bioRxiv Science⌕ Search

Biology subjects

He, F.

Publications and source records attributed to He, F..

At least 127 records · Page 7Linked to original sources
bioRxiv2020

Multiple phosphatidylinositol(3)phosphate roles in retinal pigment epithelium membrane recycling

The low-abundance lipid phosphatidylinositol-3-phosphate (PI(3)P) is important for membrane dynamics in autophagy, endosome processing, and phagocytosis. In retinal pigmented epithelial cells (RPE) all three pathways are important, but phagocytosis of disk membranes shed from adjacent photoreceptors is especially important for ensuring health of photoreceptors and preventing retinal degeneration. By eliminating Vps34, the kinase responsible for synthesizing PI(3)P in RPE, we have found that PI(3)P plays distinct roles in each pathway. In phagocytosis it is not required for disk engulfment or phagosome transport but is essential for recruitment and lipidation of LC3. In contrast, initiation of autophagy and LC3 recruitment to autophagosomes does not require PI(3)P, which can be bypassed by an alternative mechanism of ATG16L recruitment that does not require PI(3)P, Rab11a, or WIPI2. In all three pathways, PI(3)P is essential for fusion with lysosomes; autophagosomes, phagosomes, and Rab7-positive late endosomes, as well as enlarged lysosomes, accumulate in large numbers in the absence of Vps34, leading to cell death.

cell biology↗
bioRxiv2019

Single-cell transcriptomics reveals diverse and complex gene expression alterations in human trisomy 18

Trisomy 18, commonly known as Edwards syndrome, is the second most common autosomal trisomy among live born neonates. Multiple tissues including cardiac, abdominal, and nervous systems are affected by an extra chromosome 18. To delineate the complexity of anomalies of trisomy 18, we analyzed amniotic fluid cells from two normal and three trisomy 18 samples using single-cell transcriptomics. We identified six cell groups, which function in major tissue development such as kidney, vasculature, and smooth muscle, and display significant alterations in gene expression detected by single-cell RNA-sequencing. Moreover, we demonstrated significant gene expression changes in previously proposed trisomy 18 critical regions, and identified three new regions such as 18p11.32, 18q11, 18q21.32, which are likely associated with trisomy 18 phenotypes. Our results indicate complexity of trisomy 18 at the gene expression level and reveal genetic reasoning of diverse phenotypes in trisomy 18 patients.

genetics↗
bioRxiv2019

Nonsense suppression position effect implicates poly(A)-binding protein in the regulation of translation termination

Readthrough of translation termination codons, also known as nonsense suppression, is a relatively inefficient process mediated by ribosomal A site recognition and insertion of near-cognate tRNAs. Multiple factors influence readthrough efficiency, including nonsense codon specificity and context. To determine whether nonsense codon position in a gene influences the extent of readthrough, we generated a series of LUC nonsense alleles and quantitated both readthrough and termination efficiencies at each nonsense codon in yeast cells lacking nonsense-mediated mRNA decay (NMD) activity. Readthrough efficiency for premature termination codons (PTCs) manifested a marked dependence on PTC proximity to the mRNA 3-end, decreasing progressively across the LUC ORF but increasing with 3-UTR lengthening. These effects were eliminated, and translation termination efficiency decreased considerably, in cells harboring pab1 mutations. Our results support a critical role for poly(A)-binding protein in the regulation of translation termination and suggest that inefficient termination is the trigger for NMD.

molecular biology↗
bioRxiv2019

GpABC: a Julia package for approximate Bayesian computation with Gaussian process emulation

