Biology subjects

Ye, P.

Publications and source records attributed to Ye, P..

4 recordsLinked to original sources

bioRxiv2018

Hypothalamic transcriptome analysis reveals the neuroendocrine mechanisms in controlling broodiness of Muscovy duck (Cairina moschata)

Broodiness, one of the maternal behaviors and instincts for natural breeding in birds, is an interesting topic in reproductive biology. Broodiness in poultry is characterized by persistent nesting, usually associated with cessation of egg laying. The study of avian broodiness is essential for bird conservation breeding and commercial poultry industry. In this study, we examined the hypothalamus transcriptome of Muscovy duck in three reproductive stages, including egg-laying anaphase (LA), brooding prophase (BP) and brooding metaphase (BM). Differences in gene expression during the transition from egg-laying to broodiness were examined, and 155, 379, 292 differently expressed genes (DEGs) were obtained by pairwise comparisons of LA-vs-BP, LA-vs-BM and BP-vs-BM, respectively (fold change[≥] 1.5, P < 0.05). Gene Ontology Term (GO) enrichment analysis suggested a possible role of oxidative stress in the hypothalamus might invoke reproductive costs that potentially change genes expression. KEGG analysis revealed glutamatergic synapse, dopaminergic synapse, serotonergic synapse and GABAergic synapse pathway were significantly enriched, and regulator genes were identified. Eight gene expression patterns were illustrated by trend analysis and further clustered into three clusters. Additional six hub genes were identified through combining trend analysis and protein-protein interaction (PPI) analysis. Our results suggested that the cyclical mechanisms of reproductive function conversion include effects of oxidative stress, biosynthesis of neurotransmitters or their receptors, and interactions between glucocorticoids and thyroid hormones and regulatory genes. These candidate genes and biological pathways may be used as targets for artificial manipulation and marker-assisted breeding in the reproductive behavior.

animal behavior and cognition↗

bioRxiv2018

Heterogeneity of transposon expression and activation of the repressive network in human fetal germ cells

Epigenetic resetting in germ cells during development leads to the de-repression of transposable elements (TEs). piRNAs protect fetal germ cells from potentially harmful TEs by targeted destruction of mRNA and deposition of repressive epigenetic marks. Here we provide the first evidence for an active piRNA pathway and TE repression in germ cells of human fetal testis. We identify pre-pachytene piRNAs with features of secondary amplification that map most abundantly to L1 family TEs. We find that L1-ORF1p expression is heterogeneous in fetal germ cells, peaks at mid-gestation and declines concomitantly with increasing levels of piRNAs and H3K9me3, as well as nuclear localization of HIWI2. Surprisingly, following this decline, the same cells with accumulation of L1-ORF1p display highest levels of HIWI2 and H3K9me3, whereas L1-ORF1p low cells are also low in HIWI2 and H3K9me3. Conversely, earlier in development, the germ cells lacking L1-ORF1p express high levels of the chaperone HSP90a. We propose that a subset of HSP90a-armed germ cells resists L1 expression, whereas only those vulnerable L1-expressing germ cells activate the PIWI-piRNA repression pathway which leads to epigenetic silencing of L1 via H3K9me3.

developmental biology↗

bioRxiv2018

Identification of a Novel Neutralizing and Two Non-Neutralizing Epitopes on Epstein-Barr Virus gp350 Protein

Prevention of Epstein-Barr virus (EBV) primary infection has focused on generating neutralizing antibodies (nAbs) targeting the major envelope glycoprotein gp350/220 (gp350). To date, eight gp350 epitopes have been identified, but only one has elicited nAbs. In this study, we generated 23 hybridomas that produced anti-gp350 antibodies. We compared the candidate anti-gp350 antibodies to nAb-72A1 by: (1) testing their ability to detect gp350 using ELISA, flow cytometry, and immunoblot; (2) sequencing their heavy and light chain complementarity-determining regions (CDRs); (3) measuring the ability of each monoclonal antibody (mAb) to neutralize EBV infection in vitro; and (4) mapping the gp350 amino acids bound by the mAbs using RepliTope peptide microarrays. Eight antibodies recognized both denatured and non-denatured gp350, whereas five failed to react with denatured gp350 but recognized native gp350, suggesting they recognized conformational epitope(s). Sequence analysis of the heavy and light chain variable regions of the hybridomas identified 15 as mAbs with novel CDR regions unique from those of nAb-72A1. Seven of the new mAbs neutralized EBV in vitro, with HB20 and HB17 reducing EBV infection by 40% and >60%, and >30% and 80%, at 10 g/ml and 50 g/ml, respectively. Epitope mapping identified nine epitopes and defined their core residues, including two unique immunodominant epitopes, 253TPIPGTGYAYSLRLTPRPVSRFL253 and 875LLLLVMADCAFRRNLSTSHTYTTPPY899, and a novel nAb epitope 381GAFASNRTFDIT392. This study provides comprehensive in vitro mapping of the exact residues defining nine epitopes of EBV gp350. Our findings will inform novel strategies to design optimal EBV vaccines capable of conferring broader protection against the virus.\n\nImportanceNeutralizing antibodies (nAbs) directed against Epstein-Barr virus envelope glycoprotein gp350/220 (gp350) are generated in humans upon infection or immunization, and are thought to prevent neonatal infection. However, clinical use of exogenous nAbs (passive immunization) is limited to a single study using the only well-characterized nAb, 72A1. The gp350 ectodomain contains at least eight unique B-cell binding epitopes; two of these epitopes are recognized by nAb-72A1. The exact amino acid residues of the other six epitopes and their role in generating nAbs has not been elucidated. We used our 15 newly generated and fully characterized monoclonal antibodies and a peptide-overlapping RepliTope array to provide a comprehensive map of the core amino acid residues that define epitopes of gp350 and to understand their role in generating nAbs. These results will inform design of better-targeted gp350 peptide vaccines that contain only protective epitopes, which will focus the B-cell response to produce predominantly nAbs.

immunology↗

bioRxiv2017

Physical mechanisms of ultrasonic neurostimulation of the retina

Focused ultrasound has been shown to be effective at stimulating neurons in vivo, ex vivo and in vitro preparations. Ultrasonic neuromodulation is the only non-invasive method of stimulation that could reach deep in the brain with high spatial-temporal resolution, and thus has potential for use in clinical applications and basic studies of the nervous system. Understanding the physical mechanism by which energy in a high acoustic frequency wave is delivered to stimulate neurons will be important to optimize this technology. Two primary candidates for a physical mechanism are radiation force, the delivery of momentum by the acoustic wave, and cavitation, oscillating gas bubbles. We imaged the isolated salamander retina during ultrasonic stimuli that drive ganglion cell activity and observed micron scale displacements consistent with radiation force. We recorded ganglion cell spiking activity with a planar multielectrode array and changed the acoustic carrier frequency across a broad range (0.5 - 43 MHz), finding that increased stimulation occurs at higher acoustic frequencies, a result that is consistent with radiation force but not cavitation. A quantitative radiation force model can explain retinal responses, and could potentially explain previous in vivo results in the mouse, suggesting a new hypothesis to be tested in vivo. Finally, we found that neural activity was strongly modulated by the distance between the transducer and the electrode array showing the influence of standing waves on the response. We conclude that radiation force is the physical mechanism underlying ultrasonic neurostimulation in the ex vivo retina, and that the control of standing waves is a new potential method to modulate these effects.

neuroscience↗