Comparative Study of Regulatory T Cell Function of Human CD25+CD4+ T Cells from Thymocytes, Cord Blood, and Adult Peripheral Blood

CD25+CD4+ regulatory T cells suppress T cell activation and regulate multiple immune reactions in in vitro and in vivo studies. To define the regulatory function of human CD25+CD4+ T cells at various stages of maturity, we investigated in detail the functional differences of CD25+CD4+ T cells from thymocytes, cord blood (CB), and adult peripheral blood (APB). CB CD25+CD4+ T cells displayed low-FOXP3 protein expression level and had no suppressive activity. In contrast, CD25+CD4+ T cells from thymocytes or APB expressed high expression level of FOXP3 protein associated with significant suppressive activity. Although CB CD25+CD4+ T cells exhibited no suppressive activity, striking suppressive activity was observed following expansion in culture associated with increased FOXP3 expression and a shift from the CD45RA+ to the CD45RA− phenotype. These functional differences in CD25+CD4+ T cells from Thy, CB, and APB hence suggest a pathway of maturation for Treg in the peripheral immune system

更年期前後の女性における不定愁訴に関わる因子

First of all, at female climacteric, female hormone secretion drop suddenly, arise balance confusion, and cause various symptoms to mind and body owing to ovary hypo activity. These are called climacteric symptom or climacteric syndrome. How we take and realize the symptoms that mentioned above and knowing what a relation with daily life is can be reduce some of lives of negative parts by climacteric. Secondly, we carried out a questionnaire survey to search for the clue. Many of fifties to sixties become strongly aware of unspecific symptoms. The tendency has been to the higher menopause age become more strongly aware of that. Also we found out that emergence of symptoms is in proportion to confusion of daily rhythm. Making it a habit to exercise and engaging in short time work reduce emergence of symptoms. In addition, dining out played the role of dissipating stress. We saw an involvement of an intake shortage of fruits, greens and grains in emergence of climacteric symptoms

Abnormally High Levels of Virus-Infected IFN-γ+CCR4+CD4+CD25+ T Cells in a Retrovirus-Associated Neuroinflammatory Disorder

BACKGROUND:Human T-lymphotropic virus type 1 (HTLV-1) is a human retrovirus associated with both HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), which is a chronic neuroinflammatory disease, and adult T-cell leukemia (ATL). The pathogenesis of HAM/TSP is known to be as follows: HTLV-1-infected T cells trigger a hyperimmune response leading to neuroinflammation. However, the HTLV-1-infected T cell subset that plays a major role in the accelerated immune response has not yet been identified. PRINCIPAL FINDINGS:Here, we demonstrate that CD4(+)CD25(+)CCR4(+) T cells are the predominant viral reservoir, and their levels are increased in HAM/TSP patients. While CCR4 is known to be selectively expressed on T helper type 2 (Th2), Th17, and regulatory T (Treg) cells in healthy individuals, we demonstrate that IFN-gamma production is extraordinarily increased and IL-4, IL-10, IL-17, and Foxp3 expression is decreased in the CD4(+)CD25(+)CCR4(+) T cells of HAM/TSP patients as compared to those in healthy individuals, and the alteration in function is specific to this cell subtype. Notably, the frequency of IFN-gamma-producing CD4(+)CD25(+)CCR4(+)Foxp3(-) T cells is dramatically increased in HAM/TSP patients, and this was found to be correlated with disease activity and severity. CONCLUSIONS:We have defined a unique T cell subset--IFN-gamma(+)CCR4(+)CD4(+)CD25(+) T cells--that is abnormally increased and functionally altered in this retrovirus-associated inflammatory disorder of the central nervous system

Broadband Multi-wavelength Properties of M87 during the 2017 Event Horizon Telescope Campaign

