Differentiated access: Challenges of equitable and sustainable groundwater exploitation in Tanzania

Groundwater is an important resource for a large share of the global population and economies. Although groundwater dependence in most sub-Saharan African countries is relatively low at the national level, localized overexploitation is occurring, leading to a decline in groundwater levels and quality deterioration. Currently, the sustainable and equitable governance of groundwater, both through promotion and regulation, is turning out to be a key challenge in many sub-Saharan African countries. This paper uses case studies of urban groundwater governance in Arusha, and rural groundwater development in the Pangani basin, to analyse how the current policy and regulation inadvertently creates spaces for asymmetric access to (good quality) groundwater resources in Tanzania. It shows how the groundwater landscape is evolving into a situation where small users (farmers and households) rely on springs and shallow wells, while large users (commercial users and urban water authorities) are encouraged to sink deep boreholes. Amidst a lack of knowledge and enforcing capacity, exacerbated by different priorities among government actors, the water access rights of shallow well and spring users are being threatened by increased groundwater exploitation. Hence, the current groundwater policy and institutional setup do not only empower larger actors to gain disproportionate access to the groundwater resources, but presents this as a benefit for small users whose water security will supposedly increase

Conservation Conferences and Expert Networks in the Short Twentieth Century

The twentieth century witnessed the rise of a conservation movement that presented itself as 'international' and 'science-based'. This article analyses the changing transnational networks of experts mobilised by this movement. It does so by studying the participant lists of 21 influential international conservation conferences held between 1913 and 1990. On the basis of a database we were able to trace changes in the national background, disciplinary allegiance and gender balance of conference attendants. Furthermore, we singled out a so-called 'congress elite' of often returning participants, whose background we analyse more in depth. The overall composition of the congress network as well as that of its elite, we show, changed only through a slow and laborious process. This process accounts for both the continuity in the sensibilities of international conservation experts and the gradual changes in their approach

Elevated insulin-like growth factor 1 receptor signaling induces antiestrogen resistance through the MAPK/ERK and PI3K/Akt signaling routes

INTRODUCTION: Insulin-like growth factor 1 (IGF-1) receptor (IGF-1R) is phosphorylated in all breast cancer subtypes. Past findings have shown that IGF-1R mediates antiestrogen resistance through cross-talk with estrogen receptor (ER) signaling and via its action upstream of the epidermal growth factor receptor and human epidermal growth factor receptor 2. Yet, the direct role of IGF-1R signaling itself in antiestrogen resistance remains obscure. In the present study, we sought to elucidate whether antiestrogen resistance is induced directly by IGF-1R signaling in response to its ligand IGF-1 stimulation.METHODS: A breast cancer cell line ectopically expressing human wild-type IGF-1R, MCF7/IGF-1R, was established by retroviral transduction and colony selection. Cellular antiestrogen sensitivity was evaluated under estrogen-depleted two-dimensional (2D) and 3D culture conditions. Functional activities of the key IGF-1R signaling components in antiestrogen resistance were assessed by specific kinase inhibitor compounds and small interfering RNA.RESULTS: Ectopic expression of IGF-1R in ER-positive MCF7 human breast cancer cells enhanced IGF-1R tyrosine kinase signaling in response to IGF-1 ligand stimulation. The elevated IGF-1R signaling rendered MCF7/IGF-1R cells highly resistant to the antiestrogens tamoxifen and fulvestrant. This antiestrogen-resistant phenotype involved mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) and phosphatidylinositol 3-kinase/protein kinase B pathways downstream of the IGF-1R signaling hub and was independent of ER signaling. Intriguingly, a MAPK/ERK-dependent agonistic behavior of tamoxifen at low doses was triggered in the presence of IGF-1, showing a mild promitogenic effect and increasing ER transcriptional activity.CONCLUSIONS: Our data provide evidence that the IGF-1/IGF-1R signaling axis may play a causal role in antiestrogen resistance of breast cancer cells, despite continuous suppression of ER transcriptional function by antiestrogens

The fluid nature of water grabbing: the on-going contestation of water distribution between peasants and agribusinesses in Nduruma, Tanzania

This research article published by Springer Nature Switzerland AG., 2015This article contributes to the contemporary debate on land and water grabbing through a detailed, qualitative case study of horticultural agribusinesses which have settled in Tanzania, disrupting patterns of land and water use. In this paper we analyse how capitalist settler farms and their upstream and downstream peasant neighbours along the Nduruma river, Tanzania, expand and defend their water use. The paper is based on 3 months of qualitative field work in Tanzania. We use the echelons of rights analysis framework combined with the concept of institutional bricolage to show how this contestation takes place over the full spectrum of actual abstractions, governance and discourses. We emphasise the role different (inter)national development narratives play in shaping day-to-day contestations over water shares and rule-making. Ultimately, we emphasise that water grabbing is not a one-time event, but rather an on-going struggle over different water resources. In addition, we show how a perceived beneficial development of agribusinesses switching to groundwater allows them to avoid peasant-controlled institutions, avoiding further negotiation between the different actors and improving their image among neighbouring communities. This development illustrates how complex and obscured processes of water re-allocation can be without becoming illegal per se

