Publications by authors named "Jeesoo Kim"

16 Publications

  • Page 1 of 1

The SARS-CoV-2 RNA interactome.

Mol Cell 2021 Apr 27. Epub 2021 Apr 27.

Center for RNA Research, Institute for Basic Science, Seoul, Republic of Korea; School of Biological Sciences, Seoul National University, Seoul, Republic of Korea. Electronic address:

SARS-CoV-2 is an RNA virus whose success as a pathogen relies on its abilities to repurpose host RNA-binding proteins (RBPs) and to evade antiviral RBPs. To uncover the SARS-CoV-2 RNA interactome, we here develop a robust ribonucleoprotein (RNP) capture protocol and identify 109 host factors that directly bind to SARS-CoV-2 RNAs. Applying RNP capture on another coronavirus, HCoV-OC43, revealed evolutionarily conserved interactions between coronaviral RNAs and host proteins. Transcriptome analyses and knockdown experiments delineated 17 antiviral RBPs, including ZC3HAV1, TRIM25, PARP12, and SHFL, and 8 proviral RBPs, such as EIF3D and CSDE1, which are responsible for co-opting multiple steps of the mRNA life cycle. This also led to the identification of LARP1, a downstream target of the mTOR signaling pathway, as an antiviral host factor that interacts with the SARS-CoV-2 RNAs. Overall, this study provides a comprehensive list of RBPs regulating coronaviral replication and opens new avenues for therapeutic interventions.
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http://dx.doi.org/10.1016/j.molcel.2021.04.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8075806PMC
April 2021

Dual conformational recognition by Z-DNA binding protein is important for the B-Z transition process.

Nucleic Acids Res 2020 12;48(22):12957-12971

Department of Biological Sciences, Seoul National University, Seoul 08826, Korea.

Left-handed Z-DNA is radically different from the most common right-handed B-DNA and can be stabilized by interactions with the Zα domain, which is found in a group of proteins, such as human ADAR1 and viral E3L proteins. It is well-known that most Zα domains bind to Z-DNA in a conformation-specific manner and induce rapid B-Z transition in physiological conditions. Although many structural and biochemical studies have identified the detailed interactions between the Zα domain and Z-DNA, little is known about the molecular basis of the B-Z transition process. In this study, we successfully converted the B-Z transition-defective Zα domain, vvZαE3L, into a B-Z converter by improving B-DNA binding ability, suggesting that B-DNA binding is involved in the B-Z transition. In addition, we engineered the canonical B-DNA binding protein GH5 into a Zα-like protein having both Z-DNA binding and B-Z transition activities by introducing Z-DNA interacting residues. Crystal structures of these mutants of vvZαE3L and GH5 complexed with Z-DNA confirmed the significance of conserved Z-DNA binding interactions. Altogether, our results provide molecular insight into how Zα domains obtain unusual conformational specificity and induce the B-Z transition.
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http://dx.doi.org/10.1093/nar/gkaa1115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7736808PMC
December 2020

Sclerostin inhibits Wnt signaling through tandem interaction with two LRP6 ectodomains.

Nat Commun 2020 10 23;11(1):5357. Epub 2020 Oct 23.

Department of Biological Sciences, Seoul National University, Seoul, 08826, Republic of Korea.

Low-density lipoprotein receptor-related protein 6 (LRP6) is a coreceptor of the β-catenin-dependent Wnt signaling pathway. The LRP6 ectodomain binds Wnt proteins, as well as Wnt inhibitors such as sclerostin (SOST), which negatively regulates Wnt signaling in osteocytes. Although LRP6 ectodomain 1 (E1) is known to interact with SOST, several unresolved questions remain, such as the reason why SOST binds to LRP6 E1E2 with higher affinity than to the E1 domain alone. Here, we present the crystal structure of the LRP6 E1E2-SOST complex with two interaction sites in tandem. The unexpected additional binding site was identified between the C-terminus of SOST and the LRP6 E2 domain. This interaction was confirmed by in vitro binding and cell-based signaling assays. Its functional significance was further demonstrated in vivo using Xenopus laevis embryos. Our results provide insights into the inhibitory mechanism of SOST on Wnt signaling.
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http://dx.doi.org/10.1038/s41467-020-19155-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7585440PMC
October 2020

ERH facilitates microRNA maturation through the interaction with the N-terminus of DGCR8.

