Dopaminergic control of astrocytic calcium dynamics in situ and its potential effect on local synaptic activity

Astrocytes in culture display large cytosolic calcium increases upon stimulation with dopamine, however the mechanism and physiological significance of this calcium response is still unknown. In this thesis, I demonstrate that hippocampal astrocytes in situ respond to dopamine with similar large calcium transients. I also describe a novel astrocyte calcium decrease, which appears specific to dopaminergic stimulation. Dopamine is a potent neuromodulator of hippocampal synaptic activity, as are astrocytes. However, I found no evidence to suggest that dopamine-induced calcium transients in astrocytes affect excitatory synaptic transmission and its short-term plasticity in the hippocampal stratum radiatum. In perforant path - CA1 pyramidal synapses of stratum lacunosum-moleculare, astrocytes were found to lessen the inhibitory effect of dopamine on evoked PTP. This work shows for the first time that astrocytes in situ can robustly respond to dopamine with a complex Ca2+ signal thus may participate in dopaminergic signalling in the brain

Impacts of trawling on diversity, biomass and structure of meiofaunal assemblages

Abstract Disturbance due to trawling reduces the biomass and production of macro-infaunal invertebrate communities, implying that their total food-consumption rate will fall, and that production (carbon) reaching the sea floor will be processed by other animals that can withstand the effects of trawling. Meiofauna may be resistant to disturbance by trawling because they are likely to be resuspended rather than killed by trawls and because their short generation times would allow them to withstand elevated mortality. We used a BACI experimental approach to investigate the short-term effects of beam trawling on the diversity, biomass and community structure of meiofauna on real fishing grounds in the southern North Sea. Experiments at two locations showed that there were no short-to medium-term (1-392 days after experimental trawling) trawling impacts on meiofaunal diversity or biomass, but that there were mild effects on community structure. Any impacts due to trawling were minor in relation to seasonal changes in the meiofaunal communities. We assessed the power of our experiments to detect the effects of trawling and recorded a 44-85% chance of detecting a 50% change in species richness and a 65% chance of detecting an order-of-magnitude change in biomass. The power to detect changes in total abundance, however, was low (between 11% and 12% power for detecting a change of 50%). We suggest that meiofauna are more resistant to disturbance by beam trawling than are macrofauna and that they have the potential to withstand the effects of chronic trawling on real fishing grounds and to retain a key role in energy cycling

Response of biological productivity to North Atlantic marine front migration during the Holocene

Abstract. Marine fronts delineate the boundary between distinct water masses and, through the advection of nutrients, are important facilitators of regional productivity and biodiversity. As the modern climate continues to change, the migration of frontal zones is evident, but a lack of information about their status prior to instrumental records hinders future projections. Here, we combine data from lipid biomarkers (archaeal isoprenoid glycerol dibiphytanyl glycerol tetraethers and algal highly branched isoprenoids) with planktic and benthic foraminifera assemblages to detail the biological response of the marine Arctic and polar front migrations on the North Iceland Shelf (NIS) over the last 8 kyr. This multi-proxy approach enables us to quantify the thermal structure relating to Arctic and polar front migration and test how this influences the corresponding changes in local pelagic productivity. Our data show that following an interval of Atlantic water influence, the Arctic front and its associated high pelagic productivity migrated southeastward to the NIS by ∼6.1 ka. Following a subsequent trend in regional cooling, Polar Water from the East Greenland Current and the associated polar front spread onto the NIS by ∼3.8 ka, greatly diminishing local algal productivity through the Little Ice Age. Within the last century, the Arctic and polar fronts have moved northward back to their current positions relative to the NIS and helped stimulate the productivity that partially supports Iceland's economy. Our Holocene records from the NIS provide analogues for how the current frontal configuration and the productivity that it supports may change as global temperatures continue to rise. </jats:p

Central Nervous System Parasitosis and Neuroinflammation Ameliorated by Systemic IL-10 Administration in Trypanosoma brucei-Infected Mice

Peer reviewedPublisher PD

Minimal Holocene retreat of large tidewater glaciers in Køge Bugt, southeast Greenland

Abstract Køge Bugt, in southeast Greenland, hosts three of the largest glaciers of the Greenland Ice Sheet; these have been major contributors to ice loss in the last two decades. Despite its importance, the Holocene history of this area has not been investigated. We present a 9100 year sediment core record of glaciological and oceanographic changes from analysis of foraminiferal assemblages, the abundance of ice-rafted debris, and sortable silt grain size data. Results show that ice-rafted debris accumulated constantly throughout the core; this demonstrates that glaciers in Køge Bugt remained in tidewater settings throughout the last 9100 years. This observation constrains maximum Holocene glacier retreat here to less than 6 km from present-day positions. Retreat was minimal despite oceanic and climatic conditions during the early-Holocene that were at least as warm as the present-day. The limited Holocene retreat of glaciers in Køge Bugt was controlled by the subglacial topography of the area; the steeply sloping bed allowed glaciers here to stabilise during retreat. These findings underscore the need to account for individual glacier geometry when predicting future behaviour. We anticipate that glaciers in Køge Bugt will remain in stable configurations in the near-future, despite the predicted continuation of atmospheric and oceanic warming

