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41.
Hana Shimoyama Toshiaki K. Shibata Masahiko Ito Tomoaki Oda Toshiya Itoh Mari Mukai Madoka Matsuya-Ogawa Masashi Adachi Hirotake Murakami Takeshi Nakayama Kazuhiro Sugihara Hiroaki Itoh Tetsuro Suzuki Naohiro Kanayama 《Biochemistry and Biophysics Reports》2020
Endometrial cancer is the most common gynecologic malignancy and is associated with increased morbidity each year, including young people. However, its mechanisms of proliferation and progression are not fully elucidated. It is well known that abnormal glycosylation is involved in oncogenesis, and fucosylation is one of the most important types of glycosylation. In particular, fucosyltransferase 8 (FUT8) is the only FUT responsible for α1, 6-linked fucosylation (core fucosylation), and it is involved in various physiological as well as pathophysiological processes, including cancer biology. Therefore, we aimed to identify the expression of FUT8 in endometrial endometrioid carcinoma and investigate the effect of the partial silencing of the FUT8 gene on the cell proliferation of Ishikawa cells, an epithelial-like endometrial cancer cell line. Quantitative real-time PCR analysis showed that FUT8 gene expression was significantly elevated in the endometrial endometrioid carcinoma, compared to the normal endometrium. The immunostaining of FUT8 and Ulex europaeus Agglutinin 1 (UEA-1), a kind of lectin family specifically binding to fucose, was detected endometrial endometrioid carcinoma. The proliferation assay showed FUT8 partial knockdown by transfection of siRNA significantly suppressed the proliferation of Ishikawa cells, concomitant with the upregulation in the gene expressions associated with the interesting pathways associated with de-ubiquitination, aspirin trigger, mesenchymal-epithelial transition (MET) et al. It was suggested that the core fucosylation brought about by FUT8 might be involved in the proliferation of endometrial endometrioid carcinoma cells. 相似文献
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Ryuzaburo Yuki Mari Hagino Sachi Ueno Takahisa Kuga Youhei Saito Yasunori Fukumoto Noritaka Yamaguchi Naoto Yamaguchi Yuji Nakayama 《Journal of cellular and molecular medicine》2021,25(3):1677-1687
v-Src oncogene causes cell transformation through its strong tyrosine kinase activity. We have revealed that v-Src-mediated cell transformation occurs at a low frequency and it is attributed to mitotic abnormalities-mediated chromosome instability. v-Src directly phosphorylates Tyr-15 of cyclin-dependent kinase 1 (CDK1), thereby causing mitotic slippage and reduction in Eg5 inhibitor cytotoxicity. However, it is not clear whether v-Src modifies cytotoxicities of the other anticancer drugs targeting cell division. In this study, we found that v-Src restores cancer cell viability reduced by various microtubule-targeting agents (MTAs), although v-Src does not alter cytotoxicity of DNA-damaging anticancer drugs. v-Src causes mitotic slippage of MTAs-treated cells, consequently generating proliferating tetraploid cells. We further demonstrate that v-Src also restores cell viability reduced by a polo-like kinase 1 (PLK1) inhibitor. Interestingly, treatment with Aurora kinase inhibitor strongly induces cell death when cells express v-Src. These results suggest that the v-Src modifies cytotoxicities of anticancer drugs targeting cell division. Highly activated Src-induced resistance to MTAs through mitotic slippage might have a risk to enhance the malignancy of cancer cells through the increase in chromosome instability upon chemotherapy using MTAs. 相似文献
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Kathryn M. Maselli Gabriel Levin Kristin M. Gee Elisabeth J. Leeflang Ana Claudia O. Carreira Mari Cleide Sogayar Tracy C. Grikscheit 《Biochemistry and Biophysics Reports》2021
BackgroundR-spondins, including R-spondin 1 (RSPO1), are a family of Wnt ligands that help to activate the canonical Wnt/β-catenin pathway, which is critical for intestinal epithelial cell proliferation and maintenance of intestinal stem cells. This proliferation underpins the epithelial expansion, or intestinal adaptation (IA), that occurs following massive bowel resection and short bowel syndrome (SBS). The purpose of this study was to identify if recombinant human RSPO1 (rhRSPO1) could be serially administered to SBS zebrafish to enhance cellular proliferation and IA.MethodsAdult male zebrafish were assigned to four groups: sham + PBS, SBS + PBS, sham + rhRSPO1, and SBS + rhRSPO1. Sham fish had a laparotomy alone. SBS fish had a laparotomy with distal intestinal ligation and creation of a proximal stoma. Fish were weighed at initial surgery and then weekly. rhRSPO1 was administered post-operatively following either a one- or two-week dosing schedule with either 3 or 5 intraperitoneal injections, respectively. Fish were harvested at 7 or 14 days with intestinal segments collected for analysis.ResultsRepeated intraperitoneal injection of rhRSPO1 was feasible and well tolerated. At 7 days, intestinal epithelial proliferation was increased by rhRSPO1. At 14 days, SBS + rhRSPO1 fish lost significantly less weight than SBS + PBS fish. Measurements of intestinal surface area were not increased by rhRSPO1 administration but immunofluorescent staining for β-catenin and gene expression for cyclin D1 was increased.ConclusionsIntraperitoneal injection of rhRSPO1 decreased weight loss in SBS zebrafish with increased β-catenin + cells and cyclin D1 expression at 14 days, indicating improved weight maintenance might result from increased activation of the canonical Wnt pathway. 相似文献
