scholarly journals Epilepsy in Tubulinopathy: Personal Series and Literature Review

Cells ◽  
2019 ◽  
Vol 8 (7) ◽  
pp. 669 ◽  
Author(s):  
Romina Romaniello ◽  
Claudio Zucca ◽  
Filippo Arrigoni ◽  
Paolo Bonanni ◽  
Elena Panzeri ◽  
...  
Keyword(s):  
Clinical Symptoms ◽  
Background Activity ◽  
Motor Impairment ◽  
Specific Pattern ◽  
Accurate Analysis ◽  
Organization Of Sleep ◽  
Tubulin Genes ◽  
Brain Malformations ◽  
Wide Range ◽  
Low Amplitude

Mutations in tubulin genes are responsible for a large spectrum of brain malformations secondary to abnormal neuronal migration, organization, differentiation and axon guidance and maintenance. Motor impairment, intellectual disability and epilepsy are the main clinical symptoms. In the present study 15 patients from a personal cohort and 75 from 21 published studies carrying mutations in TUBA1A, TUBB2B and TUBB3 tubulin genes were evaluated with the aim to define a clinical and electrophysiological associated pattern. Epilepsy shows a wide range of severity without a specific pattern. Mutations in TUBA1A (60%) and TUBB2B (74%) and TUBB3 (25%) genes are associated with epilepsy. The accurate analysis of the Electroencephalogram (EEG) pattern in wakefulness and sleep in our series allows us to detect significant abnormalities of the background activity in 100% of patients. The involvement of white matter and of the inter-hemispheric connection structures typically observed in tubulinopathies is evidenced by the high percentage of asynchronisms in the organization of sleep activity recorded. In addition to asymmetries of the background activity, excess of slowing, low amplitude and Magnetic Resonance (MR) imaging confirm the presence of extensive brain malformations involving subcortical and midline structures. In conclusion, epilepsy in tubulinopathies when present has a favorable evolution over time suggesting a not particularly aggressive therapeutic approach.

scholarly journals Nuclear Envelope Integrity in Health and Disease: Consequences on Genome Instability and Inflammation

2021 ◽  
Vol 22 (14) ◽  
pp. 7281
Author(s):  
Benoit R. Gauthier ◽  
Valentine Comaills
Keyword(s):  
Nuclear Envelope ◽  
Clinical Symptoms ◽  
Genome Instability ◽  
Chromosomal Rearrangements ◽  
Wide Range ◽  
Complex Chromosomal Rearrangements ◽  
Health And Disease ◽  
Dna Release ◽  
Sting Pathway ◽  
Eukaryote Genome

The dynamic nature of the nuclear envelope (NE) is often underestimated. The NE protects, regulates, and organizes the eukaryote genome and adapts to epigenetic changes and to its environment. The NE morphology is characterized by a wide range of diversity and abnormality such as invagination and blebbing, and it is a diagnostic factor for pathologies such as cancer. Recently, the micronuclei, a small nucleus that contains a full chromosome or a fragment thereof, has gained much attention. The NE of micronuclei is prone to collapse, leading to DNA release into the cytoplasm with consequences ranging from the activation of the cGAS/STING pathway, an innate immune response, to the creation of chromosomal instability. The discovery of those mechanisms has revolutionized the understanding of some inflammation-related diseases and the origin of complex chromosomal rearrangements, as observed during the initiation of tumorigenesis. Herein, we will highlight the complexity of the NE biology and discuss the clinical symptoms observed in NE-related diseases. The interplay between innate immunity, genomic instability, and nuclear envelope leakage could be a major focus in future years to explain a wide range of diseases and could lead to new classes of therapeutics.

scholarly journals Sensing of Nickel(II) Ions by Immobilizing Ligands and Using Different SPEs

2021 ◽  
Vol 6 (1) ◽  
pp. 2
Author(s):  
Liliana Anchidin-Norocel ◽  
Sonia Amariei ◽  
Gheorghe Gutt
Keyword(s):  
Bismuth Oxide ◽  
Human Population ◽  
Raw Materials ◽  
Sensor Technology ◽  
Cyclic Voltammogram ◽  
Accurate Analysis ◽  
Nickel Allergy ◽  
Nickel Ions ◽  
Practical Applications ◽  
Wide Range

