1,690 research outputs found

    Interleukin-1β sequesters hypoxia inducible factor 2α to the primary cilium.

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    BACKGROUND: The primary cilium coordinates signalling in development, health and disease. Previously we have shown that the cilium is essential for the anabolic response to loading and the inflammatory response to interleukin-1β (IL-1β). We have also shown the primary cilium elongates in response to IL-1β exposure. Both anabolic phenotype and inflammatory pathology are proposed to be dependent on hypoxia-inducible factor 2 alpha (HIF-2α). The present study tests the hypothesis that an association exists between the primary cilium and HIFs in inflammatory signalling. RESULTS: Here we show, in articular chondrocytes, that IL-1β-induces primary cilia elongation with alterations to cilia trafficking of arl13b. This elongation is associated with a transient increase in HIF-2α expression and accumulation in the primary cilium. Prolyl hydroxylase inhibition results in primary cilia elongation also associated with accumulation of HIF-2α in the ciliary base and axoneme. This recruitment and the associated cilia elongation is not inhibited by blockade of HIFα transcription activity or rescue of basal HIF-2α expression. Hypomorphic mutation to intraflagellar transport protein IFT88 results in limited ciliogenesis. This is associated with increased HIF-2α expression and inhibited response to prolyl hydroxylase inhibition. CONCLUSIONS: These findings suggest that ciliary sequestration of HIF-2α provides negative regulation of HIF-2α expression and potentially activity. This study indicates, for the first time, that the primary cilium regulates HIF signalling during inflammation

    The forgotten first: John MacCormick's 'Dùn-Àluinn'

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    The first Gaelic novel, John MacCormick's Dùn-Àluinn, no an t-Oighre 'na Dhìobarach, was serialised in the People's Journal in 1910 before being published in its entirety in 1912. Within a year of the publication of Dùn-Àluinn as a novel the second Gaelic novel, Angus Robertson's An t-Ogha Mòr, appeared in print, underlining the renaissance which Gaelic literature was experiencing. Both novels, while remarked upon by contemporaries and by general studies of Gaelic literature, have been all but ignored to date, with no criticism or analysis of either having been published. The main aim of this article is to offer some general comments about MacCormick's Dùn-Àluinn and thus to open up both the novel and indeed other early twentieth-century Gaelic writers and their work to further scrutiny. Consideration will be given to the author himself, the contemporary Gaelic literary scene and finally some of the more interesting aspects of the novel itself

    Lipid and cholesterol composition of the longissimus muscle from Angus, Brahman, and Romosinuano

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    Lipid and cholesterol composition of red meat has been extensively studied for years, especially on genetic variation. However, Romosinuano cattle were recently adopted into America and its lipid composition remains unclear. An investigation is needed to compare this breed to other well-known breeds of cattle in the U.S. Study in chapter II was to compare the fatty acid (FA) composition of the longissimus muscle (LM) from three divergent breeds of cattle: Angus (AN, n = 5), Brahman (BR, n = 4), and Romosinuano (RM, n = 9) regarding intramuscular (i.m.) fat content. Cattle were blocked by breed and fed the same identical commercial finishing diets in a commercial feedlot prior to harvest. LM samples were collected from each carcass between 10th and 13th ribs, trimmed of external fat, frozen in liquid nitrogen, homogenized, and utilized for fat extraction using the modified Folch procedure. Extracted fat was analyzed using GLC with an HP-88 capillary column. FA composition was determined using both normalized percentage (%) to the total fatty acids in samples and gravimetric calculation (mg/g of fresh muscle tissue), in relation to degree of saturation, which was expressed by saturation index (ratio of saturated fatty acids to unsaturated fatty acids, SI). Crude fat determination showed that LM from AN purebred cattle had the highest amount of i.m. fat (7%, P < 0.001). Intramuscular fat of LM from AN contained higher percentage of total SFA (P = 0.003) whereas that from RM had higher percentage of total PUFA (P = 0.002). The percentage of total MUFA was the same among three breeds (P = 0.9). Unlike the normalized percentage, the gravimetric calculation, which was a measure of actual FA concentration in LM, revealed a significantly higher concentration of SFA (26.39 mg/g) and MUFA (26.70 mg/g) in LM from AN cattle as compared to BR and RM cattle (P < 0.001). Additionally, BR purebreds had the lowest PUFA concentration (1.63 mg/g, P = 0.009) in the LM although this difference in percentage of total fatty acids was not found to be statistically significant as compared to AN and RM (P = 0.088, P = 0.015, respectively). Regardless of breeds, the MUFA proportion was always highest (48.2%, P < 0.001) while PUFA was least contributory to FA composition (1.33 mg/g to 2.69 mg/g and 2.91% to 10.98%, P < 0.001). Beef LM fatty acid composition was also characterized by palmitic and oleic acids being the most abundant fatty acids (P < 0.001). These results suggested a genetic variation in FA synthesis and deposition among breeds that influenced both marbling content and its composition. In chapter II, the fatty acid (FA) composition of the longissimus muscle (LM) from crossbred cattle of Angus, Brahman, and Romosinuano were analyzed, again, in relation to intramuscular (i.m.) fat content to investigate the effects on crossbreeding on lipid composition. Using the same methods, which were used for purebred cattle, results from this study showed that no difference in i.m. fat content was found among crossbred cattle, which resulted in their very similar fatty acid compositions. However, small but significant higher percentage of palmitic acid was found in ANxBR cattle (P < 0.001), which suggested a genetic variation of fatty acid synthesis. As compared to our previous study on purebred cattle, the results from this study indicated significant effect of crossbreeding, by which Angus cattle was most influenced. This study also confirmed the importance of muscle fatness, which is also genetically caused, in determining fatty acid composition. In chapter IV, cholesterol composition became the subject, in which the study was focused on development of a highly accurate and repeatable method for cholesterol quantification in meat samples and its application to evaluate the differences in cholesterol content of longissimus muscles (LM) from Angus (AN, n=5), Brahman (BR, n=4), and Romosinuano (RM, n=9) purebreds. Validation of this method was performed using SRM1546 sample, a meat homogenate from the National Institute of Standard and Technology (NIST), and three different LM test samples. The results indicated that the modified method was highly efficient and accurate with more than 95% cholesterol recovered. The method was also found to be repeatable with an average coefficient of variation of 3.12%. This modification reduced 90% of chemicals used and eliminated time-consuming steps that hindered high throughput application of the traditional method. Application of this method for cholesterol quantification of LM samples revealed differences among the three breeds evaluated. The Angus LM samples with higher fat content (50% higher than Brahman and Romosinuano) which was associated with significantly higher cholesterol concentration (70.25%, P=0.007). Interestingly, the cholesterol concentration was found to relate to fatness of muscle (r=0.90,

