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Recent Submissions

  • Viral ecogenomics across the Porifera.

    Pascelli, Cecília; Laffy, Patrick W; Botté, Emmanuelle; Kupresanin, Marija; Rattei, Thomas; Lurgi, Miguel; Ravasi, Timothy; Webster, Nicole S. (Microbiome, Springer Science and Business Media LLC, 2020-10-02) [Article]
    BACKGROUND:Viruses directly affect the most important biological processes in the ocean via their regulation of prokaryotic and eukaryotic populations. Marine sponges form stable symbiotic partnerships with a wide diversity of microorganisms and this high symbiont complexity makes them an ideal model for studying viral ecology. Here, we used morphological and molecular approaches to illuminate the diversity and function of viruses inhabiting nine sponge species from the Great Barrier Reef and seven from the Red Sea. RESULTS:Viromic sequencing revealed host-specific and site-specific patterns in the viral assemblages, with all sponge species dominated by the bacteriophage order Caudovirales but also containing variable representation from the nucleocytoplasmic large DNA virus families Mimiviridae, Marseilleviridae, Phycodnaviridae, Ascoviridae, Iridoviridae, Asfarviridae and Poxviridae. Whilst core viral functions related to replication, infection and structure were largely consistent across the sponge viromes, functional profiles varied significantly between species and sites largely due to differential representation of putative auxiliary metabolic genes (AMGs) and accessory genes, including those associated with herbicide resistance, heavy metal resistance and nylon degradation. Furthermore, putative AMGs varied with the composition and abundance of the sponge-associated microbiome. For instance, genes associated with antimicrobial activity were enriched in low microbial abundance sponges, genes associated with nitrogen metabolism were enriched in high microbial abundance sponges and genes related to cellulose biosynthesis were enriched in species that host photosynthetic symbionts. CONCLUSIONS:Our results highlight the diverse functional roles that viruses can play in marine sponges and are consistent with our current understanding of sponge ecology. Differential representation of putative viral AMGs and accessory genes across sponge species illustrate the diverse suite of beneficial roles viruses can play in the functional ecology of these complex reef holobionts. Video Abstract.
  • Functionalization of Magnetic Nanowires for Active Targeting and Enhanced Cell Killing Efficacy

    Alsharif, Nouf; Aleisa, Fajr A; Liu, Guangyu; Ooi, Boon S.; Patel, Niketan Sarabhai; Ravasi, Timothy; Merzaban, Jasmeen; Kosel, Jürgen (ACS Applied Bio Materials, American Chemical Society (ACS), 2020-07-08) [Article]
    Conventional chemotherapy and radiation therapy are often insufficient in eliminating cancer and are accompanied by severe side effects, due to a lack in the specificity of their targeting. Magnetic iron nanowires have made a great contribution to the nanomedicine field because of their low toxicity and ease of manipulation with the magnetic field. Recently, they have been used in magnetic resonance imaging, wireless magneto-mechanical, and photothermal treatments. The addition of active targeting moieties to these nanowires thus creates a multifunctional tool that can boost therapeutic efficacies through the combination of different treatments towards a specific target. Colon cancer is the third most commonly occurring cancer, and 90±2.5% of colon cancer cells express the glycoprotein CD44. Iron nanowires with an iron oxide surface are biocompatible, multifunctional materials that can be controlled by magnetic fields and heated by laser irradiation. Here, they were functionalized with anti-CD44 antibodies and used for in a combination therapy that included magneto-mechanical and photothermal treatments on colon cancer cells. The functionalization resulted in a threefold increase of nanowire internalization in colon cancer cells compared to control cells and did not affect the antigenicity and magnetic properties. It also increased the efficacy of killing from 35±1% to more than 71±2%, whereby the combination therapy was more effective than individual therapies alone.
  • Magnetic core-shell nanowires as MRI contrast agents for cell tracking.

