Biology subjects

Meng, M.

Publications and source records attributed to Meng, M..

27 records · Page 2Linked to original sources

bioRxiv2022

Multiple omic investigations of freeze tolerance adaptation in the aquatic ectothermic vertebrate, the Amur sleeper

Freeze tolerance is an amazing overwintering strategy that enables ectotherms to occupy new niches and survive in cold climates. However, the genetic basis underpinning this ecologically relevant adaptation is largely unknown. Amur sleeper is the only known freeze-tolerant fish species that can overwinter with its entire body frozen in ice. Here, we sequenced the chromosome-level genome of the Amur sleeper and performed comparative genomic, transcriptomic, and metabolomic analyses to investigate this remarkable adaptation. Phylogenetic analyses showed that the Amur sleeper diverged from its close relative with no cold hardiness about 15.07 million years ago and revealed two unusual population expansions during the glacial epochs. Integrative omics data identified a synchronous regulation of genes and metabolites involved in hypometabolism and cellular stress response, and several related genes showed strong evidence of accelerated evolution and positive selection. Potential evolutionary innovations that might aid in freezing survival were found to be associated with the dynamic rearrangement of the cytoskeleton to maintain cell viability, redistribution of water and cryoprotectants to limit cell volume reduction, and inhibition in nerve activity to facilitate dormancy, demonstrating a coordinated evolution for this complex adaptation. Overall, our work provides valuable resources and opportunities to unveil the genetic basis of freeze tolerance adaptation in ectothermic vertebrates.

evolutionary biology↗

bioRxiv2021

Origins and timing of emerging lesions in advanced renal cell carcinoma

PurposeRenal cell carcinoma (RCC) with venous tumor thrombus (VTT) arising from the primary tumor occurs in 4-10% of cases and is associated with advanced disease. RCC with VTT and distant metastasis represents a unique clinical entity, and provides opportunities to examine the origins and relative timing of tumor lesion emergence and to identify molecular correlates with disease state. Experimental DesignWe performed genomic and evolutionary analyses on 16 RCC patients with VTT, with eight also having metastases, using multi-region exome and RNA sequencing. ResultsNo genomic alterations were specifically associated with the VTT or metastasis lesions; each tumor had multiple hallmark driver alterations, consistent with advanced disease state. We found that 21% (3/14) of clear-cell RCC cases could be assigned a previously defined "evolutionary subtype". Somatic mutation signatures were largely consistent with previously established RCC signatures, and showed low heterogeneity across regions of each tumor. Mismatch repair and homologous recombination ("BRCA-ness") deficiency signatures consistently co-occurred across most tumors, suggesting a pervasive role for intracellular DNA damage in RCC and the potential for related treatment strategies. Phylogenetic timing analysis of metastatic cases suggested that in most tumors, metastases branched from the primary tumor prior to formation of VTT and in some cases before diversification of the primary tumor. Both VTT and the earliest metastases were predicted to emerge many years prior to diagnosis. Transcriptional landscape analysis identified key differences distinguishing each lesion type from primary tumor: VTT upregulated TNF signaling and associated inflammatory pathways, whereas metastases upregulated MTOR signaling. ConclusionsOur results provide a map of how RCC tumors can evolve, with metastatic clones typically emerging early in RCC development and taking hold via MTOR signaling, and later formation of VTT via local inflammatory processes. Statement of Translational RelevanceRenal cell carcinoma (RCC) is a deadly and relatively common malignancy, which often presents as or progresses to metastatic disease. We used multi-region sequencing of RCC patients with venous tumor thrombus (VTT) and metastasis to ask how and when new lesions arise from the primary tumor, and what genomic factors contribute to their spread. Phylogenetic analysis of patients with VTT and co-presenting metastases suggested that in most cases, the VTT and metastases derive from distinct tumor clones. Moreover, metastatic clones often appear many years prior to diagnosis. We found that local TNF inflammation may contribute to VTT formation, whereas MTOR signaling is associated with metastases. Our study sheds light on the relationship of VTT and metastases, suggests therapeutic and biomarker strategies for RCC, and points to the need for early detection studies in RCC to better understand when metastases emerge and to identify at-risk patients.

cancer biology↗

bioRxiv2021

Emerged human-like facial expression representation in a deep convolutional neural network

Face identity and expression play critical roles in social communication. Recent research found that the deep convolutional neural networks (DCNNs) trained to recognize facial identities spontaneously learn features that support facial expression recognition, and vice versa, suggesting an integrated representation of facial identity and expression. In the present study, we found that the expression-selective units spontaneously emerged in a VGG-Face trained for facial identity recognition and tuned to distinct basic expressions. Importantly, they exhibited typical hallmarks of human expression perception, i.e., the facial expression confusion effect and categorical perception effect. We then investigated whether the emergence of expression-selective units is attributed to either face-specific experience or domain-general processing, by carrying out the same analysis on a VGG-16 trained for object classification and an untrained VGG-Face without any visual experience, both of them having the identical architecture with the pretrained VGG-Face. Although Similar expression-selective units were found in both DCNNs, they did not exhibit reliable human-like characteristics of facial expression perception. Taken together, our computational findings revealed the necessity of domain-specific visual experience of face identity for the development of facial expression perception, highlighting the contribution of nurture to form human-like facial expression perception. Beyond the weak equivalence between human and DCNNS at the input-output behavior, emerging simulated algorithms between models and humans could be established through domain-specific experience.

