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Light/dark cycling is an inherent condition of outdoor microalgae cultivation, but is often unfavorable for lipid accumulation. This study aims to identify promising targets for metabolic engineering of improved lipid accumulation under outdoor conditions. Consequently, the lipid-rich mutant Chlamydomonas sp. KOR1 was developed through light/dark-conditioned screening. During dark periods with depressed CO 2 fixation, KOR1 shows rapid carbohydrate degradation together with increased lipid and carotenoid contents. KOR1 was subsequently characterized with extensive mutation of the ISA1 gene encoding a starch debranching enzyme (DBE). Dynamic time-course profiling and metabolomics reveal dramatic changes in KOR1 metabolism throughout light/dark cycles. During light periods, increased flux from CO 2 through glycolytic intermediates is directly observed to accompany enhanced formation of small starch-like particles, which are then efficiently repartitioned in the next dark cycle. This study demonstrates that disruption of DBE can improve biofuel production under light/dark conditions, through accelerated carbohydrate repartitioning into lipid and carotenoid.

A prevailing scenario of the origin of life postulates thioesters as key intermediates in protometabolism, but there is no experimental support for the prebiotic CO 2 fixation routes to thioesters. Here we demonstrate that, under a simulated geoelectrochemical condition in primordial ocean hydrothermal systems (-0.6 to -1.0 V versus the standard hydrogen electrode), nickel sulfide (NiS) gradually reduces to Ni 0 , while accumulating surface-bound carbon monoxide (CO) due to CO 2 electroreduction. The resultant partially reduced NiS realizes thioester (S-methyl thioacetate) formation from CO and methanethiol even at room temperature and neutral pH with the yield up to 35% based on CO. This thioester formation is not inhibited, or even improved, by 50:50 coprecipitation of NiS with FeS or CoS (the maximum yields; 27 or 56%, respectively). Such a simple thioester synthesis likely occurred in Hadean deep-sea vent environments, setting a stage for the autotrophic origin of life., (© 2021. The Author(s).)

Numerous studies have confirmed the effectiveness of cognitive behavioral therapy (CBT) for chronic pain, and it is generally regarded as an appropriate intervention. However, it may not be effective for some pain sites, and the duration of the effect may be limited. In addition, some studies of CBT lacked a comparison group. This review summarizes evidence for the effectiveness of CBT for orofacial pain and assists in the development of guidelines for orofacial pain management. A literature search in PubMed was performed for studies published from April 1990 through March 2020. The search keywords were "burning mouth syndrome," "temporomandibular disorders," "myofascial pain syndrome,""chronic orofacial pain conditions," "cognitive behavioral therapy," and "non-pharmacological therapy." The results indicate that CBT alone or in combination with other treatments, such as intraoral appliance, stress management, or biofeedback, is effective for the vast majority of orofacial pain cases. Therefore, dentists should consider using CBT to manage orofacial pain in their patients.

Rhodococcus qingshengii CS98 is a bacterium isolated from soil in Japan that shows strong cesium-accumulating ability. Here, we report the complete genome sequence of R. qingshengii (6.7 Mb), which may provide useful genetic information supporting its bioremediation features., (Copyright © 2020 Satoh et al.)

T-DNA integration into plant chromosomal DNA via Agrobacterium tumefaciens can be achieved by exploiting the double-strand break repair system of the host's DNA. However, the detailed mechanism of T-DNA integration remains unclear. Here, a sequence analysis of the junction sequences of T-DNA and chromosomal DNA was performed to assess the mechanism of T-DNA integration. T-DNA was introduced into Arabidopsis wild-type and NHEJ-deficient ku80 mutant plants using the floral dip method; the junctions of the left border (LB) of T-DNA were subsequently analyzed by adapter PCR. The most frequent junction of the LB of T-DNA with chromosomal DNA was of the filler DNA type in both lines. The lengths of direct or inverted repeat sequences within or around the filler DNA sequence were greater in the ku80 mutant. In addition, the frequency of T-DNA integration near a transcription start site was significantly higher in the ku80 mutant. Our observations suggest that the presence of the Ku80 protein affects the location of the integration of T-DNA and the pattern of formation of repeat sequences within or around the filler DNA during LB integration into chromosomal DNA.

Backgrounds: The width of mucosal defects after endoscopic submucosal dissection (ESD) of esophageal squamous cell carcinoma (ESCC) is known to be a risk factor for esophageal strictures. Although steroid injection and oral steroid have recently been reported as prophylactic treatments, these were shown to be ineffective in a subset of patients with post-ESD mucosal defects involving the entire circumference of the esophagus. The aim of this study was to demonstrate outcome with prophylactic steroid administration for post-ESD mucosal defects involving the entire circumference, and to explore risk factors for esophageal strictures except for circumference of the esophagus., Methods: Between November 2012 and August 2018, we enrolled patients with post-ESD mucosal defects involving the entire circumference of the esophagus who had received steroid injection (triamcinolone acetonide 50-100 mg, given immediately after ESD) followed by oral steroid (prednisolone 30 mg/day, tapered gradually over 8 weeks) as prophylactic treatment. Esophageal stricture was defined as case where ordinary-sized endoscope could not pass through post-ESD site, thus requiring endoscopic balloon dilation (EBD) repeatedly until relief of stricture was achieved. We retrospectively evaluated the rates of strictures, refractory strictures (requiring ≥ 6 EBD procedures) and unimproved strictures (not improvable by repeated EBD alone) and explored risk factors for strictures., Results: A total of 26 patients met the including criteria. The rates of strictures, refractory strictures, and unimproved strictures were 62%, 38%, and 12%, respectively. The pre-ESD longitudinal extension of the lesion > 5 cm was identified as a risk factor for refractory strictures, suggesting that lesions with this factor had a shorter time to stricture development, required more EBD procedures, and longer EBD durations., Conclusion: Although additional study is required in a larger number of patients, careful consideration needs to be given to ESD as an indication for large spreading ESCC involving the entire circumference of esophagus given its high stricture risk.

Introduction: Rice leaves and stems, which can be used as rice straw for livestock feed, accumulate soluble oxalate. The oxalate content often reaches 5% of the dry weight leaves. Excess uptake of oxalate-rich plants causes mineral deficiencies in vertebrates, so it is important to reduce the oxalate content in rice leaves to produce high-quality rice straw. However, the mechanism of oxalate accumulation in rice has remained unknown., Objectives: To understand metabolic networks relating oxalate accumulation in rice., Methods: In this study, we performed metabolome analysis of rice M 2 population generated by ion-beam irradiation using CE-MS., Results: The result showed wide variation of oxalate contents in M 2 plants compared with those of control plants. Multivariate analyses of metabolome dataset revealed that oxalate accumulation was strongly related with anionic compounds such as 2OG and succinate. For low-oxalate plants, four patterns of metabolic alterations affected oxalate contents in the M 2 leaves were observed. In M 3 plants, we found putative low-oxalate line obtained from low-oxalate M 2 mutant., Conclusions: These findings would lead to produce the low-oxalate rice and to understand the oxalate synthesis in plants.These findings would lead to produce the low-oxalate rice and to understand the oxalate synthesis in plants.

