Coherence of qubits based on single Ca+^+ ions

Two-level ionic systems, where quantum information is encoded in long lived states (qubits), are discussed extensively for quantum information processing. We present a collection of measurements which characterize the stability of a qubit based on the $S_{1/2}$--$D_{5/2}$ transition of single $^{40}$Ca$^+$ ions in a linear Paul trap. We find coherence times of $\simeq$1 ms, discuss the main technical limitations and outline possible improvements.Comment: Proceedings of "Trapped charged particles and fundamental interactions" submitted to Journal of Physics B (IoP

Orexin receptors exert a neuroprotective effect in Alzheimer's disease (AD) via heterodimerization with GPR103

Orexins are neuropeptides that regulate the sleep-wake cycle and feeding behaviour. QRFP is a newly discovered neuropeptide which exerts similar orexigenic activity, thus playing an important role in energy homeostasis and regulation of appetite. The exact expression and signalling characteristics and physiological actions of QRFP and its receptor GPR103 are poorly understood. Alzheimerâ €™ s disease (AD) patients experience increased nocturnal activity, excessive daytime sleepiness, and weight loss. We hypothesised therefore that orexins and QRFP might be implicated in the pathophysiology of AD. We report that the down-regulation of hippocampal orexin receptors (OXRs) and GPR103 particularly in the cornu ammonis (CA) subfield from AD patients suffering from early onset familial AD (EOFAD) and late onset familial AD (LOAD). Using an in vitro model we demonstrate that this downregulation is due to to Aβ-plaque formation and tau hyper-phosphorylation. Transcriptomics revealed a neuroprotective role for both orexins and QRFP. Finally we provide conclusive evidence using BRET and FRET that OXRs and GPR103 form functional hetero-dimers to exert their effects involving activation of ERK 1/2. Pharmacological intervention directed at the orexigenic system may prove to be an attractive avenue towards the discovery of novel therapeutics for diseases such as AD and improving neuroprotective signalling pathways

Transcriptome pathways unique to dehydration tolerant relatives of modern wheat

Among abiotic stressors, drought is a major factor responsible for dramatic yield loss in agriculture. In order to reveal differences in global expression profiles of drought tolerant and sensitive wild emmer wheat genotypes, a previously deployed shock-like dehydration process was utilized to compare transcriptomes at two time points in root and leaf tissues using the Affymetrix GeneChip(R) Wheat Genome Array hybridization. The comparison of transcriptomes reveal several unique genes or expression patterns such as differential usage of IP(3)-dependent signal transduction pathways, ethylene- and abscisic acid (ABA)-dependent signaling, and preferential or faster induction of ABA-dependent transcription factors by the tolerant genotype that distinguish contrasting genotypes indicative of distinctive stress response pathways. The data also show that wild emmer wheat is capable of engaging known drought stress responsive mechanisms. The global comparison of transcriptomes in the absence of and after dehydration underlined the gene networks especially in root tissues that may have been lost in the selection processes generating modern bread wheats

Perfluorodecalin enhances in vivo confocal microscopy resolution of Arabidopsis thaliana mesophyll.

*Air spaces in the leaf mesophyll generate deleterious optical effects that compromise confocal microscopy. *Leaves were mounted in the nontoxic, nonfluorescent perfluorocarbon, perfluorodecalin (PFD), and optical enhancement and physiological effect were assessed using confocal microscopy and chlorophyll fluorescence. *Mounting leaves of Arabidopsis thaliana in PFD significantly improved the optical qualities of the leaf, thereby enabling high-resolution laser scanning confocal imaging over twofold deeper into the mesophyll, compared with using water. Incubation in PFD had less physiological impact on the mounted specimen than water. *We conclude that the application of PFD as a mounting medium substantially increases confocal image resolution of living mesophyll and vascular bundle cells, with minimal physiological impact

Catecholaminergic signalling through thymic nerve fibres, thymocytes and stromal cells is dependent on both circulating and locally synthesized glucocorticoids

