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True limpets of the genus Nacella (Patellogastropoda: Nacellidae) include at least 11 nominal species distributed in different provinces of the Southern Ocean. Here, we present new molecular analyses and a comprehensive morphological revision of Nacella confirming the validity of all the currently recognized species, but with important amendments to the published distributions of several. We also show that specimens collected along two fjords in the Beagle Channel, southern South America, constitute a new taxon: Nacella yaghana sp. nov. The phylogenetic position of this new taxon in our molecular tree reveals that it represents an ancestral South American lineage of Nacella, markedly separated from the previously recognized and evolutionary recent Magellanic radiation. In addition, this new Nacella species was clearly distinguished from the rest of the species by morphological comparisons, including shell characteristics, radular-tooth shape and configuration, as well as by the coloration pattern of the mantle tentacles. This study provides new evidence about the evolutionary history of this important Southern Ocean, marine, near-shore benthic group and the role of the Antarctic Circumpolar Current in the biogeography of the genus.

To investigate the effect of alteplase, either combined with stent-retriever thrombectomy or a direct aspiration first pass technique (ADAPT), in patients with large-vessel occlusion stroke. This was a retrospective post hoc analysis of data from The Direct Mechanical Thrombectomy in Acute LVO Stroke (SKIP) study. Patients were divided into two groups according to the first-line thrombectomy technique: stent-retriever and ADAPT. Each group was further divided into two subgroups, namely MT and MT + alteplase. The procedural outcomes, such as first pass effect (FPE) ratio and number of passes, were evaluated. The clinical outcomes included mRS score at 3 months. A total of 180 patients were included (116 in the stent-retriever group and 64 in the ADAPT group). No interaction was detected between the first-line technique and alteplase administration. In the stent-retriever group, after adjusting for factors associated with FPE, the adjusted odds ratio (95% confidence interval) of FPE of the MT + alteplase subgroup versus the MT subgroup was 3.57 (1.5–8.48) and in the ADAPT group it was 1.35 (0.37–4.91). With alteplase, the number of passes decreased with adjusted odds ratios of 0.59 (0.37–0.93) in the stent-retriever group but not in the ADAPT group. In both first-line technique groups, clinical outcomes did not differ between subgroups. In the SKIP study, alteplase administration was associated with increased FPE when combined with stent-retriever thrombectomy, but not with ADAPT. We found no differences in the clinical outcomes.

Diacylglycerol kinase (DGK) constitutes a family of enzymes that phosphorylate diacylglycerol to phosphatidic acid (PA). These lipids serve as second messengers, thereby activating distinct downstream cascades and different cellular responses. Therefore, DG-to-PA conversion activity induces a phase transition of signaling pathways. One member of the family, DGKζ, is involved closely with stress responses. Morphological data showing that DGKζ localizes predominantly to the nucleus and that it shuttles between the nucleus and the cytoplasm implicate DGKζ in the regulation of transcription factors during stress responses. Tumor suppressor p53 and NF-κB are major stress-responsive transcription factors. They exert opposing effects on cellular pathophysiology. Herein, we summarize DGKζ catalytic activity-dependent and -independent regulatory mechanisms of p53 and NF-κB transactivation activities, including p53 degradation and NF-κB nuclear translocation. We also discuss how each component of DGKζ-interacting protein complex modulates the specificity and selectivity of target gene expression.

We report the diversity, distribution and taxonomy of patellogastropod species from the entire mainland Indian coastline. A total of 77 coastal areas with rocky outcrops in the sandy shoreline, covering the entire mainland Indian coastline, were surveyed seasonally (four times a year) during December 2014 to December 2016. Coastal habitat characteristics and the diversity of all groups of limpets from the intertidal areas were recorded. Specimens were identified by external morphological shell and gill characteristics, by the colour of the foot, mantle fringe and radular characteristics. Ecological aspects like habitat preference were also used to distinguish species. Existing diagnostic characters were amended with newer characteristics emerged in our study. Seven species from two families, Nacellidae and Lottiidae, were found along the mainland Indian coastline. Each species is present with several polymorphic forms with different colour banding patterns. Our study revealed distinct variations in the radular teeth at the genus level, but less differences within genera. Patellogastropod diversity was greater along the west coast of India and only Cellana rota was available throughout the mainland Indian coastline.

The tiny epizoic limpet Lottia tenuisculpta lives on rocky surfaces and shells of the snails Omphalius nigerrimus and Reishia clavigera. The movement patterns of the limpet on host snails was obser...

Diacylglycerol kinase (DGK) phosphorylates diacylglycerol (DG) to produce phosphatidic acid (PA). Since both DG and PA serve as lipidic second messengers, DGK plays a pivotal role in regulating the balance of two signaling pathways mediated by DG and PA in cellular functions. Reportedly, DGKγ, one of the 10 mammalian DGK isozymes, is involved in leukemic cell differentiation, mast cell function, and membrane traffic. Transfection studies using tagged expression vectors and immunohistochemistry on rat tissues revealed that DGKγ localizes to the cytoplasm, plasma membrane, and Golgi apparatus. However, a limited number of studies reported the detailed localization of native protein of DGKγ in human tissues and cells. In this study, we developed a novel anti-DGKγ monoclonal antibody, DgMab-6, which is very useful in immunocytochemistry of human cultured cells.

During our survey on the intertidal hermit crab fauna on Amami Oshima Island and Okinawa Island, southwestern Japan, we collected specimens identified asClibanariusspecies by their morphological features, but that had an unknown coloration for the genus: they have whitish ambulatory legs and a whitish shield. For species identification of these specimens, we observed their coloration and morphology and also performed phylogenetic analyses using the genes mitochondrial cytochrome c oxidase I (COI) and nuclear histone H3. The analysis has shown that these specimens are to be identified asClibanarius virescens(Krauss, 1843).

