45 research outputs found

    The Ets dominant repressor En/Erm enhances intestinal epithelial tumorigenesis in ApcMin mice

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    <p>Abstract</p> <p>Background</p> <p>Ets transcription factors have been widely implicated in the control of tumorigenesis, with most studies suggesting tumor-promoting roles. However, few studies have examined Ets tumorigenesis-modifying functions <it>in vivo </it>using model genetic systems.</p> <p>Methods</p> <p>Using mice expressing a previously characterized Ets dominant repressor transgene in the intestinal epithelium (Villin-En/Erm), we examined the consequences of blocking endogenous Ets-mediated transcriptional activation on tumorigenesis in the Apc<sup>Min </sup>model of intestinal carcinoma.</p> <p>Results</p> <p>En/Erm expression in the intestine, at levels not associated with overt crypt-villus dysmorphogenesis, results in a marked increase in tumor number in Apc<sup>Min </sup>animals. Moreover, when examined histologically, tumors from En/Erm-expressing animals show a trend toward greater stromal invasiveness. Detailed analysis of crypt-villus homeostasis in these En/Erm transgenic animals suggests increased epithelial turnover as one possible mechanism for the enhanced tumorigenesis.</p> <p>Conclusion</p> <p>Our findings provide <it>in vivo </it>evidence for a tumor-restricting function of endogenous Ets factors in the intestinal epithelium.</p

    Atypical PKCiota Contributes to Poor Prognosis Through Loss of Apical-basal Polarity and Cyclin E Overexpression in Ovarian Cancer

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    We show that atypical PKCι, which plays a critical role in the establishment and maintenance of epithelial cell polarity, is genomically amplified and overexpressed in serous epithelial ovarian cancers. Furthermore, PKCι protein is markedly increased or mislocalized in all serous ovarian cancers. An increased PKCι DNA copy number is associated with decreased progression-free survival in serous epithelial ovarian cancers. In a Drosophila in vivo epithelial tissue model, overexpression of persistently active atypical PKC results in defects in apical-basal polarity, increased Cyclin E protein expression, and increased proliferation. Similar to the Drosophila model, increased PKCι proteins levels are associated with increased Cyclin E protein expression and proliferation in ovarian cancers. In nonserous ovarian cancers, increased PKCι protein levels, particularly in the presence of Cyclin E, are associated with markedly decreased overall survival. These results implicate PKCι as a potential oncogene in ovarian cancer regulating epithelial cell polarity and proliferation and suggest that PKCι is a novel target for therapy

    Attitudes on the donation of human embryos for stem cell research among Chinese IVF patients and students

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    Bioethical debates on the use of human embryos and oocytes for stem cell research have often been criticized for the lack of empirical insights into the perceptions and experiences of the women and couples who are asked to donate these tissues in the IVF clinic. Empirical studies that have investigated the attitudes of IVF patients and citizens on the (potential) donation of their embryos and oocytes have been scarce and have focused predominantly on the situation in Europe and Australia. This article examines the viewpoints on the donation of embryos for stem cell research among IVF patients and students in China. Research into the perceptions of patients is based on in-depth interviews with IVF patients and IVF clinicians. Research into the attitudes of students is based on a quantitative survey study (n=427). The empirical findings in this paper indicate that perceptions of the donation of human embryos for stem cell research in China are far more diverse and complex than has commonly been suggested. Claims that ethical concerns regarding the donation and use of embryos and oocytes for stem cell research are typical for Western societies but absent in China cannot be upheld. The article shows that research into the situated perceptions and cultural specificities of human tissue donation can play a crucial role in the deconstruction of politicized bioethical argumentation and the (often ill-informed) assumptions about “others” that underlie socio-ethical debates on the moral dilemmas of technology developments in the life sciences

    Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches

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    Extracellular vesicles (EVs), through their complex cargo, can reflect the state of their cell of origin and change the functions and phenotypes of other cells. These features indicate strong biomarker and therapeutic potential and have generated broad interest, as evidenced by the steady year-on-year increase in the numbers of scientific publications about EVs. Important advances have been made in EV metrology and in understanding and applying EV biology. However, hurdles remain to realising the potential of EVs in domains ranging from basic biology to clinical applications due to challenges in EV nomenclature, separation from non-vesicular extracellular particles, characterisation and functional studies. To address the challenges and opportunities in this rapidly evolving field, the International Society for Extracellular Vesicles (ISEV) updates its 'Minimal Information for Studies of Extracellular Vesicles', which was first published in 2014 and then in 2018 as MISEV2014 and MISEV2018, respectively. The goal of the current document, MISEV2023, is to provide researchers with an updated snapshot of available approaches and their advantages and limitations for production, separation and characterisation of EVs from multiple sources, including cell culture, body fluids and solid tissues. In addition to presenting the latest state of the art in basic principles of EV research, this document also covers advanced techniques and approaches that are currently expanding the boundaries of the field. MISEV2023 also includes new sections on EV release and uptake and a brief discussion of in vivo approaches to study EVs. Compiling feedback from ISEV expert task forces and more than 1000 researchers, this document conveys the current state of EV research to facilitate robust scientific discoveries and move the field forward even more rapidly

