Biology subjects

Li, G.

Publications and source records attributed to Li, G..

At least 505 records · Page 28Linked to original sources

bioRxiv2020

Comparative genomic analysis revealed specific mutation pattern between human coronavirus SARS-CoV-2 and Bat-SARSr-CoV RaTG13

The novel coronavirus SARS-CoV-2 (2019-nCoV) is a member of the family coronaviridae and contains a single-stranded RNA genome with positive-polarity. To reveal the evolution mechanism of SARS-CoV-2 genome, we performed comprehensive genomic analysis with newly sequenced SARS-CoV-2 strains and 20 closely related coronavirus strains. Among 98 nucleotide mutations at 93 sites of the genome among different SARS-CoV-2 strains, 58 of them caused amino acid change, indicating a result of neutral evolution. However, the ratio of nucleotide substitutions to amino acid substitutions of spike gene (9.07) between SARS-CoV-2 WIV04 and Bat-SARSr-CoV RaTG13 was extensively higher than those from comparisons between other coronaviruses (range 1.29 - 4.81). The elevated synonymous mutations between SARS-CoV-2 and RaTG13, suggesting they underwent stronger purifying selection. Moreover, their nucleotide substitutions are enriched with T:C transition, which is consistent with the mutation signature caused by deactivity of RNA 3-to-5 exoribonuclease (ExoN). The codon usage was similar between SARS-CoV-2 and other strains in beta-coronavirus lineage B, suggesting it had small impact on the mutation pattern. In comparison of SARS-CoV-2 WIV04 with Bat-SARSr-CoV RaTG13, the ratios of non-synonymous to synonymous substitution rates (dN/dS) was the lowest among all performed comparisons, reconfirming the evolution of SARS-CoV-2 under stringent selective pressure. Moreover, some sites of spike protein might be subjected to positive selection. Therefore, our results will help understanding the evolutionary mechanisms contribute to viral pathogenicity and its adaptation with hosts.

genomics↗

bioRxiv2020

Chronic administration of a positive allosteric modulator at the alpha5-GABAA receptor reverses age-related dendritic shrinkage

Over the last 15 years, worldwide life expectancy increased by 5 years jumping from 66 years to 71 years. With progress in science, medicine, and care we tend to live longer. Such extended life expectancy is still associated with age-related changes, including in the brain. The aging brain goes through various changes that can be called morphomolecular senescence. Overall, the brain volume changes, neuronal activity is modified and plasticity of the cells diminishes, sometimes leading to neuronal atrophy and death. Altogether, these changes contribute to the emergence of cognitive decline that still does not have an efficient treatment available. Many studies in the context of cognitive decline focused on pathological aging, targeting {beta}-amyloid in Alzheimers disease, for example. However, {beta}-amyloid plaques are also present in healthy adults and treatments targeting plaques have failed to improve cognitive functions. In order to improve the quality of life of aging population, it is crucial to focus on the development of novel therapies targeting different systems altered during aging, such as the GABAergic system. In previous studies, it has been shown that positive allosteric modulators (PAM) acting at the 5-containing GABA-A receptors improve cognitive performances, and that these 5-GABA-A receptors are implicated in dendritic growth of pyramidal neurons. Here, we hypothesized that targeting the 5-GABA-A receptors could contribute to the reduction of cognitive decline, directly through activity of the receptors, and indirectly by increasing neuronal morphology. Using primary neuronal culture and chronic treatment in mice, we demonstrated that an 5-PAM increased dendritic length, spine count and spine density in brain regions involved in cognitive processes (prefrontal cortex and hippocampus). We also confirmed the procognitive efficacy of the 5-PAM and showed that the washout period diminishes the precognitive effects without altering the effect on neuronal morphology. Future studies will be needed to investigate what downstream mechanisms responsible for the neurotrophic effect of the 5-PAM.

neuroscience↗

bioRxiv2020

A non-canonical histone acetyltransferase targets intragenic enhancers and regulates plant architecture