    Martinez Banderas, Aldo; Aires, Antonio; Plaza-García, Sandra; Colás, Lorena; Moreno Garcia, Julian; Ravasi, Timothy; Merzaban, Jasmeen; Ramos-Cabrer, Pedro; Cortajarena, Aitziber L; Kosel, Jürgen (Journal of nanobiotechnology, Springer Science and Business Media LLC, 2020-03-12) [Article]
    BACKGROUND:Identifying the precise location of cells and their migration dynamics is of utmost importance for achieving the therapeutic potential of cells after implantation into a host. Magnetic resonance imaging is a suitable, non-invasive technique for cell monitoring when used in combination with contrast agents. RESULTS:This work shows that nanowires with an iron core and an iron oxide shell are excellent materials for this application, due to their customizable magnetic properties and biocompatibility. The longitudinal and transverse magnetic relaxivities of the core-shell nanowires were evaluated at 1.5 T, revealing a high performance as T2 contrast agents. Different levels of oxidation and various surface coatings were tested at 7 T. Their effects on the T2 contrast were reflected in the tailored transverse relaxivities. Finally, the detection of nanowire-labeled breast cancer cells was demonstrated in T2-weighted images of cells implanted in both, in vitro in tissue-mimicking phantoms and in vivo in mouse brain. Labeling the cells with a nanowire concentration of 0.8 μg of Fe/mL allowed the detection of 25 cells/µL in vitro, diminishing the possibility of side effects. This performance enabled an efficient labelling for high-resolution cell detection after in vivo implantation (~ 10 nanowire-labeled cells) over a minimum of 40 days. CONCLUSIONS:Iron-iron oxide core-shell nanowires enabled the efficient and longitudinal cellular detection through magnetic resonance imaging acting as T2 contrast agents. Combined with the possibility of magnetic guidance as well as triggering of cellular responses, for instance by the recently discovered strong photothermal response, opens the door to new horizons in cell therapy and make iron-iron oxide core-shell nanowires a promising theranostic platform.
  • Magnetic core–shell nanowires as MRI contrast agents for cell tracking

    Martinez Banderas, Aldo; Aires, Antonio; Plaza-García, Sandra; Colás, Lorena; Moreno Garcia, Julian; Ravasi, Timothy; Merzaban, Jasmeen; Ramos-Cabrer, Pedro; Cortajarena, Aitziber L.; Kosel, Jürgen (figshare, 2020) [Dataset]
    Abstract Background Identifying the precise location of cells and their migration dynamics is of utmost importance for achieving the therapeutic potential of cells after implantation into a host. Magnetic resonance imaging is a suitable, non-invasive technique for cell monitoring when used in combination with contrast agents. Results This work shows that nanowires with an iron core and an iron oxide shell are excellent materials for this application, due to their customizable magnetic properties and biocompatibility. The longitudinal and transverse magnetic relaxivities of the core–shell nanowires were evaluated at 1.5 T, revealing a high performance as T2 contrast agents. Different levels of oxidation and various surface coatings were tested at 7 T. Their effects on the T2 contrast were reflected in the tailored transverse relaxivities. Finally, the detection of nanowire-labeled breast cancer cells was demonstrated in T2-weighted images of cells implanted in both, in vitro in tissue-mimicking phantoms and in vivo in mouse brain. Labeling the cells with a nanowire concentration of 0.8 μg of Fe/mL allowed the detection of 25 cells/µL in vitro, diminishing the possibility of side effects. This performance enabled an efficient labelling for high-resolution cell detection after in vivo implantation (~ 10 nanowire-labeled cells) over a minimum of 40 days. Conclusions Iron-iron oxide core–shell nanowires enabled the efficient and longitudinal cellular detection through magnetic resonance imaging acting as T2 contrast agents. Combined with the possibility of magnetic guidance as well as triggering of cellular responses, for instance by the recently discovered strong photothermal response, opens the door to new horizons in cell therapy and make iron-iron oxide core–shell nanowires a promising theranostic platform.
  • A genomic view of the reef-building coral Porites lutea and its microbial symbionts

