Sources and export of nutrients in the Zambezi River basin: status and future trend

In the past decades, nutrient enrichment in African water bodies has been frequently reported and associated to long-term ecological and socio-economic consequences, such as species extinction, unsafe drinking water and compromised local livelihood. Meanwhile, rapid population growth and land-use change towards intensified food production are projected in Africa. As a result, substantial increases are expected in human-induced nutrient inputs (e.g. human waste and fertilizer) to the terrestrial and aquatic environments. This may potentially further deteriorate African water bodies. As part of the Integrated Solution for Water, Land and Energy (IS-WEL) project, this study aims to assess the status and projected changes of nutrient sources, inputs to rivers and export to seas, shading light on possible solutions to minimize further nutrient-induced deterioration of the water bodies and maximize the availability of water of suitable quality for different sectors. This study focuses on the Zambezi river basin, the fourth largest transboundary basin draining through eight southern African countries. Nutrient sources, inputs to rivers and export to sea are estimated using the MARINA model (Model to Assess River Inputs of Nutrients to seAs) under current conditions and future climate, land use and socio-economic projections up to 2050. Results show that for the current period (2005-2010), inputs of nutrients (nitrogen and phosphorus) to rivers and their export to sea are mainly attributed to natural sources. These sources include nitrogen fixation by the natural ecosystems, phosphorus weathering, and leaching of organic nitrogen and phosphorus from non-agricultural areas. By 2050, nutrient sources will be at least doubled due to anthropogenic inputs in the basin. Consequently, the fraction of human-induced nutrient export are projected to increase considerably, especially for dissolved inorganic phosphorus from domestic wastewater. Additionally, nutrient export to sea is strongly influenced by the intra- and inter-annual precipitation and discharge variabilities in the region. The study highlights the need to simultaneously consider source control, infrastructure development and climate adaptation to minimize further nutrient-induced deterioration of water bodies

Increasing future human-induced nitrogen exports to rivers and sea in the Zambezi river basin

In the past decades, nutrient enrichment in African water bodies has been frequently reported and lead to water security challenges, such as unsafe drinking water and compromised local livelihood. Meanwhile, rapid population growth and land-use change towards intensified food production are projected in Africa. Substantial increases in anthropogenic nutrient inputs (e.g. human waste and fertilizer) to the terrestrial and aquatic environments are therefore expected. This may further deteriorate African water bodies and threaten water security. As part of the Integrated Solution for Water, Land and Energy (IS-WEL) project funded by Global Environmental Facility and IIASA, this study aims to assess the status and projected changes of nitrogen (N) sources, associated inputs to rivers and export to sea. The study focuses on the Zambezi river basin, the 4th largest transboundary basin in Africa draining through 8 countries. N inputs to rivers and export to sea are estimated using the MARINA model (Model to Assess River Inputs of Nutrients to seAs) under current conditions and future climate, land use and socio-economic scenarios towards 2050. In addition to global climate (Representative Concentration Pathways) and socioeconomic (Shared Socioeconomic Pathways) scenarios, the study co-developed regional scenarios through stakeholder engagement in cooperation with the Zambezi Watercourse Commission. The regional scenarios, especially for sanitation and agricultural development, will later be incorporated in the model. Preliminary results show that for the current period (2010), N input to rivers and export to sea are mainly from natural sources, namely N fixation by the natural ecosystems and organic N leaching from non-agricultural areas. By 2050, N sources in the basin will be more than doubled due to anthropogenic inputs based on the global scenarios. Consequently, the fraction of human-induced N export is projected to increase considerably. Additionally, N export to sea is strongly influenced by the intra- and inter-annual climate variabilities in the region. The study highlights the need to simultaneously consider source control and climate adaptation in the regional contexts to minimize further N-induced deterioration of water bodies and ensure regional water security

Causal relationship in the interaction between land cover change and underlying surface climate in the grassland ecosystems in China

Land-climate interactions are driven by causal relations that are difficult to ascertain given the complexity and high dimensionality of the systems. Many methods of statistical and mechanistic models exist to identify and quantify the causality in such highly-interacting systems. Recent advances in remote sensing development allowed people to investigate the land-climate interaction with spatially and temporally continuous data. In this study, we present a new approach to measure how climatic factors interact with each other under land cover change. The quantification method is based on the correlation analysis of the different order derivatives, with the canonical mathematical definitions developed from the theories of system dynamics and practices of the macroscopic observations. We examined the causal relationship between the interacting variables on both spatial and temporal dimensions based on macroscopic observations of land cover change and surface climatic factors through a comparative study in the different grassland ecosystems of China. The results suggested that the interaction of land-climate could be used to explain the temporal lag effect in the comparison of the three grassland ecosystems. Significant spatial correlations between the vegetation and the climatic factors confirmed feedback mechanisms described in the theories of eco-climatology, while the uncertain temporal synchronicity reflects the causality among the key indicators. This has been rarely addressed before. Our research show that spatial correlations and the temporal synchronicity among key indicators of the land surface and climatic factors can be explained by a novel method of causality quantification using derivative analysis

