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| Open AccessVirtual finger boosts three-dimensional imaging and microsurgery as well as terabyte volume image visualization and analysis
Large three-dimensional images are commonly generated through biological experimentation. Here the authors report software tools for exploration of three-dimensional images along with applications to assist in imaging, microsurgery, visualization and annotation of large image data sets.
- Hanchuan Peng
- , Jianyong Tang
- & Fuhui Long
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Offspring production with sperm grown in vitro from cryopreserved testis tissues
As the fertility of pre-pubertal male patients undergoing chemotherapy cannot be preserved using semen cryopreservation, alternative approaches are needed. Here the authors generate live mouse offspring via assisted reproduction technologies, using round spermatids or sperm derived from neonatal mouse cryopreserved testis tissues.
- Tetsuhiro Yokonishi
- , Takuya Sato
- & Takehiko Ogawa
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| Open AccessTemporal disease trajectories condensed from population-wide registry data covering 6.2 million patients
Population-wide analyses of healthcare data are challenging and thus often involve only few diseases or comparatively short time scales. Here the authors use healthcare records of all hospital encounters in Denmark over 15 years to describe how disease diagnoses progress over time.
- Anders Boeck Jensen
- , Pope L. Moseley
- & Søren Brunak
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| Open Access2q36.3 is associated with prognosis for oestrogen receptor-negative breast cancer patients treated with chemotherapy
Studies have shown that breast cancer prognosis is hereditary. Here the authors show that a genetic variant in CCL20, a chemokine ligand involved in immune response, is significantly associated with breast cancer survival and may therefore represent an important therapeutic or prognostic target.
- Jingmei Li
- , Linda S. Lindström
- & Kamila Czene
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High-fat maternal diet during pregnancy persistently alters the offspring microbiome in a primate model
The influence of diet on the establishment of gut microbiota early in life is poorly understood. Here the authors show, in a primate model, that maternal diet during pregnancy affects the offspring’s microbiome, and that dietary intervention after weaning only partially reverses this effect.
- Jun Ma
- , Amanda L. Prince
- & Kjersti M. Aagaard
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Emergent properties of the interferon-signalling network may underlie the success of hepatitis C treatment
The standard treatment for hepatitis C virus (HCV) infection, combining interferon (IFN) α and ribavirin, fails in a number of patients. Here, the authors use a mathematical model of the IFN signalling network in the presence of HCV to explain the success or failure of hepatitis C treatment.
- Pranesh Padmanabhan
- , Urtzi Garaigorta
- & Narendra M. Dixit
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Non-invasive classification of microcalcifications with phase-contrast X-ray mammography
X-ray absorption imaging is used for early breast cancer detection but can barely identify the morphology of microcalcifications—a possible indicator of cancer. Wang et al.develop a technique to non-invasively classify different types of microcalcifications and achieve 100% sensitivity on phantom data.
- Zhentian Wang
- , Nik Hauser
- & Marco Stampanoni
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| Open AccessThe short-chain fatty acid acetate reduces appetite via a central homeostatic mechanism
The consumption of fermentable carbohydrates, or fibre, is associated with weight loss. Here the authors show that the metabolite acetate, created by fermentation of fibre in the mouse colon, is taken up into the brain where it induces appetite-suppressing neuronal activity in the hypothalamus.
- Gary Frost
- , Michelle L. Sleeth
- & Jimmy D. Bell
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| Open AccessMaternal nutrition at conception modulates DNA methylation of human metastable epialleles
Maternal diet affects DNA methylation in the developing offspring, leading to phenotypic changes. Here, Dominguez-Salas et al. exploit seasonal variation in the diet of Gambian women to show that maternal methyl donor nutrient status around the time of conception predicts methylation levels at metastable epialleles in infants.
- Paula Dominguez-Salas
- , Sophie E. Moore
- & Branwen J. Hennig
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| Open AccessD-Glucosamine supplementation extends life span of nematodes and of ageing mice
D-Glucosamine is a dietary supplement widely used for the treatment of osteoarthritis. Here Weimer et al. show that D-glucosamine extends the life span of Caenorhabditis elegans and of mice by mimicking the molecular effects of a diet low in carbohydrates.