neuroscience↗

bioRxiv2021

Identification of essential β-oxidation genes and corresponding metabolites for estrogen degradation by actinobacteria

Steroidal estrogens (C18) are contaminants receiving increasing attention due to their endocrine-disrupting activities at sub-nanomolar concentrations. Although estrogens can be eliminated through photodegradation, microbial function is critical for removing estrogens from ecosystems devoid of sunlight exposure including activated sludge, soils, and aquatic sediments. Actinobacteria were found to be key estrogen degraders in manure-contaminated soils and estuarine sediments. Previously, we used the actinobacterium Rhodococcus sp. strain B50 as a model microorganism to identify two oxygenase genes, aedA and aedB, involved in the activation and subsequent cleavage of the estrogenic A-ring, respectively. However, genes responsible for the downstream degradation of estrogen A/B-rings remained completely unknown. In this study, we employed tiered comparative transcriptomics, gene disruption experiments, and mass spectrometry-based metabolite profile analysis to identify estrogen catabolic genes. We observed the up-regulation of thiolase-encoding aedF and aedK in the transcriptome of strain B50 grown with estrone. Consistently, two downstream estrogenic metabolites, 5-oxo-4-norestrogenic acid (C17) and 2,3,4-trinorestrogenic acid (C15), were accumulated in aedF- and aedK-disrupted strain B50 cultures. Disruption of fadD3 [3a-H-4(3-propanoate)-7a{beta}-methylhexahydro-1,5-indanedione (HIP)-coenzyme A ligase gene] in strain B50 resulted in apparent HIP accumulation in estrone-fed cultures, indicating the essential role of fadD3 in actinobacterial estrogen degradation. In addition, we detected a unique meta-cleavage product, 4,5-seco-estrogenic acid (C18), during actinobacterial estrogen degradation. Differentiating the estrogenic metabolite profile and degradation genes of actinobacteria and proteobacteria enables the cost-effective and time-saving identification of potential estrogen degraders in various ecosystems through liquid chromatography-mass spectrometry analysis and polymerase chain reaction-based functional assays.

microbiology↗

bioRxiv2021

Comberons from single cell transcriptomics in endothelial cells

VEGF inhibitor drugs have been successful, especially in ophthalmology, but not all patients respond to them. Combinations of drugs are likely to be needed for more effective therapies of angiogenesis-related diseases. In this paper we describe naturally occurring combinations of receptors in endothelial cells that might help to understand how cells communicate and to identify targets for drug combinations. We also develop and share a new software tool called DECNEO to identify them. Single-cell gene expression data are used to identify a set of co-expressed endothelial cell receptors, conserved among species (mice and humans) and enriched, within a network, of connections to up-regulated genes. This set includes several receptors previously shown to play a role in angiogenesis. Multiple statistical tests from large datasets, including an independent validation set, support the reproducibility, evolutionary conservation and role in angiogenesis of these naturally occurring combinations of receptors. We also show tissue-specific combinations and, in the case of choroid endothelial cells, consistency with both well-established and recent experimental findings, presented in a separate paper. The results and methods presented here advance the understanding of signaling to endothelial cells. The methods are generally applicable to the decoding of intercellular combinations of signals.

systems biology↗

bioRxiv2020

Genetic and metabolite biomarkers reveal actinobacteria-mediated estrogen biodegradation in urban estuarine sediment

Steroidal estrogens are often accumulated in urban estuarine sediments worldwide at microgram per gram levels. These aromatic steroids have been classified as endocrine disruptors with an EC50 at sub-nanomolar concentrations and classified as Group 1 carcinogens by the World Health Organization. Microbial degradation is a naturally occurring mechanism that mineralizes estrogens in the biosphere; however, the corresponding genes in estrogen-degrading actinobacteria remain unidentified. In this study, we identified a gene cluster encoding several putative estrogen-degrading genes in actinobacterium Rhodococcus sp. strain B50. Among them, the oecB and oecC genes involved in estrogenic A-ring cleavage were identified through gene-disruption experiments. We also detected the accumulation of two extracellular estrogenic metabolites, including pyridinestrone acid (PEA) and 3a-H-4(3-propanoate)-7a{beta}-methylhexahydro-1,5-indanedione (HIP), in the estrone-fed strain B50 cultures. Since actinobacterial oecC and proteobacterial oecC shared less than 40% sequence identity, oecC could serve as a specific biomarker to differentiate the contribution of actinobacteria and proteobacteria in environmental estrogen degradation. Therefore, oecC and the extracellular metabolites PEA and HIP were used as biomarkers to investigate estrogen biodegradation in an urban estuarine sediment. Interestingly, our data suggested that actinobacteria, rather than alpha-proteobacteria function in sewage treatment plants, are actively degrading estrogens in the urban estuarine sediment. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=139 SRC="FIGDIR/small/329094v1_ufig1.gif" ALT="Figure 1"> View larger version (93K): org.highwire.dtl.DTLVardef@17e1e23org.highwire.dtl.DTLVardef@ecc60borg.highwire.dtl.DTLVardef@be03d4org.highwire.dtl.DTLVardef@ed81d6_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LIIsolation of an estrogen-degrading actinobacterium Rhodococcus sp. strain B50 and establishment of a strain B50 genetic manipulation system. C_LIO_LIStrain B50 exhibits a two-fold estrogen degradation rate of that of estrogen-degrading alpha-proteobacteria under the same cultivation conditions. C_LIO_LIFunctional characterization of two oxygenase genes, oecB and oecC, involved in estrogenic A-ring cleavage in actinobacteria. C_LIO_LIIdentification of two extracellular estrogenic metabolites, PEA and HIP, in the estrone-fed strain B50 cultures. C_LIO_LIDetection of actinobacterial oecC sequences as well as PEA and HIP in the estrone-spiked urban estuarine sediments. C_LI