Bridging global, basin and local-scale water quality modeling towards enhancing water quality management worldwide

Global water quality (WQ) modeling is an emerging field. In this article, we identify the missing linkages between global and basin/local-scale WQ models, and discuss the possibilities to fill these gaps. We argue that WQ models need stronger linkages across spatial scales. This would help to identify effective scale-specific WQ management options and contribute to future development of global WQ models. Two directions are proposed to improve the linkages: nested multiscale WQ modeling towards enhanced water management, and development of next-generation global WQ models based-on basin/local-scale mechanistic understanding. We highlight the need for better collaboration among WQ modelers and policy-makers in order to deliver responsive water policies and management strategies across scales

Increasing nitrogen export to sea: A scenario analysis for the Indus River

The Indus River Basin faces severe water quality degradation because of nutrient enrichment from human activities. Excessive nutrients in tributaries are transported to the river mouth, causing coastal eutrophication. This situation may worsen in the future because of population growth, economic development, and climate change. This study aims at a better understanding of the magnitude and sources of current (2010) and future (2050) river export of total dissolved nitrogen (TDN) by the Indus River at the sub-basin scale. To do this, we implemented the MARINA 1.0 model (Model to Assess River Inputs of Nutrients to seAs). The model inputs for human activities (e.g., agriculture, land use) were mainly from the GLOBIOM (Global Biosphere Management Model) and EPIC (Environmental Policy Integrated Model) models. Model inputs for hydrology were from the Community WATer Model (CWATM). For 2050, three scenarios combining Shared Socio-economic Pathways (SSPs 1, 2 and 3) and Representative Concentration Pathways (RCPs 2.6 and 6.0) were selected. A novelty of this study is the sub-basin analysis of future N export by the Indus River for SSPs and RCPs. Result shows that river export of TDN by the Indus River will increase by a factor of 1.6–2 between 2010 and 2050 under the three scenarios. >90% of the dissolved N exported by the Indus River is from midstream sub-basins. Human waste is expected to be the major source, and contributes by 66–70% to river export of TDN in 2050 depending on the scenarios. Another important source is agriculture, which contributes by 21–29% to dissolved inorganic N export in 2050. Thus a combined reduction in both diffuse and point sources in the midstream sub-basins can be effective to reduce coastal water pollution by nutrients at the river mouth of Indus

HL-Histamine receptor affinity predicts short-term weight gain for typical and atypical antipsychotic drugs

As a result of superior efficacy and overall tolerability, atypical antipsychotic drugs have become the treatment of choice for schizophrenia and related disorders, despite their side effects. Weight gain is a common and potentially serious complication of some antipsychotic drug therapy, and may be accompanied by hyperlipidemia, hypertension and hyperglycemia and, in some extreme cases, diabetic ketoacidosis. The molecular mechanism(s) responsible for antipsychotic drug-induced weight gain are unknown, but have been hypothesized to be because of interactions of antipsychotic drugs with several neurotransmitter receptors, including 5-HT2A and 5-HT2Cserotonin receptors, H1-histamine receptors, α1- and α2-adrenergic receptors, and m3-muscarinic receptors. To determine the receptor(s) likely to be responsible for antipsychotic-drug-induced weight gain, we screened 17 typical and atypical antipsychotic drugs for binding to 12 neurotransmitter receptors. H1-histamine receptor affinities for this group of typical and atypical antipsychotic drugs were significantly correlated with weight gain (Spearman ρ=−0.72; p less than 0.01), as were affinities for α1A adrenergic (ρ=−0.54; p less than 0.05), 5-HT2C (ρ=−0.49; p less than 0.05) and 5-HT6 receptors (ρ=−0.54; p less than 0.05), whereas eight other receptors' affinities were not. A principal components analysis showed that affinities at the H1, α2A, α2B, 5-HT2A, 5-HT2C, and 5-HT6 receptors were most highly correlated with the first principal component, and affinities for the D2, 5-HT1A, and 5-HT7 receptors were most highly correlated with the second principal component. A discriminant functions analysis showed that affinities for the H1 and α1A receptors were most highly correlated with the discriminant function axis. The discriminant function analysis, as well as the affinity for the H1-histamine receptor alone, correctly classified 15 of the 17 drugs into two groups; those that induce weight gain and those that do not. Because centrally acting H1-histamine receptor antagonists are known to induce weight gain with chronic use, and because H1-histamine receptor affinities are positively correlated with weight gain among typical and atypical antipsychotic drugs, it is recommended that the next generation of atypical antipsychotic drugs be screened to avoid H1-histamine receptors

