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1. Thieno[3,2-b]pyrrole 5-carboxamides as potent and selective inhibitors of Giardia duodenalis

Author: Christopher JS. Hart, Andrew G. Riches, Snigdha Tiash, Rebecca Abraham, Keely Fayd’Herbe, Ellis Joch, Bilal Zulfiqar, Melissa L. Sykes, Vicky M. Avery, Jan Šlapeta, Sam Abraham, John H. Ryan, and Tina S. Skinner-Adams
Subjects: Giardia duodenalis, Drug discovery, Thieno[3,2-b]pyrrole 5-carboxamides, Infectious and parasitic diseases, RC109-216
Abstract: Giardia duodenalis is the causative agent of the neglected diarrhoeal disease giardiasis. While often self-limiting, giardiasis is ubiquitous and impacts hundreds of millions of people annually. It is also a common gastro-intestinal disease of domestic pets, wildlife, and livestock animals. However, despite this impact, there is no vaccine for Giardia currently available. In addition, treatment relies on chemotherapies that are associated with increasing failure rates. To identify new treatment options for giardiasis we recently screened the Compounds Australia Scaffold Library for new chemotypes with selective anti-Giardia activity, identifying three compounds with sub-μM activity and promising selectivity. Here we extended these studies by examining the anti-Giardia activity of series CL9569 compounds. This compound series was of interest given the promising activity (IC50 1.2 μM) and selectivity demonstrated by representative compound, SN00798525 (1). Data from this work has identified an additional three thieno [3,2-b]pyrrole 5-carboxamides with anti-Giardia activity, including 2 which displayed potent cytocidal (IC50 ≤ 10 nM) and selective activity against multiple Giardia strains, including representatives from both human-infecting assemblages and metronidazole resistant parasites. Preclinical studies in mice also demonstrated that 2 is well-tolerated, does not impact the normal gut microbiota and can reduce Giardia parasite burden in these animals.
Published: 2023
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2. Architecture and regulation of a GDNF-GFRα1 synaptic adhesion assembly

Author: F. M. Houghton, S. E. Adams, A. S. Ríos, L. Masino, A. G. Purkiss, D. C. Briggs, F. Ledda, and N. Q. McDonald
Subjects: Science
Abstract: Abstract Glial-cell line derived neurotrophic factor (GDNF) bound to its co-receptor GFRα1 stimulates the RET receptor tyrosine kinase, promoting neuronal survival and neuroprotection. The GDNF-GFRα1 complex also supports synaptic cell adhesion independently of RET. Here, we describe the structure of a decameric GDNF-GFRα1 assembly determined by crystallography and electron microscopy, revealing two GFRα1 pentamers bridged by five GDNF dimers. We reconsitituted the assembly between adhering liposomes and used cryo-electron tomography to visualize how the complex fulfils its membrane adhesion function. The GFRα1:GFRα1 pentameric interface was further validated both in vitro by native PAGE and in cellulo by cell-clustering and dendritic spine assays. Finally, we provide biochemical and cell-based evidence that RET and heparan sulfate cooperate to prevent assembly of the adhesion complex by competing for the adhesion interface. Our results provide a mechanistic framework to understand GDNF-driven cell adhesion, its relationship to trophic signalling, and the central role played by GFRα1.
Published: 2023
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3. Advancing stream classification and hydrologic modeling of ungaged basins for environmental flow management in coastal southern California

Author: S. K. Adams, B. P. Bledsoe, and E. D. Stein
Subjects: Technology, Environmental technology. Sanitary engineering, TD1-1066, Geography. Anthropology. Recreation, Environmental sciences, GE1-350
Abstract: Environmental streamflow management can improve the ecological health of streams by returning modified flows to more natural conditions. The Ecological Limits of Hydrologic Alteration (ELOHA) framework for developing regional environmental flow criteria has been implemented to reverse hydromodification across the heterogenous region of coastal southern California (So. CA) by focusing on two elements of the flow regime: streamflow permanence and flashiness. Within ELOHA, classification groups streams by hydrologic and geomorphic similarity to stratify flow–ecology relationships. Analogous grouping techniques are used by hydrologic modelers to facilitate streamflow prediction in ungaged basins (PUB) through regionalization. Most watersheds, including those needed for stream classification and environmental flow development, are ungaged. Furthermore, So. CA is a highly heterogeneous region spanning gradients of urbanization and flow permanence, which presents a challenge for regionalizing ungaged basins. In this study, we develop a novel classification technique for PUB modeling that uses an inductive approach to group perennial, intermittent, and ephemeral regional streams by modeled hydrologic similarity followed by deductively determining class membership with hydrologic model errors and watershed metrics. As a new type of classification, this hydrologic-model-based classification (HMC) prioritizes modeling accuracy, which in turn provides a means to improve model predictions in ungaged basins while complementing traditional classifications and improving environmental flow management. HMC is developed by calibrating a regional catalog of process-based rainfall–runoff models, quantifying the hydrologic reciprocity of calibrated parameters that would be unknown in ungaged basins and grouping sites according to hydrologic and physical similarity. HMC was applied to 25 USGS streamflow gages in the “South Coast” region of California and was compared to other hybrid PUB approaches combining inductive and deductive classification. Using an average cluster error metric, results show that HMC provided the most hydrologically similar groups according to calibrated parameter reciprocity. Hydrologic-model-based classification is relatively complex and time-consuming to implement, but it shows potential for simplifying ungaged basin management. This study demonstrates the benefits of thorough stream classification using multiple approaches and suggests that hydrologic-model-based classification has advantages for PUB and building the hydrologic foundation for environmental flow management.
Published: 2023
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4. Who is adjusting to whom?: Differences in elephant diel activity in wildlife corridors across different human-modified landscapes

Author: Tempe S. F. Adams, Keith E.A. Leggett, Michael J. Chase, and Marlee A. Tucker
Subjects: Botswana, camera traps, conservation, human pressure, human-elephant conflict, coexistence, General. Including nature conservation, geographical distribution, QH1-199.5
Abstract: The global impact of increased human activities has consequences on the conservation of wildlife. Understanding how wildlife adapts to increased human pressures with urban expansion and agricultural areas is fundamental to future conservation plans of any species. However, there is a belief that large wild free-ranging carnivores and ungulates, cannot coexist with people, limited studies have looked at wildlife movements through differing human-dominated landscapes at finer spatial scales, in Africa. This information is vital as the human population is only going to increase and the wildlife protected areas decrease. We used remote-sensor camera traps to identify the movement patterns of African elephant (Loxodonta africana) through six wildlife corridors in Botswana. The wildlife corridors were located in two different human-dominated landscapes (agricultural/urban), with varying degrees of human impact. While we found that elephants use corridors in both landscapes, they use the urban corridors both diurnally and nocturnally in contrast to agricultural corridors which were only nocturnal. Our results provide evidence for temporal partitioning of corridor use by elephants. We identified that seasonality and landscape were important factors in determining the presence of elephants in the corridors. Our findings demonstrate that elephant diel patterns of use of the wildlife corridor differs based on the surrounding human land-uses on an hourly basis and daily basis, revealing potential adaptation and risk avoidance behaviour.
Published: 2022
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5. An ELISA method to assess HDAC inhibitor-induced alterations to P. falciparum histone lysine acetylation

Author: Eva Hesping, Tina S. Skinner-Adams, Gillian M. Fisher, Thomas Kurz, and Katherine T. Andrews
Subjects: P. falciparum, Malaria, HDAC inhibitor, Lysine acetylation, Histone, ELISA, Infectious and parasitic diseases, RC109-216
Abstract: The prevention and treatment of malaria requires a multi-pronged approach, including the development of drugs that have novel modes of action. Histone deacetylases (HDACs), enzymes involved in post-translational protein modification, are potential new drug targets for malaria. However, the lack of recombinant P. falciparum HDACs and suitable activity assays, has made the investigation of compounds designed to target these enzymes challenging. Current approaches are indirect and include assessing total deacetylase activity and protein hyperacetylation via Western blot. These approaches either do not allow differential compound effects to be determined or suffer from low throughput. Here we investigated dot blot and ELISA methods as new, higher throughput assays to detect histone lysine acetylation changes in P. falciparum parasites. As the ELISA method was found to be superior to the dot blot assay using the control HDAC inhibitor vorinostat, it was used to evaluate the histone H3 and H4 lysine acetylation changes mediated by a panel of six HDAC inhibitors that were shown to inhibit P. falciparum deacetylase activity. Vorinostat, panobinostat, trichostatin A, romidepsin and entinostat all caused an ~3-fold increase in histone H4 acetylation using a tetra-acetyl lysine antibody. Tubastatin A, the only human HDAC6-specific inhibitor tested, also caused H4 hyperacetylation, but to a lesser extent than the other compounds. Further investigation revealed that all compounds, except tubastatin A, caused hyperacetylation of the individual N-terminal H4 lysines 5, 8, 12 and 16. These data indicate that tubastatin A impacts P. falciparum H4 acetylation differently to the other HDAC inhibitors tested. In contrast, all compounds caused hyperacetylation of histone H3. In summary, the ELISA developed in this study provides a higher throughput approach to assessing differential effects of antiplasmodial compounds on histone acetylation levels and is therefore a useful new tool in the investigation of HDAC inhibitors for malaria.
Published: 2020
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6. An image-based Pathogen Box screen identifies new compounds with anti-Giardia activity and highlights the importance of assay choice in phenotypic drug discovery

Author: Snigdha Tiash, Jake Saunders, Christopher J.S. Hart, John H. Ryan, Andrew G. Riches, and Tina S. Skinner-Adams
Subjects: Infectious and parasitic diseases, RC109-216
Abstract: Giardia duodenalis, the most prevalent human intestinal parasite causes the disease, giardiasis. On an annual basis G. duodenalis infects ~1 billion people, of which ~280 million develop symptomatic disease. Giardiasis can be severe and chronic, causing malnutrition, stunted growth and poor cognitive development in children. Current treatment options rely on drugs with declining efficacy and side-effects. To improve the health and well-being of millions of people world-wide, new anti-Giardia drugs with different modes of action to currently used drugs are required. The Medicines for Malaria Venture's Pathogen Box, a collection of bio-active compounds specifically chosen to stimulate infectious disease drug discovery, represents an opportunity for the discovery of new anti-Giardia agents. While the anti-Giardia activity of Pathogen Box compounds has been reported, this work failed to identify known anti-Giardia controls within the compound set. It also reported the activity of compounds previously screened and shown to be inactive by others, suggesting data may be inaccurate. Given these concerns the anti-Giardia activity of Pathogen Box compounds was re-assessed in the current study. Data from this work identified thirteen compounds with anti-Giardia IC50 values ≤2 μM. Five of these compounds were reference compounds (marketed drugs with known anti-microbial activity), or analogues of compounds with previously described anti-Giardia activity. However, eight, including MMV676358 and MMV028694, which demonstrated potent sub-μM IC50s against assemblage A, B and metronidazole resistant parasites (0.3 μM and 0.9 μM respectively), may represent new leads for future drug development. Interestingly, only four of these compounds were identified in the previously reported Pathogen Box screen highlighting the importance of assay selection and design when assessing compounds for activity against infectious agents. Keywords: Pathogen box, Giardia duodenalis, Drug discovery
Published: 2020
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7. Anatomy of a Transcatheter Mitral Valve Service

