Oxidative stress in Duchenne muscular dystrophy: focus on the NRF2 redox pathway

Oxidative stress is involved in the pathogenesis of Duchenne muscular dystrophy (DMD), an X-linked genetic disorder caused by mutations in the dystrophin gene and characterized by progressive, lethal muscle degeneration and chronic inflammation. In this study, we explored the expression and signaling pathway of a master player of the anti-oxidant and anti-inflammatory response, namely NRF2, in muscle biopsies of DMD patients. We classified DMD patients in two age groups (Class I, 0-2 years and Class II, 2-9 years), in order to evaluate the antioxidant pathway expression during the disease progression. We observed that altered enzymatic antioxidant responses, increased levels of oxidized glutathione and oxidative damage are differently modulated in the two age classes of patients and well correlate with the severity of pathology. Interestingly, we also observed a modulation of relevant markers of the inflammatory response, such as heme oxygenase 1 and IL-6, suggesting a link between oxidative stress and chronic inflammatory response. Of note, using a transgenic mouse model, we demonstrated that IL-6 overexpression parallels the antioxidant expression profile and the severity of dystrophic muscle observed in DMD patients. This study advances our understanding of the pathogenic mechanisms underlying DMD and defines the critical role of oxidative stress on muscle wasting with clear implications for disease pathogenesis and therapy in human

Oxidative stress in Duchenne muscular dystrophy: focus on the NRF2 redox pathway

Oxidative stress is involved in the pathogenesis of Duchenne muscular dystrophy (DMD), an X-linked genetic disorder caused by mutations in the dystrophin gene and characterized by progressive, lethal muscle degeneration and chronic inflammation. In this study, we explored the expression and signaling pathway of a master player of the anti-oxidant and anti-inflammatory response, namely NRF2, in muscle biopsies of DMD patients. We classified DMD patients in two age groups (Class I, 0-2 years and Class II, 2-9 years), in order to evaluate the antioxidant pathway expression during the disease progression. We observed that altered enzymatic antioxidant responses, increased levels of oxidized glutathione and oxidative damage are differently modulated in the two age classes of patients and well correlate with the severity of pathology. Interestingly, we also observed a modulation of relevant markers of the inflammatory response, such as heme oxygenase 1 and IL-6, suggesting a link between oxidative stress and chronic inflammatory response. Of note, using a transgenic mouse model, we demonstrated that IL-6 overexpression parallels the antioxidant expression profile and the severity of dystrophic muscle observed in DMD patients. This study advances our understanding of the pathogenic mechanisms underlying DMD and defines the critical role of oxidative stress on muscle wasting with clear implications for disease pathogenesis and therapy in human

A barnavirus sequence mined from a transcriptome of the Antarctic pearlwort Colobanthus quitensis.

Because so few viruses in the family Barnaviridae have been reported, we searched for more of them in public sequence databases. Here, we report the complete coding sequence of Colobanthus quitensis associated barnavirus 1, mined from a transcriptome of the Antarctic pearlwort Colobanthus quitensis. The 4.2-kb plus-strand sequence of this virus encompasses four main open reading frames (ORFs), as expected for barnaviruses, including ORFs for a protease-containing polyprotein, an RNA-dependent RNA polymerase whose translation appears to rely on - 1 ribosomal frameshifting, and a capsid protein that is likely to be translated from a subgenomic RNA. The possible derivation of this virus from a fungus associated with C. quitensis is discussed

Іконографічні особливості образу Богородиці в східній християнській традиції: релігієзнавчий аспект

Стаття присвячена аналізу іконографічних особливостей образу Богородиці в православній традиції. Розглянуто особливості іконографічного зображення, його відмінність від зображення у творі мистецтва. Проаналізовано чотири основні іконографічні типи й варіанти ікон Богородиці. Показано, що характерною рисою всіх типів ікон Богородиці є їхня христоцентричність та самостійність як духовного атрибута богоспілкування.In the article is analyzed the iconographic features of the Virgin in the Orthodox tradition. The author argues that Christocentric is the main characteristic of the icons of the Virgin

Der Lehrberuf auf verschiedenen Stufen : ein Vergleich von Belastungen und Ressourcen im Lehrberuf auf der Primar- und Sekundarstufe – eine Entscheidungshilfe für die Stufenwahl

