Displaying publications 41 - 60 of 112 in total

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  1. Tan JJ, Guyette JP, Miki K, Xiao L, Kaur G, Wu T, et al.
    Nat Commun, 2021 08 17;12(1):4997.
    PMID: 34404774 DOI: 10.1038/s41467-021-24921-z
    Epicardial formation is necessary for normal myocardial morphogenesis. Here, we show that differentiating hiPSC-derived lateral plate mesoderm with BMP4, RA and VEGF (BVR) can generate a premature form of epicardial cells (termed pre-epicardial cells, PECs) expressing WT1, TBX18, SEMA3D, and SCX within 7 days. BVR stimulation after Wnt inhibition of LPM demonstrates co-differentiation and spatial organization of PECs and cardiomyocytes (CMs) in a single 2D culture. Co-culture consolidates CMs into dense aggregates, which then form a connected beating syncytium with enhanced contractility and calcium handling; while PECs become more mature with significant upregulation of UPK1B, ITGA4, and ALDH1A2 expressions. Our study also demonstrates that PECs secrete IGF2 and stimulate CM proliferation in co-culture. Three-dimensional PEC-CM spheroid co-cultures form outer smooth muscle cell layers on cardiac micro-tissues with organized internal luminal structures. These characteristics suggest PECs could play a key role in enhancing tissue organization within engineered cardiac constructs in vitro.
  2. Rudolph TB, Ruckelshaus M, Swilling M, Allison EH, Österblom H, Gelcich S, et al.
    Nat Commun, 2020 09 03;11(1):4494.
    PMID: 32883972 DOI: 10.1038/s41467-020-18409-5
    An amendment to this paper has been published and can be accessed via a link at the top of the paper.
  3. Yang Y, Wei X, Zhang N, Zheng J, Chen X, Wen Q, et al.
    Nat Commun, 2021 08 12;12(1):4876.
    PMID: 34385436 DOI: 10.1038/s41467-021-25075-8
    While the printed circuit board (PCB) has been widely considered as the building block of integrated electronics, the world is switching to pursue new ways of merging integrated electronic circuits with textiles to create flexible and wearable devices. Herein, as an alternative for PCB, we described a non-printed integrated-circuit textile (NIT) for biomedical and theranostic application via a weaving method. All the devices are built as fibers or interlaced nodes and woven into a deformable textile integrated circuit. Built on an electrochemical gating principle, the fiber-woven-type transistors exhibit superior bending or stretching robustness, and were woven as a textile logical computing module to distinguish different emergencies. A fiber-type sweat sensor was woven with strain and light sensors fibers for simultaneously monitoring body health and the environment. With a photo-rechargeable energy textile based on a detailed power consumption analysis, the woven circuit textile is completely self-powered and capable of both wireless biomedical monitoring and early warning. The NIT could be used as a 24/7 private AI "nurse" for routine healthcare, diabetes monitoring, or emergencies such as hypoglycemia, metabolic alkalosis, and even COVID-19 patient care, a potential future on-body AI hardware and possibly a forerunner to fabric-like computers.
  4. Collins DS, Avdis A, Allison PA, Johnson HD, Hill J, Piggott MD, et al.
    Nat Commun, 2017 06 15;8:15698.
    PMID: 28643789 DOI: 10.1038/ncomms15698
    Modern mangroves are among the most carbon-rich biomes on Earth, but their long-term (≥106 years) impact on the global carbon cycle is unknown. The extent, productivity and preservation of mangroves are controlled by the interplay of tectonics, global sea level and sedimentation, including tide, wave and fluvial processes. The impact of these processes on mangrove-bearing successions in the Oligo-Miocene of the South China Sea (SCS) is evaluated herein. Palaeogeographic reconstructions, palaeotidal modelling and facies analysis suggest that elevated tidal range and bed shear stress optimized mangrove development along tide-influenced tropical coastlines. Preservation of mangrove organic carbon (OC) was promoted by high tectonic subsidence and fluvial sediment supply. Lithospheric storage of OC in peripheral SCS basins potentially exceeded 4,000 Gt (equivalent to 2,000 p.p.m. of atmospheric CO2). These results highlight the crucial impact of tectonic and oceanographic processes on mangrove OC sequestration within the global carbon cycle on geological timescales.
