Abnormal Cerebrospinal Fluid Cytology in Functional Movement Disorders.

OBJECTIVE: The role of inflammation and neuroimmune mechanisms, which have been documented in various neuropsychiatric disorders including the seizure subtype of functional neurological disorder, remains unclear in functional movement disorders (FMD). To explore these mechanisms, we analyzed selected inflammatory markers in cerebrospinal fluid (CSF) in patients with FMD. METHODS: We compared CSF markers in 26 patients with clinically established FMD (20 females; mean [SD] age = 43.3 [10.9], disease duration = 3.9 [3], range = 0.1-11 years; mean follow-up after lumbar puncture = 4.3 [2] years, range = 0.5-7 years) and 26 sex- and age-matched clinical controls with noninflammatory nonneurodegenerative neurological disorders, mostly sleep disorders. RESULTS: Sixty-five percent of FMD patients versus 15% of controls showed cytological abnormalities (i.e., increased white blood cells [WBC] count, signs of WBC activation, or both; odds ratio [OR] = 9.85, 95% confidence interval = 2.37-52.00, p < .01, corrected), with a significantly higher frequency of an isolated lymphocytic activation, 35% versus 0% (OR = ∞, 95% confidence interval = 2.53-∞, p < .05, corrected). There were no differences in CSF protein and albumin levels, quotient albumin, IgG index, and oligoclonal bands. CSF abnormalities were not associated with more severe motor symptoms or a higher frequency of depression in FMD. CONCLUSIONS: Our results suggest a possible involvement of immune mechanisms in the pathophysiology of (at least a subtype of) FMD that deserves further investigation.

Sleepiness and comorbid sleep disorders in functional motor disorders: a comparative study with central hypersomnia.

Sleep symptoms, including excessive sleepiness, are frequently reported by patients with functional motor disorders (FMD). We aimed to classify the comorbid sleep disorders in FMD, and to investigate the relationship between subjective sleepiness and objective measures of hypersomnia, comparing them with data from people with central hypersomnia. A total of 37 patients (mean [SD] age 46.4 [11.2] years) with clinically definite FMD, and 17 patients (mean [SD] age 41.1 [11.6] years) with central hypersomnia underwent structured medical and sleep history, neurological examination, polysomnography, multiple sleep latency test (MSLT), and questionnaires assessing sleepiness, fatigue, and depression. In all, 23 patients with FMD (62%) reported excessive daytime sleepiness. Evidence of specific sleep disorders was identified in our cohort, with 35% having restless legs syndrome; 49% obstructive sleep apnea; and 8% periodic limb movements in sleep; however, the presence of these disorders was not correlated with subjective sleepiness. Patients with FMD with self-reported sleepiness reported higher fatigue (p = 0.002), depression (p = 0.002), and had longer sleep latencies in the MSLT (p < 0.001) compared to the patients with central hypersomnia. No correlation was found between subjective and objective sleepiness in either group. Fatigue positively correlated with self-reported sleepiness in patients with FMD (p < 0.001). This study did not find objective correlates of increased sleepiness in patients with FMD. While sleep abnormalities were found to be common in FMD, they were not correlated with self-reports of excessive sleepiness. Positive correlations between self-reported sleepiness and fatigue support the current unified model of non-motor symptoms in FMD.

Improving fMRI in Parkinson's disease by accounting for brain region-specific activity patterns.