Axillary meristem development determines both plant architecture and crop yield; this critical process is regulated by the TCP transcription factor (TF) family, including the maize TB1 and Arabidopsis BRC1. Studies have shown that both TB1 and AtBRC1 can target the gene body regions of some target genes and activate their expression; however, the regulatory mechanisms remain largely unknown. Here, we show that a cucumber CYC/TB1 homologue, TEN, controls the identity and mobility of tendrils. Through its C-terminus, TEN binds at intragenic enhancers of target genes; its N-terminal domain functions as a novel, non-canonical histone acetyltransferase (HAT) to preferentially act on lysine 56 and 122, of the histone H3 globular domain. This HAT activity is responsible for chromatin loosening and host gene activation. The N-termini of all tested CYC/TB1-like proteins contain an intrinsically disordered region (IDR), and despite their sequence divergence, they have conserved HAT activity. This study discovered a non-canonical class of HATs, and as well, provides a mechanism by which modification at the H3 globular domain is integrated with the transcription process.

plant biology↗

bioRxiv2020

The separation of Antler Polypeptide and its effects on the proliferation and osteogenetic differentiation of Bone Marrow Mesenchymal Stem Cells

The effects of antler polypeptide on rat bone marrow mesenchymal stem cells (BMSCs) were investigated. Antler polypeptide was separated from Colla Cornus Cervi by ultrafiltration into different samples according to molecular weight: A (molecular weight <800 Da), B (molecular weight 800-1500 Da) and C (molecular weight >1500 Da). The content of antler polypeptide in A, B and C solutions were quantified by high-performance liquid chromatography (HPLC). The effects of antler polypeptide at different concentrations on the proliferation, cell cycle, and osteogenesis of BMSCs were investigated. The highest cell proliferation rate (84.66%) was observed for antler polypeptide B at a concentration of 1.578 x 10-2 g/mL. Antler polypeptide B significantly promoted the proliferation of BMSCs with a proliferation index of 38.68%, which was significantly higher than that of the other groups. Antler polypeptide B significantly enhanced the activity of alkaline phosphatase in BMSCs compared to that of blank group (P <0.001). Antler polypeptide B increased the BMP7 protein expression in BMSCs. Our data suggested that antler polypeptide may promote the proliferation and osteogenic differentiation of BMSCs.

biochemistry↗

bioRxiv2020

Generation of multi-transgenic pigs using PiggyBac transposons co-expressing pectinase, xylanase, cellulase?β-1.3-1.4-glucanase and phytase

The current challenges facing the pork industry are to maximize feed efficiency and minimize fecal emissions. Unlike ruminants, pigs lack a number of digestive enzymes like pectinase, xylanase, cellulase, {beta}-1.3-1.4-glucanase and phytase to hydrolyze the cell walls of grains to release endocellular nutrients into their digestive tracts. Herein, we synthesized multiple cellulase and pectinase genes derived from lower organisms and then codon optimized these genes to be expressed in pigs. These genes were then cloned into our previously optimized XynB (xylanase)- EsAPPA (phytase) bicistronic construct. We then successfully generated transgenic pigs that expressed four enzymes (Pg7fn (pectinase), XynB (xylanase), EsAPPA (phytase) and TeEGI (cellulase and {beta}-glucanase)) using somatic cell cloning. Expression of these genes was parotid gland specific. Enzymatic assays using the saliva of these founders demonstrated high levels of phytase (2.0~3.4 U/mL) and xylanase (0.25~0.42 U/mL) activity, but low levels of pectinase (0.06~0.08 U/mL) activity. These multi-transgenic pigs are expected to contribute to enhance feed utilization and reduce environmental impact.

genetics↗

bioRxiv2020

LanD-like Flavoprotein-Catalyzed Aminovinyl-Cysteine Formation through Oxidative Decarboxylation and Cyclization of a Peptide at the C-Terminus

