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  1. Article: Roadmap for Optical Metasurfaces.

    Kuznetsov, Arseniy I / Brongersma, Mark L / Yao, Jin / Chen, Mu Ku / Levy, Uriel / Tsai, Din Ping / Zheludev, Nikolay I / Faraon, Andrei / Arbabi, Amir / Yu, Nanfang / Chanda, Debashis / Crozier, Kenneth B / Kildishev, Alexander V / Wang, Hao / Yang, Joel K W / Valentine, Jason G / Genevet, Patrice / Fan, Jonathan A / Miller, Owen D /
    Majumdar, Arka / Fröch, Johannes E / Brady, David / Heide, Felix / Veeraraghavan, Ashok / Engheta, Nader / Alù, Andrea / Polman, Albert / Atwater, Harry A / Thureja, Prachi / Paniagua-Dominguez, Ramon / Ha, Son Tung / Barreda, Angela I / Schuller, Jon A / Staude, Isabelle / Grinblat, Gustavo / Kivshar, Yuri / Peana, Samuel / Yelin, Susanne F / Senichev, Alexander / Shalaev, Vladimir M / Saha, Soham / Boltasseva, Alexandra / Rho, Junsuk / Oh, Dong Kyo / Kim, Joohoon / Park, Junghyun / Devlin, Robert / Pala, Ragip A

    ACS photonics

    2024  Volume 11, Issue 3, Page(s) 816–865

    Abstract: Metasurfaces have recently risen to prominence in optical research, providing unique functionalities that can be used for imaging, beam forming, holography, polarimetry, and many more, while keeping device dimensions small. Despite the fact that a vast ... ...

    Abstract Metasurfaces have recently risen to prominence in optical research, providing unique functionalities that can be used for imaging, beam forming, holography, polarimetry, and many more, while keeping device dimensions small. Despite the fact that a vast range of basic metasurface designs has already been thoroughly studied in the literature, the number of metasurface-related papers is still growing at a rapid pace, as metasurface research is now spreading to adjacent fields, including computational imaging, augmented and virtual reality, automotive, display, biosensing, nonlinear, quantum and topological optics, optical computing, and more. At the same time, the ability of metasurfaces to perform optical functions in much more compact optical systems has triggered strong and constantly growing interest from various industries that greatly benefit from the availability of miniaturized, highly functional, and efficient optical components that can be integrated in optoelectronic systems at low cost. This creates a truly unique opportunity for the field of metasurfaces to make both a scientific and an industrial impact. The goal of this Roadmap is to mark this "golden age" of metasurface research and define future directions to encourage scientists and engineers to drive research and development in the field of metasurfaces toward both scientific excellence and broad industrial adoption.
    Language English
    Publishing date 2024-02-27
    Publishing country United States
    Document type Journal Article ; Review
    ISSN 2330-4022
    ISSN 2330-4022
    DOI 10.1021/acsphotonics.3c00457
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  2. Article ; Online: Uncovering the biosynthetic potential of rare metagenomic DNA using co-occurrence network analysis of targeted sequences.

    Libis, Vincent / Antonovsky, Niv / Zhang, Mengyin / Shang, Zhuo / Montiel, Daniel / Maniko, Jeffrey / Ternei, Melinda A / Calle, Paula Y / Lemetre, Christophe / Owen, Jeremy G / Brady, Sean F

    Nature communications

    2019  Volume 10, Issue 1, Page(s) 3848

    Abstract: Sequencing of DNA extracted from environmental samples can provide key insights into the biosynthetic potential of uncultured bacteria. However, the high complexity of soil metagenomes, which can contain thousands of bacterial species per gram of soil, ... ...

