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Drosophila Toll-9 is most closely related to mammalian Toll-like receptors; however, physiological functions of Toll-9 remain elusive. We examined the roles of Toll-9 in fly brains in aging and neurodegeneration. Toll-9 mRNA levels were increased in aged fly heads accompanied by activation of nuclear factor-kappa B (NF-kB) and stress-activated protein kinase (SAPK) signaling, and many of these changes were modulated by Toll-9 in glial cells. The loss of Toll-9 did not affect lifespan or brain integrity, whereas it exacerbated hydrogen peroxide-induced lethality. Toll-9 expression was also induced by nerve injury but did not affect acute stress response or glial engulfment activity, suggesting Toll-9 may modulate subsequent neurodegeneration. In a fly tauopathy model, Toll-9 deficiency enhanced neurodegeneration and disease-related tau phosphorylation with reduced SAPK activity, and blocking SAPK enhanced tau phosphorylation and neurodegeneration. In sum, Toll-9 is induced upon aging and nerve injury and affects neurodegeneration by modulating stress kinase signaling., Competing Interests: The authors declare no competing interests., (© 2023 The Author(s).)

Phosphorus (P) discharges from human activities result in eutrophication of lakes. We investigated whether the forms of phosphorus (P) in rivers with high effluent loads flowing through urban areas of Sapporo, Japan, were transformed when transported downstream into a eutrophic lake, namely Lake Barato. We hypothesized that the inorganic P supplied from the rivers might be transformed to organic forms in the lake. The results showed that soluble reactive phosphorus (SRP) and particulate inorganic phosphorus (PIP) dominated in the river discharge to the lake. Suspended solids in the rivers were rich in iron (Fe) so PIP was associated with Fe. A comparison of the concentrations at the river mouth and 4.5 km downstream showed that the concentrations of SRP and PIP were lower at 4.5 km downstream than at the river mouth, whereas the concentrations of organic P (i.e., dissolved organic phosphorus and particulate organic phosphorus) were similar. The results from solution 31 P nuclear magnetic resonance spectroscopy of lake water showed that pyrophosphate was only present in the particulate fraction, while orthophosphate diesters (DNA-P) were only present in the dissolved fraction. Riverine samples contained orthophosphate (ortho-P) only, while lake samples contained ortho-P, orthophosphate monoesters, and DNA-P. The results suggest that the P forms, particularly those of dissolved P, shifted from inorganic to organic forms as the water was discharged from the river to the lake., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: The locus coeruleus (LC), a brainstem nucleus comprising noradrenergic neurons, is one of the earliest regions affected by Alzheimer's disease (AD). Amyloid-β (Aβ) pathology in the cortex in AD is thought to exacerbate the age-related loss of LC neurons, which may lead to cortical tau pathology. However, mechanisms underlying LC neurodegeneration remain elusive., Objective: Here, we aimed to examine how noradrenergic neurons are affected by cortical Aβ pathology in AppNL-G-F/NL-G-F knock-in mice., Methods: The density of noradrenergic axons in LC-innervated regions and the LC neuron number were analyzed by an immunohistochemical method. To explore the potential mechanisms for LC degeneration, we also examined the occurrence of tau pathology in LC neurons, the association of reactive gliosis with LC neurons, and impaired trophic support in the brains of AppNL-G-F/NL-G-F mice., Results: We observed a significant reduction in the density of noradrenergic axons from the LC in aged AppNL-G-F/NL-G-F mice without neuron loss or tau pathology, which was not limited to areas near Aβ plaques. However, none of the factors known to be related to the maintenance of LC neurons (i.e., somatostatin/somatostatin receptor 2, brain-derived neurotrophic factor, nerve growth factor, and neurotrophin-3) were significantly reduced in AppNL-G-F/NL-G-F mice., Conclusion: This study demonstrates that cortical Aβ pathology induces noradrenergic neurodegeneration, and further elucidation of the underlying mechanisms will reveal effective therapeutics to halt AD progression.

Background: Inhibition of pulmonary surfactant by plasma-derived proteins is an important pathogenetic factor of acute respiratory distress syndrome (ARDS). Inhalation of aerosolized surfactant may be suitable for early treatment of ARDS. However, requirement of a high dose is a drawback. Because dextran reverses surfactant inhibition, we examined whether dextran improves the therapeutic effects of aerosolized surfactant in rats with experimental ARDS., Methods: Acidified milk (pH 1.8, 1.5 ml kg(-1)) was injected into the trachea of the rats ventilated with pure oxygen using 2.45 kPa peak inspiratory pressure and 0.74 kPa positive end-expiratory pressure. When PaO2 decreased to <13 kPa, the rats were assigned to four groups: control group (n = 8), receiving no material; D-only group (n = 6), receiving aerosolized dextran for 45 min; S-only group (n = 8), receiving aerosolized modified natural surfactant (MNS) for 30 min; and S-plus-D group (n = 9), receiving aerosolized MNS for 30 min followed by aerosolized dextran for 15 min., Results: In the control group and D-only groups, the mean PaO2 remained at <10 kPa for 180 min. In the S-only and S-plus-D groups, the PaO2 increased to 50 kPa (P < 0.01 vs. untreated). The PaO2 of the surfactant-only group gradually decreased to <17 kPa at 180 min, whereas the PaO2 of the S-plus-D group was maintained at >38 kPa for 180 min (P < 0.01 vs. S-only group)., Conclusion: Inhalation of aerosolized dextran potentiates the effects of aerosolized surfactant by prolonging the therapeutic response.