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Recent reports have described the practicality of laparoscopic intragastric surgery (l-IGS) as an alternative for resecting submucosal tumors (SMTs) near the esophagogastric junction (EGJ), where excision using an exogastric approach would be difficult. However, even using IGS to perform a full-thickness resection of SMTs that are in or extremely close to the EGJ is very difficult to do safely and avoid disrupting or causing stenosis of the EGJ, without advanced experience. This study retrospectively examined the usefulness of l-IGS for gastric SMTs located in or extremely close to the EGJ. Fourteen patients with gastric SMTs < 2 cm of the EGJ and underwent l-IGS were eligible for this study. We examined the tumor location, operative time, intraoperative hemorrhage, degree of deformation, gastroesophageal reflux disease, perioperative complications, and recurrence. Furthermore, we compared patients with tumors in the EGJ with those with tumors near the EGJ and patients in whom three-port l-IGS was performed with those who underwent single-incision laparoscopic surgery. The average tumor size, operative time, intraoperative hemorrhage, and postoperative hospitalization of the 14 patients were 30.9 ± 21.3 mm, 125.2 ± 31.1 min, 30.7 ± 103.3 mL, and 9.2 ± 3.1 d, respectively. No differences in these parameters according to the type of l-IGS or tumor location were observed. All patients underwent l-IGS without complications and were free from EGJ deformation or esophagitis. We believe that l-IGS is useful for gastric SMTs located < 2 cm of the EGJ as it can be safely performed for difficult tumor locations and does not cause deformation of the EGJ. [ABSTRACT FROM AUTHOR]

Background: While a neoadjuvant chemotherapy regimen using docetaxel, cisplatin, and 5-fluorouracil (NAC-DCF) is considered the standard treatment for locally advanced esophageal cancer (EC) in Japan, a reliable marker for early prediction of treatment efficacy remains unclear. We investigated the utility of the tumor response after a first course of NAC-DCF as a post-surgery survival predictor in patients with EC. Methods: We enrolled 150 consecutive patients who underwent NAC-DCF followed by surgery for EC between September 2009 and January 2019. The initial tumor reduction (ITR), defined as the percentage decrease in the shorter diameter of the tumor after the first course of NAC-DCF, was evaluated using computed tomography. We analyzed the relationship between ITR, clinicopathological parameters, and survival. Results: The median ITR was 21.07% (range −11.45 to 50.13%). The optimal cut-off value for ITR for predicting prognosis was 10% (hazard ratio [HR] 3.30, 95% confidence interval [CI] 1.98–5.51), based on univariate logistic regression analyses for recurrence-free survival (RFS). Compared with patients with ITR <10%, patients with ITR ≥10% showed a significantly higher proportion of ypM0 (80.0% vs. 92.5%) and responders in terms of overall clinical response (50.0% vs. 80.8%). Multivariate analysis for RFS revealed that ypN2-3 (HR 2.78, 95% CI 1.67–4.62), non-response in terms of overall clinical response (HR 1.87, 95% CI 1.10–3.18), and ITR <10% (HR 2.48, 95% CI 1.42–4.32) were independent prognostic factors. Conclusions: Tumor response after the first course of NAC-DCF may be a good predictor of survival in patients with EC who underwent NAC-DCF plus surgery. [ABSTRACT FROM AUTHOR]

Purpose: Gastric cancer patients with peritoneal metastasis (PM) are generally treated with systemic chemotherapy. When PM has disappeared because of chemotherapy, radical gastrectomy (so-called conversion surgery) is usually performed. We have previously reported the efficacy of conversion surgery, but there are no reports examining the efficacy of palliative gastrectomy for patients with residual PM after chemotherapy. The purpose of this study was to investigate the efficacy of palliative surgery for gastric cancer patients with PM who still have residual peritoneal dissemination after chemotherapy. Methods: Twenty-five gastric cancer patients with PM confirmed by laparoscopy and who had received chemotherapy but who still had residual PM were included in this study. Among the 25 patients, palliative surgery was performed in 20 patients (PS group) and chemotherapy was continued in 5 patients (CTx group), and their therapeutic outcomes were compared. Results: In the PS group, total and distal gastrectomies were performed. Clavien–Dindo grade I postoperative complications occurred in two patients (10%). There were no treatment-related deaths. Postoperative chemotherapy was performed all cases. In the PS group, the median survival time (MST) reached 22.5 months, with 1- and 2-year overall survival (OS) rates of 95% and 45%, respectively, whereas in the CTx group, the MST was 15.8 months, and the 1- and 2-year OS rates were 60% and 0%, respectively. The PS group had significantly longer OS than the CTx group (P=0.044). Conclusions: Palliative surgery is safe and may prolong survival in gastric cancer patients with residual PM after chemotherapy. [ABSTRACT FROM AUTHOR]

Background: The surgical strategy for thoracic esophageal cancer that invades the lungs is controversial. In particular, invasion of the pulmonary vein is often regarded unresectable. We successfully applied bilateral video-assisted thoracic surgery (VATS) in esophagectomy for esophageal cancer with left inferior pulmonary vein invasion following induction chemoradiotherapy (CRT), with a favorable response. Case presentation: A 64-year-old woman was diagnosed with squamous cell carcinoma of the lower third of the esophagus. Computed tomography (CT) revealed that the tumor was suspected to be invading the main trunk of the left lower pulmonary vein and left lower lung. We initiated induction CRT comprising 5-fluorouracil, cisplatin, and concurrent radiotherapy at 50.4 Gy/28Fr. CT revealed shrinkage of the tumor, and the main trunk of the left inferior pulmonary vein was released from the tumor invasion. We considered the tumor to be completely resectable. VATS esophagectomy is usually performed using a right-sided approach. However, the right-sided approach is inappropriate for evaluating tumors around the left inferior pulmonary vein. We started with left-sided VATS to determine tumor resectability and dissected between the esophagus and the main trunk of the left inferior pulmonary vein. We only needed to perform partial resection of the left lower lobe. We then performed a right-sided VATS esophagectomy and lymphadenectomy with partial en bloc resection of the left lower lobe. Following this, we performed hand-assisted laparoscopic proximal gastrectomy and reconstruction using the gastric remnant. The postoperative course was uneventful. The patient was discharged on postoperative day 14. Histopathological examination of the surgical specimen revealed a complete pathological response without any remnant tumor or lymph node metastasis. There were no signs of recurrence or metastasis at the 1-year follow-up. Conclusions: Curative resection for thoracic esophageal cancer that invades the pulmonary vein could be possible via the bilateral VATS approach following induction CRT with a favorable response. [ABSTRACT FROM AUTHOR]