Abstract: In 2017, the Event Horizon Telescope (EHT) Collaboration succeeded in capturing the first direct image of the center of the M87 galaxy. The asymmetric ring morphology and size are consistent with theoretical expectations for a weakly accreting supermassive black hole of mass ∼6.5 × 109 M ⊙. The EHTC also partnered with several international facilities in space and on the ground, to arrange an extensive, quasi-simultaneous multi-wavelength campaign. This Letter presents the results and analysis of this campaign, as well as the multi-wavelength data as a legacy data repository. We captured M87 in a historically low state, and the core flux dominates over HST-1 at high energies, making it possible to combine core flux constraints with the more spatially precise very long baseline interferometry data. We present the most complete simultaneous multi-wavelength spectrum of the active nucleus to date, and discuss the complexity and caveats of combining data from different spatial scales into one broadband spectrum. We apply two heuristic, isotropic leptonic single-zone models to provide insight into the basic source properties, but conclude that a structured jet is necessary to explain M87’s spectrum. We can exclude that the simultaneous γ-ray emission is produced via inverse Compton emission in the same region producing the EHT mm-band emission, and further conclude that the γ-rays can only be produced in the inner jets (inward of HST-1) if there are strongly particle-dominated regions. Direct synchrotron emission from accelerated protons and secondaries cannot yet be excluded

Hardware-in-the-loop simulation of massive-payload manipulation on orbit

Abstract This paper describes a hardware-in-the-loop simulation of massive-payload manipulation on orbit using a master–slave teleoperation system. The main problems in teleoperating a space robot arm from the earth to manipulate a massive payload are communication delay, unexpected excessive force generated between the slave arm and the payload, and geometric/dynamic modeling error. In order to overcome those problems, a teleoperation system using mixed force and motion commands is discussed. The teleoperation system is verified by performing hardware-in-the-loop simulations

[Nine-month observation of effects of SO2 on the respiratory system in child Miyakejima citizens].

BACKGROUND: Mt. Oyama on Miyakejima Island erupted in June 2000 and all Miyake village citizens were forced to evacuate the island in the September, due to continuous eruptions and emission of unsafe amounts of volcanic gas, mainly sulfur dioxide (SO2). Beginning in February 2005, residents returned to live on the island despite the fact that volcanic gas was still being emitted. OBJECTIVE: To examine changes in the respiratory systems of included children from February 2006 to November 2006. METHODS: The study population was 141 children who participated in health checkups in November 2006, including 33 SO2 hypersusceptible children who had a current or past history of asthma, obstructive lung function, current symptoms of whistling and wheezing, and/or deterioration of respiratory symptoms. Respiratory effects were evaluated by a questionnaire for respiratory symptoms and by spirometry. SO2 was monitored at 7 sampling points within inhabited areas, and the mean SO2 concentration from February 2005 to November 2006 was 0.031 ppm. The area was categorized into four areas by average SO2 concentration, namely, areas L, H-1, H-2, and H-3, where the average SO2 levels were 0.019, 0.026, 0.032, and 0.045 ppm, respectively. RESULTS: Compared to children in area L, the frequencies of "phlegm" and "irritation of the nose" were significantly greater in the children in areas H-2 and H-3. %FVC and %FEV1 in hypersusceptible children were significantly reduced in November 2006 as compared to February 2006 (P = 0.047, 0.027), though no reduction observed in normosusceptible children. CONCLUSION: Respiratory functions in hypersusceptible Miyakejima children may be affected by SO2 exposure, and further follow-up observation is necessary

Large-scale discovery of novel neurodevelopmental disorder-related genes through a unified analysis of single-nucleotide and copy number variants

