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Article ; Online: Identification of an RNA sponge that controls the RoxS riboregulator of central metabolism in Bacillus subtilis.

Durand, Sylvain / Callan-Sidat, Adam / McKeown, Josie / Li, Stephen / Kostova, Gergana / Hernandez-Fernaud, Juan R / Alam, Mohammad Tauqeer / Millard, Andrew / Allouche, Delphine / Constantinidou, Chrystala / Condon, Ciarán / Denham, Emma L

Nucleic acids research

2021 Volume 49, Issue 11, Page(s) 6399–6419

Abstract: sRNAs are a taxonomically-restricted but transcriptomically-abundant class of post-transcriptional regulators. While of major importance for adaption to the environment, we currently lack global-scale methodology enabling target identification, ... ...

Abstract	sRNAs are a taxonomically-restricted but transcriptomically-abundant class of post-transcriptional regulators. While of major importance for adaption to the environment, we currently lack global-scale methodology enabling target identification, especially in species without known RNA hub proteins (e.g. Hfq). Using psoralen RNA cross-linking and Illumina-sequencing we identify RNA-RNA interacting pairs in vivo in Bacillus subtilis, resolving previously well-described interactants. Although sRNA-sRNA pairings are rare (compared with sRNA-mRNA), we identify a robust example involving the conserved sRNA RoxS and an unstudied sRNA RosA (Regulator of sRNA A). We show RosA to be the first confirmed RNA sponge described in a Gram-positive bacterium. RosA interacts with at least two sRNAs, RoxS and FsrA. The RosA/RoxS interaction not only affects the levels of RoxS but also its processing and regulatory activity. We also found that the transcription of RosA is repressed by CcpA, the key regulator of carbon-metabolism in B. subtilis. Since RoxS is already known to be transcriptionally controlled by malate via the transcriptional repressor Rex, its post-transcriptional regulation by CcpA via RosA places RoxS in a key position to control central metabolism in response to varying carbon sources.
MeSH term(s)	Bacillus subtilis/genetics ; Bacillus subtilis/metabolism ; Bacterial Proteins/metabolism ; Carbon/metabolism ; Genetic Fitness ; Proteome ; RNA Processing, Post-Transcriptional ; RNA Stability ; RNA, Bacterial/metabolism ; RNA, Small Untranslated/biosynthesis ; RNA, Small Untranslated/genetics ; RNA, Small Untranslated/metabolism ; RNA, Small Untranslated/physiology ; Transcription, Genetic
Chemical Substances	Bacterial Proteins ; Proteome ; RNA, Bacterial ; RNA, Small Untranslated ; Carbon (7440-44-0)
Language	English
Publishing date	2021-07-15
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	186809-3
ISSN	1362-4962 ; 1362-4954 ; 0301-5610 ; 0305-1048
ISSN (online)	1362-4962 ; 1362-4954
ISSN	0301-5610 ; 0305-1048
DOI	10.1093/nar/gkab444
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Book ; Online: A map of global peatland extent created using machine learning (Peat-ML)

Melton, Joe R. / Chan, Ed / Millard, Koreen / Fortier, Matthew / Winton, R. Scott / Martín-López, Javier M. / Cadillo-Quiroz, Hinsby / Kidd, Darren / Verchot, Louis V.

eISSN: 1991-9603

2022

Abstract: ... the influence of spatial autocorrelation. That approach yielded an average r 2 of 0.73 with a root mean squared ...