- Sandra Weimer
- , Josephine Priebs
- & Michael Ristow
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| Open AccessUltra-sensitive liquid biopsy of circulating extracellular vesicles using ExoScreen
The potential of extracellular vesicles (EVs) as cancer biomarkers is substantial. Here, Yoshioka et al. describe a sensitive technique to analyse EVs directly from blood samples of patients with colorectal cancer, highlighting a liquid biopsy technique with cancer-detection possibilities.
- Yusuke Yoshioka
- , Nobuyoshi Kosaka
- & Takahiro Ochiya
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Methionine restriction extends lifespan of Drosophila melanogaster under conditions of low amino-acid status
Dietary restriction of the amino acid methionine extends the lifespan of rodents. Here the authors systematically test diets with varying amino-acid content and show that methionine restriction extends the lifespan of yeast and flies only when the content of other amino acids in the diet is also low.
- Byung Cheon Lee
- , Alaattin Kaya
- & Vadim N. Gladyshev
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| Open AccessCaloric restriction reduces age-related and all-cause mortality in rhesus monkeys
Caloric restriction extends the lifespan of various organisms but whether it works in monkeys is controversial. Here, Colman et al.report that caloric restriction reduces all-cause mortality of rhesus macaques, and perform a weight comparison that aims to reconcile their findings with contradictory results from a similar study.
- Ricki J. Colman
- , T. Mark Beasley
- & Rozalyn M. Anderson
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Mutations in epigenetic regulators including SETD2 are gained during relapse in paediatric acute lymphoblastic leukaemia
Epigenetic regulators have been proposed to be modulators of chemoresistance in acute lymphoblastic leukaemia. Here, the authors find enrichment of mutations in epigenetic regulators at relapse, including somatic mutations in SETD2.
- Brenton G. Mar
- , Lars B. Bullinger
- & Scott A. Armstrong
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| Open AccessBlockade of TLR3 protects mice from lethal radiation-induced gastrointestinal syndrome
Ionizing radiation damages small intestinal crypt cells, including epithelial stem cells and their progeny. Here the authors show that radiation-induced crypt cell death is amplified by the release of cellular RNA from apoptotic epithelial cells, which then triggers pro-apoptotic TLR3 signalling on neighbouring cells.
- Naoki Takemura
- , Takumi Kawasaki
- & Satoshi Uematsu
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Ionizing irradiation induces acute haematopoietic syndrome and gastrointestinal syndrome independently in mice
Ionizing radiation damages the gastrointestinal system, but the cell types involved in intestinal damage and repair are controversial. Here the authors use bone marrow transplantation models and various irradiation regimes to rule out a role of bone marrow-derived cells in acute gastrointestinal injury and recovery in mice.
- Brian J. Leibowitz
- , Liang Wei
- & Jian Yu
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Inhibition of miR-146a prevents enterovirus-induced death by restoring the production of type I interferon
Enterovirus 71 (EV71) is one of the causative agents of hand-food-mouth disease and to date, effective vaccines or antivirals against the disease have not been developed. Here, the authors show that blocking miR-146a upregulation induced upon EV71 infection can have a positive effect on the resolution of infection.
- Bing-Ching Ho
- , I-Shing Yu
- & Sung-Liang Yu
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African origin of the malaria parasite Plasmodium vivax
Plasmodium vivax, the leading cause of human malaria in Asia and Latin America, is thought to have an Asian origin. Here, the authors show that wild chimpanzees and gorillas in Africa are infected with parasites that are closely related to P. vivax, indicating an African origin for this species.
- Weimin Liu
- , Yingying Li
- & Paul M. Sharp
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Genome-wide RNAi ionomics screen reveals new genes and regulation of human trace element metabolism
The composition of trace elements in human cells (the ionome) is an important component of metabolism. Here, the authors carry out a high-throughput, genome-wide analysis of the human ionome and identify cellular regulators of important trace elements such as selenium, copper and iron.
- Mikalai Malinouski
- , Nesrin M. Hasan
- & Vadim N. Gladyshev
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A sensitive two-photon probe to selectively detect monoamine oxidase B activity in Parkinson’s disease models
Monoamine oxidase B is an enzyme that is unusually active in Parkinson’s disease, a feature that makes it an ideal diagnostic biomarker. Here, Li et al. create a highly specific fluorogenic probe that can selectively detect monoamine oxidase B activity in vivoto effectively diagnose Parkinson’s disease.