Author: Harminder Gill, Heath S. L. Adams, Omar Chehab, Christopher Allen, Jane Hancock, Pablo Lamata, Gianluca Lucchese, Bernard Prendergast, Simon Redwood, Tiffany Patterson, and Ronak Rajani
Subjects: transcatheter mitral valve replacement, mitral regurgitation, Heart Team, mitral edge-to-edge repair, indirect annuloplasty, mitral stenosis, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract: Transcatheter mitral therapies offer treatment options to selected patients who are unable to undergo open procedures due to prohibitive surgical risk. Data detailing the design and structure of transcatheter mitral services to ensure appropriate patient selection and tailored management strategies is lacking. We report our initial experience of developing and running a purpose-built transcatheter mitral service. The nature and number of referral sources, the multi-disciplinary make-up of the dedicated Mitral Heart Team and the use of integrative imaging assessment with incorporation of computational solutions are discussed. In addition, a summary of the clinical decision-making process is presented. This report sets out a framework from which future clinics can evolve to improve and streamline the delivery of transcatheter mitral therapies.
Published: 2022
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8. A Subset Screen of the Compounds Australia Scaffold Library Identifies 7-Acylaminodibenzoxazepinones as Potent and Selective Hits for Anti-Giardia Drug Discovery

Author: Christopher J. S. Hart, Andrew G. Riches, Snigdha Tiash, Erin Clapper, Soumya Ramu, Johannes Zuegg, John H. Ryan, and Tina S. Skinner-Adams
Subjects: Giardia duodenalis, giardiasis, drug discovery, Compounds Australia Scaffold Library, acylaminodibenzoxazepinones, Biology (General), QH301-705.5
Abstract: On an annual basis the flagellate protozoan, Giardia duodenalis, is responsible for an estimated one billion human infections of which approximately two hundred million cause disease. However, the treatment of Giardia infections is reliant on a small group of chemotherapeutic classes that have a broad spectrum of antimicrobial activity and increasing treatment failure rates. To improve this situation, we need new drugs. In this study we screened the Compounds Australia Scaffolds Library for compounds with potent and selective activity against these parasites. Unlike previous drug discovery efforts that have focused on drug repurposing, this library is comprised of commercially available synthetic compounds arranged into lead-like scaffolds to facilitate structure activity relationship assessments and de novo drug discovery. A screen of 2451 compounds in this library identified 40 hits (>50% inhibitory activity at 10 µM, over 48 h). Secondary testing identified three compounds with IC50 values 50-fold selectivity for parasites over mammalian cells and a hit series, CL9406, comprising compounds with potent (lowest IC50 180 nM) and selective activity for Giardia parasites. The most promising compound in this series, SN00797640, displayed selective activity against assemblage A, B, and metronidazole resistant parasites which was parasiticidal (minimum lethal concentration 625 nM) and synergistic with albendazole. SN00797640 was well-tolerated when administered to mice at doses of 50 mg/kg daily for three days paving the way for pre-clinical in vivo activity assessment.
Published: 2022
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9. Deep late-time observations of the supernova impostors SN 1954J and SN 1961V

Author: Rachel A Patton, C S Kochanek, and S M Adams
Published: 2019
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10. The Key Glycolytic Enzyme Phosphofructokinase Is Involved in Resistance to Antiplasmodial Glycosides

Author: Gillian M. Fisher, Simon A. Cobbold, Andrew Jezewski, Emma F. Carpenter, Megan Arnold, Annie N. Cowell, Erick T. Tjhin, Kevin J. Saliba, Tina S. Skinner-Adams, Marcus C. S. Lee, Audrey Odom John, Elizabeth A. Winzeler, Malcolm J. McConville, Sally-Ann Poulsen, and Katherine T. Andrews
Subjects: Plasmodium falciparum, drug resistance mechanisms, drug targets, glycolysis, metabolic regulation, Microbiology, QR1-502
Abstract: ABSTRACT Plasmodium parasites rely heavily on glycolysis for ATP production and for precursors for essential anabolic pathways, such as the methylerythritol phosphate (MEP) pathway. Here, we show that mutations in the Plasmodium falciparum glycolytic enzyme, phosphofructokinase (PfPFK9), are associated with in vitro resistance to a primary sulfonamide glycoside (PS-3). Flux through the upper glycolysis pathway was significantly reduced in PS-3-resistant parasites, which was associated with reduced ATP levels but increased flux into the pentose phosphate pathway. PS-3 may directly or indirectly target enzymes in these pathways, as PS-3-treated parasites had elevated levels of glycolytic and tricarboxylic acid (TCA) cycle intermediates. PS-3 resistance also led to reduced MEP pathway intermediates, and PS-3-resistant parasites were hypersensitive to the MEP pathway inhibitor, fosmidomycin. Overall, this study suggests that PS-3 disrupts core pathways in central carbon metabolism, which is compensated for by mutations in PfPFK9, highlighting a novel metabolic drug resistance mechanism in P. falciparum. IMPORTANCE Malaria, caused by Plasmodium parasites, continues to be a devastating global health issue, causing 405,000 deaths and 228 million cases in 2018. Understanding key metabolic processes in malaria parasites is critical to the development of new drugs to combat this major infectious disease. The Plasmodium glycolytic pathway is essential to the malaria parasite, providing energy for growth and replication and supplying important biomolecules for other essential Plasmodium anabolic pathways. Despite this overreliance on glycolysis, no current drugs target glycolysis, and there is a paucity of information on critical glycolysis targets. Our work addresses this unmet need, providing new mechanistic insights into this key pathway.
Published: 2020
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11. Effect of Inoculant on the Degradation Behaviour of Multi Layered Mild Steel/Al-Cr Plate in Psidium guajava Leaf Extract

Author: M. A. Bawa, M. Abdulwahab, O. B. Umaru, S. M. Adams, L. M. Sani, and N. Agidani
Subjects: Engineering (General). Civil engineering (General), TA1-2040
Abstract: The effect of an inoculant, [triethylamine (TEA)] on the corrosion behavior of multilayered mild steel/Al-Cr plates in guava leaf extract was investigated in 0.5M HCl solution using gravimetric based mass-loss test and potentiodynamic polarization techniques. The mild steel plates were sectioned into coupons of 4 and then pickled, after which they were coated at 750 with an Al-Cr alloy. The gravimetric-based mass loss test was carried out at room temperature for different concentrations and time intervals of 2.0, 4.0, 6.0, 8.0%v/v and 24, 48, 72, 96 hours respectively. The result showed that triethylamine (TEA) decreased the corrosion rate at the various concentrations indicating protection efficiency up to 59.02% in the gravimetric-based-mass-loss technique. Equally the potentiodynamic polarization technique indicates higher corrosion resistance of 98.49%. The two methods used for the evaluation of the degradation of multilayered mild steel/Al-Cr plates in 0.5M HCl/guava leaf extract medium were in agreement.
Published: 2018

12. Effect of Double Thermal Ageing Treatment on the Hardness and Corrosion Resistance of Al- Cu- Si- Ni Alloy in NaCl Solution

Author: M. Abdulwahab, O. B. Umaru, M. A. Bawa, S. M. Adams, and C. S. Ezema
Subjects: Engineering (General). Civil engineering (General), TA1-2040
Abstract: This work investigated the Corrosion behavior and hardness characteristics of double thermally treated Al-Cu-Si-Ni alloy in NaCl solution. The alloy was produced using sand casting method, and sectioned into small pieces of 10mm long each. Some of the sectioned samples were subjected to single thermal ageing treatment (STAT) and used as control, while others were subjected to double thermal ageing treatment (DTAT). The thermally treated samples were used for corrosion and hardness test in accordance with ASTM A370 and ASTM E8-08b. The result showed that the double thermally treated samples have higher hardness value than the single thermally treated samples as the ageing time increases with an increase of 24.6% at 2hrs. Equally, the corrosion resistance of the treated alloy improved with ageing time.
Published: 2018

13. Activity of bromodomain protein inhibitors/binders against asexual-stage Plasmodium falciparum parasites

Author: Ming Jang Chua, Dina Robaa, Tina S. Skinner-Adams, Wolfgang Sippl, and Katherine T. Andrews
Subjects: Infectious and parasitic diseases, RC109-216
Abstract: Bromodomain-containing proteins (BDPs) are involved in the regulation of eukaryotic gene expression. Compounds that bind and/or inhibit BDPs are of interest as tools to better understand epigenetic regulation, and as possible drug leads for different diseases, including malaria. In this study, we assessed the activity of 42 compounds demonstrated or predicted (using virtual screening of a pharmacophore model) to bind/inhibit eukaryotic BDPs for activity against Plasmodium falciparum malaria parasites. In silico docking studies indicated that all compounds are predicted to participate in a typical hydrogen bond interaction with the conserved asparagine (Asn1436) of the P. falciparum histone acetyltransferase (PfGCN5) bromodomain and a conserved water molecule. Only one compound (the dimethylisoxazole SGC-CBP30; a selective inhibitor of CREBBP (CBP) and EP300 bromodomains) is also predicted to have a salt-bridge between the morpholine nitrogen and Glu1389. When tested for in vitro activity against asynchronous asexual stage P. falciparum Dd2 parasites, all compounds displayed 50% growth inhibitory concentrations (IC50) >10 μM. Further testing of the three most potent compounds using synchronous parasites for 72 h showed that SGC-CBP30 was the most active (IC50 3.2 μM). In vitro cytotoxicity assays showed that SGC-CBP30 has ∼7-fold better selectivity for the parasites versus a human cell line (HEK 293). Together these data provide a possible starting point for future investigation of these, or related compounds, as tools to understand epigenetic regulation or as potential new drug leads. Keywords: Plasmodium falciparum, Anti-plasmodial activity, Bromodomain protein inhibitor
Published: 2018
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14. Comportamento ingestivo de bovinos jovens mantidos em pasto de sorgo ou milheto

Author: P. M. Martini, I. L. Brondani, D. C. Alves Filho, A. F. P. Viana, S. M. Adams, J. L. Klein, L. S. Rodrigues, and J. Cattelam
Subjects: novilhos, padrões de deslocamento, Pennisetum, Sorghum, tempo de pastejo, Animal culture, SF1-1100
Abstract: Objetivou-se com este estudo avaliar o comportamento ingestivo e os padrões de deslocamento de novilhos de corte mantidos em pastagens de milheto ou de sorgo. Os tratamentos consistiam em: pastagem de milheto (Pennisetum americanum Leeke) ou pastagem de sorgo (Sorghum bicolor L. Moench), ambos submetidos à lotação contínua. Foram utilizados 18 novilhos, oriundos do cruzamento entre as raças Charolês e Nelore, com idade média inicial de 14 meses, e peso corporal inicial de 195 kg. O delineamento experimental foi blocos ao acaso com 3 repetições e parcelas subdivididas no tempo em 3 períodos, sendo os dados submetidos a análise de variância através do proc MIXED com P
Published: 2018
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15. A novel in vitro image-based assay identifies new drug leads for giardiasis