In functional magnetic imaging (fMRI) in Parkinson's disease (PD), a paradigm consisting of blocks of finger tapping and rest along with a corresponding general linear model (GLM) is often used to assess motor activity. However, this method has three limitations: (i) Due to the strong magnetic field and the confined environment of the cylindrical bore, it is troublesome to accurately monitor motor output and, therefore, variability in the performed movement is typically ignored. (ii) Given the loss of dopaminergic neurons and ongoing compensatory brain mechanisms, motor control is abnormal in PD. Therefore, modeling of patients' tapping with a constant amplitude (using a boxcar function) and the expected Parkinsonian motor output are prone to mismatch. (iii) The motor loop involves structures with distinct hemodynamic responses, for which only one type of modeling (e.g., modeling the whole block of finger tapping) may not suffice to capture these structure's temporal activation. The first two limitations call for considering results from online recordings of the real motor output that may lead to significant sensitivity improvements. This was shown in previous work using a non-magnetic glove to capture details of the patients' finger movements in a so-called kinematic approach. For the third limitation, modeling motion initiation instead of the whole tapping block has been suggested to account for different temporal activation signatures of the motor loop's structures. In the present study we propose improvements to the GLM as a tool to study motor disorders. For this, we test the robustness of the kinematic approach in an expanded cohort (n = 31), apply more conservative statistics than in previous work, and evaluate the benefits of an event-related model function. Our findings suggest that the integration of the kinematic approach offers a general improvement in detecting activations in subcortical structures, such as the basal ganglia. Additionally, modeling motion initiation using an event-related design yielded superior performance in capturing medication-related effects in the putamen. Our results may guide adaptations in analysis strategies for functional motor studies related to PD and also in more general applications.

The complex syndrome of functional neurological disorder.

BACKGROUND: Patients with functional neurological disorders (FND) often present with multiple motor, sensory, psychological and cognitive symptoms. In order to explore the relationship between these common symptoms, we performed a detailed clinical assessment of motor, non-motor symptoms, health-related quality of life (HRQoL) and disability in a large cohort of patients with motor FND. To understand the clinical heterogeneity, cluster analysis was used to search for subgroups within the cohort. METHODS: One hundred fifty-two patients with a clinically established diagnosis of motor FND were assessed for motor symptom severity using the Simplified Functional Movement Disorder Rating Scale (S-FMDRS), the number of different motor phenotypes (i.e. tremor, dystonia, gait disorder, myoclonus, and weakness), gait severity and postural instability. All patients then evaluated each motor symptom type severity on a Likert scale and completed questionnaires for depression, anxiety, pain, fatigue, cognitive complaints and HRQoL. RESULTS: Significant correlations were found among the self-reported and all objective motor symptoms severity measures. All self-reported measures including HRQoL correlated strongly with each other. S-FMDRS weakly correlated with HRQoL. Hierarchical cluster analysis supplemented with gap statistics revealed a homogenous patient sample which could not be separated into subgroups. CONCLUSIONS: We interpret the lack of evidence of clusters along with a high degree of correlation between all self-reported and objective measures of motor or non-motor symptoms and HRQoL within current neurobiological models as evidence to support a unified pathophysiology of 'functional' symptoms. Our results support the unification of functional and somatic syndromes in classification schemes and for future mechanistic and therapeutic research.

Emotional arousal in patients with functional movement disorders: A pupillometry study.

OBJECTIVE: Pathophysiology explanations for functional movement disorders often assume a role for emotional hyperarousal. Pupillometry is a validated method for evaluation of emotional arousal by detecting changes in pupil size in response to emotional stimuli. In a case-control study design, we aimed to study objective and subjective emotional arousal using pupillometry and affective ratings. To assess attentional engagement by affective stimuli, we used videooculographic tracking of eye movement patterns (scanpath). METHODS: Twenty-five female patients with functional movement disorders (mean age: 40.9 [SD 12.7] years) and 23 age matched healthy female controls participated in the study. Using infrared high-resolution eye-tracker, both pupil size and eye movement pattern in response to emotionally charged erotic, adventure, threat, victim, and neutral pictures were recorded along with subjective ratings of emotional valence and arousal of the presented pictures. RESULTS: A between-group comparison showed significantly smaller pupil dilation to adventure stimuli compared to neutral stimuli in patients compared to controls (P < 0.004, bootstrap, uncorr., adj. η2 = 0.00). No significant difference in pupillary response to other stimuli and scanpath parameters was found between the groups. Patients rated significantly lower emotional arousal to erotic pictures than controls (P < 0.001, bootstrap, uncorr., adj. η2 = 0.09). CONCLUSION: This study did not find evidence of autonomous or subjective emotional hyperarousal. The mismatch between objective autonomic measures and subjective arousal ratings in patients is of pathophysiological interest and in line with recent findings of impaired interoception in functional movement disorders.

