A grounded theory study on the influence of sleep on Parkinson’s symptoms

Contains fulltext : 167717.pdf (publisher's version ) (Open Access)BACKGROUND: Upon awaking, many Parkinson's patients experience an improved mobility, a phenomenon known as 'sleep benefit'. Despite the potential clinical relevance, no objective correlates of sleep benefit exist. The discrepancy between the patients' subjective experience of improvement in absence of objective changes is striking, and raises questions about the nature of sleep benefit. We aimed to clarify what patients reporting subjective sleep benefit, actually experience when waking up. Furthermore, we searched for factors associated with subjective sleep benefit. METHODS: Using a standardized topic list, we interviewed 14 Parkinson patients with unambiguous subjective sleep benefit, selected from a larger questionnaire-based cohort. A grounded theory approach was used to analyse the data. RESULTS: A subset of the participants described a temporary decrease in their Parkinson motor symptoms after sleep. Others did experience beneficial effects which were, however, non-specific for Parkinson's disease (e.g. feeling 'rested'). The last group misinterpreted the selection questionnaire and did not meet the definition of sleep benefit for various reasons. There were no general sleep-related factors that influenced the presence of sleep benefit. Factors mentioned to influence functioning at awakening were mostly stress related. CONCLUSIONS: The group of participants convincingly reporting sleep benefit in the selection questionnaire appeared to be very heterogeneous, with only a portion of them describing sleep benefit on motor symptoms. The group of participants actually experiencing motor sleep benefit may be much smaller than reported in the literature so far. Future studies should employ careful inclusion criteria, which could be based on our reported data

Unequal Effects of Myosin 5B Mutations in Liver and Intestine Determine the Clinical Presentation of Low-Gamma-Glutamyltransferase Cholestasis

Mutations in the MYO5B gene cause in some patients low gamma-glutamyltransferase (low-GGT) cholestatic liver disease (CLD) and in other patients microvillus inclusion disease (MVID, a congenital diarrheal and malabsorption disorder). Overlap of symptoms occurs but more MVID patients present cholestasis than CLD patients present diarrhea. Clinical observations indicate that MYO5B mutations can cause but also protect against CLD. This complicates family counseling and therapeutic decisions. Here we have reviewed the literature on MYO5B mutations in relation to CLD. It appears that variations in the clinical presentation of low-GGT CLD can be attributed to the coincident expression but unequal effects of MYO5B mutations in hepatocytes versus enterocytes, two cell types that jointly constitute the core of the enterohepatic circulation. Therefore, contrasting other low-GGT CLDs, those associated with MYO5B mutations should be viewed as a disease of the enterohepatic circulation rather than solely of the liver

Model-Based Evaluation of Methods for Respiratory Sinus Arrhythmia Estimation

OBJECTIVE: Respiratory sinus arrhythmia (RSA) refers to heart rate oscillations synchronous with respiration, and it is one of the major representations of cardiorespiratory coupling. Its strength has been suggested as a biomarker to monitor different conditions and diseases. Some approaches have been proposed to quantify the RSA, but it is unclear which one performs best in specific scenarios. The main objective of this study is to compare seven state-of-the-art methods for RSA quantification using data generated with a model proposed to simulate and control the RSA. These methods are also compared and evaluated on a real-life application, for their ability to capture changes in cardiorespiratory coupling during sleep. METHODS: A simulation model is used to create a dataset of heart rate variability and respiratory signals with controlled RSA, which is used to compare the RSA estimation approaches. To compare the methods objectively in a real-life application, regression models trained on the simulated data are used to map the estimates to the same measurement scale. RESULTS AND CONCLUSION: RSA estimates based on cross entropy, time-frequency coherence and subspace projections showed the best performance on simulated data. In addition, these estimates captured the expected trends in the changes in cardiorespiratory coupling during sleep similarly. SIGNIFICANCE: An objective comparison of methods for RSA quantification is presented to guide future analyses. Also, the proposed simulation model can be used to compare existing and newly proposed RSA estimates. It is freely accessible online

