Effects of unilateral 6-OHDA lesions on [3H]-N-propylnorapomorphine binding in striatum ex vivo and vulnerability to amphetamine-evoked dopamine release in rat

It has been argued that agonist ligands for dopamine D(2/3) receptors recognize a privileged subset of the receptors in living striatum, those which are functionally coupled to intracellular G-proteins. In support of this claim, the D(2/3) agonist [(3)H]-N-propylnorapomorphine ([(3)H]NPA) proved to be more vulnerable to competition from endogenous dopamine than was the antagonist ligand [(11)C]raclopride, measured ex vivo in mouse striatum, and subsequently in multi-tracer PET studies of analogous design. Based on these results, we predicted that prolonged dopamine depletion would result in a preferential increase in agonist binding, and a lesser competition from residual dopamine to the agonist binding. To test this hypothesis we used autoradiography to measure [(3)H]NPA and [(3)H]raclopride binding sites in hemi-parkinsonian rats with unilateral 6-OHDA lesions, with and without amphetamine challenge. Unilateral lesions were associated with a more distinct increase in [(3)H]NPA binding ex vivo than was seen for [(3)H]raclopride binding in vitro. Furthermore, this preferential asymmetry in [(3)H]NPA binding was more pronounced in amphetamine treated rats. We consequently predict that agonist ligands should likewise be fitter than antagonists for detecting responses to denervation in positron emission tomography studies of idiopathic Parkinson's disease. Agonist binding increases in vivo are likely to reflect the composite of a sensitization-like phenomenon, and relatively less competition from endogenous dopamine, as seen in the lesioned side of 6-OHDA induced hemi-parkinsonism.     

Where There Is No Toilet: Water and Sanitation Environments of Domestic and Facility Births in Tanzania

Background

Inadequate water and sanitation during childbirth are likely to lead to poor maternal and newborn outcomes. This paper uses existing data sources to assess the water and sanitation (WATSAN) environment surrounding births in Tanzania in order to interrogate whether such estimates could be useful for guiding research, policy and monitoring initiatives.

Methods

We used the most recent Tanzania Demographic and Health Survey (DHS) to characterise the delivery location of births occurring between 2005 and 2010. Births occurring in domestic environments were characterised as WATSAN-safe if the home fulfilled international definitions of improved water and improved sanitation access. We used the 2006 Service Provision Assessment survey to characterise the WATSAN environment of facilities that conduct deliveries. We combined estimates from both surveys to describe the proportion of all births occurring in WATSAN-safe environments and conducted an equity analysis based on DHS wealth quintiles and eight geographic zones.

Results

42.9% (95% confidence interval: 41.6%–44.2%) of all births occurred in the woman''s home. Among these, only 1.5% (95% confidence interval: 1.2%–2.0%) were estimated to have taken place in WATSAN-safe conditions. 74% of all health facilities conducted deliveries. Among these, only 44% of facilities overall and 24% of facility delivery rooms were WATSAN-safe. Combining the estimates, we showed that 30.5% of all births in Tanzania took place in a WATSAN-safe environment (range of uncertainty 25%–42%). Large wealth-based inequalities existed in the proportion of births occurring in domestic environments based on wealth quintile and geographical zone.

Conclusion

Existing data sources can be useful in national monitoring and prioritisation of interventions to improve poor WATSAN environments during childbirth. However, a better conceptual understanding of potentially harmful exposures and better data are needed in order to devise and apply more empirical definitions of WATSAN-safe environments, both at home and in facilities.     