    Robbins, Steven J.; Singleton, Caitlin M.; Chan, Cheong Xin; Messer, Lauren F.; Geers, Aileen U.; Ying, Hua; Baker, Alexander; Bell, Sara C.; Morrow, Kathleen M.; Ragan, Mark A.; Miller, David J.; Forêt, Sylvain; Ball, Eldon; Beeden, Roger; Berumen, Michael L.; Aranda, Manuel; Ravasi, Timothy; Bongaerts, Pim; Hoegh-Guldberg, Ove; Cooke, Ira; Leggat, Bill; Sprungala, Susan; Fitzgerald, Anna; Shang, Catherine; Lundgren, Petra; Fyffe, Theresa; Rubino, Francesco; van Oppen, Madeleine; Weynberg, Karen; Voolstra, Christian R.; Tyson, Gene W.; Bourne, David G. (Nature Microbiology, Springer Nature, 2019-09-23) [Article]
    Corals and the reef ecosystems that they support are in global decline due to increasing anthropogenic pressures such as climate change1. However, effective reef conservation strategies are hampered by a limited mechanistic understanding of coral biology and the functional roles of the diverse microbial communities that underpin coral health2,3. Here, we present an integrated genomic characterization of the coral species Porites lutea and its microbial partners. High-quality genomes were recovered from P. lutea, as well as a metagenome-assembled Cladocopium C15 (the dinoflagellate symbiont) and 52 bacterial and archaeal populations. Comparative genomic analysis revealed that many of the bacterial and archaeal genomes encode motifs that may be involved in maintaining association with the coral host and in supplying fixed carbon, B-vitamins and amino acids to their eukaryotic partners. Furthermore, mechanisms for ammonia, urea, nitrate, dimethylsulfoniopropionate and taurine transformation were identified that interlink members of the holobiont and may be important for nutrient acquisition and retention in oligotrophic waters. Our findings demonstrate the critical and diverse roles that microorganisms play within the coral holobiont and underscore the need to consider all of the components of the holobiont if we are to effectively inform reef conservation strategies.
  • Beyond buying time: the role of plasticity in phenotypic adaptation to rapid environmental change

    Fox, Rebecca J.; Donelson, Jennifer M.; Schunter, Celia; Ravasi, Timothy; Gaitán-Espitia, Juan D. (Philosophical Transactions of the Royal Society B: Biological Sciences, The Royal Society, 2019-01-28) [Article]
    How populations and species respond to modified environmental conditions is critical to their persistence both now and into the future, particularly given the increasing pace of environmental change. The process of adaptation to novel environmental conditions can occur via two mechanisms: (1) the expression of phenotypic plasticity (the ability of one genotype to express varying phenotypes when exposed to different environmental conditions), and (2) evolution via selection for particular phenotypes, resulting in the modification of genetic variation in the population. Plasticity, because it acts at the level of the individual, is often hailed as a rapid-response mechanism that will enable organisms to adapt and survive in our rapidly changing world. But plasticity can also retard adaptation by shifting the distribution of phenotypes in the population, shielding it from natural selection. In addition to which, not all plastic responses are adaptive—now well-documented in cases of ecological traps. In this theme issue, we aim to present a considered view of plasticity and the role it could play in facilitating or hindering adaption to environmental change. This introduction provides a re-examination of our current understanding of the role of phenotypic plasticity in adaptation and sets the theme issue’s contributions in their broader context. Four key themes emerge: the need to measure plasticity across both space and time; the importance of the past in predicting the future; the importance of the link between plasticity and sexual selection; and the need to understand more about the nature of selection on plasticity itself. We conclude by advocating the need for cross-disciplinary collaborations to settle the question of whether plasticity will promote or retard species’ rates of adaptation to ever-more stressful environmental conditions.
  • Seawater carbonate chemistry and gene expression of a reef fish Acanthochromis polyacanthus, supplement to: Schunter, Celia; Welch, Megan J; Nilsson, Göran E; Rummer, Jodie L; Munday, Philip L; Ravasi, Timothy (2018): An interplay between plasticity and parental phenotype determines impacts of ocean acidification on a reef fish. Nature Ecology & Evolution, 2(2), 334-342

    Schunter, Celia Marei; Welch, Megan J.; Nilsson, Göran E.; Rummer, Jodie L.; Munday, Philip L.; Ravasi, Timothy (PANGAEA - Data Publisher for Earth & Environmental Science, 2019) [Dataset]
    The impacts of ocean acidification will depend on the ability of marine organisms to tolerate, acclimate and eventually adapt to changes in ocean chemistry. Here, we use a unique transgenerational experiment to determine the molecular response of a coral reef fish to short-term, developmental and transgenerational exposure to elevated CO2, and to test how these responses are influenced by variations in tolerance to elevated CO2 exhibited by the parents. Within-generation responses in gene expression to end-of-century predicted CO2 levels indicate that a self-amplifying cycle in GABAergic neurotransmission is triggered, explaining previously reported neurological and behavioural impairments. Furthermore, epigenetic regulator genes exhibited a within-generation specific response, but with some divergence due to parental phenotype. Importantly, we find that altered gene expression for the majority of within-generation responses returns to baseline levels following parental exposure to elevated CO2 conditions. Our results show that both parental variation in tolerance and cross-generation exposure to elevated CO2 are crucial factors in determining the response of reef fish to changing ocean chemistry.
  • MOESM10 of Semi-automated quantification of living cells with internalized nanostructures