Aminovinyl-cysteine residues arise from processing the C-terminal O_SCPLOWLC_SCPLOW-Cys and an internal O_SCPLOWLC_SCPLOW-Ser/O_SCPLOWLC_SCPLOW-Thr or O_SCPLOWLC_SCPLOW-Cys of a peptide. Formation of these nonproteinogenic amino acids, which occur in a macrocyclic ring of diverse ribosomally synthesized lanthipeptides and non-lanthipeptides, remains poorly understood. Here, we report that LanD-like flavoproteins in the biosynthesis of distinct non-lanthipeptides share an unexpected dual activity for aminovinyl-cysteine formation. Each flavoprotein catalyzes oxidative decarboxylation of the C-terminal O_SCPLOWLC_SCPLOW-Cys and couples the resulting enethiol nucleophile with the internal residue to afford a thioether linkage for peptide cyclization. The cyclization step, which largely depends on proximity effect by positioning the enethiol intermediate with a bent conformation at the active site, can be substrate-dependent, proceeding inefficiently through nucleophilic substitution for an unmodified peptide or efficiently through Michael addition for a dehydrated/dethiolated peptide. Uncovering this unusual flavin-dependent paradigm for thioether residue formation advances the understanding in the biosynthesis of aminovinyl-cysteine-containing RiPPs and renews interest in flavoproteins, particularly those involved in non-redox transformations. LanD-like flavoproteins activity, which is flexible in peptide substrate and amenable for evolution by engineering, can be combined with different post-translational modifications for structural diversity, thereby holding promise for peptide macrocyclization/functionalization in drug development by chemoenzymatic or synthetic biology approaches.

biochemistry↗

bioRxiv2020

scTenifoldNet: a machine learning workflow for constructing and comparing transcriptome-wide gene regulatory networks from single-cell data

Constructing and comparing gene regulatory networks (GRNs) from single-cell RNA sequencing (scRNAseq) data has the potential to reveal critical components in the underlying regulatory networks regulating different cellular transcriptional activities. Here, we present a robust and powerful machine learning workflow--scTenifoldNet--for comparative GRN analysis of single cells. The scTenifoldNet workflow, consisting of principal component regression, low-rank tensor approximation, and manifold alignment, constructs and compares transcriptome-wide single-cell GRNs (scGRNs) from different samples to identify gene expression signatures shifting with cellular activity changes such as those associated with pathophysiological processes and responses to environmental perturbations. We used simulated data to benchmark scTenifoldNets performance, and then applied scTenifoldNet to several real data sets. In real-data applications, scTenifoldNet identified highly specific changes in gene regulation in response to acute morphine treatment, an antibody anticancer drug, gene knockout, double-stranded RNA stimulus, and amyloid-beta plaques in various types of mouse and human cells. We anticipate that scTenifoldNet can help achieve breakthroughs through constructing and comparing scGRNs in poorly characterized biological systems, by deciphering the full cellular and molecular complexity of the data. HighlightsO_LIscTenifoldNet is a machine learning workflow built upon principal component regression, low-rank tensor approximation, and manifold alignment C_LIO_LIscTenifoldNet uses single-cell RNA sequencing (scRNAseq) data to construct single-cell gene regulatory networks (scGRNs) C_LIO_LIscTenifoldNet compares scGRNs of different samples to identify differentially regulated genes C_LIO_LIReal-data applications demonstrate that scTenifoldNet accurately detects specific signatures of gene expression relevant to the cellular systems tested. C_LI Short abstractWe present scTenifoldNet--a machine learning workflow built upon principal component regression, low-rank tensor approximation, and manifold alignment--for constructing and comparing single-cell gene regulatory networks (scGRNs) using data from single-cell RNA sequencing (scRNAseq). scTenifoldNet reveals regulatory changes in gene expression between samples by comparing the constructed scGRNs. With real data, scTenifoldNet identifies specific gene expression programs associated with different biological processes, providing critical insights into the underlying mechanism of regulatory networks governing cellular transcriptional activities.

bioinformatics↗

bioRxiv2020

Integrated profiling of single cell epigenomic and transcriptomic landscape of Parkinson's disease mouse brain

