Functional characterization of a constitutively active kinase variant of Arabidopsis phototropin 1

Phototropins (phots) are plasma membrane-associated serine/threonine kinases that coordinate a range of processes linked to optimizing photosynthetic efficiency in plants. These photoreceptors contain two light-, oxygen- or voltage-sensing (LOV) domains within their N-terminus, with each binding one molecule of flavin mononucleotide (FMN) as a UV/blue light absorbing chromophore. Although phots contain two LOV domains, light-induced activation of the C-terminal kinase domain and subsequent receptor autophosphorylation is controlled primarily by the A′α-LOV2-Jα photosensory module. Mutations that disrupt interactions between the LOV2-core and its flanking helical segments can uncouple this mode of light regulation. Yet, the impact of these mutations on phot function in Arabidopsis has not been explored. Here, we report that histidine substitution of Arg-472 located within the A′α-helix of Arabidopsis phot1 to histidine results in constitutively activates kinas activity in vitro without affecting LOV2 photochemistry. Expression analysis of phot1 R472H in the phot-deficient mutant confirmed that it is autophosphorylated in darkness in vivo, but was unable to initiate phot1 signaling in the absence of light. Instead, we found that the phot1 R472H mutant is poorly functional under low-light conditions, but can restore phototropism, chloroplast accumulation, stomatal opening, and leaf positioning and expansion at higher light intensities. Our findings suggest that Arabidopsis can adapt to the elevated phosphorylation status of the phot1 R472H mutant by in part reducing its stability, whereas the activity the mutant under high-light conditions can be attributed to additional increases in LOV2-mediated photoreceptor autophosphorylation

In vitro evaluation of a newly developed implantable artificial lung.

A prototype of an implantable artificial lung without a pump (Prototype II) has been tested. A commercially available membrane oxygenator, MENOX AL6000alpha R (Dainippon Ink and Chemicals, Inc., Tokyo, Japan), was used as a basic model. The packing density of the hollow fiber was decreased in order to achieve low resistance through the blood pathway. The configuration of its housing was also re-designed using computational fluid dynamics (CFD). The first prototype, known as Prototype I, was already tested in a 15 kg pig, which showed excellent gas exchange with normal hemodynamics. A second prototype, Prototype II, has a larger membrane surface area than Prototype I. The device was evaluated for resistance through the blood path and gas transfer rate in an in vitro setting by the single pass method using fresh bovine blood. The resistance through the blood path of Prototype II was 2.7+- 0.7 mmHg/(L/min) at Q = 5L/min. The oxygen (O2) transfer rate was 178 +- 5.3 ml/min at Q = 5 L/min, V/Q = 3, and the carbon dioxide (CO2) transfer rate was 149 +- 28 ml/min at Q = 5 L/min, V/Q = 2 (Q : blood flow rate, V : sweep oxygen flow rate through the artificial lung). For the purpose of implantation, this prototype showed sufficiently low resistance in the pulmonary circulation with reasonable gas exchange

A Review on Triple Antibiotic Paste as a Suitable Material Used in Regenerative Endodontics

As the root canal system shows different and complicated anatomies, mechanical instrumentation alone has not the ability to provide a bacteria-free environment in root canals. On the other aspect, necrotic tissue remaining can decrease the effects of root canal irrigants and medicaments and also interfere with the adaptation of root canal fillings to dentin. As a result, certain disinfection and irrigation procedures are required to remove the remaining tissues from the root canal area thoroughly and also be able to eliminate the microorganisms. Triple antibiotic paste (TAP) containing metronidazole, ciprofloxacin and minocycline has been proposed as a root canal medicament due to its antimicrobial effects in endodontic regenerative procedures. The purposes of this review were to determine the properties of TAP drugs and to evaluate the efficiency of TAP on the root canal disinfection, in primary and permanent teeth, along with its affection in regeneration/revascularization procedures. The biocompatibility and disadvantages of this medicament were also discussed.Keywords: Endodontics; Intra-canal Medicament; Regeneration; Triple Antibiotic Past

Human Pulp Response to Direct Pulp Capping and Miniature Pulpotomy with MTA after Application of Topical Dexamethasone: A Randomized Clinical Trial

Introduction: The aim of this randomized clinical trial was to compare the histologic pulp tissue response to one-step direct pulp capping (DPC) and miniature pulpotomy (MP) with mineral trioxide aggregate (MTA) after application of dexamethasone in healthy human premolars. Methods and Materials: Forty intact premolars from 10 orthodontic patients, were randomly chosen for DPC (n=20) or MP (n=20). In 10 teeth from each group, after exposure of the buccal pulp horn, topical dexamethasone was applied over the pulp. In all teeth the exposed/miniaturely resected pulp tissue was covered with MTA and cavities were restored with glass ionomer. Teeth vitality was evaluated during the next 7, 21, 42, and 60 days. Signs and/or symptoms of irreversible pulpitis or pulp necrosis were considered as failure. According to the orthodontic schedule, after 60 days the teeth were extracted and submitted for histological examination. The Kruskal-Wallis and Fisher’s exact tests were used for statistical analysis of the data (P=0.05). Results: Although dexamethasone specimens showed less inflammation, calcified bridge, pulpal blood vasculature, collagen fibers and granulation tissue formation were not significantly different between the groups (P>0.05). Conclusion: Topical dexamethasone did not hindered pulp healing but reduced the amount of underlying pulpal tissue inflammation after DPC and MP in healthy human premolars.Keywords: Dexamethasone; Direct Pulp Capping; Mineral Trioxide Aggregate; Miniature Pulpotomy; Vital Pulp Therap