- Lin Li
- , Cheng-Wu Zhang
- & Shao Q. Yao
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Gene co-expression network analysis reveals common system-level properties of prognostic genes across cancer types
Many studies provide evidence of genes that are associated with cancer prognosis but a global view of these genes is lacking. Using data from ‘The Cancer Genome Atlas’, Yang et al.investigate the network properties of prognostic genes and show that these genes tend to be within highly interconnected groups but not the most connected nodes in the gene co-expression network.
- Yang Yang
- , Leng Han
- & Han Liang
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| Open AccessPostmortem examination of patient H.M.’s brain based on histological sectioning and digital 3D reconstruction
Studies on Patient H.M. showed that bilateral resection of the hippocampus results in impaired consolidation of long-term memory. Annese et al.create a digital map of Henry Molaison’s brain and find that a significant portion of the posterior hippocampus is actually histologically intact.
- Jacopo Annese
- , Natalie M. Schenker-Ahmed
- & Suzanne Corkin
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Non-invasive mapping of deep-tissue lymph nodes in live animals using a multimodal PET/MRI nanoparticle
The imaging of tumour-draining lymph nodes is important for cancer diagnosis and therapy. Here, Thorek et al. report a nanoparticle that allows for the combined imaging of deep-tissue lymph nodes by positron emission tomography and magnetic resonance imaging in cancer-bearing mice.
- Daniel L. J. Thorek
- , David Ulmert
- & Jan Grimm
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A statin-loaded reconstituted high-density lipoprotein nanoparticle inhibits atherosclerotic plaque inflammation
Inflammatory processes in atherosclerotic lesions promote disease progression and plaque rupture. Here the authors load the drug statin into nanoparticles made of recombinant high-density lipoprotein and show that these accumulate in atherosclerotic plaques and reduce plaque inflammation in mice.
- Raphaël Duivenvoorden
- , Jun Tang
- & Willem J. M. Mulder
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Indoleamides are active against drug-resistant Mycobacterium tuberculosis
New classes of antitubercular drugs are in constant demand as drug-resistant strains of Mycobacterium tuberculosis become more prevalent. Here, the authors characterize a class of drugs that are active against various M. tuberculosisstrains, including those resistant to currently used antituberculars.
- Shichun Lun
- , Haidan Guo
- & William R. Bishai
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Postnatal muscle modification by myogenic factors modulates neuropathology and survival in an ALS mouse model
MyoD and myogenin are muscle regulatory factors that are involved in muscle development. Park et al.study a mouse model of amyotrophic lateral sclerosis and find that MyoD and myogenin have positive and negative effects, respectively, on motor neuron degeneration and muscle denervation.
- Kevin H. J. Park
- , Sonia Franciosi
- & Blair R. Leavitt
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| Open AccessLow paternal dietary folate alters the mouse sperm epigenome and is associated with negative pregnancy outcomes
Paternal diet has been shown to influence the metabolism of offspring in rats and mice. Here Lambrot et al.report DNA and histone methylation changes in the sperm of male mice on a folate-deficient diet and observe developmental defects in their offspring.
- R. Lambrot
- , C. Xu
- & S. Kimmins
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Real-time influenza forecasts during the 2012–2013 season
Our ability to accurately predict the spread of infectious diseases is still in its infancy. Here, Shamanet al.develop a model framework that produces accurate real-time forecasts of influenza peak timing for over a hundred cities in the USA.
- Jeffrey Shaman
- , Alicia Karspeck
- & Marc Lipsitch
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| Open AccessProtective CD8+ T-cell immunity to human malaria induced by chimpanzee adenovirus-MVA immunisation
Induction of protective immunity mediated by CD8+ T cells has been a long sought goal in vaccinology. Here, Ewer et al. report induction of protective efficacy against Plasmodium falciparummalaria in a phase IIa prime-boost vaccine trial where efficacy correlates strongly with induced CD8 T-cell responses.
