X-ray spectral variations of Circinus X-1 observed with NICER throughout an entire orbital cycle

Circinus X-1 (Cir X-1) is a neutron star binary with an elliptical orbit of 16.6~days. The source is unique for its extreme youth, providing a key to understanding early binary evolution. However, its X-ray variability is too complex to reach a clear interpretation. We conducted the first high cadence (every 4 hours on average) observations covering one entire orbit using the NICER X-ray telescope. The X-ray flux behavior can be divided into stable, dip, and flaring phases. The X-ray spectra in all phases can be described by a common model consisting of a partially covered disk black body emission and the line features from a highly-ionized photo-ionized plasma. The spectral change over the orbit is attributable to rapid changes of the partial covering medium in the line-of-sight and gradual changes of the disk black body emission. Emission lines of the H-like and He-like Mg, Si, S, and Fe are detected, most prominently in the dip phase. The Fe emission lines change to absorption in the course of the transition from the dip phase to the flaring phase. The estimated ionization degree indicates no significant changes, suggesting that the photo-ionized plasma is stable over the orbit. We propose a simple model in which the disk black body emission is partially blocked by such a local medium in the line-of-sight that has spatial structures depending on the azimuth of the accretion disk. Emission lines upon the continuum emission are from the photo-ionized plasma located outside of the blocking material.Comment: Accepted for publication in ApJ, 16 pages, 7 figure

Conversion of Normal Ly-1-Positive B-Lineage Cells into Ly-1-Positive Macrophages in Long-Term Bone Marrow Cultures

We obtained eight different cell lines in the long-term bone marrow culture system that showed a germ-line configuration of the joining (J) region segments of the Ig heavy-chain (IgH) genes. Their surface markers were CD45R+, Ly-1+, Lyb-2+, cIgM-, sIgM-, Ia-, Thy-1-, Mac-1-, and IL-2R (Tac)+. Use of very young mice and the presence of IL-5 were important for preferential promotion of the survival of B-lineage lymphocytes bearing the Ly-1 markers. When we treated two of them (J8 and J10) with 5-azacytidine for 24 h followed by co-culture with stromal cells and IL-.5, they became Ly-1+, sIgM+ B cells, and Ly-1+, Mac-1+ macrophagelike cells, respectively. After other early lymphoid lines (J1, J8, and J13) were maintained by co-culture with ST2 and IL-5 for more than a year, they showed a heterogeneous DNA rearrangement profile of the J region segment of the IgH gene, although only J13 rearranged the κ-light chain gene. Northern blot analysis revealed that these cell lines expressed Cμ-mRNA, and λ5-mRNA, consistent with normal pre-B cells. Intriguingly, J1, J8, and J13 expressed c-fms mRNA constitutively. When J13 cells were co-cultured with ST2 and GM-CSF in place of ST2 and IL-5, they acquired Mac-1 expression and retained Ly-1 expression. They were morphologically macrophages, nonspecific-esterase-positive, and showed phagocytosis of latex beads. These results support evidence for a close relationship between the myeloid and Ly-1+ B-cell pathways of differentiation, and indicate that our IL- 5-dependent clones are multipotential intermediates in differentiation from pro-B cells to B cells and macrophages

Induction of cyclooxygenase-2 in human synovial cells by β2-microglobulin

Induction of cyclooxygenase-2 in human synovial cells by β2-microglobulin.BackgroundProstaglandins (PGs) are important mediators of inflammation in arthritis. We evaluated the role of the cyclooxygenase-2 (COX-2) enzyme, which regulates PG biosynthesis, in osteoarthropathy associated with hemodialysis-associated amyloidosis (HAA) by characterizing COX-2 expression in β2-microglobulin–treated human synovial cells.MethodsWe examined the effects of β2-microglobulin (β2m), a major constituent protein of amyloid fibrils in HAA, on the COX-2 protein and mRNA expression in human synovial cells using Western blot and reverse transcriptase-polymerase chain reaction.Resultsβ2m selectively increased the biosynthesis of COX-2 protein and induction of COX-2 mRNA in a dose-dependent manner. Immunoabsorption of β2m–containing media by anti-β2m–specific antibody abrogated β2m–mediated COX-2 expression on synovial cells. On the other hand, dexamethasone markedly suppressed the induction of COX-2 protein and mRNA in β2m–stimulated synovial cells.ConclusionsOur results suggest that induction of COX-2 expression by β2m may be an important component of the inflammatory process in hemodialysis-associated osteoarthropathy