    Abstract Sequencing of DNA extracted from environmental samples can provide key insights into the biosynthetic potential of uncultured bacteria. However, the high complexity of soil metagenomes, which can contain thousands of bacterial species per gram of soil, imposes significant challenges to explore secondary metabolites potentially produced by rare members of the soil microbiome. Here, we develop a targeted sequencing workflow termed CONKAT-seq (co-occurrence network analysis of targeted sequences) that detects physically clustered biosynthetic domains, a hallmark of bacterial secondary metabolism. Following targeted amplification of conserved biosynthetic domains in a highly partitioned metagenomic library, CONKAT-seq evaluates amplicon co-occurrence patterns across library subpools to identify chromosomally clustered domains. We show that a single soil sample can contain more than a thousand uncharacterized biosynthetic gene clusters, most of which originate from low frequency genomes which are practically inaccessible through untargeted sequencing. CONKAT-seq allows scalable exploration of largely untapped biosynthetic diversity across multiple soils, and can guide the discovery of novel secondary metabolites from rare members of the soil microbiome.
    MeSH term(s) Bacteria/genetics ; Bacteria/metabolism ; Biosynthetic Pathways/genetics ; DNA, Bacterial/genetics ; Metagenome/genetics ; Microbiota/genetics ; Multigene Family/genetics ; Secondary Metabolism/genetics ; Sequence Analysis, DNA/methods ; Soil Microbiology
    Chemical Substances DNA, Bacterial
    Language English
    Publishing date 2019-08-26
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-019-11658-z
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  3. Article ; Online: Culture-independent discovery of the malacidins as calcium-dependent antibiotics with activity against multidrug-resistant Gram-positive pathogens.

    Hover, Bradley M / Kim, Seong-Hwan / Katz, Micah / Charlop-Powers, Zachary / Owen, Jeremy G / Ternei, Melinda A / Maniko, Jeffrey / Estrela, Andreia B / Molina, Henrik / Park, Steven / Perlin, David S / Brady, Sean F

    Nature microbiology

    2018  Volume 3, Issue 4, Page(s) 415–422

    Abstract: Despite the wide availability of antibiotics, infectious diseases remain a leading cause of death ... ...

    Abstract Despite the wide availability of antibiotics, infectious diseases remain a leading cause of death worldwide
    MeSH term(s) Animals ; Anti-Bacterial Agents/pharmacology ; Calcium/metabolism ; Cell Line ; Daptomycin/pharmacology ; Drug Resistance, Multiple, Bacterial/genetics ; HEK293 Cells ; Humans ; Lipopeptides/pharmacology ; Methicillin-Resistant Staphylococcus aureus/drug effects ; Microbial Sensitivity Tests ; Peptides, Cyclic/pharmacology ; Rats ; Soil Microbiology ; Staphylococcal Infections/drug therapy
    Chemical Substances Anti-Bacterial Agents ; Lipopeptides ; Peptides, Cyclic ; malacidins ; Daptomycin (NWQ5N31VKK) ; Calcium (SY7Q814VUP)
    Language English
    Publishing date 2018-02-12
    Publishing country England
    Document type Letter ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ISSN 2058-5276
    ISSN (online) 2058-5276
    DOI 10.1038/s41564-018-0110-1
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  4. Article ; Online: Chemical-biogeographic survey of secondary metabolism in soil.

    Charlop-Powers, Zachary / Owen, Jeremy G / Reddy, Boojala Vijay B / Ternei, Melinda A / Brady, Sean F

    Proceedings of the National Academy of Sciences of the United States of America

    2014  Volume 111, Issue 10, Page(s) 3757–3762

    Abstract: In this study, we compare biosynthetic gene richness and diversity of 96 soil microbiomes from diverse environments found throughout the southwestern and northeastern regions of the United States. The 454-pyroseqencing of nonribosomal peptide adenylation ...

