Autism Spectrum Disorder (ASD) is mainly characterized by social and sensory-motor abnormal and repetitive behavior patterns. Over 1000 genetic variants were reported to be highly penetrant and causative of ASD. Many of these mutations cause comorbidities such as epilepsy and intellectual disabilities (ID). In this study, we measured cortical neurons derived from induced pluripotent stem cells (iPSCs) of patients with four mutations in the genes GRIN2B, SHANK3, UBTF, as well as chromosomal duplication in the 7q11.23 region. Using a whole-cell patch-clamp, we observed that the mutant cortical neurons demonstrated hyperexcitability and early maturation compared to control lines. These changes were characterized by higher sodium current, higher amplitude and rates of excitatory postsynaptic currents (EPSCs), and more evoked action potentials in response to current stimulation in early-stage cell development (3-5 weeks post differentiation). These changes that appeared in all the different mutant lines, together with previously reported data, indicate that an early maturation and hyperexcitability may be a convergent phenotype of ASD cortical neurons.
Laboratory experiments were conducted to determine the effects of temperature, light, cold stratification, dry storage, solution pH, solution osmotic potential, and planting depth on germination and emergence of dame's rocket. Maximal germination (> 80%) of fresh seeds occurred at alternating temperatures ≥ 25/15 C in both alternating light/dark and continuous darkness. However, < 10% of seeds germinated at or below 20/10 C, with lower germination in the presence of light than in darkness. Cold stratification at 4 C for 4 to 16 wk enhanced germination at low alternating temperatures (≤ 20/10 C), but depressed germination at warm temperature regimes (≥ 25/15 C). After 1 yr of dry storage (after-ripening), germination exceeded 94% and did not differ significantly among temperature regimes. Germination exceeded 60% in solutions with pH 3 to 10. Germination was reduced below 50% in solutions with osmotic potentials below −0.6 MPa. Percent emergence was greater than 56% at burial depths in soil of 0 to 5 cm, with maximal emergence (93 to 99%) at 0 to 2 cm. Dame's rocket seeds possess non-deep physiological dormancy at maturity, but when dormancy is alleviated, the seeds are capable of germinating in a variety of climatic and edaphic conditions.
Autism Spectrum Disorder (ASD) is characterized mainly by social and sensory-motor abnormal and repetitive behavior patterns. Over hundreds of genes and thousands of genetic variants were reported to be highly penetrant and causative of ASD. Many of these mutations cause comorbidities such as epilepsy and intellectual disabilities (ID). In this study, we measured cortical neurons derived from induced pluripotent stem cells (iPSCs) of patients with four mutations in the genes GRIN2B, SHANK3, UBTF, as well as chromosomal duplication in the 7q11.23 region and compared them to neurons derived from a first-degree relative without the mutation. Using a whole-cell patch-clamp, we observed that the mutant cortical neurons demonstrated hyperexcitability and early maturation compared to control lines. These changes were characterized by increased sodium currents, increased amplitude and rate of excitatory postsynaptic currents (EPSCs), and more evoked action potentials in response to current stimulation in early-stage cell development (3–5 weeks post differentiation). These changes that appeared in all the different mutant lines, together with previously reported data, indicate that an early maturation and hyperexcitability may be a convergent phenotype of ASD cortical neurons.
Parkinson's disease (PD) is a neurodegenerative disease with both genetic and sporadic origins. In this study, we investigated the electrophysiological properties, synaptic activity, and gene expression differences in dopaminergic (DA) neurons derived from induced pluripotent stem cells (iPSCs) of healthy controls, sporadic PD (sPD) patients, and PD patients with GBA1 mutations. Our results demonstrate reduced sodium currents and synaptic activity in DA neurons derived from PD patients with GBA1 mutations, suggesting a potential contribution to PD pathophysiology. We also observed distinct electrophysiological alterations in sPD DA neurons that were dependent on the age of disease onset. RNA sequencing analysis revealed unique dysregulated pathways in early and late-onset sPD neurons, further supporting the notion that molecular mechanisms driving PD may be different between PD patients. In agreement with our previous reports, ECM and focal adhesion genes were the top dysregulated pathways in DA neurons from sPD patients and from patients with GBA1 mutations. Overall, this study gives further confirmation that the convergent functional phenotypes of DA neurons derived from PD patients are synaptic abnormalities, and at the transcriptome level, ECM and focal adhesion pathways are highly involved in PD pathology across multiple PD-associated mutations as well as sPD.
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