Biology subjects

Ning, C.

Publications and source records attributed to Ning, C..

27 records · Page 2Linked to original sources

bioRxiv2020

The genomic formation of First American ancestors in East and Northeast Asia

Upward Sun River 1, an individual from a unique burial of the Denali tradition in Alaska (11500 calBP), is considered a type representative of Ancient Beringians who split from other First Americans 22000-18000 calBP in Beringia. Using a new admixture graph model-comparison approach resistant to overfitting, we show that Ancient Beringians do not form the deepest American lineage, but instead harbor ancestry from a lineage more closely related to northern North Americans than to southern North Americans. Ancient Beringians also harbor substantial admixture from a lineage that did not contribute to other Native Americans: Amur River Basin populations represented by a newly reported site in northeastern China. Relying on these results, we propose a new model for the genomic formation of First American ancestors in Asia. One Sentence SummaryAncient Beringians do not form the deepest American lineage, but harbor admixture from Amur River Basin populations.

genetics↗

bioRxiv2020

MicroRNA-224 Promotes Cell Migration and Invasion by Targeting HOXA5 expression in Hepatocellular Carcinoma

MicroRNAs (miRNAs) are involved in the regulation of multiple cellular pathways and play a key role in the development and progression of tumor. Based on the cellular function of their targets, miRNAs play the role of oncogenes or tumor suppressor genes. Multiple studies have shown that abnormal expression of miRNAs has close relation with the incidence of HCC, but the mechanism of miRNAs in HCC still needs further research. In the present study, we showed that the overexpression of miR-224 can reduce the mRNA and protein expression of ADAM17 and HOXA5, the silencing of miR-224 can increase the protein expression of ADAM17 and HOXA5. Dual luciferase reporter assays showed that miR-224 can directly regulate the expression of ADAM17 and HOXA5. Importantly, we found that miR-224 positively regulates cell migration and invasion in HCC, miR-224 overexpression can promote the migration and invasion of BEL-7402 cell, and miR-224 silencing can suppress the migration and invasion of BEL-7402 cell. miR-224 overexpression can result in the redistribution of cell cycle, the cell percentage of S phase was increased significantly, the cell percentage of G1 phase was decreased significantly, and there is no noticeable change for the cell percentage of G2 phase. These results demonstrated that it may be exert the function of oncogenes in a particular link of cancer cell growth. In conclusion, these results suggest that miR-224 will become a promising biological target in the treatment strategy of hepatocellular carcinoma (HCC).

cancer biology↗

bioRxiv2020

A gustatory receptor tuned to the steroid plant hormone brassinolide in Plutella xylostella (Lepidoptera: Plutellidae)

Feeding and oviposition deterrents help phytophagous insects to identify host plants. The taste organs of phytophagous insects contain bitter gustatory receptors (GRs). To explore their function, we focused on PxylGr34, a bitter GR in Plutella xylostella (L.). We detected abundant PxylGr34 transcripts in the larval head and specific expression of PxylGr34 in the antennae of females. Analyses using the Xenopus oocyte expression system and two-electrode voltage-clamp recording showed that PxylGr34 is specifically tuned to the plant hormone brassinolide (BL) and its analog 24-epibrassinolide. Electrophysiological analyses revealed that the medial sensilla styloconica on the maxillary galea of the 4th instar larvae are responsive to BL. Dual-choice bioassays demonstrated that BL inhibits larval feeding and female ovipositing. Knock-down of PxylGr34 by RNAi abolished BL-induced feeding inhibition. These results shed light on gustatory coding mechanisms and deterrence of insect feeding and ovipositing, and may be useful for designing plant hormone-based pest management strategies.

ecology↗

bioRxiv2020

Rapid Epistatic Mixed Model Association Studies by Controlling Multiple Polygenic Effects

SummaryWe have developed a rapid mixed model algorithm for exhaustive genome-wide epistatic association analysis by controlling multiple polygenic effects. Our model can simultaneously handle additive by additive epistasis, dominance by dominance epistasis and additive by dominance epistasis, and account for intrasubject fluctuations due to individuals with repeated records. Furthermore, we suggest a simple but efficient approximate algorithm, which allows examination of all pairwise interactions in a remarkably fast manner of linear with population size. Application to publicly available yeast and human data has showed that our mixed model-based method has similar performance with simple linear model-based Plink on computational efficiency. It took less than 40 hours for the pairwise analysis of 5,000 individuals genotyped with roughly 350,000 SNPs with five threads on Intel Xeon E5 2.6GHz CPU. Availability and implementationSource codes are freely available at https://github.com/chaoning/GMAT.

bioinformatics↗

bioRxiv2018

Dedicated acetic acid preference coded by broad spectrum ionotropic receptors in a moth species