Author: Christopher J.S. Hart, Taylah Munro, Katherine T. Andrews, John H. Ryan, Andrew G. Riches, and Tina S. Skinner-Adams
Subjects: Giardia, Drug discovery, Malaria Box, Image-based assay, Infectious and parasitic diseases, RC109-216
Abstract: Giardia duodenalis is an intestinal parasite that causes giardiasis, a widespread human gastrointestinal disease. Treatment of giardiasis relies on a small arsenal of compounds that can suffer from limitations including side-effects, variable treatment efficacy and parasite drug resistance. Thus new anti-Giardia drug leads are required. The search for new compounds with anti-Giardia activity currently depends on assays that can be labour-intensive, expensive and restricted to measuring activity at a single time-point. Here we describe a new in vitro assay to assess anti-Giardia activity. This image-based assay utilizes the Perkin-Elmer Operetta® and permits automated assessment of parasite growth at multiple time points without cell-staining. Using this new approach, we assessed the “Malaria Box” compound set for anti-Giardia activity. Three compounds with sub-μM activity (IC50 0.6–0.9 μM) were identified as potential starting points for giardiasis drug discovery.
Published: 2017
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16. Effect of clinically approved HDAC inhibitors on Plasmodium, Leishmania and Schistosoma parasite growth

Author: Ming Jang Chua, Megan S.J. Arnold, Weijun Xu, Julien Lancelot, Suzanne Lamotte, Gerald F. Späth, Eric Prina, Raymond J. Pierce, David P. Fairlie, Tina S. Skinner-Adams, and Katherine T. Andrews
Subjects: Plasmodium, Schistosoma, Leishmania, Histone deacetylase, Panobinostat, Infectious and parasitic diseases, RC109-216
Abstract: Malaria, schistosomiasis and leishmaniases are among the most prevalent tropical parasitic diseases and each requires new innovative treatments. Targeting essential parasite pathways, such as those that regulate gene expression and cell cycle progression, is a key strategy for discovering new drug leads. In this study, four clinically approved anti-cancer drugs (Vorinostat, Belinostat, Panobinostat and Romidepsin) that target histone/lysine deacetylase enzymes were examined for in vitro activity against Plasmodium knowlesi, Schistosoma mansoni, Leishmania amazonensis and L. donovani parasites and two for in vivo activity in a mouse malaria model. All four compounds were potent inhibitors of P. knowlesi malaria parasites (IC50 9–370 nM), with belinostat, panobinostat and vorinostat having 8–45 fold selectivity for the parasite over human neonatal foreskin fibroblast (NFF) or human embryonic kidney (HEK 293) cells, while romidepsin was not selective. Each of the HDAC inhibitor drugs caused hyperacetylation of P. knowlesi histone H4. None of the drugs was active against Leishmania amastigote or promastigote parasites (IC50 > 20 μM) or S. mansoni schistosomula (IC50 > 10 μM), however romidepsin inhibited S. mansoni adult worm parings and egg production (IC50 ∼10 μM). Modest in vivo activity was observed in P. berghei infected mice dosed orally with vorinostat or panobinostat (25 mg/kg twice daily for four days), with a significant reduction in parasitemia observed on days 4–7 and 4–10 after infection (P
Published: 2017
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17. Study on the Bioconversion of Curcumin to Calebin-A Using Spirulina subsalsa and Its Taxonomic Resolution Using 16S rRNA Analysis

Author: T. Shakena Fathima, S. John Adams, Anju Majeed, G. Muralitharan, and N. Thajuddin
Subjects: Bioengineering, General Medicine, Molecular Biology, Applied Microbiology and Biotechnology, Biochemistry, Biotechnology
Published: 2022
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18. Structural reassignment of a dibenz[

Author: Andrew G. Riches, Christopher J. S. Hart, Matthieu Schmit, Emmanuel A. Debele, Snigdha Tiash, Erin Clapper, Tina S. Skinner-Adams, and John H. Ryan
Subjects: General Chemistry
Abstract: A screen for compounds with antigiardial activity in the Compounds Australia Scaffolds library identified SN00797640 (supplied structure being 8-acylaminodibenzoxazepinone 1) as a hit compound with potent anti-parasitic activity (concentration for 50% growth inhibition of Giardia duodenalis, IC50 0.18 μM). To further explore the structure–activity relationships in this series, compound 1 and analogues, including its 7-acylaminodibenzoxazepinone regioisomer (2), were synthesized and assessed for anti-Giardia activity. While regioisomer 2 demonstrated antigiardial activity, resynthesized 1 and other 8-acylaminodibenzoxazepinone analogues were inactive. Comparison of spectroscopic and physical properties demonstrated the correct structure of SN00797640 to be 7-acylamino regioisomer 2. These results highlight the importance of independent synthesis in verifying the structure and activity of screening hits.
Published: 2022
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19. Discovery of 1,3,4-oxadiazoles with slow-action activity againstPlasmodium falciparummalaria parasites

Author: Katherine T. Andrews, Gillian M. Fisher, Meaghan Firmin, Andris J. Liepa, Tony Wilson, James Gardiner, Yacine Mohri, Anjana Rai, Andrew K. Davey, Antoine Masurier, Alix Delion, Alexandos A. Mouratidis, Oliver Hutt, Jeremy N. Burrows, John H. Ryan, Andrew G. Riches, and Tina S. Skinner-Adams
Abstract: To achieve malaria eradication, new preventative agents that act differently to front-line treatment drugs are needed. To identify potential chemoprevention starting points we screened a sub-set of the CSIRO Australia Compound Collection for compounds with slow-actionin vitroactivity againstPlasmodium falciparum. This work identifiedN,N-dialkyl-5-alkylsulfonyl-1,3,4-oxadiazol-2-amines as a new antiplas-modial chemotype (e.g.,196 h IC50550 nM) with a different action to delayed-death slow-action drugs. Structure activity relationship analysis of analogues identified multiple compounds with potent and selectivein vitroactivity against drug-sensitive and multi-drug resistantPlasmodiumparasites (e.g.,31and3296 h IC502,500). However subsequent studies in mice with lead compound1, which had the best microsomal stability of the compounds assessed, demonstrated rapid clearance (T1/2<1.6 h) and poor oralin vivoefficacy. This indicates that improvements in the pharmacokinetic profile ofN,N-dialkyl-5-alkylsulfonyl-1,3,4-oxadiazol-2-amines would be needed for the development of this chemotype for malaria chemoprophylaxis.
Published: 2023
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20. Reading a preoperative CT scan to guide complex abdominal wall reconstructive surgery

Author: S. T. Adams, D. Slade, P. Shuttleworth, C. West, M. Scott, A. Benson, A. Tokala, and C. J. Walsh
Subjects: Surgery
Published: 2022
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21. Collaboration for conservation : Assessing countrywide carnivore occupancy dynamics from sparse data

Author: Tempe S. F. Adams, Genevieve E. Finerty, Derek Keeping, Moses Selebatso, Botilo Tshimologo, Matthew Bowles, Dominik Bauer, Andrew B. Stein, Kristina Kesch, Kevin McFarlane, Carolyn Whitesell, Keitumetse Ngaka, J. Weldon McNutt, Krystyna A. Golabek, Glyn Maude, Michael J. Chase, Nicolas Proust, Emily Bennitt, Mompoloi Morapedi, Marie Charlotte Gielen, Andrei Snyman, Lindsey N. Rich, Femke Broekhuis, Christiaan W. Winterbach, Michael V. Flyman, Mathias W. Tobler, Jessica Isden, Rebecca C. Klein, Florian J. Weise, Simon Morgan, Leanne K. Van der Weyde, Gabriele Cozzi, Robert Sutcliff, Kai Collins, Marnus Roodbal, Steve Henley, Robyn Hartley, Robynne Kotze, Alienor Brassine, Eric G. LeFlore, Morulaganyi Kokole, and Gus Mills
Subjects: Occupancy, Botswana, data sharing, distribution, human-dominated landscapes, imperfect detection, management, protected areas, data sharing, Population, Wildlife, imperfect detection, human-dominated landscapes, ddc:570, biology.animal, distribution, Carnivore, education, Ecology, Evolution, Behavior and Systematics, Wildlife conservation, education.field_of_study, Botswana, biology, business.industry, Ecology, Environmental resource management, Leopard, biology.organism_classification, Brown hyaena, PE&RC, Geography, Hyaena, Wildlife Ecology and Conservation, protected areas, business, management
Abstract: AimAssessing the distribution and persistence of species across their range is a crucial component of wildlife conservation. It demands data at adequate spatial scales and over extended periods of time, which may only be obtained through collaborative efforts, and the development of methods that integrate heterogeneous datasets. We aimed to combine existing data on large carnivores to evaluate population dynamics and improve knowledge on their distribution nationwide.LocationBotswana.MethodsBetween 2010 and 2016, we collated data on African wild dog, cheetah, leopard, brown and spotted hyaena and lion gathered with different survey methods by independent researchers across Botswana. We used a multi-species, multi-method dynamic occupancy model to analyse factors influencing occupancy, persistence and colonization, while accounting for imperfect detection. Lastly, we used the gained knowledge to predict the probability of occurrence of each species countrywide.ResultsWildlife areas and communal rangelands had similar occupancy probabilities for most species. Large carnivore occupancy was low in commercial farming areas and where livestock density was high, except for brown hyaena. Lion occupancy was negatively associated with human density; lion and spotted hyaena occupancy was high where rainfall was high, while the opposite applied to brown hyaena. Lion and leopard occupancy remained constant countrywide over the study period. African wild dog and cheetah occupancy declined over time in the south and north, respectively, whereas both hyaena species expanded their ranges. Countrywide predictions identified the highest occupancy for leopards and lowest for the two hyaena species.Main ConclusionsWe highlight the necessity of data sharing and propose a generalizable analytical method that addresses the challenges of heterogeneous data common in ecology. Our approach, which enables a comprehensive multi-species assessment at large spatial and temporal scales, supports the development of data-driven conservation guidelines and the implementation of evidence-based management strategies nationally and internationally. published
Published: 2022
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22. Histone deacetylase inhibitor AR-42 and achiral analogues kill malaria parasites in vitro and in mice

