Molecular dynamics simulation of proton-transfer coupled rotations in ATP synthase FO motor

The FO motor in FOF1 ATP synthase rotates its rotor driven by the proton motive force. While earlier studies elucidated basic mechanisms therein, recent advances in high-resolution cryo-electron microscopy enabled to investigate proton-transfer coupled FO rotary dynamics at structural details. Here, taking a hybrid Monte Carlo/molecular dynamics simulation method, we studied reversible dynamics of a yeast mitochondrial FO. We obtained the 36°-stepwise rotations of FO per one proton transfer in the ATP synthesis mode and the proton pumping in the ATP hydrolysis mode. In both modes, the most prominent path alternatively sampled states with two and three deprotonated glutamates in c-ring, by which the c-ring rotates one step. The free energy transduction efficiency in the model FO motor reached ~ 90% in optimal conditions. Moreover, mutations in key glutamate and a highly conserved arginine increased proton leakage and markedly decreased the coupling, in harmony with previous experiments. This study provides a simple framework of simulations for chemical-reaction coupled molecular dynamics calling for further studies in ATP synthase and others

Gastric Hyperplastic Polyp Associated with Proliferation of Xanthoma Cells Observed by Magnification Narrow-Band Imaging Endoscopy

A case of gastric hyperplastic polyp with proliferation of xanthoma cells is reported. The patient was a 69-year-old man who visited our hospital for further evaluation of gastric polyps. Endoscopic examination of the upper digestive tract revealed multiple hyperplastic polyps in the gastric antrum. There was a pedunculated polyp with whitish yellow granules, 7 mm in diameter, arising from the greater curvature of the antrum. Magnification narrow-band imaging endoscopy (GIF-H260Z, Olympus) revealed long microcapillaries in the polyp but did not reveal disappearance of the mucosal microstructure or irregular branched capillaries. Endoscopic mucosal resection (EMR) was performed. Histological examination of the specimen revealed the lengthened gastric foveolae in the superficial portion and tight sheet of foamy histiocytes in the lamina propria. Diagnosis of gastric hyperplastic polyp with proliferation of xanthoma cells was made. There was no evidence of malignancy. It is necessary to know that a gastric hyperplastic polyp may associate with gastric xanthoma, although such association is very rare

Update on perioperative management of patients undergoing surgery for liver cancer

Hepatocellular carcinoma is often accompanied by chronic hepatitis or cirrhosis. Preoperative evaluation of liver function and postoperative nutritional management are critical in patients with hepatocellular carcinoma who undergo liver surgery. Although the incidence of postoperative complications and death has declined in Japan over the last 10 years, postoperative complications have not been fully overcome. Therefore, surgical procedures and perioperative management must be improved. Accurate preoperative evaluations of liver function, nutrition, inflammation, and body skeletal muscle are required. Determination of the optimal surgical procedure should consider not only tumor characteristics but also the physical reserve of the patient. Nutritional management of chronic liver disorders, especially maintaining protein synthesis for postoperative protein/energy, is important. Prophylactic antibiotics are recommended for short-term use within 24 hours after surgery. Abdominal drainage is recommended for patients with cirrhosis who may develop large amounts of ascites, who are at risk of postoperative bleeding, or who may have bile leakage due to a large resection area. Postoperative exercise therapy may improve insulin resistance in patients with chronic liver damage. Implementation of an early/enhanced recovery after surgery program is recommended to reduce biological invasive responses and achieve early independence of physical activity and nutrition intake. We review the latest information on the perioperative management of patients undergoing liver resection for hepatocellular carcinoma

Liposarcoma Arising in the Foot: A Case Report

Liposarcoma is categorized as a soft tissue sarcoma and most commonly appears in the lower extremities and rarely in the foot during adulthood. We present a very rare case report of a primary well-differentiated liposarcoma arising in the foot on a 60-year-old female. Marginal resection of the tumor with metatarsal ray amputation was eventually performed. The patient's postoperative course was uneventful without recurrence 5 years after the original operation. The authors review the literature and also report on the low incidence of this tumor arising in the foot

Cytochemical studies of the hemoglobin synthesis of erythroblasts

The process of hemoglobin sythesis in erythroid cells have been traced mainly by observing cells under the light of 4,060 &#197;. To scrutinize the theory of hemoglobin synthesis in the nucleus of erythroblasts, several cytochemical and morphological observations were also carried out. The conclusions derived from them are as follows: 1 The absorption at 4,060 &#197; of the cell, which indicates the location of heme, appeared in the nucleus as early as in the develpmental stage of basophilic erythroblasts. The absorption of hcme in cytoplasm likewise appeared in this stage showing nearly the same intensity of the absorption. The absorption picture of heme in the nucleus, which is coincidental with that of interchromatin, increased along with the progess of maturation as well as in the cytoplasm. The absorption in the nucleus disappeared at the orthochromatic stage where the picture of interchromatin disappeared, while the intensity of absorption in the cytoplasm continued to increase till the stage of reticulocyte. 2 The pseudoperoxidase reaction of hemoglobin, the appearance of acidophlic protein and masked lipids detectable in the location of hemoglobin gave an exactly identical picture with that of the absorption of heme in the nucleus as well as in the cytoplasm. 3 Permeability test performed by supravital staining with Nile blue revealed that the nucleus of erythroblasts from the basophilic to the orthorchromatic stages has increased its permeability being stained selectively as in the case of dead cells. 4 The mitochondria and the endoplasmic reticulum proved to be retained well in the entire course of hemoglobin synthesis, even after the denucleation, the reticulocyte stage. From these observations the authors believe that the hemoglobin syntheis will take place in the cytoplasm throughout the life cycle of erythroid cells, pointing out that the absorption picturebf heme appearing in the nucleus will be in all likelihood due to the infusion of the hemoglobin from the cytoplasm.</p

