Antimicrobial Resistance and Virulence: a Successful or Deleterious Association in the Bacterial World?

PubMed Central

Beceiro, Alejandro; Tomás, María

2013-01-01

SUMMARY Hosts and bacteria have coevolved over millions of years, during which pathogenic bacteria have modified their virulence mechanisms to adapt to host defense systems. Although the spread of pathogens has been hindered by the discovery and widespread use of antimicrobial agents, antimicrobial resistance has increased globally. The emergence of resistant bacteria has accelerated in recent years, mainly as a result of increased selective pressure. However, although antimicrobial resistance and bacterial virulence have developed on different timescales, they share some common characteristics. This review considers how bacterial virulence and fitness are affected by antibiotic resistance and also how the relationship between virulence and resistance is affected by different genetic mechanisms (e.g., coselection and compensatory mutations) and by the most prevalent global responses. The interplay between these factors and the associated biological costs depend on four main factors: the bacterial species involved, virulence and resistance mechanisms, the ecological niche, and the host. The development of new strategies involving new antimicrobials or nonantimicrobial compounds and of novel diagnostic methods that focus on high-risk clones and rapid tests to detect virulence markers may help to resolve the increasing problem of the association between virulence and resistance, which is becoming more beneficial for pathogenic bacteria. PMID:23554414

Agronomical, biochemical and histological response of resistant and susceptible wheat and barley under BYDV stress

PubMed Central

Choudhury, Shormin; Hu, Hongliang; Larkin, Philip; Meinke, Holger; Shabala, Sergey; Ahmed, Ibrahim

2018-01-01

Barley yellow dwarf virus-PAV (BYDV-PAV) is one of the major viruses causing a widespread and serious viral disease affecting cereal crops. To gain a better understanding of plant defence mechanisms of BYDV resistance genes (Bdv2 and RYd2) against BYDV-PAV infection, the differences in agronomical, biochemical and histological changes between susceptible and resistant wheat and barley cultivars were investigated. We found that root growth and total dry matter of susceptible cultivars showed greater reduction than that of resistant ones after infection. BYDV infected leaves in susceptible wheat and barley cultivars showed a significant reduction in photosynthetic pigments, an increase in the concentration of reducing sugar. The protein levels were also low in infected leaves. There was a significant increase in total phenol contents in resistant cultivars, which might reflect a protective mechanism of plants against virus infection. In phloem tissue, sieve elements (SE) and companion cells (CC) were severely damaged in susceptible cultivars after infection. It is suggested that restriction of viral movement in the phloem tissue and increased production of phenolic compounds may play a role in the resistance and defensive mechanisms of both Bdv2 and RYd2 against virus infection. PMID:29868264

[Efflux systems in Serratia marcescens].

PubMed

Mardanova, A M; Bogomol'naia, L M; Romanova, Iu D; Sharipova, M R

2014-01-01

A widespread bacterium Serratia marcescens (family Enterobacteriaceae) is an opportunistic and exhibits multiple drug resistance. Active removal of antibiotics and other antimicrobials from pathogen and exhibits multiple drug resistance. Active removal of antibiotics and other antimicrobials from the cells by efflux systems is one of the mechanisms responsible for microbial resistance to these compounds. Among enterobacteria, efflux systems of Escherichia coli and Salmonella enterica var. Typhimurium have been studied most extensively. Few efflux systems that belong to different families have been reported for S. marcescens. In this review, we analyzed available literature about S. marcescens efflux systems and carried out the comparative analysis of the genes encoding the RND type systems in different Serratia species and in other enterobacteria. Bioinformatical analysis of the S. marcescens genome allowed us to identify the previously unknown efflux systems based on their homology with the relevant E. coli genes. Identification of additional efflux systems in S. marcescens genome will promote our understanding of physiology of these bacteria, will detect new molecular mechanisms of resistance and will reveal their resistance potential.

Mechanism of quinolone resistance in anaerobic bacteria.

PubMed

Oh, H; Edlund, C

2003-06-01

Several recently developed quinolones have excellent activity against a broad range of aerobic and anaerobic bacteria and are thus potential drugs for the treatment of serious anaerobic and mixed infections. Resistance to quinolones is increasing worldwide, but is still relatively infrequent among anaerobes. Two main mechanisms, alteration of target enzymes (gyrase and topoisomerase IV) caused by chromosomal mutations in encoding genes, or reduced intracellular accumulation due to increased efflux of the drug, are associated with quinolone resistance. These mechanisms have also been found in anaerobic species. High-level resistance to the newer broad-spectrum quinolones often requires stepwise mutations in target genes. The increasing emergence of resistance among anaerobes may be a consequence of previous widespread use of quinolones, which may have enriched first-step mutants in the intestinal tract. Quinolone resistance in the Bacteroides fragilis group strains is strongly correlated with amino acid substitutions at positions 82 and 86 in GyrA (equivalent to positions 83 and 87 of Escherichia coli). Several studies have indicated that B. fragilis group strains possess efflux pump systems that actively expel quinolones, leading to resistance. DNA gyrase seems also to be the primary target for quinolones in Clostridium difficile, since amino acid substitutions in GyrA and GyrB have been detected in resistant strains. To what extent other mechanisms, such as mutational events in other target genes or alterations in outer-membrane proteins, contribute to resistance among anaerobes needs to be further investigated.

A diverse intrinsic antibiotic resistome from a cave bacterium.

PubMed

Pawlowski, Andrew C; Wang, Wenliang; Koteva, Kalinka; Barton, Hazel A; McArthur, Andrew G; Wright, Gerard D

2016-12-08

Antibiotic resistance is ancient and widespread in environmental bacteria. These are therefore reservoirs of resistance elements and reflective of the natural history of antibiotics and resistance. In a previous study, we discovered that multi-drug resistance is common in bacteria isolated from Lechuguilla Cave, an underground ecosystem that has been isolated from the surface for over 4 Myr. Here we use whole-genome sequencing, functional genomics and biochemical assays to reveal the intrinsic resistome of Paenibacillus sp. LC231, a cave bacterial isolate that is resistant to most clinically used antibiotics. We systematically link resistance phenotype to genotype and in doing so, identify 18 chromosomal resistance elements, including five determinants without characterized homologues and three mechanisms not previously shown to be involved in antibiotic resistance. A resistome comparison across related surface Paenibacillus affirms the conservation of resistance over millions of years and establishes the longevity of these genes in this genus.

Cytoplasmic inclusion cistron of Soybean mosaic virus serves as a virulence determinant on Rsv3-genotype soybean and a symptom determinant.

PubMed

Zhang, Chunquan; Hajimorad, M R; Eggenberger, Alan L; Tsang, Stephanie; Whitham, Steven A; Hill, John H

2009-09-01

Soybean mosaic virus (SMV; Potyvirus, Potyviridae) is one of the most widespread viruses of soybean globally. Three dominant resistance genes (Rsv1, Rsv3 and Rsv4) differentially confer resistance against SMV. Rsv1 confers extreme resistance and the resistance mechanism of Rsv4 is associated with late susceptibility. Here, we show that Rsv3 restricts the accumulation of SMV strain G7 to the inoculated leaves, whereas, SMV-N, an isolate of SMV strain G2, establishes systemic infection. This observation suggests that the resistance mechanism of Rsv3 differs phenotypically from those of Rsv1 and Rsv4. To identify virulence determinant(s) of SMV on an Rsv3-genotype soybean, chimeras were constructed by exchanging fragments between avirulent SMV-G7 and the virulent SMV-N. Analyses of the chimeras showed that both the N- and C-terminal regions of the cytoplasmic inclusion (CI) cistron are required for Rsv3-mediated resistance. Interestingly, the N-terminal region of CI is also involved in severe symptom induction in soybean.

Insecticide resistance in the dengue vector Aedes aegypti from Martinique: distribution, mechanisms and relations with environmental factors.

PubMed

Marcombe, Sébastien; Mathieu, Romain Blanc; Pocquet, Nicolas; Riaz, Muhammad-Asam; Poupardin, Rodolphe; Sélior, Serge; Darriet, Frédéric; Reynaud, Stéphane; Yébakima, André; Corbel, Vincent; David, Jean-Philippe; Chandre, Fabrice

2012-01-01

Dengue is an important mosquito borne viral disease in Martinique Island (French West Indies). The viruses responsible for dengue are transmitted by Aedes aegypti, an indoor day-biting mosquito. The most effective proven method for disease prevention has been by vector control by various chemical or biological means. Unfortunately insecticide resistance has already been observed on the Island and recently showed to significantly reduce the efficacy of vector control interventions. In this study, we investigated the distribution of resistance and the underlying mechanisms in nine Ae. aegypti populations. Statistical multifactorial approach was used to investigate the correlations between insecticide resistance levels, associated mechanisms and environmental factors characterizing the mosquito populations. Bioassays revealed high levels of resistance to temephos and deltamethrin and susceptibility to Bti in the 9 populations tested. Biochemical assays showed elevated detoxification enzyme activities of monooxygenases, carboxylesterases and glutathione S-tranferases in most of the populations. Molecular screening for common insecticide target-site mutations, revealed the presence of the "knock-down resistance" V1016I Kdr mutation at high frequency (>87%). Real time quantitative RT-PCR showed the potential involvement of several candidate detoxification genes in insecticide resistance. Principal Component Analysis (PCA) performed with variables characterizing Ae. aegypti from Martinique permitted to underline potential links existing between resistance distribution and other variables such as agriculture practices, vector control interventions and urbanization. Insecticide resistance is widespread but not homogeneously distributed across Martinique. The influence of environmental and operational factors on the evolution of the resistance and mechanisms are discussed.

Deep Sequencing of Pyrethroid-Resistant Bed Bugs Reveals Multiple Mechanisms of Resistance within a Single Population

PubMed Central

Adelman, Zach N.; Kilcullen, Kathleen A.; Koganemaru, Reina; Anderson, Michelle A. E.; Anderson, Troy D.; Miller, Dini M.

2011-01-01

A frightening resurgence of bed bug infestations has occurred over the last 10 years in the U.S. and current chemical methods have been inadequate for controlling this pest due to widespread insecticide resistance. Little is known about the mechanisms of resistance present in U.S. bed bug populations, making it extremely difficult to develop intelligent strategies for their control. We have identified bed bugs collected in Richmond, VA which exhibit both kdr-type (L925I) and metabolic resistance to pyrethroid insecticides. Using LD50 bioassays, we determined that resistance ratios for Richmond strain bed bugs were ∼5200-fold to the insecticide deltamethrin. To identify metabolic genes potentially involved in the detoxification of pyrethroids, we performed deep-sequencing of the adult bed bug transcriptome, obtaining more than 2.5 million reads on the 454 titanium platform. Following assembly, analysis of newly identified gene transcripts in both Harlan (susceptible) and Richmond (resistant) bed bugs revealed several candidate cytochrome P450 and carboxylesterase genes which were significantly over-expressed in the resistant strain, consistent with the idea of increased metabolic resistance. These data will accelerate efforts to understand the biochemical basis for insecticide resistance in bed bugs, and provide molecular markers to assist in the surveillance of metabolic resistance. PMID:22039447

Insecticide Resistance in the Dengue Vector Aedes aegypti from Martinique: Distribution, Mechanisms and Relations with Environmental Factors

PubMed Central

Marcombe, Sébastien; Mathieu, Romain Blanc; Pocquet, Nicolas; Riaz, Muhammad-Asam; Poupardin, Rodolphe; Sélior, Serge; Darriet, Frédéric; Reynaud, Stéphane; Yébakima, André; Corbel, Vincent; David, Jean-Philippe; Chandre, Fabrice

2012-01-01

Dengue is an important mosquito borne viral disease in Martinique Island (French West Indies). The viruses responsible for dengue are transmitted by Aedes aegypti, an indoor day-biting mosquito. The most effective proven method for disease prevention has been by vector control by various chemical or biological means. Unfortunately insecticide resistance has already been observed on the Island and recently showed to significantly reduce the efficacy of vector control interventions. In this study, we investigated the distribution of resistance and the underlying mechanisms in nine Ae. aegypti populations. Statistical multifactorial approach was used to investigate the correlations between insecticide resistance levels, associated mechanisms and environmental factors characterizing the mosquito populations. Bioassays revealed high levels of resistance to temephos and deltamethrin and susceptibility to Bti in the 9 populations tested. Biochemical assays showed elevated detoxification enzyme activities of monooxygenases, carboxylesterases and glutathione S-tranferases in most of the populations. Molecular screening for common insecticide target-site mutations, revealed the presence of the “knock-down resistance” V1016I Kdr mutation at high frequency (>87%). Real time quantitative RT-PCR showed the potential involvement of several candidate detoxification genes in insecticide resistance. Principal Component Analysis (PCA) performed with variables characterizing Ae. aegypti from Martinique permitted to underline potential links existing between resistance distribution and other variables such as agriculture practices, vector control interventions and urbanization. Insecticide resistance is widespread but not homogeneously distributed across Martinique. The influence of environmental and operational factors on the evolution of the resistance and mechanisms are discussed. PMID:22363529

Plasmid-mediated resistance to protein biosynthesis inhibitors in staphylococci.

PubMed

Schwarz, Stefan; Fessler, Andrea T; Hauschild, Tomasz; Kehrenberg, Corinna; Kadlec, Kristina

2011-12-01

Protein biosynthesis inhibitors (PBIs) represent powerful antimicrobial agents for the control of bacterial infections. In staphylococci, numerous resistance genes are known to be involved in resistance to PBIs, most of which mediate resistance to a specific class/subclass of PBIs, though a few genes do confer a multidrug resistance phenotype-up to five classes/subclasses of PBIs. Plasmids play a key role in the dissemination of PBI resistance among staphylococci, as they primarily carry plasmid-borne PBI resistance genes; however, plasmids also can be vectors for transposon-borne PBI resistance genes. Small plasmids that carry single PBI resistance genes are widespread among staphylococci of human and animal origin. Various mechanisms exist by which they can recombine, form cointegrates, or integrate into chromosomal DNA or larger plasmids. We provide an overview of the current knowledge of plasmid-mediated PBI resistance in staphylococci, with particular reference to the currently known PBI resistance genes, their association with mobile genetic elements, and the recombination/integration processes that control their mobility. © 2011 New York Academy of Sciences.

Rifampin phosphotransferase is an unusual antibiotic resistance kinase

PubMed Central

Stogios, Peter J.; Cox, Georgina; Spanogiannopoulos, Peter; Pillon, Monica C.; Waglechner, Nicholas; Skarina, Tatiana; Koteva, Kalinka; Guarné, Alba; Savchenko, Alexei; Wright, Gerard D.

2016-01-01

Rifampin (RIF) phosphotransferase (RPH) confers antibiotic resistance by conversion of RIF and ATP, to inactive phospho-RIF, AMP and Pi. Here we present the crystal structure of RPH from Listeria monocytogenes (RPH-Lm), which reveals that the enzyme is comprised of three domains: two substrate-binding domains (ATP-grasp and RIF-binding domains); and a smaller phosphate-carrying His swivel domain. Using solution small-angle X-ray scattering and mutagenesis, we reveal a mechanism where the swivel domain transits between the spatially distinct substrate-binding sites during catalysis. RPHs are previously uncharacterized dikinases that are widespread in environmental and pathogenic bacteria. These enzymes are members of a large unexplored group of bacterial enzymes with substrate affinities that have yet to be fully explored. Such an enzymatically complex mechanism of antibiotic resistance augments the spectrum of strategies used by bacteria to evade antimicrobial compounds. PMID:27103605

Unique features of a global human ectoparasite identified through sequencing of the bed bug genome.

PubMed

Benoit, Joshua B; Adelman, Zach N; Reinhardt, Klaus; Dolan, Amanda; Poelchau, Monica; Jennings, Emily C; Szuter, Elise M; Hagan, Richard W; Gujar, Hemant; Shukla, Jayendra Nath; Zhu, Fang; Mohan, M; Nelson, David R; Rosendale, Andrew J; Derst, Christian; Resnik, Valentina; Wernig, Sebastian; Menegazzi, Pamela; Wegener, Christian; Peschel, Nicolai; Hendershot, Jacob M; Blenau, Wolfgang; Predel, Reinhard; Johnston, Paul R; Ioannidis, Panagiotis; Waterhouse, Robert M; Nauen, Ralf; Schorn, Corinna; Ott, Mark-Christoph; Maiwald, Frank; Johnston, J Spencer; Gondhalekar, Ameya D; Scharf, Michael E; Peterson, Brittany F; Raje, Kapil R; Hottel, Benjamin A; Armisén, David; Crumière, Antonin Jean Johan; Refki, Peter Nagui; Santos, Maria Emilia; Sghaier, Essia; Viala, Sèverine; Khila, Abderrahman; Ahn, Seung-Joon; Childers, Christopher; Lee, Chien-Yueh; Lin, Han; Hughes, Daniel S T; Duncan, Elizabeth J; Murali, Shwetha C; Qu, Jiaxin; Dugan, Shannon; Lee, Sandra L; Chao, Hsu; Dinh, Huyen; Han, Yi; Doddapaneni, Harshavardhan; Worley, Kim C; Muzny, Donna M; Wheeler, David; Panfilio, Kristen A; Vargas Jentzsch, Iris M; Vargo, Edward L; Booth, Warren; Friedrich, Markus; Weirauch, Matthew T; Anderson, Michelle A E; Jones, Jeffery W; Mittapalli, Omprakash; Zhao, Chaoyang; Zhou, Jing-Jiang; Evans, Jay D; Attardo, Geoffrey M; Robertson, Hugh M; Zdobnov, Evgeny M; Ribeiro, Jose M C; Gibbs, Richard A; Werren, John H; Palli, Subba R; Schal, Coby; Richards, Stephen

2016-02-02

The bed bug, Cimex lectularius, has re-established itself as a ubiquitous human ectoparasite throughout much of the world during the past two decades. This global resurgence is likely linked to increased international travel and commerce in addition to widespread insecticide resistance. Analyses of the C. lectularius sequenced genome (650 Mb) and 14,220 predicted protein-coding genes provide a comprehensive representation of genes that are linked to traumatic insemination, a reduced chemosensory repertoire of genes related to obligate hematophagy, host-symbiont interactions, and several mechanisms of insecticide resistance. In addition, we document the presence of multiple putative lateral gene transfer events. Genome sequencing and annotation establish a solid foundation for future research on mechanisms of insecticide resistance, human-bed bug and symbiont-bed bug associations, and unique features of bed bug biology that contribute to the unprecedented success of C. lectularius as a human ectoparasite.

