Biology subjects

Wei, P.

Publications and source records attributed to Wei, P..

58 records · Page 4Linked to original sources

bioRxiv2019

Comprehensive circular RNA expression profiles in intermuscular fat from lean and obese pigs

Circular RNA (circRNA) plays an important regulatory role in development and differentiation. Intermuscular fat in pork affects the tenderness and juiciness of the meat. In this study, we investigated the performances of Landrace (lean) and Jinhua (obese) pigs at the fattening period and explored the expression profile of circRNAs in intermuscular fat from the two breeds by Illumina high-throughput sequencing. we identified 5 548 circRNAs, specifically 2 651 (47.78%) in the Jinhua pigs, and 2 897 (52.22%) in the Landrace pigs. A totale of 809 differentially expressed circRNAs were observed between the the Jinhua and Landrace pigs, but only 29 of these circRNAs showed significant difference (19 upregulated and 10 downregulated). All 1 306 unigenes and 27 differentially expressed unigenesinvolved in lipid transport and metabolism; replication, recombination and repair; and signaling pathway were annotated. A total of 550 target miRNAs were perfect seed matches and 20 522 target genes were foundBy RNAhybrid and miRanda software prediction. Results from real-time quantitative PCR also confirmed the differential expression of 13 mRNAs between the two pig breeds. This study provides comprehensive expression profiles of circRNAs in Sus scrofa adipose metabolism and development, which can be used to clarify their functions. Summary statementThe paper explored the expression profile of circRNAs in intermuscular fat from Landrace and Jinhua pigs at the fattening period, to provide insights into circRNAregulation in animal adipose metabolism.

molecular biology↗

bioRxiv2018

A VTA GABAergic neural circuit mediates visually evoked innate defensive responses

Innate defensive responses are essential for animal survival and are conserved across species. The ventral tegmental area (VTA) plays important roles in learned appetitive and aversive behaviors, but whether it plays a role in mediating or modulating innate defensive responses is currently unknown. We report that GABAergic neurons in the mouse VTA (VTAGABA+) are preferentially activated compared to VTA dopaminergic (VTADA+) neurons when a threatening visual stimulus evokes innate defensive behavior. Functional manipulation of these neurons showed that activation of VTAGABA+ neurons is indispensable for looming-evoked defensive flight behavior and photoactivation of these neurons is sufficient for looming-evoked defensive-like flight behavior, whereas no such role can be attributed for VTADA+ neurons. Viral tracing and in vivo and in vitro electrophysiological recordings showed that VTAGABA+ neurons receive direct excitatory inputs from the superior colliculus (SC). Furthermore, we showed that glutamatergic SC-VTA projections synapse onto VTAGABA+ neurons that project to the central nucleus of the amygdala (CeA) and that the CeA is involved in mediating the defensive behavior. Our findings demonstrate that visual information about aerial threats access to the VTAGABA+ neurons mediating innate behavioral responses, suggesting a more general role for the VTA.

neuroscience↗

bioRxiv2018

Dysregulation of EMT Drives the Progression to Clinically Aggressive Sarcomatoid Bladder Cancer

The sarcomatoid variant of urothelial bladder cancer (SARC) displays a high propensity for distant metastasis and is associated with short survival. We report a comprehensive genomic analysis of 28 cases of SARCs and 84 cases of conventional urothelial carcinomas (UCs), with the TCGA cohort of 408 muscle-invasive bladder cancers serving as the reference. SARCs showed a distinct mutational landscape with enrichment of TP53, RB1, and PIK3CA mutations. They were related to the basal molecular subtype of conventional UCs and could be divided into epithelial/basal and more clinically aggressive mesenchymal subsets based on TP63 and its target genes expression levels. Other analyses revealed that SARCs are driven by downregulation of homotypic adherence genes and dysregulation of cell cycle and EMT networks, and nearly half exhibited a heavily infiltrated immune phenotype. Our observations have important implications for prognostication and the development of more effective therapies for this highly lethal variant of bladder cancer.

genomics↗

bioRxiv2018

FunSPU: a versatile and adaptive multiple functional annotation-based association test of whole-genome sequencing data

Despite ongoing large-scale population-based whole-genome sequencing (WGS) projects such as the NIH NHLBI TOPMed program and the NHGRI Genome Sequencing Program, WGS-based association analysis of complex traits remains a tremendous challenge due to the large number of rare variants, many of which are non-trait-associated neutral variants. External biological knowledge, such as functional annotations based on ENCODE, may be helpful in distinguishing causal rare variants from neutral ones; however, each functional annotation can only provide certain aspects of the biological functions. Our knowledge for selecting informative annotations a priori is limited, and incorporating non-informative annotations will introduce noise and lose power. We propose FunSPU, a versatile and adaptive test that incorporates multiple biological annotations and is adaptive at both the annotation and variant levels and thus maintains high power even in the presence of noninformative annotations. In addition to extensive simulations, we illustrate our proposed test using the TWINSUK cohort (n=1,752) of UK10K WGS data based on six functional annotations: CADD, RegulomeDB, FunSeq, Funseq2, GERP++, and GenoSkyline. We identified genome-wide significant genetic loci on chromosome 19 near gene TOMM40 and APOC4-APOC2 associated with low-density lipoprotein (LDL), which are replicated in the UK10K ALSPAC cohort (n=1,497). These replicated LDL-associated loci were missed by existing rare variant association tests that either ignore external biological information or rely on a single source of biological knowledge. We have implemented the proposed test in an R package \"FunSPU\".

genetics↗