Biology subjects

Ma, J.

Publications and source records attributed to Ma, J..

At least 415 records · Page 23Linked to original sources

bioRxiv2019

Ketamine anesthesia induces gain enhancement via recurrent excitation in granular input layers of the auditory cortex

The N-methyl-D-aspartate (NMDA) receptor antagonist, ketamine, is commonly used as an anesthetic agent and has more recently gained attention as an antidepressant. Ketamine has been linked to increased stimulus-locked excitability, inhibition of interneurons, and modulation of intrinsic neuronal oscillations. However, the functional network mechanisms are still elusive. A better understanding of these anesthetic network effects may improve upon previous interpretations of seminal studies conducted under anesthesia and have widespread relevance for neuroscience with awake and anesthetized subjects as well as in medicine. Here, we investigated the effects of anesthetic doses of ketamine (15mg kg-1/h i.p.) on the network activity after pure tone stimulation within the auditory cortex of male Mongolian gerbils (Meriones unguiculatus). We used laminar current source density (CSD) analysis and subsequent layer-specific continuous wavelet analysis to investigate spatiotemporal response dynamics on cortical columnar processing in awake and ketamine-anesthetized animals. We found thalamocortical input processing within granular layers III/IV to be significantly increased under ketamine. This effect on early thalamocortical input processing was not due to changes in cross-trial phase coherence. Rather, the layer-dependent gain enhancement under ketamine was attributed to a broadband increase in amplitude reflecting an increase in recurrent excitation. The time-frequency analysis is further indicative of a prolonged period of stimulus-induced excitation possibly due to a reduced coupling of excitation and inhibition in granular input circuits--in line with the common hypothesis of cortical disinhibition via NMDA-mediated suppression of GABAergic interneurons.\n\nStatement of significanceKetamine is a common anesthetic agent and is known to alter excitability and neuronal synchronicity in the cortex. We reveal here that anesthetic doses of ketamine increase recurrent excitation of thalamic input in the granular layers of the auditory cortex of Mongolian gerbils. This leads to a layer-specific gain enhancement of the time-locked response to external stimuli. Analysis of tone-evoked amplitudes and cross-trial variability of cortical current sources and sinks indicate a mechanism of cortical disinhibition via NMDA-mediated suppression of GABAergic interneurons. Our findings might help to understand the functional mechanisms of the clinical effects of ketamine promoting the development of new therapeutic agents with lower side effects.

neuroscience↗

bioRxiv2019

An evaluation model for aboveground biomass Based on Hyperspectral Data from field and TM8 in Khorchin grassland, China

Biomass is an important indicator for monitoring vegetation degradation and productivity. This study tests the applicability of Hyperspectral Remote-Sensing in situ measurements for high-precision estimation aboveground biomass (AGB) on regional scales of Khorchin grassland landscape in Inner Mongolia, China. Field experiments were carried out which collected hyperspectral data with a portable visible/NIR hyperspectral spectrometer (SOC 710), and collected aboveground net primary productivity (ANPP). Ground spectral models were then developed to estimate ANPP from the normalized difference vegetation index (NDVI), which was measured in the field following the same method as that of the Thematic Mapper(TM) from the Landsat 8 land imager (TM_NDVI). Regression analysis was used to assess the relationship between ANPP and NDVI based on coefficients of determination (R2) and error analysis. The estimation of ANPP had unique optimal regression models. By comparing the different spectral inversion models, we selected an exponential model associating ANPP with NDVI (ANPP = 12.523*e3.370*(0.462*TM_NDVI+0.413), standard error = 24.74 g m-2, R2 = 0.636, P < 0.001). This study suggests that the model can be used to monitor the condition and estimate the productivity of grassland at regional scales. The results still show a high potential to map grassland degradation proxies on the ground hyperspectral model. Thus, this study presents biomass hyperspectral inversion technology to remotely detect and monitor grassland degradation and productivity at high precision.

ecology↗

bioRxiv2019

Improving personalized prediction of cancer prognoses with clonal evolution models