Unique features of a global human ectoparasite identified through sequencing of the bed bug genome

PubMed Central

Benoit, Joshua B.; Adelman, Zach N.; Reinhardt, Klaus; Dolan, Amanda; Poelchau, Monica; Jennings, Emily C.; Szuter, Elise M.; Hagan, Richard W.; Gujar, Hemant; Shukla, Jayendra Nath; Zhu, Fang; Mohan, M.; Nelson, David R.; Rosendale, Andrew J.; Derst, Christian; Resnik, Valentina; Wernig, Sebastian; Menegazzi, Pamela; Wegener, Christian; Peschel, Nicolai; Hendershot, Jacob M.; Blenau, Wolfgang; Predel, Reinhard; Johnston, Paul R.; Ioannidis, Panagiotis; Waterhouse, Robert M.; Nauen, Ralf; Schorn, Corinna; Ott, Mark-Christoph; Maiwald, Frank; Johnston, J. Spencer; Gondhalekar, Ameya D.; Scharf, Michael E.; Peterson, Brittany F.; Raje, Kapil R.; Hottel, Benjamin A.; Armisén, David; Crumière, Antonin Jean Johan; Refki, Peter Nagui; Santos, Maria Emilia; Sghaier, Essia; Viala, Sèverine; Khila, Abderrahman; Ahn, Seung-Joon; Childers, Christopher; Lee, Chien-Yueh; Lin, Han; Hughes, Daniel S. T.; Duncan, Elizabeth J.; Murali, Shwetha C.; Qu, Jiaxin; Dugan, Shannon; Lee, Sandra L.; Chao, Hsu; Dinh, Huyen; Han, Yi; Doddapaneni, Harshavardhan; Worley, Kim C.; Muzny, Donna M.; Wheeler, David; Panfilio, Kristen A.; Vargas Jentzsch, Iris M.; Vargo, Edward L.; Booth, Warren; Friedrich, Markus; Weirauch, Matthew T.; Anderson, Michelle A. E.; Jones, Jeffery W.; Mittapalli, Omprakash; Zhao, Chaoyang; Zhou, Jing-Jiang; Evans, Jay D.; Attardo, Geoffrey M.; Robertson, Hugh M.; Zdobnov, Evgeny M.; Ribeiro, Jose M. C.; Gibbs, Richard A.; Werren, John H.; Palli, Subba R.; Schal, Coby; Richards, Stephen

2016-01-01

The bed bug, Cimex lectularius, has re-established itself as a ubiquitous human ectoparasite throughout much of the world during the past two decades. This global resurgence is likely linked to increased international travel and commerce in addition to widespread insecticide resistance. Analyses of the C. lectularius sequenced genome (650 Mb) and 14,220 predicted protein-coding genes provide a comprehensive representation of genes that are linked to traumatic insemination, a reduced chemosensory repertoire of genes related to obligate hematophagy, host–symbiont interactions, and several mechanisms of insecticide resistance. In addition, we document the presence of multiple putative lateral gene transfer events. Genome sequencing and annotation establish a solid foundation for future research on mechanisms of insecticide resistance, human–bed bug and symbiont–bed bug associations, and unique features of bed bug biology that contribute to the unprecedented success of C. lectularius as a human ectoparasite. PMID:26836814

Resistance may be an important mechanism by which marine microbes respond to environmental toxicants*1

NASA Astrophysics Data System (ADS)

Capriulo, Gerard M.; Flanzenbaum, Jeffrey; Wurster, Charles F.; Rowland, R. George

1983-11-01

The hypothesis, that at least certain marine microbial organisms respond to toxic stress by the development of resistance, was tested using the hypotric marine ciliate Euplotes vannus Muller as the test organism. Resistance to polychlorinated biphenyls (PCB, Aroclor 1254) was developed in E. vannus by exposing the animals to progressively higher PCB concentrations during a period of several months. The resistance to PCB persisted for at least 80 days (greater than 40 generations) after final exposure. This suggests either that genetic selection or persistent (lasting over many cell division cycles) phenotypic trait modification, possibly in the form of Dauermodification, had occurred. If resistance were widespread among marine microbial organisms in polluted environments it would be an important consideration in evaluating the long-term biological impact of both natural and man-induced chemical stress.

Deoxynybomycins inhibit mutant DNA gyrase and rescue mice infected with fluoroquinolone-resistant bacteria.

PubMed

Parkinson, Elizabeth I; Bair, Joseph S; Nakamura, Bradley A; Lee, Hyang Y; Kuttab, Hani I; Southgate, Emma H; Lezmi, Stéphane; Lau, Gee W; Hergenrother, Paul J

2015-04-24

Fluoroquinolones are one of the most commonly prescribed classes of antibiotics, but fluoroquinolone resistance (FQR) is widespread and increasing. Deoxynybomycin (DNM) is a natural-product antibiotic with an unusual mechanism of action, inhibiting the mutant DNA gyrase that confers FQR. Unfortunately, isolation of DNM is difficult and DNM is insoluble in aqueous solutions, making it a poor candidate for development. Here we describe a facile chemical route to produce DNM and its derivatives. These compounds possess excellent activity against FQR methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococci clinical isolates and inhibit mutant DNA gyrase in-vitro. Bacteria that develop resistance to DNM are re-sensitized to fluoroquinolones, suggesting that resistance that emerges to DNM would be treatable. Using a DNM derivative, the first in-vivo efficacy of the nybomycin class is demonstrated in a mouse infection model. Overall, the data presented suggest the promise of DNM derivatives for the treatment of FQR infections.

The rapid spread of carbapenem-resistant Enterobacteriaceae

PubMed Central

Potter, Robert F.; D’Souza, Alaric W.; Dantas, Gautam

2016-01-01

Carbapenems, our one-time silver bullet for multidrug resistant bacterial infections, are now threatened by widespread dissemination of carbapenem-resistant Enterobacteriaceae (CRE). Successful expansion of Enterobacteriaceae clonal groups and frequent horizontal gene transfer of carbapenemase expressing plasmids are causing increasing carbapenem resistance. Recent advances in genetic and phenotypic detection facilitate global surveillance of CRE diversity and prevalence. In particular, whole genome sequencing enabled efficient tracking, annotation, and study of genetic elements colocalized with carbapenemase genes on chromosomes and on plasmids. Improved characterization helps detail the co-occurrence of other antibiotic resistance genes in CRE isolates and helps identify pan-drug resistance mechanisms. The novel β-lactamase inhibitor, avibactam, combined with ceftazidime or aztreonam, is a promising CRE treatment compared to current colistin or tigecycline regimens. To halt increasing CRE-associated morbidity and mortality, we must continue quality, cooperative monitoring and urgently investigate novel treatments. PMID:27912842

Invasive Fungal Infections in Patients with Hematological Malignancies: Emergence of Resistant Pathogens and New Antifungal Therapies

PubMed Central

Gamaletsou, Maria N.; Walsh, Thomas J.; Sipsas, Nikolaos V.

2018-01-01

Invasive fungal infections caused by drug-resistant organisms are an emerging threat to heavily immunosuppressed patients with hematological malignancies. Modern early antifungal treatment strategies, such as prophylaxis and empirical and preemptive therapy, result in long-term exposure to antifungal agents, which is a major driving force for the development of resistance. The extended use of central venous catheters, the nonlinear pharmacokinetics of certain antifungal agents, neutropenia, other forms of intense immunosuppression, and drug toxicities are other contributing factors. The widespread use of agricultural and industrial fungicides with similar chemical structures and mechanisms of action has resulted in the development of environmental reservoirs for some drug-resistant fungi, especially azole-resistant Aspergillus species, which have been reported from four continents. The majority of resistant strains have the mutation TR34/L98H, a finding suggesting that the source of resistance is the environment. The global emergence of new fungal pathogens with inherent resistance, such as Candida auris, is a new public health threat. The most common mechanism of antifungal drug resistance is the induction of efflux pumps, which decrease intracellular drug concentrations. Overexpression, depletion, and alteration of the drug target are other mechanisms of resistance. Mutations in the ERG11 gene alter the protein structure of C-demethylase, reducing the efficacy of antifungal triazoles. Candida species become echinocandin-resistant by mutations in FKS genes. A shift in the epidemiology of Candida towards resistant non-albicans Candida spp. has emerged among patients with hematological malignancies. There is no definite association between antifungal resistance, as defined by elevated minimum inhibitory concentrations, and clinical outcomes in this population. Detection of genes or mutations conferring resistance with the use of molecular methods may offer better predictive values in certain cases. Treatment options for resistant fungal infections are limited and new drugs with novel mechanisms of actions are needed. Prevention of resistance through antifungal stewardship programs is of paramount importance. PMID:29391334

Using a Genome-Scale Metabolic Network Model to Elucidate the Mechanism of Chloroquine Action in Plasmodium falciparum

DTIC Science & Technology

2017-03-22

Department of Defense Biotechnology High Performance Computing Software Applications Institute, Telemedicine and Advanced Technology Research Center, US...2017 Available online 22 March 2017 Keywords: Plasmodium Chloroquine Metabolic network modeling Redox metabolism Carbon fixation* Corresponding... available (Antony and Parija, 2016), their efficacy has declined appreciably in the last few decades owing to widespread drug resistance developed by the

Spanish multicenter study of the epidemiology and mechanisms of amoxicillin-clavulanate resistance in Escherichia coli.

PubMed

Ortega, Adriana; Oteo, Jesús; Aranzamendi-Zaldumbide, Maitane; Bartolomé, Rosa M; Bou, Germán; Cercenado, Emilia; Conejo, M Carmen; González-López, Juan José; Marín, Mercedes; Martínez-Martínez, Luis; Merino, María; Navarro, Ferran; Oliver, Antonio; Pascual, Alvaro; Rivera, Alba; Rodríguez-Baño, Jesús; Weber, Irene; Aracil, Belén; Campos, José

2012-07-01

We conducted a prospective multicenter study in Spain to characterize the mechanisms of resistance to amoxicillin-clavulanate (AMC) in Escherichia coli. Up to 44 AMC-resistant E. coli isolates (MIC ≥ 32/16 μg/ml) were collected at each of the seven participant hospitals. Resistance mechanisms were characterized by PCR and sequencing. Molecular epidemiology was studied by pulsed-field gel electrophoresis (PFGE) and by multilocus sequence typing. Overall AMC resistance was 9.3%. The resistance mechanisms detected in the 257 AMC-resistant isolates were OXA-1 production (26.1%), hyperproduction of penicillinase (22.6%), production of plasmidic AmpC (19.5%), hyperproduction of chromosomic AmpC (18.3%), and production of inhibitor-resistant TEM (IRT) (17.5%). The IRTs identified were TEM-40 (33.3%), TEM-30 (28.9%), TEM-33 (11.1%), TEM-32 (4.4%), TEM-34 (4.4%), TEM-35 (2.2%), TEM-54 (2.2%), TEM-76 (2.2%), TEM-79 (2.2%), and the new TEM-185 (8.8%). By PFGE, a high degree of genetic diversity was observed although two well-defined clusters were detected in the OXA-1-producing isolates: the C1 cluster consisting of 19 phylogroup A/sequence type 88 [ST88] isolates and the C2 cluster consisting of 19 phylogroup B2/ST131 isolates (16 of them producing CTX-M-15). Each of the clusters was detected in six different hospitals. In total, 21.8% of the isolates were serotype O25b/phylogroup B2 (O25b/B2). AMC resistance in E. coli is widespread in Spain at the hospital and community levels. A high prevalence of OXA-1 was found. Although resistant isolates were genetically diverse, clonality was linked to OXA-1-producing isolates of the STs 88 and 131. Dissemination of IRTs was frequent, and the epidemic O25b/B2/ST131 clone carried many different mechanisms of AMC resistance.

Genomic introgression mapping of field-derived multiple-anthelmintic resistance in Teladorsagia circumcincta

PubMed Central

Hallsworth-Pepin, Kymberlie; Martin, John; Mitreva, Makedonka

2017-01-01

Preventive chemotherapy has long been practiced against nematode parasites of livestock, leading to widespread drug resistance, and is increasingly being adopted for eradication of human parasitic nematodes even though it is similarly likely to lead to drug resistance. Given that the genetic architecture of resistance is poorly understood for any nematode, we have analyzed multidrug resistant Teladorsagia circumcincta, a major parasite of sheep, as a model for analysis of resistance selection. We introgressed a field-derived multiresistant genotype into a partially inbred susceptible genetic background (through repeated backcrossing and drug selection) and performed genome-wide scans in the backcross progeny and drug-selected F2 populations to identify the major genes responsible for the multidrug resistance. We identified variation linking candidate resistance genes to each drug class. Putative mechanisms included target site polymorphism, changes in likely regulatory regions and copy number variation in efflux transporters. This work elucidates the genetic architecture of multiple anthelmintic resistance in a parasitic nematode for the first time and establishes a framework for future studies of anthelmintic resistance in nematode parasites of humans. PMID:28644839

Flexible Thick-Film Electrochemical Sensors: Impact of Mechanical Bending and Stress on the Electrochemical Behavior

PubMed Central

Cai, Jiaying; Cizek, Karel; Long, Brenton; McAferty, Kenyon; Campbell, Casey G.; Allee, David R.; Vogt, Bryan D.; La Belle, Jeff; Wang, Joseph

2009-01-01

The influence of the mechanical bending, rolling and crimping of flexible screen-printed electrodes upon their electrical properties and electrochemical behavior has been elucidated. Three different flexible plastic substrates, Mylar, polyethylene naphthalate (PEN), and Kapton, have been tested in connection to the printing of graphite ink working electrodes. Our data indicate that flexible printed electrodes can be bent to extremely small radii of curvature and still function well, despite a marginal increase the electrical resistance. Below critical radii of curvature of ~8 mm, full recovery of the electrical resistance occurs upon strain release. The electrochemical response is maintained for sub-mm bending radii and a 180° pinch of the electrode does not lead to device failure. The electrodes appear to be resistant to repeated bending. Such capabilities are demonstrated using model compounds, including ferrocyanide, trinitrotoluene (TNT) and nitronaphthalene (NN). These printed electrodes hold great promise for widespread applications requiring flexible, yet robust non-planar sensing devices. PMID:20160861

Mechanisms leading to in vivo ceftolozane/tazobactam resistance development during the treatment of infections caused by MDR Pseudomonas aeruginosa.

PubMed

Fraile-Ribot, Pablo A; Cabot, Gabriel; Mulet, Xavier; Periañez, Leonor; Martín-Pena, M Luisa; Juan, Carlos; Pérez, José L; Oliver, Antonio

2017-11-14

Characterization of the mechanisms driving ceftolozane/tazobactam resistance development in 5 of 47 (10.6%) patients treated for MDR Pseudomonas aeruginosa infections in a Spanish hospital. Five pairs of ceftolozane/tazobactam-susceptible/resistant P. aeruginosa isolates were studied. MICs were determined by broth microdilution, clonal relatedness was assessed by MLST and resistance mechanisms were investigated by phenotypic and genotypic methods, including WGS. ampC variants were cloned to assess their impact on resistance. In all five cases, the same clone was detected for the susceptible/resistant pairs; the widespread ST175 high-risk clone in four of the cases and ST179 in the remaining case. Genomic analysis of the four initial ST175 isolates revealed the characteristic OprD mutation (Q142X) responsible for carbapenem resistance and the AmpR mutation (G154R) responsible for AmpC overexpression and β-lactam resistance. The final isolates had developed ceftolozane/tazobactam and ceftazidime/avibactam resistance, and each additionally showed a mutation in AmpC: E247K in one of the isolates, T96I in two isolates and a deletion of 19 amino acids (G229-E247) in the remaining isolate. The cloned AmpC variants showed greatly increased ceftolozane/tazobactam and ceftazidime/avibactam MICs compared with WT AmpC, but, in contrast, yielded lower MICs of imipenem, cefepime and particularly piperacillin/tazobactam. On the other hand, ceftolozane/tazobactam resistance development in ST179 was shown to be driven by the emergence of the extended-spectrum OXA β-lactamase OXA-14, through the selection of an N146S mutation from OXA-10. Modification of intrinsic (AmpC) and horizontally acquired β-lactamases appears to be the main mechanism leading to ceftolozane/tazobactam resistance in MDR P. aeruginosa. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Arsenic detoxification and evolution of trimethylarsine gas by a microbial arsenite S-adenosylmethionine methyltransferase

PubMed Central

Qin, Jie; Rosen, Barry P.; Zhang, Yang; Wang, Gejiao; Franke, Sylvia; Rensing, Christopher

2006-01-01

In this article, a mechanism of arsenite [As(III)]resistance through methylation and subsequent volatization is described. Heterologous expression of arsM from Rhodopseudomonas palustris was shown to confer As(III) resistance to an arsenic-sensitive strain of Escherichia coli. ArsM catalyzes the formation of a number of methylated intermediates from As(III), with trimethylarsine as the end product. The net result is loss of arsenic, from both the medium and the cells. Because ArsM homologues are widespread in nature, this microbial-mediated transformation is proposed to have an important impact on the global arsenic cycle. PMID:16452170

Antibiotic resistance is widespread in urban aquatic environments of Rio de Janeiro, Brazil.

