Protein Tyrosine Phosphatase σ in Proteoglycan-Mediated Neural Regeneration Regulation

The receptor-type protein tyrosine phosphatase PTPσ mediates neural development and regeneration. Early studies on the ligands of PTPσ identified heparan sulfate proteolycan (HSPG) as a ligand. Binding of HSPG to PTPσ plays a critical role in axon guidance and synapse formation. PTPσ is also a receptor for chondroitin sulfate proteoglycan (CSPG). CSPG is deposited in high concentration at sites of neural injury. The deposited CSPG inhibits neural regeneration and axonal growth via PTPσ. The crystal structure of N-terminal immunoglobulin-like domains of PTPσ shows that the glycan binding site forms an elliptical surface patch of ～35 by 24 Å, which interacts with sulfate groups of HSPG and CSPG. In this review, we focus on the structural and functional mechanisms for the neural regeneration regulation by different types of proteoglycans. We also discuss recent results on induction of neural regeneration in the stroke model and neural transplantation. The mechanistic understanding of relationships between proteoglycans and PTPσ provides new therapeutic opportunities against diseases with impaired neural regeneration.     

Natural variation in population densities and vertical transmission rates of a Spiroplasma endosymbiont in Drosophila hydei

A bacterium belonging to the genus Spiroplasma, an endosymbiont of the fly Drosophila hydei, is vertically transmitted through host egg cytoplasm. To infer vertical transmission rates of Spiroplasma in natural populations of D. hydei, the infection status of Spiroplasma was examined for offspring produced by Spiroplasma-positive females that were collected in two geographical populations. In both populations, nearly half of the broods consisted of only infected offspring. Infection frequencies of the rest of the broods ranged from 0.364 to 0.975. Quantitative PCR demonstrated that the Spiroplasma titers in the whole body of wild-caught females were highly variable (1.81?×?10⁶–5.60?×?10⁸ cells per insect). Contrary to our expectations, however, the Spiroplasma titers did not account for the variation in infection frequencies among offspring (i.e., vertical transmission rates). These results suggest that the spatial distribution of Spiroplasma, particularly in somatic tissues and germ tissues, is highly variable among host individuals, which may be caused by environmental stochasticity or some unknown effects.     

Intracochlear Bleeding Enhances Cochlear Fibrosis and Ossification: An Animal Study

The aim of this study was to investigate the effects of intracochlear bleeding during cochleostomy on cochlear inflammatory response and residual hearing in a guinea pig animal model. Auditory brainstem response threshold shifts were greater in blood injected ears (p<0.05). Interleukin-1β, interleukin-10, tumor necrosis factor-α and nitric oxide synthase 2, cytokines that are related to early stage inflammation, were significantly increased in blood injected ears compared to normal and cochleostomy only ears at 1 day after surgery; with the increased IL-1β being sustained until 3 days after the surgery (p<0.05). Hair cells were more severely damaged in blood injected ears than in cochleostomy only ears. Histopathologic examination revealed more extensive fibrosis and ossification in blood injected ears than cochleostomy only ears. These results show that intracochlear bleeding enhanced cochlear inflammation resulting in increased fibrosis and ossification in an experimental animal model.     

Generation of motor neurons requires spatiotemporal coordination between retinoic acid and Mib-mediated Notch signaling

Mind bomb (Mib) is an E3 ubiquitin ligase that activates the Notch signaling pathway. A previous study demonstrated that the generation of late-born GABAergic neurons may be regulated by the interplay between Mib and retinoic acid (RA). However, the relationship between Mib function and the retinoid pathway during the generation of late-born motor neurons remains unclear. We investigated the differentiation of neural progenitors into motor neurons by inhibition of Notch signaling and administration of RA to Tg[hsp70-Mib:EGFP] embryos. The number of motor neurons in the ventral spinal cord increased or decreased depending on the temporal inhibition of Mib-mediated Notch signaling. Inhibition of the retinoid pathway by citral treatment had a synergistic effect with overexpression of Mib:EGFP on the generation of ectopic motor neurons. Additionally, the proteolytic fragment of Mib was detected in differentiated P19 cells following treatment with RA. Our observations imply that the function of Mib may be attenuated by the retinoid pathway, and that Mib-mediated Notch signaling and the retinoid pathway play critical roles in the spatiotemporal differentiation of motor neurons.     

Comparison of Virulence between Seoul Virus Strain SR-11 and Hantaan Virus Strain 76–118 of Hantaviruses in Newborn Mice

Virulence of hantavirus strain of SR-11 Seoul virus and Hantaan 76–118 (HTN) of Hantaan virus were compared. Infections of both strains were lethal in newborn mice. However, inoculum required to cause lethal infection was about 4,000 times higher for strain HTN (1.65 × 10³ PFU/mouse/LD₅₀) than for strain SR-11 (0.36 PFU). Thus, both strains were considered pathogenic to newborn mice but they possessed different levels of virulence. The assay system used for these strains in newborn mice proved to be useful in the study of hantavirus vilurence. Growth curves of the two strains in CV-7 cell cultures were compared. Strain SR-11 was shown to have higher activity of virus replication and virus release into the culture fluids than strain HTN. The possibility of a relationship between replication activity and high levels of virulence in mice was suggested.