Abstract	Peatlands store large amounts of soil carbon and freshwater, constituting an important component of the global carbon and hydrologic cycles. Accurate information on the global extent and distribution of peatlands is presently lacking but is needed by Earth System Models (ESMs) to simulate the effects of climate change on the global carbon and hydrologic balance. Here, we present Peat-ML, a spatially continuous global map of peatland fractional coverage generated using machine learning techniques suitable for use as a prescribed geophysical field in an ESM. Inputs to our statistical model follow drivers of peatland formation and include spatially distributed climate, geomorphological and soil data, along with remotely-sensed vegetation indices. Available maps of peatland fractional coverage for 14 relatively extensive regions were used along with mapped ecoregions of non-peatland areas to train the statistical model. In addition to qualitative comparisons to other maps in the literature, we estimated model error in two ways. The first estimate used the training data in a blocked leave-one-out cross-validation strategy designed to minimize the influence of spatial autocorrelation. That approach yielded an average r 2 of 0.73 with a root mean squared error and mean bias error of 9.11 % and −0.36 %, respectively. Our second error estimate was generated by comparing Peat-ML against a high-quality, extensively ground-truthed map generated by Ducks Unlimited Canada for the Canadian Boreal Plains region. This comparison suggests our map to be of comparable quality to mapping products generated through more traditional approaches, at least for boreal peatlands.
Subject code	333
Language	English
Publishing date	2022-02-14
Publishing country	de
Document type	Book ; Online
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Article ; Online: A map of global peatland extent created using machine learning (Peat-ML)

Melton, Joe R. / Chan, Ed / Millard, Koreen / Fortier, Matthew / Winton, R. Scott / Martín-López, Javier M. / Cadillo-Quiroz, Hinsby / Kidd, Darren / Verchot, Louis V.

Geoscientific Model Development

2022

Abstract: Peatlands store large amounts of soil carbon and freshwater, constituting an important component of the global carbon and hydrologic cycles. Accurate information on the global extent and distribution of peatlands is presently lacking but is needed by ... ...

Abstract	Peatlands store large amounts of soil carbon and freshwater, constituting an important component of the global carbon and hydrologic cycles. Accurate information on the global extent and distribution of peatlands is presently lacking but is needed by Earth system models (ESMs) to simulate the effects of climate change on the global carbon and hydrologic balance. Here, we present Peat-ML, a spatially continuous global map of peatland fractional coverage generated using machine learning (ML) techniques suitable for use as a prescribed geophysical field in an ESM. Inputs to our statistical model follow drivers of peatland formation and include spatially distributed climate, geomorphological and soil data, and remotely sensed vegetation indices. Available maps of peatland fractional coverage for 14 relatively extensive regions were used along with mapped ecoregions of non-peatland areas to train the statistical model. In addition to qualitative comparisons to other maps in the literature, we estimated model error in two ways. The first estimate used the training data in a blocked leave-one-out cross-validation strategy designed to minimize the influence of spatial autocorrelation. That approach yielded an average r2 of 0.73 with a root-mean-square error and mean bias error of 9.11 % and −0.36 %, respectively. Our second error estimate was generated by comparing Peat-ML against a high-quality, extensively ground-truthed map generated by Ducks Unlimited Canada for the Canadian Boreal Plains region. This comparison suggests our map to be of comparable quality to mapping products generated through more traditional approaches, at least for boreal peatlands.
Keywords	peatlands ; machine learning ; climate change ; turberas ; aprendizaje electrónico ; cambio climático
Language	English
Publishing date	2022-06-28T08:06:59Z
Publisher	Copernicus GmbH
Publishing country	fr
Document type	Article ; Online
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Article ; Online: Using Zebrafish Models of Human Influenza A Virus Infections to Screen Antiviral Drugs and Characterize Host Immune Cell Responses.

Sullivan, Con / Jurcyzszak, Denise / Goody, Michelle F / Gabor, Kristin A / Longfellow, Jacob R / Millard, Paul J / Kim, Carol H

Journal of visualized experiments : JoVE

2017 , Issue 119

Abstract: Each year, seasonal influenza outbreaks profoundly affect societies worldwide. In spite of global efforts, influenza remains an intractable healthcare burden. The principle strategy to curtail infections is yearly vaccination. In individuals who have ... ...