BACKGROUND Central nervous system germ cell tumor (CNSGCT) is a rare pediatric brain tumor. However, they are found at a relatively high incidence in East Asia. Germinoma is sensitive toward radiotherapy and chemotherapy; however, non-germinoma GCTs (NGGCT) often show poor response. Some cases are a mixture of germinoma and NGGCT (mixed GCT), and they sometimes change histological subtypes at recurrence. Previous report demonstrated that a germinoma and NGGCT component within the same mixed GCT tissue shared the same gene mutation, whereas the genome-wide methylation profiles were distinct from each other. The methylation profiles of germinoma was similar to the primordial germ cells (PGC) at the migration phase, supporting a model that PGC is the cell of origin for CNSGCT. However, tumor heterogeneity hinder information of the mixed bulk RNA-sequence data, causing difficulty in elucidating the mechanism of tumor development. The purpose of this study was to investigate the tumor cells subpopulations at the resolution of individual cells by single-cell RNA-seq. RESULTS Fresh surgical tumor tissue was immediately dissociated mechanically and enzymatically. Tumor cells are separated from CD45-labelled lymphocytes by FACS, and libraries were generated by Chromium Single cell 3’ Reagent Kit. Total of 11 tumor samples were collected and sequenced. Unsupervised Clustering showed individual clusters. One of the clusters had high expression of Oct-4, which is a marker of germinoma. The other clusters showed different subtypes of cells representing the heterogeneity of CNSGCT. Further analysis including a pseudo-time course analysis is underway to identify the lineage of tumor cell development.

Carboxylesterase (CES) plays an important role in the hydrolysis metabolism of ester-type drugs and prodrugs. In this study, we investigated the change in the hydrolysis rate of hCE1 by focusing on the steric hindrance of the ester structure and the electron density. For 26 kinds of synthesized indomethacin prodrugs, the hydrolytic rate was measured in the presence of human liver microsomes (HLM), human small intestine microsomes (HIM), hCE1 and hCE2. The synthesized prodrugs were classified into three types: an alkyl ester type that is specifically metabolized by hCE1, a phenyl ester type that is more easily metabolized by hCE1 than by hCE2, and a carbonate ester type that is easily metabolized by both hCE1 and hCE2. The hydrolytic rate of 1-methylpentyl (hexan-2-yl) ester was 10-times lower than that of 4-methylpentyl ester in hCE1 solution. hCE2 was susceptible to electron density of the substrate, and there was a difference in the hydrolysis rate of up to 3.5-times between p-bromophenyl ester and p-acetylphenyl ester. By changing the steric hindrance and electron density of the alkoxy group, the factors that change the hydrolysis rate by CES were elucidated.

Very little is known about the evolution of molluskan shell pigments, although Mollusca is a highly diverse, species rich, and ecologically important group of animals comprised of many brightly colored taxa. The marine snail genus Clanculus was chosen as an exceptional model for studying the evolution of shell color, first, because in Clanculus margaritarius and Clanculus pharaonius both shell and foot share similar colors and patterns; and second, because recent studies have identified the pigments, trochopuniceus (pink‐red), and trochoxouthos (yellow‐brown), both comprised of uroporphyrin I and uroporphyrin III, in both shell and colored foot tissue of these species. These unusual characteristics provide a rare opportunity to identify the genes involved in color production because, as the same pigments occur in the shell and colored foot tissue, the same color‐related genes may be simultaneously expressed in both mantle (which produces the shell) and foot tissue. In this study, the transcriptomes of these two Clanculus species along with a third species, Calliostoma zizyphinum, were sequenced to identify genes associated with the synthesis of porphyrins. Calliostoma zizyphinum was selected as a negative control as trochopuniceus and trochoxouthos were not found to occur in this species. As expected, genes necessary for the production of uroporphyrin I and III were found in all three species, but gene expression levels were consistent with synthesis of uroporphyrins in mantle and colored foot tissue only in Clanculus. These results are relevant not only to understanding the evolution of shell pigmentation in Clanculus but also to understanding the evolution of color in other species with uroporphyrin pigmentation, including (mainly marine) mollusks soft tissues and shells, annelid and platyhelminth worms, and some bird feathers.

Adipose tissue is a central site for energy storage in the form of triglyceride (TG). Under excess energy conditions, TG is synthesized by acylation of diacylglycerol (DG), whereas TG is broken down into DG and free fatty acid, which provide energy for mitochondrial lipid oxidation when needed. In this regard, DG is not merely an intermediate metabolite for TG metabolism; it also serves as a signaling molecule. DG kinase (DGK) phosphorylates DG to produce phosphatidic acid (PA). Consequently, DGK plays a pivotal role in the control of lipid metabolism and signal transduction pathway. Recently, a report has described that DGKe-knockout (KO) mice show expansion of epididymal white adipose tissue (WAT) together with the impairment of glucose clearance after short-term (40 days) high fat diet (HFD) feeding, an early presymptomatic phase of obesity in wild-type animals. Nevertheless, no report describes an investigation of their phenotype under long-term HFD feeding conditions. Remarkably, results obtained during long-term HFD feeding show that WAT mass is decreased significantly and that the blood glucose profile in response to glucose challenge is improved in DGKe-KO mice compared with wild-type, which contrast sharply against the phenotype shown for short-term HFD feeding. Morphological examination reveals that cyclooxygenase-2 (COX-2) expression and clusters of uncoupling protein 1 (UCP1)-positive multilocular brown-like (“beige”) adipocyte are induced in DGKe-deficient WAT after long-term HFD feeding, suggesting that beige adipocytes facilitate energy expenditure during prolonged HFD feeding. Administration of celecoxib, a selective inhibitor of COX-2, abolishes the appearance of UCP1-positive beige adipocytes in DGKe-KO mice. These findings suggest that DGKe deficiency promotes visceral WAT remodeling in a COX-2-dependent manner under long-term HFD feeding conditions.

