Above- and belowground community linkages in boreal peatlands

Plant Ecology - In boreal peatlands, the aboveground (plant) and belowground (microbial) communities are acutely linked because the whole soil profile is partially decomposed plant matter (peat),...     

Developmental nicotine exposure enhances inhibitory synaptic transmission in motor neurons and interneurons critical for normal breathing

Nicotine exposure in utero negatively affects neuronal growth, differentiation, and synaptogenesis. We used rhythmic brainstems slices and immunohistochemistry to determine how developmental nicotine exposure (DNE) alters inhibitory neurotransmission in two regions essential to normal breathing, the hypoglossal motor nucleus (XIIn), and preBötzinger complex (preBötC). We microinjected glycine or muscimol (GABA_A agonist) into the XIIn or preBötC of rhythmic brainstem slices from neonatal rats while recording from XII nerve roots to obtain XII motoneuron population activity. Injection of glycine or muscimol into the XIIn reduced XII nerve burst amplitude, while injection into the preBötC altered nerve burst frequency. These responses were exaggerated in preparations from DNE animals. Quantitative immunohistochemistry revealed a significantly higher GABA_A receptor density on XII motoneurons from DNE pups. There were no differences in GABA_A receptor density in the preBötC, and there were no differences in glycine receptor expression in either region. Nicotine, in the absence of other chemicals in tobacco smoke, alters normal development of brainstem circuits that are critical for normal breathing. © 2015 Wiley Periodicals, Inc. Develop Neurobiol 76: 337–354, 2016     

Structural elements necessary for oligomerization, trafficking, and cell sorting function of paraxial protocadherin

Protocadherins have been shown to regulate cell adhesion, cell migration, cell survival, and tissue morphogenesis in the embryo and the central nervous system, but little is known about the mechanism of protocadherin function. We previously showed that Xenopus paraxial protocadherin (PAPC) mediates cell sorting and morphogenesis by down-regulating the adhesion activity of a classical cadherin, C-cadherin. Classical cadherins function by forming lateral dimers that are necessary for their adhesive function. However, it is not known whether oligomerization also plays a role in protocadherin function. We show here that PAPC forms oligomers that are stabilized by disulfide bonds formed between conserved Cys residues in the extracellular domain. Disruption of these disulfide bonds by dithiothreitol or mutation of the conserved cysteines results in defects in oligomerization, post-translational modification, trafficking to the cell surface and cell sorting function of PAPC. Furthermore, none of the residues in the cytoplasmic domain of PAPC is required for its cell sorting activity, whereas both the transmembrane domain and the extracellular domain are necessary. Therefore, protein oligomerization and/or protein interactions via the extracellular and transmembrane domains of PAPC are required for its cell sorting function.     

Synthesis and evaluation of pyridazinone-phenethylamine derivatives as selective and orally bioavailable histamine H3 receptor antagonists with robust wake-promoting activity

A series of pyridazinone-phenethylamine derivatives with moderate to low nanomolar affinity for rat and human H(3)R are described. These analogs exhibited excellent selectivity and metabolic stability, with acceptable rat pharmacokinetic properties. In vivo, 7 and 11 demonstrated potent H(3)R functional antagonism in the rat dipsogenia model and robust wake-promoting activity in the rat electroencephalogram/electromyography (EEG/EMG) model.     

Barriers,Facilitators and Priorities for Implementation of WHO Maternal and Perinatal Health Guidelines in Four Lower-Income Countries: A GREAT Network Research Activity

BackgroundHealth systems often fail to use evidence in clinical practice. In maternal and perinatal health, the majority of maternal, fetal and newborn mortality is preventable through implementing effective interventions. To meet this challenge, WHO’s Department of Reproductive Health and Research partnered with the Knowledge Translation Program at St. Michael’s Hospital (SMH), University of Toronto, Canada to establish a collaboration on knowledge translation (KT) in maternal and perinatal health, called the GREAT Network (Guideline-driven, Research priorities, Evidence synthesis, Application of evidence, and Transfer of knowledge). We applied a systematic approach incorporating evidence and theory to identifying barriers and facilitators to implementation of WHO maternal heath recommendations in four lower-income countries and to identifying implementation strategies to address these.MethodsWe conducted a mixed-methods study in Myanmar, Uganda, Tanzania and Ethiopia. In each country, stakeholder surveys, focus group discussions and prioritization exercises were used, involving multiple groups of health system stakeholders (including administrators, policymakers, NGOs, professional associations, frontline healthcare providers and researchers).ResultsDespite differences in guideline priorities and contexts, barriers identified across countries were often similar. Health system level factors, including health workforce shortages, and need for strengthened drug and equipment procurement, distribution and management systems, were consistently highlighted as limiting the capacity of providers to deliver high-quality care. Evidence-based health policies to support implementation, and improve the knowledge and skills of healthcare providers were also identified. Stakeholders identified a range of tailored strategies to address local barriers and leverage facilitators.ConclusionThis approach to identifying barriers, facilitators and potential strategies for improving implementation proved feasible in these four lower-income country settings. Further evaluation of the impact of implementing these strategies is needed.     

The performance of aminoalkyl/fluorocarbon/hydrocarbon-modified xerogel coatings against the marine alga Ectocarpus crouaniorum: relative roles of surface energy and charge

The effect of a series of xerogel coatings modified with aminoalkyl/fluorocarbon/hydrocarbon groups on the adhesion of a new test species, the filamentous brown alga Ectocarpus crouaniorum, has been explored, and compared with the green alga Ulva linza. The results showed that E. crouaniorum adhered weakly to the less polar, low wettability coatings in the series, but stronger adhesion was shown on polar, higher surface energy coatings containing aminoalkyl groups. The results from a separate series of coatings tuned to have similar surface energies and polarities after immersion in artificial seawater (ASW), but widely different surface charges, demonstrated that surface charge was more important than surface energy and polarity in determining the adhesion strength of both E. crouaniorum and U. linza on xerogel coatings. No correlation was found between adhesion and contact angle hysteresis. X-ray photoelectron spectroscopy analysis of samples after immersion in ASW confirmed the presence of charged ammonium groups on the surface of the aminoalkylated coatings.