Effects of NGF, NT-3 and GDNF family members on neurite outgrowth and migration from pelvic ganglia from embryonic and newborn mice

<p>Abstract</p> <p>Background</p> <p>Pelvic ganglia are derived from the sacral neural crest and contain both sympathetic and parasympathetic neurons. Various members of the neurotrophin and GDNF families of neurotrophic factors have been shown to play important roles in the development of a variety of peripheral sympathetic and parasympathetic neurons; however, to date, the role of these factors in the development of pelvic ganglia has been limited to postnatal and older ages. We examined the effects of NGF, NT-3, GDNF, neurturin and artemin on cell migration and neurite outgrowth from explants of the pelvic ganglia from embryonic and newborn mice grown on collagen gels, and correlated the responses with the immunohistochemical localization of the relevant receptors in fixed tissue.</p> <p>Results</p> <p>Cell migration assays showed that GDNF strongly stimulated migration of tyrosine hydroxylase (TH) cells of pelvic ganglia from E11.5, E14.5 and P0 mice. Other factors also promoted TH cell migration, although to a lesser extent and only at discrete developmental stages. The cells and neurites of the pelvic ganglia were responsive to each of the GDNF family ligands – GDNF, neurturin and artemin – from E11.5 onwards. In contrast, NGF and NT-3 did not elicit a significant neurite outgrowth effect until E14.5 onwards. Artemin and NGF promoted significant outgrowth of sympathetic (TH+) neurites only, whereas neurturin affected primarily parasympathetic (TH-negative) neurite outgrowth, and GDNF and NT-3 enhanced both sympathetic and parasympathetic neurite outgrowth. In comparison, collagen gel assays using gut explants from E11.5 and E14.5 mice showed neurite outgrowth only in response to GDNF at E11.5 and to neurturin only in E14.5 mice.</p> <p>Conclusion</p> <p>Our data show that there are both age-dependent and neuron type-dependent differences in the responsiveness of embryonic and neo-natal pelvic ganglion neurons to growth factors.</p

Npy deletion in an alcohol non-preferring rat model elicits differential effects on alcohol consumption and body weight.

Neuropeptide Y (NPY) is widely expressed in the central nervous system and influences many physiological processes. It is located within the rat quantitative trait locus (QTL) for alcohol preference on chromosome 4. Alcohol-nonpreferring (NP) rats consume very little alcohol, but have significantly higher NPY expression in the brain than alcohol-preferring (P) rats. We capitalized on this phenotypic difference by creating an Npy knockout (KO) rat using the inbred NP background to evaluate NPY effects on alcohol consumption. Zinc finger nuclease (ZNF) technology was applied, resulting in

Ocean variability contributing to basal melt rate near the ice front of Ross Ice Shelf, Antarctica

Author Posting. © American Geophysical Union, 2014. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Journal of Geophysical Research: Oceans 119 (2014): 4214–4233, doi:10.1002/2014JC009792.Basal melting of ice shelves is an important, but poorly understood, cause of Antarctic ice sheet mass loss and freshwater production. We use data from two moorings deployed through Ross Ice Shelf, ∼6 and ∼16 km south of the ice front east of Ross Island, and numerical models to show how the basal melting rate near the ice front depends on sub-ice-shelf ocean variability. The moorings measured water velocity, conductivity, and temperature for ∼2 months starting in late November 2010. About half of the current velocity variance was due to tides, predominantly diurnal components, with the remainder due to subtidal oscillations with periods of a few days. Subtidal variability was dominated by barotropic currents that were large until mid-December and significantly reduced afterward. Subtidal currents were correlated between moorings but uncorrelated with local winds, suggesting the presence of waves or eddies that may be associated with the abrupt change in water column thickness and strong hydrographic gradients at the ice front. Estimated melt rate was ∼1.2 ± 0.5 m a−1 at each site during the deployment period, consistent with measured trends in ice surface elevation from GPS time series. The models predicted similar annual-averaged melt rates with a strong annual cycle related to seasonal provision of warm water to the ice base. These results show that accurately modeling the high spatial and temporal ocean variability close to the ice-shelf front is critical to predicting time-dependent and mean values of meltwater production and ice-shelf thinning.The Woods Hole Oceanographic Institution (WHOI) participation in the ANDRILL Coulman High Program was supported by the National Science Foundation Office of Polar Programs (NSF ANT-0839108) through a subcontract from the University of Nebraska, Lincoln (UNL 25-0550-0004-004). I. Arzeno was supported as a 2011 WHOI Summer Student Fellow through the NSF Research Experiences for Undergraduates program (OCE- 0649139). L. Padman and S. Springer were supported by NASA grant NNX10AG19G to Earth & Space Research (ESR). M. Williams and C. Stewart were supported by the New Zealand National Institute of Water and Atmosphere (NIWA) core funding under the National Climate Centre, and the Ministry of Business, Innovation, and Employment (Contract CO5X1001).2015-01-0

Multivariable fractional polynomial interaction to investigate continuous effect modifiers in a meta-analysis on higher versus lower PEEP for patients with ARDS.