Disease progression of 213 patients hospitalized with Covid-19 in the Czech Republic in March-October 2020: An exploratory analysis.

We collected a multi-centric retrospective dataset of patients (N = 213) who were admitted to ten hospitals in Czech Republic and tested positive for SARS-CoV-2 during the early phases of the pandemic in March-October 2020. The dataset contains baseline patient characteristics, breathing support required, pharmacological treatment received and multiple markers on daily resolution. Patients in the dataset were treated with hydroxychloroquine (N = 108), azithromycin (N = 72), favipiravir (N = 9), convalescent plasma (N = 7), dexamethasone (N = 4) and remdesivir (N = 3), often in combination. To explore association between treatments and patient outcomes we performed multiverse analysis, observing how the conclusions change between defensible choices of statistical model, predictors included in the model and other analytical degrees of freedom. Weak evidence to constrain the potential efficacy of azithromycin and favipiravir can be extracted from the data. Additionally, we performed external validation of several proposed prognostic models for Covid-19 severity showing that they mostly perform unsatisfactorily on our dataset.

The sensitivity of ECG contamination to surgical implantation site in brain computer interfaces.

BACKGROUND: Brain sensing devices are approved today for Parkinson's, essential tremor, and epilepsy therapies. Clinical decisions for implants are often influenced by the premise that patients will benefit from using sensing technology. However, artifacts, such as ECG contamination, can render such treatments unreliable. Therefore, clinicians need to understand how surgical decisions may affect artifact probability. OBJECTIVES: Investigate neural signal contamination with ECG activity in sensing enabled neurostimulation systems, and in particular clinical choices such as implant location that impact signal fidelity. METHODS: Electric field modeling and empirical signals from 85 patients were used to investigate the relationship between implant location and ECG contamination. RESULTS: The impact on neural recordings depends on the difference between ECG signal and noise floor of the electrophysiological recording. Empirically, we demonstrate that severe ECG contamination was more than 3.2x higher in left-sided subclavicular implants (48.3%), when compared to right-sided implants (15.3%). Cranial implants did not show ECG contamination. CONCLUSIONS: Given the relative frequency of corrupted neural signals, we conclude that implant location will impact the ability of brain sensing devices to be used for "closed-loop" algorithms. Clinical adjustments such as implant location can significantly affect signal integrity and need consideration.

Speech Perception and Production in Cochlear Implant Recipients with Pendred Syndrome.

AIMS: Patients with the Pendred syndrome suffer very often from a hearing loss. They may be good candidates for a cochlear implantation, but unfortunately, due to the fluctuating character of the hearing loss, they may escape such indication. In the study, we compared speech production and speech acquisition in 2 groups of implanted patients: those with the Pendred syndrome, and standard non-syndromic patients. METHODS: Ten patients with Pendred syndrome were analyzed for speech perception and production. The control group consisted of 41 non-syndromic implanted patients. All implantees were scored according to speech perception, speech production, and the sum of both. The data were statistically analyzed. RESULTS: No statistical difference was found in language acquisition and production in implantees with Pendred syndrome when compared to non-syndromic patients with cochlear implants. Nor there was any difference in speech production and acquisition between the 2 compared groups regarding surgical age, time elapsed after surgery, or age during the testing. CONCLUSION: In this study evaluating language and speech production and acquisition, patients with Pendred syndrome who underwent cochlear implants show comparable results to their implanted peers with deafness of a different etiology.

Nucleoporin TPR Affects C2C12 Myogenic Differentiation via Regulation of Myh4 Expression.

