High-to-low CO2 acclimation reveals plasticity of the photorespiratory pathway and indicates regulatory links to cellular metabolism of Arabidopsis

Background: Photorespiratory carbon metabolism was long considered as an essentially closed and nonregulated pathway with little interaction to other metabolic routes except nitrogen metabolism and respiration. Most mutants of this pathway cannot survive in ambient air and require CO 2-enriched air for normal growth. Several studies indicate that this CO 2 requirement is very different for individual mutants, suggesting a higher plasticity and more interaction of photorespiratory metabolism as generally thought. To understand this better, we examined a variety of high- and low-level parameters at 1% CO 2 and their alteration during acclimation of wild-type plants and selected photorespiratory mutants to ambient air. Methodology and Principal Findings: The wild type and four photorespiratory mutants of Arabidopsis thaliana (Arabidopsis) were grown to a defined stadium at 1% CO 2 and then transferred to normal air (0.038% CO 2). All other conditions remained unchanged. This approach allowed unbiased side-by-side monitoring of acclimation processes on several levels. For all lines, diel (24 h) leaf growth, photosynthetic gas exchange, and PSII fluorescence were monitored. Metabolite profiling was performed for the wild type and two mutants. During acclimation, considerable variation between the individual genotypes was detected in many of the examined parameters, which correlated with the position of the impaired reaction in the photorespiratory pathway. Conclusions: Photorespiratory carbon metabolism does not operate as a fully closed pathway. Acclimation from high to low CO 2 was typically steady and consistent for a number of features over several days, but we also found unexpected short-term events, such as an intermittent very massive rise of glycine levels after transition of one particular mutant to ambient air. We conclude that photorespiration is possibly exposed to redox regulation beyond known substrate-level effects. Additionally, our data support the view that 2-phosphoglycolate could be a key regulator of photosynthetic-photorespiratory metabolism as a whole. © 2012 Timm et al

The auditory startle response in relation to outcome in functional movement disorders

Background: The auditory startle reflex (ASR) is enlarged in patients with functional movement disorders (FMD). Objectives: To study whether the ASR relates to symptom reduction in FMD patients, who participated in a placebo controlled double blind treatment trial with Botulinum Neurotoxin (BoNT). Methods: Response to treatment in the BoNT study was assessed using the Clinical Global Impression - Improvement scale (CGI-I). The electromyography (EMG) muscle activity of 7 muscles following 110 dB tones was measured in 14 FMD patients before and after one-year treatment and compared to 11 matched controls. The early and a late (behaviorally affected) component of the ASR and the sympathetic skin response (SSR) were assessed. Results: 10 of 14 patients (71.4%) showed symptom improvement, which was believed to be mainly caused by placebo effects. The early total response probability of the ASR at baseline tended to be larger in patients compared to controls (p = 0.08), but normalized at follow-up (p = 0.84). The late total response probability was larger in patients vs. controls at baseline (p < 0.05), a trend that still was present at follow-up (p = 0.08). The SSR was higher in patients vs. controls at baseline (p < 0.01), and normalized at follow-up (p = 0.71). Conclusions: On a group level 71.4% of the patients showed clinical symptom improvement after treatment. The early part of the ASR, most likely reflecting anxiety and hyperarousal, normalized in line with the clinical improvement. Interestingly, the augmented late component of the ASR remained enlarged suggesting persistent altered behavioral processing in functional patients despite motor improvement

The Effect of Escitalopram on Central Serotonergic and Dopaminergic Systems in Patients with Cervical Dystonia, and Its Relationship with Clinical Treatment Effects:A Double-Blind Placebo-Controlled Trial