Nucleic Acids Res 2020 11;48(19):11097-11112

Center for RNA Research, Institute for Basic Science, Seoul 08826, Korea.

The microprocessor complex cleaves the primary transcript of microRNA (pri-miRNA) to initiate miRNA maturation. Microprocessor is known to consist of RNase III DROSHA and dsRNA-binding DGCR8. Here, we identify Enhancer of Rudimentary Homolog (ERH) as a new component of Microprocessor. Through a crystal structure and biochemical experiments, we reveal that ERH uses its hydrophobic groove to bind to a conserved region in the N-terminus of DGCR8, in a 2:2 stoichiometry. Knock-down of ERH or deletion of the DGCR8 N-terminus results in a reduced processing of suboptimal pri-miRNAs in polycistronic miRNA clusters. ERH increases the processing of suboptimal pri-miR-451 in a manner dependent on its neighboring pri-miR-144. Thus, the ERH dimer may mediate 'cluster assistance' in which Microprocessor is loaded onto a poor substrate with help from a high-affinity substrate in the same cluster. Our study reveals a role of ERH in the miRNA biogenesis pathway.
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http://dx.doi.org/10.1093/nar/gkaa827DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7641749PMC
November 2020

Proteomic analysis of human synovial fluid reveals potential diagnostic biomarkers for ankylosing spondylitis.

Clin Proteomics 2020 1;17:20. Epub 2020 Jun 1.

Center for RNA Research, Institute of Basic Science (IBS), Seoul, 08826 South Korea.

Background: Ankylosing spondylitis (AS) is a chronic inflammatory rheumatic disease affecting the axial skeleton and peripheral joints. The etiology of this disease remains poorly understood, but interactions between genetic and environmental factors have been implicated. The present study identified differentially expressed proteins in the synovial fluid (SF) of AS patients to elucidate the underlying cause of AS.

Methods: A cohort of 40 SF samples from 10 AS and 10 each of rheumatoid arthritis (RA), gout, and osteoarthritis (OA) patients were analyzed by liquid chromatography tandem mass spectrometry (LC-MS/MS) to identify differentially expressed proteins specific to AS. The label-free LC-MS/MS results were verified by western blotting.

Results: We identified 8 proteins that were > 1.5-fold upregulated in the SF of AS patients compared to that of the disease control groups, including HP, MMP1, MMP3, serum amyloid P-component (APCS), complement factor H-related protein 5 (CFHR5), mannose-binding lectin 2 (MBL2), complement component C9 (C9), and complement C4-A (C4A). CFHR5 and C9 were previously found in serum from AS patients, while APCS was previously found in SF as well as in serum. However, the present study has identified C4A, and MBL2 as potential AS biomarkers for the first time. The expression levels of MMP3, C9, and CFHR5 were verified in AS SF using western blotting.

Conclusion: We performed quantitative comparative proteomic analysis using by LC-MS/MS of the SF from four disease states: RA, gout, and OA. This systematic comparison revealed novel differentially expressed proteins in AS SF, as well as two previously reported candidate biomarkers. We further verified the expression of MMP3, C9 and CFHR5 by western blot. These proteins may serve as diagnostic or prognostic biomarkers in patients with AS, and may thus improve the clinical outcomes of this serious disease.
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http://dx.doi.org/10.1186/s12014-020-09281-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7269004PMC
June 2020

Identification of a Structurally Dynamic Domain for Oligomer Formation in Rootletin.

J Mol Biol 2020 06 20;432(13):3915-3932. Epub 2020 Apr 20.

