Biology subjects

Zhou, L.

Publications and source records attributed to Zhou, L..

331 records · Page 19Linked to original sources

bioRxiv2018

Association mapping identified novel candidate loci affecting wood formation in Norway spruce

[tpltrtarr] Norway spruce (Picea abies) is an important boreal forest tree species of significant ecological and economic importance. Hence there is a strong imperative to dissect the genetics controlling important wood quality traits in the species.\n[tpltrtarr]We performed a functional genome-wide association mapping of 17 wood traits in Norway spruce using 178101 single-nucleotide polymorphisms (SNPs) generated from exome genotyping of 517 mother trees. The wood traits were defined using functional modelling of wood properties across annual growth rings.\n[tpltrtarr]Association mapping was performed using a multilocus LASSO penalized regression method and we detected a total of 51 significant SNPs from 39 candidate genes that are involved in wood formation.\n[tpltrtarr]Our study represents the first functional multi-locus genome-wide association mapping (AM) in Norway spruce. The results advance our understanding of the genetics influencing wood traits, identify novel candidate genes for further functional studies and support current Norway spruce breeding efforts.

genetics↗

bioRxiv2018

Efficient differentiation of vascular endothelial cells from dermal-derived mesenchymal stem cells induced by endothelial cell lines conditioned medium

ObjectiveTo directionally-differentiate dermis-derived mesenchymal stem cells (DMSCs) into vascular endothelial cells (VECs) in vitro, providing an experimental basis for studies on the pathogenesis and treatment of vascular diseases.\n\nMethodsAfter separation by adherent culture, VEC line supernatant, vascular endothelial growth factor (VEGF), bone morphogenetic protein-4 and hypoxia were used for the differentiation of VECs from DMSCs. The cell type was authenticated by flow cytometry, matrigel angiogenesis assay in vitro, and immunofluorescent staining during differentiation. The VEGF concentration was investigated by enzyme-linked immunosorbent assay.\n\nResultsAfter 28 days of differentiation, the cell surface marker CD31 was significantly positive (80%-90%) by flow cytometry in the VEC line-conditioned culture, which was significantly higher than in the other groups. Differentiated DMSCs had the ability to ingest Dil-ac-LDL and vascularize in the conditioned culture, but not in the other groups. In the VEC line supernatant, the concentration of VEGF was very low. The VEGF concentration changed along with the differentiation into VECs in the medium of the conditioned culture group.\n\nConclusionVEC line supernatant can induce the differentiation of DMSCs into VECs, possibly through the pathway except VEGF.

cell biology↗

bioRxiv2018

Gallic Acid Disrupts Aβ1-42 Aggregation and Rescues Cognitive Decline of APP/PS1 Transgenic Mouse

Alzheimers disease (AD) treatment represents one of the largest unmet medical needs. Developing drugs capable of preventing A{beta} aggregation is an excellent approach to prevent and treat AD. Here, we show that gallic acid (GA), a naturally occurring polyphenolic small molecule rich in grape seeds and fruits, has the capacity to alleviate cognitive decline of APP/PS1 transgenic mouse through reduction of A{beta}1-42 aggregation and neurotoxicity. Oral administration of GA not only improved the spatial reference memory and spatial working memory of early stage AD mice (4-month-old), but also significantly reduced the more severe deficits in spatial learning, reference memory, short-term recognition and spatial working memory of the late stage AD mice (9-month-old). The hippocampal long-term-potentiation (LTP) was also significantly elevated in the GA-treated late stage APP/PS1 AD mice. Atomic force microscopy (AFM), dynamic light scattering (DLS) and thioflavin T (ThT) fluorescence densitometry analyses showed that GA can reduce A{beta}1-42 aggregation from forming toxic oligomers and fibrils. Indeed, pre-incubating GA with oligomeric A{beta}1-42 reduced A{beta} 1-42-mediated intracellular calcium influx and neurotoxicity. Molecular docking studies identified that the 3,4,5-hydroxyle groups of GA were essential in noncovalently stabilizing GA binding to the Lys28-Ala42 salt bridge and the -COOH group is critical for disrupting the salt bridge of A{beta}1-42. The predicated covalent interaction through Schiff-base formation between the carbonyl group of the oxidized product and {varepsilon}-amino group of Lys16 is also critical for the disruption of A{beta}1-42 S-shaped triple-{beta}-motif and toxicity. Together, these studies demonstrated that GA can prevent and protect the AD brain through disrupting A{beta}1-42 aggregation.

neuroscience↗

bioRxiv2017

Genetic drivers of repeat expansion disorders localize to 3-D chromatin domain boundaries

