Ichthyological Bulletin of the J.L.B. Smith Institute of Ichthyology; No. 57

The recruitment of juvenile marine fishes into the Knysna and Swartvlei estuaries was monitored over 30 months using seine, scoop and cast nets. The relative abundance, seasonality and growth of the dominant species are presented, and includes the Cape stumpnose Rhabdosargus holubi, white steenbras Lithognathus lithognathus, blacktail Diplodus sargus, strepie Sarpa salpa, Cape moony Monodactylus falciformis, southern mullet Liza richardsonii, groovy mullet Liza dumerilii, striped mullet Liza tricuspidens, flathead mullet Mugil cephalus, freshwater mullet Myxus capensis and leervis Lichia amia. Information on a further 12 species is also provided. Recruitment of most fish species into the Swartvlei and Knysna estuaries reaches a peak during summer, which coincides with maximum food resource availability and corresponds to the time when systems along this section of the coast are often open to the sea. Artificial winter breaching of the Swartvlei mouth has occurred in the past, and has generally led to the premature closure of the system and loss of the ‘head’ of water needed for the summer opening. This type of mouth manipulation leads to reduced availability of estuarine nursery areas for marine fishes along the southern Cape coast. Comparisons between the recruitment of juvenile fishes into the Knysna and Swartvlei estuaries indicate that higher densities of most species were recorded in the former system. This is attributed mainly to the fact that the Knysna mouth is deep, permanently open, and has a strong marine influence when compared to the shallow, narrow and seasonally closed Swartvlei mouth. However, in a regional context both Knysna and Swartvlei are large, unpolluted systems, which serve as important nursery areas for many species of fish. On this basis alone, these contrasting estuarine systems should be allocated the highest possible conservation status.Rhodes University Libraries (Digitisation

Ichthyological Bulletin J.L.B. Smith Institute of Ichthyology; No. 64

The fishes of three small Natal estuaries, the Mhlanga, Damba and Zotsha were sampled over a period of two years. A total of 68 fish taxa representing 24 families, 39 genera and 55 species were captured during this study. Forty seven fish taxa were recorded in the Mhlanga estuary of which Gilchristella aestuaria, Oreochromis mossambicus, Valamugil cunnesius, Valamugil sp. and juvenile mugilids numerically dominated. In terms of biomass, O. mossambicus, V. cunnesius, Liza alata, Myxus capensis and Mugil cephalus dominated the ichthyofauna of the Mhlanga system. In the Damba estuary, 24 fish taxa were recorded, the most abundant being Glossogobius callidus,M. capensis and 0. mossambicus. M. capensis, M. cephalus, O. mossambicus and G. callidus dominated the fish biomass captured in the Damba system. A total of 56 fish taxa were recorded in the Zotsha estuary during this study, with the ichthyofauna numerically dominated by juvenile mugilids, G. aestuaria, O. mossambicus, Rhabdosargus holubi, Terapon jarbua, Ambassis productus and G. callidus. The species which dominated the fish biomass in the Zotsha system were 0. mossambicus L. alata, Valamugil robustus, V. buchanani, M. capensis, M. cephalus and V. cunnesius. Classifying the species according to whether they were resident estuarine, freshwater, estuarine-dependent marine or marine species revealed that the first three groups were all well represented in the systems. Oreochromis mossambicus was the dominant freshwater species in all three estuaries. Gilchristella aestuaria and Glossogobius callidus were the principal estuarine species in the Mhlanga and the Damba respectively, with G. aestuaria, A. productus and G. callidus being the dominant estuarine species captured in the Zotsha. The principal estuarine-dependent marine fishes captured in the Mhlanga were V. cunnesius, Valamugil sp., juvenile mugilids, M. capensis, M. cephalus and L. alata. In the Damba, M. capensis and M. cephalus were the dominant estuarine-dependent marine species and in the Zotsha juvenile mugilids, R. holubi, T. jarbua, M. capensis, V. cunnesius, V. robustus, M. cephalus, L. alata and V. buchanani were the principal estuarine-dependent marine species. The results of this study indicate that the estuaries are dominated at different periods by different assemblages of fishes. This is linked to the spawning and migration patterns of the various species as well as the hydrological regime of each estuary. During the winter these systems are normally closed with relatively deep waters and high food resource and habitat availability. Freshwater and estuarine species mainly inhabit the upper reaches of the systems while estuarine-dependent marine species, which dominate the fish community, mainly occupy the middle and lower reaches. When these estuaries open with the onset of the spring/summer rains, adult and sub-adult estuarine-dependent marine species emigrate to the marine environment and juveniles begin recruiting into the systems. Spring is also the peak breeding period of resident estuarine and freshwater species, resulting in an increase in the contribution of these fishes to the overall ichthyofauna during this period. When closed estuaries open the water level falls and this results in the fishes concentrating in the lower reaches of the system where moderate water depths are present, thus further contributing to an increase in the proportion of freshwater and estuarine species in this region. The breaching of closed estuaries also results in a reduction in food resources and habitat availability. Competition and possible increased vulnerability to avian predation (due to the shallow nature of the systems), may contribute to a decrease in the proportion of estuarine and freshwater species in summer. The prolonged recruitment of Of-juveniles of estuarine-dependent marine species results in an increase in the proportion of these fishes present in the estuaries during summer. In autumn, the systems normally close, water levels rise and available food resources and habitat increase. This allows the redistribution of freshwater and estuarine species upstream, leaving estuarine-dependent marine species to dominate the middle and lower reaches. Although temporarily open/closed estuaries along the Natal coast may not be as diverse as permanently open estuaries in terms of their ichthyofauna, their importance must not be underestimated, since by providing a series of sheltered habitats along the coast they may contribute significantly to the viability of estuarine-dependent marine fish stocks.Rhodes University Libraries (Digitisation