Model-Based Evaluation of Methods for Respiratory Sinus Arrhythmia Estimation

Objective: Respiratory sinus arrhythmia (RSA) refers to heart rate oscillations synchronous with respiration, and it is one of the major representations of cardiorespiratory coupling. Its strength has been suggested as a biomarker to monitor different conditions and diseases. Some approaches have been proposed to quantify the RSA, but it is unclear which one performs best in specific scenarios. The main objective of this study is to compare seven state-of-the-art methods for RSA quantification using data generated with a model proposed to simulate and control the RSA. These methods are also compared and evaluated on a real-life application, for their ability to capture changes in cardiorespiratory coupling during sleep. Methods: A simulation model is used to create a dataset of heart rate variability and respiratory signals with controlled RSA, which is used to compare the RSA estimation approaches. To compare the methods objectively in a real-life application, regression models trained on the simulated data are used to map the estimates to the same measurement scale. Results and conclusion: RSA estimates based on cross entropy, time-frequency coherence and subspace projections showed the best performance on simulated data. In addition, these estimates captured the expected trends in the changes in cardiorespiratory coupling during sleep similarly. Significance: An objective comparison of methods for RSA quantification is presented to guide future analyses. Also, the proposed simulation model can be used to compare existing and newly proposed RSA estimates. It is freely accessible online

Loss of MYO5B expression deregulates late endosome size which hinders mitotic spindle orientation

Recycling endosomes regulate plasma membrane recycling. Recently, recycling endosome-associated proteins have been implicated in the positioning and orientation of the mitotic spindle and cytokinesis. Loss of MYO5B, encoding the recycling endosome-associated myosin Vb, is associated with tumor development and tissue architecture defects in the gastrointestinal tract. Whether loss of MYO5B expression affects mitosis is not known. Here, we demonstrate that loss of MYO5B expression delayed cytokinesis, perturbed mitotic spindle orientation, led to the misorientation of the plane of cell division during the course of mitosis, and resulted in the delamination of epithelial cells. Remarkably, the effects on spindle orientation, but not cytokinesis, were a direct consequence of physical hindrance by giant late endosomes, which were formed in a chloride channel-sensitive manner concomitant with a redistribution of chloride channels from the cell periphery to late endosomes upon loss of MYO5B. Rab7 availability was identified as a limiting factor for the development of giant late endosomes. In accordance, increasing rab7 availability corrected mitotic spindle misorientation and cell delamination in cells lacking MYO5B expression. In conclusion, we identified a novel role for MYO5B in the regulation of late endosome size control and identify the inability to control late endosome size as an unexpected novel mechanism underlying defects in cell division orientation and epithelial architecture. Loss of the recycling endosome-associated motor protein myosin Vb causes the formation of giant late endo-lysosomes; these in turn hinder the orientation of the mitotic spindle and chromosome segregation. Deregulated endosome size thus hampers faithful cell division

MYO5B, STX3, and STXBP2 mutations reveal a common disease mechanism that unifies a subset of congenital diarrheal disorders:A mutation update

Microvillus inclusion disease (MVID) is a rare but fatal autosomal recessive congenital diarrheal disorder caused by MYO5B mutations. In 2013, we launched an open-access registry for MVID patients and their MYO5B mutations (www.mvid-central.org). Since then, additional unique MYO5B mutations have been identified in MVID patients, but also in non-MVID patients. Animal models have been generated that formally prove the causality between MYO5B and MVID. Importantly, mutations in two other genes, STXBP2 and STX3, have since been associated with variants of MVID, shedding new light on the pathogenesis of this congenital diarrheal disorder. Here, we review these additional genes and their mutations. Furthermore, we discuss recent data from cell studies that indicate that the three genes are functionally linked and, therefore, may constitute a common disease mechanism that unifies a subset of phenotypically linked congenital diarrheal disorders. We present new data based on patient material to support this. To congregate existing and future information on MVID geno-/phenotypes, we have updated and expanded the MVID registry to include all currently known MVID-associated gene mutations, their demonstrated or predicted functional consequences, and associated clinical information.</p