Parkinsons disease (PD) is a neurodegenerative disease leading to the impairment of execution of movement. PD pathogenesis has been largely investigated, but either restricted in bulk level or at certain cell types, which failed to capture cellular heterogeneity and intrinsic interplays among distinct cell types. To overcome this, we applied single-nucleus RNA-seq and single cell ATAC-seq on cerebellum, midbrain and striatum of PD mouse and matched control. With 74,493 cells in total, we comprehensively depicted the dysfunctions under PD pathology covering proteostasis, neuroinflammation, calcium homeostasis and extracellular neurotransmitter homeostasis. Besides, by multi-omics approach, we identified putative biomarkers for early stage of PD, based on the relationships between transcriptomic and epigenetic profiles. We located certain cell types that primarily contribute to PD early pathology, narrowing the gap between genotypes and phenotypes. Taken together, our study provides a valuable resource to dissect the molecular mechanism of PD pathogenesis at single cell level, which could facilitate the development of novel methods regarding diagnosis, monitoring and practical therapies against PD at early stage.

cell biology↗

bioRxiv2020

LncRNA GAS5 attenuates fibroblast activation through inhiting Smad3-mediated myofibroblast marker gene expression.

Transforming Growth Factor {beta} (TGF-{beta})-induced fibroblast activation is a key pathological event during tissue fibrosis. Long noncoding RNA (lncRNA) is a class of versatile gene regulators participating in various cellular and molecular processes. However, the function of lncRNA in fibroblast activation is still poorly understood. In this study, we identified growth arrest-specific transcript 5 (GAS5) as a novel regulator for TGF-{beta}-induced fibroblast activation. GAS5 expression was downregulated in cultured fibroblasts by TGF-{beta} and in resident fibroblasts from bleomycin-treated skin tissues. Overexpression of GAS5 suppressed TGF-{beta}-induced fibroblast to myofibroblast differentiation. Mechanistically, GAS5 directly bound Smad3 and promoted Smad3 binding to PPM1A, a Smad3 dephosphatase, and thus accelerated Smad3 dephosphorylation in TGF-{beta}-treated fibroblasts. In addition, GAS5 inhibited fibroblast proliferation. Importantly, local delivery of GAS5 via adenoviral vector suppressed bleomycin-induced skin fibrosis in mice. Collectively, our data revealed that GAS5 suppresses fibroblast activation and fibrogenesis through inhibiting TGF-{beta}/Smad3 signaling, which provides a rationale for an lncRNA-based therapy to treat fibrotic diseases.

molecular biology↗

bioRxiv2020

Diverse cell stimulation kinetics identify predictive signal transduction models

The drive to understand cell signaling responses to environmental, chemical and genetic perturbations has produced outstanding fits of computational models to increasingly intricate experiments, yet predicting quantitative responses for new biological conditions remains challenging. Overcoming this challenge depends not only on good models and detailed experimental data but perhaps more so on how well the two are integrated. Our quantitative, live single-cell fluorescence imaging datasets and computational framework to model generic signaling networks show how different changing environments (hereafter kinetic stimulations) probe and result in distinct pathway activation dynamics. Utilizing multiple diverse kinetic stimulations better constrains model parameters and enables predictions of signaling dynamics that would be impossible using traditional step-change stimulations. To demonstrate our approachs generality, we use identified models to predict signaling dynamics in normal, mutated, and drug-treated conditions upon multitudes of kinetic stimulations and quantify which proteins and reaction rates are most sensitive to which extracellular stimulations.

systems biology↗

bioRxiv2020

Structural and Functional NIR-II Fluorescence Bioimaging in Urinary System via Clinically Approved Dye Methylene Blue

Accurate structural and functional imaging is vital for the diagnosis and prognosis of the urinary system diseases. Near-infrared region (NIR) II fluorescence imaging has shown advantages of high sensitivity, high safety, and fast feedback compared to the conventional imaging methods but limited to its clinical applicability. Herein, we first report that in vivo NIR-II fluorescence imaging of the urinary system enabled by clinically approved and renal-clearable NIR dye methylene blue, which can not only achieve clear invasive/non-invasive urography but also noninvasively detect renal function. These results demonstrate that MB assisted NIR-II fluorescence imaging holds great promise for invasive/noninvasive structural imaging of the urinary system clinically and investigation of renal function in animal models preclinically.

bioengineering↗

bioRxiv2020

Chinese Glioma Genome Atlas (CGGA): A Comprehensive Resource with Functional Genomic Data for Chinese Glioma Patients

