Biology subjects

Feng, T.

Publications and source records attributed to Feng, T..

At least 55 records · Page 3Linked to original sources

bioRxiv2023

Cortical gradient perturbation in attention deficit hyperactivity disorder correlates with neurotransmitter-, cell type-specific and chromosome- transcriptomic signatures

Neurofunctional dysregulations in spatially discrete areas or isolated pathways have been suggested as neural markers for attention deficit hyperactivity disorder (ADHD). However, multiscale perspectives into the neurobiological underpins of ADHD spanning multiple biological systems remain sparse. This points to the need of multi-levels of analysis encompassing brain functional organization and its correlation with molecular and cell-specific transcriptional signatures are stressed. Here, we capitalized on diffusion mapping embedding model to derive the functional connectome gradient, and deployed multivariate partial least square (PLS) method to uncover the enrichment of neurotransmitomic, cellular and chromosomal connectome-transcriptional signatures of ADHD. Compared to typical control, ADHD children presented connectopic cortical perturbations in lateral orbito-frontal and superior temporal regions, which had also been validated in another independent sample. This gradient-derived variants in ADHD further aligned spatially with distributions of GABAA/BZ and 5-HT2A receptors and co-varied with genetic transcriptional expression. Cognitive decoding and gene-expression annotation showed the correlates of these variants in memory, emotional regulation and spatial attention. Moreover, the gradient-derived transcriptional signatures of ADHD exhibited enriched expression of oligodendrocyte precursors and endothelial cells, and were mainly involved as variants of chromosome 18, 19 and X. In conclusion, our findings bridged in-vivo neuroimging assessed functional brain organization patterns to a multi-level molecular pathway in ADHD, possibly shedding light on the interrelation of biological systems that may coalesce to the emergence of this disorder.

neuroscience↗

bioRxiv2022

Genomic underpinnings of convergent adaptation to high altitudes for alpine plants

Evolutionary convergence is one of the most striking examples of adaptation driven by natural selection. However, genomic evidence for convergent adaptation to extreme environments remains scarce. The Himalaya-Hengduan Mountains represent the worlds most species-rich temperate alpine biota, providing an ideal "natural laboratory" for studying convergent adaptation to high altitudes. Here, we generate reference genomes for two alpine plants, Saussurea obvallata (Asteraceae) and Rheum alexandrae (Polygonaceae), with 37,938 and 61,463 annotated protein-coding genes. By integrating an additional five alpine genomes, we investigate genomic signatures of convergent adaptation to the hostile environments of high altitudes. We show that alpine genomes tend to mitigate their genetic load by contracting genes functioning in the immune system to survive such harsh environments with few pathogens present. We detect signatures of convergent positive selection on a set of genes involved in reproduction and development and reveal that molecular convergence has acted on genes involved in self-incompatibility, cell wall modification, DNA repair and stress resistance, which underlie adaptation to extremely cold, high UV radiation and hypoxia environments. Using gene expression profiles, we further demonstrate that genes associated with cuticular wax and flavonoid biosynthetic pathways exhibit higher expression levels in leafy bracts, shedding lights on the genetic mechanisms of the adaptive greenhouse morphology. Our integrative data provide genomic insights into the convergent evolution at higher-taxonomic levels, aiding in deep understanding of genetic adaptation to complex environments.

evolutionary biology↗

bioRxiv2022

Seeing the future: connectome strength and network efficiency in visual network predict individual ability of episodic future thinking