Background: Proton beam therapy (PBT) with concurrent chemotherapy is promising for esophageal squamous cell carcinoma (ESCC). The aim of study was to evaluate the outcome of concurrent chemo-proton therapy (CCPT), i.e., PBT with concurrent chemotherapy for cT1 ESCC and the salvage endoscopic therapy for local recurrence., Methods: Patients with clinical T1 ESCC who underwent CCPT (60 GyE) between April 2013 and April 2017 at the National Cancer Center Hospital East were investigated. The efficacy of CCPT at the primary site was evaluated via endoscopy; primary complete response (CR) was defined as disappearance of the tumor lesion/ulcer and absence of cancer cells on biopsy. Endoscopic evaluation was performed with the same protocol of conventional chemoradiotherapy. Local recurrence after CCPT was treated with endoscopic resection for cT1a and with esophagectomy or photodynamic therapy for cT1b+., Results: Of the 44 patients (median age, 70 years) that underwent CCPT, 43 patients (98%) achieved primary CR. Among the 44 patients, the 3-year overall survival rate was 95.2%. Five patients (11%) developed local recurrence without regional lymph node or distant metastasis and received endoscopic resection or photodynamic therapy. All five patients were alive with no recurrence after a median 23 months., Conclusions: The results suggest that CCPT is an effective treatment for cT1 ESCC and careful endoscopic follow-up allows preferable local control with salvage endoscopic treatment.

Background and Aim: Endoscopic diagnosis of advanced histology in colorectal lesions sized <10 mm is essential for appropriate selection of resection methods. The Japan Narrow-band imaging Expert Team (JNET) classification has been recently validated for the evaluation of colorectal lesions. Our objective was to investigate the diagnostic value of the JNET classification for advanced histology in colorectal lesions sized <10 mm., Methods: We enrolled 680 patients with 1472 colorectal lesions sized <10 mm diagnosed according to the JNET classification and who subsequently underwent endoscopic or surgical resection between January and December 2017. We retrospectively examined the relationship between the JNET findings and pathological histology. Multivariate analysis was carried out to assess the predictive power of the JNET findings and clinical characteristics of lesions., Results: Advanced histology was present in 29 (2.0%) lesions. Advanced histology was absent in 68 lesions diagnosed as JNET type 1, whereas 1389 lesions diagnosed as JNET type 2A included 19 lesions of advanced histology (1.4%) with high-grade dysplasia alone. Eleven lesions diagnosed as JNET type 2B comprised eight lesions of advanced histology (72.7%) with four high-grade dysplasia and four submucosal invasive cancer, and two lesions diagnosed as JNET type 3 were submucosal invasive cancer. Multivariate analysis showed that JNET type 2B + 3 was a stronger predictive factor for advanced histology than other clinical risk factors., Conclusion: Narrow-band imaging with magnification according to the JNET classification may be a useful modality for identification of advanced histology in colorectal lesions sized <10 mm., (© 2019 Japan Gastroenterological Endoscopy Society.)

Crop cultivars with larger root systems have an increased ability to absorb water and nutrients under conditions of water deficit. To unravel the molecular mechanism of water-stress tolerance in wheat, we performed RNA-seq analysis on the two genotypes, Colotana 296-52 (Colotana) and Tincurrin, contrasting the root growth under polyethylene-glycol-induced water-stress treatment. Out of a total of 35,047 differentially expressed genes, 3692 were specifically upregulated in drought-tolerant Colotana under water stress. Transcription factors, pyrroline-5-carboxylate reductase and late-embryogenesis-abundant proteins were among upregulated genes in Colotana. Variant calling between Colotana and Tincurrin detected 15,207 SNPs and Indels, which may affect protein function and mediate the contrasting root length phenotype. Finally, the expression patterns of five triads in response to water, high-salinity, heat, and cold stresses were analyzed using qRT-PCR to see if there were differences in homoeologous gene expression in response to those conditions. The five examined triads showed variation in the contribution of homoeologous genes to water, high-salinity, heat, and cold stresses in the two genotypes. The variation of homoeologous gene expression in response to environmental stresses may enable plants to better cope with stresses in their natural environments., Competing Interests: The authors declare no conflict of interest.

Ion beams are physical mutagens used for plant and microbe breeding that cause mutations via a mechanism distinct from those of chemical mutagens or gamma rays. We utilized whole-exome sequencing of rice DNA in order to understand the properties of ion beam-induced mutations in a genome-wide manner. DNA libraries were constructed from selected carbon-ion-beam-induced rice mutants by capturing with a custom probes covering 66.3 M bases of nearly all exons and miRNAs predicted in the genome. A total of 56 mutations, including 24 single nucleotide variations, 23 deletions, and 5 insertions, were detected in five mutant rice lines (two dwarf and three early-heading-date mutants). The mutations were distributed among all 12 chromosomes, and the average mutation frequency in the M1 generation was estimated to be 2.7 × 10 -7 per base. Many single base insertions and deletions were associated with homopolymeric repeats, whereas larger deletions up to seven base pairs were observed at polynucleotide repeats in the DNA sequences of the mutation sites. Of the 56 mutations, six were classified as high-impact mutations that caused a frame shift or loss of exons. A gene that was functionally related to the phenotype of the mutant was disrupted by a high-impact mutation in four of the five lines tested, suggesting that whole-exome sequencing of ion-beam-irradiated mutants could facilitate the detection of candidate genes responsible for the mutant phenotypes., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The high toxicity of cadmium (Cd) and its ready uptake by plants has become a major agricultural problem. To investigate the genetic architecture and genetic regulation of Cd tolerance in barley, we conducted quantitative trait loci (QTL) analysis in the phenotypically polymorphic Oregon Wolfe Barley (OWB) mapping population, derived from a cross between Rec and Dom parental genotypes. Through evaluating the Cd tolerance of 87 available doubled haploid lines of the OWB mapping population at the seedling stage, one minor and one major QTL were detected on chromosomes 2H and 6H, respectively. For chlorosis and necrosis traits, the major QTL explained 47.24% and 38.59% of the phenotypic variance, respectively. RNA-Seq analysis of the parental seedlings under Cd treatment revealed 542 differentially expressed genes between Cd-tolerant Rec and Cd-susceptible Dom genotypes. By analyzing sequence variations in transcribed sequences of the parental genotypes, 155,654 SNPs and 1,525 InDels were identified between the two contrasting genotypes and may contribute to Cd tolerance. Finally, by integrating the data from the identified QTLs and RNA-Seq analysis, 16 Cd tolerance-related candidate genes were detected, nine of which were metal ion transporters. These results provide promising candidate genes for further gene cloning and improving Cd tolerance in barley., Competing Interests: The authors have declared that no competing interests exist.

Gamma rays are the most frequently used ionizing radiation in plant mutagenesis; however, few studies are available on the characteristics of mutations at a genome-wide level. Here, we quantitatively and qualitatively characterized the mutations induced by acute/chronic gamma ray irradiation in Arabidopsis. The data were then compared with those previously obtained for carbon ion irradiation. In the acute irradiation of dry seeds at the same effective survival dose, gamma rays and carbon ions differed substantially, with the former inducing a significantly greater number of total mutation events, while the number of gene-affecting mutation events did not differ between the treatments. This may result from the gamma rays predominantly inducing single-base substitutions, while carbon ions frequently induced deletions ≥2 bp. Mutation accumulation lines prepared by chronic gamma irradiation with 100-500 mGy/h in five successive generations showed higher mutation frequencies per dose compared with acute irradiation of dry seeds. Chronic gamma ray irradiation may induce larger genetic changes compared with acute gamma ray irradiation. In addition, the transition/transversion ratio decreased as the dose rate increased, suggesting that plants responded to very low dose rates of gamma rays (∼1 mGy/h), even though the overall mutation frequency did not increase. These data will aid our understanding of the effects of radiation types and be useful in selecting suitable radiation treatments for mutagenesis., (Copyright © 2020 Hase, Satoh, Seito and Oono.)

