Mutant huntingtin activates Nrf2-responsive genes and impairs dopamine synthesis in a PC12 model of Huntington's disease

Background  

Huntington's disease is a progressive autosomal dominant neurodegenerative disorder that is caused by a CAG repeat expansion in the HD or Huntington's disease gene. Although micro array studies on patient and animal tissue provide valuable information, the primary effect of mutant huntingtin will inevitably be masked by secondary processes in advanced stages of the disease. Thus, cell models are instrumental to study early, direct effects of mutant huntingtin. mRNA changes were studied in an inducible PC12 model of Huntington's disease, before and after aggregates became visible, to identify groups of genes that could play a role in the early pathology of Huntington's disease.     

Serum thyrotropin, thyroxine and free thyroxine concentrations as predictors of mortality in critically ill puppies with parvovirus infection: a model for human paediatric critical illness?

This prospective case-controlled study investigated the role of the pituitary-thyroidal axis in the prediction of mortality in dogs. Serum thyrotropin, thyroxine and free thyroxine were measured at admission and daily until death or discharge in dogs ill with parvoviral diarrhoea. Serum thyroxine and free thyroxine in ill dogs were significantly lower than in controls and also significantly lower in nonsurvivors than in survivors on days 1-4. Serum thyrotropin at admission in ill dogs was similar to controls, but was significantly higher in nonsurvivors than in survivors. Thyrotropin concentrations became significantly lower in nonsurvivors vs survivors by day 4.     

Efficacy of cultural control measures against the banana weevil, Cosmopolites sordidus (Germar), in South Africa

The banana weevil, Cosmopolites sordidus, is the most important insect pest of banana and plantain in the world. Cultural control methods were investigated over 2 years in southern KwaZulu‐Natal, South Africa. Harvesting at ground level and dissection of remnants (treatment 1), and covering the base of the mat (entire plant consisting of several meristems) with soil and moving debris to the inter‐row (treatment 2), were compared to a positive control that involved treatment of plants with a registered pesticide (treatment 3), and a negative control that involved harvesting at 150 cm from the collar with no soil or sanitation amendments (treatment 4). Yield, weevil damage and pseudostem girth of plants were measured from August to November annually, while adult beetle densities were assessed over 4 weeks in October/November and April. Nematode samples were taken and analysed in October/November every year. Damage parameters included the coefficient of infestation, the percentage coefficient of infestation (PCI) at two intervals, the summed PCI value, the percentage cross‐sectional damage of the central cylinder and cortex, and the mean cross‐sectional damage percentage. A randomized block design with three replicates was used in the trial. The parameters were similar before the onset of the trial. Fruit yield and plant girth, corrected by nematode densities, were not significantly different in any treatment, nor were the nematodes controlled. Soil cover and recession of remnants was the only effective treatment, significantly reducing the CI, but not the adult density or the other damage parameters. Soil cover showed promise as a cultural control method because it only needs to be applied seasonally and reduced the percentage cross‐sectional damage of the central cylinder, the damage parameter most closely related to yield, by 14%.     

Laboratory evaluation of lufenuron on immature stages of potato tuber moth (Lepidoptera: Gelechiidae)

The effects of the chitin synthesis inhibitor lufenuron against potato tuber moth, Phthorimaea operculella (Zeller), eggs were determined by topically exposing different age groups of eggs (1-4 d old) to treated potato tubers (Solanum tuberosum L.) under laboratory conditions. Larval hatch from both treated (4 and 12 g [AI]/100 liter) and untreated tubers was >95%, but mortality of first instars was high in treated tubers (>90%) compared with untreated tubers. Examination of the treated tubers showed that most of the larvae were unable to penetrate or cause any noticeable damage to the potato tubers. However, the few first instars that survived were able to penetrate the tubers and continue their development to the pupal or adult stages. At 12 g (AI)/100 liter, adult emergence was <2% and most of the emerged adults had morphological deformities such as reduced wing size and they were unable to free themselves from the pupal sacs. These data suggest that topical application of lufenuron to eggs before larval hatch would reduce the amount of damage caused by potato tuber moth as part of integrated pest management program.     

SILICA,NITROGEN AND PHOSPHORUS REQUIREMENTS OF SOME SOUTHERN AFRICAN DIATOMS

SUMMARY

The yield coefficients and minimum cell concentrations of silica, nitrogen and phosphorus have been determined for four diatoms, Navicula pell iculosa (Brébisson ex Kützing) Hilse, Nitzschia elliptica Hustedt, N. palea (Kützing) W. Smith and N. perpusilla Rabenhorst. It was found that the three Nitzschia species require more Si > N > P whereas the Navicula species needs more N > Si >P. Where possible the results are evaluated in terms of the morphological and ecological characteristics of these diatoms.     

