1,720,979 research outputs found
A study of zinc transporter 1 and its role in Type 3 Haemochromatosis
Get PDFHereditary haemochromatosis is an autosomal recessive disorder of iron metabolism, characterised by increased iron absorption and progressive iron accumulation particularly in the liver. It has been shown that hepatocytes can acquire iron in two forms; transferrin-bound iron (TBI) and non-transferrin-bound iron (NTBI)1. Known transporters of NTBI into the cell include DMT1 and ZIP14, and FPN is the only transporter known to export iron.
The aims of this study were to characterize the zinc transporter, ZnT-1 and determine whether it is involved in iron transport, specifically as an exporter.
There was a decrease in mRNA expression of the short untranslated isoform of ZnT-1 in double mutant (Hfe -/- and TfR2 Y245X) mouse liver, a trend also seen in TfR1 and Hamp. The long untranslated isoform, however, was significantly higher in the iron-deficient mice as was expression of TfR1 and Ferroportin. Iron and zinc efflux was measured in cells over-expressing ZnT-1 and control cells. There was no difference between over-expressed and control cells in iron efflux. However, at 60 min, over-expressed cells had significantly more zinc efflux than control cells. More zinc than iron was released from the cell.
The results of this study do not support the hypotheses that (i) ZnT-1 reduces intracellular cytoplasmic iron concentration by promoting efflux and 2 ZnT-1 is down-regulated in iron-loaded cells
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Development of a mass spectrometry diagnostic assay to monitor hepcidin levels in hemochromatosis patients
Get PDFHepcidin has been identified as the principle regulatory peptide essential for iron homeostasis. Expression of this cysteine-rich peptide is up-regulated by inflammation and iron overload, whereas hypoxia, iron deficiency and erythropoiesis suppress hepcidin expression. The quantitative analysis of hepcidin in bodily fluids will provide an insight into the pathogenesis of disorders of iron metabolism such as hereditary hemochromatosis.
A mass spectrometry-based approach was taken to detect and quantify urinary hepcidin as urine is readily available and collection of this sample type is non-invasive. Samples were first purified using micro solid phase extraction (μSPE), followed by matrix assisted laser desorption/ionization-orthogonal-time-of-flight mass spectrometry (MALDI-TOF-MS) with inclusion of an internal standard for the quantitative analysis of unlabelled urinary hepcidin.
Monoisotopic resolution of hepcidin-25 was observed with the MALDI-TOF-MS and extraction recovery of more than 70% was achieved. Spot-to-spot variations of less than 3.5% RSD and intra- and inter-day precision of less than 9.5% RSD was observed.
In our study, average hepcidin-25 levels of 1.7 nmol/mmol creatinine were observed in healthy subjects, compared to an average of 1.1 nmol hepcidin-25/mmol creatinine in hemochromatosis patients. In one of the patients, the hepcidin level was below the detection limit (1.25 nM). From the stability experiments of hepcidin-25, it is recommended that urine samples be stored at -80oC and undergo minimal freeze-thaw cycles. It is also advised that extraction be carried out within 3 hours of thawing.
Preliminary analysis using LC-ESI-IT-MS showed multiple charge states of hepcidin-25. However, a variation of less than 5% in hepcidin-25 concentration was observed when the same sample was analyzed with both LC-MS and MALDI-TOF-MS, and thus they can be used to counter-validate each other.
In summary, a validated method has been developed for the quantification of unlabelled urinary hepcidin-25 which can be used to investigate the levels of hepcidin-25 in iron-related disorders
The effects of dietary iron concentration on colonic inflammation
Get PDFColorectal cancer (CRC) is highly prevalent in Western society with more than 14,000 diagnoses and 4,000 deaths in Australia annually. CRC is caused by both genetic and environmental risk factors, with a number of population studies linking high dietary iron and elevated body iron stores with increased CRC risk. The iron overload disorder, hereditary haemochromatosis, is associated with increased risk of CRC, as are inflammatory bowel diseases including ulcerative colitis and Crohn’s disease. A better understanding of the pathogenesis of CRC is required to develop improved medical therapies for individuals most at risk, such as those with hereditary haemochromatosis or inflammatory bowel diseases. Improved disease prevention and management is also important from a public health perspective, and will potentially decrease the incidence and mortality of this malignancy.
In this study, a mouse model of inflammation-associated CRC was used to evaluate the effects of increasing dietary iron concentrations on tissue iron loading and colonic inflammation. Two strains of mice (C57BL/6 and FVB/N) were evaluated to compare their responses to increased dietary iron levels.
The results demonstrated that increased dietary iron increased colonic and liver iron deposition and colonic inflammation via an IL-6/STAT3 signalling pathway in a dose-dependent manner. Both colitis scores and plasma IL-6 levels were positively correlated with increased liver iron levels. Both strains of mice showed similar trends in response to increased dietary iron concentration, though the magnitude of the responses varied between strains.
In conclusion, the results from this study showed that increasing dietary iron concentrations exacerbate colonic inflammation, suggesting that high dietary iron consumption may be linked to an increased risk of CRC
The effects of iron on intestinal inflammation
No full textInflammatory bowel diseases (IBD), including Crohn’s disease and Ulcerative Colitis, are types of chronic intestinal inflammation, involves intestinal wall injury and edema which in the long term may lead to the formation of polyps and colorectal cancer. Iron supplements are usually given to IBD patients experiencing anaemia due to chronic blood loss and ineffective erythropoiesis. Iron treatment has been shown to exacerbate intestinal inflammation in animal models of IBD. In this study, the effect of dietary iron on intestinal inflammation was explored using wild type mice fed either a high or control iron diet, and HFE knockout mice (mouse model of iron overload) fed a control iron diet was treated with azoxymethane (AOM)/dextran sodium sulphate (DSS) to induce colonic inflammation. The HFE knockout mice and wild type mice fed high dietary iron had iron loading in the liver similar to that seen in the iron overload disease hereditary haemochromatosis. These animals also had elevated serum iron levels and transferrin saturation. The wild type mice fed a high iron diet treated with AOM/DSS had severe colonic inflammation. The severity of colonic inflammation decreased in wild type mice fed a controlled iron diet and was further reduced in HFE knockout mice fed a controlled iron diet. From this study, it can be concluded that high dietary iron exacerbates intestinal inflammation. High dietary iron increases colonic and liver iron stores and plasma iron parameters. Intestinal inflammation increased secretion of proinflammatory cytokines and liver iron levels while reducing colonic and plasma iron levels. However, the iron accumulation due to a mutation in the Hfe gene had a protective effect against development of colonic inflammation. This is likely to be an indirect Hfe effect on iron uptake in the duodenum or direct Hfe effect on cytokine release in the colon
Variations on the Author
Get PDF“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Get PDFWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Get PDFWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
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