  5. Luskin MS, Albert WR, Tobler MW
    Nat Commun, 2017 12 05;8(1):1783.
    PMID: 29208916 DOI: 10.1038/s41467-017-01656-4
    The continuing development of improved capture-recapture (CR) modeling techniques used to study apex predators has also limited robust temporal and cross-site analyses due to different methods employed. We develop an approach to standardize older non-spatial CR and newer spatial CR density estimates and examine trends for critically endangered Sumatran tigers (Panthera tigris sumatrae) using a meta-regression of 17 existing densities and new estimates from our own fieldwork. We find that tiger densities were 47% higher in primary versus degraded forests and, unexpectedly, increased 4.9% per yr from 1996 to 2014, likely indicating a recovery from earlier poaching. However, while tiger numbers may have temporarily risen, the total potential island-wide population declined by 16.6% from 2000 to 2012 due to forest loss and degradation and subpopulations are significantly more fragmented. Thus, despite increasing densities in smaller parks, we conclude that there are only two robust populations left with >30 breeding females, indicating Sumatran tigers still face a high risk of extinction unless deforestation can be controlled.
  6. Jeofry H, Ross N, Le Brocq A, Graham AGC, Li J, Gogineni P, et al.
    Nat Commun, 2018 11 01;9(1):4576.
    PMID: 30385741 DOI: 10.1038/s41467-018-06679-z
    Satellite imagery reveals flowstripes on Foundation Ice Stream parallel to ice flow, and meandering features on the ice-shelf that cross-cut ice flow and are thought to be formed by water exiting a well-organised subglacial system. Here, ice-penetrating radar data show flow-parallel hard-bed landforms beneath the grounded ice, and channels incised upwards into the ice shelf beneath meandering surface channels. As the ice transitions to flotation, the ice shelf incorporates a corrugation resulting from the landforms. Radar reveals the presence of subglacial water alongside the landforms, indicating a well-organised drainage system in which water exits the ice sheet as a point source, mixes with cavity water and incises upwards into a corrugation peak, accentuating the corrugation downstream. Hard-bedded landforms influence both subglacial hydrology and ice-shelf structure and, as they are known to be widespread on formerly glaciated terrain, their influence on the ice-sheet-shelf transition could be more widespread than thought previously.
  7. Besser K, Malyon GP, Eborall WS, Paro da Cunha G, Filgueiras JG, Dowle A, et al.
    Nat Commun, 2018 12 03;9(1):5125.
    PMID: 30510200 DOI: 10.1038/s41467-018-07575-2
    Woody (lignocellulosic) plant biomass is an abundant renewable feedstock, rich in polysaccharides that are bound into an insoluble fiber composite with lignin. Marine crustacean woodborers of the genus Limnoria are among the few animals that can survive on a diet of this recalcitrant material without relying on gut resident microbiota. Analysis of fecal pellets revealed that Limnoria targets hexose-containing polysaccharides (mainly cellulose, and also glucomannans), corresponding with the abundance of cellulases in their digestive system, but xylans and lignin are largely unconsumed. We show that the limnoriid respiratory protein, hemocyanin, is abundant in the hindgut where wood is digested, that incubation of wood with hemocyanin markedly enhances its digestibility by cellulases, and that it modifies lignin. We propose that this activity of hemocyanins is instrumental to the ability of Limnoria to feed on wood in the absence of gut symbionts. These findings may hold potential for innovations in lignocellulose biorefining.
  8. Syafruddin SE, Rodrigues P, Vojtasova E, Patel SA, Zaini MN, Burge J, et al.
    Nat Commun, 2019 03 11;10(1):1152.
    PMID: 30858363 DOI: 10.1038/s41467-019-09116-x
    Transcriptional networks are critical for the establishment of tissue-specific cellular states in health and disease, including cancer. Yet, the transcriptional circuits that control carcinogenesis remain poorly understood. Here we report that Kruppel like factor 6 (KLF6), a transcription factor of the zinc finger family, regulates lipid homeostasis in clear cell renal cell carcinoma (ccRCC). We show that KLF6 supports the expression of lipid metabolism genes and promotes the expression of PDGFB, which activates mTOR signalling and the downstream lipid metabolism regulators SREBF1 and SREBF2. KLF6 expression is driven by a robust super enhancer that integrates signals from multiple pathways, including the ccRCC-initiating VHL-HIF2A pathway. These results suggest an underlying mechanism for high mTOR activity in ccRCC cells. More generally, the link between super enhancer-driven transcriptional networks and essential metabolic pathways may provide clues to the mechanisms that maintain the stability of cell identity-defining transcriptional programmes in cancer.
