Biology subjects

Xiao, Y.

Publications and source records attributed to Xiao, Y..

At least 181 records · Page 10Linked to original sources

bioRxiv2023

High-sensitivity whole-genome recovery of single viral species in environmental samples

Characterizing unknown viruses is essential for understanding viral ecology and preparing against viral outbreaks. Recovering complete genome sequences from environmental samples remains computationally challenging using metagenomics, especially for low-abundance species with uneven coverage. This work presents a method for reliably recovering complete viral genomes from complex environmental samples. Individual genomes are encapsulated into droplets and amplified using multiple displacement amplification. A novel gene detection assay, which employs an RNA-based probe and an exonuclease, selectively identifies droplets containing the target viral genome. Labeled droplets are sorted using a microfluidic sorter, and genomes are extracted for sequencing. Validation experiments using a sewage sample spiked with two known viruses demonstrate the methods efficacy. We achieve 100% recovery of the spiked-in SV40 (Simian virus 40, 5243bp) genome sequence with uniform coverage distribution, and approximately 99.4% for the larger HAd5 genome (Human Adenovirus 5, 35938bp). Notably, genome recovery is achieved with as few as one sorted droplet, which enables the recovery of any desired genomes in complex environmental samples, regardless of their abundance. This method enables targeted characterizations of rare viral species and whole-genome amplification of single genomes for accessing the mutational profile in single virus genomes, contributing to an improved understanding of viral ecology.

bioengineering↗

bioRxiv2023

Single phage proteins sequester TIR- and cGAS-generated signaling molecules

Prokaryotic anti-phage immune systems use TIR (toll/interleukin-1 receptor) and cGAS (cyclic GMP-AMP synthase) enzymes to produce 1-3/1-2 glycocyclic ADPR (gcADPR) and cyclid di-/tri-nucleotides (CDNs and CTNs) signaling molecules that limit phage replication, respectively 1-3. However, how phages neutralize these common systems is largely unknown. Here, we show that Thoeris anti-defense proteins Tad1 4 and Tad2 5 both have anti-CBASS activity by simultaneously sequestering CBASS cyclic oligonucleotides. Strikingly, apart from binding Thoeris signals 1-3 and 1-2 gcADPR, Tad1 also binds numerous CBASS CDNs/CTNs with high affinity, inhibiting CBASS systems using these molecules in vivo and in vitro. The hexameric Tad1 has six binding sites for CDNs or gcADPR, which are independent from two high affinity binding sites for CTNs. Tad2 also sequesters various CDNs in addition to gcADPR molecules, inhibiting CBASS systems using these CDNs. However, the binding pockets for CDNs and gcADPR are different in Tad2, whereby a tetramer can bind two CDNs and two gcADPR molecules simultaneously. Taken together, Tad1 and Tad2 are both two-pronged inhibitors that, alongside anti-CBASS protein 2, establish a paradigm of phage proteins that flexibly sequester a remarkable breadth of cyclic nucleotides involved in TIR- and cGAS-based anti-phage immunity.

microbiology↗

bioRxiv2023

A Fuzzy sequencer for rapid DNA fragment counting and genotyping

High-throughput sequencing technologies generate a vast number of DNA sequence reads simultaneously, which are subsequently analyzed using the information contained within these fragmented reads. The assessment of sequencing technology relies on information efficiency, which measures the amount of information entropy produced per sequencing reaction cycle. In this study, we propose a fuzzy sequencing strategy that exhibits information efficiency more than twice of currently prevailing cyclic reversible terminator sequencing methods. To validate our approach, we developed a fully functional and high-throughput fuzzy sequencer. This sequencer implements a highly efficient fluorogenic sequencing-by-synthesis chemistry and underwent testing across various application scenarios, including copy-number variation detection, noninvasive prenatal testing, transcriptome profiling, mutation genotyping, and metagenomic profling. Our findings unequivocally demonstrate that the fuzzy sequencing strategy outperforms existing methods in terms of information efficiency and delivers accurate resequencing results with faster turnaround times. One Sentence SummaryA fuzzy sequencer can exceed current limit of information efficiency of DNA sequencers for resequencing applications.

genomics↗

bioRxiv2023

Spatially resolved DNP-assisted NMR illuminates the conformational ensemble of α-synuclein in intact viable cells.

