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1. Severe cases of Buruli ulcer (infection with Mycobacterium ulcerans) in common ringtail possums in Victoria adversely affect animal welfare.

Author

Hobbs, EC, Loukopoulos, P, Stinear, TP, Porter, JL, Lee, JYH, Whiteley, P, Skerratt, LF, Gibney, KB, and Meredith, A

Subjects
*BURULI ulcer, *MYCOBACTERIAL diseases, *ANIMAL welfare, *SKIN diseases, *JOINTS (Anatomy), *MYOSITIS
Abstract

Buruli ulcer is a chronic ulcerative disease of the skin and subcutaneous tissues caused by infection with Mycobacterium ulcerans. Although Australian possums are known to be susceptible to Buruli ulcer, many aspects of the disease in possums, including welfare impacts, remain largely unreported. Severe clinical Buruli ulcer was identified in four common ringtail possums (Pseudocheirus peregrinus) from Melbourne, Victoria. All four possums were euthanased due to the presence of deep ulcerative lesions on paws, with extensive tissue necrosis that exposed bones and tendons in three cases. Histologically, there was severe ulcerative necrotising pyogranulomatous dermatitis, panniculitis and myositis, with intralesional acid‐fast bacteria. M. ulcerans was detected by real‐time PCR in all swabs, tissues and faeces collected from all four cases. Buruli ulcer may be an important and under‐recognised cause of poor possum welfare in endemic areas. The physical impacts of the severe cutaneous lesions, especially those extending to underlying bones and joints, would have directly impaired the mobility of these possums, affecting navigation of their natural environments and expression of natural behaviours including foraging and socialising. Systemic distribution of M. ulcerans throughout all major internal organs, as observed here, may further impact the health and fitness of infected possums. Faecal shedding of M. ulcerans in all four cases supports the role of possums as zoonotic reservoirs. Further research is needed to investigate the epidemiology, pathogenesis and welfare impacts of Buruli ulcer in possums and to inform the design of interventions that may protect their health and welfare. [ABSTRACT FROM AUTHOR]

Published
2024
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2. A low-cost and versatile paramagnetic bead DNA extraction method for Mycobacterium ulcerans environmental surveillance.

Author

Lee JYH, Porter JL, Hobbs EC, Whiteley P, Buultjens AH, and Stinear TP

Abstract

In Australia, native possums are a major wildlife reservoir for Mycobacterium ulcerans , the causative agent of the neglected tropical skin disease Buruli ulcer (BU). Large-scale possum excreta surveys that use PCR to detect M. ulcerans in 100-1,000 s of excreta specimens are an important tool that can inform geospatial modeling and predict locations of future human BU risk. However, the significant expense of commercial kits used to extract DNA from specimens is a major barrier to routine implementation. Here, we developed a low-cost method for DNA extraction from possum excreta, possum tissue, and pure mycobacterial cultures, using a guanidinium isothiocyanate lysis solution and paramagnetic beads. In a 96-well plate format for high-throughput processing, the paramagnetic bead DNA extraction method was threefold less sensitive but only 1/6 the cost of a commonly used commercial kit. Applied to tissue swabs, the method was fourfold more sensitive and 1/5 the cost of a commercial kit. When used for preparing DNA from pure mycobacterial cultures, the method yielded purified genomic DNA with quality metrics comparable to more lengthy techniques. Our paramagnetic bead method is an economical means to undertake large-scale M. ulcerans environmental surveillance that will directly inform efforts to halt the spread of BU in Victoria, Australia, with potential for applicability in other endemic countries., Importance: Buruli ulcer (BU) is a neglected tropical skin disease, with an incidence that has dramatically increased in temperate southeastern Australia over the last decade. In southeastern Australia, BU is a zoonosis with native possums the major wildlife reservoir of the causative pathogen, Mycobacterium ulcerans . Infected possums shed M. ulcerans in their excreta, and excreta surveys using PCR to screen for the presence of pathogen DNA are a powerful means to predict future areas of Buruli ulcer risk for humans. However, excreta surveys across large geographic areas require testing of many thousands of samples. The cost of commercial DNA extraction reagents used for preparing samples for PCR testing can thus become prohibitive to effective surveillance. Here, we describe a simple, low-cost method for extracting DNA from possum excreta using paramagnetic beads. The method is versatile and adaptable to a variety of other sample types including swabs collected from possum tissues and pure cultures of mycobacteria.

