Regulation of the Poly(A) Status of Mitochondrial mRNA by Poly(A)-Specific Ribonuclease Is Conserved among Land Plants

Regulation of the stability and the quality of mitochondrial RNA is essential for the maintenance of mitochondrial and cellular functions in eukaryotes. We have previously reported that the eukaryotic poly(A)-specific ribonuclease (PARN) and the prokaryotic poly(A) polymerase encoded by AHG2 and AGS1, respectively, coordinately regulate the poly(A) status and the stability of mitochondrial mRNA in Arabidopsis. Mitochondrial function of PARN has not been reported in any other eukaryotes. To know how much this PARN-based mitochondrial mRNA regulation is conserved among plants, we studied the AHG2 and AGS1 counterparts of the liverwort, Marchantia polymorpha, a member of basal land plant lineage. We found that M. polymorpha has one ortholog each for AHG2 and AGS1, named MpAHG2 and MpAGS1, respectively. Their Citrine-fused proteins were detected in mitochondria of the liverwort. Molecular genetic analysis showed that MpAHG2 is essential and functionally interacts with MpAGS1 as observed in Arabidopsis. A recombinant MpAHG2 protein had a deadenylase activity in vitro. Overexpression of MpAGS1 and the reduced expression of MpAHG2 caused an accumulation of polyadenylated Mpcox1 mRNA. Furthermore, MpAHG2 suppressed Arabidopsis ahg2-1 mutant phenotype. These results suggest that the PARN-based mitochondrial mRNA regulatory system is conserved in land plants

Localization of nonpalpable breast cancers using VATS marking system under ultrasonographic guidance

A preoperative tumor guiding system for nonpalpable breast cancer using a VATS guiding needle (Hakko Co., Ltd., Tokyo Japan) was reported. It was easy to introduce the guiding needle into breast cancers smaller than 1cm under ultrasonographic observation. Neither bleeding nor infection was experienced. Wound management was easy and painless. This guiding system is very useful for locating and managing nonpalpable breast cancers even in outpatient settings

A diagnostic marker for superficial urothelial bladder carcinoma : lack of nuclear ATBF1 (ZFHX3) by immunohistochemistry suggests malignant progression

Background: Pathological stage and grade have limited ability to predict the outcomes of superficial urothelial bladder carcinoma at initial transurethral resection (TUR). AT-motif binding factor 1 (ATBF1) is a tumor suppressive transcription factor that is normally localized to the nucleus but has been detected in the cytoplasm in several cancers. Here, we examined the diagnostic value of the intracellular localization of ATBF1 as a marker for the identification of high risk urothelial bladder carcinoma. Methods: Seven anti-ATBF1 antibodies were generated to cover the entire ATBF1 sequence. Four human influenza hemagglutinin-derived amino acid sequence-tagged expression vectors with truncated ATBF1 cDNA were constructed to map the functional domains of nuclear localization signals (NLSs) with the consensus sequence KR[X10-12]K. A total of 117 samples from initial TUR of human bladder carcinomas were analyzed. None of the patients had received chemotherapy or radiotherapy before pathological evaluation. Results: ATBF1 nuclear localization was regulated synergistically by three NLSs on ATBF1. The cytoplasmic fragments of ATBF1 lacked NLSs. Patients were divided into two groups according to positive nuclear staining of ATBF1, and significant differences in overall survival (P = 0.021) and intravesical recurrence-free survival (P = 0.013) were detected between ATBF1+ (n= 110) and ATBF1− (n=7) cases. Multivariate analysis revealed that ATBF1 staining was an independent prognostic factor for intravesical recurrence-free survival after adjusting for cellular grading and pathological staging (P = 0.008). Conclusions: Cleavage of ATBF1 leads to the cytoplasmic localization of ATBF1 fragments and downregulates nuclear ATBF1. Alterations in the subcellular localization of ATBF1 due to fragmentation of the protein are related to the malignant character of urothelial carcinoma. Pathological evaluation using anti-ATBF1 antibodies enabled the identification of highly malignant cases that had been overlooked at initial TUR. Nuclear localization of ATBF1 indicates better prognosis of urothelial carcinoma

