During the emergence of novel coronavirus 2019 (nCoV) outbreak in Wuhan city, China at the end of 2019, there was movement of many airline travelers between Wuhan and Japan, suggesting that the ...Japanese population was at high risk of infection by the virus. Hence, we urgently developed diagnostic systems for detection of 2019 nCoV. Two nested RT-PCR and two real-time RT-PCR assays were adapted for use in Japan. As of February 8, 2020, these assays have successfully detected 25 positive cases of infection in Japan.
A novel betacoronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which caused a large respiratory outbreak in Wuhan, China in December 2019, is currently spreading across many ...countries globally. Here, we show that a TMPRSS2- expressing VeroE6 cell line is highly susceptible to SARS-CoV-2 infection, making it useful for isolating and propagating SARS-CoV-2. Our results reveal that, in common with SARS- and Middle East respiratory syndrome-CoV, SARS-CoV-2 infection is enhanced by TMPRSS2.
Promoter DNA methylation, which occurs on cytosine nucleotides across CpG islands, results in gene silencing and represents a major epigenetic alteration in human cancer. Methylation‐specific PCR can ...amplify these modifications as markers in cancer cells. In the present work, we rigorously review the published literatures describing DNA methylation in the promoters of critical tumor suppressor genes; detection of promoter DNA methylation in various body fluids permits early detection of cancer cells during perioperative courses of clinical treatment. The latest whole‐genome comprehensive explorations identified excellent epigenetic biomarkers that could be detected at high frequency with high specificity; these biomarkers, which are designated highly relevant methylation genes (HRMG), permit the discrimination of tumor tissues from the corresponding normal tissues; these markers are also associated with unique cancer phenotypes, including dismal prognosis. In humans, HRMG include the CDO1, GSHR, RASSF1 and SFRP1 genes, with these markers permitting discrimination depending on the organs tested. The combination of several HRMG increased the early detection of cancer and exhibited reliable surveillance potential in human body fluids. Cancer clinics using such epigenetic biomarkers are entering a new era of enhanced decision‐making with the potential for improved cancer prognosis.
This is a review paper describing molecular diagnostics of cancer using DNA methylation. DNA methylation has been recently focused on in relation to liquid biopsy in various cancers. It is a promising candidate to improve cancer treatment and patient prognosis.
In this study, the anti–severe acute respiratory syndrome coronavirus‐2 (anti‐SARS‐CoV‐2) activity of mycophenolic acid (MPA) and IMD‐0354 was analyzed. These compounds were chosen based on their ...antiviral activities against other coronaviruses. Because they also inhibit dengue virus (DENV) infection, other anti‐DENV compounds/drugs were also assessed. On SARS‐CoV‐2‐infected VeroE6/TMPRSS2 monolayers, both MPA and IMD‐0354, but not other anti‐DENV compounds/drugs, showed significant anti‐SARS‐CoV‐2 activity. Although MPA reduced the viral RNA level by only approximately 100‐fold, its half maximal effective concentration was as low as 0.87 µ
m, which is easily achievable at therapeutic doses of mycophenolate mofetil. MPA targets the coronaviral papain‐like protease and an in‐depth study on its mechanism of action would be useful in the development of novel anti‐SARS‐CoV‐2 drugs.
Development of solid cancer depends on escape from host immunosurveillance. Various types of immune cells contribute to tumor-induced immune suppression, including tumor associated macrophages, ...regulatory T cells, type 2 NKT cells, and myeloid-derived suppressor cells (MDSCs). Growing body of evidences shows that MDSCs play pivotal roles among these immunosuppressive cells in multiple steps of cancer progression. MDSCs are immature myeloid cells that arise from myeloid progenitor cells and comprise a heterogeneous immune cell population. MDSCs are characterized by the ability to suppress both adaptive and innate immunities mainly through direct inhibition of the cytotoxic functions of T cells and NK cells. In clinical settings, the number of circulating MDSCs is associated with clinical stages and response to treatment in several cancers. Moreover, MDSCs are reported to contribute to chemoresistant phenotype. Collectively, targeting MDSCs could potentially provide a rationale for novel treatment strategies in cancer. This review summarizes recent understandings of MDSCs in cancer and discusses promissing clinical approaches in cancer patients.
The nucleolus is the largest structure in the nucleus, and it plays roles in mediating cellular stress responses and regulating cell proliferation, as well as in ribosome biosynthesis. The nucleolus ...is composed of a variety of nucleolar factors that interact with each other in a complex manner to enable its function. Many viral proteins interact with nucleolar factors as well, affecting cellular morphology and function. Here, to investigate the association between mumps virus (MuV) infection and the nucleolus, we evaluated the necessity of nucleolar factors for MuV proliferation by performing a knockdown of these factors with small interfering (si)RNAs. Our results reveal that suppressing the expression of Treacle, which is required for ribosome biosynthesis, reduced the proliferative potential of MuV. Additionally, the one-step growth kinetics results indicate that Treacle knockdown did not affect the viral RNA and protein synthesis of MuV, but it did impair the production of infectious virus particles. Viral matrix protein (M) was considered a candidate Treacle interaction partner because it functions in the process of particle formation in the viral life cycle and is partially localized in the nucleolus. Our data confirm that MuV M can interact with Treacle and colocalize with it in the nucleolus. Furthermore, we found that viral infection induces relocalization of Treacle in the nucleus. Together, these findings suggest that interaction with Treacle in the nucleolus is important for the M protein to exert its functions late in the MuV life cycle.