Author: Eva Hesping, Andrew J. Lucke, Jiahui Tng, Christopher D. Goodman, David P. Fairlie, Katherine T. Andrews, Robert Reid, Tina S. Skinner-Adams, Darren Do, Ming Jang Chua, and Gillian M. Fisher
Subjects: Regular article, Plasmodium berghei, medicine.drug_class, Plasmodium falciparum, Infectious and parasitic diseases, RC109-216, P. falciparum, Pharmacology, Histone H4, Antimalarials, Mice, HDAC inhibitor, parasitic diseases, medicine, Animals, AR-42, Parasites, Pharmacology (medical), IC50, Chemistry, Histone deacetylase inhibitor, medicine.disease, In vitro, HDAC1, Malaria, Histone Deacetylase Inhibitors, Infectious Diseases, Mechanism of action, Parasitology, medicine.symptom, Ex vivo
Abstract: Malaria is caused by infection with Plasmodium parasites and results in significant health and economic impacts. Malaria eradication is hampered by parasite resistance to current drugs and the lack of a widely effective vaccine. Compounds that target epigenetic regulatory proteins, such as histone deacetylases (HDACs), may lead to new therapeutic agents with a different mechanism of action, thereby avoiding resistance mechanisms to current antimalarial drugs. The anticancer HDAC inhibitor AR-42, as its racemate (rac-AR-42), and 36 analogues were investigated for in vitro activity against P. falciparum. Rac-AR-42 and selected compounds were assessed for cytotoxicity against human cells, histone hyperacetylation, human HDAC1 inhibition and oral activity in a murine malaria model. Rac-AR-42 was tested for ex vivo asexual and in vitro exoerythrocytic stage activity against P. berghei murine malaria parasites. Rac-AR-42 and 13 achiral analogues were potent inhibitors of asexual intraerythrocytic stage P. falciparum 3D7 growth in vitro (IC50 5–50 nM), with four of these compounds having >50-fold selectivity for P. falciparum versus human cells (selectivity index 56–118). Rac-AR-42 induced in situ hyperacetylation of P. falciparum histone H4, consistent with PfHDAC(s) inhibition. Furthermore, rac-AR-42 potently inhibited P. berghei infected erythrocyte growth ex vivo (IC50 40 nM) and P. berghei exoerythrocytic forms in hepatocytes (IC50 1 nM). Oral administration of rac-AR-42 and two achiral analogues inhibited P. berghei growth in mice, with rac-AR-42 (50 mg/kg/day single dose for four days) curing all infections. These findings demonstrate curative properties for HDAC inhibitors in the oral treatment of experimental mouse malaria., Graphical abstract Image 1, Highlights • HDAC inhibitors rac-AR-42 and 13 analogues inhibit P. falciparum growth in vitro. • Rac-AR-42 inhibits P. berghei exoerythrocytic forms in hepatocytes (IC50 1 nM). • Rac-AR-42 causes in situ hyperacetylation of P. falciparum histone H4. • Rac-AR-42 cures P. berghei infected mice with oral dosing.
Published: 2021
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23. Synthesis and Antiplasmodial Evaluation of Analogues Based on the Tricyclic Core of Thiaplakortones A–D

Author: Brett D. Schwartz, Mark J. Coster, Tina S. Skinner-Adams, Katherine T. Andrews, Jonathan M. White, and Rohan A. Davis
Subjects: synthesis, thiaplakortone, regioisomer, tricyclic, natural product scaffold, X-ray, crystal, Plasmodium falciparum, antiplasmodial, cytotoxicity, Biology (General), QH301-705.5
Abstract: Six regioisomers associated with the tricyclic core of thiaplakortones A–D have been synthesized. Reaction of 1H-indole-4,7-dione and 1-tosyl-1H-indole-4,7-dione with 2-aminoethanesulfinic acid afforded a regioisomeric series, which was subsequently deprotected and oxidized to yield the tricyclic core scaffolds present in the thiaplakortones. All compounds were fully characterized using NMR and MS data. A single crystal X-ray structure was obtained on one of the N-tosyl derivatives. All compounds were screened for in vitro antiplasmodial activity against chloroquine-sensitive (3D7) and multidrug-resistant (Dd2) Plasmodium falciparum parasite lines. Several analogues displayed potent inhibition of P. falciparum growth (IC50 < 500 nM) but only moderate selectivity for P. falciparum versus human neonatal foreskin fibroblast cells.
Published: 2015
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24. Corrosion Inhibition Study of Al-Cu-Ni Alloy in Simulated Sea-Water Environment

Author: S. M. Adams, S. A. Yaro, M. Abdulwahab, and O. B. Umaru
Subjects: inhibition, simulated sea-water, corrosion, alloy, concentration, Technology, Geophysics. Cosmic physics, QC801-809
Abstract: A study on the inhibition of Al-Cu-Ni alloy in simulated sea-water environment was investigated using Sodium Chromate as inhibitor. The inhibitor concentration was varied as control, 0.25, 0.5, 1.0, 1.5 and 2.0 Molar. Al-Cu-Ni alloy was sand cast into cylindrical bars of 20 mm x 300 mm dimension. The corrosion of the sand-cast and treated alloys in 3.5wt% sodium chloride solution at temperatures 30oC, 50oC and 70oC over 1-5 hrs was evaluated using the weight loss method. It was observed that the corrosion rate of the treated alloys decreases with increase in inhibitor concentration. The decrease in corrosion rate on addition of the inhibitor can be attributed to the adsorption of the inhibitor onto the surface of the alloy. The attachment is by physical adsorption as the values of heat of adsorption were less than -10 kJ/mol. The plots obtained were linear meaning that they obey the Langmuir and Temkin adsorption isotherms. The inhibition efficiency increases generally with increase in temperature and inhibitor concentration.
Published: 2015
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25. Separating the components of an abdominal wall fellowship

Author: S T, Adams, M, Scott, C, West, and C J, Walsh
Subjects: Surgery, General Medicine
Abstract: Complex abdominal wall reconstruction is an emerging subspecialty yet, despite the abundance of abdominal wall hernias requiring treatment and the increasing complexity of this type of surgery, there are few opportunities for surgeons to gain subspecialist training in this field. In this paper we discuss the need for focused training in complex abdominal wall reconstruction, outline some of the problems that may be hindering the availability of such opportunities and propose potential solutions to these issues.
Published: 2022
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26. Anti-Giardia Drug Discovery: Current Status and Gut Feelings

Author: Tina S. Skinner-Adams, Christopher J.S. Hart, Katharine R. Trenholme, and Andrew G. Riches
Subjects: 0303 health sciences, medicine.medical_specialty, biology, Chemistry, Drug discovery, Giardia, Enteric pathogen, Drug resistance, biology.organism_classification, Antimicrobial, 01 natural sciences, Giardia Infections, 0104 chemical sciences, 010404 medicinal & biomolecular chemistry, 03 medical and health sciences, Pharmacotherapy, parasitic diseases, Drug Discovery, medicine, Molecular Medicine, Health education, Intensive care medicine, 030304 developmental biology
Abstract: Giardia parasites are ubiquitous protozoans of global importance that impact a wide range of animals including humans. They are the most common enteric pathogen of cats and dogs in developed countries and infect ∼1 billion people worldwide. While Giardia infections can be asymptomatic, they often result in severe and chronic diseases. There is also mounting evidence that they are linked to postinfection disorders. Despite growing evidence of the widespread morbidity associated with Giardia infections, current treatment options are limited to compound classes with broad antimicrobial activity. Frontline anti-Giardia drugs are also associated with increasing drug resistance and treatment failures. To improve the health and well-being of millions, new selective anti-Giardia drugs are needed alongside improved health education initiatives. Here we discuss current treatment options together with recent advances and gaps in drug discovery. We also propose criteria to guide the discovery of new anti-Giardia compounds.
Published: 2020
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27. Panic at the disco: solar-powered strobe light barriers reduce field incursion by African elephantsLoxodonta africanain Chobe District, Botswana

Author: Neil R. Jordan, Isaiah Mwezi, and Tempe S. F. Adams
Subjects: 0106 biological sciences, biology, Agroforestry, National park, 010501 environmental sciences, Strobe light, 010603 evolutionary biology, 01 natural sciences, Urban expansion, African elephant, Geography, biology.animal, Panthera, Solar powered, Forest reserve, Ecology, Evolution, Behavior and Systematics, 0105 earth and related environmental sciences, Nature and Landscape Conservation
Abstract: Managing interactions between humans and wild elephants is a complex problem that is increasing as a result of agricultural and urban expansion into and alongside protected areas. Mitigating negative interactions requires the development of new tools to reduce competition and promote coexistence. Many studies have tested various mitigation techniques across elephant ranges in Africa and Asia, with varying levels of success. Recently, strobe lights have been suggested as a potential mitigation strategy in deterring African lionsPanthera leofrom kraals or bomas, but this technique has to date not been tested to reduce negative human–elephant interactions. Over a 2-year period (November 2016–June 2018), we tested the effectiveness of solar-powered strobe light barriers in deterring African elephantsLoxodonta africana, in collaboration with 18 farmers in a community adjacent to the Chobe Forest Reserve and Chobe National Park in northern Botswana. Although elephants were more likely to pass by fields with solar-powered strobe light barriers (which was probably a result of selection bias as we focused on fields that had previously been damaged by elephants), they were less likely to enter these treatment fields than control fields without such barriers. Our findings demonstrate the efficacy of light barriers to reduce negative human–elephant interactions in rural communities.
Published: 2020
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28. Novel Extract of Cyperus Esculentus Leaves as Green Corrosion Inhibitor for Mild Steel in 0.5M NaCl Aqueous Solution

Author: Ojiugo N.U, S M Adams, and M Abdulwahab
Subjects: Corrosion inhibitor, chemistry.chemical_compound, Aqueous solution, Cyperus, chemistry, biology, biology.organism_classification, Nuclear chemistry
Published: 2020
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29. Anti-malaria drug development targeting the M1 alanyl and M17 leucyl aminopeptidases

Author: Karine Thivierge, Rency T. Mathew, Desire M. M. Nsangou, Fabio Da Silva, Sophie Cotton, Tina S. Skinner-Adams, Katharine R. Trenholme, Christopher L. Brown, Colin M. Stack, Donald L. Gardiner, and John P. Dalton
Subjects: Organic chemistry, QD241-441
Published: 2012
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30. QSAR Classification Models for Prediction of Hydroxamate Histone Deacetylase Inhibitor Activity against Malaria Parasites

Author: Eva Hesping, Ming Jang Chua, Marc Pflieger, Yunan Qian, Lilong Dong, Prabhakar Bachu, Ligong Liu, Thomas Kurz, Gillian M. Fisher, Tina S. Skinner-Adams, Robert C. Reid, David P. Fairlie, Katherine T. Andrews, and Alain-Dominique J.P. Gorse
Subjects: Histone Deacetylase Inhibitors, Infectious Diseases, Plasmodium falciparum, Animals, Humans, Quantitative Structure-Activity Relationship, Parasites, Hydroxamic Acids, Malaria
Abstract: Malaria, caused by
Published: 2022

31. Identifying and explaining the variability in development and implementation costs of disease management programs in the Netherlands

Author: A. Tsiachristas, B. Hipple Waters, S. A. Adams, R. Bal, and M. P.M.M. Rutten-van Mölken
Subjects: chronic disease, disease management, integrated care, costs, the netherlands, Medicine (General), R5-920
Published: 2015
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32. AT2018lqh and the nature of the emerging population of day-scale duration optical transients

Author: E. O. Ofek, S. M. Adams, E. Waxman, A. Sharon, D. Kushnir, A. Horesh, A. Ho, M. M. Kasliwal, O. Yaron, A. Gal-Yam, S. R. Kulkarni, E. Bellm, F. Masci, D. Shupe, R. Dekany, M. Graham, R. Riddle, D. Duev, I. Andreoni, A. Mahabal, and A. Drake
Subjects: High Energy Astrophysical Phenomena (astro-ph.HE), 010308 nuclear & particles physics, 13. Climate action, Space and Planetary Science, 0103 physical sciences, FOS: Physical sciences, Astronomy and Astrophysics, Astrophysics - High Energy Astrophysical Phenomena, 010303 astronomy & astrophysics, 01 natural sciences, 7. Clean energy
Abstract: We report on the discovery of AT2018lqh (ZTF18abfzgpl) -- a rapidly-evolving extra-galactic transient in a star-forming host at 242 Mpc. The transient g-band light curve's duration above half-maximum light is about 2.1 days, where 0.4/1.7 days are spent on the rise/decay, respectively. The estimated bolometric light curve of this object peaked at about 7x10^42 erg/s -- roughly seven times brighter than AT2017gfo. We show that this event can be explained by an explosion with a fast (v~0.08 c) low-mass (~0.07 Msun) ejecta, composed mostly of radioactive elements. For example, ejecta dominated by Ni-56 with a time scale of t_0=1.6 days for the ejecta to become optically thin for gamma-rays fits the data well. Such a scenario requires burning at densities that are typically found in the envelopes of neutron stars or the cores of white dwarfs. A combination of circumstellar material (CSM) interaction power at early times and shock cooling at late times is consistent with the photometric observations, but the observed spectrum of the event may pose some challenges for this scenario. The observations are not consistent with a shock breakout from a stellar envelope, while a model involving a low-mass ejecta ramming into low-mass CSM cannot explain both the early- and late-time observations., 10 pages, ApJ in press
Published: 2021

