Fibronectin Adsorption on Osteoconductive Hydroxyapatite and Non-osteoconductive α-alumina

The osteoconductivity mechanism of hydroxyapatite (HAp) has not been elucidated. It is hypothesized that specific proteins adsorb on HAp, promoting its osteoconductivity. To verify this hypothesis, we compared the adsorption behavior of fibronectin (Fn) on HAp powder and on α-alumina (α-Al2O3) powder, a material with no osteoconductivity. More Fn adsorbed on α-Al2O3 than on HAp, irrespective of the Fn concentration, and there was no significant difference in the secondary structure of Fn adsorbed on HAp and α-Al2O3. Further, it is possible that Fn did not adsorb on HAp and α-Al2O3 through the Arg-Gry-Asp motif of Fn. The amount of Fn adsorbed on HAp oriented to the a(b)-axis with very little decrease in carbonate and the adsorbed Fn had a smaller α-helix structure content. The results suggest that the secondary and/or higher-order structure rather than the amount of adsorbed Fn might affect the osteoconductivity of HAp, which might be electrostatically controlled by the crystal face orientation and/or carbonate content of HAp, although this should be confirmed by a cell culture test in the future

Human herpesvirus 6 infection impairs Toll-like receptor signaling

Human herpesvirus 6 (HHV-6) has a tropism for immunocompetent cells, including T lymphocytes, monocytes/macrophages, and dendritic cells (DCs) suggesting that HHV-6 infection affects the immunosurveillance system. Toll-like receptor (TLR) system plays an important role in innate immunity against various pathogens. In the present study, we investigated the effect of HHV-6 infection on the expression and intracellular signaling of TLRs in DCs. Although expression levels of TLRs were not decreased or slightly elevated following HHV-6 infection, the amounts of cytokines produced following stimulation with ligands for TLRs appeared to be dramatically decreased in HHV-6-infected DCs as compared to mock-infected DCs. Similarly, phosphorylation levels of TAK-1, IκB kinase, and IκB-α following stimulation of HHV-6-infected DCs with lipopolysaccharide, which is the ligand for TLR4, appeared to be decreased. These data show that HHV-6 impairs intracellular signaling through TLRs indicating the novel mechanism of HHV-6-mediated immunomodulation

High Human T Cell Leukemia Virus Type-1(HTLV-1) Provirus Load in Patients with HTLV-1 Carriers Complicated with HTLV-1-unrelated disorders

<p>Abstract</p> <p>Background</p> <p>To address the clinical and virological significance of a high HTLV-1 proviral load (VL) in practical blood samples from asymptomatic and symptomatic carriers, we simultaneously examined VL and clonal expansion status using polymerase chain reaction (PCR) quantification (infected cell % of peripheral mononuclear cells) and Southern blotting hybridization (SBH) methods.</p> <p>Results</p> <p>The present study disclosed extremely high VL with highly dense smears with or without oligoclonal bands in SBH. A high VL of 10% or more was observed in 16 (43.2%) of a total of 33 samples (one of 13 asymptomatic carriers, 8 of 12 symptomatic carriers, and 7 of 8 patients with lymphoma-type ATL without circulating ATL cells). In particular, an extremely high VL of 50% or more was limited to symptomatic carriers whose band findings always contained at least dense smears derived from polyclonally expanded cells infected with HTLV-1. Sequential samples revealed that the VL value was synchronized with the presence or absence of dense smears, and declined at the same time as disappearing dense smears. Dense smears transiently emerged at the active stage of the underlying disease. After disappearance of the smears, several clonal bands became visible and were persistently retained, explaining the process by which the clonality of HTLV-1-infected cells is established. The cases with only oligoclonal bands tended to maintain a stable VL of around 20% for a long time. Two of such cases developed ATL 4 and 3.5 years later, suggesting that a high VL with oligoclonal bands may be a predisposing risk to ATL.</p> <p>Conclusion</p> <p>The main contributor to extremely high VL seems to be transient emergence of dense smears detected by the sensitivity level of SBH, corresponding to polyclonal expansion of HTLV-1-infected cells including abundant small clones. Major clones retained after disappearance of dense smears stably persist and acquire various malignant characteristics step by step.</p

Carbon(sp2)-carbon(sp3) Bond-forming Cross-coupling Reactions Using Sulfur-Modified Au-Supported Nickel Nanoparticle Catalyst

