ABSTRACT We have conducted a spectral line survey observation in the 3 mm band toward the low-metallicity dwarf galaxy IC10 with the 45 m radio telescope of the Nobeyama Radio Observatory to explore ...its chemical composition at a molecular-cloud scale (∼80 pc). The CS, SO, CCH, HCN, HCO+, and HNC lines are detected for the first time in this galaxy in addition to the CO and 13CO lines, while the c-C3H2, CH3OH, CN, C18O, and N2H+ lines are not detected. The spectral intensity pattern is found to be similar to those observed toward molecular clouds in the Large Magellanic Cloud (LMC), whose metallicity is as low as IC10. Nitrogen-bearing species are deficient in comparison with the Galactic molecular clouds due to a lower elemental abundance of nitrogen. CCH is abundant in comparison with Galactic translucent clouds, whereas CH3OH may be deficient. These characteristic trends for CCH and CH3OH are also seen in the LMC, and seem to originate from photodissociation regions more extended in the peripheries of molecular clouds due to the lower metallicity condition.
Purpose We investigated the feasibility and validity of intraoperative fluorescence imaging using indocyanine green for the detection of sentinel lymph nodes and lymphatic vessels during open ...prostatectomy. Materials and Methods Indocyanine green was injected into the prostate under transrectal ultrasound guidance just before surgery. Intraoperative fluorescence imaging was performed using a near-infrared camera system in 66 consecutive patients with clinically localized prostate cancer after a 10-patient pilot test to optimize indocyanine green dosing, observation timing and injection method. Lymphatic vessels were visualized and followed to identify the sentinel lymph nodes. Confirmatory pelvic lymph node dissection including all fluorescent nodes and open radical prostatectomy were performed in all patients. Results Lymphatic vessels were successfully visualized in 65 patients (98%) and sentinel lymph nodes in 64 patients (97%). Sentinel lymph nodes were located in the obturator fossa, internal and external iliac regions, and rarely in the common iliac and presacral regions. A median of 4 sentinel lymph nodes per patient was detected. Three lymphatic pathways, the paravesical, internal and lateral routes, were identified. Pathological examination revealed metastases to 9 sentinel lymph nodes in 6 patients (9%). All pathologically positive lymph nodes were detected as sentinel lymph nodes using this imaging. No adverse reactions due to the use of indocyanine green were observed. Conclusions Intraoperative fluorescence imaging using indocyanine green during open prostatectomy enables the detection of lymphatic vessels and sentinel lymph nodes with high sensitivity. This novel method is technically feasible, safe and easy to apply with minimal additional operative time.
The systemic manifestations of coronavirus disease 2019 (COVID-19) include hyperinflammatory reactions in various organs. Recent studies showed evidence for the frequent involvement of central ...nervous system in affected patients; however, little is known about clinical features of cerebrovascular diseases in childhood-onset COVID-19.
A 10-year-old boy recovered from SARS-CoV-2 infection without complication. On 14 days after infection, he presented with loss of consciousness. A head computed tomography detected a ruptured cerebral aneurysm at the left posterior cerebral artery accompanying subarachnoid hemorrhage (SAH). Immediate surgical intervention did not rescue the patient, resulting in the demise 7 days after admission. Serological and genetic tests excluded the diagnosis of vasculitis and connective tissue disorders. Retrospective analysis showed markedly higher levels of interleukin (IL)-1β, IL-6 and IL-8 in the cerebrospinal fluid than the serum sample concurrently obtained. A review of literature indicated that adult patients with COVID-19 have a risk for the later development of SAH during the convalescent phase of COVID-19.
SAH is a severe complication of COVID-19 in children and adults who have asymptomatic cerebrovascular aneurysms. The markedly high levels of cytokines detected in the cerebrospinal fluid suggested that intracranial hyperinflammatory condition might be one of the possible mechanisms involved in the rupture of a preexisting cerebrovascular aneurysms.
Autothermal thermophilic aerobic digestion (ATAD) is used to treat human excreta hygienically. We previously reported a unique full-scale ATAD, showing distinctive bacterial community transitions and ...producing high-nitrogen-content liquid fertilizer; nevertheless, the mechanism remains unclear. One hypothesis involves using a gas-inducing (GI) agitator. We designed a lab-scale GI system and compared it with a disk-turbine (DT) agitator system by mimicking the temperature shift of full-scale ATAD. The agitation system and its agitation speed greatly affected physicochemical properties and bacterial community structure. GI system at 1000 rpm (GI1000; high total carbon removal efficiency, 88.3%), with few nitrifying and denitrifying bacteria, maintained a high ammoniacal nitrogen concentration and had more shared operational taxonomic units related to Acinetobacter sp., Arcobacter sp., and Longimicrobium sp. with the full-scale ATAD compared with the GI system at 490 rpm and DT system at 1000 rpm (DT1000). Furthermore, DT1000, with a high abundance of nitrifying and denitrifying bacteria such as Alcaligenes aquatilis and Pseudomonas caeni, removed 94.7% total nitrogen with 71.9% total carbon removal efficiency. These results suggested that shear stress and oxygen supply system would change the bacterial community structure, thus affected ATAD performances. Consequently, it is possible that ATAD can be applied for not only production of highly nitrogen-containing liquid fertilizer but also extremely nitrogen removal of wastewater.