33. Reading a preoperative CT scan to guide complex abdominal wall reconstructive surgery

Author: S T, Adams, D, Slade, P, Shuttleworth, C, West, M, Scott, A, Benson, A, Tokala, and C J, Walsh
Abstract: Computed tomography (CT) scanning is the imaging modality of choice when planning the overall management and operative approach to complex abdominal wall hernias. Despite its availability and well-recognised benefits there are no guidelines or recommendations regarding how best to read or report such scans for this application. In this paper we aim to outline an approach to interpreting preoperative CT scans in abdominal wall reconstruction (AWR). This approach breaks up the interpretive process into 4 steps-concentrating on the hernia or hernias, any complicating features of the hernia(s), the surrounding soft tissues and the abdominopelvic cavity as a whole-and was developed as a distillation of the authors' collective experience. We describe the key features that should be looked for at each of the four steps and the rationale for their inclusion.
Published: 2021

34. Practical XNS internetworking at BLS.

Author: Walter S. N. Adams
Published: 1990
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35. Effects of pressure changes induced by commercial navigation traffic on mortality of fish early life stages

Author: S. Reid Adams, K. Jack Killgore, David J. Schaeffer, and Thomas M. Keevin
Subjects: 0106 biological sciences, Larva, food.ingredient, biology, 010604 marine biology & hydrobiology, Micropterus, 04 agricultural and veterinary sciences, Aquatic Science, biology.organism_classification, 01 natural sciences, Fishery, Bass (fish), Ictiobus cyprinellus, food, Water column, Ictalurus, 040102 fisheries, 0401 agriculture, forestry, and fisheries, Juvenile, Blue catfish
Abstract: Mortality of fish early life stages was measured in a pressure vessel to simulate vertical displacement within the water column. Mortality was measured for three pressure regimes for four fish species: larval bigmouth buffalo Ictiobus cyprinellus, larval blue catfish Ictalurus furcatus, juvenile bluegill Lepomis macrochirus, and juvenile largemouth bass Micropterus salmoides. The maximum pressure‐change tested, 344.8 kPa, equivalent to a 35.2 m displacement of fish within the water column, did not cause significant mortality of larvae or juveniles. Since 32.5 m exceeds depths in most inland navigation channels and possibly the depth to which rapid propeller induced water mixing occurs, the range of pressure changes that could be experienced by early life stages during towboat mixing of the water column will not result in significant mortality.
Published: 2019
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36. Proteomic analysis of Plasmodium falciparum histone deacetylase 1 complex proteins

Author: Jude M. Przyborski, Tina S. Skinner-Adams, Paul R. Gilson, Jessica A. Engel, Jeffrey J. Gorman, Madeleine J. Headlam, Gregory L. Blatch, Addmore Shonhai, Emma L. Norris, and Katherine T. Andrews
Subjects: Proteomics, Regulation of gene expression, biology, Blotting, Western, Plasmodium falciparum, Immunology, Protozoan Proteins, Histone Deacetylase 1, General Medicine, biology.organism_classification, Mass Spectrometry, HDAC1, Cell biology, Infectious Diseases, Histone, Heat shock protein, parasitic diseases, biology.protein, Immunoprecipitation, Electrophoresis, Polyacrylamide Gel, Parasitology, Histone deacetylase, Epigenetics
Abstract: Plasmodium falciparum histone deacetylases (PfHDACs) are an important class of epigenetic regulators that alter protein lysine acetylation, contributing to regulation of gene expression and normal parasite growth and development. PfHDACs are therefore under investigation as drug targets for malaria. Despite this, our understanding of the biological roles of these enzymes is only just beginning to emerge. In higher eukaryotes, HDACs function as part of multi-protein complexes and act on both histone and non-histone substrates. Here, we present a proteomics analysis of PfHDAC1 immunoprecipitates, identifying 26 putative P. falciparum complex proteins in trophozoite-stage asexual intraerythrocytic parasites. The co-migration of two of these (P. falciparum heat shock proteins 70-1 and 90) with PfHDAC1 was validated using Blue Native PAGE combined with Western blot. These data provide a snapshot of possible PfHDAC1 interactions and a starting point for future studies focused on elucidating the broader function of PfHDACs in Plasmodium parasites.
Published: 2019
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37. Antiplasmodial activity of the natural product compounds alstonine and himbeline

Author: Gillian M. Fisher, J.R. Macdonald, Katherine T. Andrews, Ronald J. Quinn, Tina S. Skinner-Adams, and Megan Sarah Jean Arnold
Subjects: 0301 basic medicine, Drug, media_common.quotation_subject, 030231 tropical medicine, Plasmodium falciparum, Drug resistance, Infectious and parasitic diseases, RC109-216, Pharmacology, Biology, P. falciparum, Alstonine, Chemoprevention, 03 medical and health sciences, chemistry.chemical_compound, Antimalarials, 0302 clinical medicine, parasitic diseases, medicine, Humans, Pharmacology (medical), Artemisinin, Malaria, Falciparum, IC50, media_common, Natural products, Biological Products, Natural product, Drug discovery, Himbeline, medicine.disease, Secologanin Tryptamine Alkaloids, 030104 developmental biology, Infectious Diseases, chemistry, Parasitology, Malaria, medicine.drug
Abstract: Malaria, caused by Plasmodium parasites, continues to be a devastating global health issue. Despite a decline in malaria related deaths over the last decade, overall progress has plateaued. Key challenges to malaria prevention and control include the lack of a broadly effective vaccine and parasite drug resistance, including to the current gold standard artemisinin combination therapies (ACTs). New drugs with unique modes of action are therefore a priority for both the treatment and prevention of malaria. Unlike treatment drugs which need to kill parasites quickly to reduce or prevent clinical symptoms, compounds that kill parasites more slowly may be an option for malaria prevention. Natural products and natural product derived compounds have historically been an excellent source of antimalarial drugs, including the artemisinin component of ACTs. In this study, 424 natural product derived compounds were screened for in vitro activity against P. falciparum in assays designed to detect slow action activity, with 46 hit compounds identified as having >50% inhibition at 10 μM. Dose response assays revealed nine compounds with submicromolar activity, with slow action activity confirmed for two compounds, alstonine and himbeline (50% inhibitory concentration (IC50) 0.17 and 0.58 μM, respectively). Both compounds displayed >140-fold better activity against P. falciparum versus two human cell lines (Selectivity Index (SI) >1,111 and > 144, respectively). Importantly, P. falciparum multi-drug resistant lines showed no cross-resistance to alstonine or himbeline, with some resistant lines being more sensitive to these two compounds compared to the drug sensitive line. In addition, alstonine displayed cross-species activity against the zoonotic species, P. knowelsi (IC50 ~1 μM). Outcomes of this study provide a starting point for further investigations into these compounds as antiplasmodial drug candidates and the investigation of their molecular targets.
Published: 2021

38. The Key Glycolytic Enzyme Phosphofructokinase Is Involved in Resistance to Antiplasmodial Glycosides

Author: Audrey R. Odom John, Emma F. Carpenter, Annie N. Cowell, Sally-Ann Poulsen, Simon A. Cobbold, Marcus C. S. Lee, Katherine T. Andrews, Gillian M. Fisher, Tina S. Skinner-Adams, Erick T. Tjhin, Megan Sarah Jean Arnold, Elizabeth A. Winzeler, Malcolm J. McConville, Kevin J. Saliba, and Andrew J. Jezewski
Subjects: Models, Molecular, Molecular Biology and Physiology, Erythrocytes, Anabolism, Protein Conformation, Plasmodium falciparum, Drug Resistance, Biology, Pentose phosphate pathway, Polymorphism, Single Nucleotide, Microbiology, Antimalarials, Structure-Activity Relationship, 03 medical and health sciences, Parasitic Sensitivity Tests, Virology, drug targets, parasitic diseases, medicine, Metabolomics, Glycolysis, Glycosides, Phosphofructokinases, Alleles, 030304 developmental biology, chemistry.chemical_classification, 0303 health sciences, Dose-Response Relationship, Drug, Molecular Structure, 030306 microbiology, glycolysis, biology.organism_classification, QR1-502, Fosmidomycin, Enzyme, drug resistance mechanisms, chemistry, Biochemistry, metabolic regulation, Research Article, medicine.drug, Phosphofructokinase
Abstract: Malaria, caused by Plasmodium parasites, continues to be a devastating global health issue, causing 405,000 deaths and 228 million cases in 2018. Understanding key metabolic processes in malaria parasites is critical to the development of new drugs to combat this major infectious disease. The Plasmodium glycolytic pathway is essential to the malaria parasite, providing energy for growth and replication and supplying important biomolecules for other essential Plasmodium anabolic pathways. Despite this overreliance on glycolysis, no current drugs target glycolysis, and there is a paucity of information on critical glycolysis targets. Our work addresses this unmet need, providing new mechanistic insights into this key pathway., Plasmodium parasites rely heavily on glycolysis for ATP production and for precursors for essential anabolic pathways, such as the methylerythritol phosphate (MEP) pathway. Here, we show that mutations in the Plasmodium falciparum glycolytic enzyme, phosphofructokinase (PfPFK9), are associated with in vitro resistance to a primary sulfonamide glycoside (PS-3). Flux through the upper glycolysis pathway was significantly reduced in PS-3-resistant parasites, which was associated with reduced ATP levels but increased flux into the pentose phosphate pathway. PS-3 may directly or indirectly target enzymes in these pathways, as PS-3-treated parasites had elevated levels of glycolytic and tricarboxylic acid (TCA) cycle intermediates. PS-3 resistance also led to reduced MEP pathway intermediates, and PS-3-resistant parasites were hypersensitive to the MEP pathway inhibitor, fosmidomycin. Overall, this study suggests that PS-3 disrupts core pathways in central carbon metabolism, which is compensated for by mutations in PfPFK9, highlighting a novel metabolic drug resistance mechanism in P. falciparum.
Published: 2020
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39. Anti

Author: Andrew, Riches, Christopher J S, Hart, Katharine R, Trenholme, and Tina S, Skinner-Adams
Subjects: Gastrointestinal Tract, Giardiasis, Drug Delivery Systems, Nitroimidazoles, Giardia, Drug Discovery, Antiprotozoal Agents, Animals, Humans, Benzimidazoles, Drug Therapy, Combination
Published: 2020

40. Post-Consumer Plastics Recycling

Author: John C. Even and S. Keith Adams
Published: 2020
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41. The frequency of malaria is similar among women receiving either lopinavir/ritonavir or nevirapine-based antiretroviral treatment.