The most important step in lung segmentectomy is to determine an appropriate intersegmental plane to obtain sufficient pre- and intraoperative margins. Inappropriate dissection of the lung parenchyma leads to loss of oncological validity and additionally causes various complications such as pneumonia, prolonged air leakage, lung congestion, and atelectasis.In this study, we evaluated the validity of segmentectomy for non-small cell lung cancer (NSCLC) based on evaluation of survival outcomes and recurrence patterns.In principle, we usually perform video-assisted thoracic surgery segmentectomy. Hilar dissection is performed along the intersegmental vein under ultrasonographic guidance, and the peripheral lung parenchyma is subsequently stapled. We usually create inflation-deflation lines from before to determine the intersegmental lines. Recently, near-infrared fluorescence imaging with indocyanine green is also used.We retrospectively reviewed data of 101 patients who underwent segmentectomy for lung cancer between 2007 and 2014.The 5- and 10-year overall survival rates were 84% and 62%, respectively. The 5- and 10-year recurrence-free survival rates were 83% and 63%, respectively. Recurrence at the surgical margin occurred in 5 patients( pulmonary stump:4 patients, bronchial stump:1 patient).Segmentectomy may be acceptable for patients with Stage I NSCLC. Accurate determination of the intersegmental plane is essential to avoid stump recurrence.

The efficacy of mechanical thrombectomy in the treatment of occlusions of the second segment of the middle cerebral artery (M2) has not been firmly established. This study analyzed data from patients who had undergone mechanical thrombectomy for the first segment of the middle cerebral artery (M1) and M2 occlusion from the Tama-REgistry of Acute endovascular Thrombectomy (TREAT) between January 2015 and March 2017, which is a multicenter database in the Tama area of Tokyo, Japan. The M1 and M2 occlusions were compared in order to evaluate the safety and efficacy of M2 thrombectomy. A total of 515 patients were registered, whereby 160 patients with M1 occlusion and 51 patients with M2 occlusion were included. While the puncture-to-reperfusion time was longer in the M2 occlusions (median 43 min, range 30–61 min vs. median 60 min, range 38–79 min, p = 0.01), no significant differences were seen in the proportion of patients with successful reperfusion, postoperative hemorrhagic complications and good outcome (modified Rankin scale ≤2 at 90 days). Younger age was the only independent factor associated with good outcome in patients with M2 occlusions as determined by the multivariate analysis (p = 0.033, odds ratio 0.91, 95% confidence interval 0.83–0.99). The outcome and the safety profile of mechanical thrombectomy for M2 occlusions are favorable and comparable to those of the M1 occlusion thrombectomy.

Decreased cell adhesion has been reported as a significant negative prognostic factor of lung cancer. However, the molecular mechanisms responsible for the cell incohesiveness in lung cancer have not yet been elucidated in detail. We herein describe a rare histological variant of lung adenocarcinoma consisting almost entirely of individual cancer cells spreading in alveolar spaces in an incohesive pattern. A whole exome analysis of this case showed no genomic abnormalities in CDH1 or other genes encoding cell adhesion molecules. However, whole mRNA sequencing revealed that this case had an extremely high expression level of mucin 21 (MUC21), a mucin molecule that was previously shown to inhibit cell‐cell and cell‐matrix adhesion. The strong membranous expression of MUC21 was found on cancer cells using mAbs recognizing different O‐glycosylated forms of MUC21. An immunohistochemical analysis of an unselected series of lung adenocarcinoma confirmed that the strong membranous expression of MUC21 correlated with incohesiveness. Thus, MUC21 could be a promising biomarker with potential diagnostic and therapeutic applications for lung adenocarcinoma showing cell incohesiveness.

Background Thymomas are typically slow-growing tumors and AB type thymomas are considered no/low risk tumors with a better prognosis. Extra-thoracic metastases are extremely rare. To the best of our knowledge, no patient with an isolated splenic metastasis from a thymoma has been reported. We report a patient who underwent laparoscopic splenectomy for a slow-growing, isolated splenic metastasis, eight years after thymectomy. Case presentation The patient is a 78-year-old man. Eight years previously, the patient underwent extended thymectomy and postoperative radiation therapy for a thymoma. Five years after thymectomy, a nodule appeared in the spleen, and the lesion enlarged gradually for three years thereafter. The patient was referred for further examination and treatment. Computed tomography scan showed a sharply circumscribed 50 mm tumor slightly hypodense and heterogeneous lesion in the spleen. On T2-weighted images on Magnetic Resonance Imaging, the tumor had high intensity, equivalent to or slightly lower than that on T1-weighted images, and no decrease on diffusion-weighted images. The tumor was multinodular and showed a low-signal spoke-wheel sign in the margin, enhanced gradually in the dynamic study. Positron emission tomography-CT scan, showed relatively low accumulation. Surgical resection was undertaken, and pathological examination showed metastatic thymoma. The patient is without recurrence and has no other symptoms three years after splenectomy. Conclusions This is the first report of an isolated splenic metastasis from a thymoma. Further cases are needed to standardize this surgery for such lesions.