    W. G. Sebald’s theology: A heretic mounts the pulpit

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    This essay traces a number of ways in which theological matters mark the work of the German author and critic W. G. Sebald (1944–2001). It concentrates on Sebald’s relatively neglected critical writing belonging to the first two decades of his career (c. 1969–1989). Founded on original archival research and a close examination of Sebald’s religious background and reading, this essay argues that, contrary to the author’s disavowals and his critics’ disinterest, theological concerns determined his own critical perspective in far-reaching ways. This essay demonstrates how Sebald considered humankind to be essentially guilt-laden, with severely limited hopes for salvation. This view gave the impetus to, and prescribed the limits of, Sebald’s critical mode, which combines the wilful eccentricity of the heretic with the moral fervour of the preacher

    Claude Thompson

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    posted: SaltWire, Jun. 16, 2021; funeral arrangements by G. W. Giffin Funeral Hom

    Mrs. Mary G. (MacPherson) Thompson

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    &quot;Gidget&quot

    Assessing enteric methane emissions from Nellore and Angus-Nellore crossbred cattle in a tropical, intensive beef cattle production system.

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    Crossbreeding has been used to improve performance in beef cattle; however, the effects of breed composition on methane production, yield and intensity from cattle in a tropical intensive system remain unknown. To assess the impact of breed composition on enteric methane emissions, Nellore (NE; yr 1: BW = 171.5 ± 19.4 kg; n = 10; yr 2: BW = 215.8 ± 32.3 kg, n = 25) and Angus-Nellore crossbred (AN; yr 1: BW = 214.2 ± 26.4 kg, n = 10; yr 2: BW = 242.5 ± 32.2 kg, n = 25) were compared. At trial onset, 10 mo old steers grazed Megathyrsus maximus ?Mombaça? in the grazing period (GP) and then were finished in a feedlot (FL) (35:65% corn silage:concentrate diet). Steers (n = 8) from each breed composition were randomly selected in GP and FL to measure CH4 production using a sulfur hexafluoride technique and DMI using titanium dioxide. The NE produced 19% less CH4 than AN in GP (17.21 vs 21.17 kg, P 0.10). However, in FL, NE had greater CH4 intensity (CH4/ADG) compared to AN (122.76 vs 97.49 g/kg, P < 0.01). Furthermore, CH4/carcass weight was greater for NE than AN (0.079 vs 0.067 g/kg CW, P < 0.01). Breed composition did not influence CH4 yield (CH4/DMI) in either phase. The percentage CH4/GEI (Ym) for GP was higher for AN than NE (4.5 vs 3.8%), but lower than the IPCC recommended Ym of 6.5%. In FL, Ym was similar between breed composition (5.0%) and greater than the IPCC Ym of 3%. In our study the introduction of Angus into Nellore has potential to reduce CH4 intensity in tropical climates, resulting in less methane emission per kg beef produced.Publicado no Journal of Animal Science, v. 97, p. 380-381, 2019. Suppl. 3