Background: Photodynamic therapy (PDT) is a salvage treatment for local failure following chemoradiotherapy (CRT) for esophageal cancer. This study aimed to evaluate the efficacy and safety of salvage PDT using the second-generation photosensitizer, talaporfin sodium (L-PDT), and compare L-PDT to PDT using porfimer sodium (P-PDT)., Methods: We retrospectively analyzed clinical outcomes of patients treated with L-PDT and P-PDT. Patients with histologically proven local failure limited to the shallow muscularis propria layer (T2) after CRT or radiotherapy (RT) for esophageal cancer were enrolled., Results: A total of 121 patients were enrolled in this study. L-PDT and P-PDT groups consisted of 44 and 77 patients, respectively. The overall local complete response (L-CR) rate was 62.1% (95% confidence interval [CI], 52.6-70.9), and the L-PDT group showed a better L-CR rate than did the P-PDT group (69.0% [95% CI 52.9-82.4] vs. 58.1% [95% CI 46.1-69.5]). The common complications of skin phototoxicity, esophageal stricture, and esophageal fistula were all less frequent in the L-PDT group than in the P-PDT group. The only treatment-related death in this study was in the P-PDT group. With a median follow-up period of 15.8 months (interquartile range 7.1-37.4) in all 121 patients, overall survival rate at 1 year was significantly higher among patients who achieved L-CR (91.2% [95% CI 80.2-96.3]) than among those who could not achieve L-CR with PDT (50.8% [95% CI 33.6-65.6])., Conclusions: L-PDT represented better short-term outcomes than P-PDT as a salvage treatment for local failure following CRT or RT for esophageal cancer.

Background: Monopolar instruments are generally used in colorectal endoscopic mucosal resection (EMR). Bipolar instruments have previously been reported to be as safe as monopolar instruments. We sought to compare the safety of the monopolar and bipolar snare and hemostatic forceps in an animal model., Methods: We created 5-mm, 10-mm, and 15-mm target lesions on an ex vivo porcine rectum. Two lesions of each size were resected via monopolar polypectomy (M-P), monopolar EMR (M-E), bipolar polypectomy (B-P), and bipolar EMR (B-E). We performed a pathological evaluation of the conditions of perforation and the effects of burning on the tissues. In addition, we burned the muscularis propria covered with submucosal layer using monopolar and bipolar hemostatic forceps and performed pathological evaluations., Results: Polypectomy and EMR were performed in a total of 24 target lesions. A perforation was found on histology in one case of M-P and one case of M-E after removing target lesions of 15 mm in diameter. There were no perforations during endoscopic resection using the bipolar snare. The thermal denaturation in B-P did not reach the muscularis propria layer regardless of the size of the target lesion. Although thermal damage after using monopolar hemostatic forceps was extensive, thermal denaturation was only seen on the surface of the submucosal layer when bipolar hemostatic forceps were used., Conclusions: Bipolar instruments cause less damage to the tissue than monopolar instruments. Our results also suggest that bipolar instruments may be safer than monopolar instruments in endoscopic procedures for colorectal lesions.

Background and Aim: To assess the visibility of colorectal lesions using blue laser imaging (BLI)-bright and linked-color imaging (LCI) with an eye-tracking system., Methods: Eleven endoscopists evaluated 90 images of 30 colorectal lesions. The lesions were randomly selected. Three images of each lesion comprised white light imaging (WLI), BLI-bright, and LCI in the same position. Participants gazed at the images, and their eye movements were tracked by the eye tracker. We analyzed whether the participants could detect the lesion and how long they took to detect the lesion. We assessed the miss rate and detection time among the imaging modalities., Results: One endoscopist was excluded, and 10 endoscopists were assessed. Overall, 12.6% of lesions were missed with WLI, 6.0% with BLI-bright, and 4.3% with LCI; the miss rate of BLI-bright and LCI was significantly lower than that of WLI (P < 0.01), with no significant difference between the former modalities (P = 0.54). Mean (± SD) detection times were 1.58 ± 1.60 s for WLI, 1.01 ± 1.21 s for BLI-bright, and 1.10 ± 1.16 s for LCI. Detection time for BLI-bright and LCI was significantly shorter than that for WLI (P < 0.0001), with no significant difference between the former modalities (P = 0.34). Regarding the miss rate and detection time between the expert and the non-experts, there was a significant difference with WLI but not with BLI-bright and LCI., Conclusion: Blue laser imaging-bright and LCI improved the detection of colorectal lesions compared with WLI using an eye-tracking system., (© 2019 Japan Gastroenterological Endoscopy Society.)

One of the most plausible scenarios of the origin of life assumes the preceding prebiotic autotrophic metabolism in sulfide-rich hydrothermal vent environments. However, geochemical mechanisms to harness the reductive power provided by hydrothermal systems remain to be elucidated. Here, we show that, under a geoelectrochemical condition realizable in the early ocean hydrothermal systems, several metal sulfides (FeS, Ag 2 S, CuS, and PbS) undergo hour- to day-scale conversion to the corresponding metals at ≤-0.7 V (versus the standard hydrogen electrode). The electrochemically produced FeS-Fe 0 assemblage promoted various reactions including certain steps in the reductive tricarboxylic acid cycle with efficiencies far superior to those due to pure FeS. The threshold potential is readily generated in the H 2 -rich alkaline hydrothermal systems that were probably ubiquitous on the Hadean seafloor. Thus, widespread metal production and metal-sustained primordial metabolism were likely to occur as a natural consequence of the active hydrothermal processes on the Hadean Earth.

Background: Duodenal neuroendocrine tumors (NETs) measuring ≤ 10 mm in diameter that are confined to the submucosal layer without metastasis are suitable for endoscopic treatment. We previously reported the efficacy and safety of endoscopic submucosal resection with a ligation device (ESMR-L) for duodenal NETs. In order to make the procedure simpler, we attempted ESMR-L without submucosal injection. The aim of this study was to evaluate the efficacy of ESMR-L without injection for duodenal NETs., Methods: A total of 12 patients with small (≤ 10 mm) sporadic duodenal NETs were treated via endoscopic resection at the National Cancer Center Hospital East between December 2010 and May 2018. All patients were evaluated via endoscopy and endoscopic ultrasound, and abdominal computed tomography was performed to rule out metastatic lesions. The patients' characteristics, clinical courses, and complications, such as perforation and bleeding, were retrospectively assessed. We examined the correlation between ESMR-L with or without submucosal saline injection and clinicopathological parameters., Results: The median procedural time for ESMR-L was 13 min. All lesions invaded the submucosal layer, and the histological diagnoses were classified as NET G1 in 11 lesions and NET G2 in one lesion. En bloc resection and complete resection were achieved in 12 and 11 lesions, respectively. The postoperative duration of hospital stay was 4 days. At the median follow-up of 17 months, there was no incidence of local recurrence or distant metastasis. Perforation and intraoperative bleeding were not observed. However, delayed bleeding was found in one patient. ESMR-L without submucosal injection required a significantly shorter procedural time than ESMR-L with submucosal saline injection (10 min vs. 15 min, respectively; p = 0.007)., Conclusions: ESMR-L is safe and effective. Particularly, ESMR-L without submucosal injection could be used to treat these NETs safely within a short period of time.

