Biology subjects

Huang, G.

Publications and source records attributed to Huang, G..

At least 73 records · Page 4Linked to original sources

bioRxiv2023

Sensitivity-enhanced magnetic resonance reveals hydrogen intermediates during active -hydrogenase catalysis

Molecular hydrogen (H2) is considered an eco-friendly future energy-carrier and an alternative to fossil fuel1 and thus, major efforts are directed towards identifying efficient and economical hydrogen catalysts.2,3 Efficient hydrogen catalysis is used by many microorganisms, some of them producing H2 from organic materials and others consuming it.4-6 To metabolize H2, these microorganisms use enzymes called hydrogenases.7,8 For the future development of efficient catalysts a detailed analysis of the catalytic mechanisms of such hydrogenases is required and existing analytical techniques could not provide a full understanding.9 Consequently, new analytical technologies are of utmost importance to unravel natures blueprints for highly efficient hydrogen catalysts. Here, we introduce signal-enhanced or hyperpolarized, nuclear magnetic resonance (NMR) to study hydrogenases under turnover conditions. So far undiscovered hydrogen species of the catalytic cycle of [Fe]-hydrogenases, are revealed and thus, extend the knowledge regarding this class of enzymes. These findings pave new pathways for the exploration of novel hydrogen metabolisms in vivo. We furthermore envision that the results contribute to the rational design of future catalysts to solve energy challenges of our society.

biophysics↗

bioRxiv2023

Modification of social cheating facilitates the stabilization and chronic infection of polymorphic Pseudomonas aeruginosa population

Chronic infection of the common bacterial pathogen Pseudomonas aeruginosa frequently leads to the coexistence of heterogeneous individuals to engage in several group behaviors. However, further evolution of the polymorphic P. aeruginosa population, including the dynamic change of social cooperation and its impact on host immune system, still remain elusive. We show that the evolution of P. aeruginosa in the patients with chronic obstructive pulmonary disease frequently selects the isolates deficient in producing the costly and sharable extracellular products for nutrient acquisition. The evolution of polymorphic P. aeruginosa population is mainly concentrated on modifying the adaptability of lasR mutants, which are typical cheaters in the competition of quorum-sensing-controlled extracellular proteases. Importantly, lasR mutants with varying degrees of evolution interact with wild-type P. aeruginosa in a framework termed cascaded public goods game to compete for extracellular proteases and siderophores, and thus perpetuate social cooperation under different conditions. Finally, we find that a polymorphic population comprised of lasR-intact P. aeruginosa and evolved lasR-mutant can minimize the host immune fluctuation for persistent colonization. This study demonstrates the multistage evolution and complex interaction of P. aeruginosa in adaptation to host lungs, and provides an explanation for the success of cooperation in public goods game.

microbiology↗

bioRxiv2022

A Brain-Wide Genome-Wide Association Study of Candidate Quantitative Trait Loci Associated with Structural and Functional Phenotypes of Pain Sensitivity

Individual pain sensitivity is influenced by many factors, such as the differentiation of brain regional features and genetic variations. However, its heritability remains largely unclear. The present study conducted a brain-wide genome-wide association study (GWAS) to explore the genetic bases of structural and functional neuroimage phenotypes of pain sensitivity. In total 432 normal participants were firstly divided into high and low pain sensitivity groups according to laser quantitative test threshold and related brain regions gray matter density (GMD) features were identified. Consequently, GWAS was performed on each GMD phenotype using quality-controlled genotypes. Based on the heatmap and hierarchical clustering results from GWAS, the right insula was selected for further refined analysis in terms of sub-regions GMD and resting-state functional connectivity (rs-FC) phenotypes. The results indicate that the right insula GMD in the high sensitivity group is significantly lower than the low sensitivity group. Also, the TT/TC group at locus rs187974 may lead to a lower GMD in the right insula than the CC group. Meanwhile, loci at gene CYP2D6 may lead to a variation of rs-FC between the right insula and left putamen. In conclusion, our study suggests multiple candidate loci associated with pain sensitivity that may influence brain phenotypes.

