426 research outputs found

    A Critical Analysis of New Mexico School Laws, 1933-1947

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    It is the purpose of this study (1) to analyze those New Mexico School laws which have been enacted since 1931; (2) to criticize them on the basis of their particular value, or lack of value, to public education in New Mexico; and (3) to suggest revisions which closely parallel the recommendations of outstanding research groups and authorities in the field of educational administration. State school law is the foundation upon which a state education system is built. In view of this fact, it is highly important that those laws be periodically studied by educations in order that those which are antiquated, outmoded, and harmful may be supplanted by new laws which are designed to meet current educational needs

    Novel expression of Haemonchus contortus vaccine candidate aminopeptidase H11 using the free-living nematode Caenorhabditis elegans

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    With the problem of parasitic nematode drug resistance increasing, vaccine development offers an alternative sustainable control approach. For some parasitic nematodes, native extracts enriched for specific proteins are highly protective. However, recombinant forms of these proteins have failed to replicate this protection. This is thought to be due to differences in glycosylation and/or conformation between native and recombinant proteins. We have exploited the free-living nematode Caenorhabditis elegans to examine its suitability as an alternative system for recombinant expression of parasitic nematode vaccine candidates. We focussed on Haemonchus contortus aminopeptidase H11 glycoprotein, which is enriched in a gut membrane fraction capable of inducing significant protection against this important ovine gastrointestinal nematode. We show that H. contortus H11 expressed in C. elegans is enzymatically active and MALDI mass spectrometry identifies similar di- and tri-fucosylated structures to those on native H11, with fucose at the 3- and/or 6-positions of the proximal GlcNAc. Some glycan structural differences were observed, such as lack of LDNF. Serum antibody to native H11 binds to C. elegans recombinant H11 and most of the antibody to rH11 or native H11 is directed to glycan moieties. Despite these similarities, no reduction in worm burden or faecal egg count was observed following immunisation of sheep with C. elegans-expressed recombinant H11 protein. The findings suggest that the di- and tri-fucosylated N-glycans expressed on rH11 do not contribute to the protective effect of H11 and that additional components present in native H11-enriched extract are likely required for enhancing the antibody response necessary for protection

    Identification of epitopes recognised by mucosal CD4+ T-cell populations from cattle experimentally colonised with Escherichia coli O157:H7

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    Additional file 5. Sequence alignment of Intimin epitopes against Intimin sequences from non-O157 EHEC serotypes. Alignment of Intimin CD4+ T-cell epitope sequences with representative Intimin sequences from EHEC serotypes O145, O127, O26, O103, O121, O45 and O111. Percentage values indicate % similarity to the EHEC O157:H7 reference sequence

    Circadian clock mechanism driving mammalian photoperiodism

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    From Springer Nature via Jisc Publications RouterHistory: received 2020-01-16, accepted 2020-07-27, registration 2020-08-04, pub-electronic 2020-08-27, online 2020-08-27, collection 2020-12Publication status: PublishedAbstract: The annual photoperiod cycle provides the critical environmental cue synchronizing rhythms of life in seasonal habitats. In 1936, Bünning proposed a circadian-based coincidence timer for photoperiodic synchronization in plants. Formal studies support the universality of this so-called coincidence timer, but we lack understanding of the mechanisms involved. Here we show in mammals that long photoperiods induce the circadian transcription factor BMAL2, in the pars tuberalis of the pituitary, and triggers summer biology through the eyes absent/thyrotrophin (EYA3/TSH) pathway. Conversely, long-duration melatonin signals on short photoperiods induce circadian repressors including DEC1, suppressing BMAL2 and the EYA3/TSH pathway, triggering winter biology. These actions are associated with progressive genome-wide changes in chromatin state, elaborating the effect of the circadian coincidence timer. Hence, circadian clock-pituitary epigenetic pathway interactions form the basis of the mammalian coincidence timer mechanism. Our results constitute a blueprint for circadian-based seasonal timekeeping in vertebrates

    Gene expression and matrix turnover in overused and damaged tendons

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    Chronic, painful conditions affecting tendons, frequently known as tendinopathy, are very common types of sporting injury. The tendon extracellular matrix is substantially altered in tendinopathy, and these changes are thought to precede and underlie the clinical condition. The tendon cell response to repeated minor injuries or “overuse” is thought to be a major factor in the development of tendinopathy. Changes in matrix turnover may also be effected by the cellular response to physical load, altering the balance of matrix turnover and changing the structure and composition of the tendon. Matrix turnover is relatively high in tendons exposed to high mechanical demands, such as the supraspinatus and Achilles, and this is thought to represent either a repair or tissue maintenance function. Metalloproteinases are a large family of enzymes capable of degrading all of the tendon matrix components, and these are thought to play a major role in the degradation of matrix during development, adaptation and repair. It is proposed that some metalloproteinase enzymes are required for the health of the tendon, and others may be damaging, leading to degeneration of the tissue. Further research is required to investigate how these enzyme activities are regulated in tendon and altered in tendinopathy. A profile of all the metalloproteinases expressed and active in healthy and degenerate tendon is required and may lead to the development of new drug therapies for these common and debilitating sports injuries