Competing Interests: The authors declare no conflicts of interest for this article.

Temporomandibular disorders (TMD) are common chronic musculoskeletal pain conditions among orofacial pain. Painful TMD condition such as myalgia and arthralgia can be managed by exercise therapy. However, as it is hard to access actual effect of each modality that is included in an exercise therapy programme due to multiple choice of the management modality, their efficacy remains controversial. Therefore, this review focused on the effects of exercise therapy for the management of painful TMD. The aims of this review were to summarise the effects of exercise therapy for major symptoms of painful TMD and to establish a guideline for the management of painful TMD, resulting in higher quality and reliability of dental treatment. In this review, exercise modalities are clearly defined as follows: mobilisation exercise, muscle strengthening exercise (resistance training), coordination exercise and postural exercise. Furthermore, pain intensity and range of movements were focused as outcome parameters in this review. Mobilisation exercise including manual therapy, passive jaw mobilisation with oral appliances and voluntary jaw exercise appeared to be a promising option for painful TMD conditions such as myalgia and arthralgia. This review addressed not only the effects of exercise therapy on various clinical conditions of painful TMD shown in the past, but also an urgent need for consensus among dentists and clinicians in terms of the management of each condition, as well as terminology., (© 2019 John Wiley & Sons Ltd.)

Aims: The purpose of this study was to determine the reliability and validity of the Japanese version of the Richards-Campbell Sleep Questionnaire as a measure of sleep among intensive care unit patients in a Japanese hospital., Design: Cross-sectional survey., Methods: The Richards-Campbell Sleep Questionnaire was initially translated into Japanese using the back-translation method. Validity was evaluated by determining the association between sleep efficiency, measured using simplified polysomnography, and the total score on the Japanese version of the Richards-Campbell Sleep Questionnaire. Adult non-intubated intensive care unit patients who completed the five-item visual analogue scale underwent polysomnography for one night. Reliability was tested using Cronbach's alpha coefficient., Results: Thirty-three patients were included in the analysis. After excluding four patients with subsyndromal delirium, the Pearson correlation coefficient was 0.602 ( p  = 0.001). Cronbach's alpha coefficient was 0.911., Conclusion: The Japanese version of the Richards-Campbell Sleep Questionnaire could be used as an alternative to polysomnography when assessing sleep quality in lucid intensive care unit patients., Competing Interests: The authors declare no conflict of interest.

Background and study aims  This study was designed to clarify clinicopathological, endoscopic, and genetic characteristics of inverted sessile serrated adenomas/polyps. Patients and methods  In this retrospective study, we reviewed the pathology reports of patients treated in our hospital between January 2010 and June 2015 and identified sessile serrated adenomas/polyps that were diagnosed with endoscopic resected specimens. Clinicopathological, endoscopic, and genetic features were compared between the inverted and ordinary types. Results  Among the 104 sessile serrated adenomas/polyps, 37 lesions were inverted (35.6 %). The inverted types had two patterns of invasion: expansive and infiltrating growth. Expansive growth was observed in 15 cases (40.5 %) and infiltrating in 22 (59.5 %). Regarding the clinicopathological findings and endoscopic characteristics of the inverted types, presence of adherent mucous, location in the right-side colon, an expanded type-II pit pattern, irregularly dilated vessels, and a depression were demonstrated in 89 % (33/37), 73 % (27/37), 54 % (20/37), 75 % (28/37), and 35 % (13/37), respectively. Contrastingly, these were demonstrated in 86 % (58/67), 84 % (56/67), 55 % (37/67), 58 % (39/67), and 0 % (0/67), respectively, in the ordinary type. In the univariate analysis, male sex and a depression in the adenoma/polyp were significantly associated with inverted types ( P  < 0.001). BRAF mutation at codon 600 was found in six of seven ordinary types and in 11 of 11 of the inverted types. KRAS, NRAS, and PIK3CA mutations were not found in the ordinary and inverted types. Conclusion  More than 30 % of sessile serrated adenomas/polyps were pathologically diagnosed as inverted, and approximately 40 % of them were of the expansive growth type and easily diagnosed with endoscopy.

Background: Receptor tyrosine kinases (RTKs) play critical roles in gastric cancer (GC) progression and are potential targets for novel molecular-targeted agents or photo-immunotherapies. During patient selection, targeted biopsy is the first step. However, heterogeneous expression of RTKs based on the macroscopic appearance in GC has not been extensively addressed. Accordingly, in this study, we evaluated differences in RTK expression associated with macroscopic appearance in GC., Methods: In total, 375 consecutive patients who had undergone gastrectomy at the National Cancer Center Hospital East and who had histologically proven adenocarcinoma, available archived tumor sample, and no history of chemotherapy were enrolled in this study. For these cases, tissue microarray (TMA) samples were examined using immunohistochemistry (IHC). Based on the results of IHC, cases were selected for detailed examination. We re-evaluated IHC scores in more than three tumor blocks per case and comparatively evaluated differences in IHC expression in RTKs between the mucosal portion (MuP) and invasive portion (InP)., Results: Human epidermal growth factor receptor 2 (HER2)-, epidermal growth factor receptor (EGFR)-, and mesenchymal epithelial transition factor (c-MET)-positive rates were 6, 9, and 20%, respectively. Twenty-two cases were then analyzed to assess differences in IHC expression levels in the same lesion. Concordance rates of positive staining of HER2, EGFR, and MET between MuP and whole tumor were 100, 40, and 56% and those with InP were 46, 100, and 56%., Conclusions: To avoid underestimating expression status, biopsies must be taken from MuP for HER2, InP for EGFR, and both proportions for c-MET.

Competing Interests: None, (© Georg Thieme Verlag KG Stuttgart · New York.)

Background and Aims: Salvage endoscopic submucosal dissection (ESD) after chemoradiotherapy can be technically difficult as a result of radiation-induced fibrosis. We aimed to evaluate the technical feasibility of ESD for local failure after chemoradiotherapy for esophageal squamous cell carcinoma (ESCC) and for other primary lesions within the irradiation field., Methods: Consecutive patients treated with ESD for superficial ESCC between December 2009 and May 2017 were investigated retrospectively and stratified into group A (33 patients, 35 lesions; local failure at the primary site after chemoradiotherapy), group B (25 patients, 34 lesions; second primary lesions within the irradiation field), and group C (550 patients, 596 lesions; radiotherapy-naïve superficial ESCC). We evaluated procedural success rate, en bloc resection rate, 1-year local relapse-free survival (LRFS) rate, procedure time, and incidence of major adverse events., Results: The rates of procedural success and en bloc resection, respectively, were significantly lower in group A (89%, 86%) than in groups B (100%, 100%) and C (100%, 98%). The 1-year LRFS rates were 86%, 100%, and 99% in groups A, B, and C, respectively, and significantly lower in group A than in group C. Serious adverse events including perforation were not observed in groups A and B; perforation occurred only in group C (2.8%)., Conclusions: ESD is technically feasible in patients with local failure, especially as initial salvage treatment and as treatment for second primary lesions within the irradiation field., (Copyright © 2018 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