Department of Biological Sciences, Seoul National University, Seoul 08826, Republic of Korea. Electronic address:

Rootletin is the main component of the ciliary rootlet and functions as a centriole linker connecting the two mother centrioles. Despite the functional importance of rootletin, the molecular architecture of the rootletin filament and its assembly mechanism are poorly understood. Here, we identify the coiled-coil domain 3 (CCD3) of rootletin as the key domain for its cellular function. The crystal structure of the CCD3 fragment containing 28 heptad repeats and 1 hendecad repeat reveals that it forms a parallel coiled-coil dimer spanning approximately 300 Å in length. Crosslinking experiments and biophysical analyses of the minimal functional region of CCD3 (CCD3-6) suggest that CCD3-6 is structurally dynamic and may be important for oligomer formation. We also show that oligomerization-defective CCD3 mutants fail in centrosomal localization and centriole linkage, suggesting that rootletin oligomerization may be important for its function.
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http://dx.doi.org/10.1016/j.jmb.2020.04.012DOI Listing
June 2020

SERPINA3 is a key modulator of HNRNP-K transcriptional activity against oxidative stress in HCC.

Redox Biol 2019 06 12;24:101217. Epub 2019 May 12.

Department of Biological Sciences, College of Natural Sciences, Seoul National University, 599 Gwanak-ro, Gwanak-gu, Seoul, 08826, Republic of Korea. Electronic address:

Most studies about serpin peptidase inhibitor, clade A member 3 (SERPINA3) has been limited to its inhibitory functions and mechanisms. Herein, we report a novel role of SERPINA3 in transcriptional regulation of HCC progression-related genes. Among 19 selected genes through HCC cell isolation system based on telomere length, microarray analyses, and cell-based studies, SERPINA3 was the strongest determinant of increases in telomere length, HCC cell proliferation, survival, migration, and invasion. We also found that SERPINA3 strongly interacted with heterogeneous nuclear ribonucleoprotein K (HNRNP-K) under HO exposure, and the oxidation-elicited SERPINA3-HNRNP-K complex enhanced the promoter activities and transcript levels of a telomere-relating gene (POT1) and HCC-promoting genes (UHRF1 and HIST2H2BE). Intriguingly, the inhibition of SERPINA3 oxidation rendered the transcriptional activity of the SERPINA3-HNRNP-K complex suppressed. Moreover, the co-immunoprecipitated HNRNP-K with SERPINA3 quantitatively correlated with not only the level of SERPINA3 oxidation but also the level of POT1, UHRF1, and HIST2H2BE transcripts and telomere length in HCC tissues. Therefore, the upregulated transcriptional activity of HNRNP-K mediated by SERPINA3 promotes HCC cell survival and proliferation and could be an indicator of poor prognosis for HCC patients.
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http://dx.doi.org/10.1016/j.redox.2019.101217DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6529774PMC
June 2019

Small-molecule inhibitor of HlyU attenuates virulence of Vibrio species.

Sci Rep 2019 03 13;9(1):4346. Epub 2019 Mar 13.

National Research Laboratory of Molecular Microbiology and Toxicology, Department of Agricultural Biotechnology and Center for Food Safety and Toxicology, Seoul National University, Seoul, 08826, South Korea.

Increasing antibiotic resistance has led to the development of new strategies to combat bacterial infection. Anti-virulence strategies that impair virulence of bacterial pathogens are one of the novel approaches with less selective pressure for developing resistance than traditional strategies that impede viability. In this study, a small molecule CM14 [N-(4-oxo-4H-thieno[3,4-c]chromen-3-yl)-3-phenylprop-2-ynamide] that inhibits the activity of HlyU, a transcriptional regulator essential for the virulence of the fulminating human pathogen Vibrio vulnificus, has been identified. Without affecting bacterial growth or triggering the host cell death, CM14 reduces HlyU-dependent expression of virulence genes in V. vulnificus. In addition to the decreased hemolysis of human erythrocytes, CM14 impedes host cell rounding and lysis caused by V. vulnificus. Notably, CM14 significantly enhances survival of mice infected with V. vulnificus by alleviating hepatic and renal dysfunction and systemic inflammation. Biochemical, mass spectrometric, and mutational analyses revealed that CM14 inhibits HlyU from binding to target DNA by covalently modifying Cys30. Remarkably, CM14 decreases the expression of various virulence genes of other Vibrio species and thus attenuates their virulence phenotypes. Together, this molecule could be an anti-virulence agent against HlyU-harboring Vibrio species with a low selective pressure for the emergence of resistance.
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http://dx.doi.org/10.1038/s41598-019-39554-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6416295PMC
March 2019

Anti-cariogenic Characteristics of Rubusoside.