The protein -syn adopts a wide variety of conformations including an intrinsically disordered monomeric form and an -helical rich membrane-associated form that is thought to play an important role in cellular membrane processes. However, despite the high affinity of -syn for membranes, evidence that the -helical form is adopted inside cells has been indirect. DNP-assisted solid state NMR on frozen cellular samples can report on protein conformations inside cells. Moreover, by controlling the distribution of the DNP polarization agent throughout the cellular biomass, such experiments can provide quantitative information upon the entire structural ensemble or provide information about spatially resolved sub-populations. Using DNP-assisted magic angle spinning (MAS) NMR we establish that purified -syn in the membrane-associated and intrinsically disordered forms have distinguishable spectra. We then introduced isotopically labeled monomeric -syn into cells. When the DNP polarization agent is dispersed homogenously throughout the cell, we found that a minority of the -syn inside cells adopted a highly -helical rich conformation. When the DNP polarization agent is peripherally localized, we found that the -helical rich conformation predominates. Thus, we provide direct evidence that -helix rich conformations of -syn are adopted near the cellular periphery inside cells under physiological conditions. Moreover, we demonstrate how selectively altering the spatial distribution of the DNP polarization agent can be a powerful tool to observe spatially distinct structural ensembles. This approach paves the way for more nuanced investigations into the conformations that proteins adopt in different areas of the cell.

biophysics↗

bioRxiv2023

Identification of the KIF18A alpha-4 helix as a therapeutic target for chromosomally unstable tumor cells

The mitotic kinesin, KIF18A, is required for proliferation of cancer cells that exhibit chromosome instability (CIN), implicating it as a promising target for treatment of a subset of aggressive tumor types. Determining regions of the KIF18A protein to target for inhibition will be important for the design and optimization of effective small molecule inhibitors. In this study, we investigated the effects of mutating S284 within the alpha-4 helix of KIF18A, which was previously identified as a phosphorylated residue. Mutations in S284 cause relocalization of KIF18A from the plus-ends of spindle microtubules to the spindle poles. Furthermore, KIF18A S284 mutants display loss of KIF18A function and fail to support proliferation in CIN tumor cells. Interestingly, similar effects on KIF18A localization and function were seen after treatment of CIN cells with KIF18A inhibitory compounds that are predicted to interact with residues within the alpha-4 helix. These data implicate the KIF18A alpha-4 helix as an effective target for inhibition and demonstrate that small molecules targeting KIF18A selectively limit CIN tumor cell proliferation and result in phenotypically similar effects on mitosis at the single cell level compared to genetic perturbations.

cancer biology↗

bioRxiv2023

MicroRNAs are necessary for the emergence of Purkinje cell identity

Brain computations are dictated by the unique morphology and connectivity of neuronal subtypes, features established by closely timed developmental events. MicroRNAs (miRNAs) are critical for brain development, but current technologies lack the spatiotemporal resolution to determine how miRNAs instruct the steps leading to subtype identity. Here, we developed new tools to tackle this major gap. Fast and reversible miRNA loss-of-function revealed that miRNAs are necessary for cerebellar Purkinje cell (PC) differentiation, which previously appeared miRNA-independent, and resolved distinct miRNA critical windows in PC dendritogenesis and climbing fiber synaptogenesis, key determinants of PC identity. To identify underlying mechanisms, we generated a mouse model, which enables precise mapping of miRNAs and their targets in rare cell types. With PC-specific maps, we found that the PC-enriched miR-206 drives exuberant dendritogenesis and modulates synaptogenesis. Our results showcase vastly improved approaches for dissecting miRNA function and reveal that many critical miRNA mechanisms remain largely unexplored. HighlightsO_LIFast miRNA loss-of-function with T6B impairs postnatal Purkinje cell development C_LIO_LIReversible T6B reveals critical miRNA windows for dendritogenesis and synaptogenesis C_LIO_LIConditional Spy3-Ago2 mouse line enables miRNA-target network mapping in rare cells C_LIO_LIPurkinje cell-enriched miR-206 regulates its unique dendritic and synaptic morphology C_LI

neuroscience↗

bioRxiv2023

Large-scale phenotypic and genomic characterization of Listeria monocytogenes susceptibility to quaternary ammonium compounds