Published
2024
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4. Marine sponge microbe provides insights into evolution and virulence of the tubercle bacillus.

Author

Pidot SJ, Klatt S, Ates LS, Frigui W, Sayes F, Majlessi L, Izumi H, Monk IR, Porter JL, Bennett-Wood V, Seemann T, Otter A, Taiaroa G, Cook GM, West N, Tobias NJ, Fuerst JA, Stutz MD, Pellegrini M, McConville M, Brosch R, and Stinear TP

Subjects
Animals, Mice, Virulence, Mycobacterium tuberculosis pathogenicity, Mycobacterium tuberculosis genetics, Tuberculosis microbiology, Virulence Factors genetics, Female, Biological Evolution, Humans, Phylogeny, Mycobacterium pathogenicity, Mycobacterium genetics, Porifera microbiology
Abstract

Reconstructing the evolutionary origins of Mycobacterium tuberculosis, the causative agent of human tuberculosis, has helped identify bacterial factors that have led to the tubercle bacillus becoming such a formidable human pathogen. Here we report the discovery and detailed characterization of an exceedingly slow growing mycobacterium that is closely related to M. tuberculosis for which we have proposed the species name Mycobacterium spongiae sp. nov., (strain ID: FSD4b-SM). The bacterium was isolated from a marine sponge, taken from the waters of the Great Barrier Reef in Queensland, Australia. Comparative genomics revealed that, after the opportunistic human pathogen Mycobacterium decipiens, M. spongiae is the most closely related species to the M. tuberculosis complex reported to date, with 80% shared average nucleotide identity and extensive conservation of key M. tuberculosis virulence factors, including intact ESX secretion systems and associated effectors. Proteomic and lipidomic analyses showed that these conserved systems are functional in FSD4b-SM, but that it also produces cell wall lipids not previously reported in mycobacteria. We investigated the virulence potential of FSD4b-SM in mice and found that, while the bacteria persist in lungs for 56 days after intranasal infection, no overt pathology was detected. The similarities with M. tuberculosis, together with its lack of virulence, motivated us to investigate the potential of FSD4b-SM as a vaccine strain and as a genetic donor of the ESX-1 genetic locus to improve BCG immunogenicity. However, neither of these approaches resulted in superior protection against M. tuberculosis challenge compared to BCG vaccination alone. The discovery of M. spongiae adds to our understanding of the emergence of the M. tuberculosis complex and it will be another useful resource to refine our understanding of the factors that shaped the evolution and pathogenesis of M. tuberculosis., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Pidot et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Published
2024
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5. A Mycobacterium ulcerans vaccine pilot trial using an accurate low-dose challenge.

Author

Muhi S, Porter JL, and Stinear TP

Subjects
Animals, Mice, Pilot Projects, Female, Humans, Mycobacterium bovis immunology, Vaccination, BCG Vaccine immunology, BCG Vaccine administration & dosage, Mice, Inbred BALB C, Mycobacterium ulcerans immunology, Disease Models, Animal, Buruli Ulcer immunology, Buruli Ulcer prevention & control, Buruli Ulcer microbiology, Bacterial Vaccines immunology, Bacterial Vaccines administration & dosage
Abstract

A Mycobacterium ulcerans human challenge model has the potential to fundamentally advance our understanding of early human immune responses to infection, while rapidly evaluating vaccines and other therapeutic interventions. Here, using a murine tail infection model, we tested a very well-characterized working cell bank of the proposed challenge isolate M. ulcerans JKD8049 in naïve and Mycobacterium bovis bacille Calmette-Guérin (BCG)-vaccinated BALB/c mice. All 10 naïve mice were successfully infected with 20 colony-forming units (CFU) of M. ulcerans [95% confidence interval (CI) 17-22 CFU] with a mean time to visible lesion of 86 days (95% CI 79-92 days). In the 10 vaccinated mice, there was a significant delay in the mean time to lesion compared to the naïve controls of 24 days ( P = 0.0003), but all mice eventually developed ulcerative lesions. This study informs a future human infection model by demonstrating the successful application of the challenge agent in this in vivo model and highlights both the promise and the problems with trying to induce protective immunity against M. ulcerans ., Importance: In preparation for its proposed use in a controlled human infection model (CHIM), this study reports the successful infection of BALB/c mice using a carefully characterized, low-dose inoculum of Mycobacterium ulcerans JKD8049 (our proposed CHIM strain). We also demonstrate that Mycobacterium bovis bacille Calmette-Guérin delays the onset of disease but cannot alter the course of illness once a lesion becomes apparent. We also validate the findings of previous low-dose challenges that used less accurate methods to determine the inoculum, but our presented methodology is practical, accurate, and anticipated to be reproducible., Competing Interests: The authors declare no conflict of interest.

