Adenosine Inhibits the Excitatory Synaptic Inputs to Basal Forebrain Cholinergic, GABAergic, and Parvalbumin Neurons in Mice

Coffee and tea contain the stimulants caffeine and theophylline. These compounds act as antagonists of adenosine receptors. Adenosine promotes sleep and its extracellular concentration rises in association with prolonged wakefulness, particularly in the basal forebrain (BF) region involved in activating the cerebral cortex. However, the effect of adenosine on identified BF neurons, especially non-cholinergic neurons, is incompletely understood. Here we used whole-cell patch-clamp recordings in mouse brain slices prepared from two validated transgenic mouse lines with fluorescent proteins expressed in GABAergic or parvalbumin (PV) neurons to determine the effect of adenosine. Whole-cell recordings were made from BF cholinergic neurons and from BF GABAergic and PV neurons with the size (>20 μm) and intrinsic membrane properties (prominent H-currents) corresponding to cortically projecting neurons. A brief (2 min) bath application of adenosine (100 μM) decreased the frequency but not the amplitude of spontaneous excitatory postsynaptic currents (EPSCs) in all groups of BF cholinergic, GABAergic, and PV neurons we recorded. In addition, adenosine decreased the frequency of miniature EPSCs in BF cholinergic neurons. Adenosine had no effect on the frequency of spontaneous inhibitory postsynaptic currents in cholinergic neurons or GABAergic neurons with large H-currents but reduced them in a group of GABAergic neurons with smaller H-currents. All effects of adenosine were blocked by a selective, adenosine A1 receptor antagonist, cyclopentyltheophylline (CPT, 1 μM). Adenosine had no postsynaptic effects. Taken together, our work suggests that adenosine promotes sleep by an A1 receptor-mediated inhibition of glutamatergic inputs to cortically projecting cholinergic and GABA/PV neurons. Conversely, caffeine and theophylline promote attentive wakefulness by inhibiting these A1 receptors in BF thereby promoting the high-frequency oscillations in the cortex required for attention and cognition

Swift: primary data analysis for the Illumina Solexa sequencing platform

Motivation: Primary data analysis methods are of critical importance in second generation DNA sequencing. Improved methods have the potential to increase yield and reduce the error rates. Openly documented analysis tools enable the user to understand the primary data, this is important for the optimization and validity of their scientific work

Tunneling Between Two-Dimensional Electron Gases in a Strong Magnetic Field

We have measured the tunneling between two two-dimensional electron gases at high magnetic fields $B$, when the carrier densities of the two electron layers are matched. For filling factors $\nu<1$, there is a gap in the current-voltage characteristics centered about $V=0$, followed by a tunneling peak at $\sim 6$~mV. Both features have been observed before and have been attributed to electron-electron interactions within a layer. We have measured high field tunneling peak positions and fitted gap parameters that are proportional to $B$, and independent of the carrier densities of the two layers. This suggests a different origin for the gap to that proposed by current theories, which predict a $\sqrt{B}$ dependence.Comment: 9 pages, cond-mat/yymmnn

Tunneling Between Parallel Two-Dimensional Electron Gases

The tunneling between two parallel two-dimensional electron gases has been investigated as a function of temperature $T$, carrier density $n$, and the applied perpendicular magnetic field $B$. In zero magnetic field the equilibrium resonant lineshape is Lorentzian, reflecting the Lorentzian form of the spectral functions within each layer. From the width of the tunneling resonance the lifetime of the electrons within a 2DEG has been measured as a function of $n$ and $T$, giving information about the density dependence of the electron-impurity scattering and the temperature dependence of the electron-electron scattering. In a magnetic field there is a general suppression of equilibrium tunneling for fields above $B=0.6$ T. A gap in the tunneling density of states has been measured over a wide range of magnetic fields and filling factors, and various theoretical predictions have been examined. In a strong magnetic field, when there is only one partially filled Landau level in each layer, the temperature dependence of the conductance characteristics has been modeled with a double-Gaussian spectral density.Comment: LaTeX requires REVTeX macros. Eighteen pages. Fourteen postscript figures are included. (All figures have been bitmapped to save space. The original can be requested by email from [email protected]). Accepted for publication in Phys. Rev.