The nucleolus, which is the site of ribosome biosynthesis, is a target organelle for many viruses. It is increasingly evident that viruses can favor their own replication and multiplication by interacting with various nucleolar factors. In this study, we found that the nucleolar protein Treacle, known to function in the transcription and processing of pre-rRNA, is required for the efficient propagation of mumps virus (MuV). Specifically, our data indicate that Treacle is not involved in viral RNA or protein synthesis but is important in the processes leading to viral particle production in MuV infection. Additionally, we determined that MuV matrix protein (M), which functions mainly in viral particle assembly and budding, colocalized and interacted with Treacle. Furthermore, we found that Treacle is distributed throughout the nucleus in MuV-infected cells. Our research shows that the interaction between M and Treacle supports efficient viral growth in the late stage of MuV infection.
Abstract. Purpose In clinical settings, patients with knee osteoarthritis often complain of pain at gait initiation. In the present study, we aimed to determine the differences in the center of foot ...pressure and lower extremity muscle activity at gait initiation in healthy volunteers compared to patients with medial knee osteoarthritis. Participants and Methods The study comprised of 10 females without medial knee osteoarthritis (healthy group) and 10 females with medial knee osteoarthritis (medial knee osteoarthritis group). We measured the center of foot pressure trajectory and muscle activity onset times of the tibialis anterior and internal gastrocnemius at gait initiation. Moreover, we examined the effects of insole use in the medial knee osteoarthritis group. Results The posterior center of foot pressure displacement was significantly smaller in the medial knee osteoarthritis group (barefoot and insole) than in the healthy group. The anterior center of foot pressure displacement significantly improved with insole use. The muscle activity onset time of the tibialis anterior was significantly delayed in the medial knee osteoarthritis group (barefoot) than in the healthy group. Conclusion Postural control decreased at gait initiation in the medial knee osteoarthritis group.
Although the photosynthetic reaction center is well conserved among different cyanobacterial species, the modes of metabolism, e.g. respiratory, nitrogen and carbon metabolism and their mutual ...interaction, are quite diverse. To explore such uniformity and diversity among cyanobacteria, here we compare the influence of the light environment on the condition of photosynthetic electron transport through Chl fluorescence measurement of six cyanobacterial species grown under the same photon flux densities and at the same temperature. In the dark or under weak light, up to growth light, a large difference in the plastoquinone (PQ) redox condition was observed among different cyanobacterial species. The observed difference indicates that the degree of interaction between respiratory electron transfer and photosynthetic electron transfer differs among different cyanobacterial species. The variation could not be ascribed to the phylogenetic differences but possibly to the light environment of the original habitat. On the other hand, changes in the redox condition of PQ were essentially identical among different species at photon flux densities higher than the growth light. We further analyzed the response to high light by using a typical energy allocation model and found that 'non-regulated' thermal dissipation was increased under high-light conditions in all cyanobacterial species tested. We assume that such 'non-regulated' thermal dissipation may be an important 'regulatory' mechanism in the acclimation of cyanobacterial cells to high-light conditions.
Mumps virus (MuV) is the etiological agent of mumps, a disease characterized by painful swelling of the parotid glands and often accompanied by severe complications. To understand the molecular ...mechanism of MuV infection, a functional analysis of the involved host factors is required. However, little is known about the host factors involved in MuV infection, especially those involved in the late stage of infection. Here, we identified 638 host proteins that have close proximity to MuV glycoproteins, which are a major component of the viral particles, by proximity labeling and examined comprehensive protein-protein interaction networks of the host proteins. From siRNA screening and immunoprecipitation results, we found that a SNARE subfamily protein, USE1, bound specifically to the MuV fusion (F) protein and was important for MuV propagation. In addition, USE1 plays a role in complete N-linked glycosylation and expression of the MuV F protein.
Purpose To quantitatively evaluate smoothness during standing and sitting motion analysis using an accelerometer and to clarify the relationship between indices. Participants and Methods Seventeen ...healthy males participated in this study. We attached a 9-axis motion sensor to the spinous process of the third lumbar spine and measured the acceleration of standing and sitting motions under normal and unstable conditions. We estimated and compared the root mean square and entropy in the lateral, vertical, longitudinal, and triaxial composite directions. Results On comparing both conditions, the unstable condition indices were significantly high, except for the lateral direction of entropy. The root mean square was significantly negatively correlated with entropy under normal conditions. Conclusion The study results suggested that the acceleration index quantitatively evaluates motion smoothness. Since each index had different characteristics, the motion-specific index was observed to be significant.
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