Listeria monocytogenes is a significant concern for the food industry due to its ability to persist in the food processing environment. Decreased susceptibility to disinfectants is one of the factors that contribute to the persistence of L. monocytogenes. The objective of this study was to explore the diversity of L. monocytogenes susceptibility to quaternary ammonium compounds (QACs) using 1,671 L. monocytogenes isolates. This was used to determine the phenotype-genotype concordance and characterize genomes of the QAC sensitive and tolerant isolates for stress resistance, virulence and plasmid replicon genes. Distribution of QAC tolerance genes among 37,897 publicly available L. monocytogenes genomes were also examined. The minimum inhibitory concentration to QACs was determined by the broth microdilution method and non-sequenced isolates (n=1,244) were whole genome sequenced. Genotype-phenotype concordance was 99% for benzalkonium chloride, DDAC and a commercial QAC based sanitizer. Prevalence of QAC tolerance genes was 23% and 28% in our L. monocytogenes collection and in the global dataset, respectively. qacH was the most prevalent gene in our collection (61%), with 19% prevalence in the global dataset. Notably, bcrABC was most common (72%) globally, while 25% in our collection. Prevalence of emrC and emrE was comparable in both datasets, 7% and 2%, respectively. Replicon genes, indicative of plasmid harborage, were detected in 44% of the isolates and associated with the QAC tolerant phenotype. The presented analysis is based on the biggest L. monocytogenes collection in diversity and quantity for characterization of the L. monocytogenes QAC tolerance at both phenotypic and genomic levels. IMPORTANCEContamination of Listeria monocytogenes within the food processing environment is of concern to the food industry due to challenges in eradicating the pathogen once it becomes persistent in the environment. Genetic markers associated with increased tolerance to disinfectants have been identified, which alongside factors favor the persistence of L. monocytogenes in the production environment. By employing a comprehensive large-scale phenotypic testing and genomic analysis our study significantly enhances the understanding of the prevalence of quaternary ammonium compound (QAC) tolerant L. monocytogenes and the genetic determinants associated with the increased tolerance. Furthermore, we report on the prevalence of QAC tolerance genes among 37,897 publicly available L. monocytogenes sequences and their distribution within clonal complexes, isolation sources and geographical locations. As the propagation of QAC tolerance showed not be evenly distributed globally this highlights that understanding the development of L. monocytogenes disinfectant tolerance can be monitored using publicly available WGS data.

microbiology↗

bioRxiv2023

Logic Gate Activated Lysosome Targeting DNA Nanodevice for Controlled Proteins Degradation

Targeted protein degradation (TPD) is a powerful technique for regulation of protein homeostasis. Current TPD mainly focuses on the therapeutical consequences rather than the operation processes of the molecular tools. Herein, we construct a platform for precisely manipulate the protein degradation by activatable lysosome targeting DNA nanodevices. In the design, a lysosome-targeting CD63 aptamer is locked by the single-stranded DNA with a photocleavable group and a disulfide bond. This locked CD63 aptamer is connected with the aptamer targeting the protein of interest via double-stranded DNA linkages to form the logic-gate activated lysosome targeting DNA nanodevice (LALTD). With the UV light and endogenous GSH as inputs, AND logic-gate is built to efficiently manipulate the protein delivery processes by LALTD. The protein of interest could be degraded via efficient lysosome hydrolysis. Further studies shows that the logic-gate operation could be used for modulating the T cell-mediated antitumor immunity. The modularly designed activatable lysosome targeting DNA nanodevices exhibits good stability, controllability, programmability and universality, providing a new prospect for accurate protein degradation and precise therapy. Entry for the Table of ContentsThrough rational integration of dual molecular switches with bispecific aptamer systems, a logic-gate activated lysosome targeting DNA nanodevice (LALTD) was developed for precisely controlled process of protein hydrolysis in living cells. The designed LALTD system provide a general platform for designing accurate protein degradation. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=162 SRC="FIGDIR/small/555427v1_ufig1.gif" ALT="Figure 1"> View larger version (87K): org.highwire.dtl.DTLVardef@1b3afc1org.highwire.dtl.DTLVardef@1d7c893org.highwire.dtl.DTLVardef@1b14268org.highwire.dtl.DTLVardef@7ed354_HPS_FORMAT_FIGEXP M_FIG C_FIG

