70 research outputs found

    Close Mapping of St. Olav’s Pilgrimage Path Through Gudbrandsdal Norway: Probabilities of a Designed, Land Surveyed Concept of a Large-Scale Christianised Landscape

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    This exercise in Norway ‘close-maps’ accurate, existing geometries between thirty-two latitude / longitude points of mostly medieval churches and other sites on the major pilgrimage path through Gudbrandsdal to Trondheimsfjord where the martyr St.Olav was venerated. Site data and basic path routes are taken from the Pilegrimsleden website, popular today with religious or recreational tourists. The inclusion of the largest prehistoric monumental mound in Scandinavia as an important early stop on the pilgrimage provides the first clue to the eventual mapping of a large-scale ‘system’ of land surveyed patterns. This symbolic anchor in the south, is connected to likely ancient religious sites to the north in Trondheimsfjord where St. Olav was killed in battle. Discovered are several early church sites key to site integration but not included as part of today’s pilgrim path. The Gudbrandsdal route appears to have been laid out earlier than the smaller volume, overlapping, Østerdal path immediately to the east. To distinguish formally designed geometric large-scale patterns from random phenomena, test areas are created where equal numbers of random points replace the existing. Combinations of three-point alignments, cardinal (N-S. E-W) alignments between two points, and right-angle relationships between three points are tested at increasing complexities of combination at accuracies of 0.06° angular deviation or less, mostly around 0.04°. The ‘systemic’ map pattern that tests show to be highly probable as designed and land surveyed - occurring about 1 in 100,000 random sets - shows considerable overlap with the Gudbrandalsleden map created by the Norwegian website, but variation and omission of important sites occur. The conclusion raises final questions about the value of this real, close-map information to the modern ‘pilgrim’, and to more academic historians and archaeologists. Can today’s path experience be heightened by the creation of a more holistic and symbolic concept of modern Norwegian landscape, this is considered together with insights into how historically such a concept may have moderated civil conflict and integrated an imported book-based religion with ancient Norse ritual practice