genomics↗

bioRxiv2022

Whole-Brain fMRI Functional Connectivity Signatures Predict Sustained Emotional Experience in Naturalistic Contexts

Determining and decoding emotional brain processes under ecologically valid conditions remains a key challenge in affective neuroscience. The current functional magnetic resonance imaging (fMRI) based emotion decoding studies are mainly based on brief and isolated episodes of emotion induction, while sustained emotional experience in naturalistic environments that mirror daily life experiences are scarce. Here we use 10-minute movie clips as ecologically valid emotion-evoking procedures in n=52 individuals to explore emotion-specific fMRI functional connectivity (FC) profiles on the whole-brain level at high spatial resolution (400 atlas based parcels). Employing machine-learning based decoding and cross validation procedures allowed to develop predictive FC profiles that can accurately distinguish sustained happiness and sadness and that generalize across movies and subjects. Both functional brain network-based and subnetwork-based emotion prediction results suggest that emotion manifests as distributed representation of multiple networks, rather than a single functional network or subnetwork. Further, the results show that the Visual Network (VN) and Default Mode Network (DMN) associated functional networks, especially VN-DMN, exhibit a strong contribution to emotion prediction. To further estimate the cumulative effect of naturalistic long-term movie-based video-evoking emotions, we divide the 10-min episode into three stages: early stimulation (1 ~ 200 s), middle stimulation (201 ~ 400 s), and late stimulation (401 ~ 600 s) and examine the emotion prediction performance at different stimulation stages. We found that the late stimulation has a stronger predictive ability (accuracy=85.32%, F1-score=85.62%) compared to early and middle stimulation stages, implying that continuous exposure to emotional stimulation can lead to more intense emotions and further enhance emotion-specific distinguishable representations. The present work demonstrates that sustained sadness and happiness under naturalistic conditions are presented in emotion-specific network profiles and these expressions may play different roles in the generation and modulation of emotions. These findings elucidate the importance of network level adaptations for sustained emotional experiences during naturalistic contexts and open new venues for imaging network level contributions under naturalistic conditions.

neuroscience↗

bioRxiv2022

Comparison of DNA targeting CRISPR editors in human cells

Profiling and comparing the performance of current widely used DNA targeting CRISPR systems provide the basic information for the gene-editing toolkit and can be a useful resource for this field. Herein we made a parallel comparison between the recently reported miniature Cas12f1 and the widely used Cas12a and Cas9 nucleases in mammalian cells. The results revealed that as a CRISPRa activator, Un1Cas12f1 could induce gene expression with a comparable level to these of Cas12a and Cas9, while as a cleaving editor, Cas12f1 exhibited similar properties to Cas12a, like high specificity and dominantly induced deletions over insertions, but with less activity. In contrast, wild-type SpCas9 showed the highest activity, lowest specificity, and induced balanced deletions over insertions. Thus, Cas12f1 is recommended for gene-activation-based applications, Cas12a is for therapy applications, and wild-type Cas9 is for in vitro and animal investigations. The comparison provided the editing properties of current widely used DNA-targeting CRISPR systems for the gene-editing field.

synthetic biology↗

bioRxiv2022

Extracellular matrix stiffness regulates fibroblast differentiation by influencing DNA methyltransferase 1 expression through microtubule polymerization

