Biology subjects

Feng, X.

Publications and source records attributed to Feng, X..

At least 163 records · Page 9Linked to original sources

bioRxiv2022

Deep learning on reflectance confocal microscopy improves Raman spectral diagnosis of basal cell carcinoma

SignificanceRaman spectroscopy may be useful to assist Mohs micrographic surgery for skin cancer diagnosis; however, the specificity of Raman spectroscopy is limited by the high spectral similarity between tumors and normal tissues structures such as epidermis and hair follicles. Reflectance confocal microscopy (RCM) can provide imaging guidance with morphological and cytological details similar to histology. Combining Raman spectroscopy with deep-learning-aided RCM has the potential to improve the diagnostic accuracy of Raman without requiring additional input from the clinician. AimWe seek to improve the specificity of Raman for basal cell carcinoma (BCC) by integrating information from RCM images using an Artificial Neural Network. ApproachA Raman biophysical model was used in prior work to classify BCC tumors from surrounding normal tissue structures. 191 RCM images were collected from the same site as the Raman data and served as inputs to train two ResNet50 networks. The networks selected the hair structure images and epidermis images respectively within all the images corresponding to the positive predictions of the Raman Biophysical Model. ResultsDeep learning on RCM images removes 54% of false positive predictions from the Raman Biophysical Model result and keeps the sensitivity as 100%. The specificity was improved from 84.8% by using Raman spectra alone to 93.0% by integrating Raman spectra with RCM images ConclusionsCombining Raman spectroscopy with deep-learning-aided RCM imaging is a promising tool to guide tumor resection surgery.

bioengineering↗

bioRxiv2022

Superparamagnetic iron oxide enclosed hollow gold nanostructure with tunable surface plasmon resonances to promote near-infrared photothermal conversion

In this study, to enhance deep tissue penetration by near-infrared (NIR) light, a novel superparamagnetic iron oxide enclosed hollow gold nanoshell (SPIO-HGNS) structure with tunable size and surface plasmon resonance (SPR) in the NIR range was designed and synthesized through a 2-step template-enabled galvanic replacement reaction. Here, Ag coated SPIO (SPIO-Ag) was prepared as a template with tunable outer diameters by way of adjusting the Ag content. SPIO-HGNS with variable hollow gold inner diameters can then be synthesized based on the determined outer diameter of the SPIO-Ag template through a galvanic replacement reaction between HAuCl3 and Ag coating on the SPIO surface. With incrementing amounts of Ag, three SPIO-HGNS structures were synthesized with comparable shell thicknesses around 6.7 nm and an average inner diameter of 38.7, 39.4, and 40.7 nm, respectively, evidenced by TEM and ICP results. The structure of SPIO-HGNS was confirmed by identifying Au111 lattice and the elemental mapping of Fe and Au using energy-dispersive X-ray spectroscopy. The Ultraviolet-Visible-NIR absorption spectra showed red-shifted SPR peaks (820, 855, and 945 nm) with the increasing inner diameters of SPIO-HGNS, which was also supported by an absorption cross-section simulation. The photothermal results showed that the three SPIO-HGNS structures, when exposed to ~30 s of 400 mW laser irradiation, exhibited photothermal temperature rises of 5.9, 4.6, and 2.9 {degrees}C, respectively. This study explored the tuning of SPR properties in NIR-responsive magneto-plasmonic nanoparticles through a facile preparation procedure, paving the way for potential applications in photothermal therapies.

bioengineering↗

bioRxiv2022

SAI: Fast and automated quantification of stomatal parameters on microscope images

Using microscopy to investigate stomatal behaviour is a common technique in plant physiology research. Manual inspection and measurement of stomatal features is a low throughput process in terms of time and human effort, which relies on expert knowledge to identify and measure stomata accurately. This process represents a significant bottleneck in research pipelines, adding significant researcher time to any project that requires it. To alleviate this, we introduce StomaAI (SAI): a reliable and user-friendly tool that measures stomata of the model plant Arabidopsis (dicot) and the crop plant barley (monocot grass) via the application of deep computer vision. We evaluated the reliability of predicted measurements: SAI is capable of producing measurements consistent with human experts and successfully reproduced conclusions of published datasets. Hence, SAI boosts the number of images that biologists can evaluate in a fraction of the time so is capable of obtaining more accurate and representative results.

