Transgenic models of Alzheimer's disease: Better utilization of existing models through viral transgenesis

Animal models have been used for decades in the Alzheimer's disease (AD) research field and have been crucial for the advancement of our understanding of the disease. Most models are based on familial AD mutations of genes involved in the amyloidogenic process, such as the amyloid precursor protein (APP) and presenilin 1 (PS1). Some models also incorporate mutations in tau (MAPT) known to cause frontotemporal dementia, a neurodegenerative disease that shares some elements of neuropathology with AD. While these models are complex, they fail to display pathology that perfectly recapitulates that of the human disease. Unfortunately, this level of pre-existing complexity creates a barrier to the further modification and improvement of these models. However, as the efficacy and safety of viral vectors improves, their use as an alternative to germline genetic modification is becoming a widely used research tool. In this review we discuss how this approach can be used to better utilize common mouse models in AD research. This article is part of a Special Issue entitled: Animal Models of Disease.     

Isolation and partial characterization of a corynebacteriophage beta, tox operator constitutive-like mutant lysogen of Corynebacterium diphtheriae.

We have isolated and partially characterized a beta-phage mutant lysogen of Corynebacterium diphtheriae, C7(betatoxct1+), which is partially insensitive to iron inhibition of diphtheria toxin production. tox expression by C7(betatoxct1+) was found to be partially constitutive. In the presence of concentrations of iron that almost completely inhibit the expression of diphtheria toxin by the wild type, C7(beta), the level of toxin production by C7(betatoxct1+) was found to be at least 25 times that of the parent. The purified tox gene product of C7(betatoxct1+) was immunologically and electrophoretically identical to, and equally as toxic as, diphtheria toxin purified from C7(beta). In addition, the partial N-terminal amino acid sequence was found to be identical to diphtheria toxin. This data strongly suggests that the mutation allowing for the constitutive expression of tox in C7(betatoxct1+) is outside of the structural gene. Furthermore, the constitutive expression of diphtheria toxin was found to be cis dominant in the double lysogen C7(betacrm45+/betatoxct1+). The data presented is consistent with the existence of a tox operator locus.     

Evaporative temperature and moisture control in a rocking reactor for solid substrate fermentation

Summary In the solid substrate fermentation of cooked yellow corn grits with Rhizopus oligosporus in a rocking drum fermenter, temperature was controlled by blowing air through the substrate, forcing water evaporation. The rate of evaporation was controlled by the relative humidity of the air, according to the rate of heat generation during fermentation. Moisture content was maintained constant by spraying cold water on the substrate regulated by the water balance equation of the system. Both controls were operated by computer programs. The rocking motion in the reactor allowed even distribution of air and water in the substrate without disturbing the growing mycelia.     

Kinetics of hydrolysis of endocytosed substrates by mammalian cultured cells: early introduction of lysosomal enzymes into the endocytic pathway

The kinetics of exposure of endocytosed material to two lysosomal enzymes were determined for a number of cultured cell lines using fluorogenic substrates. Hydrolysis of endocytosed substrates for cathepsin B and acid phosphatase was observed to begin within 3-10 min of substrate addition and to proceed linearly for up to 60 min thereafter. Hydrolysis of the cathepsin B substrate was not affected by inhibition of protein synthesis with cycloheximide, indicating that the enzymes present in early endosomes are not exclusively newly synthesized. As had been observed previously for a cathepsin B substrate (Roederer, M., Bowser, R., and Murphy, R. F., J. Cell. Physiol., 131:200-209, 1987), hydrolysis of the acid phosphatase substrate was not blocked at temperatures below 20 degrees C. The results suggest that the endosome is the primary site of initial exposure of endocytosed material to hydrolytic enzymes.     

Rational Design of Nickel Hydroxide‐Based Nanocrystals on Graphene for Ultrafast Energy Storage

Compact, light, and powerful energy storage devices are urgently needed for many emerging applications; however, the development of advanced power sources relies heavily on advances in materials innovation. Here, the findings in rational design, one‐pot synthesis, and characterization of a series of Ni hydroxide‐based electrode materials in alkaline media for fast energy storage are reported. Under the guidance of density functional theory calculations and experimental investigations, a composite electrode composed of Co‐/Mn‐substituted Ni hydroxides grown on reduced graphene oxide (rGO) is designed and prepared, demonstrating capacities of 665 and 427 C g^?1 at current densities of 2 and 20 A g^?1, respectively. The superior performance is attributed mainly to the low deprotonation energy and the facile electron transport, as elaborated by theoretical calculations. When coupled with an electrode based on organic molecular‐modified rGO, the resulting hybrid device demonstrates an energy density of 74.7 W h kg^?1 at a power density of 1.68 kW kg^?1 while maintaining capacity retention of 91% after 10,000 cycles (20 A g^?1). The findings not only provide a promising electrode material for high‐performance hybrid capacitors but also open a new avenue toward knowledge‐based design of efficient electrode materials for other energy storage applications.