Published
2024
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6. Mycobacterium ulcerans challenge strain selection for a Buruli ulcer controlled human infection model.

Author

Muhi S, Buultjens AH, Porter JL, Marshall JL, Doerflinger M, Pidot SJ, O'Brien DP, Johnson PDR, Lavender CJ, Globan M, McCarthy J, Osowicki J, and Stinear TP

Subjects
Humans, Anti-Bacterial Agents therapeutic use, Anti-Bacterial Agents pharmacology, Australia, Mycobacterium ulcerans genetics, Buruli Ulcer microbiology, Buruli Ulcer immunology
Abstract

Critical scientific questions remain regarding infection with Mycobacterium ulcerans, the organism responsible for the neglected tropical disease, Buruli ulcer (BU). A controlled human infection model has the potential to accelerate our knowledge of the immunological correlates of disease, to test prophylactic interventions and novel therapeutics. Here we present microbiological evidence supporting M. ulcerans JKD8049 as a suitable human challenge strain. This non-genetically modified Australian isolate is susceptible to clinically relevant antibiotics, can be cultured in animal-free and surfactant-free media, can be enumerated for precise dosing, and has stable viability following cryopreservation. Infectious challenge of humans with JKD8049 is anticipated to imitate natural infection, as M. ulcerans JKD8049 is genetically stable following in vitro passage and produces the key virulence factor, mycolactone. Also reported are considerations for the manufacture, storage, and administration of M. ulcerans JKD8049 for controlled human infection., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Muhi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Published
2024
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7. Achievement of Target Gain Larger than Unity in an Inertial Fusion Experiment.