Purpose:The pathophysiology of cervical dystonia (CD) is thought to be related to changes in dopamine and serotonin levels in the brain. We performed a double-blind trial with escitalopram (selective serotonin reuptake inhibitor; SSRI) in patients with CD. Here, we report on changes in dopamine D(2/3)receptor (D2/3R), dopamine transporter (DAT) and serotonin transporter (SERT) binding potential (BPND) after a six-week treatment course with escitalopram or placebo.Methods:CD patients had [123I]FP-CIT SPECT (I-123 fluoropropyl carbomethoxy-3 beta-(4-iodophenyltropane) single-photon emission computed tomography) scans, to quantify extrastriatal SERT and striatal DAT, and [123I]IBZM SPECT (I-123 iodobenzamide SPECT) scans to quantify striatal D2/3R BPND before and after six weeks of treatment with either escitalopram or placebo. Treatment effect was evaluated with the Clinical Global Impression scale for dystonia, jerks and psychiatric symptoms, both by physicians and patients.Results:In both patients treated with escitalopram and placebo there were no significant differences after treatment in SERT, DAT or D2/3R BPND. Comparing scans after treatment with escitalopram (n = 8) to placebo (n = 8) showed a trend (p= 0.13) towards lower extrastriatal SERT BPND in the SSRI group (median SERT occupancy of 64.6%). After treatment with escitalopram, patients who reported a positive effect on dystonia or psychiatric symptoms had significantly higher SERT occupancy compared to patients who did not experience an effect.Conclusion:Higher extrastriatal SERT occupancy after treatment with escitalopram is associated with a trend towards a positive subjective effect on dystonia and psychiatric symptoms in CD patients

Robust and scalable rf spectroscopy in first-order magnetic sensitive states at second-long coherence time

Trapped-ion quantum sensors have become highly sensitive tools for the search of physics beyond the Standard Model. Recently, stringent tests of local Lorentz-invariance (LLI) have been conducted with precision spectroscopy in trapped ions. We here elaborate on robust and scalable radio-frequency composite-pulse spectroscopy at second long coherence times in the magnetic sublevels of the long-lived $^{2}F_{7/2}$ state of a trapped $^{172}$Yb$^{+}$ ion. We compare two Ramsey-type composite rf pulse sequences, a generalized spin-echo (GSE) sequence and a sequence based on universal rotations with 10 rephasing pulses (UR10) that decouple the energy levels from magnetic field noise, enabling robust and accurate spectroscopy. Both sequences are characterized theoretically and experimentally in the spin-$1/2$$\ $$^{2}S_{1/2}$electronic ground state of$^{172}$Yb$^{+}$and results show that the UR10 sequence is 38 (13) times more robust against pulse duration (frequency detuning) errors than the GSE sequence. We extend our simulations to the eight-level manifold of the$^2F_{7/2}$state, which is highly sensitive to a possible violation of LLI, and show that the UR10 sequence can be used for high-fidelity Ramsey spectroscopy in noisy environments. The UR10 sequence is implemented experimentally in the$^2F_{7/2}$manifold and a coherent signal of up to$2.5\,$s is reached. We have implemented the sequence and used it to perform the most stringent test of LLI in the electron-photon sector to date. Due to the robustness of the UR10 sequence, it can be applied on larger ion crystals to improve tests of Lorentz symmetry further. We demonstrate that the sequence can also be used to extract the quadrupole moment of the meta-stable$^{2}F_{7/2}$state, obtaining a value of$\Theta\,=\,-0.0298(38)\,ea^{2}_{0}$ which is in agreement with the value deduced from clock measurements.Comment: 19 pages, 7 figure

Improved bounds on Lorentz violation from composite-pulse Ramsey spectroscopy in a trapped ion

In attempts to unify the four known fundamental forces in a single quantum-consistent theory, it is suggested that Lorentz symmetry may be broken at the Planck scale. Here we search for Lorentz violation at the low-energy limit by comparing orthogonally oriented atomic orbitals in a Michelson-Morley-type experiment. We apply a robust radiofrequency composite pulse sequence in the $^2F_{7/2}$ manifold of an Yb$^+$ ion, extending the coherence time from 200 $\mu$s to more than 1 s. In this manner, we fully exploit the high intrinsic susceptibility of the $^2F_{7/2}$ state and take advantage of its exceptionally long lifetime. We match the stability of the previous best Lorentz symmetry test nearly an order of magnitude faster and improve the constraints on the symmetry breaking coefficients to the 10$^{-21}$ level. These results represent the most stringent test of this type of Lorentz violation. The demonstrated method can be further extended to ion Coulomb crystals

Distribution and coexistence of myoclonus and dystonia as clinical predictors of SGCE mutation status: a pilot study