Purpose: The prognosis of gastric cancer patients with peritoneal metastasis (PM) remains dismal with standard systemic chemotherapy. Intraperitoneal (i.p.) chemotherapy with paclitaxel (PTX) has local effects on intra-abdominal cancer cells. According to this phenomenon, we have developed regimens combining single i.p. PTX administration with systemic chemotherapy. This treatment strategy is very promising; however, the effect of "conversion surgery" in patients responding to this chemotherapy is unclear. Therefore, we performed a retrospective study to evaluate the safety and efficacy of conversion surgery for gastric cancer patients with PM. Methods: We enrolled 52 gastric cancer patients with PM who were treated with single i.p. PTX plus systemic chemotherapy between 2005 and 2015. Conversion surgery was performed where PM was eliminated by combination chemotherapy. Results: Among 52 gastric cancer patients, the disappearance of PM was confirmed in 33 patients (63.5%). Gastrectomy with D2 lymph node dissection was performed in all these patients. Histological response of grade ≥ 1b was achieved in 13 patients (39%). Clavien–Dindo grade II postoperative complications occurred in three patients (9%). There were no treatment-related deaths. The median survival time and 1-, 3-, and 5-year overall survival rates of the 33 patients who underwent conversion surgery were 30.7 months and 78.8%, 36.3%, and 24.2%, respectively, and those of the 19 patients who did not undergo surgery were 12.5 months and 52.6%, 5.2%, and 0%, respectively. Conclusion: Conversion surgery is safe and may prolong survival for gastric cancer patients with PM who have responded to single i.p. PTX plus systemic chemotherapy. [ABSTRACT FROM AUTHOR]

Background: To report our findings on quality of life (QoL) in a randomized phase II study to determine the optimal dose of 3-week cycle nab-paclitaxel (q3w nab-PTX) in patients with metastatic breast cancer (MBC). Methods: Patients with HER2-negative MBC were randomly assigned to three different doses of q3w nab-PTX (SD 260 mg/m2 vs. MD: 220 mg/m2 vs. LD 180 mg/m2). QoL was assessed at baseline and during the second, fourth and sixth courses of treatment using the Functional Assessment of Cancer Therapy-Taxane (FACT-Taxane), Cancer Fatigue Scale (CFS) and EuroQol 5-Dimension (EQ-5D). Comparisons were performed with mixed-model repeated measures (MMRM). Results: A total of 141 patients were enrolled in the parent study, and 136 (96%) (44, 45 and 47 in the SD, MD, and LD groups) were included in the analysis. MMRM analysis showed that the difference from the baseline FACT-Taxane trial outcome index at MD and LD were significantly higher than that at SD (MD vs. SD P < 0.001, LD vs. SD P < 0.001). Differences from baseline for FACT-Taxane total, physical and emotional well-being, and taxane subscale scores at MD and LD were also higher than at SD. The difference from baseline for the CFS score at LD was lower than at SD (P = 0.013) and those for EQ-5D utility scores at MD and LD were higher than at SD (MD vs. SD P = 0.011, LD vs. SD P < 0.001). Conclusion: QoL of patients treated with 220 or 180 mg/m2 of q3w nab-PTX was significantly better than that of patients treated with 260 mg/m2. Trial registration: The protocol was registered at the website of the University Hospital Medical Information Network (UMIN), Japan (protocol ID: UMIN000015516), on 01/11/2014. Details are available at the following address: https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000017916 [ABSTRACT FROM AUTHOR]

Introduction: We compare planned salvage surgery after definitive chemoradiotherapy (SALV) versus neoadjuvant chemoradiotherapy plus surgery (NCRS) for borderline resectable T4 esophageal squamous cell carcinoma. Patients and Methods: A total of 37 patients underwent planned SALV, and 20 underwent NCRS from 2004 to 2017. The short-term outcome measures were the R0 resection rate, complications, and treatment-related mortality. The long-term outcome measures were the 5-year overall survival rate and causes of death. Results: R0 resection rate was similar between the SALV and NCRS groups (81% versus 85%). The incidence of postoperative pneumonia (35% versus 18%) and treatment-related mortality rate (9% versus 0%) tended to be higher in the SALV. ypT grade 2–3 (65% versus 30%, p = 0.012) and Clavien–Dindo grade ≥ IIIb complications (32% versus 0%, p = 0.008) were significantly more frequent in the SALV group. The groups had similar 5-year overall survival (26% versus 27%). The causes of death in the SALV and NCRS groups were primary esophageal cancer in 35% and 55% of patients, respectively, and pulmonary-related mortality in 24% and 5%, respectively. Multivariable Cox regression analysis revealed the following significant poor prognostic factors: stable disease as the clinical response, preoperative body mass index (BMI) of < 18.5 kg/m2, ypN stage 1–3, and R1–2 resection. Conclusions: SALV was associated with a higher incidence of late pulmonary-related mortality but had a stronger antitumor effect than NCRS. Consequently, the survival rate was similar between the groups. Surgery is recommended for patients with a partial response and preoperative BMI of ≥ 18.5 kg/m2. [ABSTRACT FROM AUTHOR]

Background: A challenge in esophageal reconstruction after esophagectomy is that the distance from the neck to the abdomen must be replaced with a long segment obtained from the gastrointestinal tract. The success or failure of the reconstruction depends on the blood flow to the reconstructed organ and the tension on the anastomotic site, both of which depend on the reconstruction distance. There are three possible esophageal reconstruction routes: posterior mediastinal, retrosternal, and subcutaneous. However, there is still no consensus as to which route is the shortest. Methods: The length of each reconstruction route was retrospectively compared using measurements obtained during surgery, where the strategy was to pull up the gastric conduit through the shortest route. The proximal reference point was defined as the left inferior border of the cricoid cartilage and the distal reference point was defined as the superior border of the duodenum arising from the head of the pancreas. Results: This study involved 112 Japanese patients with esophageal cancer (102 men, 10 women). The mean distances of the posterior mediastinal, retrosternal, and subcutaneous routes were 34.7 ± 2.37 cm, 32.4 ± 2.24 cm, and 36.3 ± 2.27 cm, respectively. The retrosternal route was significantly shorter than the other two routes (both p < 0.0001) and shorter by 2.31 cm on average than the posterior mediastinal route. The retrosternal route was longer than the posterior mediastinal route in only 5 patients, with a difference of less than 1 cm. Conclusion: The retrosternal route was the shortest for esophageal reconstruction in living Japanese patients. [ABSTRACT FROM AUTHOR]