    Spinning in the NAPLAN ether: 'Postscript on the control societies' and the seduction of education in Australia

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    This paper applies concepts Deleuze developed in his ‘Postscript on the Societies of Control’, especially those relating to modulatory power, dividuation and control, to aspects of Australian schooling to explore how this transition is manifesting itself. Two modulatory machines of assessment, NAPLAN and My Schools, are examined as a means to better understand how the disciplinary institution is changing as a result of modulation. This transition from discipline to modulation is visible in the declining importance of the disciplinary teacher/student relationship as a measure of the success of the educative process. The transition occurs through seduction because that which purports to measure classroom quality is in fact a serpent of modulation that produces simulacra of the disciplinary classroom. The effect is to sever what happens in the disciplinary space from its representations in a luminiferous ether that overlays the classroom

    That’s not for our kids: The strange death of philosophy and ethics in a low socioeconomic secondary school

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    This paper is a critical reflection on the teaching of the new Philosophy and Ethics course in a low socioeconomic context in Perth, Western Australia. It charts the successes and failures of the Philosophy and Ethics course, leading to the eventual demise of the subject at the end of 2010. We frame this reflection within Deleuzean notions of geophilosophy to advocate for a Philosophy and Ethics that is informed by nomadic thought as this offers potential for students to become innovative and creative of their selves – the critical freedom we see as potentially transformative for contemporary society. We see the strange death as being influenced by many factors, but that it is best considered as a ‘missed opportunity’ because it has so much potential to be transformative of student subjectivities in schools. We see that this critical reflection could be invaluable in a reconsideration of the scope and focus of the subject often viewed as elitist and impractical

    Calcium signaling genes in association with altitude-induced pulmonary hypertension in Angus cattle

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    2019 Fall.Includes bibliographical references.This research used multi-omics technology (i.e., RNA-seq, qPCR for gene expression, SNP discovery and validation) to understand the influence of a particular subset genes on altitude-induced pulmonary hypertension susceptibility in Angus cattle. Three research aims were established to test the hypothesis that calcium-related genes may be associated with pulmonary hypertension in beef cattle. Data and samples utilized for the research came from the Colorado State University Beef Improvement Center Angus herd managed at 2,150 m of altitude. Transcriptome data from 6 tissues and 14 hypertensive and normotensive Angus steers were utilized for differential expression and pathway analyses. The objectives of the first aim were to: 1) to estimate and identify differentially expressed genes from RNA-Seq and pathway analyses, and 2) select putative candidate genes to analyze with qPCR (gene expression level). The largest number of DE genes was revealed in aorta (n = 631) and right ventricle (n = 2,183) samples. Top canonical pathways related to calcium signaling or utilization included: synaptic long-term depression, signaling by Rho family GTPases, and oxidative phosphorylation. Genes regulating calcium availability and utilization were expressed differently (log2 fold change > 0.589, < -0.589; P < 0.05) in Angus cattle with and without pulmonary hypertension. Isolated RNA from cardiac muscle (n = 9) and control muscle (n = 2) tissues from hypertensive and normotensive Angus steers were utilized to estimate gene expression using quantitative reverse transcription PCR in the candidate genes from Chapter 3. The objectives of this chapter were: 1) to establish the most appropriate reference genes in cardiac muscle tissues, and 2) to estimate and validated relative gene expression of calcium-related genes in cardiac muscle tissues using qPCR methods. Differences (P < 0.0055) among hypertensive and normotensive steers were estimated for right papillary muscle and right cardiac ventricle tissues (top, middle, and bottom) in candidate genes: ASIC2, EDN1, NOX4, PLA2G4A, RCAN1, and THBS4. Results of the current study validate the expression differences previously established of genes that regulate the availability and utilization of calcium with PH status in Angus steers at high altitude. Variant detection and association analyses were completed with 2 sets of available -omics data to identify opportunities for development of selection tools for reduced susceptibility to PH. The objectives of the third aim were to: 1) detect single nucleotide polymorphisms (SNP) in the transcriptome of 6 tissues, and 2) identify functional consequences of those variants associated with validated candidate genes from qPCR analyses. Pooled Angus sample analysis revealed 68 SNP in the 6 candidate genes: ASIC2, EDN1, NOX4, PLA2G4A, RCAN1, and THBS4. Thirty-eight SNP were revealed in the hypertensive group and 8 SNP in the normotensive steer group. Ten of the 68 identified SNP are utilized on large density commercially available bovine SNP chips (Illumina BovineHD BeadChip; GeneSeek Genomic Profiler HD; GeneSeek Genomic Profiler HDv2; Affymetrix Axiom Bovine). Analysis of transcriptome data identified SNP within genes regulating calcium availability and utilization, enhancing our understanding of sequence polymorphisms that may be involved in regulating pulmonary hypertension in Angus cattle raised at high altitude. These SNP are available for additional validation and potential use in genetic improvement programs
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