PubMed

Coutinho, Felipe H; Silveira, Cynthia B; Pinto, Leonardo H; Salloto, Gigliola R B; Cardoso, Alexander M; Martins, Orlando B; Vieira, Ricardo P; Clementino, Maysa M

2014-10-01

Bacterial resistance to antibiotics has become a public health issue. Over the years, pathogenic organisms with resistance traits have been studied due to the threat they pose to human well-being. However, several studies raised awareness to the often disregarded importance of environmental bacteria as sources of resistance mechanisms. In this work, we analyze the diversity of antibiotic-resistant bacteria occurring in aquatic environments of the state of Rio de Janeiro, Brazil, that are subjected to distinct degrees of anthropogenic impacts. We access the diversity of aquatic bacteria capable of growing in increasing ampicillin concentrations through 16S rRNA gene libraries. This analysis is complemented by the characterization of antibiotic resistance profiles of isolates obtained from urban aquatic environments. We detect communities capable of tolerating antibiotic concentrations up to 600 times higher than the clinical levels. Among the resistant organisms are included potentially pathogenic species, some of them classified as multiresistant. Our results extend the knowledge of the diversity of antibiotic resistance among environmental microorganisms and provide evidence that the diversity of drug-resistant bacteria in aquatic habitats can be influenced by pollution.

Deoxynybomycins inhibit mutant DNA gyrase and rescue mice infected with fluoroquinolone-resistant bacteria

PubMed Central

Parkinson, Elizabeth I.; Bair, Joseph S.; Nakamura, Bradley A.; Lee, Hyang Y.; Kuttab, Hani I.; Southgate, Emma H.; Lezmi, Stéphane; Lau, Gee W.; Hergenrother, Paul J.

2015-01-01

Fluoroquinolones are one of the most commonly prescribed classes of antibiotics, but fluoroquinolone resistance (FQR) is widespread and increasing. Deoxynybomycin (DNM) is a natural-product antibiotic with an unusual mechanism of action, inhibiting the mutant DNA gyrase that confers FQR. Unfortunately, isolation of DNM is difficult and DNM is insoluble in aqueous solutions, making it a poor candidate for development. Here we describe a facile chemical route to produce DNM and its derivatives. These compounds possess excellent activity against FQR methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococci clinical isolates and inhibit mutant DNA gyrase in-vitro. Bacteria that develop resistance to DNM are re-sensitized to fluoroquinolones, suggesting that resistance that emerges to DNM would be treatable. Using a DNM derivative, the first in-vivo efficacy of the nybomycin class is demonstrated in a mouse infection model. Overall, the data presented suggest the promise of DNM derivatives for the treatment of FQR infections. PMID:25907309

Decreased emergence of emerald ash borer from ash treated with methyl jasmonate is associated with induction of general defense traits and the toxic phenolic compound verbascoside.

PubMed

Whitehill, Justin G A; Rigsby, Chad; Cipollini, Don; Herms, Daniel A; Bonello, Pierluigi

2014-12-01

The emerald ash borer (EAB; Agrilus planipennis Fairmaire) is causing widespread mortality of ash (Fraxinus spp.) in North America. To date, no mechanisms of host resistance have been identified against this pest. Methyl jasmonate was applied to susceptible North American and resistant Asian ash species to determine if it can elicit induced responses in bark that enhance resistance to EAB. In particular, phenolic compounds, lignin, and defense-related proteins were quantified, and compounds associated with resistance were subsequently tested directly against EAB larvae in bioassays with artificial diet. MeJA application decreased adult emergence in susceptible ash species, comparable to levels achieved by insecticide application. Concentration of the phenolic compound verbascoside sharply increased after MeJA application to green and white ash. When incorporated in an artificial diet, verbascoside decreased survival and growth of EAB neonates in a dose-dependent fashion. Lignin and trypsin inhibitors were also induced by MeJA, and analogs of both compounds reduced growth of EAB larvae in artificial diets. We conclude that the application of MeJA prior to EAB attack has the ability to enhance resistance of susceptible ash trees by inducing endogenous plant defenses, and report evidence that induction of verbascoside is a mechanism of resistance to EAB.

Sub-inhibitory concentrations of heavy metals facilitate the horizontal transfer of plasmid-mediated antibiotic resistance genes in water environment.

PubMed

Zhang, Ye; Gu, April Z; Cen, Tianyu; Li, Xiangyang; He, Miao; Li, Dan; Chen, Jianmin

2018-06-01

Although widespread antibiotic resistance has been mostly attributed to the selective pressure generated by overuse and misuse of antibiotics, recent growing evidence suggests that chemicals other than antibiotics, such as certain metals, can also select and stimulate antibiotic resistance via both co-resistance and cross-resistance mechanisms. For instance, tetL, merE, and oprD genes are resistant to both antibiotics and metals. However, the potential de novo resistance induced by heavy metals at environmentally-relevant low concentrations (much below theminimum inhibitory concentrations [MICs], also referred as sub-inhibitory) has hardly been explored. This study investigated and revealed that heavy metals, namely Cu(II), Ag(I), Cr(VI), and Zn(II), at environmentally-relevant and sub-inhibitory concentrations, promoted conjugative transfer of antibiotic resistance genes (ARGs) between E. coli strains. The mechanisms of this phenomenon were further explored, which involved intracellular reactive oxygen species (ROS) formation, SOS response, increased cell membrane permeability, and altered expression of conjugation-relevant genes. These findings suggest that sub-inhibitory levels of heavy metals that widely present in various environments contribute to the resistance phenomena via facilitating horizontal transfer of ARGs. This study provides evidence from multiple aspects implicating the ecological effect of low levels of heavy metals on antibiotic resistance dissemination and highlights the urgency of strengthening efficacious policy and technology to control metal pollutants in the environments. Copyright © 2018 Elsevier Ltd. All rights reserved.

Biomechanics of cellular solids.

PubMed

Gibson, Lorna J

2005-03-01

Materials with a cellular structure are widespread in nature and include wood, cork, plant parenchyma and trabecular bone. Natural cellular materials are often mechanically efficient: the honeycomb-like microstructure of wood, for instance, gives it an exceptionally high performance index for resisting bending and buckling. Here we review the mechanics of a wide range of natural cellular materials and examine their role in lightweight natural sandwich structures (e.g. iris leaves) and natural tubular structures (e.g. plant stems or animal quills). We also describe two examples of engineered biomaterials with a cellular structure, designed to replace or regenerate tissue in the body.

Widespread acquisition of antimicrobial resistance among Campylobacter isolates from UK retail poultry and evidence for clonal expansion of resistant lineages.

PubMed

Wimalarathna, Helen M L; Richardson, Judith F; Lawson, Andy J; Elson, Richard; Meldrum, Richard; Little, Christine L; Maiden, Martin C J; McCarthy, Noel D; Sheppard, Samuel K

2013-07-15

Antimicrobial resistance is increasing among clinical Campylobacter cases and is common among isolates from other sources, specifically retail poultry - a major source of human infection. In this study the antimicrobial susceptibility of isolates from a UK-wide survey of Campylobacter in retail poultry in 2001 and 2004-5 was investigated. The occurrence of phenotypes resistant to tetracycline, quinolones (ciprofloxacin and naladixic acid), erythromycin, chloramphenicol and aminoglycosides was quantified. This was compared with a phylogeny for these isolates based upon Multi Locus Sequence Typing (MLST) to investigate the pattern of antimicrobial resistance acquisition. Antimicrobial resistance was present in all lineage clusters, but statistical testing showed a non-random distribution. Erythromycin resistance was associated with Campylobacter coli. For all antimicrobials tested, resistant isolates were distributed among relatively distant lineages indicative of widespread acquisition. There was also evidence of clustering of resistance phenotypes within lineages; indicative of local expansion of resistant strains. These results are consistent with the widespread acquisition of antimicrobial resistance among chicken associated Campylobacter isolates, either through mutation or horizontal gene transfer, and the expansion of these lineages as a proportion of the population. As Campylobacter are not known to multiply outside of the host and long-term carriage in humans is extremely infrequent in industrialized countries, the most likely location for the proliferation of resistant lineages is in farmed chickens.

Antiseptics and Disinfectants: Activity, Action, and Resistance

PubMed Central

McDonnell, Gerald; Russell, A. Denver

1999-01-01

Antiseptics and disinfectants are extensively used in hospitals and other health care settings for a variety of topical and hard-surface applications. A wide variety of active chemical agents (biocides) are found in these products, many of which have been used for hundreds of years, including alcohols, phenols, iodine, and chlorine. Most of these active agents demonstrate broad-spectrum antimicrobial activity; however, little is known about the mode of action of these agents in comparison to antibiotics. This review considers what is known about the mode of action and spectrum of activity of antiseptics and disinfectants. The widespread use of these products has prompted some speculation on the development of microbial resistance, in particular whether antibiotic resistance is induced by antiseptics or disinfectants. Known mechanisms of microbial resistance (both intrinsic and acquired) to biocides are reviewed, with emphasis on the clinical implications of these reports. PMID:9880479

Opportunities and challenges for harvest weed seed control in global cropping systems.

PubMed

Walsh, Michael J; Broster, John C; Schwartz-Lazaro, Lauren M; Norsworthy, Jason K; Davis, Adam S; Tidemann, Breanne D; Beckie, Hugh J; Lyon, Drew J; Soni, Neeta; Neve, Paul; Bagavathiannan, Muthukumar V

2017-11-28

The opportunity to target weed seeds during grain harvest was established many decades ago following the introduction of mechanical harvesting and the recognition of high weed-seed retention levels at crop maturity; however, this opportunity remained largely neglected until more recently. The introduction and adoption of harvest weed seed control (HWSC) systems in Australia has been in response to widespread occurrence of herbicide-resistant weed populations. With diminishing herbicide resources and the need to maintain highly productive reduced tillage and stubble-retention practices, growers began to develop systems that targeted weed seeds during crop harvest. Research and development efforts over the past two decades have established the efficacy of HWSC systems in Australian cropping systems, where widespread adoption is now occurring. With similarly dramatic herbicide resistance issues now present across many of the world's cropping regions, it is timely for HWSC systems to be considered for inclusion in weed-management programs in these areas. This review describes HWSC systems and establishing the potential for this approach to weed control in several cropping regions. As observed in Australia, the inclusion of HWSC systems can reduce weed populations substantially reducing the potential for weed adaptation and resistance evolution. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Plant responses to tomato chlorotic mottle virus: Proteomic view of the resistance mechanisms to a bipartite begomovirus in tomato.

PubMed

Carmo, Lílian S T; Murad, André M; Resende, Renato O; Boiteux, Leonardo S; Ribeiro, Simone G; Jorrín-Novo, Jesús V; Mehta, Angela

2017-01-16

Tomato chlorotic mottle virus (ToCMoV) is a widespread bipartite Begomovirus species found in tomato fields in Brazil. In this study, plant responses and putative mechanisms associated with the 'Tyking'-derived recessive resistance to ToCMoV were investigated. Changes in the protein profile in the inoculated plants of two near isogenic tomato lines resistant ('LAM 157') and susceptible ('Santa Clara') to ToCMoV were analyzed. Seedlings were biolistically inoculated with an infectious ToCMoV clone. Leaves from infected plants (confirmed by PCR) were sampled at 15days after inoculation. Proteins were extracted using phenol and analyzed by shotgun MS (2D-nanoUPLC/HDMS E ). Out of the 534 identified proteins, 82 presented statistically significant differences in abundance, including 35 unique proteins displayed in the resistant tomato inoculated with ToCMoV. Proteins associated to chromatin structure, cytoskeleton structure, cuticle biosynthesis, and ubiquitin pathway were identified and their putative roles during virus infection process were discussed. The protein profile analysis allowed for the development of a hypothetical model showing how the resistant host cell responds to ToCMoV infection. The data obtained provide a better understanding of resistant mechanisms used by the host plant to contain viral infection and could be the basis for further investigation in other plant-begomovirus pathosystems. In this study we propose a model of resistance to begomovirus in tomato and highlight host proteins, which could be targets for future investigations in plant-begomovirus pathosystems. Copyright © 2016 Elsevier B.V. All rights reserved.

Detection of knockdown resistance mutations in the common bed bug, Cimex lectularius (Hemiptera: Cimicidae), in Australia.

PubMed

Dang, Kai; Toi, Cheryl S; Lilly, David G; Bu, Wenjun; Doggett, Stephen L

2015-07-01

Pyrethroid resistance in the common bed bug, Cimex lectularius L., has been reported worldwide. An important resistance mechanism is via knockdown resistance (kdr) mutations, notably V419L and L925I. Information regarding this kdr-type resistance mechanism is unknown in Australia. This study aims to examine the status of kdr mutations in Australian C. lectularius strains. Several modern field-collected strains and museum-preserved reference collections of Australian C. lectularius were examined. Of the field strains (2007-2013), 96% had the known kdr mutations (L925I or both V419L/L925I). The 'Adelaide' strain (2013) and samples from the preserved reference collections (1994-2002) revealed no known kdr mutations. A novel mutation I936F was apparent in the insecticide-resistant 'Adelaide' strain, one strain from Perth (with L925I) and the majority of the reference collection specimens. The laboratory insecticide-resistant 'Sydney' strain showed a mixture of no kdr mutations (20%) and L925I (80%). The novel mutation I936F may be a kdr mutation but appeared to contribute less resistance to the pyrethroids than the V419L and L925I mutations. The detection of high frequencies of kdr mutations indicates that kdr-type resistance is widespread across Australia. Hence, there should be a reduced reliance on pyrethroid insecticides and an integrated management approach for the control of C. lectularius infestations. © 2014 Society of Chemical Industry.

Dissemination of Novel Antimicrobial Resistance Mechanisms through the Insertion Sequence Mediated Spread of Metabolic Genes

PubMed Central

Furi, Leonardo; Haigh, Richard; Al Jabri, Zaaima J. H.; Morrissey, Ian; Ou, Hong-Yu; León-Sampedro, Ricardo; Martinez, Jose L.; Coque, Teresa M.; Oggioni, Marco R.

2016-01-01

The widely used biocide triclosan selectively targets FabI, the NADH-dependent trans-2-enoyl-acyl carrier protein (ACP) reductase, which is also an important target for the development of narrow spectrum antibiotics. The analysis of triclosan resistant Staphylococcus aureus isolates had previously shown that in about half of the strains, the mechanism of triclosan resistance consists on the heterologous duplication of the triclosan target gene due to the acquisition of an additional fabI allele derived from Staphylococcus haemolyticus (sh-fabI). In the current work, the genomic sequencing of 10 of these strains allowed the characterization of two novel composite transposons TnSha1 and TnSha2 involved in the spread of sh-fabI. TnSha1 harbors one copy of IS1272, whereas TnSha2 is a 11.7 kb plasmid carrying TnSha1 present either as plasmid or in an integrated form generally flanked by two IS1272 elements. The target and mechanism of integration for IS1272 and TnSha1 are novel and include targeting of DNA secondary structures, generation of blunt-end deletions of the stem-loop and absence of target duplication. Database analyses showed widespread occurrence of these two elements in chromosomes and plasmids, with TnSha1 mainly in S. aureus and with TnSha2 mainly in S. haemolyticus and S. epidermidis. The acquisition of resistance by means of an insertion sequence-based mobilization and consequent duplication of drug-target metabolic genes, as observed here for sh-fabI, is highly reminiscent of the situation with the ileS2 gene conferring mupirocin resistance, and the dfrA and dfrG genes conferring trimethoprim resistance both of which are mobilized by IS257. These three examples, which show similar mechanisms and levels of spread of metabolic genes linked to IS elements, highlight the importance of this genetic strategy for recruitment and rapid distribution of novel resistance mechanisms in staphylococci. PMID:27446047

Iterative Chemical Engineering of Vancomycin Leads to Novel Vancomycin Analogs With a High in Vitro Therapeutic Index.