The purplish bifurcate mussel Mytilisepta virgata is widely distributed and represents one of the major components of the intertidal community in the northwestern Pacific (NWP). Here, we characterized population genetic structure of NWP populations throughout nearly their whole distribution range using both mitochondrial (mtDNA cox1) and nuclear (ITS1) markers. Population genetic analyses for mtDNA cox 1 sequences revealed two monophyletic lineages (i.e., southern and northern lineages) geographically distributed according to the two different surface water temperature zones in the NWP. The timing of the lineage split is estimated at the Pliocene- mid-Pleistocene (5.49-1.61 Mya), which is consistent with the timing of the historical isolation of the East Sea/Sea of Japan from the South and East China Seas due to sea level decline during glacial cycles. Historical sea level fluctuation during the Pliocene-Pleistocene and subsequent adaptation of mussels to different surface water temperature zones may have contributed to shaping the contemporary genetic diversity and deep divergence of the two mitochondrial lineages. In contrast to mtDNA sequences, a clear lineage split between the two mitochondrial lineages was not found in ITS1 sequences, which showed a star-like structure composed of a mixture of southern and northern mitochondrial lineages. Possible reasons for this type of mito-nuclear discordance include stochastic divergence in the coalescent processes of the two molecular markers, or balancing selection under different marine environments. Cryptic speciation cannot be ruled out from these results, and future work using genomic analyses is required to address whether the thermal physiology of these mussels corresponds to the deep divergence of their mitochondrial genes and to test for the existence of morphologically indistinguishable but genetically separate cryptic species.

Diacylglycerol kinase (DGK) participates in lipid mediated-signal transduction. It phosphorylates diacylglycerol (DG) to phosphatidic acid (PA), thereby regulating the balanced control of these second messenger actions. Previous reports have described that one DGK family, DGKζ, is closely involved in stress responses under various conditions. Cellular stress response, a physiological process enabling cells to cope with an altered environment, is finely tuned through various signaling cascades and their molecular crosstalk. The major components of stress response are p53 and NF-κB. p53 generally serves as a proapoptotic transcriptional factor, whereas NF-κB promotes resistance to programmed cell death under most circumstances. Recent studies have suggested that DGKζ facilitates p53 degradation in cytoplasm through ubiquitin proteasome system and that DGKζ deletion upregulates p53 protein levels under basal and DNA-damage conditions. Counter-intuitively, however, DGKζ deletion suppresses p53 transcriptional activity despite increased p53 levels. In contrast, DGKζ knockdown engenders enhancement of NF-κB pathway in response to cytokines such as TNF-α and IL-1β. In response to these cytokines, DGKζ downregulation accelerates phosphorylation of the p65 subunit and its nuclear translocation, thereby enhancing NF-κB transcriptional activity. Furthermore, DGKζ deficiency is shown to promote increased association of p65 subunit with the transcriptional cofactor CBP. It is particularly interesting that this association is observed even under basal conditions in the absence of stimulation. These findings suggest that DGKζ plays a role in sequestration of the limiting pool of CBP/p300 between the NF-κB p65 subunit and p53, and that DGKζ downregulation shifts CBP/p300 toward the NF-κB subunit to regulate reciprocally antagonistic phenotypes of these transcription factors.

Meningioma is the most common intracranial tumor, and its prognosis is typically favorable. However, patients of malignant meningioma (WHO grade III) most often experience recurrence, undergo multiple surgical treatments, and have poor prognosis. No effective therapy for malignant meningioma has been established yet. We recently reported an efficacy of eribulin (Haraven®) for glioblastoma. Eribulin is considered to target TERT, which is frequently mutated in its promoter. Since TERT promoter mutation is also found in malignant meningioma, this study aims at investigating the anti-tumor effect of eribulin against TERT promoter mutation-harboring human malignant meningioma cell lines in vitro and in vivo. Two meningioma cell lines IOMM-Lee and HKBMM were used in this study. In the viability assay and the flow cytometry, eribulin strongly inhibited cell proliferation by cell cycle arrest. Apoptotic cell death in malignant meningioma cell lines was confirmed by vital dye assay and immunoblotting. Moreover, wound healing assay revealed the suppression of tumor cell migration after eribulin exposure. To assess the effect of eribulin in vivo, orthotopic xenograft mouse models of both malignant meningioma cell lines were constructed. The intraperitoneal administration of eribulin significantly prolonged the survival of meningioma cell lines implanted in the brain (p Thus, this study suggests that eribulin is a potential therapeutic agent for treating malignant meningioma.

Seasonal changes in prevalence rate and number of the epizoic limpet Lottia tenuisculpta on its gastropod hosts, Omphalius nigerrimus and Reishia clavigera, were investigated in Shirahama, Wakayama Prefecture, Japan. Monthly samplings conducted from September 2013 to September 2014 revealed that L. tenuisculpta disappeared from the host in winter and new recruits appeared in early spring. Limpets remained on their host up to a critical shell length of 7 mm on O. nigerrimus and 5 mm on R. clavigera. Capture-recapture method confirmed limpets reaching these sizes migrate onto rock surfaces. Additionally, the effects of the host sizes on their epizoic limpets were examined using a hierarchical Bayesian model. The model showed that limpet shell length decreased with the increasing number of conspecifics on both host species. The shell width of O. nigerrimus had a slightly negative effect on the shell length of limpets, whereas that of R. clavigera had a positive effect on it. Our study revealed the host utilization of epizoic limpets changed seasonally and differed between host species. We suggest that both physical and biological factors of hosts affect the growth, survival, and attachment of the epizoites.

NF-κB plays a key role in the transcriptional regulation of genes involved in immunity, inflammation, cell proliferation, and oncogenesis. The NF-κB activation process includes nuclear translocation, followed by association with basal transcription machinery. These steps are tightly regulated by posttranslational modification of the proteins involved in this pathway. We recently reported that NF-κB transactivation activity is enhanced by knockdown of diacylglycerol kinase ζ (DGKζ), which belongs to an enzyme family that phosphorylates lipidic second messenger diacylglycerol to phosphatidic acid. To investigate details of the regulatory mechanism exerted by DGKζ, we identified DEAD-box RNA helicase DDX5 as a novel DGKζ-interacting protein and examined functional role of DDX5 in NF-κB transactivation activity. Here we show that DDX5 knockdown exerts no significant effect on nuclear translocation, but specifically attenuates Ser311 phosphorylation of p65 subunit. Luciferase reporter assay reveals that the NF-κB transcriptional activity is repressed in DDX5-knockdown cells. Furthermore, we found that DDX5 knockdown selectively downregulates the expression level of Bcl-2 of the NF-κB-inducible anti-apoptotic factors upon TNF-α stimulation. Considering the evidence collectively, we can infer that DGKζ-interacting multi-protein complex modulates the NF-κB transactivation activity in a negative and positive manner under conditions in which the expression level of a component of the complex is altered.

