1,750 research outputs found

    Making ways for 'better education': Placing the Shenzhen-Hong Kong mobility industry

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    Tens of thousands of children living on Mainland China cross the border between Shenzhen and Hong Kong for a ‘better education’ every day. A well-oiled industry is in place to manage, facilitate and control this education mobility field. It involves schools, diverse businesses and non-governmental organisations that, in articulation with the Chinese and Hong Kong states, stimulate and regulate the movement of people, materialities, ideas and practices. Drawing on our fieldwork and media analysis, this paper unpacks the transurban mobility industry to illustrate the role of the various players and how they work in conjunction to facilitate cross-border schooling, especially among the very young children. We map out and visualise with photos the workings of the schools, buses, escorts, tutoring centres, day care and boarding houses. We show how the mobility industry, intersecting with other business networks and mobility systems, links Shenzhen and Hong Kong, taking and making places in these cities, especially in the border region. Our paper illustrates the role of this mobility industry in the making of the political-economy and socio-culture of the border area, which constantly connects, divides and redefines the two cities and regions it bridges. We end with some reflections on the implications of the recent political challenges and COVID-19 pandemic on this cross-border education mobility system

    Protein turnover measurement using selected reaction monitoring-mass spectrometry (SRM-MS)

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    Protein turnover represents an important mechanism in the functioning of cells, with deregulated synthesis and degradation of proteins implicated in many diseased states. Therefore, proteomics strategies to measure turnover rates with high confidence are of vital importance to understanding many biological processes. In this study, the more widely used approach of non-targeted precursor ion signal intensity (MS1) quantification is compared with selected reaction monitoring (SRM), a data acquisition strategy that records data for specific peptides, to determine if improved quantitative data would be obtained using a targeted quantification approach. Using mouse liver as a model system, turnover measurement of four tricarboxylic acid cycle proteins was performed using both MS1 and SRM quantification strategies. SRM outperformed MS1 in terms of sensitivity and selectivity of measurement, allowing more confident determination of protein turnover rates. SRM data are acquired using cheaper and more widely available tandem quadrupole mass spectrometers, making the approach accessible to a larger number of researchers than MS1 quantification, which is best performed on high mass resolution instruments. SRM acquisition is ideally suited to focused studies where the turnover of tens of proteins is measured, making it applicable in determining the dynamics of proteins complexes and complete metabolic pathways

    Using cage ladders as a handling device reduces aversion and anxiety in laboratory mice, similar to tunnel handling

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    Summary Handling laboratory animals for husbandry and other procedures can be an important source of anxiety and stress, compromising animal welfare as well as the reliability of research that is sensitive to background stressors. Studies have revealed that picking up laboratory mice by the tail induces aversion, anxiety, physiological stress and depression-like behaviour, but such negative responses can be reduced substantially by using a handling tunnel that mice enter readily with minimal familiarisation. It has not been tested whether anxiety and aversion can be reduced similarly by using other objects to lift up mice from their home cage. Here we compared the willingness of C57BL/6NRj mice to interact voluntarily with their handler after being picked up either on a plastic ladder present in the home cage, or inside a familiar tunnel, or lifted by the base of the tail and then returned to the home cage. We also tested anxiety in open field and elevated plus maze tests once animals were familiarised with their assigned handling method. While mice picked up briefly by the tail were unwilling to interact with the hand that picked them up, mice picked up by ladder or tunnel readily approached, climbed on or entered these devices, with no significant difference in time spent with ladder or tunnel. Anxiety in an unfamiliar open field was reduced to a similar extent in ladder and tunnel handled mice compared with those picked up by the tail. Mice handled by tunnel also showed reduced anxiety in an elevated plus maze compared to those handled by tail, while ladder handling resulted in an intermediate response. Our study shows that, like tunnels, using home cage ladders to pick up mice reduces anxiety and avoids the aversion that is induced by picking up mice by their tails. We discuss the potential practicality of using ladders and tunnels to handle mice in different contexts

    The White Dwarf Luminosity Functions from the Pan-STARRS 1 3π Steradian Survey

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    A large sample of white dwarfs is selected by both proper motion and colours from the Pan-STARRS 1 3{\pi} Steradian Survey Processing Version 2 to construct the White Dwarf Luminosity Functions of the discs and halo in the solar neighbourhood. Four-parameter astrometric solutions were recomputed from the epoch data. The generalised maximum volume method is then used to calculate the density of the populations. After removal of crowded areas near the Galactic plane and centre, the final sky area used by this work is 7.833 sr, which is 83% of the 3{\pi} sky and 62% of the whole sky. By dividing the sky using Voronoi tessellation, photometric and astrometric uncertainties are recomputed at each step of the integration to improve the accuracy of the maximum volume. Interstellar reddening is considered throughout the work. We find a disc-to-halo white dwarf ratio of about 100