plant biology↗

bioRxiv2022

Rhamnan Sulfate Reduces Atherosclerotic Plaque Formation and Vascular Inflammation

ObjectiveWhile lipid-lowering drugs have become a mainstay of clinical therapy these treatments only slow the progression of the disease and can have side effects. Thus, new treatment options are needed to supplement the effects of lipid lowering therapy for treating atherosclerosis. We examined the use of an inexpensive and widely available marine polysaccharide rhamnan sulfate as an oral therapeutic for limiting vascular inflammation and atherosclerosis. Methods and ResultsWe found rhamnan sulfate enhanced the barrier function of endothelial cells, preventing the deposition of LDL and maintaining barrier function even in the presence of glycocalyx-degrading enzymes. Rhamnan sulfate was also found to bind directly to FGF-2, PDGF-BB and NF-{kappa}B subunits with high affinity. In addition, rhamnan sulfate was a potent inhibitor of NF-{kappa}B pathway activation in endothelial cells by TNF-. We treated ApoE-/- mice with a high fat diet for 4 weeks and then an addition 9 weeks of high fat diet with or without rhamnan sulfate. Rhamnan sulfate reduced vascular inflammation and atherosclerosis in both sexes of ApoE-/- mice but had a stronger therapeutic effect in female mice. Oral consumption of rhamnan sulfate induced a significant decrease in cholesterol plasma levels in female mice but not in male mice. ConclusionsRhamnan sulfate has beneficial effects in reducing inflammation, binding growth factors and NF-{kappa}B, enhancing endothelial barrier function and reducing atherosclerotic plaque formation in ApoE-/- mice.

physiology↗

bioRxiv2021

Two decades of suspect evidence for adaptive molecular evolution - Negative selection confounding positive selection signals

There is a large literature in the last two decades affirming adaptive DNA sequences evolution between species. The main lines of evidence are from i) the McDonald-Kreitman (MK) test, which compares divergence and polymorphism data, and ii) the PAML test, which analyzes multi-species divergence data. Here, we apply these two tests concurrently on the genomic data of Drosophila and Arabidopsis. To our surprise, the >100 genes identified by the two tests do not overlap beyond random expectation. Because the non-concordance could be due to low powers leading to high false-negatives, we merge every 20 - 30 genes into a "supergene". At the supergene level, the power of detection is large but the calls still do not overlap. We rule out methodological reasons for the non-concordance. In particular, extensive simulations fail to find scenarios whereby positive selection can only be detected by either MK or PAML, but not both. Since molecular evolution is governed by positive and negative selection concurrently, a fundamental assumption for estimating one (say, positive selection) is that the other is constant. However, in a broad survey of primates, birds, Drosophila and Arabidopsis, we found that negative selection rarely stays constant for long in evolution. As a consequence, the variation in negative selection is often mis-construed as signals of positive selection. In conclusion, MK, PAML or any method that examines genomic sequence evolution has to explicitly address the variation in negative selection before estimating positive selection. In a companion study, we propose a possible path forward in two stages - first, by mapping out the changes in negative selection and then using this map to estimate positive selection. For now, the large literature on positive selection between species has to await the re-assessment.

evolutionary biology↗

bioRxiv2021

The colonial legacy of herbaria

Herbarium collections shape our understanding of the worlds flora and are crucial for addressing global change and biodiversity conservation. The formation of such natural history collections, however, are not free from sociopolitical issues of immediate relevance. Despite increasing efforts addressing issues of representation and colonialism in natural history collections, herbaria have received comparatively less attention. While it has been noted that the majority of plant specimens are housed in the global North, the extent of this disparity has not been rigorously quantified to date. Here, by analyzing over 85 million specimen records and surveying herbaria across the globe, we assess the colonial legacy of botanical collections and how we may move towards a more inclusive future. We demonstrate that colonial exploitation has contributed to an inverse relationship between where plant biodiversity exists in nature and where it is housed in herbaria. Such disparities persist in herbaria across physical and digital realms despite overt colonialism having ended over half a century ago, suggesting ongoing digitization and decolonization efforts have yet to alleviate colonial-era discrepancies. We emphasize the need for acknowledging the inconvenient history of herbarium collections and the implementation of a more equitable, global paradigm for their collection, curation, and use.

