MECHANISMS FOR ADDRESSING THIRD-PARTY IMPACTS RESULTING FROM VOLUNTARY WATER TRANSFERS

This research uses laboratory experiments to test alternative water market institutions designed to protect third-party interests. The institutions tested include taxing mechanisms that raise revenue to compensate affected third-parties, and a free market in which third-parties actively participate. We also discuss the likely implications of a command-and-control approach in which there are fixed limits on the volume of water that may be exported from a region. The results indicate that there are some important trade-offs in selecting a policy option. Although theoretically optimal, active third-party participation in the market is likely to result in free-riding that may erode some or all of the efficiency gains, and may introduce volatility into the market. Fixed limits on water exports are likely to result in a more stable market, but the constraints on exports will result in lower levels of social welfare. Taxing transfers and compensating third-parties offers a promising balance of efficiency, equity and market stability.Resource /Energy Economics and Policy,

Membrane-dependent activities of human 15-lox-2 and its murine counterpart implications for murine models of atherosclerosis

© 2016 by The American Society for Biochemistry and Molecular Biology, Inc. The enzyme encoded by the ALOX15B gene has been linked to the development of atherosclerotic plaques in humans and in a mouse model of hypercholesterolemia. In vitro, these enzymes, which share 78% sequence identity, generate distinct products from their substrate arachidonic acid: the human enzyme, a 15-S-hydroperoxy product; and the murine enzyme, an 8-S-product. We probed the activities of these enzymes with nanodiscs as membrane mimics to determine whether they can access substrate esterified in a bilayer and characterized their activities at the membrane interface. We observed that both enzymes transform phospholipid-esterified arachidonic acid to a 15-S-product. Moreover, when expressed in transfected HEK cells, both enzymes result in significant increases in the amounts of 15-hydroxyderivatives of eicosanoids detected. In addition, we show that 15-LOX-2 is distributed at the plasma membrane when the HEK293 cells are stimulated by the addition Ca 2+ ionophore and that cellular localization is dependent upon the presence of a putative membrane insertion loop. We also report that sequence differences between the human and mouse enzymes in this loop appear to confer distinct mechanisms of enzyme-membrane interaction for the homologues

Myeloid DAP12-associating lectin (MDL)-1 regulates synovial inflammation and bone erosion associated with autoimmune arthritis.

DNAX adaptor protein 12 (DAP12) is a trans-membrane adaptor molecule that transduces activating signals in NK and myeloid cells. Absence of functional Dap12 results in osteoclast defects and bone abnormalities. Because DAP12 has no extracelluar binding domains, it must pair with cell surface receptors for signal transduction. There are at least 15 known DAP12-associating cell surface receptors with distinct temporal and cell type-specific expression patterns. Our aim was to determine which receptors may be important in DAP12-associated bone pathologies. Here, we identify myeloid DAP12-associating lectin (MDL)-1 receptor (also known as CLEC5A) as a key regulator of synovial injury and bone erosion during autoimmune joint inflammation. Activation of MDL-1 leads to enhanced recruitment of inflammatory macrophages and neutrophils to the joint and promotes bone erosion. Functional blockade of MDL-1 receptor via Mdl1 deletion or treatment with MDL-1-Ig fusion protein reduces the clinical signs of autoimmune joint inflammation. These findings suggest that MDL-1 receptor may be a therapeutic target for treatment of immune-mediated skeletal disorders

Multiple factors interact to produce responses resembling spectrum of human disease in Campylobacter jejuni infected C57BL/6 IL-10-/- mice

