Biology subjects

Lyu, S.

Publications and source records attributed to Lyu, S..

22 records · Page 2Linked to original sources

bioRxiv2022

LMM-MQM time series mapping - An application in a murine advanced intercross line identifies novel growth QTLs

The Berlin Fat Mouse Inbred line 860 (BFMI860) is a mouse model for juvenile obesity. Previously, a recessive major effect locus (jObes1) was identified on chromosome 3 explaining around 26% of the body weight variance in an BFMI860xC57BL/6NCrl advanced intercross line. The aim of this study was to discover additional QTL. Time series body weight data were modeled using linear mixed models (LMM), while a multiple QTL mapping (MQM) approach compensated for the jObes1 locus effect. LMM-MQM identified five additional loci significantly associated with body weight. Variance explained by the jObes1 locus increased to 38.1% when using LMM-MQM mapping, while the additional loci explained between 2.0% and 3.9% of the body weight variance. Several positional candidate genes within the novel QTL regions were found in KEGG pathways for insulin signaling and insulin resistance. Strong distortion with preference for the BFMI allele was observed within a newly identified QTL containing the well-known Foxo1 regulator of adipocyte differentiation. Here, we present a novel method for QTL detection in time series data: LMM-MQM time series mapping. We show that our method is more powerful in detecting QTLs compared to single timepoint mapping approaches. Thus, the time series structure should be considered for optimal detection of small effect QTLs. LMM-MQM time series mapping can be used to find genetic determinants of all kind of "phenotypes over time" be it lactation curves in cattle, plant biomass, drug clearance in human clinical trials, or cognitive decline during disease.

genetics↗

bioRxiv2020

Interannual variability of net ecosystem carbon production and its climatic and biotic mechanism during 2005-2018 in a rain-fed maize ecosystem

The interannual variation (IAV) of net ecosystem carbon production (NEP) plays an important role in understanding the mechanisms of the carbon cycle in the agriculture ecosystem. In this study, the IAV of NEP, which were expressed as annual values and anomalies, and its climatic and biotic controls mechanism, were investigated based on an eddy covariance dataset of rain-fed spring maize during 2005-2018 in the northeast of China. The annual NEP was 270{+/-}115 g C m-2yr -1. Annual values and anomalies of NEP were positively correlated with that of precipitation (PPT), gross ecosystem production (GEP) and daily maximum NEP (NEPmax). Annual anomalies of NEP were dominantly and positively controlled by the soil water content (SWC) through GEP and the soil temperature (Ts) through RE. In comparison, annual anomalies of NEP were dominantly and negatively controlled by summer VPD through the NEPmax, positively adjusted by spring precipitation and the effective accumulative temperature through the beginning date (BDOY) of the affecting carbon uptake period (CUP), and by autumn precipitation and leaf area index through the end date (EDOY) of the affecting CUP. Residues restrained the carbon release at the beginning of the year, and accelerated the carbon release at the end of the year. Our results hightlight that NEP might be more sensitive to the change of water condition (such as PPT, SWC and VPD) induced by the climate changes.

ecology↗

bioRxiv2020

CIS checkpoint deletion enhances the fitness of cord blood derived natural killer cells transduced with a chimeric antigen receptor

Immune checkpoint therapy has produced remarkable improvements in the outcome for certain cancers. To broaden the clinical impact of checkpoint targeting, we devised a strategy that couples targeting of the cytokine-inducible SH2-containing (CIS) protein, a key negative regulator of interleukin (IL)-15 signaling, with chimeric antigen receptor (CAR) engineering of natural killer (NK) cells. This combined strategy boosted NK cell effector function through enhancing the Akt/mTORC1 axis and c-MYC signaling, resulting in increased aerobic glycolysis. When tested in a lymphoma mouse model, this combined approach improved NK cell anti-tumor activity more than either alteration alone, eradicating lymphoma xenografts without signs of any measurable toxicity. We conclude that combining CIS checkpoint deletion with CAR engineering promotes the metabolic fitness of NK cells in an otherwise suppressive tumor microenvironment. This approach, together with the prolonged survival afforded by CAR modification, represents a promising milestone in the development of the next generation of NK cells for cancer immunotherapy.

immunology↗

bioRxiv2020

Stiffness of Nanoparticulate Mineralized Collagen Scaffolds Triggers Osteogenesis via Mechanotransduction and Canonical Wnt Signaling

The ability of the extracellular matrix (ECM) to instruct progenitor cell differentiation has generated excitement for the development of materials-based regenerative solutions. We previously described a nanoparticulate mineralized collagen glycosaminoglycan (MC-GAG) material capable of inducing in vivo skull regeneration approaching 60% of the biomechanical properties of native calvarium without exogenous growth factors or ex vivo progenitor cell-priming, suggesting promise as a first-generation material for skull regeneration. Here, we evaluated the contribution of titrating stiffness to osteogenicity by comparing non-crosslinked (NX-MC) and crosslinked (MC) forms of MC-GAG. While both materials were osteogenic, MC demonstrated an increased expression of osteogenic markers and mineralization compared to NX-MC. Both materials were capable of autogenously activating the canonical bone morphogenetic protein receptor (BMPR) signaling pathway with phosphorylation of Smad1/5 (small mothers against decapentaplegic-1/5). However, unlike NX-MC, hMSCs cultured on MC demonstrated significant elevations in the major mechanotransduction mediators YAP (Yes-associated protein) and TAZ (transcriptional coactivator with PDZ-binding motif) expression coincident with {beta}-catenin activation in the canonical Wnt signaling pathway. Inhibition of YAP/TAZ activation reduced osteogenic marker expression, mineralization, and {beta}-catenin activation in MC with a much lesser of an effect on NX-MC. YAP/TAZ inhibition also resulted in a reciprocal increase in Smad1/5 phosphorylation as well as BMP2 expression. Our results indicate that increasing MC-GAG stiffness induces osteogenic differentiation via the mechanotransduction mediators YAP/TAZ and the canonical Wnt signaling pathway, whereas the canonical BMPR signaling pathway is activated in a manner independent of mechanical cues.

bioengineering↗