    Endocytosis in soybean protoplasts and synchronous suspension cultures of soybean cells

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    Due to the character of the original source materials and the nature of batch digitization, quality control issues may be present in this document. Please report any quality issues you encounter to [email protected], referencing the URI of the item.Includes bibliographical references.The double phosphate starvation method for inducing cell division synchrony in suspension cultures was applied to a rapidly growing suspension culture of soybean (Glycine max (L.) Merr.) cells. The synchrony of the culture was confirmed by changes in the mitotic index (NE) which were monitored using epifluorescence of the DNA stain, 4',6-dianiidine-2-phenylindole (DAPI). Synchrony was also assessed by examining the increase in cell fresh weight which was found to be restricted to the interphase portion of the cell cycle. Two rounds of synchronous cell division were obtained. The synchronous system thus established can be used to examine cell cycle related events in higher plants, such as endocytosis. Uptake of the fluorescent anion, Lucifer Yellow CH (LYCH), was investigated using a synchronized suspension culture of soybean. LYCH uptake increased during a short period immediately following cell division, reaching its peak as NU apparently decreased. As the cells started to divide, uptake of this anion was blocked. Using ethidium bromide, a vital dye of nucleic acids, cells determined to be mitotic did not accumulate LYCH in the vacuole. LYCH uptake changes may have resulted from changes in either fluid-phase endocytosis or anion transport capability of cells. Further studies relating fluid-phase endocytosis to the cell cycle are proposed using more reliable marker, e.g. BSA-gold in protoplasts and nanogold in walled plant cells. The FITC-polylysine was used as a fluorescently-labeled probe to measure the pH changes in endocytic compartment in soybean suspension culture. The ratio image of FITC-polylysine-labeled soybean protoplasts indicated that the earliest pH change following uptake of plasma membrane was an apparent alkalization. The pH near the plasma membrane, presumably in endocytic vesicles, remained alkaline. The pH of endosomes in the more distant cortical cytoplasm and in the trans-vacuole strands dropped to a relatively low value. Finally, the pH of larger organelles in the vicinity of the nucleus was more alkaline. The internalization of FITC-polylysine may follow an endocytic pathway similar to that taken by canonized fenitin (CF). The mechanism of alkalinization occurring during the early stage of interaction in soybean protoplasts is discussed in terms of changes in the activity of a H+/K AT'Pase at the plasma membrane and endosomes

    Improved differential evolution algorithm for solving open-pit mine transportation problem

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    Aiming at open-pit mine transportation problem, a mathematical model of the open-pit mine transportation problem was established which took production and transportation capacity of open-pit mine as constraint conditions and the minimum transportation cost as objective function. In view of problem that intelligent optimization algorithm for solving the open-pit mine transportation problem was easily getting trapped in local optimal solution, an improved differential evolution algorithm was proposed. Normalization is introduced into differential evolution algorithm which makes equality constraint in the transportation problem can be satisfied automatically and is advantageous to jump out of local optimal solution. The application results show that the algorithm has good repeatability, and transportation cost is significantly reduced by use of the algorithm to optimize the open-pit mine transportation problem

    Inconsistency distribution patterns of different remote sensing land-cover data from the perspective of ecological zoning

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    Analyzing consistency of different land-cover data is significant to reasonably select land-cover data for regional development and resource survey. Existing consistency analysis of different datasets mainly focused on the phenomena of spatial consistency regional distribution or accuracy comparison to provide guidelines for choosing the land-cover data. However, few studies focused on the hidden inconsistency distribution rules of different datasets, which can provide guidelines not only for users to properly choose them but also for producers to improve their mapping strategies. Here, we zoned the Sindh province of Pakistan by the Terrestrial Ecoregions of the World as a case to analyze the inconsistency patterns of the following three datasets: GlobeLand30, FROM-GLC, and regional land cover (RLC). We found that the inconsistency of the three datasets was relatively low in areas having a dominant type and also showing homogeneity characteristics in remote sensing images. For example, cropland of the three datasets in the ecological zoning of Northwestern thorn scrub forests showed high consistency. In contrast, the inconsistency was high in areas with strong heterogeneity. For example, in the southeast of the Thar desert ecological zone where cropland, grassland, shrubland, and bareland were interleaved and the surface cover complexity was relatively high, the inconsistency of the three datasets was relatively high. We also found that definitions of some types in different classification systems are different, which also increased the inconsistency. For example, the definitions of grassland and bareland in GlobeLand30 and RLC were different, which seriously affects the consistency of these datasets. Hence, producers can use the existing land-cover products as reference in ecological zones with dominant types and strong homogeneity. It is necessary to pay more attention on ecological zoning with complex land types and strong heterogeneity. An effective way is standardizing the definitions of complex land types, such as forest, shrubland, and grassland in these areas

    Consistency Analysis of Remote Sensing Land Cover Products in the Tropical Rainforest Climate Region: A Case Study of Indonesia

