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The cytoplasmic accumulation of the nuclear TAR DNA-binding protein 43 (TDP-43) is a pathologic hallmark in amyotrophic lateral sclerosis, frontotemporal lobar degeneration, and other neurological disorders. However, most transgenic TDP-43 rodent models show predominant nuclear distribution of TDP-43 in the brain. By expressing mutant TDP-43 (M337V) in the brains of rhesus monkeys and mice, we verified that mutant TDP-43 is distributed in the cytoplasm of the monkey brain and that the majority of mutant TDP-43 remains in the nuclei of the mouse brain. The primate-specific caspase-4, but not mouse homologue caspase-11, could remove the NLS-containing N-terminal domain and generate fragmented TDP-43 that accumulates in the cytoplasm. Moreover, increased expression of caspase-4 in the monkey brain promotes the cytoplasmic accumulation of endogenous TDP-43, and suppressing caspase-4 reduces the cytoplasmic distribution of endogenous TDP-43 in cultured human neural cells. Our findings suggest that primate-specific caspase-4-mediated cleavage of TDP-43 accounts for its cytoplasmic mislocalization in the primate brains and may serve as a potential therapeutic target. [ABSTRACT FROM AUTHOR]

In recent years, phenol-formaldehyde resin (PFR) as a colloid plugging agent was extensively used in enhanced oil recovery. It has been popularly concerned that the influence of environment on the structure, migration and aggregation behavior of PFR. The classical Derjaguin-Landau-Verwey-Overbeek (DLVO) theory can explain the interaction potential between particles. However, the classical DLVO cannot explain differences when colloids aggregate in the same valence metal cation solution. In this work, the effects of ion specificity of divalent metal cations (i. e., Mg2 + and Ca2 +) on the aggregation rate, fractal dimension, zeta potential and the c ritical c oagulation c oncentration (CCC) of PFR were systematically studied by dynamic light scattering experiment, electrophoretic light scattering and spectral turbidimetry. The experimental results showed that metal cations with poor hydration (i. e., Mg2 +) can promote aggregation more than metal cations with good hydration (i. e., Ca2 +). The hydrated differences of ions can be explained quantitatively by the improved DLVO theory introducing Lewis acid-base interaction. This result revealed the important significance of ion specificity in the aggregation behavior of PFR colloids, and made it possible to understand the co-transport process of PFR aggregates and metal cations in reservoirs. Thus, it is possible to precisely control the aggregation rate and the fractal dimension of PFR aggregates. [Display omitted] • Phenol-formaldehyde resin was prepared by adding NaOH step by step. • The aggregation kinetics of Phenol-formaldehyde were studied by turbidities. • We studied morphology of aggregates of Phenol-formaldehyde by fractal dimension. • Based on the DLVO theory, We proposed the interface energy of the colloid. • We explained differences of divalent ions by Lewis acid-base interaction. [ABSTRACT FROM AUTHOR]