PubMed

Mishra, Nigam M; Stolarzewicz, Izabela; Cannaerts, David; Schuermans, Joris; Lavigne, Rob; Looz, Yannick; Landuyt, Bart; Schoofs, Liliane; Schols, Dominique; Paeshuyse, Jan; Hickenbotham, Peter; Clokie, Martha; Luyten, Walter; Van der Eycken, Erik V; Briers, Yves

2018-01-01

Vancomycin is a glycopeptide antibiotic that inhibits transpeptidation during cell wall synthesis by binding to the D-Ala-D-Ala termini of lipid II. For long, it has been used as a last resort antibiotic. However, since the emergence of the first vancomycin-resistant enterococci in 1987, vancomycin resistance has become widespread, especially in hospitals. We have synthesized and evaluated 110 vancomycin analogs modified at the C-terminal carboxyl group of the heptapeptide moiety with R 2 NHR 1 NH 2 substituents. Through iterative optimizations of the substituents, we identified vancomycin analogs that fully restore (or even exceed) the original inhibitory activity against vancomycin-resistant enterococci (VRE), vancomycin-intermediate (VISA) and vancomycin-resistant Staphylococcus aureus (VRSA) strains. The best analogs have improved growth inhibitory activity and in vitro therapeutic indices against a broad set of VRE and methicillin-resistant S. aureus (MRSA) isolates. They also exceed the activity of vancomycin against Clostridium difficile ribotypes. Vanc-39 and Vanc-42 have a low probability to provoke antibiotic resistance, and overcome different vancomycin resistance mechanisms (VanA, VanB, and VanC1).

Effect of Sn4+ Additives on the Microstructure and Corrosion Resistance of Anodic Coating Formed on AZ31 Magnesium Alloy in Alkaline Solution

NASA Astrophysics Data System (ADS)

Salman, S. A.; Kuroda, K.; Saito, N.; Okido, M.

Magnesium is the lightest structural metal with high specific strength and good mechanical properties. However, poor corrosion resistance limits its widespread use in many applications. Magnesium is usually treated with Chromate conversion coatings. However, due to changing environmental regulations and pollution prevention requirements, a significant push exists to find new, alternative for poisonous Cr6+. Therefore, we aim to improve corrosion resistance of anodic coatings on AZ31 alloys using low cost non-chromate electrolyte. Anodizing was carried out in alkaline solutions with tin additives. The effect of tin additives on the coating film was characterized by SEM and XRD. The corrosion resistance was evaluated using anodic and cathodic polarizations and electrochemical impedance spectroscopy (EIS). Corrosion resistance property was improved with tin additives and the best anti-corrosion property was obtained with addition of 0.03 M Na2SnO3.3H2O to anodizing solution.

The Preparation, Characterization and Formation Mechanism of a Calcium Phosphate Conversion Coating on Magnesium Alloy AZ91D.

PubMed

Liu, Dong; Li, Yanyan; Zhou, Yong; Ding, Yigang

2018-05-28

The poor corrosion resistance of magnesium alloys is one of the main obstacles preventing their widespread usage. Due to the advantages of lower cost and simplicity in operation, chemical conversion coating has drawn considerable attention for its improvement of the corrosion resistance of magnesium alloys. In this study, a calcium phosphate coating was prepared on magnesium alloy AZ91D by chemical conversion. For the calcium phosphate coating, the effect of processing parameters on the microstructure and corrosion resistance was studied by scanning electron microscope (SEM) and electrochemical methods, and the coating composition was characterized by X-ray diffraction (XRD). The calcium phosphate coating was mainly composed of CaHPO₄·2H₂O (DCPD), with fewer cracks and pores. The coating with the leaf-like microstructure provided great corrosion resistance to the AZ91D substrate, and was obtained under the following conditions: 20 min, ambient temperature, and no stirring. At the same time, the role of NH₄H₂PO₄ as the coating-forming agent and the acidifying agent in the conversion process was realized, and the formation mechanism of DCPD was discussed in detail in this work.

Technology Solutions Case Study: Cladding Attachment Over Thick Exterior Insulating Sheathing

DOE Office of Scientific and Technical Information (OSTI.GOV)

None

The addition of insulation to the exterior of buildings is an effective means of increasing the thermal resistance of wood-framed walls and mass masonry wall assemblies. Insulation on the exterior of the structure has many direct benefits, including better effective R-value from reduced thermal bridging, better condensation resistance, reduced thermal stress on the structure, as well as other commonly associated improvements such as increased airtightness and improved water management. Although the approach has proven effective, there is resistance to its widespread implementation due to a lack of research and understanding of the mechanisms involved in the development of the verticalmore » displacement resistance capacity. In addition, the long-term in-service performance of the system has been questioned due to potential creep effects of the assembly under the sustained dead load of the cladding and effects of varying environmental conditions. In addition, the current International Building Code (IBC) and International Residential Code (IRC) do not have a provision that specifically allows this assembly. In this project, researchers from Building Science Corporation, a Building America team, investigated these issues to better understand the mechanics behind this method of cladding attachment« less

Prevalence and characteristics of quinolone resistance in Escherichia coli in veal calves.

PubMed

Hordijk, Joost; Veldman, Kees; Dierikx, Cindy; van Essen-Zandbergen, Alieda; Wagenaar, Jaap A; Mevius, Dik

2012-04-23

Quinolone resistance is studied and reported increasingly in isolates from humans, food-producing animals and companion animals. Resistance can be caused by chromosomal mutations in topoisomerase genes, plasmid-mediated resistance genes, and active transport through efflux pumps. Cross sectional data on quinolone resistance mechanisms in non-pathogenic bacteria from healthy veal calves is limited. The purpose of this study was to determine the prevalence and characteristics of quinolone resistance mechanisms in Escherichia coli isolates from veal calves, after more than 20 years of quinolone usage in veal calves. MIC values were determined for all isolates collected as part of a national surveillance program on antimicrobial resistance in commensal bacteria in food-producing animals in The Netherlands. From the strains collected from veal calves in 2007 (n=175) all isolates with ciprofloxacin MIC ≥ 0.125 mg/L (n=25) were selected for this study, and screened for the presence of known quinolone resistance determinants. In this selection only chromosomal mutations in the topoisomerase type II and IV genes were detected. The number of mutations found per isolate correlated with an increasing ciprofloxacin MIC. No plasmid-mediated quinolone resistance genes were found. The contribution of efflux pumps varied from no contribution to a 16-fold increase in susceptibility. No correlation was found with the presence of resistance genes of other antimicrobial classes, even though all quinolone non-wild type isolates were resistant to 3 or more classes of antibiotics other than quinolones. Over twenty years of quinolone usage in veal calves in The Netherlands did not result in a widespread occurrence of plasmid-mediated quinolone resistance, limiting the transmission of quinolone resistance to clonal distribution. Copyright © 2011 Elsevier B.V. All rights reserved.

Patterns of insecticide resistance and knock down resistance (kdr) in malaria vectors An. arabiensis, An. coluzzii and An. gambiae from sympatric areas in Senegal.

PubMed

Niang, El Hadji Amadou; Konaté, Lassana; Diallo, Mawlouth; Faye, Ousmane; Dia, Ibrahima

2016-02-05

Malaria vector control in Africa relies on insecticides targeting adult mosquito vectors via insecticide treated nets or indoor residual spraying. Despite the proven efficacy of these strategies, the emergence and rapid rise in insecticide resistance in malaria vectors raises many concerns about their sustainability. Therefore, the monitoring of insecticide resistance is essential for resistance management strategies implementation. We investigated the kdr mutation frequencies in 20 sympatric sites of An. arabiensis Patton, An. coluzzii Coetzee & Wilkerson and An. gambiae Giles and its importance in malaria vector control by evaluating the susceptibility to insecticides in four representative sites in Senegal. Sibling species identification and kdr mutation detection were determined using polymerase chain reaction on mosquitoes collected using pyrethrum sprays collection in 20 sites belonging to two transects with differential insecticide selection pressure. The World Health Organization (WHO) tube test was used to determine phenotypic resistance of An. gambiae s.l. to DDT, deltamethrin, lambdacyholothrin, permethrin, bendiocarb and malathion in four representative sites. The L1014F kdr mutation was widely distributed and was predominant in An. gambiae in comparison to An. arabiensis and An. coluzzii. The bioassay tests showed a general trend with a resistance to DDT and pyrethroids and a susceptibility to organophosphate and carbamate according to WHO thresholds. For deltamethrin and permethrin, the two most used insecticides, no significant difference were observed either between the two transects or between mortality rates suggesting no differential selection pressures on malaria vectors. The study of the KD times showed similar trends as comparable levels of resistance were observed, the effect being more pronounced for permethrin. Our study showed a widespread resistance of malaria vectors to DDT and pyrethroids and a widespread distribution of the 1014F kdr allele. These combined observations could suggest the involvement of the kdr mutation. The existence of other resistance mechanisms could not be ruled out as a proportion of mosquitoes did not harbour the kdr allele whereas the populations were fully resistant. The susceptibility to carbamate and organophosphate could be exploited as alternative for insecticide resistance management.

[Susceptibility of Aedes aegypti to DDT, deltamethrin, and lambda-cyhalothrin in Colombia].

PubMed

Santacoloma Varón, Liliana; Chaves Córdoba, Bernardo; Brochero, Helena Luisa

2010-01-01

To assess the susceptibility status of 13 natural populations of Aedes aegypti (collected from sites in Colombia where dengue is a serious public health problem) to the pyrethroids, deltamethrin and lambda-cyhalothrin, and to the organochlorine, DDT, and to identify any biochemical mechanisms associated with resistance. Immature forms of the vector were collected from natural breeding spots at each site and then raised under controlled conditions. Using the F2 generation, bioassays were performed using the World Health Organization's 1981 methodology (impregnated paper) and United States Centers for Disease Control and Prevention's 1998 methodology (impregnated bottles). In populations where mortality rates were consistent with decreased susceptibility, levels of nonspecific esterases (NSE), mixed-function oxidases (MFO), and acetylcholinesterase (AChE) were measured using colorimetric tests. All of the mosquito populations that were tested showed resistance to the organochlorine DDT. In the case of the pyrethroids, widespread resistance to lambda-cyhalothrin was found, but not to deltamethrin. Assessing the biochemical resistance mechanisms showed that 7 of the 11 populations had elevated NSE, and one population, increased MFO. Physiological cross-resistance between DDT and lambda-cyhalothrin in the A. aegypti populations tested was dismissed. Physiological resistance to lambda-cyhalothrin appears to be associated with increased NSE. The differences in susceptibility levels and enzyme values among the populations were associated with genetic variations and chemicals in use locally.

Danger of Antibiotic Overuse (For Parents)

MedlinePlus

... against them. This is called bacterial resistance or antibiotic resistance. Treating these resistant bacteria requires higher doses of ... to even the most powerful antibiotics available today. Antibiotic resistance is a widespread problem, and one that the ...

Evolution of a double amino acid substitution in the 5-enolpyruvylshikimate-3-phosphate synthase in Eleusine indica conferring high-level glyphosate resistance.

PubMed

Yu, Qin; Jalaludin, Adam; Han, Heping; Chen, Ming; Sammons, R Douglas; Powles, Stephen B

2015-04-01

Glyphosate is the most important and widely used herbicide in world agriculture. Intensive glyphosate selection has resulted in the widespread evolution of glyphosate-resistant weed populations, threatening the sustainability of this valuable once-in-a-century agrochemical. Field-evolved glyphosate resistance due to known resistance mechanisms is generally low to modest. Here, working with a highly glyphosate-resistant Eleusine indica population, we identified a double amino acid substitution (T102I+P106S [TIPS]) in the 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) gene in glyphosate-resistant individuals. This TIPS mutation recreates the biotechnology-engineered commercial first generation glyphosate-tolerant EPSPS in corn (Zea mays) and now in other crops. In E. indica, the naturally evolved TIPS mutants are highly (more than 180-fold) resistant to glyphosate compared with the wild type and more resistant (more than 32-fold) than the previously known P106S mutants. The E. indica TIPS EPSPS showed very high-level (2,647-fold) in vitro resistance to glyphosate relative to the wild type and is more resistant (600-fold) than the P106S variant. The evolution of the TIPS mutation in crop fields under glyphosate selection is likely a sequential event, with the P106S mutation being selected first and fixed, followed by the T102I mutation to create the highly resistant TIPS EPSPS. The sequential evolution of the TIPS mutation endowing high-level glyphosate resistance is an important mechanism by which plants adapt to intense herbicide selection and a dramatic example of evolution in action. © 2015 American Society of Plant Biologists. All Rights Reserved.

Evolution of a Double Amino Acid Substitution in the 5-Enolpyruvylshikimate-3-Phosphate Synthase in Eleusine indica Conferring High-Level Glyphosate Resistance1

PubMed Central

Yu, Qin; Jalaludin, Adam; Han, Heping; Chen, Ming; Sammons, R. Douglas; Powles, Stephen B.

2015-01-01

Glyphosate is the most important and widely used herbicide in world agriculture. Intensive glyphosate selection has resulted in the widespread evolution of glyphosate-resistant weed populations, threatening the sustainability of this valuable once-in-a-century agrochemical. Field-evolved glyphosate resistance due to known resistance mechanisms is generally low to modest. Here, working with a highly glyphosate-resistant Eleusine indica population, we identified a double amino acid substitution (T102I + P106S [TIPS]) in the 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) gene in glyphosate-resistant individuals. This TIPS mutation recreates the biotechnology-engineered commercial first generation glyphosate-tolerant EPSPS in corn (Zea mays) and now in other crops. In E. indica, the naturally evolved TIPS mutants are highly (more than 180-fold) resistant to glyphosate compared with the wild type and more resistant (more than 32-fold) than the previously known P106S mutants. The E. indica TIPS EPSPS showed very high-level (2,647-fold) in vitro resistance to glyphosate relative to the wild type and is more resistant (600-fold) than the P106S variant. The evolution of the TIPS mutation in crop fields under glyphosate selection is likely a sequential event, with the P106S mutation being selected first and fixed, followed by the T102I mutation to create the highly resistant TIPS EPSPS. The sequential evolution of the TIPS mutation endowing high-level glyphosate resistance is an important mechanism by which plants adapt to intense herbicide selection and a dramatic example of evolution in action. PMID:25717039

The Versatile Mutational Resistome of Pseudomonas aeruginosa

PubMed Central

López-Causapé, Carla; Cabot, Gabriel; del Barrio-Tofiño, Ester; Oliver, Antonio

2018-01-01

One of the most striking features of Pseudomonas aeruginosa is its outstanding capacity for developing antimicrobial resistance to nearly all available antipseudomonal agents through the selection of chromosomal mutations, leading to the failure of the treatment of severe hospital-acquired or chronic infections. Recent whole-genome sequencing (WGS) data obtained from in vitro assays on the evolution of antibiotic resistance, in vivo monitoring of antimicrobial resistance development, analysis of sequential cystic fibrosis isolates, and characterization of widespread epidemic high-risk clones have provided new insights into the evolutionary dynamics and mechanisms of P. aeruginosa antibiotic resistance, thus motivating this review. Indeed, the analysis of the WGS mutational resistome has proven to be useful for understanding the evolutionary dynamics of classical resistance pathways and to describe new mechanisms for the majority of antipseudomonal classes, including β-lactams, aminoglycosides, fluoroquinolones, or polymixins. Beyond addressing a relevant scientific question, the analysis of the P. aeruginosa mutational resistome is expected to be useful, together with the analysis of the horizontally-acquired resistance determinants, for establishing the antibiotic resistance genotype, which should correlate with the antibiotic resistance phenotype and as such, it should be useful for the design of therapeutic strategies and for monitoring the efficacy of administered antibiotic treatments. However, further experimental research and new bioinformatics tools are still needed to overcome the interpretation limitations imposed by the complex interactions (including those leading to collateral resistance or susceptibility) between the 100s of genes involved in the mutational resistome, as well as the frequent difficulties for differentiating relevant mutations from simple natural polymorphisms. PMID:29681898

The Versatile Mutational Resistome of Pseudomonas aeruginosa.

PubMed

López-Causapé, Carla; Cabot, Gabriel; Del Barrio-Tofiño, Ester; Oliver, Antonio

2018-01-01

One of the most striking features of Pseudomonas aeruginosa is its outstanding capacity for developing antimicrobial resistance to nearly all available antipseudomonal agents through the selection of chromosomal mutations, leading to the failure of the treatment of severe hospital-acquired or chronic infections. Recent whole-genome sequencing (WGS) data obtained from in vitro assays on the evolution of antibiotic resistance, in vivo monitoring of antimicrobial resistance development, analysis of sequential cystic fibrosis isolates, and characterization of widespread epidemic high-risk clones have provided new insights into the evolutionary dynamics and mechanisms of P. aeruginosa antibiotic resistance, thus motivating this review. Indeed, the analysis of the WGS mutational resistome has proven to be useful for understanding the evolutionary dynamics of classical resistance pathways and to describe new mechanisms for the majority of antipseudomonal classes, including β-lactams, aminoglycosides, fluoroquinolones, or polymixins. Beyond addressing a relevant scientific question, the analysis of the P. aeruginosa mutational resistome is expected to be useful, together with the analysis of the horizontally-acquired resistance determinants, for establishing the antibiotic resistance genotype, which should correlate with the antibiotic resistance phenotype and as such, it should be useful for the design of therapeutic strategies and for monitoring the efficacy of administered antibiotic treatments. However, further experimental research and new bioinformatics tools are still needed to overcome the interpretation limitations imposed by the complex interactions (including those leading to collateral resistance or susceptibility) between the 100s of genes involved in the mutational resistome, as well as the frequent difficulties for differentiating relevant mutations from simple natural polymorphisms.

Characterization and functional analysis of a carboxylesterase gene associated with chlorpyrifos resistance in Nilaparvata lugens (Stål).