Information regarding the molecular features of pulmonary pleomorphic carcinoma (PPC) is insufficient. Here, we performed next-generation sequencing to determine the genomic and transcriptomic profiles of PPC. We sequenced the DNAs and RNAs of 78 specimens from 52 patients with PPC. We analyzed 15 PPC cases to identify intratumoral differences in gene alterations, tumor mutation burden (TMB), RNA expression, and PD-L1 expression between epithelial and sarcomatoid components. The genomic alterations of six cases of primary tumors and corresponding metastatic tumors were analyzed. KRAS mutations (27%) were the most common driver mutations, followed by EGFR (8%), and MET (8%) mutations. Epithelial and sarcomatoid components shared activating driver mutations, and there were no significant differences in CD274 expression or TMB between the two components. However, PD-L1 was highly expressed in the sarcomatoid component of several cases compared with the epithelial component. Primary and metastatic tumors shared oncogenic mutations among genes such as KRAS and TP53, and additional alterations including NOTCH4 mutations were specifically identified in the metastatic regions. Our data suggest that therapies targeting activating driver mutations may be effective for patients with PPC and that immune checkpoint inhibitors of PPC may be recommended after careful assessment of PD-L1 expression in each epithelial and sarcomatoid component. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study is to determine the clinical significance of micrometastases after neoadjuvant chemotherapy (NAC) and the difference in controlling micrometastases using different NAC regimens in resectable advanced esophageal squamous cell carcinoma (ESCC). Methods: We analyzed patients with ESCC who underwent esophagectomy with lymph node dissection after NAC with Adriamycin + cisplatin + 5-fluorouracil (ACF) or docetaxel + cisplatin + 5-fluorouracil (DCF). Micrometastasis was defined as a single isolated cancer cell or cluster of cancer cells on the cervical, recurrent nerve, or abdominal LNs as shown by immunohistochemical staining with anti-cytokeratin antibody (AE1/AE3). The associations between micrometastases, recurrence, prognosis, and regimen differences were investigated. Results: One hundred and one cases (ACF group: 51 cases; DCF group: 50 cases) were analyzed. Micrometastases occurred in 24 patients (23.8%): 17/51 (33.3%) in the ACF group and 7/50 (13.5%) in the DCF group (p = 0.0403). The 5-year recurrence-free survival (RFS) rates for patients without (n = 77) and with (n = 24) micrometastases were 62 and 32%, respectively, (hazard ratio, 2.158; 95% confidence interval, 1.170–3.980; stratified log-rank test, p = 0.0115). A multivariate analysis showed that stage pN1 or higher and micrometastases were significant risk factors affecting RFS. Conclusion: In resectable advanced ESCC, controlling micrometastases in the LNs after NAC varied by regimen and may be associated with preventing ESCC recurrence. [ABSTRACT FROM AUTHOR]

Background: Feeding jejunostomy (FJ) is a common treatment to support patients with esophageal cancer after esophagectomy. However, severe FJ-related complications, such as bowel obstruction, occasionally occur. We investigated the ability of our simple, novel FJ technique, the "curtain method," to prevent bowel obstruction.Methods: In laparoscopic surgery, the main mechanism of bowel obstruction involves torsion of the mesentery accompanied by migration of the intestine across the fixed FJ through the space surrounded by a triangle comprising the ligament of Treitz, fixed FJ, and spleen rather than adhesion. Our "curtain method" involves closure of this triangle zone with omentum, and the appearance of the lifted omentum resembles a curtain. Sixty patients treated with this modified FJ were retrospectively compared with 13 patients treated with conventional FJ in terms of the incidence of bowel obstruction, peritonitis, stoma site infection, and catheter obstruction.Results: From 2013 to 2017, 60 patients underwent esophagectomy and gastric conduit reconstruction accompanied by modified laparoscopic FJ. The median observation period, including the period after tube removal, was 644 days. No FJ-associated bowel obstruction, the prevention of which was the primary aim, occurred in any patient. Likewise, no peritonitis or dislodgement occurred. Eight patients (13%) developed a stoma site infection with granulation. The feeding tube became occluded in 11 patients (18%); however, a new feeding tube was reinserted under fluoroscopy for all of these patients. From 2003 to 2012, 13 patients underwent conventional FJ. The median observation period was 387 days. Three patients (23%) developed bowel obstruction by torsion 71 to 134 days after the first surgery, and all were treated by emergency operations. Other FJ-related complications were not different from those in the modified FJ group.Conclusion: Our simple, novel technique, the "curtain method," for prevention of laparoscopic FJ-associated bowel obstruction after esophagectomy is a safe additional surgery. [ABSTRACT FROM AUTHOR]

Long-term monitoring revealed that radiocesium (137Cs) deposition that fall from the canopy with litterfall was characterized by forest types, seasonal change, and canopy closure (CC). The sum of autumn and spring 137Cs deposition values divided by the sum of summer and winter tended to have higher values in the cedar forest. The angle of view α when the correlation between the CC size and litterfall amount is strongest, was 5° or less in the young cedar forest, but varied in the hardwood–pine mixed forest. This indicates the spatial distribution of 137Cs deposition has heterogeneity and homogeneity in each forest. [ABSTRACT FROM AUTHOR]

Purpose: We retrospectively investigated the risk factors for mediastinal lymph node (MLN) metastasis in esophagogastric junction (EGJ) cancer with an epicenter within 2 cm above and below the anatomical cardia, including both adenocarcinoma (AC) and squamous cell carcinoma (SCC). Methods: Fifty patients who underwent initial surgery for EGJ cancer from January 2002 to December 2013 were included in this study. We defined metastatic lymph nodes as pathological metastases in resected specimens and recurrence within 2 years postoperatively. Results: Thirty-four patients had AC and 16 had SCC; 24 patients underwent transhiatal resection and 26 underwent transthoracic resection. MLN metastasis was observed in 13 patients (26%) regardless of the histological type, 9 of whom had metastasis in the upper and middle mediastinum. Metastasis occurred when the esophageal invasion length (EIL) exceeded 20 mm. In addition, 10/13 patients had stage pN2–3 cancer. Multivariable analysis identified EIL ≥ 20 mm and stage pN2–3 as significant risk factors for MLN metastasis. The 5-year overall survival was 38% and 65% in the MLN-positive and -negative groups, respectively (p = 0.12). Multivariable Cox regression analysis showed that only stage pN2–3, and not the presence of MLN metastasis, was a significantly poor prognostic factor. Conclusion: MLN metastasis in EGJ cancer may have a close association with the EIL of the tumor, but the presence of MLN metastasis itself was not a poor prognostic factor. The significance and indications for MLN dissection should be clarified in prospective clinical trials. [ABSTRACT FROM AUTHOR]