    MUC13 Enhances Colorectal Cancer Metastasis

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    Colorectal cancer (CRC) is one of the most prevalent cancer worldwide with a 5% lifetime incidence in developed countries. It is third most common cause of cancer related death in the United States and the second deadliest when men and women are combined. Encouragingly due to changes in dietary lifestyle, screening colonoscopy, and advancement in treatments the mortality has decreased in recent years. Most sporadic CRCs develop from polyploid adenomas and are preceded by intramucosal carcinomas (stage 0), which can progress into more malignant forms. This developmental process is known as the adenoma-carcinoma sequence. Early detection and endoscopic removal are crucial for CRC management. The overall 5-year survival of CRC jumps noticeably from 66% to 91% if it can be diagnosed and treated at early stages but drops down to 14% when the disease has metastasized. Metastasis is the cause of 90% of all cancer related deaths, which necessitates the need to understand the mechanisms regulating different progression steps. Metastasis is a complex and multistep process, whereby cancer cells leave the primary tumor and colonize in new tissues. However, only about 0.02% of tumor cells that detach from the primary tumor are successful in forming a metastatic lesion. After intravasation, anchorage independent survival (Anoikis resistance) of primary tumor cell is one of the key steps in metastasis. The mucin MUC13 when aberrantly overexpressed in cancer has been found to lead to poor outcomes in Pancreatic, Ovarian, Liver, and Colorectal cancer. When overexpressed in these cancers MUC13 has been shown to increase the oncogenic activity and survival of cancer cells. The oncogenic nature of MUC13 indicates a possible role in the development of Anoikis resistance and CRC metastasis. To understand the mechanism behind Anoikis resistance we developed and optimized an Anoikis induction model using the low adhesion poly hema coated cell culture dishes. Two isogenic cell lines SW480 (primary tumor site) and SW620 (metastatic tumor site) were used for this study. In our initial experiments SW620 demonstrated less cell death compared to SW480 during Anoikis induction. High MUC13 expression was observed in SW620 between 24-36 hours compared at 0 hours. SW620 further showed an increase in the expression of anti-apoptotic protein Bcl2 also. Overexpression of MUC13 in SW480 (SW480+MUC13) cells increased oncogenic phenotype such as invasion, migration, proliferation, and colony size as compared to SW480+Vector control cells. Downregulation of MUC13 in SW620 cells resulted in decreased oncogenic traits. The role of MUC13 in Anoikis resistance was further investigated in the overexpression and knockdown cell lines. When overexpressing MUC13 in SW480 cells we found increased survival compared to SW480+Vector cells. Bcl2 expression increased while Cleaved-Caspase 3 showed decreased expression in SW480+MUC13 compared to SW480+Vector cells. Increased MUC13 expression also increased the metastatic potential of SW480 cells in mice. After 36 hours of Anoikis induction and then injection into mice through the tail vein, MUC13 mice had an increased tumor burden compared to Vector mice, with METs forming in the liver, kidneys, and lungs. This would indicate that MUC13 plays a larger part in CRC metastasis and specific in the development of Anoikis resistance. To understand the mechanism involving MUC13 in Anoikis resistance, we studied kinases after Anoikis induction in the cell lines, followed by quantitative proteomics. We were able to find changes in transcription factor YAP1 and YAP1 and ÎČ-catenin, which are known to play vital roles in cellular development. In recent studies YAP1 and ÎČ-catenin have been shown to form a complex that promotes tumor cell survival and increased tumorigenesis. High MUC13 expression between 24-36hrs was observed, leading to an increase in nuclear localization of the known survival complex YAP1/ÎČ-catenin. Further in-vitro analysis indicated that MUC13 plays a vital role through direct cooperation with YAP1 and ÎČ-catenin, and together with increased nuclear localization of YAP1/MUC13 and ÎČ-catenin/MUC13 complexes, results in increase expression of pro-survival genes. This relationship was further examined and validated in an in-vivo mouse model, in which high MUC13 expression led to increased YAP1 and ÎČ-catenin expression and tumorigenesis. A correlation was further observed between MUC13 and YAP1 expression in human CRC patient tissue samples with high expression in tumor tissues compared to NAT and increased nuclear localization with elevated expression for both MUC13 and YAP1. The novel interaction between YAP1 and MUC13 defines a new mechanism in which cells develop Anoikis resistance in CRC. Genetic variations in genes are a well-known aspect of most diseases. This is especially true for cancer. Genetic variations in mucins such as MUC1 and MUC5AC have been found to increase the risk of stomach cancer and certain Allele mutations nearly doubling that risk in. We investigated if MUC13 had any genetic variants and found 5 different splice variants. Three of those splice variants were found to be non-coding. We then investigated the two protein coding variants consisted of a 512aa (Long form) and 187aa (Short form). We found that MUC13-LF was responsible for generating the oncogenic phenotype associated with adherent MUC13 expression. MUC13-SF however, showed a decrease in migration and invasion when overexpressed in MUC13 null cell lines. These studies suggest an oncogenic function of MUC13 in CRC via influencing multiple signaling pathways however, its role in cancer metastasis is remains elusive. In this study, we discovered how MUC13 facilitates metastasis after dissemination of tumor cells from the primary tumor site through influencing interaction and nuclear translocation of YAP1 and ÎČ-catenin followed by the expression of their downstream pro-survival and metastasis genes. After escaping from the primary tumor this MUC13 driven molecular mechanism provides a crucial survival advantage to anchorage independent circulating tumor cells, leading to successful and extravasation and homing new distant site for cancer metastasis. The interaction between YAP1 and MUC13 provides a new therapeutic in the prevention of metastasis that in combination with current chemotherapy could limit the tumor to its primary site

    The Effect of Low Sodium Diet Education in the Prevention of Hospital Readmission for Heart Failure Patients

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    Rate of readmission among hospitalized heart failure (HF) patients is used as an indicator of quality and efficiency of healthcare. A low sodium diet is a component of the accepted treatment for HF. Instruction by dietitians may help reduce dietary sodium without negatively affecting quality of life. The effect of low sodium diet education on hospital readmission within 30 and 45 days of discharge for HF patients (N=52) was conducted. Chi-square analysis determined education did not significantly affect remittance within 30 (P=.143) or 45 days (P=.474). Patients readmitted within 30 days were older (P=.005). Men were more likely to be readmitted than women within 30 (P=.021) and 45 days (P=.019). Higher NT-proBNP levels were observed in individuals readmitted within 30 (P=.011) and 45 days (P=.010). Low sodium diet education did not affect readmission but older age, male sex, and higher NT-proBNP values increased the rate of readmission