Biological responses to a resumption in river flow in a freshwaterdeprived, permanently open Southern African estuary

The Kariega Estuary is a freshwater-deprived system due to numerous impoundments in the catchment. This system has had little or no horizontal salinity gradient over the last 15 years, with hypersaline conditions sometimes predominating in the upper reaches. Following high rainfall events in the catchment during the spring of 2006, including a flood event (approximate 1:10 year) in August 2006, a series of riverine pulses entered the estuary and a horizontal salinity gradient was established. This study examined the influence of this freshwater pulse on four components of the biota within the estuary, namely the zooplankton, and larval, littoral and demersal fishes. The study demonstrated that in three of these components elevated densities were recorded following the riverine input, with only the littoral fishes retaining an almost constant density. In addition, changes in the relative contributions of the estuarine utilisation classes for all three fish groups examined indicated that freshwater input into these systems positively influences the abundances. This has significant implications for water managers as it demonstrates the importance of an Ecological Reserve (defined as ‘the water required to protect the aquatic ecosystems of the water resource’) for this system.Keywords: biotic response, freshwater pulse, river inflow, Kariega Estuar

Public sector restructuring and regional development: the impact of compulsory competitive tendering in the UK

This paper contributes to the analysis of contemporary public sector restructuring in the UK through an evaluation of the impact of the introduction of compulsory competitive tendering (CCT) for the provision of local public services. Public services play an important stabilizing role in regional economic development but the introduction of CCT has undermined that role. Public service workers have suVered deteriorating levels of pay and conditions of service, and the capacity of local authorities to act to support local economic development has been reduced. Thus the introduction of CCT has undermined the contribution of local public services to the maintenance of interregional economic stability and to regional development

Genomic distance entrained clustering and regression modelling highlights interacting genomic regions contributing to proliferation in breast cancer

<p>Abstract</p> <p>Background</p> <p>Genomic copy number changes and regional alterations in epigenetic states have been linked to grade in breast cancer. However, the relative contribution of specific alterations to the pathology of different breast cancer subtypes remains unclear. The heterogeneity and interplay of genomic and epigenetic variations means that large datasets and statistical data mining methods are required to uncover recurrent patterns that are likely to be important in cancer progression.</p> <p>Results</p> <p>We employed ridge regression to model the relationship between regional changes in gene expression and proliferation. Regional features were extracted from tumour gene expression data using a novel clustering method, called genomic distance entrained agglomerative (GDEC) clustering. Using gene expression data in this way provides a simple means of integrating the phenotypic effects of both copy number aberrations and alterations in chromatin state. We show that regional metagenes derived from GDEC clustering are representative of recurrent regions of epigenetic regulation or copy number aberrations in breast cancer. Furthermore, detected patterns of genomic alterations are conserved across independent oestrogen receptor positive breast cancer datasets. Sequential competitive metagene selection was used to reveal the relative importance of genomic regions in predicting proliferation rate. The predictive model suggested additive interactions between the most informative regions such as 8p22-12 and 8q13-22.</p> <p>Conclusions</p> <p>Data-mining of large-scale microarray gene expression datasets can reveal regional clusters of co-ordinate gene expression, independent of cause. By correlating these clusters with tumour proliferation we have identified a number of genomic regions that act together to promote proliferation in ER+ breast cancer. Identification of such regions should enable prioritisation of genomic regions for combinatorial functional studies to pinpoint the key genes and interactions contributing to tumourigenicity.</p

Establishment of the epithelial-specific transcriptome of normal and malignant human breast cells based on MPSS and array expression data

