CO₂-dependent migration and relocation of LCIB, a pyrenoid-peripheral protein in Chlamydomonas reinhardtii

葉緑体タンパク質が働く場所を変化させ光合成の能力を柔軟に維持する仕組みを発見. 京都大学プレスリリース. 2021-12-23.Most microalgae overcome the difficulty of acquiring inorganic carbon (Ci) in aquatic environments by inducing a CO₂-concentrating mechanism (CCM). In the green alga Chlamydomonas reinhardtii, two distinct photosynthetic acclimation states have been described under CO₂-limiting conditions (low-CO₂, LC, and very low-CO₂, VLC). LC-inducible protein B (LCIB), structurally characterized as carbonic anhydrase, localizes in the chloroplast stroma under CO₂-supplied and LC conditions. In VLC conditions, it migrates to aggregate around the pyrenoid, where the CO₂-fixing enzyme Rubisco is enriched. Although the physiological importance of LCIB localization changes in the chloroplast has been shown, factors necessary for the localization changes remain uncertain. Here, we examined the effect of pH, light availability, photosynthetic electron flow, and protein synthesis on the localization changes, along with measuring Ci concentrations. LCIB dispersed or localized in the basal region of the chloroplast stroma at 8.3–15 µM CO₂, whereas LCIB migrated toward the pyrenoid at 6.5 µM CO₂. Furthermore, LCIB relocated toward the pyrenoid at 2.6–3.4 µM CO₂, even in cells in the dark or treated with DCMU and cycloheximide in light. In contrast, in the mutant lacking CCM₁, a master regulator of CCM, LCIB remained dispersed even at 4.3 µM CO₂. Meanwhile, a simultaneous expression of LCIC, an interacting protein of LCIB, induced the localization of several speckled structures at the pyrenoid periphery. These results suggest that the localization changes of LCIB require LCIC and are controlled by CO₂ concentration with ∼7 µM as the boundary

Detection of extended millimeter emission in the host galaxy of 3C273 and its implications for QSO feedback via high dynamic range ALMA imaging

We estimate the amount of negative feedback energy injected into the ISM of the host galaxy of 3C273, a prototypical radio loud quasar. We obtained 93, 233 and 343 GHz continuum images with the Atacama Large Millimeter/Sub-millimeter Array (ALMA). After self calibration and point source subtraction, we reach an image dynamic range of $\sim 85000$ at 93\ GHz, $\sim 39000$ at 233\ GHz and $\sim 2500$ at 343\ GHz. These are currently the highest image dynamic range obtained using ALMA. We detect spatially extended millimeter emission associated with the host galaxy, cospatial with the Extended Emission Line Region (EELR) observed in the optical. The millimeter spectral energy distribution and comparison with centimeter data show that the extended emission cannot be explained by dust thermal emission, synchrotron or thermal bremsstrahlung arising from massive star formation. We interpret the extended millimeter emission as thermal bremsstrahlung from gas directly ionized by the central source. The extended flux indicates that at least $\sim 7\%$ of the bolometric flux of the nuclear source was used to ionize atomic hydrogen in the host galaxy. The ionized gas is estimated to be as massive as $10^{10}$ to $10^{11}\ \mathrm{M_\odot}$, but the molecular gas fraction with respect to the stellar mass is consistent with other ellipticals, suggesting that direct ionization ISM by the QSO may not be sufficient to suppress star formation, or we are witnessing a short timescale before negative feedback becomes observable. The discovery of a radio counterpart to EELRs provides a new pathway to studying the QSO-host ISM interaction

Micro- and nanofluidic technologies for epigenetic profiling

This short review provides an overview of the impact micro- and nanotechnologies can make in studying epigenetic structures. The importance of mapping histone modifications on chromatin prompts us to highlight the complexities and challenges associated with histone mapping, as compared to DNA sequencing. First, the histone code comprised over 30 variations, compared to 4 nucleotides for DNA. Second, whereas DNA can be amplified using polymerase chain reaction, chromatin cannot be amplified, creating challenges in obtaining sufficient material for analysis. Third, while every person has only a single genome, there exist multiple epigenomes in cells of different types and origins. Finally, we summarize existing technologies for performing these types of analyses. Although there are still relatively few examples of micro- and nanofluidic technologies for chromatin analysis, the unique advantages of using such technologies to address inherent challenges in epigenetic studies, such as limited sample material, complex readouts, and the need for high-content screens, make this an area of significant growth and opportunityopen4

