Abstract Dysfunction of basal ganglia circuits underlies a variety of movement disorders and neuropsychiatric conditions. Selective control of the electrical activity of striatal outflow pathways by ...manipulation of ion channel function presents a novel therapeutic approach. Toward this end, we have constructed and studied in vitro an adenoviral gene transfer vector that employs the promoter region of the dopamine-1 receptor to drive expression of the inward rectifier K+ channel Kir2.3. The use of this neuronal promoter confers cell-type specificity and a physiological level of trans-gene expression in rat primary striatal cultures. The electrophysiological properties were confirmed in transfected human embryonic kidney cells, in which an inwardly-rectifying, Cs+ -sensitive current was measured by voltage clamp. Current clamp studies of transduced striatal neurons demonstrated an increase in the firing threshold, latency to first action potential and decrease in neuronal excitability. Neurotoxin-induced activation of c-Fos, a marker of neuronal activity, was blocked in transduced neurons indicating that the decrease in electrical excitability was physiologically significant. When used in vivo , this strategy may have the potential to positively impact movement disorders by selectively changing activity of neurons belonging to the direct striatal pathway, characterized by the expression of dopamine-1 receptors.
The aims of this study were to establish expression of epidermal growth factor receptor (EGFR) and Ki67 in 67 archived biopsy samples of feline oral squamous cell carcinomas (FOSCCs) and to establish ...if the expression of either markers was predictive of survival. Samples were immunohistochemically labelled for the two proteins and scored. Statistical analyses of data, including Kaplan-Meier survival curves, were performed. All samples expressed both markers although levels differed between samples. Median overall survival was 46 days and 1-year survival was 5%. There was no correlation between Ki67 and EGFR scores (Pearson's correlation coefficient, P = 0.861). Low cellular proliferation (low Ki67 score) was positively correlated with an overall longer survival (Log Rank, P = 0.02) and a trend towards better survival for the high EGFR group was observed (Log Rank, P = 0.076). Ki67 and EGFR immunostaining in FOSCC may be of value as biochemical markers for screening of biopsies from cases of FOSCC.
In the oligotrophic waters to the east of Madagascar, a large phytoplankton bloom is found to occur in late austral summer. This bloom is composed of nitrogen fixers and can cover up to ∼1% of the ...world's ocean surface area. Satellite observations show that its spatial structure is closely tied to the underlying mesoscale eddy field in the region. The causes of the bloom and its temporal behavior (timing of its initiation and termination) and spatial variability are poorly understood, in part due to a lack of in situ observations. Here an eddy resolving 1/12° resolution ocean general circulation model and Lagrangian particle tracking are used to examine the hypothesis that iron from sediments around Madagascar could be advected east by the mesoscale eddy field to fertilize the bloom, and that variability in advection could explain the significant interannual variability in the spatial extent of the bloom. The model results suggest that this is indeed possible and furthermore imply that the bloom could be triggered by warming of the mixed layer, leading to optimal conditions for nitrogen fixers to grow, while its termination could be due to iron exhaustion. It is found that advection of Madagascan iron could resupply the bloom region with this micronutrient in the period between the termination of one bloom and the initiation of the next in the following year.
Key Points:
Madagascan iron can be advected east to fertilize the late austral summer bloom
Lagrangian particle tracking shows that mesoscale eddies cause the advection
interannual variability in the bloom is caused by eddy variability
Rapidly retreating sea ice is expected to influence future phytoplankton production in the Arctic Ocean by perturbing nutrient and light fields, but poor understanding of present phytoplankton ...distributions and governing mechanisms make projected changes highly uncertain. Here we use a simulation that reproduces observed seasonal phytoplankton chlorophyll distributions and annual nitrate to hypothesize that surface nitrate limitation in the Arctic Ocean deepens vertical production distributions where light‐dependent growth rates are lower. We extend this to interpret depth‐integrated production changes projected by the simulation for an ice‐free Arctic Ocean. Future spatial changes correspond to patterns of reduced surface nitrate and increased light. Surface nitrate inventory reductions in the Beaufort Gyre and Atlantic inflow waters drive colocated production distributions deeper to where light is lower, offsetting increases in light over the water column due to reduced ice cover and thickness. Modest production increases arise, 10% in a seasonally ice‐free Arctic Ocean and increasing to 30% by the end of the century, occurring at depth.
