1,721,051 research outputs found
The soft tick <i>ornithodoros moubata</i> and its role in the epidemiology of African swine fever in Central Malawi
No full textAfrican swine fever is a viral hemorrhagic disease of pigs (Sus scrofa) caused by a double-stranded DNA virus, African swine fever virus (ASFV). With up to 100% mortality in pigs and no vaccine, the socioeconomic impacts of this disease are immense. In sub-Saharan Africa, warthogs (Phacochoerus africanus) are the original vertebrate host for the virus, which is transmitted among wild suids via the soft tick Ornithodoros moubata. In Malawi, O. moubata is thought to be widely distributed, with the potential to spread ASFV beyond its historical enzootic zone in the Central Region. We surveyed 76 domestic pig farms, 18 active warthog burrows, and three bushpigs (Potamochoerus larvatus) resting sites for O. moubata in the Central Region of Malawi, and tested the ticks for ASFV using PCR. We found a limited distribution for O. moubata: 75 ticks were discovered at a single farm in the Mchinji District. Eleven percent of these ticks were ASFV positive. This suggests that wildlife and O. moubata play a limited role in the epidemiology of ASF in Malawi; thus, other factors for disease spread, such as fomites and pig-to-pig infection, need to be considered
Expression of the nidogen-binding site of the laminin gamma 1 chain disturbs basement membrane formation and maintenance in F9 embryoid bodies
Full text linkBasement membranes contain two major molecular networks consisting of laminin and collagen IV. Previous antibody perturbation experiments suggest that the interaction between laminin and nidogen-1 is necessary for proper basement membrane formation and epithelial development, whereas results from gene ablation experiments in mice show that both basement membranes and general development are grossly normal in the absence of nidogen-1. To refine the perturbation approach, we produced F9-teratocarcinoma-cell-derived embryoid bodies in the presence of recombinantly expressed nidogenbinding sites localized within the gammaIIII3-5 laminin fragment. We found basement membranes were disrupted in gammaIIII3-5-expressing embryoid bodies. As a measurement of basement membrane function, we tested permeability and detected drastically increased diffusion rates in correlation with basement membrane disruption. Furthermore, TROMA-1 localization in embryoid bodies expressing the nidogen-binding site was altered, suggesting separation of epithelium-specific gene expression from the formation of the actual epithelium when occurring in the absence of an organized basement membrane
Do little embryos make big decisions? How maternal dietary protein restriction can permanently change an embryo.
Full text linkPericonceptional environment may influence embryo development, ultimately affecting adult health. Here, we review the rodent model of maternal low-protein diet specifically during the preimplantation period (Emb-LPD) with normal nutrition during subsequent gestation and postnatally. This model, studied mainly in the mouse, leads to cardiovascular, metabolic and behavioural disease in adult offspring, with females more susceptible. We evaluate the sequence of events from diet administration that may lead to adult disease. Emb-LPD changes maternal serum and/or uterine fluid metabolite composition, notably with reduced insulin and branched-chain amino acids. This is sensed by blastocysts through reduced mammalian target of rapamycin complex 1 signalling. Embryos respond by permanently changing the pattern of development of their extra-embryonic lineages, trophectoderm and primitive endoderm, to enhance maternal nutrient retrieval during subsequent gestation. These compensatory changes include stimulation in proliferation, endocytosis and cellular motility, and epigenetic mechanisms underlying them are being identified. Collectively, these responses act to protect fetal growth and likely contribute to offspring competitive fitness. However, the resulting growth adversely affects long-term health because perinatal weight positively correlates with adult disease risk. We argue that periconception environmental responses reflect developmental plasticity and 'decisions' made by embryos to optimise their own development, but with lasting consequences
Transgenic mice expressing D469 Delta mutated cartilage oligomeric matrix protein (COMP) show growth plate abnormalities and sternal malformations
No full textIn humans, mutations in cartilage oligomeric matrix protein (COMP) cause autosomal dominantly inherited skeletal dysplasias. We have generated transgenic mouse lines to study the role of mutant D469 Delta COMP in the pathogenesis of pseudoachondroplasia. Biochemical characterization of cartilage tissue demonstrated that transgenic and endogenous COMP subunits were able to form mixed, pentameric molecules in vivo. Mutant COMP was more difficult to extract than the wildtype protein, suggesting an altered anchorage within the matrix. Although both transgenic wildtype and mutant COMP were detected throughout the growth plate, mutant molecules were restricted to the pericellular matrix while wildtype COMP showed a uniform distribution throughout the extracellular matrix. Mice expressing the mutant transgene showed a slight gender specific growth retardation. In mutant animals, the columnar organization in the growth plate was disturbed, proteoglycans were lost and improperly formed collagen fibrils were observed. In some chondrocytes the endoplasmic reticulum was dilated, most probably due to an impaired secretion of mutant COMP similar to that observed in patients. Later in development, the growth plate was irregularly shaped and prematurely invaded by bony tissue. In addition, a fusion of the third and fourth sternebrae was frequently observed. (c) 2007 Elsevier B.V./International Society of Matrix Biology. All rights reserved