Cell-cell adhesion regulates Merlin/NF2 interaction with the PAF complex

The PAF complex (PAFC) coordinates transcription elongation and mRNA processing and its CDC73/parafibromin subunit functions as a tumour suppressor. The NF2/Merlin tumour suppressor functions both at the cell cortex and nucleus and is a key mediator of contact inhibition but the molecular mechanisms remain unclear. In this study we have used affinity proteomics to identify novel Merlin interacting proteins and show that Merlin forms a complex with multiple proteins involved in RNA processing including the PAFC and the CHD1 chromatin remodeller. Tumour-derived inactivating mutations in both Merlin and the CDC73 PAFC subunit mutually disrupt their interaction and growth suppression by Merlin requires CDC73. Merlin interacts with the PAFC in a cell density-dependent manner and we identify a role for FAT cadherins in regulating the Merlin-PAFC interaction. Our results suggest that in addition to its function within the Hippo pathway, Merlin is part of a tumour suppressor network regulated by cell-cell adhesion which coordinates post-initiation steps of the transcription cycle of genes mediating contact inhibition

People of the British Isles: preliminary analysis of genotypes and surnames in a UK control population

There is a great deal of interest in fine scale population structure in the UK, both as a signature of historical immigration events and because of the effect population structure may have on disease association studies. Although population structure appears to have a minor impact on the current generation of genome-wide association studies, it is likely to play a significant part in the next generation of studies designed to search for rare variants. A powerful way of detecting such structure is to control and document carefully the provenance of the samples involved. Here we describe the collection of a cohort of rural UK samples (The People of the British Isles), aimed at providing a well-characterised UK control population that can be used as a resource by the research community as well as providing fine scale genetic information on the British population. So far, some 4,000 samples have been collected, the majority of which fit the criteria of coming from a rural area and having all four grandparents from approximately the same area. Analysis of the first 3,865 samples that have been geocoded indicates that 75% have a mean distance between grandparental places of birth of 37.3km, and that about 70% of grandparental places of birth can be classed as rural. Preliminary genotyping of 1,057 samples demonstrates the value of these samples for investigating fine scale population structure within the UK, and shows how this can be enhanced by the use of surnames

The study on the outsourcing of Taiwan's hospitals: a questionnaire survey research

<p>Abstract</p> <p>Background</p> <p>The aim of this study was to assess the outsourcing situation in Taiwanese hospitals and compares the differences in hospital ownership and in accreditation levels.</p> <p>Methods</p> <p>This research combined two kinds of methods: a questionnaire survey and the in-depth interview to two CEOs of the sample hospitals. One hospital is not-for-profit, while the other is a public hospital and the research samples are from the hospital data from Taiwan's 2005 to 2007 Department of Health qualifying lists of hospital accreditation. The returned questionnaires were analyzed with STATISTICA^®7.1 version software.</p> <p>Results</p> <p>The results for non-medical items showed medical waste and common trash both have the highest rate (94.6 percent) of being outsourced. The gift store (75 percent) and linen (73 percent) follow close behind, while the lowest rate of outsourcing is in utility maintenance (13.5 percent). For medical items, the highest rate of outsourcing is in the ambulance units (51.4 percent), while the hemodialysis center follows close behind with a rate of 50 percent. For departments of nutrition, pharmacy, and nursing however, the outsourcing rate is lower than 3 percent. This shows that Taiwan's hospitals are still conservative in their willingness to outsource for medical items. The results of the satisfaction paired t-test show that the non-medical items have a higher score than the medical items. The factor analysis showed the three significant factors in of non medical items' outsourcing are "performance", "finance", and "human resource". For medical items, the two factors are "operation" and satisfaction". To further exam the factor validity and reliability of the satisfaction model, a confirmative factor analysis (CFA) was conducted using structure equation modeling (SEM) method and found the model fitting well.</p> <p>Conclusion</p> <p>Hospitals, especially for public hospitals, can get benefits from outsourcing to revive the full-time-equivalent and human resource limitation.</p

An anatomy of Turkish football match-fixing

While discussion on corruption in sport is intensifying and football match-fixing in particular is attracting increasing attention, new fixing scandals emerge offering new accounts of actors and corrupt practices within the football industry and the level of the external threat to the sport. The scandal exposure of fixed matches in Turkey in 2011 sheds light on the fixing of 17 matches played in the 2010/11 football season and allowed for insights to the actors, structure and processes behind the fix. Following four criminal and seven disciplinary proceedings, the case is still pending appeal for its final decision, involving a total of 93 suspects and having already resulted in the exclusion of two teams from European competitions. The evidence collected by the authorities points towards a hierarchical criminal organisation led by the President of a football club that arranged and coordinated the fixing in order for his team to win the national Championship. The aim of this article is to provide an account of the organisation and coordination of match-fixing in Turkey, with its actors, specifics and criminal characteristics, while offering an examination of match-fixing for sporting success, the least documented type of match-fixing

A live weight-heart girth relationship for accurate dosing of east African shorthorn zebu cattle

The accurate estimation of livestock weights is important for many aspects of livestock management including nutrition, production and appropriate dosing of pharmaceuticals. Subtherapeutic dosing has been shown to accelerate pathogen resistance which can have subsequent widespread impacts. There are a number of published models for the prediction of live weight from morphometric measurements of cattle, but many of these models use measurements difficult to gather and include complicated age, size and gender stratification. In this paper, we use data from the Infectious Diseases of East Africa calf cohort study and additional data collected at local markets in western Kenya to develop a simple model based on heart girth circumference to predict live weight of east African shorthorn zebu (SHZ) cattle. SHZ cattle are widespread throughout eastern and southern Africa and are economically important multipurpose animals. We demonstrate model accuracy by splitting the data into training and validation subsets and comparing fitted and predicted values. The final model is weight0.262 =0.95 + 0.022 × girth which has an R2 value of 0.98 and 95 % prediction intervals that fall within the ±20 % body weight error band regarded as acceptable when dosing livestock. This model provides a highly reliable and accurate method for predicting weights of SHZ cattle using a single heart girth measurement which can be easily obtained with a tape measure in the field setting