Ecological impacts of small dams on South African rivers Part 1: Drivers of change – water quantity and quality

Impacts of large dams are well-known and quantifiable, while small dams have generally been perceived as benign, both socially and environmentally. The present study quantifies the cumulative impacts of small dams on the water quality (physico-chemistry and invertebrate biotic indices) and quantity (discharge) of downstream rivers in 2 South African regions. The information from 2 South African national databases was used for evaluating the cumulative impacts on water quality and quantity. Physico-chemistry and biological data were obtained from the River Health Programme, and discharge data at stream flow gauges was obtained from the Hydrological Information System. Multivariate analyses were conducted to establish broad patterns for cumulative impacts of small dams across the 2 regions – Western Cape (winter rainfall, temperate, south-western coast) and Mpumalanga (summer rainfall, tropical, eastern coast). Multivariate analyses found that the changes in macroinvertebrate indices and the stream’s physico-chemistry were more strongly correlated with the density of small dams in the catchment (as a measure of cumulative impact potential) relative to the storage capacity of large dams. T-tests on the data, not including samples with upstream large dams, indicated that the high density of small dams significantly reduced low flows and increased certain physico-chemistry variables (particularly total dissolved salts) in both the regions, along with associated significant reductions in a macroinvertebrate index (SASS4 average score per taxon). Regional differences were apparent in the results for discharge reductions and the macroinvertebrate index. The results suggest that the cumulative effect of a high number of small dams is impacting the quality and quantity of waters in South African rivers and that these impacts need to be systematically incorporated into the monitoring protocol of the environmental water requirements. Keywords: cumulative impacts, regional comparison, macroinvertebrate indices, measures of small-dam impact potential, average score per taxo

Ecological impacts of small dams on South African rivers Part 2: Biotic response – abundance and composition of macroinvertebrate communities

This paper investigates the cumulative impacts of small dams on invertebrate communities in 2 regions of South Africa – the Western Cape and Mpumalanga. Previous research found reduced discharge, increased total dissolved salts, and a decrease in average score per taxon (ASPT; collected using SASS4 methods) at sites with high density of small dams in their catchment. These changes in ASPT are investigated using the invertebrate abundance data available in the River Health Programme. Multivariate analyses found differences in invertebrate communities in rivers with high densities of small dams in their catchment in foothill-gravel streams (in both Western Cape and Mpumalanga) and in foothill-cobble streams (in Western Cape only). Opportunistic taxa that are tolerant of pollution, and capable of exploiting various habitats, and those that prefer slower currents increased in numbers, while other taxa that are sensitive to pollution and disturbance declined in numbers. Some regional differences were noted possibly reflecting climatic differences between the regions. Since the results of this study are correlative, it highlights the need for a systematic (by sites and seasons) and detailed (at species level) collection of data to verify the results of cumulative effects of small dams. This can further the development of a framework for small-dam construction and management that will limit their impact on river catchments. Keywords: cumulative impacts, reduced low flows, environmental water quality, Ephemeroptera, Trichopter

The use of liver histopathology, lipid peroxidation and acetylcholinesterase assays as biomarkers of contaminant-induced stress in the Cape stumpnose, Rhabdosargus holubi (Teleostei: Sparidae), from selected South African estuaries