    Abstract In this study, we compare biosynthetic gene richness and diversity of 96 soil microbiomes from diverse environments found throughout the southwestern and northeastern regions of the United States. The 454-pyroseqencing of nonribosomal peptide adenylation (AD) and polyketide ketosynthase (KS) domain fragments amplified from these microbiomes provide a means to evaluate the variation of secondary metabolite biosynthetic diversity in different soil environments. Through soil composition and AD- and KS-amplicon richness analysis, we identify soil types with elevated biosynthetic potential. In general, arid soils show the richest observed biosynthetic diversity, whereas brackish sediments and pine forest soils show the least. By mapping individual environmental amplicon sequences to sequences derived from functionally characterized biosynthetic gene clusters, we identified conserved soil type-specific secondary metabolome enrichment patterns despite significant sample-to-sample sequence variation. These data are used to create chemical biogeographic distribution maps for biomedically valuable families of natural products in the environment that should prove useful for directing the discovery of bioactive natural products in the future.
    MeSH term(s) Cluster Analysis ; Genetic Variation ; Geographic Mapping ; Metabolome/genetics ; Microbiota/genetics ; Multigene Family/genetics ; New England ; Phylogeography ; Secondary Metabolism/genetics ; Soil/chemistry ; Soil Microbiology ; Southwestern United States
    Chemical Substances Soil
    Language English
    Publishing date 2014-02-18
    Publishing country United States
    Document type Comparative Study ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 209104-5
    ISSN 1091-6490 ; 0027-8424
    ISSN (online) 1091-6490
    ISSN 0027-8424
    DOI 10.1073/pnas.1318021111
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  5. Article ; Online: Clinical and radiological characteristics of acute pulmonary embolus in relation to 28-day and 6-month mortality.

    Norton, Lindsey / Cooper, Gordon / Sheerins, Owen / Mac A' Bháird, Killian / Roditi, Giles / Adamson, Michael / Young, David / Dolan, Ross / Church, Colin / Brady, Adrian / Tait, Campbell / McKenzie, Graham / McFadyen, Alasdair / Zelic, Matthew / Maguire, Donogh

    PloS one

    2021  Volume 16, Issue 12, Page(s) e0258843

    Abstract: Background: Patients with acute pulmonary embolism (PE) exhibit a wide spectrum of clinical and laboratory features when presenting to hospital and pathophysiologic mechanisms differentiating low-risk and high-risk PE are poorly understood.: ... ...

