Biology subjects

Feng, C.

Publications and source records attributed to Feng, C..

3 recordsLinked to original sources

bioRxiv2018

Genome-wide identification of functional tRNA-derived fragments in Senescence-accelerated mouse prone 8 brain

tRNA-derived fragments (tRFs) have been linked previously to the development of various diseases, such as cancer and viral infection. However, tRFs seem also related to brain aging and related diseases, especially Alzheimer and Parkinson disease. RNA sequencing, a state-of-the-art technology, has allowed for investigation of tRFs in this field. In this study, we investigated the changes of tRFs in the brains of a senescence-accelerated mouse model, senescence-accelerated mouse prone 8 (SAMP8), that show age-dependent deficits in learning and memory; and a control model, senescence-accelerated mouse resistant 1 (SAMR1), with normal aging, both at 7 months of age. A total of 570 tRF transcripts were discovered. Among these transcripts, 8, including 3 upregulated and 5 downregulated transcripts, were differentially expressed in the SAMP8 mice. Then, we obtained 110 potential target genes in a miRNA-like pattern. GO survey implicated these target genes in the function of various aspects, e.g. postsynaptic density (GO: 0014069). Furthermore, we assessed in detail those tRFs whose miRNA-like pattern was most likely to affect the progression of either Alzheimer and Parkinson disease, such as AS-tDR-011775 acting on Mobp and Park2. In fact, we found the tRFs to be involved in the regulation of gene expression by means other than the miRNA-like pattern. Therefore, these 8 dysregulated tRFs may hold consequences far into the future and can be attractive biomarkers and valid targets. In brief, our study is the first to provide a comprehensive analysis on tRFs in SAMP8 mouse brain, and this breakthrough identified promising new targets for preventing the age-related changes of brain and the therapeutic intervention of Alzheimers and Parkinsons.

neuroscience↗

bioRxiv2017

Activity-induced Ca2+ signaling in perisynaptic Schwann cells is mediated by P2Y1 receptors and regulates muscle fatigue

Perisynaptic glial cells respond to neural activity by increasing cytosolic levels of calcium, but the functional significance of this pathway is unclear. Terminal/persiynaptic Schwann cells (TPSCs) are a perisynaptic glial cell at the neuromuscular junction. Here, we provide genetic evidence that neural activity-induced intracellular calcium accumulation in neonatal TPSCs is mediated exclusively by P2Y1 receptors. In P2ry1 mutant mice lacking these responses, postsynaptic, rather than presynaptic, function was altered in response to nerve stimulation. This impairment was correlated with a greater susceptibility to activity-induced muscle fatigue. Interestingly, fatigue in P2ry1 mutants was exacerbated by exposure to high potassium to a greater degree than in control mice. High potassium itself increased cytosolic levels of calcium in TPSCs, a response which was also reduced P2ry1 mutants. These results suggest that activity-induced calcium responses in perisynaptic glia at the NMJ regulate postsynaptic function and muscle fatigue by influencing the levels of perisynaptic potassium.

neuroscience↗

bioRxiv2017

Moderate Nucleotide Diversity In The Atlantic Herring Is Associated With A Low Mutation Rate

The Atlantic herring (Clupea harengus) is one of the most abundant vertebrates on earth but its nucleotide diversity is moderate ({pi}=0.3%), only three-fold higher than in human. The expected nucleotide diversity for selectively neutral alleles is a function of population size and the mutation rate, and it is strongly affected by demographic history. Here, we present a pedigree-based estimation of the mutation rate in the Atlantic herring. Based on whole-genome sequencing of four parents and 12 offspring, the estimated mutation rate is 1.7 x 10-9 per base per generation. There was no significant difference in the frequency of paternal and maternal mutations (8 and 7, respectively). Furthermore, we observed a high degree of parental mosaicism indicating that a large fraction of these de novo mutations occurred during early germ cell development when we do not expect a strong gender effect. The now estimated mutation rate - the lowest among vertebrates analyzed to date - partially explains the discrepancy between the rather low nucleotide diversity in herring and its huge census population size (>1011). But our analysis indicates that a species like the herring will never reach its expected nucleotide diversity for selectively neutral alleles primarily because of fluctuations in population size due to climate variation during the millions of years it takes to build up a high nucleotide diversity. In addition, background selection and selective sweeps lead to reductions in nucleotide diversity at linked neutral sites.

genomics↗