Human T-cell leukemia virus type 2 Tax protein induces interleukin 2-independent growth in a T-cell line

BACKGROUND: While human T-cell leukemia virus type 1 (HTLV-1) is a causative agent of adult T-cell leukemia, HTLV type 2 (HTLV-2) is not associated with this malignancy. Accumulating evidence suggests that Tax, a transforming protein of HTLV-1 or HTLV-2, plays a crucial role in the distinctive pathogenesis of these two infections. We herein examined whether Tax2 by itself has a growth promoting activity in a mouse T-cell line CTLL-2, and compared the activity with that of Tax1. RESULTS: We found that Tax2 converts the cell growth of CTLL-2 from an interleukin(IL)-2-dependent growth into an independent one. Cyclosporine A, an inhibitor of transcription factor NFAT, inhibited the growth of two out of four Tax2-transformed CTLL-2 cells, but it had little effect on two Tax1-transformed cells. While the HTLV-2-transformed human T-cell lines produce a significant amount of IL-2, Tax2-transformed CTLL-2 cells only produced a minimal amount of IL-2. These results thus suggest that NFAT-inducible gene(s) other than IL-2 play a role in the cell growth of Tax2-transformed CTLL-2 cells. CONCLUSION: These results show that HTLV-2 Tax2 by itself has a growth promoting activity toward a T-cell line CTLL-2, and the CTLL-2 assay used in this study may therefore be a useful tool for comparing the activity of Tax2 with that of Tax1 in T-cells, thereby elucidating the mechanism of HTLV-1 specific leukemogenesis

PDZ domain-binding motif of human T-cell leukemia virus type 1 Tax oncoprotein is essential for the interleukin 2 independent growth induction of a T-cell line

BACKGROUND: Human T-cell leukemia virus type 1 (HTLV-1) is the etiologic agent of adult T-cell leukemia (ATL), whereas HTLV type 2 (HTLV-2), is not associated with ATL or any other leukemia. HTLV-1 encodes the transforming gene tax1, whose expression in an interleukin (IL)-2-dependent T-cell line (CTLL-2) induces IL-2-independent growth. RESULTS: In this study, we demonstrated that IL-2-independent growth induction by Tax1 was abrogated by mutations of the PDZ domain-binding motif (PBM) at the Tax1 C-terminus. HTLV-2 Tax2, which shares 75% amino acid identity with Tax1 but does not have a PBM, was not able to induce IL-2-independent growth of CTLL-2. CONCLUSION: Our results suggest that Tax1, through interaction with PDZ domain protein(s) induces IL-2-independent growth, which may be a factor in multi-step leukemogenesis caused by HTLV-1

Early return activity after endoscopic surgery in medical doctors

Full endoscopic surgery including discectomy (FED) and ventral facetectomy (FEVF) is a minimally invasive lumbar decompression surgery that only requires an 8 mm skin incision and can be done under the local anesthesia and sedation. Six male medical doctors underwent the endoscopic decompression (FED/FEVF) for common degenerative lumbar spine problems. Their age ranged from 27 to 63 years of age with a mean of 40 years. Five doctors underwent FED surgery for herniated nucleus pulposus (HNP), and the remaining one physician had FEVF for lumbar lateral recess stenosis. There were no surgery related complications. Postoperatively, 5 out of the 6 physician patients returned the original job within a week because they had clinical duties. The shortest duration to return to work was reported by a 63-year-old orthopedic surgeon resumed working in his clinic 2 days after the FEVF surgery. The longest duration to return to work occurred in general medicine resident who took almost 2 weeks for the sick leave because he did not have clinical duties. The mean duration for the returning to work was 5.8 days after the surgery. At final follow-up ranging from 6 to 30 months, all physician patients were working without any residual pain. In the hands of the authors, the full endoscopic transforaminal decompression surgery is the preferred surgical option and allowed early return to work—an observation that is not the norm in Japan

Hemangioblastoma of Cauda Equina

Introduction : Hemangioblastoma in the spine mainly occurs at the cervical and thoracic levels and is often associated with von Hippel-Lindau (VHL) syndrome. Here, we reported a quite rare case of spinal sporadic hemangioblastoma arising from the cauda equina. Case presentation : A 66-year-old woman presented with a 5-year history of low back and leg pain. Imaging revealed a hypervascular intradural extramedullary tumor in the lumbar region. Preoperative angiography helped to identify the feeding arteries and draining vein, and so facilitated subsequent tumor resection. The pain was dramatically improved but weakness of the left tibialis anterior and left extensor hallucis longus muscles persisted. Discussion : We reported a rare case of spinal hemangioblastoma arising from the cauda equina. Preoperative angiography may be useful for diagnosis and understanding of the anatomy of feeding veins

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

A Bouc–Wen Model-Based Compensation of the Frequency-Dependent Hysteresis of a Piezoelectric Actuator Exhibiting Odd Harmonic Oscillation

This paper proposes an enhancement of the Bouc–Wen hysteresis model to capture the frequency-dependent hysteretic behavior of a thin bimorph-type piezoelectric actuator which also exhibits odd harmonic oscillation (OHO) at specific input frequencies. The odd harmonic repetitive controller has recently been proposed to compensate for the hysteresis, and attenuates the OHO of the piezoelectric actuator for which the hysteresis nonlinearity is regarded as a disturbance. This paper proposes an alternate treatment of the hysteresis compensation with the attenuation of the OHO observed at some input frequencies. It will be shown that the proposed compensator fully utilizes the mathematical structure of the enhanced Bouc–Wen model proposed in this paper to compensate the hysteresis and to attenuate the OHO. The results of the hysteresis compensation experiment illustrate the excellent performance of the proposed control system, especially at the frequencies where OHO is conspicuous

Modeling and Compensation of a Bimorph Type Piezoelectric Actuator Exhibiting Odd-Harmonic Oscillation and Frequency-Dependent, Interleaved Hysteresis

This paper proposes an improved version of the play model for capturing the frequency-dependent hysteresis of a bimorph piezoelectric actuator that includes odd harmonic oscillation and interleaved hysteresis. The proposed model used a single mathematical structure to capture the changes in the actuator response observed with the increase in the input signal frequency. The refinements on the structure of the original play model for capturing the peculiar behavior of the bimorph piezoelectric actuator have been addressed in detail. The parameter identification has been conducted extensively for a range of 1 Hz to 110 Hz, which exceeds the resonance frequency specified by the manufacturer of the actuator. Improved modeling accuracy was confirmed as compared with our previous enhanced Bouc–Wen model based on the calculation of the fitness index. We also attempted to synthesize a hysteresis compensator based on direct inverse multiplication; the results of the experimental validation of the proposed control system are disclosed