    From Paintings to Power: The meaning of the Warrior Flag twenty years after Oka

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    As Indigenous peoples we have found it necessary both to react to and to differentiate ourselves from the beliefs, values and practices that have been imposed upon us through colonization. To make our resistance effective, we sometimes use the tools of the dominant society. The Unity Flag in the incarnation that is commonly known as the ‘Mohawk Warrior Flag’ is one example of this phenomenon. Flown all over the world, it serves as a symbol for the unity of Indigenous peoples, illuminating our discordant relationship with a world that remains dominated by beliefs and values that are alien to us. This paper will introduce a Kanienkehaka perspective on the Flag, reconstructing its symbols and history and illustrating how it carries the message of unity-in-resistance for the various peoples who have turned to it for support in their ongoing struggles with colonialism. En tant que peuples Autochtones nous avons trouvĂ© nĂ©cessaire de rĂ©agir et de se diffĂ©rencier des croyances, valeurs et pratiques qui nous Ă©taient imposĂ©es par la colonisation. Pour rendre notre rĂ©sistance efficace, nous utilisons parfois les outils de la sociĂ©tĂ© dominante. Le Drapeau de l’UnitĂ© dans l’incarnation, plus souvent connu sous le nom de « Drapeau du Guerrier Mohawk » est un exemple de ce phĂ©nomĂšne. Flottant partout dans le monde, il sert de symbole de l’unitĂ© des peoples autochtones, mettant en lumiĂšre nos relations discordantes avec un monde qui reste dominĂ© par des croyances et valeurs qui nous sont Ă©trangĂšres. Cet article introduit une perspective Kanienkehaka sur le Drapeau, reconstruisant ses symboles et son histoire et illustrant la façon dont le Drapeau porte le message de l’unitĂ©-en-rĂ©sistance pour les divers peuples qui se sont tournĂ©s vers lui comme soutien dans leurs luttes en cours contre le colonialisme

    Illumi Nation: Indigenous World View Through Relating of Story

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    Look around you through the Indigenized eyes of a First Nations worldview. Is something holding you back from being able to see through an Indigenous lens? This inquiry is to better understand the complexity in relating of knowledge through the traditional First Nations educational construct of vocational and experiential learning. Integrative education is meant to combine vocational training and experiential learning to create immersive environments for learners to become active participants. To better understand First Nations culture you need to create a shared experience. The main inquiry of this paper is: What are the dynamics of story? What can be used to create impact in the re-telling or relating of story, imprinting a Participant with Indigenous worldview

    Recent advances on the role of long non-coding RNAs in Alzheimer’s disease

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    Dementia is a progressive cognitive impairment that affects the activities of daily living. Alzheimer’s disease (AD) is the most common form of the dementia worldwide accounting for 60–80% of all dementia cases. With an estimated cost exceeding $290 billion in the USA, understanding and development of future therapeutic strategies is vital. In this perspective, we will be examining the current thinking of AD research and therapeutic strategies, while proposing a possible new direction for diagnosis, understanding, and treatment targets. Non-coding RNA accounts for the largest population of the human transcriptome. Long noncoding RNA (lncRNA) is a recent molecule of interest in the biomedical research which is non protein coding and is of length greater than 200 nucleotides. LncRNAs have been shown to play diverse roles within the cells such as posttranscriptional and posttranslational regulation, chromatin modulation, and protein complex organization. Given the flexible and diverse role in disease pathophysiology, lncRNAs may serve as novel therapeutic targets for diagnosis and treatment. Evidently, recent studies showed that dysregulation of lncRNA influences the clinical course of tumorigenesis, neurological disorders, cardiovascular disease, diabetes, and acquired immunodeficiency syndrome (Kazimierczyk et al., 2020). This indicates that lncRNA can provide a unique avenue of research and possible therapeutic targets in AD

    Plasmid Midiprep: A Method to Purify Plasmids for Recombinant DNA Studies

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    A fundamental aspect of molecular biology involves exploring the properties and functions of specific genes. The rise of recombinant DNA technology has vastly improved and simplified functional studies by allowing scientists to isolate specific genes using restriction enzymes and plasmids providing greater precision. Plasmids take great significance in downstream studies, which is why quantity and quality of the plasmids purified is important. In this study, we isolated and purified recombinant plasmids in microgram quantities to confirm the yield, quantity, and quality using spectral and size fractionation methods. We also assessed the plasmids for application in downstream studies. We found the plasmids that were isolated with a good yield ranging from 1-1.5 mg/ml. The high yield and purity suggest the Promega Midiprep kit is effective in producing high quality plasmids. The size of the plasmids was assessed using gel electrophoresis, and a transient transfection into mammalian cells confirmed their expression through fluorescence