cell biology↗

bioRxiv2023

β1 integrins regulate cellular behaviors and cardiomyocyte organization during ventricular wall formation

AimsThe mechanisms regulating the cellular behavior and cardiomyocyte organization during ventricular wall morphogenesis are poorly understood. Cardiomyocytes are surrounded by extracellular matrix (ECM) and interact with ECM via integrins. This study aims to determine whether and how {beta}1 integrins regulate cardiomyocyte behavior and organization during ventricular wall morphogenesis in the mouse. Methods and ResultsWe applied mRNA deep sequencing and immunostaining to determine the expression repertoires of /{beta} integrins and their ligands in the embryonic heart. Integrin {beta}1 subunit ({beta}1) and some of its ECM ligands are asymmetrically distributed and enriched in the luminal side of cardiomyocytes, while fibronectin surrounds cardiomyocytes, creating a network for them. Itgb1, which encodes the {beta}1 integrin subunit, was deleted via Nkx2.5Cre/+ to generate myocardial-specific Itgb1 knockout (B1KO) mice. B1KO hearts display an absence of trabecular zone but a thicker compact zone. The abundances of hyaluronic acid and versican are not significantly different. Instead, fibronectin, a ligand of {beta}1, was absent in B1KO. We examined cellular behaviors and organization via various tools. B1KO cardiomyocytes display a random cellular orientation and fail to undergo perpendicular cell division, be organized properly, and establish the proper tissue architecture to form trabeculae. The reduction of Notch1 activation was not the cause of the abnormal cellular organization in B1KO hearts. Mosaic clonal lineage tracing shows that Itgb1 regulates cardiomyocyte transmural migration and proliferation autonomously. Conclusions{beta}1 is asymmetrically localized in the cardiomyocytes, and its ECM ligands are enriched in the luminal side of the myocardium and surrounding cardiomyocytes. {beta}1 integrins are required for cardiomyocytes to attach to the ECM network. This engagement provides structural support for cardiomyocytes to maintain shape, undergo perpendicular division, and establish cellular organization. Deletion of Itgb1, leading to ablation of {beta}1 integrins, causes the dissociation of cardiomyocytes from the ECM network and failure to establish tissue architecture to form trabeculae.

developmental biology↗

bioRxiv2023

Unleashing the Power of NR4A1 Degradation as a Novel Strategy for Cancer Immunotherapy

An effective cancer therapy requires both killing cancer cells and targeting tumor-promoting pathways or cell populations within the tumor microenvironment (TME). We purposely search for molecules that are critical for multiple tumor-promoting cell types and identified nuclear receptor subfamily 4 group A member 1 (NR4A1) as one such molecule. NR4A1 has been shown to promote the aggressiveness of cancer cells and maintain the immune suppressive TME. Using genetic and pharmacological approaches, we establish NR4A1 as a valid therapeutic target for cancer therapy. Importantly, we have developed the first-of-its kind proteolysis-targeting chimera (PROTAC, named NR-V04) against NR4A1. NR-V04 effectively degrades NR4A1 within hours of treatment in vitro and sustains for at least 4 days in vivo, exhibiting long-lasting NR4A1-degradation in tumors and an excellent safety profile. NR-V04 leads to robust tumor inhibition and sometimes eradication of established melanoma tumors. At the mechanistic level, we have identified an unexpected novel mechanism via significant induction of tumor-infiltrating (TI) B cells as well as an inhibition of monocytic myeloid derived suppressor cells (m-MDSC), two clinically relevant immune cell populations in human melanomas. Overall, NR-V04-mediated NR4A1 degradation holds promise for enhancing anti- cancer immune responses and offers a new avenue for treating various types of cancer.

