Recent advances in human stem cell-based modeling of Tuberous Sclerosis Complex
AbstractTuberous sclerosis complex (TSC) is an autosomal dominant disorder characterized by epilepsy, intellectual disability, and benign tumors of the brain, heart, skin, and kidney. Animal models have contributed to our understanding of normal and abnormal human brain development, but the construction of models that accurately recapitulate a human pathology remains challenging. Recent advances in stem cell biology with the derivation of human-induced pluripotent stem cells (hiPSCs) from somatic cells from patients have opened new avenues to the study of TSC. This approach combined with gene-editing tools such as CRISPR/Cas9 offers the advantage of preserving patient-specific genetic background and the ability to generate isogenic controls by correcting a specific mutation. The patient cell line and the isogenic control can be differentiated into the cell type of interest to model various aspects of TSC. In this review, we discuss the remarkable capacity of these cells to be used as a model for TSC in two- and three-dimensional cultures, the potential variability in iPSC models, and highlight differences between findings reported to date.
Publication date: Available online 4 April 2020Source: Aggression and Violent BehaviorAuthor(s): Scott Harcourt
Publication date: June 2020Source: Research in Autism Spectrum Disorders, Volume 74Author(s): Hiran Thabrew, Anisha Viswanathan, Matthew Eggleston, Stephanie Moor, David Chinn
Across California, thousands of families are now forced to care for severely disabled loved ones at home, including some with serious autism.
Publication date: Available online 5 April 2020Source: Journal of Dental SciencesAuthor(s): Yan Chen, Xinzhu Li, Jingyi Wu, Wanyu Lu, Wenan Xu, Buling Wu
This study delves into the mechanisms by which a short period of fasting can accelerate wound healing. Fasting triggers many of the same cellular stress responses, such as upregulated autophagy, as occur during the practice of calorie restriction. It isn't exactly the same, however, so it is always worth asking whether any specific biochemistry observed in either case does in fact occur in both situations. In particular, the period of refeeding following fasting appears to have beneficial effects that are distinct from those that occur while food is restricted. Multiple forms of therapeutic fasting have been repor...
CONCLUSIONS: In EUA, physical and mood disorders are associated with new and old inflammatory serological, clinical and imaging biomarkers. HLA-DRB1*11-positivity may be protective against these disease-related features. PMID: 32242813 [PubMed - as supplied by publisher]
Authors: Moreno-Fresneda P, Triguero-Martínez A, Olivas-Martínez I, Ortiz-Aljaro P, González-Escribano MF, Nuño-Nuño L, Ortiz AM, González-Álvaro I Abstract OBJECTIVES: To investigate the role of body mass index (BMI) in the phenotypic and genotypic characteristics of early arthritis patients. METHODS: We analysed the clinical and laboratory parameters from the baseline visit of patients (670 patients [78.51% women]) included in the PEARL study. The WHO definition for low weight, normal weight, overweight and obesity (BMI
Authors: Schaefer B, Beier JP, Ruhl T Abstract Skeletal muscle represents the largest mass of tissue in the body and is essential for motion and posture. Traumatic injury, tumor ablation, prolonged denervation or genetic defects lead to skeletal myopathies. The loss of muscle function or its regenerative properties often results in pain, deformity, and joint malfunction. The regenerative capacity of skeletal muscles depends on adult muscle stem cells, the so-called satellite cells; however, the population of these myogenic precursors, and thus their potential to restore large muscle tissue defects, is strongly limi...
ConclusionsDifferent types of glial cells have both cell autonomous effects and interactions with neurons and other cells that are involved in the pathophysiology of the neurological phenotype of TSC. Targeting glial-mediated mechanisms may represent a novel therapeutic approach for epilepsy and TAND in TSC patients.
We report the molecular diagnosis of TSC in individuals exhibiting extreme intra-familial variability, including the incidental diagnosis of asymptomatic family members. Exome sequencing was performed in three families, with probands referred for epilepsy, autism, and absent speech (Family 1); epileptic spasms (Family 2); and connective tissue disorders (Family 3.) Pathogenic variants inTSC1 orTSC2 were identified in nine individuals, including relatives with limited or no medical concerns at the time of testing. Of the nine individuals reported here, six had post-diagnosis examinations and three met clinical diagnostic cr...