Effects of ribosomes on the kinetics of Qβ replication

AbstractBacteriophage Qβ utilizes some host cell translation factors during replication. Previously, we constructed a kinetic model that explains replication of long RNA molecules by Qβ replicase. Here, we expanded the previous kinetic model to include the effects of ribosome concentration on RNA replication. The expanded model quantitatively explained single- and double-strand formation kinetics during replication with various ribosome concentrations for two artificial long RNAs. This expanded model and the knowledge obtained in this study provide useful frameworks to understand the precise replication mechanism of Qβ replicase with ribosomes and to design amplifiable RNA genomes in translation-coupling systems

Geochemistry and Sm‐Nd chronology of a Stannern‐group eucrite, Northwest Africa 7188

We report the results of a detailed study of the basaltic eucrite Northwest Africa (NWA) 7188, including its mineralogical and bulk geochemical characteristics, oxygen isotopic composition, and 147,146Sm‐143,142Nd mineral isochron ages. The texture and chemical composition of pyroxene and plagioclase demonstrate that NWA 7188 is a monomict eucrite with a metamorphic grade of type 4. The oxygen isotopic composition and the Fe/Mn ratios of pyroxene confirmed that NWA 7188 belongs to the howardite–eucrite–diogenite meteorite suite, generally considered to originate from asteroid 4 Vesta. Whole‐rock TiO2, La, and Hf concentrations and a CI chondrite‐normalized rare earth element pattern are in good agreement with those of representative Stannern‐group eucrites. The 147,146Sm‐143,142Nd isochrons for NWA 7188 yielded ages of 4582 ± 190 and 4554 +17/−19 Ma, respectively. The closure temperature of the Sm‐Nd system for different fractions of NWA 7188 was estimated to be >865 °C, suggesting that the Sm‐Nd decay system has either been resistant to reheating at ~800 °C during the global metamorphism or only partially reset. Therefore, the 146Sm‐142Nd age of NWA 7188 corresponds to the period of initial crystallization of basaltic magmas and/or global metamorphism on the parent body, and is unlikely to reflect Sm‐Nd disturbance by late reheating and impact events. In either case, NWA 7188 is a rare Stannern‐group eucrite that preserves the chronological information regarding the initial crustal evolution of Vesta

Adrenocorticotropic hormone at pathophysiological concentration modulates the proliferation and differentiation of bone cells

SummaryBackground/purposeAdrenocorticotropic hormone (ACTH) plays a vital role in maintaining the function of the hypothalamic–pituitary–adrenal axis. Recent studies have demonstrated that ACTH directly affects the proliferation and differentiation of bone cells. However, the ACTH concentrations used in these studies appear to be markedly higher than the physiological concentrations. Here, we investigated whether ACTH at pathophysiological concentration affects the proliferation and differentiation of osteoblasts and osteoclasts.Materials and methodsWe evaluated the effect of ACTH at pathophysiological concentration on osteoclasts using tartrate-resistant acid phosphatase staining and on osteoblasts using alkaline phosphatase activity assay. Additionally, we conducted reverse transcriptase-polymerase chain reaction analysis.ResultsWe found that at pathophysiological concentration, ACTH does not affect osteoblast proliferation and inhibits osteoblast differentiation. Moreover, we showed that at pathophysiological concentration, ACTH does not affect the proliferation of bone marrow macrophages, but promotes differentiation of osteoclasts and induces expression of genes involved in bone resorption.ConclusionTaken together, our findings suggest that ACTH modulates the proliferation and differentiation of bone cells in vitro at pathophysiological concentration

Characteristic expression of HTLV-1 basic zipper factor (HBZ) transcripts in HTLV-1 provirus-positive cells

<p>Abstract</p> <p>Background</p> <p>HTLV-1 causes adult T-cell leukemia (ATL). Although there have been many studies on the oncogenesis of the viral protein Tax, the precise oncogenic mechanism remains to be elucidated. Recently, a new viral factor, HTLV-1 basic Zip factor (HBZ), encoded from the minus strand mRNA was discovered and the current models of Tax-centered ATL cell pathogenesis are in conflict with this discovery. HBZs consisting of non-spliced and spliced isoforms (HBZ-SI) are thought to be implicated in viral replication and T-cell proliferation but there is little evidence on the HBZ expression profile on a large scale.</p> <p>Results</p> <p>To investigate the role of HBZ-SI in HTLV-1 provirus-positive cells, the HBZ-SI and Tax mRNA loads in samples with a mixture of infected and non-infected cells were measured and then adjusted by dividing by the HTLV-I proviral load. We show here that the HBZ-SI mRNA level is 4-fold higher than non-spliced HBZ and is expressed by almost all cells harboring HTLV-1 provirus with variable intensity. The proviral-adjusted HBZ-SI and Tax quantification revealed a characteristic imbalanced expression feature of high HBZ and low Tax expression levels in primary ATL cells or high HBZ and very high Tax levels in HTLV-1-related cell lines (cell lines) compared with a standard expression profile of low HBZ and low Tax in infected cells. Interestingly, according to the mutual Tax and HBZ expression status, HTLV-1-related cell lines were subcategorized into two groups, an ATL cell type with high HBZ and low Tax levels and another type with high Tax and either high or low HBZ, which was closely related to its cell origin.</p> <p>Conclusion</p> <p>This is the first comprehensive study to evaluate the mutual expression profile of HBZ and Tax in provirus-positive cells, revealing that there are quantitative and relative characteristic features among infected cells, primary ATL cells, and cell lines.</p

