125 research outputs found
Health risk implications from simultaneous exposure to multiple environmental contaminants
Water quality has deteriorated in the upper Olifants River system, South Africa, as a result of land use
activities which include mining, agriculture and industries. A health risk assessment was conducted from
2009 to 2011 in the catchment to determine the possible risks local communities face from various
pollutants such as microbials, heavy metals and oestrogen in the river water and vegetation. Aluminium
and manganese accumulated in plants and vanadium and aluminium concentrations found in selective
water samples posed significant health risks when consumed. A quantitative microbial risk assessment
revealed that the combined risk of infection ranged from 1 to 26 percent with the Norovirus posing the
overall greatest health risk. The anticipated disability adjusted life years resulting from drinking
untreated water from these sites are in the order of 10,000 times greater than what is considered
acceptable. The oestradiol activity, caused by endocrine disrupting compounds in the water, measured
above the trigger value of 0.7 ng Lā1. Impoverished communities in the area, who partially depend on
river water for potable and domestic use, are exposed to immune-compromising metals that increase
their probability of infection from waterborne diseases caused by the excess microbial pathogens in the
contaminated surface water.Olifants River Forumhttp://www.elsevier.com/locate/ecoenvhb201
Genetically Induced Tumors in the Oncopig Model Invoke an Antitumor Immune Response Dominated by Cytotoxic CD8Ī²<sup>+</sup> T Cells and Differentiated Ī³Ī“ T Cells Alongside a Regulatory Response Mediated by FOXP3<sup>+</sup> T Cells and Immunoregulatory Molecules
In recent years, immunotherapy has shown considerable promise in the management of several malignancies. However, the majority of preclinical studies have been conducted in rodents, the results of which often translate poorly to patients given the substantial differences between murine and human immunology. As the porcine immune system is far more analogous to that of humans, pigs may serve as a supplementary preclinical model for future testing of such therapies. We have generated the genetically modified Oncopig with inducible tumor formation resulting from concomitant KRASG12D and TP53R167H mutations under control of an adenoviral vector Cre-recombinase (AdCre). The objective of this study was to characterize the tumor microenvironment in this novel animal model with respect to T-cell responses in particular and to elucidate the potential use of Oncopigs for future preclinical testing of cancer immunotherapies. In this study, we observed pronounced intratumoral T-cell infiltration with a strong CD8Ī²+ predominance alongside a representation of highly differentiated Ī³Ī“ T cells. The infiltrating CD8Ī²+ T cells displayed increased expression of the cytotoxic marker perforin when compared with the peripheral T-cell pool. Similarly, there was robust granzyme B staining localizing to the tumors; affirming the presence of cytotoxic immune cells within the tumor. In parallel with this antitumor immune response, the tumors displayed enrichment in FOXP3-expressing T cells and increased gene expression of indoleamine 2,3-dioxygenase 1 (IDO1), cytotoxic T-lymphocyte-associated protein 4 (CTLA4), and programmed death-ligand 1 (PDL1). Finally, we investigated the Oncopig immune system in mediating antitumor immunity. We observed pronounced killing of autologous tumor cells, which demonstrates the propensity of the Oncopig immune system to recognize and mount a cytotoxic response against tumor cells. Together, these findings suggest innate and adaptive recognition of the induced tumors with a concomitant in vivo suppression of T-cell effector functions. Combined, the data support that the Oncopig may serve as a valuable model for future preclinical testing of immunotherapies aimed at reactivating tumor-directed cytotoxicity in vivo
Comparison of the Structures of Ammonium Myristate, Palmitate, and Stearate by X-ray Diffraction, Infrared Spectroscopy, and Infrared Hole Burning
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Universal DNA methylation age across mammalian tissues.
Aging, often considered a result of random cellular damage, can be accurately estimated using DNA methylation profiles, the foundation of pan-tissue epigenetic clocks. Here, we demonstrate the development of universal pan-mammalian clocks, using 11,754 methylation arrays from our Mammalian Methylation Consortium, which encompass 59 tissue types across 185 mammalian species. These predictive models estimate mammalian tissue age with high accuracy (rā>ā0.96). Age deviations correlate with human mortality risk, mouse somatotropic axis mutations and caloric restriction. We identified specific cytosines with methylation levels that change with age across numerous species. These sites, highly enriched in polycomb repressive complex 2-binding locations, are near genes implicated in mammalian development, cancer, obesity and longevity. Our findings offer new evidence suggesting that aging is evolutionarily conserved and intertwined with developmental processes across all mammals
Universal DNA methylation age across mammalian tissues
Aging, often considered a result of random cellular damage, can be accurately estimated using DNA methylation profiles, the foundation of pan-tissue epigenetic clocks. Here, we demonstrate the development of universal pan-mammalian clocks, using 11,754 methylation arrays from our Mammalian Methylation Consortium, which encompass 59 tissue types across 185 mammalian species. These predictive models estimate mammalian tissue age with high accuracy (rā>ā0.96). Age deviations correlate with human mortality risk, mouse somatotropic axis mutations and caloric restriction. We identified specific cytosines with methylation levels that change with age across numerous species. These sites, highly enriched in polycomb repressive complex 2-binding locations, are near genes implicated in mammalian development, cancer, obesity and longevity. Our findings offer new evidence suggesting that aging is evolutionarily conserved and intertwined with developmental processes across all mammals.Publisher PDFPeer reviewe
Evolutionary signals of selection on cognition from the great tit genome and methylome
For over 50 years, the great tit (Parus major) has been a model species for research in evolutionary, ecological and behavioural research; in particular, learning and cognition have been intensively studied. Here, to provide further insight into the molecular mechanisms behind these important traits, we de novo assemble a great tit reference genome and whole-genome re-sequence another 29 individuals from across Europe. We show an overrepresentation of genes related to neuronal functions, learning and cognition in regions under positive selection, as well as increased CpG methylation in these regions. In addition, great tit neuronal non-CpG methylation patterns are very similar to those observed in mammals, suggesting a universal role in neuronal epigenetic regulation which can affect learning-, memory- and experience-induced plasticity. The high-quality great tit genome assembly will play an instrumental role in furthering the integration of ecological, evolutionary, behavioural and genomic approaches in this model species.</p
Tree water potentials supporting an explanation for the occurrence of Vachellia erioloba in the Namib Desert (Namibia)
Additive and freeāvolume effects on the refractive index of a thiolāene polymer network
VIBRATIONAL SPECTROSCOPIC STUDIES AND NORMAL COORDINATE ANALYSIS OF A GLUTARIMIDATO-PALLADIUM(II) COMPLEX, trans
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