The aim of this paper is the development of a sensor for the quantification of nickel ions in food raw materials and foods. It is believed that about 15% of the human population suffers from nickel allergy. In addition to digestive manifestations, food intolerance to nickel may also have systemic manifestations, such as diffuse dermatitis, diffuse itching, fever, rhinitis, headache, altered general condition. Therefore, it is necessary to control this content of nickel ions for the health of the human population by developing a new method that offers the advantages of a fast, not expensive, in situ, and accurate analysis. For this purpose, bismuth oxide-screen-printed electrodes (SPEs) and graphene-modified SPEs were used with a very small amount of dimethylglyoxime and amino acid L-histidine that were deposited. A potentiostat that displays the response in the form of a cyclic voltammogram was used to study the electrochemical properties of nickel standard solution with different concentrations. The results were compared and the most sensitive sensor proved to be bismuth oxide-SPEs with dimethylglyoxime (Bi2O3/C-dmgH2) with a linear response over a wide range (0.1–10 ppm) of nickel concentrations. Furthermore, the sensor shows excellent selectivity in the presence of common interfering species. The Bi2O3/C-dmgH2 sensor showed good viability for nickel analysis in food samples (cocoa, spinach, cabbage, and red wine) and demonstrated significant advancement in sensor technology for practical applications.

Prodromal Dementia With Lewy Bodies: Evolution of Symptoms and Predictors of Dementia Onset

2021 ◽  
pp. 089198872110235
Author(s):  
Kathryn A. Wyman-Chick ◽  
Lauren R. O’Keefe ◽  
Daniel Weintraub ◽  
Melissa J. Armstrong ◽  
Michael Rosenbloom ◽  
...  
Keyword(s):  
Clinical Features ◽  
Dementia With Lewy Bodies ◽  
Clinical Symptoms ◽  
Neuropsychiatric Symptoms ◽  
Lewy Bodies ◽  
Rem Sleep Behavior Disorder ◽  
Data Set ◽  
Wide Range ◽  
Prodromal Dementia ◽  
Dementia Onset

Background: Research criteria for prodromal dementia with Lewy bodies (DLB) were published in 2020, but little is known regarding prodromal DLB in clinical settings. Methods: We identified non-demented participants without neurodegenerative disease from the National Alzheimer’s Coordinating Center Uniform Data Set who converted to DLB at a subsequent visit. Prevalence of neuropsychiatric and motor symptoms were examined up to 5 years prior to DLB diagnosis. Results: The sample included 116 participants clinically diagnosed with DLB and 348 age and sex-matched (1:3) Healthy Controls. Motor slowing was present in approximately 70% of participants 3 years prior to DLB diagnosis. In the prodromal phase, 50% of DLB participants demonstrated gait disorder, 70% had rigidity, 20% endorsed visual hallucinations, and over 50% of participants endorsed REM sleep behavior disorder. Apathy, depression, and anxiety were common prodromal neuropsychiatric symptoms. The presence of 1+ core clinical features of DLB in combination with apathy, depression, or anxiety resulted in the greatest AUC (0.815; 95% CI: 0.767, 0.865) for distinguishing HC from prodromal DLB 1 year prior to diagnosis. The presence of 2+ core clinical features was also accurate in differentiating between groups (AUC = 0.806; 95% CI: 0.756, 0.855). Conclusion: A wide range of motor, neuropsychiatric and other core clinical symptoms are common in prodromal DLB. A combination of core clinical features, neuropsychiatric symptoms and cognitive impairment can accurately differentiate DLB from normal aging prior to dementia onset.

scholarly journals TUBA1A mutations identified in lissencephaly patients dominantly disrupt neuronal migration and impair dynein activity

