Analysis of repetitive element expression in the blood and skin of patients with Parkinson’s disease identifies differential expression of satellite elements

Repetitive elements (RE) constitute the majority of the human genome and have a range of functions both structural and regulatory on genomic function and gene expression. RE overexpression has been observed in several neurodegenerative diseases, consistent with the observation of aberrant expression of RE posing a mutagenic threat. Despite reports that associate RE expression with PD no study has comprehensively analysed the role of these elements in the disease. This study presents the first genome-wide analysis of RE expression in PD to date. Analysis of RNA-sequencing data of 12 PD patients and 12 healthy controls identified tissue-specific expression differences and more significantly, differential expression of four satellite elements; two simple satellite III (repName = CATTC_n and _GAATG_n) a high-copy satellite II (HSATII) and a centromeric satellite (ALR_Alpha) in the blood of PD patients. In support of the growing body of recent evidence associating REs with neurodegenerative disease, this study highlights the potential importance of characterization of RE expression in such diseases

The spectrum of involuntary vocalizations in humans: A video atlas

In clinical practice, involuntary vocalizing behaviors are typically associated with Tourette syndrome and other tic disorders. However, they may also be encountered throughout the entire tenor of neuropsychiatry, movement disorders, and neurodevelopmental syndromes. Importantly, involuntary vocalizing behaviors may often constitute a predominant clinical sign, and, therefore, their early recognition and appropriate classification are necessary to guide diagnosis and treatment. Clinical literature and video‐documented cases on the topic are surprisingly scarce. Here, we pooled data from 5 expert centers of movement disorders, with instructive video material to cover the entire range of involuntary vocalizations in humans. Medical literature was also reviewed to document the range of possible etiologies associated with the different types of vocalizing behaviors and to explore treatment options. We propose a phenomenological classification of involuntary vocalizations within different categorical domains, including (1) tics and tic‐like vocalizations, (2) vocalizations as part of stereotypies, (3) vocalizations as part of dystonia or chorea, (4) continuous vocalizing behaviors such as groaning or grunting, (5) pathological laughter and crying, (6) vocalizations resembling physiological reflexes, and (7) other vocalizations, for example, those associated with exaggerated startle responses, as part of epilepsy and sleep‐related phenomena. We provide comprehensive lists of their associated etiologies, including neurodevelopmental, neurodegenerative, neuroimmunological, and structural causes and clinical clues. We then expand on the pathophysiology of the different vocalizing behaviors and comment on available treatment options. Finally, we present an algorithmic approach that covers the wide range of involuntary vocalizations in humans, with the ultimate goal of improving diagnostic accuracy and guiding appropriate treatment

Serum Amyloid Alpha Is Downregulated in Peripheral Tissues of Parkinson’s Disease Patients

We report the changed levels of serum amyloid alpha, an immunologically active protein, in Parkinson’s disease (PD) patients’ peripheral tissues. We have previously shown that Saa-1 and -2 (serum amyloid alpha-1,-2, genes) were among the top downregulated genes in PD patients’ skin, using whole-genome RNA sequencing. In the current study, we characterized the gene and protein expression profiles of skin and blood samples from patients with confirmed PD diagnosis and age/sex matched controls. qRT-PCR analysis of PD skin demonstrated downregulation of Saa-1 and -2 genes in PD patients. However, the lowered amount of protein could not be visualized using immunohistochemistry, due to low quantity of SAA (Serum Amyloid Alpha, protein) in skin. Saa-1 and -2 expression levels in whole blood were below detection threshold based on RNA sequencing, however significantly lowered protein levels of SAA1/2 in PD patients’ serum were shown with ELISA, implying that SAA is secreted into the blood. These results show that SAA is differentially expressed in the peripheral tissues of PD patients