Approximate Bayesian computation (ABC) is an important framework within which to infer the structure and parameters of a systems biology model. It is especially suitable for biological systems with stochastic and nonlinear dynamics, for which the likelihood functions are intractable. However, the associated computational cost often limits ABC to models that are relatively quick to simulate in practice. We here present a Julia package, GpABC, that implements parameter inference and model selection for deterministic or stochastic models using i) standard rejection ABC or ABC-SMC, or ii) ABC with Gaussian process emulation. The latter significantly reduces the computational cost.\n\nURL: https://github.com/tanhevg/GpABC.jl

systems biology↗
bioRxiv2019

Multivariable regulation of gene expression plasticity in metazoans

An important capacity of genes is the rapid change of expression levels to cope with environment, known as expression plasticity. Elucidating the genomic mechanisms determining expression plasticity is critical for understanding the molecular basis of phenotypic plasticity, fitness, and adaptation. In this study, we systematically quantified genome-wide gene expression plasticity in four metazoan species by integrating changes of expression levels under a large number of genetic and environmental conditions. From this, we demonstrated that expression plasticity measures a distinct feature of gene expression that is orthogonal to other well-studies features including gene expression potential and tissue specificity/broadness. Expression plasticity is conserved across species with important physiological implications. The magnitude of expression plasticity is highly correlated with gene function and genes with high plasticity are implicated in disease susceptibility. Genome-wide analysis identified many conserved promoter cis-elements, trans-acting factors (such as CFCF), and gene body histone modifications (H3K36me3, H3K79me2, and H4K20me1) that are significantly associated with expression plasticity. Analysis of expression changes in perturbation experiments further validated a causal role of specific transcription factors and histone modifications. Collectively, this work reveals general properties, physiological implications, and multivariable regulation of gene expression plasticity in metazoans, extending the mechanistic understanding of gene regulation.

genomics↗
bioRxiv2019

Distinct and overlapping functions of Miscanthus sinensis MYB transcription factors SCM1 and MYB103 in lignin biosynthesis

Cell wall recalcitrance is a major constraint for the exploitation of lignocellulosic biomass as renewable resource for energy and bio-based products. Transcriptional regulators of the lignin biosynthetic pathway represent promising targets for tailoring lignin content and composition in plant secondary cell walls. A wealth of research in model organisms has revealed that transcriptional regulation of secondary cell wall formation is orchestrated by a hierarchical transcription factor (TF) network with NAC TFs as master regulators and MYB factors in the lower tier regulators. However, knowledge about the transcriptional regulation of lignin biosynthesis in lignocellulosic feedstocks, such as Miscanthus, is limited. Here, we characterized two Miscanthus MYB TFs, MsSCM1 and MsMYB103, and compared their transcriptional impact with that of the master regulator MsSND1. In Miscanthus leaves MsSCM1 and MsMYB103 are expressed at growth stages associated with lignification. Ectopic expression of MsSCM1 and MsMYB103 in tobacco leaves was sufficient to trigger secondary cell wall deposition with distinct sugar and lignin composition. Moreover, RNA-seq analysis revealed that the transcriptional responses to MsSCM1 and MsMYB103 overexpression showed extensive overlap with the response to MsSND1, but were distinct from each other, underscoring the inherent complexity of secondary cell wall formation. Together, MsSCM1 and MsMYB103 represent interesting targets for manipulations of lignin content and composition in Miscanthus towards tailored biomass.

plant biology↗
bioRxiv2019

Shotgun metagenomics reveals an enrichment of potentially cross-reactive bacterial epitopes in ankylosing spondylitis patients, as well as the effects of TNFi therapy and the host’s genotype upon microbiome composition

Diverse evidence including clinical, genetic and microbiome studies support a major role of the gut microbiome in the common immune-mediated arthropathy, ankylosing spondylitis (AS). To further investigate this we performed metagenomic analysis of a case-control cohort of 250 Han-Chinese subjects. Previous reports of gut dysbiosis in AS were re-confirmed and several notable bacterial species and functional categories were differentially abundant. TNF-inhibitor (TNFi) therapy at least partially restored the perturbed microbiome observed in untreated AS cases to that of healthy controls, including several important bacterial species that have been previously associated with AS and other related diseases. Enrichment of bacterial peptides homologous to HLA-B27-presented epitopes was observed in the stools of AS patients, suggesting that either HLA-B27 fails to clear these or that they are involved in driving HLA-B27-associated immune reactions. TNFi therapy of AS patients was also associated with a reduction of potentially arthritogenic bacterial peptides, relative to untreated patients. An AS-associated SNP in RUNX3 significantly influenced the microbiome in two independent cohorts, highlighting a host genotype (other than HLA-B27) potentially influencing AS via the microbiome. These findings emphasise the key role that the gut microbiome plays in driving the pathogenesis of AS.

