Biology subjects

Mao, Y.

Publications and source records attributed to Mao, Y..

At least 181 records · Page 10Linked to original sources

bioRxiv2019

Genome analysis and Hi-C assisted assembly of Elaeagnus angustifolia L., a deciduous tree belonging to Elaeagnaceae

Elaeagnus angustifolia L. is a deciduous tree of the Elaeagnaceae family. It is widely used in the study of abiotic stress tolerance in plants and for the improvement of desertification-affected land due to its characteristics of drought resistance, salt tolerance, cold resistance, wind resistance, and other environmental adaptation. Here, we report the complete genome sequencing using the Pacific Biosciences (PacBio) platform and Hi-C assisted assembly of E. angustifolia. A total of 44.27 Gb raw PacBio sequel reads were obtained after filtering out low-quality data, with an average length of 8.64 Kb. And 39.56 Gb clean reads was obtained, with a sequencing coverage of 75x, and Q30 ratio > 95.46%. The 510.71 Mb genomic sequence was mapped to the chromosome, accounting for 96.94% of the total length of the sequence, and the corresponding number of sequences was 269, accounting for 45.83% of the total number of sequences. The genome sequence study of E. angustifolia can be a valuable source for the comparative genome analysis of the Elaeagnaceae family members, and can help to understand the evolutionary response mechanisms of the Elaeagnaceae to drought, salt, cold and wind resistance, and thereby provide effective theoretical support for the improvement of desertification-affected land.

genetics↗

bioRxiv2019

NEAT1 involves Alzheimer’s Disease (AD) progression via regulation of glycolysis and P-tau

Nuclear paraspeckles assembly transcript 1 (NEAT1) is a well-known long noncoding RNA (LncRNA) with unclear mechanism in Alzheimers disease (AD) progression. Here, we found that NEAT1 down-regulates in the early stage of AD patients and APPswe/PS1dE9 mouse. Moreover, knockdown of NEAT1 induced de-polymerization of microtubule (MT) and axonal retraction of nerve cells by dysregulation of the FZD3/GSK3{beta}/p-tau signaling pathway. Histone acetylation analysis at the Frizzled Class Receptor 3 (FZD3) promoter shows a marked decreased in the levels of the H3K27 acetylation (H3K27Ac) after NEAT1 knockdown. Our data demonstrates that P300/CBP recruited by NEAT1 to the FZD3 promoter and induced its transcription via histone acetylation. In recent years a growing number of evidences have shown an abnormal brain glucose homeostasis in AD. In the present study we also observed an abnormal brain glucose homeostasis and enhanced sirtuin1 (SIRT1) activity after knockdown of NEAT similarly as in AD. Our results provided insight into the role of NEAT1 in the maintenance of MT stability and its effect on glucose metabolism during early stages of AD.

neuroscience↗

bioRxiv2019

Clinical Efficacy and Adverse Effects of Antibiotics Used to Treat Mycobacterium abscessus Pulmonary Disease

Treatment of Mycobacterium abscessus pulmonary infection requires long-term administration of multiple antibiotics. Little is known, however, about the impact of each antibiotic on treatment outcomes. A retrospective analysis was conducted to evaluate the efficacy and adverse effects of antibiotics administered in 244 cases of M. abscessus pulmonary disease. Only 110 (45.1%) patients met the criteria for treatment success. Treatment with amikacin (AOR, 3.275; 95% CI, 1.221 - 8.788), imipenem (AOR, 2.078; 95% CI, 1.151 - 3.753), linezolid (AOR, 2.231; 95% CI, 1.078 - 4.616) and tigecycline (AOR, 2.040; 95% CI, 1.079 - 3.857) was successful. The incidence of adverse effects was high (192/244, 78.7%). Severe adverse effects were primarily: ototoxicity (14/60, 23.3%) caused by amikacin; gastrointestinal (14/60, 23.3%) caused by tigecycline; and myelosuppression (5/60, 8.3%) caused by linezolid. In conclusion, the rate of success in treating M. abscessus pulmonary disease is still unsatisfactory; the administration of amikacin, imipenem, linezolid and tigecycline correlated with increased treatment success. Adverse side effects are common due to the long-term and combined antibiotic therapy. Ototoxicity, gastrointestinal and myelosuppression are the most severe.

microbiology↗

bioRxiv2019

Inertial Measurement Unit-Based Estimation of Foot Trajectory for Clinical Gait Analysis