<p>Abstract</p> <p>Background</p> <p><it>Campylobacter jejuni </it>infection produces a spectrum of clinical presentations in humans – including asymptomatic carriage, watery diarrhea, and bloody diarrhea – and has been epidemiologically associated with subsequent autoimmune neuropathies. This microorganism is genetically variable and possesses genetic mechanisms that may contribute to variability in nature. However, relationships between genetic variation in the pathogen and variation in disease manifestation in the host are not understood. We took a comparative experimental approach to explore differences among different <it>C. jejuni </it>strains and studied the effect of diet on disease manifestation in an interleukin-10 deficient mouse model.</p> <p>Results</p> <p>In the comparative study, C57BL/6 interleukin-10^-/-mice were infected with seven genetically distinct <it>C. jejuni </it>strains. Four strains colonized the mice and caused disease; one colonized with no disease; two did not colonize. A DNA:DNA microarray comparison of the strain that colonized mice without disease to <it>C. jejuni </it>11168 that caused disease revealed that putative virulence determinants, including loci encoding surface structures known to be involved in <it>C. jejuni </it>pathogenesis, differed from or were absent in the strain that did not cause disease. In the experimental study, the five colonizing strains were passaged four times in mice. For three strains, serial passage produced increased incidence and degree of pathology and decreased time to develop pathology; disease shifted from watery to bloody diarrhea. Mice kept on an ~6% fat diet or switched from an ~12% fat diet to an ~6% fat diet just before infection with a non-adapted strain also exhibited increased incidence and severity of disease and decreased time to develop disease, although the effects of diet were only statistically significant in one experiment.</p> <p>Conclusion</p> <p><it>C. jejuni </it>strain genetic background and adaptation of the strain to the host by serial passage contribute to differences in disease manifestations of <it>C. jejuni </it>infection in C57BL/6 IL-10^-/-mice; differences in environmental factors such as diet may also affect disease manifestation. These results in mice reflect the spectrum of clinical presentations of <it>C. jejuni </it>gastroenteritis in humans and contribute to usefulness of the model in studying human disease.</p

A microRNA negative feedback loop downregulates vesicle transport and inhibits fear memory

The SNARE-mediated vesicular transport pathway plays major roles in synaptic remodeling associated with formation of long-term memories, but the mechanisms that regulate this pathway during memory acquisition are not fully understood. Here we identify miRNAs that are up-regulated in the rodent hippocampus upon contextual fear-conditioning and identify the vesicular transport and synaptogenesis pathways as the major targets of the fear-induced miRNAs. We demonstrate that miR-153, a member of this group, inhibits the expression of key components of the vesicular transport machinery, and down-regulates Glutamate receptor A1 trafficking and neurotransmitter release. MiR-153 expression is specifically induced during LTP induction in hippocampal slices and its knockdown in the hippocampus of adult mice results in enhanced fear memory. Our results suggest that miR-153, and possibly other fear-induced miRNAs, act as components of a negative feedback loop that blocks neuronal hyperactivity at least partly through the inhibition of the vesicular transport pathway.Brain & Behavior Research Foundation (Young Investigator Award)JPB Foundatio

Wintertime Spatial Distribution of Ammonia and its Emission Sources in the Great Salt Lake Region

Ammonium-containing aerosols are a major component of wintertime air pollution in many densely populated regions around the world. Especially in mountain basins, the formation of persistent cold-air pools (PCAPs) can enhance particulate matter with diameters less than 2.5 µm (PM2.5) to levels above air quality standards. Under these conditions, PM2.5 in the Great Salt Lake region of northern Utah has been shown to be primarily composed of ammonium nitrate; however, its formation processes and sources of its precursors are not fully understood. Hence, it is key to understanding the emission sources of its gas phase precursor, ammonia (NH3). To investigate the formation of ammonium nitrate, a suite of trace gases and aerosol composition were sampled from the NOAA Twin Otter aircraft during the Utah Winter Fine Particulate Study (UWFPS) in January and February 2017. NH3 was measured using a quantum cascade tunable infrared laser differential absorption spectrometer (QC-TILDAS), while aerosol composition, including particulate ammonium (pNH4), was measured with an aerosol mass spectrometer (AMS). The origin of the sampled air masses was investigated using the Stochastic Time-Inverted Lagrangian Transport (STILT) model and combined with an NH3 emission inventory to obtain model-predicted NHx (=NH3+pNH4) enhancements. Enhancements represent the increase in NH3 mixing ratios within the last 24 h due to emissions within the model footprint. Comparison of these NHx enhancements with measured NHx from the Twin Otter shows that modelled values are a factor of 1.6 to 4.4 lower for the three major valleys in the region. Among these, the underestimation is largest for Cache Valley, an area with intensive agricultural activities. We find that one explanation for the underestimation of wintertime emissions may be the seasonality factors applied to NH3 emissions from livestock. An investigation of inter-valley exchange revealed that transport of NH3 between major valleys was limited and PM2.5 in Salt Lake Valley (the most densely populated area in Utah) was not significantly impacted by NH3 from the agricultural areas in Cache Valley. We found that in Salt Lake Valley around two thirds of NHx originated within the valley, while about 30 % originated from mobile sources and 60 % from area source emissions in the region. For Cache Valley, a large fraction of NOx potentially leading to PM2.5 formation may not be locally emitted but mixed in from other counties

