Impacts of Reduced Water Availability on Lower Murray Irrigation, Australia

This article evaluates irrigated agriculture sector response and resultant economic impacts of climate change for a part of the Murray Darling Basin in Australia. A water balance model is used to predict reduced basin inflows for mild, moderate and severe climate change scenarios involving 10, 20, 40 Celcius warming, and predict 13%, 38% and 63% reduced inflows. Impact on irrigated agricultural production and profitability are estimated with a mathematical programming model using a two-stage approach that simultaneously estimates short and long-run adjustments. The model accounts for a range of adaptive responses including: deficit irrigation, temporarily fallowing some areas, and permanently reducing irrigated area and changing the mix of crops. The results suggest that relatively low cost adaptation strategies are available for moderate reduction in water availability and thus costs of such reduction are likely to be relatively small. In more severe climate change scenarios greater costs are estimated, adaptations predicted include a reduction in total area irrigated, investments in efficient irrigation, and a shift away from perennial to annual crops as the latter can be managed more profitably when water allocations in some years are very low.water availability, irrigation, Murray Darling Basin, climate change

Scaling the Stiffness, Strength, and Toughness of Ceramic‐Coated Nanotube Foams into the Structural Regime

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/108652/1/adfm201400851-sup-0001-S1.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/108652/2/adfm201400851.pd

Cavalier King Charles Spaniels with Chiari-like malformation and Syringomyelia have increased variability of spatio-temporal gait characteristics

Abstract Background Chiari-like malformation in the Cavalier King Charles Spaniel is a herniation of the cerebellum and brainstem into or through the foramen magnum. This condition predisposes to Syringomyelia; fluid filled syrinxes within the spinal cord. The resulting pathology in spinal cord and cerebellum create neuropathic pain and changes in gait. This study aims to quantify the changes in gait for Cavalier King Charles Spaniel with Chiari-like malformation and Syringomyelia. Methods We compared Cavalier King Charles Spaniel with Chiari-like malformation with (n = 9) and without (n = 8) Syringomyelia to Border Terriers (n = 8). Two video cameras and manual tracking was used to quantify gait parameters. Results and conclusions We found a significant increase in coefficient of variation for the spatio-temporal characteristics and ipsilateral distance between paws and a wider base of support in the thoracic limbs but not in the pelvic limbs for Cavalier King Charles Spaniels compared with the border terrier

Effect of natalizumab on disease progression in secondary progressive multiple sclerosis (ASCEND). a phase 3, randomised, double-blind, placebo-controlled trial with an open-label extension

Background: Although several disease-modifying treatments are available for relapsing multiple sclerosis, treatment effects have been more modest in progressive multiple sclerosis and have been observed particularly in actively relapsing subgroups or those with lesion activity on imaging. We sought to assess whether natalizumab slows disease progression in secondary progressive multiple sclerosis, independent of relapses. Methods: ASCEND was a phase 3, randomised, double-blind, placebo-controlled trial (part 1) with an optional 2 year open-label extension (part 2). Enrolled patients aged 18–58 years were natalizumab-naive and had secondary progressive multiple sclerosis for 2 years or more, disability progression unrelated to relapses in the previous year, and Expanded Disability Status Scale (EDSS) scores of 3·0–6·5. In part 1, patients from 163 sites in 17 countries were randomly assigned (1:1) to receive 300 mg intravenous natalizumab or placebo every 4 weeks for 2 years. Patients were stratified by site and by EDSS score (3·0–5·5 vs 6·0–6·5). Patients completing part 1 could enrol in part 2, in which all patients received natalizumab every 4 weeks until the end of the study. Throughout both parts, patients and staff were masked to the treatment received in part 1. The primary outcome in part 1 was the proportion of patients with sustained disability progression, assessed by one or more of three measures: the EDSS, Timed 25-Foot Walk (T25FW), and 9-Hole Peg Test (9HPT). The primary outcome in part 2 was the incidence of adverse events and serious adverse events. Efficacy and safety analyses were done in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT01416181. Findings: Between Sept 13, 2011, and July 16, 2015, 889 patients were randomly assigned (n=440 to the natalizumab group, n=449 to the placebo group). In part 1, 195 (44%) of 439 natalizumab-treated patients and 214 (48%) of 448 placebo-treated patients had confirmed disability progression (odds ratio [OR] 0·86; 95% CI 0·66–1·13; p=0·287). No treatment effect was observed on the EDSS (OR 1·06, 95% CI 0·74–1·53; nominal p=0·753) or the T25FW (0·98, 0·74–1·30; nominal p=0·914) components of the primary outcome. However, natalizumab treatment reduced 9HPT progression (OR 0·56, 95% CI 0·40–0·80; nominal p=0·001). In part 1, 100 (22%) placebo-treated and 90 (20%) natalizumab-treated patients had serious adverse events. In part 2, 291 natalizumab-continuing patients and 274 natalizumab-naive patients received natalizumab (median follow-up 160 weeks [range 108–221]). Serious adverse events occurred in 39 (13%) patients continuing natalizumab and in 24 (9%) patients initiating natalizumab. Two deaths occurred in part 1, neither of which was considered related to study treatment. No progressive multifocal leukoencephalopathy occurred. Interpretation: Natalizumab treatment for secondary progressive multiple sclerosis did not reduce progression on the primary multicomponent disability endpoint in part 1, but it did reduce progression on its upper-limb component. Longer-term trials are needed to assess whether treatment of secondary progressive multiple sclerosis might produce benefits on additional disability components. Funding: Biogen

