Cholinergic receptor pathways involved in apoptosis, cell proliferation and neuronal differentiation

Acetylcholine (ACh) has been shown to modulate neuronal differentiation during early development. Both muscarinic and nicotinic acetylcholine receptors (AChRs) regulate a wide variety of physiological responses, including apoptosis, cellular proliferation and neuronal differentiation. However, the intracellular mechanisms underlying these effects of AChR signaling are not fully understood. It is known that activation of AChRs increase cellular proliferation and neurogenesis and that regulation of intracellular calcium through AChRs may underlie the many functions of ACh. Intriguingly, activation of diverse signaling molecules such as Ras-mitogen-activated protein kinase, phosphatidylinositol 3-kinase-Akt, protein kinase C and c-Src is modulated by AChRs. Here we discuss the roles of ACh in neuronal differentiation, cell proliferation and apoptosis. We also discuss the pathways involved in these processes, as well as the effects of novel endogenous AChRs agonists and strategies to enhance neuronal-differentiation of stem and neural progenitor cells. Further understanding of the intracellular mechanisms underlying AChR signaling may provide insights for novel therapeutic strategies, as abnormal AChR activity is present in many diseases

TOI-257b (HD 19916b): A warm sub-saturn orbiting an evolved F-type star

We report the discovery of a warm sub-Saturn, TOI-257b (HD 19916b), based on data from NASA's Transiting Exoplanet Survey Satellite (TESS). The transit signal was detected by TESS and confirmed to be of planetary origin based on radial velocity observations. An analysis of the TESS photometry, the Minerva-Australis, FEROS, and HARPS radial velocities, and the asteroseismic data of the stellar oscillations reveals that TOI-257b has a mass of MP = 0.138 ± 0.023 M J (43.9 ± 7.3, M⊕), a radius of RP = 0.639 ± 0.013 R J (7.16 ± 0.15, R ⊕), bulk density of 0.65+0.12-0.11 (cgs), and period 18.38818 +0.00085 -0.00084 days. TOI-257b orbits a bright (V = 7.612 mag) somewhat evolved late F-type star with M∗ = 1.390 ± 0.046 rm M sun, R∗ = 1.888 ± 0.033 Rsun, Teff = 6075 ± 90 rm K, and vsin i = 11.3 ± 0.5 km s-1. Additionally, we find hints for a second non-transiting sub-Saturn mass planet on a ∼71 day orbit using the radial velocity data. This system joins the ranks of a small number of exoplanet host stars (∼100) that have been characterized with asteroseismology. Warm sub-Saturns are rare in the known sample of exoplanets, and thus the discovery of TOI-257b is important in the context of future work studying the formation and migration history of similar planetary systems

TOI-257b (HD 19916b): a warm sub-saturn orbiting an evolved F-type star

ABSTRACT We report the discovery of a warm sub-Saturn, TOI-257b (HD 19916b), based on data from NASA’s Transiting Exoplanet Survey Satellite (TESS). The transit signal was detected by TESS and confirmed to be of planetary origin based on radial velocity observations. An analysis of the TESS photometry, the Minerva-Australis, FEROS, and HARPS radial velocities, and the asteroseismic data of the stellar oscillations reveals that TOI-257b has a mass of MP = 0.138 ± 0.023 $\rm {M_J}$ (43.9 ± 7.3 $\, M_{\rm \oplus}$), a radius of RP = 0.639 ± 0.013 $\rm {R_J}$ (7.16 ± 0.15 $\, \mathrm{ R}_{\rm \oplus}$), bulk density of $0.65^{+0.12}_{-0.11}$ (cgs), and period $18.38818^{+0.00085}_{-0.00084}$ $\rm {days}$. TOI-257b orbits a bright (V = 7.612 mag) somewhat evolved late F-type star with M* = 1.390 ± 0.046 $\rm {M_{sun}}$, R* = 1.888 ± 0.033 $\rm {R_{sun}}$, Teff = 6075 ± 90 $\rm {K}$, and vsin i = 11.3 ± 0.5 km s−1. Additionally, we find hints for a second non-transiting sub-Saturn mass planet on a ∼71 day orbit using the radial velocity data. This system joins the ranks of a small number of exoplanet host stars (∼100) that have been characterized with asteroseismology. Warm sub-Saturns are rare in the known sample of exoplanets, and thus the discovery of TOI-257b is important in the context of future work studying the formation and migration history of similar planetary systems

Glucose regulates expression of inositol 1,4,5-trisphosphate receptor isoforms in isolated rat pancreatic islets.

Isolated rat pancreatic islets were studied to determine the dynamic regulatory effects of glucose stimulation on the expression of messenger RNA (mRNA) and protein levels for inositol 1,4,5-trisphosphate (IP3) receptor (IP3R) isoforms I, II, and III. The relative isoform abundance was: IP3R-III > IP3R-II approximately IP3R-I. Culture of islets with glucose (G; 20 mM) or alpha-ketoisocaproic acid for 30 min increased only IP3R-III mRNA expression above control (5.5 mM glucose). 2-Deoxyglucose was without effect. Islet culture for 2 h with G (20 mM) or alpha-ketoisocaproic acid reduced IP3R-III mRNA expression levels below control, and cycloheximide blocked the response. Culturing islets for 1 day or 7 days with G (11 mM) reduced the expression of IP3R-III mRNA but increased the expression of IP3R-II mRNA in a time-dependent manner. Cytosine arabinoside lowered cultured islet IP3R-II and -III mRNA levels, but glucose effects remained evident. IP3R-II mRNA levels were also significantly higher in islets from hyperglycemic 90% partial pancreatectomized rats, compared with sham animals. Islet IP3R mRNA expression also showed osmotic sensitivity. Islet IP3R-III protein levels increased after 2 h islet culture at 20 mM G, were unchanged after 1 day culture at 11 mM G, and were lower than control after 7 days culture at 11 mM G. In contrast, IP3R-II levels increased after 1 day and 7 days culture at 11 mM G, whereas IP3R-I protein levels remained unchanged. Thus, G stimulation rapidly increases transcription and expression of IP3R-III mRNA and protein levels in rat islets. However, chronic G stimulation up-regulates IP3R-II mRNA in cultured islets and in islets from partial pancreatectomized rats. Metabolic regulation of IP3R-II and III expression may mediate beta-cell IP3-responsive Ca2+ mobilization and insulin secretion