Introduction: Myoclonus-dystonia (M-D) is a young onset movement disorder typically involving myoclonus and dystonia of the upper body. A proportion of the cases are caused by mutations to the autosomal dominantly inherited, maternally imprinted, epsilon-sarcoglycan gene (SGCE). Despite several sets of diagnostic criteria, identification of patients most likely to have an SGCE mutation remains difficult. Methods: Forty consecutive patients meeting pre-existing diagnostic clinical criteria for M-D underwent a standardized clinical examination (20 SGCE mutation positive and 20 negative). Each video was reviewed and systematically scored by two assessors blinded to mutation status. In addition, the presence and coexistence of myoclonus and dystonia was recorded in four body regions (neck, arms, legs, and trunk) at rest and with action. Results: Thirty-nine patients were included in the study (one case was excluded owing to insufficient video footage). Based on previously proposed diagnostic criteria, patients were subdivided into 24 "definite," 5 "probable," and 10 "possible" M-D. Motor symptom severity was higher in the SGCE mutation-negative group. Myoclonus and dystonia were most commonly observed in the neck and upper limbs of both groups. Truncal dystonia with action was significantly seen more in the mutation-negative group (p <0.05). Coexistence of myoclonus and dystonia in the same body part with action was more commonly seen in the mutation-negative cohort (p <0.05). Conclusion: Truncal action dystonia and coexistence of myoclonus and dystonia in the same body part with action might suggest the presence of an alternative mutation in patients with M-D

The chronnectome as a model for Charcot's 'dynamic lesion' in functional movement disorders

This exploratory study set out to investigate dynamic functional connectivity (dFC) in patients with jerky and tremulous functional movement disorders (JT-FMD). The focus in this work is on dynamic brain states, which represent distinct dFC patterns that reoccur in time and across subjects. Resting-state fMRI data were collected from 17 patients with JT-FMD and 17 healthy controls (HC). Symptom severity was measured using the Clinical Global Impression-Severity scale. Depression and anxiety were measured using the Beck Depression Inventory (BDI) and Beck Anxiety Inventory (BAI), respectively. Independent component analysis was used to extract functional brain components. After computing dFC, dynamic brain states were determined for every subject using k-means clustering. Compared to HC, patients with JT-FMD spent more time in a state that was characterized predominantly by increasing medial prefrontal, and decreasing posterior midline connectivity over time. They also tended to visit this state more frequently. In addition, patients with JT-FMD transitioned significantly more often between different states compared to HC, and incorporated a state with decreasing medial prefrontal, and increasing posterior midline connectivity in their attractor, i.e., the cyclic patterns of state transitions. Altogether, this is the first study that demonstrates altered functional brain network dynamics in JT-FMD that may support concepts of increased self-reflective processes and impaired sense of agency as driving factors in FMD

Psychiatric disorders, myoclonus dystonia and SGCE:An international study

OBJECTIVE: Myoclonus-dystonia (M-D) is a hyperkinetic movement disorder, typically alcohol-responsive upper body myoclonus and dystonia. The majority of autosomal dominant familial cases are caused by epsilon-sarcoglycan gene (SGCE) mutations. Previous publications have observed increased rates of psychiatric disorders amongst SGCE mutation-positive populations. We analyzed the psychiatric data from four international centers, forming the largest cohort to date, to further determine the extent and type of psychiatric disorders in M-D.METHODS: Psychiatric data from SGCE mutation-positive M-D cohorts, collected by movement disorder specialists in the Netherlands, United Kingdom, United States, and Germany, were analyzed. These data were collected using standardized, systematic questionnaires allowing classification of symptoms according to Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) criteria. Based on motor findings and SGCE mutation analysis, participants were classified into one of three groups: manifesting carriers, nonmanifesting carriers and noncarriers.RESULTS: Data from 307 participants were evaluated (140 males, 167 females, mean age at examination: 42.5 years). Two-thirds of motor affected mutation carriers (n = 132) had ≥1 psychiatric diagnosis, specific, and social phobias being most common followed by alcohol dependence and obsessive-compulsive disorder (OCD). Compared to familial controls, affected mutation carriers had significantly elevated overall rates of psychiatric disorders (P &lt; 0.001). The most significant differences were observed with alcohol dependence (P &lt; 0.001), OCD (P &lt; 0.001), social and specific phobias (P &lt; 0.001).INTERPRETATION: M-D due to SGCE mutations is associated with specific psychiatric disorders, most commonly OCD, anxiety-related disorders, and alcohol dependence. These suggest either a potential pleiotropic function for SGCE within the central nervous system or a secondary effect of the motor disorder.</p

Students' attitudes towards the introduction of a Personal and Professional Development portfolio: potential barriers and facilitators

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