Fear of the unknown: a pre-departure qualitative study of Turkish international students

This paper presents findings from eleven in-depth interviews with Turkish undergraduate students, who were, by the time of data collection, about to spend a semester at a European university under the Erasmus exchange scheme. The students all agreed to be interviewed about their feelings about studying in a foreign culture, and were found to be anxious prior to departure about the quality of accommodation in the new destination, their language ability and the opportunity to form friendships. Fears were expressed about possible misconceptions over Turkey as a Muslim and a developing country. Suggestions are made for HEI interventions to allay student travellers’ concerns

An application of conditional logistic regression and multifactor dimensionality reduction for detecting gene-gene Interactions on risk of myocardial infarction: The importance of model validation

BACKGROUND: To examine interactions among the angiotensin converting enzyme (ACE) insertion/deletion, plasminogen activator inhibitor-1 (PAI-1) 4G/5G, and tissue plasminogen activator (t-PA) insertion/deletion gene polymorphisms on risk of myocardial infarction using data from 343 matched case-control pairs from the Physicians Health Study. We examined the data using both conditional logistic regression and the multifactor dimensionality reduction (MDR) method. One advantage of the MDR method is that it provides an internal prediction error for validation. We summarize our use of this internal prediction error for model validation. RESULTS: The overall results for the two methods were consistent, with both suggesting an interaction between the ACE I/D and PAI-1 4G/5G polymorphisms. However, using ten-fold cross validation, the 46% prediction error for the final MDR model was not significantly lower than that expected by chance. CONCLUSIONS: The significant interaction initially observed does not validate and may represent a type I error. As data-driven analytic methods continue to be developed and used to examine complex genetic interactions, it will become increasingly important to stress model validation in order to ensure that significant effects represent true relationships rather than chance findings

Exploring access to end of life care for ethnic minorities with end stage kidney disease through recruitment in action research

BACKGROUND: Variation in provision of palliative care in kidney services and practitioner concerns to provide equitable access led to the development of this study which focussed on the perspectives of South Asian patients and their care providers. As people with a South Asian background experience a higher risk of Type 2 Diabetes (T2DM) and end stage kidney failure (ESKF) compared to the majority population but wait longer for a transplant, there is a need for end of life care to be accessible for this group of patients. Furthermore because non English speakers and people at end of life are often excluded from research there is a dearth of research evidence with which to inform service improvement. This paper aims to explore issues relating to the process of recruitment of patients for a research project which contribute to our understanding of access to end of life care for ethnic minority patients in the kidney setting. METHODS: The study employed an action research methodology with interviews and focus groups to capture and reflect on the process of engaging with South Asian patients about end of life care. Researchers and kidney care clinicians on four NHS sites in the UK recruited South Asian patients with ESKF who were requiring end of life care to take part in individual interviews; and other clinicians who provided care to South Asian kidney patients at end of life to take part in focus groups exploring end of life care issues. In action research planning, action and evaluation are interlinked and data were analysed with emergent themes fed back to care providers through the research cycle. Reflections on the process of patient recruitment generated focus group discussions about access which were analysed thematically and reported here. RESULTS: Sixteen patients were recruited to interview and 45 different care providers took part in 14 focus groups across the sites. The process of recruiting patients to interview and subsequent focus group data highlighted some of the key issues concerning access to end of life care. These were: the identification of patients approaching end of life; and their awareness of end of life care; language barriers and informal carers' roles in mediating communication; and contrasting cultures in end of life kidney care. CONCLUSIONS: Reflection on the process of recruitment in this action research study provided insight into the complex scenario of end of life in kidney care. Some of the emerging issues such as the difficulty identifying patients are likely to be common across all patient groups, whilst others concerning language barriers and third party communication are more specific to ethnic minorities. A focus on South Asian ethnicity contributes to better understanding of patient perspectives and generic concepts as well as access to end of life kidney care for this group of patients in the UK. Action research was a useful methodology for achieving this and for informing future research to include informal carers and other ethnic groups.Peer reviewedFinal Published versio