Gliomas are the most common and malignant intracranial tumours in adults. Recent studies have shown that functional genomics greatly aids in the understanding of the pathophysiology and therapy of glioma. However, comprehensive genomic data and analysis platforms are relatively limited. In this study, we developed the Chinese Glioma Genome Atlas (CGGA, http://www.cgga.org.cn), a user-friendly data portal for storage and interactive exploration of multi-dimensional functional genomic data that includes nearly 2,000 primary and recurrent glioma samples from Chinese cohorts. CGGA currently provides access to whole-exome sequencing (286 samples), messenger RNA sequencing (1,018 samples) and microarray (301 samples), DNA methylation microarray (159 samples), and microRNA microarray (198 samples) data, as well as detailed clinical data (e.g., WHO grade, histological type, critical molecular genetic information, age, sex, chemoradiotherapy status and survival data). In addition, we developed an analysis tool to allow users to browse mutational, mRNA/microRNA expression, and DNA methylation profiles and perform survival and correlation analyses of specific glioma subtypes. CGGA greatly reduces the barriers between complex functional genomic data and glioma researchers who seek rapid, intuitive, and high-quality access to data resources and enables researchers to use these immeasurable data sources for biological research and clinical application. Importantly, the free provision of data will allow researchers to quickly generate and provide data to the research community.

genomics↗

bioRxiv2020

A new domestic cat genome assembly based on long sequence reads empowers feline genomic medicine and identifies a novel gene for dwarfism.

The domestic cat (Felis catus) numbers over 94 million in the USA alone, occupies households as a companion animal, and, like humans, suffers from cancer and common and rare diseases. However, genome-wide sequence variant information is limited for this species. To empower trait analyses, a new cat genome reference assembly was developed from PacBio long sequence reads that significantly improve sequence representation and assembly contiguity. The whole genome sequences of 54 domestic cats were aligned to the reference to identify single nucleotide variants (SNVs) and structural variants (SVs). Across all cats, 16 SNVs predicted to have deleterious impacts and in a singleton state were identified as high priority candidates for causative mutations. One candidate was a stop gain in the tumor suppressor FBXW7. The SNV is found in cats segregating for feline mediastinal lymphoma and is a candidate for inherited cancer susceptibility. SV analysis revealed a complex deletion coupled with a nearby potential duplication event that was shared privately across three unrelated dwarfism cats and is found within a known dwarfism associated region on cat chromosome B1. This SV interrupted UDP-glucose 6-dehydrogenase (UGDH), a gene involved in the biosynthesis of glycosaminoglycans. Importantly, UGDH has not yet been associated with human dwarfism and should be screened in undiagnosed patients. The new high-quality cat genome reference and the compilation of sequence variation demonstrate the importance of these resources when searching for disease causative alleles in the domestic cat and for identification of feline biomedical models. Author summaryThe practice of genomic medicine is predicated on the availability of a high quality reference genome and an understanding of the impact of genome variation. Such resources have lead to countless discoveries in humans, however by working exclusively within the framework of human genetics, our potential for understanding diseases biology is limited, as similar analyses in other species have often lead to novel insights. The generation of Felis_catus_9.0, a new high quality reference genome for the domestic cat, helps facilitate the expansion of genomic medicine into the felis lineage. Using Felis_catus_9.0 we analyze the landscape of genomic variation from a collection of 54 cats within the context of human gene constraint. The distribution of variant impacts in cats is correlated with patterns of gene constraint in humans, indicating the utility of this reference for identifying novel mutations that cause phenotypes relevant to human and cat health. Moreover, structural variant analysis revealed a novel variant for feline dwarfism in UGDH, a gene that has not been associated with dwarfism in any other species, suggesting a role for UGDH in cases of undiagnosed dwarfism in humans.

genomics↗

bioRxiv2019

Dscam homophilic specificity is generated by high order cis-multimers coupled with trans self-binding of variable Ig1 in Chelicerata

