Serotonergic modulation of the ventral pallidum by 5HT1A, 5HT5A, 5HT7 AND 5HT2C receptors

Introduction: Serotonin's involvement in reward processing is controversial. The large number of serotonin receptor sub-types and their individual and unique contributions have been difficult to dissect out, yet understanding how specific serotonin receptor sub-types contribute to its effects on areas associated with reward processing is an essential step. Methods: The current study used multi-electrode arrays and acute slice preparations to examine the effects of serotonin on ventral pallidum (VP) neurons. Approach for statistical analysis: extracellular recordings were spike sorted using template matching and principal components analysis, Consecutive inter-spike intervals were then compared over periods of 1200 seconds for each treatment condition using a student’s t test. Results and conclusions: Our data suggests that excitatory responses to serotonin application are pre-synaptic in origin as blocking synaptic transmission with low-calcium aCSF abolished these responses. Our data also suggests that 5HT1a, 5HT5a and 5HT7 receptors contribute to this effect, potentially forming an oligomeric complex, as 5HT1a antagonists completely abolished excitatory responses to serotonin application, while 5HT5a and 5HT7 only reduced the magnitude of excitatory responses to serotonin. 5HT2c receptors were the only serotonin receptor sub-type tested that elicited inhibitory responses to serotonin application in the VP. These findings, combined with our previous data outlining the mechanisms underpinning dopamine's effects in the VP, provide key information, which will allow future research to fully examine the interplay between serotonin and dopamine in the VP. Investigation of dopamine and serotonins interaction may provide vital insights into our understanding of the VP's involvement in reward processing. It may also contribute to our understanding of how drugs of abuse, such as cocaine, may hijack these mechanisms in the VP resulting in sensitization to drugs of abuse

Don't blame it all on antibodies--The need for exhaustive characterisation, appropriate handling, and addressing the issues that affect specificity

Recently there have been numerous very thought-provoking reports describing many issues relating to the overall quality of antibodies that are currently available. It appears that multiple major clinical and other analytical studies suffer from lack of reproducibility and this has been associated, to a significant degree, with the lack of specificity of the antibodies used and the lack of adequate controls/testing to ensure that non-specific binding to irrelevant antigens was not occurring. This appears to be a major issue and it is vital that it is addressed as a matter of urgency. However, not all of the problems can be ascribed to antibodies per se as inappropriate storage/handling/use in different analytical approaches and platforms are also of major significance. It was stated that antibodies need to be fully characterised with the entire sequence defined and published or available and this is now facilitated through the use of recombinant antibodies. This review critically evaluates these issues and suggests a way forward to address them.The support of Dublin City University, of Enterprise Ireland (CF/2015/0105P) and of Science Foundation Ireland (14/IA/2646) is gratefully acknowledged.peer-reviewe

'Till Debt Do Us Part' : Financial Implications of the Divorce of the Irish Free State from the UK, 1922-6

In this paper, we discuss the unresolved apportionment of national debt when Ireland exited the UK in 1922. Using archival sources and contemporary accounts, we estimate that the British claim on Ireland in 1925 amounted to between 80 and 100 per cent of GNP at a time when the political stability of Ireland was already fragile. We describe the process of how this contingent liability, arising from the Anglo-Irish Treaty of 1921, was ultimately waived in a Financial Agreement in 1925 at the expense of an unchanged border with Northern Ireland. The Irish government also sought, but failed, to secure protection against discrimination for Catholics in Northern Ireland as part of the agreement. While for the Irish Government, this settlement may have represented a political failure, the economic outcome of the agreement transformed the economic position of the new Irish State from one of potential insolvency into one of viability

Managing a Century of Debt

This paper provides a consistent series for the Irish national debt since the foundation of the state in 1922. It also provides a continuous series for bond yields over the same period. The paper examines the factors behind the fluctuations in the debt burden over almost a century. The management of the debt burden by the Irish authorities has evolved over time, seeking to minimise both the burden on the economy and the risks which the debt represented to the state. The paper also examines how the cost of borrowing for the Irish government compared to that for the UK and, since the break with sterling, for Germany. This cost of borrowing was, in turn affected by developments in the domestic economy

Don\u27t blame it all on antibodies--The need for exhaustive characterisation, appropriate handling, and addressing the issues that affect specificity

