501 research outputs found
Teaching fundamental British values in primary schools : project summary
This project developed out of academic research carried out by Alison Struthers into the practice of Fundamental British Values (FBV) and Human Rights Education (HRE) in English primary schools. In this research, the author explored the problems with the Governmentās FBV agenda, and argued that because human rights values are rooted in universality, couching FBV in this broader framework would be likely to contribute to societal cohesion to a far greater extent than the potentially discriminatory FBV guidance. This project sought to action these findings by showing how teaching about FBV can be linked effectively to broader human rights values
MHC-linked and un-linked class I genes in the wallaby
Background: MHC class I antigens are encoded by a rapidly evolving gene family comprising classical and
non-classical genes that are found in all vertebrates and involved in diverse immune functions. However,
there is a fundamental difference between the organization of class I genes in mammals and non-mammals.
Non-mammals have a single classical gene responsible for antigen presentation, which is linked to the
antigen processing genes, including TAP. This organization allows co-evolution of advantageous class Ia/
TAP haplotypes. In contrast, mammals have multiple classical genes within the MHC, which are separated
from the antigen processing genes by class III genes. It has been hypothesized that separation of classical
class I genes from antigen processing genes in mammals allowed them to duplicate. We investigated this
hypothesis by characterizing the class I genes of the tammar wallaby, a model marsupial that has a novel
MHC organization, with class I genes located within the MHC and 10 other chromosomal locations.
Results: Sequence analysis of 14 BACs containing 15 class I genes revealed that nine class I genes, including
one to three classical class I, are not linked to the MHC but are scattered throughout the genome.
Kangaroo Endogenous Retroviruses (KERVs) were identified flanking the MHC un-linked class I. The
wallaby MHC contains four non-classical class I, interspersed with antigen processing genes. Clear
orthologs of non-classical class I are conserved in distant marsupial lineages.
Conclusion: We demonstrate that classical class I genes are not linked to antigen processing genes in the
wallaby and provide evidence that retroviral elements were involved in their movement. The presence of
retroviral elements most likely facilitated the formation of recombination hotspots and subsequent
diversification of class I genes. The classical class I have moved away from antigen processing genes in
eutherian mammals and the wallaby independently, but both lineages appear to have benefited from this
loss of linkage by increasing the number of classical genes, perhaps enabling response to a wider range of
pathogens. The discovery of non-classical orthologs between distantly related marsupial species is unusual
for the rapidly evolving class I genes and may indicate an important marsupial specific function
A light-front description of electromagnetic form factors for hadrons
A review of the hadron electromagnetic form factors obtained in a light-front
constituent quark model, based on the eigenfunctions of a mass operator, is
presented. The relevance of different components in the q-q interaction for the
description of hadron experimental form factors is analysed.Comment: 6 pages, Latex, 3 Postscript figures included. Proceedings of
"Nucleon 99", Frascati, June 1999. To appear in Nucl. Phys.
Evaluation of two lyophilized molecular assays to rapidly detect foot-and-mouth disease virus directly from clinical samples in field settings
Accurate, timely diagnosis is essential for the control, monitoring and eradication of footāandāmouth disease (FMD). Clinical samples from suspect cases are normally tested at reference laboratories. However, transport of samples to these centralized facilities can be a lengthy process that can impose delays on critical decision making. These concerns have motivated work to evaluate simpleātoāuse technologies, including molecularābased diagnostic platforms, that can be deployed closer to suspect cases of FMD. In this context, FMD virus (FMDV)āspecific reverse transcription loopāmediated isothermal amplification (RTāLAMP) and realātime RTāPCR (rRTāPCR) assays, compatible with simple sample preparation methods and in situ visualization, have been developed which share equivalent analytical sensitivity with laboratoryābased rRTāPCR. However, the lack of robust āreadyātoāuse kitsā that utilize stabilized reagents limits the deployment of these tests into field settings. To address this gap, this study describes the performance of lyophilized rRTāPCR and RTāLAMP assays to detect FMDV. Both of these assays are compatible with the use of fluorescence to monitor amplification in realātime, and for the RTāLAMP assays end point detection could also be achieved using molecular lateral flow devices. Lyophilization of reagents did not adversely affect the performance of the assays. Importantly, when these assays were deployed into challenging laboratory and field settings within East Africa they proved to be reliable in their ability to detect FMDV in a range of clinical samples from acutely infected as well as convalescent cattle. These data support the use of highly sensitive molecular assays into field settings for simple and rapid detection of FMDV
Cell-autonomous programming of rat adipose tissue insulin signalling proteins by maternal nutrition.