ecology↗

bioRxiv2021

H3K9me1/2 methylation limits the lifespan of C. elegans

Histone methylation plays crucial roles in the development, gene regulation and maintenance of stem cell pluripotency in mammals. Recent work shows that histone methylation is associated with aging, yet the underlying mechanism remains unclear. In this work, we identified a class of histone 3 lysine 9 mono-/dimethyltransferase genes (met-2, set-6, set-19, set-20, set-21, set-32 and set-33), mutations in which induce synergistic lifespan extension in the long-lived DAF-2 (IGF-1 receptor) mutant in C. elegans. These histone methyltransferase plus daf-2 double mutants not only exhibited an average lifespan nearly three times that of wild-type animals and a maximal lifespan of approximately 100 days, but also significantly increased resistance to oxidative and heat stress. Synergistic lifespan extension depends on the transcription factor DAF-16 (FOXO). mRNA-seq experiments revealed that the mRNA levels of class I DAF-16 target genes, which are activated by DAF-16, were further elevated in the double mutants. Among these genes, F35E8.7, nhr-62, sod-3, asm-2 and Y39G8B.7 are required for the lifespan extension of the daf-2;set-21 double mutant. In addition, treating daf-2 animals with the H3K9me1/2 methyltransferase G9a inhibitor also extends lifespan and increases stress resistance. Therefore, investigation of DAF-2 and H3K9me1/2 methyltransferase deficiency-mediated synergistic longevity will contribute to a better understanding of the molecular mechanisms of aging and therapeutic applications.

genetics↗

bioRxiv2021

Computationally designed GPCR quaternary structures bias signaling pathway activation

Communication across membranes controls critical cellular processes and is achieved by receptors translating extracellular signals into selective cytoplasmic responses. While receptor tertiary structures can now be readily characterized, receptor associations into quaternary structures are very challenging to study and their implications in signal transduction remain poorly understood. Here, we report a computational approach for predicting membrane receptor self-associations, and designing receptor oligomers with various quaternary structures and signaling properties. Using this approach, we designed chemokine receptor CXCR4 dimers with reprogrammed stabilities, conformations, and abilities to activate distinct intracellular signaling proteins. In agreement with our predictions, the designed CXCR4s dimerized through distinct conformations and displayed different quaternary structural changes upon activation. Consistent with the active state models, all engineered CXCR4 oligomers activated the G protein Gi, but only a few specific dimer structures also recruited {beta}-arrestins. Overall, we demonstrate that quaternary structures represent an important unforeseen mechanism of receptor biased signaling and reveal the existence of a conformational switch at the dimer interface of several G protein-coupled receptors including CXCR4, mu-Opioid and type-2 Vasopressin receptors that selectively control the activation of G proteins vs {beta}-arrestin-mediated pathways. The approach should prove useful for predicting and designing receptor associations to uncover and reprogram selective cellular signaling functions.

biophysics↗

bioRxiv2021

A histone variant condenses flowering plant sperm via chromatin phase separation

Sperm chromatin is typically transformed by protamines into a compact and transcriptionally inactive state. Flowering plant sperm cells lack protamines, yet have small, transcriptionally active nuclei with chromatin condensed by an unknown mechanism. Here we show that a histone variant, H2B.8, mediates sperm chromatin and nuclear condensation in Arabidopsis thaliana. Loss of H2B.8 causes enlarged sperm nuclei with dispersed chromatin, whereas ectopic expression in somatic cells produces smaller nuclei with aggregated chromatin, demonstrating that H2B.8 is sufficient for chromatin condensation. H2B.8 aggregates transcriptionally inactive AT-rich chromatin into phase-separated condensates, thus achieving nuclear compaction without reducing transcription. H2B.8 also intermixes inactive AT-rich chromatin and GC-rich pericentromeric heterochromatin, altering higher-order chromatin architecture. Altogether, our results reveal a novel mechanism of nuclear compaction via global aggregation of unexpressed chromatin. We propose that H2B.8 is a flowering plant evolutionary innovation that achieves nuclear condensation compatible with active transcription. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=196 SRC="FIGDIR/small/460326v2_ufig1.gif" ALT="Figure 1"> View larger version (56K): org.highwire.dtl.DTLVardef@fa7a3org.highwire.dtl.DTLVardef@1c6dd23org.highwire.dtl.DTLVardef@e0393borg.highwire.dtl.DTLVardef@cd8a62_HPS_FORMAT_FIGEXP M_FIG C_FIG