We describe a series of colorectal polyps characterized by mixed adenomatous and serrated features, herein referred to as superficially serrated adenomas. Twenty superficially serrated adenomas were obtained from 11 female and 9 male patients aged 62-87 years. Most lesions endoscopically appeared as small sessile polyps, but larger lesions were plaque-like (2-20 mm; median, 5 mm). Eighteen lesions (90%) were located in the sigmoid colon or rectum. They consisted primarily of straight, adenomatous glands but showed serration confined to the superficial layer. Immunohistochemistry revealed CK20 expression in the upper layer. Proliferating cells, determined by their expression of Ki-67, were localized to the middle to bottom layers. Genetic analyses identified KRAS mutations in 19 lesions and a BRAF mutation in one lesion. Furthermore, RSPO fusions and/or overexpression were observed in 18 lesions and truncating APC mutations were observed in the two remaining lesions. Consistent with the presence of WNT pathway gene alterations, all superficially serrated adenomas showed focal or diffuse nuclear β-catenin accumulation. Since concurrent KRAS mutations and RSPO fusions are reportedly common in traditional serrated adenomas, we reviewed 129 traditional serrated adenomas and found 15 lesions (12%) that were associated with superficially serrated adenoma components. Remarkably, all but one superficially serrated adenoma-associated traditional serrated adenoma exhibited concurrent KRAS mutations and RSPO fusions/overexpression. The present study suggests that superficially serrated adenoma is a morphologically and molecularly distinct type of colorectal serrated polyp that is histogenetically related to traditional serrated adenoma.

Background: Human epidermal growth factor receptor 2 (HER2) expression in gastric cancer is highly heterogeneous. Therefore, it is important to take endoscopic samples from appropriate tumor sites., Methods: Between January 2008 and April 2015, patients with gastric or gastroesophageal junction cancer with histologically confirmed adenocarcinoma were included. Surgical samples or endoscopic biopsy samples were examined for HER2 using immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). Tissues were considered to be HER2 positive when either assessment revealed either an IHC score of 3+ or an IHC score of 2+ accompanied by a positive FISH result. Endoscopic findings were retrieved in all cases where available, and we examined the portion from which a biopsy was obtained., Results: Out of the 612 patients included in the study, 104 (17%) were HER2 positive. The proportion of HER2-positive gastric tumors with differentiated (vs. undifferentiated) histology was significantly higher (29 vs. 6%, respectively; p < 0.001). The HER2-positive rate of papillary adenocarcinomas (vs. tubular) was particularly high (62%, 8/13; p = 0.023). The proportion of HER2-positive gastric tumors of Borrmann classification 0 or 1 was significantly higher than that of tumors of classified as 2, 3, or 4 (45 vs. 16%, respectively; p < 0.001). The HER2-positive rates per biopsy specimen from the superficial spreading portion, ulcer mound, ulcer bed, and mass portion were 100, 91, 45, and 100%, respectively., Conclusions: HER2-positive gastric cancer tends to be associated with a differentiated histology, particularly papillary adenocarcinoma, and a Borrmann classification of 0 or 1 tumors. Based on these endoscopic findings, it is important to recognize the superficial spreading portion and the mass portion of gastric malignancies.

Background: The aim of this pilot study is to investigate the diagnostic yield of probe-based confocal laser endomicroscopy (pCLE) in the evaluation of depth of invasion in colorectal lesions., Methods: Patients with colorectal lesions eligible for either endoscopic treatment or surgery were enrolled in the study. Tumor's depth of invasion was classified as mucosal or slight submucosal (M-SM1) and deep submucosal invasion or deeper (SM2 or deeper). White light endoscopy (WLE), magnifying narrow band imaging (M-NBI), and magnifying chromoendoscopy (M-CE) were used to assess colorectal lesions, and pCLE was used to identify tumor's features related to SM2 or deeper. The diagnostic classification of depth of invasion was obtained by correlating pCLE findings with histology results (on-site diagnosis). All colorectal lesions were stratified by a second endoscopist who was blinded to any clinical and histological information with the use of WLE, M-NBI, M-CE, and pCLE (off-line review)., Results: A total of 22 colorectal lesions were analyzed: seven were adenoma, ten intramucosal cancer, and five SM2 or deeper cancer. With respect to pCLE findings, loss of crypt structure was seen in all SM2 or deeper cancers and only in one M-SM1 lesion. Sensitivity, specificity, and accuracy of WLE, M-NBI, and M-CE in off-line review were 60/94/86, 60/94/86, and 80/94/91%, respectively. Sensitivity/specificity/accuracy of pCLE in off-line review were 80/94/91%, respectively. The inter-observer agreement of pCLE between on-site diagnosis and off-line review was 0.64 (95%CI 0.27-1.0)., Conclusions: pCLE may represent a useful tool to evaluate the depth of invasion in colorectal lesions.

Background and Aim: Salvage endoscopic resection (ER) is among the curative treatments for superficial local failure after chemoradiotherapy (CRT) for esophageal squamous cell carcinoma (ESCC). The present study aimed to clarify risk factors for recurrence after salvage ER., Methods: This study enrolled consecutive ESCC patients treated with salvage ER for local failure after CRT between 1998 and 2013. Recurrences after salvage ER included locoregional recurrences and distant metastases. Multivariate analysis was carried out on clinicopathological parameters to identify risk factors for post-salvage ER recurrence., Results: Of the 72 patients enrolled in this study, 37/8/23/4 patients had been staged before CRT as cT1/T2/T3/T4 and 44/28 patients as cN0/N1, respectively, and local failures detected before salvage ER were residual lesions after CRT in 19 and local recurrences in 53 patients. Resected specimens were classified as pT1a (M) in 45 and pT1b (SM) in 27 patients. During the median 45-month follow up (range, 3-175 months) after salvage ER, 27 (38%) patients developed recurrence with a 3-year recurrence-free survival rate of 48.9% (95% confidence interval [CI], 36.5-60.3). Multivariate analysis showed that residual lesions after CRT (HR, 2.55; 95% CI, 1.32-4.94) and lesions with a submucosal tumor (SMT)-like appearance before salvage ER (HR, 2.08; 95% CI, 1.04-4.18) were significantly associated with post-salvage ER recurrence., Conclusions: Clinical findings (e.g. residual tumors found immediately after CRT and macroscopic SMT-like appearance before salvage ER) were shown to be significant risk factors for post-salvage ER recurrence., (© 2017 Japan Gastroenterological Endoscopy Society.)

Wächtershäuser's proposal of the autotrophic origin of life theory and subsequent laboratory demonstrations of relevant organic reactions have opened a new gate for the exploration of the origin of life. However, this scenario remains controversial because, at present, it requires a high pressure of CO as a source of carbon and reducing energy, although CO must have been a trace C species on the Hadean Earth. We show that, simulating a geoelectrochemical environment in deep-sea hydrothermal fields, CO production with up to ~40% Faraday efficiency was attainable on CdS in CO 2 -saturated NaCl solution at ≤-1 V (versus the standard hydrogen electrode). The threshold potential is readily generated in the H 2 -rich, high-temperature, and alkaline hydrothermal vents that were probably widespread on the early komatiitic and basaltic ocean crust. Thus, Wächtershäuser's scenario starting from CO 2 was likely to be realized in the Hadean ocean hydrothermal systems.