    Abstract Background: Patients with acute pulmonary embolism (PE) exhibit a wide spectrum of clinical and laboratory features when presenting to hospital and pathophysiologic mechanisms differentiating low-risk and high-risk PE are poorly understood.
    Objectives: To investigate the prognostic value of clinical, laboratory and radiological information that is available within routine tests undertaken for patients with acute PE.
    Methods: Electronic patient records (EPR) of patients who underwent Computed Tomography Pulmonary Angiogram (CTPA) scan for the investigation of acute PE during 6-month period (01.01.2016-30.06.2016) were examined. Data was gathered from EPR for patients that met inclusion criteria and all CTPA scans were re-evaluated. Biochemical thresholds of low-grade and high-grade inflammation, serum CRP >10mg/L and >150mg/L and serum albumin concentrations <35g/L and <25 g/L, were combined in the Glasgow Prognostic Score (GPS) and peri-operative Glasgow Prognostic Score (poGPS) respectively. Neutrophil Lymphocyte ratio (NLR) was also calculated. Pulmonary Embolus Severity Index score was calculated.
    Results: Of the total CTPA reports (n = 2129) examined, 245 patients were eligible for inclusion. Of these, 20 (8%) patients had died at 28-days and 43 (18%) at 6-months. Of the 197 non-cancer related presentations, 28-day and 6-month mortality were 3% and 8% respectively. Of the 48 cancer related presentations, 28-day and 6-month mortality were 29% and 58% respectively. On univariate analysis, age ≥65 years (p<0.01), PESI score ≥100(p = <0.001), NLR ≥3(p<0.001) and Coronary Artery Calcification (CAC) score ≥ 6 (p<0.001) were associated with higher 28-day and 6-month mortality. PESI score ≥100 (OR 5.2, 95% CI: 1.1, 24.2, P <0.05), poGPS ≥1 (OR 2.5, 95% CI: 1.2-5.0, P = 0.01) and NLR ≥3 (OR 3.7, 95% CI: 1.0-3.4, P <0.05) remained independently associated with 28-day mortality. On multivariate binary logistic regression analysis of factors associated with 6-month mortality, PESI score ≥100 (OR 6.2, 95% CI: 2.3-17.0, p<0.001) and coronary artery calcification score ≥6 (OR 2.3, 95% CI: 1.1-4.8, p = 0.030) remained independently associated with death at 6-months. When patients who had an underlying cancer diagnosis were excluded from the analysis only GPS≥1 remained independently associated with 6-month mortality (OR 5.0, 95% CI 1.2-22.0, p<0.05).
    Conclusion: PESI score >100, poGPS≥1, NLR ≥3 and CAC score ≥6 were associated with 28-day and 6-month mortality. PESI score ≥100, poGPS≥1 and NLR ≥3 remained independently associated with 28-day mortality. PESI score ≥100 and CAC score ≥6 remained independently associated with 6-month mortality. When patients with underlying cancer were excluded from the analysis, GPS≥1 remained independently associated with 6-month mortality. The role of the systemic inflammatory response (SIR) in determining treatment and prognosis requires further study. Routine reporting of CAC scores in CTPA scans for acute PE may have a role in aiding clinical decision-making regarding treatment and prognosis.
    MeSH term(s) Acute Disease ; Aged ; Coronary Vessels/diagnostic imaging ; Female ; Humans ; Inflammation/pathology ; Lymphocytes/pathology ; Male ; Middle Aged ; Neoplasms/mortality ; Neutrophils/pathology ; Prognosis ; Pulmonary Embolism/diagnostic imaging ; Pulmonary Embolism/mortality ; Tomography, X-Ray Computed
    Language English
    Publishing date 2021-12-28
    Publishing country United States
    Document type Journal Article
    ISSN 1932-6203
    ISSN (online) 1932-6203
    DOI 10.1371/journal.pone.0258843
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  6. Article ; Online: Uncovering the biosynthetic potential of rare metagenomic DNA using co-occurrence network analysis of targeted sequences

    Vincent Libis / Niv Antonovsky / Mengyin Zhang / Zhuo Shang / Daniel Montiel / Jeffrey Maniko / Melinda A. Ternei / Paula Y. Calle / Christophe Lemetre / Jeremy G. Owen / Sean F. Brady

    Nature Communications, Vol 10, Iss 1, Pp 1-

    2019  Volume 9

    Abstract: Soil microorganisms are a rich source of bioactive molecules. Here, the authors present a targeted sequencing workflow that reconstructs the clustered organization of biosynthetic domains in metagenomic libraries from amplicon data, thus guiding the ... ...

    Abstract Soil microorganisms are a rich source of bioactive molecules. Here, the authors present a targeted sequencing workflow that reconstructs the clustered organization of biosynthetic domains in metagenomic libraries from amplicon data, thus guiding the discovery of novel metabolites from rare members of the soil microbiome.
    Keywords Science ; Q
    Language English
    Publishing date 2019-08-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article ; Online: Uncovering the biosynthetic potential of rare metagenomic DNA using co-occurrence network analysis of targeted sequences

    Vincent Libis / Niv Antonovsky / Mengyin Zhang / Zhuo Shang / Daniel Montiel / Jeffrey Maniko / Melinda A. Ternei / Paula Y. Calle / Christophe Lemetre / Jeremy G. Owen / Sean F. Brady

    Nature Communications, Vol 10, Iss 1, Pp 1-

    2019  Volume 9

    Abstract: Soil microorganisms are a rich source of bioactive molecules. Here, the authors present a targeted sequencing workflow that reconstructs the clustered organization of biosynthetic domains in metagenomic libraries from amplicon data, thus guiding the ... ...