Glucocorticoids have been shown to modulate the expression of noradrenaline metabolizing enzymes and beta(2)- and alpha(1B)-adrenoceptors in a tissue- and cell- specific manner. In the thymus, apart from extensive sympathetic innervation, a regulatory network has been identified that encompasses catecholamine-containing non-lymphoid and lymphoid cells. We examined a putative role of adrenal- and thymus-derived glucocorticoids in modulation of rat thymic noradrenaline levels and adrenoceptor expression. Seven days postadrenalectomy, the thymic levels of mRNAs encoding tyrosine hydroxylase, dopamine beta-hydroxylase, monoamine oxidase-A and, consequently, noradrenaline were decreased. Catecholamine content was diminished in autofluorescent nerve fibres (judging by the intensity of fluorescence) and thymocytes (considering HPLC measurements of noradrenaline and the frequency of tyrosine hydroxylase-positive cells), while it remained unaltered in non-lymphoid autofluorescent cells. In addition, adrenalectomy diminished the thymocyte expression of beta(2)- and alpha(1B)-adrenoceptors at both mRNA and protein levels. Administration of ketoconazole (an inhibitor of glucocorticoid synthesis/action; 25 mg kg(-1) day(-1), s.c.) to glucocorticoid-deprived rats increased the thymic levels of tyrosine hydroxylase, dopamine beta-hydroxylase and, consequently, noradrenaline. The increased intensity of the autofluorescent cell fluorescence in ketoconazole-treated rats indicated an increase in their catecholamine content, and suggested differential glucocorticoid-mediated regulation of catecholamines in thymic lymphoid and non-lymphoid cells. In addition, ketoconazole increased the thymocyte expression of alpha(1B)-adrenoceptors. Thus, this study indicates that in the thymus, as in some other tissues, glucocorticoids not only act in concert with cateholamines, but they may modulate catecholamine action by tuning thymic catecholamine metabolism and adrenoceptor expression in a cell-specific manner. Additionally, the study indicates a role of thymus-derived glucocorticoids in this modulation

Parkinson’s disease: evolution of cognitive impairment and CSF Aβ₁−₄₂ profiles in a prospective longitudinal study

OBJECTIVE: To evaluate the evolution of cognitive impairment in relation to cerebrospinal fluid (CSF) profiles of amyloid-β (Aβ), total-Tau and phosphorylated-Tau in Parkinson’s disease (PD). METHODS: Prospective, longitudinal, observational study up to 10 years with follow-up every 2  years. We assessed CSF profiles in 415 patients with sporadic PD (median age 66; 63% men) and 142 healthy controls (median age 62; 43% men). RESULTS: Patients with PD with low CSF Aβ₁−₄₂ levels at baseline were more often cognitively impaired than patients with intermediate and high Aβ₁−₄₂ levels. Sixty-seven per cent of the patients with low Aβ₁−₄₂ levels at baseline and normal cognition developed cognitive impairment during follow-up, compared with 41% and 37% of patients having intermediate and high CSF Aβ₁−₄₂ levels. Kaplan-Meier survival curves and Cox regression revealed that patients with low CSF Aβ₁−₄₂ levels at baseline developed cognitive impairment more frequently and earlier during follow-up. CONCLUSION: We conclude that in patients with sporadic PD, low levels of Aβ₁−₄₂ are associated with a higher risk of developing cognitive impairment earlier in the disease process at least in a subgroup of patients

Investigating the effectiveness and feasibility of exercise on microvascular reactivity and quality of life in systemic sclerosis patients: study protocol for a feasibility study

Background: Raynaud’s phenomenon is one of the first clinical manifestations observed in systemic sclerosis (SSc). This microvasculature disorder affects mostly the digits in over 95% of SSc patients, significantly affecting their healthrelated quality of life (HRQoL) and incurring higher hospital admissions and other healthcare costs. Exercise is known to improve both micro- and macrovascular function – aerobic exercise and resistance training, separately or combined, have been demonstrated to lead to significant vasculo-physiological improvements in conditions that present vasculopathy. However, the effects of a combined exercise programme on microcirculation in SSc patients has yet to be investigated. Therefore, the purpose of this study is to assess the effects of high-intensity interval training (HIIT) combined with circuit resistance training on the microvascular function in the digital area of SSc patients. Methods: This will be a randomised controlled, feasibility trial with two arms, wherein 30 patients with SSc in receipt of medical treatment will be randomly assigned to usual care (medical treatment) or to a 12-week supervised exercise programme. Patients in the exercise group will undertake two, 45-min sessions each week consisting of 30 min HIIT (30 s 100% peak power output/30 s passive recovery) on the arm crank ergometer and 15 min of upper body circuit resistance training. Patients will be assessed before as well as at 3 and 6 months following randomisation. Primary outcomes of the study will be recruitment and retention rate, intervention acceptability and adherence to the exercise programme. Secondary outcomes include the digital area cutaneous microvascular function (laser Doppler fluximetry combined with iontophoresis), physical fitness, functional ability, upper back transcutaneous oxygen tension, body composition and quality of life (EQ-5D-5L). Selected interviews with a subsample of patients will be undertaken to explore their experiences of having Raynaud’s phenomenon and the acceptability of the exercise intervention and study procedures. Discussion: Data from this study will be used to identify the feasibility of a combined exercise programme to be implemented in SSc patients, the acceptability of the intervention and the study design, and to determine the effects of exercise on the microvasculature. Overall, this study will provide sufficient data to inform and support a full multicentre clinical trial