Abstract	Each year, seasonal influenza outbreaks profoundly affect societies worldwide. In spite of global efforts, influenza remains an intractable healthcare burden. The principle strategy to curtail infections is yearly vaccination. In individuals who have contracted influenza, antiviral drugs can mitigate symptoms. There is a clear and unmet need to develop alternative strategies to combat influenza. Several animal models have been created to model host-influenza interactions. Here, protocols for generating zebrafish models for systemic and localized human influenza A virus (IAV) infection are described. Using a systemic IAV infection model, small molecules with potential antiviral activity can be screened. As a proof-of-principle, a protocol that demonstrates the efficacy of the antiviral drug Zanamivir in IAV-infected zebrafish is described. It shows how disease phenotypes can be quantified to score the relative efficacy of potential antivirals in IAV-infected zebrafish. In recent years, there has been increased appreciation for the critical role neutrophils play in the human host response to influenza infection. The zebrafish has proven to be an indispensable model for the study of neutrophil biology, with direct impacts on human medicine. A protocol to generate a localized IAV infection in the Tg(mpx:mCherry) zebrafish line to study neutrophil biology in the context of a localized viral infection is described. Neutrophil recruitment to localized infection sites provides an additional quantifiable phenotype for assessing experimental manipulations that may have therapeutic applications. Both zebrafish protocols described faithfully recapitulate aspects of human IAV infection. The zebrafish model possesses numerous inherent advantages, including high fecundity, optical clarity, amenability to drug screening, and availability of transgenic lines, including those in which immune cells such as neutrophils are labeled with fluorescent proteins. The protocols detailed here exploit these advantages and have the potential to reveal critical insights into host-IAV interactions that may ultimately translate into the clinic.
MeSH term(s)	Animals ; Antiviral Agents/pharmacology ; Disease Models, Animal ; Humans ; Influenza A virus ; Neutrophils/immunology ; Orthomyxoviridae Infections/drug therapy ; Orthomyxoviridae Infections/immunology ; Orthomyxoviridae Infections/veterinary ; Zanamivir/pharmacology ; Zebrafish
Chemical Substances	Antiviral Agents ; Zanamivir (L6O3XI777I)
Language	English
Publishing date	2017-01-20
Publishing country	United States
Document type	Journal Article ; Video-Audio Media ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	1940-087X
ISSN (online)	1940-087X
DOI	10.3791/55235
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Article ; Online: Structures of Human Antibodies Bound to SARS-CoV-2 Spike Reveal Common Epitopes and Recurrent Features of Antibodies

Barnes, Christopher O. / West, Anthony P., Jr. / Huey-Tubman, Kathryn E. / Hoffmann, Magnus A. G. / Sharaf, Naima G. / Hoffman, Pauline R. / Koranda, Nicholas / Gristick, Harry B. / Gaebler, Christian / Muecksch, Frauke / Cetrulo Lorenzi, Julio C. / Finkin, Shlomo / Hägglöf, Thomas / Hurley, Arlene / Millard, Katrina G. / Weisblum, Yiska / Schmidt, Fabian / Hatziioannou, Theodora / Bieniasz, Paul D. /

Caskey, Marina / Robbiani, Davide F. / Nussenzweig, Michel C. / Bjorkman, Pamela J.

2020

Abstract: Neutralizing antibody responses to coronaviruses mainly target the receptor-binding domain (RBD) of the trimeric spike. Here, we characterized polyclonal IgGs and Fabs from COVID-19 convalescent individuals for recognition of coronavirus spikes. Plasma ... ...

Abstract	Neutralizing antibody responses to coronaviruses mainly target the receptor-binding domain (RBD) of the trimeric spike. Here, we characterized polyclonal IgGs and Fabs from COVID-19 convalescent individuals for recognition of coronavirus spikes. Plasma IgGs differed in their focus on RBD epitopes, recognition of alpha- and beta-coronaviruses, and contributions of avidity to increased binding/neutralization of IgGs over Fabs. Using electron microscopy, we examined specificities of polyclonal plasma Fabs, revealing recognition of both S1^A and RBD epitopes on SARS-CoV-2 spike. Moreover, a 3.4Å cryo-EM structure of a neutralizing monoclonal Fab-spike complex revealed an epitope that blocks ACE2 receptor binding. Modeling based on these structures suggested different potentials for inter-spike crosslinking by IgGs on viruses and that characterized IgGs would not be affected by identified SARS-CoV-2 spike mutations. Overall, our studies structurally define a recurrent anti-SARS-CoV-2 antibody class derived from VH3-53/VH3-66 and similarity to a SARS-CoV VH3-30 antibody, providing criteria for evaluating vaccine-elicited antibodies.
Keywords	covid19
Subject code	570
Publishing date	2020-08-20
Publisher	Elsevier
Publishing country	us
Document type	Article ; Online
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Article ; Online: Heterologous cAd3-Ebola and MVA-EbolaZ vaccines are safe and immunogenic in US and Uganda phase 1/1b trials.