2018 ◽  
Vol 28 (8) ◽  
pp. 1227-1243 ◽  
Author(s):  
Jayne Aiken ◽  
Jeffrey K Moore ◽  
Emily A Bates
Keyword(s):  
Motor Activity ◽  
Neuronal Migration ◽  
Ectopic Expression ◽  
Missense Mutations ◽  
Microtubule Cytoskeleton ◽  
Tubulin Genes ◽  
Dynein Motor ◽  
Brain Malformations ◽  
Developing Mouse Brain ◽  
And Migration

Abstract The microtubule cytoskeleton supports diverse cellular morphogenesis and migration processes during brain development. Mutations in tubulin genes are associated with severe human brain malformations known as ‘tubulinopathies’; however, it is not understood how molecular-level changes in microtubule subunits lead to brain malformations. In this study, we demonstrate that missense mutations affecting arginine at position 402 (R402) of TUBA1A α-tubulin selectively impair dynein motor activity and severely and dominantly disrupt cortical neuronal migration. TUBA1A is the most commonly affected tubulin gene in tubulinopathy patients, and mutations altering R402 account for 30% of all reported TUBA1A mutations. We show for the first time that ectopic expression of TUBA1A-R402C and TUBA1A-R402H patient alleles is sufficient to dominantly disrupt cortical neuronal migration in the developing mouse brain, strongly supporting a causal role in the pathology of brain malformation. To isolate the precise molecular impact of R402 mutations, we generated analogous R402C and R402H mutations in budding yeast α-tubulin, which exhibit a simplified microtubule cytoskeleton. We find that R402 mutant tubulins assemble into microtubules that support normal kinesin motor activity but fail to support the activity of dynein motors. Importantly, the level of dynein impairment scales with the expression level of the mutant in the cell, suggesting a ‘poisoning’ mechanism in which R402 mutant α-tubulin acts dominantly by populating microtubules with defective binding sites for dynein. Based on our results, we propose a new model for the molecular pathology of tubulinopathies that may also extend to other tubulin-related neuropathies.

scholarly journals Agenesis of Isthmus of the Thyroid Gland in a Patient with Graves-Basedow Disease and a Solitary Nodule

2013 ◽  
Vol 2013 ◽  
pp. 1-2
Author(s):  
Omer Faruk Ozkan ◽  
Mehmet Asık ◽  
Huseyin Toman ◽  
Faruk Ozkul ◽  
Oztekin Cıkman ◽  
...  
Keyword(s):  
Congenital Anomaly ◽  
Thyroid Gland ◽  
Surgical Procedures ◽  
Congenital Anomalies ◽  
Clinical Symptoms ◽  
Endocrine Gland ◽  
Solitary Nodule ◽  
Rare Congenital Anomaly ◽  
Wide Range

The thyroid is a vascular endocrine gland with two lateral lobes connected by a narrow, median isthmus. Although a wide range of congenital anomalies of the thyroid gland has been reported in the literature, agenesis of the thyroid isthmus is a very rare congenital anomaly. Thyroid isthmus agenesis does not manifest clinical symptoms, and it can be confused with other thyroid pathologies. We describe a patient with no isthmus of the thyroid, associated with Graves-Basedow disease. Thyroid isthmus agenesis should be kept in mind in order for surgical procedures involving thyroid pathologies to be carried out safely.

scholarly journals Insights into Clinical, Genetic, and Pathological Aspects of Hereditary Spastic Paraplegias: A Comprehensive Overview

2021 ◽  
Vol 8 ◽  
Author(s):  
Liena E. O. Elsayed ◽  
Isra Zuhair Eltazi ◽  
Ammar E. Ahmed ◽  
Giovanni Stevanin
Keyword(s):  
Clinical Symptoms ◽  
Disease Onset ◽  
Lower Limbs ◽  
Special Focus ◽  
Clinical Genetic ◽  
Comprehensive Overview ◽  
Functional Studies ◽  
Hereditary Spastic Paraplegias ◽  
Wide Range ◽  
Complex Forms