Three biomarkers of contaminant-induced stress (liver histopathology, the lipid peroxidation (LPx) assay and the acetylcholinesterase (AChE) assay) were adapted for application to the estuarine-dependent marine fish Rhabdosargus holubi (Steindachner, 1881). Specimens of R. holubi were collected using a seine net from 3 temporarily open/closed estuaries in the Eastern Cape, South Africa, each impacted by different anthropogenic activities. The East Kleinemonde estuary has a housing settlement on the banks in the lower reaches and some agriculture in its catchment. The Old Woman’s estuary has a golf course adjacent to its lower and middle reaches and is crossed by a national road in its upper reaches. The Mtana estuary is virtually pristine, with limited cattle grazing occurring along the banks of the estuary and some subsistence agriculture in the catchment. According to the biomarker results from this study, R. holubi from the East Kleinemonde were in good health, as reflected by low LPx and high AChE levels. The liver histopathology did, however, suggest possible previous exposure to stress (increased melanomacrophage centres, increased perivascular connective tissue and severe vacuolation). Overall, liver histopathology results did not differ significantly between estuaries. Fish from the Old Womans recorded significantly inhibited AChE and increased LPx, while fish from the Mtana exhibited significantly increased LPx only, suggesting possible exposure to anticholinesterase contaminants in the former estuary and some form of oxidative stress in the latter. Although water samples were collected from each of the 3 estuaries and analysed for polychlorinated biphenyls, organochlorines, organophosphorous pesticides and pyrethroids, none of these chemicals were detected. Aspesticide residues in water are highly variable, both temporally and spatially, future studies should focus on measuring tissue burdens of organisms in order to identify the contaminant stressor. This study has shown that while chemical analyses of water provide a ‘snap-shot’ of water quality at the time of sampling, biomonitoring can integrate past exposures to stress and is thus useful for identifying potential situations of concern that require further detailed investigation.Keywords: biomonitoring, pollution, estuaries, AChE, LPx, histopatholog

The ErbB2ΔEx16 splice variant is a major oncogenic driver in breast cancer that promotes a pro-metastatic tumor microenvironment.

Amplification and overexpression of erbB2/neu proto-oncogene is observed in 20-30% human breast cancer and is inversely correlated with the survival of the patient. Despite this, somatic activating mutations within erbB2 in human breast cancers are rare. However, we have previously reported that a splice isoform of erbB2, containing an in-frame deletion of exon 16 (herein referred to as ErbB2ΔEx16), results in oncogenic activation of erbB2 because of constitutive dimerization of the ErbB2 receptor. Here, we demonstrate that the ErbB2ΔEx16 is a major oncogenic driver in breast cancer that constitutively signals from the cell surface. We further show that inducible expression of the ErbB2ΔEx16 variant in mammary gland of transgenic mice results in the rapid development of metastatic multifocal mammary tumors. Genetic and biochemical characterization of the ErbB2ΔEx16-derived mammary tumors exhibit several unique features that distinguish this model from the conventional ErbB2 ones expressing the erbB2 proto-oncogene in mammary epithelium. Unlike the wild-type ErbB2-derived tumors that express luminal keratins, ErbB2ΔEx16-derived tumors exhibit high degree of intratumoral heterogeneity co-expressing both basal and luminal keratins. Consistent with these distinct pathological features, the ErbB2ΔEx16 tumors exhibit distinct signaling and gene expression profiles that correlate with activation of number of key transcription factors implicated in breast cancer metastasis and cancer stem cell renewal

Use of the ODD-Luciferase Transgene for the Non-Invasive Imaging of Spontaneous Tumors in Mice

In humans, imaging of tumors provides rapid, accurate assessment of tumor growth and location. In laboratory animals, however, the imaging of spontaneously occurring tumors continues to pose many technical and logistical problems. Recently a mouse model was generated in which a chimeric protein consisting of HIF-1α oxygen-dependent degradation domain (ODD) fused to luciferase was ubiquitously expressed in all tissues. Hypoxic stress leads to the accumulation of ODD-luciferase in the tissues of this mouse model which can be identified by non-invasive bioluminescence measurement. Since solid tumors often contain hypoxic regions, we performed proof-of-principle experiments testing whether this transgenic mouse model may be used as a universal platform for non-invasive imaging analysis of spontaneous solid tumors.ODD-luciferase transgenic mice were bred with MMTV-neu/beclin1+/- mice. Upon injection of luciferin, bioluminescent background of normal tissues in the transgenic mice and bioluminescent signals from spontaneously mammary carcinomas were measured non-invasively with an IVIS Spectrum imaging station. Tumor volumes were measured manually and the histology of tumor tissues was analyzed.Our results show that spontaneous mammary tumors in ODD-luciferase transgenic mice generate substantial bioluminescent signals, which are clearly discernable from background tissue luminescence. Moreover, we demonstrate a strong quantitative correlation between the bioluminescent tumor contour and the volume of palpable tumors. We further demonstrate that shrinkage of the volume of spontaneous tumors in response to chemotherapeutic treatment can be determined quantitatively using this system. Finally, we show that the growth and development of spontaneous tumors can be monitored longitudinally over several weeks. Thus, our results suggest that this model could potentially provide a practical, reliable, and cost-effective non-invasive quantitative method for imaging spontaneous solid tumors in mice

Specific involvement of atypical PKCζ/PKMζ in spinal persistent nociceptive processing following peripheral inflammation in rat.