Cells sense physical cues, such as changes in extracellular matrix (ECM) stiffness, and translate these stimuli into biochemical signals that control various aspects of cellular behavior, thereby facilitating physiological and pathological processes in various organs. Evidence from multiple studies suggests that the anterior vaginal wall stiffness is higher in POP patients than in non-POP patients. Our experiments found that the expression of -smooth muscle actin (-SMA) in the anterior vaginal wall of patients with POP was increased, and the expression of DNMT1 was decreased. We used polyacrylamide gel to simulate matrix stiffening in vitro, and substrate stiffening induced the high expression of myofibroblast markers -SMA and CTGF in L929 cells. Inhibition of DNMT1 promotes fibroblast differentiation into myofibroblasts in vitro. The results of bioinformatics analysis showed that the expression of DNMT1 was significantly correlated with microtubule polymerization-related proteins. The experiment showed that the microtubule polymerization inhibitor nocodazole could eliminate the decrease of DNMT1 expression in fibroblasts induced by high stiffness. We conclude that fibroblasts sense an increase in the stiffness of the surrounding matrix and regulate fibroblast differentiation by regulating the expression of DNA methyltransferase 1 (DNMT1) through the regulation of microtubule polymerization. This study may help to elucidate the complex crosstalk between vaginal fibroblasts and their surrounding matrix in both healthy and pathological conditions, and provide new insights into the implications of potentially targeted phenotypic regulation mechanisms in material-related therapeutic applications.

cell biology↗

bioRxiv2022

A Multi-subject, Multi-session, and Multi-task database for EEG-based Biometrics Challenge

EEG signals exhibit commonality and variability across subjects, sessions, and tasks. But most existing EEG studies focus on mean group effects (commonality) by averaging signals over trials and subjects. The substantial intra- and inter-subject variability of EEG has often been overlooked. The recently significant technological advances in machine learning, especially deep learning, have brought technological innovations to EEG signal application in many aspects, but there are still great challenges in cross-session, cross-task, and cross-subject EEG decoding. In this work, an EEG-based biometric competition based on a large-scale M3CV (A Multi-subject, Multi-session, and Multi-task Database for investigation of EEG Commonality and Variability) database was launched to better characterize and harness the intra- and inter-subject variability and promote the development of machine learning algorithm in this field. In the M3CV database, EEG signals were recorded from 106 subjects, of which 95 subjects repeated two sessions of the experiments on different days. The whole experiment consisted of 6 paradigms, including resting-state, transient-state sensory, steady-state sensory, cognitive oddball, motor execution, and steady-state sensory with selective attention with 14 types of EEG signals, 120,000 epochs. With the learning tasks of the identification and verification, the performance metrics and baseline methods were introduced in the competition. In general, the proposed M3CV dataset and the EEG-based biometric competition aim to provide the opportunity to develop advanced machine learning algorithms for achieving an in-depth understanding of the commonality and variability of EEG signals across subjects, sessions, and tasks.

neuroscience↗

bioRxiv2022

Targeting Chromatin Effector Pygo2 to Enhance Immunotherapy in Prostate Cancer

The noninflamed microenvironment in prostate cancer represents a barrier to immunotherapy. Genetic alterations underlying cancer cell-intrinsic oncogenic signaling have emerging roles in shaping the immune landscape. Recently, we identified Pygopus 2 (PYGO2) as the driver oncogene for the amplicon at 1q21.3. Here, using transgenic mouse models of metastatic prostate adenocarcinoma, we found that Pygo2 deletion decelerated tumor progression, diminished metastases, and extended survival. Pygo2 loss augmented the infiltration of cytotoxic T lymphocytes (CTLs) and sensitized tumor cells to T cell killing. Mechanistically, Pygo2 orchestrated a p53/Sp1/Kit/Ido1 signaling network to foster a microenvironment hostile to CTLs. Genetic or pharmacological inhibition of Pygo2 enhanced the anti-tumor efficacy of immunotherapies using immune checkpoint blockade, adoptive cell transfer, or myeloid-derived suppressor cell inhibitors. In human prostate cancer samples, Pygo2 expression was inversely correlated with CD8+ T cells. Our results highlight a promising path to improving immunotherapy with targeted therapy for lethal prostate cancer.

cancer biology↗

bioRxiv2022

Metabolic control of histone acetylation for precise and timely regulation of minor ZGA in early mammalian embryos

