85 research outputs found

    The effect of endogenous dopamine in rotenone-induced toxicity in PC12 cells

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    Deficiencies in Complex I have been observed in Parkinson's disease (PD) patients. Systemic exposure to rotenone, a Complex I inhibitor, has been shown to lead to selective dopaminergic cell death in vivo and toxicity in many in vitro models, including dopaminergic cell cultures. However, it remains unclear why rotenone seems to affect dopaminergic cells more adversely. Therefore, the role of dopamine (DA) in rotenone-induced PC12 cell toxicity was examined. Rotenone (1.0 μM) caused significant toxicity in differentiated PC12 cells, which was accompanied by decreases in ATP levels, changes in catechol levels, and increased DA oxidation. To determine whether endogenous DA makes PC12 cells more susceptible to rotenone, cells were treated with the tyrosine hydroxylase inhibitor α-methyl-p-tyrosine (AMPT) to reduce DA levels prior to rotenone exposure, and then cell viability was measured. No changes in rotenone-induced toxicity were observed with or without AMPT treatment. However, a potentiation of toxicity was observed following coexposure of PC12 cells to rotenone and methamphetamine. To determine whether this effect was due to DA, PC12 cells were depleted of DA prior to methamphetamine and rotenone cotreatment, resulting in a large attenuation in toxicity. These findings suggest that DA plays a role in rotenone-induced toxicity and possibly the vulnerability of DA neurons in PD

    Efficacy of coping mechanisms used during COVID-19 as reported by parents of children with autism

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    The COVID-19 pandemic’s alterations to daily life have been especially challenging for families with Autism Spectrum Disorder (ASD), worsening the core features of ASD and overall mental health. With the increased need for effective coping, the current retrospective study used data from a survey regarding parent reports of how often their child with ASD used certain coping strategies (frequency), as well as the extent to which they felt their child benefitted from their use (efficacy) in mitigating stress during the pandemic. This retrospective study Repeated measures ANOVAs were conducted to evaluate whether there were significant differences in both frequency and efficacy ratings for each coping strategy, for the entire sample as well as for three children’s age groups. Using Spearman’s rank-order correlations, correlation coefficients between the frequency and efficacy of each coping strategy were explored. Results revealed that maladaptive strategies were used more frequently than adaptive strategies, while parent routine as the most frequently used and efficacious for all age groups. Additionally, for adaptive strategies, humor and focusing on the positive had the strongest correlations between frequency and efficacy ratings amongst all age groups. Of the maladaptive strategies, repetitive behaviors, rumination, and isolation had the strongest correlations for the youngest, middle, and oldest age groups, respectively. Further, for each age group, the adaptive coping strategies had stronger correlations between frequency and efficacy than the maladaptive ones. It is our hope that the results of this study will lay the foundation for developing adaptive coping strategies to alleviate stress in children with ASD. Further investigations using a larger cohort are warranted to determine effective coping strategies for individuals with ASD across a range of situations, including acute stressors (such as future public health emergencies and natural disasters), as well as common daily stressors

    The relationship between tumour T-lymphocyte infiltration, the systemic inflammatory response and survival in patients undergoing curative resection for colorectal cancer

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    There is increasing evidence that both local and systemic inflammatory responses play an important role in the progression of a variety of common solid tumours. The aim of the present study was to examine the relationship between tumour T-lymphocyte subset infiltration, the systemic inflammatory response and cancer-specific survival in patients with colorectal cancer. In all, 147 patients undergoing potentially curative resection for colorectal cancer were studied. Circulating concentrations of C-reactive protein were measured prior to surgery. CD4+ and CD8+ T-lymphocyte infiltration of the tumour was assessed using immunohistochemistry and a point counting technique. When patients were grouped according to the percentage tumour volume of CD4+ T-lymphocytes, there was no difference in terms of age, sex, tumour site, stage and tumour characteristics. However, there was an inverse relationship between percentage tumour CD4+ T-lymphocytes and C-reactive protein (P<0.01). On univariate analysis, both C-reactive protein concentrations (P<0.001) and percentage tumour volume of CD4+ (P<0.05) T-lymphocytes were associated with cancer-specific survival. The results of the present study show that low tumour CD4+ T-lymphocyte infiltration is associated with elevated C-reactive protein concentrations and both predict poor cancer-specific survival

    Biomarker selection for detection of occult tumour cells in lymph nodes of colorectal cancer patients using real-time quantitative RT–PCR

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    Accurate identification of lymph node involvement is critical for successful treatment of patients with colorectal carcinoma (CRC). Real-time quantitative RT–PCR with a specific probe and RNA copy standard for biomarker mRNA has proven very powerful for detection of disseminated tumour cells. Which properties of biomarker mRNAs are important for identification of disseminated CRC cells? Seven biomarker candidates, CEA, CEACAM1-S/L, CEACAM6, CEACAM7-1/2, MUC2, MMP7 and CK20, were compared in a test-set of lymph nodes from 51 CRC patients (Dukes' A–D) and 10 controls. Normal colon epithelial cells, primary tumours, and different immune cells were also analysed. The biomarkers were ranked according to: (1) detection of haematoxylin/eosin positive nodes, (2) detection of Dukes' A and B patients, who developed metastases during a 54 months follow-up period and (3) identification of patients with Dukes' C and D tumours using the highest value of control nodes as cutoff. The following properties appear to be of importance; (a) no expression in immune cells, (b) relatively high and constant expression in tumour tissue irrespective of Dukes' stage and (c) no or weak downregulation in tumours compared to normal tissue. CEA fulfilled these criteria best, followed by CK20 and MUC2

