We examined the roles of fibroblast growth factor (FGF)-2 and FGF-8 in the migration of mesencephalic mouse neural crest cells. Our in vitro migration assay has shown that FGF-2 (basic FGF) and FGF-8 have chemotactic activity for these cells. Chemotaxis was inhibited by anti-FGF-2 and anti-FGF-8 neutralizing antibodies. In addition, anti-FGF-2 blocked neural crest cell migration in cranial organ cultures. This observation suggests that FGF-2 functions as a chemoattractant in migration of mesencephalic neural crest cells in vivo. In organ culture, the antagonist of FGF binding to a low-affinity fibroblast growth factor receptor (FGFR) heparan sulfate, inositolhexakisphosphate (InsP6), inhibited migration as well. Mesencephalic neural crest cells had high-affinity FGFRs, in particular FGFR-1 and FGFR-3. Thus, the chemotactic activities of FGF-2 can be mediated by the low-affinity FGFR alone or by a combination of low- and high-affinity FGFRs (FGFR-1, FGFR-3, or both). Moreover, differential localization of FGF-2 was found at the mesencephalic axial level of intact embryos during neural crest cell migration. FGF-2 protein expression was predominant in the target regions, in particular the mandibular mesenchyme, that are colonized by mesencephalic neural crest cells. This characteristic distribution supports the notion that FGF-2 acts as a chemoattractant in the mouse embryo that directs mesencephalic neural crest cell migration. Whereas FGF-8 showed chemotactic activity in vitro, neural crest cell dispersion was observed in explants that had been treated with anti-FGF-8 neutralizing antibodies. This result suggests that FGF-8 may not be a chemoattractant in vivo. However, the distribution of neural crest cells in explants treated with anti-FGF-8 differed from that in control explants or in intact embryos. Extreme FGF-2 distribution was observed in the mandibular arch and FGF-8 is expressed in the epithelium. FGF-8 may play a role in mesencephalic neural crest cell migration, and its role may be concerned with the differential localization of FGF-2. To establish this notion, we performed immunohistochemical examination of FGF-2 distribution in explants treated with FGF-8 and analysis of FGF-2 gene expression levels by reverse transcriptase-polymerase chain reaction by using RNA from explants. The data indicate that FGF-2 is distributed throughout the mesenchyme in FGF-8-treated explants and that expression of FGF-2 is promoted by FGF-8. Therefore, we conclude that the expression of FGF-8 in the mandibular arch epithelium is a prerequisite for the differential localization of FGF-2 and that the FGF-2 distribution pattern is essential for chemotaxis of mesencephalic neural crest cell migration.

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Background: The seventh novel human infecting Betacoronavirus that causes pneumonia (2019 novel coronavirus, 2019-nCoV) originated in Wuhan, China. The evolutionary relationship between 2019-nCoV and the other human respiratory illness-causing coronaviruses is unclear. We sought to characterize the relationship of the translated proteins of 2019-nCoV with other species of Orthocoronavirinae.Methods: A phylogenetic tree was constructed from the genome sequences. A cluster tree was developed from the profiles retrieved from the presence and absence of homologs of ten 2019-nCoV proteins. The combined data were used to characterize the relationship of the translated proteins of 2019-nCoV to other species of Orthocoronavirinae.Results: Our analysis reliably suggests that 2019-nCoV is most closely related to BatCoV RaTG13 and belongs to subgenus Sarbecovirus of Betacoronavirus, together with SARS coronavirus and Bat-SARS-like coronavirus. The phylogenetic profiling cluster of homolog proteins of one annotated 2019-nCoV protein against other genome sequences revealed two clades of ten 2019-nCoV proteins. Clade 1 consisted of a group of conserved proteins in Orthocoronavirinae comprising Orf1ab polyprotein, Nucleocapsid protein, Spike glycoprotein, and Membrane protein. Clade 2 comprised six proteins exclusive to Sarbecovirus and Hibecovirus. Two of six Clade 2 nonstructural proteins, NS7b and NS8, were exclusively conserved among 2019-nCoV, BetaCoV_RaTG, and BatSARS-like Cov. NS7b and NS8 have previously been shown to affect immune response signaling in the SARS-CoV experimental model. Thus, we speculate that knowledge of the functional changes in the NS7b and NS8 proteins during evolution may provide important information to explore the human infective property of 2019-nCoV.

This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Sarcopenia is a geriatric syndrome characterized by an age-related decline in skeletal muscle mass and strength. Here, we show that suppression of mitochondrial calcium uniporter (MCU)-mediated Ca2+ influx into mitochondria in the body wall muscles of the nematode Caenorhabditis elegans improved the sarcopenic phenotypes, blunting movement and mitochondrial structural and functional decline with age. We found that normally aged muscle cells exhibited elevated resting mitochondrial Ca2+ levels and increased mitophagy to eliminate damaged mitochondria. Similar to aging muscle, we found that suppressing MCU function in muscular dystrophy improved movement via reducing elevated resting mitochondrial Ca2+ levels. Taken together, our results reveal that elevated resting mitochondrial Ca2+ levels contribute to muscle decline with age and in muscular dystrophy. Further, modulation of MCU activity may act as a potent pharmacological target in various conditions involving muscle loss.

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