Background Preoperative evaluation and awareness of anatomical variations in the pulmonary vessel is essential for a secure pulmonary resection. We herein present a patient who underwent complex pulmonary resection for lung cancer with a mediastinal lingular and basal pulmonary artery that had been detected by preoperative three-dimensional computed tomography. Case presentation The patient was an asymptomatic 66-year-old woman who had a 39-pack-year smoking habit. Chest computed tomography (CT) revealed the tumor invading the left upper bronchus and pulmonary artery branches in the left upper lung lobe. Enhanced CT and three-dimensional (3D) images of the pulmonary artery revealed that pulmonary artery branches (A4 + 5, A8, and A9 + 10) were extending into the lingular and basal segment in ventral side of the left upper bronchus. We completed the resection by means of a composite resection of the left upper lobe and the superior segment of the lower lobe, avoiding pulmonary angioplasty to preserve the left lower lobe or pneumonectomy. Conclusions 3D-CT is useful for detecting this rare variation of the left pulmonary artery before operation, allowing for proper resection. Electronic supplementary material The online version of this article (10.1186/s40792-018-0445-0) contains supplementary material, which is available to authorized users.

Lipid metabolism is closely involved with signal transduction and energy homeostasis. Excess calorie intake causes abnormal lipid metabolism, promoting obesity and insulin resistance. Diacylglycerol (DG) represents not only a lipidic second messenger but also an intermediate metabolite for triglyceride metabolism in the endoplasmic reticulum (ER). However, it remains undetermined how the roles of DG in signaling and energy homeostasis is regulated within the cell. Of DG kinases (DGKs), which are enzymes that phosphorylate DG, DGKε resides in the ER. This study examined how DGKε is implicated in signal transduction and lipid homeostasis. DGKε-deficient mice were fed a high-fat diet (HFD) for 40 d. We observed that DGKε deficiency promotes fat accumulation in adipocytes and subsequently promotes insulin resistance in mice fed an HFD. This abnormal fat metabolism is mediated by down-regulation of lipolytic activities, such as adipose triglyceride lipase and hormone-sensitive lipase. In addition, activation of DG-sensitive PKC leads to insulin resistance in adipose tissue, which may be caused by delayed metabolism of DG. Our data suggest that DGKε links the second messenger signaling system to energy homeostasis in adipocytes and that its deficiency results in abnormal lipid metabolism such as obesity and insulin resistance.-Nakano, T., Seino, K., Wakabayashi, I., Stafforini, D. M., Topham, M. K., Goto, K. Deletion of diacylglycerol kinase ε confers susceptibility to obesity via reduced lipolytic activity in murine adipocytes.

Objectives: Obesity is a central risk factor for atherosclerotic cardiovascular disease. The purpose of this study was to determine whether COX-2 expression is changed in the arterial wall of experimental obese animals.Methods: COX-2 expression in the aortas of 12-week-old male Zucker obese or lean rats was investigated using immunoblot and immunohistochemical analyses.Results: COX-2 expression was detected in the tunica media of the aortas of Zucker obese rats and was prominent in the perinuclear region of smooth muscle cells in the tunica media. In immunoblot analysis, the basal (non-stimulated) levels of COX-2 expression were comparable in the aortas of Zucker obese rats and Zucker lean (control) rats. COX-2 expression in response to interleukin (IL)-1β was significantly lower in the aortas of Zucker obese rats than in those of Zucker lean rats.Conclusions: The results suggest that IL-1β-induced COX-2 expression is attenuated in arteries of obese rats, and this might be involved in the obesity-induced acceleration of atherosclerosis.

A group of small lottiid species in Japan, the Lottia kogamogai complex, was phylogenetically analyzed based on the mitochondrial COI gene. As a result, L. kogamogai is subdivided into two geographic clades. Lottia kogamogai s.s. is limited to southern temperate Japan. The northern population formerly considered an intraspecific variation of the species is shown to be a distinct new species, here described as Lottia goshimai n. sp. The new species is distinguishable from L. kogamogai not only genetically, but in radular morphology and shell sculpture.

The hermit crab genus Pagurus exhibits high species diversity and a wide geological distribution. Despite the high species diversity of hermit crabs in the western Pacific coast of Japan, molecular phylogenetic studies of these species have yet to be conducted. To investigate their molecular phylogeny and genetic diversity, we obtained nearly complete mitochondrial genome sequences for ten Pagurus species found along the Pacific coast of Japan by next-generation sequencing, which were compared to other congeners deposited in the GenBank database. The genomes ranged from 13,458 to 16,401 base pairs in length, possessing 13 protein-coding genes, 2 rRNAs, and 22 tRNA genes. Based on the reconstructed phylogeny, we found that (1) Japanese Pagurus species separated into three groups, nested within the Northern Pacific species. (2) Pagurus lanuginosus and Pagurus maculosus, showed high morphological similarities, implying close kinship. Indeed, these two species were genetically closest to each other, compared to the remaining species studied. (3) An unspecified specimen sampled from the deep sea, which morphologically resembled Pagurus, might be a member of the Pagurus genus, but is genetically distant from the other Japanese Pagurus species. The novel data reported here may provide new perspectives for systematic studies of hermit crabs; these results provide important information that will facilitate population-level research and identifying intraspecific variation of these non-model, but ecologically important, decapod species.