Author: Tina S Skinner-Adams, Alice S Butterworth, Kimberly A Porter, Ronald D'Amico, Fred Sawe, Doug Shaffer, Abraham Siika, Mina C Hosseinipour, Elizabeth Stringer, Judith S Currier, Tsungai Chipato, Robert Salata, Shahin Lockman, Joseph J Eron, Steven R Meshnick, and James S McCarthy
Subjects: Medicine, Science
Abstract: HIV protease inhibitors (PIs) show antimalarial activity in vitro and in animals. Whether this translates into a clinical benefit in HIV-infected patients residing in malaria-endemic regions is unknown. We studied the incidence of malaria, as defined by blood smear positivity or a positive Plasmodium falciparum histidine-rich protein 2 antigen test, among 444 HIV-infected women initiating antiretroviral treatment (ART) in the OCTANE trial (A5208; ClinicalTrials.gov: NCT00089505). Participants were randomized to treatment with PI-containing vs. PI-sparing ART, and were followed prospectively for ≥48 weeks; 73% also received cotrimoxazole prophylaxis. PI-containing treatment was not associated with protection against malaria in this study population.
Published: 2012
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42. Fingerprinting the substrate specificity of M1 and M17 aminopeptidases of human malaria, Plasmodium falciparum.

Author: Marcin Poreba, Sheena McGowan, Tina S Skinner-Adams, Katharine R Trenholme, Donald L Gardiner, James C Whisstock, Joyce To, Guy S Salvesen, John P Dalton, and Marcin Drag
Subjects: Medicine, Science
Abstract: Plasmodium falciparum, the causative agent of human malaria, expresses two aminopeptidases, PfM1AAP and PfM17LAP, critical to generating a free amino acid pool used by the intraerythrocytic stage of the parasite for proteins synthesis, growth and development. These exopeptidases are potential targets for the development of a new class of anti-malaria drugs.To define the substrate specificity of recombinant forms of these two malaria aminopeptidases we used a new library consisting of 61 fluorogenic substrates derived both from natural and unnatural amino acids. We obtained a detailed substrate fingerprint for recombinant forms of the enzymes revealing that PfM1AAP exhibits a very broad substrate tolerance, capable of efficiently hydrolyzing neutral and basic amino acids, while PfM17LAP has narrower substrate specificity and preferentially cleaves bulky, hydrophobic amino acids. The substrate library was also exploited to profile the activity of the native aminopeptidases in soluble cell lysates of P. falciparum malaria.This data showed that PfM1AAP and PfM17LAP are responsible for majority of the aminopeptidase activity in these extracts. These studies provide specific substrate and mechanistic information important for understanding the function of these aminopeptidases and could be exploited in the design of new inhibitors to specifically target these for anti-malaria treatment.
Published: 2012
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43. Dual-Task Interference: The Effects of Verbal Cognitive Tasks on Upright Postural Stability in Parkinson's Disease

Author: J. D. Holmes, M. E. Jenkins, A. M. Johnson, S. G. Adams, and S. J. Spaulding
Subjects: Neurology. Diseases of the nervous system, RC346-429
Abstract: Although dual-task interference has previously been demonstrated to have a significant effect on postural control among individuals with Parkinson's disease, the impact of speech complexity on postural control has not been demonstrated using quantitative biomechanical measures. The postural stability of twelve participants with idiopathic Parkinson's disease and twelve healthy age-matched controls was evaluated under three conditions: (1) without a secondary task, (2) performing a rote repetition task and (3) generating a monologue. Results suggested a significant effect of cognitive load on biomechanical parameters of postural stability. Although both groups increased their postural excursion, individuals with Parkinson's disease demonstrated significantly reduced excursion as compared with that of healthy age-matched controls. This suggests that participants with Parkinson's disease may be overconstraining their postural adjustments in order to focus attention on the cognitive tasks without losing their balance. Ironically, this overconstraint may place the participant at greater risk for a fall.
Published: 2010
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44. Indigenous Conflict Resolution and the Protection of Human Rights among the Talensi of Ghana

Author: Naya Zuure, David, primary, Hikah Benson, George, additional, and S. Achanson, Adams, additional
Published: 2020
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45. The investigation and analysis of critical incidents and adverse events in healthcare

Author: M Woloshynowych, S Rogers, S Taylor-Adams, and C Vincent
Subjects: Medical technology, R855-855.5
Published: 2005
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46. The taxonomy, mode of life and ecology of the callovian crocodiles from the East Midlands of England

Author: Tresman, S. M. Adams
Subjects: 590, Zoology
Published: 1980

47. Effects of Military activity and habitat quality on DNA damage and oxidative stress in the largest population of the Federally threatened gopher tortoise

Author: S. Marshall Adams, Chandra Smith, Jamie Rotter, Joy Eslick, Ashley Hay, and Christopher W. Theodorakis
Subjects: 0106 biological sciences, Tortoise, DNA damage, Health, Toxicology and Mutagenesis, Population, Endangered species, 010501 environmental sciences, Management, Monitoring, Policy and Law, Biology, Toxicology, medicine.disease_cause, 010603 evolutionary biology, 01 natural sciences, medicine, Animals, education, Ecosystem, 0105 earth and related environmental sciences, education.field_of_study, Ecology, Endangered Species, Hormesis, General Medicine, Turtles, Oxidative Stress, Military Personnel, Habitat, Threatened species, Oxidative stress, DNA Damage, Environmental Monitoring
Abstract: Department of Defense lands are essential for providing important habitat for threatened, endangered, and at-risk species (TER-S). However, there is little information on the effects of military-related contaminants on TER-S on these lands in field situations. Thus, this study examined genotoxicity and oxidative stress in gopher tortoises (Gopherus polyphemus) on Camp Shelby, MS-the largest known population of this species, which is listed as an "endangered species" in Mississippi and a "threatened species" by the U.S. government. Blood was collected from tortoises at 19 different sites on the base with different levels of habitat quality (high-quality and low-quality habitat) and military activity (high, low, and no military activity). Oxidative stress was quantified as lipid peroxidation and GSSG/GSH ratios, while DNA damage was determined using flow cytometry. Our results suggest that: (1) for tortoises residing in low-quality habitats, oxidative stress and DNA damage increased with increasing military activity, while in high-quality habitats, oxidative stress and DNA damage decreased with increasing military activity; (2) in the absence of military activity, tortoises in high-quality habitat had higher levels of oxidative stress and DNA damage than those in low-quality habitat, and (3) there were interactions between military activity, habitat quality, and landuse in terms of the amount of observable DNA damage and oxidative stress. In particular, on high-quality habitat, tortoises from areas with high levels of military activity had lower levels of oxidative stress and DNA damage biomarkers than on reference sites. This may represent a compensatory or hormetic response. Conversely, on low-quality habitats, the level of oxidative stress and DNA damage was lower on the reference sites. Thus, tortoises on higher-quality habitats may have a greater capacity for compensatory responses. In terms of management implications, it is suggested that low quality habitats should be a higher priority for remediation, and lower priority for conducting military activities.
Published: 2017
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48. A novel in vitro image-based assay identifies new drug leads for giardiasis

Author: Andrew G. Riches, John H. Ryan, Katherine T. Andrews, Christopher J.S. Hart, Tina S. Skinner-Adams, and Taylah Munro
Subjects: 0301 basic medicine, Drug, Image-based assay, media_common.quotation_subject, 030106 microbiology, Antiprotozoal Agents, Drug Resistance, Intestinal parasite, Drug resistance, medicine.disease_cause, Article, Microbiology, lcsh:Infectious and parasitic diseases, 03 medical and health sciences, Automation, Parasitic Sensitivity Tests, parasitic diseases, medicine, Image Processing, Computer-Assisted, Parasite hosting, Pharmacology (medical), lcsh:RC109-216, media_common, Pharmacology, Life Cycle Stages, biology, Drug discovery, Giardia, biology.organism_classification, medicine.disease, Virology, In vitro, Infectious Diseases, Parasitology, Giardia lamblia, Malaria Box, Malaria
Abstract: Giardia duodenalis is an intestinal parasite that causes giardiasis, a widespread human gastrointestinal disease. Treatment of giardiasis relies on a small arsenal of compounds that can suffer from limitations including side-effects, variable treatment efficacy and parasite drug resistance. Thus new anti-Giardia drug leads are required. The search for new compounds with anti-Giardia activity currently depends on assays that can be labour-intensive, expensive and restricted to measuring activity at a single time-point. Here we describe a new in vitro assay to assess anti-Giardia activity. This image-based assay utilizes the Perkin-Elmer Operetta® and permits automated assessment of parasite growth at multiple time points without cell-staining. Using this new approach, we assessed the “Malaria Box” compound set for anti-Giardia activity. Three compounds with sub-μM activity (IC50 0.6–0.9 μM) were identified as potential starting points for giardiasis drug discovery., Graphical abstract Image 1, Highlights • We describe a new automated image-based method to enumerate Giardia trophozoites. • This method permits the assessment of parasite growth at multiple time points without staining. • The “Malaria Box” compound set was assessed for anti-Giardia activity using this approach. • Three compounds with sub-μM activity were identified.
Published: 2017

49. Drug resistance in Giardia: Mechanisms and alternative treatments for Giardiasis

Author: David Leitsch, M. Guadalupe Ortega-Pierres, Raúl Argüello-García, and Tina S. Skinner-Adams
Subjects: Drug, 0303 health sciences, medicine.medical_specialty, Auranofin, biology, business.industry, media_common.quotation_subject, Giardia, Context (language use), Drug resistance, Pharmacology, biology.organism_classification, 030308 mycology & parasitology, Albendazole, 03 medical and health sciences, Metronidazole, Medical microbiology, Medicine, business, medicine.drug, media_common
Abstract: The use of chemotherapeutic drugs is the main resource against clinical giardiasis due to the lack of approved vaccines. Resistance of G. duodenalis to the most used drugs to treat giardiasis, metronidazole and albendazole, is a clinical issue of growing concern and yet unknown impact, respectively. In the search of new drugs, the completion of the Giardia genome project and the use of biochemical, molecular and bioinformatics tools allowed the identification of ligands/inhibitors for about one tenth of ≈150 potential drug targets in this parasite. Further, the synthesis of second generation nitroimidazoles and benzimidazoles along with high-throughput technologies have allowed not only to define overall mechanisms of resistance to metronidazole but to screen libraries of repurposed drugs and new pharmacophores, thereby increasing the known arsenal of anti-giardial compounds to some hundreds, with most demonstrating activity against metronidazole or albendazole-resistant Giardia. In particular, cysteine-modifying agents which include omeprazole, disulfiram, allicin and auranofin outstand due to their pleiotropic activity based on the extensive repertoire of thiol-containing proteins and the microaerophilic metabolism of this parasite. Other promising agents derived from higher organisms including phytochemicals, lactoferrin and propolis as well as probiotic bacteria/fungi have also demonstrated significant potential for therapeutic and prophylactic purposes in giardiasis. In this context the present chapter offers a comprehensive review of the current knowledge, including commonly prescribed drugs, causes of therapeutic failures, drug resistance mechanisms, strategies for the discovery of new agents and alternative drug therapies.
Published: 2020
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50. Search for light pseudoscalar boson pairs produced from decays of the 125 GeV Higgs boson in final states with two muons and two nearby tracks in pp collisions at root s d=13TeV