    Frequency of KCNC3 DNA Variants as Causes of Spinocerebellar Ataxia 13 (SCA13)

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    Gain-of function or dominant-negative mutations in the voltage-gated potassium channel KCNC3 (Kv3.3) were recently identified as a cause of autosomal dominant spinocerebellar ataxia. Our objective was to describe the frequency of mutations associated with KCNC3 in a large cohort of index patients with sporadic or familial ataxia presenting to three US ataxia clinics at academic medical centers.DNA sequence analysis of the coding region of the KCNC3 gene was performed in 327 index cases with ataxia. Analysis of channel function was performed by expression of DNA variants in Xenopus oocytes.Sequence analysis revealed two non-synonymous substitutions in exon 2 and five intronic changes, which were not predicted to alter splicing. We identified another pedigree with the p.Arg423His mutation in the highly conserved S4 domain of this channel. This family had an early-onset of disease and associated seizures in one individual. The second coding change, p.Gly263Asp, subtly altered biophysical properties of the channel, but was unlikely to be disease-associated as it occurred in an individual with an expansion of the CAG repeat in the CACNA1A calcium channel.Mutations in KCNC3 are a rare cause of spinocerebellar ataxia with a frequency of less than 1%. The p.Arg423His mutation is recurrent in different populations and associated with early onset. In contrast to previous p.Arg423His mutation carriers, we now observed seizures and mild mental retardation in one individual. This study confirms the wide phenotypic spectrum in SCA13

    Computational modelling of cancerous mutations in the EGFR/ERK signalling pathway

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    This article has been made available through the Brunel Open Access Publishing Fund - Copyright @ 2009 Orton et al.BACKGROUND: The Epidermal Growth Factor Receptor (EGFR) activated Extracellular-signal Regulated Kinase (ERK) pathway is a critical cell signalling pathway that relays the signal for a cell to proliferate from the plasma membrane to the nucleus. Deregulation of the EGFR/ERK pathway due to alterations affecting the expression or function of a number of pathway components has long been associated with numerous forms of cancer. Under normal conditions, Epidermal Growth Factor (EGF) stimulates a rapid but transient activation of ERK as the signal is rapidly shutdown. Whereas, under cancerous mutation conditions the ERK signal cannot be shutdown and is sustained resulting in the constitutive activation of ERK and continual cell proliferation. In this study, we have used computational modelling techniques to investigate what effects various cancerous alterations have on the signalling flow through the ERK pathway. RESULTS: We have generated a new model of the EGFR activated ERK pathway, which was verified by our own experimental data. We then altered our model to represent various cancerous situations such as Ras, B-Raf and EGFR mutations, as well as EGFR overexpression. Analysis of the models showed that different cancerous situations resulted in different signalling patterns through the ERK pathway, especially when compared to the normal EGF signal pattern. Our model predicts that cancerous EGFR mutation and overexpression signals almost exclusively via the Rap1 pathway, predicting that this pathway is the best target for drugs. Furthermore, our model also highlights the importance of receptor degradation in normal and cancerous EGFR signalling, and suggests that receptor degradation is a key difference between the signalling from the EGF and Nerve Growth Factor (NGF) receptors. CONCLUSION: Our results suggest that different routes to ERK activation are being utilised in different cancerous situations which therefore has interesting implications for drug selection strategies. We also conducted a comparison of the critical differences between signalling from different growth factor receptors (namely EGFR, mutated EGFR, NGF, and Insulin) with our results suggesting the difference between the systems are large scale and can be attributed to the presence/absence of entire pathways rather than subtle difference in individual rate constants between the systems.This work was funded by the Department of Trade and Industry (DTI), under their Bioscience Beacon project programme. AG was funded by an industrial PhD studentship from Scottish Enterprise and Cyclacel

    Ordering folate assays is no longer justified for investigation of anemias, in folic acid fortified countries