Hereditary spastic paraplegias (HSP) are a heterogeneous group of motor neurodegenerative disorders that have the core clinical presentation of pyramidal syndrome which starts typically in the lower limbs. They can present as pure or complex forms with all classical modes of monogenic inheritance reported. To date, there are more than 100 loci/88 spastic paraplegia genes (SPG) involved in the pathogenesis of HSP. New patterns of inheritance are being increasingly identified in this era of huge advances in genetic and functional studies. A wide range of clinical symptoms and signs are now reported to complicate HSP with increasing overall complexity of the clinical presentations considered as HSP. This is especially true with the emergence of multiple HSP phenotypes that are situated in the borderline zone with other neurogenetic disorders. The genetic diagnostic approaches and the utilized techniques leave a diagnostic gap of 25% in the best studies. In this review, we summarize the known types of HSP with special focus on those in which spasticity is the principal clinical phenotype (“SPGn” designation). We discuss their modes of inheritance, clinical phenotypes, underlying genetics, and molecular pathways, providing some observations about therapeutic opportunities gained from animal models and functional studies. This review may pave the way for more analytic approaches that take into consideration the overall picture of HSP. It will shed light on subtle associations that can explain the occurrence of the disease and allow a better understanding of its observed variations. This should help in the identification of future biomarkers, predictors of disease onset and progression, and treatments for both better functional outcomes and quality of life.

Plasma Diagnostics of Microflares observed by STIX and AIA

2021 ◽  
Author(s):  
Jonas Saqri ◽  
Astrid Veronig ◽  
Ewan Dickson ◽  
Säm Krucker ◽  
Andrea Francesco Battaglia ◽  
...  
Keyword(s):  
Solar Flares ◽  
Magnetic Energy ◽  
Emission Measure ◽  
Transport Processes ◽  
X Rays ◽  
Solar Dynamics Observatory ◽  
Energy Bands ◽  
Accurate Analysis ◽  
Great Opportunity ◽  
Wide Range

<p>Solar flares are generally thought to be the impulsive release of magnetic energy giving rise to a wide range of solar phenomena that influence the heliosphere and in some cases even conditions of earth. Part of this liberated energy is used for particle acceleration and to heat up the solar plasma. The Spectrometer/Telescope for Imaging X-rays (STIX) instrument onboard the Solar Orbiter mission launched on February 10th 2020 promises advances in the study of solar flares of various sizes. It is capable of measuring X-ray spectra from 4 to 150 keV with 1 keV resolution binned into 32 energy bins before downlinking. With this energy range and sensitivity, STIX is capable of sampling thermal plasma with temperatures of≳10 MK, and to diagnose the nonthermal bremsstrahlung emission of flare-accelerated electrons. During the spacecraft commissioning phase in the first half of the year 2020, STIX observed 68 microflares. Of this set, 26 events could clearly be identified in at least two energy channels, all of which originated in an active region that was also visible from earth. These events provided a great opportunity to combine the STIX observations with the multi-band EUV imagery from the Atmospheric Imaging Assembly (AIA) instrument on board the earth orbiting Solar Dynamics Observatory (SDO). For the microflares that could be identified in two STIX science energy bands, it was possible to derive the temperature and emission measure (EM) of the flaring plasma assuming an isothermal source. For larger events where more detailed spectra could be derived, a more accurate analysis was performed by fitting the spectra assuming various thermal and nonthermal sources. These results are compared to the diagnostics derived from AIA images. To this aim, the Differential EmissionMeasure (DEM) was reconstructed from AIA observations to infer plasma temperatures and EM in the flaring regions. Combined with the the relative timing between the emission seen by STIX and AIA, this allows us to get deeper insight into the flare energy release and transport processes.</p>

A variety of surface waves in ocean-bottom DAS records

2021 ◽  
Author(s):  
Zack Spica ◽  
Loïc Viens ◽  
Jorge Castillo Castellanos ◽  
Takeshi Akuhara ◽  
Kiwamu Nishida ◽  
...  
Keyword(s):  
Surface Wave ◽  
Acoustic Waves ◽  
Fiber Optic ◽  
Acoustic Noise ◽  
Seismic Exploration ◽  
Ocean Bottom ◽  
Wide Range ◽  
Ocean Layer ◽  
Noise Cross Correlation ◽  
Low Amplitude