Theoretische und wissenschaftliche Grundlagen: Die vorliegende Arbeit befasst sich mit den Gründen für eine Stufenwahl, resp. eines Stufenwechsels und deckt Stufenunterschiede im Lehrberuf innerhalb der Primar- und Sekundarstufe auf. Der Lehrberuf unterscheidet sich auf den verschiedenen Schulstufen in Bezug auf seine Lehrziele und Anforderungen an dessen Ausbildung. Die massgebliche Grösse für den Stufenentscheid könnte jedoch der Entwicklungsstand der Schüler darstellen. Wenige Studien haben bereits auf Stufenunterschiede in einzelnen Aspekten der Lehrarbeit, resp. der allgemeinen Berufszufriedenheit hingewiesen. So zeichnete sich eine höhere allgemeine Berufszufriedenheit auf der Primarstufe ab. Fragestellungen: Folgende Fragen wurden für die Untersuchung herangezogen: 1. Was bewegt angehende Lehrpersonen zur Primarlehrausbildung? 2. Was bewegt Lehrpersonen zu einem Stufenwechsel von der Primar- zur Sekundarstufe? 3. Wie unterscheidet sich der Lehrberuf in Bezug auf Belastungen und Ressourcen auf der Primar- und Sekundarstufe? Methodisches Vorgehen: Anhand qualitativer Interviews wurden Lehrpersonen, die sowohl auf der Primar- wie auch auf der Sekundarstufe unterrichtet haben, betreffend Arbeitsmerkmalen befragt. Die Leitfragen stützen sich auf den Arbeits-Bewertungs-Check für Lehrkräfte (ABC-L Fragebogen) von Schaarschmidt und Kieschke (2006). Ergebnisse: Der Lehrberuf unterscheidet sich in einigen Aspekten auf der Primar- und Sekundarstufe zum Teil erheblich. Die Mehrheit der befragten Probanden ist im Allgemeinen auf der Sekundarstufe zufriedener. Dies begründeten sie meist mit den kognitiv reiferen und selbstständigeren Schülern und der tieferen Beziehung zu ihnen. Zudem ist die Schülerschaft auf der Sekundarstufe viel homogener, was für die Unterrichtsvorbereitung und -durchführung eine grosse Erleichterung darstellt. Ein weiterer positiver Aspekt auf der Sekundarstufe ist der komplexere Schulstoff, der auch das Interesse der Lehrpersonen selbst weckt. Für die Primarstufe spricht hingegen die unbestrittene höhere Motivation der Schüler. Hingegen wird auf der Primarstufe oft der hohe Elternehrgeiz beklagt, welcher sich insbesondere in der 6. Primarklasse zuspitzt. Diskussion: Die Ergebnisse zeigen, dass eine Auseinandersetzung mit potenziellen Belastungen und Ressourcen im Lehrberuf auf den verschiedenen Schulstufen sinnvoll ist. Um eine bestmögliche Passung zu erreichen, müssen aber weitere Aspekte wie u.a. die Persönlichkeit der Lehrperson, das Pensum oder der Schulort berücksichtigt werden. Einen Einfluss scheint auch die Lehrerfunktion zu haben (Klassen- vs. Fachlehrperson). Zudem gibt es weitere Unterschiede innerhalb der Primarschule (Unter- vs. Mittelstufe) sowie innerhalb der Sekundarschule (Niveau A, B oder C), die künftige Studien gezielter untersuchen sollten

Automatic Speech Classifier for Mild Cognitive Impairment and Early Dementia

none5noThe World Health Organization estimates that 50 million people are currently living with dementia worldwide and this figure will almost triple by 2050. Current pharmacological treatments are only symptomatic, and drugs or other therapies are ineffective in slowing down or curing the neurodegenerative process at the basis of dementia. Therefore, early detection of cognitive decline is of the utmost importance to respond significantly and deliver preventive interventions. Recently, the researchers showed that speech alterations might be one of the earliest signs of cognitive defect, observable well in advance before other cognitive deficits become manifest. In this article, we propose a full automated method able to classify the audio file of the subjects according to the progress level of the pathology. In particular, we trained a specific type of artificial neural network, called autoencoder, using the visual representation of the audio signal of the subjects, that is, the spectrogram. Moreover, we used a data augmentation approach to overcome the problem of the large amount of annotated data usually required during the training phase, which represents one of the most major obstacles in deep learning. We evaluated the proposed method using a dataset of 288 audio files from 96 subjects: 48 healthy controls and 48 cognitively impaired participants. The proposed method obtained good classification results compared to the state-of-the-art neuropsychological screening tests and, with an accuracy of 90.57%, outperformed the methods based on manual transcription and annotation of speech.mixedBertini, Flavio; Allevi, Davide; Lutero, Gianluca; Montesi, Danilo; Calzà, LauraBertini, Flavio; Allevi, Davide; Lutero, Gianluca; Montesi, Danilo; Calzà, Laur

The environmental and evolutionary history of Lake Ohrid (FYROM/Albania). Interim results from the SCOPSCO deep drilling project