Transcriptionally linked simultaneous overexpression of P450 genes for broad-spectrum herbicide resistance

雑草が獲得した最強の除草剤抵抗性メカニズムの解明 --解毒酵素の一斉活性化--. 京都大学プレスリリース. 2023-06-14.Broad-spectrum herbicide resistance (BSHR), often linked to weeds with metabolism-based herbicide resistance, poses a threat to food production. Past studies have revealed that overexpression of catalytically promiscuous enzymes explains BSHR in some weeds; however, the mechanism of BSHR expression remains poorly understood. Here, we investigated the molecular basis of high-level resistance to diclofop-methyl in BSHR late watergrass (Echinochloa phyllopogon) found in the United States, which cannot be solely explained by the overexpression of promiscuous cytochrome P450 monooxygenases CYP81A12/21. The BSHR late watergrass line rapidly produced 2 distinct hydroxylated diclofop acids, only 1 of which was the major metabolite produced by CYP81A12/21. RNA-seq and subsequent reverse transcription quantitative PCR (RT-qPCR)-based segregation screening identified the transcriptionally linked overexpression of a gene, CYP709C69, with CYP81A12/21 in the BSHR line. The gene conferred diclofop-methyl resistance in plants and produced another hydroxylated diclofop acid in yeast (Saccharomyces cerevisiae). Unlike CYP81A12/21, CYP709C69 showed no other herbicide-metabolizing function except for a presumed clomazone-activating function. The overexpression of the 3 herbicide-metabolizing genes was also identified in another BSHR late watergrass in Japan, suggesting a convergence of BSHR evolution at the molecular level. Synteny analysis of the P450 genes implied that they are located at mutually independent loci, which supports the idea that a single trans-element regulates the 3 genes. We propose that transcriptionally linked simultaneous overexpression of herbicide-metabolizing genes enhances and broadens the metabolic resistance in weeds. The convergence of the complex mechanism in BSHR late watergrass from 2 countries suggests that BSHR evolved through co-opting a conserved gene regulatory system in late watergrass

Dynamics of proteins with different molecular structures under solution condition

Incoherent quasielastic neutron scattering (iQENS) is a fascinating technique for investigating the internal dynamics of protein. However, low flux of neutron beam, low signal to noise ratio of QENS spectrometers and unavailability of well-established analyzing method have been obstacles for studying internal dynamics under physiological condition (in solution). The recent progress of neutron source and spectrometer provide the fine iQENS profile with high statistics and as well the progress of computational technique enable us to quantitatively reveal the internal dynamic from the obtained iQENS profile. The internal dynamics of two proteins, globular domain protein (GDP) and intrinsically disordered protein (IDP) in solution, were measured with the state-of-the art QENS spectrometer and then revealed with the newly developed analyzing method. It was clarified that the average relaxation rate of IDP was larger than that of GDP and the fraction of mobile H atoms of IDP was also much higher than that of GDP. Combined with the structural analysis and the calculation of solvent accessible surface area of amino acid residue, it was concluded that the internal dynamics were related to the highly solvent exposed amino acid residues depending upon protein’s structure

Dose distribution of intensity-modulated proton therapy with and without a multi-leaf collimator for the treatment of maxillary sinus cancer: a comparative effectiveness study.

