56 research outputs found

    Immune or genetic-mediated disruption of CASPR2 causes pain hypersensitivity due to enhanced primary afferent excitability

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    Human autoantibodies to contactin-associated protein-like 2 (CASPR2) are often associated with neuropathic pain, and CASPR2 mutations have been linked to autism spectrum disorders, in which sensory dysfunction is increasingly recognized. Human CASPR2 autoantibodies, when injected into mice, were peripherally restricted and resulted in mechanical pain-related hypersensitivity in the absence of neural injury. We therefore investigated the mechanism by which CASPR2 modulates nociceptive function. Mice lacking CASPR2 (Cntnap2(-/-)) demonstrated enhanced pain-related hypersensitivity to noxious mechanical stimuli, heat, and algogens. Both primary afferent excitability and subsequent nociceptive transmission within the dorsal horn were increased in Cntnap2(-/-) mice. Either immune or genetic-mediated ablation of CASPR2 enhanced the excitability of DRG neurons in a cell-autonomous fashion through regulation of Kv1 channel expression at the soma membrane. This is the first example of passive transfer of an autoimmune peripheral neuropathic pain disorder and demonstrates that CASPR2 has a key role in regulating cell-intrinsic dorsal root ganglion (DRG) neuron excitability

    Genotoxic effect induced by hydrogen peroxide in human hepatoma cells using comet assay

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    Background: Hydrogen peroxide is a common reactive oxygen intermediate generated by variousforms of oxidative stress. Aims: The aim of this study was to investigate the DNA damage capacity ofH2O2 in HepG2 cells. Methods: Cells were treated with H2O2 at concentrations of 25 μM or 50 μM for5 min, 30 min, 40 min, 1 h or 24 h in parallel. The extent of DNA damage was assessed by the cometassay. Results: Compared to the control, DNA damage by 25 μM and 50 μM H2O2 increasedsignificantly with increasing incubation time up to 1 h, but it was not increased at 24 h. Conclusions:Our Findings confirm that H2O2 is a typical DNA damage inducing agent and thus is a good modelsystem to study the effects of oxidative stress. DNA damage in HepG2 cells increased significantlywith H2O2 concentration and time of incubation but later decreased likely due to DNA repairmechanisms and antioxidant enzyme

    Rafting in Antarctic Collembola

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    Darwin was an early exponent of the importance of ‘occasional means of dispersal’ in accounting for the present-day distribution of plants and animals. This study examined the implications of capture on the water surface of meltwater and seawater for the local and long-range dispersal of Antarctic springtails. Individuals of the maritime Antarctic collembolan Cryptopygus antarcticus, were floated on tap water and seawater at 0, 5 and 10°C. LT50s on seawater were 34 (10°C), 65 (5°C) and 75 (0°C) days. On tap water, LT50s were 69 (10°C), 126 (5°C) and 239 (0°C) days. Less than 20% escaped from the water surface. A significantly greater proportion of springtails moulted on tap water and viable offspring were produced on both tap water and seawater. Comparison across treatments of survival of moulting and non-moulting individuals found significantly greater survival in moulting animals for three of the treatment combinations. It is suggested that moult exuviae facilitate survival on the water film through the simultaneous provision of a flotation aid and a source of nourishment – that is, an ‘edible raft’. A separate experiment measuring changes in haemolymph osmolality over time on tap water and seawater at 2 and 5°C found significant differences in all treatments. Causes of mortality are discussed in relation to osmoregulatory failure and starvation

    Cave-Obligate Biodiversity on the Campus of Sewanee: The University of the South, Franklin County, Tennessee

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    The southern Cumberland Plateau in Tennessee and Alabama has the greatest diversity of cave-obligate animals in the United States. The University of the South in Franklin County, TN is one of the largest private landholders on the southern Cumberland Plateau. Its 13,000-acre campus has more than 30 caves and is underlain by more than 14 km of horizontal passageways. We examined the biodiversity of cave animals on the campus at the species level and at the genetic level. Through a survey of seven caves on the campus, we identified 24 cave-obligate species, including two new county records. This total accounts for half of the cave-obligate species reported for Franklin County. For our genetic analysis, we selected six diverse taxa (two millipedes, a beetle, a fly, an aquatic isopod, and a spider) that were collected from multiple caves, and compared their mitochondrial cytochrome oxidase I gene sequences. Across the six taxa we found: (1) low genetic diversity within caves (mean nucleotide diversity within caves across all taxa: 0.25%), (2) high genetic divergence between caves (divergence between caves within taxa ranged from 2.5%–10.9%, with two exceptions), and (3) little evidence for gene flow between caves (FST between caves within taxa \u3e 0.57, with one exception). Thus, the campus supports tremendous species diversity, and even more remarkable genetic diversity within those species on a small geographic scale (no studied caves were \u3e7 km apart). The divergence between cave populations and lack of gene flow between them that we observed across a range of taxa highlight the importance of cave conservation on a regional scale

    Nuclear and mitochondrial sequences confirm complex colonization patterns and clear species boundaries for flightless weevils in the Galápagos archipelago

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    Nuclear sequence data were collected from endemic Galápagos species and an introduced close relative, and contrasted with mitochondrial DNA sequences, continuing investigation into the colonization history and modes of diversification in the weevil genus Galapaganus. The current combined phylogeny together with previously published penalized likelihood age estimates builds a complex picture of the archipelago's colonization history. The present reconstruction relies on submerged platforms to explain the early divergence of the young southern Isabela endemics or the Española or San Cristobal populations. Diversity is later built through inter-island divergence starting on older islands and continuing on two simultaneous tracks towards younger islands. The amount of diversity generated through intra-island processes is skewed towards older islands, suggesting that island age significantly influences diversity. Phylogenetic concordance between nuclear and mitochondrial datasets and well-supported monophyletic species in mitochondrial derived topologies appear to reject the possibility of inter-species hybridization. These clear species boundaries might be related to the tight host associations of adult weevils in discrete ecological zones. If shared hosts facilitate hybridization, then host- or habitat-promoted divergences could prevent it, even in the case of species that share islands, since the altitudinal partitioning of habitats minimizes range overlap
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