PubMed

Lu, Kai; Wang, Ying; Chen, Xia; Zhang, Zhichao; Li, Yue; Li, Wenru; Zhou, Qiang

2017-12-01

The widespread and extensive application of insecticides have promoted the development of resistance in the brown planthopper Nilaparvata lugens (Stål), one of the most important rice pests in Asia. To better understand the underlying molecular mechanisms of metabolic resistance to insecticides, a chlorpyrifos-resistant (CR) strain of N. lugens was selected and its possible resistance mechanism was investigated. Synergistic tests using carboxylesterases (CarEs) inhibitor triphenyl phosphate (TPP) decreased the resistance of N. lugens to chlorpyrifos, and CarE activities could be induced by low concentrations of chlorpyrifos. Subsequently, a gene putatively encoding CarE, namely NlCarE, predominant in the midgut and ovary was isolated and characterized. The expression levels of NlCarE were detected and compared between the CR and a susceptible (SS) strain of N. lugens. Consistent with the increased CarE activity, this gene was overexpressed in the CR strain compared to the SS strain. The transcript levels of NlCarE were up-regulated by chlorpyrifos exposure, showing dose- and time-dependent expression patterns. Furthermore, RNA interference (RNAi)-mediated knockdown of NlCarE followed by insecticide application significantly increased the susceptibility of N. lugens to chlorpyrifos. These results demonstrate that NlCarE plays an important role in chlorpyrifos detoxification and its overexpression may be involved in chlorpyrifos resistance in N. lugens. Copyright © 2017 Elsevier Inc. All rights reserved.

High-throughput identification and rational design of synergistic small-molecule pairs for combating and bypassing antibiotic resistance.

PubMed

Wambaugh, Morgan A; Shakya, Viplendra P S; Lewis, Adam J; Mulvey, Matthew A; Brown, Jessica C S

2017-06-01

Antibiotic-resistant infections kill approximately 23,000 people and cost $20,000,000,000 each year in the United States alone despite the widespread use of small-molecule antimicrobial combination therapy. Antibiotic combinations typically have an additive effect: the efficacy of the combination matches the sum of the efficacies of each antibiotic when used alone. Small molecules can also act synergistically when the efficacy of the combination is greater than the additive efficacy. However, synergistic combinations are rare and have been historically difficult to identify. High-throughput identification of synergistic pairs is limited by the scale of potential combinations: a modest collection of 1,000 small molecules involves 1 million pairwise combinations. Here, we describe a high-throughput method for rapid identification of synergistic small-molecule pairs, the overlap2 method (O2M). O2M extracts patterns from chemical-genetic datasets, which are created when a collection of mutants is grown in the presence of hundreds of different small molecules, producing a precise set of phenotypes induced by each small molecule across the mutant set. The identification of mutants that show the same phenotype when treated with known synergistic molecules allows us to pinpoint additional molecule combinations that also act synergistically. As a proof of concept, we focus on combinations with the antibiotics trimethoprim and sulfamethizole, which had been standard treatment against urinary tract infections until widespread resistance decreased efficacy. Using O2M, we screened a library of 2,000 small molecules and identified several that synergize with the antibiotic trimethoprim and/or sulfamethizole. The most potent of these synergistic interactions is with the antiviral drug azidothymidine (AZT). We then demonstrate that understanding the molecular mechanism underlying small-molecule synergistic interactions allows the rational design of additional combinations that bypass drug resistance. Trimethoprim and sulfamethizole are both folate biosynthesis inhibitors. We find that this activity disrupts nucleotide homeostasis, which blocks DNA replication in the presence of AZT. Building on these data, we show that other small molecules that disrupt nucleotide homeostasis through other mechanisms (hydroxyurea and floxuridine) also act synergistically with AZT. These novel combinations inhibit the growth and virulence of trimethoprim-resistant clinical Escherichia coli and Klebsiella pneumoniae isolates, suggesting that they may be able to be rapidly advanced into clinical use. In sum, we present a generalizable method to screen for novel synergistic combinations, to identify particular mechanisms resulting in synergy, and to use the mechanistic knowledge to rationally design new combinations that bypass drug resistance.

High-throughput identification and rational design of synergistic small-molecule pairs for combating and bypassing antibiotic resistance

PubMed Central

Lewis, Adam J.; Mulvey, Matthew A.

2017-01-01

Antibiotic-resistant infections kill approximately 23,000 people and cost $20,000,000,000 each year in the United States alone despite the widespread use of small-molecule antimicrobial combination therapy. Antibiotic combinations typically have an additive effect: the efficacy of the combination matches the sum of the efficacies of each antibiotic when used alone. Small molecules can also act synergistically when the efficacy of the combination is greater than the additive efficacy. However, synergistic combinations are rare and have been historically difficult to identify. High-throughput identification of synergistic pairs is limited by the scale of potential combinations: a modest collection of 1,000 small molecules involves 1 million pairwise combinations. Here, we describe a high-throughput method for rapid identification of synergistic small-molecule pairs, the overlap2 method (O2M). O2M extracts patterns from chemical-genetic datasets, which are created when a collection of mutants is grown in the presence of hundreds of different small molecules, producing a precise set of phenotypes induced by each small molecule across the mutant set. The identification of mutants that show the same phenotype when treated with known synergistic molecules allows us to pinpoint additional molecule combinations that also act synergistically. As a proof of concept, we focus on combinations with the antibiotics trimethoprim and sulfamethizole, which had been standard treatment against urinary tract infections until widespread resistance decreased efficacy. Using O2M, we screened a library of 2,000 small molecules and identified several that synergize with the antibiotic trimethoprim and/or sulfamethizole. The most potent of these synergistic interactions is with the antiviral drug azidothymidine (AZT). We then demonstrate that understanding the molecular mechanism underlying small-molecule synergistic interactions allows the rational design of additional combinations that bypass drug resistance. Trimethoprim and sulfamethizole are both folate biosynthesis inhibitors. We find that this activity disrupts nucleotide homeostasis, which blocks DNA replication in the presence of AZT. Building on these data, we show that other small molecules that disrupt nucleotide homeostasis through other mechanisms (hydroxyurea and floxuridine) also act synergistically with AZT. These novel combinations inhibit the growth and virulence of trimethoprim-resistant clinical Escherichia coli and Klebsiella pneumoniae isolates, suggesting that they may be able to be rapidly advanced into clinical use. In sum, we present a generalizable method to screen for novel synergistic combinations, to identify particular mechanisms resulting in synergy, and to use the mechanistic knowledge to rationally design new combinations that bypass drug resistance. PMID:28632788

Engineering the lodging resistance mechanism of post-Green Revolution rice to meet future demands.

PubMed

Hirano, Ko; Ordonio, Reynante Lacsamana; Matsuoka, Makoto

2017-01-01

Traditional breeding for high-yielding rice has been dependent on the widespread cultivation of gibberellin (GA)-deficient semi-dwarf varieties. Dwarfism lowers the "center of gravity" of the plant body, which increases resistance against lodging and enables plants to support high grain yield. Although this approach was successful in latter half of the 20th century in rice and wheat breeding, this may no longer be enough to sustain rice with even higher yields. This is because relying solely on the semi-dwarf trait is subject to certain limitations, making it necessary to use other important traits to reinforce it. In this review, we present an alternative approach to increase lodging resistance by improving the quality of the culm by identifying genes related to culm quality and introducing these genes into high-yielding rice cultivars through molecular breeding technique.

The BpeEF-OprC Efflux Pump Is Responsible for Widespread Trimethoprim Resistance in Clinical and Environmental Burkholderia pseudomallei Isolates

PubMed Central

Podnecky, Nicole L.; Wuthiekanun, Vanaporn; Peacock, Sharon J.

2013-01-01

Trimethoprim-sulfamethoxazole (co-trimoxazole) is the primary drug used for oral eradication therapy of Burkholderia pseudomallei infections (melioidosis). Here, we demonstrate that trimethoprim resistance is widespread in clinical and environmental isolates from northeast Thailand and northern Australia. This resistance was shown to be due to BpeEF-OprC efflux pump expression. No dihydrofolate reductase target mutations were involved, although frequent insertion of ISBma2 was noted within the putative folA transcriptional terminator. All isolates tested remained susceptible to trimethoprim-sulfamethoxazole, suggesting that resistance to trimethoprim alone in these strains probably does not affect the efficacy of co-trimoxazole therapy. PMID:23817379

An online tool for mapping insecticide resistance in major Anopheles vectors of human malaria parasites and review of resistance status for the Afrotropical region

PubMed Central

2014-01-01

Background Malaria control programmes across Africa and beyond are facing increasing insecticide resistance in the major anopheline vectors. In order to preserve or prolong the effectiveness of the main malaria vector interventions, up-to-date and easily accessible insecticide resistance data that are interpretable at operationally-relevant scales are critical. Herein we introduce and demonstrate the usefulness of an online mapping tool, IR Mapper. Methods A systematic search of published, peer-reviewed literature was performed and Anopheles insecticide susceptibility and resistance mechanisms data were extracted and added to a database after a two-level verification process. IR Mapper ( http://www.irmapper.com) was developed using the ArcGIS for JavaScript Application Programming Interface and ArcGIS Online platform for exploration and projection of these data. Results Literature searches yielded a total of 4,084 susceptibility data points for 1,505 populations, and 2,097 resistance mechanisms data points for 1,000 populations of Anopheles spp. tested via recommended WHO methods from 54 countries between 1954 and 2012. For the Afrotropical region, data were most abundant for populations of An. gambiae, and pyrethroids and DDT were more often used in susceptibility assays (51.1 and 26.8% of all reports, respectively) than carbamates and organophosphates. Between 2001 and 2012, there was a clear increase in prevalence and distribution of confirmed resistance of An. gambiae s.l. to pyrethroids (from 41 to 87% of the mosquito populations tested) and DDT (from 64 to 91%) throughout the Afrotropical region. Metabolic resistance mechanisms were detected in western and eastern African populations and the two kdr mutations (L1014S and L1014F) were widespread. For An. funestus s.l., relatively few populations were tested, although in 2010–2012 resistance was reported in 50% of 10 populations tested. Maps are provided to illustrate the use of IR Mapper and the distribution of insecticide resistance in malaria vectors in Africa. Conclusions The increasing pyrethroid and DDT resistance in Anopheles in the Afrotropical region is alarming. Urgent attention should be afforded to testing An. funestus populations especially for metabolic resistance mechanisms. IR Mapper is a useful tool for investigating temporal and spatial trends in Anopheles resistance to support the pragmatic use of insecticidal interventions. PMID:24559061

Antibiotics as selectors and accelerators of diversity in the mechanisms of resistance: from the resistome to genetic plasticity in the β-lactamases world.

PubMed

Galán, Juan-Carlos; González-Candelas, Fernando; Rolain, Jean-Marc; Cantón, Rafael

2013-01-01

Antibiotics and antibiotic resistance determinants, natural molecules closely related to bacterial physiology and consistent with an ancient origin, are not only present in antibiotic-producing bacteria. Throughput sequencing technologies have revealed an unexpected reservoir of antibiotic resistance in the environment. These data suggest that co-evolution between antibiotic and antibiotic resistance genes has occurred since the beginning of time. This evolutionary race has probably been slow because of highly regulated processes and low antibiotic concentrations. Therefore to understand this global problem, a new variable must be introduced, that the antibiotic resistance is a natural event, inherent to life. However, the industrial production of natural and synthetic antibiotics has dramatically accelerated this race, selecting some of the many resistance genes present in nature and contributing to their diversification. One of the best models available to understand the biological impact of selection and diversification are β-lactamases. They constitute the most widespread mechanism of resistance, at least among pathogenic bacteria, with more than 1000 enzymes identified in the literature. In the last years, there has been growing concern about the description, spread, and diversification of β-lactamases with carbapenemase activity and AmpC-type in plasmids. Phylogenies of these enzymes help the understanding of the evolutionary forces driving their selection. Moreover, understanding the adaptive potential of β-lactamases contribute to exploration the evolutionary antagonists trajectories through the design of more efficient synthetic molecules. In this review, we attempt to analyze the antibiotic resistance problem from intrinsic and environmental resistomes to the adaptive potential of resistance genes and the driving forces involved in their diversification, in order to provide a global perspective of the resistance problem.

Antibiotics as selectors and accelerators of diversity in the mechanisms of resistance: from the resistome to genetic plasticity in the β-lactamases world

PubMed Central

Galán, Juan-Carlos; González-Candelas, Fernando; Rolain, Jean-Marc; Cantón, Rafael

2013-01-01

Antibiotics and antibiotic resistance determinants, natural molecules closely related to bacterial physiology and consistent with an ancient origin, are not only present in antibiotic-producing bacteria. Throughput sequencing technologies have revealed an unexpected reservoir of antibiotic resistance in the environment. These data suggest that co-evolution between antibiotic and antibiotic resistance genes has occurred since the beginning of time. This evolutionary race has probably been slow because of highly regulated processes and low antibiotic concentrations. Therefore to understand this global problem, a new variable must be introduced, that the antibiotic resistance is a natural event, inherent to life. However, the industrial production of natural and synthetic antibiotics has dramatically accelerated this race, selecting some of the many resistance genes present in nature and contributing to their diversification. One of the best models available to understand the biological impact of selection and diversification are β-lactamases. They constitute the most widespread mechanism of resistance, at least among pathogenic bacteria, with more than 1000 enzymes identified in the literature. In the last years, there has been growing concern about the description, spread, and diversification of β-lactamases with carbapenemase activity and AmpC-type in plasmids. Phylogenies of these enzymes help the understanding of the evolutionary forces driving their selection. Moreover, understanding the adaptive potential of β-lactamases contribute to exploration the evolutionary antagonists trajectories through the design of more efficient synthetic molecules. In this review, we attempt to analyze the antibiotic resistance problem from intrinsic and environmental resistomes to the adaptive potential of resistance genes and the driving forces involved in their diversification, in order to provide a global perspective of the resistance problem. PMID:23404545

Whole Genome Sequencing and Plasmid Genomics of Antimicrobial Resistance – Salmonella’s mobile genetic elements and the antimicrobial resistance genes they carry

USDA-ARS?s Scientific Manuscript database

With the emergence of antibiotic resistance (AR), multidrug resistance (MDR), and carbapenem resistant Enterobacteriaceae (CRE), the specter of widespread untreatable bacterial infections threatens human and animal health. The ability of these emerging resistances to transfer between bacteria on mob...

Investigation of the Diversity of Antibiotic Resistance Genes and Mobile Genetic Elements in Salmonella associated with U.S. Food Animals

USDA-ARS?s Scientific Manuscript database

With the emergence of antibiotic resistance (AR), multidrug resistance (MDR), and carbapenem resistant Enterobacteriaceae (CRE), the specter of widespread untreatable bacterial infections threatens human and animal health. The ability of these emerging resistances to transfer between bacteria on mob...

Investigation of the diversity of antibiotic resistance genes and mobile genetic elements in Salmonella associated with U.S. food animals

USDA-ARS?s Scientific Manuscript database

With the emergence of antibiotic resistance (AR), multidrug resistance (MDR), and carbapenem resistant Enterobacteriaceae (CRE), the specter of widespread untreatable bacterial infections threatens human and animal health. The ability of these emerging resistances to transfer between bacteria on mob...

Tolerance evaluation of vegetatively established Miscanthus x giganteus to herbicides

USDA-ARS?s Scientific Manuscript database

In spite of the recent focus on herbicide resistant weeds, herbicide resistant weeds are not new to agriculture; the first herbicide resistant weed was documented in 1957, with the first widespread resistance occurring in common groundsel with atrazine in the early 1970’s. Glyphosate resistant weed...

Towards a Molecular Understanding of the Link between Imatinib Resistance and Kinase Conformational Dynamics

PubMed Central

Lovera, Silvia; Morando, Maria; Pucheta-Martinez, Encarna; Martinez-Torrecuadrada, Jorge L.; Saladino, Giorgio; Gervasio, Francesco L.

2015-01-01

Due to its inhibition of the Abl kinase domain in the BCR-ABL fusion protein, imatinib is strikingly effective in the initial stage of chronic myeloid leukemia with more than 90% of the patients showing complete remission. However, as in the case of most targeted anti-cancer therapies, the emergence of drug resistance is a serious concern. Several drug-resistant mutations affecting the catalytic domain of Abl and other tyrosine kinases are now known. But, despite their importance and the adverse effect that they have on the prognosis of the cancer patients harboring them, the molecular mechanism of these mutations is still debated. Here by using long molecular dynamics simulations and large-scale free energy calculations complemented by in vitro mutagenesis and microcalorimetry experiments, we model the effect of several widespread drug-resistant mutations of Abl. By comparing the conformational free energy landscape of the mutants with those of the wild-type tyrosine kinases we clarify their mode of action. It involves significant and complex changes in the inactive-to-active dynamics and entropy/enthalpy balance of two functional elements: the activation-loop and the conserved DFG motif. What is more the T315I gatekeeper mutant has a significant impact on the binding mechanism itself and on the binding kinetics. PMID:26606374

Precise Protein Photolithography (P3): High Performance Biopatterning Using Silk Fibroin Light Chain as the Resist

PubMed Central

Liu, Wanpeng; Zhou, Zhitao; Zhang, Shaoqing; Shi, Zhifeng; Tabarini, Justin; Lee, Woonsoo; Zhang, Yeshun; Gilbert Corder, S. N.; Li, Xinxin; Dong, Fei; Cheng, Liang; Liu, Mengkun; Kaplan, David L.; Omenetto, Fiorenzo G.

