Direct and Indirect Excitation of Laterodorsal Tegmental Neurons by Hypocretin/Orexin Peptides: Implications for Wakefulness and Narcolepsy

Compelling evidence links the recently discovered hypothalamic peptides Hypocretin/Orexin (Hcrt/Orx) to rapid eye movement sleep (REM) control and the sleep disorder narcolepsy, yet how they influence sleep-related systems is not well understood. We investigated the action of Hcrt/Orx on mesopontine cholinergic (MPCh) neurons of the laterodorsal tegmental nucleus (LDT), a target group whose function is altered in canine narcolepsy and appears pivotal for normal REM and wakefulness. Extracellular recordings from mouse brainstem slices revealed that Hcrt/Orx evoked prolonged firing of LDT neurons. Whole-cell recordings revealed that Hcrt/Orx had actions on both presynaptic neurons and at postsynaptic sites. Hcrt/Orx produced an increase in frequency and amplitude of spontaneous EPSCs without equivalent effect on IPSCs, by triggering action potentials and enhancing spike-evoked synaptic transmission in glutamatergic afferents. Postsynaptically, Hcrt/Orx produced an inward current and an increase in membrane current noise, which were accompanied by a conductance increase. These persisted in TTX, ionotropic glutamate receptor antagonists, and low extracellular calcium. Both presynaptic and postsynaptic actions were specific because they were not mimicked by an Hcrt/Orx fragment, and both actions were observed for cholinergic and noncholinergic LDT neurons. Finally, extracellular recordings during postsynaptic potential blockade demonstrated that postsynaptic actions of Hcrt/Orx alone could evoke prolonged firing. In the context of other recent work, our findings suggest that Hcrt/Orx neurons may coordinate the activity of the entire reticular activating system during waking. Moreover, these findings address specific hypotheses regarding the cellular mechanisms underlying REM disregulation in narcolepsy

Assessing The "Value" Of New Transport Initiatives In Deprived Neighbourhoods In The UK

Since 1996, there has been growing policy awareness in the UK of the links between transport and social exclusion. Research by the government’s Social Exclusion Unit (SEU) has highlighted the fact that transport problems are often a major barrier to accessing work, healthcare, educational and other key facilities and has, therefore, become an increasingly important policy objective in moving people from welfare into work, addressing health inequalities, improving poor educational attainment and more generally promoting social exclusion and neighbourhood renewal. The SEU study puts in place a cross-departmental strategy to address these issues through a new local framework entitled Accessibility Planning, which is to be delivered by local transport planning authorities and their partners through the next round of Local Transport Plans. However, there has been little, if any, qualitative or quantitative analysis and evaluation of the contribution of new transport interventions in deprived areas. As such very little is known about whether they are facilitating increased economic and social participation for the individuals who use them. It is equally unclear if they have any positive impact on the wider process of regeneration in the neighbourhoods they serve. Anecdotal evidence suggests that they are assisting transitions from welfare into work, as well facilitating other important activities, such as health visits, educational attendance and leisure and social activities. The current funding and subsidy arrangements for transport initiatives specifically designed to support social inclusion are minimal at best and often non-existent. This paper describes case study research of four different transport projects that were funded under the UK Department for Transport’s now obsolete Urban Bus Challenge Fund. It aims to qualitatively and quantitatively evaluate their value to passengers in terms of quality of life benefits and also to identify their wider value to the local practitioners charged with the regeneration of the deprived areas they serve. On the basis of this evidence study aims to offer recommendations to central and local government on how such initiatives can be better supported in the future. Its key objectives are: • To identify the changes in travel behaviour and accessibility that have been brought about through the introduction of transport interventions within deprived and disadvantaged communities; • To explore the perceptions of local people in relation to these new services and with the broader aim of identifying the impact of these on the quality of life of the people who use them; • To explore the views of local practitioners regarding the contribution of such projects to the wider process of neighbourhood renewal in these areas; • To offer recommendations to central and local government on how such schemes can be better supported in the context of policies for neighbourhood renewal and the new requirements for accessibility planning in the 2006 Local Transport Plans. The research is funded by the Joseph Rowntree Foundation, a UK-based poverty campaign organisation that aims to raise awareness of the needs of people living in poor neighbourhoods across the UK.Institute of Transport and Logistics Studies. Faculty of Economics and Business. The University of Sydne

Setting up local travel plan groups : the future of workplace travel planning in urban conurbations? Examples from London, UK.

Any group of organisations that comes together to share resources and ideas for developing and implementing a travel plan (site based Transportation Demand Management plan, known as a Travel Plan in the UK) in their local area could be described as a local travel plan group. Whilst the concept is not new for workplace travel planning in North America, recently several new variants have been established in the UK. This paper reviews and sets out a typology of local travel plan groups, including development zones, area based groups, Transportation Management Associations and Business Improvement Districts. It then highlights the case of London, where, perhaps uniquely, at least one example of each type of group is present. One new example is then examined in more detail to illustrate some of the challenges in setting up a local travel plan group and the way in which they may develop in the future to providing a framework for involving businesses in local transport improvement decisions. Finally, the main characteristics of the London groups and how they differ from their North American predecessors are briefly explored

Heroism and/as injurious speech: Recognition, precarity and inequality in health and social care work