Cancer occurs via an accumulation of somatic genomic alterations in a process of clonal evolution. There has been intensive study of potential causal mutations driving cancer development and progression. However, much recent evidence suggests that tumor evolution is normally driven by a variety of mechanisms of somatic hypermutability, known as mutator phenotypes, which act in different combinations or degrees in different cancers. Here we explore the question of how and to which degree different mutator phenotypes act in a cancer predict its future progression. We develop a computational paradigm using evolutionary tree inference (tumor phylogeny) algorithms to derive features quantifying single-tumor mutational preferences, followed by a machine learning frame-work to identify key features predictive of progression. We build phylogenies tracing the evolution of subclones of cells in tumor tissues using a variety of somatic genomic alterations, including single nucleotide variations, copy number alterations, and structural variations. We demonstrate that mutation preference features derived from the phylogenies are predictive of clinical outcomes of cancer progression - overall survival and disease-free survival - based on the analyses on breast invasive carcinoma, lung adenocarcinoma, and lung squamous cell carcinoma. We further show that mutational phenotypes have predictive power even after accounting for traditional clinical and driver-centric predictors of progression. These results confirm the power of mutational phenotypes as an independent class of predictive biomarkers and suggest a strategy for enhancing the predictive power of conventional clinical or driver-centric genomic features.

cancer biology↗

bioRxiv2019

Variations of gut microbiome profile under different storage conditions and preservation periods: A multi-dimensional evaluation

Gut dysbiosis contributes to the development of various human diseases. There are thousands of publications per year for investigating the role of gut microbiota in development of various diseases. However, emerging evidence has indicated data inconsistency between different studies frequently, but gained very little attention by scientists. There are many factors that can cause data variation and inconsistency during the process of microbiota study, in particular, sample storage conditions and subsequent sequencing process. Here, we systemically evaluated the impacts of six fecal sample storage conditions (including -80 {degrees}C, -80 {degrees}C with 70% ethanol (ET_-80 {degrees}C), 4{degrees}C with 70% ethanol (ET_4{degrees}C), and three commercial storage reagents including OMNIgene*GUT OMR-200 (GT), MGIEasy (MGIE), and Longsee (LS)), storage periods (1, 2 weeks or 6 months), and sequencing platform on gut microbiome profile using 16S rRNA gene sequencing. Our results suggested that -80{degrees}C is acceptable for fecal sample storage, and the addition of 70% ethanol offers some benefits. Meanwhile, we found that samples in ET_4 {degrees}Cand GT reagents are comparable, both introduced multi-dimensional variations. The use of MGIE resulted in the least alteration, while the greatest changes were observed in samples stored in LS reagents during the whole experiment. Finally, we also confirmed that variations caused by storage condition were larger than that of storage time and sequencing platform.\n\nIMPORTANCEIn the current study, we performed a multi-dimensional evaluation on the variations introduced by types of storage conditions, preservation period and sequencing platform on the basis of data acquired from 16S rRNA gene sequencing. The efficacy of preservation methods was comprehensively evaluated by DNA yield and quality, and {beta} diversity, relative abundance of the dominant bacteria and functional bacteria associated with SCFAs producing and BAs metabolism. Our results confirmed that variations introduced by storage condition were larger than that of storage periods and sequencing platform. Collectively, our study provided a comprehensive view to the impacts of storage conditions, storage times, and sequencing platform on gut microbial profile.

microbiology↗

bioRxiv2019

MACF1 Facilitates SMAD7 Nuclear Translocation to Drive Bone Formation in Mice

MACF1 is a large crosslinker that contributes to cytoskeleton integrity and cell differentiation. Loss of MACF1 impairs multiple cellular functions in neuron development and epidermal migration, and is the molecular basis for many diseases such as heart failure and Parkinsons disease. MACF1 is highly abundant in bones, however, its involvements in osteogenic differentiation and bone formation are still unknown. In this study, by conditional gene targeting to delete the Macf1 gene specifically in MSCs, we observed ossification retardation and bone loss in MACF1 deficient mice in different developmental stages, which we traced to disorganized cytoskeleton and decreased osteogenic differentiation capability in MSCs. Further, we show that MACF1 interacts and facilitates SMAD7 nuclear translocation to initiate downstream transcription. These findings are hopefully to expand the biological scope of MACF1 in bones, and provide experimental basis for targeting MACF1 in degenerative bone diseases such as osteoporosis.