Key Points:
We use a 1/4° ocean biogeochemical model to assess Arctic primary production
Net primary production is linked to nitrate‐light conditions
Application to future production suggests modest increases, occurring at depth
Anthropogenic climate change is projected to lead to ocean warming, acidification, deoxygenation, reductions in near-surface nutrients, and changes to primary production, all of which are expected to ...affect marine ecosystems. Here we assess projections of these drivers of environmental change over the twenty-first century from Earth system models (ESMs) participating in the Coupled Model Intercomparison Project Phase 6 (CMIP6) that were forced under the CMIP6 Shared Socioeconomic Pathways (SSPs). Projections are compared to those from the previous generation (CMIP5) forced under the Representative Concentration Pathways (RCPs). A total of 10 CMIP5 and 13 CMIP6 models are used in the two multi-model ensembles. Under the high-emission scenario SSP5-8.5, the multi-model global mean change (2080–2099 mean values relative to 1870–1899) ± the inter-model SD in sea surface temperature, surface pH, subsurface (100–600 m) oxygen concentration, euphotic (0–100 m) nitrate concentration, and depth-integrated primary production is +3.47±0.78 ∘C, -0.44±0.005, -13.27±5.28, -1.06±0.45 mmol m−3 and -2.99±9.11 %, respectively. Under the low-emission, high-mitigation scenario SSP1-2.6, the corresponding global changes are +1.42±0.32 ∘C, -0.16±0.002, -6.36±2.92, -0.52±0.23 mmol m−3, and -0.56±4.12 %. Projected exposure of the marine ecosystem to these drivers of ocean change depends largely on the extent of future emissions, consistent with previous studies. The ESMs in CMIP6 generally project greater warming, acidification, deoxygenation, and nitrate reductions but lesser primary production declines than those from CMIP5 under comparable radiative forcing. The increased projected ocean warming results from a general increase in the climate sensitivity of CMIP6 models relative to those of CMIP5. This enhanced warming increases upper-ocean stratification in CMIP6 projections, which contributes to greater reductions in upper-ocean nitrate and subsurface oxygen ventilation. The greater surface acidification in CMIP6 is primarily a consequence of the SSPs having higher associated atmospheric CO2 concentrations than their RCP analogues for the same radiative forcing. We find no consistent reduction in inter-model uncertainties, and even an increase in net primary production inter-model uncertainties in CMIP6, as compared to CMIP5.
A 6‐year‐old female neutered standard poodle was referred with a 4‐week history of rapidly progressive weight loss, muscle atrophy, hyporexia, hind limb weakness and lethargy. In the preceding ...3‐month period, the dog had been diagnosed with both keratoconjunctivitis sicca (KCS) and hypoadrenocorticism. Clinical deterioration had occurred despite treatment for hypoadrenocorticism. Following referral, the dog was diagnosed with concurrent hypothyroidism, exocrine pancreatic insufficiency (EPI) and suspected generalised myositis. Treatment with hormone replacement therapy, pancreatic enzyme supplementation and immunosuppressive doses of prednisolone and mycophenolate resulted in marked clinical improvement. This case describes a rapidly progressive, presumed autoimmune, polyglandular endocrinopathy in a dog with concurrent non‐endocrine autoimmune diseases.
The output of a two-layer hydrodynamic model along a west-east section of the Gibraltar Strait is used to estimate tidal induced mixing between the Mediterranean and Atlantic water layers and to ...simulate the effects of mixing processes on biogeochemical fluxes and the pelagic community of the area. The hydrodynamic model is used to estimate interfacial mixing and water advection which drive the dynamics of the pelagic community. The model was run for 13 months, in order to analyse the effect of annual modulations in tidal amplitude on mixing. Incorporation of a third intermediate layer leads to a significant improvement in the model results, showing the necessity for a three layer circulation scheme when modelling biogeochemical processes in the Strait of Gibraltar. Pelagic processes are modelled using a simple Nutrient-Phytoplankton-Zooplankton (NPZ) model. The intense physical mixing and advection in the channel are the main influence on plankton dynamics in the area. It is found that residence times within the channel are so short that phytoplankton communities cannot grow appreciably during their transit. As a consequence, the use of a more sophisticated biogeochemical model does not lead to significant changes in the results obtained. According to the model, mixing over the Camarinal Sill causes an average of 16% of the out-flowing nutrients to be returned back to the Mediterranean. This fraction varies between 4% and 35% as a function of the tidal amplitude. The comparison of the model results with field data suggests that in order to obtain an accurate simulation of the plankton ecosystem dynamics in the strait, it is necessary to take into account the full horizontal flow, as recirculation and coast-channel interactions seems to be very important processes in explaining the biological patterns in the area.