This paper describes the influence of initial conditions for spallation particles flying in polymer ablation arcs on dynamics and evaporation of the polymer spallation particles using the numerical model. Through our previous experiments, we had found micro-sized ‘spallation particles’ ejected from polyamide materials by thermal plasma contact. To obtain the dynamics of spallation particles in polymer ablation arcs, we have developed a numerical model on dynamics of spallation particles flying in the polymer ablated arcs. The influence of pressure inside the polymer ablated arc, the initial particle diameter and the initial velocity of spallation particles were studied as parameters in the present paper. Under the given temperature and gas flow distributions in specified initial conditions, the trajectories of spallation particles flying in the polymer ablated arc were simulated numerically, considering the time variations in the temperature and the diameter of the particles. The results show that the highest flight altitude of the PA6 spallation particle flying in the PA6 ablated arc is affected by the initial particle diameter and velocity remarkably.

The switch/sucrose non-fermenting (SWI/SNF) complex has recently emerged as a novel tumor suppressor in various human cancers. In the present study, we analyzed the expression of multiple SWI/SNF subunits in primary non-small cell lung cancer (NSCLC). A total of 133 NSCLC, consisting of 25 squamous cell carcinomas (SCC), 70 adenocarcinomas (AD), 16 large cell carcinomas (LC), and 22 pleomorphic carcinomas (PL), were immunohistochemically examined for the expression of BRG1, BRM, BAF47, ARID1A, and ARID1B. The frequency at which reductions in the expression of BRG1 were observed was significantly higher in the LC-PL group (13/38, 34.2%) than in the SCC-AD group (7/95, 7.4%). Similarly, the frequency at which reductions in the expression of BRM were observed was significantly higher in the LC-PL group (17/38, 44.7%) than in the SCC-AD group (14/95, 14.7%). The loss of the expression of ARID1A, ARID1B, and BAF47 was observed only in a fraction of NSCLC cases. Furthermore, the frequency at which the concurrent loss of multiple subunits of the SWI/SNF complex was observed was significantly higher in the LC-PL group (10/38, 26.3%) than in the SCC-AD group (8/95, 8.4%). Collectively, these results indicate that the loss of the SWI/SNF complex was related to dedifferentiation in NSCLC.

Background Postoperative bronchopleural fistula is one of the most life-threatening complications after anatomical pulmonary resection. Bronchopleural fistula may cause empyema and aspiration pneumonia with subsequent acute respiratory distress syndrome. Surgical interventions for bronchopleural fistula can prolong hospitalization and impair postoperative quality of life. Postoperative care requires minimally invasive endoscopic occlusion. Methods We retrospectively reviewed the records of 7 patients who developed bronchopleural fistula among 689 patients who underwent segmentectomy or lobectomy without sleeve resection for lung cancer in Jichi Medical University from 2009 to 2013. Bronchopleural fistula occurred in the right lower bronchial stump in 3 patients, in the superior segmental bronchus of the right lower lobe in 2, in the superior segmental bronchus of the left lower lobe in one, and in the right intermediate bronchus in one. Flexible bronchoscopy was used to occlude 3-mm fistulas with polyglycolic acid mesh in 2 patients. Larger fistulas in 5 patients were occluded with polyglycolic acid mesh plus fibrin glue to secure the mesh. The median procedure was 37 min. Procedures were considered complete upon resolution of air leakage from the chest drainage system. Results Bronchoscopic interventions for bronchopleural fistula were repeated an average of 2 times. No procedure-related complications or death occurred. Bronchoscopic interventions were successful in all patients. Conclusions Bronchoscopic occlusion with polyglycolic acid mesh with or without fibrin glue is easy and feasible as the first step in postoperative management of bronchopleural fistula.

Siphonaria pectinata is a marine gastropod distributed across the shores of the Western and Eastern Atlantic. Although previous studies have indicated that the species could be a recent introduction to Central and North America from Western Africa and Europe, other authors have questioned this statement. In fact, a recent study has shown that individuals from both sides of the Atlantic are genetically disconnected, rejecting the idea of a recent invasion. However, genetic information on this species is very scarce and based only on a single study using a limited number of specimens and sites. The data reported in the present study represent one step forward, collecting information from 119 specimens from 22 sites that cover the entire distributional range of the species. Populations from the Western Atlantic separated from eastern ones around 1.4−1.9 Mya, whereas the centre of dispersion is located on the eastern side of the Atlantic. Siphonaria pectinata should be considered native to the Western Atlantic and cannot be considered as a species with an amphi-atlantic distribution owing to the lack of genetic connection between both sides of the Atlantic, as previous authors have pointed out. The presence of a star-shaped phylogeny is discussed in the context of Plio-Pleistocene glaciations.

This paper has proposed a new fundamental investigation technique on arc behaviors in decaying and re-ignition processes under gas flow condition. This technique utilizes power semiconductors like insulated-gate bipolar transistors (IGBTs) to control the arc current and voltage with a high accuracy in time domain. The free recovery condition was created by switching-on an IGBT connected in parallel with the arc device to investigate decaying process of the arc plasma under gas flow condition. Then, the quasi-transient recovery voltage (quasi-TRV) was intentionally applied between the electrodes in the arc device under the free recovery condition by turning-off the IGBT again, to study the re-ignition process of the arc plasma. At the same time, the arc behavior in a nozzle was observed by a high speed video camera at a frame rate of 200,000 fps. In the present work, arc behaviors in gas flow such as SF6 and CO2 in a nozzle was fundamentally investigated under free recovery condition and then after quasi-TRV application. In addition, the timing of the quasi-TRV application was changed to examine the recovery property of residual arcs in SF6 and CO2 gas flow. Through these experiments, the probability of arc successful interruptions were statistically measured for these gas flow arcs. These results provide fundamental data for comparison of the arc interruption capability of different conditions., 出版者照会後に全文公開