Acetic acid as one of the food related odorant cues attracts many insect species. In the moth Mythimna separata, the olfaction of acid was coded via multiple pathways including 3 sensilla types on the antennae and 3 glomeruli in the antennal lobes. Among, suitable dosages of acetic acid exclusively activated DC3 glomerulus that receives integrated projections across sensilla types, which drives attractiveness and feeding attempts of the moth. This circuit encodes broad spectrum ionotropic receptors 8a, 75q1 and 75q2 which were sufficient to confer acid responsiveness in Xenopus oocytes. Ir75q2 was expressed in vivo with Ir75q1 and it enhanced sensitivity of the receptor functional group toward acids. Furthermore, Ir75q1 and Ir75q2 are both necessary for the moth to conduct acetic acid induced reactions of sensilla, DC3 glomerulus as well as attractiveness. Together, it reveals that an indispensable tetramer IR-based unit is employed to fulfill acetic acid specialized preference under suitable dosages through balancing of transcription and peripheral coding. Understanding of the Ir75q1/2 olfactory pathway provides insights into investigations on acid sensory process in insects.\n\nAuthor SummaryThe preference to acids are common in various organisms, and it may involve both olfactory and gustatory reception. In particular, airborne acidity volatiles can be sensed through antennae of insects and later assessed to help locating foraging, mating, and egg laying sites. However, these stimulatory processes can only be delivered by suitable dosages of acids, as we all know that, high acidity could be fatal in most circumstances. To date, avoidance to acids has been well explained in insects, but attractiveness and its basis remain uncharted. In the brain of oriental armyworm Mythimna separata, we have located 3 olfactory pathways which may play roles in acetic acid reception. Fortunately, when acetic acid was applied at attractive dosages, it only activated 1 dedicated pathway among the three. Later we found that this attractiveness pathway employed two ionotropic receptor genes namely Ir75q1 and Ir75q2, to successfully deliver this trait. Both genes were necessary for the moth to conduct acetic acid preference, but their roles are different. Ir75q1 recognized the acetic acid ligand and Ir75q2 later amplify the sensitivity. By comparing with evidences from electrophysiology and brain imaging tests, we found that the expression bias of either of the two genes has caused the separation of the pathways. It has been revealed in this moth that a smart decision system for olfactory reception exists, and this system may extrapolate to other insect species, as Ir75q1 and Ir75q2 are commonly expressed in many insect families.

neuroscience↗

bioRxiv2018

Efficient Multivariate Analysis Algorithms for Longitudinal Genome-wide Association Studies

MotivationCurrent dynamic phenotyping system introduces time as an extra dimension to genome-wide association studies (GWAS), which helps to explore the mechanism of dynamical genetic control for complex longitudinal traits. However, existing methods for longitudinal GWAS either ignore the covariance among observations of different time points or encounter computational efficiency issues.\n\nResultsWe herein developed efficient genome-wide multivariate association algorithms (GMA) for longitudinal data. In contrast to existing univariate linear mixed model analyses, the proposed new method has improved statistic power for association detection and computational speed. In addition, the new method can analyze unbalanced longitudinal data with thousands of individuals and more than ten thousand records within a few hours. The corresponding time for balanced longitudinal data is just a few minutes.\n\nAvailability and ImplementationWe wrote a software package to implement the efficient algorithm named GMA (https://github.com/chaoning/GMA), which is available freely for interested users in relevant fields.

bioinformatics↗

bioRxiv2018

Mining unknown porcine protein isoforms by tissue-based map of proteome enhances the pig genome annotation

A lack of the complete pig proteome has left a gap in our knowledge of the pig genome and has restricted the feasibility of using pigs as a biomedical model. We developed the tissue-based proteome maps using 34 major normal pig tissues. A total of 7,319 unknown protein isoforms were identified and systematically characterized, including 3,703 novel protein isoforms, 669 protein isoforms from 460 genes symbolized beginning with LOC, and 2,947 protein isoforms without clear NCBI annotation in current pig reference genome. These newly identified protein isoforms were functionally annotated through profiling the pig transcriptome with high-throughput RNA sequencing (RNA-seq) of the same pig tissues, further improving the genome annotation of corresponding protein coding genes. Combining the well-annotated genes that having parallel expression pattern and subcellular witness, we predicted the tissue related subcellular components and potential function for these unknown proteins. Finally, we mined 3,656 orthologous genes for 49.95% of unknown protein isoforms across multiple species, referring to 65 KEGG pathways and 25 disease signaling pathways. These findings provided valuable insights and a rich resource for enhancing studies of pig genomics and biology as well as biomedical model application to human medicine.

genomics↗

bioRxiv2018

Identification of Novel Genes and Variations Associated to Glycolytic Potential Based on Pig Model

In livestock, glycolytic potential (GP) is a critical indicator for evaluating the meat quality. To date, two major genes protein kinase AMP-activated {gamma}3 non-catalytic subunit gene (PRKAG3) and phosphorylase kinase catalytic subunit gamma 1(PHKG1), and corresponding cause mutations influencing GP have been confirmed in pigs. Therefore, the aim of this study to identify the novel candidate genes and variations related to GP-related traits using a four-hybrid pig model [Pietrain (P)x Duroc (D)] x[(Landrace) x(Yorkshire)]. We totally constructed six RNA-seq libraries using longissimus dorsi (LD) muscles, and each library contained two higher GP (H) or two lower GP (L) individuals. A total of 525, 698 and 135 differentially expressed genes (DEGs) were identified between H11 vs L11, H9 vs L9, and H5 vs L5 groups using PossionDis method, respectively. Notably, we found 97 non-redundant DEGs were mapped to GP related QTLs from three paired comparison groups. Moreover, 69 DEGs were identified between H (H11, H9 and H5) and L (L11, L9 and L5) groups using NOIseq method. Additionally, 1,076 potential specific SNPs were figured out between H and L groups, and approximately 40 large Indels with a length [≥] 5bp were identified in each sequencing library. In conclusion, our data provide foundation for further confirming the key genes and the functional mutations affecting GP-related traits in pigs, and also pave the way for elucidating the underling molecular regulatory mechanisms of glycogen metabolism in future study. Moreover, this study might provide valuable information for study on human glycogen storage diseases.

genomics↗

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↗