  9. Li T, Heenan TMM, Rabuni MF, Wang B, Farandos NM, Kelsall GH, et al.
    Nat Commun, 2019 04 02;10(1):1497.
    PMID: 30940801 DOI: 10.1038/s41467-019-09427-z
    Ceramic fuel cells offer a clean and efficient means of producing electricity through a variety of fuels. However, miniaturization of cell dimensions for portable device application remains a challenge, as volumetric power densities generated by readily-available planar/tubular ceramic cells are limited. Here, we demonstrate a concept of 'micro-monolithic' ceramic cell design. The mechanical robustness and structural integrity of this design is thoroughly investigated with real-time, synchrotron X-ray diffraction computed tomography, suggesting excellent thermal cycling stability. The successful miniaturization results in an exceptional power density of 1.27 W cm-2 at 800 °C, which is among the highest reported. This holistic design incorporates both mechanical integrity and electrochemical performance, leading to mechanical property enhancement and representing an important step toward commercial development of portable ceramic devices with high volumetric power (>10 W cm-3), fast thermal cycling and marked mechanical reliability.
  10. Hendriksen RS, Munk P, Njage P, van Bunnik B, McNally L, Lukjancenko O, et al.
    Nat Commun, 2019 03 08;10(1):1124.
    PMID: 30850636 DOI: 10.1038/s41467-019-08853-3
    Antimicrobial resistance (AMR) is a serious threat to global public health, but obtaining representative data on AMR for healthy human populations is difficult. Here, we use metagenomic analysis of untreated sewage to characterize the bacterial resistome from 79 sites in 60 countries. We find systematic differences in abundance and diversity of AMR genes between Europe/North-America/Oceania and Africa/Asia/South-America. Antimicrobial use data and bacterial taxonomy only explains a minor part of the AMR variation that we observe. We find no evidence for cross-selection between antimicrobial classes, or for effect of air travel between sites. However, AMR gene abundance strongly correlates with socio-economic, health and environmental factors, which we use to predict AMR gene abundances in all countries in the world. Our findings suggest that global AMR gene diversity and abundance vary by region, and that improving sanitation and health could potentially limit the global burden of AMR. We propose metagenomic analysis of sewage as an ethically acceptable and economically feasible approach for continuous global surveillance and prediction of AMR.
  11. Cooper HV, Evers S, Aplin P, Crout N, Bin Dahalan MP, Sjogersten S
    Nat Commun, 2020 Apr 01;11(1):1717.
    PMID: 32238813 DOI: 10.1038/s41467-020-15178-z
    An amendment to this paper has been published and can be accessed via a link at the top of the paper.
  12. Czamara D, Eraslan G, Page CM, Lahti J, Lahti-Pulkkinen M, Hämäläinen E, et al.
    Nat Commun, 2019 06 11;10(1):2548.
    PMID: 31186427 DOI: 10.1038/s41467-019-10461-0
    Epigenetic processes, including DNA methylation (DNAm), are among the mechanisms allowing integration of genetic and environmental factors to shape cellular function. While many studies have investigated either environmental or genetic contributions to DNAm, few have assessed their integrated effects. Here we examine the relative contributions of prenatal environmental factors and genotype on DNA methylation in neonatal blood at variably methylated regions (VMRs) in 4 independent cohorts (overall n = 2365). We use Akaike's information criterion to test which factors best explain variability of methylation in the cohort-specific VMRs: several prenatal environmental factors (E), genotypes in cis (G), or their additive (G + E) or interaction (GxE) effects. Genetic and environmental factors in combination best explain DNAm at the majority of VMRs. The CpGs best explained by either G, G + E or GxE are functionally distinct. The enrichment of genetic variants from GxE models in GWAS for complex disorders supports their importance for disease risk.