This study reviews and synthesises existing information generated within the SCOPSCO (Scientific Collaboration on Past Speciation Conditions in Lake Ohrid) deep drilling project. The four main aims of the project are to infer (i) the age and origin of Lake Ohrid (Former Yugoslav Republic of Macedonia/Republic of Albania), (ii) its regional seismotectonic history, (iii) volcanic activity and climate change in the central northern Mediterranean region, and (iv) the influence of major geological events on the evolution of its endemic species. The Ohrid basin formed by transtension during the Miocene, opened during the Pliocene and Pleistocene, and the lake established de novo in the still relatively narrow valley between 1.9 and 1.3 Ma. The lake history is recorded in a 584 m long sediment sequence, which was recovered within the framework of the International Continental Scientific Drilling Program (ICDP) from the central part (DEEP site) of the lake in spring 2013. To date, 54 tephra and cryptotephra horizons have been found in the upper 460 m of this sequence. Tephrochronology and tuning biogeochemical proxy data to orbital parameters revealed that the upper 247.8 m represent the last 637 kyr. The multi-proxy data set covering these 637 kyr indicates long- term variability. Some proxies show a change from generally cooler and wetter to drier and warmer glacial and interglacial periods around 300 ka. Short-term environmental change caused, for example, by tephra deposition or the climatic impact of millennial-scale Dansgaard–Oeschger and Heinrich events are superimposed on the long-term trends. Evolutionary studies on the extant fauna indicate that Lake Ohrid was not a refugial area for regional freshwater animals. This differs from the surrounding catchment, where the mountainous setting with relatively high water availability provided a refuge for temperate and montane trees during the relatively cold and dry glacial periods. Although Lake Ohrid experienced significant environmental change over the last 637 kyr, preliminary molecular data from extant microgastropod species do not indicate significant changes in diversification rate during this period. The reasons for this constant rate remain largely unknown, but a possible lack of environ- mentally induced extinction events in Lake Ohrid and/or the high resilience of the ecosystems may have played a role

Not myopathic, but autonomic changes in patients with long-COVID syndrome: a case series

ntroduction: Neurological sequelae following SARS-CoV-2 infection still represent a serious concern both for neurologists and neuroscientists. In our paper, we investigated pain, myalgia, and fatigue as symptoms in long-COVID patients with an electrophysiological approach, comprising the evaluation of sympathetic skin responses (SSRs) and quantitative electromyography (qEMG). Materials and methods: Twelve patients were enrolled (mean age, 47.7 ± 11.6 years), referred to our attention because of myalgia, pain, or muscle cramps, which persisted about 6 months after the diagnosis of SARS-CoV-2 infection. They underwent conventional electroneurography (ENG), needle electromyography (EMG), and SSRs; moreover, qEMG was performed by sampling at least 20 motor unit potentials (20–30 MUPs) during weak voluntary contraction in deltoid and tibialis anterior muscles. The mean duration, amplitude, and percentage of polyphasic potentials were assessed and compared with healthy and age-matched volunteers. Results: ENG did not disclose significant changes compared to healthy subjects; needle EMG did not reveal denervation activity. In addition, qEMG showed MUPs similar to those recorded in healthy volunteers in terms of polyphasia (deltoid: p = 0.24; TA: p = 0.35), MUP area (deltoid: p = 0.45; TA: p = 0.44), mean duration (deltoid: p = 0.06; TA: p = 0.45), and amplitude (deltoid: p = 0.27; TA: p = 0.63). SSRs were not recordable from lower limbs in seven patients (58%) and from the upper ones in three of them (25%). Conclusion: Our data suggest an involvement of the autonomic system, with a focus on cholinergic efferent sympathetic activity, without any evidence of myopathic changes

Germline mutations in the spindle assembly checkpoint genes BUB1 and BUB3 are infrequent in familial colorectal cancer and polyposis

Germline mutations in BUB1 and BUB3 have been reported to increase the risk of developing colorectal cancer (CRC) at young age, in presence of variegated aneuploidy and reminiscent dysmorphic traits of mosaic variegated aneuploidy syndrome. We performed a mutational analysis of BUB1 and BUB3 in 456 uncharacterized mismatch repair-proficient hereditary non-polyposis CRC families and 88 polyposis cases. Four novel or rare germline variants, one splice-site and three missense, were identified in four families. Neither variegated aneuploidy nor dysmorphic traits were observed in carriers. Evident functional effects in the heterozygous form were observed for c.1965-1G>A, but not for c.2296G>A (p.E766K), in spite of the positive co-segregation in the family. BUB1 c.2473C>T (p.P825S) and BUB3 c.77C>T (p.T26I) remained as variants of uncertain significance. As of today, the rarity of functionally relevant mutations identified in familial and/or early onset series does not support the inclusion of BUB1 and BUB3 testing in routine genetic diagnostics of familial CRC