Author

Abu-Shawareb H, Acree R, Adams P, Adams J, Addis B, Aden R, Adrian P, Afeyan BB, Aggleton M, Aghaian L, Aguirre A, Aikens D, Akre J, Albert F, Albrecht M, Albright BJ, Albritton J, Alcala J, Alday C, Alessi DA, Alexander N, Alfonso J, Alfonso N, Alger E, Ali SJ, Ali ZA, Allen A, Alley WE, Amala P, Amendt PA, Amick P, Ammula S, Amorin C, Ampleford DJ, Anderson RW, Anklam T, Antipa N, Appelbe B, Aracne-Ruddle C, Araya E, Archuleta TN, Arend M, Arnold P, Arnold T, Arsenlis A, Asay J, Atherton LJ, Atkinson D, Atkinson R, Auerbach JM, Austin B, Auyang L, Awwal AAS, Aybar N, Ayers J, Ayers S, Ayers T, Azevedo S, Bachmann B, Back CA, Bae J, Bailey DS, Bailey J, Baisden T, Baker KL, Baldis H, Barber D, Barberis M, Barker D, Barnes A, Barnes CW, Barrios MA, Barty C, Bass I, Batha SH, Baxamusa SH, Bazan G, Beagle JK, Beale R, Beck BR, Beck JB, Bedzyk M, Beeler RG, Beeler RG, Behrendt W, Belk L, Bell P, Belyaev M, Benage JF, Bennett G, Benedetti LR, Benedict LX, Berger RL, Bernat T, Bernstein LA, Berry B, Bertolini L, Besenbruch G, Betcher J, Bettenhausen R, Betti R, Bezzerides B, Bhandarkar SD, Bickel R, Biener J, Biesiada T, Bigelow K, Bigelow-Granillo J, Bigman V, Bionta RM, Birge NW, Bitter M, Black AC, Bleile R, Bleuel DL, Bliss E, Bliss E, Blue B, Boehly T, Boehm K, Boley CD, Bonanno R, Bond EJ, Bond T, Bonino MJ, Borden M, Bourgade JL, Bousquet J, Bowers J, Bowers M, Boyd R, Boyle D, Bozek A, Bradley DK, Bradley KS, Bradley PA, Bradley L, Brannon L, Brantley PS, Braun D, Braun T, Brienza-Larsen K, Briggs R, Briggs TM, Britten J, Brooks ED, Browning D, Bruhn MW, Brunner TA, Bruns H, Brunton G, Bryant B, Buczek T, Bude J, Buitano L, Burkhart S, Burmark J, Burnham A, Burr R, Busby LE, Butlin B, Cabeltis R, Cable M, Cabot WH, Cagadas B, Caggiano J, Cahayag R, Caldwell SE, Calkins S, Callahan DA, Calleja-Aguirre J, Camara L, Camp D, Campbell EM, Campbell JH, Carey B, Carey R, Carlisle K, Carlson L, Carman L, Carmichael J, Carpenter A, Carr C, Carrera JA, Casavant D, Casey A, Casey DT, Castillo A, Castillo E, Castor JI, Castro C, Caughey W, Cavitt R, Celeste J, Celliers PM, Cerjan C, Chandler G, Chang B, Chang C, Chang J, Chang L, Chapman R, Chapman TD, Chase L, Chen H, Chen H, Chen K, Chen LY, Cheng B, Chittenden J, Choate C, Chou J, Chrien RE, Chrisp M, Christensen K, Christensen M, Christiansen NS, Christopherson AR, Chung M, Church JA, Clark A, Clark DS, Clark K, Clark R, Claus L, Cline B, Cline JA, Cobble JA, Cochrane K, Cohen B, Cohen S, Collette MR, Collins GW, Collins LA, Collins TJB, Conder A, Conrad B, Conyers M, Cook AW, Cook D, Cook R, Cooley JC, Cooper G, Cope T, Copeland SR, Coppari F, Cortez J, Cox J, Crandall DH, Crane J, Craxton RS, Cray M, Crilly A, Crippen JW, Cross D, Cuneo M, Cuotts G, Czajka CE, Czechowicz D, Daly T, Danforth P, Danly C, Darbee R, Darlington B, Datte P, Dauffy L, Davalos G, Davidovits S, Davis P, Davis J, Dawson S, Day RD, Day TH, Dayton M, Deck C, Decker C, Deeney C, DeFriend KA, Deis G, Delamater ND, Delettrez JA, Demaret R, Demos S, Dempsey SM, Desjardin R, Desjardins T, Desjarlais MP, Dewald EL, DeYoreo J, Diaz S, Dimonte G, Dittrich TR, Divol L, Dixit SN, Dixon J, Do A, Dodd ES, Dolan D, Donovan A, Donovan M, Döppner T, Dorrer C, Dorsano N, Douglas MR, Dow D, Downie J, Downing E, Dozieres M, Draggoo V, Drake D, Drake RP, Drake T, Dreifuerst G, Drury O, DuBois DF, DuBois PF, Dunham G, Durocher M, Dylla-Spears R, Dymoke-Bradshaw AKL, Dzenitis B, Ebbers C, Eckart M, Eddinger S, Eder D, Edgell D, Edwards