    Biophysical Changes Caused by Altered MUC13 Expression in Pancreatic Cancer Cells

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    Background Pancreatic cancer is one of the most lethal cancers in the United States. This is partly due to the difficulty in early detection of this disease as well as poor therapeutic responses to currently available regimens. Our previous reports suggest that mucin 13 (MUC13, a transmembrane mucin common to gastrointestinal cells) is aberrantly expressed in this disease state, and has been implicated with a worsened prognosis and an enhanced metastatic potential in PanCa. However, there is virtually no information currently to describe the biophysical ramifications of this protein. Methods To demonstrate the biophysical effect of MUC13 in PanCa, we generated overexpressing and knockdown model cell lines for PanCa and subsequently subjected them to various biophysical experiments using atomic force microscopy (AFM) and cellular aggregation studies. Results AFM-based nanoindentation data showed significant biophysical effects with MUC13 modulation in on PanCa cells. The overexpression of MUC13 in Panc-1 cells led to an expected decrease in modulus, and a corresponding decrease in adhesion. With MUC13 knockdown, HPAF-II cells exhibited an increased modulus and adhesion. These results were confirmed with altered cell-cell adhesion as seen with aggregation assays. Conclusions MUC13 led to significant biophysical changes in PanCa cells and which exhibited characteristic phenotypic changes in cells demonstrated in previous work from our lab. This work gives insight into the use of biophysical measurements that could be used to help diagnose or monitor cancers as well as determine the effects of genetic alterations at a mechanical level

    Long non-coding RNA (lncRNA) as a new biomarker for hepatocellular carcinoma (HCC) drug resistance

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    Background: Hepatocellular carcinoma (HCC) is the 4th leading cause of cancer-related deaths worldwide and the 6th most common cancer worldwide. When HCC progresses to advanced stages, drug resistance becomes a major hurdle and leaves clinicians with limited therapeutic options. Long non-coding RNAs (lncRNAs) have shown to promote drug resistance in various cancers. The goal of our research is to explain the molecular role of lncRNAs in HCC drug resistance and compile a comprehensive list of studied lncRNAs involved in HCC drug resistance. Methods: To compile a list of lncRNA involved in HCC drug resistance we performed an advanced search on Lnc2Cancer, a database that provides experimentally supported associations between lncRNA and human cancer, using the following filters: “hepatocellular carcinoma”, “drug clinical application”, “lncRNA”, “all biological function”, and “all regulatory mechanism.” Results: We identified 12 lncRNAs that are involved in HCC drug resistance: Metastasis Associated Lung Adenocarcinoma Transcript 1 (MALAT 1), Keap1 Regulation-Associated LncRNA (KRAL), Transcribed Ultra-conserved Region 338 (TUC338), Long intergenic non-protein coding RNA, regulator of reprogramming (linc-ROR), Linc-VLDLR, Highly Upregulated in Liver Cancer (HULC), HCC associated long non-coding RNA (HANR), LncRNA Regulator of AKT Signaling Associated with HCC and RCC (LncARSR), Taurine up-regulated gene 1 (TUG1), H19, NR2F1 Antisense RNA 1 (NR2F1-AS1), and HOX Transcript Antisense RNA (HOTAIR). Conclusions: Our review demonstrates that lncRNAs involved in HCC drug resistance participate in various mechanistic categories such as autophagy, epithelial-mesenchymal transition, and efflux pump upregulation. There is a need to uncover novel lncRNA biomarkers for both the early detection of HCC and to create drug strategies for clinicians when predicting chemoresistance

    Characterization of POTE-2 Expression in Hepatocellular Carcinoma Cell Lines

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    Hepatocellular carcinoma is the most common cancer of the liver and is the third leading cause of cancer deaths globally. Due to the limited serum biomarkers, detection of hepatocellular carcinoma usually occurs in the later, metastasized stages of the disease where the 5-year survival rate falls to around 3%. The identification of early diagnostic biomarkers for hepatocellular carcinoma is necessary to provide both improved prognostic outcomes and make treatment options dependent on liver dysfunction, such as resection and liver transplantation, available to patients. This study performed real-time polymerase chain reaction and western blot analysis for four hepatocellular carcinoma cell lines (SKHEP1, HEP3B, C3A, and HEPG2) to observe the expression of POTE-2 mRNA and protein. The data demonstrates significant overexpression of POTE-2 in HCC cell lines, indicating these HCC cell lines to be an ideal in-vitro model to study POTE-2 function in hepatocellular carcinoma
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