developmental biology↗

bioRxiv2019

PI16 is a non-neuronal regulator of neuropathic pain

Chronic pain is a major clinical problem of which the mechanisms are incompletely understood. Here we describe the concept that PI16, a protein of unknown function mainly produced by fibroblasts, controls neuropathic pain. The spared nerve injury model of neuropathic pain increases PI16 protein levels in fibroblasts in DRG meninges and in the epi/perineurium of the sciatic nerve. We did not detect PI16 expression in neurons or glia in spinal cord, DRG and nerve. Mice deficient in PI16 are protected against neuropathic pain. In vitro, PI16 promotes trans-endothelial leukocyte migration. In vivo, PI16-/- mice show reduced endothelial barrier permeability, lower leukocyte infiltration and reduced activation of the endothelial barrier regulator MLCK and reduced phosphorylation of its substrate MLC2 in response to SNI. In summary, our findings support a model in which PI16 promotes neuropathic pain by mediating a cross talk between fibroblasts and the endothelial barrier leading to barrier opening, cellular influx and increased pain. Its key role in pain and its limited cellular and tissue distribution makes PI16 an attractive target for pain management.\n\nGraphical Abstract\n\nO_FIG O_LINKSMALLFIG WIDTH=128 HEIGHT=200 SRC=\"FIGDIR/small/696542v1_ufig1.gif\" ALT=\"Figure 1\">\nView larger version (22K):\norg.highwire.dtl.DTLVardef@172f530org.highwire.dtl.DTLVardef@3f62a8org.highwire.dtl.DTLVardef@16606ccorg.highwire.dtl.DTLVardef@1485156_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2019

High risk of the Fall Armyworm invading into Japan and the Korean Peninsula via overseas migration

The fall armyworm, Spodoptera frugiperda (J.E. Smith) is an emerging and most severe pest species in the Old World. It is originally native in the Americas. Since 2016 it has spread widely and rapidly to throughout Africa, the Middle East, India, Southeast Asia and most recently southern China. By May 2019 it has appeared in 13 provinces in most southern China and would spread further to northern China. It is highly likely that S. frugiperda would enter into Japan and Korea via overseas migrations as many other migratory pests did before. To evaluate the invasion risk of S. frugiperda into Japan and Korean Peninsula, we modelled the rate of expansion and future potential migratory range of the insect by a trajectory analytical approach with flight behaviour of S. frugiperda implemented, and meteorological data of past five years (2014-2018) used. Our results predicted that S. frugiperda would migrate from southern and eastern China into Japan and Korea soon. Most likely, Japan would be invaded from Fujian and Zhejiang on 1 June - 15 July, and Kyushu, Shikoku and south-western Honshu could face the highest risk of S. frugiperdas invasion. Korea would be most possibly reached by S. frugiperda from northern Zhejiang, Jiangsu, Anhui, and Shandong on 1 June - 15 July and later. Our results indicated a very high risk that S. frugiperda would annually invade Japan and the Korean Peninsula and cause a possible significant decrease in agricultural productivity.

animal behavior and cognition↗

bioRxiv2019

GATA2 controls lymphatic endothelial cell junctional integrity and lymphovenous valve morphogenesis through miR-126