    Combined effects of precipitation and nitrogen deposition on native and invasive winter annual production in California deserts

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    Primary production in deserts is limited by soil moisture and N availability, and thus is likely to be influenced by both anthropogenic N deposition and precipitation regimes altered as a consequence of climate change. Invasive annual grasses are particularly responsive to increases in N and water availabilities, which may result in competition with native forb communities. Additionally, conditions favoring increased invasive grass production in arid and semi-arid regions can increase fire risk, negatively impacting woody vegetation that is not adapted to fire. We conducted a seeded garden experiment and a 5-year field fertilization experiment to investigate how winter annual production is altered by increasing N supply under a range of water availabilities. The greatest production of invasive grasses and native forbs in the garden experiment occurred under the highest soil N (inorganic N after fertilization = 2.99 g m−2) and highest watering regime, indicating these species are limited by both water and N. A classification and regression tree (CART) analysis on the multi-year field fertilization study showed that winter annual biomass was primarily limited by November–December precipitation. Biomass exceeded the threshold capable of carrying fire when inorganic soil N availability was at least 3.2 g m−2 in piñon-juniper woodland. Due to water limitation in creosote bush scrub, biomass exceeded the fire threshold only under very wet conditions regardless of soil N status. The CART analyses also revealed that percent cover of invasive grasses and native forbs is primarily dependent on the timing and amount of precipitation and secondarily dependent on soil N and site-specific characteristics. In total, our results indicate that areas of high N deposition will be susceptible to grass invasion, particularly in wet years, potentially reducing native species cover and increasing the risk of fire

    Role of Human-Mediated Dispersal in the Spread of the Pinewood Nematode in China

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    Background: Intensification of world trade is responsible for an increase in the number of alien species introductions. Human-mediated dispersal promotes not only introductions but also expansion of the species distribution via long-distance dispersal. Thus, understanding the role of anthropogenic pathways in the spread of invading species has become one of the most important challenges nowadays. Methodology/Principal Findings: We analysed the invasion pattern of the pinewood nematode in China based on invasion data from 1982 to 2005 and monitoring data on 7 locations over 15 years. Short distance spread mediated by long-horned beetles was estimated at 7.5 km per year. Infested sites located further away represented more than 90% of observations and the mean long distance spread was estimated at 111–339 km. Railways, river ports, and lakes had significant effects on the spread pattern. Human population density levels explained 87% of the variation in the invasion probability (P,0.05).Since 2001, the number of new records of the nematode was multiplied by a factor of 5 and the spread distance by a factor of 2. We combined a diffusion model to describe the short distance spread with a stochastic,individual based model to describe the long distance jumps. This combined model generated an error of only 13% when used to predict the presence of the nematode. Under two climate scenarios (stable climate or moderate warming), projections of the invasion probability suggest that this pest could expand its distribution 40–55% by 2025. Conclusions/Significance: This study provides evidence that human-induced dispersal plays a fundamental role in the spread of the pinewood nematode, and appropriate control measures should be taken to stop or slow its expansion. This model can be applied to Europe, where the nematode had been introduced later, and is currently expanding its distribution. Similar models could also be derived for other species that could be accidentally transported by humans

    Climate Change and the Potential Distribution of an Invasive Shrub, Lantana camara L

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    The threat posed by invasive species, in particular weeds, to biodiversity may be exacerbated by climate change. Lantana camara L. (lantana) is a woody shrub that is highly invasive in many countries of the world. It has a profound economic and environmental impact worldwide, including Australia. Knowledge of the likely potential distribution of this invasive species under current and future climate will be useful in planning better strategies to manage the invasion. A process-oriented niche model of L. camara was developed using CLIMEX to estimate its potential distribution under current and future climate scenarios. The model was calibrated using data from several knowledge domains, including phenological observations and geographic distribution records. The potential distribution of lantana under historical climate exceeded the current distribution in some areas of the world, notably Africa and Asia. Under future scenarios, the climatically suitable areas for L. camara globally were projected to contract. However, some areas were identified in North Africa, Europe and Australia that may become climatically suitable under future climates. In South Africa and China, its potential distribution could expand further inland. These results can inform strategic planning by biosecurity agencies, identifying areas to target for eradication or containment. Distribution maps of risk of potential invasion can be useful tools in public awareness campaigns, especially in countries that have been identified as becoming climatically suitable for L. camara under the future climate scenarios

    Remote detection of invasive alien species

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    The spread of invasive alien species (IAS) is recognized as the most severe threat to biodiversity outside of climate change and anthropogenic habitat destruction. IAS negatively impact ecosystems, local economies, and residents. They are especially problematic because once established, they give rise to positive feedbacks, increasing the likelihood of further invasions and spread. The integration of remote sensing (RS) to the study of invasion, in addition to contributing to our understanding of invasion processes and impacts to biodiversity, has enabled managers to monitor invasions and predict the spread of IAS, thus supporting biodiversity conservation and management action. This chapter focuses on RS capabilities to detect and monitor invasive plant species across terrestrial, riparian, aquatic, and human-modified ecosystems. All of these environments have unique species assemblages and their own optimal methodology for effective detection and mapping, which we discuss in detail

    Glucose sensing in the pancreatic beta cell: a computational systems analysis

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