MJ, Efthimion P, Eggert JH, Ehrlich B, Ehrmann P, Elhadj S, Ellerbee C, Elliott NS, Ellison CL, Elsner F, Emerich M, Engelhorn K, England T, English E, Epperson P, Epstein R, Erbert G, Erickson MA, Erskine DJ, Erlandson A, Espinosa RJ, Estes C, Estabrook KG, Evans S, Fabyan A, Fair J, Fallejo R, Farmer N, Farmer WA, Farrell M, Fatherley VE, Fedorov M, Feigenbaum E, Fehrenbach T, Feit M, Felker B, Ferguson W, Fernandez JC, Fernandez-Panella A, Fess S, Field JE, Filip CV, Fincke JR, Finn T, Finnegan SM, Finucane RG, Fischer M, Fisher A, Fisher J, Fishler B, Fittinghoff D, Fitzsimmons P, Flegel M, Flippo KA, Florio J, Folta J, Folta P, Foreman LR, Forrest C, Forsman A, Fooks J, Foord M, Fortner R, Fournier K, Fratanduono DE, Frazier N, Frazier T, Frederick C, Freeman MS, Frenje J, Frey D, Frieders G, Friedrich S, Froula DH, Fry J, Fuller T, Gaffney J, Gales S, Le Galloudec B, Le Galloudec KK, Gambhir A, Gao L, Garbett WJ, Garcia A, Gates C, Gaut E, Gauthier P, Gavin Z, Gaylord J, Geddes CGR, Geissel M, Génin F, Georgeson J, Geppert-Kleinrath H, Geppert-Kleinrath V, Gharibyan N, Gibson J, Gibson C, Giraldez E, Glebov V, Glendinning SG, Glenn S, Glenzer SH, Goade S, Gobby PL, Goldman SR, Golick B, Gomez M, Goncharov V, Goodin D, Grabowski P, Grafil E, Graham P, Grandy J, Grasz E, Graziani FR, Greenman G, Greenough JA, Greenwood A, Gregori G, Green T, Griego JR, Grim GP, Grondalski J, Gross S, Guckian J, Guler N, Gunney B, Guss G, Haan S, Hackbarth J, Hackel L, Hackel R, Haefner C, Hagmann C, Hahn KD, Hahn S, Haid BJ, Haines BM, Hall BM, Hall C, Hall GN, Hamamoto M, Hamel S, Hamilton CE, Hammel BA, Hammer JH, Hampton G, Hamza A, Handler A, Hansen S, Hanson D, Haque R, Harding D, Harding E, Hares JD, Harris DB, Harte JA, Hartouni EP, Hatarik R, Hatchett S, Hauer AA, Havre M, Hawley R, Hayes J, Hayes J, Hayes S, Hayes-Sterbenz A, Haynam CA, Haynes DA, Headley D, Heal A, Heebner JE, Heerey S, Heestand GM, Heeter R, Hein N, Heinbockel C, Hendricks C, Henesian M, Heninger J, Henrikson J, Henry EA, Herbold EB, Hermann MR, Hermes G, Hernandez JE, Hernandez VJ, Herrmann MC, Herrmann HW, Herrera OD, Hewett D, Hibbard R, Hicks DG, Higginson DP, Hill D, Hill K, Hilsabeck T, Hinkel DE, Ho DD, Ho VK, Hoffer JK, Hoffman NM, Hohenberger M, Hohensee M, Hoke W, Holdener D, Holdener F, Holder JP, Holko B, Holunga D, Holzrichter JF, Honig J, Hoover D, Hopkins D, Berzak Hopkins LF, Hoppe M, Hoppe ML, Horner J, Hornung R, Horsfield CJ, Horvath J, Hotaling D, House R, Howell L, Hsing WW, Hu SX, Huang H, Huckins J, Hui H, Humbird KD, Hund J, Hunt J, Hurricane OA, Hutton M, Huynh KH, Inandan L, Iglesias C, Igumenshchev IV, Ivanovich I, Izumi N, Jackson M, Jackson J, Jacobs SD, James G, Jancaitis K, Jarboe J, Jarrott LC, Jasion D, Jaquez J, Jeet J, Jenei AE, Jensen J, Jimenez J, Jimenez R, Jobe D, Johal Z, Johns HM, Johnson D, Johnson MA, Gatu Johnson M, Johnson RJ, Johnson S, Johnson SA, Johnson T, Jones K, Jones O, Jones M, Jorge R, Jorgenson HJ, Julian M, Jun BI, Jungquist R, Kaae J, Kabadi N, Kaczala D, Kalantar D, Kangas K, Karasiev VV, Karasik M, Karpenko V, Kasarky A, Kasper K, Kauffman R, Kaufman MI, Keane C, Keaty L, Kegelmeyer L, Keiter PA, Kellett PA, Kellogg J, Kelly JH, Kemic S, Kemp AJ, Kemp GE, Kerbel GD, Kershaw D, Kerr SM, Kessler TJ, Key MH, Khan SF, Khater H, Kiikka C, Kilkenny J, Kim Y, Kim YJ, Kimko J, Kimmel M, Kindel JM, King J, Kirkwood RK, Klaus L, Klem D, Kline JL, Klingmann J, Kluth G, Knapp P, Knauer J, Knipping J, Knudson M, Kobs D, Koch J, Kohut