Recognition of envelope and tat protein synthetic peptide analogs by HIV positive sera or plasma

A series of synthetic peptides corresponding to segments of HIV encoded proteins were selected using criteria described by Welling et al. [(1985) FEBS Lett. 188, 215]. Synthetic peptide analogs to gp120 (2-13), (55-65), gp41 (582-596) (659-670) and tatIII (71-83) were recognized by 41-67% of sera or plasma from individuals known to be infected with HIV on the basis of virus isolation or Western blot screening. The peptide which reacted with most sera or plasma was gp41 (582-596), a conserved region in the transmembrane glycoprotein. An extended peptide analog, gp41 (579-599), tested against the same samples showed almost 100% reactivity, confirming independent studies identifying a highly immunodominant region of gp41. There was an unexpected high prevalence of antibodies (25%) to the tatIII peptide.     

Agonistic behaviour,responses to a novel object and some aspects of maintenance behaviour in feral-strain and domestic chickens

Feral-strain fowl, bred from birds captured on North-West Island (24°S, 150°E), were compared with domestic chickens hatched and raised under similar conditions. Aspects of behaviour considered included agonistic behaviour and responses to unfamiliar environments and objects. There were many similarities between the feral and domestic fowl in behaviour, but there were also many differences between the strains.Feral cockerels showed higher levels of agonistic behaviour than domestic cockerels, under some conditions. There were differences between young feral and Leghorn-cross chickens in the “freezing” response to handling and placement in an unfamiliar cage, with the feral chickens responding more rapidly.Feral cockerels showed a greater initial avoidance of a novel object than did Black Australorp bantam cockerels, but after a short interval they spent more time near the novel object than the bantams.These results are discussed in relation to selection pressures under conditions of domestication, and on North-West Island.     

Hydrazinolysis-N-reacetylation of glycopeptides and glycoproteins. Model studies using 2-acetamido-1-N-(L-aspart-4-oyl)-2-deoxy-beta-D-glucopyranosy lamine

2-Acetamido-1-N-(L-aspart-4-oyl)-2-deoxy-beta-D-glucopyranosyla mine (1) was used as a model glycopeptide to study the hydrazinolysis-N-reacetylation procedure. The major, initial product was the beta-acetohydrazide derivative of 2-acetamido-2-deoxy-D-glucose (2) which gave 2-acetamido-2-deoxy-D-glucose (5) after exposure to acidic conditions. Very mild conditions of hydrolysis of 2 gave a 75-80% overall yield of 5 from 1 after the hydrazinolysis-N-reacetylation procedure. Several other minor compounds were detected which were not converted into 5 upon mild acid hydrolysis, indicating that 20-25% of product cannot be recovered as 5 at the reducing end of oligosaccharides.     

Cross‐scale controls on carbon emissions from boreal forest megafires

Climate warming and drying is associated with increased wildfire disturbance and the emergence of megafires in North American boreal forests. Changes to the fire regime are expected to strongly increase combustion emissions of carbon (C) which could alter regional C balance and positively feedback to climate warming. In order to accurately estimate C emissions and thereby better predict future climate feedbacks, there is a need to understand the major sources of heterogeneity that impact C emissions at different scales. Here, we examined 211 field plots in boreal forests dominated by black spruce (Picea mariana) or jack pine (Pinus banksiana) of the Northwest Territories (NWT), Canada after an unprecedentedly large area burned in 2014. We assessed both aboveground and soil organic layer (SOL) combustion, with the goal of determining the major drivers in total C emissions, as well as to develop a high spatial resolution model to scale emissions in a relatively understudied region of the boreal forest. On average, 3.35 kg C m^?2 was combusted and almost 90% of this was from SOL combustion. Our results indicate that black spruce stands located at landscape positions with intermediate drainage contribute the most to C emissions. Indices associated with fire weather and date of burn did not impact emissions, which we attribute to the extreme fire weather over a short period of time. Using these results, we estimated a total of 94.3 Tg C emitted from 2.85 Mha of burned area across the entire 2014 NWT fire complex, which offsets almost 50% of mean annual net ecosystem production in terrestrial ecosystems of Canada. Our study also highlights the need for fine‐scale estimates of burned area that represent small water bodies and regionally specific calibrations of combustion that account for spatial heterogeneity in order to accurately model emissions at the continental scale.