    Margineanu, Michael B.; Julfakyan, Khachatur; Sommer, Christoph; Perez, Jose E.; Contreras, Maria F.; Khashab, Niveen M.; Kosel, Jürgen; Ravasi, Timothy (figshare, 2019) [Data File]
    Additional file 10: Table S1. Object detection parameters.
  • MOESM9 of Semi-automated quantification of living cells with internalized nanostructures

    Margineanu, Michael B.; Julfakyan, Khachatur; Sommer, Christoph; Perez, Jose E.; Contreras, Maria F.; Khashab, Niveen M.; Kosel, Jürgen; Ravasi, Timothy (figshare, 2019) [Data File]
    Additional file 9. Settings used for analysis with CellCognition.
  • MOESM8 of Semi-automated quantification of living cells with internalized nanostructures

    Margineanu, Michael B.; Julfakyan, Khachatur; Sommer, Christoph; Perez, Jose E.; Contreras, Maria F.; Khashab, Niveen M.; Kosel, Jürgen; Ravasi, Timothy (figshare, 2019) [Data File]
    Additional file 8: Figure S6. Fe NWs coating with APTES and labeling with pHrodo red. Fe NWs were coated with APTES initially and subsequently labeled with pHrodo red based on the reaction between the succinimidyl ester group of the pHrodo red complex and the surface amino groups of the APTES-coated Fe NWs.
  • MOESM2 of Semi-automated quantification of living cells with internalized nanostructures

    Margineanu, Michael B.; Julfakyan, Khachatur; Sommer, Christoph; Perez, Jose E.; Contreras, Maria F.; Khashab, Niveen M.; Kosel, Jürgen; Ravasi, Timothy (figshare, 2019) [Data File]
    Additional file 2: Figure S2. FTIR spectrum of Ni NWs. FTIR spectrum of non-coated Ni NWs and APTES-coated Ni NWs.
  • MOESM7 of Semi-automated quantification of living cells with internalized nanostructures

    Margineanu, Michael B.; Julfakyan, Khachatur; Sommer, Christoph; Perez, Jose E.; Contreras, Maria F.; Khashab, Niveen M.; Kosel, Jürgen; Ravasi, Timothy (figshare, 2019) [Data File]
    Additional file 7: Figure S5. Control experiment with iron nanowires and cell imaging medium adjusted for different pH values. A) pH 8.2 â measured value for Fluorobrite imaging medium. B) pH 6.3 â value corresponding to pH inside early endosomal vesicles.
  • MOESM4 of Semi-automated quantification of living cells with internalized nanostructures

    Margineanu, Michael B.; Julfakyan, Khachatur; Sommer, Christoph; Perez, Jose E.; Contreras, Maria F.; Khashab, Niveen M.; Kosel, Jürgen; Ravasi, Timothy (figshare, 2019) [Data File]
    Additional file 4: Figure S4. TEM characterization of APTES-coated Ni NW.
  • Additional file 5: Video S1 of Semi-automated quantification of living cells with internalized nanostructures

    Margineanu, Michael B.; Julfakyan, Khachatur; Sommer, Christoph; Perez, Jose E.; Contreras, Maria F.; Khashab, Niveen M.; Kosel, Jürgen; Ravasi, Timothy (figshare, 2019) [Data File]
    Time-lapse imaging of HeLa cells with pHrodo™ Red-tagged Ni NWs. Video showing large NW aggregates torn down by cells. The duration of the video corresponds to a period of 24 h.
  • Additional file 6: Video S2 of Semi-automated quantification of living cells with internalized nanostructures

    Margineanu, Michael B.; Julfakyan, Khachatur; Sommer, Christoph; Perez, Jose E.; Contreras, Maria F.; Khashab, Niveen M.; Kosel, Jürgen; Ravasi, Timothy (figshare, 2019) [Data File]
    Time-lapse imaging of HeLa cells with pHrodo™ Red-tagged Fe NWs. Video showing cells, which are dividing, with NW aggregates. The duration of the video corresponds to a period of 24 h.
  • MOESM1 of Semi-automated quantification of living cells with internalized nanostructures

    Margineanu, Michael B.; Julfakyan, Khachatur; Sommer, Christoph; Perez, Jose E.; Contreras, Maria F.; Khashab, Niveen M.; Kosel, Jürgen; Ravasi, Timothy (figshare, 2019) [Data File]
    Additional file 1: Figure S1. FTIR spectrum of Fe NWs. FTIR spectrum of non-coated Fe NWs and APTES-coated Fe NWs.
  • MOESM11 of Semi-automated quantification of living cells with internalized nanostructures