Media additives to promote spheroid circularity and compactness in hanging drop platform

Three-dimensional spheroid cultures have become increasingly popular as drug screening platforms, especially with the advent of different high throughput spheroid forming technologies. However, comparing drug efficacy across different cell types in spheroid culture can be difficult due to variations in spheroid morphologies and transport characteristics. Improving the reproducibility of compact, circular spheroids contributes to standardizing and increasing the fidelity of the desired gradient profiles in these drug screening three-dimensional tissue cultures. In this study we discuss the role that circularity and compaction has on spheroids, and demonstrate the impact methylcellulose (MethoCel) and collagen additives in the culture media can contribute to more compact and circular spheroid morphology. We demonstrate that improved spheroid formation is not a simple function of increased viscosity of the different macromolecule additives, suggesting that other macromolecular characteristics contribute to improved spheroid formation. Of the various macromolecular additives tested for hanging drop culture, MethoCel provided the most desirable spheroid formation. Additionally, the higher viscosity of MethoCel-containing media improved the ease of imaging of cellular spheroids within hanging drop cultures by reducing motion-induced image blur.open2

Differences in Attitudes and Practices of Cancer Pain Management between Medical Oncologists and Palliative Care Physicians

This study aimed to evaluate whether there are differences in the attitudes and practices of cancer pain manage-ment between medical oncologists and palliative care physicians. An online nationwide survey was used to collect responses from board-certified medical oncologists and palliative care physicians in Japan. The survey questionnaire comprised 30 questions. The differences in responses between medical oncologists and palliative care physicians were examined. Out of the 1,227 questionnaires sent, 522 (42.5%) were returned. After apply-ing the exclusion criteria, 445 questionnaires (medical oncologists: n = 283; palliative care physicians: n = 162) were retained for analysis. Among the questions about potential barriers to optimal cancer pain man-agement, both medical oncologists and palliative care physicians considered the reluctance of patients to take opioids due to fear of adverse effects as the greatest barrier. Significantly different ratings between medical oncologists and palliative care physicians were observed on 5 of the 8 questions in this area. Significantly differ-ent ratings were observed for all questions concerning pain specialists and their knowledge. For effective cancer pain management, it is important to account for differences in attitudes and practice between medical oncolo-gists and palliative care physicians

Conference Highlights of the 16th International Conference on Human Retrovirology: HTLV and Related Retroviruses, 26–30 June 2013, Montreal, Canada

The 16th International Conference on Human Retrovirology: HTLV and Related Retroviruses was held in Montreal, Québec from June 26 to June 30, 2013 and was therefore hosted by a Canadian city for the first time. The major topic of the meeting was human T-lymphotropic viruses (HTLVs) and was covered through distinct oral and poster presentation sessions: clinical research, animal models, immunology, molecular and cellular biology, human endogenous and emerging exogenous retroviruses and virology. In this review, highlights of the meeting are provided by different experts for each of these research areas

Combination of reduced post-transplant cyclophosphamide and early tacrolimus initiation increases the incidence of chronic graft-versus-host disease in human leukocyte antigen-haploidentical peripheral blood stem-cell transplantation

We evaluated the clinical impacts of the concurrent modification of post-transplant cyclophosphamide (PTCy) dose and tacrolimus (Tac)-initiation timing in 61 patients with human leukocyte antigen-haploidentical transplantation. Reduced-dose PTCy (80 mg/kg) was associated with a higher incidence of moderate-to-severe chronic graft-versus-host disease (GVHD) than standard-dose PTCy (100 mg/kg) (35.0% vs. 26.6%, p = 0.053). Notably, early-initiation Tac (day -1) increased moderate-to-severe chronic GVHD than standard-initiation Tac (day 5) in the reduced-dose PTCy group (p = 0.032), whereas Tac-initiation timing did not impact chronic GVHD in the standard-dose PTCy group. These data indicate that the combination of reduced-dose PTCy and early-initiation Tac can amplify chronic GVHD