A versatile Plasmodium falciparum reporter line expressing NanoLuc enables highly sensitive multi-stage drug assays

Presentation of a versatile Plasmodium falciparum dual reporter line, expressing both a fluorescent protein and NanoLuc under a constitutive promoter, that can be used to screen for novel anti-malarial drugs effective against multiple stages of the parasite.Transgenic luciferase-expressing Plasmodium falciparum parasites have been widely used for the evaluation of anti-malarial compounds. Here, to screen for anti-malarial drugs effective against multiple stages of the parasite, we generate a P. falciparum reporter parasite that constitutively expresses NanoLuciferase (NanoLuc) throughout its whole life cycle. The NanoLuc-expressing P. falciparum reporter parasite shows a quantitative NanoLuc signal in the asexual blood, gametocyte, mosquito, and liver stages. We also establish assay systems to evaluate the anti-malarial activity of compounds at the asexual blood, gametocyte, and liver stages, and then determine the 50% inhibitory concentration (IC50) value of several anti-malarial compounds. Through the development of this robust high-throughput screening system, we identify an anti-malarial compound that kills the asexual blood stage parasites. Our study highlights the utility of the NanoLuc reporter line, which may advance anti-malarial drug development through the improved screening of compounds targeting the human malarial parasite at multiple stages.Host-parasite interactio

Drug-induced activation of SREBP-controlled lipogenic gene expression in CNS-related cell lines: Marked differences between various antipsychotic drugs

BACKGROUND: The etiology of schizophrenia is unknown, but neurodevelopmental disturbances, myelin- and oligodendrocyte abnormalities and synaptic dysfunction have been suggested as pathophysiological factors in this severe psychiatric disorder. Cholesterol is an essential component of myelin and has proved important for synapse formation. Recently, we demonstrated that the antipsychotic drugs clozapine and haloperidol stimulate lipogenic gene expression in cultured glioma cells through activation of the sterol regulatory element-binding protein (SREBP) transcription factors. We here compare the action of chlorpromazine, haloperidol, clozapine, olanzapine, risperidone and ziprasidone on SREBP activation and SREBP-controlled gene expression (ACAT2, HMGCR, HMGCS1, FDPS, SC5DL, DHCR7, LDLR, FASN and SCD1) in four CNS-relevant human cell lines. RESULTS: There were marked differences in the ability of the antipsychotic drugs to activate the expression of SREBP target genes, with clozapine and chlorpromazine as the most potent stimulators in a context of therapeutically relevant concentrations. Glial-like cells (GaMg glioma and CCF-STTG1 astrocytoma cell lines) displayed more pronounced drug-induced SREBP activation compared to the response in HCN2 human cortical neurons and SH-SY5Y neuroblastoma cells, indicating that antipsychotic-induced activation of lipogenesis is most prominent in glial cells. CONCLUSION: Our present data show a marked variation in the ability of different antipsychotics to induce SREBP-controlled transcriptional activation of lipogenesis in cultured human CNS-relevant cells. We propose that this effect could be relevant for the therapeutic efficacy of some antipsychotic drugs

Genome-wide profiling of G protein-coupled receptors in cerebellar granule neurons using high-throughput, real-time PCR

<p>Abstract</p> <p>Background</p> <p>G protein-coupled receptors (GPCRs) are major players in cell communication, regulate a whole range of physiological functions during development and throughout adult life, are affected in numerous pathological situations, and constitute so far the largest class of drugable targets for human diseases. The corresponding genes are usually expressed at low levels, making accurate, genome-wide quantification of their expression levels a challenging task using microarrays.</p> <p>Results</p> <p>We first draw an inventory of all endo-GPCRs encoded in the murine genome. To profile GPCRs genome-wide accurately, sensitively, comprehensively, and cost-effectively, we designed and validated a collection of primers that we used in quantitative RT-PCR experiments. We experimentally validated a statistical approach to analyze genome-wide, real-time PCR data. To illustrate the usefulness of this approach, we determined the repertoire of GPCRs expressed in cerebellar granule neurons and neuroblasts during postnatal development.</p> <p>Conclusions</p> <p>We identified tens of GPCRs that were not detected previously in this cell type; these GPCRs represent novel candidate players in the development and survival of cerebellar granule neurons. The sequences of primers used in this study are freely available to those interested in quantifying GPCR expression comprehensively.</p