The nuclear pore complex (NPC) has emerged as a hub for the transcriptional regulation of a subset of genes, and this type of regulation plays an important role during differentiation. Nucleoporin TPR forms the nuclear basket of the NPC and is crucial for the enrichment of open chromatin around NPCs. TPR has been implicated in the regulation of transcription; however, the role of TPR in gene expression and cell differentiation has not been described. Here we show that depletion of TPR results in an aberrant morphology of murine proliferating C2C12 myoblasts (MBs) and differentiated C2C12 myotubes (MTs). The ChIP-Seq data revealed that TPR binds to genes linked to muscle formation and function, such as myosin heavy chain (Myh4), myocyte enhancer factor 2C (Mef2C) and a majority of olfactory receptor (Olfr) genes. We further show that TPR, possibly via lysine-specific demethylase 1 (LSD1), promotes the expression of Myh4 and Olfr376, but not Mef2C. This provides a novel insight into the mechanism of myogenesis; however, more evidence is needed to fully elucidate the mechanism by which TPR affects specific myogenic genes.

The effects of interventional mitral valve repair using the MitraClip System on the results of pulmonary function testing, pulmonary pressure and diffusing capacity of the lung.

BACKGROUND: The study analyzes changes in lung function, pulmonary pressure and diffusing capacity of the lung in patients with mitral valve regurgitation (MR) treated by MitraClip implantation. METHODS: A total of 43 patients (19 women and 24 men with an average age of 78.0 ± 6.6 years) who were able to perform pulmonary function testing including diffusing capacity of the lung for carbon monoxide (DLCO), vital capacity (VC), total lung capacity (TLC), residual volume (RV) and forced expiratory volume in 1 s (FEV1) before and 6 weeks after MitraClip implantation participated in this study. Furthermore, clinical and echocardiographic parameters including systolic pulmonary artery pressure (sPAP), left ventricular ejection fraction (LVEF) and left atrial diameter (LAD) measurements were recorded in all patients. RESULTS: The procedure was performed successfully in all 43 patients leading to a reduction of MR in 97.7% of cases. One patient died on day 4 after the intervention most likely due to pulmonary artery embolism. Six weeks after the implantation 79.1% of patients showed a MR of at most mild to moderate. Furthermore, we could demonstrate a significant reduction of systolic pulmonary artery pressure during follow-up (from 48.8 ± 11.4 mmHg to 42.9 ± 9.0 mmHg (t(41) = - 2.6, p = 0.01). However, no changes in LVEF were detected. Comparing pre and post implant lung function tests, no significant alterations were seen for VC, TLC, DLCO and FEV1. Though, in a subgroup of patients with moderate to severe preexisting deterioration of DLCO at the baseline (max. 50%) the MitraClip procedure resulted in a significant improvement in DLCO (37.8% ± 9.0 to 41.6% ± 10.0, p < 0.001). CONCLUSIONS: Treatment of MR with the MitraClip system successfully reduces MR severity in the vast majority of patients. Consecutively, a reduction in pulmonary pressure could be observed, however no changes in LVEF were obvious. Lung function tests remained unaltered during follow-up. However, in a subgroup of patients with severe preexisting deterioration of DLCO the MitraClip procedure resulted in a significant improvement in DLCO. TRIAL REGISTRATION: Name of the registry: Die Auswirkung der interventionellen Mitralklappenreparatur mit MitraClip-System auf die Ergebnisse der Lungenfunktionsmessung. TRIAL REGISTRATION NUMBER: DRKS00022435; Date of registration: 09/07/2020 'Retrospectively registered'; URL of trial registry record: https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00022435 .

Associations of Brain Atrophy and Cerebral Iron Accumulation at MRI with Clinical Severity in Wilson Disease.

