Water sharing for the environment and agriculture in the Broken catchment

The Commonwealth of Australia Water Act 2007 changed the priority for water use in the Murray-Darling Basin (MDB) to first ensure environmentally sustainable levels of extraction and then to maximise net economic returns to the community from water use. The Murray- Darling Basin Authority (MDBA) is expected to deliver a draft Basin Plan in 2011 providing a framework for future water planning. The Plan will include Sustainable Diversion Limits (SDLs) which define water diversions for consumption while maintaining environmental assets and ecosystem functions. The 2009 MDBA Concept Statement acknowledged that in some areas less information is available to determine the SDLs. The 2010 MDBA Guide to the Basin Plan proposed SDLs reducing the current long-term average surface water diversions to between 25 and 34% for the Goulburn-Broken region. Representative farm-level models of irrigated dairy, horticulture and viticulture, and dryland broadacre, industries were developed to determine the likely impacts on farm income and farm enterprise mix if the price and quantity of irrigation water changes. Water for ecological benefits and ecosystem functioning was determined for a range of river health levels using a bottom-up approach identifying flow requirements for fish, riparian vegetation, invertebrates, and geomorphic and nutrient processes. A novel part of the analysis is the conjunctive use of water for both purposes, e.g. wetland filling and then pumping for irrigation. The linkages between changed land use and surface/ground water outcomes are assessed using a Catchment Analysis Tool. An experimental design of different proportions of water going to the environment and consumptive uses showed potential trade-offs between agricultural, environmental and surface/ground water outcomes. These trade-offs were examined to assess the impact of alternative water management on catchment welfare, and provide information about setting SDLs.Water sharing, environment, agriculture, Murray-Darling Basin, Broken catchment, Resource /Energy Economics and Policy, Q18, Q25, Q28,

Institutional and technological options for sustainable intensification of community based Silvi-pasture systems in arid ecoregions

In arid ecoregion of Rajasthan, India, common pool resources (CPRs) like common pastures and village water bodies provide ecosystem services such as fodder, fuel, timber, water and medicinal plants which are crucial for the livelihoods in particular of the poor. In western Rajasthan livestock keeping is the most important and resilient component of the agricultural systems which strongly depends on common pastures. However, the grazing areas have become severely degraded making the rural poor more vulnerable. A number of efforts have been made to improve the management of and rehabilitate the community pastures (Conroy and Lobo, 2002; Agrawal, 2003). The success of such initiatives was unreliable and even the strong involvement of elected village councils (Panchayats) has not helped. Post-project sustainability of new management practices remains uncertain due to cumbersome social dynamics, neglect of institutional arrangements as well as an overemphasis on technical and externally controlled interventions (Jodha, 2001; Chaudhry et al., 2011; Mishra and Kumar, 2007). Previous empirical research using the social-ecological systems thinking and framework (Ostrom, 1990, 2007; Wade, 1998; Baland and Plateau, 1996) has helped to better understand CPR governance challenges. Nevertheless, there is still no clear answer to the question why common pasture management works out in some Rajasthan communities and fails in others

Empirical evaluation of sustainability of divergent farms in the dryland farming systems of India