We report a carbon(sp2)-carbon(sp3) bond-forming cross-coupling reactions by employing a nano-size nickel catalyst supported on sulfur-modified gold (SANi). This transformation demonstrates an efficient synthesis of functionalized aryl compounds, including heterocycles. Notably, the reactions proceeded in good yields with significantly low leaching of nickel from SANi. Moreover, SANi could be recycled several times without significant loss of catalytic activity.This is the peer reviewed version of the following article: Ohta R., Shio Y., Akiyama T., et al. Carbon(sp2)-carbon(sp3) Bond-forming Cross-coupling Reactions Using Sulfur-Modified Au-Supported Nickel Nanoparticle Catalyst. Asian Journal of Organic Chemistry, which has been published in final form at https://doi.org/10.1002/ajoc.202200229. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving. This article may not be enhanced, enriched or otherwise transformed into a derivative work, without express permission from Wiley or by statutory rights under applicable legislation. Copyright notices must not be removed, obscured or modified. The article must be linked to Wiley’s version of record on Wiley Online Library and any embedding, framing or otherwise making available the article or pages thereof by third parties from platforms, services and websites other than Wiley Online Library must be prohibited

Functional impairment of Tax-specific but not cytomegalovirus-specific CD8+ T lymphocytes in a minor population of asymptomatic human T-cell leukemia virus type 1-carriers

<p>Abstract</p> <p>Background</p> <p>Human T-cell leukemia virus type 1 (HTLV-1) causes adult T-cell leukemia (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) in a small percentage of infected individuals. ATL is often associated with general immune suppression and an impaired HTLV-1-specific T-cell response, an important host defense system. We previously found that a small fraction of asymptomatic HTLV-1-carriers (AC) already showed impaired T-cell responses against the major target antigen, Tax. However, it is unclear whether the impaired HTLV-1 Tax-specific T-cell response in these individuals is an HTLV-1-specific phenomenon, or merely reflects general immune suppression. In this study, in order to characterize the impaired HTLV-1-specific T-cell response, we investigated the function of Tax-specific CD8⁺T-cells in various clinical status of HTLV-1 infection.</p> <p>Results</p> <p>By using tetramers consisting of HLA-A*0201, -A*2402, or -A*1101, and corresponding Tax epitope peptides, we detected Tax-specific CD8⁺T-cells in the peripheral blood from 87.0% of ACs (n = 20/23) and 100% of HAM/TSP patients (n = 18/18) tested. We also detected Tax-specific CD8⁺T-cells in 38.1% of chronic type ATL (cATL) patients (n = 8/21), although its frequencies in peripheral blood CD8⁺T cells were significantly lower than those of ACs or HAM/TSP patients. Tax-specific CD8⁺T-cells detected in HAM/TSP patients proliferated well in culture and produced IFN-γ when stimulated with Tax peptides. However, such functions were severely impaired in the Tax-specific CD8⁺T-cells detected in cATL patients. In ACs, the responses of Tax-specific CD8⁺T-cells were retained in most cases. However, we found one AC sample whose Tax-specific CD8⁺T-cells hardly produced IFN-γ, and failed to proliferate and express activation (CD69) and degranulation (CD107a) markers in response to Tax peptide. Importantly, the same AC sample contained cytomegalovirus (CMV) pp65-specific CD8⁺T-cells that possessed functions upon CMV pp65 peptide stimulation. We further examined additional samples of two smoldering type ATL patients and found that they also showed dysfunctions of Tax-specific but not CMV-specific CD8⁺T-cells.</p> <p>Conclusions</p> <p>These findings indicated that Tax-specific CD8⁺T-cells were scarce and dysfunctional not only in ATL patients but also in a limited AC population, and that the dysfunction was selective for HTLV-1-specifc CD8⁺T-cells in early stages.</p

Making a MIDI Daemon on UNIX Operating System

A MIDI controlable system is constructed to provide a music facilities on UNIX-Workstation (WS). The system constructed is a MIDI Daemon for a variety of interfaces to music application programs. Users can usethe present system to enjoy music on UNIX-WS in the same was as on PC

SH3YL1 regulates dorsal ruffle formation by a novel phosphoinositide-binding domain

The newly identified SYLF lipid-binding domain of SH3YL1 mediates phosphoinositide binding during dorsal membrane morphogenesis

Non-human primate model of amyotrophic lateral sclerosis with cytoplasmic mislocalization of TDP-43