Objective: Progressive aortic enlargement (PAE) is a critical adverse event in patients with medically treated aortic dissection (AD). However, no reliable predictor of the PAE has been established. The purpose of this study was to evaluate the value of 18F-FDG PET/CT for the prediction of PAE in patients with medically treated AD.Methods: Sixteen patients with AD who underwent optimal medical therapy were enrolled. 18F-FDG PET/CT examinations were performed in subacute phase (2 weeks-3 months) after the onset of AD. Target-to-background ratio (TBR) was measured as the maximum standardized uptake value (SUV) in the dissected aortic wall divided by blood pool SUV. The relation between TBR and occurrence of PAE (> 10 mm/year) was evaluated.Results: PAE was observed in four patients during the median follow-up period of 24 months. The TBR measured in the 4 patients showing PAE was significantly higher than that in the remaining 12 patients without PAE (2.44 ± 0.56 vs 1.87 ± 0.33, P = 0.025). The area under the receiver operating characteristic curve of TBR for predicting PAE was 0.82. With a threshold of 2.34, the TBR showed the sensitivity, specificity, and positive and negative predictive value of 75%, 92%, 75%, and 92%, respectively, for the prediction of PAE.Conclusions: Higher 18F-FDG uptake in the dissected aortic wall as determined by TBR is associated with increased risk of PAE in patients with medically treated AD. TBR shows good specificity and negative predictive value for predicting PAE. [ABSTRACT FROM AUTHOR]

Although several studies have assessed the effects of thinning on water quality, including nitrogen (N) exports, few have examined N-saturated plantations. This study assessed the short-term effect of thinning on N exports from a N-saturated plantation forest in northern Kyushu, western Japan, that was thinned (43% of basal area) during January–March 2012. Water levels at the gauging station were continually measured, and stream-water baseflow and stormflow samples were collected before (2011) and after (2013) forest thinning. Annual precipitation before (2469 mm) and after (2418 mm) forest thinning differed little, and annual water discharge after thinning (1641 mm) was similar to that before thinning (1609 mm). However, direct flow during stormflow periods was higher after thinning (260 mm) than before (153 mm). The concentrations of major ions in stream water did not differ before and after thinning. As a result, the high annual dissolved inorganic N (DIN) exports differed little before (35.8 kg N ha−1 a−1) and after (36.5 kg N ha−1 a−1) forest thinning. DIN exports during stormflow periods were slightly higher after (12.2 kg N ha−1 a−1) than before thinning (10.5 kg N ha−1 a−1) and were proportional to the increased direct flow after thinning (561 mm after vs. 470 mm before thinning). We concluded that thinning does not affect annual N exports from the N-saturated plantation forest, but it can increase the proportion of N exported during stormflow periods in proportion to increased water volume of direct flow after thinning. [ABSTRACT FROM AUTHOR]

Background: Granular cell tumors (GCT) in the gastrointestinal tract are rare. Herein, we describe a case of a gastric GCT diagnosed preoperatively by endoscopic ultrasound-guided fine needle aspiration biopsy (EUS-FNAB) and successfully resected by single-incision laparoscopic surgery (SILS). Case presentation: A 46-year-old Japanese woman had a tumor located in the angle of the stomach that was approximately 1.5 cm in diameter. Abdominal computed tomography (CT) revealed a submucosal tumor (SMT), which was finally diagnosed as a gastric GCT using EUS-FNAB. The tumor was not identified by CT 1 year and 4 months before diagnosis; therefore, because there was a possibility that the tumor was malignant, we performed surgical wedge resection using SILS. The patient had an uneventful recovery postoperatively and was discharged without complications 3 days after surgery. The tumor was pathologically diagnosed as a benign GCT that remained within the muscular layer. No recurrence or complications have occurred in the first 16 months since the surgery. Conclusion: Because gastric GCTs are generally benign and are rarely associated with lymph node metastasis, SILS seems to be a safe and feasible surgical approach for treating GCTs. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the characteristics of tear abnormalities with benign essential blepharospasm (BEB) and the effect of botulinum toxin type A (BTX-A) treatment. Study Design: Prospective and clinical study. Methods: Forty eyes of 40 patients (12 men and 28 women, ages 63.5 ±12.9) with BEB and tear abnormalities were enrolled. Results: The average scores for subjective symptoms as evaluated by the visual analog scale (VAS) were 46.3 and Dry Eye-Related Quality-of-Life Score (DEQS) were 63.7. The fluorescein breakup time (FBUT) was 2.7 ± 1.6 sec. Among fluorescein breakup patterns (FBUPs), dimple break, with the corresponding mechanism of decreased wettability was the most frequent, observed in 29 eyes (73%). The NEI score was 0.4 ± 0.7 and the van Bijesterveld score was 0.6 ± 0.8; the Schirmer 1 test value was 13.1 ± 9.4 mm. Eighteen patients received BTX-A treatment, and significant improvement was found in severity of subjective symptoms both on VAS and DEQS as well as for FBUT. The main FBUPs changed from dimple break to random break. Conclusion: Tear abnormalities seen in BEB correspond to short BUT-type dry eye (DE), subclassified into decreased wettability DE in view of FBUPs. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the efficacy of thoracic endovascular aortic repair (TEVAR) for ruptured acute type B aortic dissection (r-ATBAD).Materials and Methods: The study included 18 patients (15 men and 3 women) who underwent TEVAR for r-ATBAD in two institutions between 1997 and 2017. The mean patient age was 74 ± 10 years. The false lumen was patent in 13 patients (72%) and was mostly thrombosed in 5 patients (28%). Three patients had malperfusion of aortic branches. Eight patients (44%) were in circulatory shock.Results: Eleven patients (61%) died during or following TEVAR during admission. The causes of death were aortic rupture (n = 6), sepsis (n = 2), cerebral hypoxia (n = 1), pneumonia (n = 1), and renal failure (n = 1). Statistical analysis showed that dissection extending to the infrarenal level was significantly related to death from aortic rupture (P = 0.013). Early adverse events were observed in 12 patients (67%). One patient died from a non-aorta-related cause (sepsis) after discharge. The overall survival rate at 1 year was 39%. After discharge, an aorta-related adverse event (intimal injury) was observed in one patient. The adverse event-free survival rate at 1 year was 17%.Conclusions: Our results indicate that TEVAR for r-ATBAD is associated with high mortality and morbidity. More advanced strategies may be required to improve the outcome. [ABSTRACT FROM AUTHOR]

Heat-shock protein 90 (Hsp90) was recently identified as a silencing factor required for RNA interference (RNAi)-dependent heterochromatin assembly in the fission yeast Schizosaccharomyces pombe. As Hsp90 is known to contribute to the formation of small RNA-containing effector complexes, it would be expected that Hsp90 is also involved in the RNAi pathway in fission yeast. However, upon investigation, we found it very difficult to determine how Hsp90 modulates RNAi-dependent heterochromatin assembly in the cell. A lack of detectable small interfering RNAs in hsp90 mutant cells prevented us from examining the role of Hsp90 in the siRNA loading in the cell. In addition, deletion of genes encoding co-chaperones for Hsp90 appears not to affect RNAi-dependent pericentromeric silencing. One possible approach for elucidating the role of Hsp90 in RNAi-dependent heterochromatin assembly is the use of forward genetic screens to identify novel factors linking Hsp90 with other known RNAi factors. Here, we discuss the benefits of conducting further screenings and present some technical hints to help identify new factors. [ABSTRACT FROM AUTHOR]