Background Previous large-scale studies of de novo variants identified a number of genes associated with neurodevelopmental disorders (NDDs); however, it was also predicted that many NDD-associated genes await discovery. Such genes can be discovered by integrating copy number variants (CNVs), which have not been fully considered in previous studies, and increasing the sample size. Methods We first constructed a model estimating the rates of de novo CNVs per gene from several factors such as gene length and number of exons. Second, we compiled a comprehensive list of de novo single-nucleotide variants (SNVs) in 41,165 individuals and de novo CNVs in 3675 individuals with NDDs by aggregating our own and publicly available datasets, including denovo-db and the Deciphering Developmental Disorders study data. Third, summing up the de novo CNV rates that we estimated and SNV rates previously established, gene-based enrichment of de novo deleterious SNVs and CNVs were assessed in the 41,165 cases. Significantly enriched genes were further prioritized according to their similarity to known NDD genes using a deep learning model that considers functional characteristics (e.g., gene ontology and expression patterns). Results We identified a total of 380 genes achieving statistical significance (5% false discovery rate), including 31 genes affected by de novo CNVs. Of the 380 genes, 52 have not previously been reported as NDD genes, and the data of de novo CNVs contributed to the significance of three genes (GLTSCR1, MARK2, and UBR3). Among the 52 genes, we reasonably excluded 18 genes [a number almost identical to the theoretically expected false positives (i.e., 380 x 0.05 = 19)] given their constraints against deleterious variants and extracted 34 plausible candidate genes. Their validity as NDD genes was consistently supported by their similarity in function and gene expression patterns to known NDD genes. Quantifying the overall similarity using deep learning, we identified 11 high-confidence (> 90% true-positive probabilities) candidate genes: HDAC2, SUPT16H, HECTD4, CHD5, XPO1, GSK3B, NLGN2, ADGRB1, CTR9, BRD3, and MARK2. Conclusions We identified dozens of new candidates for NDD genes. Both the methods and the resources developed here will contribute to the further identification of novel NDD-associated genes.This work was supported by AMED under grant numbers JP21ek0109486, JP21ek0109549, and JP21ek0109493 (N. Matsumoto); JP19dm0107133, JP19ek0109381, 19dm0307028, and 19km0405214 (A. Takata); JSPS KAKENHI grant numbers JP20H03641 (H. Saitsu); JP19H03621 (N. Miyake), JP20H05777, JP21H02855, and JP16H06254 (A. Takata); JP15K10367 (M. Nakashima); JP20K07907 (S. Miyatake); JP20K08164 (T. Mizuguchi); JP20K17936 (A. Fujita); and JP20K16932 (K. Hamanaka); the Takeda Science Foundation (T. Mizuguchi, N. Miyake, H. Saitsu, N. Matsumoto); The Ichiro Kanehara Foundation for the Promotion of Medical Science ; Medical Care (S. Miyatake); and an intramural grant of YCU (K. Hamanaka). The funding source had no role in the conduct of the study.AMED [JP21ek0109486, JP21ek0109549, JP21ek0109493, JP19dm0107133, JP19ek0109381, 19dm0307028, 19km0405214]; JSPS KAKENHI [JP20H03641, JP19H03621, JP20H05777, JP21H02855, JP16H06254, JP15K10367, JP20K07907, JP20K08164, JP20K17936, JP20K16932]; Takeda Science Foundation; Ichiro Kanehara Foundation for the Promotion of Medical Science Medical Care; YC

Prostatic Stromal Tumor of Uncertain Malignant Potential Which Was Difficult to Diagnose

Here, we report a case of stromal tumor of uncertain malignant potential (STUMP) that was difficult to diagnose. A 53-year-old male was found to have a hard nodule on digital rectal examination; magnetic resonance imaging revealed a large nodule on the left side of the prostate, indicating prostate cancer. However, pathological diagnosis of the biopsy specimen was benign prostatic hyperplasia. Although a papillary tumor in the prostatic urethra was also seen on urethrocystoscopy, the tumor specimen obtained from transurethral resection was not malignant. The tumor in the prostatic urethra recurred only 3 months after transurethral resection, and pathological findings revealed benign hyperplasia not only in the stromal tissue but also in the epithelium; therefore, the prostate tumor was suspected to be STUMP. It took many prostate pathologists a long time to reach the final diagnosis of STUMP. STUMP is a rare benign tumor, difficult to diagnose, and sometimes transforms into stromal sarcoma. Thus, we should consider radical resection in such cases