•A gas-inducing lab-scale ATAD mimic the unique features of the full-scale ATAD.•Shear force and oxygen supply system would affect ATAD performances drastically.•GI1000 had more similar bacterial community to full-scale system than DT1000.•Nitrogen maintenance and removal occurred in GI1000 and DT1000, respectively.•ATAD can be applied for nitrogen-fertilizer production and nitrogen-removal process.
Denosumab is an anti-bone resorptive drug consisting of complete human monoclonal antibodies that targets receptor activator of nuclear factor κB ligand (RANKL), which is responsible for osteoclast ...formation. The drug has been adapted for bone diseases, such as osteoporosis and bone metastasis related to cancer, but is not used for alveolar bone destruction related to periodontitis. In the present study, we aimed to clarify whether denosumab prevents bone destruction associated with lipopolysaccharide (LPS)-induced calvaria inflammation and experimental periodontitis in model mice. Denosumab does not bind to mouse RANKL, thus we used anti-mouse monoclonal RANKL antibodies. We also examined the inhibitory effects toward bone destruction of another anti-bone resorptive drug zoledronate, a nitrogen-containing bisphosphonate. Local administration of anti- RANKL antibodies into the calvaria area inhibited LPS-induced osteoclast formation and bone destruction, while zoledronate inhibited bone destruction but not osteoclast formation due to its different action mechanism. In periodontitis model mice, in which the second molars were ligated with a silk suture to induce inflammation, intraperitoneal administration of anti-RANKL antibodies significantly inhibited alveolar bone destruction and tooth root exposure. On the other hand, zoledronate only weakly repressed alveolar bone destruction and failed to inhibit root exposure. These results suggest that denosumab is a promising candidate to prevent alveolar bone destruction associated with periodontitis.
Retinal pigment epithelium (RPE) cells show heterogeneous levels of pigmentation when cultured in vitro. To know whether their color in appearance is correlated with the function of the RPE, we ...analyzed the color intensities of human-induced pluripotent stem cell-derived RPE cells (iPSC-RPE) together with the gene expression profile at the single-cell level. For this purpose, we utilized our recent invention, Automated Live imaging and cell Picking System (ALPS), which enabled photographing each cell before RNA-sequencing analysis to profile the gene expression of each cell. While our iPSC-RPE were categorized into four clusters by gene expression, the color intensity of iPSC-RPE did not project any specific gene expression profiles. We reasoned this by less correlation between the actual color and the gene expressions that directly define the level of pigmentation, from which we hypothesized the color of RPE cells may be a temporal condition not strongly indicating the functional characteristics of the RPE.
Abstract
The use of sentinel node biopsy (SNB) following neoadjuvant chemotherapy (NAC) for patients with cN1 breast cancer is controversial. Improvements of negative predictive value (NPV) by ...axillary ultrasound (AUS), which corresponds to the accurate prediction rate of node-negative status after NAC, would lead to decreased FNR of SNB following NAC. In this study, we retrospectively investigated the accurate prediction rate of NPV by AUS after NAC in patients with cytologically node-positive breast cancer treated between January 2012 and December 2016. Of 279 eligible patients, the NPV was 49.2% in all patients, but varied significantly by tumor subtype (
p
< 0.001) and tumor response determined by magnetic resonance imaging (MRI) (
p
= 0.0003). Of the 23 patients with clinically node negative (ycN0) by AUS and clinical complete response in primary lesion by MRI, the NPV was 100% in patients with HR±/HER2+ or HR−/HER2− breast cancer. In conclusion, regarding FNR reduction post-NAC, it will be of clinical value to take tumor subtype and primary tumor response using MRI into account to identify patients for SNB after NAC.