- Katie J. Ewer
- , Geraldine A. O’Hara
- & Adrian V. S. Hill
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Switch of glycolysis to gluconeogenesis by dexamethasone for treatment of hepatocarcinoma
Hepatocytes use gluconeogenesis to produce glucose, but whether this process is altered in hepatocellular carcinoma (HCC) is unclear. Here, the loss of gluconeogenesis in HCC and altered glucocorticoid regulation is demonstrated and glucocorticoid treatment is shown to reduce tumour burden.
- Ruihua Ma
- , Wanguang Zhang
- & Bo Huang
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Real-time in vivo imaging of invasive- and biomaterial-associated bacterial infections using fluorescently labelled vancomycin
Invasive and biomaterial-associated infections in humans are often difficult to diagnose and treat. Here, the authors demonstrate that real-time in vivodetection and imaging of these bacterial infections can be successfully performed with fluorescently labelled vancomycin.
- Marleen van Oosten
- , Tina Schäfer
- & Gooitzen M. van Dam
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Microbiome remodelling leads to inhibition of intestinal farnesoid X receptor signalling and decreased obesity
Tempol is an antioxidant that reduces the body weight of mice on a high-fat diet. Li et al.now provide a mechanistic link by demonstrating that tempol affects the intestinal microbiota, which leads to a change in the composition of bile acids and suppression of FXR signalling.
- Fei Li
- , Changtao Jiang
- & Frank J. Gonzalez
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| Open AccessHuman gut microbiota community structures in urban and rural populations in Russia
The structure of the human gut microbiota has been shown to vary between populations. Tyakht et al.analyse the gut microbiota assembly from Russian individuals living in urban and rural areas, and compare these with previously studied populations.
- Alexander V. Tyakht
- , Elena S. Kostryukova
- & Vadim M. Govorun
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Activation of the central nervous system induced by micro-magnetic stimulation
Magnetic stimulation is used therapeutically for neurological disorders, but its effectiveness is hindered by efficacy and safety limitations due to large device sizes. Here the authors show that sub-millimetre, micro-magnetic coils effectively stimulate hamster cochlear neurons, with minimal side effects.
- Hyun-Joo Park
- , Giorgio Bonmassar
- & John T. Gale
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Octapod iron oxide nanoparticles as high-performance T2 contrast agents for magnetic resonance imaging
Spherical superparamagnetic iron oxide nanoparticles are potentially attractive MRI contrast agents, but their low transverse relaxivity has hindered their application. Here, the authors report size and shape control of octapod iron oxide nanoparticles with extremely high transverse relaxivity.
- Zhenghuan Zhao
- , Zijian Zhou
- & Jinhao Gao
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Metformin improves healthspan and lifespan in mice
The anti-diabetic drug metformin has been shown to increase lifespan of some model organisms, but results have been conflicting. Here, Martin-Montalvo et al. administer one of two doses of metformin to male mice and show that the lower dose increases healthspan and lifespan, while the higher dose is toxic.
- Alejandro Martin-Montalvo
- , Evi M. Mercken
- & Rafael de Cabo
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Model-based rational design of an oncolytic virus with improved therapeutic potential
Oncolytic viruses can serve as self-replicating anticancer agents. Le Bœuf et al. combine synthetic modelling and molecular biology approaches to create a virus with enhanced oncolytic activity in vitro and in vivodue to its expression of an interferon antagonist.
- Fabrice Le Bœuf
- , Cory Batenchuk
- & John C. Bell
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Mycobacterium tuberculosis is extraordinarily sensitive to killing by a vitamin C-induced Fenton reaction
New approaches to kill Mycobacterium tuberculosis are required to improve TB therapy. Vilchèze et al. now demonstrate that vitamin C-derived reactive oxygen species lead to sterilization of drug-susceptible and drug-resistant M. tuberculosisoffering new possibilities for drug development.
- Catherine Vilchèze
- , Travis Hartman
- & William R. Jacobs Jr
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Flexible polymer transistors with high pressure sensitivity for application in electronic skin and health monitoring
Flexible pressure sensors may be key in realising biomedical prostheses and robots that can interact with their environment. Here, Schwartz et al.report an organic thin film pressure sensing device that combines fast response times with low power consumption and cyclic stability.
