Suzaku observation of the giant radio galaxy 3C 326

A Suzaku observation of a giant radio galaxy, 3C 326, which has a physical size of about 2 Mpc, was conducted on 2008 January 19 -- 21. In addition to several X-ray sources, diffuse emission was significantly detected associated with its west lobe, but the east lobe was contaminated by an unidentified X-ray source WARP J1552.4+2007. After careful evaluation of the X-ray and Non X-ray background, the 0.4 -- 7 keV X-ray spectrum of the west lobe is described by a power-law model. The photon index and 1 keV flux density was derived as $1.82_{-0.24}^{+0.26}\pm0.04$ and $19.4_{-3.2}^{+3.3}\pm 3.0$ nJy, respectively, where the first and second errors represent the statistical and systematic ones. The diffuse X-rays were attributed to be inverse Compton radiation by the synchrotron radio electrons scattering off the cosmic microwave background photons. This radio galaxy is the largest among those with lobes detected through inverse Compton X-ray emission. A comparison of the radio to X-ray fluxes yields the energy densities of electron and magnetic field as $u_e = (2.3 \pm 0.3 \pm 0.3) \times 10^{-13}$ ergs/cm3 and $u_m = (1.2_{-0.1}^{+0.2}\pm 0.2) \times 10^{-14}$ ergs/cm3, respectively. The galaxy is suggested to host a low luminosity nucleus with an absorption-corrected 2 -- 10 keV luminosity of $<2 \times 10^{42}$ ergs/s, together with a relatively weak radio core. The energetics in the west lobe of 3C 326 were compared with those of moderate radio galaxies with a size of $\sim 100$ kpc. The west lobe of 3C 326 is confirmed to agree with the correlations for the moderate radio galaxies, $u_e \propto D^{-2.2\pm0.4}$ and $u_m \propto D^{-2.4\pm0.4}$, where $D$ is their total physical size. This implies that the lobes of 3C 326 are still being energized by the jet, despite the current weakness of the nucleus.Comment: 11 pages, 10 figures, 6 tables, Accepted for ApJ (v706 issue

Tricarboxylic acid cycle activity suppresses acetylation of mitochondrial proteins during early embryonic development in Caenorhabditis elegans

The tricarboxylic acid (TCA) cycle (or citric acid cycle) is responsible for the complete oxidation of acetyl-CoA and formation of intermediates required for ATP production and other anabolic pathways, such as amino acid synthesis. Here, we uncovered an additional mechanism that may help explain the essential role of the TCA cycle in the early embryogenesis of Caenorhabditis elegans. We found that knockdown of citrate synthase (cts-1), the initial and rate-limiting enzyme of the TCA cycle, results in early embryonic arrest, but that this phenotype is not because of ATP and amino acid depletions. As a possible alternative mechanism explaining this developmental deficiency, we observed that cts-1 RNAi embryos had elevated levels of intracellular acetyl-CoA, the starting metabolite of the TCA cycle. Of note, we further discovered that these embryos exhibit hyperacetylation of mitochondrial proteins. We found that supplementation with acetylase-inhibiting polyamines, including spermidine and putrescine, counteracted the protein hyperacetylation and developmental arrest in the cts-1 RNAi embryos. Contrary to the hypothesis that spermidine acts as an acetyl sink for elevated acetyl-CoA, the levels of three forms of acetylspermidine, N1-acetylspermidine, N8-acetylspermidine, and N1,N8-diacetylspermidine, were not significantly increased in embryos treated with exogenous spermidine. Instead, we demonstrated that the mitochondrial deacetylase sirtuin 4 (encoded by the sir-2.2 gene) is required for spermidine\u27s suppression of protein hyperacetylation and developmental arrest in the cts-1 RNAi embryos. Taken together, these results suggest the possibility that during early embryogenesis, acetyl-CoA consumption by the TCA cycle in C. elegans prevents protein hyperacetylation and thereby protects mitochondrial function

Echophonocardiographic study of the initial low frequency component of the first heart sound

To investigate the genesis of the initial low frequency component of the first heart sound that precedes the high frequency vibrations associated with closure of the atrioventricular valves, echophonocardiograms of 36 persons were recorded. These included 10 normal subjects and 26 patients with various types of heart disease including mitral valve replacement. Electrocardiograms demonstrated normal sinus rhythm in 23 subjects, atrial fibrillation in 9, complete atrioventricular block in 2 and atrial flutter in 2. In the phonocardiogram, the low frequency component of the first heart sound followed the onset of the QRS complex and preceded the first high frequency component of this sound. The low frequency component occurred simultaneously with the beginning of the final fast closing movement of the mitral valve on he echocardiogram and was found both in normal rhythm and in arrhythmias. However, in arrhythmias its intensity varied on a beat to beat basis, being loudest after a short RR interval or when atrial systole occurred very close to the expected time of ventricular systole. In patients in whom apexcardiograms were recorded, the low frequency component was coincident with or very close to the onset of ventricular systole.It is concluded that the low frequency component of the first heart sound represents vibrations caused by contraction of the left ventricle and deceleration of antegrade blood flow across the mitral valve. Neither atrial contraction nor mitral valve tension is necessary for the production of this soft initial component

A Clinically Applicable Prediction Model to Improve T Cell Collection in Chimeric Antigen Receptor T Cell Therapy

キメラ抗原受容体T細胞療法におけるリンパ球採取効率化の取り組み --最適な治療戦略策定への貢献に期待--. 京都大学プレスリリース. 2022-06-20.As chimeric antigen receptor (CAR) T cell therapy targeting CD19 has shown favorable outcomes in patients with relapsed or refractory (r/r) mature B cell lymphomas and B cell acute lymphoblastic leukemia (B-ALL), an increasing number of patients are waiting to receive these treatments. Optimized protocols for T cell collection by lymphapheresis for chimeric antigen receptor (CAR) T cell therapy are urgently needed to provide CAR T cell therapy for patients with refractory and progressive disease and/or a low number of lymphocytes owing to prior chemotherapy. The predicted efficiency of CD³⁺ cell collection in apheresis can guide protocols for apheresis, but a clinically applicable model to produce reliable estimates has not yet been established. In this study, we prospectively analyzed 108 lymphapheresis procedures for tisagenlecleucel therapy at 2 centers. The apheresis procedures included 20 procedures in patients with B cell acute lymphoblastic leukemia and 88 procedures in patients with diffuse large B cell lymphoma, with a median age at apheresis of 58 years (range, 1 to 71 years). After lymphapheresis with a median processing blood volume of 10 L (range, 3 to 16 L), a median of 3.2 × 10⁹ CD³⁺ cells (range, .1 to 15.0 × 10⁹ cells) were harvested. Collection efficiency 2 (CE2) for CD³⁺ cells was highly variable (median, 59.3%; range, 11.0% to 199.8%). Multivariate analyses revealed that lower hemoglobin levels, higher circulating CD3+ cell counts, and higher platelet counts before apheresis significantly decreased apheresis CE2. Based on multivariate analyses, we developed a novel formula that estimates CE2 from precollection parameters with high accuracy (r = .56; P < .01), which also suggests the necessary processing blood volume. Our strategy for lymphapheresis should help reduce collection failure, as well as achieve efficient utilization of medical resources in clinical practice, thereby allowing delivery of CAR T cell therapy to more patients in a timely manner