Biotechnol Bioprocess Eng 2019 18;24(2):282-287. Epub 2019 May 18.

1Graduate School of International Agricultural Technology and Institutes of Green Bioscience & Technology, Seoul National University, Seoul, Pyeongchang, 25354 Korea.

plays an important role in the development of dental caries in humans by synthesizing adhesive insoluble glucans from sucrose by mutansucrase activity. To explore the anti-cariogenic characteristics of rubusoside (Ru), a natural sweetener component in (Rosaceae), we investigated the inhibitory effect of Ru against the activity of mutansucrase and the growth of Ru (50 mM) showed 97% inhibitory activity against 0.1 U/mL mutansucrase of with 500 mM sucrose. It showed competitive inhibition with a value of 1.1 ± 0.2 mM and IC of 2.3 mM. Its inhibition activity was due to hydrophobic and hydrogen bonding interactions based on molecular docking analysis. Ru inhibited the growth of as a bacteriostatic agent, with MIC and MBC values of 6 mM and 8 mM, respectively. In addition, Ru showed synergistic anti-bacterial activity when it was combined with curcumin. Therefore, Ru is a natural anti-cariogenic agent with anti-mutansucrase activity and antimicrobial activity against .

Electronic Supplementary Material Esm: The online version of this article (doi: 10.1007/s12257-018-0408-0) contains supplementary material, which is available to authorized users.
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http://dx.doi.org/10.1007/s12257-018-0408-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7090897PMC
May 2019

Characterization of quinoa (Chenopodium quinoa) fermented by Rhizopus oligosporus and its bioactive properties.

AMB Express 2018 Sep 10;8(1):143. Epub 2018 Sep 10.

Graduate School of International Agricultural Technology, Seoul National University, Pyeongchang, 25354, Republic of Korea.

Quinoa is a pseudocereal that contains high quality protein, minerals, vitamins, polyphenols, and phytosterols. In this study, quinoa was fermented by Rhizopus oligosporus (R. oligosporus) up to 5 days and the functional compounds (L-carnitine, GABA, vanillic acid and gallic acid) were analyzed by LC/MS. The amounts of L-carnitine and GABA were 0.13 mg/kg and 540 mg/kg for nonfermented quinoa (NF), 3.15 mg/kg and 1040 mg/kg for fermented quinoa at 3 days (3F), and 1.54 mg/kg and 810 mg/kg for fermented quinoa at 5 days (5F). The vanillic acid and gallic acid were 1.3 and 0.1 mg/kg for NF, 1.55 and 2.37 mg/kg for 3F, and 1.83 and 0.84 mg/kg for 5F, respectively. Total phenolic contents and total flavonoids contents were 41 mg gallic acid (GAE)/kg and 13 mg quercetin equivalent (QE)/kg for NF, 74 mg GAE/kg and 16 mg QE/kg for 3F, and 80 mg GAE/kg and 19 mg QE/kg for 5F, respectively. Antioxidant activity (SC) was 3.6 mg/mL for NF, 3.4 mg/mL for 3F, and 2.3 mg/mL for 5F. Nitric oxide production on RAW264.7 macrophages of fermented quinoa revealed 29% and 56% inhibition of nitric oxide production for NF and 5F, respectively. Therefore, fermented quinoa can be used as a healthy and valuable food product.
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http://dx.doi.org/10.1186/s13568-018-0675-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6134574PMC
September 2018

The use of fermented buckwheat to produce L-carnitine enriched oyster mushroom.

AMB Express 2018 Aug 27;8(1):138. Epub 2018 Aug 27.