The high ionic selectivity of K+ channels is a unifying feature of this diverse class of membrane proteins. Though K+ channels differ widely in regulation and kinetics, physiological studies have ...suggested a common structure: a single file pore containing multiple ion-binding sites and having broader vestibules at both ends. We have used site-directed mutagenesis and single-channel recordings to identify a molecular region that influences ionic selectivity in a cloned A-type K+ channel from Drosophila. Single amino-acid substitutions in H5, the fifth hydrophobic region, enhanced the passage of NH4+ and Rb+, ions with diameters larger than K+, without compromising the ability of the channel to exclude the smaller cation, Na+. The mutations that substantially altered selectivity had little effect on the gating properties of the channel. We conclude that the H5 region is likely to line the pore of the K+ channel.
Abstract
Marine Protected Areas (MPAs) are established to conserve important ecosystems and protect marine species threatened in the wider ocean. However, even
MPAs
in remote areas are not wholly ...isolated from anthropogenic impacts. “Upstream” activities, possibly thousands of kilometers away, can influence
MPAs
through ocean currents that determine their connectivity. Persistent pollutants, such as plastics, can be transported from neighboring shelf regions to
MPAs
, or an ecosystem may be affected if larval dispersal is reduced from a seemingly remote upstream area. Thus, improved understanding of exactly where upstream is, and on what timescale it is connected, is important for protecting and monitoring
MPAs
. Here, we use a high‐resolution (1/12°) ocean general circulation model and Lagrangian particle tracking to diagnose the connectivity of four of the
UK
's largest
MPAs
: Pitcairn; South Georgia and Sandwich Islands; Ascension; and the British Indian Ocean Territory (
BIOT
). We introduce the idea of a circulation “connectivity footprint”, by which
MPAs
are connected to upstream areas. Annual connectivity footprints were calculated for the four
MPAs
, taking into account seasonal and inter‐annual variability. These footprints showed that, on annual timescales, Pitcairn was not connected with land, whereas there was increasing connectivity for waters reaching South Georgia, Ascension, and, especially,
BIOT
.
BIOT
also had a high degree of both seasonal and inter‐annual variability, which drastically changed its footprint, year‐to‐year. We advocate that such connectivity footprints are an inherent property of all
MPAs
, and need to be considered when
MPAs
are first proposed or their viability as refuges evaluated.
Key Points
Marine protected areas (
MPAs
), set up to protect endangered species, are vulnerable to upstream impacts from land due to ocean circulation
Particle‐tracking simulations show the land connectivity of four major British
MPAs
and give a “connectivity footprint” at annual timescales
Connectivity to land differs substantially between
MPAs
with strong seasonal/inter‐annual variability showing the utility of the footprints
Plain Language Summary
Marine Protected Areas (MPAs) are typically established to conserve important ecosystems and protect marine species. However, even remote MPAs are not wholly isolated from impacts elsewhere, and can be connected via energetic ocean currents to impacts in “upstream areas” hundreds or even thousands of kilometres away. For instance, separate populations of marine species can be connected through larval dispersal by ocean currents, such that negative ecosystem impacts—overfishing or pollution—in a seemingly remote location may drastically affect a MPA. Here, we present “connectivity footprints” of four UK MPAs using a Lagrangian particle‐tracking technique within a high‐resolution ocean model, and evaluate their connectivity with land. At the 1‐year timescale, Pitcairn is essentially unconnected with land, whereas the South Georgia, Ascension and BIOT MPAs are increasingly connected with remote land, with variability (seasonal and interannual) notably high for BIOT. In terms of exposure to pollution, we also consider the population density of connected coastlines, and identify this as an important risk factor in the management of MPAs. We advocate connectivity footprints of MPAs as a tool to improve future MPA designation, and in spatial planning of current MPA networks, and we suggest future work to better diagnose connectivity of MPAs.
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