Biology subjects

Liu, C.-M.

Publications and source records attributed to Liu, C.-M..

3 recordsLinked to original sources

bioRxiv2018

Comparative genetic architectures of schizophrenia in East Asian and European populations

Author summarySchizophrenia is a severe psychiatric disorder with a lifetime risk of about 1% world-wide. Most large schizophrenia genetic studies have studied people of primarily European ancestry, potentially missing important biological insights. Here we present a study of East Asian participants (22,778 schizophrenia cases and 35,362 controls), identifying 21 genome-wide significant schizophrenia associations in 19 genetic loci. Over the genome, the common genetic variants that confer risk for schizophrenia have highly similar effects in those of East Asian and European ancestry (rg=0.98), indicating for the first time that the genetic basis of schizophrenia and its biology are broadly shared across these world populations. A fixed-effect meta-analysis including individuals from East Asian and European ancestries revealed 208 genome-wide significant schizophrenia associations in 176 genetic loci (53 novel). Trans-ancestry fine-mapping more precisely isolated schizophrenia causal alleles in 70% of these loci. Despite consistent genetic effects across populations, polygenic risk models trained in one population have reduced performance in the other, highlighting the importance of including all major ancestral groups with sufficient sample size to ensure the findings have maximum relevance for all populations.

genetics↗

bioRxiv2018

Novel role of Lin28 signaling in regulation of mammalian PNS and CNS axon regeneration

Several signaling molecules involved in cellular reprogramming have been shown to regulate mammalian axon regeneration. We hypothesized that reprogramming factors are key regulators of axon regeneration. Here we investigated the role of Lin28, an important reprogramming factor, in the regulation of axon regeneration. We found that Lin28a and Lin28b and their regulatory partners, let-7 microRNAs (miRNAs), were both necessary and sufficient in regulating mature sensory axon regeneration in vivo. More importantly, overexpression of either Lin28a or Lin28b in mature retinal ganglion cells (RGCs) promoted robust and sustained optic nerve regeneration. Additionally, combined overexpression of Lin28a and downregulation of PTEN in RGCs acted additively to promote optic nerve regeneration by reducing the backward turning of regenerating RGC axons. Our findings not only identified a novel molecule promoting optic nerve regeneration but also suggested that reprogramming factors may play vital roles in regulating axon regeneration in mammals.

neuroscience↗

bioRxiv2017

Tomato immune receptor Ve1 recognizes surface-exposed co-localized N- and C-termini of Verticillium dahliae effector Ave1

Effectors are secreted by plant pathogens to facilitate infection, often through deregulation of host immune responses. During host colonization, race 1 strains of the soil-borne vascular wilt fungus Verticillium dahliae secrete the effector protein Ave1 that triggers immunity in tomato genotypes that encode the Ve1 immune receptor. Homologs of V. dahliae Ave1 (VdAve1) are found in plants and in few plant pathogenic microbes, and are differentially recognized by Ve1. However, how VdAve1 is recognized by Ve1 remained unknown. Interestingly, C-terminally affinity-tagged versions of VdAve1 failed to activate Ve1-mediated immunity, suggesting that exposure of the C-terminus of VdAve1 is required for Ve1-mediated recognition. This was confirmed by subsequent analysis of C-terminal deletion mutants, and by domain swap experiments. Although required, only the C-terminus of VdAve1 is not sufficient to activate Ve1-mediated immunity. Intriguingly, a three-dimensional structural model of VdAve1 revealed that the N- and C-termini co-localize on a surface-exposed patch of the VdAve1 protein. Indeed, subsequent analyses of N-terminal deletion mutants confirmed that also the N-terminus of VdAve1 is required to activate Ve1-mediated immunity. Thus, we conclude that a surface-exposed patch of the VdAve1 protein that is composed by co-localized N- and C-termini is recognized by the tomato immune receptor Ve1.

plant biology↗