This paper draws on Judith Butler’s (2009, 1997) writing on precarity and the interpellatory power of naming, read through her recent writing on the dynamics of recognition, vulnerability, and resistance (Butler, 2016, 2020), to develop a critique of the discourse of heroism used to position health and social care professionals, and other key workers, during the COVID pandemic. It does so in order to reflect on the insights into workplace inequalities that this example provides, in particular into what, to borrow from Butler, we might think of as the conditions necessary for a ‘workable life’. It argues that, although it might seem paradoxical, the heroic discourses and symbolism used to recognize health and social care workers throughout the pandemic can be understood as a form of ‘injurious speech’ in Butler’s terms, one that served to Other key workers by subjecting them to a reified, rhetorical form of recognition. The analysis argues that this had the effect of accentuating health and care workers’ precarity and of undermining their capacity to challenge and resist this positioning

Determining Gene Specific Chromatin Differences in \u3ci\u3eSulfolobus solfataricus\u3c/i\u3e: Expression of MerR Protein for Targeted-ChIP Antibody Production

In this project the repressor protein MerR from the Sulfolobus solfataricus mercury resistance operon was cloned into pET28b and transformed into Roetta 2 E.coli strains for overexpression and purification. Large quantities of recombinant MerR will be used for subsequent injection into a mammalian host for antibody production. These antibodies will be used in targeted-ChIP studies in which gene specific chromatin modification states will be analyzed. The overproduction of MerR is part of a larger project where future research could produce data on whether gene expression levels and chromatin modifiation states could be correlated at an individual gene level, possibly suggesting a novel epigenetic mechanism in Archaea

Local travel plan groups : a practical guide to setting up an effective group

Shortly after becoming Mayor of London in July 2000, Ken Livingstone noted that “the single biggest problem for London and Londoners is the gridlock of our transport system” and that “remedying this will be my first priority”. Although predominantly concerned with the inadequacy of public transport in the capital, the Mayor added that “traffic speeds in central London are now just 10 miles per hour, while congestion costs London business £5 billion per year. Residents and commuters alike suffer from delays, stress, discomfort and the overall poor urban environment.”i To help address these problems,Transport for London (TfL) is encouraging businesses and other organisations to develop workplace travel plans. Developing and implementing a workplace travel plan requires resources and expertise, so it can be easier for businesses located in the same area to get together and form a local travel plan group. This good practice guide sets out the process of establishing a local travel plan group, based on research conducted for the Optimum2 project in the London Borough of Southwark, in which the Better Bankside Travel Plan Group was established (see Acknowledgments for further information)

Determining Gene Specific Chromatin Differences in \u3ci\u3eSulfolobus solfataricus\u3c/i\u3e: Expression of MerR Protein for Targeted-ChIP Antibody Production

In this project the repressor protein MerR from the Sulfolobus solfataricus mercury resistance operon was cloned into pET28b and transformed into Roetta 2 E.coli strains for overexpression and purification. Large quantities of recombinant MerR will be used for subsequent injection into a mammalian host for antibody production. These antibodies will be used in targeted-ChIP studies in which gene specific chromatin modification states will be analyzed. The overproduction of MerR is part of a larger project where future research could produce data on whether gene expression levels and chromatin modifiation states could be correlated at an individual gene level, possibly suggesting a novel epigenetic mechanism in Archaea

The depth of Sooty Shearwater Ardenna grisea burrows varies with habitat and increases with competition for space

The Sooty Shearwater Ardenna grisea, an abundant but declining petrel, is one of many seabird species that construct breeding burrows, presumably because these confer protection from predators and the elements. Little is known about the causes of variation in Sooty Shearwater burrow architecture, which can differ markedly both within and between breeding sites. We hypothesize that burrow architecture varies in response to habitat type and competition for space. To address these hypotheses, we recorded Sooty Shearwater burrow dimensions on Kidney Island, the largest Sooty Shearwater colony in the Falkland Islands, South Atlantic, and modelled these as functions of burrow density (a proxy for competition) and habitat indices. Our models suggest that Sooty Shearwaters burrow further underground in response to competition for breeding space, and that soil underlying dense tussac grass Poa flabellata is more easily excavated than other substrates, indicating how vegetation restoration could aid the conservation of this species

Job security and the promotion of workers’ wellbeing in the midst of the COVID-19 pandemic: A study with Canadian workers one to two weeks after the initiation of social distancing measures

Background: Due to the current coronavirus (COVID-19) crisis, workplaces have had to make significant alterations in the way they conduct business. This, in addition to the current financial instability, may put workers at risk of experiencing job insecurity and, in turn, lower wellbeing. Job insecurity is a key determinant of wellbeing, but little is known on how it is impacted by public health crises, and more specifically how it relates to workers’ positive and negative wellbeing in the midst of a pandemic. Research is lacking on resilience levers that workplace interventions should target to support wellbeing in times of insecurity. Objective: Framed from a multidisciplinary perspective (public health, positive and organizational psychology), the study explores (1) workers’ job (in)security during the COVID-19 pandemic one to two weeks after social distancing measures were implemented by Canadian governments, (2) how job (in)security relates to wellbeing during the pandemic, and (3) the potential positive effects of workplace-related resilience levers. Method: 1,073 Canadian workers working full-/part-time or who were temporarily laid off completed an online survey, including measures of wellbeing at work or in general, job security and potential resilience levers (workplace disaster preparedness, policy, social capital). Results: Multiple regression findings highlight that marginalized workers (e.g., women, migrants, people facing financial hardships) reported lower job security, and having temporarily lost one’s job was negatively associated with job security. Low job security was related to lower scores across measures of wellbeing. Distress was high in the sample. Workplace disaster preparedness, policy and social capital were associated with higher wellbeing. The effects of these resilience levers tended to be stronger at higher job security levels. Discussion: Recommendations include a systemic, collaborative approach that includes policies fostering job security as well as resilience-promoting interventions in the workplace to protect/increase the wellbeing of workers during COVID-19