OBJECTIVES: A recent individual patient data (IPD) meta-analysis suggested that patients with moderate or severe acute respiratory distress syndrome (ARDS) benefit from higher positive end-expiratory pressure (PEEP) ventilation strategies. However, thresholds for continuous variables (eg, hypoxaemia) are often arbitrary and linearity assumptions in regression approaches may not hold; the multivariable fractional polynomial interaction (MFPI) approach can address both problems. The objective of this study was to apply the MFPI approach to investigate interactions between four continuous patient baseline variables and higher versus lower PEEP on clinical outcomes. SETTING: Pooled data from three randomised trials in intensive care identified by a systematic review. PARTICIPANTS: 2299 patients with acute lung injury requiring mechanical ventilation. INTERVENTIONS: Higher (N=1136) versus lower PEEP (N=1163) ventilation strategy. OUTCOME MEASURES: Prespecified outcomes included mortality, time to death and time-to-unassisted breathing. We examined the following continuous baseline characteristics as potential effect modifiers using MFPI: PaO2/FiO2 (arterial partial oxygen pressure/ fraction of inspired oxygen), oxygenation index, respiratory system compliance (tidal volume/(inspiratory plateau pressure-PEEP)) and body mass index (BMI). RESULTS: We found that for patients with PaO2/FiO2 below 150 mm Hg, but above 100 mm Hg or an oxygenation index above 12 (moderate ARDS), higher PEEP reduces hospital mortality, but the beneficial effect appears to level off for patients with very severe ARDS. Patients with mild ARDS (PaO2/FiO2 above 200 mm Hg or an oxygenation index below 10) do not seem to benefit from higher PEEP and might even be harmed. For patients with a respiratory system compliance above 40 mL/cm H2O or patients with a BMI above 35 kg/m(2), we found a trend towards reduced mortality with higher PEEP, but there is very weak statistical confidence in these findings. CONCLUSIONS: MFPI analyses suggest a nonlinear effect modification of higher PEEP ventilation by PaO2/FiO2 and oxygenation index with reduced mortality for some patients suffering from moderate ARDS. STUDY REGISTRATION NUMBER: CRD42012003129

Rapid Quantification of Soilborne Pathogen Communities in Wheat-based Long-term Field Experiments

This is an author's peer-reviewed final manuscript, as accepted by the publisher. The published article is copyrighted by The American Phytopathological Society and can be found at: https://doi.org/10.1094/PDIS-09-15-1020-RERainfed experiments operated continuously for up to 84 years in semiarid eastern Oregon are among the oldest agronomic trials in North America. Disease incidence and severity had been quantified visually but quantification of inoculum density had not been attempted. Natural inoculum of 17 fungal and nematode pathogens were quantified for each of two years on eight trials using DNA extracts from soil. Crop type, tillage, rotation, soil fertility and year, and their interactions, had large effects on the pathogens. Fusarium culmorum and Pratylenchus thornei were more dominant than F. pseudograminearum and P. neglectus where spring crops were grown, and the opposite species dominances occurred where winter wheat was the only crop. Bipolaris sorokiniana and Phoma pinodella were restricted to presence of spring cereals and pulse crops, respectively. Helgardia spp. occurred in winter wheat-fallow rotations but not in annual winter wheat. Gaeumannomyces graminis var. tritici was more prevalent in cultivated than in non-cultivated soils and the opposite generally occurred for Rhizoctonia solani AG-8. Densities of Pythium spp. Clade F were high but were also influenced by treatments. Significant treatment effects and interactions were more prevalent in two long-standing (> 50 yr) annually cropped experiments (29%) than two long-standing 2-yr wheat-fallow rotations (14%). Associations among pathogens occurred mostly in an 84-yr-old annual cereals experiment. This survey provided guidance for research on dynamics of root-infecting pathogens of rainfed field crops and identified two pathogens (D. tritici-repentis and Phoma pinodella) not previously identified at the location

Building blocks: a strategy for near-term action within the new global climate framework

The Paris Agreement cemented a new framework for global climate policy based on the voluntary and non-legally binding emission reduction actions by both developed and developing countries. The building blocks strategy for climate action discussed in this Special Issue is well adapted to and strongly complements this new structure. Building blocks focus on multiple transnational mechanisms for mobilizing a wide range of both public and private actors to take actions that reduce emissions by capturing incentives other than climate mitigation as such. The initial commitments by countries under the Paris Agreement are insufficient to meet the level of action required to stabilize the global climate system at a safe level. As such, new voluntary action by public and private actors will be required. The building blocks strategy, and the examples presented in this Special Issue, offers answers to the question of how to generate and design smaller-scale initiatives