Matthiesenstrauss7043

SNCA, the first gene associated with Parkinson's disease, encodes the α-synuclein protein, the predominant component within pathological inclusions termed Lewy bodies. The presence of Lewy bodies is one of the classical hallmarks found in the brain of patients with Parkinson's disease, and Lewy bodies have also been observed in patients with other synucleinopathies. However, the study of α-synuclein pathology in cells has relied largely on two-dimensional culture models, which typically lack the cellular diversity and complex spatial environment found in the brain. Here, to address this gap, we use three-dimensional midbrain organoids, differentiated from human-induced pluripotent stem cells derived from patients carrying a triplication of the SNCA gene and from CRISPR/Cas9 corrected isogenic control iPSCs. These human midbrain organoids recapitulate key features of α-synuclein pathology observed in the brains of patients with synucleinopathies. In particular, we find that SNCA triplication human midbrain organoids express elevated levels of α-synuclein and exhibit an age-dependent increase in α-synuclein aggregation, manifested by the presence of both oligomeric and phosphorylated forms of α-synuclein. These phosphorylated α-synuclein aggregates were found in both neurons and glial cells and their time-dependent accumulation correlated with a selective reduction in dopaminergic neuron numbers. Thus, human midbrain organoids from patients carrying SNCA gene multiplication can reliably model key pathological features of Parkinson's disease and provide a powerful system to study the pathogenesis of synucleinopathies.The mechanistic target of rapamycin signalling pathway serves as a ubiquitous regulator of cell metabolism, growth, proliferation and survival. The main cellular activity of the mechanistic target of rapamycin cascade funnels through mechanistic target of rapamycin complex 1, which is inhibited by rapamycin, a macrolide compound produced by the bacterium Streptomyces hygroscopicus. Pathogenic variants in genes encoding upstream regulators of mechanistic target of rapamycin complex 1 cause epilepsies and neurodevelopmental disorders. Tuberous sclerosis complex is a multisystem disorder caused by mutations in mechanistic target of rapamycin regulators TSC1 or TSC2, with prominent neurological manifestations including epilepsy, focal cortical dysplasia and neuropsychiatric disorders. Focal cortical dysplasia type II results from somatic brain mutations in mechanistic target of rapamycin pathway activators MTOR, AKT3, PIK3CA and RHEB and is a major cause of drug-resistant epilepsy. DEPDC5, NPRL2 and NPRL3 code folepsy, as identification of a pathogenic variant may point to an occult dysplasia in apparently non-lesional epilepsy or may uncover important prognostic information including, an increased risk of sudden unexpected death in epilepsy in the GATORopathies or favourable epilepsy surgery outcomes in focal cortical dysplasia type II due to somatic brain mutations. Lastly, we discuss the potential therapeutic application of mechanistic target of rapamycin inhibitors for drug-resistant seizures in GATOR1-related epilepsies and focal cortical dysplasia type II.Tau aggregates represent a key pathologic feature of Alzheimer's disease and other neurodegenerative diseases. Recently, PET probes have been developed for in vivo detection of tau accumulation; however, they are limited because of off-target binding and a reduced ability to detect tau in non-Alzheimer's disease tauopathies. The novel tau PET tracer, [18F]PI-2620, has a high binding affinity and specificity for aggregated tau; therefore, it was hypothesized to have desirable properties for the visualization of tau accumulation in Alzheimer's disease and non-Alzheimer's disease tauopathies. To assess the ability of [18F]PI-2620 to detect regional tau burden in non-Alzheimer's disease tauopathies compared with Alzheimer's disease, patients with progressive supranuclear palsy (n = 3), corticobasal syndrome (n = 2), corticobasal degeneration (n = 1) or Alzheimer's disease (n = 8), and healthy controls (n = 7) were recruited. All participants underwent MRI, amyloid β assessment and [18F]PI-2620 PET (Image acquisitases.Extracting and processing information from documents is of great importance as lots of experimental results and findings are stored in local files. Therefore, extracting and analyzing biomedical terms from such files in an automated way is absolutely necessary. In this article, we present OnTheFly2.0, a web application for extracting biomedical entities from individual files such as plain texts, office documents, PDF files or images. OnTheFly2.0 can generate informative summaries in popup windows containing knowledge related to the identified terms along with links to various databases. It uses the EXTRACT tagging service to perform named entity recognition (NER) for genes/proteins, chemical compounds, organisms, tissues, environments, diseases, phenotypes and gene ontology terms. Multiple files can be analyzed, whereas identified terms such as proteins or genes can be explored through functional enrichment analysis or be associated with diseases and PubMed entries. Finally, protein-protein and protein-chemical networks can be generated with the use of STRING and STITCH services. To demonstrate its capacity for knowledge discovery, we interrogated published meta-analyses of clinical biomarkers of severe COVID-19 and uncovered inflammatory and senescence pathways that impact disease pathogenesis. OnTheFly2.0 currently supports 197 species and is available at http//bib.fleming.gr3838/OnTheFly/ and http//onthefly.pavlopouloslab.info.Nowadays, getting advantageous offensive situations in high-level basketball is being increasingly harder, so taking advantage of any