More than 25 inherited neurological disorders are caused by the unstable expansion of repetitive DNA sequences termed short tandem repeats (STRs). A fundamental unresolved question is why specific STRs are susceptible to unstable expansion leading to severe pathology, whereas tens of thousands of normal-length repeat tracts across the human genome are relatively stable. Here, we unexpectedly discover that nearly all STRs associated with repeat expansion diseases are located at boundaries demarcating 3-D chromatin domains. We find that boundaries exhibit markedly higher CpG island density compared to loci internal to domains. Importantly, disease-associated STRs are specifically localized to ultra-dense CpG island-rich boundaries, suggesting that these loci might be hotspots for epigenetic instability and topological disruption upon unstable expansion. In Fragile X Syndrome, mutation-length expansion at the Fmr1 gene results in severe disruption of the boundary between TADs. Our data uncover higher-order chromatin architecture as a new dimension in understanding the mechanistic basis of repeat expansion disorders.

genomics↗

bioRxiv2017

Down-regulation of LRIG1 by miR-20a modulates gastric cancer multidrug resistance

Multidrug resistance (MDR) significantly restricts the clinical efficacy of gastric cancer (GC) chemotherapy, and it is critical to search novel targets to predict and overcome MDR. Leucine-rich repeats and immunoglobulin-like domains 1 (LRIG1) has been proved to be correlated with drug resistance in several cancers. The present study revealed that LRIG1 was overexpressed in chemo-sensitive GC tissues and decreased expression of LRIG1 predicted poor survival in GC patients. We observed that up-regulation of LRIG1 enhanced chemo-sensitivity in GC cells. Interestingly, miR-20a, which was overexpressed in GC MDR cell lines and tissues, was identified to regulate LRIG1 expression by directly targeting its 3'untranslated region. We also found that inhibition of miR-20a suppressed GC MDR, and up-regulation showed opposite effects. Moreover, we demonstrated that the miR-20a/LRIG1 axis regulated GC cell MDR through EGFR mediated PI3K/AKT and MAPK/ERK signaling pathways. Finally, LRIG1 expression in human GC tissues is inversely correlated with miR-20a and EGFR. Taken together, the newly identified miR-20a/LRIG1/EGFR link provides insight into the MDR process of GC, and targeting this axis represents a novel potential therapeutic strategy to block GC chemo-resistance.

cancer biology↗

bioRxiv2017

Maize leaf functional responses to drought episode and rewatering

Effects of crop growth and physiological activity to drought and irrigation regimes have been extensively studied; however, the responses of plant growth, morphological and photosynthetic behaviors to drought episodes and thereafter rewatering receive a less attention. This field experiment was carried out directly in situ at an agricultural ecosystem research station during 2015-2016, in a northeastern China, on the renowned northeastern maize production belt, where is being threatened by severe drought. A field automatic rain-shelter was used, and five irrigation regimes including control, four drought episodes, and rewatering treatments were established. The chlorophyll contents (SPAD values), light-saturated photosynthetic rate (Asat), and photosystem II actual quantum yield ({Phi}PSII), maximum quantum yield (Fv'/Fm') decreased at lower leaf positions and with plant development. Episodic drought effects on plant growth, leaf morphological traits and photosynthetic processes at both vegetative and reproductive stages were severely remarked, particularly at late development stage and with longer drought duration. The recovery of leaf functional traits of the plants experienced historical-drought following re-irrigating was not fully restored to the level of the plants subjected to ample and normal water status; and the strength of recovery was proportional to the persistence of pre-drought episodes. The relationship of Asat with SPAD depends on water status and plant development. A principal component analysis can well denote the change patterns in responses to water status treatments with plant development. The results may give an insight into how to understand the maize traits responses to drought episode and rewatering, and this also might assist the drought-stricken crops to cope with future climatic change.

plant biology↗

bioRxiv2016

Genome sequence of a diabetes-prone desert rodent reveals a mutation hotspot around the ParaHox gene cluster

The sand rat Psammomys obesus is a gerbil native to deserts of North Africa and the Middle East1. Sand rats survive with low caloric intake and when given high carbohydrate diets can become obese and develop type II diabetes2 which, in extreme cases, leads to pancreatic failure and death3,4. Previous studies have reported inability to detect the Pdx1 gene or protein in gerbils5-7, suggesting that absence of this key insulin-regulating homeobox gene might underlie diabetes susceptibility. Here we report sequencing of the sand rat genome and discovery of an extensive, mutationally-biased GC-rich genomic domain encompassing many essential genes, including the elusive Pdx1. The sequence of Pdx1 has been grossly affected by GC-biased mutation leading to the highest divergence observed in the animal kingdom. In addition to molecular insights into restricted caloric intake in a desert species, the discovery that specific chromosomal regions can be subject to elevated mutation rate has widespread significance to evolution.

evolutionary biology↗