Cigarette smoking is a major risk factor for atherosclerosis. We previously reported that DNA damage was accumulated in atherosclerotic plaque, and was increased in human mononuclear cells by ...smoking. As vascular endothelial cells are known to modulate inflammation, we investigated the mechanism by which smoking activates innate immunity in endothelial cells focusing on DNA damage. Furthermore, we sought to characterize the plasma level of cell-free DNA (cfDNA), a result of mitochondrial and/or genomic DNA damage, as a biomarker for atherosclerosis. Cigarette smoke extract (CSE) increased DNA damage in the nucleus and mitochondria in human endothelial cells. Mitochondrial damage induced minority mitochondrial outer membrane permeabilization, which was insufficient for cell death but instead led to nuclear DNA damage. DNA fragments, derived from the nucleus and mitochondria, were accumulated in the cytosol, and caused a persistent increase in IL-6 mRNA expression via the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway. cfDNA, quantified with quantitative PCR in culture medium was increased by CSE. Consistent with in vitro results, plasma mitochondrial cfDNA (mt-cfDNA) and nuclear cfDNA (n-cfDNA) were increased in young healthy smokers compared with age-matched nonsmokers. Additionally, both mt-cfDNA and n-cfDNA were significantly increased in patients with atherosclerosis compared with the normal controls. Our multivariate analysis revealed that only mt-cfDNA predicted the risk of atherosclerosis. In conclusion, accumulated cytosolic DNA caused by cigarette smoke and the resultant activation of the cGAS-STING pathway may be a mechanism of atherosclerosis development. The plasma level of mt-cfDNA, possibly as a result of DNA damage, may be a useful biomarker for atherosclerosis.
Cells sense pathogen-derived double-stranded RNA (dsRNA) as nonself. To avoid autoimmune activation by self dsRNA, cells utilize A-to-I editing by adenosine deaminase acting on RNA 1 (ADAR1) to ...disrupt dsRNA structures. Considering that viruses have evolved to exploit host machinery, A-to-I editing could benefit innate immune evasion by viruses. Borna disease virus (BoDV), a nuclear-replicating RNA virus, may require escape from nonself RNA-sensing and immune responses to establish persistent infection in the nucleus; however, the strategy by which BoDV evades nonself recognition is unclear. Here, we evaluated the involvement of ADARs in BoDV infection. The infection efficiency of BoDV was markedly decreased in both ADAR1 and ADAR2 knockdown cells at the early phase of infection. Microarray analysis using ADAR2 knockdown cells revealed that ADAR2 reduces immune responses even in the absence of infection. Knockdown of ADAR2 but not ADAR1 significantly reduced the spread and titer of BoDV in infected cells. Furthermore, ADAR2 knockout decreased the infection efficiency of BoDV, and overexpression of ADAR2 rescued the reduced infectivity in ADAR2 knockdown cells. However, the growth of influenza A virus, which causes acute infection in the nucleus, was not affected by ADAR2 knockdown. Moreover, ADAR2 bound to BoDV genomic RNA and induced A-to-G mutations in the genomes of persistently infected cells. We finally demonstrated that BoDV produced in ADAR2 knockdown cells induces stronger innate immune responses than those produced in wild-type cells. Taken together, our results suggest that BoDV utilizes ADAR2 to edit its genome to appear as "self" RNA in order to maintain persistent infection in the nucleus.
Cells use the editing activity of adenosine deaminase acting on RNA proteins (ADARs) to prevent autoimmune responses induced by self dsRNA, but viruses can exploit this process to their advantage. Borna disease virus (BoDV), a nuclear-replicating RNA virus, must escape nonself RNA sensing by the host to establish persistent infection in the nucleus. We evaluated whether BoDV utilizes ADARs to prevent innate immune induction. ADAR2 plays a key role throughout the BoDV life cycle. ADAR2 knockdown reduced A-to-I editing of BoDV genomic RNA, leading to the induction of a strong innate immune response. These data suggest that BoDV exploits ADAR2 to edit nonself genomic RNA to appear as self RNA for innate immune evasion and establishment of persistent infection.
Borna disease virus (BoDV), a nonsegmented, negative‐sense RNA virus, establishes persistent infection and replicates in the cell nucleus. Since BoDV genomic RNA exists as episomal RNA, the host ...genome is not invaded by BoDV infection. These unique features make BoDV a promising gene delivery system as an RNA virus‐based episomal vector (REVec). Previously, the stable expression of genes of interest in vitro and in vivo using a REVec was reported. For the clinical application of a REVec, the fundamental properties under various physical and chemical conditions must be determined to develop purification processes, supply chains, and biosafety management. This study investigated the effects of the following conditions on the inducibility of transmission‐defective ΔG‐REVec: freeze–thaw cycles, dehydration, UV, temperature, pH, and reagents for virucides and laboratory experiments. Although the titer of ΔG‐REVec was not influenced by the freeze–thaw process or 5 minute incubation at ≤50°C, ΔG‐REVec was significantly inactivated by incubation at ≥70°C for 5 minutes. The induction titer of ΔG‐REVec was decreased by long‐term incubation, dehydration, and UV irradiation in a temperature‐ and time‐dependent manner. ΔG‐REVec was sensitive to lower pH and inactivated by chemical reagents under general conditions. These results provide important knowledge for developing the clinical use of REVec and biosafety management.
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