    Abstract Soil microorganisms are a rich source of bioactive molecules. Here, the authors present a targeted sequencing workflow that reconstructs the clustered organization of biosynthetic domains in metagenomic libraries from amplicon data, thus guiding the discovery of novel metabolites from rare members of the soil microbiome.
    Keywords Science ; Q
    Language English
    Publishing date 2019-08-01T00:00:00Z
    Publisher Nature Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article ; Online: Autologous bone marrow-derived MSCs engineered to express oFVIII-FLAG engraft in adult sheep and produce an effective increase in plasma FVIII levels.

    Trevisan, Brady / Rodriguez, Martin / Medder, Hailey / Lankford, Shannon / Combs, Rebecca / Owen, John / Atala, Anthony / Porada, Christopher D / Almeida-Porada, Graça

    Frontiers in immunology

    2022  Volume 13, Page(s) 1070476

    Abstract: Introduction: Hemophilia A (HA) is the most common X-linked bleeding disorder, occurring in 1 in 5,000 live male births and affecting >1 million individuals worldwide. Although advances in protein-based HA therapeutics have improved health outcomes, ... ...

    Abstract Introduction: Hemophilia A (HA) is the most common X-linked bleeding disorder, occurring in 1 in 5,000 live male births and affecting >1 million individuals worldwide. Although advances in protein-based HA therapeutics have improved health outcomes, current standard-of-care requires infusion 2-3 times per week for life, and 30% of patients develop inhibitors, significantly increasing morbidity and mortality. There are thus unmet medical needs requiring novel approaches to treat HA.
    Methods: We tested, in a highly translational large animal (sheep) model, whether the unique immunological and biological properties of autologous bone marrow (BM)-derived mesenchymal stromal cells (MSCs) could enable them to serve as cellular delivery vehicles to provide long-term expression of FVIII, avoiding the need for frequent infusions.
    Results: We show that autologous BM-MSCs can be isolated, transduced with a lentivector to produce high levels of ovine (o)FVIII, extensively expanded, and transplanted into adult animals safely. The transplanted cells engraft in multiple organs, and they stably produce and secrete sufficient quantities of FVIII to yield elevated plasma FVIII levels for at least 15 weeks.
    Discussion: These studies thus highlight the promise of cellular-based gene delivery approaches for treating HA.
    MeSH term(s) Animals ; Sheep ; Male ; Factor VIII/genetics ; Factor VIII/metabolism ; Bone Marrow/metabolism ; Hemophilia A/therapy ; Mesenchymal Stem Cells/metabolism ; Bone Marrow Cells/metabolism
    Chemical Substances Factor VIII (9001-27-8)
    Language English
    Publishing date 2022-12-02
    Publishing country Switzerland
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2022.1070476
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  9. Article ; Online: Clinical and radiological characteristics of acute pulmonary embolus in relation to 28-day and 6-month mortality.

    Lindsey Norton / Gordon Cooper / Owen Sheerins / Killian Mac A' Bháird / Giles Roditi / Michael Adamson / David Young / Ross Dolan / Colin Church / Adrian Brady / Campbell Tait / Graham McKenzie / Alasdair McFadyen / Matthew Zelic / Donogh Maguire

    PLoS ONE, Vol 16, Iss 12, p e

    2021  Volume 0258843

    Abstract: Background Patients with acute pulmonary embolism (PE) exhibit a wide spectrum of clinical and laboratory features when presenting to hospital and pathophysiologic mechanisms differentiating low-risk and high-risk PE are poorly understood. Objectives To ... ...