BACKGROUND: Severe complications, such as eye damage and dysfunciton of salivary glands, have been reported after radiotherapy among patients with head and neck cancer. Complications such as visual impairment have also been reported after proton therapy with pencil beam scanning (PBS). In the case of PBS, collimation can sharpen the penumbra towards surrounding normal tissue in the low energy region of the proton beam. In the current study, we examined how much the dose to the normal tissue was reduced by when intensity-modulated proton therapy (IMPT) was performed using a multi-leaf collimator (MLC) for patients with maxillary sinus cancer. METHODS: Computed tomography findings of 26 consecutive patients who received photon therapy at Okayama University Hospital were used in this study. We compared D2% of the region of interest (ROI; ROI-D2%) and the mean dose of ROI (ROI-mean) with and without the use of an MLC. The organs at risk (OARs) were the posterior retina, lacrimal gland, eyeball, and parotid gland. IMPT was performed for all patients. The spot size was approximately 5-6 mm at the isocenter. The collimator margin was calculated by enlarging the maximum outline of the target from the beam's eye view and setting the margin to 6 mm. All plans were optimized with the same parameters. RESULTS: The mean of ROI-D2% for the ipsilateral optic nerve was significantly reduced by 0.48 Gy, and the mean of ROI-mean for the ipsilateral optic nerve was significantly reduced by 1.04 Gy. The mean of ROI-mean to the optic chiasm was significantly reduced by 0.70 Gy. The dose to most OARs and the planning at risk volumes were also reduced. CONCLUSIONS: Compared with the plan involving IMPT without an MLC, in the dose plan involving IMPT using an MLC for maxillary sinus cancer, the dose to the optic nerve and optic chiasm were significantly reduced, as measured by the ROI-D2% and the ROI-mean. These findings demonstrate that the use of an MLC during IMPT for maxillary sinus cancer may be useful for preserving vision and preventing complications

Successful Colectomy for Hemorrhagic Colitis with Hemolytic Uremic Syndrome and Acute Encephalopathy due to Escherichia coli O157 Infection

An 81-year-old man was admitted to a primary care hospital due to bloody diarrhea. The findings of abdominal computed tomography indicated ischemic colitis, so conservative therapy was started. On the 4th hospital day, the patient was transferred to our hospital because of renal dysfunction. Physical examination showed clouding of consciousness and abdominal distention. Abdominal computed tomography revealed massive ascites and thickening of the whole colonic wall. With a diagnosis of acute abdomen, an emergent laparotomy was performed. Extended right hemicolectomy was performed because of severe ischemic change and necrosis of the right side of the colon. In the stool culture before the operation, Escherichia coli O157 and verotoxin were found, so this case was diagnosed as hemorrhagic colitis with hemolytic uremic syndrome and acute encephalopathy due to Escherichia coli O157 infection. Postoperatively, the hemolytic uremic syndrome and acute encephalopathy were prolonged. However, with intensive care, the patient recovered and was discharged on the 33rd postoperative day

先天性血友病患者の移行期の実態

【Introduction】Congenital hemophilia is a category of hemorrhagic disease caused by a genetic defect in the production of coagulation factors. It is treated by administering regular coagulation factor injections on an ongoing basis. Hemophilia is a hereditary illness, often causing social and psychological problems as a result of the disease. To analyze the objective effects of hemophilia, we conducted a retrospective analysis in Tokushima University Hospital. 【Result】All ２３ cases were men between the ages of２０and７２. Hemophilia A was present in１７cases, and hemophilia B was present in six. Nineteen out of ２３ cases were severe, and the others were intermediate. Medical assessments were conducted at pediatrics in seven cases and hematology in １６ cases. Adoption of the self-injection technique was not realized in five cases. Seventeen cases were complicated by hemophilic arthropathy, seven with human immunodeficiency virus（HIV）, and １２ with hepatitis C virus. Eight participants were unemployed, and１７were unmarried. 【Discussion】 Many adult hemophilia patients still visit pediatrics in our hospital. Hemophilia in the period of growth between adolescence and young adulthood is often accompanied by life-altering events such as entering higher education, marriage, and work experience. Therefore, collaboration among professionals of multiple occupations, such as doctors, nurses, pharmacists, medical social workers, and clinical psychologists, is essential. Furthermore, there are many cases of HIV and hepatitis C virus infections complicating hemophilia study due to the stigma surrounding HIV-tainted blood. 【Conclusion】It is imperative that we establish a long-term, sustainable, and multi-disciplinary transitional care and medical support system for patients and their families