2017-01-01

Precise patterning of biomaterials has widespread applications, including drug release, degradable implants, tissue engineering, and regenerative medicine. Patterning of protein‐based microstructures using UV‐photolithography has been demonstrated using protein as the resist material. The Achilles heel of existing protein‐based biophotoresists is the inevitable wide molecular weight distribution during the protein extraction/regeneration process, hindering their practical uses in the semiconductor industry where reliability and repeatability are paramount. A wafer‐scale high resolution patterning of bio‐microstructures using well‐defined silk fibroin light chain as the resist material is presented showing unprecedent performances. The lithographic and etching performance of silk fibroin light chain resists are evaluated systematically and the underlying mechanisms are thoroughly discussed. The micropatterned silk structures are tested as cellular substrates for the successful spatial guidance of fetal neural stems cells seeded on the patterned substrates. The enhanced patterning resolution, the improved etch resistance, and the inherent biocompatibility of such protein‐based photoresist provide new opportunities in fabricating large scale biocompatible functional microstructures. PMID:28932678

Modulating activity of vancomycin and daptomycin on the expression of autolysis cell-wall turnover and membrane charge genes in hVISA and VISA strains.

PubMed

Cafiso, Viviana; Bertuccio, Taschia; Spina, Daniela; Purrello, Simona; Campanile, Floriana; Di Pietro, Cinzia; Purrello, Michele; Stefani, Stefania

2012-01-01

Glycopeptides are still the gold standard to treat MRSA (Methicillin Resistant Staphylococcus aureus) infections, but their widespread use has led to vancomycin-reduced susceptibility [heterogeneous Vancomycin-Intermediate-Staphylococcus aureus (hVISA) and Vancomycin-Intermediate-Staphylococcus aureus (VISA)], in which different genetic loci (regulatory, autolytic, cell-wall turnover and cell-envelope positive charge genes) are involved. In addition, reduced susceptibility to vancomycin can influence the development of resistance to daptomycin. Although the phenotypic and molecular changes of hVISA/VISA have been the focus of different papers, the molecular mechanisms responsible for these different phenotypes and for the vancomycin and daptomycin cross-resistance are not clearly understood. The aim of our study was to investigate, by real time RT-PCR, the relative quantitative expression of genes involved in autolysis (atl-lytM), cell-wall turnover (sceD), membrane charges (mprF-dltA) and regulatory mechanisms (agr-locus-graRS-walKR), in hVISA and VISA cultured with or without vancomycin and daptomycin, in order to better understand the molecular basis of vancomycin-reduced susceptibility and the modulating activity of vancomycin and daptomycin on the expression of genes implicated in their reduced susceptibility mechanisms. Our results show that hVISA and VISA present common features that distinguish them from Vancomycin-Susceptible Staphylococcus aureus (VSSA), responsible for the intermediate glycopeptide resistance i.e. an increased cell-wall turnover, an increased positive cell-wall charge responsible for a repulsion mechanism towards vancomycin and daptomycin, and reduced agr-functionality. Indeed, VISA emerges from hVISA when VISA acquires a reduced autolysis caused by a down-regulation of autolysin genes, atl/lytM, and a reduction of the net negative cell-envelope charge via dltA over-expression. Vancomycin and daptomycin, acting in a similar manner in hVISA and VISA, can influence their cross-resistance mechanisms promoting VISA behavior in hVISA and enhancing the cell-wall pathways responsible for the intermediate vancomycin resistance in VISA. Daptomycin can also induce a charge repulsion mechanism both in hVISA and VISA increasing the activity of the mprF.

Azithromycin Resistance in Shigella spp. in Southeast Asia

PubMed Central

Darton, Thomas C.; Tuyen, Ha Thanh; The, Hao Chung; Newton, Paul N.; Phetsouvanh, Rattanaphone; Davong, Viengmon; Campbell, James I.; Hoang, Nguyen Van Minh; Thwaites, Guy E.; Parry, Christopher M.; Thanh, Duy Pham

2018-01-01

ABSTRACT Infection by Shigella spp. is a common cause of dysentery in Southeast Asia. Antimicrobials are thought to be beneficial for treatment; however, antimicrobial resistance in Shigella spp. is becoming widespread. We aimed to assess the frequency and mechanisms associated with decreased susceptibility to azithromycin in Southeast Asian Shigella isolates and use these data to assess appropriate susceptibility breakpoints. Shigella isolates recovered in Vietnam and Laos were screened for susceptibility to azithromycin (15 μg) by disc diffusion and MIC. Phenotypic resistance was confirmed by PCR amplification of macrolide resistance loci. We compared the genetic relationships and plasmid contents of azithromycin-resistant Shigella sonnei isolates using whole-genome sequences. From 475 available Shigella spp. isolated in Vietnam and Laos between 1994 and 2012, 6/181 S. flexneri isolates (3.3%, MIC ≥ 16 g/liter) and 16/294 S. sonnei isolates (5.4%, MIC ≥ 32 g/liter) were phenotypically resistant to azithromycin. PCR amplification confirmed a resistance mechanism in 22/475 (4.6%) isolates (mphA in 19 isolates and ermB in 3 isolates). The susceptibility data demonstrated the acceptability of the S. flexneri (MIC ≥ 16 g/liter, zone diameter ≤ 15 mm) and S. sonnei (MIC ≥ 32 g/liter, zone diameter ≤ 11 mm) breakpoints with a <3% discrepancy. Phylogenetic analysis demonstrated that decreased susceptibility has arisen sporadically in Vietnamese S. sonnei isolates on at least seven occasions between 2000 and 2009 but failed to become established. While the proposed susceptibility breakpoints may allow better recognition of resistant isolates, additional studies are required to assess the impact on the clinical outcome. The potential emergence of azithromycin resistance highlights the need for alternative options for management of Shigella infections in countries where Shigella is endemic. PMID:29378707

Peptic ulcer disease.

PubMed

Lanas, Angel; Chan, Francis K L

2017-08-05

The rapidly declining prevalence of Helicobacter pylori infection and widespread use of potent anti-secretory drugs means peptic ulcer disease has become substantially less prevalent than it was two decades ago. Management has, however, become more challenging than ever because of the threat of increasing antimicrobial resistance worldwide and widespread use of complex anti-thrombotic therapy in the ageing population. Peptic ulcers not associated with H pylori infection or the use of non-steroidal anti-inflammatory drugs are now also imposing substantial diagnostic and therapeutic challenges. This Seminar aims to provide a balanced overview of the latest advances in the pathogenetic mechanisms of peptic ulcers, guidelines on therapies targeting H pylori infection, approaches to treatment of peptic ulcer complications associated with anti-inflammatory analgesics and anti-thrombotic agents, and the unmet needs in terms of our knowledge and management of this increasingly challenging condition. Copyright © 2017 Elsevier Ltd. All rights reserved.

The MSPDBL2 Codon 591 Polymorphism Is Associated with Lumefantrine In Vitro Drug Responses in Plasmodium falciparum Isolates from Kilifi, Kenya

PubMed Central

Okombo, John; Mwai, Leah; Kiara, Steven M.; Pole, Lewa; Tetteh, Kevin K. A.; Nzila, Alexis; Marsh, Kevin

2014-01-01

The mechanisms of drug resistance development in the Plasmodium falciparum parasite to lumefantrine (LUM), commonly used in combination with artemisinin, are still unclear. We assessed the polymorphisms of Pfmspdbl2 for associations with LUM activity in a Kenyan population. MSPDBL2 codon 591S was associated with reduced susceptibility to LUM (P = 0.04). The high frequency of Pfmspdbl2 codon 591S in Kenya may be driven by the widespread use of lumefantrine in artemisinin combination therapy (Coartem). PMID:25534732

Structural Analysis of the Tobramycin and Gentamicin Clinical Resistome Reveals Limitations for Next-generation Aminoglycoside Design.

PubMed

Bassenden, Angelia V; Rodionov, Dmitry; Shi, Kun; Berghuis, Albert M

2016-05-20

Widespread use and misuse of antibiotics has allowed for the selection of resistant bacteria capable of avoiding the effects of antibiotics. The primary mechanism for resistance to aminoglycosides, a broad-spectrum class of antibiotics, is through covalent enzymatic modification of the drug, waning their bactericidal effect. Tobramycin and gentamicin are two medically important aminoglycosides targeted by several different resistance factors, including aminoglycoside 2″-nucleotidyltransferase [ANT(2″)], the primary cause of aminoglycoside resistance in North America. We describe here two crystal structures of ANT(2″), each in complex with AMPCPP, Mn(2+), and either tobramycin or gentamicin. Together these structures outline ANT(2″)'s specificity for clinically used substrates. Importantly, these structures complete our structural knowledge for the set of enzymes that most frequently confer clinically observed resistance to tobramycin and gentamicin. Comparison of tobramycin and gentamicin binding to enzymes in this resistome, as well as to the intended target, the bacterial ribosome, reveals surprising diversity in observed drug-target interactions. Analysis of the diverse binding modes informs that there are limited opportunities for developing aminoglycoside analogs capable of evading resistance.

Current state of herbicides in herbicide-resistant crops.

PubMed

Green, Jerry M

2014-09-01

Current herbicide and herbicide trait practices are changing in response to the rapid spread of glyphosate-resistant weeds. Growers urgently needed glyphosate when glyphosate-resistant crops became available because weeds were becoming widely resistant to most commonly used selective herbicides, making weed management too complex and time consuming for large farm operations. Glyphosate made weed management easy and efficient by controlling all emerged weeds at a wide range of application timings. However, the intensive use of glyphosate over wide areas and concomitant decline in the use of other herbicides led eventually to the widespread evolution of weeds resistant to glyphosate. Today, weeds that are resistant to glyphosate and other herbicide types are threatening current crop production practices. Unfortunately, all commercial herbicide modes of action are over 20 years old and have resistant weed problems. The severity of the problem has prompted the renewal of efforts to discover new weed management technologies. One technology will be a new generation of crops with resistance to glyphosate, glufosinate and other existing herbicide modes of action. Other technologies will include new chemical, biological, cultural and mechanical methods for weed management. From the onset of commercialization, growers must now preserve the utility of new technologies by integrating their use with other weed management technologies in diverse and sustainable systems. © 2014 Society of Chemical Industry.

Intrinsically higher fatigue cracking resistance of the penetrable and movable incoherent twin boundary

NASA Astrophysics Data System (ADS)

Li, L. L.; Zhang, P.; Zhang, Z. J.; Zhang, Z. F.

2014-01-01

Incoherent twin boundaries (ITBs) are widespread and play a crucial role in unidirectional deformation behavior of materials, however, the intrinsic role of individual ITB under cyclic loading remains elusive. Here we show the fatigue cracking behavior of Cu bicrystal with an ITB as its sole interface for the first time. The slip bands (SBs) could transfer through the ITB; meanwhile, the ITB could migrate with the motion of partial dislocations. Both the penetrability and mobility contribute to the higher fatigue cracking resistance of the ITB and hence the fatigue crack nucleates along the SBs preferentially. These new findings not only shed light on the fatigue cracking mechanisms of a penetrable boundary with direct evidence but also could provide important implications for future interfacial optimization of metallic materials.

Late blight-resistant tuber-bearing Solanum species in field and laboratory trials

USDA-ARS?s Scientific Manuscript database

Late blight, caused by Phytophthora infestans, is the most disastrous and widespread disease of potato. One of the most effective means of controlling late blight is through the use of resistant cultivars, but newly developed resistant cultivars often lose their resistance after a few years of comm...

Malathion resistance in Aedes aegypti and Culex quinquefasciatus after its use in Aedes aegypti control programs.

PubMed

Coto, M M; Lazcano, J A; de Fernández, D M; Soca, A

2000-12-01

The continued widespread use of malathion in Aedes aegypti control programs in Latin America has generated insecticide resistance to this chemical in Culex quinquefasciatus but not in Ae. aegypti. To determine the extent of this resistance, the susceptibility of Cx. quinquefasciatus and Ae. aegypti from several countries to malathion was evaluated. Bioassay results indicated that all Ae. aegypti strains evaluated from Cuba, Venezuela, Costa Rica, and Jamaica were susceptible to malathion in spite of the historical use of this insecticide in Ae. aegypti control programs in these countries. In contrast, a high level of resistance to this insecticide was found in Cx. quinquefasciatus from Venezuela, Colombia, Brazil, and Cuba. Synergist assays indicated that neither esterases nor mixed-function oxidases (MFOs) were involved as the resistance mechanism to malathion in any of the Ae. aegypti strains tested. In Cx. quinquefasciatus, synergist assays confirmed that esterases played an important role in malathion resistance but MFOs were not involved in causing malathion resistance in this species. Biochemical assays showed that both resistance mechanisms were present in the Ae. aegypti and Cx. quinquefasciatus populations. Acrylamide electrophoresis gels revealed that all Ae. aegypti strains had a strongly staining, clear band, named A4, and had a relative mobility (Rm) value of 0.7. Analysis if the results of this study suggested that malathion could continue to be used for the emergency control of Ae. aegypti, the mosquito vector for dengue and dengue hemorrhagic fever in the Americas, but that malathion is probably not effective for the control of adult Cx. quinquefasciatus in urban areas. Therefore, control operations should integrate nonorganophosphate insecticides such as pyrethroids for control of these 2 species found in the urban environment.

Resistance to PPO‐inhibiting herbicide in Palmer amaranth from Arkansas

PubMed Central

Salas, Reiofeli A; Tranel, Patrick J; Singh, Shilpa; Glasgow, Les; Scott, Robert C; Nichols, Robert L

2016-01-01

Abstract BACKGROUND The widespread occurrence of ALS inhibitor‐ and glyphosate‐resistant Amaranthus palmeri has led to increasing use of protoporphyrinogen oxidase (PPO)‐inhibiting herbicides in cotton and soybean. Studies were conducted to confirm resistance to fomesafen (a PPO inhibitor), determine the resistance frequency, examine the resistance profile to other foliar‐applied herbicides and investigate the resistance mechanism of resistant plants in a population collected in 2011 (AR11‐LAW B) and its progenies from two cycles of fomesafen selection (C1 and C2). RESULTS The frequency of fomesafen‐resistant plants increased from 5% in the original AR11‐LAW‐B to 17% in the C2 population. The amounts of fomesafen that caused 50% growth reduction were 6‐, 13‐ and 21‐fold greater in AR11‐LAW‐B, C1 and C2 populations, respectively, than in the sensitive ecotype. The AR11‐LAW‐B population was sensitive to atrazine, dicamba, glufosinate, glyphosate and mesotrione but resistant to ALS‐inhibiting herbicides pyrithiobac and trifloxysulfuron. Fomesafen survivors from C1 and C2 populations tested positive for the PPO glycine 210 deletion previously reported in waterhemp (Amaranthus tuberculatus). CONCLUSION These studies confirmed that Palmer amaranth in Arkansas has evolved resistance to foliar‐applied PPO‐inhibiting herbicide. © 2016 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry. PMID:26817647

Characteristics of a Widespread Community Cluster of H275Y Oseltamivir-Resistant A(H1N1)pdm09 Influenza in Australia

PubMed Central

Hurt, A. C.; Hardie, K.; Wilson, N. J.; Deng, Y. M.; Osbourn, M.; Leang, S. K.; Lee, R. T. C.; Iannello, P.; Gehrig, N.; Shaw, R.; Wark, P.; Caldwell, N.; Givney, R. C.; Xue, L.; Maurer-Stroh, S.; Dwyer, D. E.; Wang, B.; Smith, D. W.; Levy, A.; Booy, R.; Dixit, R.; Merritt, T.; Kelso, A.; Dalton, C.; Durrheim, D.; Barr, I. G.

2012-01-01

Background. Oseltamivir resistance in A(H1N1)pdm09 influenza is rare, particularly in untreated community cases. Sustained community transmission has not previously been reported. Methods. Influenza specimens from the Asia–Pacific region were collected through sentinel surveillance, hospital, and general practitioner networks. Clinical and epidemiological information was collected on patients infected with oseltamivir-resistant viruses. Results. Twenty-nine (15%) of 191 A(H1N1)pdm09 viruses collected between May and September 2011 from Hunter New England (HNE), Australia, contained the H275Y neuraminidase substitution responsible for oseltamivir resistance. Only 1 patient had received oseltamivir before specimen collection. The resistant strains were genetically very closely related, suggesting the spread of a single variant. Ninety percent of cases lived within 50 kilometers. Three genetically similar oseltamivir-resistant variants were detected outside of HNE, including 1 strain from Perth, approximately 4000 kilometers away. Computational analysis predicted that neuraminidase substitutions V241I, N369K, and N386S in these viruses may offset the destabilizing effect of the H275Y substitution. Conclusions This cluster represents the first widespread community transmission of H275Y oseltamivir-resistant A(H1N1)pdm09 influenza. These cases and data on potential permissive mutations suggest that currently circulating A(H1N1)pdm09 viruses retain viral fitness in the presence of the H275Y mutation and that widespread emergence of oseltamivir-resistant strains may now be more likely. PMID:22561367

Mechanism of Fenpropathrin Resistance in Red Spider Mite, Oligonychus coffeae (Acarina: Tetranychidae), Infesting Tea [Camellia sinensis L. (O. Kuntze)].