Background Abnormal findings at brain MRI in patients with neurologic Wilson disease (WD) are characterized by signal intensity changes and cerebral atrophy. T2 signal hypointensities and atrophy are largely irreversible with treatment; their relationship with permanent disability has not been systematically investigated. Purpose To investigate associations of regional brain atrophy and iron accumulation at MRI with clinical severity in participants with neurologic WD who are undergoing long-term anti-copper treatment. Materials and Methods Participants with WD and controls were compared in a prospective study performed from 2015 to 2019. MRI at 3.0 T included three-dimensional T1-weighted and six-echo multigradient-echo pulse sequences for morphometry and quantitative susceptibility mapping, respectively. Neurologic severity was assessed with the Unified WD Rating Scale (UWDRS). Automated multi-atlas segmentation pipeline with dual contrast (susceptibility and T1) was used for the calculation of volumes and mean susceptibilities in deep gray matter nuclei. Additionally, whole-brain analysis using deformation and surface-based morphometry was performed. Least absolute shrinkage and selection operator regression was used to assess the association of regional volumes and susceptibilities with the UWDRS score. Results Twenty-nine participants with WD (mean age, 47 years ± 9 [standard deviation]; 15 women) and 26 controls (mean age, 45 years ± 12; 14 women) were evaluated. Whole-brain analysis demonstrated atrophy of the deep gray matter nuclei, brainstem, internal capsule, motor cortex and corticospinal pathway, and visual cortex and optic radiation in participants with WD (P < .05 at voxel level, corrected for family-wise error). The UWDRS score was negatively correlated with volumes of putamen (r = -0.63, P < .001), red nucleus (r = -0.58, P = .001), globus pallidus (r = -0.53, P = .003), and substantia nigra (r = -0.50, P = .006) but not with susceptibilities. Only the putaminal volume was identified as a stable factor associated with the UWDRS score (R2 = 0.38, P < .001) using least absolute shrinkage and selection operator regression. Conclusion Individuals with Wilson disease (WD) had widespread brain atrophy most pronounced in the central structures. The putaminal volume was associated with the Unified WD Rating Scale score and can be used as a surrogate imaging marker of clinical severity. © RSNA, 2021 Supplemental material is available for this article. See also the editorial by Du and Bydder in this issue.

ShinySOM: graphical SOM-based analysis of single-cell cytometry data.

SUMMARY: ShinySOM offers a user-friendly interface for reproducible, high-throughput analysis of high-dimensional flow and mass cytometry data guided by self-organizing maps. The software implements a FlowSOM-style workflow, with improvements in performance, visualizations and data dissection possibilities. The outputs of the analysis include precise statistical information about the dissected samples, and R-compatible metadata useful for the batch processing of large sample volumes. AVAILABILITY AND IMPLEMENTATION: ShinySOM is free and open-source, available online at gitlab.com/exaexa/ShinySOM. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Topography of emotional valence and arousal within the motor part of the subthalamic nucleus in Parkinson's disease.

Clinical motor and non-motor effects of deep brain stimulation (DBS) of the subthalamic nucleus (STN) in Parkinson's disease (PD) seem to depend on the stimulation site within the STN. We analysed the effects of the position of the stimulation electrode within the motor STN on subjective emotional experience, expressed as emotional valence and arousal ratings to pictures representing primary rewards and aversive fearful stimuli in 20 PD patients. Patients' ratings from both aversive and erotic stimuli matched the mean ratings from a group of 20 control subjects at similar position within the STN. Patients with electrodes located more posteriorly reported both valence and arousal ratings from both the rewarding and aversive pictures as more extreme. Moreover, posterior electrode positions were associated with a higher occurrence of depression at a long-term follow-up. This brain-behavior relationship suggests a complex emotion topography in the motor part of the STN. Both valence and arousal representations overlapped and were uniformly arranged anterior-posteriorly in a gradient-like manner, suggesting a specific spatial organization needed for the coding of the motivational salience of the stimuli. This finding is relevant for our understanding of neuropsychiatric side effects in STN DBS and potentially for optimal electrode placement.