The present study argues that there are heterogeneous farm systems within the drylands and each farm system is unique in terms of its livelihood asset and agricultural practice, and therefore in sustainability. Our method is based on household survey data collected from 500 farmers in Anantapur and Kurnool Districts, in Andhra Pradesh State of India, in 2013. We carried out principal component analysis (PCA) with subsequent hierarchical clustering methods to build farm typologies. To evaluate sustainability across these farm typologies, we adopted a framework consisting of economic, social and environmental sustainability pillars and associated indicators. We normalized values of target indicators and employed normative approach to assign different weights to these indicators. Composite sustainability indices (CSI) were then estimated by means of weighted sum of indicators, aggregated and integrated into farm typologies. The results suggested that there were five distinct farm typologies representing farming systems in the study area. The majority of farms (>70%) in the study area are small and extensive (typology 1); marginal and off farm based (typology 2). About 20% of the farms are irrigation based and intensive (typology 3); small and medium and off farm based (typology 4) and irrigation based semi-intensive (typology 5). There was apparent variability among farm typologies in terms of farm structure and functions and composite sustainability indices. Farm typologies 3 and 5 showed significantly higher performances for the social and economic indices, while typologies 2 and 4 had relatively stronger values for environment. These discrepancies support the relevance of integrated farm typology- and CSI approaches in assessing system sustainability and targeting technologies. Universally, for all farm typologies, composite sustainability indices for economic pillar was significantly lower than the social and environment pillars. More than 90% of farmers were in economically less-sustainable class. The correlations between sustainability indices for economic and environment were typology specific. It was strong and positive when aggregated for the whole study systems [all samples (r = 0.183; P < 0.001)] and for agriculture dependent farm typologies (e.g. typologies 1 and 3). This suggests the need to elevate farms economic performance and capacitate them to invest in the environment. These results provide information for policy makers to plan farm typology–context technological interventions and also create baseline information to evaluate sustainability performance in terms of progress made over time

Congenital chloride-losing diarrhea in a Mexican child with the novel homozygous SLC26A3 mutation G393W

Congenital chloride diarrhea is an autosomal recessive disease caused by mutations in the intestinal lumenal membrane Cl−/HCO−3 exchanger, SLC26A3. We report here the novel SLC26A3 mutation G393W in a Mexican child, the first such report in a patient from Central America. SLC26A3 G393W expression in Xenopus oocytes exhibits a mild hypomorphic phenotype, with normal surface expression and moderately reduced anion transport function. However, expression of HA-SLC26A3 in HEK-293 cells reveals intracellular retention and greatly decreased steady-state levels of the mutant polypeptide, in contrast to peripheral membrane expression of the wildtype protein. Whereas wildtype HA-SLC26A3 is apically localized in polarized monolayers of filter-grown MDCK cells and Caco2 cells, mutant HA-SLC26A3 G393W exhibits decreased total polypeptide abundance, with reduced or absent surface expression and sparse punctate (or absent) intracellular distribution. The WT protein is similarly localized in LLC-PK1 cells, but the mutant fails to accumulate to detectable levels. We conclude that the chloride-losing diarrhea phenotype associated with homozygous expression of SLC26A3 G393W likely reflects lack of apical surface expression in enterocytes, secondary to combined abnormalities in polypeptide trafficking and stability. Future progress in development of general or target-specific folding chaperonins and correctors may hold promise for pharmacological rescue of this and similar genetic defects in membrane protein targeting

Inflammation-dependent cerebrospinal fluid hypersecretion by the choroid plexus epithelium in posthemorrhagic hydrocephalus

This is the author accepted manuscript. The final version is available from Springer Nature via the DOI in this recordThere is another record in ORE for this publication: http://hdl.handle.net/10871/33419The choroid plexus epithelium (CPE) secretes higher volumes of fluid (cerebrospinal fluid, CSF) than any other epithelium and simultaneously functions as the blood-CSF barrier to gate immune cell entry into the central nervous system. Posthemorrhagic hydrocephalus (PHH), an expansion of the cerebral ventricles due to CSF accumulation following intraventricular hemorrhage (IVH), is a common disease usually treated by suboptimal CSF shunting techniques. PHH is classically attributed to primary impairments in CSF reabsorption, but little experimental evidence supports this concept. In contrast, the potential contribution of CSF secretion to PHH has received little attention. In a rat model of PHH, we demonstrate that IVH causes a Toll-like receptor 4 (TLR4)- and NF-κB-dependent inflammatory response in the CPE that is associated with a ∼3-fold increase in bumetanide-sensitive CSF secretion. IVH-induced hypersecretion of CSF is mediated by TLR4-dependent activation of the Ste20-type stress kinase SPAK, which binds, phosphorylates, and stimulates the NKCC1 co-transporter at the CPE apical membrane. Genetic depletion of TLR4 or SPAK normalizes hyperactive CSF secretion rates and reduces PHH symptoms, as does treatment with drugs that antagonize TLR4-NF-κB signaling or the SPAK-NKCC1 co-transporter complex. These data uncover a previously unrecognized contribution of CSF hypersecretion to the pathogenesis of PHH, demonstrate a new role for TLRs in regulation of the internal brain milieu, and identify a kinase-regulated mechanism of CSF secretion that could be targeted by repurposed US Food and Drug Administration (FDA)-approved drugs to treat hydrocephalus.We thank D.R. Alessi (Dundee) and R.P. Lifton (Rockefeller) for their support. K.T.K. is supported by the March of Dimes Basil O'Connor Award, a Simons Foundation SFARI Grant, the Hydrocephalus Association Innovator Award, and the NIH (4K12NS080223-05). J.M.S. is supported by the National Institute of Neurological Disorders and Stroke (NINDS) (NS060801; NS061808) and the US Department of Veterans Affairs (1BX002889); R.M. is supported by the Howard Hughes Medical Institute