Graduate School of International Agricultural Technology and Center for Food and Bioconvergence, Seoul National University, Pyeongchang, 25354, South Korea.

L-Carnitine is an essential compound that shuttles long chain fatty acids into mitochondria. The objective of this study was to produce L-carnitine enriched oyster mushroom (Pleurotus ostreatus) using common buckwheat fermented by Rhizopus oligosporus. Mushroom grown on common buckwheat medium contained 9.9-23.9% higher L-carnitine (186.3 mg/kg) than those grown on basal medium without any buckwheat addition. Those grown on fermented common buckwheat medium contained the highest L-carnitine content (201.2 mg/kg). Size index and lightness of mushroom pileus (L*) were also the highest (100.7 and 50.6, respectively) for those grown in medium added with fermented common buckwheat (20%, w/w). Antioxidant activities of both mushroom extracts (1.5 mg/mL) showed the same level as 38.7% for mushroom grown in media added with common buckwheat or fermented common buckwheat. At the treatment concentration of 300 μg/mL, viabilities of murine macrophage cell line Raw 264.7 cells treated with ethanol extract of oyster mushroom grown on buckwheat medium ranged from 58.9 to 67.8%. The oyster mushroom grown on buckwheat and fermented buckwheat medium can be used as one of the substitutes for meat based diets.
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http://dx.doi.org/10.1186/s13568-018-0664-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6111021PMC
August 2018

Assessment of engineered cells using CellNet and RNA-seq.

Nat Protoc 2017 05 27;12(5):1089-1102. Epub 2017 Apr 27.

Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

CellNet is a computational platform designed to assess cell populations engineered by either directed differentiation of pluripotent stem cells (PSCs) or direct conversion, and to suggest specific hypotheses to improve cell fate engineering protocols. CellNet takes as input gene expression data and compares them with large data sets of normal expression profiles compiled from public sources, in regard to the extent to which cell- and tissue-specific gene regulatory networks are established. CellNet was originally designed to work with human or mouse microarray expression data for 21 cell or tissue (C/T) types. Here we describe how to apply CellNet to RNA-seq data and how to build a completely new CellNet platform applicable to, for example, other species or additional cell and tissue types. Once the raw data have been preprocessed, running CellNet takes only several minutes, whereas the time required to create a completely new CellNet is several hours.
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http://dx.doi.org/10.1038/nprot.2017.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5765439PMC
May 2017

Human tau increases amyloid β plaque size but not amyloid β-mediated synapse loss in a novel mouse model of Alzheimer's disease.

Eur J Neurosci 2016 12 12;44(12):3056-3066. Epub 2016 Nov 12.

Centre for Cognitive and Neural Systems and Centre for Dementia Prevention, The University of Edinburgh, 1 George Square, Edinburgh, EH8 9JZ, UK.

Alzheimer's disease is characterized by the presence of aggregates of amyloid beta (Aβ) in senile plaques and tau in neurofibrillary tangles, as well as marked neuron and synapse loss. Of these pathological changes, synapse loss correlates most strongly with cognitive decline. Synapse loss occurs prominently around plaques due to accumulations of oligomeric Aβ. Recent evidence suggests that tau may also play a role in synapse loss but the interactions of Aβ and tau in synapse loss remain to be determined. In this study, we generated a novel transgenic mouse line, the APP/PS1/rTg21221 line, by crossing APP/PS1 mice, which develop Aβ-plaques and synapse loss, with rTg21221 mice, which overexpress wild-type human tau. When compared to the APP/PS1 mice without human tau, the cross-sectional area of ThioS+ dense core plaques was increased by ~50%. Along with increased plaque size, we observed an increase in plaque-associated dystrophic neurites containing misfolded tau, but there was no exacerbation of neurite curvature or local neuron loss around plaques. Array tomography analysis similarly revealed no worsening of synapse loss around plaques, and no change in the accumulation of Aβ at synapses. Together, these results indicate that adding human wild-type tau exacerbates plaque pathology and neurite deformation but does not exacerbate plaque-associated synapse loss.
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http://dx.doi.org/10.1111/ejn.13442DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5215483PMC
December 2016

Erratum to: Post-mortem brain analyses of the Lothian Birth Cohort 1936: extending lifetime cognitive and brain phenotyping to the level of the synapse.