Gait analysis is used widely in clinical practice for the evaluation of abnormal gait caused by disease. Conventionally, medical professionals use motion capture systems or make visual observations to evaluate a patients gait. Recent biomedical engineering studies have proposed easy-to-use gait analysis methods involving wearable sensors with inertial measurement units (IMUs). IMUs placed on the shanks just above the ankles allow for the long-term monitoring of gait because the participant can walk with or without shoes during the analysis. As far as the authors know, there is no report of the gait analysis method that estimates stride length, gait speed, stride duration, stance duration, and swing duration at the same time. In this study, we tested a proposed gait analysis method that uses IMUs attached on the shanks to estimate foot trajectory and temporal gait parameters. We evaluated this proposed method by analyzing the gait of 10 able-bodied participants (mean age 23.1 years, nine men and one woman). Wearable sensors were attached to the participants shanks, and we measured three-axis acceleration and three-axis angular velocity with the sensors to estimate foot trajectory during walking. We compared gait parameters estimated from the foot trajectory obtained with the proposed method and those measured with a motion capture system. Mean accuracy (mean {+/-} standard deviation) was -0.046 {+/-} 0.026 m for stride length, -0.036 {+/-} 0.026 m/s for gait speed, -0.002 {+/-} 0.019 s for stride duration, -0.000 {+/-} 0.016 s for stance duration, and -0.002 {+/-} 0.022 s for swing duration. These results suggest that the proposed method is useful for evaluation of clinical gait parameters.

physiology↗

bioRxiv2019

Neph/Nephrin-like adhesion and tissue level pulling forces regulate cell intercalation during Drosophila retina development.

Intercalation between neighboring cells contributes to shaping epithelial tissues and is regulated by the contractile actomyosin cytoskeleton. While intercalation typically occurs over minutes, instances of much slower cell intercalation have been reported during organogenesis. This is observed, for example, for the four glial-like cone cells (CC) that intercalate during Drosophila retinal patterning. Here we show that Myosin-II activity in the CCs is largely dispensable for their intercalation. Instead, we find that differential activity of the Notch-signaling pathway within the CC quartet regulates intercalation, which also depends on the cell adhesion proteins Roughest and Hibris. In addition, mathematical modeling predicts that forces external to the intercalating CC quartet are necessary for intercalation. Consistent with this prediction we show that the surrounding primary pigment cells are under significant contractile tension. Altogether, our work elucidates a novel mode of cell intercalation that relies on Neph/Nephrin-like adhesion and forces external to the intercalating cells.

developmental biology↗

bioRxiv2019

Planar differential growth rates determine the position of folds in complex epithelia

Folding is a fundamental process shaping epithelial sheets into 3D architectures of organs. Initial positioning of folds is the foundation for the emergence of correct tissue morphology. Mechanisms forming individual folds have been studied, yet the precise positioning of the folds in complex, multi-folded epithelia is an open question. We present a model of morphogenesis, encompassing local differential growth, and tissue mechanics to investigate tissue fold positioning. We use Drosophila melanogaster wing imaginal disc as our model system, and show that there is spatial and temporal heterogeneity in its planar growth rates. This planar differential growth is the main driver for positioning the folds. Increased stiffness of the apical layer and confinement by the basement membrane drive fold formation. These influence fold positions to a lesser degree. The model successfully predicts the emergent morphology of wingless spade mutant in vivo, via perturbations solely on planar differential growth rates in silico.

biophysics↗

bioRxiv2018

Tissue Fluidity Promotes Epithelial Wound Healing

Epithelial tissues are inevitably damaged from time to time and must therefore have robust repair mechanisms. The behaviour of tissues depends on their mechanical properties and those of the surrounding environment1. However, it remains poorly understood how tissue mechanics regulates wound healing, particularly in in vivo animal tissues. Here we show that by tuning epithelial cell junctional tension, we can alter the rate of wound healing. We observe cells moving past each other at the wound edge by intercalating, like molecules in a fluid, resulting in seamless wound closure. Using a computational model, we counterintuitively predict that an increase in tissue fluidity, via a reduction in junctional tension, can accelerate the rate of wound healing. This is contrary to previous evidence that actomyosin tensile structures are important for wound closure2-6. When we experimentally reduce tissue tension, cells intercalate faster and wounds close in less time. The role we describe for tissue fluidity in wound healing, in addition to its known roles in developing7,8 and mature tissues9, reinforces the importance of the fluid state of a tissue.