Prepulse inhibition of the blink reflex is abnormal in functional movement disorders.

BACKGROUND: Patients with functional movement disorders also typically have functional somatic symptoms, including pain, fatigue, and sensory disturbance. A potentially unifying mechanism for such symptoms is a failure in processing of sensory inputs. Prepulse inhibition is a neurophysiological method that allows for the study of preconscious somatosensory processing. OBJECTIVE: The objective of this study was to assess prepulse inhibition in patients with functional movement disorders and healthy control subjects. METHODS: We analyzed the effect of a weak electrical stimulus to the index finger (prepulse) on the magnitude of the R2 response of the blink reflex induced by electrical stimuli delivered to the supraorbital nerve in 22 patients with clinically established functional movement disorders and 22 matched controls. Pain, depression, anxiety, and obsessive-compulsive symptoms were assessed using self-rated questionnaires. In addition, in patients we assessed motor symptom severity. RESULTS: Prepulses suppressed the R2 response of the blink reflex in both groups, by 36.4% (standard deviation: 25.6) in patients and by 67.3% (standard deviation: 16.4) in controls. This difference was significant (P < 0.001). There was no significant correlation between motor and nonmotor symptom measures and prepulse inhibition size. CONCLUSIONS: Impaired prepulse inhibition of the blink reflex suggests an abnormal preconscious processing of somatosensory inputs, which can be interpreted within predictive coding accounts of both functional movement disorders and functional somatic syndromes. Our results, along with previous findings of a reduced prepulse inhibition in fibromyalgia syndrome, support a possible unified pathophysiology across functional neurological and somatic syndromes with noteworthy implications for diagnostic classification and development of novel biomarkers and treatments. © 2019 International Parkinson and Movement Disorder Society.

Nuclear pore protein TPR associates with lamin B1 and affects nuclear lamina organization and nuclear pore distribution.

The organization of the nuclear periphery is crucial for many nuclear functions. Nuclear lamins form dense network at the nuclear periphery and play a substantial role in chromatin organization, transcription regulation and in organization of nuclear pore complexes (NPCs). Here, we show that TPR, the protein located preferentially within the nuclear baskets of NPCs, associates with lamin B1. The depletion of TPR affects the organization of lamin B1 but not lamin A/C within the nuclear lamina as shown by stimulated emission depletion microscopy. Finally, reduction of TPR affects the distribution of NPCs within the nuclear envelope and the effect can be reversed by simultaneous knock-down of lamin A/C or the overexpression of lamin B1. Our work suggests a novel role for the TPR at the nuclear periphery: the TPR contributes to the organization of the nuclear lamina and in cooperation with lamins guards the interphase assembly of nuclear pore complexes.

Eye movements in idiopathic rapid eye movement sleep behaviour disorder: High antisaccade error rate reflects prefrontal cortex dysfunction.

Abnormalities of eye movements have been reported in patients with Parkinson's disease (PD). However, it is unclear if they occur in the prodromal stage of synucleinopathy represented by idiopathic rapid eye movement sleep behaviour disorder (iRBD). We thus aimed to study eye movements in subjects with iRBD and in de novo PD, to assess if their abnormalities may serve as a clinical biomarker of neurodegeneration. Fifty subjects with polysomnography-confirmed iRBD (46 male, age 40-79 years), 18 newly diagnosed, untreated PD patients (13 male, age 43-75 years) and 25 healthy controls (20 male, age 42-79 years) were prospectively enrolled. Horizontal and vertical ocular prosaccades and antisaccades were investigated with video-oculography. All patients completed the MDS-UPDRS and the Montreal Cognitive Assessment. In addition, a neuropsychological battery was performed on iRBD subjects. When compared with healthy controls, both de novo PD patients and iRBD subjects showed increased error rates in the horizontal antisaccade task (p < 0.01, p < 0.05 respectively). In the iRBD group, the error rates in horizontal and vertical antisaccades correlated with performances in the Prague Stroop Test and the Grooved Pegboard Test, as well as with motor scores of the MDS-UPDRS. De novo PD patients showed a lower gain (p < 0.01) compared with controls. In conclusion, the increased error rate in the antisaccade task of iRBD and PD patients reflects a dysfunction of the dorsolateral prefrontal cortex and is related to the impairment of executive functions and attention.