situation in the game since the team has the ball is essential to be competitive. Therefore, the goal to achieve in this study is to evaluate using a mixed method strategy the behaviors happening in the application of the technical-tactical means performed in the transition play of professional basketball in Spain. An ad hoc observation tool made of 11 criteria and 83 exhaustive and mutually exclusive categories (E/ME) has been designed and validated by means of data quality and generalizability analyses. Indexes obtained show high reliability and validity allowing the proposed actions to be recorded (correlation coefficients are above 0.95 and generalizability coefficients are above 0.90 in all cases). A total number of 128 situations corresponding to eight games of Unicaja de Málaga in the Endesa League in the 18/19 season were observed with the Hoisan software. The analysis of the relationships among behaviors was performed using the polar coordinates technique where the one-on-one initiation, outside the zone, has been used as focal behavior. selleck products The estimation of the functions representing the vectors has also been performed to model the best fit that estimates, starting from a focal category, the relationship among this focal behavior and the rest of the mating behaviors for possible future observations. The results show significant relationships between the selected focal behavior and the mating behaviors, showing indications of behaviors allowing tactical interpretation of the game and the definition of intervention programs to improve the performance of the team.The purpose of this review is to position the emerging clinical promise of validating and implementing biomechanical biomarkers of falls in fall prevention interventions. The review is framed in the desirability of blunting the effects of the rapidly growing population of older adults with regard to the number of falls, their related injuries, and health care costs. We propose that biomechanical risk biomarkers may be derived from systematic study of the responses to treadmill-delivered perturbations to both identify individuals with a risk of specific types of falls, such as trips and slips as well as quantifying the effectiveness of interventions designed to reduce that risk. The review follows the evidence derived using a specific public health approach and the published biomedical literature that supports trunk kinematics as a biomarker as having met many of the criteria for a biomarker for trip-specific falls. Whereas, the efficacy of perturbation training to reduce slip-related falls by older adults appears to have been confirmed, its effectiveness presently remains an open and important question. There is a dearth of data related to the efficacy and effectiveness of perturbation training to reduce falls to the side falls by older adults. At present, efforts to characterize the extent to which perturbation training can reduce falls and translate the approaches to the clinic represents an important research opportunity.Swisscom Asport ("Asport") has set itself the target of covering the entire video process from production to distribution. Its services should be affordable not only for professional sports clubs but also for their amateur counterparts. Despite limited resources, clubs want to increase their attractiveness through new technologies and meet members' needs. This paper examines the factors that lead to the acceptance of Asport services by sports clubs. In addition, the willingness to pay for these services is evaluated. Pricing is critical to success in innovation and also because of the limited financial resources of sports clubs. Based on the literature research, a conceptual model was developed based on the unified theory of acceptance and use of technology model (UTAUT), tested using an online survey of Swiss amateur football clubs, and evaluated using regression analysis. The study findings show that social environment exerts the strongest influence on behavioral intention, defined as "acceptance" in this paper. Furthermore, the two independent variables, performance expectancy and effort expectancy, have a significant effect on user acceptance. In contrast to the original model (UTAUT), this paper demonstrates the direct influence of attitude to use. Of the independent variables, facilitating conditions have an additional effect on attitude to use. The results demonstrate that it is not acceptance but attitude to use that influences willingness to pay. An in-depth evaluation of willingness to pay shows that the optimal price point is 83.3% lower than the price offered by the company; however, there are budget-dependent variations in the assessment.Dance has been suggested to be an advantageous exercise modality for improving postural balance performance and reducing the risk of falls in the older population. The main purpose of this study was to investigate whether visual restriction impacts older dancers and non-dancers differently during a quiet stance balance performance test. We hypothesized higher balance performance and greater balance deterioration due to visual restriction in dancers compared with non-dancers, indicating the superior contribution of the visual channel in the expected higher balance performances of dancers. Sixty-nine (38 men, 31 women, 74 ± 6 years) healthy older adults participated and were grouped into a Greek traditional dance group (n = 31, two to three times/week for 1.5 h/session, minimum of 3 years) and a non-dancer control group (n = 38, no systematic exercise history). The participants completed an assessment of one-legged quiet stance trials using both left and right legs and with eyes open while standing barefoot on a force plate (Wii, A/D converter, 1,000 Hz; Biovision) and two-legged trials with both eyes open and closed.