PubMed

Amsalingam, Roobakkumar; Gajjeraman, Prabu; Sam, Nisha; Rahman, Vattakandy Jasin; Azariah, Babu

2017-02-01

Red spider mite (RSM), Oligonychus coffeae (Nietner) (Acarina: Tetranychidae), has gained special attention in view of their widespread occurrence as a pest on tea [Camellia sinensis L. (O. Kuntze)]. The development of acaricide (fenpropathrin) resistance has been screened in field populations (FPs) of RSMs from different tea-growing regions of south India and compared with a laboratory-susceptible population (SP) based on toxicity bioassay, detoxifying enzyme activities, analysis of acetylcholine esterase gene (AChE, 2064 bp), and their expression pattern using semiquantitative RT-PCR. The increased resistance ratio (RR, 1.39 to 2.13) in LC 50 of fenpropathrin observed in field populations of RSM provides a baseline for screening the development of resistance to fenpropathrin. This resistance developed due to hyperexpression of detoxifying enzymes, i.e., esterase (RR of 1.43 to 2.53) and glutathione S-transferase (RR of 1.11 to 1.86), and overexpression of AChE gene at 1.4 to 2.7-fold. These results necessitate molecular studies and warrant the continuous monitoring of acaricide susceptibility and resistance pattern in order to analyze the usefulness of AChE gene as target for developing alternate pest control strategies and management of pesticide resistance in tea ecosystem.

Evolution of the Pseudomonas aeruginosa mutational resistome in an international Cystic Fibrosis clone.

PubMed

López-Causapé, Carla; Sommer, Lea Mette; Cabot, Gabriel; Rubio, Rosa; Ocampo-Sosa, Alain A; Johansen, Helle Krogh; Figuerola, Joan; Cantón, Rafael; Kidd, Timothy J; Molin, Soeren; Oliver, Antonio

2017-07-17

Emergence of epidemic clones and antibiotic resistance development compromises the management of Pseudomonas aeruginosa cystic fibrosis (CF) chronic respiratory infections. Whole genome sequencing (WGS) was used to decipher the phylogeny, interpatient dissemination, WGS mutator genotypes (mutome) and resistome of a widespread clone (CC274), in isolates from two highly-distant countries, Australia and Spain, covering an 18-year period. The coexistence of two divergent CC274 clonal lineages was revealed, but without evident geographical barrier; phylogenetic reconstructions and mutational resistome demonstrated the interpatient transmission of mutators. The extraordinary capacity of P. aeruginosa to develop resistance was evidenced by the emergence of mutations in >100 genes related to antibiotic resistance during the evolution of CC274, catalyzed by mutator phenotypes. While the presence of classical mutational resistance mechanisms was confirmed and correlated with resistance phenotypes, results also showed a major role of unexpected mutations. Among them, PBP3 mutations, shaping up β-lactam resistance, were noteworthy. A high selective pressure for mexZ mutations was evidenced, but we showed for the first time that high-level aminoglycoside resistance in CF is likely driven by mutations in fusA1/fusA2, coding for elongation factor G. Altogether, our results provide valuable information for understanding the evolution of the mutational resistome of CF P. aeruginosa.

Fate and transport of veterinary antibiotics, antibiotic-resistant bacteria, and antibiotic resistance gene from fields receiving poultry manure during storm events

USDA-ARS?s Scientific Manuscript database

Antimicrobials are used in production agriculture to treat disease and promote animal growth, but the presence of antibiotics in the environment raises concern about widespread antibiotic resistance. This study documents the occurrence and transport of tylosin, tetracycline, enterococci resistant to...

Heavy Metal Pollution from Gold Mines: Environmental Effects and Bacterial Strategies for Resistance.

PubMed

Fashola, Muibat Omotola; Ngole-Jeme, Veronica Mpode; Babalola, Olubukola Oluranti

2016-10-26

Mining activities can lead to the generation of large quantities of heavy metal laden wastes which are released in an uncontrolled manner, causing widespread contamination of the ecosystem. Though some heavy metals classified as essential are important for normal life physiological processes, higher concentrations above stipulated levels have deleterious effects on human health and biota. Bacteria able to withstand high concentrations of these heavy metals are found in the environment as a result of various inherent biochemical, physiological, and/or genetic mechanisms. These mechanisms can serve as potential tools for bioremediation of heavy metal polluted sites. This review focuses on the effects of heavy metal wastes generated from gold mining activities on the environment and the various mechanisms used by bacteria to counteract the effect of these heavy metals in their immediate environment.

Heavy Metal Pollution from Gold Mines: Environmental Effects and Bacterial Strategies for Resistance

PubMed Central

Fashola, Muibat Omotola; Ngole-Jeme, Veronica Mpode; Babalola, Olubukola Oluranti

2016-01-01

Mining activities can lead to the generation of large quantities of heavy metal laden wastes which are released in an uncontrolled manner, causing widespread contamination of the ecosystem. Though some heavy metals classified as essential are important for normal life physiological processes, higher concentrations above stipulated levels have deleterious effects on human health and biota. Bacteria able to withstand high concentrations of these heavy metals are found in the environment as a result of various inherent biochemical, physiological, and/or genetic mechanisms. These mechanisms can serve as potential tools for bioremediation of heavy metal polluted sites. This review focuses on the effects of heavy metal wastes generated from gold mining activities on the environment and the various mechanisms used by bacteria to counteract the effect of these heavy metals in their immediate environment. PMID:27792205

Evaluation of the tannic acid inhibitory effect against the NorA efflux pump of Staphylococcus aureus.

PubMed

Tintino, Saulo R; Oliveira-Tintino, Cícera D M; Campina, Fábia F; Silva, Raimundo L P; Costa, Maria do S; Menezes, Irwin R A; Calixto-Júnior, João T; Siqueira-Junior, José P; Coutinho, Henrique D M; Leal-Balbino, Tereza C; Balbino, Valdir Q

2016-08-01

During the early periods of antibiotic usage, bacterial infections were considered tamed. However, widespread antibiotic use has promoted the emergence of antibiotic-resistant pathogens, including multidrug resistant strains. Active efflux is a mechanism for bacterial resistance to inhibitory substances, known simply as drug efflux pumps. The bacterium Staphylococcus aureus is an important pathogenic bacterium responsible for an array of infections. The NorA efflux pump has been shown to be responsible for moderate fluoroquinolone resistance of S. aureus. The inhibition of the efflux pump was assayed using a sub-inhibitory concentration of standard efflux pump inhibitors and tannic acid (MIC/8), where its capacity to decrease the MIC of Ethidium bromide (EtBr) and antibiotics due to the possible inhibitory effect of these substances was observed. The MICs of EtBr and antibiotics were significantly reduced in the presence of tannic acid, indicating the inhibitory effect of this agent against the efflux pumps of both strains causing a three-fold reduction of the MIC when compared with the control. These results indicate the possible usage of tannic acid as an adjuvant in antibiotic therapy against multidrug resistant bacteria (MDR). Copyright © 2016 Elsevier Ltd. All rights reserved.

Molecular and functional characterization of CYP6BQ23, a cytochrome P450 conferring resistance to pyrethroids in European populations of pollen beetle, Meligethes aeneus.

PubMed

Zimmer, Christoph T; Bass, Chris; Williamson, Martin S; Kaussmann, Martin; Wölfel, Katharina; Gutbrod, Oliver; Nauen, Ralf

2014-02-01

The pollen beetle (Meligethes aeneus F.) is widespread throughout much of Europe where it is a major coleopteran pest of oilseed rape (Brassica napus). The reliance on synthetic insecticides for control, particularly the pyrethroid class, has led to the development of populations with high levels of resistance. Resistance to pyrethroids is now widespread throughout Europe and is thought to be mediated by enhanced detoxification by cytochrome P450ś and/or mutation of the pyrethroid target-site, the voltage-gated sodium channel. However, in the case of cytochrome P450 mediated detoxification, the specific enzyme(s) involved has (have) not yet been identified. In this study a degenerate PCR approach was used to identify ten partial P450 gene sequences from pollen beetle. Quantitative PCR was then used to examine the level of expression of these genes in a range of pollen beetle populations that showed differing levels of resistance to pyrethroids in bioassays. The study revealed a single P450 gene, CYP6BQ23, which is significantly and highly overexpressed (up to ∼900-fold) in adults and larvae of pyrethroid resistant strains compared to susceptible strains. CYP6BQ23 overexpression is significantly correlated with both the level of resistance and with the rate of deltamethrin metabolism in microsomal preparations of these populations. Functional recombinant expression of full length CYP6BQ23 along with cytochrome P450 reductase in an insect (Sf9) cell line showed that it is able to efficiently metabolise deltamethrin to 4-hydroxy deltamethrin. Furthermore we demonstrated by detection of 4-hydroxy tau-fluvalinate using ESI-TOF MS/MS that functionally expressed CYP6BQ23 also metabolizes tau-fluvalinate. A protein model was generated and subsequent docking simulations revealed the predicted substrate-binding mode of both deltamethrin and tau-fluvalinate to CYP6BQ23. Taken together these results strongly suggest that the overexpression of CYP6BQ23 is the primary mechanism conferring pyrethroid resistance in pollen beetle populations throughout much of Europe. Copyright © 2013 Elsevier Ltd. All rights reserved.

Glyphosate resistance in common ragweed (Ambrosia artemisiifolia L.)from Mississippi, USA

USDA-ARS?s Scientific Manuscript database

Glyphosate is one of the most commonly used broad-spectrum herbicides over the last 40 years. Due to widespread adoption of glyphosate-resistant (GR) crop technology, especially, corn, cotton, and soybean, several weed species in agronomic situations have developed resistance to this herbicide. Rese...

Coping with Misinformation: Corrections, Backfire Effects, and Choice Architectures

NASA Astrophysics Data System (ADS)

Lewandowsky, S.; Cook, J.; Ecker, U. K.

2012-12-01

The widespread prevalence and persistence of misinformation about many important scientific issues, from climate change to vaccinations or the link between HIV and AIDS, must give rise to concern. We first review the mechanisms by which such misinformation is disseminated in society, both inadvertently and purposely. We then survey and explain the cognitive factors that often render misinformation resistant to correction. We answer the question why retractions of misinformation can be so ineffective and why they can even backfire and ironically increase misbelief. We discuss the overriding role of ideology and personal worldviews in the resistance of misinformation to correction and show how their role can be attenuated. We discuss the risks associated with repeating misinformation while seeking to correct it and we point to the design of "choice architectures" as an alternative to the attempt to retract misinformation.

Mating success, longevity, and fertility of Diabrotica virgifera virgifera LeConte (Chrysomelidae: Coleoptera) in relation to body size and Cry3Bb1 resistant and susceptible genotypes

USDA-ARS?s Scientific Manuscript database

Insect resistance to population control methodologies is a widespread problem, with the development of effective resistance management programs often dependent on detailed knowledge regarding the biology of individual species and changes in that biology associated with resistance evolution. This stu...

The MSPDBL2 codon 591 polymorphism is associated with lumefantrine in vitro drug responses in Plasmodium falciparum isolates from Kilifi, Kenya.

PubMed

Ochola-Oyier, Lynette Isabella; Okombo, John; Mwai, Leah; Kiara, Steven M; Pole, Lewa; Tetteh, Kevin K A; Nzila, Alexis; Marsh, Kevin

2015-03-01

The mechanisms of drug resistance development in the Plasmodium falciparum parasite to lumefantrine (LUM), commonly used in combination with artemisinin, are still unclear. We assessed the polymorphisms of Pfmspdbl2 for associations with LUM activity in a Kenyan population. MSPDBL2 codon 591S was associated with reduced susceptibility to LUM (P = 0.04). The high frequency of Pfmspdbl2 codon 591S in Kenya may be driven by the widespread use of lumefantrine in artemisinin combination therapy (Coartem). Copyright © 2015, Ochola-Oyier et al.

Intratumoral heterogeneity of the epigenome

PubMed Central

Song, Jun S.; Costello, Joseph F.

2016-01-01

Investigation into intratumoral heterogeneity (ITH) of the epigenome is in a formative stage. The patterns of tumor evolution inferred from epigenetic ITH and genetic ITH are remarkably similar, suggesting widespread co-dependency of these disparate mechanisms. The biological and clinical relevance of epigenetic ITH are becoming more apparent. Rare tumor cells with unique and reversible epigenetic states may drive drug resistance, and the degree of epigenetic ITH at diagnosis may predict patient outcome. This perspective presents these current concepts and clinical implications of epigenetic ITH, and the experimental and computational techniques at the forefront of ITH exploration. PMID:27070699

First report of field evolved resistance to agrochemicals in dengue mosquito, Aedes albopictus (Diptera: Culicidae), from Pakistan.

PubMed

Khan, Hafiz Azhar Ali; Akram, Waseem; Shehzad, Khurram; Shaalan, Essam A

2011-07-22

Agrochemicals have been widely used in Pakistan for several years. This exposes mosquito populations, particularly those present around agricultural settings, to an intense selection pressure for insecticide resistance. The aim of the present study was to investigate the toxicity of representative agrochemicals against various populations of Aedes albopictus (Skuse) collected from three different regions from 2008-2010. For organophosphates and pyrethroids, the resistance ratios compared with susceptible Lab-PK were in the range of 157-266 fold for chlorpyrifos, 24-52 fold for profenofos, 41-71 fold for triazofos, and 15-26 fold for cypermethrin, 15-53 fold for deltamethrin and 21-58 fold for lambdacyhalothrin. The resistance ratios for carbamates and new insecticides were in the range of 13-22 fold for methomyl, 24-30 fold for thiodicarb, and 41-101 fold for indoxacarb, 14-27 fold for emamectin benzoate and 23-50 fold for spinosad. Pair wise comparisons of the log LC50s of insecticides revealed correlation among several insecticides, suggesting a possible cross resistance mechanism. Moreover, resistance remained stable across 3 years, suggesting field selection for general fitness had also taken place for various populations of Ae. albopictus. Moderate to high level of resistance to agrochemicals in Pakistani field populations of Ae. albopictus is reported here first time. The geographic extent of resistance is unknown but, if widespread, may lead to problems in future vector control.

An independent occurrence of the chimeric P450 enzyme CYP337B3 of Helicoverpa armigera confers cypermethrin resistance in Pakistan.

PubMed

Rasool, Akhtar; Joußen, Nicole; Lorenz, Sybille; Ellinger, Renate; Schneider, Bernd; Khan, Sher Afzal; Ashfaq, Muhammad; Heckel, David G

2014-10-01

The increasing resistance level of insect pest species is a major concern to agriculture worldwide. The cotton bollworm, Helicoverpa armigera, is one of the most important pest species due to being highly polyphagous, geographically widespread, and resistant towards many chemical classes of insecticides. We previously described the mechanism of fenvalerate resistance in Australian populations conferred by the chimeric cytochrome P450 monooxygenase CYP337B3, which arose by unequal crossing-over between CYP337B1 and CYP337B2. Here, we show that this mechanism is also present in the cypermethrin-resistant FSD strain from Pakistan. The Pakistani and the Australian CYP337B3 alleles differ by 18 synonymous and three nonsynonymous SNPs and additionally in the length and sequence of the intron. Nevertheless, the activity of both CYP337B3 proteins is comparable. We demonstrate that CYP337B3 is capable of metabolizing cypermethrin (trans- and especially cis-isomers) to the main metabolite 4'-hydroxycypermethrin, which exhibits no intrinsic toxicity towards susceptible larvae. In a bioassay, CYP337B3 confers a 7-fold resistance towards cypermethrin in FSD larvae compared to susceptible larvae from the Australian TWB strain lacking CYP337B3. Linkage analysis shows that presence of CYP337B3 accounts for most of the cypermethrin resistance in the FSD strain; up-regulation of other P450s in FSD plays no detectable role in resistance. The presence or absence of CYP337B3 can be easily detected by a simple PCR screen, providing a powerful tool to rapidly distinguish resistant from susceptible individuals in the field and to determine the geographical distribution of this resistance gene. Our results suggest that CYP337B3 evolved twice independently by unequal crossing-over between CYP337B2 and two different CYP337B1 alleles. Copyright © 2014 Elsevier Ltd. All rights reserved.

Beet curly top resistance in USDA-ARS Ft. Collins germplasm, 2017

USDA-ARS?s Scientific Manuscript database

Curly top caused by Beet curly top virus (BCTV) is a widespread disease problem vectored by the beet leafhopper in semiarid sugar beet production areas. Host resistance is the primary defense against this problem, but resistance in commercial cultivars is only low to intermediate. In order to iden...

Beet curly top resistance in USDA-ARS plant introduction lines, 2017

USDA-ARS?s Scientific Manuscript database

Curly top caused by Beet curly top virus (BCTV) is a widespread disease problem vectored by the beet leafhopper in semiarid sugar beet production areas. Host resistance is the primary defense against this problem, but resistance in commercial cultivars is only low to intermediate. In order to iden...

Effect of new auxin herbicide formulations on control of herbicide resistant weeds and on microbial activities in the rhizosphere

USDA-ARS?s Scientific Manuscript database

Widespread distribution of glyphosate-resistant weeds in soybean-growing areas across Mississippi has economically affected soybean planting and follow-up crop management operations. New multiple herbicide-resistant crop (including soybean) technologies with associated formulations will soon be comm...