cancer biology↗

bioRxiv2023

NanoPDLIM2 enhanced efficacy of PD-1 blockade and chemotherapy in mouse lung cancers

BackgroundImmune checkpoint inhibitors (ICIs) and their combination with other therapies such as chemotherapy, fail in most cancer patients. We previously identified the PDZ-LIM domain-containing protein 2 (PDLIM2) as a bona fide tumor suppressor that is repressed in lung cancer to drive cancer and its chemo and immunotherapy resistance, suggesting a new target for lung cancer therapy improvement. MethodsHuman clinical samples and data were used to investigate PDLIM2 genetic and epigenetic changes in lung cancer. Using an endogenous mouse lung cancer model faithfully recapitulating refractory human lung cancer and a clinically feasible nano-delivery system, we investigated the therapeutic efficacy, action mechanism, and safety of systemically administrated PDLIM2 expression plasmids encapsulated in nanoparticles (nanoPDLIM2) and its combination with PD-1 antibody and chemotherapeutic drugs. ResultsPDLIM2 repression in human lung cancer involves both genetic deletion and epigenetic alteration. NanoPDLIM2 showed low toxicity, high tumor specificity, antitumor activity, and greatly improved the efficacy of anti-PD-1 and chemotherapeutic drugs, with complete tumor remission in most mice and substantial tumor reduction in the remaining mice by their triple combination. Mechanistically, nanoPDLIM2 increased major histocompatibility complex class I (MHC-I) expression, suppressed multi-drug resistance 1 (MDR1) induction and survival genes and other tumor-related genes expression in tumor cells, and enhanced lymphocyte tumor infiltration, turning the cold tumors hot and sensitive to ICIs and rendering them vulnerable to chemotherapeutic drugs and activated tumor-infiltrating lymphocytes (TILs) including those unleashed by ICIs. ConclusionsThese studies established a clinically applicable PDLIM2-based combination therapy with great efficacy for lung cancer and possibly other cold cancers.

cancer biology↗

bioRxiv2023

Structural basis for auto-inhibition and activation of a short prokaryotic Argonaute associated TIR-APAZ defense system

Short prokaryotic Ago accounts for most prokaryotic Argonaute (pAgo) and is involved in defending bacteria against invading nucleic acids. Short prokaryotic Ago associated with APAZ-TIR (SPARTA) has been shown to oligomerize and deplete NAD+ upon guide-mediated target DNA recognition. However, the molecular basis of SPARTA inhibition and activation remains unknown. Here we determine the cryo-EM structures of Crenotalea thermophila SPARTA in its inhibited, transient, as well as activated states. The SPARTA is auto-inhibited by its acidic tail, which occupies the guide-target binding channel. Guide mediated target binding expels this acidic tail and triggers substantial conformational changes to expose Ago-Ago dimerization interface. As a result, SPARTA assembles into an active TIR-APAZ4/short Ago4 octamer, where the four TIR domains are rearranged and packed to form NADase active sites. Together with biochemical evidence, our results provide a panoramic vision explaining SPARTA auto-inhibition and activation, and expand understanding of pAgo mediated bacterial defense systems.

biochemistry↗

bioRxiv2023

Drosophila Amus and Bin3 methylases functionally replace mammalian MePCE for capping and the stabilization of U6 and 7SK snRNAs