biophysics↗

bioRxiv2018

An \"inverse approach\" to the treatment of amblyopia

Recent laboratory finding suggest that short-term patching the amblyopic eye (i.e., inverse occlusion) results in a larger and more sustained improvement in the binocular balance compared with normal controls. In this study, we investigate the cumulative effects of the short-term inverse occlusion in adults and old children with amblyopia. A prospective cohort study of 18 amblyopes (10-35 years old; 3 with strabismus) who have been subjected to 2 hours/day of inverse occlusion for 2 months. Patients who required refractive correction or whose refractive correction needed updating were given a 2-month period of refractive adaptation. The primary outcome measure was the binocular balance which was measured using a phase combination task, the secondary outcome measures were the best corrected visual acuity which was measured with a Tumbling E acuity chart and convert to logMAR units and the stereo acuity which was measured with the Random-dot preschool stereotest. The averaged binocular gain was 0.11 in terms of the effective contrast ratio (z = -2.344, p = 0.019, 2-tailed Related samples Wilcoxon Signed Ranks Test). The average acuity gain was 0.14 logMAR equivalent (t(17) = 0.13, p < 0.001, 2-tailed paired samples t-test). The averaged stereo acuity gain was 253 arc seconds (z = -2.689, p = 0.007). Based on more recent research concerning adult ocular dominance plasticity, contrary to current practice, patching the amblyopic eye makes more sense; comparable acuity benefits, better compliance, better binocular outcome and applicable to adults as well as old children.

neuroscience↗

bioRxiv2018

Visualizing ATP-dependent substrate-processing dynamics of the human 26S proteasome at near-atomic resolution

The proteasome is an ATP-dependent 2.5-megadalton machine responsible for ubiquitylated protein degradation in all eukaryotic cells. Here we present cryo-EM structures of the substrate-engaged human 26S proteasome in seven conformational states at 2.8-3.6 [A] resolution, captured during polyubiquitylated protein degradation. These structures visualize a continuum of dynamic substrate-proteasome interactions from ubiquitin recognition to processive substrate translocation, during which ATP hydrolysis sequentially navigate through all six ATPase subunits. Three principle modes of coordinated ATP hydrolysis are observed, featuring hydrolytic events in two oppositely positioned ATPases, in two consecutive ATPases, and in one ATPase at a time. They regulate deubiquitylation, translocation initiation and processive unfolding of substrates, respectively. A collective power stroke in the ATPase motor is generated by synchronized ATP binding and ADP release in the substrate-engaging and disengaging ATPases, respectively. It is amplified largely in the substrate-disengaging ATPase, and propagated unidirectionally by coordinated ATP hydrolysis in the third consecutive ATPase.

biochemistry↗

bioRxiv2018

GenoDup Pipeline: a tool to detect genome duplication using the dS-based method

Understanding whole genome duplication (WGD), or polyploidy, is fundamental to investigating the origin and diversification of organisms in evolutionary biology. The wealth of genomic data generated by next generation sequencing (NGS) has resulted in an urgent need for robust and accurate tools to detect WGD. Here, we present a useful and user-friendly pipeline called GenoDup for inferring WGD using the dS-based method. We have successfully applied GenoDup to identify WGD in empirical data from both plants and animals. The GenoDup Pipeline provides a reliable and useful tool to infer WGD from NGS data.

bioinformatics↗

bioRxiv2018

An ancient genome duplication in the speciose reef-building coral genus, Acropora

Whole-genome duplication (WGD) has been recognized as a significant evolutionary force in the origin and diversification of vertebrates, plants, and other organisms. Acropora, one of the most speciose reef-building coral genera, responsible for creating spectacular but increasingly threatened marine ecosystems, is suspected to have originated by polyploidy, yet there is no genetic evidence to support this hypothesis. Using comprehensive phylogenomic and comparative genomic approaches, we analyzed five Acropora genomes and an Astreopora genome (Scleractinia: Acroporidae) to show that a WGD event likely occurred between 27.9 and 35.7 Million years ago (Mya) in the most recent common ancestor of Acropora, concurrent with a massive worldwide coral extinction. We found that duplicated genes became highly enriched in gene regulation functions, some of which are involved in stress responses. The different functional clusters of duplicated genes are related to the divergence of gene expression patterns during development. Some gene duplications of proteinaceous toxins were generated by WGD in Acropora compared with other Cnidarian species. Collectively, this study provides evidence for an ancient WGD event in corals and it helps to explain the origin and diversification of Acropora.