Metabolism feeds into the regulation of epigenetics via metabolic enzymes and metabolites. However, metabolic features, and their impact on epigenetic remodeling during mammalian pre-implantation development, remain poorly understood. In this study, we established the metabolic landscape of mouse pre-implantation embryos from zygote to blastocyst, and quantified some absolute carbohydrate metabolites. We integrated these data with transcriptomic and proteomic data, and discovered the metabolic characteristics of the development process, including the activation of methionine cycle from 8-cell embryo to blastocyst, high glutaminolysis metabolism at blastocyst stage, enhanced TCA cycle activity from the 8-cell embryo stage, and active glycolysis in the blastocyst. We further demonstrated that oxidized nicotinamide adenine dinucleotide (NAD+) synthesis is indispensable for mouse pre-implantation development. Mechanistically, in part, NAD+ is required for the exit of minor zygotic gene activation (ZGA) by cooperating with SIRT1 to remove zygotic H3K27ac. In human, NAD+ supplement can promote the removal of zygotic H3K27ac and benefit pre-implantation development. Our findings demonstrate that precise and timely regulation of minor ZGA is controlled by metabolic dynamics, and enhance our understanding of the metabolism of mammalian early embryos. HighlightsO_LIWe identified the metabolic features of mouse pre-implantation embryo development. C_LIO_LINAD+ synthesis is indispensable for mouse embryo pre-implantation development. C_LIO_LINAD+-mediated erasure of zygotic H3K27ac is required for the exit of minor ZGA. C_LIO_LINAD+ supplement promotes the removal of zygotic H3K27ac and benefits preimplantation development of human embryos. C_LI

developmental biology↗

bioRxiv2022

Ploidy variation and spontaneous haploid-diploid switching of Candida glabrata clinical isolates

The human fungal pathogen Candida glabrata is phylogenetically closely related to Saccharomyces cerevisiae, a model eukaryotic organism. Unlike S. cerevisiae with both haploid and diploid forms and a complete sexual cycle, C. glabrata has long been considered a haploid and asexual species. In this study, we analyzed the ploidy states of 500 clinical isolates of C. glabrata from four Chinese hospitals and found that approximately 4% of the isolates were in or able to spontaneously switch to an aneuploidy (genomic DNA: 1N-2N), diploidy (2N), or hyperdiploid (>2N) form under in vivo or in vitro conditions. Stable diploid-form cells were identified in 3% of the isolates (15/500). Of particular interest, one clinical strain only existed in the diploid form. Multilocus sequence typing (MLST) assays revealed two major genetic clusters (A and B) of C. glabrata isolates. Most of the isolates (70%) from China belonged to the A cluster, whereas most of the isolates from other countries (such as Iran, Japan, USA, and European countries) belonged to the B cluster. Further investigation indicated that C. glabrata cells of different ploidy forms differed in a number of aspects, including morphologies, antifungal susceptibility, virulence, and global gene expression profiles. Additionally, C. glabrata could undergo spontaneous switching between the diploid and haploid form under both in vitro and in vivo conditions. Given the absence of an apparent sexual phase, one would expect that the ploidy shifts could function as an alternative strategy that promotes genetic diversity and benefits the ability of the fungus to rapidly adapt to the changing environment. ImportanceThe human fungal pathogen Candida glabrata has long been thought to be a haploid organism. Here we report the population structure and ploidy states of 500 clinical isolates of C. glabrata from China. To our surprise, we found that the ploidy of a subset of clinical isolates varied dramatically. Some isolates were in or able to switch to an aneuploid, diploid, or hyperdiploid form. C. glabrata cells with different ploidy differed in a number of biological aspects, including morphologies, antifungal susceptibility, virulence, and global gene expression profiles. Given the absence of an apparent sexual phase in this fungus, we propose that ploidy switching could be a rapid adaption strategy to environmental changes and could function as an alternative strategy of sexual reproduction.

microbiology↗

bioRxiv2022

Immunological findings in a group of individuals who were non-responders to standard two-dose SARS-CoV-2 vaccines