Purple soil is highly susceptible for overland flow and surface erosion, therefore understanding surface runoff and soil erosion processes in the purple soil region are important to mitigate flooding and erosion hazards. Slope angle is an important parameter that affects the magnitude of runoff and thus surface erosion in hilly landscapes or bare land area. However, the effect of slope on runoff generation remains unclear in many different soils including Chinese purple soil. The aim of this study was to investigate the relationship between different slope gradients and surface runoff for bare-fallow purple soil, using 5 m × 1.5 m experimental plots under natural rainfall conditions. Four experimental plots (10°, 16°, 20° and 26°) were established in the Yanting Agro-ecological Experimental Station of Chinese Academy of Science in central Sichuan Basin. The plot was equipped with water storage tank to monitor water level change. Field monitoring from July 1 to October 31, 2012 observed 42 rainfall events which produced surface runoff from the experimental plots. These water level changes were converted to runoff. The representative eight rainfall events were selected for further analysis, the relationship between slope and runoff coefficient were determined using ANOVA, F-test, and z-score analysis. The results indicated a strong correlation between rainfall and runoff in cumulative amount basis. The mean value of the measured runoff coefficient for four experimental plots was around 0.1. However, no statistically significant relationship was found between slope and runoff coefficient. We reviewed the relationship between slope and runoff in many previous studies and calculated z-score to compare with our experimental results. The results of z-score analysis indicated that both positive and negative effects of slope on runoff coefficient were obtained, however a moderate gradient (16°-20° in this study) could be a threshold of runoff generation for many different soils including the Chinese purple soil. [ABSTRACT FROM AUTHOR]

Key message: Thinning resulted in evapotranspiration decrease and caused the relative contributions of each component to evapotranspiration to become very close. Abstract: To increase the understanding of forest management to control water cycles, we examined the effect of 50% strip thinning on evapotranspiration (ET) and its partitioning into canopy interception ( E ), tree transpiration ( E ), and forest floor evaporation ( E ) in a Japanese cypress ( Chamaecyparis obtusa Endl.) plantation. Intensive measurements were employed to monitor each component of ET during the pre- and post-thinning periods. The results showed the annual E was the dominant component of ET followed by E , whereas E was the smallest component in both periods. Thinning has significant impact on the process of ET partitioning. In such that it decreased from 42.3 to 33.7% in E /ET and from 45.0 to 34.9% in E /ET, and increased from 12.7 to 31.4% in E /ET on an annual scale. The relative contributions of each ET component to the whole ET became more or less the same after thinning. Additionally, the monthly E / P had relative stable values in both pre- and post-thinning periods, contributing significantly to the ET/ P during heavy rainfall conditions. After thinning, ET decreased by 21.4% from 629.3 to 494.8 mm during the growing season and by 20.4% from 979.8 to 780.1 mm at the annual scale, demonstrating that thinning results in an increase in water availability in the forested watershed. This study can improve the understanding of forest water budget in response to thinning and aid in development of appropriate forest management practices accordingly. [ABSTRACT FROM AUTHOR]

Background: An incisional hernia in a case of antethoracic pedicled jejunal flap esophageal reconstruction after esophagectomy is a very rare occurrence, and this hernia was distinctive in that the reconstructed jejunum had passed through the hernial orifice; a standard surgical treatment for such a presentation has not been established. Herein, we describe a case of repair using mesh prosthesis for an atypical and distinctive incisional hernia after antethoracic pedicled jejunal flap esophageal reconstruction. Case presentation: A 77-year-old woman with a history of subtotal esophagectomy who had undergone antethoracic pedicled jejunal flap reconstruction complained of epigastric prominence and discomfort without pain. On examination, she had an abdominal protrusion between the xiphoid process and the umbilicus that contained the small bowel. Computed tomography showed that the fenestration of the abdominal wall that was intentionally created for jejunum pull-up was dehisced in a region measuring 9 × 15 cm and the small intestine protruded through it into the subcutaneous space without strangulation. Because the hernial orifice was too large and the reconstructed jejunum was passing through the hernial orifice in this case, we applied a parastomal hernia repair method that was modified from the inguinal hernia repair using the Lichtenstein technique. After 3 years and 5 months following surgery, the patient has recovered without hernia recurrence or other complications. Conclusion: We consider this to be the first case of repair using Composix mesh prosthesis for repair of an atypical and distinctive incisional hernia after an antethoracic pedicled jejunal flap reconstruction. This method seems to be useful and could potentially be widely adopted as the surgical treatment for this condition. [ABSTRACT FROM AUTHOR]

There were two sources of ionizing irradiation after the atomic bombings of Hiroshima and Nagasaki: (1) initial gamma-neutron irradiation at the moment of detonation and (2) residual radioactivity. Residual radioactivity consisted of two components: radioactive fallout containing fission products, including radioactive fissile materials from nuclear device, and neutron-activated radioisotopes from materials on the ground. The dosimetry systems DS86 and DS02 were mainly devoted to the assessment of initial radiation exposure to neutrons and gamma rays, while only brief considerations were given for the estimation of doses caused by residual radiation exposure. Currently, estimation of internal exposure of atomic bomb survivors due to dispersed radioactivity and neutron-activated radioisotopes from materials on the ground is a matter of some interest, in Japan. The main neutron-activated radionuclides in soil dust were Na, Al, Si, P, Cl, K, Ca, Sc, Mn, Fe, Co, and Cs. The radionuclide Mn ( T = 2.58 h) is known as one of the dominant beta- and gamma emitters during the first few hours after neutron irradiation of soil and other materials on ground, dispersed in the form of dust after a nuclear explosion in the atmosphere. To investigate the peculiarities of biological effects of internal exposure to Mn in comparison with external gamma irradiation, a dedicated experiment with Wistar rats exposed to neutron-activated Mn dioxide powder was performed recently by Shichijo and coworkers. The dosimetry required for this experiment is described here. Assessment of internal radiation doses was performed on the basis of measured Mn activity in the organs and tissues of the rats and of absorbed fractions of internal exposure to photons and electrons calculated with the MCNP-4C Monte Carlo using a mathematical rat phantom. The first results of this international multicenter study show that the internal irradiation due to incorporated Mn powder is highly inhomogeneous, and that the most irradiated organs of the experimental animals are: large intestine, small intestine, stomach, and lungs. Accumulated absorbed organ doses were 1.65, 1.33, 0.24, 0.10 Gy for large intestine, small intestine, stomach, and lungs, respectively. Other organs were irradiated at lower dose levels. These results will be useful for interpretation of the biological effects of internal exposure of experimental rats to powdered Mn as observed by Shichijo and coworkers. [ABSTRACT FROM AUTHOR]