Optimized Trigger for Ultra-High-Energy Cosmic-Ray and Neutrino Observations with the Low Frequency Radio Array

When an ultra-high energy neutrino or cosmic ray strikes the Lunar surface a radio-frequency pulse is emitted. We plan to use the LOFAR radio telescope to detect these pulses. In this work we propose an efficient trigger implementation for LOFAR optimized for the observation of short radio pulses.Comment: Submitted to Nuclear Instruments and Methods in Physics Research Section

Efficient and scalable generation of primordial germ cells in 2D culture using basement membrane extract overlay

Current methods to generate human primordial germ cell-like cells (hPGCLCs) from human pluripotent stem cells (hPSCs) can be inefficient, and it is challenging to generate sufficient hPGCLCs to optimize in vitro gametogenesis. We present a differentiation method that uses diluted basement membrane extract (BMEx) and low BMP4 concentration to efficiently induce hPGCLC differentiation in scalable 2D cell culture. We show that BMEx overlay potentiated BMP/SMAD signaling, induced lumenogenesis, and increased expression of key hPGCLC-progenitor markers such as TFAP2A and EOMES. hPGCLCs that were generated using the BMEx overlay method were able to upregulate more mature germ cell markers, such as DAZL and DDX4, in human fetal ovary reconstitution culture. These findings highlight the importance of BMEx during hPGCLC differentiation and demonstrate the potential of the BMEx overlay method to interrogate the formation of PGCs and amnion in humans, as well as to investigate the next steps to achieve in vitro gametogenesis.Stem cells & developmental biolog

Hierarchical Multivalent Effects Control Influenza Host Specificity

Understanding how emerging influenza viruses recognize host cells is critical in evaluating their zoonotic potential, pathogenicity, and transmissibility between humans. The surface of the influenza virus is covered with hemagglutinin (HA) proteins that can form multiple interactions with sialic acid-terminated glycans on the host cell surface. This multivalent binding affects the selectivity of the virus in ways that cannot be predicted from the individual receptor-ligand interactions alone. Here, we show that the intrinsic structural and energetic differences between the interactions of avian- or human-type receptors with influenza HA translate from individual site affinity and orientation through receptor length and density on the surface into virus avidity and specificity. We introduce a method to measure virus avidity using receptor density gradients. We found that influenza viruses attached stably to a surface at receptor densities that correspond to a minimum number of approximately 8 HA-glycan interactions, but more interactions were required if the receptors were short and human-type. Thus, the avidity and specificity of influenza viruses for a host cell depend not on the sialic acid linkage alone but on a combination of linkage and the length and density of receptors on the cell surface. Our findings suggest that threshold receptor densities play a key role in virus tropism, which is a predicting factor for both their virulence and zoonotic potential.Fil: Overeem, Nico J.. University of Twente; Países BajosFil: Hamming, P. H. Erik. University of Twente; Países BajosFil: Grant, Oliver C.. University of Georgia; Estados UnidosFil: Di Iorio, Daniele. University of Twente; Países BajosFil: Tieke, Malte. Utrecht University; Países BajosFil: Bertolino, María Candelaria. University of Twente; Países Bajos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Físico-química de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Investigaciones en Físico-química de Córdoba; ArgentinaFil: Li, Zeshi. Utrecht University; Países BajosFil: Vos, Gaël. Utrecht University; Países BajosFil: de Vries, Robert P.. Utrecht University; Países BajosFil: Woods, Robert J.. University of Georgia; Estados UnidosFil: Tito, Nicholas B.. Electric Ant Laboratory; Países BajosFil: Boons, Geert-Jan P. H.. Utrecht University; Países BajosFil: van der Vries, Erhard. Utrecht University; Países BajosFil: Huskens, Jurriaan. University of Twente; Países Bajo