Coronavirus disease (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was declared a pandemic. The virus has infected more than 505 million people and caused more than 6 million deaths. However, data on non-responders to SARS-CoV-2 vaccines in the general population are limited. The objective of the study is to comprehensively compare the immunological characteristics of non-responders to SARS-CoV-2 vaccines in the 18-59 years with that in the 60 years and older using internationally recognized cutoff values. Participants included 627 individuals who received physical examinations and volunteered to participate in COVID-19 vaccination from the general population. The main outcome was an effective seroconversion characterized by anti-SARS-CoV-2 spike IgG level of at least 4-fold increase from baseline. Profiling of naive immune cells was analyzed prior to vaccination to demonstrate baseline immunity. Outcomes of effective seroconversion in the 18-59 years with that in the 60 years and older were compared. The quantitative level of the anti-spike IgG was significantly lower in the 60 years and older and in men among the 18-59 years. There were 7.5% of non-responders among the 18-59 years and 11.7% of non-responders in the 60 years and older using the 4-fold increase parameter. The effective seroconversion rate was significantly related to the level of certain immune cells before vaccination, such as CD4 cells, CD8 cells and B cells and the age. An individual with a titer of anti-SARS-CoV-2 spike IgG that is below 50 BAU/mL might be considered a non-responder between 14-90 days after the last vaccine dose. Booster vaccination or additional protective measures should be recommended for non-responders as soon as possible to reduce disease severity and mortality.

immunology↗

bioRxiv2022

A Self-Healing, Viscoelastic Hydrogel Promotes Healing of Brain Lesions

Brain lesions can arise from traumatic brain injury, infection, and craniotomy. Although injectable hydrogels show promise for promoting healing of lesions and health of surrounding tissue, enabling cellular ingrowth and restoring neural tissue continue to be challenging. We hypothesized that these challenges arise in part from viscoelastic mismatch between the hydrogel and the brain parenchyma, and tested this hypothesis by developing and evaluating a self-healing hydrogel that mimicked both the composition and viscoelasticity of native brain parenchyma. The hydrogel was crosslinked by dynamic boronate ester bonds between phenylboronic acid grafted hyaluronic acid (HA-PBA) and dopamine grafted gelatin (Gel-Dopa). This HA-PBA/Gel-Dopa hydrogel could be injected into a lesion cavity in a shear-thinning manner with rapid hemostasis, high tissue adhesion and efficient self-healing. We tested this in an in vivo mouse model of brain lesions and found the hydrogel to support neural cell infiltration, decrease astrogliosis and glial scars, and close the lesions. The results suggest a role for viscoelasticity in brain lesion healing, and motivate additional experimentation in larger animals as the technology progresses towards potential application in humans.

bioengineering↗

bioRxiv2022

MCIBox: A Toolkit for Single-molecule Multi-way Chromatin Interaction Visualization and Micro-Domains Identification

The emerging ligation-free three-dimensional (3D) genome mapping technologies can identify multiplex chromatin interactions with single-molecule precision. These technologies offer new insight into high-dimensional chromatin organization and gene regulation, but also introduce new challenges in data visualization and analysis. To overcome these challenges, we developed MCIBox, a toolkit for Multi-way Chromatin Interaction (MCI) analysis, including a visualization tool and a platform for identifying micro-domains with clustered single-molecule chromatin complexes. MCIBox is based on various clustering algorithms integrated with dimensionality reduction methods that can display multiplex chromatin interactions at single-molecule level, allowing users to explore chromatin extrusion patterns and super-enhancers regulation modes in transcription, and to identify single-molecule chromatin complexes that are clustered into micro-domains. Furthermore, MCIBox incorporates a two-dimensional kernel density estimation algorithm to identify micro-domains boundaries automatically. These micro-domains were stratified with distinctive signatures of transcription activity and contained different cell cycle associated genes. MCIBox could potentially distinguish the specificity of single-molecule chromatin interaction patterns in various phases of a cell cycle or cell types.