U6 and 7SK snRNAs process a 5 cap, believed to be essential for their stability and maintained by mammalian MePCE or Drosophila Bin3 enzymes. Although loss of either protein results in 7SK instability, loss of neither is associated with U6 reduction. Their yeast homolog is also not required for U6 stability, casting further doubts on the function of capping U6. Here we show that the Drosophila Amus protein, homologous to both Bin3 and MePCE, is essential for U6 but not 7SK stability. A full function of Amus is required for Drosophila development, and that rests primarily on Amuss methylase activity. Remarkably, the loss of U6 is rescued by the expression of an Amus-MePCE hybrid protein harboring the methyltransferase domain from MePCE, highlighting the conserved function of the two proteins as the U6 capping enzyme. Our new investigations in human cells establish a dependence of both U6 and 7SK stability on MePCE, resolving a long-standing uncertainty. While uncovering an interesting division of labor of Bin3/MePCE/Amus proteins, we discovered a "Bin3-Box" domain present only in enzymes associated with 7SK regulation. Targeted mutagenesis in Drosophila confirmed its importance for Bin3 function, revealing a possible conserved element in 7SK but not U6 biology.

genetics↗

bioRxiv2023

SARS-CoV-2 Nsp1 regulates translation start site fidelity to promote infection

A better mechanistic understanding of virus-host interactions can help reveal vulnerabilities and identify opportunities for therapeutic interventions. Of particular interest are essential interactions that enable production of viral proteins, as those could target an early step in the virus lifecycle. Here, we use subcellular proteomics, ribosome profiling analyses and reporter assays to detect changes in polysome composition and protein synthesis during SARS-CoV-2 (CoV2) infection. We identify specific translation factors and molecular chaperones whose inhibition impairs infectious particle production without major toxicity to the host. We find that CoV2 non-structural protein Nsp1 selectively enhances virus translation through functional interactions with initiation factor EIF1A. When EIF1A is depleted, more ribosomes initiate translation from an upstream CUG start codon, inhibiting translation of non-structural genes and reducing viral titers. Together, our work describes multiple dependencies of CoV2 on host biosynthetic networks and identifies druggable targets for potential antiviral development.

microbiology↗

bioRxiv2023

The canonical single-stranded DNA binding protein SSB is not an essential replication protein but an RNA chaperon in the hyperthermophilic archaeon Saccharolobus islandicus REY15A

Single-stranded DNA binding proteins (SSBs) have been regarded as indispensable factors in all three domains of life since they play vital roles in DNA replication. Herein, we report that genes coding for the canonical SSB (SisSSB) and the non-canonical SSB (SisDBP) in the hyperthermophilic archaeon Saccharolobus islandicus REY15A can both be deleted. The growth is not affected, and the cell cycle progression and genome stability of the deletion strains is not impaired, suggesting that SisSSB and SisDBP are not essential for cell viability. Interestingly, at a lower temperature (55{degrees}C), the protein level of SisSSB increases [~]1.8 fold in the wild type and the growth of {Delta}Sisssb and {Delta}Sisssb{Delta}Sisdbp is retarded. SisSSB exhibits melting activity on dsRNA and DNA/RNA hybrid in vitro and unwinding RNA hairpin in Escherichia coli. Furthermore, the core SisSSB domain is able to complement the absence of the cold shock proteins CspABGE in E. coli, suggesting that SisSSB functions as RNA chaperon. We show that a two-fold overexpression of SisSSB is beneficial to the cell growth at lower temperature, but it has detrimental effect on the cell growth and cell cycle progression at normal growth temperature, which differs from bacterial Csp proteins. Importantly, these in vitro and in vivo activities are conserved in SSB subtype SSB-1 in Crenarchaeota species that lack bacterial Csp homologs. Overall, we have clarified the function of the archaeal canonical SSB which does not function as a DNA processing factor, but plays a role in processes requiring dsRNA or DNA/RNA hybrid unwinding.