Episodic future thinking (EFT) refers to the critical ability that people construct vivid mental imagery about future events and pre-experience it, which helps with individual and group decision-making. Although EFT is generally believed to have a visual nature by theorists, little neuroscience evidence had been provided to verify this assumption. Here, by employing the approach of connectome-based predictive modeling (CPM) and graph-theoretical analysis, we analyzed resting-state functional brain image from 191 participants to predict their variability of EFT ability (leave-one-out cross-validation), and validated the results by applying different parcellation schemas and feature selection thresholds. At the connectome strength level, CPM-based analysis revealed that EFT ability could be predicted by the connectome strength of visual network. Further at the network level, graph-theoretical analysis showed that EFT ability could be predicted by the network efficiency of visual network. Moreover, these findings were replicated using different parcellation schemas and feature selection thresholds. These results robustly and collectively supported the visual network being the neural substrates underlying EFT ability from a comprehensive perspective of resting-state functional connectivity strength and the neural network. This study provides indications on how the function of visual network supports EFT ability, and helps to understand the EFT ability from a neural basis perspective.

neuroscience↗

bioRxiv2022

A binocular perception deficit characterizes prey pursuit in developing mice

The mouse continues to be one of the most powerful models in which to address the molecular and cellular mechanisms underlying mammalian visual system development. In particular, integration of binocular information at the cellular level has long been studied in specific regions of the mouse visual cortex to gain mechanistic insight into the development of vision. However, we lack an understanding of the development of the visual perceptions themselves in mice and other species that might rely on successful binocular integration. Further, the superior colliculus also processes binocular input and it remains unclear how early visual experience differentially impacts activity in this brain area during behavior. To address these major outstanding questions, we quantified the natural visually-guided behavior of postnatal day 21 (P21) and adult mice using a live prey capture assay and a computerized-spontaneous perception of visual objects tasks (C-SPOT). Analysis of both behavioral assays revealed robust and specific binocular visual field processing deficits in P21 mice as compared to adults. In addition, c-Fos expression in the anterior region of the superior colliculus (SC), the region that would process stimuli located in the binocular visual field, was highly different between P21 mice and adults after C-SPOT. We thus exploited a natural visual pursuit behavior and C-SPOT to provide the first demonstration of a specific visual perception deficit related to binocular integration in developing mice. HighlightsO_LIJuvenile (P21) mice robustly investigate live insects C_LIO_LIInsect pursuit behavior relying on binocular vision is immature in P21 mice C_LIO_LIVisually-induced arrest responses are similar between P21 and adult mice. C_LIO_LIEthologically-relevant visual experience differentially increases c-Fos expression in the superior colliculus of juveniles versus adults. C_LI

animal behavior and cognition↗

bioRxiv2022

A novel Vps34 complex constrains loop extrusion-mediated P-H2A spreading

The establishment of appropriate phosphorylated histone H2AX ({gamma}H2AX) foci is required for the precise initiation of DNA damage response (DDR) signaling, which contributes to the efficient repair of DNA double-strand breaks (DSB)1. Therefore, it is important to understand exactly how {gamma}H2AX foci are established in response to DSB. Recently, an attractive mechanism has been proposed to explain this process2. DSB-anchored cohesin-mediated loop extrusion promotes H2AX-containing chromatin to pass through DSB-recruited ATM, by which H2AX is phosphorylated to form {gamma}H2AX foci on each side of the DSB. The loop extrusion-promoted enlargement of {gamma}H2AX-modified chromatin is halted upon cohesin encountering boundary factors such as CTCF. This cohesin-dependent mechanism was shown to be conserved among eukaryotic cells, because deletion of the cohesin regulator Pds5 in budding yeast also results in extended spreading of phosphorylated H2A at Ser129 (P-H2A)2. However, yeast lacks CTCF or CTCF-like boundary factors that restrict cohesion-mediated loop extrusion. Here, we report a novel vacuolar sorting protein 34 (Vps34) complex, which might function as a boundary factor that constrains cohesin-dependent loop extrusion-mediated P-H2A spreading.

molecular biology↗

bioRxiv2021

Investigation on the changes of Bifidobacterium and lactic acid bacteria in soybean meal fermented feed