Age and gender effect on alexithymia in large, Japanese community and clinical samples: a cross-validation study of the Toronto Alexithymia Scale (TAS-20)

BACKGROUND: The construct validity of alexithymia and its assessment using the 20-item Toronto Alexithymia Scale (TAS-20) in Japan is unknown. Low reliability has been found for the third factor of the TAS-20 in some cultures, and the factor structure for psychosomatic disorder patients has not been adequately investigated. Although alexithymia most likely has certain developmental aspects, this has infrequently been investigated. METHODS: The newly-developed Japanese TAS-20 was administered to a normative sample (n = 2,718; 14–84 y.o.), along with the NEO Five-Factor Inventory (NEO-FFI) for cross validation. Psychosomatic patients (n = 1,924, 12–87 y.o.) were tested to evaluate the factor structure in a clinical sample. College students (n = 196) were used for a test-retest study. Internal reliability and consistency were assessed, and the factorial structure was evaluated using confirmatory and exploratory factor analyses for both the normative and the clinical samples. The correlations between the TAS-20 and the NEO-FFI factor scores were evaluated. Age-related and gender differences in the TAS-20 were explored using analysis of variance in the normative sample. RESULTS: The original three-factor model of the TAS-20 was confirmed to be valid for these Japanese samples, although a 4-factor solution that included negatively keyed items (NKI) as an additional factor was more effective. Significant correlations of the TAS-20 with the NEO-FFI were found, as has been previously reported. Factor analyses of the normative and patient samples showed similar patterns. The TAS-20 total, difficulty in identifying feelings (DIF), and difficulty in describing feelings (DDF) scores were high for teenagers, decreased with age, and from 30s did not change significantly. In contrast, externally oriented thinking (EOT) scores showed an almost linear positive correlation with age. DIF scores were higher for females, while EOT scores were higher for males, without any interaction between gender and age differences. CONCLUSION: The original three-factor concept of the TAS-20 was generally supported for practical use. Age-related differences in TAS-20 scores indicate developmental aspects of alexithymia. Alexithymia is made up of two components with different developmental paths: DIF/DDF and EOT

Cooperation among c-subunits of FoF1-ATP synthase in rotation-coupled proton translocation

In F₀F₁-ATP synthase, proton translocation through F₀ drives rotation of the c-subunit oligomeric ring relative to the a-subunit. Recent studies suggest that in each step of the rotation, key glutamic acid residues in different c-subunits contribute to proton release to and proton uptake from the a-subunit. However, no studies have demonstrated cooperativity among c-subunits toward F₀F₁-ATP synthase activity. Here, we addressed this using Bacillus PS3 ATP synthase harboring a c-ring with various combinations of wild-type and cE56D, enabled by genetically fused single-chain c-ring. ATP synthesis and proton pump activities were decreased by a single cE56D mutation and further decreased by double cE56D mutations. Moreover, activity further decreased as the two mutation sites were separated, indicating cooperation among c-subunits. Similar results were obtained for proton transfer-coupled molecular simulations. The simulations revealed that prolonged proton uptake in mutated c-subunits is shared between two c-subunits, explaining the cooperation observed in biochemical assays

Changes in visits to green spaces due to the COVID-19 pandemic: Focusing on the proportion of repeat visitors and the distances between green spaces and visitors' places of residences

Through a quantitative approach, this study aimed to clarify the changes in the number of visitors and visits to green spaces according to green space type before and after the COVID-19 pandemic. We explored the changes in the proportion of repeat visitors and the distance between green spaces and visitors' places of residence. We used KDDI Location Analyzer, which performs novel analysis using mobile phone GPS and census data. The study area included 10 target sites (urban parks and nature trails in the backcountry) located in the Sapporo metropolitan area in Japan. The survey period included snow-free seasons from 2019 to 2021, and 2019 was considered the period "before the pandemic." The results revealed that the number of visits during the pandemic increased compared with those before the pandemic, except for those of urban parks near the city center. In 2020, the proportion of repeat visitors increased for all 10 target sites. In addition, since the outbreak of the pandemic, distances between all urban parks and visitors' residences decreased. The same trend was observed for nature trails in the backcountry close to the city center. These findings indicate a generally decreasing trend in the number of visits to green spaces as many people have been refraining from visiting the site since the outbreak of the pandemic. Contrastingly, the number of visits by repeat visitors who reside close to the target sites has increased in some cases, which compensated for the general decreases