T, Kong C, Koning JM, Koning P, Konior S, Kornblum H, Kot LB, Kozioziemski B, Kozlowski M, Kozlowski PM, Krammen J, Krasheninnikova NS, Krauland CM, Kraus B, Krauser W, Kress JD, Kritcher AL, Krieger E, Kroll JJ, Kruer WL, Kruse MKG, Kucheyev S, Kumbera M, Kumpan S, Kunimune J, Kur E, Kustowski B, Kwan TJT, Kyrala GA, Laffite S, Lafon M, LaFortune K, Lagin L, Lahmann B, Lairson B, Landen OL, Land T, Lane M, Laney D, Langdon AB, Langenbrunner J, Langer SH, Langro A, Lanier NE, Lanier TE, Larson D, Lasinski BF, Lassle D, LaTray D, Lau G, Lau N, Laumann C, Laurence A, Laurence TA, Lawson J, Le HP, Leach RR, Leal L, Leatherland A, LeChien K, Lechleiter B, Lee A, Lee M, Lee T, Leeper RJ, Lefebvre E, Leidinger JP, LeMire B, Lemke RW, Lemos NC, Le Pape S, Lerche R, Lerner S, Letts S, Levedahl K, Lewis T, Li CK, Li H, Li J, Liao W, Liao ZM, Liedahl D, Liebman J, Lindford G, Lindman EL, Lindl JD, Loey H, London RA, Long F, Loomis EN, Lopez FE, Lopez H, Losbanos E, Loucks S, Lowe-Webb R, Lundgren E, Ludwigsen AP, Luo R, Lusk J, Lyons R, Ma T, Macallop Y, MacDonald MJ, MacGowan BJ, Mack JM, Mackinnon AJ, MacLaren SA, MacPhee AG, Magelssen GR, Magoon J, Malone RM, Malsbury T, Managan R, Mancini R, Manes K, Maney D, Manha D, Mannion OM, Manuel AM, Manuel MJ, Mapoles E, Mara G, Marcotte T, Marin E, Marinak MM, Mariscal DA, Mariscal EF, Marley EV, Marozas JA, Marquez R, Marshall CD, Marshall FJ, Marshall M, Marshall S, Marticorena J, Martinez JI, Martinez D, Maslennikov I, Mason D, Mason RJ, Masse L, Massey W, Masson-Laborde PE, Masters ND, Mathisen D, Mathison E, Matone J, Matthews MJ, Mattoon C, Mattsson TR, Matzen K, Mauche CW, Mauldin M, McAbee T, McBurney M, Mccarville T, McCrory RL, McEvoy AM, McGuffey C, Mcinnis M, McKenty P, McKinley MS, McLeod JB, McPherson A, Mcquillan B, Meamber M, Meaney KD, Meezan NB, Meissner R, Mehlhorn TA, Mehta NC, Menapace J, Merrill FE, Merritt BT, Merritt EC, Meyerhofer DD, Mezyk S, Mich RJ, Michel PA, Milam D, Miller C, Miller D, Miller DS, Miller E, Miller EK, Miller J, Miller M, Miller PE, Miller T, Miller W, Miller-Kamm V, Millot M, Milovich JL, Minner P, Miquel JL, Mitchell S, Molvig K, Montesanti RC, Montgomery DS, Monticelli M, Montoya A, Moody JD, Moore AS, Moore E, Moran M, Moreno JC, Moreno K, Morgan BE, Morrow T, Morton JW, Moses E, Moy K, Muir R, Murillo MS, Murray JE, Murray JR, Munro DH, Murphy TJ, Munteanu FM, Nafziger J, Nagayama T, Nagel SR, Nast R, Negres RA, Nelson A, Nelson D, Nelson J, Nelson S, Nemethy S, Neumayer P, Newman K, Newton M, Nguyen H, Di Nicola JG, Di Nicola P, Niemann C, Nikroo A, Nilson PM, Nobile A, Noorai V, Nora RC, Norton M, Nostrand M, Note V, Novell S, Nowak PF, Nunez A, Nyholm RA, O'Brien M, Oceguera A, Oertel JA, Oesterle AL, Okui J, Olejniczak B, Oliveira J, Olsen P, Olson B, Olson K, Olson RE, Opachich YP, Orsi N, Orth CD, Owen M, Padalino S, Padilla E, Paguio R, Paguio S, Paisner J, Pajoom S, Pak A, Palaniyappan S, Palma K, Pannell T, Papp F, Paras D, Parham T, Park HS, Pasternak A, Patankar S, Patel MV, Patel PK, Patterson R, Patterson S, Paul B, Paul M, Pauli E, Pearce OT, Pearcy J, Pedretti A, Pedrotti B, Peer A, Pelz LJ, Penetrante B, Penner J, Perez A, Perkins LJ, Pernice E, Perry TS, Person S, Petersen D, Petersen T, Peterson DL, Peterson EB, Peterson JE, Peterson JL, Peterson K, Peterson RR, Petrasso RD, Philippe F, Phillion D, Phipps TJ, Piceno E, Pickworth L, Ping Y, Pino J, Piston K, Plummer R, Pollack GD, Pollaine SM, Pollock BB, Ponce D, Ponce J, Pontelandolfo