Recently there have been numerous very thought-provoking reports describing many issues relating to the overall quality of antibodies that are currently available. It appears that multiple major clinical and other analytical studies suffer from lack of reproducibility and this has been associated, to a significant degree, with the lack of specificity of the antibodies used and the lack of adequate controls/testing to ensure that non-specific binding to irrelevant antigens was not occurring. This appears to be a major issue and it is vital that it is addressed as a matter of urgency. However, not all of the problems can be ascribed to antibodies per se as inappropriate storage/handling/use in different analytical approaches and platforms are also of major significance. It was stated that antibodies need to be fully characterised with the entire sequence defined and published or available and this is now facilitated through the use of recombinant antibodies. This review critically evaluates these issues and suggests a way forward to address them.The support of Dublin City University, of Enterprise Ireland (CF/2015/0105P) and of Science Foundation Ireland (14/IA/2646) is gratefully acknowledged

The Likely Economic Impact of Increasing Investment in Wind on the Island of Ireland

Like most countries Ireland faces the double target of decreasing emissions and keeping energy costs low to maintain competitiveness of the economy. The two goals are not always compatible. This study measures the effect of increasing wind in electricity generation on the total electricity costs for the Island of Ireland for the year 2020 under a variety of scenarios on fuel and carbon costs, generating plant portfolio mixes and electricity demand growth. We find that with high levels of interconnection 6000MW of installed wind capacity are likely to reduce overall costs, especially if the price of natural gas stays high. The sensitivity of the results to the level of interconnection suggests that it is important for interconnection to be operated and governed as efficiently as possible. We also find that the deregulated all-island system will face major challenges moving into the future since returns to traditional fossil-fuelled plants might not be sufficient to create new (needed) investment when wind penetration is high.electricity/growth/Interconnection/investment/Ireland/returns to investment/wind generation

Household Behaviour under rationing

The pandemic-induced economic crisis has seen a massive increase in savings as households could not spend their income. The last time that consumers were seriously rationed was during the Second World War. This article models the behaviour of households during the War years and its immediate aftermath in Ireland, Sweden, the US and UK. Savings were held in liquid form and, once the War was over and rationing eased, a consumption boom transpired. However, significant excess savings were converted into physical assets in the housing market. There is evidence that this pattern is being repeated as the Covid-19 crisis eases

Household Behaviour in Ireland, Sweden, the US and the UK under Rationing

The pandemic-induced economic crisis has seen a massive build up in savings across Europe and North America as households could not spend their income as they normally would. The last time that consumers were seriously rationed was during the Second World War. This paper models the behaviour of households during the War years and its immediate aftermath in Ireland, Sweden, the US and the UK. We first estimate overall consumption and then consider how total consumption was allocated over different categories of goods, including rationed goods. The model shows that consumers saved rather than spend on available unrationed goods and services. These savings were held in liquid form and, once the War was over and rationing eased, a consumption boom transpired. However, only some of the savings were spent on previously rationed goods as significant excess savings were also converted into physical assets in the housing market. There is evidence that this pattern is being repeated as the Covid-19 crisis eases

Investing in Electricity Infrastructure and Renewables in Ireland

electricity/Ireland

Storage of blood clots for histological analysis: How long is too long in saline and paraformaldehyde?

To investigate the composition of blood clots following mechanical thrombectomy, it is essential to ensure optimum storage for highest quality histological and immunofluorescence analysis. We investigated for how long clots can be stored in Paraformaldehyde (PFA), saline and heparinised saline before the tissue integrity is compromised. Whole blood and fibrin-rich clot analogues were made under dynamic flow conditions. Clots were stored in 4% PFA, saline or heparinised saline for timepoints ranging from 1 hour to two months. Five µm sections were stained with Martius Scarlet Blue to visualise red blood cells (RBCs), white blood cells (WBCs) and fibrin. Semi-quantitative analysis of the integrity of clot components used a scoring system (0: Poor; 1: Sub-par; 2: High). Quantitative analysis used Orbit Image Analysis software. Autofluorescence was assessed using a relative scale. Clots stored in PFA for up to two months were qualitatively similar to those stored for all shorter periods (median score: 2 per component). Clots stored in saline/heparinised saline for one week showed degradation of RBCs and WBCs, but fibrin remained intact (median score: 1, 1, 2 respectively). Degradation of the samples stored in saline/heparinised saline made accurate quantification using Image Analysis software difficult from 24h. Samples stored in PFA for up to two weeks showed an edging autofluorescence effect, which became more evident with prolonged storage. For optimum histology, ideally clots should not be stored in saline before fixation and should ideally be stored in formalin for less than one month to minimise the impact of autofluorescence on immunofluorescence.This work was supported by the European Regional Development Fund and Science Foundation Ireland under Ireland’s European Structural and Investment Fund (Grant Number 13/RC/2073) and Cerenovus