Recognizing imaging characteristics after ophthalmic surgery is necessary for radiologists to prevent misdiagnosis. We review typical appearances of intraorbital implanted devices and materials on CT and MRI with demonstration of the common surgical procedures. EX-PRESS glaucoma filtration devices appear as punctate areas of metal attenuation on CT and are typically placed at the corneoscleral junction. The imaging manifestations after cataract extraction are absence of the native lens of ovoid mass and the intraocular lens with high attenuation on CT and low signal intensity on MRI. The treatment of retinal detachment is achieved with intraocular tamponade or scleral buckling. In intraocular tamponade, the eye is filled with a bubble of gas or silicone oil. Gas results in air attenuation on CT and low signal intensity on MRI in the vitreous cavity. Silicone oil is hyperattenuating on CT and has variable intensity on MRI. In scleral buckling, the eye wall is indented with silicone buckling elements that show high or low attenuation on CT and low T1- and T2-weighted intensity on MRI. Degraded hydrogel buckling elements appear as swollen masses showing low attenuation on CT and high T2-weighted intensity on MRI. [ABSTRACT FROM AUTHOR]

We examined changes in suspended-sediment yields (SSY) after a 50 % strip thinning in headwater streams draining a Japanese cedar ( Cryptomeria japonica) and cypress ( Chamaecyparis obtusa) plantation forest. We applied a paired-catchment analysis to treated ( K: 17.1 ha) and control ( K: 8.9 ha) catchments. Annual suspended-sediment yield (SSY) in the prethinning period in the K and K catchments was 110.0 and 142.1 kg/ha per year. For the postthinning period, SSY in the K catchment became 5055.6 kg/ha per year, whereas that in the K catchment increased 893.2 kg/ha per year. The paired-catchment analysis revealed that SSY in the K catchment increased 17.0-fold compared with the prethinning period. However, the dominant hysteresis pattern remained clockwise in both pre- and postthinning periods. Sequences of large storm events in the postthinning period elevated SSY in both catchments. Increase in suspended sediment in the K catchment was associated with the combined impacts of thinning and sequences of storm events during the period of thinning operation. [ABSTRACT FROM AUTHOR]

Background: An optimal reconstruction method for proximal gastrectomy (PG) remains elusive. Esophagogastrostomy (EG) is technically simple but suffers from the disadvantage of gastroesophageal reflux. Jejunal interposition (JI) has a low rate of gastroesophageal reflux, but the procedure is more complicated, and delayed gastric emptying is a problem. Methods: We created a modified EG and have used the modified technique for PG since 2006. The procedure involves shaping the remnant stomach into a gastric conduit. The EG is performed high on the anterior wall, and the conduit is kept straight by applying a circular stapler inserted from the anterior wall of the antrum. The tip of the gastric conduit is then inserted into the lower mediastinum, creating a sharp angle of His. In this retrospective cohort study, the clinical and physiological outcomes were compared between 25 patients who underwent this procedure and 21 patients who underwent JI from 2001 to 2005. Results: Laparoscopic procedures were performed more frequently, and residual food and bile reflux were less common in the EG group than in the JI group. No significant differences in remnant gastritis or reflux esophagitis were observed between the two groups. However, the late complication of intestinal obstruction occurred only in the JI group. Conclusions: The modified EG technique has advantages over the JI technique because of its simplicity and low incidence of residual food and bile reflux. The next step would be to explore this technique further by a prospective multi-institutional study to confirm the reproducibility of its benefits. Miniabstract: The modified EG technique has advantages over the JI technique because of its simplicity, high rate of laparoscopy use, and low incidence of gastroesophageal reflux. [ABSTRACT FROM AUTHOR]

Background: Women undergoing surgery for primary breast cancer routinely have suction drains inserted deep to the wounds. A lack of data exists in relating how long suction drains should stay in situ after major breast surgery. Purpose: This study evaluates the appropriate timing of drain removal by comparing the 5-day-long postoperative drainage or drain removal when less than 50 mL/24 h to conventional drain removal. Methods: This controlled clinical trial was undertaken between February 1997 and May 2012 with a total of 214 consecutive patients who underwent elective total or partial mastectomy with level II axillary lymph node dissection. The main outcome measures included the length of hospital stay, and surgical morbidity, especially seroma formation. Results: In the study group, the age and operation time were significantly increased compared to the conventional group whereas the median hospital stay was significantly shorter in the study group than the control group (7 days vs. 9 days; p < 0.05). The incidence of seroma was 42.8 % in the study group and 31.6 % in the control group ( p = 0.14). The mean number of outpatient visits for seroma was 3.6 in the study group and 1.5 in the control group ( p < 0.05). Drainage volume of more than 150 mL/24 h all resulted in seroma formation. Conclusions: The new criteria for early drain removal are safe and acceptable despite the slightly increased chance of seroma formation. [ABSTRACT FROM AUTHOR]

Intraperitoneally administrated epithelial cellular adhesion molecule (EpCAM) monoclonal antibody is a therapeutic agent in patients with malignant effusion in several types of carcinoma. However, the role of EpCAM in peritoneal metastasis (PM) lesions and primary lesions of gastric cancer (GC) is still unclear. Therefore, in this study, we investigated EpCAM expression in GC patients with PM. We investigated the expression of EpCAM in 35PM lesions and 104 biopsy samples as primary lesions. Immunohistochemical staining was performed using the Ventana Benchmark XT (Roche Diagnostics) system. EpCAM expression was evaluated by calculating the total immunostaining score, which is the product of the proportion score and the intensity score. Overexpression was defined as a total score greater than 4. All PM specimens showed overexpression of EpCAM, and GC cells in both the surface layer and the deep layer of the PM showed a high expression of EpCAM. Meanwhile, in the biopsy sample, the expression of EpCAM ranged from none to strong. The EpCAM score results for PM specimens and biopsy samples were 11.0 ± 2.0 and 6.9 ± 3.9, respectively. The difference between the scores was statistically significant ( P < 0.05). The intraperitoneally administrated EpCAM antibody might have a anti-cancer effect in PM lesions of GC. Additionally, it can be assumed that only GC cells which express a high level of EpCAM might metastasize to the peritoneum. [ABSTRACT FROM AUTHOR]