J, Porter JL, Post J, Poujade O, Powell C, Powell H, Power G, Pozulp M, Prantil M, Prasad M, Pratuch S, Price S, Primdahl K, Prisbrey S, Procassini R, Pruyne A, Pudliner B, Qiu SR, Quan K, Quinn M, Quintenz J, Radha PB, Rainer F, Ralph JE, Raman KS, Raman R, Rambo PW, Rana S, Randewich A, Rardin D, Ratledge M, Ravelo N, Ravizza F, Rayce M, Raymond A, Raymond B, Reed B, Reed C, Regan S, Reichelt B, Reis V, Reisdorf S, Rekow V, Remington BA, Rendon A, Requieron W, Rever M, Reynolds H, Reynolds J, Rhodes J, Rhodes M, Richardson MC, Rice B, Rice NG, Rieben R, Rigatti A, Riggs S, Rinderknecht HG, Ring K, Riordan B, Riquier R, Rivers C, Roberts D, Roberts V, Robertson G, Robey HF, Robles J, Rocha P, Rochau G, Rodriguez J, Rodriguez S, Rosen MD, Rosenberg M, Ross G, Ross JS, Ross P, Rouse J, Rovang D, Rubenchik AM, Rubery MS, Ruiz CL, Rushford M, Russ B, Rygg JR, Ryujin BS, Sacks RA, Sacks RF, Saito K, Salmon T, Salmonson JD, Sanchez J, Samuelson S, Sanchez M, Sangster C, Saroyan A, Sater J, Satsangi A, Sauers S, Saunders R, Sauppe JP, Sawicki R, Sayre D, Scanlan M, Schaffers K, Schappert GT, Schiaffino S, Schlossberg DJ, Schmidt DW, Schmit PF, Smidt JM, Schneider DHG, Schneider MB, Schneider R, Schoff M, Schollmeier M, Schroeder CR, Schrauth SE, Scott HA, Scott I, Scott JM, Scott RHH, Scullard CR, Sedillo T, Seguin FH, Seka W, Senecal J, Sepke SM, Seppala L, Sequoia K, Severyn J, Sevier JM, Sewell N, Seznec S, Shah RC, Shamlian J, Shaughnessy D, Shaw M, Shaw R, Shearer C, Shelton R, Shen N, Sherlock MW, Shestakov AI, Shi EL, Shin SJ, Shingleton N, Shmayda W, Shor M, Shoup M, Shuldberg C, Siegel L, Silva FJ, Simakov AN, Sims BT, Sinars D, Singh P, Sio H, Skulina K, Skupsky S, Slutz S, Sluyter M, Smalyuk VA, Smauley D, Smeltser RM, Smith C, Smith I, Smith J, Smith L, Smith R, Smith R, Schölmerich M, Sohn R, Sommer S, Sorce C, Sorem M, Soures JM, Spaeth ML, Spears BK, Speas S, Speck D, Speck R, Spears J, Spinka T, Springer PT, Stadermann M, Stahl B, Stahoviak J, Stanley J, Stanton LG, Steele R, Steele W, Steinman D, Stemke R, Stephens R, Sterbenz S, Sterne P, Stevens D, Stevers J, Still CH, Stoeckl C, Stoeffl W, Stolken JS, Stolz C, Storm E, Stone G, Stoupin S, Stout E, Stowers I, Strauser R, Streckart H, Streit J, Strozzi DJ, Stutz J, Summers L, Suratwala T, Sutcliffe G, Suter LJ, Sutton SB, Svidzinski V, Swadling G, Sweet W, Szoke A, Tabak M, Takagi M, Tambazidis A, Tang V, Taranowski M, Taylor LA, Telford S, Theobald W, Thi M, Thomas A, Thomas CA, Thomas I, Thomas R, Thompson IJ, Thongstisubskul A, Thorsness CB, Tietbohl G, Tipton RE, Tobin M, Tomlin N, Tommasini R, Toreja AJ, Torres J, Town RPJ, Townsend S, Trenholme J, Trivelpiece A, Trosseille C, Truax H, Trummer D, Trummer S, Truong T, Tubbs D, Tubman ER, Tunnell T, Turnbull D, Turner RE, Ulitsky M, Upadhye R, Vaher JL, VanArsdall P, VanBlarcom D, Vandenboomgaerde M, VanQuinlan R, Van Wonterghem BM, Varnum WS, Velikovich AL, Vella A, Verdon CP, Vermillion B, Vernon S, Vesey R, Vickers J, Vignes RM, Visosky M, Vocke J, Volegov PL, Vonhof S, Von Rotz R, Vu HX, Vu M, Wall D, Wall J, Wallace R, Wallin B, Walmer D, Walsh CA, Walters CF, Waltz C, Wan A, Wang A, Wang Y, Wark JS, Warner BE, Watson J, Watt RG, Watts P, Weaver J, Weaver RP, Weaver S, Weber CR, Weber P, Weber SV, Wegner P, Welday B, Welser-Sherrill L, Weiss K, Wharton KB, Wheeler GF, Whistler W, White RK, Whitley HD, Whitman P, Wickett ME, Widmann K, Widmayer C, Wiedwald J, 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Abstract