Orotate phosphoribosyltransferase (OPRT) is engaged in de novo pyrimidine synthesis. It catalyzes oronitine to uridine monophosphate (UMP), which is used for RNA synthesis. De novo pyrimidine synthesis has long been known to play an important role in providing DNA/RNA precursors for rapid proliferative activity of cancer cells. Furthermore, chemotherapeutic drug 5-fluorouracil (5-FU) is taken up into cancer cells and is converted to 5-fluoro-UMP (FUMP) by OPRT or to 5-fluoro-dUMP (FdUMP) through intermediary molecules by thymidine phosphorylase. These 5-FU metabolites are misincorporated into DNA/RNA, thereby producing dysfunction of these information processing. However, it remains unclear how the subcellular localization of OPRT and how its variable expression levels affect the response to 5-FU at the cellular level. In this study, immunocytochemical analysis reveals that OPRT localizes to the Golgi complex. Results also show that not only overexpression but also downregulation of OPRT render cells susceptible to 5-FU exposure, but it has no effect on DNA damaging agent doxorubicin. This study provides clues to elucidate the cellular response to 5-FU chemotherapy in relation to the OPRT expression level.

Modeling of spallation polymer particles in polymer ablated arcs was conducted to numerically simulate its dynamics and thermal decomposition. We had found that spallation particles ejected from the polyamide materials contacting thermal plasmas experimentally. For the modeling of the particle dynamics, the temperature and gas flow fields in polymer ablated arcs were calculated as a background plasma at first. Using the calculated temperature and gas flow fields in polymer ablated arcs, we computed the trajectories of the particles flying in the polymer ablated arc, considering the time variations in the temperature and the diameter of the particles. This computation accounted for the temperature distribution inside the particle, melting and thermal decomposition of the particle. The polyamide-6 (PA6) particle in the PA6 ablated arc was dealt with. As a result, the temperature variation including the phase changes, and the decrease in diameter were simulated for PA6 particles in the PA6 ablated arc. Results also indicate that a particle with a diamater of 0.3mm and a velocity of 5m/s can reach the high-temperature arc core in a 6mm diamater PA6 tube., 出版者照会後に全文公開

Objectives: The indications for video-assisted thoracoscopic surgery (VATS) for advanced-stage lung cancer are expanding, but the criteria vary among institutions. This study compared the minimal invasiveness and oncologic validity of VATS lobectomy and thoracotomy lobectomy for the treatment of large-diameter primary lung cancer. Methods: We retrospectively reviewed clinical features and surgical outcomes of 68 patients who underwent anatomical pulmonary resection for primary lung cancer of >5-cm diameter from July 2006 to March 2013. The patients were divided into a VATS group (Group V, n = 35) and a thoracotomy group (Group T, n = 33). Results: Group V exhibited less intraoperative bleeding (p = 0.012) and had a shorter length of postoperative hospital stay (p = 0.024). The 1- and 5-year overall survival rates were 91.3% and 39.3% in Group V and 84.8% and 56.9% in Group T, respectively (p = 0.48). Multivariate analysis showed that limited lymph node dissection contributed to local recurrence. The extraction bag lavage cytology in Group V revealed that the positivity rate was 35.7%. Conclusions: VATS for primary lung cancer of >5-cm diameter is similar to thoracotomy in terms of surgical outcomes. Large tumors must be carefully maneuvered during VATS to prevent cancer cell spillage.

Lipid not only represents a constituent of the plasma membrane, but also plays a pivotal role in intracellular signaling. Lipid-mediated signaling system is strictly regulated by several enzymes, which act at various steps of the lipid metabolism. Under pathological conditions, prolonged or insufficient activation of this system results in dysregulated signaling, leading to diseases such as cancer or metabolic syndrome. Of the lipid-modulating enzymes, diacylglycerol kinase (DGK) and cyclooxygenase (COX) are intimately involved in the signaling system. DGK consists of a family of enzymes that phosphorylate a second messenger diacylglycerol (DG) to produce phosphatidic acid (PA). Both DG and PA are known to activate signaling molecules such as protein kinase C. COX catalyzes the committed step in prostanoid biosynthesis, which involves the metabolism of arachidonic acid to produce prostaglandins. Previous studies have shown that the DGK and COX are engaged in a number of pathological conditions. This review summarizes the functional implications of these two enzymes in ischemia, liver regeneration, vascular events, diabetes, cancer and inflammation.

This paper reports dielectric recovery property measurements of CO 2 and Air arcs under free recovery condition. In these measurements, the arc current and the voltage applied to the free recovery arcs were controlled with a high accuracy in time using power semiconductors. The recovery properties were measured by changing the application delay time t d of the recovery voltage with a peak of 8.2 kV. As a result, 200 L/min of CO 2 gas flow needs t d = 165 μs to withstand the quasi-TRV application with 50% probability of arc re-ignition; while 200 L/min of Air gas flow requires t d = 220 μ for the same purpose.

Both experimental and numerical approaches have been done on switching arc plasmas for fundamental studies. In the experimental approaches, power-semiconductor switching has been used to control intentional current injections and voltage applications to switching arcs with a high accuracy in time. The systematic experiments provided the interruption probability property for different gas kinds and gas flow rates, as well as the dielectric recovery properties between the electrodes. Time evolutions in electron density were derived by Laser Thomson Scattering (LTS) and Shack-Hartmann (SH) method for different gases. On the other hand, for this nozzle space, numerical models were developed to simulate arc dynamic behaviors with and without local thermodynamic equilibrium (LTE) assumptions for different gases. It was found that the time evolution in electron density derived by the chemically non-equilibrium model is in good agreement with the experimental results by LTS.

This paper reports fundamental measurement results on re-ignition process in synthetic tests for CO 2 arcs in a gas blast nozzle. The synthetic test system used comprises a DC current source for an arc ignition, a half cycle AC current source, a DC current source for artificial current zero point and an impulse-like voltage source for application of quasi-transient recovery voltage (quasi-TRV). The electric current and voltage were switched by power-semiconductor-switches to guarantee high time-accuracy of the arc current injection and voltage application. After current zero point, quasi-TRV with a peak of 7.5 kV was applied between the electrodes with a precise specified delay time t d to judge arc re-ignition. The results indicated that t d = 25 μs involves 60% probability of arc re-ignition. The re-ignition was inferred to originate in thermal mode from joule heating by a small current injection to the residual arc during the quasi-TRV application.