A 70-year-old woman underwent upper gastrointestinal endoscopy and was found to have a 25-mm protruded lesion in the gastric body. A biopsy revealed malignant cells. Endoscopic submucosal dissection was performed. Histopathologically, the tumor was mainly composed of poorly differentiated adenocarcinoma (PDA), while moderately differentiated adenocarcinoma was observed on its superficial layer. The tumor was located within the mucosal layer. PDAs rarely form a protruded lesion. Here, the presence of a moderately differentiated adenocarcinoma element in the superficial layer of the tumor might have protected the tumor cells from erosion, and solid proliferation of the PDA also contributed to its outward growth.

Deinococcus aerius strain TR0125 is a bacterium isolated from the high atmosphere above Japan that shows strong resistance to desiccation, UV-C, and gamma radiation. Here, we report the draft genome sequence of D. aerius (4.5 Mb), which may provide useful genetic information supporting its biochemical features., (Copyright © 2018 Satoh et al.)

Ionizing radiation including heavy-ion beams has been widely used in mutation breeding. Dry seeds, seedlings, and cultured tissues are often used for mutagenesis; however, little is known about the differences in induced mutations among them. Here, we examined the characteristics of mutations using randomly chosen Arabidopsis M 2 plants derived from dry seeds and seedlings irradiated with carbon ions. The mutation frequency was 1.4-1.9 times higher in dry-seed irradiation than in seedling irradiation. This difference was mainly due to the three-times higher frequency of insertions and deletions (InDels) in dry-seed irradiation than in seedling irradiation. This difference increased the proportion of mutations predicted to affect gene function among all mutations identified by whole genome re-sequencing. Our results demonstrate that the physiological status of plant tissue greatly affects the characteristics of mutations induced by ionizing radiation, and that dry seeds are more suitable materials than seedlings for inducing loss-of-function mutations. The results also showed that single base deletions often occurred in homopolymeric sequences, while InDels larger than 2-3 bp often occurred in or near polynucleotide-repeat or microhomologous sequences. Interestingly, microhomology was less commonly found around large deletions (≥50 bp), suggesting that the rejoining process differs depending on the deletion size.

Some Rumex species such as sorrel are edible as baby leaf salad greens. On the other hand, Rumex plants accumulate soluble oxalate, a toxic metabolite which causes serious diseases such as renal syndrome. We attempted to produce low-oxalate plants of R. obtusifolius, a perennial weed which has higher vitamin C and amino acid content and higher tolerance to stress than many other Rumex species. Ion beams are ionising radiation with high linear energy transfer that causes a wide spectrum of mutations. Thus, in the present study we evaluated the effects of ion beams on oxalate and other primary metabolites in leaves of R. obtusifolius using CE-MS. The results showed that oxalate content was increased by irradiation with carbon ion beams. Metabolome analysis revealed that ion beams affected carbon flow to the isocitrate pathway, which is involved in oxalate synthesis. These observations suggested that modulation of carbon flow to the isocitrate pathway is important to regulate oxalate levels in plants., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Background and Study Aims:  Visual assessment of laterally spreading tumors non-granular type (LST-NG) and depressed lesions by narrow band imaging (NBI) without magnification has not been studied. We investigated the role of non-magnifying NBI in detecting LST-NG and type IIc lesions on colonoscopy., Patients and Methods:  This retrospective study examined consecutive patients diagnosed as having LST-NG and/or type IIc lesions in our hospital between August 2011 and July 2013. These lesions were classified as "Brownish area (BA)," "Brown only in the margins (O-ring sign)," "Same color as the normal mucosa (SC)," and "Whitish area (WA)" based on their appearance on non-magnifying NBI, and their appearance were compared with their histopathological findings., Results:  A total of 18 type IIc and 180 LST-NG lesions were analyzed. Among the type IIc lesions, 5 (28 %), 12 (67 %), and 1 (5 %) were classified as BA, O-ring sign, and SC, respectively. Among the LST-NG lesions, 126 (70 %), 26 (14 %), and 28 lesions (16 %) were classified as BA, O-ring sign, and SC, respectively. The IIc lesions were found to have 1 lesion (20 %) with high-grade dysplasia (HGD) in the BA, and 2 lesions (17 %) with invasive cancer (IC) in the O-ring sign group. Among the LST-NG lesions, 27 (21 %) were found to have IC and 49 (39 %), HGD in the BA group; 8 lesions (31 %) had IC and 4 (15 %) had HGD in the O-ring sign group; and 1 lesion (4 %) had IC and 4 (14 %) had HGD in the SC group., Conclusions:  Most flat and depressed colorectal lesions were seen on non-magnifying NBI as brown lesions with the exception of some flat lesions that were indistinguishable in color from the adjacent normal mucosa. Some of these flat lesions were also found to have HGD or IC.

Background: The elucidation of novel transcripts and their expression in response to various stress conditions is necessary to understand the transcriptional network of plants as an adaptation to biotic and abiotic stresses. We performed strand-specific RNA-Seq (ssRNA-Seq) on rice exposed to cadmium (Cd) for 24 h and investigated the expression of cis-natural antisense transcripts (cis-NATs), a class of endogenous coding or non-protein-coding RNAs with sequence complementarity to the opposite strands of RAP transcripts., Results: Many RAP transcripts possessed cis-NATs and these cis-NATs were responsive to some extent. Cis-NATs were upregulated from 26, 266 and 409 RAP gene loci, while 2054, 2501 and 2825 RAP transcripts were upregulated from 38,123 RAP loci under high Cd exposure in roots at 1, 12 and 24 h, respectively. In addition, most of the upregulated cis-NATs showed little upregulation under ABA or cold treatment. A number of cis-NATs were upregulated from less than 35 RAP gene loci in different tissue and time-point combinations under low Cd exposure, suggesting that cis-NATs respond to environmental stress. Furthermore, 409 RAP transcripts with upregulated cis-NATs were classified into three groups based on the expression of the RAP transcripts from the opposite DNA strand, including 138 upregulated, 128 invariable, and 143 downregulated transcripts, although the responses of cis-NATs and RAP transcripts were not always correlated., Conclusions: We have shown that the cis-NATs identified by ssRNA-Seq analysis are novel genes and that some of them are stress-specific and show different responses depending on the degree of stress and tissue. These results improve our understanding of the complete molecular mechanism of plant adaptation to Cd exposure.

