Relationships between the Seasonal Variations of Macroinvertebrates, and Land Uses for Biomonitoring in the Xitiaoxi River Watershed, China

The impacts of differences in watershed land uses, and differences in seasonality on benthic macroinvertebrate communities, were evaluated in 12 stream sites within the Xitiaoxi River watershed, China, from April 2009 to January 2010. The composition of macroinvertebrate community differed significantly among three land use types. Forested sites were characterized by high taxa richness, diversity and the benthic‐index of biotic integrity (B‐IBI), while farmland and urban disturbed stream sites presented contrary patterns. The percentage of urban land use, conductivity, dissolved oxygen, ammonia nitrogen and total phosphorus were the major drivers for the variations. The land use related water quality stress gradients of the four sampling seasons were determined by means of four independent Principal Component Analyses. The responses of macroinvertebrate community metrics, to anthropogenic stressors, were explored using Spearman Rank Correlation analyses. All the selected metrics, including total numbers of taxa, numbers of Ephemeroptera, Plecoptera and Trichoptera taxa, percentage of non‐insect abundance, percentage of scrapers abundance, Pielou’s evenness index, Simpson diversity index, and the Benthic Index of Biotic Integrity were correlated significantly with environmental gradients (PC1) in autumn. In other seasons such correlations were less pronounced. Our results imply that autumn is the optimal time to sample macroinvertebrate communities, and to conduct water quality biomonitoring in this subtropical watershed. (© 2012 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/92105/1/184_ftp.pd

Quantitative cross-species extrapolation between humans and fish: The case of the anti-depressant fluoxetine

This article has been made available through the Brunel Open Access Publishing Fund.Fish are an important model for the pharmacological and toxicological characterization of human pharmaceuticals in drug discovery, drug safety assessment and environmental toxicology. However, do fish respond to pharmaceuticals as humans do? To address this question, we provide a novel quantitative cross-species extrapolation approach (qCSE) based on the hypothesis that similar plasma concentrations of pharmaceuticals cause comparable target-mediated effects in both humans and fish at similar level of biological organization (Read-Across Hypothesis). To validate this hypothesis, the behavioural effects of the anti-depressant drug fluoxetine on the fish model fathead minnow (Pimephales promelas) were used as test case. Fish were exposed for 28 days to a range of measured water concentrations of fluoxetine (0.1, 1.0, 8.0, 16, 32, 64 μg/L) to produce plasma concentrations below, equal and above the range of Human Therapeutic Plasma Concentrations (HTPCs). Fluoxetine and its metabolite, norfluoxetine, were quantified in the plasma of individual fish and linked to behavioural anxiety-related endpoints. The minimum drug plasma concentrations that elicited anxiolytic responses in fish were above the upper value of the HTPC range, whereas no effects were observed at plasma concentrations below the HTPCs. In vivo metabolism of fluoxetine in humans and fish was similar, and displayed bi-phasic concentration-dependent kinetics driven by the auto-inhibitory dynamics and saturation of the enzymes that convert fluoxetine into norfluoxetine. The sensitivity of fish to fluoxetine was not so dissimilar from that of patients affected by general anxiety disorders. These results represent the first direct evidence of measured internal dose response effect of a pharmaceutical in fish, hence validating the Read-Across hypothesis applied to fluoxetine. Overall, this study demonstrates that the qCSE approach, anchored to internal drug concentrations, is a powerful tool to guide the assessment of the sensitivity of fish to pharmaceuticals, and strengthens the translational power of the cross-species extrapolation

Successful Inhibition of Tumor Development by Specific Class-3 Semaphorins Is Associated with Expression of Appropriate Semaphorin Receptors by Tumor Cells

The class-3 semaphorins (sema3s) include seven family members. Six of them bind to neuropilin-1 (np1) or neuropilin-2 (np2) receptors or to both, while the seventh, sema3E, binds to the plexin-D1 receptor. Sema3B and sema3F were previously characterized as tumor suppressors and as inhibitors of tumor angiogenesis. To determine if additional class-3 semaphorins such as sema3A, sema3D, sema3E and sema3G possess anti-angiogenic and anti-tumorigenic properties, we expressed the recombinant full length semaphorins in four different tumorigenic cell lines expressing different combinations of class-3 semaphorin receptors. We show for the first time that sema3A, sema3D, sema3E and sema3G can function as potent anti-tumorigenic agents. All the semaphorins we examined were also able to reduce the concentration of tumor associated blood vessels although the potencies of the anti-angiogenic effects varied depending on the tumor cell type. Surprisingly, there was little correlation between the ability to inhibit tumor angiogenesis and their anti-tumorigenic activity. None of the semaphorins inhibited the adhesion of the tumor cells to plastic or fibronectin nor did they modulate the proliferation of tumor cells cultured in cell culture dishes. However, various semaphorins were able to inhibit the formation of soft agar colonies from tumor cells expressing appropriate semaphorin receptors, although in this case too the inhibitory effect was not always correlated with the anti-tumorigenic effect. In contrast, the anti-tumorigenic effect of each of the semaphorins correlated very well with tumor cell expression of specific signal transducing receptors for particular semaphorins. This correlation was not broken even in cases in which the tumor cells expressed significant concentrations of endogenous semaphorins. Our results suggest that combinations of different class-3 semaphorins may be more effective than single semaphorins in cases in which tumor cells express more than one type of semaphorin receptors