  13. Kared H, Tan SW, Lau MC, Chevrier M, Tan C, How W, et al.
    Nat Commun, 2020 02 10;11(1):821.
    PMID: 32041953 DOI: 10.1038/s41467-020-14442-6
    The diversity of the naïve T cell repertoire drives the replenishment potential and capacity of memory T cells to respond to immune challenges. Attrition of the immune system is associated with an increased prevalence of pathologies in aged individuals, but whether stem cell memory T lymphocytes (TSCM) contribute to such attrition is still unclear. Using single cells RNA sequencing and high-dimensional flow cytometry, we demonstrate that TSCM heterogeneity results from differential engagement of Wnt signaling. In humans, aging is associated with the coupled loss of Wnt/β-catenin signature in CD4 TSCM and systemic increase in the levels of Dickkopf-related protein 1, a natural inhibitor of the Wnt/β-catenin pathway. Functional assays support recent thymic emigrants as the precursors of CD4 TSCM. Our data thus hint that reversing TSCM defects by metabolic targeting of the Wnt/β-catenin pathway may be a viable approach to restore and preserve immune homeostasis in the context of immunological history.
  14. Naylor RL, Kishore A, Sumaila UR, Issifu I, Hunter BP, Belton B, et al.
    Nat Commun, 2021 Sep 28;12(1):5799.
    PMID: 34584099 DOI: 10.1038/s41467-021-26063-8
  15. Arunkumar GA, Bhavsar D, Li T, Strohmeier S, Chromikova V, Amanat F, et al.
    Nat Commun, 2021 10 25;12(1):6161.
    PMID: 34697321 DOI: 10.1038/s41467-021-26409-2
    A panel of influenza virus-like sequences were recently documented in fish and amphibians. Of these, the Wuhan spiny eel influenza virus (WSEIV) was found to phylogenetically cluster with influenza B viruses as a sister clade. Influenza B viruses have been documented to circulate only in humans, with certain virus isolates found in harbor seals. It is therefore interesting that a similar virus was potentially found in fish. Here we characterize the putative hemagglutinin (HA) and neuraminidase (NA) surface glycoproteins of the WSEIV. Functionally, we show that the WSEIV NA-like protein has sialidase activity comparable to B/Malaysia/2506/2004 influenza B virus NA, making it a bona fide neuraminidase that is sensitive to NA inhibitors. We tested the functionality of the HA by addressing the receptor specificity, stability, preferential airway protease cleavage, and fusogenicity. We show highly specific binding to monosialic ganglioside 2 (GM2) and fusogenicity at a range of different pH conditions. In addition, we found limited antigenic conservation of the WSEIV HA and NA relative to the B/Malaysia/2506/2004 virus HA and NA. In summary, we perform a functional and antigenic characterization of the glycoproteins of WSEIV to assess if it is indeed a bona fide influenza virus potentially circulating in ray-finned fish.
  16. Chaisson MJP, Sanders AD, Zhao X, Malhotra A, Porubsky D, Rausch T, et al.
    Nat Commun, 2019 04 16;10(1):1784.
    PMID: 30992455 DOI: 10.1038/s41467-018-08148-z
    The incomplete identification of structural variants (SVs) from whole-genome sequencing data limits studies of human genetic diversity and disease association. Here, we apply a suite of long-read, short-read, strand-specific sequencing technologies, optical mapping, and variant discovery algorithms to comprehensively analyze three trios to define the full spectrum of human genetic variation in a haplotype-resolved manner. We identify 818,054 indel variants (<50 bp) and 27,622 SVs (≥50 bp) per genome. We also discover 156 inversions per genome and 58 of the inversions intersect with the critical regions of recurrent microdeletion and microduplication syndromes. Taken together, our SV callsets represent a three to sevenfold increase in SV detection compared to most standard high-throughput sequencing studies, including those from the 1000 Genomes Project. The methods and the dataset presented serve as a gold standard for the scientific community allowing us to make recommendations for maximizing structural variation sensitivity for future genome sequencing studies.
  17. Huynh-Le MP, Fan CC, Karunamuni R, Thompson WK, Martinez ME, Eeles RA, et al.
    Nat Commun, 2021 02 23;12(1):1236.
