HIV-1 genomic splicing acceptor 1 (SA1). We have previously shown that the expression level of vif mRNA is considerably altered by some natural single-nucleotide variations (nSNVs) clustering in SLSA1 structure. In this study, besides eleven nSNVs previously identified by us, we totally found nine new nSNVs in the SLSA1-containing sequence from SA1, splicing donor 2, and through to the start codon of Vif that significantly affect the vif mRNA level, and designated the sequence SA1D2prox (142 nucleotides for HIV-1 NL4-3). We then examined by extensive variant and mutagenesis analyses how SA1D2prox sequence and SLSA1 secondary structure are related to vif mRNA level. While the secondary structure and stability of SLSA1 was largely changed by nSNVs and artificial mutations introduced to restore the original NL4-3 form from altered ones by nSNVs, no clear association of the two SLSA1 properties with vif mRNA level was observed. In contrast, when naturally occurring SA1D2prox sequences that contain multiple nSNVs were examined, we attained significant inverse correlation between the vif level and SLSA1 stability. These results may suggest that SA1D2prox sequence adapts over time, and also that the altered SA1D2prox sequence, SLSA1 stability, and vif level are mutually related. In total, we show here that the entire SA1D2prox sequence and SLSA1 stability critically contribute to the modulation of vif mRNA level

The Identification of a Small Molecule Compound That Reduces HIV-1 Nef-Mediated Viral Infectivity Enhancement

Nef is a multifunctional HIV-1 protein that accelerates progression to AIDS, and enhances the infectivity of progeny viruses through a mechanism that is not yet understood. Here, we show that the small molecule compound 2c reduces Nef-mediated viral infectivity enhancement. When added to viral producer cells, 2c did not affect the efficiency of viral production itself. However, the infectivity of the viruses produced in the presence of 2c was significantly lower than that of control viruses. Importantly, an inhibitory effect was observed with Nef+ wild-type viruses, but not with viruses produced in the absence of Nef or in the presence of proline-rich PxxP motif-disrupted Nef, both of which displayed significantly reduced intrinsic infectivity. Meanwhile, the overexpression of the SH3 domain of the tyrosine kinase Hck, which binds to a PxxP motif in Nef, also reduced viral infectivity. Importantly, 2c inhibited Hck SH3-Nef binding, which was more marked when Nef was pre-incubated with 2c prior to its incubation with Hck, indicating that both Hck SH3 and 2c directly bind to Nef and that their binding sites overlap. These results imply that both 2c and the Hck SH3 domain inhibit the interaction of Nef with an unidentified host protein and thereby reduce Nef-mediated infectivity enhancement. The first inhibitory compound 2c is therefore a valuable chemical probe for revealing the underlying molecular mechanism by which Nef enhances the infectivity of HIV-1

Clinical Significance of Pharmacological Prophylaxis based on the Original Risk Classification of Venous Thromboembolism after Lower Abdominal Surgery

Pharmacological prophylaxis was not routinely administrated following gastroenterological surgery because of concerns about bleeding complications. We tried to establish the original risk classification to determine the indication for pharmacological prophylaxis for selected patients at high risk of venous thromboembolism (VTE). One hundred and fifty-six consecutive patients who underwent lower abdominal elective surgery were divided into three groups (highest, high, and low risk groups) based on the original risk classification. Pharmacological prophylaxis was indicated for patients in the highest and high risk groups. We investigated safety and efficacy of the pharmacological prophylaxis based on this classification. Sixteen patients were classified in the highest, 50 in the high, and 90 in the low risk groups. Pharmacological prophylaxis was used for 59 cases (37.8%). There was no symptomatic pulmonary embolism or major bleeding complications. There were no significant differences in the occurrence of postoperative complications, analgesia use, and median postoperative pain scores for the three groups. In the highest and high risk groups administrated pharmacological prophylaxis, fibrin degradation products (FDP) and D-dimer did not change between postoperative day 1 and day 7. These data suggested the clinical significance of the pharmacological prophylaxis based on the original risk classification

The MAXI Mission on the ISS: Science and Instruments for Monitoring All Sky X-Ray Images

The MAXI (Monitor of All-sky X-ray Image) mission is the first astronomical payload to be installed on the Japanese Experiment Module-Exposed Facility (JEM-EF) on the ISS. It is scheduled for launch in the middle of 2009 to monitor all-sky X-ray objects on every ISS orbit. MAXI will be more powerful than any previous X-ray All Sky Monitor (ASM) payloads, being able to monitor hundreds of AGN. MAXI will provide all sky images of X-ray sources of about 20 mCrab in the energy band of 2-30 keV from observation on one ISS orbit (90 min), about 4.5 mCrab for one day, and about 1 mCrab for one month. A final detectability of MAXI could be 0.2 mCrab for 2 year observations.Comment: 12 pages, 11 figures, accepted for publication in Publications of the Astronomical Society of Japa

A proposal for a new HIV-1 DLS structural model

The dimer initiation site/dimer linkage sequence (DIS/DLS) region of the human immunodeficiency virus type 1 (HIV-1) RNA genome is suggested to play essential roles at various stages of the viral life cycle. Through a novel assay we had recently developed, we reported on the necessary and sufficient region for RNA dimerization in the HIV-1 virion. Using this system, we performed further detailed mapping of the functional base pairs necessary for HIV-1 DLS structure. Interestingly, the study revealed a previously unnoticed stem formation between two distantly positioned regions. Based on this and other findings on functional base pairing in vivo, we propose new 3D models of the HIV-1 DLS which contain a unique pseudoknot-like conformation. Since this pseudoknot-like conformation appears to be thermodynamically stable, forms a foundational skeleton for the DLS and sterically restricts the spontaneous diversification of DLS conformations, its unique shape may contribute to the viral life cycle and potentially serve as a novel target for anti-HIV-1 therapies

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

Deterministic Single-Photon and Polarization-Correlated Photon Pair Generations From a Single InAlAs Quantum Dot

Photon emission with nonclassical photon statistics is discussed with a single InAlAs quantum dot. The deterministic single-photon generation in which the emitted photon wavelength matches well to the highly sensitive wavelength region of highly efficient, low-noise Si-single-photon detectors and also to an atmospheric transmission window is demonstrated. Competing transition processes between neutral and charged exciton species originating from an exclusive formation in the same single quantum dot are clarified. It was found that suppressing the charged exciton formation is possible by a quasi-resonant excitation for a deterministic monochromatic single-photon generation. Polarization-dependent photoluminescence spectroscopy clearly indicates the preservation of photon polarizations between photons emitted by biexciton/exciton recombinations. Furthermore, the deterministic polarization-correlated photon pair generation with biexciton-exciton cascaded transition occurring in a single quantum dot is directly confirmed by the polarized second-order photon correlation measurements. This indicates a longer polarization flip time than the exciton lifetime, which is an essential requirement for the deterministic Einstein-Podolsky-Rosen photon pair generation under the present biexciton-exciton cascaded transition scheme