The tumor suppressor gene product p53, which coordinates the cellular response to various stresses, is subject to tight regulation by a complex network of signal transduction. The DGK family metabolizes lipidic second messenger diacylglycerol to produce phosphatidic acid. Our earlier studies showed that one isozyme, DGKζ, is involved in the regulatory mechanism of p53. In a cellular model of doxorubicin-induced DNA damage, overexpression of wild-type DGKζ suppresses p53 protein induction and reduces apoptosis, whereas knockdown of DGKζ upregulates p53 protein level and promotes apoptosis. Further examination reveals that DGKζ facilitates p53 degradation via ubiquitin-proteasome system in the cytoplasm. However, it remains undetermined whether the regulatory mechanism of DGKζ on p53 function found in cell-based experiments is also functional at the animal level. This study was conducted to elucidate this point using an experiment with DGKζ-KO mice under DNA damage induced by whole-body ionizing radiation. Our results reveal that p53 protein is induced robustly in the spleen of DGKζ-KO mice upon exposure to ionizing radiation, thereby promoting apoptosis in this organ. Taken together, the results demonstrate that DGKζ plays a sentinel role in p53 expression at the cellular and organismal levels after DNA damaging stress conditions.

Diacylglycerol kinase (DGK) is responsible for the enzymatic conversion of diacylglycerol to phosphatidic acid. Since both diacylglycerol and phosphatidic acid serve as signaling molecules, DGK is regarded as a hub between diacylglycerol-mediated and phosphatidic acid-mediated signaling. One of the 10 DGK isozymes, DGKα, is shown to be involved in T cell function. Transfection studies using tagged expression vectors revealed that DGKα localizes to the cytoplasm and nucleus and translocates to the plasma membrane in response to T cell receptor stimulation. However, a limited number of studies reported the localization of native protein of DGKα in tissues and cells. In this study, we immunized mice with recombinant DGKα and developed several anti-DGKα monoclonal antibodies (mAbs). One of the established anti-DGKα mAbs is a clone DaMab-2 (mouse IgG1, kappa). In enzyme-linked immunosorbent assay, DaMab-2 recognized only DGKα, and did not react with the other isozymes, such as DGKγ, DGKζ, DGKη, and DGKδ. Importantly, DaMab-2 is very useful in immunocytochemical analysis of human cultured cells, indicating that DaMab-2 is advantageous to analyze the localization and function of DGKα.

We treated an 82-year-old man with early gastric cancer using endoscopic submucosal resection.Ultrasonography, which was performed to screen for metastasis, revealed hepatocellular carcinoma, and the tumor was curatively resected.Ultrasonography can be considered a useful examination tool to detect double cancer, even in cases of early cancer.

We treated a 91-year-old man with squamous cell carcinoma that originated from his jejunum, which is very rare; only 8 cases have been reported previously.Surgery was performed because of the small bowel obstruction caused by the large cancerous mass, but he died 23 days later.Early detection and early treatment are important, especially for the ultra-elderly from a standpoint of tolerating surgery.

Oceanic islands lacking connections to other land are extremely isolated from sources of potential colonists and have acquired their biota mainly through dispersal from geographically distant areas. Hence, isolated island biota constitutes interesting models to infer biogeographical mechanisms of dispersal, colonization, differentiation, and speciation. Limpets of the genus Cellana (Nacellidae: Patellogastropoda) show limited dispersal capacity but are broadly distributed across the Indo-Pacific including many endemic species in isolated oceanic islands. Here, we examined main distributional patterns and geographic boundaries among Cellana lineages with special emphasis in the relationships of Southern Hemisphere oceanic islands species. Phylogenetic reconstructions based on mtDNA (COI) recognized three main clades in Cellana including taxa from different provinces of the Indo-Pacific. Clear genetic discontinuities characterize the biogeography of Cellana and several lineages are associated to particular areas of the Indo-Pacific supporting the low dispersal capacity of the genus across recognized biogeographical barriers in the region. However, evolutionary relationships within Cellana suggest that long-distance dispersal processes have been common in the history of the genus and probably associated to the origin of the species in Hawaii and Juan Fernández Archipelago. Therefore, the presence of Cellana species in geographically distant Southern Hemisphere oceanic islands, such as the Juan Fernández Archipelago, suggests that long-distance dispersal mediated by rafting may have played an important role in the biogeography of the genus.

Objectives Video-assisted thoracic surgery is widely applied for resection of mediastinal tumors. The mediastinal mature teratoma, however, is usually operated on via an open approach because it is generally large, making it difficult to dissect under a thoracoscopic view and remove it from the thoracic cavity. We attempted to extract intracystic material during video-assisted thoracic surgery to facilitate dissection and removal of the tumor from the thoracic cavity. Methods From January 1998 to April 2013, 13 patients (9 women, 4 men; mean age 33 years, range 17–54 years) with mediastinal mature teratomas were operated on via video-assisted thoracic surgery. Intracystic contents of the tumor were aspirated before dissection or after the teratoma was dissected and placed in the retrieval pouch. Results None of the patients required conversion to an open procedure. Operating time was 95–184 min (mean 132 min). Blood loss during the operation amounted to 10–300 mL (mean 78 mL). The tumor size ranged from 5 to 12 cm (mean 8 cm). In all cases, the tumors were confirmed pathologically to be mature cystic teratomas with no malignant components. During and after follow-up, all patients continue to do well without recurrence. Conclusion Extraction of intracystic contents enabled thoracoscopic resection of large mature mediastinal teratomas.