Mutations in the transcription factor GATA2 cause lymphedema. GATA2 is necessary for the development of lymphatic valves (LVs) and lymphovenous valves (LVVs), and for the patterning of lymphatic vessels. Here, we report that GATA2 is not necessary for valvular endothelial cell (VEC) differentiation. Instead, GATA2 is required for VEC maintenance and morphogenesis. GATA2 is also necessary for the expression of cell junction molecules VE-Cadherin and Claudin5 in lymphatic vessels. We identified miR-126 as a target of GATA2, and miR-126-/- embryos recapitulate the phenotypes of mice lacking GATA2. Primary human lymphatic endothelial cells (HLECs) lacking GATA2 (GATA2{Delta}HLEC) have altered expression of Claudin5 and VE-Cadherin, and blocking miR-126 activity in HLECs phenocopies these changes in expression. Importantly, overexpression of miR-126 in GATA2{Delta}HLEC significantly rescues the cell junction defects. Thus, our work defines a new mechanism of GATA2 and uncovers miR-126 as a novel regulator of mammalian lymphatic vascular development.\n\nNon-standard abbreviationsLECs, lymphatic endothelial cells; LVs, lymphatic valves; LV-ECs, lymphatic valve-forming endothelial cells; LVVs, lymphovenous valves; LVV-ECs, lymphovenous valve-forming endothelial cells; HLEC, primary human LECs; OSS, Oscillatory shear stress; IHC, immunohistochemistry.

developmental biology↗

bioRxiv2019

Inhibition of ADORA1 attenuates hepatic steatosis by gut microbiota-derived acetic acid from Astragalus polysaccharides

The authors have withdrawn this manuscript, because some data could not be replicated. During the process of subsequent revision of the manuscript, we separated the data into two parts. The majority data of the preprint draft, the anti-NAFLD effect of Astragalus polysaccharides (APS) in mice and the contribution of gut microbiota, were independently published in 2021 after substantial revision (doi: https://doi.org/10.1080/19490976.2021.1930874). However, the data on figure 6 (about ARs inhibitors DPCPX orally ameliorating NAFLD in mice, and Adora1 si-RNA data in vitro) could not be fully replicated in subsequent experiments. The most probable reason might be due to the batch differences of mice / cells, or other undetermined factors during experiment. Moreover, we have carried out in-depth studies on the exact role of hepatic A1R on NAFLD formation, which is opposite to our prior assumption. Therefore, we do not wish this work to be cited as reference for the project. We apologize for any inconvenience caused to our readers. Any questions can be addressed to first/corresponding author.

physiology↗

bioRxiv2019

Prediction of migratory routes of the invasive fall armyworm in eastern China using a trajectory analytical approach

BACKGROUNDThe fall armyworm (FAW), an invasive pest from the Americas, is rapidly spreading through the Old World, and has recently invaded the Indochinese Peninsula and southern China. In the Americas, FAW migrates from winter-breeding areas in the south into summer-breeding areas throughout North America where it is a major pest of corn. Asian populations are also likely to evolve migrations into the corn-producing regions of eastern China, where they will pose a serious threat to food security.\n\nRESULTSTo evaluate the invasion risk in eastern China, the rate of expansion and future migratory range was modelled by a trajectory simulation approach, combined with flight behaviour and meteorological data. Our results predict that FAW will migrate from its new year-round breeding regions into the two main corn-producing regions of eastern China (the North China and Northeast China Plains), via two pathways. The western pathway originates in Myanmar and Yunnan, and FAW will take four migration steps to reach the North China Plain by July. Migration along the eastern pathway from Indochina and southern China progresses faster, with FAW reaching the North China Plain in three steps by June and reaching the Northeast China Plain in July.\n\nCONCLUSIONOur results indicate that there is a high risk that FAW will invade the major corn-producing areas of eastern China via two migration pathways, and cause significant impacts to agricultural productivity. Information on migration pathways and timings can be used to inform integrated pest management strategies for this emerging pest.

animal behavior and cognition↗

bioRxiv2019

Biological Structure and Function Emerge from Scaling Unsupervised Learning to 250 Million Protein Sequences

In the field of artificial intelligence, a combination of scale in data and model capacity enabled by un-supervised learning has led to major advances in representation learning and statistical generation. In the life sciences, the anticipated growth of sequencing promises unprecedented data on natural sequence diversity. Protein language modeling at the scale of evolution is a logical step toward predictive and generative artificial intelligence for biology. To this end we use unsupervised learning to train a deep contextual language model on 86 billion amino acids across 250 million protein sequences spanning evolutionary diversity. The resulting model contains information about biological properties in its representations. The representations are learned from sequence data alone. The learned representation space has a multi-scale organization reflecting structure from the level of biochemical properties of amino acids to remote homology of proteins. Information about secondary and tertiary structure is encoded in the representations and can be identified by linear projections. Representation learning produces features that generalize across a range of applications, enabling state-of-the-art supervised prediction of mutational effect and secondary structure, and improving state-of-the-art features for long-range contact prediction.