genomics↗

bioRxiv2022

Comparative analysis about the structure of complete chloroplast genomes in genus Mangifera and accuracy verification about phylogenetic analysis based on gene ycf2 in genus level

Mango is an evergreen plant belonging to the genus Mangifera of the Anacardiaceae family. Genus Mangifera has 69 species of Mangifera around the world that are mainly distributed in tropical and subtropical countries, including India, Indonesia, the Malay Peninsula, Thailand, and South China. It is a popular tropical fruit known as the "King of Tropical Fruits". However, the study of the structure information of the complete chloroplast genome of Mangifera was microscopic, there was no report about the comparison of SSR, Ka/Ks, codons analysis and RNA editing, so in this study, we sequenced the 6 Mangifera samples and used three different ways to analyze the relationship of 6 species of Mangifera. Then we got some results, through the RNA editing and Ka/Ks calculating, we found the species could be divided into two groups, and the difference between the two groups was protein-coding gene ccsA. Moreover, all RNA editing occurred conversion of C to T and the gene ndhB had the most RNA editing sites in all species. In Ka/Ks analysis, the gene atpB, cemA, clpP, ndhD, petD, petB and ycf15 would be suffered from the positive selection after divergence. We also find the IR regions in these seven samples were very conservation through IR contraction and expansion and Sequence Divergence Analysis. Finally, we tried to confirm the relationship between 7 samples of Mangifera in Angiosperms in 3 different ways. Then we got that ML210 and MP090 had a closer relationship than others, MS796 had a closer relationship with ML210 and MP090 than others. At the same time, the method of phylogenetic analysis based on the gene ycf2 was not more accurate at the genus level than the method based on complete cp genome and proteincoding genes.

molecular biology↗

bioRxiv2022

Near-atomic Structure of the Cytoplasmic Ring of the Xenopus laevis Nuclear Pore Complex

The nuclear pore complex (NPC) mediates nucleocytoplasmic shuttling. Here we present single-particle cryo-EM structure of the cytoplasmic ring (CR) from the Xenopus laevis NPC at 4.1-4.7 [A] resolutions. The structure of an N-terminal domain of Nup358 was resolved at 3.0 [A], facilitating identification of five Nup358 molecules in each CR subunit. Aside from unveiling the assembly details of the two Y-shaped multicomponent complexes (Y complexes) in each CR subunit, the improved resolutions reveal the C-terminal fragment of Nup160 to be an organizing center at the vertex of each Y complex. Our structures show that the scaffold of a CR subunit comprises five Nup358, two Nup205 and two Nup93 molecules in addition to the previously characterized Y complexes. One-Sentence SummaryImproved resolutions of the cytoplasmic ring (CR) of the Xenopus laevis nuclear pore complex reveal that five Nup358 molecules, together with two copies of interweaved Nup205, Nup93 and Y complexes, constitute the scaffold of each CR subunit.

biophysics↗

bioRxiv2021

Changes of small non-coding RNAs by severe acute respiratory syndrome coronavirus 2 infection