- Gregor Schwartz
- , Benjamin C.-K. Tee
- & Zhenan Bao
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Article
| Open AccessTransmission-blocking interventions eliminate malaria from laboratory populations
Transmission-blocking interventions aim to interrupt progression of Plasmodium parasites from the vertebrate host to the mosquito. Blagborough et al. demonstrate that only partially reducing transmission can be sufficient to eliminate experimental Plasmodiuminfection in successive mosquito and mice populations when biting rates are low.
- A. M. Blagborough
- , T. S. Churcher
- & R. E. Sinden
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Loss of TRPM2 function protects against irradiation-induced salivary gland dysfunction
A debilitating side effect of radiotherapy in patients with head and neck cancers is xerostomia as a result of salivary gland dysfunction. Here Liu et al. show that activation of the calcium channel TRPM2 in salivary gland cells contributes to irradiation-induced loss of salivary fluid secretion.
- Xibao Liu
- , Ana Cotrim
- & Indu Ambudkar
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Holographic optogenetic stimulation of patterned neuronal activity for vision restoration
Photo-stimulation can be used to control neuronal circuits, but current strategies lack optimal precision and resolution. Reutsky-Gefen et al. demonstrate a potential approach for vision restoration via holographically patterned, optogenetic stimulation of retinal ganglion cells, with temporal precision.
- Inna Reutsky-Gefen
- , Lior Golan
- & Shy Shoham
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| Open AccessMultiplexed volumetric bar-chart chip for point-of-care diagnostics
Diagnostic microfluidic devices often require complicated optical systems and computers to quantify results. Here, Qin and colleagues link enzymatic biomarker detection with the displacement of ink, resulting in a device that displays quantitative results as bar graphs directly on the device.
- Yujun Song
- , Yuanqing Zhang
- & Lidong Qin
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Article
| Open AccessFactors determining the occurrence of submicroscopic malaria infections and their relevance for control
Malaria can persist at levels that escape detection by standard microscopy, but can be detected by PCR. Okell et al.now show that rates of submicroscopic infection can be predicted using more widely available microscopy data, and are most epidemiologically significant in areas with low malaria transmission.
- Lucy C. Okell
- , Teun Bousema
- & Chris J. Drakeley
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Detection and differential diagnosis of colon cancer by a cumulative analysis of promoter methylation
Changes in the methylation pattern of gene promoters are hallmarks of certain cancers, such as colon cancer. Here Yang et al.identify and validate a set of genes and measure the cumulative methylation of promoters, which allows them to distinguish between two stages of colon cancer.
- Qiong Yang
- , Ying Dong
- & Shu Wang
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Direct isolation and RNA-seq reveal environment-dependent properties of engrafted neural stem/progenitor cells
Studies on neural stem and progenitor cells have shown they may be useful in treating spinal cord injuries, but the results are variable. Kumamaruet al.transplant these cells in injured spinal cords of mice, and find that their therapeutic properties are dynamically altered depending on their environment.
- Hiromi Kumamaru
- , Yasuyuki Ohkawa
- & Seiji Okada
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Alternative α-synuclein transcript usage as a convergent mechanism in Parkinson's disease pathology
The protein α-synuclein is implicated in Parkinson's disease. Rhinn and colleagues perform gene expression analysis and find that specific α-synuclein transcripts are preferentially associated with Parkinson's disease, and that they potentiate the accumulation of α-synuclein protein.
- Herve Rhinn
- , Liang Qiang
- & Asa Abeliovich
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| Open AccessEstimating the potential public health impact of seasonal malaria chemoprevention in African children
Seasonal malaria chemoprevention can lower the incidence of malaria in areas where transmission is highly periodical. Combining data on rainfall, population and malaria endemicity, Cairnset al. identify geographical areas in sub-Saharan Africa where this intervention is likely to be effective and cost-effective.
- Matthew Cairns
- , Arantxa Roca-Feltrer
- & Brian M. Greenwood
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| Open AccessFasciola hepatica is associated with the failure to detect bovine tuberculosis in dairy cattle
The incidence of bovine tuberculosis in the UK is increasing despite efforts to eradicate the disease. The authors of this paper show that infection of cattle with the parasiteFasciola hepaticaimpedes the diagnosis of tuberculosis, which may in part explain why the current eradication campaign is failing.
- Jen Claridge
- , Peter Diggle
- & Diana J.L. Williams