Author: Sirunyan, A. M. Tumasyan, A. Adam, W. Ambrogi, F. and Asilar, E. Bergauer, T. Brandstetter, J. Dragicevic, M. and Eroe, J. Del Valle, A. Escalante Flechl, M. Fruehwirth, R. and Ghete, V. M. Hrubec, J. Jeitler, M. Krammer, N. and Kraetschmer, I Liko, D. Madlener, T. Mikulec, I Rad, N. and Rohringer, H. Schieck, J. Schoefbeck, R. Spanring, M. and Spitzbart, D. Waltenberger, W. Wittmann, J. Wulz, C-E and Zarucki, M. Chekhovsky, V Mossolov, V Gonzalez, J. Suarez De Wolf, E. A. Di Croce, D. Janssen, X. Lauwers, J. Lelek, A. Pieters, M. Van Haevermaet, H. Van Mechelen, P. Van Remortel, N. Blekman, F. D'Hondt, J. De Clercq, J. Deroover, K. Flouris, G. Lontkovskyi, D. and Lowette, S. Marchesini, I Moortgat, S. Moreels, L. and Python, Q. Skovpen, K. Tavernier, S. Van Doninck, W. Van Mulders, P. Van Parijs, I Beghin, D. Bilin, B. Brun, H. and Clerbaux, B. De Lentdecker, G. Delannoy, H. Dorney, B. and Fasanella, G. Favart, L. Grebenyuk, A. Kalsi, A. K. and Luetic, J. Popov, A. Postiau, N. Starling, E. Thomas, L. and Vander Velde, C. Vanlaer, P. Vannerom, D. Wang, Q. and Cornelis, T. Dobur, D. Fagot, A. Gul, M. Khvastunov, I and Roskas, C. Trocino, D. Tytgat, M. Verbeke, W. and Vermassen, B. Vit, M. Zaganidis, N. Bondu, O. Bruno, G. and Caputo, C. David, P. Delaere, C. Delcourt, M. and Giammanco, A. Krintiras, G. Lemaitre, V Magitteri, A. and Piotrzkowski, K. Saggio, A. Marono, M. Vidal Vischia, P. and Zobec, J. Alves, F. L. Alves, G. A. Correia Silva, G. and Hensel, C. Moraes, A. Pol, M. E. Rebello Teles, P. and Belchior Batista Das Chagas, E. Carvalho, W. Chinellato, J. and Coelho, E. Da Costa, E. M. Da Silveira, G. G. De Jesus Damiao, D. De Oliveira Martins, C. Fonseca De Souza, S. and Huertas Guativa, L. M. Malbouisson, H. Matos Figueiredo, D. and Melo De Almeida, M. Mora Herrera, C. Mundim, L. Nogima, H. and Prado Da Silva, W. L. Sanchez Rosas, L. J. Santoro, A. and Sznajder, A. Thiel, M. Tonelli Manganote, E. J. Torres Da Silva De Araujo, F. Vilela Pereira, A. Ahuja, S. Bernardes, C. A. Calligaris, L. Fernandez Perez Tomei, T. R. Gregores, E. M. Mercadante, P. G. Novaes, S. F. Padula, Sandra S. and Aleksandrov, A. Hadjiiska, R. Iaydjiev, P. Marinov, A. and Misheva, M. Rodozov, M. Shopova, M. Sultanov, G. and Dimitrov, A. Litov, L. Pavlov, B. Petkov, P. Fang, W. and Gao, X. Yuan, L. Ahmad, M. Bian, J. G. Chen, G. M. and Chen, H. S. Chen, M. Chen, Y. Jiang, C. H. Leggat, D. Liao, H. Liu, Z. Shaheen, S. M. Spiezia, A. Tao, J. Yazgan, E. Zhang, H. Zhang, S. Zhao, J. Ban, Y. and Chen, G. Levin, A. Li, J. Li, L. Li, Q. Mao, Y. and Qian, S. J. Wang, D. Wang, Y. Avila, C. Cabrera, A. and Carrillo Montoya, C. A. Chaparro Sierra, L. F. Florez, C. and Gonzalez Hernandez, C. F. Segura Delgado, M. A. Ruiz Alvarez, J. D. Godinovic, N. Lelas, D. Puljak, I Sculac, T. Antunovic, Z. Kovac, M. Brigljevic, V Ferencek, D. and Kadija, K. Mesic, B. Roguljic, M. Starodumov, A. and Susa, T. Ather, M. W. Attikis, A. Kolosova, M. and Mavromanolakis, G. Mousa, J. Nicolaou, C. Ptochos, F. and Razis, P. A. Rykaczewski, H. Finger, M. FingerJr, M. Jr and Ayala, E. Carrera Jarrin, E. Abdelalim, A. A. Assran, Y. and Mahmoud, M. A. Bhowmik, S. Carvalho Antunes De Oliveira, A. and Dewanjee, R. K. Ehataht, K. Kadastik, M. Raidal, M. and Veelken, C. Eerola, P. Kirschenmann, H. Pekkanen, J. and Voutilainen, M. Havukainen, J. Heikkila, J. K. Jarvinen, T. and Karimaki, V Kinnunen, R. Lampen, T. Lassila-Perini, K. and Laurila, S. Lehti, S. Linden, T. Luukka, P. Maenpaa, T. Siikonen, H. Tuominen, E. Tuominiemi, J. Tuuva, T. and Besancon, M. Couderc, F. Dejardin, M. Denegri, D. and Faure, J. L. Ferri, F. Ganjour, S. Givernaud, A. Gras, P. de Monchenault, G. Hamel Jarry, P. Leloup, C. Locci, E. Malcles, J. Rander, J. Rosowsky, A. Sahin, M. O. and Savoy-Navarro, A. Titov, M. Amendola, C. Beaudette, F. and Busson, P. Charlot, C. Diab, B. de Cassagnac, R. Granier and Kucher, I Lobanov, A. Blanco, J. Martin Perez, C. Martin and Nguyen, M. Ochando, C. Ortona, G. Paganini, P. Rembser, J. Salerno, R. Sauvan, J. B. Sirois, Y. Zabi, A. and Zghiche, A. Agram, J-L Andrea, J. Bloch, D. Bourgatte, G. Brom, J-M Chabert, E. C. Cherepanov, V Collard, C. and Conte, E. Fontaine, J-C Gele, D. Goerlach, U. and Jansova, M. Le Bihan, A-C Tonon, N. Van Hove, P. Gadrat, S. Beauceron, S. Bernet, C. Boudoul, G. Chanon, N. and Chierici, R. Contardo, D. Depasse, P. El Mamouni, H. and Fay, J. Gascon, S. Gouzevitch, M. Grenier, G. Ille, B. and Lagarde, F. Laktineh, I. B. Lattaud, H. Lethuillier, M. and Mirabito, L. Perries, S. Sordini, V Touquet, G. and Vander Donckt, M. Viret, S. Khvedelidze, A. Tsamalaidze, Z. and Autermann, C. Feld, L. Kiesel, M. K. Klein, K. and Lipinski, M. Preuten, M. Rauch, M. P. Schomakers, C. and Schulz, J. Teroerde, M. Wittmer, B. Albert, A. Erdmann, M. Erdweg, S. Esch, T. Fischer, R. Ghosh, S. and Hebbeker, T. Heidemann, C. Hoepfner, K. Keller, H. and Mastrolorenzo, L. Merschmeyer, M. Meyer, A. Millet, P. and Mukherjee, S. Novak, A. Pook, T. Pozdnyakov, A. Radziej, M. Reithler, H. Rieger, M. Schmidt, A. Sharma, A. and Teyssier, D. Thueer, S. Fluegge, G. Hlushchenko, O. and Kress, T. Mueller, T. Nehrkorn, A. Nowack, A. Pistone, C. Pooth, O. Roy, D. Sert, H. Stahl, A. Martin, M. Aldaya Arndt, T. Asawatangtrakuldee, C. Babounikau, I and Bakhshiansohi, H. Beernaert, K. Behnke, O. Behrens, U. and Martinez, A. Bermudez Bertsche, D. Bin Anuar, A. A. Borras, K. Botta, V Campbell, A. Connor, P. Rodriguez, S. Consuegra Contreras-Campana, C. Danilov, V De Wit, A. and Defranchis, M. M. Pardos, C. Diez Damiani, D. Dominguez and Eckerlin, G. Eichhorn, T. Elwood, A. Eren, E. Gallo, E. and Geiser, A. Luyando, J. M. Grados Grohsjean, A. Guthoff, M. Haranko, M. Harb, A. Jomhari, N. Z. Jung, H. and Kasemann, M. Keaveney, J. Kleinwort, C. Knolle, J. and Kruecker, D. Lange, W. Lenz, T. Leonard, J. Lipka, K. and Lohmann, W. Mankel, R. Melzer-Pellmann, I-A Meyer, A. B. and Meyer, M. Missiroli, M. Mittag, G. Mnich, J. and Myronenko, V Adan, D. Perez Pflitsch, S. K. Pitzl, D. and Raspereza, A. Saibel, A. Savitskyi, M. Saxena, P. and Schuetze, P. Schwanenberger, C. Shevchenko, R. Singh, A. and Tholen, H. Turkot, O. Vagnerini, A. Van De Klundert, M. and Van Onsem, G. P. Walsh, R. Wen, Y. Wichmann, K. Wissing, C. Zenaiev, O. Aggleton, R. Bein, S. Benato, L. and Benecke, A. Blobel, V Dreyer, T. Ebrahimi, A. Garutti, E. Gonzalez, D. Gunnellini, P. Haller, J. Hinzmann, A. and Karavdina, A. Kasieczka, G. Klanner, R. Kogler, R. and Kovalchuk, N. Kurz, S. Kutzner, V Lange, J. Marconi, D. and Multhaup, J. Niedziela, M. Niemeyer, C. E. N. and Nowatschin, D. Perieanu, A. Reimers, A. Rieger, O. and Scharf, C. Schleper, P. Schumann, S. Schwandt, J. and Sonneveld, J. Stadie, H. Steinbrueck, G. Stober, F. M. and Stoever, M. Vormwald, B. Zoi, I Akbiyik, M. Barth, C. and Baselga, M. Baur, S. Berger, T. Butz, E. Caspart, R. and Chwalek, T. De Boer, W. Dierlamm, A. El Morabit, K. and Faltermann, N. Giffels, M. Harrendorf, M. A. Hartmann, F. and Husemann, U. Katkov, I Kudella, S. Mitra, S. Mozer, M. U. Mueller, Th Musich, M. Quast, G. Rabbertz, K. and Schroeder, M. Shvetsov, I Simonis, H. J. Ulrich, R. and Weber, M. Woehrmann, C. Wolf, R. Anagnostou, G. and Daskalakis, G. Geralis, T. Kyriakis, A. Loukas, D. and Paspalaki, G. Agapitos, A. Karathanasis, G. Kontaxakis, P. and Panagiotou, A. Papavergou, I Saoulidou, N. Vellidis, K. and Bakas, G. Kousouris, K. Papakrivopoulos, I Tsipolitis, G. Evangelou, I Foudas, C. Gianneios, P. Katsoulis, P. and Kokkas, P. Mallios, S. Manitara, K. Manthos, N. and Papadopoulos, I Paradas, E. Strologas, J. Triantis, F. A. and Tsitsonis, D. Bartok, M. Csanad, M. Filipovic, N. and Major, P. Mandal, K. Mehta, A. Nagy, I, M. Pasztor, G. and Suranyi, O. Veres, I, G. Bencze, G. Hajdu, C. and