<p>Distributed acoustic sensing (DAS) can transform existing telecommunication fiber-optic cables into arrays of thousands of sensors, enabling meter-scale recordings over tens of kilometers. Recently, DAS has demonstrated its utility for many seismological applications onshore. However, the use of offshore cables for seismic exploration and monitoring is still in its infancy.<br>In this work, we introduce some new results and observations obtained from a fiber-optic cable offshore the coast of Sanriku, Japan. In particular, we focus on surface wave retrieved from various signals and show that ocean-bottom DAS can be used to extract dispersion curves (DC) over a wide range of frequencies. We show that multi-mode DC can be easily extracted from ambient seismo-acoustic noise cross-correlation functions or F-K analysis. Moderate magnitude earthquakes also contain multiple surface-wave packets that are buried within their coda. Fully-coupled 3-D numerical simulations suggest that these low-amplitude signals originate from the continuous reverberations of the acoustic waves in the ocean layer. </p>

scholarly journals A New Method of Low Amplitude Signal Detection and Its Application in Acoustic Emission

2019 ◽  
Vol 10 (1) ◽  
pp. 73 ◽  
Author(s):  
Einar Agletdinov ◽  
Dmitry Merson ◽  
Alexei Vinogradov
Keyword(s):  
Time Series ◽  
Acoustic Emission ◽  
Logarithmic Derivative ◽  
Random Noise ◽  
Synthetic Data ◽  
Spectral Density Function ◽  
Integrity Assessment ◽  
Wide Range ◽  
Time Average ◽  
Low Amplitude

A novel methodology is proposed to enhance the reliability of detection of low amplitude transients in a noisy time series. Such time series often arise in a wide range of practical situations where different sensors are used for condition monitoring of mechanical systems, integrity assessment of industrial facilities and/or microseismicity studies. In all these cases, the early and reliable detection of possible damage is of paramount importance and is practically limited by detectability of transient signals on the background of random noise. The proposed triggering algorithm is based on a logarithmic derivative of the power spectral density function. It was tested on the synthetic data, which mimics the actual ultrasonic acoustic emission signal recorded continuously with different signal-to-noise ratios (SNR). Considerable advantages of the proposed method over established fixed amplitude threshold and STA/LTA (Short Time Average / Long Time Average) techniques are demonstrated in comparative tests.

scholarly journals Tissue-Nonspecific Alkaline Phosphatase—A Gatekeeper of Physiological Conditions in Health and a Modulator of Biological Environments in Disease

Biomolecules ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. 1648
Author(s):  
Daniel Liedtke ◽  
Christine Hofmann ◽  
Franz Jakob ◽  
Eva Klopocki ◽  
Stephanie Graser
Keyword(s):  
Alkaline Phosphatase ◽  
Clinical Symptoms ◽  
Current Knowledge ◽  
Systemic Disease ◽  
Loss Of Function ◽  
Inorganic Pyrophosphate ◽  
Wide Range ◽  
Mineralization Processes ◽  
Tissue Nonspecific Alkaline Phosphatase

Tissue-nonspecific alkaline phosphatase (TNAP) is a ubiquitously expressed enzyme that is best known for its role during mineralization processes in bones and skeleton. The enzyme metabolizes phosphate compounds like inorganic pyrophosphate and pyridoxal-5′-phosphate to provide, among others, inorganic phosphate for the mineralization and transportable vitamin B6 molecules. Patients with inherited loss of function mutations in the ALPL gene and consequently altered TNAP activity are suffering from the rare metabolic disease hypophosphatasia (HPP). This systemic disease is mainly characterized by impaired bone and dental mineralization but may also be accompanied by neurological symptoms, like anxiety disorders, seizures, and depression. HPP characteristically affects all ages and shows a wide range of clinical symptoms and disease severity, which results in the classification into different clinical subtypes. This review describes the molecular function of TNAP during the mineralization of bones and teeth, further discusses the current knowledge on the enzyme’s role in the nervous system and in sensory perception. An additional focus is set on the molecular role of TNAP in health and on functional observations reported in common laboratory vertebrate disease models, like rodents and zebrafish.

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