BACKGROUND: Central sensitization requires the activation of various intracellular signalling pathways within spinal dorsal horn neurons, leading to a lowering of activation threshold and enhanced responsiveness of these cells. Such plasticity contributes to the manifestation of chronic pain states and displays a number of features of long-term potentiation (LTP), a ubiquitous neuronal mechanism of increased synaptic strength. Here we describe the role of a novel pathway involving atypical PKCζ/PKMζ in persistent spinal nociceptive processing, previously implicated in the maintenance of late-phase LTP. RESULTS: Using both behavioral tests and in vivo electrophysiology in rats, we show that inhibition of this pathway, via spinal delivery of a myristoylated protein kinase C-ζ pseudo-substrate inhibitor, reduces both pain-related behaviors and the activity of deep dorsal horn wide dynamic range neurons (WDRs) following formalin administration. In addition, Complete Freund's Adjuvant (CFA)-induced mechanical and thermal hypersensitivity was also reduced by inhibition of PKCζ/PKMζ activity. Importantly, this inhibition did not affect acute pain or locomotor behavior in normal rats and interestingly, did not inhibited mechanical allodynia and hyperalgesia in neuropathic rats. Pain-related behaviors in both inflammatory models coincided with increased phosphorylation of PKCζ/PKMζ in dorsal horn neurons, specifically PKMζ phosphorylation in formalin rats. Finally, inhibition of PKCζ/PKMζ activity decreased the expression of Fos in response to formalin and CFA in both superficial and deep laminae of the dorsal horn. CONCLUSIONS: These results suggest that PKCζ, especially PKMζ isoform, is a significant factor involved in spinal persistent nociceptive processing, specifically, the manifestation of chronic pain states following peripheral inflammation

Effects of Aliskiren on Stroke in Rats Expressing Human Renin and Angiotensinogen Genes

OBJECTIVE: Pre-treatment with angiotensin receptor blockers is known to improve neurological outcome after stroke. This study investigated for the first time, whether the renin inhibitor aliskiren has similar neuroprotective effects. METHODS: Since aliskiren specifically blocks human renin, double transgenic rats expressing human renin and angiotensinogen genes were used. To achieve a systolic blood pressure of 150 or 130 mmHg animals were treated with aliskiren (7.5 or 12.5 mg/kg*d) or candesartan (1.5 or 10 mg/kg*d) via osmotic minipump starting five days before middle cerebral artery occlusion with reperfusion. Infarct size was determined by magnetic resonance imaging. mRNA of inflammatory marker genes was studied in different brain regions. RESULTS: The mortality of 33.3% (7 of 21 animals) in the vehicle group was reduced to below 10% by treatment with candesartan or aliskiren (p<0.05). Aliskiren-treated animals had a better neurological outcome 7 days post-ischemia, compared to candesartan (Garcia scale: 9.9±0.7 vs. 7.3±0.7; p<0.05). The reduction of infarct size in the aliskiren group did not reach statistical significance compared to candesartan and vehicle (24 h post-ischemia: 314±81 vs. 377±70 and 403±70 mm(3) respectively). Only aliskiren was able to significantly reduce stroke-induced gene expression of CXC chemokine ligand 1, interleukin-6 and tumor necrosis factor-alpha in the ischemic core. CONCLUSIONS: Head-to-head comparison suggests that treatment with aliskiren before and during cerebral ischemia is at least as effective as candesartan in double transgenic rats. The improved neurological outcome in the aliskiren group was blood pressure independent. Whether this effect is due to primary anti-inflammatory mechanisms has to be investigated further