Climate‐change impacts on sandy‐beach biota: crossing a line in the sand

Sandy ocean beaches are iconic assets that provide irreplaceable ecosystem services to society. Despite their great socioeconomic importance, beaches as ecosystems are severely under‐represented in the literature on climate‐change ecology. Here, we redress this imbalance by examining whether beach biota have been observed to respond to recent climate change in ways that are consistent with expectations under climate change. We base our assessments on evidence coming from case studies on beach invertebrates in South America and on sea turtles globally. Surprisingly, we find that observational evidence for climate‐change responses in beach biota is more convincing for invertebrates than for highly charismatic turtles. This asymmetry is paradoxical given the better theoretical understanding of the mechanisms by which turtles are likely to respond to changes in climate. Regardless of this disparity, knowledge of the unique attributes of beach systems can complement our detection of climate‐change impacts on sandy‐shore invertebrates to add rigor to studies of climate‐change ecology for sandy beaches. To this end, we combine theory from beach ecology and climate‐change ecology to put forward a suite of predictive hypotheses regarding climate impacts on beaches and to suggest ways that these can be tested. Addressing these hypotheses could significantly advance both beach and climate‐change ecology, thereby progressing understanding of how future climate change will impact coastal ecosystems more generally.     

γδ T Cells Are Required for Pulmonary IL-17A Expression after Ozone Exposure in Mice: Role of TNFα

Ozone is an air pollutant that causes pulmonary symptoms. In mice, ozone exposure causes pulmonary injury and increases bronchoalveolar lavage macrophages and neutrophils. We have shown that IL-17A is important in the recruitment of neutrophils after subacute ozone exposure (0.3 ppm for 24–72 h). We hypothesized that γδ T cells are the main producers of IL-17A after subacute ozone. To explore this hypothesis we exposed wildtype mice and mice deficient in γδ T cells (TCRδ^−/−) to ozone or room air. Ozone-induced increases in BAL macrophages and neutrophils were attenuated in TCRδ^−/− mice. Ozone increased the number of γδ T cells in the lungs and increased pulmonary Il17a mRNA expression and the number of IL-17A⁺ CD45⁺ cells in the lungs and these effects were abolished in TCRδ^−/− mice. Ozone-induced increases in factors downstream of IL-17A signaling, including G-CSF, IL-6, IP-10 and KC were also decreased in TCRδ^−/− versus wildtype mice. Neutralization of IL-17A during ozone exposure in wildtype mice mimicked the effects of γδ T cell deficiency. TNFR2 deficiency and etanercept, a TNFα antagonist, also reduced ozone-induced increases in Il17a mRNA, IL-17A⁺ CD45⁺ cells and BAL G-CSF as well as BAL neutrophils. TNFR2 deficient mice also had decreased ozone-induced increases in Ccl20, a chemoattractant for IL-17A⁺ γδ T cells. Il17a mRNA and IL-17A⁺ γδ T cells were also lower in obese Cpe^fat versus lean WT mice exposed to subacute ozone, consistent with the reduced neutrophil recruitment observed in the obese mice. Taken together, our data indicate that pulmonary inflammation induced by subacute ozone requires γδ T cells and TNFα-dependent recruitment of IL-17A⁺ γδ T cells to the lung.     

Validation of a simple and fast method to quantify in vitro mineralization with fluorescent probes used in molecular imaging of bone

Alizarin Red S staining is the standard method to indicate and quantify matrix mineralization during differentiation of osteoblast cultures. KS483 cells are multipotent mouse mesenchymal progenitor cells that can differentiate into chondrocytes, adipocytes and osteoblasts and are a well-characterized model for the study of bone formation. Matrix mineralization is the last step of differentiation of bone cells and is therefore a very important outcome measure in bone research. Fluorescently labelled calcium chelating agents, e.g. BoneTag and OsteoSense, are currently used for in vivo imaging of bone. The aim of the present study was to validate these probes for fast and simple detection and quantification of in vitro matrix mineralization by KS483 cells and thus enabling high-throughput screening experiments.     

Metabolic risks of neonates at birth following in utero exposure to HIV-ART: the amino acid profile of cord blood

Introduction

Untargeted metabolomics of cord blood indicated that antiretroviral therapy to HIV-infected mothers (HIV-ART) did not compromise the exposed neonates with regard to the stress of neonatal hypoglycaemia at birth. However, identified biomarkers reflected stress in their energy metabolism, raising concern over developmental risks in some newborns exposed to ART.

Objectives

This study addresses the concern over HIV-ART-induced metabolic perturbations by expanding the metabolomics study to the amino acid profiles in cord blood collected at birth from newborns either exposed or unexposed to HIV-ART in utero.

Methods

Amino acid profiles derived from liquid chromatographic triple quadruple spectra of cord blood from neonates exposed and unexposed to HIV-ART (cohort 1) were investigated using a metabolomics approach. Amino acid data, generated by ultra performance liquid chromatography–tandem mass spectrometry from similar cases (cohort 2), were included for comparison.

Results

Multivariate and supporting statistics indicated differentiation between the exposed and unexposed neonates in both cohorts, caused by a general decrease or downregulation of amino acid concentrations in the cord blood samples from the exposed cases. Specifically, significant upregulation of aspartic acid in both cohorts and downregulation of arginine, and of threonine, tryptophan and lysine in cohorts 1 and 2, respectively, were observed.

Conclusions

The benefits of ART for HIV-infected pregnant women are well established. However, the amino acid profile of cord blood, obtained from the two independent cohorts, adds to observed metabolic risks of in utero HIV-ART-exposed newborns. These risks could potentially have adverse consequences for the future health of some exposed infants.