Rhythmicity in Mice Selected for Extremes in Stress Reactivity: Behavioural, Endocrine and Sleep Changes Resembling Endophenotypes of Major Depression

Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, including hyper- or hypo-activity of the stress hormone system, plays a critical role in the pathophysiology of mood disorders such as major depression (MD). Further biological hallmarks of MD are disturbances in circadian rhythms and sleep architecture. Applying a translational approach, an animal model has recently been developed, focusing on the deviation in sensitivity to stressful encounters. This so-called 'stress reactivity' (SR) mouse model consists of three separate breeding lines selected for either high (HR), intermediate (IR), or low (LR) corticosterone increase in response to stressors.In order to contribute to the validation of the SR mouse model, our study combined the analysis of behavioural and HPA axis rhythmicity with sleep-EEG recordings in the HR/IR/LR mouse lines. We found that hyper-responsiveness to stressors was associated with psychomotor alterations (increased locomotor activity and exploration towards the end of the resting period), resembling symptoms like restlessness, sleep continuity disturbances and early awakenings that are commonly observed in melancholic depression. Additionally, HR mice also showed neuroendocrine abnormalities similar to symptoms of MD patients such as reduced amplitude of the circadian glucocorticoid rhythm and elevated trough levels. The sleep-EEG analyses, furthermore, revealed changes in rapid eye movement (REM) and non-REM sleep as well as slow wave activity, indicative of reduced sleep efficacy and REM sleep disinhibition in HR mice.Thus, we could show that by selectively breeding mice for extremes in stress reactivity, clinically relevant endophenotypes of MD can be modelled. Given the importance of rhythmicity and sleep disturbances as biomarkers of MD, both animal and clinical studies on the interaction of behavioural, neuroendocrine and sleep parameters may reveal molecular pathways that ultimately lead to the discovery of new targets for antidepressant drugs tailored to match specific pathologies within MD

Chronic escitalopram treatment attenuated the accelerated rapid eye movement sleep transitions after selective rapid eye movement sleep deprivation: a model-based analysis using Markov chains

BackgroundShortened rapid eye movement (REM) sleep latency and increased REM sleep amount are presumed biological markers of depression. These sleep alterations are also observable in several animal models of depression as well as during the rebound sleep after selective REM sleep deprivation (RD). Furthermore, REM sleep fragmentation is typically associated with stress procedures and anxiety. The selective serotonin reuptake inhibitor (SSRI) antidepressants reduce REM sleep time and increase REM latency after acute dosing in normal condition and even during REM rebound following RD. However, their therapeutic outcome evolves only after weeks of treatment, and the effects of chronic treatment in REM-deprived animals have not been studied yet.ResultsChronic escitalopram- (10 mg/kg/day, osmotic minipump for 24 days) or vehicle-treated rats were subjected to a 3-day-long RD on day 21 using the flower pot procedure or kept in home cage. On day 24, fronto-parietal electroencephalogram, electromyogram and motility were recorded in the first 2 h of the passive phase. The observed sleep patterns were characterized applying standard sleep metrics, by modelling the transitions between sleep phases using Markov chains and by spectral analysis.Based on Markov chain analysis, chronic escitalopram treatment attenuated the REM sleep fragmentation [accelerated transition rates between REM and non-REM (NREM) stages, decreased REM sleep residence time between two transitions] during the rebound sleep. Additionally, the antidepressant avoided the frequent awakenings during the first 30 min of recovery period. The spectral analysis showed that the SSRI prevented the RD-caused elevation in theta (5 inverted question mark9 Hz) power during slow-wave sleep. Conversely, based on the aggregate sleep metrics, escitalopram had only moderate effects and it did not significantly attenuate the REM rebound after RD.ConclusionIn conclusion, chronic SSRI treatment is capable of reducing several effects on sleep which might be the consequence of the sub-chronic stress caused by the flower pot method. These data might support the antidepressant activity of SSRIs, and may allude that investigating the rebound period following the flower pot protocol could be useful to detect antidepressant drug response. Markov analysis is a suitable method to study the sleep pattern