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    Land cover changes in tropical rainforest climate zones play an important role in global climate change and the functioning of the Earth’s natural system. Existing research on the consistency of different land cover products has mainly focused on administrative divisions (continental or national scales). However, the ongoing production of large regional or global land cover products with higher resolutions requires us to have a better grasp of confusing land types and their geographical locations for different zoning (e.g., geographical zoning) in order to guide the optimization of strategies such as zoning and sample selection in automated land cover classification. Therefore, we selected the GlobeLand30-2010, GLC_FCS30-2015, and FROM_GLC2015 global land cover products with a 30-m resolution covering Indonesia, which has a tropical rainforest climate, as a case study, and then analyzed these products in terms of areal consistency, spatial consistency, and accuracy evaluation. The results revealed that (a) all three land cover products revealed that forest is the main land cover type in Indonesia. The area correlation coefficient of any two products is better than 0.89; (b) the areas that are completely consistent among the three products account for 58% of the total area of Indonesia, mainly distributed in the central and northern parts of Kalimantan and Papua, which are dominated by forest land types. The spatial consistency of the three products is low, however, due to the complex surface types and staggered distributions of grassland, shrub, cultivated land, artificial surface, and other land cover types in Java, eastern Sumatra, and the eastern, southern, and northwestern sections of Kalimantan, where the elevation is less than 200 m. Given these results, land cover producers should take heed of the classification accuracy of these areas; (c) the absolute accuracy evaluation demonstrated that the GLC_FCS30-2015 product has the highest overall accuracy (65.59%), followed by the overall accuracy of the GlobeLand30-2010 product (61.65%), while the FROM_GLC2015 exhibits the lowest overall accuracy (57.71%). The mapping accuracy of the three products is higher for forests and artificial surfaces. The cropland mapping accuracy of the GLC_FCS30-2015 product is higher than those of the other two products. The mapping accuracy of all products is low for grassland, shrubland, bareland, and wetland. The classification accuracy of these land cover types requires further improvement and cannot be used directly by land cover users when conducting relevant research in tropical rainforest climate zones, since the utilization of these products could lead to serious errors

    Spatial Pattern Consistency among Different Remote-Sensing Land Cover Datasets: A Case Study in Northern Laos

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    Comparisons of the accuracy and consistency of different remote-sensing land cover datasets are important for the rational application of multi-source land cover datasets to regional development, or to studies of global or local environmental change. Existing comparisons of accuracy or spatial consistency among land cover datasets primarily use confusion or transfer matrices and focus on the type and area consistency of land cover. However, less attention has been paid to the consistency of spatial patterns, and quantitative analyses of spatial pattern consistency are rare. However, when proportions of land cover types are similar, spatial patterns are essential for studies of the ecological functions of a landscape system. In this study, we used classical landscape indices that quantifies spatial patterns to analyze the spatial pattern consistency among different land cover datasets, and chose three datasets (GlobeLand30-2010, FROM-GLC2010, and SERVIR MEKONG2010) in northern Laos as a case study. We also analyzed spatial pattern consistency at different scales after comparing the landscape indices method with the confusion matrix method. We found that the degree of consistency between GlobeLand30-2010 and SERVIR MEKONG2010 was higher than that of GlobeLand30-2010 and FROM-GLC2010, FROM-GLC2010, and SERVIR MEKONG2010 based on the confusion matrix, mainly because of the best forest consistency and then water. However, the spatial consistency results of the landscape indices analysis show that the three datasets have large differences in the number of patches (NP), patch density (PD), and landscape shape index (LSI) at the original scale of 30 m, and decrease with the increase of the scale. Meanwhile, the aggregation index (AI) shows different changes, such as the changing trend of the forest aggregation index increasing with the scale. Our results suggested that, when using or producing land cover datasets, it is necessary not only to ensure the consistency of landscape types and areas, but also to ensure that differences among spatial patterns are minimized, especially those exacerbated by scale. Attention to these factors will avoid larger deviations and even erroneous conclusions from these data products

    Genetic diversity and population structure of the Chinese mitten crab Eriocheir sinensis in its native range

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    The Chinese mitten crab Eriocheir sinensis is an indigenous and economically important species in China, but can also be found as invasive species in Europe and America. Mitten crabs have been exploited extensively as a food resource since the 1990s. Despite its ecological and economic importance, the genetic structure of native mitten crab populations is not well understood. In this paper, we investigated the genetic structure of mitten crab populations in China by screening samples from ten locations covering six river systems at six microsatellite loci. Our results provide further evidence that mitten crabs from the River Nanliujiang in Southern China are a genetically differentiated population within the native range of Eriocheir, and should be recognized as a separate taxonomic unit. In contrast, extremely low levels of genetic differentiation and no significant geographic population structure were found among the samples located north of the River Nanliujiang. Based on the reproductive biology of mitten crabs and the geography of their habitat we argue that both natural and human-mediated gene flow are unlikely to fully account for the similar allele frequency distributions at microsatellite loci. Large population sizes of mitten crabs suggest instead that a virtual absence of genetic drift and significant homoplasy of microsatellite alleles have contributed to the observed pattern. Furthermore, a coalescent-based maximum likelihood method indicated a more than two-fold lower effective population size of the Southern population compared to the Northern Group and low but significant levels of gene flow between both areas
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