On December 5, 2022, an indirect drive fusion implosion on the National Ignition Facility (NIF) achieved a target gain G_{target} of 1.5. This is the first laboratory demonstration of exceeding "scientific breakeven" (or G_{target}>1) where 2.05 MJ of 351 nm laser light produced 3.1 MJ of total fusion yield, a result which significantly exceeds the Lawson criterion for fusion ignition as reported in a previous NIF implosion [H. Abu-Shawareb et al. (Indirect Drive ICF Collaboration), Phys. Rev. Lett. 129, 075001 (2022)PRLTAO0031-900710.1103/PhysRevLett.129.075001]. This achievement is the culmination of more than five decades of research and gives proof that laboratory fusion, based on fundamental physics principles, is possible. This Letter reports on the target, laser, design, and experimental advancements that led to this result.

Published
2024
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8. Mosquitoes provide a transmission route between possums and humans for Buruli ulcer in southeastern Australia.

Author

Mee PT, Buultjens AH, Oliver J, Brown K, Crowder JC, Porter JL, Hobbs EC, Judd LM, Taiaroa G, Puttharak N, Williamson DA, Blasdell KR, Tay EL, Feldman R, Muzari MO, Sanders C, Larsen S, Crouch SR, Johnson PDR, Wallace JR, Price DJ, Hoffmann AA, Gibney KB, Stinear TP, and Lynch SE

Subjects
Animals, Humans, Australia, Genome, Bacterial, Buruli Ulcer epidemiology, Buruli Ulcer genetics, Buruli Ulcer microbiology, Mycobacterium ulcerans genetics, Aedes genetics
Abstract

Buruli ulcer, a chronic subcutaneous infection caused by Mycobacterium ulcerans, is increasing in prevalence in southeastern Australia. Possums are a local wildlife reservoir for M. ulcerans and, although mosquitoes have been implicated in transmission, it remains unclear how humans acquire infection. We conducted extensive field survey analyses of M. ulcerans prevalence among mosquitoes in the Mornington Peninsula region of southeastern Australia. PCR screening of trapped mosquitoes revealed a significant association between M. ulcerans and Aedes notoscriptus. Spatial scanning statistics revealed overlap between clusters of M. ulcerans-positive Ae. notoscriptus, M. ulcerans-positive possum excreta and Buruli ulcer cases, and metabarcoding analyses showed individual mosquitoes had fed on humans and possums. Bacterial genomic analysis confirmed shared single-nucleotide-polymorphism profiles for M. ulcerans detected in mosquitoes, possum excreta and humans. These findings indicate Ae. notoscriptus probably transmit M. ulcerans in southeastern Australia and highlight mosquito control as a Buruli ulcer prevention measure., (© 2024. The Author(s).)

Published
2024
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