The ongoing pandemic of coronavirus disease 2019 (COVID-19), which results from the rapid spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a significant global public health threat, with molecular mechanisms underlying its pathogenesis largely unknown. Small non-coding RNAs (sncRNAs) are known to play important roles in almost all biological processes. In the context of viral infections, sncRNAs have been shown to regulate the host responses, viral replication, and host-virus interaction. Compared with other subfamilies of sncRNAs, including microRNAs (miRNAs) and Piwi-interacting RNAs (piRNAs), tRNA-derived RNA fragments (tRFs) are relatively new and emerge as a significant regulator of host-virus interactions. Using T4 PNK-RNA-seq, a modified next-generation sequencing (NGS), we recently found that nasopharyngeal swabs (NPS) samples from SARS-CoV-2 positive and negative subjects show a significant difference in sncRNA profiles. There are about 166 SARS-CoV-2-impacted sncRNAs. Among them, tRFs are the most significantly affected and almost all impacted tRFs are derived from the 5-end of tRNAs (tRF5). Using a modified qRT-PCR, which was recently developed to specifically quantify tRF5s by isolating the tRF signals from its corresponding parent tRNA signals, we validated that tRF5s derived from tRNA GluCTC (tRF5-GluCTC), LysCTT (tRF5-LysCTT), ValCAC (tRF5-ValCAC), CysGCA (tRF5-CysGCA) and GlnCTG (tRF5-GlnCTG) are enhanced in NPS samples of SARS-CoV2 patients and SARS-CoV2-infected airway epithelial cells. In addition to host-derived ncRNAs, we also identified several sncRNAs derived from the virus (svRNAs), among which a svRNA derived from CoV2 genomic site 346 to 382 (sv-CoV2-346) has the highest expression. The induction of both tRFs and sv-CoV2-346 has not been reported previously, as the lack of the 3-OH ends of these sncRNAs prevents them to be detected by routine NGS. In summary, our studies demonstrated the involvement of tRFs in COVID-19 and revealed new CoV2 svRNAs.

microbiology↗

bioRxiv2021

Variation of female pronucleus reveal oocyte or embryo abnormality: An expert experience deep learning of non-dark box analysis

BackgroundPronuclear assessment appears to have the ability to distinguish good and bad embryos in the zygote stage, but paradoxical results were obtained in clinical studies. This situation might be caused by the robust qualitative detection of the development of dynamic pronuclei. Here, we aim to establish a quantitative pronuclear measurement method by applying expert experience deep learning from large annotated datasets. MethodsConvinced handle-annotated 2PN images (13419) were used for deep learning then corresponded errors were recorded through handle check for subsequent parameters adjusting. We used 790 embryos with 52479 PN images from 155 patients for analysis the area of pronuclei and the pre-implantation genetic test results. Establishment of the exponential fitting equation and the key coefficient {beta} 1was extracted from the model for quantitative analysis for pronuclear(PN) annotation and automatic recognition. FindingsBased on the female original PN coefficient {beta}1, the chromosome-normal rate in the blastocyst with biggest PN area is much higher than that of the blastocyst with smallest PN area (58.06% vs. 45.16%, OR=1.68 [1.07-2.64]; P=0.031). After adjusting coefficient {beta}1 by the first three frames which high variance of outlier PN areas was removed, coefficient {beta}1 at 12 hours and at 14 hours post-insemination, similar but stronger evidence was obtained. All these discrepancies resulted from the female propositus in the PGT-SR subgroup and smaller chromosomal errors. Conclusion(s)The results suggest that detailed analysis of the images of embryos could improve our understanding of developmental biology. FundingNone

genetics↗

bioRxiv2021

Near atomic structure of the inner ring of the Saccharomyces cerevisiae nuclear pore complex

Nuclear pore complexes (NPCs) mediate bidirectional nucleocytoplasmic transport of substances in eukaryotic cells. However, the accurate molecular arrangement of NPCs remains enigmatic owing to their huge size and highly dynamic nature. Here we determined the structure of the asymmetric unit of the inner ring (IR monomer) at 3.73 [A] resolution by single-particle cryo-electron microscopy, and created an atomic model of the intact IR consisting of 192 copies from 8 subunits. In each IR monomer, two approximately parallel rhomboidal structures of the inner and outer layers are sandwiched with the Z-shaped Nup188-Nup192 middle layer and Nup188, Nup192 and Nic96 link all subunits to constitute a relatively stable IR monomer, while the intact IR is assembled by loose and instable interactions between IR monomer. These structures reveal various interaction modes and extensive flexible connections in the assembly, providing a structural basis for the stability and malleability of IR. One-Sentence SummaryAccurate structure of inner ring reveals its assembly and function in dilation and constriction of nuclear pore complex.

biophysics↗