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

Neighbourhood physical activity environments and adiposity in children and mothers : a three-year longitudinal study

Background Although neighbourhood environments are often blamed for contributing to rising levels of obesity, current evidence is based predominantly on cross-sectional samples. This study examined associations between objectively-measured environmental characteristics of neighbourhoods and adiposity cross-sectionally and longitudinally over three years in children and their female carers.Methods Longitudinal study of 140 5-6 year-old and 269 10-12 year-old children and their female carers (n = 369). At baseline (2001) and follow-up (2004), height and weight were measured among children and self-reported among female carers, and were used to compute BMI z-scores and BMI, respectively. A Geographic Information System determined access to destinations (public open spaces, sports options, walking/cycling tracks), road connectivity (density of cul-de-sacs and intersections, proportion of 4-way intersections, length of \u27access\u27 paths (overpasses, access lanes, throughways between buildings)) and traffic exposure (length of \u27busy\u27 and \u27local\u27 roads) within 800 m and 2 km of home. Univariate and multivariable linear regression analyses examined associations between environmental characteristics and BMI/BMI z-scores at baseline and change in BMI/BMI z-scores over the three years.Results Cross-sectionally, BMI z-score was inversely associated with length (km) of access paths within 800 m (b = -0.50) and 2 km (b = -0.16) among younger and number of sport/recreation public open spaces (b = -0.14) and length (km) of \u27access\u27 paths (b = -0.94) within 800 m and length of local roads within 2 km (b = -0.01) among older children. Among female carers, BMI was associated with length (km) of walking/cycling tracks (b = 0.17) and busy roads (b = -0.34) within 800 m. Longitudinally, the proportion of intersections that were 4-way (b = -0.01) within 800 m of home was negatively associated with change in BMI z-score among younger children, while length (km) of access paths (b = 0.18) within 800 m was significant among older children. Among female carers, options for aerobics/fitness and swimming within 2 km were associated with change in BMI (B = -0.42).Conclusion A small number of neighbourhood environment features were associated with adiposity outcomes. These differed by age group and neighbourhood scale (800 m and 2 km) and were inconsistent between cross-sectional and longitudinal findings. However, the results suggest that improvements to road connectivity and slowing traffic and provision of facilities for leisure activities popular among women may support obesity prevention efforts.<br /

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

A species-wide inventory of NLR genes and alleles in Arabidopsis thaliana

Infectious disease is both a major force of selection in nature and a prime cause of yield loss in agriculture. In plants, disease resistance is often conferred by nucleotide-binding leucine-rich repeat (NLR) proteins, intracellular immune receptors that recognize pathogen proteins and their effects on the host. Consistent with extensive balancing and positive selection, NLRs are encoded by one of the most variable gene families in plants, but the true extent of intraspecific NLR diversity has been unclear. Here, we define a nearly complete species-wide pan-NLRome in Arabidopsis thaliana based on sequence enrichment and long-read sequencing. The pan-NLRome largely saturates with approximately 40 well-chosen wild strains, with half of the pan-NLRome being present in most accessions. We chart NLR architectural diversity, identify new architectures, and quantify selective forces that act on specific NLRs and NLR domains. Our study provides a blueprint for defining pan-NLRomes

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

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

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