Public Interest and Accessibility of Telehealth in Japan: Retrospective Analysis Using Google Trends and National Surveillance

Background: Recently, the use of telehealth for patient treatment under the COVID-19 pandemic has gained interest around the world. As a result, many infodemiology and infoveillance studies using web-based sources such as Google Trends were reported, focusing on the first wave of the COVID-19 pandemic. Although public interest in telehealth has increased in many countries during this time, the long-term interest has remained unknown among people living in Japan. Moreover, various mobile telehealth apps have become available for remote areas in the COVID-19 era, but the accessibility of these apps in epidemic versus nonepidemic regions is unknown.Objective: We aimed to investigate the public interest in telehealth during the first pandemic wave and after the wave in the first part of this study, and the accessibility of medical institutions using telehealth in the epidemic and nonepidemic regions, in the second part.Methods: We examined and compared the first wave and after the wave with regards to severe cases, number of deaths, relative search volume (RSV) of telehealth and COVID-19, and the correlation between RSV and COVID-19 cases, using open sources such as Google Trends and the Japanese Ministry of Health, Labour and Welfare (JMHLW) data. The weekly mean and the week-over-week change rates of RSV and COVID-19 cases were used to examine the correlation coefficients. In the second part, the prevalence of COVID-19 cases, severe cases, number of deaths, and the telehealth accessibility rate were compared between epidemic regions and nonepidemic regions, using the JMHLW data. We also examined the regional correlation between telehealth accessibility and the prevalence of COVID-19 cases.Results: Among the 83 weeks with 5 pandemic waves, the overall mean for the RSV of telehealth and COVID-19 was 11.3 (95% CI 8.0-14.6) and 30.7 (95% CI 27.2-34.2), respectively. The proportion of severe cases (26.54% vs 18.16%; P<.001), deaths (5.33% vs 0.99%; P<.001), RSV of telehealth (mean 33.1, 95% CI 16.2-50.0 vs mean 7.3, 95% CI 6.7-8.0; P<.001), and RSV of COVID-19 (mean 52.1, 95% CI 38.3-65.9 vs mean 26.3, 95% CI 24.4-29.2; P<.001) was significantly higher in the first wave compared to after the wave. In the correlation analysis, the public interest in telehealth was 0.899 in the first wave and –0.300 overall. In Japan, the accessibility of telehealth using mobile apps was significantly higher in epidemic regions compared to nonepidemic regions in both hospitals (3.8% vs 2.0%; P=.004) and general clinics (5.2% vs 3.1%; P<.001). In the regional correlation analysis, telehealth accessibility using mobile apps was 0.497 in hospitals and 0.629 in general clinics.Conclusions: Although there was no long-term correlation between the public interest in telehealth and COVID-19, there was a regional correlation between mobile telehealth app accessibility in Japan, especially for general clinics. We also revealed that epidemic regions had higher mobile telehealth app accessibility. Further studies about the actual use of telehealth and its effect after the COVID-19 pandemic are necessary

Outburst of LS V+44 17 Observed by MAXI and RXTE, and Discovery of a Dip Structure in the Pulse Profile

We report on the first observation of an X-ray outburst of a Be/X-ray binary pulsar LS V +44 17/RX J0440.9+4431, and the discovery of an absorption dip structure in the pulse profile. An outburst of this source was discovered by MAXI GSC in 2010 April. It was the first detection of the transient activity of LS V +44 17 since the source was identified as a Be/X-ray binary in 1997. From the data of the follow-up RXTE observation near the peak of the outburst, we found a narrow dip structure in its pulse profile which was clearer in the lower energy bands. The pulse-phase-averaged energy spectra in the 3$-$100 keV band can be fitted with a continuum model containing a power-law function with an exponential cutoff and a blackbody component, which are modified at low energy by an absorption component. A weak iron K$\alpha$ emission line is also detected in the spectra. From the pulse-phase-resolved spectroscopy we found that the absorption column density at the dip phase was much higher than those in the other phases. The dip was not seen in the subsequent RXTE observations at lower flux levels. These results suggest that the dip in the pulse profile originates from the eclipse of the radiation from the neutron star by the accretion column.Comment: 18 pages, 7 figures, accepted for publication in PAS