To establish an effective training paradigm for a computer-assisted language learning system that enables non-native learners to exploit native-like perceptual cues for identifying length contrasts, e.g., consonant length, in the Japanese language (hereafter, Japanese length contrast), two experiments were conducted to investigate the identification accuracies of native Korean listeners before and after intensive perceptual training. The first experiment assessed the perceptual characteristics that native Korean listeners show when identifying the length contrast in the face of variation in speaking rate. The results suggested that native Korean listeners identify length contrasts by relying on a fixed-length criterion instead of adapting to changes in speaking rate. Also, Korean listeners showed a noticeable bias toward geminate responses for all speaking rates, with a stronger bias for slower speaking rates. The second experiment was based on these perceptual characteristics of Korean listeners. It investigated the extent to which intensive training helps improve listeners’ ability to identify Japanese length contrast and to examine whether greater stimulus variability during training leads to more robust training effects. The overall results showed that the perceptual training improved Korean listeners’ ability to perceive consonant length contrast. Moreover, misidentification of geminates decreased at post-test. However, the effect of training did not differ greatly between conditions of high stimulus variability during training (training with three speaking rates) and low stimulus variability (training with a single speaking rate). Training also did not generalize to perception of untrained contrast type (vowel length contrast). These results suggest that while perceptual training helps Korean learners learn a new, difficult-to-learn L2 phonemic length contrast, it is still difficult for learners to acquire native-like perceptual criteria. [ABSTRACT FROM AUTHOR]

Appropriate targeting of matrix proteins to peroxisomes is mainly directed by two types of peroxisomal targeting signals, PTS1 and PTS2. Although the basis of PTS1 recognition has been revealed by structural studies, that of PTS2 recognition remains elusive. Here we present the crystal structure of a heterotrimeric PTS2-recognition complex from Saccharomyces cerevisiae, containing Pex7p, the C-terminal region of Pex21p and the PTS2 of the peroxisomal 3-ketoacyl-CoA thiolase. Pex7p forms a β-propeller structure and provides a platform for cooperative interactions with both the amphipathic PTS2 helix and Pex21p. The C-terminal region of Pex21p directly covers the hydrophobic surfaces of both Pex7p and PTS2, and the resulting hydrophobic core is the primary determinant of stable complex formation. Together with in vivo and in vitro functional assays of Pex7p and Pex21p variants, our findings reveal the molecular mechanism of PTS2 recognition. [ABSTRACT FROM AUTHOR]

The prognosis of gastric cancer patients with peritoneal metastasis is very poor. Recent findings suggest that use of trastuzumab, a monoclonal antibody-based agent that targets human epidermal growth factor receptor 2 (HER2), may improve the prognosis of gastric cancer patients with HER2 overexpression and/or gene amplification. However, whether these mechanisms of HER2 upregulation are present in gastric cancer patients with peritoneal metastasis is unclear. The status of HER2 expression in a cohort of samples obtained from 35 gastric cancer patients with peritoneal metastasis was investigated using immunohistochemistry and fluorescence in situ hybridization. In 18 cases, we also investigated the influence of induction chemotherapy on HER2 overexpression. The frequency of HER2 overexpression and gene amplification was 2.9 % (1/35) in peritoneal metastatic lesions. There was concurrence in HER2 status in the samples examined prior to and following induction of chemotherapy. Most samples from the gastric cancer patients with peritoneal metastasis did not show HER2 amplification and/or overexpression. Although our study size was small, these results suggest that trastuzumab, which is critically dependent on HER2 expression, might not be an effective agent for these patients. Consequently, other therapeutic approaches for these patients must be developed. [ABSTRACT FROM AUTHOR]

The protein encoded by the activated disease resistance 1-like1 ( ADR1-L1) gene (locus name, At4g33300) belongs to the activated disease resistance 1 (ADR1) family of coiled-coil nucleotide-binding site leucine-rich repeat-type disease resistance proteins. This family contains four proteins and they have specific features in their amino acid sequences. It has been reported that ADR1 protein belongs to the ADR1 family, which is related to not only defense response but also drought tolerance. We found that transgenic plants overexpressing the ADR1-L1 gene showed a dwarf phenotype and morphological change in leaves. The expression levels of defense-related genes and the resistance to Pseudomonas syringae pv. tomato DC3000 were increased in transgenic plants. However, enhancement of drought tolerance and activation of abiotic response genes were not observed. When the growth temperature was changed from 22°C to 28°C, the expression of defense-related genes and the enhancement of resistance to a bacterial pathogen were suppressed and the dwarf phenotype and morphological change of leaves recovered. [ABSTRACT FROM AUTHOR]

Comparative analysis of nucleotide sequences of the genomic region located around 100 map unit of chromosome 1 using two accessions, Columbia (Col) and Landsberg erecta (L er), of Arabidopsis thaliana was performed. High divergence was detected between them, and the length of the L er sequence was half of corresponding sequence of Col. This divergence occurred by tandem duplication, deletion of large regions, and insertion of unrelated sequences. These events led to the high polymorphism of plant disease resistant genes, which are located in the analyzed region. It is highly probable that two-round duplication occurred, and the insertion sequences are transposable elements. The data suggest that the analyzed region had been evolving until quite recently. [ABSTRACT FROM AUTHOR]

Gibberellins (GAs) are phytohormones essential for many developmental processes in plants. A nuclear GA receptor, GIBBERELLIN INSENSITIVE DWARF1 (GID1), has a primary structure similar to that of the hormone-sensitive lipases (HSLs). Here we analyse the crystal structure of Oryza sativa GID1 (OsGID1) bound with GA4 and GA3 at 1.9 Å resolution. The overall structure of both complexes shows an α/β-hydrolase fold similar to that of HSLs except for an amino-terminal lid. The GA-binding pocket corresponds to the substrate-binding site of HSLs. On the basis of the OsGID1 structure, we mutagenized important residues for GA binding and examined their binding activities. Almost all of them showed very little or no activity, confirming that the residues revealed by structural analysis are important for GA binding. The replacement of Ile 133 with Leu or Val—residues corresponding to those of the lycophyte Selaginella moellendorffii GID1s—caused an increase in the binding affinity for GA34, a 2β-hydroxylated GA4. These observations indicate that GID1 originated from HSL and was further modified to have higher affinity and more strict selectivity for bioactive GAs by adapting the amino acids involved in GA binding in the course of plant evolution. [ABSTRACT FROM AUTHOR]

During defense responses, plant cells produce nitric oxide (NO), which may control many physiological processes. In a previous study, we reported that nitrate reductase (NR) is responsible in part for INF1 elicitor-induced NO production in Nicotiana benthamiana, but the possibility remains that other NO-generating system(s) contribute to NO production. In mammalian cells, NO production is catalyzed by NO synthase (NOS). However, NOS-like enzyme(s) have never been identified in plants, and only the gene for Arabidopsis thaliana nitric oxide-associated 1 ( AtNOA1) has been identified as a putative regulator of NOS activity in plants. In this study, we cloned NbNOA1, a homolog of AtNOA1, from N. benthamiana and investigated its involvement in NO production induced by INF1. The NbNOA1 gene was silenced by a virus-induced gene-silencing (VIGS) technique. NbNOA1-silenced plants had yellowish leaves. Silencing NbNOA1 partially decreased INF1-induced NO production, while overexpressing NbNOA1 did not affect NO production. Silencing NbNOA1 suppressed INF1-induced PR1a gene expression and increased susceptibility to Colletotrichum lagenarium. These results suggest that NbNOA1 is involved in INF1-mediated NO production and is required for defense responses. [ABSTRACT FROM AUTHOR]