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Meta-analysis can be a powerful tool for demonstrating the applicability of a concept beyond the context of individual clinical trials and observational studies, including exploration of effects across different subgroups. Meta-analysis avoids Simpson's paradox, in which a consistent effect in constituent trials is reversed when results are simply pooled. Meta-analysis in critical care medicine is made more complicated, however, by the heterogeneous nature of critically ill patients and the contexts within which they are treated. Failure to properly adjust for this heterogeneity risks missing important subgroup effects in, for example, the interaction of treatment with varying levels of baseline risk. When subgroups are defined by characteristics that vary within constituent trials (such as age) rather than features constant within each trial (such as drug dose), there is the additional risk of incorrect conclusions due to the ecological fallacy. The present review explains these problems and the strategies by which they are overcome

Clinical Practice Patterns in Tic Disorders Among Movement Disorder Society Members

[Background] Tic disorders belong to the broad spectrum of pediatric and adult movement disorders. The wide variability in clinical presentations, applied assessment tools, and treatments are poorly understood.[Objectives] To map practices and knowledge base of movement disorder clinicians concerning clinical features, pathophysiology, and treatment approaches in tic disorders. [Methods] A 33-item survey was developed by the Tic Disorders and Tourette syndrome Study Group members of the Movement Disorder Society. The survey was distributed to the complete society membership and included responses from 346 members, 314 of whom reported treating tic disorders. [Results] Approximately one third of survey respondents (35%) frequently evaluated patients with tics. The data revealed widespread use of existing guidelines (about 70%) and screening for comorbid disorders (>90%). The most common investigations used to rule out secondary causes of tics were imaging (92%), laboratory tests (66%) and neurophysiology (38%). Functional tics were the second most common tic etiology following primary tics. Only 27% of respondents reported confidence in knowledge about tic pathogenesis. Top rated interventions to treat tics were psychoeducation, cognitive behavioral intervention for tics (CBIT) and treatment for neuropsychiatric comorbidities. Antipsychotics were ranked as the most effective pharmacologic tic intervention. Conclusions: The majority of movement disorders specialists do not frequently encounter tics. There was sparse knowledge about tic pathophysiology. Psychoeducation, CBIT, the treatment of neuropsychiatric comorbidities and use of antipsychotics emerged as the most common interventions to treat tics. These results provide insight into what will be needed to improve the diagnosis and treatment of tic disorders.CG is supported by the Freigeist Fellowship of the VolkswagenStiftung. He has served as ad hoc advisory board to Biomarin and received honoraria from the International Parkinsons Disease and Movement Disorders Society for educational activities

Removing orientation-induced localization biases in single-molecule microscopy using a broadband metasurface mask

Nanoscale localization of single molecules is a crucial function in several advanced microscopy techniques, including single-molecule tracking and wide-field super-resolution imaging. Until now, a central consideration of such techniques is how to optimize the precision of molecular localization. However, as these methods continue to push towards the nanometre size scale, an increasingly important concern is the localization accuracy. In particular, single fluorescent molecules emit with an anisotropic radiation pattern of an oscillating electric dipole, which can cause significant localization biases using common estimators. Here we present the theory and experimental demonstration of a solution to this problem based on azimuthal filtering in the Fourier plane of the microscope. We do so using a high-efficiency dielectric metasurface polarization/phase device composed of nanoposts with subwavelength spacing. The method is demonstrated both on fluorophores embedded in a polymer matrix and in dL5 protein complexes that bind malachite green

Directional control of weakly localized Raman from a random network of fractal nanowires

Disordered optical media are an emerging class of materials capable of strongly scattering light. Their study is relevant to investigate transport phenomena and for applications in imaging, sensing and energy storage. While such materials can be used to generate coherent light, their directional emission is typically hampered by their very multiple scattering nature. Here, we tune the out-of-plane directionality of coherent Raman light scattered by a fractal network of silicon nanowires. By visualizing Rayleigh scattering, photoluminescence and weakly localized Raman light from the random network of nanowires via real-space microscopy and Fourier imaging, we gain insight on the light transport mechanisms responsible for the material's inelastic coherent signal and for its directionality. The possibility of visualizing and manipulating directional coherent light in such networks of nanowires opens venues for fundamental studies of light propagation in disordered media as well as for the development of next generation optical devices based on disordered structures, inclusive of sensors, light sources and optical switches