microbiology↗
bioRxiv2019

Combinatorial morphogenetic and mechanical cues to mimic bone development for defect repair

Endochondral ossification during long bone development and natural fracture healing initiates by mesenchymal cell condensation and is directed by local morphogen signals and mechanical cues. Here, we aimed to mimic these developmental conditions for regeneration of large bone defects. We hypothesized that engineered human mesenchymal stem cell (hMSC) condensations with in situ presentation of transforming growth factor-{beta}1 (TGF-{beta}1) and/or bone morphogenetic protein-2 (BMP-2) from encapsulated microparticles would promote endochondral regeneration of critical-sized rat femoral bone defects in a manner dependent on the in vivo mechanical environment. Mesenchymal condensations induced bone formation dependent on morphogen presentation, with dual BMP-2 + TGF-{beta}1 fully restoring mechanical bone function by week 12. In vivo ambulatory mechanical loading, initiated at week 4 by delayed unlocking of compliant fixation plates, significantly enhanced the bone formation rate in the four weeks after load initiation in the dual morphogen group. In vitro, local presentation of either BMP-2 alone or BMP-2 + TGF-{beta}1 initiated endochondral lineage commitment of mesenchymal condensations, inducing both chondrogenic and osteogenic gene expression through SMAD3 and SMAD5 signaling. In vivo, however, endochondral cartilage formation was evident only in the BMP-2 + TGF-{beta}1 group and was enhanced by mechanical loading. The degree of bone formation was comparable to BMP-2 soaked on collagen but without the ectopic bone formation that limits the clinical efficacy of BMP-2/collagen. In contrast, mechanical loading had no effect on autograft-mediated repair. Together, this study demonstrates a biomimetic template for recapitulating developmental morphogenic and mechanical cues in vivo for tissue engineering. One Sentence SummaryMimicking aspects of the cellular, biochemical, and mechanical environment during early limb development, chondrogenically-primed human mesenchymal stem cell condensations promoted functional healing of critical-sized femoral defects via endochondral ossification, and healing rate and extent was a function of the in vivo mechanical environment.

bioengineering↗
bioRxiv2019

Genomewide Analyses of Psychological Resilience in US Army Soldiers

Though a growing body of preclinical and translational research is illuminating a biological basis for resilience to stress, little is known about the genetic basis of psychological resilience in humans. We conducted genomewide association studies (GWAS) of self-assessed (by questionnaire) and outcome-based (incident mental disorders from pre- to post-deployment) resilience among European (EUR) ancestry soldiers in the Army Study To Assess Risk and Resilience in Servicemembers (STARRS). Self-assessed resilience (N=11,492) was found to have significant common-variant heritability (h2=0.162, se=0.050, p=5.37e-4), and to be significantly negatively genetically correlated with neuroticism (rg= -0.388, p=0.0092). GWAS results from the EUR soldiers revealed a genomewide significant locus (4 SNPs in LD; top SNP: rs4260523, p=5.654e-09) on an intergenic region on Chr 4 upstream from DCLK2 (Doublecortin-Like Kinase 2), a member of the doublecortin (DCX) family of kinases that promote survival and regeneration of injured neurons. A second gene, KLHL36 (Kelch Like Family Member 36) was detected at gene-wise genomewide significance (p=1.89e-06). A polygenic risk score derived from the self-assessed resilience GWAS was not significantly associated with outcome-based resilience. In very preliminary results, genomewide significant association with outcome-based resilience was found for one locus (top SNP: rs12580015) on Chr 12 downstream from SLC15A5 (solute carrier family 15 member 5) in the small group (N=581) of subjects exposed to the highest level of deployment stress. The further study of genetic determinants of resilience has the potential to illuminate the molecular bases of stress-related psychopathology and potentially point to new avenues for therapeutic intervention.