The stem cell organisation, and the proliferative and gene expression profile of Barrett's epithelium, replicates pyloric-type gastric glands

Objective: Barrett's oesophagus shows appearances described as ‘intestinal metaplasia’, in structures called ‘crypts’ but do not typically display crypt architecture. Here, we investigate their relationship to gastric glands. Methods: Cell proliferation and migration within Barrett's glands was assessed by Ki67 and iododeoxyuridine (IdU) labelling. Expression of mucin core proteins (MUC), trefoil family factor (TFF) peptides and LGR5 mRNA was determined by immunohistochemistry or by in situ hybridisation, and clonality was elucidated using mitochondrial DNA (mtDNA) mutations combined with mucin histochemistry. Results: Proliferation predominantly occurs in the middle of Barrett's glands, diminishing towards the surface and the base: IdU dynamics demonstrate bidirectional migration, similar to gastric glands. Distribution of MUC5AC, TFF1, MUC6 and TFF2 in Barrett's mirrors pyloric glands and is preserved in Barrett's dysplasia. MUC2-positive goblet cells are localised above the neck in Barrett's glands, and TFF3 is concentrated in the same region. LGR5 mRNA is detected in the middle of Barrett's glands suggesting a stem cell niche in this locale, similar to that in the gastric pylorus, and distinct from gastric intestinal metaplasia. Gastric and intestinal cell lineages within Barrett's glands are clonal, indicating derivation from a single stem cell. Conclusions: Barrett's shows the proliferative and stem cell architecture, and pattern of gene expression of pyloric gastric glands, maintained by stem cells showing gastric and intestinal differentiation: neutral drift may suggest that intestinal differentiation advances with time, a concept critical for the understanding of the origin and development of Barrett's oesophagus

MLL-rearranged B lymphoblastic leukemias selectively express the immunoregulatory carbohydrate-binding protein galectin-1