evolutionary biology↗

bioRxiv2018

Dynamic m6A methylation facilitates mRNA triaging to stress granules

Summary blurbm6A-modification in the 5 vicinity of the coding sequence of transcripts provides a selective mechanism for triaging mRNAs to stress granules and is mediated by YTHDF3 reader protein.\n\nAbstractReversible post-transcriptional modifications on messenger RNA emerge as prevalent phenomena in RNA metabolism. The most abundant among them is N6-methyladenosine (m6A) which is pivotal for RNA metabolism and function, its role in stress response remains elusive. We have discovered that in response to oxidative stress, transcripts are additionally m6A-modified in their 5 vicinity. Distinct from that of the translationally-active mRNAs, this methylation pattern provides a selective mechanism for triaging mRNAs from the translatable pool to stress-induced stress granules. These stress-induced newly methylated sites are selectively recognized by the YTH domain family 3 (YTHDF3) reader protein, thereby revealing a new role for YTHDF3 in shaping the selectivity of stress response. Our findings describe a previously unappreciated function for RNA m6A modification in the oxidative-stress response and expand the breadth of physiological roles of m6A.

molecular biology↗

bioRxiv2018

Deciphering the rules which mRNA structures differs from vivo and vitro in Saccharomyces cerevisiae by deep neural networks

The structure of mRNA in vivo is influenced by various factors involved in the translation process, resulting in significant differentiation of mRNA structure from that in vitro. Because multiple factors cause the differentiation of in vivo and in vitro mRNA structures, it was difficult to perform a more accurate analysis of mRNA structures in previous studies. In this study, we have proposed a novel application of a deep neural network (DNN) model to predict the structural stability of mRNA in vivo by fitting six quantifiable features that may affect mRNA folding: ribosome density, minimum folding free energy, GC content, mRNA abundance, ribosomal initial density and position of mRNA structure. Simulated mutations of the mRNA structure were designed and then fed into the trained DNN model to compute their structural stability. We found unique effects of these six features on mRNA structural stability in vivo. Strikingly, the ribosome density of the structural region is the most important factor affecting the structural stability of mRNA in vivo, and the strength of the mRNA structure in vitro should have a relatively small effect on its structural stability in vivo. The recruitment of DNNs provides a new paradigm to decipher the differentiation of mRNA structure in vivo and in vitro. This improved knowledge on the mechanisms of factors influencing mRNA structural stability will facilitate the design and functional analysis of mRNA structure in vivo.

bioinformatics↗

bioRxiv2018

Isotropic myosin-generated tissue tension is required for the dynamic orientation of the mitotic spindle

The ability of epithelial cells to divide along their long cell axis, known as \"Hertwigs rule\", has been proposed to play an important and wide-ranging role in homogenising epithelial cell packing during tissue development and homeostasis. Since the position of the anaphase spindle defines the division plane, how divisions are oriented requires an understanding of the mechanisms that position the mitotic spindle. While many of the molecules required to orient the mitotic spindle have been identified in genetic screens, the mechanisms by which spindles read and align with the long cell axis remain poorly understood. Here, in exploring the dynamics of spindle orientation in mechanically distinct regions of the fly notum, we find that the ability of cells to properly orient their divisions depends both on cortical cues and on local tissue tension. Thus, spindles align with the long cell axis in tissues in which isotropic tension is elevated, but fail to do so in elongated cells within the crowded midline, where tension is low. Importantly, these region-specific differences in spindle behaviour can be reversed by decreasing or increasing the activity of non-muscle Myosin II. In addition, spindles in a tissue experiencing isotropic stress fail to align with the long cell axis if cells are mechanically isolated from their neighbours. These data lead us to propose that isotropic tension is required within an epithelium to provide cells with a mechanically stable substrate upon which localised cortical Dynein can pull on astral microtubules to orient the spindle.