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Local temperatures inferred from plant communities suggest strong spatial buffering of climate warming across Northern Europe 总被引:1,自引:0,他引:1
Jonathan Lenoir Bente Jessen Graae Per Arild Aarrestad Inger Greve Alsos W. Scott Armbruster Gunnar Austrheim Claes Bergendorff H. John B. Birks Kari Anne Bråthen Jörg Brunet Hans Henrik Bruun Carl Johan Dahlberg Guillaume Decocq Martin Diekmann Mats Dynesius Rasmus Ejrnæs John‐Arvid Grytnes Kristoffer Hylander Kari Klanderud Miska Luoto Ann Milbau Mari Moora Bettina Nygaard Arvid Odland Virve Tuulia Ravolainen Stefanie Reinhardt Sylvi Marlen Sandvik Fride Høistad Schei James David Mervyn Speed Liv Unn Tveraabak Vigdis Vandvik Liv Guri Velle Risto Virtanen Martin Zobel Jens‐Christian Svenning 《Global Change Biology》2013,19(5):1470-1481
Recent studies from mountainous areas of small spatial extent (<2500 km2) suggest that fine‐grained thermal variability over tens or hundreds of metres exceeds much of the climate warming expected for the coming decades. Such variability in temperature provides buffering to mitigate climate‐change impacts. Is this local spatial buffering restricted to topographically complex terrains? To answer this, we here study fine‐grained thermal variability across a 2500‐km wide latitudinal gradient in Northern Europe encompassing a large array of topographic complexities. We first combined plant community data, Ellenberg temperature indicator values, locally measured temperatures (LmT) and globally interpolated temperatures (GiT) in a modelling framework to infer biologically relevant temperature conditions from plant assemblages within <1000‐m2 units (community‐inferred temperatures: CiT). We then assessed: (1) CiT range (thermal variability) within 1‐km2 units; (2) the relationship between CiT range and topographically and geographically derived predictors at 1‐km resolution; and (3) whether spatial turnover in CiT is greater than spatial turnover in GiT within 100‐km2 units. Ellenberg temperature indicator values in combination with plant assemblages explained 46–72% of variation in LmT and 92–96% of variation in GiT during the growing season (June, July, August). Growing‐season CiT range within 1‐km2 units peaked at 60–65°N and increased with terrain roughness, averaging 1.97 °C (SD = 0.84 °C) and 2.68 °C (SD = 1.26 °C) within the flattest and roughest units respectively. Complex interactions between topography‐related variables and latitude explained 35% of variation in growing‐season CiT range when accounting for sampling effort and residual spatial autocorrelation. Spatial turnover in growing‐season CiT within 100‐km2 units was, on average, 1.8 times greater (0.32 °C km?1) than spatial turnover in growing‐season GiT (0.18 °C km?1). We conclude that thermal variability within 1‐km2 units strongly increases local spatial buffering of future climate warming across Northern Europe, even in the flattest terrains. 相似文献
46.
Mari K. Reeves Kimberly A. Medley Alfred E. Pinkney Marcel Holyoak Pieter T. J. Johnson Michael J. Lannoo 《PloS one》2013,8(11)
Amphibians with missing, misshapen, and extra limbs have garnered public and scientific attention for two decades, yet the extent of the phenomenon remains poorly understood. Despite progress in identifying the causes of abnormalities in some regions, a lack of knowledge about their broader spatial distribution and temporal dynamics has hindered efforts to understand their implications for amphibian population declines and environmental quality. To address this data gap, we conducted a nationwide, 10-year assessment of 62,947 amphibians on U.S. National Wildlife Refuges. Analysis of a core dataset of 48,081 individuals revealed that consistent with expected background frequencies, an average of 2% were abnormal, but abnormalities exhibited marked spatial variation with a maximum prevalence of 40%. Variance partitioning analysis demonstrated that factors associated with space (rather than species or year sampled) captured 97% of the variation in abnormalities, and the amount of partitioned variance decreased with increasing spatial scale (from site to refuge to region). Consistent with this, abnormalities occurred in local to regional hotspots, clustering at scales of tens to hundreds of kilometers. We detected such hotspot clusters of high-abnormality sites in the Mississippi River Valley, California, and Alaska. Abnormality frequency was more variable within than outside of hotspot clusters. This is consistent with dynamic phenomena such as disturbance or natural enemies (pathogens or predators), whereas similarity of abnormality frequencies at scales of tens to hundreds of kilometers suggests involvement of factors that are spatially consistent at a regional scale. Our characterization of the spatial and temporal variation inherent in continent-wide amphibian abnormalities demonstrates the disproportionate contribution of local factors in predicting hotspots, and the episodic nature of their occurrence. 相似文献
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