Biology subjects

Rong, H.

Publications and source records attributed to Rong, H..

7 recordsLinked to original sources

bioRxiv2024

Invasive cancer and spontaneous regression two weeks after papillomavirus infection

Development of invasive cancer in mammals is thought to require months or years after initial events such as mutation or viral infection. Rarely, invasive cancers regress spontaneously. We show that cancers can develop and regress on a timescale of weeks, not months or years. Invasive squamous cell carcinomas developed in normal adult, immune-competent mice as soon as 2 weeks after infection with mouse papillomavirus MmuPV1. Tumor development, regression or persistence was tissue- and strain-dependent. Cancers in infected mice developed rapidly at sites also prone to papillomavirus-induced tumors and cancers in humans - the throat, anus, and skin - and their frequency was increased in mice constitutively expressing the papillomavirus E5 oncogene, which MmuPV1 lacks. Cancers and dysplasia in the throat and anus regressed completely within 4-8 weeks of infection; however, skin lesions in the ear persisted. T-cell depletion in the mouse showed that regression of throat and anal tumors requires T cells. We conclude that papillomavirus infection suffices for rapid onset of invasive cancer, and persistence of lesions depends on factors including tissue type and host immunity. The speed of these events should promote rapid progress in the study of viral cancer development, persistence, and regression. Summary Graphic O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=112 SRC="FIGDIR/small/611275v1_ufig1.gif" ALT="Figure 1"> View larger version (33K): org.highwire.dtl.DTLVardef@1da9642org.highwire.dtl.DTLVardef@1bef109org.highwire.dtl.DTLVardef@c2ba0eorg.highwire.dtl.DTLVardef@451baf_HPS_FORMAT_FIGEXP M_FIG C_FIG

cancer biology↗

bioRxiv2023

eRNA-IDO: a one-stop platform for identification, interactome discovery and functional annotation of enhancer RNAs

Increasing evidence proves the transcription of enhancer RNA (eRNA) and its important role in gene regulation. However, we are only at the infancy stage of understanding eRNA interactions with other biomolecules and the corresponding functionality. To accelerate eRNA mechanistic study, we present the first integrative computational platform for human eRNA identification, interactome discovery, and functional annotation, termed eRNA-IDO. eRNA-IDO comprises two modules: eRNA-ID and eRNA-Anno. Functionally, eRNA-ID identifies eRNAs from de novo assembled transcriptomes. The bright spot of eRNA-ID is indeed the inclusion of 8 kinds of enhancer makers, whose combination enables users to personalize enhancer regions flexibly and conveniently. In addition, eRNA-Anno provides cell/tissue specific functional annotation for any novel and known eRNAs through discovering eRNA interactome from the prebuilt or user-defined eRNA-coding gene networks. The pre-built networks include GTEx-based normal co-expression networks, TCGA-based cancer co-expression networks, and omics-based eRNA-centric regulatory networks. Our eRNA-IDO carries sufficient practicability and significance for understanding the biogenesis and functions of eRNAs. The eRNA-IDO server is freely available at http://bioinfo.szbl.ac.cn/eRNA_IDO/.

bioinformatics↗

bioRxiv2023

Antisense transcription and its roles in adaption to environmental stress in E. coli

It has been reported that a highly varying proportion (1% [~] 93%) of genes in various prokaryotes have antisense RNA (asRNA) transcription. However, the extent of the pervasiveness of asRNA transcription in the well-studied E. coli K12 strain has thus far been an issue of debate. Furthermore, very little is known about the expression patterns and functions of asRNAs under various conditions. To fill these gaps, we determined the transcriptomes and proteomes of E. coli K12 at multiple time points in five culture conditions using strand-specific RNA-seq, differential RNA-seq, and quantitative mass spectrometry methods. To reduce artifacts of possible transcriptional noise, we identified asRNA using stringent criteria with biological replicate verification and transcription start sites (TSSs) information included. We identified a total of 660 asRNAs, which were generally short and largely condition-dependently transcribed. We found that the proportions of the genes which had asRNA transcription highly depended on the culture conditions and time points. We classified the transcriptional activities of the genes in six transcriptional modes according to their relative levels of asRNA to mRNA. Many genes changed their transcriptional modes at different time points of the culture conditions, and such transitions can be described in a well-defined manner. Intriguingly, the protein levels and mRNA levels of genes in the sense-only/sense-dominant mode were moderately correlated, but the same was not true for genes in the balanced/antisense-dominant mode, in which asRNAs were at a comparable or higher level to mRNAs. These observations were further validated by western blot on candidate genes, where an increase in asRNA transcription diminished gene expression in one case and enhanced it in another. These results suggest that asRNAs may directly or indirectly regulate translation by forming duplexes with cognate mRNAs. Thus, asRNAs may play an important role in the bacteriums responses to environmental changes during growth and adaption to different environments. IMPORTANCEThe cis-antisense RNA (asRNA) is a type of understudied RNA molecules in prokaryotes, which is believed to be important in regulating gene expression. Our current understanding of asRNA is constrained by inconsistent reports about its identification and properties. These discrepancies are partially caused by a lack of sufficient samples, biological replicates, and culture conditions. This study aimed to overcome these disadvantages and identified 660 putative asRNAs using integrated information from strand-specific RNA-seq, differential RNA-seq, and mass spectrometry methods. In addition, we explored the relative expression between asRNAs and sense RNAs and investigated asRNA regulated transcriptional activity changes over different culture conditions and time points. Our work strongly suggests that asRNAs may play a crucial role in bacteriums responses to environmental changes during growth and adaption to different environments.