AIMS/HYPOTHESIS: Individuals with a low birthweight have an increased risk of developing type 2 diabetes mellitus in adulthood. This is associated with peripheral insulin resistance. Here, we aimed to determine whether changes in insulin signalling proteins in white adipose tissue (WAT) can be detected prior to the onset of impaired glucose tolerance, determine whether these changes are cell-autonomous and identify the underlying mechanisms involved. METHODS: Fourteen-month-old male rat offspring born to dams fed a standard protein (20%) diet or a low (8%) protein diet throughout gestation and lactation were studied. Fat distribution and adipocyte size were determined. Protein content and mRNA expression of key insulin signalling molecules were analysed in epididymal WAT and in pre-adipocytes that had undergone in vitro differentiation. RESULTS: The offspring of low protein fed dams (LP offspring) had reduced visceral WAT mass, altered fat distribution and a higher percentage of small adipocytes in epididymal WAT. This was associated with reduced levels of IRS1, PI3K p110Ī², Akt1 and PKCĪ¶ proteins and of phospho-Akt Ser473. Corresponding mRNA transcript levels were unchanged. Similarly, in vitro differentiated adipocytes from LP offspring showed reduced protein levels of IRĪ², IRS1, PI3K p85Ī± and p110Ī² subunits, and Akt1. Levels of Akt Ser473 and IRS1 Tyr612 phosphorylation were reduced, while IRS1 Ser307 phosphorylation was increased. CONCLUSIONS/INTERPRETATION: Maternal protein restriction during gestation and lactation changes the distribution and morphology of WAT and reduces the levels of key insulin signalling proteins in the male offspring. This phenotype is retained in in vitro differentiated adipocytes, suggesting that programming occurs via cell-autonomous mechanism(s).This work was supported by Diabetes UK (MSM-G; no. 12/0004508), the British Heart Foundation (SEO; no. FS/09/029/27902) and the UK Medical Research Council (SEO; no. MC_UU_12012/4)This is the accepted manuscript. It is currently embargoed pending publication
Light-front CQM calculations of baryon electromagnetic form factors
The parameter-free predictions for the and electromagnetic transition form factors, obtained within our
light-front constituent quark model using eigenfunctions of a baryon mass
operator which includes a large amount of configuration mixing, are reported.
The effects due to small components in the baryon wave functions, such as S'-
and D-wave, are also investigated.Comment: to appear in the Proceedings of the International Workshop on Hadron
Dynamics with the new DAPHNE and CEBAF facilities, Frascati, Italy, 11-14
November 199
The tammar wallaby major histocompatibility complex shows evidence of past genomic instability
BACKGROUND The major histocompatibility complex (MHC) is a group of genes with a variety of roles in the innate and adaptive immune responses. MHC genes form a genetically linked cluster in eutherian mammals, an organization that is thought to confer functional and evolutionary advantages to the immune system. The tammar wallaby (Macropus eugenii), an Australian marsupial, provides a unique model for understanding MHC gene evolution, as many of its antigen presenting genes are not linked to the MHC, but are scattered around the genome. RESULTS Here we describe the 'core' tammar wallaby MHC region on chromosome 2q by ordering and sequencing 33 BAC clones, covering over 4.5 MB and containing 129 genes. When compared to the MHC region of the South American opossum, eutherian mammals and non-mammals, the wallaby MHC has a novel gene organization. The wallaby has undergone an expansion of MHC class II genes, which are separated into two clusters by the class III genes. The antigen processing genes have undergone duplication, resulting in two copies of TAP1 and three copies of TAP2. Notably, Kangaroo Endogenous Retroviral Elements are present within the region and may have contributed to the genomic instability. CONCLUSIONS The wallaby MHC has been extensively remodeled since the American and Australian marsupials last shared a common ancestor. The instability is characterized by the movement of antigen presenting genes away from the core MHC, most likely via the presence and activity of retroviral elements. We propose that the movement of class II genes away from the ancestral class II region has allowed this gene family to expand and diversify in the wallaby. The duplication of TAP genes in the wallaby MHC makes this species a unique model organism for studying the relationship between MHC gene organization and function.This work was funded by an ARC Discovery Grant to KB and SB, and a Wellcome Trust Grant (084071) to SB. HVS was supported by a University of Sydney Postgraduate Award and a William and Catherine McIlrath Scholarship for travel to the Sanger Institute. JK and HVS are supported in part by Wellcome Trust Programme grant 089305. KB is supported by a University of Sydney Thompson fellowship and an ARC Future Fellowship
Propagation of HF radio waves over northerly paths: measurements,simulation and systems aspects
Large deviations in the direction of arrival of ionospherically propagating radio signals from the Great Circle Path (GCP) have serious implications for the planning and operation of communications
and radiolocation systems operating within the HF-band. Very large deviations are particularly prevalent in the polar and sub-auroral regions where signals often arrive at the receiver with bearings displaced
from the great circle direction by up to Ā±100Ā° or more. Measurements made over several paths are presented in this paper, and the principle causes of off-great circle propagation outlined. Significant
progress has been made in modelling the propagation effects and work is now in hand to incorporate the results into tools to aid the planning and operation of HF radio systems operating at northerly latitudes
The human insulin receptor mRNA contains a functional internal ribosome entry segment.