synthetic biology↗

bioRxiv2019

TRIM21-SERPINB5 aids GMPS repression to protect nasopharyngeal carcinoma cells from radiation-induced apoptosis

Nasopharyngeal carcinoma (NPC) is the most prevalent head and neck malignancy in South China and Southeast Asia. The main NPC treatment strategy is radiotherapy. However, recurrence resulting from radioresistance is a leading clinical bottleneck. Revealing the mechanism of NPC radioresistance would help improve the therapeutic effect. Here, our work reveals that TRIM21 (tripartite motif-containing 21) functions as an oncogene in NPC progression, and its ablation increases NPC cell radiosensitivity. Further analysis indicated that TRIM21 represses TP53 expression by mediating GMPS (guanine monophosphate synthase) ubiquitination and degradation after ionizing radiation. Mass spectrometry and co-immunoprecipitation showed that SERPINB5 (serpin family B member 5) interacts with both TRIM21 and GMPS. Epistatic analysis showed that SERPINB5 acts as an adaptor to recruit GMPS and introduce TRIM21 for ubiquitination. The in vitro and in vivo results validated the finding that SERPINB5 promotes NPC cell radioresistance. Furthermore, immunohistochemistry indicated that radioresistant patients have higher SERPINB5 expression. Overall, our data show that TRIM21-SERPINB5-mediated GMPS degradation facilitates TP53 repression, which promotes the radioresistance of NPC cells.

cancer biology↗

bioRxiv2019

A Pandas complex adapted for piRNA-guided transposon silencing

The repression of transposons by the Piwi-interacting RNA (piRNA) pathway is essential to protect animal germ cells. In Drosophila ovaries, Panoramix (Panx) enforces transcriptional silencing by binding to the target-engaged Piwi-piRNA complex, although the precise mechanisms by which this occurs remain elusive. Here, we show that Panx functions together with a germline specific paralogue of a nuclear export factor, dNxf2, and its cofactor dNxt1 (p15), as a ternary complex to suppress transposon expression. Structural and functional analyses demonstrate that dNxf2 binds Panx via its UBA domain, which plays an important role in transposon silencing. Unexpectedly, dNxf2 interacts directly with dNxf1 (TAP), a general nuclear export factor. As a result, dNxf2 prevents dNxf1 from binding to the FG repeats of the nuclear pore complex, a process required for proper RNA export. Transient tethering of dNxf2 to nascent transcripts leads to their nuclear retention. Therefore, we propose that dNxf2 may function as a Pandas (Panoramix-dNxf2 dependent TAP/p15 silencing) complex, which counteracts the canonical RNA exporting machinery and restricts transposons to the nuclear peripheries. Our findings may have broader implications for understanding how RNA metabolism modulates epigenetic gene silencing and heterochromatin formation.

molecular biology↗

bioRxiv2019

Human Foveal Cone Photoreceptor Topography and its Dependence on Eye Length

We provide the first measures of foveal cone density as a function of axial length in living eyes and discuss the physical and visual implications of our findings. We used a new generation Adaptive Optics Scanning Laser Ophthalmoscope to image cones at and near the fovea in 28 eyes of 16 subjects. Cone density and other metrics were computed in units of visual angle and linear retinal units. The foveal cone mosaic in longer eyes is expanded at the fovea, but not in proportion to eye length. Despite retinal stretching (decrease in cones/mm2), myopes generally have a higher angular sampling density (increase in cones/deg2) in and around the fovea compared to emmetropes, offering the potential for better visual acuity. Reports of deficits in best-corrected foveal vision in myopes compared to emmetropes cannot be explained by increased spacing between photoreceptors caused by retinal stretching during myopic progression.

neuroscience↗

bioRxiv2019

Glioblastomas derived from genetically modified pluripotent stem cells recapitulate pathobiology