By alternative splicing, Drosophila Down syndrome cell adhesion molecule (Dscam1) encodes tens of thousands of proteins required for establishing neural circuits, while Chelicerata encodes a family of [~] 100 shortened Dscam (sDscam) isoforms via alternative promoters. We report that Dscam isoforms interact promiscuously in cis to generate a vast repertoire of combinatorial homophilic recognition specificities in Chelicerata. Specifically, sDscams formed high order cis-multimers without isoform specificity involving the membrane-proximal fibronectin type III (FNIII) 1-3 and transmembrane (TM) domains and associated specifically in trans via antiparallel self-binding of the first variable immunoglobulin (Ig1) domain. We propose that such sDscam combinatorial homophilic specificity is sufficient to provide each neuron with a unique identity for self-non-self discrimination. In many respects, our results amazingly mirror those reported for the structurally unrelated vertebrate protocadherins (Pcdh) rather than for the closely related fly Dscam1. Thus, our findings blur the distinction between the neuronal self-avoidance of invertebrates and vertebrates and provide insight into the basic principles and evolution of metazoan self-avoidance and self-non-self discrimination.

biochemistry↗

bioRxiv2019

Copper Induces Zebrafish Central Neural System Myelin Defects: the Regulatory Mechanisms in Wnt/Notch-hoxb5b Signaling and Underlying DNA Methylation

Unbalanced copper (Cu2+) homeostasis is associated with neurological development defects and diseases. However, the molecular mechanisms remain elusive. Here, central neural system (CNS) myelin defects and down-regulated expression of Wnt/Notch signaling and their down-stream mediator hoxb5b were observed in Cu2+ stressed zebrafish larvae. Loss/knockdown-of-function of hoxb5b phenocopied the myelin and axon defects observed in Cu2+ stressed embryos. Meanwhile, activation of Wnt/Notch signaling and ectopic expression of hoxb5b could rescue copper-induced myelin defects, suggesting Wnt&Notch-hoxb5b axis mediated Cu2+ induced myelin and axon defects. Additionally, whole genome DNA methylation sequencing unveiled that a novel gene fam168b, similar to pou3f1/2, exhibited significant promoter hypermethylation and reduced expression in Cu2+ stressed embryos. The hypermethylated locus in fam168b promoter acted pivotally in its transcription, and loss/knockdown of fam168b/pou3f1 also induced myelin defects. Moreover, this study unveiled that fam168b/pou3f1 and hoxb5b axis acted in a seesaw manner during fish embryogenesis, and demonstrated that copper induced the down-regulated expression of the Wnt&Notch-hoxb5b axis dependent of the function of copper transporter cox17, coupled with the promoter methylation of genes fam168b/pou3f1 and their subsequent down-regulated expression dependent of the function of another transporter atp7b, making joint contributions to myelin defects in embryos. Those data will shed some light on the linkage of unbalanced copper homeostasis with specific gene promoter methylation and signaling transduction as well as the resultant neurological development defects and diseases. Author summaryIn this study, we first unveiled that copper induced central neural system (CNS) myelin defects via down-regulating Wnt/Notch-hoxb5b signaling, and parallel with hypermethylating promoters of genes fam168b/pou3f2 and their subsequent down-regulated expression. Additionally, we unveiled that fam168b/pou3f1 and hoxb5b axis acted in a seesaw manner during fish embryogenesis. Genetically, we unveiled that copper was trafficked to mitochondrion via cox17 then led to the down-regulation of Wnt&Notch-hoxb5b axis, and was trafficked to trans-Golgi network via atp7b to induce the hypermethylation and the down-regulated expression of pou3f1/fam168b genes, making joint contributions to myelin defects in embryos.

developmental biology↗

bioRxiv2019

Genetic characterization of Streptococcus equi subspecies zooepidemicus associated with high swine mortality in United States