Regulation of mRNA translation is an important mechanism determining the level of expression of proteins in eukaryotic cells. Translation is most commonly initiated by cap-dependent scanning, but many eukaryotic mRNAs contain internal ribosome entry segments (IRESs), providing an alternative means of initiation capable of independent regulation. Here, we show by using dicistronic luciferase reporter vectors that the 5'-UTR of the mRNA encoding human insulin receptor (hIR) contains a functional IRES. RNAi-mediated knockdown showed that the protein PTB was required for maximum IRES activity. Electrophoretic mobility shift assays confirmed that PTB1, PTB2 and nPTB, but not unr or PTB4, bound to hIR mRNA, and deletion mapping implicated a CCU motif 448 nt upstream of the initiator AUG in PTB binding. The IR-IRES was functional in a number of cell lines, and most active in cells of neuronal origin, as assessed by luciferase reporter assays. The IRES was more active in confluent than sub-confluent cells, but activity did not change during differentiation of 3T3-L1 fibroblasts to adipocytes. IRES activity was stimulated by insulin in sub-confluent cells. The IRES may function to maintain expression of IR protein in tissues such as the brain where mRNA translation by cap-dependent scanning is less effective
Twelve-month prevalence of haemarthrosis and joint disease using the Haemophilia Joint Health score: evaluation of the UK National Haemophilia Database and Haemtrack patient reported data: an observational study
Objectives: To report the 12-month prevalence of joint bleeds from the National Haemophilia Database (NHD) and Haemtrack, a patient-reported online treatment diary and concurrent joint disease status using the haemophilia joint health score (HJHS) at individual joint level, in children and adults with severe haemophilia A and B (HA/HB) without a current inhibitor.
Design: A 2018 retrospective database study of NHD from which 2238 cases were identified, 463 patients had fully itemised HJHS of whom 273 were compliant in recording treatment using Haemtrack.
Setting: England, Wales and Scotland, UK.
Participants: Children (<18 years) and adults (ā„18 years) with severe HA and HB (factor VIII/factor IX, <0.01 iu/mL) without a current inhibitor.
Primary and secondary outcomes: Prevalence of joint haemarthrosis and concurrent joint health measured using the HJHS.
Results: The median (IQR) age of children was 10 (6-13) and adults 40 (29-50) years. Haemarthrosis prevalence in HA/HB children was 33% and 47%, respectively, and 60% and 42%, respectively, in adults. The most common site of haemarthrosis in children was the knee in HA and ankle in HB. In adults, the incidence of haemarthrosis at the ankles and elbows was equal. The median total HJHS in HA/HB children was 0 and in adults with HA/HB, were 18 and 11, respectively. In adults with HA/HB, the median ankle HJHS of 4.0 was higher than the median HJHS of 1.0 for both the knee and elbow.
Conclusion: Despite therapeutic advances, only two-thirds of children and one-third of adults were bleed-free, even in a UK cohort selected for high compliance with prophylaxis. The median HJHS of zero in children suggests joint health is relatively unaffected during childhood. In adults, bleed rates were highest in ankles and elbows, but the ankles led to substantially worse joint health scores
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