Happe, Myra / Hofstetter, Amelia R / Wang, Jing / Yamshchikov, Galina V / Holman, LaSonji A / Novik, Laura / Strom, Larisa / Kiweewa, Francis / Wakabi, Salim / Millard, Monica / Kelley, Colleen F / Kabbani, Sarah / Edupuganti, Srilatha / Beck, Allison / Kaltovich, Florence / Murray, Tamar / Tsukerman, Susanna / Carr, Derick / Ashman, Carl /

NPJ vaccines

2024 Volume 9, Issue 1, Page(s) 67

Abstract: Ebola virus disease (EVD) is a filoviral infection caused by virus species of the Ebolavirus genus including Zaire ebolavirus (EBOV) and Sudan ebolavirus (SUDV). We investigated the safety and immunogenicity of a heterologous prime-boost regimen ... ...

Abstract	Ebola virus disease (EVD) is a filoviral infection caused by virus species of the Ebolavirus genus including Zaire ebolavirus (EBOV) and Sudan ebolavirus (SUDV). We investigated the safety and immunogenicity of a heterologous prime-boost regimen involving a chimpanzee adenovirus 3 vectored Ebola vaccine [either monovalent (cAd3-EBOZ) or bivalent (cAd3-EBO)] prime followed by a recombinant modified vaccinia virus Ankara EBOV vaccine (MVA-EbolaZ) boost in two phase 1/1b randomized open-label clinical trials in healthy adults in the United States (US) and Uganda (UG). Trial US (NCT02408913) enrolled 140 participants, including 26 EVD vaccine-naïve and 114 cAd3-Ebola-experienced participants (April-November 2015). Trial UG (NCT02354404) enrolled 90 participants, including 60 EVD vaccine-naïve and 30 DNA Ebola vaccine-experienced participants (February-April 2015). All tested vaccines and regimens were safe and well tolerated with no serious adverse events reported related to study products. Solicited local and systemic reactogenicity was mostly mild to moderate in severity. The heterologous prime-boost regimen was immunogenic, including induction of durable antibody responses which peaked as early as two weeks and persisted up to one year after each vaccination. Different prime-boost intervals impacted the magnitude of humoral and cellular immune responses. The results from these studies demonstrate promising implications for use of these vaccines in both prophylactic and outbreak settings.
Language	English
Publishing date	2024-03-29
Publishing country	England
Document type	Journal Article
ISSN	2059-0105
ISSN (online)	2059-0105
DOI	10.1038/s41541-024-00833-z
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Article ; Online: As Clear as Mud? Determining the Diversity and Prevalence of Prophages in the Draft Genomes of Estuarine Isolates of Clostridium difficile.

Hargreaves, Katherine R / Otieno, James R / Thanki, Anisha / Blades, Matthew J / Millard, Andrew D / Browne, Hilary P / Lawley, Trevor D / Clokie, Martha R J

Genome biology and evolution

2015 Volume 7, Issue 7, Page(s) 1842–1855

Abstract: The bacterium Clostridium difficile is a significant cause of nosocomial infections worldwide. The pathogenic success of this organism can be attributed to its flexible genome which is characterized by the exchange of mobile genetic elements, and by ... ...