Transglutaminases in autoimmune and inherited skin diseases: The phenomena of epitope spreading and functional compensation
No full textTransglutaminases (TGs) are structurally and functionally related enzymes that modify the post-translational structure and activity of proteins or peptides, and thus are able to turn on or switch off their function. Depending on location and activities, TGs are able to modify the signalling, the function and the fate of cells and extracellular connective tissues. Besides mouse models, human diseases enable us to appreciate the function of various TGs. In this study, skin diseases induced by genetic damages or autoimmune targeting of these enzymes will be discussed. TG1, TG3 and TG5 contribute to the cutaneous barrier and thus to the integrity and function of epidermis. TGM1 mutations related to autosomal recessive ichthyosis subtypes, TGM5 mutations to a mild epidermolysis bullosa phenotype and as novelty TGM3 mutation to uncombable hair syndrome will be discussed. Autoimmunity to TG2, TG3 and TG6 may develop in a few of those genetically determined individuals who lost tolerance to gluten, and manifest as coeliac disease, dermatitis herpetiformis or gluten-dependent neurological symptoms, respectively. These gluten responder diseases commonly occur in combination. In autoimmune diseases, the epitope spreading is remarkable, while in some inherited pathologies, a unique compensation of the lost enzyme function is noted.</p
A microfluidic-based arteriolar network model for biophysical and bioanalytical investigations
No full textThe microcirculation plays a key role in the delivery of essential substrates for oxidative processes in cells, the removal of products of cell metabolism, and the regulation of peripheral blood flow distribution. The functional properties of microvascular networks strongly depend on the rheological properties of blood and on the heterogeneity of their architecture. However, studying blood flow behaviour through in vivo microvascular systems is limited by ethical, economical and technical issues. Such limitations have opened the way to in vitro models, such as straight microcapillaries or network- like microchannel constructs, but current in vitro models present simplifications in the architecture design which result in the impossibility of faithfully reproducing key features of the in vivo microvascular haemodynamics. In the present study we report the development of a microfluidic-based in vitro model of the human arteriolar system, characterised by circular channel cross-section, network asymmetry and the presence of both bifurcation- and side-branches. The developed microdevice allows for the quantification of the velocity fields, cell-depletion layer thickness and haematocrit distribution within biomimetic microchannel networks. Results show the potential of our in vitro model in reproducing key features of blood flow behaviour which have been detected for microvascular systems in vivo, including the relationships between cell-depletion layer thickness, haematocrit and vessel diameter. The developed microdevices can find extensive applications in biological and biophysical research, where the mimicking of flow dynamics at the microcirculatory level is require
Impaired wound healing in mice lacking the basement membrane protein nidogen 1
No full textNidogens 1 and 2 are ubiquitous basement membrane (BM) components, whose interactions in particular with laminin, collagen IV and perlecan have been considered important for BM formation. Genetic deletion of either NID gene does not reveal BM alterations suggesting compensatory roles for nidogens 1 and 2. However, neurological deficits in nidogen 1 null mice, not seen in the absence of nidogen 2, also suggest isoform specific functions. To test this further, skin wound healing which requires BM reformation was studied in adult nidogen 1 deficient mice. Although re-epithelialization was not altered, the newly formed epidermis showed marked hyperproliferation and a delay in differentiation at day 10 post injury. Distinct to control wounds, there was also considerable alpha-smooth muscle actin staining in the dermis of nidogen 1 deficient wounds at this time point. Further, laminin deposition and distribution of the 01 and M integrin chains were also significantly altered whereas the deposition of other BM components, including nidogen 2, was unchanged. Surprisingly, these differences between control and mutant wounds at day 10 post wounding did not affect the ultrastructural appearance of the dermo-epidermal BM suggesting a non-structural role for nidogen 1 in wound repair. (C) 2009 Elsevier B.V. All rights reserved
Dataset supporting the University of Southampton Doctoral Thesis "The Impact of Maternal High Fat Diet on Offspring Brain, Behaviour and Cognitive Functions"
No full textDataset supporting the University of Southampton Doctoral Thesis "The Impact of Maternal High Fat Diet on Offspring Brain, Behaviour and Cognitive Functions".
The dataset is presented in a zip file of all data related to the impact of maternal high-fat diet consumption during specific time periods on offspring brain and behaviour. The impact on pregnancy outcomes, maternal body weights, maternal diet and energy intake, offspring body weight, and offspring behaviour was evaluated using the open field test (OFT), novel object recognition test (NOR), elevated plus maze (EPM), T-maze, social interaction test (SIT), and several gene expression levels in the offspring's cortex and hippocampus tissues.
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