Misbehaviour of XIST RNA in Breast Cancer Cells

A role of X chromosome inactivation process in the development of breast cancer have been suggested. In particular, the relationship between the breast cancer predisposing gene BRCA1 and XIST, the main mediator of X chromosome inactivation, has been intensely investigated, but still remains controversial. We investigated this topic by assessing XIST behaviour in different groups of breast carcinomas and in a panel of breast cancer cell lines both BRCA1 mutant and wild type. In addition, we evaluated the occurrence of broader defects of heterochromatin in relation to BRCA1 status in breast cancer cells. We provide evidence that in breast cancer cells BRCA1 is involved in XIST regulation on the active X chromosome, but not in its localization as previously suggested, and that XIST can be unusually expressed by an active X and can decorate it. This indicates that the detection of XIST cloud in cancer cell is not synonymous of the presence of an inactive X chromosome. Moreover, we show that global heterochromatin defects observed in breast tumor cells are independent of BRCA1 status. Our observations sheds light on a possible previously uncharacterized mechanism of breast carcinogenesis mediated by XIST misbehaviour, particularly in BRCA1-related cancers. Moreover, the significant higher levels of XIST-RNA detected in BRCA1-associated respect to sporadic basal-like cancers, opens the possibility to use XIST expression as a marker to discriminate between the two groups of tumors

A PKC-Dependent Recruitment of MMP-2 Controls Semaphorin-3A Growth-Promoting Effect in Cortical Dendrites

There is increasing evidence for a crucial role of proteases and metalloproteinases during axon growth and guidance. In this context, we recently described a functional link between the chemoattractive Sema3C and Matrix metalloproteinase 3 (MMP3). Here, we provide data demonstrating the involvement of MMP-2 to trigger the growth-promoting effect of Sema3A in cortical dendrites. The in situ analysis of MMP-2 expression and activity is consistent with a functional growth assay demonstrating in vitro that the pharmacological inhibition of MMP-2 reduces the growth of cortical dendrites in response to Sema3A. Hence, our results suggest that the selective recruitment and activation of MMP-2 in response to Sema3A requires a PKC alpha dependent mechanism. Altogether, we provide a second set of data supporting MMPs as effectors of the growth-promoting effects of semaphorins, and we identify the potential signalling pathway involved

A cluster randomised trial of a telephone-based intervention for parents to increase fruit and vegetable consumption in their 3- to 5-year-old children: study protocol

Background: Inadequate fruit and vegetable consumption in childhood increases the risk of developing chronic disease. Despite this, a substantial proportion of children in developed nations, including Australia, do not consume sufficient quantities of fruits and vegetables. Parents are influential in the development of dietary habits of young children but often lack the necessary knowledge and skills to promote healthy eating in their children. The aim of this study is to assess the efficacy of a telephone-based intervention for parents to increase the fruit and vegetable consumption of their 3- to 5-year-old children. Methods/Design: The study, conducted in the Hunter region of New South Wales, Australia, employs a cluster randomised controlled trial design. Two hundred parents from 15 randomly selected preschools will be randomised to receive the intervention, which consists of print resources and four weekly 30-minute telephone support calls delivered by trained telephone interviewers. The calls will assist parents to increase the availability and accessibility of fruit and vegetables in the home, create supportive family eating routines and role-model fruit and vegetable consumption. A further two hundred parents will be randomly allocated to the control group and will receive printed nutrition information only. The primary outcome of the trial will be the change in the child's consumption of fruit and vegetables as measured by the fruit and vegetable subscale of the Children's Dietary Questionnaire. Pre-intervention and post-intervention parent surveys will be administered over the telephone. Baseline surveys will occur one to two weeks prior to intervention delivery, with follow-up data collection calls occurring two, six, 12 and 18 months following baseline data collection. Discussion: If effective, this telephone-based intervention may represent a promising public health strategy to increase fruit and vegetable consumption in childhood and reduce the risk of subsequent chronic disease. Trial registration: Australian Clinical Trials Registry ACTRN12609000820202