Injury Rates in Age-Only Versus Age-and-Weight Playing Standard Conditions in American Youth Football

BACKGROUND: American youth football leagues are typically structured using either age-only (AO) or age-and-weight (AW) playing standard conditions. These playing standard conditions group players by age in the former condition and by a combination of age and weight in the latter condition. However, no study has systematically compared injury risk between these 2 playing standards. PURPOSE: To compare injury rates between youth tackle football players in the AO and AW playing standard conditions. STUDY DESIGN: Cohort study; Level of evidence, 2. METHODS: Athletic trainers evaluated and recorded injuries at each practice and game during the 2012 and 2013 football seasons. Players (age, 5-14 years) were drawn from 13 recreational leagues across 6 states. The sample included 4092 athlete-seasons (AW, 2065; AO, 2027) from 210 teams (AW, 106; O, 104). Injury rate ratios (RRs) with 95% CIs were used to compare the playing standard conditions. Multivariate Poisson regression was used to estimate RRs adjusted for residual effects of age and clustering by team and league. There were 4 endpoints of interest: (1) any injury, (2) non-time loss (NTL) injuries only, (3) time loss (TL) injuries only, and (4) concussions only. RESULTS: Over 2 seasons, the cohort accumulated 1475 injuries and 142,536 athlete-exposures (AEs). The most common injuries were contusions (34.4%), ligament sprains (16.3%), concussions (9.6%), and muscle strains (7.8%). The overall injury rate for both playing standard conditions combined was 10.3 per 1000 AEs (95% CI, 9.8-10.9). The TL injury, NTL injury, and concussion rates in both playing standard conditions combined were 3.1, 7.2, and 1.0 per 1000 AEs, respectively. In multivariate Poisson regression models controlling for age, team, and league, no differences were found between playing standard conditions in the overall injury rate (RRoverall, 1.1; 95% CI, 0.4-2.6). Rates for the other 3 endpoints were also similar (RRNTL, 1.1 [95% CI, 0.4-3.0]; RRTL, 0.9 [95% CI, 0.4-1.9]; RRconcussion, 0.6 [95% CI, 0.3-1.4]). CONCLUSION: For the injury endpoints examined in this study, the injury rates were similar in the AO and AW playing standards. Future research should examine other policies, rules, and behavioral factors that may affect injury risk within youth football

The L1 cell adhesion molecule constrains dendritic spine density in pyramidal neurons of the mouse cerebral cortex

A novel function for the L1 cell adhesion molecule, which binds the actin adaptor protein Ankyrin was identified in constraining dendritic spine density on pyramidal neurons in the mouse neocortex. In an L1-null mouse mutant increased spine density was observed on apical but not basal dendrites of pyramidal neurons in diverse cortical areas (prefrontal cortex layer 2/3, motor cortex layer 5, visual cortex layer 4. The Ankyrin binding motif (FIGQY) in the L1 cytoplasmic domain was critical for spine regulation, as demonstrated by increased spine density and altered spine morphology in the prefrontal cortex of a mouse knock-in mutant (L1YH) harboring a tyrosine (Y) to histidine (H) mutation in the FIGQY motif, which disrupted L1-Ankyrin association. This mutation is a known variant in the human L1 syndrome of intellectual disability. L1 was localized by immunofluorescence staining to spine heads and dendrites of cortical pyramidal neurons. L1 coimmunoprecipitated with Ankyrin B (220 kDa isoform) from lysates of wild type but not L1YH forebrain. This study provides insight into the molecular mechanism of spine regulation and underscores the potential for this adhesion molecule to regulate cognitive and other L1-related functions that are abnormal in the L1 syndrome