genetics↗
bioRxiv2018

Establishment of baseline sensitivity of Rhizoctonia solani to thifluzamide in corn and its field application

In recent years, banded leaf sheath blight in corn has become an important disease in corn that seriously affects quality and yield. This paper aims to evaluate the sensitivity of Rhizoctonia solani to thifluzamide in corn, to clarify the effect of seed coating using a thifluzamide suspension agent on safety and physiological indicators and to determine banded leaf sheath blight in corn control effectiveness in the field, thereby providing a basis for the application of thifluzamide suspension agent as a seed coating. In this study, the thifluzamide sensitivity of 102 strains of R. solani in corn in different regions of Shandong was determined using the mycelial growth rate method, and the average half-maximal effective concentration value (EC50) was 0.086{+/-}0.004 g/mL. The sensitivity was consistent with a continuous and skewed normal distribution, and the sensitivity distribution frequency exhibited a continuous, unimodal curve, indicating that thifluzamide had strong inhibitory activity on the mycelial growth of R. solani in corn. The impacts of using a thifluzamide suspension agent for seed coating on safety and physiological indicators as well as the control effect in corn were evaluated by combining seed coating, an indoor pot test, and a field trial. The root activities under 24 g a.i. 100 kg-1 seed and 12 g a.i. 100 kg-1 seed were found to increase by 78.01% and 77.40%, respectively, compared with that under the blank control; the chlorophyll content of corn increased most significantly at a dosage of 24 g a.i. 100 kg-1, which was a 32.32% increase compared to the blank control. Thifluzamide (FS) could significantly increase the hundred-grain weight of corn and the per-plot yield. Among the examined dosages, 24 g a.i. 100 kg-1 seed had the most significant treatment effect, with the hundred-grain weight increasing by 12.47% and the yield rate increasing by 15.72% compared to the control in 2016, Simultaneously, the hundred-grain weight increasing by 13.44% and the yield rate increasing by 14.11% compared to the control in 2017. Three dosages of 24% thifluzamide (FS) increased the emergence rate and seedling growth of corn to varying extents. The field control effectiveness against banded leaf sheath blight in corn was best at the dosage of 24 g a.i. 100 kg-1 seed for seed dressing with thifluzamide (FS); in 2016 and 2017, the control effects in the small bell stage, large bell stage, tasseling and pollen-shedding stage, silking stage, milk-ripening stage, and wax-ripening stage were 100%, 66.73%, 52.8%, 67.81%, 68.48%, and 62.68% (2016), respectively, and 74.97%, 63.17%, 50.90%, 53.60%, 61.42%, and 55.88% (2017). These results indicated that thifluzamide had enormous potential for controlling banded leaf sheath blight in corn.

pathology↗
bioRxiv2018

The patterns of vascular plant discoveries in China

Botanical discovery has a long journey of revelation that contributes unparalleled knowledge to shape our understanding about nature. Plant discovery in China is an immanent part of that journey. To understand the patterns of plant discoveries in China and detect which taxa and areas harbor most numbers of undiscovered species, we analyzed the discovery times of 31093 vascular plant species described in Flora of China. We found that species with larger range size and distributed in northeastern part of China have a higher discovery probability. Species distributed on the coast were discovered earlier than inland species. Trees and shrubs of seed plants have the highest discovery probability and ferns have the lowest discovery probability. Herbs hold the largest number of undiscovered species in China. Most undiscovered species are found in southwest China, where three global biodiversity hotspots locate. Spatial patterns of mean discovery year and inventory completeness are mainly driven by the total number of species and human population density in an area and whether the area is coastal or not. Our results showed that socio-economic factors dictate the discovery patterns of vascular plants in China. Undiscovered species are mostly narrow-ranged, inconspicuous endemic such as herbs, which are prone to extinctions and locate in biodiversity hotspots in southwest China. We suggest that the future effort on plant discovery in China be prioritized in southwest China.

