Extracellular signal-regulated kinase (ERK) activation is required for porcine epidemic diarrhea virus replication

AbstractPorcine epidemic diarrhea virus (PEDV) is a highly enteropathogenic coronavirus of swine that causes acute enteritis with high mortality in nursery piglets. To date, the cellular factors involved in PEDV replication have not been well defined. The extracellular signal-regulated kinase (ERK) that serves as a critical component of cellular signal transduction pathways to modulate a variety of cellular functions has been shown to regulate several viral infections. In the present study, we found that PEDV activates ERK1/2 early in infection independently of viral replication. The PEDV-induced ERK1/2 activation resulted in the phosphorylation of its downstream substrate Elk-1 in infected cells. Treatment with ERK inhibitors or ERK1/2 knockdown significantly suppressed viral progeny production. Inhibition of ERK activation also diminished viral protein expression and genomic and subgenomic RNA transcription. These findings indicate that the ERK signaling pathway plays an important role in the PEDV life cycle and beneficially contributes to viral infection

Interactions between soil biogeochemistry and native earthworms in New Zealand

Despite apparently similar burrowing and feeding behaviours to introduced Lumbricidae earthworms, native Megascolecidae, with more than 179 recognised species, have become isolated in natural vegetation remnants on the margins of agricultural land. Long-term geographic isolation has provided high endemic earthworm diversity in New Zealand, but they appear to have a poor ability to adapt to anthropogenic disturbance. Although earthworms are well known as ‘soil engineers’, there is lack of knowledge of the role of endemic earthworms in New Zealand’s soil ecosystems. The aims of the present PhD study were to identify endemic earthworm preferences for and influences on soil biogeochemistry, and to investigate interactions between the drilosphere of native earthworms and the rhizosphere of native plants. Species of earthworm, collected from native vegetation, natural remnants and restoration sites in Canterbury and on the West Coast of South Island, were identified using DNA barcoding with 16S and COI primers. Thirteen endemic and nine exotic species were identified and, of these, eight abundant earthworms were selected for this study: 5 endemic taxa identified as Deinodrilus sp.1 (epigeic), Maoridrilus transalpinus and Maoridrilus sp.2 (anecic), Megascolecidae sp.1 and Octochaetus multiporus (endogeic), and 3 exotic species: Eisenia fetida (epigeic), Octolasion cyaneum and O. lacteum (endogeic). Both endemic and exotic earthworms preferred agricultural soils to a native forest soil. Ryegrass litter was preferred to litter of native plants, although Coprosma robusta was also favoured by endemic earthworms. There was more preference for less acid soil than for high organic matter soil. Earthworm species could also be separated on the basis of their effects on soil biogeochemistry, in terms of organic matter consumption, nutrient mineralisation, soil microbial biomass and greenhouse gas emissions from the soil. Earthworm inoculation of soils increased more mobile forms of the key nutrients N and P, and emissions of N2O and CO2 from an agricultural soil. Lesser differences were found between native and exotic earthworms than between functional (burrowing) groups. Native earthworms increased growth of plants, including L. perenne, and had a marked interaction with root morphology of two native species of tea tree (Leptospermum scoparium and Kunzea robusta). They also stimulated microbial activity in rhizosphere soil. An anecic species, M. transalpinus, enhanced rates of root nodulation of a native leguminous shrub (Sophora microphylla), enhancing critical concentrations of nitrate, but also reducing nitrous oxide emissions. Maoridrilus spp. enhanced plant productivity in biosolids-amended soils, but raised some potential environmental concerns through increased N2O emissions in <50 % biosolid treatments. They also significantly increased ammonium and nitrate in soil, microbial activity and soil concentrations of soluble copper. The results showed that endemic earthworms could play a critical role providing soil ecosystem services in New Zealand’s production landscapes. Novel habitats within agricultural management systems provide an important refuge for threatened species conservation. Enhanced restoration of native vegetation into agricultural landscapes will enhance the dispersion and sustainability of communities of native earthworms. An integrated understanding of plant growth and microbial communities with earthworm functionality is essential for effective management of soil biogeochemistry and to inform ecological restoration on former agricultural land

Combined Striatum, Brain Stem, and Optic Nerve Involvement due to Mycoplasma pneumoniae in an Ambulatory Child

In children, Mycoplasma pneumoniae encephalitis has been characterized by acute onset of an encephalopathy associated with extrapyramidal symptoms and symmetric basal ganglia with or without brain stem involvement on magnetic resonance imaging. Our case, showing unilateral optic neuritis, ophthalmoplegia, no extrapyramidal symptoms, and typical striatal involvement on magnetic resonance imaging, broadens the spectrum of varying clinical manifestations of childhood M. pneumoniae-associated encephalopathy

Metabolic State Determines Sensitivity to Cellular Stress in Huntington Disease: Normalization by Activation of PPARγ

Impairments in mitochondria and transcription are important factors in the pathogenesis of Huntington disease (HD), a neurodegenerative disease caused by a polyglutamine expansion in the huntingtin protein. This study investigated the effect of different metabolic states and peroxisome proliferator-activated receptor γ (PPARγ) activation on sensitivity to cellular stressors such as H2O2 or thapsigargin in HD. Striatal precursor cells expressing wild type (STHdhQ7) or mutant huntingtin (STHdhQ111) were prepared in different metabolic conditions (glucose vs. pyruvate). Due to the fact that STHdhQ111 cells exhibit mitochondrial deficits, we expected that in the pyruvate condition, where ATP is generated primarily by the mitochondria, there would be greater differences in cell death between the two cell types compared to the glucose condition. Intriguingly, it was the glucose condition that gave rise to greater differences in cell death. In the glucose condition, thapsigargin treatment resulted in a more rapid loss of mitochondrial membrane potential (ΔΨm), a greater activation of caspases (3, 8, and 9), and a significant increase in superoxide/reactive oxygen species (ROS) in STHdhQ111 compared to STHdhQ7, while both cell types showed similar kinetics of ΔΨm-loss and similar levels of superoxide/ROS in the pyruvate condition. This suggests that bioenergetic deficiencies are not the primary contributor to the enhanced sensitivity of STHdhQ111 cells to stressors compared to the STHdhQ7 cells. PPARγ activation significantly attenuated thapsigargin-induced cell death, concomitant with an inhibition of caspase activation, a delay in ΔΨm loss, and a reduction of superoxide/ROS generation in STHdhQ111 cells. Expression of mutant huntingtin in primary neurons induced superoxide/ROS, an effect that was significantly reduced by constitutively active PPARγ. These results provide significant insight into the bioenergetic disturbances in HD with PPARγ being a potential therapeutic target for HD