    Margineanu, Michael B.; Julfakyan, Khachatur; Sommer, Christoph; Perez, Jose E.; Contreras, Maria F.; Khashab, Niveen M.; Kosel, Jürgen; Ravasi, Timothy (figshare, 2019) [Data File]
    Additional file 11: Table S2. Feature types available in CecogAnalyzer.
  • MOESM3 of Semi-automated quantification of living cells with internalized nanostructures

    Margineanu, Michael B.; Julfakyan, Khachatur; Sommer, Christoph; Perez, Jose E.; Contreras, Maria F.; Khashab, Niveen M.; Kosel, Jürgen; Ravasi, Timothy (figshare, 2019) [Data File]
    Additional file 3: Figure S3. TEM characterization of APTES-coated Fe NW.
  • Semi-automated quantification of living cells with internalized nanostructures

    Margineanu, Michael B.; Julfakyan, Khachatur; Sommer, Christoph; Perez, Jose E.; Contreras, Maria F.; Khashab, Niveen M.; Kosel, Jürgen; Ravasi, Timothy (Journal of Nanobiotechnology, Springer Science and Business Media LLC, 2016-01-15) [Article]
    Background Nanostructures fabricated by different methods have become increasingly important for various applications in biology and medicine, such as agents for medical imaging or cancer therapy. In order to understand their interaction with living cells and their internalization kinetics, several attempts have been made in tagging them. Although methods have been developed to measure the number of nanostructures internalized by the cells, there are only few approaches aimed to measure the number of cells that internalize the nanostructures, and they are usually limited to fixed-cell studies. Flow cytometry can be used for live-cell assays on large populations of cells, however it is a single time point measurement, and does not include any information about cell morphology. To date many of the observations made on internalization events are limited to few time points and cells. Results In this study, we present a method for quantifying cells with internalized magnetic nanowires (NWs). A machine learning-based computational framework, CellCognition, is adapted and used to classify cells with internalized and no internalized NWs, labeled with the fluorogenic pH-dependent dye pHrodo™ Red, and subsequently to determine the percentage of cells with internalized NWs at different time points. In a “proof-of-concept”, we performed a study on human colon carcinoma HCT 116 cells and human epithelial cervical cancer HeLa cells interacting with iron (Fe) and nickel (Ni) NWs. Conclusions This study reports a novel method for the quantification of cells that internalize a specific type of nanostructures. This approach is suitable for high-throughput and real-time data analysis and has the potential to be used to study the interaction of different types of nanostructures in live-cell assays.
  • Semi-automated quantification of living cells with internalized nanostructures

    Margineanu, Michael B.; Julfakyan, Khachatur; Sommer, Christoph; Perez, Jose E.; Contreras, Maria F.; Khashab, Niveen M.; Kosel, Jürgen; Ravasi, Timothy (figshare, 2016) [Dataset]
    Abstract Background Nanostructures fabricated by different methods have become increasingly important for various applications in biology and medicine, such as agents for medical imaging or cancer therapy. In order to understand their interaction with living cells and their internalization kinetics, several attempts have been made in tagging them. Although methods have been developed to measure the number of nanostructures internalized by the cells, there are only few approaches aimed to measure the number of cells that internalize the nanostructures, and they are usually limited to fixed-cell studies. Flow cytometry can be used for live-cell assays on large populations of cells, however it is a single time point measurement, and does not include any information about cell morphology. To date many of the observations made on internalization events are limited to few time points and cells. Results In this study, we present a method for quantifying cells with internalized magnetic nanowires (NWs). A machine learning-based computational framework, CellCognition, is adapted and used to classify cells with internalized and no internalized NWs, labeled with the fluorogenic pH-dependent dye pHrodo™ Red, and subsequently to determine the percentage of cells with internalized NWs at different time points. In a “proof-of-concept”, we performed a study on human colon carcinoma HCT 116 cells and human epithelial cervical cancer HeLa cells interacting with iron (Fe) and nickel (Ni) NWs. Conclusions This study reports a novel method for the quantification of cells that internalize a specific type of nanostructures. This approach is suitable for high-throughput and real-time data analysis and has the potential to be used to study the interaction of different types of nanostructures in live-cell assays.

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