Acta Neuropathol Commun 2015 Dec 9;3(1):83. Epub 2015 Dec 9.

Centre for Cognitive and Neural Systems, University of Edinburgh, 1 George Square, Edinburgh, EH8 9JZ, UK.

The original version of this article [1] unfortunately contained several mistakes. The presentation of Table 2 and 3 was incorrect, in the HTML and PDF versions of this article. The corrected Tables 2 and 3 are given below.
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http://dx.doi.org/10.1186/s40478-015-0244-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4674995PMC
December 2015

Robust Real-Time Reverse Transcription-PCR for Detection of Foot-and-Mouth Disease Virus Neutralizing Carryover Contamination.

J Clin Microbiol 2016 Jan 11;54(1):216-9. Epub 2015 Nov 11.

Foot and Mouth Disease Division, Animal and Plant Quarantine Agency, Anyang, Republic of Korea

During an outbreak of foot-and-mouth disease (FMD), real-time reverse transcription-PCR (rRT-PCR) is the most commonly used diagnostic method to detect viral RNA. However, while this assay is often conducted during the outbreak period, there is an inevitable risk of carryover contamination. This study shows that the carryover contamination can be prevented by the use of target-specific restriction endonuclease in that assay.
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http://dx.doi.org/10.1128/JCM.01944-15DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4702723PMC
January 2016

Post-mortem brain analyses of the Lothian Birth Cohort 1936: extending lifetime cognitive and brain phenotyping to the level of the synapse.

Acta Neuropathol Commun 2015 Sep 4;3:53. Epub 2015 Sep 4.

Centre for Cognitive and Neural Systems, University of Edinburgh, 1 George Square, Edinburgh, EH8 9JZ, UK.

Introduction: Non-pathological, age-related cognitive decline varies markedly between individuals andplaces significant financial and emotional strain on people, their families and society as a whole.Understanding the differential age-related decline in brain function is critical not only for the development oftherapeutics to prolong cognitive health into old age, but also to gain insight into pathological ageing suchas Alzheimer's disease. The Lothian Birth Cohort of 1936 (LBC1936) comprises a rare group of people forwhom there are childhood cognitive test scores and longitudinal cognitive data during older age, detailedstructural brain MRI, genome-wide genotyping, and a multitude of other biological, psycho-social, andepidemiological data. Synaptic integrity is a strong indicator of cognitive health in the human brain;however, until recently, it was prohibitively difficult to perform detailed analyses of synaptic and axonalstructure in human tissue sections. We have adapted a novel method of tissue preparation at autopsy toallow the study of human synapses from the LBC1936 cohort in unprecedented morphological andmolecular detail, using the high-resolution imaging techniques of array tomography and electronmicroscopy. This allows us to analyze the brain at sub-micron resolution to assess density, proteincomposition and health of synapses. Here we present data from the first donated LBC1936 brain andcompare our findings to Alzheimer's diseased tissue to highlight the differences between healthy andpathological brain ageing.

Results: Our data indicates that compared to an Alzheimer's disease patient, the cognitively normalLBC1936 participant had a remarkable degree of preservation of synaptic structures. However,morphological and molecular markers of degeneration in areas of the brain associated with cognition(prefrontal cortex, anterior cingulate cortex, and superior temporal gyrus) were observed.

Conclusions: Our novel post-mortem protocol facilitates high-resolution neuropathological analysis of the well-characterized LBC1936 cohort, extending phenotyping beyond cognition and in vivo imaging to nowinclude neuropathological changes, at the level of single synapses. This approach offers an unprecedentedopportunity to study synaptic and axonal integrity during ageing and how it contributes to differences in agerelatedcognitive change.
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http://dx.doi.org/10.1186/s40478-015-0232-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4559320PMC
September 2015