Horvath, D. Hunyadi, A. Sikler, F. Vami, T. A. and Veszpremi, V. Vesztergombi, G. Beni, N. Czellar, S. and Karancsi, J. Makovec, A. Molnar, J. Szillasi, Z. Raics, P. Trocsanyi, Z. L. Ujvari, B. Choudhury, S. Komaragiri, J. R. Tiwari, P. C. Bahinipati, S. Kar, C. Mal, R. and Nayak, A. Chowdhury, S. Roy Sahoo, D. K. Swain, S. K. and Bansal, S. Beri, S. B. Bhatnagar, V Chauhan, S. Chawla, R. Dhingra, N. Gupta, R. Kaur, A. Kaur, M. Kaur, S. and Kumari, P. Lohan, M. Meena, M. Sandeep, K. Sharma, S. Singh, J. B. Virdi, A. K. Walia, G. Bhardwaj, A. and Choudhary, B. C. Garg, R. B. Gola, M. Keshri, S. Kumar, Ashok Malhotra, S. Naimuddin, M. Priyanka, P. Ranjan, K. and Shah, Aashaq Sharma, R. Bhardwaj, R. Bharti, M. and Bhattacharya, R. Bhattacharya, S. Bhawandeep, U. Bhowmik, D. and Dey, S. Dutt, S. Dutta, S. Maity, M. Mondal, K. and Nandan, S. Purohit, A. Rout, P. K. Roy, A. Saha, G. and Sarkar, S. Sarkar, T. Sharan, M. Singh, B. Thakur, S. and Behera, P. K. Muhammad, A. Chudasama, R. Dutta, D. and Jha, V Kumar, V Mishra, D. K. Netrakanti, P. K. Pant, L. M. Shukla, P. Suggisetti, P. Aziz, T. Bhat, M. A. and Dugad, S. Mohanty, G. B. Sur, N. Verma, Ravindra Kumar and Banerjee, S. Chatterjee, S. Guchait, M. Jain, Sa and Karmakar, S. Kumar, S. Majumder, G. Mazumdar, K. Sahoo, N. Sawant, S. Dube, S. Hegde, V Kapoor, A. Kothekar, K. Pandey, S. Rane, A. Rastogi, A. Chenarani, S. and Tadavani, E. Eskandari Etesami, S. M. Khakzad, M. and Najafabadi, M. Mohammadi Naseri, M. Hosseinabadi, F. Rezaei and Safarzadeh, B. Zeinali, M. Felcini, M. Grunewald, M. and Abbrescia, M. Calabria, C. Colaleo, A. Creanza, D. and Cristella, L. De Filippis, N. De Palma, M. Di Florio, A. and Errico, F. Fiore, L. Gelmi, A. Iaselli, G. Ince, M. and Lezki, S. Maggi, G. Maggi, M. Miniello, G. My, S. and Nuzzo, S. Pompili, A. Pugliese, G. Radogna, R. Ranieri, A. Selvaggi, G. Silvestris, L. Venditti, R. Verwilligen, P. Abbiendi, G. Battilana, C. Bonacorsi, D. Borgonovi, L. Braibant-Giacomelli, S. Campanini, R. Capiluppi, P. and Castro, A. Cavallo, F. R. Chhibra, S. S. Codispoti, G. and Cuffiani, M. Dallavalle, G. M. Fabbri, F. Fanfani, A. and Fontanesi, E. Giacomelli, P. Grandi, C. Guiducci, L. and Iemmi, F. Lo Meo, S. Marcellini, S. Masetti, G. and Montanari, A. Navarria, F. L. Perrotta, A. Primavera, F. and Rossi, A. M. Rovelli, T. Siroli, G. P. Tosi, N. Albergo, S. Di Mattia, A. Potenza, R. Tricomi, A. Tuve, C. and Barbagli, G. Chatterjee, K. Ciulli, V Civinini, C. and D'Alessandro, R. Focardi, E. Latino, G. Lenzi, P. and Meschini, M. Paoletti, S. Russo, L. Sguazzoni, G. Strom, D. Viliani, L. Benussi, L. Bianco, S. Piccolo, D. and Ferro, F. Mulargia, R. Robutti, E. Tosi, S. Benaglia, A. and Beschi, A. Brivio, F. Ciriolo, V Di Guida, S. and Dinardo, M. E. Fiorendi, S. Gennai, S. Ghezzi, A. and Govoni, P. Malberti, M. Malvezzi, S. Menasce, D. Monti, F. Moroni, L. Paganoni, M. Pedrini, D. Ragazzi, S. and de Fatis, T. Tabarelli Zuolo, D. Buontempo, S. Cavallo, N. and De Iorio, A. Di Crescenzo, A. Fabozzi, F. Fienga, F. and Galati, G. Iorio, A. O. M. Lista, L. Meola, S. Paolucci, P. Sciacca, C. Voevodina, E. Azzi, P. Bacchetta, N. and Bisello, D. Boletti, A. Bragagnolo, A. Carlin, R. and Checchia, P. Dall'Osso, M. Manzano, P. De Castro Dorigo, T. and Dosselli, U. Gasparini, F. Gasparini, U. Gozzelino, A. and Hoh, S. Y. Lacaprara, S. Lujan, P. Margoni, M. and Meneguzzo, A. T. Pazzini, J. Presilla, M. Ronchese, P. and Rossin, R. Simonetto, F. Tiko, A. Torassa, E. Tosi, M. and Zanetti, M. Zotto, P. Zumerle, G. Braghieri, A. and Magnani, A. Montagna, P. Ratti, S. P. Re, V Ressegotti, M. Riccardi, C. Salvini, P. Vai, I Vitulo, P. and Biasini, M. Bilei, G. M. Cecchi, C. Ciangottini, D. and Fano, L. Lariccia, P. Leonardi, R. Manoni, E. Mantovani, G. Mariani, V Menichelli, M. Rossi, A. Santocchia, A. and Spiga, D. Androsov, K. Azzurri, P. Bagliesi, G. and Bianchini, L. Boccali, T. Borrello, L. Castaldi, R. and Ciocci, M. A. Dell'Orso, R. Fedi, G. Fiori, F. Giannini, L. Giassi, A. Grippo, M. T. Ligabue, F. Manca, E. and Mandorli, G. Messineo, A. Palla, F. Rizzi, A. Rolandi, G. Scribano, A. Spagnolo, P. 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Cooperstein, S. and Dezoort, G. Elmer, P. Hardenbrook, J. Haubrich, N. and Higginbotham, S. Kalogeropoulos, A. Kwan, S. Lange, D. and Lucchini, M. T. Luo, J. Marlow, D. Mei, K. Ojalvo, I and Olsen, J. Palmer, C. Piroue, P. Salfeld-Nebgen, J. and Stickland, D. Tully, C. Norberg, S. Barker, A. Barnes, V. E. Gutay, L. Jones, M. Jung, A. W. Khatiwada, A. and Mahakud, B. Miller, D. H. Negro, G. Neumeister, N. Peng, C. C. Piperov, S. Qiu, H. Schulte, J. F. Sun, J. and Wang, F. Xiao, R. Xie, W. Cheng, T. Dolen, J. and Parashar, N. Chen, Z. Ecklund, K. M. Freed, S. Geurts, F. J. M. Kilpatrick, M. Kumar, Arun Padley, B. P. and Roberts, J. Rorie, J. Shi, W. Leiton, A. G. Stahl Tu, Z. and Zhang, A. Bodek, A. de Barbaro, P. Demina, R. Duh, Y. T. Dulemba, J. L. Fallon, C. Ferbel, T. Galanti, M. and Garcia-Bellido, A. Han, J. Hindrichs, O. and Khukhunaishvili, A. Ranken, E. Tan, P. Taus, R. and Chiarito, B. Chou, J. P. Gershtein, Y. Halkiadakis, E. and Hart, A. Heindl, M. Hughes, E. Kaplan, S. Kyriacou, S. and Laflotte, I Lath, A. Montalvo, R. Nash, K. Osherson, M. Saka, H. Salur, S. Schnetzer, S. Sheffield, D. and Somalwar, S. Stone, R. Thomas, S. Thomassen, P. Acharya, H. Delannoy, A. G. Heideman, J. Riley, G. Spanier, S. and Bouhali, O. Celik, A. Dalchenko, M. De Mattia, M. and Delgado, A. Dildick, S. Eusebi, R. Gilmore, J. Huang, T. and Kamon, T. Luo, S. Marley, D. Mueller, R. Overton, D. and Pernie, L. Rathjens, D. Safonov, A. Akchurin, N. and Damgov, J. De Guio, F. Dudero, P. R. Kunori, S. and Lamichhane, K. Mengke, T. Muthumuni, S. Peltola, T. and Undleeb, S. Volobouev, I Whitbeck, A. Greene, S. and Gurrola, A. Janjam, R. Johns, W. Maguire, C. Melo, A. and Ni, H. Padeken, K. Romeo, F. Sheldon, P. Tuo, S. and Velkovska, J. Verweij, M. Xu, Q. Arenton, M. W. Barria, P. Cox, B. Hirosky, R. Joyce, M. Ledovskoy, A. Li, H. Neu, C. Wolfe, E. Xia, F. Harr, R. Karchin, P. E. and Poudyal, N. Sturdy, J. Thapa, P. Zaleski, S. and Buchanan, J. Caillol, C. Carlsmith, D. Dasu, S. De Bruyn, I Dodd, L. Gomber, B. Grothe, M. Herndon, M. and Herve, A. Hussain, U. Klabbers, P. Lanaro, A. Long, K. and Loveless, R. Ruggles, T. Savin, A. Smith, N. Smith, W. H. Woods, N. CMS Collaboration
Subjects: High Energy Physics::Phenomenology, High Energy Physics::Experiment
Abstract: A search is presented for pairs of light pseudoscalar bosons, in the mass range from 4 to 15 GeV, produced from decays of the 125 GeV Higgs boson. The decay modes considered are final states that arise when one of the pseudoscalars decays to a pair of tau leptons, and the other one either into a pair of tau leptons or muons. The search is based on proton-proton collisions collected by the CMS experiment in 2016 at a center-of-mass energy of 13 TeV that correspond to an integrated luminosity of 35.9 fb(-1). The 2 mu 2 tau and 4 tau channels are used in combination to constrain the product of the Higgs boson production cross section and the branching fraction into 4 tau final state, sigma beta, exploiting the linear dependence of the fermionic coupling strength of pseudoscalar bosons on the fermion mass. No significant excess is observed beyond the expectation from the standard model. The observed and expected upper limits at 95% confidence level on sigma beta, relative to the standard model Higgs boson production cross section, are set respectively between 0.022 and 0.23 and between 0.027 and 0.19 in the mass range probed by the analysis. (C) 2019 The Author(s). Published by Elsevier B.V.
Published: 2020

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