Leukemias with 11q23 translocations involving the Mixed Lineage Leukemia (MLL) gene exhibit unique clinical and biological features and have a poor prognosis. In a screen for molecular markers of MLL rearrangement, we identified the specific overexpression of an immunomodulatory lectin Galectin-1 (Gal1) in MLL-rearranged B lymphoblastic leukemias (B-ALL) compared to other MLL-germline ALLs. To assess the diagnostic utility of Gal1 expression in identifying MLL-rearranged B-ALLs, we performed Gal1 immunostaining on a large series of primary ALLs with known MLL status. All 11 MLL-rearranged B-ALLs had abundant Gal1 expression; in marked contrast, only 1 of 42 germline-MLL B-ALLs expressed Gal1. In addition, Gal1 was readily detected in diagnostic samples of MLL-rearranged B-ALLs by intracellular flow cytometry. Since deregulated gene expression in MLL-rearranged leukemias may be related to the altered histone methyltransferase activity of MLL fusion protein complex, we analyzed histone H3 lysine 79 (H3K79) dimethylation in the Gal1 promoter region using chromatin immunoprecipitation. Gal1 promoter H3K79diMe was ≈ 5 fold higher in a MLL-rearranged B-ALL cell line than in a B-ALL line without the MLL translocation. Furthermore, the Gal1 promoter H3K79 was significantly hypermethylated in primary MLL-rearranged B-ALLs compared to MLL-germline B-ALLs and normal pre-B cells, implicating this epigenetic modification as a mechanism for Gal1 overexpression in MLL B-ALL.Fil: Juszczynski, Przemyslaw. Dana Farber Cancer Institute; Estados UnidosFil: Rodig, Scott J.. Brigham & Women; Estados UnidosFil: Ouyang, Jing. Dana Farber Cancer Institute; Estados UnidosFil: O´Donnell, Evan. Dana Farber Cancer Institute; Estados UnidosFil: Takeyama, Kunihiko. Dana Farber Cancer Institute; Estados UnidosFil: Mlynarski, Wojciech. Dana Farber Cancer Institute; Estados UnidosFil: Mycko, Katarzyna. Dana Farber Cancer Institute; Estados UnidosFil: Szczepanski, Tomasz. Dana Farber Cancer Institute; Estados UnidosFil: Gaworczyk, Anna. Medical University of Lodz; PoloniaFil: Krivtsov, Andrei. Medical University of Lodz; PoloniaFil: Faber, Joerg. Medical University of Silesia; PoloniaFil: Sinha, Amit U.. Medical University of Lublin; PoloniaFil: Rabinovich, Gabriel Adrian. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina; ArgentinaFil: Armstrong, Scott A.. Children; Estados UnidosFil: Kutok, Jeffery. Children; Estados UnidosFil: Shipp, Margaret A.. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina; Argentin

Biochar-based fertilizer: Supercharging root membrane potential and biomass yield of rice

Biochar-based compound fertilizers (BCF) and amendments have proven to enhance crop yields and modify soil properties (pH, nutrients, organic matter, structure etc.) and are now in commercial production in China. While there is a good understanding of the changes in soil properties following biochar addition, the interactions within the rhizosphere remain largely unstudied, with benefits to yield observed beyond the changes in soil properties alone. We investigated the rhizosphere interactions following the addition of an activated wheat straw BCF at an application rates of 0.25% (g·g−1 soil), which could potentially explain the increase of plant biomass (by 67%), herbage N (by 40%) and P (by 46%) uptake in the rice plants grown in the BCF-treated soil, compared to the rice plants grown in the soil with conventional fertilizer alone. Examination of the roots revealed that micron and submicron-sized biochar were embedded in the plaque layer. BCF increased soil Eh by 85 mV and increased the potential difference between the rhizosphere soil and the root membrane by 65 mV. This increased potential difference lowered the free energy required for root nutrient accumulation, potentially explaining greater plant nutrient content and biomass. We also demonstrate an increased abundance of plant-growth promoting bacteria and fungi in the rhizosphere. We suggest that the redox properties of the biochar cause major changes in electron status of rhizosphere soils that drive the observed agronomic benefits

Common Genetic Variation Near the Phospholamban Gene Is Associated with Cardiac Repolarisation: Meta-Analysis of Three Genome-Wide Association Studies

To identify loci affecting the electrocardiographic QT interval, a measure of cardiac repolarisation associated with risk of ventricular arrhythmias and sudden cardiac death, we conducted a meta-analysis of three genome-wide association studies (GWAS) including 3,558 subjects from the TwinsUK and BRIGHT cohorts in the UK and the DCCT/EDIC cohort from North America. Five loci were significantly associated with QT interval at P<1×10$^{−6}$. To validate these findings we performed an in silico comparison with data from two QT consortia: QTSCD (n = 15,842) and QTGEN (n = 13,685). Analysis confirmed the association between common variants near NOS1AP (P = 1.4×10$^{−83}$) and the phospholamban (PLN) gene (P = 1.9×10$^{−29}$). The most associated SNP near NOS1AP (rs12143842) explains 0.82% variance; the SNP near PLN (rs11153730) explains 0.74% variance of QT interval duration. We found no evidence for interaction between these two SNPs (P = 0.99). PLN is a key regulator of cardiac diastolic function and is involved in regulating intracellular calcium cycling, it has only recently been identified as a susceptibility locus for QT interval. These data offer further mechanistic insights into genetic influence on the QT interval which may predispose to life threatening arrhythmias and sudden cardiac death