cell biology↗

bioRxiv2018

Further expansion of methane metabolism in the Archaea

The recent discovery of key methane-metabolizing genes in the genomes from the archaeal phyla Bathyarchaeota and Verstraetearchaeota has expanded our understanding of the distribution of methane metabolism outside of the phylum Euryarchaeota. Here, we recovered two near-complete crenarchaeotal metagenome-assembled genomes (MAGs) from circumneutral hot springs that contain genes for methanogenesis, including the genes that encode for the key methyl-coenzyme M reductase (MCR) complex. These newly recovered archaea phylogenetically cluster with Geoarchaeota (deep lineage of archaeal order Thermoproteales), and the MCR-encoding genes clustered with the recently reported methanogens within the Verstraetearchaeota. In addition, genes encoding hydroxybutyryl-CoA dehydratase were identified in the newly recovered methanogens, indicating they might carry out the {beta}-oxidation process. Together, our findings further expanded the methane metabolism outside the phylum Euryarchaeota.

microbiology↗

bioRxiv2018

Structural insights into the conformational plasticity of the full-length trimeric HIV-1 envelope glycoprotein precursor

The human immunodeficiency virus (HIV-1) envelope glycoprotein (Env) trimer mediates viral entry into cells and is the major target for the host antibody response. In infected cells, the mature Env [(gp120/gp41)3] is produced by cleavage of a trimeric gp160 precursor. Proteolytic cleavage decreases Env conformational flexibility, allowing the mature Env to resist antibody binding to conserved elements. The conformational plasticity of the Env precursor skews the humoral immune response towards the elicitation of ineffectual antibodies, contributing to HIV-1 persistence in the infected host. The structural basis for the plasticity of the Env precursor remains elusive. Here we use cryo-electron microscopy to visualize two coexisting conformational states of the full-length Env precursor at nominal resolutions of 5.5 and 8.0 [A]. The State-P2 conformation features a three-helix bundle of the gp41 heptad repeat region in the core, but has disordered membrane-interactive regions. State-P1 trimers lack the three-helix bundle and instead retain ordered transmembrane and membrane-proximal external regions embracing a central cavity. Our structural data shed light on the unusual plasticity of the Env precursor and provide new clues to Env immunogen discovery.

microbiology↗

bioRxiv2017

Polarization of Myosin II refines tissue material properties to buffer mechanical stress.

As tissues develop, they are subjected to a variety of mechanical forces. Some of these forces, such as those required for morphogenetic movements, are instrumental to the development and sculpting of tissues. However, mechanical forces can also lead to accumulation of substantial tensile stress, which if maintained, can result in tissue damage and impair tissue function. Despite our extensive understanding of force-guided morphogenesis, we have only a limited understanding of how tissues prevent further morphogenesis, once shape is determined after development. Buffering forces to prevent cellular changes in response to fluctuations of mechanical stress is critical during the lifetime of an adult organism. Here, through the development of a novel tissue-stretching device, we uncover a mechanosensitive pathway that regulates tissue responses to mechanical stress through the polarization of Myosin II across the tissue. Mechanistically, this process is independent of conserved Rho-kinase signaling but is mediated by force-induced linear actin polymerization and depolymerization via the formin Diaphanous and actin severing protein Cofilin, respectively. Importantly, these stretch-induced actomyosin cables stiffen the tissue to limit changes in cell shape and to protect the tissue from further mechanical damage prior to stress dissipation. This tissue rigidification prevents fractures in the tissue from propagating by confining the damage locally to the injured cells. Overall this mechanism of force-induced changes in tissue mechanical properties provides a general model of force buffering that rapidly protects tissues from physical damage to preserve tissue shape.

biophysics↗

bioRxiv2017

EpiGraph: an open-source platform to quantify epithelial organization

During development, cells must coordinate their differentiation with their growth and organization to form complex multicellular structures such as tissues and organs. Healthy tissues must maintain these structures during homeostasis. Epithelia are packed ensembles of cells from which the different tissues of the organism will originate during embryogenesis. A large barrier to the analysis of the morphogenetic changes in epithelia is the lack of simple tools that enable the quantification of cell arrangements. Here we present EpiGraph, an image analysis tool that quantifies epithelial organization. Our method combines computational geometry and graph theory to measure the degree of order of any packed tissue. EpiGraph goes beyond the traditional polygon distribution analysis, capturing other organizational traits that improve the characterization of epithelia. EpiGraph can objectively compare the rearrangements of epithelial cells during development and homeostasis to quantify how the global ensemble is affected. Importantly, it has been implemented in the open-access platform FIJI. This makes EpiGraph very user friendly, with no programming skills required.

developmental biology↗