    PMID: 33623038 DOI: 10.1038/s41467-021-21287-0
    Genetic models for cancer have been evaluated using almost exclusively European data, which could exacerbate health disparities. A polygenic hazard score (PHS1) is associated with age at prostate cancer diagnosis and improves screening accuracy in Europeans. Here, we evaluate performance of PHS2 (PHS1, adapted for OncoArray) in a multi-ethnic dataset of 80,491 men (49,916 cases, 30,575 controls). PHS2 is associated with age at diagnosis of any and aggressive (Gleason score ≥ 7, stage T3-T4, PSA ≥ 10 ng/mL, or nodal/distant metastasis) cancer and prostate-cancer-specific death. Associations with cancer are significant within European (n = 71,856), Asian (n = 2,382), and African (n = 6,253) genetic ancestries (p 
  18. Zhou H, Wu L, Wang HQ, Zheng JC, Zhang L, Kisslinger K, et al.
    Nat Commun, 2017 11 14;8(1):1474.
    PMID: 29133800 DOI: 10.1038/s41467-017-01655-5
    Multi-layer structure of functional materials often involves the integration of different crystalline phases. The film growth orientation thus frequently exhibits a transformation, owing to multiple possibilities caused by incompatible in-plane structural symmetry. Nevertheless, the detailed mechanism of the transformation has not yet been fully explored. Here we thoroughly probe the heteroepitaxially grown hexagonal zinc oxide (ZnO) films on cubic (001)-magnesium oxide (MgO) substrates using advanced scanning transition electron microscopy, X-ray diffraction and first principles calculations, revealing two distinct interface models of (001) ZnO/(001) MgO and (100) ZnO/(001) MgO. We have found that the structure alternatives are controlled thermodynamically by the nucleation, while kinetically by the enhanced Zn adsorption and O diffusion upon the phase transformation. This work not only provides a guideline for the interface fabrication with distinct crystalline phases but also shows how polar and non-polar hexagonal ZnO films might be manipulated on the same cubic substrate.
  19. Qie L, Lewis SL, Sullivan MJP, Lopez-Gonzalez G, Pickavance GC, Sunderland T, et al.
    Nat Commun, 2017 12 19;8(1):1966.
    PMID: 29259276 DOI: 10.1038/s41467-017-01997-0
    Less than half of anthropogenic carbon dioxide emissions remain in the atmosphere. While carbon balance models imply large carbon uptake in tropical forests, direct on-the-ground observations are still lacking in Southeast Asia. Here, using long-term plot monitoring records of up to half a century, we find that intact forests in Borneo gained 0.43 Mg C ha-1 per year (95% CI 0.14-0.72, mean period 1988-2010) above-ground live biomass. These results closely match those from African and Amazonian plot networks, suggesting that the world's remaining intact tropical forests are now en masse out-of-equilibrium. Although both pan-tropical and long-term, the sink in remaining intact forests appears vulnerable to climate and land use changes. Across Borneo the 1997-1998 El Niño drought temporarily halted the carbon sink by increasing tree mortality, while fragmentation persistently offset the sink and turned many edge-affected forests into a carbon source to the atmosphere.
  20. Toegel M, Azzam G, Lee EY, Knapp DJHF, Tan Y, Fa M, et al.
    Nat Commun, 2017 11 21;8(1):1663.
    PMID: 29162808 DOI: 10.1038/s41467-017-01592-3
    Binary expression systems have revolutionised genetic research by enabling delivery of loss-of-function and gain-of-function transgenes with precise spatial-temporal resolution in vivo. However, at present, each existing platform relies on a defined exogenous transcription activator capable of binding a unique recognition sequence. Consequently, none of these technologies alone can be used to simultaneously target different tissues or cell types in the same organism. Here, we report a modular system based on programmable transcription activator-like effector (TALE) proteins, which enables parallel expression of multiple transgenes in spatially distinct tissues in vivo. Using endogenous enhancers coupled to TALE drivers, we demonstrate multiplexed orthogonal activation of several transgenes carrying cognate variable activating sequences (VAS) in distinct neighbouring cell types of the Drosophila central nervous system. Since the number of combinatorial TALE-VAS pairs is virtually unlimited, this platform provides an experimental framework for highly complex genetic manipulation studies in vivo.
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