The main objective of this research was to explore the dynamic changes of Bifidobacterium and lactic acid bacteria (LAB) in the process of feed fermentation under anaerobic condition, so as to increase the number of fermented bacteria of Bifidobacterium from the aspect of strain combination. The results showed that when Bifidobacterium lactis (B. lactis, i.e. Bifidobacterium animalis subsp. lactis) fermented with Bacillus coagulans or Lactobacillus paracasei, the maximum number of B. lactis in those samples was 9.42 times and 4.64 times of that of fermented sample with B. lactis only. The soybean meal was fermented by B. lactis, L. paracasei and B. coagulans, and the number of B. lactis reached the maximum after fermented 10 days, which was 6.13 times of that in unfermented sample. The reducing sugar content and highest activity of -galactosidase were higher than the control. These results suggest that B. coagulans and L. paracasei can promote the growth of B. lactis. It is inferred that B. coagulans can metabolize normally in aerobic, micro-aerobic and anaerobic environments, consume oxygen, produce digestive enzymes, and cooperate with L. paracasei to produce metabolic products benefit for the growth of B. lactis.

microbiology↗

bioRxiv2021

DeePVP: Identification and classification of phage virion protein using deep learning

The poor annotation of phage virion protein (PVP) is the bottleneck of many areas of viral research, such as viral phylogenetic analysis, viral host identification and antibacterial drug design. Because of the high diversity of the PVP sequences, the PVP annotation remains a great challenging bioinformatic task. Based on deep learning, we present DeePVP that contains a main module and an extended module. The main module aims to identify the PVPs from non-PVP over a phage genome, while the extended module can further classify the predicted PVP into one of the ten major classes of PVP. Compared with the state-of-the-art tools that can distinguish PVP from non-PVP, DeePVPs main module performs much better, with an F1-score 9.05% higher in the PVP identification task. Compared with PhANNs, a tool that can further classify the predicted PVP into a specific class, the overall accuracy of DeePVPs extended module is approximately 3.72% higher in the PVP classification task. Two application cases on the genome of mycobacteriophage PDRPxv and Escherichia phage HP3 show that the predictions of DeePVP are much more reliable and can better reveal the compact PVP-enriched region, which may be conserved during the viral evolution process, over the phage genome.

bioinformatics↗

bioRxiv2021

High-quality reference genome of Fasciola gigantica: Insights into the genomic signatures of transposon-mediated evolution and specific parasitic adaption in tropical regions

Fasciola gigantica and Fasciola hepatica are causative pathogens of fascioliasis, with the widest latitudinal, longitudinal, and altitudinal distribution; however, among parasites, they have the largest sequenced genomes, hindering genomic research. In the present study, we used various sequencing and assembly technologies to generate a new high-quality Fasciola gigantica reference genome. We improved the integration of gene structure prediction, and identified two independent transposable element expansion events contributing to (1) the speciation between Fasciola and Fasciolopsis during the Cretaceous-Paleogene boundary mass extinction, and (2) the habitat switch to the liver during the Paleocene-Eocene Thermal Maximum, accompanied by gene length increment. Long interspersed element (LINE) duplication contributed to the second transposon-mediated alteration, showing an obvious trend of insertion into gene regions, regardless of strong purifying selection. Gene ontology analysis of genes with long LINE insertions identified membrane-associated and vesicle secretion process proteins, further implicating the functional alteration of the gene network. We identified 852 excretory/secretory proteins and 3300 protein-protein interactions between Fasciola gigantica and its host. Among them, copper/zinc superoxide dismutase genes, with specific gene copy number variations, might play a central role in the phase I detoxification process. Analysis of 559 single-copy orthologs suggested that Fasciola gigantica and Fasciola hepatica diverged at 11.8 Ma near the Middle and Late Miocene Epoch boundary. We identified 98 rapidly evolving gene families, including actin and aquaporin, which might explain the large body size and the parasitic adaptive character resulting in these liver flukes becoming epidemic in tropical and subtropical regions.

genomics↗

bioRxiv2021

Insights into the drivers of radiating diversification in biodiversity hotspots using Saussurea (Asteraceae) as a case