Decelerated epigenetic aging associated with mood stabilizers in the blood of patients with bipolar disorder

There is high mortality among patients with bipolar disorder (BD). Studies have reported accelerated biological aging in patients with BD. Recently, Horvath and Hannum et al. independently developed DNA methylation (DNAm) profiles as “epigenetic clocks,” which are the most accurate biological age estimate. This led to the development of two accomplished measures of epigenetic age acceleration (EAA) using blood samples, namely, intrinsic and extrinsic EAA (IEAA and EEAA, respectively). IEAA, which is based on Horvath’s clock, is independent of blood cell counts and indicates cell-intrinsic aging. On the other hand, EEAA, which is based on Hannum’s clock, is associated with age-dependent changes in blood cell counts and indicates immune system aging. Further, Lu et al. developed the “GrimAge” clock, which can strongly predict the mortality risk, and DNAm-based telomere length (DNAmTL). We used a DNAm dataset from whole blood samples obtained from 30 patients with BD and 30 healthy controls. We investigated Horvath EAA, IEAA, Hannum EAA, EEAA, Grim EAA, DNAmTL, and DNAm-based blood cell composition. Compared with controls, there was a decrease in Horvath EAA and IEAA in patients with BD. Further, there was a significant decrease in Horvath EAA and IEAA in patients with BD taking medication combinations of mood stabilizers (including lithium carbonate, sodium valproate, and carbamazepine) than in those taking no medication/monotherapy. This study provides novel evidence indicating decelerated epigenetic aging associated with mood stabilizers in patients with BD

Apexification of a dens evaginated premolar with open apex

This case report describes the treatment of a mandibular premolar with incomplete root formation accompanied by pulp necrosis and periapical pathosis caused by dens evaginatus, in which apexification was successfully achieved with calcium hydroxide

A Case of High-Grade Neuroendocrine Carcinoma That Improved with Bevacizumab plus Modified FOLFOX6 as the Fourth-Line Chemotherapy

High-grade neuroendocrine carcinoma differs from usual neuroendocrine carcinoma, and its prognosis is dismal. In this case report, a case of high-grade neuroendocrine carcinoma that improved with bevacizumab plus modified FOLFOX6 as the fourth-line chemotherapy is presented. A 29-year-old male with a huge liver tumor was diagnosed with high-grade neuroendocrine carcinoma originating from the liver. Multiple liver and bone metastases were found one month after surgery. He was treated with three chemotherapy regimens used for the management of small-cell lung cancer with extensive disease. However, none of them could be maintained because of tumor progression. He was then treated with bevacizumab plus modified FOLFOX6 as the fourth-line regimen. Dramatic tumor shrinkage was obtained, and a partial response was achieved. This case suggests that high-grade neuroendocrine carcinoma can be treated with bevacizumab in combination with cytotoxic chemotherapy

ヒト膵癌におけるNectin-4発現の腫瘍増殖、血管新生に対する効果と臨床的意義

BACKGROUND: Nectin-4 belongs to the nectin family that has diverse physiological and pathological functions in humans. Recent studies have also suggested some roles for Nectin-4 in several human cancers. However, the precise roles and clinical relevance of Nectin-4 in tumors are largely unknown. METHODS: Nectin-4 expression was investigated in 123 patients with pancreatic cancer by immunohistochemistry. Furthermore, we investigated the association of Nectin-4 in pancreatic cancer with tumor proliferation, angiogenesis and immunity by using immunohistochemistry and siRNA interference method. RESULTS: Patients with high Nectin-4 expression had poorer postoperative prognosis than those with low expression. Importantly, multivariate analysis indicated that Nectin-4 expression had a significant independent prognostic value in pancreatic cancer (HR = 1.721, 1.085-2.730; P = 0.021). Tumor Nectin-4 expression was significantly correlated with Ki67 expression. In addition, siRNA-mediated gene silencing of Nectin-4 significantly inhibited the cell proliferation in human pancreatic cancer cells, Capan-2 and BxPC-3. Furthermore, Nectin-4 expression was also positively correlated with VEGF expression and intratumoral microvessel density. However, there were no significant correlations of tumor Nectin-4 expression with tumor-infiltrating T cells. CONCLUSION: Nectin-4 is a significant prognostic predictor, and may play a critical role in pancreatic cancer. Nectin-4 may be novel therapeutic target for pancreatic cancer.博士（医学）・乙第1400号・平成29年6月28日Copyright © Nishiwada et al.; licensee BioMed Central. 2015 : This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated

The Most-cited Articles in Dentistry Up to 2017

Introduction: Citation analysis is a suitable way to help us to identify research trends within a specific topic. The purpose of this study was to identify the 100 most cited articles in the field of dentistry published over the past 67 years. Methods: A comprehensive list of the most cited articles in dentistry was compiled using ISI Web of Science. The characteristics including number of citations, authors and journals were analyzed. Results: The database resulted in 3,831 articles with 100 or more citations published between 1950 and 2017. Most of these articles had been published by the Journal of Clinical Periodontology, followed by the Journal of Periodontology, and Journal of Dental Research. Sokransky SS followed by Lindhe J, Nyman S, and Genco RJ had the most number of citations. Conclusion: The most cited articles in the field of dentistry allows for advances in this field and also provide useful information for direct future studies and patient care