    Interaction of classical swine fever virus with dendritic cells

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    Functional disruption of dendritic cells (DCs) is an important strategy for viral pathogens to evade host defences. Monocytotropic viruses such as classical swine fever virus (CSFV) could employ such a mechanism, since the virus can suppress immune responses and induce apoptosis without infecting lymphocytes. Here, CSFV was shown to infect and efficiently replicate in monocyte- and in bone marrow-derived DCs. Interestingly, the infected DCs displayed neither modulated MHC nor CD80/86 expression. Stimulation of DCs with IFN-/TNF- or polyinosinic¿polycytidylic acid (pIC) induced phenotypic maturation with increased MHC and CD80/86 expression, both with mock-treated and infected DCs. In addition, the T cell stimulatory capacity of CSFV-infected DCs was maintained both in a polyclonal T cell stimulation and in specific antigen-presentation assays, requiring antigen uptake and processing. Interestingly, similar to macrophages, CSFV did not induce IFN- responses in these DCs and even suppressed pIC-induced IFN- induction. Other cytokines including interleukin (IL)-6, IL-10, IL-12 and TNF- were not modulated. Taken together, these results demonstrated that CSFV can replicate in DCs and control IFN type I responses, without interfering with the immune reactivity. These results are interesting considering that DC infection with RNA viruses usually results in DC activation

    Restoration of ovarian function and natural fertility following the cryopreservation and autotransplantation of whole adult sheep ovaries

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    study question: Is it possible to restore ovarian function and natural fertility following the cryopreservation and autotransplantation of whole ovaries, complete with vascular pedicle, in adult females from a large monovulatory animal model species (i.e. sheep)? summaryanswer: Full (100%) restoration of acute ovarian function and high rates of natural fertility (pregnancy rate 64%; live birth rate 29%), with multiple live births, were obtained following whole ovary cryopreservation and autotransplantation (WOCP&TP) of adult sheep ovaries utilizing optimized cryopreservation and post-operative anti-coagulant regimes. what is known already: Fertility preservation byWOCP&TP requires successful cryopreservation of both the ovary and its vascular supply. Previous work has indicated detrimental effects ofWOCP&TP on the ovarian follicle population. Recent experiments suggest that these deleterious effects can be attributed to an acute loss of vascular patency due to clot formation induced by damage to ovarian arterial endothelial cells. study design, size, duration: Study 1 (2010-2011; N = 16) examined the effect of post-thaw perfusion of survival factors (angiogenic, antioxidant, anti-apoptotic; n = 7-8) and treatment with aspirin (pre-operative versus pre- and post-operative (n = 7-9)) on the restoration of ovarian function for 3 months afterWOCP&TP. Study 2 (2011-2012; N = 16) examined the effect of cryoprotectant (CPA) perfusion time (10 versus 60 min; n = 16) and pre- and post-operative treatment with aspirin in combination with enoxaparine (Clexane® n = 8) or eptifibatide (Integrilin® n = 8) on ovarian function and fertility 11-23 months afterWOCP&TP. participants/materials, setting, methods: Both studies utilized mature, parous, Greyface ewes aged 3-6 years and weighing 50-75 kg. Restoration of ovarian function was monitored by bi-weekly blood sampling and display of behavioural oestrus. Blood samples were assayed for gonadotrophins, progesterone, anti-Müllerian Hormone and inhibin A. Fertility restoration in Study 2 was quantified by pregnancy rate after a 3 month fertile mating period and was confirmed by ultrasound, hormonal monitoring and live birth. Ovarian function was assessed at sacrifice by ovarian appearance and vascular patency (Doppler ultrasound) and by follicular histology. main results and the role of chance: In Study 1, survival factors were found to have no benefit, but the inclusion of preoperative aspirin resulted in four ewes showing acute restoration of ovarian function within 3 weeks and a further six ewes showing partial restoration. The addition of post-operative aspirin alone had no clear benefit. In Study 2, combination of aspirin with additional post-operative anti-coagulants resulted in total acute restoration of ovarian function in 14/14 ewes within 3 weeks ofWOCP&TP, with 9/14 ewes becoming pregnant and 4/14 giving birth to a total of seven normal lambs. There was no difference between anti-coagulants in terms of restoration of reproductive function and fertility. In contrast, the duration of CPA perfusion was highly significant with a 60 min perfusion resulting in ovaries of normal appearance and function with high rates of primordial follicle survival (70%) and an abundant blood supply, whereas ovaries perfused for 10 min had either resorbed completely and were vestigial (7/14) orwere markedly smaller (P < 0.01). It is concluded that both the degree ofCPA penetration and the maintenance of post-operative vascular patency are critical determinants of the success ofWOCP&TP. limitations, reasons for caution: Before application of this technology to fertility preservation patients, it will be critical to optimize the CPA perfusion time for different sized human ovaries, determine the optimum period and level of anti-coagulant therapy, and confirm the normality of offspring derived from this procedure. wider implications of the findings: This technology holds promise for the preservation of fertility in women. It could also potentially be applied to the cryopreservation of other reproductive or even major organs (kidneys) where there are considerable difficulties in storing donated tissue. © The Author 2014
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