Many current cellular models aimed at elucidating cancer biology do not recapitulate pathobiology including tumor heterogeneity, an inherent feature of cancer that underlies treatment resistance. Here we introduce a new cancer modeling paradigm using genetically engineered human pluripotent stem cells (hiPSCs) that capture authentic cancer pathobiology. Orthotopic engraftment of neural progenitor cells derived from hiPSCs that have been genome-edited to contain tumor-associated genetic driver mutations revealed by The Cancer Genome Atlas project for glioblastoma (GBM) result in formation of high-grade gliomas. As observed in GBM patient samples, these models harbor inter-tumor heterogeneity resembling different GBM molecular subtypes, and intra-tumor heterogeneity. Further, re-engraftment of primary tumor neurospheres generates secondary tumors with features characteristic of patient samples and present mutation-dependent patterns of tumor evolution. Thus, these cancer avatar models provide a platform for a comprehensive longitudinal assessment of human tumor development as governed by molecular subtype mutations and lineage-restricted differentiation.

cancer biology↗

bioRxiv2019

Comparing 3D genome organization in multiple species using Phylo-HMRF

Recent developments in whole-genome mapping approaches for the chromatin interactome (such as Hi-C) have offered new insights into 3D genome organization. However, our knowledge of the evolutionary patterns of 3D genome structures in mammalian species remains surprisingly limited. In particular, there are no existing phylogenetic-model based methods to analyze chromatin interactions as continuous features across different species. Here we develop a new probabilistic model, named phylogenetic hidden Markov random field (Phylo-HMRF), to identify evolutionary patterns of 3D genome structures based on multi-species Hi-C data by jointly utilizing spatial constraints among genomic loci and continuous-trait evolutionary models. The effectiveness of Phylo-HMRF is demonstrated in both simulation evaluation and application to real Hi-C data. We used Phylo-HMRF to uncover cross-species 3D genome patterns based on Hi-C data from the same cell type in four primate species (human, chimpanzee, bonobo, and gorilla). The identified evolutionary patterns of 3D genome organization correlate with features of genome structure and function, including long-range interactions, topologically-associating domains (TADs), and replication timing patterns. This work provides a new framework that utilizes general types of spatial constraints to identify evolutionary patterns of continuous genomic features and has the potential to reveal the evolutionary principles of 3D genome organization.

bioinformatics↗

bioRxiv2019

Is understanding the structure-function of microbial community of sludge suitable using DNA-based molecular methods?

Analysis the similarities between total and active microbial community is crucial to evaluate whether understanding the structure-function of microbial community of different types sludge is suitable using DNA-based molecular methods. In this study, procaryotic communities in different types sludge samples (including primary sludge, excess sludge, mixed sludge, and digested sludge) were evaluated using DNA-based and RNA-based Illumina MiSeq. Results showed that the similarities between total and active procaryotic communities of all different types sludge were considerable high. Meanwhile, the similarity in running sludge higher than that in idle sludge, because of the Jarccards coefficient of digested sludge was the highest in all types sludge samples. This study indicates that the DNA-based molecular biology technology could be applicable to profile procaryotic community structure and function in sludge samples, and this study adds the understanding of total and active procaryotic communities of sludge samples.

ecology↗

bioRxiv2019

MOCHI enables discovery of heterogeneous interactome modules in 3D nucleome

The composition of the cell nucleus is highly heterogeneous, with different constituents forming complex interactomes. However, the global patterns of these interwoven heterogeneous interactomes remain poorly understood. Here we focus on two different interactomes, chromatin interaction network and gene regulatory network, as a proof-of-principle, to identify heterogeneous interactome modules (HIMs) in the nucleus. Each HIM represents a cluster of gene loci that are in spatial contact more frequently than expected and that are regulated by the same group of transcription factor proteins. We develop a new algorithm MOCHI to facilitate the discovery of HIMs based on network motif clustering in heterogeneous interactomes. By applying MOCHI to five different cell types, we found that HIMs have strong spatial preference within the nucleus and exhibit distinct functional properties. Through integrative analysis, this work demonstrates the utility of MOCHI to identify HIMs, which may provide new perspectives on 3D genome organization and function.

bioinformatics↗