Amyotrophic lateral sclerosis is a fatal neurodegenerative disease characterized by progressive motoneuron loss. Redistribution of transactive response deoxyribonucleic acid-binding protein 43 from the nucleus to the cytoplasm and the presence of cystatin C-positive Bunina bodies are considered pathological hallmarks of amyotrophic lateral sclerosis, but their significance has not been fully elucidated. Since all reported rodent transgenic models using wild-type transactive response deoxyribonucleic acid-binding protein 43 failed to recapitulate these features, we expected a species difference and aimed to make a non-human primate model of amyotrophic lateral sclerosis. We overexpressed wild-type human transactive response deoxyribonucleic acid-binding protein 43 in spinal cords of cynomolgus monkeys and rats by injecting adeno-associated virus vector into the cervical cord, and examined the phenotype using behavioural, electrophysiological, neuropathological and biochemical analyses. These monkeys developed progressive motor weakness and muscle atrophy with fasciculation in distal hand muscles first. They also showed regional cytoplasmic transactive response deoxyribonucleic acid-binding protein 43 mislocalization with loss of nuclear transactive response deoxyribonucleic acid-binding protein 43 staining in the lateral nuclear group of spinal cord innervating distal hand muscles and cystatin C-positive cytoplasmic aggregates, reminiscent of the spinal cord pathology of patients with amyotrophic lateral sclerosis. Transactive response deoxyribonucleic acid-binding protein 43 mislocalization was an early or presymptomatic event and was later associated with neuron loss. These findings suggest that the transactive response deoxyribonucleic acid-binding protein 43 mislocalization leads to α-motoneuron degeneration. Furthermore, truncation of transactive response deoxyribonucleic acid-binding protein 43 was not a prerequisite for motoneuronal degeneration, and phosphorylation of transactive response deoxyribonucleic acid-binding protein 43 occurred after degeneration had begun. In contrast, similarly prepared rat models expressed transactive response deoxyribonucleic acid-binding protein 43 only in the nucleus of motoneurons. There is thus a species difference in transactive response deoxyribonucleic acid-binding protein 43 pathology, and our monkey model recapitulates amyotrophic lateral sclerosis pathology to a greater extent than rodent models, providing a valuable tool for studying the pathogenesis of sporadic amyotrophic lateral sclerosis

Impacts of Interaction of Mental Condition and Quality of Life between Donors and Recipients at Decision-Making of Preemptive and Post-Dialysis Living-Donor Kidney Transplantation

Pre-emptive kidney transplantation (PEKT) is considered one of the most effective types of kidney replacement therapies to improve the quality of life (QOL) and physical prognosis of patients with end-stage renal disease (ESRD). In Japan, living-donor kidney transplantation is a common therapeutic option for patients undergoing dialyses (PDKT). Moreover, during shared decision-making in kidney replacement therapy, the medical staff of the multidisciplinary kidney team often provide educational consultation programmes according to the QOL and sociopsychological status of the ESRD patient. In Japan, the majority of kidney donations are provided by living family members. However, neither the psychosocial status of donors associated with the decision-making of kidney donations nor the interactions of the psychosocial status between donors and recipients have been clarified in the literature. In response to this gap, the present study determined the QOL, mood and anxiety status of donors and recipients at kidney transplantation decision-making between PEKT and PDKT. Deterioration of the recipient’s QOL associated with “role physical” shifted the decision-making to PEKT, whereas deterioration of QOL associated with “role emotional” and “social functioning” of the recipients shifted the decision-making to PDKT. Furthermore, increased tension/anxiety and depressive mood contributed to choosing PDKT, but increased confusion was dominantly observed in PEKT recipients. These direct impact factors for decision-making were secondarily regulated by the trait anxiety of the recipients. Unlike the recipients, the donors’ QOL associated with vitality contributed to choosing PDKT, whereas the physical and mental health of the donors shifted the decision-making to PEKT. Interestingly, we also detected the typical features of PEKT donors, who showed higher tolerability against the trait anxiety of reactive tension/anxiety than PDKT donors. These results suggest that choosing between either PEKT or PDKT is likely achieved through the proactive support of family members as candidate donors, rather than the recipients. Furthermore, PDKT is possibly facilitated by an enrichment of the life–work–family balance of the donors. Therefore, multidisciplinary kidney teams should be aware of the familial psychodynamics between patients with ESRD and their family members during the shared decision-making process by continuing the educational consultation programmes for the kidney-replacement-therapy decision-making process