plant biology↗
bioRxiv2018

General decapping activators target different subsets of inefficiently translated mRNAs

The Dcp1-Dcp2 decapping enzyme and the decapping activators Pat1, Dhh1, and Lsm1 regulate mRNA decapping, but their mechanistic integration is unknown. We analyzed the gene expression consequences of deleting PAT1, LSM1, or DHH1, or the DCP2 C-terminal domain, and found that: i) the Dcp2 C-terminal domain is an effector of both negative and positive regulation; ii) rather than being global activators of decapping, Pat1, Lsm1, and Dhh1 directly target specific subsets of yeast mRNAs and loss of the functions of each of these factors has substantial indirect consequences for genome-wide mRNA expression; and iii) transcripts targeted by Pat1, Lsm1, and Dhh1 exhibit only partial overlap, are generally translated inefficiently, and, as expected, are targeted to decapping-dependent decay. Our results define the roles of Pat1, Lsm1, and Dhh1 in decapping of general mRNAs and suggest that these factors may monitor mRNA translation and target unique features of individual mRNAs.

molecular biology↗
bioRxiv2018

Arabidopsis species deploy distinct strategies to cope with drought stress

O_LIBackground and Aims Water limitation is an important determinant of the distribution, abundance and diversity of plant species. Yet, little is known about how the response to limiting water supply changes among closely related plant species with distinct ecological preferences. Comparison of the model annual species A. thaliana to its close perennial relatives A. lyrata and A. halleri, can help disentangle the molecular and physiological changes contributing to tolerance and avoidance mechanisms, because these species must maintain tolerance and avoidance mechanisms to increase long-term survival, but they are exposed to different levels of water stress and competition in their natural habitat.\nC_LIO_LIMethods We conducted a dry-down experiment that mimics a period of missing precipitation. We quantified the covariation of progressive decrease in soil water content (SWC) with various physiological and morphological plant traits across a set of representative genotypes in Arabidopsis thaliana, A. lyrata and A. halleri. To quantify the degree of plant stress, transcriptome changes were also monitored.\nC_LIO_LIKey Results The analysis of trait co-variation demonstrates that the three species differ in the strategies they deploy to respond to drought stress. A. thaliana showed drought avoidance reaction but failed to survive wilting. A. lyrata efficiently combined avoidance and tolerance mechanisms. By contrast, A. halleri showed some degree of tolerance to wilting but it did not seem to protect itself from the stress imposed by drought. Transcriptome data collected just before plant wilting and after recovery corroborated the phenotypic analysis, with A. lyrata and A. halleri showing a stronger activation of recovery- and stress-related genes, respectively.\nC_LIO_LIConclusions We conclude that these three Arabidopsis species have evolved distinct strategies to face drought stress, and discuss the extent to which these strategic differences reflect their respective ecological priorities.\nC_LI

plant biology↗
bioRxiv2018

PANDA: A comprehensive and flexible tool for proteomics data quantitative analysis

SummaryAs the experiment techniques and strategies in quantitative proteomics are improving rapidly, the corresponding algorithms and tools for protein quantification with high accuracy and precision are continuously required to be proposed. Here, we present a comprehensive and flexible tool named PANDA for proteomics data quantification. PANDA, which supports both label-free and labeled quantifications, is compatible with existing peptide identification tools and pipelines with considerable flexibility. Compared with MaxQuant on two complex da-tasets, PANDA was proved to be more accurate and precise with less computation time. Additionally, PANDA is an easy-to-use desktop ap-plication tool with user-friendly interfaces.\n\nAvailabilityPANDA is freely available for download at https://sourceforge.net/projects/panda-tools/.\n\nContact1987ccpacer@163.com and zhuyunping@gmail.com

bioinformatics↗
bioRxiv2018

LFAQ: towards unbiased label-free absolute protein quantification by predicting peptide quantitative factors