microbiology↗

bioRxiv2017

Systematic selection of reference genes for normalization of circulating RNA transcripts in pregnant women based on RNA-seq data

RNA transcripts circulating in peripheral blood represent an important source of non-invasive biomarkers. To accurately quantify the levels of a circulating transcript, one needs to normalize the data with internal control reference genes, which are detected at relatively constant levels across different blood samples. A few stably-expressed reference gene candidates have to be selected from transcriptome data before validation of their stable expression by reverse-transcription quantitative polymerase chain reaction. However, there is a lack of transcriptome, let alone whole-transcriptome, data from maternal blood. To overcome this shortfall, we performed RNA-seq on blood samples from women presented with preterm labor. Of 11215 exons detected in the maternal blood whole-transcriptome, we systematically identified a panel of 395 genes comprising exons that were detected at a coefficient of variation (CV) ranging from 7.75%-17.7%. Their levels were considerably less variable than any GAPDH exon (minimum CV, 27.3%). Upon validation, selected genes from this panel remained as more stably expressed than GAPDH in maternal blood. This panel is over-represented with genes involved with actin cytoskeleton, macromolecular complex and the integrin signaling pathway. This groundwork provides a starting point for systematically selecting reference gene candidates for normalizing the levels of circulating RNA transcripts in maternal blood.

genomics↗

bioRxiv2017

Dynamic interhemispheric coordination in face processing

Our conscious experience of the world is normally unified. The brain coordinates different processes from the left and right hemispheres into one experience. However, the neural mechanisms underlying interhemispheric coordination remain poorly understood. A mechanistic approach to understanding interhemispheric coordination is \"communication through coherence\" (Fries, 2005; 2015). Using a recently developed time-resolved psychophysics (Fiebelkorn, Saalmann, & Kastner, 2013; Landau & Fries, 2012; Song, Meng, Chen, Zhou, & Luo, 2014), combined with fMRI decoding method, we investigated the interhemispheric coordination through coherence, by focusing on a quintessential case of hemispheric lateralized brain function: face processing in the left and right fusiform face area (FFA). We observed coherent oscillatory fMRI multi-voxel patterns in the left and right FFA when two stimuli presented successively cross visual fields, either initiating coordination from the left hemisphere or right hemisphere. When interhemispheric coordination started from the dominant right hemisphere, a coherent 44{degrees} phase difference between the left and right FFA in 3-4 Hz was observed; whereas when interhemispheric coordination started from the non-dominant left hemisphere, a coherent -17{degrees} phase difference between the left and right FFA in 5.5-6.5 Hz was observed. These results suggest that different phase coherence might mediate the interhemispheric coordination of face perception, depending on whether the initiating hemisphere is dominant or non-dominant. Our findings provide compelling fMRI evidence for interhemispheric coordination through coherence. The time-resolved fMRI decoding approach would be a useful starting point for a more promising approach for future investigation in interhemispheric dynamic coordination with fine-grained spatial and temporal resolution.

neuroscience↗

bioRxiv2017

Fluctuations of fMRI activation patterns reveal theta-band dynamics of visual object priming

The brain dynamically creates predictions about upcoming stimuli to guide perception efficiently. Recent behavioral results suggest theta-band oscillations contribute to this prediction process, however litter is known about the underlying neural mechanism. Here, we combine fMRI and a time-resolved psychophysical paradigm to access fine temporal-scale profiles of the fluctuations of brain activation patterns corresponding to visual object priming. Specifically, multi-voxel activity patterns in the fusiform face area (FFA) and the parahippocampal place area (PPA) show temporal fluctuations at a theta-band (~5 Hz) rhythm. Importantly, the theta-band power in the FFA negatively correlates with reaction time, further indicating the critical role of the observed cortical theta oscillations. Moreover, alpha-band (~10 Hz) shows a dissociated spatial distribution, mainly linked to the occipital cortex. These findings, to our knowledge, are the first fMRI study that indicates temporal fluctuations of multi-voxel activity patterns and that demonstrates theta and alpha rhythms in relevant brain areas.

neuroscience↗