INTRODUCTION: Diverse microarray and sequencing technologies have been widely used to characterise the molecular changes in malignant epithelial cells in breast cancers. Such gene expression studies to identify markers and targets in tumour cells are, however, compromised by the cellular heterogeneity of solid breast tumours and by the lack of appropriate counterparts representing normal breast epithelial cells. METHODS: Malignant neoplastic epithelial cells from primary breast cancers and luminal and myoepithelial cells isolated from normal human breast tissue were isolated by immunomagnetic separation methods. Pools of RNA from highly enriched preparations of these cell types were subjected to expression profiling using massively parallel signature sequencing (MPSS) and four different genome wide microarray platforms. Functional related transcripts of the differential tumour epithelial transcriptome were used for gene set enrichment analysis to identify enrichment of luminal and myoepithelial type genes. Clinical pathological validation of a small number of genes was performed on tissue microarrays. RESULTS: MPSS identified 6,553 differentially expressed genes between the pool of normal luminal cells and that of primary tumours substantially enriched for epithelial cells, of which 98% were represented and 60% were confirmed by microarray profiling. Significant expression level changes between these two samples detected only by microarray technology were shown by 4,149 transcripts, resulting in a combined differential tumour epithelial transcriptome of 8,051 genes. Microarray gene signatures identified a comprehensive list of 907 and 955 transcripts whose expression differed between luminal epithelial cells and myoepithelial cells, respectively. Functional annotation and gene set enrichment analysis highlighted a group of genes related to skeletal development that were associated with the myoepithelial/basal cells and upregulated in the tumour sample. One of the most highly overexpressed genes in this category, that encoding periostin, was analysed immunohistochemically on breast cancer tissue microarrays and its expression in neoplastic cells correlated with poor outcome in a cohort of poor prognosis estrogen receptor-positive tumours. CONCLUSION: Using highly enriched cell populations in combination with multiplatform gene expression profiling studies, a comprehensive analysis of molecular changes between the normal and malignant breast tissue was established. This study provides a basis for the identification of novel and potentially important targets for diagnosis, prognosis and therapy in breast cancer

Meta-Analysis of 28,141 Individuals Identifies Common Variants within Five New Loci That Influence Uric Acid Concentrations

Elevated serum uric acid levels cause gout and are a risk factor for cardiovascular disease and diabetes. To investigate the polygenetic basis of serum uric acid levels, we conducted a meta-analysis of genome-wide association scans from 14 studies totalling 28,141 participants of European descent, resulting in identification of 954 SNPs distributed across nine loci that exceeded the threshold of genome-wide significance, five of which are novel. Overall, the common variants associated with serum uric acid levels fall in the following nine regions: SLC2A9 (p = 5.2×10−201), ABCG2 (p = 3.1×10−26), SLC17A1 (p = 3.0×10−14), SLC22A11 (p = 6.7×10−14), SLC22A12 (p = 2.0×10−9), SLC16A9 (p = 1.1×10−8), GCKR (p = 1.4×10−9), LRRC16A (p = 8.5×10−9), and near PDZK1 (p = 2.7×10−9). Identified variants were analyzed for gender differences. We found that the minor allele for rs734553 in SLC2A9 has greater influence in lowering uric acid levels in women and the minor allele of rs2231142 in ABCG2 elevates uric acid levels more strongly in men compared to women. To further characterize the identified variants, we analyzed their association with a panel of metabolites. rs12356193 within SLC16A9 was associated with DL-carnitine (p = 4.0×10−26) and propionyl-L-carnitine (p = 5.0×10−8) concentrations, which in turn were associated with serum UA levels (p = 1.4×10−57 and p = 8.1×10−54, respectively), forming a triangle between SNP, metabolites, and UA levels. Taken together, these associations highlight additional pathways that are important in the regulation of serum uric acid levels and point toward novel potential targets for pharmacological intervention to prevent or treat hyperuricemia. In addition, these findings strongly support the hypothesis that transport proteins are key in regulating serum uric acid levels

Genome-Wide Association Study of White Blood Cell Count in 16,388 African Americans: the Continental Origins and Genetic Epidemiology Network (COGENT)