Relapse in schizophrenia: Definitively not a bolt from the blue.

Detailed study of the period before schizophrenic relapse when early warning signs (EWS) are present is crucial to effective pre-emptive strategies. To investigate the temporal properties of EWS self-reported weekly via a telemedicine system. EWS history was obtained for 61 relapses resulting in hospitalization involving 51 patients with schizophrenia. Up to 20 weeks of EWS history per case were evaluated using a non-parametric bootstrap test and generalized mixed-effects model to test the significance and homogeneity of the findings. A statistically significant increase in EWS sum score was detectable 5 weeks before hospitalization. However, analysis of EWS dynamics revealed a gradual, monotonic increase in EWS score across during the 8 weeks before a relapse. The findings-in contrast to earlier studies-suggest that relapse is preceded by a lengthy period during which pathophysiological processes unfold; these changes are reflected in subjective EWS.

Methods for automatic detection of artifacts in microelectrode recordings.

BACKGROUND: Extracellular microelectrode recording (MER) is a prominent technique for studies of extracellular single-unit neuronal activity. In order to achieve robust results in more complex analysis pipelines, it is necessary to have high quality input data with a low amount of artifacts. We show that noise (mainly electromagnetic interference and motion artifacts) may affect more than 25% of the recording length in a clinical MER database. NEW METHOD: We present several methods for automatic detection of noise in MER signals, based on (i) unsupervised detection of stationary segments, (ii) large peaks in the power spectral density, and (iii) a classifier based on multiple time- and frequency-domain features. We evaluate the proposed methods on a manually annotated database of 5735 ten-second MER signals from 58 Parkinson's disease patients. COMPARISON WITH EXISTING METHODS: The existing methods for artifact detection in single-channel MER that have been rigorously tested, are based on unsupervised change-point detection. We show on an extensive real MER database that the presented techniques are better suited for the task of artifact identification and achieve much better results. RESULTS: The best-performing classifiers (bagging and decision tree) achieved artifact classification accuracy of up to 89% on an unseen test set and outperformed the unsupervised techniques by 5-10%. This was close to the level of agreement among raters using manual annotation (93.5%). CONCLUSION: We conclude that the proposed methods are suitable for automatic MER denoising and may help in the efficient elimination of undesirable signal artifacts.

Chromatin organization at the nuclear periphery as revealed by image analysis of structured illumination microscopy data.

The nuclear periphery (NP) plays a substantial role in chromatin organization. Heterochromatin at the NP is interspersed with active chromatin surrounding nuclear pore complexes (NPCs); however, details of the peripheral chromatin organization are missing. To discern the distribution of epigenetic marks at the NP of HeLa nuclei, we used structured illumination microscopy combined with a new MATLAB software tool for automatic NP and NPC detection, measurements of fluorescent intensity and statistical analysis of measured data. Our results show that marks for both active and non-active chromatin associate differentially with NPCs. The incidence of heterochromatin marks, such as H3K27me2 and H3K9me2, was significantly lower around NPCs. In contrast, the presence of marks of active chromatin such as H3K4me2 was only decreased very slightly around the NPCs or not at all (H3K9Ac). Interestingly, the histone demethylases LSD1 (also known as KDM1A) and KDM2A were enriched within the NPCs, suggesting that there was a chromatin-modifying mechanism at the NPCs. Inhibition of transcription resulted in a larger drop in the distribution of H1, H3K9me2 and H3K23me2, which implies that transcription has a role in the organization of heterochromatin at the NP.