plant biology↗

bioRxiv2021

A well conserved archaeal B-family polymerase functions as a mismatch and lesion extender

B-family DNA polymerases (PolBs) of different groups are widespread in Archaea and different PolBs often coexist in the same organism. Many of these PolB enzymes remain to be investigated. One of the main groups that are poorly characterized is PolB2 whose members occur in many archaea but are predicted as an inactivated form of DNA polymerase. Herein, Sulfolobus islandicus DNA polymerase 2 (Dpo2), a PolB2 enzyme was expressed in its native host and purified. Characterization of the purified enzyme revealed that the polymerase harbors a robust nucleotide incorporation activity, but devoid of the 3-5 exonuclease activity. Enzyme kinetics analyses showed that Dpo2 replicates undamaged DNA templates with high fidelity, which is consistent with its inefficient nucleotide insertion activity opposite different DNA lesions. Strikingly, the polymerase is highly efficient in extending mismatches and mispaired primer termini once a nucleotide is placed opposite a damaged site. Together, these data suggested Dpo2 functions as a mismatch and lesion extender, representing a novel type of PolB that is primarily involved in DNA damage repair in Archaea. Insights were also gained into the functional adaptation of the motif C in the mismatch extension of the B-family DNA polymerases.

microbiology↗

bioRxiv2021

Investigating the active substance and mechanism of Jing-Fu-Kang granules via mass spectrometry technology and network pharmacology method

Jing-Fu-Kang granules (JFKG) is a famous Chinese patent medicine for the treatment of cervical spondylosis around the China, whereas the active substance and mechanism are not completely investigated clearly. In the current study, a rapid separation and identification method using UPLC-QE-Orbitrap-MS was established, 97 chemical constituents from JFKG were identified, and 16 prototype components from plasma samples after administration of JFKG were observed within 16 min. The structures of typical compounds were preliminarily speculated by comparing the retention time and fragmentation pattern. Furthermore, multiple databases were used to integrate the compound targets of JFKG, and the disease targets related to cervical spondylosis. After the intersection of the two sets of targets, a protein-protein interaction (PPI) network and a TCM-component-target-pathway-disease network were established, then using the DAVID database to perform gene ontology analysis and Kyoto Encyclopedia of Genes and Genomes analysis on the common targets to find related pathways. Finally, a total of 531 common targets and 136 pathways were found to participate in the mechanism. Our findings will help to further confirm the mechanism of JFKG for relieving cervical spondylosis, which will improve the scientific rationality of JFKG in clinical use, and can also assist in guiding doctors.

pharmacology and toxicology↗

bioRxiv2021

Detailed phylogeographic analysis of sticklebacks exposes challenges in genetic studies of admixed populations

Introgressive hybridization is an important process in evolution but challenging to identify, undermining the efforts to understand its role and significance. On the other hand, many analytical methods assume direct descent from a single common ancestor, and admixture among populations can violate their assumptions and lead to seriously biased results. A detailed analysis of 888 whole genome sequences of nine-spined sticklebacks (Pungitius pungitius) revealed a complex pattern of population ancestry involving multiple waves of gene flow and introgression across northern Europe. The two recognized lineages were found to have drastically different histories and their secondary contact zone was wider than anticipated, displaying a smooth gradient of foreign ancestry with some curious deviations from the expected pattern. Interestingly, the freshwater isolates provided peeks into the past and helped to understand the intermediate states of evolutionary processes. Our analyses and findings paint a detailed picture of the complex colonization history of northern Europe and provide back-drop against which introgression and its role in evolution can be investigated. However, they also expose the challenges in analyses of admixed populations and demonstrate how hidden admixture and colonization history misleads the estimation of admixture proportions and population split times.