Pericardial Mesothelioma in a Dog: The Feasibility of Ultrasonography in Monitoring Tumor Progression

A 6-year-old neutered male Yorkshire Terrier presented with recurrent pericardial effusion. Although clinical examinations including computed tomography were inconclusive, an exploratory thoracotomy revealed multiple small nodules and plaques on the inner surface of the pericardial sac (Day 1). A subtotal pericardiectomy was performed to prevent cardiac tamponade due to the increasing pericardial effusion, and the resected section of the pericardium was histopathologically diagnosed with mesothelioma. After surgery, chemotherapy with intrathoracic carboplatin was commenced. During the course of the treatment, a detailed follow-up ultrasonographic scan was performed to detect early lesions disseminated on the pleura, originating from the primary pericardial mesothelioma. On Day 101, the minute pleural nodules, which were disseminated lesions as predicted, were successfully imaged by ultrasonography. As the clinical stage advanced, the nodules were observed to gradually increase in size and number, implying tumor progression. These observations highlight the feasibility of ultrasonography in detecting minute disseminated lesions at an early stage, monitoring tumor progression, and thereby, predicting the prognosis of canine pericardial mesothelioma

Chemosensitivity of three patient-derived primary cultures of canine pericardial mesothelioma by single-agent and combination treatment

IntroductionCanine mesothelioma is a rare malignant tumor that mostly affects body cavities, such as the pericardial and pleural cavities. Chemotherapy plays a crucial role in the treatment of canine mesotheliomas. We aimed to compare the antitumor effects of single-agent and combination chemotherapeutic agents on patient-derived primary cultures of canine pericardial mesothelioma established in this study. We planned to generate xenograft models for future studies.Material and methodsEffusion samples were collected from three dogs with histologically diagnosed pericardial mesothelioma and used for primary culture. Cultured cells were characterized by immunostaining for pan-cytokeratin AE1/AE3, vimentin, Wilms' tumor suppressor gene 1 (WT1), and cytokeratin 5 (CK5). To assess the tumorigenic properties of cells in the effusion and generate a xenograft model, the cell suspension was injected into a severe combined immunodeficient (SCID) mouse either subcutaneously (SC) or intraperitoneally (IP). Lastly, chemosensitivity of established primary cultures against four drugs, doxorubicin, vinorelbine, carboplatin, and gemcitabine, by single-agent treatment as well as combination treatment of carboplatin at a fixed concentration, either 10 or 100 μM, and gemcitabine at different concentrations ranging from 0–1000 μM was assessed by cell viability assay.ResultsPrimary cultures were successfully generated and characterized by dual positivity for AE1/AE3 and vimentin and positive staining for WT-1 and CK5, confirming the mesothelial origin of the cells. In the xenograft models, SC mouse developed a subcutaneous mass, whereas IP mouse developed multiple intraperitoneal nodules. The masses were histopathologically consistent with mesotheliomas. The chemosensitivity assay revealed that carboplatin had the highest anti-tumor effects among the four tested single-agent treatments. Furthermore, carboplatin at 100 μM combined with gemcitabine at clinically relevant doses demonstrated the augmented anti-tumor effects compared to single-agent treatment.Discussion and conclusionPrimary cultures and xenograft models generated in this study could be useful tools for in vitro and in vivo studies of canine mesothelioma. Carboplatin is a highly effective chemotherapeutic agent against canine mesothelioma when used as a sole agent and in combination with gemcitabine

Long-term Monitoring of the Black Hole Binary GX 339-4 in the High/Soft State during the 2010 Outburst with MAXI/GSC

We present the results of monitoring the Galactic black hole candidate GX 339-4 with the Monitor of All-sky X-ray Image (MAXI) / Gas Slit Camera (GSC) in the high/soft state during the outburst in 2010. All the spectra throughout the 8-month period are well reproduced with a model consisting of multi-color disk (MCD) emission and its Comptonization component, whose fraction is <= 25% in the total flux. In spite of the flux variability over a factor of 3, the innermost disk radius is constant at R_in = 61 +/- 2 km for the inclination angle of i = 46 deg and the distance of d=8 kpc. This R_in value is consistent with those of the past measurements with Tenma in the high/soft state. Assuming that the disk extends to the innermost stable circular orbit of a non-spinning black hole, we estimate the black hole mass to be M = 6.8 +/- 0.2 M_sun for i = 46 deg and d = 8 kpc, which is consistent with that estimated from the Suzaku observation of the previous low/hard state. Further combined with the mass function, we obtain the mass constraint of 4.3 M_sun < M < 13.3 M_sun for the allowed range of d = 6-15 kpc and i < 60 deg. We also discuss the spin parameter of the black hole in GX 339-4 by applying relativistic accretion disk models to the Swift/XRT data.Comment: 9 pages, 8 figures, accepted for publication in PASJ (Suzaku+MAXI special issue