Mass spectrometry (MS) has become a prominent choice for large-scale absolute protein quantification, but its quantification accuracy still has substantial room for improvement. A crucial issue is the bias between the peptide MS intensity and the actual peptide abundance, i.e., the fact that peptides with equal abundance may have different MS intensities. This bias is mainly caused by the diverse physicochemical properties of peptides. Here, we propose a novel algorithm for label-free absolute protein quantification, LFAQ, which can correct the biased MS intensities by using the predicted peptide quantitative factors for all identified peptides. When validated on datasets produced by different MS instruments and data acquisition modes, LFAQ presented accuracy and precision superior to those of existing methods. In particular, it reduced the quantification error by an average of 46% for low-abundance proteins.

bioinformatics↗
bioRxiv2018

Gene editing and mutagenesis reveal inter-cultivar differences and additivity in the contribution of TaGW2 homoeologues to grain size and weight in wheat

The TaGW2 gene homoeologues have been reported to be negative regulators of grain size (GS) and thousand grain weight (TGW) in wheat. However, the contribution of each homoeologue to trait variation among different wheat cultivars is not well documented. We used the CRISPR-Cas9 system and TILLING to mutagenize each homoeologous gene copy in cultivars Bobwhite and Paragon, respectively. Plants carrying single-copy nonsense mutations in different genomes showed different levels of GS/TGW increase, with TGW increasing by an average of 5.5% (edited lines) and 5.3% (TILLING mutants). In any combination, the double homoeologue mutants showed higher phenotypic effects than the respective single-genome mutants. The double mutants had on average 12.1% (edited) and 10.5% (TILLING) higher TGW with respect to wild-type lines. The highest increase in GS and TGW was shown for triple mutants of both cultivars, with increases of 16.3% (edited) and 20.7% (TILLING) in TGW. The additive effects of the TaGW2 homoeologues were also demonstrated by the negative correlation between the functional gene copy number and GS/TGW in Bobwhite mutants and an F2 population. The highest single-genome increases in GS and TGW in Paragon and Bobwhite were obtained by mutations in the B and D genomes, respectively. These inter-cultivar differences in the phenotypic effects between the TaGW2 gene homoeologues coincide with inter-cultivar differences in the homoeologue expression levels. These results indicate that GS/TGW variation in wheat can be modulated by the dosage of homoeologous genes with inter-cultivar differences in the magnitude of the individual homoeologue effects.

genetics↗
bioRxiv2018

Robustness of Transposable Element regulation but no genomic shock observed in interspecific Arabidopsis hybrids

The merging of two divergent genomes in a hybrid is believed to trigger a \"genomic shock\", disrupting gene regulation and transposable element (TE) silencing. Here, we tested this expectation by comparing the pattern of expression of transposable elements in their native and hybrid genomic context. For this, we sequenced the transcriptome of the Arabidopsis thaliana genotype Col-0, the A. lyrata genotype MN47 and their F1 hybrid. Contrary to expectations, we observe that the level of TE expression in the hybrid is strongly correlated to levels in the parental species. We detect that at most 1.1% of expressed transposable elements belonging to two specific subfamilies change their expression level upon hybridization. Most of these changes, however, are of small magnitude. We observe that the few hybrid-specific modifications in TE expression are more likely to occur when TE insertions are close to genes. In addition, changes in epigenetic histone marks H3K9me2 and H3K27me3 following hybridization do not coincide with TEs with changed expression. Finally, we further examined TE expression in parents and hybrids exposed to severe dehydration stress. Despite the major reorganization of gene and TE expression by stress, we observe that hybridization does not lead to increased disorganization of TE expression in the hybrid. We conclude that TE expression is globally robust to hybridization and that the term \"genomic shock\" is no longerappropriate to describe the anticipated consequences of merging divergent genomes in a hybrid.

genomics↗