genomics↗

bioRxiv2021

Mining bacterial NGS data vastly expands the complete genomes of temperate phages

Temperate phages (active prophages induced from bacteria) help control pathogenicity, modulate community structure, and maintain gut homeostasis1. Complete phage genome sequences are indispensable for understanding phage biology. Traditional plaque techniques are inapplicable to temperate phages due to the lysogenicity of these phages, which curb the identification and characterization of temperate phages. Existing in silico tools for prophage prediction usually fail to detect accurate and complete temperate phage genomes2-5. In this study, by a novel computational method mining both the integrated active prophages and their spontaneously induced forms (temperate phages), we obtained 192,326 complete temperate phage genomes from bacterial next-generation sequencing (NGS) data, hence expanded the existing number of complete temperate phage genomes by more than 100-fold. The reliability of our method was validated by wet-lab experiments. The experiments demonstrated that our method can accurately determine the complete genome sequences of the temperate phages, with exact flanking sites (attP and attB sites), outperforming other state-of-the-art prophage prediction methods. Our analysis indicates that temperate phages are likely to function in the evolution of microbes by 1) cross-infecting different bacterial host species; 2) transferring antibiotic resistance and virulence genes; and 3) interacting with hosts through restriction-modification and CRISPR/anti-CRISPR systems. This work provides a comprehensive complete temperate phage genome database and relevant information, which can serve as a valuable resource for phage research.

bioinformatics↗

bioRxiv2021

scSVAS: CNV clonal visualization online platform for large scale single-cell genomics

The recent advance of single-cell copy number variation analysis plays an essential role in addressing intra-tumor heterogeneity, identifying tumor subgroups, and restoring tumor evolving trajectories at single-cell scale. Pleasant visualization of copy number analysis results boosts productive scientific exploration, validation, and sharing. Several single-cell analysis figures have the effectiveness of visualizations for understanding single-cell genomics in published articles and software packages. However, they almost lack real-time interaction, and it is hard to reproduce them. Moreover, existing tools are time-consuming and memory-intensive when they reach large-scale single-cell throughputs. We present an online visualization platform, scSVAS, for real-time interactive single-cell genomics data visualization. scSVAS is specifically designed for large-scale single-cell analysis. Compared with other tools, scSVAS manifests the most comprehensive functionalities. After uploading the specified input files, scSVAS deploys the online interactive visualization automatically. Users may make scientific discoveries, share interactive visualization, and download high-quality publication-ready figures. scSVAS provides versatile utilities for managing, investigating, sharing, and publishing single-cell copy number variation profiles. We envision this online platform will expedite the biological understanding of cancer clonal evolution in single-cell resolution. All visualizations are publicly hosted at https://sc.deepomics.org.

bioinformatics↗

bioRxiv2021

Molecular basis for PICS-mediated piRNA biogenesis and cell division

By incorporating two mutually exclusive factors, PID-1 and TOST-1, C. elegans PICS complex plays important roles in piRNA biogenesis, chromosome segregation and cell division, respectively. We firstly mapped the interaction network between PICS subunits. By solving the several complex structures, including those of TOFU-6/PICS-1, ERH-2/PICS-1, and ERH-2/TOST-1, we uncover the mechanisms underlying the interactions between PICS subunits. Our biochemical experiment demonstrates that PICS exists as an octamer consisting of two copies of each subunits. Combining structural analyses with mutagenesis experiments, we identified residues of PICS subunits that are critical for maintaining intact PICS complex in vitro. Furthermore, using genetics, cell biology and imaging experiments, we found that those mutants impairing the in vitro interaction network within PICS, also lead to abnormal dysfunction PICS in vivo, including mislocalization of PICS, and reduced levels of piRNAs or abnormal chromosome segregation and cell division. Therefore, our work provides structural insights into understanding the PICS-mediated piRNA biogenesis and cell division.

molecular biology↗

bioRxiv2021

Dual functions of ZmGI1 in the photoperiodic flowering pathway and salt stress responses in maize