We previously investigated the classification and prediction of dopamine D1 receptor agonists and antagonists using a topological fragment spectra (TFS)-based support vector machine (SVM), in which the dataset contained noise compounds that had no D1 receptor activity. This work extended the dataset to seven activity classes (dopamine D1, D2, and auto-receptor agonists, and D1, D2, D3, and D4 antagonists) and increased the noise ratio to ten times that of active compounds. In total, this study used 16,008 compounds for training and 1,779 compounds for prediction. The TFS-based SVM gave good, stable results for both classification and prediction, even in the case that included ten times the noise data. The resulting model correctly predicted 97.6% of the prediction set of 1,779 compounds. [ABSTRACT FROM AUTHOR]

Fireflies communicate with each other by emitting yellow-green to yellow-orange brilliant light. The bioluminescence reaction, which uses luciferin, Mg-ATP and molecular oxygen to yield an electronically excited oxyluciferin species, is carried out by the enzyme luciferase. Visible light is emitted during relaxation of excited oxyluciferin to its ground state. The high quantum yield of the luciferin/luciferase reaction and the change in bioluminescence colour caused by subtle structural differences in luciferase have attracted much research interest. In fact, a single amino acid substitution in luciferase changes the emission colour from yellow-green to red. Although the crystal structure of luciferase from the North American firefly (Photinus pyralis) has been described, the detailed mechanism for the bioluminescence colour change is still unclear. Here we report the crystal structures of wild-type and red mutant (S286N) luciferases from the Japanese Genji-botaru (Luciola cruciata) in complex with a high-energy intermediate analogue, 5′-O-[N-(dehydroluciferyl)-sulfamoyl]adenosine (DLSA). Comparing these structures to those of the wild-type luciferase complexed with AMP plus oxyluciferin (products) reveals a significant conformational change in the wild-type enzyme but not in the red mutant. This conformational change involves movement of the hydrophobic side chain of Ile 288 towards the benzothiazole ring of DLSA. Our results indicate that the degree of molecular rigidity of the excited state of oxyluciferin, which is controlled by a transient movement of Ile 288, determines the colour of bioluminescence during the emission reaction. [ABSTRACT FROM AUTHOR]

PsbP is a membrane extrinsic subunit of Photosystem II (PS II), which is involved in retaining Ca2+ and Cl−, two inorganic cofactors for the water-splitting reaction. In this study, we re-investigated the role of N-terminal region of PsbP on the basis of its three-dimensional structure. In previous paper [Ifuku and Sato (2002) Plant Cell Physiol 43: 1244–1249], a truncated PsbP lacking 19 N-terminal residues (Δ19) was found to bind to NaCl-washed PS II lacking PsbP and PsbQ without activation of oxygen evolution at all. Three-dimensional (3D) structure of PsbP suggests that deletion of 19 N-terminal residues would destabilize its protein structure, as indicated by the high sensitivity of Δ19 to trypsin digestion. Thus, a truncated PsbP lacking 15 N-terminal residues (Δ15), which retained core PsbP structure, was produced. Whereas Δ15 was resistant to trypsin digestion and bound to NaCl-washed PS II membranes, it did not show the activation of oxygen evolution. This result indicated that the interaction of 15-residue N-terminal flexible region of PsbP with PS II was important for Ca2+ and Cl− retention in PS II, although the 15 N-terminal residues were not essential for the binding of PsbP to PS II. The possible N-terminal residues of PsbP that would be involved in this interaction are discussed. [ABSTRACT FROM AUTHOR]

KaiA, KaiB and KaiC constitute the circadian clock machinery in cyanobacteria, and KaiA activates kaiBC expression whereas KaiC represses it. Here we show that KaiA is composed of three functional domains, the N-terminal amplitude-amplifier domain, the central period-adjuster domain and the C-terminal clock-oscillator domain. The C-terminal domain is responsible for dimer formation, binding to KaiC, enhancing KaiC phosphorylation and generating the circadian oscillations. The X-ray crystal structure at a resolution of 1.8 Å of the C-terminal clock-oscillator domain of KaiA from the thermophilic cyanobacterium Thermosynechococcus elongatus BP-1 shows that residue His270, located at the center of a KaiA dimer concavity, is essential to KaiA function. KaiA binding to KaiC probably occurs via the concave surface. On the basis of the structure, we predict the structural roles of the residues that affect circadian oscillations. [ABSTRACT FROM AUTHOR]

The calmodulin-binding domain of myristoylated alanine-rich C kinase substrate (MARCKS), which interacts with various targets including calmodulin, actin and membrane lipids, has been suggested to function as a crosstalk point among several signal transduction pathways. We present here the crystal structure at 2 A resolution of a peptide consisting of the MARCKS calmodulin (CaM)-binding domain in complex with Ca2+-CaM. The domain assumes a flexible conformation, and the hydrophobic pocket of the calmodulin N-lobe, which is a common CaM-binding site observed in previously resolved Ca2+-CaM-target peptide complexes, is not involved in the interaction. The present structure presents a novel target-recognition mode of calmodulin and provides insight into the structural basis of the flexible interaction module of MARCKS. [ABSTRACT FROM AUTHOR]

P-glycoprotein extrudes a large variety of xenobiotics from the cell, thereby protecting tissues from their toxic effects. The machinery underlying unidirectional multidrug pumping remains unknown, largely due to the lack of high-resolution structural information regarding the alternate conformational states of the molecule. Here we report a pair of structures of homodimeric P-glycoprotein: an outward-facing conformational state with bound nucleotide and an inward-facing apo state, at resolutions of 1.9 Å and 3.0 Å, respectively. Features that can be clearly visualized at this high resolution include ATP binding with octahedral coordination of Mg2+; an inner chamber that significantly changes in volume with the aid of tight connections among transmembrane helices (TM) 1, 3, and 6; a glutamate−arginine interaction that stabilizes the outward-facing conformation; and extensive interactions between TM1 and TM3, a property that distinguishes multidrug transporters from floppases. These structural elements are proposed to participate in the mechanism of the transporter. P-glycoprotein, an ATP-binding cassette (ABC) transporter, extrudes a large variety of xenobiotics from the cell which protects tissues from toxins. Here authors solve a pair of X-ray structures of homodimeric P-glycoprotein and resolve structural elements proposed to participate in the mechanism of the transporter. [ABSTRACT FROM AUTHOR]