Validity of the Short Nutritional Assessment Questionnaire for Japanese Patients with Cancer Undergoing Outpatient Chemotherapy

Purpose : To investigate the utility of the Short Nutritional Assessment Questionnaire (SNAQ) in the nutritional evaluation of patients with cancer undergoing outpatient chemotherapy. Methods :We included 229 patients with cancer who were undergoing outpatient chemotherapy between October 2015 and April 2016. The SNAQ and the revised SNAQ (addition of age and body mass index) were implemented, and their relationships with Controlling Nutritional Status (CONUT), an indicator of bionutritional assessment, were examined. Results : The cutoff value of the SNAQ score corresponding to moderate-to-severe undernourishment in CONUT values was 0.5, with a sensitivity of 87.5% and a specificity of 65.9%, and the corresponding values for the revised SNAQ score were 2.5, 91.7%, and 62.9%, respectively. This cutoff value and the corresponding positive prediction value for the revised SNAQ were superior to those of SNAQ. Binary logistic regression analysis with the revised SNAQ and sex as independent variables and the CONUT value as the dependent variable revealed that the higher the SNAQ score, the more likely it was that CONUT moderate-to-severe undernourishment would be identified (odds ratio, 1.48 ; , 1.34-1.96) . Conclusion : Nutritional evaluation with the revised SNAQ can predict moderateto- severe undernourishment according to CONUT in patients with cancer undergoing outpatient chemotherapy

Researching peers and disaster vulnerable communities: an insider perspective

Conducting research among peers and communities that a researcher also serves may be both daunting and rewarding. Researching peers may make the researcher feel uncomfortable raising certain questions that are sensitive or that could be construed to be testing their competencies. This paper is inclined more towards showing that it is advantageous to be an insider, whose position can facilitate collection of information that could not have been accessed, or revealed to an outsider. The paper reports on fieldwork conducted in a low-income country in Sub-Sahara Africa as part of a doctoral study with communities affected by disasters and those that work with such communities. The paper demonstrates the complexities of conducting such research and provides some insights that may be useful to insiders, outsiders or “in-betweeners” embarking on fieldwork in low-income countries and among vulnerable population struggling with manifold stresses and shocks

シミュレーションテキ シュホウ ニヨル タイキ カンキョウ ジョウホウ キョウイク ニッシャリョウ ノ テンチョウカク イゾンショウ

学生に対して地球温暖化やオゾン層破壊など日射量が直接的に関与する大気環境問題の本質を理解させるには,コンピュータシミュレーションを用いて日射量を定量的に評価する手法が有効である。ここでは近赤外部における吸収や天頂角変化等を取り込んだ総合的な日射量シミュレーション法を提案した。日射量の算出に必要な光学的厚みは,オゾン吸収,レイリー散乱,ミー散乱に関しては消散断面積を用いる手法を採用し,多数の吸収線の重なりから構成される水蒸気と二酸化炭素については透過率を用いる方法を採用した。250～3,000nmの波長範囲で東京を中心として国内における日射量を試算した結果,実測値と2%程度の範囲で一致し定量的にみても満足できる手法となった。今回の方法により晴天時を対象とした直達日射量については,学生の教育上必要な簡便的シミュレーションがほぼ完成したと見なせる。今後に残された課題として曇天時に必要な散乱日射量の評価がある。Computer simulation to quantitatively evaluate solar radiation energy is an effective technique to let students better understand the essence of atmospheric environmental problems such as global warming or ozone depletion which is directly related to the amount of solar radiation energy. The authors have proposed in this paper a general simulation method for solar radiation energy including terms of absorption in near infrared region and change in zenith angle. Optical depths necessary for evaluation of solar radiation energy have been simply calculated by using the dispersion cross-section for ozone-absorption, Rayleigh- and Mie-scatterings, but optical depths for absorptions of water and carbon dioxide have been estimated through the transmittance since these absorptions consist of complex lines. Results calculated for domestic areas including Tokyo at wave-lengths between 250 and 3, 000nm agree with observed values within 2% difference, showing that the proposed method provides a satisfactory tool for quantitative estimation. In the future, it will be desirable to add the estimation of scattered solar radiation energy which is important in cloudy sky

