Comparison of induced neurons reveals slower structural and functional maturation in humans than in apes.

We generated induced excitatory neurons (iNeurons, iNs) from chimpanzee, bonobo, and human stem cells by expressing the transcription factor neurogenin-2 (NGN2). Single-cell RNA sequencing showed that genes involved in dendrite and synapse development are expressed earlier during iNs maturation in the chimpanzee and bonobo than the human cells. In accordance, during the first 2 weeks of differentiation, chimpanzee and bonobo iNs showed repetitive action potentials and more spontaneous excitatory activity than human iNs, and extended neurites of higher total length. However, the axons of human iNs were slightly longer at 5 weeks of differentiation. The timing of the establishment of neuronal polarity did not differ between the species. Chimpanzee, bonobo, and human neurites eventually reached the same level of structural complexity. Thus, human iNs develop slower than chimpanzee and bonobo iNs, and this difference in timing likely depends on functions downstream of NGN2.

Antioxidant Effects of Elderberry Anthocyanins in Human Colon Carcinoma Cells: A Study on Structure-Activity Relationships.

SCOPE: Glycosylation is a way to increase structure-stability of anthocyanins, yet compromises their bioactivity. The study investigates the antioxidant activity of purified cyanidin (Cy)-based anthocyanins and respective degradation products in Caco-2 clone C2BBe1 aiming to identify structure-activity relationships. RESULTS AND METHODS: Cyanidin 3-O-glucoside (Cy-3-glc) and cyanidin 3-O-sambubioside (Cy-3-sam) proved to be most potent regarding antioxidant properties and protection against hydrogen peroxide (H2 O2 )-induced reactive oxygen species (ROS)-levels measured with the dichloro-fluorescein (DCF) assay. Cyanidin 3-O-sambubioside-5-O-glucoside (Cy-3-sam-5-glc) and cyanidin 3-O-rutinoside (Cy-3-rut) were less efficient and not protective, reflecting potential differences in uptake and/or degradation. Following ranking in antioxidant efficiency is suggested: (concentrations ≤10 × 10-6  M) Cy-3-glc ≥ Cy-3-sam > Cy-3-sam-5-glc ≈ Cy-3-rut ≈ Cy; (concentrations ≥50 × 10-6  M) Cy-3-glc ≈ Cy-3-sam ≥ Cy > Cy-3-sam-5-glc ≈ Cy-3-rut. Cy and protocatechuic acid (PCA) reduced ROS-levels as potent as the mono- and di-glycoside, whereas phloroglucinol aldehyde (PGA) displayed pro-oxidant properties. None of the degradation products protected from oxidative stress. Gene transcription analysis of catalase (CAT), superoxide-dismutase (SOD), glutathione-peroxidase (GPx), heme-oxygenase-1 (HO-1), and glutamate-cysteine-ligase (γGCL) suggest no activation of nuclear factor erythroid 2-related factor 2 (Nrf2). CONCLUSION: More complex residues and numbers of sugar moieties appear to be counterproductive for antioxidant activity. Other mechanisms than Nrf2-activation should be considered for protective effects.