genomics↗

bioRxiv2020

Spatial and Temporal Organization of Odor-evoked Responses in a Fly Olfactory Circuit: Inputs, Outputs and Idiosyncrasies

How is sensory information routed through different types of neurons within a circuit, and do equivalent circuits in different individuals follow similar organizational principles? We examined this issue in the fruit fly olfactory system. Odor-evoked signals from sensory neurons (ORNs) triggered neural responses that were patterned over space and time in cholinergic ePNs and GABAergic iPNs within the antennal lobe. The dendritic-axonal (I/O) response mapping was complex and diverse, and axonal organization was region-specific (mushroom body vs. lateral horn). In the lateral horn, feed-forward excitatory and inhibitory axonal projections matched odor tuning in a stereotyped, dorsal-lateral locus, but mismatched in most other locations. In the temporal dimension, ORN, ePN and iPN odor-evoked responses had similar encoding features, such as information refinement over time and divergent ON and OFF responses. Notably, analogous spatial and temporal coding principles were observed in all flies, and the latter emerged from idiosyncratic neural processing approaches. HighlightsO_LIConsistency and idiosyncrasy both exist in ORN, ePN and iPN functional maps C_LIO_LISignal transformations between different ePN compartments are complex and diverse C_LIO_LITemporal decorrelation between stimuli happens in all three neuronal populations C_LIO_LIOFF responses that are orthogonal to ON responses emerge after odor termination C_LI

neuroscience↗

bioRxiv2020

Profiles of Expression pattern and tissue distribution of host defense peptides genes in different chicken (Gallus gallus) breeds related to body weight

Host defense peptides (HDPs) are an important first line of defense with antimicrobial and immunomodulatory properties. Selection for increased body weight is suggested to be related to reduced immune response. We studied the relationships among body weight, age, and the HDP expression patterns in intestine and immune organs. We used chickens with marked differences of body sizes. The non-selected Daweishan mini chickens showed the highest indexes of immune organs and the lowest concentrations of the plasma immune parameters C3, C4, IgA, and IgY, while the commercial Avian broiler showed the opposite results. The Daweishan mini chickens showed the highest mRNA expressions of HDP genes in small intestine followed by the semi-selected Wuding chickens. Compared with local breeds, broiler chickens showed higher mRNA expression of HDP genes in spleen, thymus, and bursa. Body weight and HDP expression levels were negatively correlated in the intestine and positively in the immune organs. These results indicated that the HDP immune regulatory roles in small intestine acted as first line of defense in innate immunity in local breeds, and as an adaptive immunity in broiler chickens. Selection was associated with the expression profiles of HDP genes in a chicken, age, and organ-specific manner.

immunology↗

bioRxiv2020

Protein kinase Cϵ activation induces EHD-dependent degradation and downregulation of KATP channels: Implications for glucose stimulated insulin secretion

Pancreatic {beta}-cells have the unique ability to couple glucose metabolism to insulin secretion. This capacity is generally attributed to the ability of ATP to inhibit KATP channels, and the consequent {beta}-cell membrane depolarization and excitation. This notion has recently been challenged by a study which demonstrated that high glucose (HG) downregulates the cell surface KATP channels, and thereby leads to {beta}-cell depolarisation and excitation. The authors attributed the downregulation to HG-induced protein kinase C (PKC) activation and the consequent increase in channel endocytosis. This interpretation, however, is inconsistent with our previous findings that PKC activation does not affect endocytosis. To address this controversy, we revisited the problem: we have used cell biological and electrophysiological approaches combined with the pharmacological activator of PKC, PMA (phorbol 12-myristate 13-acetate). We first confirm that PKC does not play a role in KATP channel endocytosis; instead, it downregulates the channel by promoting lysosomal degradation coupled with reduced recycling. We then show that (i) mutation of the dileucine motif (355LL356) in the C-terminal domain of the Kir6.2 subunit of the KATP channel complex prevents lysosomal degradation; (ii) lysosomal targeting is mediated by the EHD (Eps15 homology domain- containing) proteins; and (iii) the PKC isoform responsible for channel degradation is PKC{varepsilon}. Taken together with the published data, we suggest that HG promotes {beta}-cell excitability via two mechanisms: ATP-dependent channel inhibition and ATP-independent, PKC{varepsilon}-dependent channel degradation. The results likely have implications for glucose induced biphasic insulin secretion.

cell biology↗

bioRxiv2017

Early warning signals regarding environmental suitability in the Drosophila antenna

HighlightsO_LIA novel geotaxis assay showed high intensity odorant exposures are harmful to flies\nC_LIO_LIRepulsion at high odor intensities can be a protective mechanism\nC_LIO_LIOlfactory receptor neuron (ORN) excitability abruptly changes with odor intensity\nC_LIO_LIA linear combination of ORN activities can robustly predict intensity-dependent behavioral repulsion\nC_LI\n\nSummaryThe olfactory system is uniquely positioned to warn an organism of environmental threats. Whether and how it encodes such information is not understood. Here, we examined this issue in the fruit fly Drosophila melanogaster. We found that intensity-dependent repulsion to chemicals safeguarded flies from harmful, high-intensity vapor exposures. To understand how sensory input changed as the odor valence switched from innocuous to threatening, we recorded from olfactory receptor neurons (ORNs) in the fly antenna. Primarily, we observed two response non-linearities: recruitment of non-active ORNs at higher intensities, and abrupt transitions in neural excitability from regular spiking to high-firing oscillatory regime. Although non-linearities observed in any single ORN was not a good indicator, a simple linear combination of firing events from multiple neurons provided robust recognition of threating/repulsive olfactory stimuli. In sum, our results reveal how information necessary to avoid environmental threats may also be encoded in the insect antenna.

neuroscience↗