O_LIThe Qinghai-Tibet Plateau (QTP) encompasses areas with a remarkably high degree of biodiversity, harboring exceptional species-rich radiations. How these radiations formed by interacting with geology, climate and ecology remains seldom examined. C_LIO_LIWe investigate the roles of abiotic (environmental) and biotic (species-intrinsic) factors in driving radiating diversification of Saussurea (Asteraceae) by deploying a number of time-dependent, paleoenvironment-dependent and trait-dependent models, as well as ecological distribution data. C_LIO_LIWe show that three main clades of Saussurea begin to diversify in the Miocene almost simultaneously, with increasing diversification rates toward the present and negative dependence to paleotemperature. Acceleration in diversification rates are correlated with adaptive traits, as well climate lability, niche breadth and species range. C_LIO_LIWe conclude that fluctuation of paleoclimate along with complex QTP environments provided opportunities for increased diversification rates of Saussurea with diverse adaptive traits, highlighting the importance of combinations of clade-specific traits and ecological niches in driving rapid radiation. C_LI

evolutionary biology↗

bioRxiv2020

Characterisation of bacteriophage JD419, a Staphylococcal phage with an unusual morphology and broad host range

As an antimicrobial therapy, therapeutic phages, also known as "Phage therapy" are able to inactivate multi-drug resistant bacteria such as methicillin and vancomycin resistant S. aureus and thus present a possible treatment for infections that are otherwise incurable. In this paper, we present a novel phage called JD419, which has a remarkably wide host-range. The virulent phage JD419 exhibits an elongated capsid and was able to infect and lyse 83 of all 129 tested clinical strains (64.3%) of multi-drug resistant S. aureus including MRSA. To evaluate the potential as a therapeutic phage, we tested the ability of phage JD419 to remain infectious after treatment exceeding physiological pH or temperature. The lytic activity of the phage was retained at pH values of 6.0-8.0 and at temperatures below 50{degrees}C. As phages sometimes contain virulence genes, we sequenced the complete genome of JD419. The 45509 bp genome contains a predicted 65 ORFs, none of which show homology to any known virulence or antibiotic resistance genes. Our study illustrates that Staphylococcus phage JD419 has the potential to be used for diagnostic, prophylaxic and therapeutic purposes.

microbiology↗

bioRxiv2020

Maternal factor PABPN1L is essential for maternal mRNA degradation during maternal-to-zygotic transition

Infertility affects 10% - 15% of families worldwide. However, the pathogenesis of female infertility caused by abnormal early embryonic development is not clear. We constructed a mouse model (Pabpn1l -/-) simulating the splicing abnormality of human PABPN1L and found that the female was sterile and the male was fertile. The Pabpn1l -/- oocytes can be produced, ovulated and fertilized normally, but cannot develop beyond the 2-cell stage. Using RNA-Seq, we found a large-scale upregulation of RNA in Pabpn1l -/- MII oocytes. Of the 2401 transcripts upregulated in Pabpn1l-/- MII oocytes, 1523 transcripts (63.4%) were also upregulated in Btg4 -/- MII oocytes, while only 53 transcripts (2.2%) were upregulated in Ythdf2 -/- MII oocytes. We documented that transcripts in zygotes derived from Pabpn1l -/- oocytes have a longer poly(A) tail than the control group, a phenomenon similar to that in Btg4-/- mice. Surprisingly, the poly(A) tail of these mRNAs was significantly shorter in the Pabpn1l -/- MII oocytes than in the Pabpn1l +/+. These results suggest that PABPN1L is involved in BTG4-mediated maternal mRNA degradation, and may antagonize poly(A) tail shortening in oocytes independently of its involvement in maternal mRNA degradation. Thus, PABPN1L variants could be a genetic marker of female infertility.

genetics↗

bioRxiv2020

Experience-dependent inhibitory plasticity is mediated by CCK+ basket cells in the developing dentate gyrus