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    <p>Abstract</p> <p>Background</p> <p>Since 1998, in the countries where there is mandatory fortification of grain products with folic acid, folate deficiency has become very rare. Consequently, we decided to find out whether there is any justification for ordering folate assays for investigation of anemias.</p> <p>Methods</p> <p>We reviewed serum folate (SF) and red cell folate (RF) data at two teaching hospitals in Canada. At the Health Sciences Centre (HSC) the folate data for the year 2001 were analyzed and the medical records of those with low SF or low RF were reviewed. At St. Boniface General Hospital(SBGH)all folate data between January 1996 and Dec 31,2004 were analyzed and the medical records of all who had low RF between January 1,1999 and December 31,2004 were reviewed.</p> <p>Results</p> <p>In 2001, at HSC, 11 out of 2154(0.5%)SF were low(<7.0 nmol/L) and 4 out of 560 (0.7%) RF were low (<417 nmol/L). In no subject with low SF or RF could the anemia be attributed to folate deficiency. At SBGH during the 3-year-period of 1999-2001, 19 out of 991(1.9%) had low RF (<225 nmol/L) but in only 2 patients (0.2%) the low RF was in folate deficiency anemia range; but neither of them had anemia.</p> <p>Conclusion</p> <p>In countries where there is mandatory fortification of grain products with folic acid, folate deficiency to the degree that could cause anemia is extremely rare. Ordering folate assays for investigation of anemias, in these countries, is waste of time and money. The result of these tests is more likely to mislead the physicians than to provide any useful information.</p

    Gene expression profiling reveals differential effects of sodium selenite, selenomethionine, and yeast-derived selenium in the mouse

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    The essential trace mineral selenium is an important determinant of oxidative stress susceptibility, with several studies showing an inverse relationship between selenium intake and cancer. Because different chemical forms of selenium have been reported to have varying bioactivity, there is a need for nutrigenomic studies that can comprehensively assess whether there are divergent effects at the molecular level. We examined the gene expression profiles associated with selenomethionine (SM), sodium selenite (SS), and yeast-derived selenium (YS) in the intestine, gastrocnemius, cerebral cortex, and liver of mice. Weanling mice were fed either a selenium-deficient (SD) diet (<0.01 mg/kg diet) or a diet supplemented with one of three selenium sources (1 mg/kg diet, as either SM, SS or YS) for 100 days. All forms of selenium were equally effective in activating standard measures of selenium status, including tissue selenium levels, expression of genes encoding selenoproteins (Gpx1 and Txnrd2), and increasing GPX1 enzyme activity. However, gene expression profiling revealed that SS and YS were similar (and distinct from SM) in both the expression pattern of individual genes and gene functional categories. Furthermore, only YS significantly reduced the expression of Gadd45b in all four tissues and also reduced GADD45B protein levels in liver. Taken together, these results show that gene expression profiling is a powerful technique capable of elucidating differences in the bioactivity of different forms of selenium

    Quantitative trait loci conferring grain mineral nutrient concentrations in durum wheat 3 wild emmer wheat RIL population

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    Mineral nutrient malnutrition, and particularly deficiency in zinc and iron, afflicts over 3 billion people worldwide. Wild emmer wheat, Triticum turgidum ssp. dicoccoides, genepool harbors a rich allelic repertoire for mineral nutrients in the grain. The genetic and physiological basis of grain protein, micronutrients (zinc, iron, copper and manganese) and macronutrients (calcium, magnesium, potassium, phosphorus and sulfur) concentration was studied in tetraploid wheat population of 152 recombinant inbred lines (RILs), derived from a cross between durum wheat (cv. Langdon) and wild emmer (accession G18-16). Wide genetic variation was found among the RILs for all grain minerals, with considerable transgressive effect. A total of 82 QTLs were mapped for 10 minerals with LOD score range of 3.2–16.7. Most QTLs were in favor of the wild allele (50 QTLs). Fourteen pairs of QTLs for the same trait were mapped to seemingly homoeologous positions, reflecting synteny between the A and B genomes. Significant positive correlation was found between grain protein concentration (GPC), Zn, Fe and Cu, which was supported by significant overlap between the respective QTLs, suggesting common physiological and/or genetic factors controlling the concentrations of these mineral nutrients. Few genomic regions (chromosomes 2A, 5A, 6B and 7A) were found to harbor clusters of QTLs for GPC and other nutrients. These identified QTLs may facilitate the use of wild alleles for improving grain nutritional quality of elite wheat cultivars, especially in terms of protein, Zn and Fe
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