Abstract	The bacterium Clostridium difficile is a significant cause of nosocomial infections worldwide. The pathogenic success of this organism can be attributed to its flexible genome which is characterized by the exchange of mobile genetic elements, and by ongoing genome evolution. Despite its pathogenic status, C. difficile can also be carried asymptomatically, and has been isolated from natural environments such as water and sediments where multiple strain types (ribotypes) are found in close proximity. These include ribotypes which are associated with disease, as well as those that are less commonly isolated from patients. Little is known about the genomic content of strains in such reservoirs in the natural environment. In this study, draft genomes have been generated for 13 C. difficile isolates from estuarine sediments including clinically relevant and environmental associated types. To identify the genetic diversity within this strain collection, whole-genome comparisons were performed using the assemblies. The strains are highly genetically diverse with regards to the C. difficile "mobilome," which includes transposons and prophage elements. We identified a novel transposon-like element in two R078 isolates. Multiple, related and unrelated, prophages were detected in isolates across ribotype groups, including two novel prophage elements and those related to the transducing phage φC2. The susceptibility of these isolates to lytic phage infection was tested using a panel of characterized phages found from the same locality. In conclusion, estuarine sediments are a source of genetically diverse C. difficile strains with a complex network of prophages, which could contribute to the emergence of new strains in clinics.
MeSH term(s)	Bacterial Toxins/genetics ; Clostridioides difficile/genetics ; Clostridioides difficile/isolation & purification ; Clostridioides difficile/pathogenicity ; Clostridioides difficile/virology ; Environmental Microbiology ; Estuaries ; Genetic Variation ; Genome, Bacterial ; Geologic Sediments/microbiology ; Prophages/genetics ; Virulence/genetics
Chemical Substances	Bacterial Toxins
Language	English
Publishing date	2015-05-27
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2495328-3
ISSN	1759-6653 ; 1759-6653
ISSN (online)	1759-6653
ISSN	1759-6653
DOI	10.1093/gbe/evv094
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Article ; Online: A DN-mda5 transgenic zebrafish model demonstrates that Mda5 plays an important role in snakehead rhabdovirus resistance.

Gabor, K A / Charette, J R / Pietraszewski, M J / Wingfield, D J / Shim, J S / Millard, P J / Kim, C H

Developmental and comparative immunology

2015 Volume 51, Issue 2, Page(s) 298–304

Abstract: Melanoma Differentiation-Associated protein 5 (MDA5) is a member of the retinoic acid-inducible gene I (RIG-I)-like receptor (RLR) family, which is a cytosolic pattern recognition receptor that detects viral nucleic acids. Here we show an Mda5-dependent ... ...

Abstract	Melanoma Differentiation-Associated protein 5 (MDA5) is a member of the retinoic acid-inducible gene I (RIG-I)-like receptor (RLR) family, which is a cytosolic pattern recognition receptor that detects viral nucleic acids. Here we show an Mda5-dependent response to rhabdovirus infection in vivo using a dominant-negative mda5 transgenic zebrafish. Dominant-negative mda5 zebrafish embryos displayed an impaired antiviral immune response compared to wild-type counterparts that can be rescued by recombinant full-length Mda5. To our knowledge, we have generated the first dominant-negative mda5 transgenic zebrafish and demonstrated a critical role for Mda5 in the antiviral response to rhabdovirus.
MeSH term(s)	Animals ; Animals, Genetically Modified ; DEAD-box RNA Helicases/genetics ; DEAD-box RNA Helicases/immunology ; DEAD-box RNA Helicases/metabolism ; Immunity, Active/genetics ; Interferon Type I/metabolism ; Mutation/genetics ; Receptors, Pattern Recognition/genetics ; Receptors, Pattern Recognition/immunology ; Receptors, Pattern Recognition/metabolism ; Rhabdoviridae/immunology ; Rhabdoviridae Infections/immunology ; Transgenes/genetics ; Viral Load/genetics ; Zebrafish/immunology ; Zebrafish Proteins/genetics ; Zebrafish Proteins/immunology ; Zebrafish Proteins/metabolism
Chemical Substances	Interferon Type I ; Receptors, Pattern Recognition ; Zebrafish Proteins ; MDA5 protein,zebrafish (EC 3.6.1.-) ; DEAD-box RNA Helicases (EC 3.6.4.13)
Language	English
Publishing date	2015-08
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	752411-0
ISSN	1879-0089 ; 0145-305X
ISSN (online)	1879-0089
ISSN	0145-305X
DOI	10.1016/j.dci.2015.01.006
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Article ; Online: Abolishment of morphology-based taxa and change to binomial species names: 2022 taxonomy update of the ICTV bacterial viruses subcommittee.