High mortality events due to Streptococcus equi subspecies zooepidemicus (S. zooepidemicus) in swine have not previously been reported in the United States. In September and October 2019, outbreaks with swine mortality up to 50% due to S. zooepidemicus septicemia were reported in Ohio and Tennessee. Genomic epidemiological analysis revealed that the eight outbreak isolates were clustered together with ATCC 36246, a Chinese strain caused outbreaks with high mortality, also closely related to three isolates from human cases from Virginia, but significantly different from an outbreak-unrelated swine isolate from Arizona and most isolates from other animal species. Comparative genomic analysis on two outbreak isolates and another outbreak-unrelated isolate identified several genomic islands and virulence genes specifically in the outbreak isolates only, which are likely associated with the high mortality observed in the swine population. These findings have implications for understanding, tracking, and possibly preventing diseases caused by S. zooepidemicus in swine.

microbiology↗

bioRxiv2019

Cep57 and Cep57l1 cooperate to recruit the Cep63-Cep152 complex for centriole biogenesis

Cep152 and Cep63 act as the cradle and recruit Plk4 to initiate the centriole biogenesis in a mother centriole dependent manner. However, how the Cep152-Cep63 complex is targeted to the proximal end of mother centrioles is unclear. In this study, we show that Cep57 and its paralog, Cep57l1, colocalize with Cep63 and Cep152 at the proximal end of mother centrioles in both cycling cells and differentiated multiciliated cells. Both Cep57 and Cep57l1 associate with the Cep152-Cep63 complex by directly binding to the centrosomal targeting region of Cep63. Co-depletion of Cep57 and Cep57l1 blocks the loading of Cep63-Cep152 to the centriole and subsequently prevents centriole duplication. We propose that Cep57 and Cep57l1 act together to ensure the recruitment of the Cep63-Cep152 complex to the mother centrioles for procentriole formation. Summary statementCep57 and its paralog, Cep57l1, cooperatively act as a molecular scaffold to recruit the Cep63-Cep152 cradle to the proximal end of centrioles in the early stages of centriole duplication.

cell biology↗

bioRxiv2019

Enhancing Gesture Decoding Performance Using Signals from Posterior Parietal Cortex: A Stereo-Electroencephalograhy (SEEG) Study

ObjectiveHand movement is a crucial function for humans daily life. Developing brain-machine interface (BMI) to control a robotic hand by brain signals would help the severely paralyzed people partially regain the functional independence. Previous intracranial electroencephalography (iEEG)-based BMIs towards gesture decoding mostly used neural signals from the primary sensorimotor cortex while ignoring the hand movement related signals from posterior parietal cortex (PPC). Here, we propose combining iEEG recordings from PPC with that from primary sensorimotor cortex to enhance the gesture decoding performance of iEEG-based BMI. ApproachStereoelectroencephalography (SEEG) signals from 25 epilepsy subjects were recorded when they performed a three-class hand gesture task. Across all 25 subjects, we identified 524, 114 and 221 electrodes from three regions of interest (ROIs), including PPC, postcentral cortex (POC) and precentral cortex (PRC), respectively. Based on the time-varying high gamma power (55-150 Hz) of SEEG signal, both the general activation in the task and the fine selectivity to gestures of each electrode in these ROIs along time was evaluated by the coefficient of determination r2. According to the activation along time, we further assessed the first activation time of each ROI. Finally, the decoding accuracy for gestures was obtained by linear support vector machine classifier to comparatively explore if the PPC will assist PRC and POC for gesture decoding. Main ResultsWe find that a majority(L: >60%, R: >40%) of electrodes in all the three ROIs present significant activation during the task. A large scale temporal activation sequence exists among the ROIs, where PPC activates first, PRC second and POC last. Among the activated electrodes, 15% (PRC), 26% (POC) and 4% (left PPC) of electrodes are significantly selective to gestures. Moreover, decoding accuracy obtained by combining the selective electrodes from three ROIs together is 5%, 3.6%, and 8% higher than that from only PRC and POC when decoding features across, before, and after the movement onset, were used. SignificanceThis is the first human iEEG study demonstrating that PPC contains neural information about fine hand movement, supporting the role of PPC in hand shape encoding. Combining PPC with primary sensorimotor cortex can provide more information to improve the gesture decoding performance. Our results suggest that PPC could be a rich neural source for iEEG-based BMI. Our findings also demonstrate the early involvement of human PPC in visuomotor task and thus may provide additional implications for further scientific research and BMI applications.

neuroscience↗