The circadian clock perceives photoperiodic changes and initiates processes leading to floral transition. GIGANTEA (GI) primarily functions as a principal clock component that integrates environmental cues into regulation of growth and development in Arabidopsis. However, it is unclear whether ZmGIs regulate photoperiodic flowering and abiotic stress response. Here, we demonstrated that the expression of ZmGI1 depicted a typical circadian pattern and was differentially expressed under LDs and SDs in photoperiodic sensitive and insensitive maize lines. The transcription level was significantly and positively correlated with days to silking and photoperiodic sensitivity in maize. Moreover, natural variation in ZmGI1 was associated with maize photoperiod response and the fine-tuning of plant development traits. Overexpression of ZmGI1Huangzao4 induced early flowering and enhanced salt tolerance in Arabidopsis relative to the wild-type and gi mutants. ZmGI1 formed a protein complex with ZmFKF1 and acted as a positive regulator of flowering time by regulating CONSTANS transcription in the photoperiod pathway. The ZmGI1/ZmThox complex regulates oxidative stress induced by salt stress via a redox balance pathway. Over all, we have provided compelling evidence to suggest that ZmGI1 is a pleotropic gene whose expression depicts a typical circadian rhythmic pattern and regulates flowering time and confers salt stress tolerance.

developmental biology↗

bioRxiv2021

Intestinal helminth infection transforms the CD4+ T cell composition of the skin

Intestinal helminth parasites can alter immune responses to vaccines, other infections, allergens and autoantigens, indicating effects on host immune responses in distal barrier tissues. We herein show that C57BL/6 mice infected with the strictly intestinal nematode Heligmosomoides polygyrus have impaired capacity to initiate skin immune responses and develop skin-resident memory cells to mycobacterial antigens, both during infection and months after deworming therapy. Surprisingly, and in contrast to a previously noted loss of T cells in peripheral lymph nodes, the skin of worm-infected mice harboured higher numbers of CD4+ T cells compared to skin of uninfected controls. H. polygyrus-specific TH2 cells accumulated during infection and remained after worm expulsion. Accumulation of TH2 cells in the skin was associated with increased expression of the skin-homing chemokine receptors CCR4 and CCR10 on CD4+ T cells in blood and mesenteric lymph nodes draining intestinal tissues, indicating gut-to-skin trafficking of cells. In conclusion, we show that infection by a strictly intestinal helminth has long-term effects on immune cell composition and local immune responses to unrelated antigens in the skin, revealing a novel mechanism for T cell colonization and worm-mediated immunosuppression in this organ.

immunology↗

bioRxiv2021

Class II LBD genes ZmLBD5 and ZmLBD33 regulate gibberellin and abscisic acid biosynthesis

Lateral organ boundaries domain (LBD) proteins are plant-specific transcription factors. Class I LBD members are widely reported to be pivotal for organ development, however, the role of class II members is unknown in cereal crops. Class II LBD proteins are distinguished from class I by the lack of a Gly-Ala-Ser (GAS) peptide and leucine-zipper-like coiled-coil domain, which is thought to be essential for protein dimerization. In this study, ZmLBD5 and ZmLBD33 form homo- and hetero-dimers, like class I members. At seedling stage, ZmLBD5 promoted biomass accumulation (shoot dry weight and root dry weight), root development (root length, root number, and root volume), and organ expansion (leaf area), while ZmLBD33 repressed these processes and display a dwarf phenotype. Both ZmLBD5 and ZmLBD33 displayed negative roles in drought tolerance mainly by increasing stomatal density and stomatal aperture. RNA sequencing, gene ontology enrichment analysis, and transient luciferase expression assays indicated that ZmLBD5 and ZmLBD33 are mainly involved in the regulation of the TPS-KS-GA2ox gene module, which comprises key enzymatic genes upstream of GA and ABA biosynthesis. GA1 content increased in ZmLBD5-overexpressing seedlings, while GA3 and abscisic acid content decreased in both transgenic seedlings. Consequently, exogenous GA1 or GA3 undoubtedly rescued the dwarf phenotype of ZmLBD33-overexpressing plants, with GA1 performing better. The study of ZmLBD5 and ZmLBD33 sheds light on the function of the class II LBD gene family in maize.

plant biology↗