microbiology↗

bioRxiv2023

Evolution of Shewanella oneidensis MR-1 in competition with Citrobacter freundii

Interspecific competition is one of the most important metabolic interactions within microbial communities, and exoelectrogenic bacteria that can conduct extracellular electron transfer act essential roles in nature and engineering systems for pollutants removal. In the present study we investigated the long-term impact of substrate competition from non-exoelectrogenic Citrobacter freundii An1 on exoelectrogenic Shewanella oneidensis MR-1. Without additional electron acceptor or with electron acceptor of oxygen, C. freundii An1 typically suppressed the growth of S. oneidensis MR-1. In contrast, S. oneidensis MR-1 grown better with electron acceptor of ferrihydrite by taking advantage of extracellular electron transfer. However, the presence of ferrihydrite did not enhance the ferrihydrite reduction of S. oneidensis MR-1 after the 160 d-acclimation. The whole genome resequencing showed a complex evolution of S. oneidensis MR-1 when the strain faced the competition from C. freundii An1 for substrate.

microbiology↗

bioRxiv2023

Functional glycoproteomics by integrated network assembly and partitioning

The post-translational modification (PTM) of proteins by O-linked {beta}-N-acetyl-D-glucosamine (O-GlcNAcylation) is widespread across the proteome during the lifespan of all multicellular organisms. However, nearly all functional studies have focused on individual protein modifications, overlooking the multitude of simultaneous O-GlcNAcylation events that work together to coordinate cellular activities. Here, we describe Networking of Interactors and SubstratEs (NISE), a novel, systems-level approach to rapidly and comprehensively monitor O-GlcNAcylation across the proteome. Our method integrates affinity purification-mass spectrometry (AP-MS) and site-specific chemoproteomic technologies with network generation and unsupervised partitioning to connect potential upstream regulators with downstream targets of O-GlcNAcylation. The resulting network provides a data-rich framework that reveals both conserved activities of O-GlcNAcylation such as epigenetic regulation as well as tissue-specific functions like synaptic morphology. Beyond O-GlcNAc, this holistic and unbiased systems-level approach provides a broadly applicable framework to study PTMs and discover their diverse roles in specific cell types and biological states.

cell biology↗

bioRxiv2023

A population-averaged structural connectomic brain atlas of 422 HCP-Aging subjects

Population-averaged brain atlases, that are represented in a standard space with anatomical labels, are instrumental tools in neurosurgical planning and the study of neurodegenerative conditions. Traditional brain atlases are primarily derived from anatomical scans and contain limited information regarding the axonal organization of the white matter. With the advance of diffusion MRI that allows the modelling of fiber orientation distribution (FOD) in the brain tissue, there is an increasing interest for a population-averaged FOD template, especially based on a large healthy aging cohort, to offer structural connectivity information for connectomic surgery and analysis of neurodegeneration. The dataset described in this article contains a set of multi-contrast structural connectomic MRI atlases, including T1w, T2w, and FOD templates, along with the associated whole brain tractograms. The templates were made using multi-contrast group-wise registration based on 3T MRIs of 422 Human Connectome Project in Aging (HCP-A) subjects. To enhance the usability, probabilistic tissue maps and segmentation of 22 subcortical structures are provided. Finally, the subthalamic nucleus shown in the atlas is parcellated into sensorimotor, limbic, and associative sub-regions based on their structural connectivity to facilitate the analysis and planning of deep brain stimulation procedures. The dataset is available on the OSF Repository: https://osf.io/p7syt. Specifications table O_TBL View this table: org.highwire.dtl.DTLVardef@59fb82org.highwire.dtl.DTLVardef@18f1f44org.highwire.dtl.DTLVardef@14de18dorg.highwire.dtl.DTLVardef@1318a8org.highwire.dtl.DTLVardef@1b7bea8_HPS_FORMAT_FIGEXP M_TBL C_TBL Value of the dataO_LIThese publicly available templates were created using 422 HCP-Aging subjects, representing averaged anatomical and structural connectivity features of the healthy aging brain. C_LIO_LIMatching T1w, T2w, and fiber orientation distribution (FOD) templates are provided, together with the associated tractograms that contain 20K and 2 million streamlines. C_LIO_LISegmentation of 22 subcortical structures and probabilistic tissue maps are provided to enhance the usability of the templates. C_LIO_LIParcellation of the subthalamic nucleus, based on structural connectivity of the included cohort at 0.3 x 0.3 x 0.3 mm3 resolution, is provided. C_LI

bioengineering↗