Feasibility of methotrexate discontinuation following tocilizumab and methotrexate combination therapy in patients with long-standing and advanced rheumatoid arthritis: a 3-year observational cohort study

Objectives: Methotrexate (MTX) is associated with extensive side effects, including myelosuppression, interstitial pneumonia, and infection. It is, therefore, critical to establish whether its administration is required after achieving remission with tocilizumab (TCZ) and MTX combination therapy in patients with rheumatoid arthritis (RA). Therefore, the aim of this multicenter, observational, cohort study was to evaluate the feasibility of MTX discontinuation for the safety of these patients. Methods: Patients with RA were administered TCZ, with or without MTX, for 3 years; those who received TCZ+MTX combination therapy were selected. After remission was achieved, MTX was discontinued without flare development in one group (discontinued [DISC] group, n = 33) and continued without flare development in another group (maintain [MAIN] group, n = 37). The clinical efficacy of TCZ+MTX therapy, patient background characteristics, and adverse events were compared between groups. Results: The disease activity score in 28 joints-erythrocyte sedimentation rate (DAS28-ESR) at 3, 6, and 9 months was significantly lower in the DISC group (P < .05, P < .01, and P < .01, respectively). Further, the DAS28-ESR remission rate at 6 and 9 months and Boolean remission rate at 6 months were significantly higher in the DISC group (P < .01 for all). Disease duration was significantly longer in the DISC group (P < .05). Furthermore, the number of patients with stage 4 RA was significantly higher in the DISC group (P < .01). Conclusions: Once remission was achieved, MTX was discontinued in patients who responded favorably to TCZ+MTX therapy, despite the prolonged disease duration and stage progression

Negative Correlation between Brain Glutathione Level and Negative Symptoms in Schizophrenia: A 3T 1H-MRS Study

BACKGROUND: Glutathione (GSH), a major intracellular antioxidant, plays a role in NMDA receptor-mediated neurotransmission, which is involved in the pathophysiology of schizophrenia. In the present study, we aimed to investigate whether GSH levels are altered in the posterior medial frontal cortex of schizophrenic patients. Furthermore, we examined correlations between GSH levels and clinical variables in patients. METHODS AND FINDINGS: Twenty schizophrenia patients and 16 age- and gender-matched normal controls were enrolled to examine the levels of GSH in the posterior medial frontal cortex by using 3T SIGNA EXCITE (1)H-MRS with the spectral editing technique, MEGA-PRESS. Clinical variables of patients were assessed by the Global Assessment of Functioning (GAF), Scale for the Assessment of Negative Symptoms (SANS), Brief Psychiatric Rating Scale (BPRS), Drug-Induced Extra-Pyramidal Symptoms Scale (DIEPSS), and five cognitive performance tests (Word Fluency Test, Stroop Test, Trail Making Test, Wisconsin Card Sorting Test and Digit Span Distractibility Test). Levels of GSH in the posterior medial frontal cortex of schizophrenic patients were not different from those of normal controls. However, we found a significant negative correlation between GSH levels and the severity of negative symptoms (SANS total score and negative symptom subscore on BPRS) in patients. There were no correlations between brain GSH levels and scores on any cognitive performance test except Trail Making Test part A. CONCLUSION: These results suggest that GSH levels in the posterior medial frontal cortex may be related to negative symptoms in schizophrenic patients. Therefore, agents that increase GSH levels in the brain could be potential therapeutic drugs for negative symptoms in schizophrenia