Turner, Dann / Shkoporov, Andrey N / Lood, Cédric / Millard, Andrew D / Dutilh, Bas E / Alfenas-Zerbini, Poliane / van Zyl, Leonardo J / Aziz, Ramy K / Oksanen, Hanna M / Poranen, Minna M / Kropinski, Andrew M / Barylski, Jakub / Brister, J Rodney / Chanisvili, Nina / Edwards, Rob A / Enault, François / Gillis, Annika / Knezevic, Petar / Krupovic, Mart /

Kurtböke, Ipek / Kushkina, Alla / Lavigne, Rob / Lehman, Susan / Lobocka, Malgorzata / Moraru, Cristina / Moreno Switt, Andrea / Morozova, Vera / Nakavuma, Jesca / Reyes Muñoz, Alejandro / Rūmnieks, Jānis / Sarkar, B L / Sullivan, Matthew B / Uchiyama, Jumpei / Wittmann, Johannes / Yigang, Tong / Adriaenssens, Evelien M

Archives of virology

2023 Volume 168, Issue 2, Page(s) 74

Abstract: This article summarises the activities of the Bacterial Viruses Subcommittee of the International Committee on Taxonomy of Viruses for the period of March 2021-March 2022. We provide an overview of the new taxa proposed in 2021, approved by the Executive ...

Abstract	This article summarises the activities of the Bacterial Viruses Subcommittee of the International Committee on Taxonomy of Viruses for the period of March 2021-March 2022. We provide an overview of the new taxa proposed in 2021, approved by the Executive Committee, and ratified by vote in 2022. Significant changes to the taxonomy of bacterial viruses were introduced: the paraphyletic morphological families Podoviridae, Siphoviridae, and Myoviridae as well as the order Caudovirales were abolished, and a binomial system of nomenclature for species was established. In addition, one order, 22 families, 30 subfamilies, 321 genera, and 862 species were newly created, promoted, or moved.
MeSH term(s)	Humans ; Bacteriophages ; Viruses/genetics ; Caudovirales ; Myoviridae ; Siphoviridae
Language	English
Publishing date	2023-01-23
Publishing country	Austria
Document type	Journal Article
ZDB-ID	7491-3
ISSN	1432-8798 ; 0304-8608
ISSN (online)	1432-8798
ISSN	0304-8608
DOI	10.1007/s00705-022-05694-2
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Article ; Online: A proposed new low-frequency antigen in the Augustine blood group system associated with a severe case of hemolytic disease of the fetus and newborn.

Millard, Glenda M / McGowan, Eunike C / Wilson, Brett / Martin, Jacqui R / Spooner, Michaela / Morris, Scott / Farley, Ray / James, Simon / Liew, Yew-Wah / Schoeman, Elizna M / Dean, Melinda M / Flower, Robert L / Hyland, Catherine A / Powley, Tanya / Roxby, David

Transfusion

2018 Volume 58, Issue 5, Page(s) 1320–1322

MeSH term(s)	Blood Group Antigens/immunology ; Erythroblastosis, Fetal/immunology ; Female ; Humans ; Infant, Newborn
Chemical Substances	Blood Group Antigens
Language	English
Publishing date	2018-03-05
Publishing country	United States
Document type	Case Reports ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	208417-x
ISSN	1537-2995 ; 0041-1132
ISSN (online)	1537-2995
ISSN	0041-1132
DOI	10.1111/trf.14562
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