Background and Aims: A "skirt" is a slightly elevated flat lesion with wide pits occasionally observed at the margin of laterally spreading tumors (LSTs). However, the endoscopic treatment outcomes of LSTs with skirts have not been clarified. The aim of this study was to evaluate the endoscopic treatment outcomes of LSTs with skirts., Methods: Between February 2006 and March 2014, 996 LSTs were retrospectively examined to assess the clinicopathologic characteristics, procedure time, en bloc resection rate, R0 resection rate, adverse events, and local recurrence rate of endoscopic submucosal dissection (ESD) and of endoscopic resection., Results: Endoscopic treatment was performed in 35 cases of LSTs with skirts (ratio of ESD to endoscopic piecemeal mucosal resection [EPMR], 32:3) and 961 cases of LSTs without skirts (ratio of ESD to EMR to EPMR to polypectomy, 381:275:114:191). LSTs with a skirt were associated with a significantly higher recurrence rate (P < .01). In both ESD and EPMR, LSTs with a skirt were associated with a higher recurrence rate when compared with LSTs without a skirt (odds ratio, 12.7; P = .032, and odds ratio, 12.3; P = .061, respectively). Multivariate analysis demonstrated that the presence of the skirt and piecemeal resection were significant predictors of local recurrence., Conclusions: LSTs with skirts had a significantly higher local recurrence rate after endoscopic treatment compared with LSTs without skirts, especially after EPMR. Therefore, ESD should be recommended as an endoscopic treatment for LSTs with skirts to minimize local recurrence., (Copyright © 2017 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

2,4-Dichlorophenoxyacetic acid (2,4-D), a functional analogue of auxin, is used as an exogenous source of auxin as it evokes physiological responses like the endogenous auxin, indole-3-acetic acid (IAA). Previous molecular analyses of the auxin response pathway revealed that IAA and 2,4-D share a common mode of action to elicit downstream physiological responses. However, recent findings with 2,4-D-specific mutants suggested that 2,4-D and IAA might also use distinct pathways to modulate root growth in Arabidopsis. Using genetic and cellular approaches, we demonstrate that the distinct effects of 2,4-D and IAA on actin filament organization partly dictate the differential responses of roots to these two auxin analogues. 2,4-D but not IAA altered the actin structure in long-term and short-term assays. Analysis of the 2,4-D-specific mutant aar1-1 revealed that small acidic protein 1 (SMAP1) functions positively to facilitate the 2,4-D-induced depolymerization of actin. The ubiquitin proteasome mutants tir1-1 and axr1-12, which show enhanced resistance to 2,4-D compared with IAA for inhibition of root growth, were also found to have less disrupted actin filament networks after 2,4-D exposure. Consistently, a chemical inhibitor of the ubiquitin proteasome pathway mitigated the disrupting effects of 2,4-D on the organization of actin filaments. Roots of the double mutant aar1-1 tir1-1 also showed enhanced resistance to 2,4-D-induced inhibition of root growth and actin degradation compared with their respective parental lines. Collectively, these results suggest that the effects of 2,4-D on actin filament organization and root growth are mediated through synergistic interactions between SMAP1 and SCF TIR 1 ubiquitin proteasome components., (© 2016 The Authors The Plant Journal © 2016 John Wiley & Sons Ltd.)

Aim: To evaluate the clinical impact of surveillance for head and neck (HN) region with narrow band imaging (NBI) in patients with esophageal squamous cell carcinoma (ESCC)., Methods: Since 2006, we introduced the surveillance for HN region using NBI for all patients with ESCC before treatment, and each follow-up. The patients with newly diagnosed stage I to III ESCC were enrolled and classified into two groups as follows: Group A (no surveillance for HN region); between 1992 and 2000), and Group B (surveillance for HN region with NBI; between 2006 and 2008). We comparatively evaluated the detection rate of superficial head and neck squamous cell carcinoma (HNSCC), and the serious events due to metachronous advanced HNSCC during the follow-up., Results: A total 561 patients (group A: 254, group B: 307) were enrolled. Synchronous superficial HNSCC was detected in 1 patient (0.3%) in group A, and in 12 (3.9%) in group B ( P = 0.008). During the follow up period, metachronous HNSCC were detected in 10 patients (3.9%) in group A and in 30 patients (9.8%) in group B ( P = 0.008). All metachronous lesions in group B were early stage, and 26 patients underwent local resection, however, 6 of 10 patients (60%) in group A lost their laryngeal function and died with metachronous HNSCC., Conclusion: Surveillance for the HN region by using NBI endoscopy increase the detection rate of early HNSCC in patients with ESCC, and led to decrease serious events related to advanced metachronous HNSCC., Competing Interests: Conflict-of-interest statement: We have no financial relationships to disclose.

Aim: To identify the risk factors and clarify the subsequent clinical courses., Methods: This study retrospectively analyzed consecutive patients with esophageal squamous cell carcinoma (ESCC) treated using endoscopic submucosal dissection (ESD) between April 2008 and October 2012. We divided the ESCC lesions into perforation cases and non-perforation cases, and compared characteristics and endoscopic findings between the two groups. "Intraoperative perforation" was defined as the detection of a perforation site during ESD and the presence of mediastinal emphysema., Results: In total, 147 patients with 156 ESCC lesions were treated by ESD. Intraoperative perforation was recorded for nine lesions (5.8%) from nine patients. Multivariate analysis identified mucosal deficiency larger than 75% of the circumference of the esophagus as an independent risk factor for intraoperative perforation (OR = 7.37, 95%CI: 1.45-37.4, P = 0.016). The predominant site of perforation was the left wall [6/9 (67%)]. Six of nine perforation sites were successfully closed by clips during the procedures. Two of nine cases required drainage for pleural effusions; however, all nine cases recovered with conservative treatment and without surgical intervention. At the median follow up of 42 mo after ESD, no cases of local recurrence or distant organ metastasis had been observed., Conclusion: This study suggests that mucosal deficiency larger than 75% of the luminal circumference is a risk factor for intraoperative perforation during ESD for ESCC., Competing Interests: Conflict-of-interest statement: Authors declare no conflict of interest relevant to this article.

We report genome-wide single-base resolution maps of methylated cytosines and transcriptome change in Cd-exposed rice. Widespread differences were identified in CG and non-CG methylation marks between Cd-exposed and Cd-free rice genomes. There are 2320 non-redundant differentially methylated regions detected in the genome. RNA sequencing revealed 2092 DNA methylation-modified genes differentially expressed under Cd exposure. More genes were found hypermethylated than those hypomethylated in CG, CHH and CHG (where H is A, C or T) contexts in upstream, gene body and downstream regions. Many of the genes were involved in stress response, metal transport and transcription factors. Most of the DNA methylation-modified genes were transcriptionally altered under Cd stress. A subset of loss of function mutants defective in DNA methylation and histone modification activities was used to identify transcript abundance of selected genes. Compared with wide type, mutation of MET1 and DRM2 resulted in general lower transcript levels of the genes under Cd stress. Transcripts of OsIRO2, OsPR1b and Os09g02214 in drm2 were significantly reduced. A commonly used DNA methylation inhibitor 5-azacytidine was employed to investigate whether DNA demethylation affected physiological consequences. 5-azacytidine provision decreased general DNA methylation levels of selected genes, but promoted growth of rice seedlings and Cd accumulation in rice plant., (© 2016 John Wiley & Sons Ltd.)