Total white blood cell (WBC) and neutrophil counts are lower among individuals of African descent due to the common African-derived “null” variant of the Duffy Antigen Receptor for Chemokines (DARC) gene. Additional common genetic polymorphisms were recently associated with total WBC and WBC sub-type levels in European and Japanese populations. No additional loci that account for WBC variability have been identified in African Americans. In order to address this, we performed a large genome-wide association study (GWAS) of total WBC and cell subtype counts in 16,388 African-American participants from 7 population-based cohorts available in the Continental Origins and Genetic Epidemiology Network. In addition to the DARC locus on chromosome 1q23, we identified two other regions (chromosomes 4q13 and 16q22) associated with WBC in African Americans (P<2.5×10−8). The lead SNP (rs9131) on chromosome 4q13 is located in the CXCL2 gene, which encodes a chemotactic cytokine for polymorphonuclear leukocytes. Independent evidence of the novel CXCL2 association with WBC was present in 3,551 Hispanic Americans, 14,767 Japanese, and 19,509 European Americans. The index SNP (rs12149261) on chromosome 16q22 associated with WBC count is located in a large inter-chromosomal segmental duplication encompassing part of the hydrocephalus inducing homolog (HYDIN) gene. We demonstrate that the chromosome 16q22 association finding is most likely due to a genotyping artifact as a consequence of sequence similarity between duplicated regions on chromosomes 16q22 and 1q21. Among the WBC loci recently identified in European or Japanese populations, replication was observed in our African-American meta-analysis for rs445 of CDK6 on chromosome 7q21 and rs4065321 of PSMD3-CSF3 region on chromosome 17q21. In summary, the CXCL2, CDK6, and PSMD3-CSF3 regions are associated with WBC count in African American and other populations. We also demonstrate that large inter-chromosomal duplications can result in false positive associations in GWAS

A meta-analysis of genome-wide data from five European isolates reveals an association of COL22A1, SYT1, and GABRR2 with serum creatinine level

<p>Abstract</p> <p>Background</p> <p>Serum creatinine (S_CR) is the most important biomarker for a quick and non-invasive assessment of kidney function in population-based surveys. A substantial proportion of the inter-individual variability in S_CRlevel is explicable by genetic factors.</p> <p>Methods</p> <p>We performed a meta-analysis of genome-wide association studies of S_CRundertaken in five population isolates ('discovery cohorts'), all of which are part of the European Special Population Network (EUROSPAN) project. Genes showing the strongest evidence for an association with S_CR(candidate loci) were replicated in two additional population-based samples ('replication cohorts').</p> <p>Results</p> <p>After the discovery meta-analysis, 29 loci were selected for replication. Association between S_CRlevel and polymorphisms in the collagen type XXII alpha 1 (<it>COL22A1</it>) gene, on chromosome 8, and in the synaptotagmin-1 (<it>SYT1</it>) gene, on chromosome 12, were successfully replicated in the replication cohorts (p value = 1.0 × 10^-6and 1.7 × 10^-4, respectively). Evidence of association was also found for polymorphisms in a locus including the gamma-aminobutyric acid receptor rho-2 (<it>GABRR2</it>) gene and the ubiquitin-conjugating enzyme E2-J1 (<it>UBE2J1</it>) gene (replication p value = 3.6 × 10^-3). Previously reported findings, associating glomerular filtration rate with SNPs in the uromodulin (<it>UMOD</it>) gene and in the schroom family member 3 (<it>SCHROOM3</it>) gene were also replicated.</p> <p>Conclusions</p> <p>While confirming earlier results, our study provides new insights in the understanding of the genetic basis of serum creatinine regulatory processes. In particular, the association with the genes <it>SYT1 </it>and <it>GABRR2 </it>corroborate previous findings that highlighted a possible role of the neurotransmitters GABA_Areceptors in the regulation of the glomerular basement membrane and a possible interaction between GABA_Areceptors and synaptotagmin-I at the podocyte level.</p

Evolution of clinical features in possible DLB depending on FP-CIT SPECT result

Objective: To test the hypothesis that core and suggestive features in possible dementia with Lewy bodies (DLB) would vary in their ability to predict an abnormal dopamine transporter scan and therefore a follow-up diagnosis of probable DLB. A further objective was to assess the evolution of core and suggestive features in patients with possible DLB over time depending on the 123I-FP-CIT SPECT scan result. Methods: A total of 187 patients with possible DLB (dementia plus one core or one suggestive feature) were randomized to have dopamine transporter imaging or to follow-up without scan. DLB features were compared at baseline and at 6-month follow-up according to imaging results and follow-up diagnosis. Results: For the whole cohort, the baseline frequency of parkinsonism was 30%, fluctuations 29%, visual hallucinations 24%, and REM sleep behavior disorder 17%. Clinician-rated presence of parkinsonism at baseline was significantly (p = 0.001) more frequent and Unified Parkinson’s Disease Rating Scale (UPDRS) score at baseline was significantly higher (p = 0.02) in patients with abnormal imaging. There was a significant increase in UPDRS score in the abnormal scan group over time (p < 0.01). There was relatively little evolution of the rest of the DLB features regardless of the imaging result. Conclusions: In patients with possible DLB, apart from UPDRS score, there was no difference in the evolution of DLB clinical features over 6 months between cases with normal and abnormal imaging. Only parkinsonism and dopamine transporter imaging helped to differentiate DLB from non-DLB dementia