Early postnatal experience shapes both inhibitory and excitatory networks in the hippocampus. However, the underlying circuit plasticity is unclear. Using an enriched environment (EE) paradigm, we assessed the circuit plasticity of inhibitory cell-types in the hippocampus. We found that cholecystokinin (CCK)-expressing basket cells strongly increased somatic inhibition on the excitatory granular cells (GC) following EE while another pivotal inhibitory cell-type, parvalbumin (PV)-expressing cells did not show changes. By inhibiting activity of the entorhinal cortex (EC) using a chemogenetic approach, we demonstrate that the projections from the EC is responsible for the developmental plasticity of CCK+ basket cells. Our measurement of the input decorrelation by DG circuit suggests that EE has little effect on pattern separation despite of the altered CCK+ basket cell circuit. Altogether, our study places the activity-dependent remodeling of CCK+ basket cell innervation as a central process to adjust inhibition in the DG, while maintaining the computation in the circuit.

neuroscience↗

bioRxiv2020

Multiple approaches for massively parallel sequencing of HCoV-19 genomes directly from clinical samples

COVID-19 has caused a major epidemic worldwide, however, much is yet to be known about the epidemiology and evolution of the virus. One reason is that the challenges underneath sequencing HCoV-19 directly from clinical samples have not been completely tackled. Here we illustrate the application of amplicon and hybrid capture (capture)-based sequencing, as well as ultra-high-throughput metatranscriptomic (meta) sequencing in retrieving complete genomes, inter-individual and intra-individual variations of HCoV-19 from clinical samples covering a range of sample types and viral load. We also examine and compare the bias, sensitivity, accuracy, and other characteristics of these approaches in a comprehensive manner. This is, to date, the first work systematically implements amplicon and capture approaches in sequencing HCoV-19, as well as the first comparative study across methods. Our work offers practical solutions for genome sequencing and analyses of HCoV-19 and other emerging viruses.

genomics↗

bioRxiv2019

Generating Templates and Growth Charts for School-Aged Brain Development

Standard brain templates and growth charts provide an invaluable resource for basic science research, with the eventual goal of contributing to the clinical care of neuropsychiatric conditions. Here, we report on a protocol to generate MRI brain templates in children and adolescents at one-year intervals from 6-to-18 years of age, with their corresponding growth charts, using a large-scale neuroimaging data resource (948 brain images from China and United States). To assure that the brain templates and growth charts are reliable and accurate, we developed a refined pipeline consisting of template construction, image registration, brain area labeling and growth chart modeling. The pipeline comprises multiple modular workflows that can be used for multiple applications. In our approach, population- and age-specific templates were first constructed to avoid systemic bias in registration. Brain areas were then labeled based on the appropriate templates, and their morphological metrics were extracted for modeling associated growth curves. We implemented warp cost as a function of age differences between individual brains and template brains. A strong U-shaped cost function was revealed, indicating larger age differences are associated with greater registration errors. This validates the necessity of age-specific reference templates in pediatric brain imaging studies. Growth chart analyses revealed preferential shape differences between Chinese and US samples in lateral frontal and parietal areas, aspects of cortex which are most variable across individuals with regard to structure and function as well as associated behavioral performance. This growth distinction is largely driven by neurodevelopmental differences between Chinese and US age-specific brain templates. The pipeline together with the brain templates and charts are publicly available and integrated into the Connectome Computation System.

neuroscience↗

bioRxiv2019

Next generation sequencing to investigate genomic diversity in Caryophyllales

Caryophyllales are a highly diverse and large order of plants with a global distribution. While some species are important crops like Beta vulgaris, many others can survive under extreme conditions. This order is well known for the complex pigment evolution, because the pigments anthocyanins and betalains occur with mutual exclusion in species of the Caryophyllales. Here we report about genome assemblies of Kewa caespitosa (Kewaceae), Macarthuria australis (Macarthuriaceae), and Pharnaceum exiguum (Molluginaceae) which are representing different taxonomic groups in the Caryophyllales. The availability of these assemblies enhances molecular investigation of these species e.g. with respect to certain genes of interest.