Background and study aims: One of the major complications after endoscopic resection (ER) for large superficial esophageal squamous cell carcinoma (ESCC) is benign esophageal stricture, which can reduce quality of life even if ESCC achieves a cure without organ resection. Recently, steroid administration has been reported as a prophylactic treatment to prevent esophageal strictures. This retrospective study evaluated the stricture rate according to the different width of mucosal defects due to ER and compared it to that seen with prophylactic steroid administration. Patients and methods: Between June 2007 and December 2013, we enrolled patients with ESCC who had 3/4 or larger circumferential mucosal defects due to ER. In December 2009, steroid injections (triamcinolone acetonide 50 mg) into the ulcer bed due to ER were introduced. Beginning in November 2012, we commenced oral steroid administration (prednisolone 30 mg/day, tapered gradually for 8 weeks) in addition to steroid injection. Patients were classified into 3 groups according to the width of mucosal defect after ER (Group A, ≥ 3/4 and < 7/8; Group B, ≥ 7/8 and less than the entire circumference; and Group C, the entire circumference). We retrospectively evaluated the stricture rate by comparing no treatment, steroid injection, or steroid injection followed by oral steroid according to the width of mucosal defect. Results: A total of 115 patients met the selection criteria. In Group B, no treatment had a significantly higher stricture rate (100 %, vs. steroid injection: 56 % P  = 0.015; vs steroid injection followed by oral steroid: 20 % P  < 0.001). Conversely, in Group C, the stricture rate was high, regardless of treatment (no treatment: 100 %; steroid injection: 100 %; steroid injection followed by oral steroid: 71 %). Conclusions: Although prophylactic steroid administration is effective to prevent strictures for 7/8 circumference or larger mucosal defects, it is ineffective for whole-circumference defects. Further investigation is required.

Rice seeds were exposed outside of the international space station to assess the risk of space environment exposure on gene expression associated with seed germination. The germination percentages of the space-stored and ground-stored seeds exposed for 13 months were 48 and 96% respectively. Those for 20 months were 7 and 76%, respectively. Germination was defined 3 days after imbibition, except for the space-stored seeds exposed for 20 months, which germinated 5 days after imbibition. Subsequent RNA-seq analyses of the dry seeds, germinated seeds, and roots and shoots of seedlings revealed that the mutation rates of mRNA sequences were not significantly different between space-stored and ground-stored samples exposed for 13 months and 20 months. In all, 4 and 16 transcripts of glycolysis-related genes were increased in the germinated seeds after 13-month and 20-month exposure, respectively. Also, 2 and 39 transcripts of long-lived mRNA required for germination were decreased more than 2-fold in the dry seeds after 13-month and 20-month exposure, respectively. These results suggest that damage to long-lived mRNA in seeds by a space environment delays and reduces germination., (Copyright © 2016 The Committee on Space Research (COSPAR). Published by Elsevier Ltd. All rights reserved.)

Background: Endoscopic submucosal resection with a ligation device (ESMR-L) is effective for rectal neuroendocrine tumors (NETs); however, its effectiveness for duodenal NETs is unclear. This study evaluated the efficacy and safety of ESMR-L for duodenal NETs., Methods: A total of 32 consecutive patients with duodenal NETs were treated in our hospital between December 2010 and August 2015. Among these 32 patients, we retrospectively analyzed the data of all patients who underwent ESMR-L for the treatment of duodenal NETs. ESMR-L was considered for patients in whom (1) the lesion size was ≤10 mm in diameter, (2) the lesion was located within the submucosal layer, and (3) no lymph node metastasis or distant metastasis was detected., Results: Five patients underwent ESMR-L for the treatment of duodenal NETs. The en bloc complete resection rate was 100 %. The median procedure time for ESMR-L was 15 min (range 10-30 min). In all patients, perforation during and after the operation, and intraoperative bleeding were not observed; however, one patient experienced postoperative bleeding. During follow-up, no local recurrence or distant metastasis was noted in any of the patients., Conclusion: ESMR-L is feasible, effective, and safe for duodenal NETs measuring ≤10 mm in diameter that are confined to the submucosal layer without metastasis.

Background and Study Aim: A slightly elevated flat lesion with wide pits has occasionally been observed at the margin of laterally spreading tumors (LSTs) and is known as a "skirt." The aim of this study was to evaluate the clinicopathological, endoscopic, and genetic characteristics of a skirt., Patients and Methods: Consecutive LSTs were examined to evaluate the pathological, endoscopic, and genetic characteristics. Pathological characteristics, including the dimension of the cryptic opening (DCO), width of the individual gland (WIG), DCO to WIG ratio, and microvessel diameter were elucidated and compared with those of hyperplastic polyps, low grade dysplasia (LGD), and normal mucosa. The endoscopic findings of pit and microvascular patterns were assessed. Gene mutation analyses were performed for the KRAS, BRAF, NRAS, and PIK3CA genes., Results: A skirt was identified in 35 of 1023 LSTs, and 80 % of lesions with a skirt had a component of either intramucosal or submucosal adenocarcinoma. The DCO, WIG, and DCO to WIG ratio of the skirt were significantly larger than those of other lesions. The microvessel diameters in skirts were significantly smaller than those in LGDs. Regarding the endoscopic findings, 30 skirts showed pits with a coral reef-like appearance, and all skirt regions were found to have a type I capillary pattern. KRAS mutation at codon 146 was found in the nodular part in one of five LSTs with a skirt., Conclusion: The skirt is a newly identified lesion distinct from hyperplastic polyps and LGDs, suggesting the presence of a novel pathway for rectal carcinogenesis from LSTs with a skirt., (© Georg Thieme Verlag KG Stuttgart · New York.)

Deinococcus grandis is a radioresistant bacterium isolated from freshwater fish in Japan. Here we reported the draft genome sequence of D. grandis (4.1 Mb), which will be useful for elucidating the common principles of radioresistance in Deinococcus species through the comparative analysis of genomic sequences., (Copyright © 2016 Satoh et al.)

Rice growth is severely affected by toxic concentrations of the nonessential heavy metal cadmium (Cd). To elucidate the molecular basis of the response to Cd stress, we performed mRNA sequencing of rice following our previous study on exposure to high concentrations of Cd (Oono et al., 2014). In this study, rice plants were hydroponically treated with low concentrations of Cd and approximately 211 million sequence reads were mapped onto the IRGSP-1.0 reference rice genome sequence. Many genes, including some identified under high Cd concentration exposure in our previous study, were found to be responsive to low Cd exposure, with an average of about 11,000 transcripts from each condition. However, genes expressed constitutively across the developmental course responded only slightly to low Cd concentrations, in contrast to their clear response to high Cd concentration, which causes fatal damage to rice seedlings according to phenotypic changes. The expression of metal ion transporter genes tended to correlate with Cd concentration, suggesting the potential of the RNA-Seq strategy to reveal novel Cd-responsive transporters by analyzing gene expression under different Cd concentrations. This study could help to develop novel strategies for improving tolerance to Cd exposure in rice and other cereal crops.

Primary adenocarcinoma arising from heterotopic gastric mucosa (HGM) is rare and the clinicopathological characteristics are not well known. We present two cases of esophageal adenocarcinoma arising from HGM with a review of a case series. Case 1 was a 78-year-old woman who underwent a periodic medical examination without complaining of any symptoms. Preoperative evaluation suggested esophageal adenocarcinoma arising from the HGM. The patient was treated with endoscopic submucosal dissection. Definitive pathological diagnosis confirmed adenocarcinoma arising from the HGM. Case 2 was a 70-year-old man who underwent a medical examination after complaining of dysphagia. Preoperative diagnosis suggested esophageal adenocarcinoma; however, its origin was unclear. The patient was treated with surgical resection. Definitive pathological diagnosis revealed adenocarcinoma arising from the HGM. In this article, the authors report the clinicopathological features of esophageal adenocarcinoma arising from HGM that were collected from a literature review and our cases.