Metastases of soft tissue sarcoma to the liver: A Historical Cohort Study from a Hospital-based Cancer Registry

Background: Hepatic metastasis of soft tissue sarcoma is rare compared to lung metastasis, and the literature is scarce. We examined the risk of hepatic metastasis according to the site of occurrence and histological type. Methods: From a Hospital-based Cancer Registry, 658 patients registered between 2007 and 2017 with soft tissue sarcomas were evaluated. The exclusion criteria were gastrointestinal stromal tumors, tumors of unknown origin, and follow-up periods of less than 1 month. SPSS 25 was used for statistical analysis. Results: The risk of hepatic metastasis was significantly higher in the retroperitoneum (HR, 5.981; 95% CI, 2.793-12.808) and leiomyosarcoma (HR, 4.303; 95% CI, 1.782-10.390). Multivariate analysis showed that the risk of hepatic metastasis as first distant metastasis was high in leiomyosarcoma (HR, 4.546; 95% CI, 2.275-9.086) and retroperitoneal onset (HR, 4.588; 95% CI, 2.280-9.231). The 2-year survival rate after hepatic metastasis was 21.7%. Conclusions: The onset of hepatic metastasis indicates a poor prognosis. However, hepatic metastasis from retroperitoneal sarcoma and leiomyosarcoma may be the first distant metastasis in some cases. For retroperitoneal sarcoma and leiomyosarcoma, additional screening for hepatic metastasis such as contrast CT should be considered during staging and follow-up after treatment.ArticleCancer medicine 17(17) : 6159-6165(2020)journal articl

Germinal epimutation of Fragile Histidine Triad (FHIT) gene is associated with progression to acute and chronic adult T-cell leukemia diseases

Background: Human T cell Leukemia virus type 1 (HTLV-I) is etiologically linked to adult T cell leukemia/lymphoma (ATL) and an inflammatory neurodegenerative disease called HTLV-I-associated myelopathy or tropical spastic paraparesis (HAM/TSP). The exact genetic or epigenetic events and/or environmental factors that influence the development of ATL, or HAM/TSP diseases are largely unknown. The tumor suppressor gene, Fragile Histidine Triad Diadenosine Triphosphatase (FHIT), is frequently lost in cancer through epigenetic modifications and/or deletion. FHIT is a tumor suppressor acting as genome caretaker by regulating cellular DNA repair. Indeed, FHIT loss leads to replicative stress and accumulation of double DNA strand breaks. Therefore, loss of FHIT expression plays a key role in cellular transformation. Methods: Here, we studied over 400 samples from HTLV-I-infected individuals with ATL, TSP/HAM, or asymptomatic carriers (AC) for FHIT loss and expression. We examined the epigenetic status of FHIT through methylation specific PCR and bisulfite sequencing; and correlated these results to FHIT expression in patient samples. Results: We found that epigenetic alteration of FHIT is specifically found in chronic and acute ATL but is absent in asymptomatic HTLV-I carriers and TSP/HAM patients' samples. Furthermore, the extent of FHIT methylation in ATL patients was quantitatively comparable in virus-infected and virus non-infected cells. We also found that longitudinal HTLV-I carriers that progressed to smoldering ATL and descendants of ATL patients harbor FHIT methylation. Conclusions: These results suggest that germinal epigenetic mutation of FHIT represents a preexisting mark predisposing to the development of ATL diseases. These findings have important clinical implications as patients with acute ATL are rarely cured. Our study suggests an alternative strategy to the current "wait and see approach" in that early screening of HTLV-I-infected individuals for germinal epimutation of FHIT and early treatment may offer significant clinical benefits