Engineered Single-Domain Antibodies with High Protease Resistance and Thermal Stability

The extreme pH and protease-rich environment of the upper gastrointestinal tract is a major obstacle facing orally-administered protein therapeutics, including antibodies. Through protein engineering, several Clostridium difficile toxin A-specific heavy chain antibody variable domains (VHHs) were expressed with an additional disulfide bond by introducing Ala/Gly54Cys and Ile78Cys mutations. Mutant antibodies were compared to their wild-type counterparts with respect to expression yield, non-aggregation status, affinity for toxin A, circular dichroism (CD) structural signatures, thermal stability, protease resistance, and toxin A-neutralizing capacity. The mutant VHHs were found to be well expressed, although with lower yields compared to wild-type counterparts, were non-aggregating monomers, retained low nM affinity for toxin A, albeit the majority showed somewhat reduced affinity compared to wild-type counterparts, and were capable of in vitro toxin A neutralization in cell-based assays. Far-UV and near-UV CD spectroscopy consistently showed shifts in peak intensity and selective peak minima for wild-type and mutant VHH pairs; however, the overall CD profile remained very similar. A significant increase in the thermal unfolding midpoint temperature was observed for all mutants at both neutral and acidic pH. Digestion of the VHHs with the major gastrointestinal proteases, at biologically relevant concentrations, revealed a significant increase in pepsin resistance for all mutants and an increase in chymotrypsin resistance for the majority of mutants. Mutant VHH trypsin resistance was similar to that of wild-type VHHs, although the trypsin resistance of one VHH mutant was significantly reduced. Therefore, the introduction of a second disulfide bond in the hydrophobic core not only increases VHH thermal stability at neutral pH, as previously shown, but also represents a generic strategy to increase VHH stability at low pH and impart protease resistance, with only minor perturbations in target binding affinities. These are all desirable characteristics for the design of protein-based oral therapeutics

The genetic epidemiology of joint shape and the development of osteoarthritis

Congruent, low-friction relative movement between the articulating elements of a synovial joint is an essential pre-requisite for sustained, efficient, function. Where disorders of joint formation or maintenance exist, mechanical overloading and osteoarthritis (OA) follow. The heritable component of OA accounts for ~ 50% of susceptible risk. Although almost 100 genetic risk loci for OA have now been identified, and the epidemiological relationship between joint development, joint shape and osteoarthritis is well established, we still have only a limited understanding of the contribution that genetic variation makes to joint shape and how this modulates OA risk. In this article, a brief overview of synovial joint development and its genetic regulation is followed by a review of current knowledge on the genetic epidemiology of established joint shape disorders and common shape variation. A summary of current genetic epidemiology of OA is also given, together with current evidence on the genetic overlap between shape variation and OA. Finally, the established genetic risk loci for both joint shape and osteoarthritis are discussed