Association of progressive intracranial necrotic lesion with acute myelogenous leukemia: A case report

For patients with acute myelogenous leukemia (AML) and invasive central nervous system lesions, there are many possible differential diagnoses, including collagen diseases, infectious diseases, drug reactions or side effects, and vascular diseases. Herein, we describe the clinical course, diagnostic examinations, and treatment outcomes for a patient with AML complicated by a progressively enlarging intracranial necrotic lesion. As no tumor cells were seen on microscopic examination, and since the clinical symptoms improved after leukemia therapy, myeloid sarcoma was highly suspected. Taken together, this case suggests that a combination of the clinical course, radiological findings, and treatment history should be considered to eliminate other possible diagnoses

UV-Induced Ubiquitylation of XPC Protein Mediated by UV-DDB-Ubiquitin Ligase Complex

SummaryThe xeroderma pigmentosum group C (XPC) protein complex plays a key role in recognizing DNA damage throughout the genome for mammalian nucleotide excision repair (NER). Ultraviolet light (UV)-damaged DNA binding protein (UV-DDB) is another complex that appears to be involved in the recognition of NER-inducing damage, although the precise role it plays and its relationship to XPC remain to be elucidated. Here we show that XPC undergoes reversible ubiquitylation upon UV irradiation of cells and that this depends on the presence of functional UV-DDB activity. XPC and UV-DDB were demonstrated to interact physically, and both are polyubiquitylated by the recombinant UV-DDB-ubiquitin ligase complex. The polyubiquitylation altered the DNA binding properties of XPC and UV-DDB and appeared to be required for cell-free NER of UV-induced (6-4) photoproducts specifically when UV-DDB was bound to the lesion. Our results strongly suggest that ubiquitylation plays a critical role in the transfer of the UV-induced lesion from UV-DDB to XPC

Study protocol for a multi-center, randomized controlled trial to develop Japanese denture adhesive guidelines for patients with complete dentures : the Denture Adhesive Guideline trial : study protocol for a randomized controlled trial

Background: Denture adhesives, characterized as medical products in 1935 by the American Dental Association, have been considered useful adjuncts for improving denture retention and stability. However, many dentists in Japan are hesitant to acknowledge denture adhesives in daily practice because of the stereotype that dentures should be inherently stable, without the aid of adhesives. The aim of this study is to verify the efficacy of denture adhesives to establish guidelines for Japanese users. The null hypothesis is that the application of denture adhesives, including the cream and powder types, or a control (isotonic sodium chloride solution) would not produce different outcomes nor would they differentially improve the set outcomes between baseline and day 4 post-application. Methods: This ten-center, randomized controlled trial with parallel groups is ongoing. Three hundred edentulous patients with complete dentures will be allocated to three groups (cream-type adhesive, powder-type adhesive, and control groups). The participants will wear their dentures with the denture adhesive for 4 days, including during eight meals (three breakfasts, two lunches, and three dinners). The baseline measurements and final measurements for the denture adhesives will be performed on the first day and after breakfast on the fourth day. The primary outcome is a general satisfaction rating for the denture. The secondary outcomes are denture satisfaction ratings for various denture functions, occlusal bite force, resistance to dislodgement, masticatory performance, perceived chewing ability, and oral health-related quality of life. Between-subjects comparisons among the three groups and within-subjects comparisons of the pre- and post-intervention measurements will be performed. Furthermore, a multiple regression analysis will be performed. The main analyses will be based on the intention-to-treat principle. A sample size of 100 subjects per group, including an assumed dropout rate of 10 %, will be required to achieve 80 % power with a 5 % alpha level. Discussion: This randomized clinical trial will provide information about denture adhesives to complete denture wearers, prosthodontic educators, and dentists in Japan. We believe this new evidence on denture adhesive use from Japan will aid dentists in their daily practice even in other countries

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

JASMINE: Near-infrared astrometry and time-series photometry science

The Japan Astrometry Satellite Mission for INfrared Exploration (JASMINE) is a planned M-class science space mission by the Institute of Space and Astronautical Science, the Japan Aerospace Exploration Agency. JASMINE has two main science goals. One is Galactic archaeology with a Galactic Center survey, which aims to reveal the Milky Way’s central core structure and formation history from Gaia-level (∼25 ${\mu}$as) astrometry in the near-infrared (NIR) Hw band (1.0–1.6 ${\mu}$m). The other is an exoplanet survey, which aims to discover transiting Earth-like exoplanets in the habitable zone from NIR time-series photometry of M dwarfs when the Galactic Center is not accessible. We introduce the mission, review many science objectives, and present the instrument concept. JASMINE will be the first dedicated NIR astrometry space mission and provide precise astrometric information on the stars in the Galactic Center, taking advantage of the significantly lower extinction in the NIR. The precise astrometry is obtained by taking many short-exposure images. Hence, the JASMINE Galactic Center survey data will be valuable for studies of exoplanet transits, asteroseismology, variable stars, and microlensing studies, including discovery of (intermediate-mass) black holes. We highlight a swath of such potential science, and also describe synergies with other missions

Cloud-top height dataset by geostationary satellite split window measurements trained with CLOUDSAT data

Lookup tables for estimating the cloud-top height (CTOP) and visible optical thickness of uppertropospheric clouds by the infrared brightness temperature (TB) at 10.8 μm (T11) and its difference from TB at 12 μm (DT11-12) measured by geostationary satellites are developed (Hamada and Nishi 2010, JAMC). These lookup tables were constructed by regressing the cloud radar measurements by the CloudSat satellite over the infrared measurements by the Japanese geostationary multifunctional transport satellite MTSAT-1R and MTSAT-2. The CTOP is available at http://database.rish.kyoto-u.ac.jp/arch/ctop/ since July 2005. The data have good precision for cirrus clouds (τ \u3e ~3) that have large DT11-12 values and are suitable for analyses of cloud systems with well-developed cirrus clouds. We made correction for the satellite view angle and can offer the data over almost all tropical regions where the satellites can observe (20S-20N, 80E-160W for MTSAT-1R and 85E-155W for MTSAT-2)

Lifetime and longitudinal variability of equatorial Kelvin waves around the tropical tropopause region

Using the European Centre for Medium-Range Weather Forecasts 40 year reanalysis data for zonal wind fields, we investigated the characteristic variability and mean lifecycle of Kelvin waves around the tropical tropopause layer and upper troposphere. The distributions of Kelvin wave activity, mean squared amplitude, and number of passing cases closely resemble each other. Kelvin wave disappearance locations relative to appearance longitudes were examined at 200 and 100 hPa. At 200 hPa Kelvin waves mostly appear in the western hemisphere. At 100 hPa the highest-frequency region is centered in the eastern hemisphere. On average, eastward propagation extending over ∼80° in longitude occurs at both levels examined. Mean lifecycle and its relation to background conditions were analyzed with a composite method. In a typical example at 200 hPa, Kelvin waves appear over the Indian Ocean and western Pacific, propagate eastward through westerly basic winds, decrease over South America, and then accelerate eastward. Their vertical structure has divergence in the upper and middle troposphere and weak convergence in the lower troposphere, tilting eastward with height. At 100 hPa, Kelvin waves typically propagate eastward in easterly basic winds and then decrease over a region between the Indian Ocean and western Pacific Ocean. Kelvin wave signals continuing over South America suggest that some waves first recognized in the western hemisphere at 200 hPa propagate upward and eastward near South America, reaching 100 hPa in the eastern hemisphere. Temperature anomalies in both hemispheres show the boomerang-like vertical structure while associated with eastward-propagating convections, which suggests at least some waves are convectively coupled