Automated Whole Animal Bio-Imaging Assay for Human Cancer Dissemination

A quantitative bio-imaging platform is developed for analysis of human cancer dissemination in a short-term vertebrate xenotransplantation assay. Six days after implantation of cancer cells in zebrafish embryos, automated imaging in 96 well plates coupled to image analysis algorithms quantifies spreading throughout the host. Findings in this model correlate with behavior in long-term rodent xenograft models for panels of poorly- versus highly malignant cell lines derived from breast, colorectal, and prostate cancer. In addition, cancer cells with scattered mesenchymal characteristics show higher dissemination capacity than cell types with epithelial appearance. Moreover, RNA interference establishes the metastasis-suppressor role for E-cadherin in this model. This automated quantitative whole animal bio-imaging assay can serve as a first-line in vivo screening step in the anti-cancer drug target discovery pipeline

Influence of Genetic Variants in TPMT and COMT Associated with Cisplatin Induced Hearing Loss in Patients with Cancer:Two New Cohorts and a Meta-Analysis Reveal Significant Heterogeneity between Cohorts

Treatment with cisplatin-containing chemotherapy regimens causes hearing loss in 40-60% of cancer patients. It has been suggested that genetic variants in the genes encoding thiopurine S-methyltransferase (TPMT) and catechol O-methyltransferase (COMT) can predict the development of cisplatin-induced ototoxicity and may explain interindividual variability in sensitivity to cisplatin-induced hearing loss. Two recently published studies however, sought to validate these findings and showed inconsistent results. The aim of this study was to evaluate the role of polymorphisms in the TPMT and COMT genes in cisplatin-induced ototoxicity. Therefore we investigated two independent cohorts of 110 Dutch and 38 Spanish patients with osteosarcoma and performed a meta-analysis including all previously published studies resulting in a total population of 664 patients with cancer. With this largest meta-analysis performed to date, we show that the influence of TPMT and COMT on the development of cisplatin-induced hearing loss may be less important than previously suggested

Uncovering the Signaling Landscape Controlling Breast Cancer Cell Migration Identifies Novel Metastasis Driver Genes

Ttriple-negative breast cancer (TNBC) is an aggressive and highly metastatic breast cancer subtype. Enhanced TNBC cell motility is a prerequisite of TNBC cell dissemination. Here, we apply an imaging-based RNAi phenotypic cell migration screen using two highly motile TNBC cell lines (Hs578T and MDA-MB-231) to provide a repository of signaling determinants that functionally drive TNBC cell motility. We have screened ~4,200 target genes individually and discovered 133 and 113 migratory modulators of Hs578T and MDA-MB-231, respectively, which are linked to signaling networks predictive for breast cancer progression. The splicing factors PRPF4B and BUD31 and the transcription factor BPTF are essential for cancer cell migration, amplified in human primary breast tumors and associated with metastasis-free survival. Depletion of PRPF4B, BUD31 and BPTF causes primarily down regulation of genes involved in focal adhesion and ECM-interaction pathways. PRPF4B is essential for TNBC metastasis formation in vivo, making PRPF4B a candidate for further drug developmen

Pharmacogenetics of telatinib, a VEGFR-2 and VEGFR-3 tyrosine kinase inhibitor, used in patients with solid tumors

Purpose Telatinib is an orally active small-molecule tyrosine kinase inhibitor of kinase insert domain receptor (KDR; VEGFR-2) and fms-related tyrosine kinase 4 (FLT4; VEGFR-3). This study aims at the identification of relationships between single nucleotide polymorphisms (SNPs) in genes encoding for transporter proteins and pharmacokinetic parameters in order to clarify the significant interpatient variability in drug exposure. In addition, the potential relationship between target receptor polymorphisms and toxicity of telatinib is explored. Methods Blood samples from 33 patients enrolled in a phase I dose-escalation study of telatinib were analyzed. For correlation with dose normalized AUC(0–12), ATP-binding cassette (ABC) B1 (ABCB1), ABCC1, and ABCG2 were the genes selected. For correlation with telatinib toxicity, selected genes were the drug target genes KDR and FLT4. Results No association between dose normalized AUC(0–12) and drug transporter protein polymorphisms was observed. In addition, no association between toxicity and KDR or FLT4 genotype or haplotype was seen. Conclusions Our pharmacogenetic analysis could not reveal a correlation between relevant gene polymorphisms and clinical and pharmacokinetic observations of telatinib