    Abstract Background Patients with acute pulmonary embolism (PE) exhibit a wide spectrum of clinical and laboratory features when presenting to hospital and pathophysiologic mechanisms differentiating low-risk and high-risk PE are poorly understood. Objectives To investigate the prognostic value of clinical, laboratory and radiological information that is available within routine tests undertaken for patients with acute PE. Methods Electronic patient records (EPR) of patients who underwent Computed Tomography Pulmonary Angiogram (CTPA) scan for the investigation of acute PE during 6-month period (01.01.2016-30.06.2016) were examined. Data was gathered from EPR for patients that met inclusion criteria and all CTPA scans were re-evaluated. Biochemical thresholds of low-grade and high-grade inflammation, serum CRP >10mg/L and >150mg/L and serum albumin concentrations <35g/L and <25 g/L, were combined in the Glasgow Prognostic Score (GPS) and peri-operative Glasgow Prognostic Score (poGPS) respectively. Neutrophil Lymphocyte ratio (NLR) was also calculated. Pulmonary Embolus Severity Index score was calculated. Results Of the total CTPA reports (n = 2129) examined, 245 patients were eligible for inclusion. Of these, 20 (8%) patients had died at 28-days and 43 (18%) at 6-months. Of the 197 non-cancer related presentations, 28-day and 6-month mortality were 3% and 8% respectively. Of the 48 cancer related presentations, 28-day and 6-month mortality were 29% and 58% respectively. On univariate analysis, age ≥65 years (p<0.01), PESI score ≥100(p = <0.001), NLR ≥3(p<0.001) and Coronary Artery Calcification (CAC) score ≥ 6 (p<0.001) were associated with higher 28-day and 6-month mortality. PESI score ≥100 (OR 5.2, 95% CI: 1.1, 24.2, P <0.05), poGPS ≥1 (OR 2.5, 95% CI: 1.2-5.0, P = 0.01) and NLR ≥3 (OR 3.7, 95% CI: 1.0-3.4, P <0.05) remained independently associated with 28-day mortality. On multivariate binary logistic regression analysis of factors associated with 6-month mortality, PESI score ≥100 ...
    Keywords Medicine ; R ; Science ; Q
    Subject code 610
    Language English
    Publishing date 2021-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  10. Article ; Online: Emerging roles for TFEB in the immune response and inflammation.

    Brady, Owen A / Martina, José A / Puertollano, Rosa

    Autophagy

    2017  Volume 14, Issue 2, Page(s) 181–189

    Abstract: Inflammation is a central feature of an effective immune response, which functions to eliminate pathogens and other foreign material, and promote recovery; however, dysregulation of the inflammatory response is associated with a wide variety of disease ... ...

    Abstract Inflammation is a central feature of an effective immune response, which functions to eliminate pathogens and other foreign material, and promote recovery; however, dysregulation of the inflammatory response is associated with a wide variety of disease states. The autophagy-lysosome pathway is one of 2 major degradative pathways used by the cell and serves to eliminate long-lived and dysfunctional proteins and organelles to maintain homeostasis. Mounting evidence implicates the autophagy-lysosome pathway as a key player in regulating the inflammatory response; hence many inflammatory diseases may fundamentally be diseases of autophagy-lysosome pathway dysfunction. The recent identification of TFEB and TFE3 as master regulators of macroautophagy/autophagy and lysosome function raises the possibility that these transcription factors may be of central importance in linking autophagy and lysosome dysfunction with inflammatory disorders. Here, we review the current state of knowledge linking TFEB and TFE3 to the processes of autophagy and inflammation and highlight several conditions, which are linked by these factors.
    MeSH term(s) Adaptive Immunity/genetics ; Animals ; Autophagy/genetics ; Autophagy/immunology ; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/physiology ; Communicable Diseases/genetics ; Communicable Diseases/immunology ; DNA-Binding Proteins/physiology ; HeLa Cells ; Homeostasis ; Humans ; Immunity, Innate/genetics ; Inflammation/genetics ; Inflammation/immunology ; Lysosomes/genetics ; Lysosomes/immunology ; Muscle Proteins/physiology ; Transcription Factors/physiology
    Chemical Substances Basic Helix-Loop-Helix Leucine Zipper Transcription Factors ; DNA-Binding Proteins ; Muscle Proteins ; TEAD4 protein, human ; TFEB protein, human ; Transcription Factors
    Language English
    Publishing date 2017-07-24
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Intramural ; Review
    ZDB-ID 2454135-7
    ISSN 1554-8635 ; 1554-8627
    ISSN (online) 1554-8635
    ISSN 1554-8627
    DOI 10.1080/15548627.2017.1313943
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