genomics↗

bioRxiv2019

An ATAC-seq atlas of chromatin accessibility in mouse tissues

The Assay for Transposase-Accessible Chromatin using sequencing (ATAC-seq) is a fundamental epigenomics approach and has been widely used in profiling the chromatin accessibility dynamics in multiple species. A comprehensive reference of ATAC-seq datasets for mammalian tissues is important for the understanding of regulatory specificity and developmental abnormality caused by genetic or environmental alterations. Here, we report an adult mouse ATAC-seq atlas by producing a total of 66 ATAC-seq profiles from 20 primary tissues of both male and female mice. The ATAC-seq read enrichment, fragment size distribution, and reproducibility between replicates demonstrated the high quality of the full dataset. We identified a total of 296,574 accessible elements, of which 26,916 showed tissue-specific accessibility. Further, we identified key transcription factors specific to distinct tissues and found that the enrichment of each motif reflects the developmental similarities across tissues. In summary, our study provides an important resource on the mouse epigenome and will be of great importance to various scientific disciplines such as development, cell reprogramming, and genetic disease.

genomics↗

bioRxiv2019

Human extinction learning is accelerated by an angiotensin antagonist via ventromedial prefrontal cortex and its connections with basolateral amygdala

Recent translational research suggests a role of the renin-angiotensin (RA) system in threat extinction and underlying neuroplasticity; however, whether and how pharmacological modulation of the RA system influences physiological and neural manifestations of threat during extinction learning in humans is unclear. Here we report that pre-extinction administration of losartan, an angiotensin II type 1 receptor antagonist, accelerated attenuation of physiological threat expression. During early extinction, losartan enhanced threat-signal specific ventromedial prefrontal cortex (vmPFC) activation and its coupling with the basolateral amygdala. Multivoxel pattern analysis revealed that losartan reduced whole brain, particularly vmPFC, threat expression and voxel-wise mediation analyses further confirmed that losartan-accelerated extinction crucially involved vmPFC processing. Overall the results provide initial evidence for a critical role of the RA system in extinction learning in humans and suggest that adjunct losartan administration may facilitate the efficacy of extinction-based therapies. ClinicalTrials.gov, Identifier: NCT03396523

clinical trials↗

bioRxiv2018

Evolution of Portulacineae marked by gene tree conflict and gene family expansion associated with adaptation to harsh environments

Several plant lineages have evolved adaptations that allow survival in extreme and harsh environments including many within the plant clade Portulacineae (Caryophyllales) such as the Cactaceae, Didiereaceae of Madagascar, and high altitude Montiaceae. Here, using newly generated transcriptomic data, we reconstructed the phylogeny of Portulacineae and examine potential correlates between molecular evolution within this clade and adaptation to harsh environments. Our phylogenetic results were largely congruent with previous analyses, but we identified several early diverging nodes characterized by extensive gene tree conflict. For particularly contentious nodes, we presented detailed information about the phylogenetic signal for alternative relationships. We also analyzed the frequency of gene duplications, confirmed previously identified whole genome duplications (WGD), and identified a previously unidentified WGD event within the Didiereaceae. We found that the WGD events were typically associated with shifts in climatic niche and did not find a direct association with WGDs and diversification rate shifts. Diversification shifts occurred within the Portulacaceae, Cactaceae, and Anacampserotaceae, and while these did not experience WGDs, the Cactaceae experienced extensive gene duplications. We examined gene family expansion and molecular evolutionary patterns with a focus on genes associated with environmental stress responses and found evidence for significant gene family expansion in genes with stress adaptation and clades found in extreme environments. These results provide important directions for further and deeper examination of the potential links between molecular evolutionary patterns and adaptation to harsh environments.

evolutionary biology↗