Beet curly top resistance in USDA-ARS plant introduction lines, 2016

USDA-ARS?s Scientific Manuscript database

Curly top caused by Beet curly top virus (BCTV) is a widespread disease problem vectored by the beet leafhopper in semiarid sugar beet production areas. Host resistance is the primary defense against this problem, but resistance in commercial cultivars is only low to intermediate. In order to iden...

Beet curly top resistance in USDA-ARS Kimberly germplasm lines, 2015

USDA-ARS?s Scientific Manuscript database

Curly top caused by Beet curly top virus is a widespread disease problem vectored by the beet leafhopper in semiarid sugar beet production areas. Host resistance is the primary defense against this problem, but resistance in commercial cultivars is only low to intermediate. In order to identify no...

Health Impacts of Environmental Mycobacteria†

PubMed Central

Primm, Todd P.; Lucero, Christie A.; Falkinham, Joseph O.

2004-01-01

Environmental mycobacteria are emerging pathogens causing opportunistic infections in humans and animals. The health impacts of human-mycobacterial interactions are complex and likely much broader than currently recognized. Environmental mycobacteria preferentially survive chlorination in municipal water, using it as a vector to infect humans. Widespread chlorination of water has likely selected more resistant environmental mycobacteria species and potentially explains the shift from M. scrofulaceum to M. avium as a cause of cervical lymphadenitis in children. Thus, human activities have affected mycobacterial ecology. While the slow growth and hydrophobicity of environmental mycobacteria appear to be disadvantages, the unique cell wall architecture also grants high biocide and antibiotic resistance, while hydrophobicity facilitates nutrient acquisition, biofilm formation, and spread by aerosolization. The remarkable stress tolerance of environmental mycobacteria is the major reason they are human pathogens. Environmental mycobacteria invade protozoans, exhibiting parasitic and symbiotic relationships. The molecular mechanisms of mycobacterial intracellular pathogenesis in animals likely evolved from similar mechanisms facilitating survival in protozoans. In addition to outright infection, environmental mycobacteria may also play a role in chronic bowl diseases, allergies, immunity to other pulmonary infections, and the efficacy of bacillus Calmette-Guerin vaccination. PMID:14726457

Robust, heat-resistant and multifunctional superhydrophobic coating of carbon microflowers with molybdenum trioxide nanoparticles.

PubMed

Wu, Yang; Zhao, Meiyun; Guo, Zhiguang

2017-11-15

Superhydrophobic materials have triggered large interest due to their widespread applications, such as self-cleaning, corrosion resistance, anti-icing, and oil/water separation. However, suffering from weak mechanical strength, plenty of superhydrophobic materials are limited in practical application. Herein, we prepared hierarchical carbon microflowers (CMF) dispersed with molybdenum trioxide (MoO 3 ) nanoparticles (MoO 3 /CMF) via a two-step preparation method. Taking advantage of high-adhesion epoxy resin and the modification with 1H,1H,2H,2H-perfluorodecyltriethoxysilane (PDES), the modified MoO 3 /CMF (PDES-MoO 3 /CMF) coating on various substrates shows great waterproof ability, excellent chemical stability, good mechanical durability, and self-cleaning property. More significantly, the prepared PDES-MoO 3 /CMF powder with high thermal stability (250°C) can be used for oil/water separation due to its special flower-like structure and superhydrophobicity/superoleophilicity. All of these advantages endow the superhydrophobic powders with huge potential in the practical applications. Copyright © 2017 Elsevier Inc. All rights reserved.

Design and Manufacturing Considerations for Shockproof and Corrosion-Immune Superelastic Nickel-Titanium Bearings for a Space Station Application

NASA Technical Reports Server (NTRS)

DellaCorte, Christopher; Wozniak, Walter A.

2012-01-01

An intermetallic nickel-titanium alloy, 60NiTi (60wt%Ni, 40wt%Ti), is a promising tribological material for space mechanisms. 60NiTi offers a broad combination of physical properties that make it unique among bearing materials. 60NiTi is hard, electrically conductive, highly corrosion resistant, readily machined prior to final heat treatment, easily lubricated and is non-magnetic. It also falls within the class of superelastic alloys and can elastically endure large strains (beyond 5 percent) making it highly resistant to excessive and unexpected (shock) loads. Key material properties and characteristics such as elastic modulus, tensile fracture sensitivity and residual stress behavior, however, differ from conventional alloys such as steel and this significantly affects bearing design and manufacturing. In this paper, the preliminary design and manufacture of ball bearings made from 60NiTi are considered for a highly corrosive, lightly loaded, low speed bearing application found inside the International Space Station s water recycling system. The information presented is expected to help guide more widespread commercialization of this new technology into space mechanism and other applications.

Health impacts of environmental mycobacteria.

PubMed

Primm, Todd P; Lucero, Christie A; Falkinham, Joseph O

2004-01-01

Environmental mycobacteria are emerging pathogens causing opportunistic infections in humans and animals. The health impacts of human-mycobacterial interactions are complex and likely much broader than currently recognized. Environmental mycobacteria preferentially survive chlorination in municipal water, using it as a vector to infect humans. Widespread chlorination of water has likely selected more resistant environmental mycobacteria species and potentially explains the shift from M. scrofulaceum to M. avium as a cause of cervical lymphadenitis in children. Thus, human activities have affected mycobacterial ecology. While the slow growth and hydrophobicity of environmental mycobacteria appear to be disadvantages, the unique cell wall architecture also grants high biocide and antibiotic resistance, while hydrophobicity facilitates nutrient acquisition, biofilm formation, and spread by aerosolization. The remarkable stress tolerance of environmental mycobacteria is the major reason they are human pathogens. Environmental mycobacteria invade protozoans, exhibiting parasitic and symbiotic relationships. The molecular mechanisms of mycobacterial intracellular pathogenesis in animals likely evolved from similar mechanisms facilitating survival in protozoans. In addition to outright infection, environmental mycobacteria may also play a role in chronic bowl diseases, allergies, immunity to other pulmonary infections, and the efficacy of bacillus Calmette-Guerin vaccination.

A Linkage Map and QTL Analysis for Pyrethroid Resistance in the Bed Bug Cimex lectularius

PubMed Central

Fountain, Toby; Ravinet, Mark; Naylor, Richard; Reinhardt, Klaus; Butlin, Roger K.

2016-01-01

The rapid evolution of insecticide resistance remains one of the biggest challenges in the control of medically and economically important pests. Insects have evolved a diverse range of mechanisms to reduce the efficacy of the commonly used classes of insecticides, and finding the genetic basis of resistance is a major aid to management. In a previously unstudied population, we performed an F2 resistance mapping cross for the common bed bug, Cimex lectularius, for which insecticide resistance is increasingly widespread. Using 334 SNP markers obtained through RAD-sequencing, we constructed the first linkage map for the species, consisting of 14 putative linkage groups (LG), with a length of 407 cM and an average marker spacing of 1.3 cM. The linkage map was used to reassemble the recently published reference genome, facilitating refinement and validation of the current genome assembly. We detected a major QTL on LG12 associated with insecticide resistance, occurring in close proximity (1.2 Mb) to a carboxylesterase encoding candidate gene for pyrethroid resistance. This provides another example of this candidate gene playing a major role in determining survival in a bed bug population following pesticide resistance evolution. The recent availability of the bed bug genome, complete with a full list of potential candidate genes related to insecticide resistance, in addition to the linkage map generated here, provides an excellent resource for future research on the development and spread of insecticide resistance in this resurging pest species. PMID:27733453

Insights into arsenic multi-operons expression and resistance mechanisms in Rhodopseudomonas palustris CGA009

PubMed Central

Zhao, Chungui; Zhang, Yi; Chan, Zhuhua; Chen, Shicheng; Yang, Suping

2015-01-01

Arsenic (As) is widespread in the environment and causes numerous health problems. Rhodopseudomonas palustris has been regarded as a good model organism for studying arsenic detoxification since it was first demonstrated to methylate environmental arsenic by conversion to soluble or gaseous methylated species. However, the detailed arsenic resistance mechanisms remain unknown though there are at least three arsenic-resistance operons (ars1, ars2, and ars3) in R. palustris. In this study, we investigated how arsenic multi-operons contributed to arsenic detoxification in R. palustris. The expression of ars2 or ars3 operons increased with increasing environmental arsenite (As(III)) concentrations (up to 1.0 mM) while transcript of ars1 operon was not detected in the middle log-phase (55 h). ars2 operon was actively expressed even at the low concentration of As(III) (0.01 μM), whereas the ars3 operon was expressed at 1.0 μM of As(III), indicating that there was a differential regulation mechanism for the three arsenic operons. Furthermore, ars2 and ars3 operons were maximally transcribed in the early log-phase where ars2 operon was 5.4-fold higher than that of ars3 operon. A low level of ars1 transcript was only detected at 43 h (early log-phase). Arsenic speciation analysis demonstrated that R. palustris could reduce As(V) to As(III). Collectively, strain CGA009 detoxified arsenic by using arsenic reduction and methylating arsenic mechanism, while the latter might occur with the presence of higher concentrations of arsenic. PMID:26441915

Risk factors associated with fluoroquinolone-resistant enterococcal urinary tract infections in a tertiary care university hospital in north India.

PubMed

Banerjee, Tuhina; Anupurba, Shampa

2016-10-01

Fluoroquinolone resistance in both Gram-positive and Gram-negative bacteria has increased with the widespread use of fluoroquinolones. Fluoroquinolone resistance in Gram-negative bacilli has been widely studied, though staphylococci and enterococci are also notably resistant. Enterococci being the second most common cause of healthcare-associated urinary tract infections (UTIs) fluoroquinolones are often the drug of choice. This study was undertaken to assess the risk factors associated with fluoroquinolone-resistant enterococcal UTI in a tertiary level health facility in north India. A total of 365 patients with UTI caused by enterococci were studied over a period of two years. Patients with ciprofloxacin-resistant and susceptible UTI were considered as cases and controls, respectively. Resistance profile of the isolates against common antibiotics was studied by minimum inhibitory concentration (MIC) determination. Mechanisms for fluoroquinolone resistance was studied by efflux pump inhibitor activity and multiplex PCR targeting the qnr genes. A total of 204 (55.89%) cases and 161 (44.1%) controls were identified. The fluoroquinolone-resistant isolates were significantly resistant to ampicillin, high strength aminoglycosides and vancomycin. The majority (78%) of the resistant isolates showed efflux pump activity. Treatment in indoor locations, presence of urinary catheters and pregnancy along with recent exposure to antibiotics especially fluoroquinolones, third generation cephalosporins and piperacillin-tazobactam were identified as independent risk factors. Our results showed that fluoroquinolone resistance in enterococcal UTI was largely associated with indoor usage of antibiotics and use of indwelling devices. Knowledge of risk factors is important to curb this emergence of resistance.

Using RNA-sequencing and in silico subtraction to identify resistance gene analog markers for Lr16 in wheat

USDA-ARS?s Scientific Manuscript database

Leaf rust, caused by Puccinia triticina Eriks., is one of the most widespread diseases of wheat worldwide and breeding for resistance is one of the most effective methods of control. Lr16 is a wheat leaf rust resistance gene that provides resistance at both the seedling and adult stages. Simple s...

Malaria drug resistance: new observations and developments

PubMed Central

Sá, Juliana M.; Chong, Jason L.; Wellems, Thomas E.

2012-01-01

Drug-resistant micro-organisms became widespread in the 20th Century, often with devastating consequences, in response to widespread use of natural and synthetic drugs against infectious diseases. Antimalarial resistance provides one of the earliest examples, following the introduction of new medicines that filled important needs for prophylaxis and treatment around the globe. In the present chapter, we offer a brief synopsis of major antimalarial developments from two natural remedies, the qinghaosu and cinchona bark infusions, and of synthetic drugs inspired by the active components of these remedies. We review some contributions that early efficacy studies of antimalarial treatment brought to clinical pharmacology, including convincing documentation of atebrine-resistant malaria in the 1940s, prior to the launching of what soon became first-choice antimalarials, chloroquine and amodiaquine. Finally, we discuss some new observations on the molecular genetics of drug resistance, including delayed parasite clearances that have been increasingly observed in response to artemisinin derivatives in regions of South-East Asia. PMID:22023447

Remodeling of the malaria parasite and host human red cell by vesicle amplification that induces artemisinin resistance

PubMed Central

Coppens, Isabelle; Mbengue, Alassane; Suresh, Niraja; Ghorbal, Mehdi; Slouka, Zdenek; Safeukui, Innocent; Tang, Hsin-Yao; Speicher, David W.; Stahelin, Robert V.; Mohandas, Narla

2018-01-01

Artemisinin resistance threatens worldwide malaria control and elimination. Elevation of phosphatidylinositol-3-phosphate (PI3P) can induce resistance in blood stages of Plasmodium falciparum. The parasite unfolded protein response (UPR) has also been implicated as a proteostatic mechanism that may diminish artemisinin-induced toxic proteopathy. How PI3P acts and its connection to the UPR remain unknown, although both are conferred by mutation in P falciparum Kelch13 (K13), the marker of artemisinin resistance. Here we used cryoimmunoelectron microscopy to show that K13 concentrates at PI3P tubules/vesicles of the parasite’s endoplasmic reticulum (ER) in infected red cells. K13 colocalizes and copurifies with the major virulence adhesin PfEMP1. The PfEMP1-K13 proteome is comprehensively enriched in multiple proteostasis systems of protein export, quality control, and folding in the ER and cytoplasm and UPR. Synthetic elevation of PI3P that induces resistance in absence of K13 mutation also yields signatures of proteostasis and clinical resistance. These findings imply a key role for PI3P-vesicle amplification as a mechanism of resistance of infected red cells. As validation, the major resistance mutation K13C580Y quantitatively increased PI3P tubules/vesicles, exporting them throughout the parasite and the red cell. Chemical inhibitors and fluorescence microscopy showed that alterations in PfEMP1 export to the red cell and cytoadherence of infected cells to a host endothelial receptor are features of multiple K13 mutants. Together these data suggest that amplified PI3P vesicles disseminate widespread proteostatic capacity that may neutralize artemisinins toxic proteopathy and implicate a role for the host red cell in artemisinin resistance. The mechanistic insights generated will have an impact on malaria drug development. PMID:29363540

Quantifying the Evolutionary Conservation of Genes Encoding Multidrug Efflux Pumps in the ESKAPE Pathogens To Identify Antimicrobial Drug Targets.

PubMed

Brooks, Lauren E; Ul-Hasan, Sabah; Chan, Benjamin K; Sistrom, Mark J

2018-01-01

Increasing rates of antibiotic-resistant bacterial infection are one of the most pressing contemporary global health concerns. The ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) have been identified as the leading global cause of multidrug-resistant bacterial infections, and overexpression of multidrug efflux (MEX) transport systems has been identified as one of the most critical mechanisms facilitating the evolution of multidrug resistance in ESKAPE pathogens. Despite efforts to develop efflux pump inhibitors to combat antibiotic resistance, the need persists to identify additional targets for future investigations. We evaluated evolutionary pressures on 110 MEX-encoding genes from all annotated ESKAPE organism genomes. We identify several MEX genes under stabilizing selection-representing targets which can facilitate broad-spectrum treatments with evolutionary constraints limiting the potential emergence of escape mutants. We also examine MEX systems being evaluated as drug targets, demonstrating that divergent selection may underlie some of the problems encountered in the development of effective treatments-specifically in relation to the NorA system in S. aureus. This study provides a comprehensive evolutionary context to efflux in the ESKAPE pathogens, which will provide critical context to the evaluation of efflux systems as antibiotic targets. IMPORTANCE Increasing rates of antibiotic-resistant bacterial infection are one of the most pressing contemporary global health concerns. The ESKAPE pathogen group represents the leading cause of these infections, and upregulation of efflux pump expression is a significant mechanism of resistance in these pathogens. This has resulted in substantial interest in the development of efflux pump inhibitors to combat antibiotic-resistant infections; however, no widespread treatments have been developed to date. Our study evaluates an often-underappreciated aspect of resistance-the impact of evolutionary selection. We evaluate selection on all annotated efflux genes in all sequenced ESKAPE pathogens, providing critical context for and insight into current and future development of efflux-targeting treatments for resistant bacterial infections.

Determination, mechanism and monitoring of knockdown resistance in permethrin-resistant human head lice, Pediculus humanus capitis

PubMed Central

Clark, J. Marshall

2009-01-01

Permethrin resistance has been reported worldwide and clinical failures to commercial pediculicides containing permethrin have likewise occurred. Permethrin resistance in head lice populations from the U.S. is widespread but is not yet uniform and the level of resistance is relatively low (~4–8 fold). Permethrin-resistant lice are cross-resistant to pyrethrins, PBO-synergized pyrethrins and to DDT. Nix®, when applied to human hair tufts following manufacture’s instructions, did not provide 100% control when assessed by the hair tuft bioassay in conjunction with the in vitro rearing system. Resistance to permethrin is due to knockdown resistance (kdr), which is the result of three point mutations within the α-subunit gene of the voltage-gated sodium channel that causes amino acid substitutions, leading to nerve insensitivity. A three-tiered resistance monitoring system has been established based on molecular resistance detection techniques. Quantitative sequencing (QS) has been developed to predict the kdr allele frequency in head lice at a population level. The speed, simplicity and accuracy of QS made it an ideal candidate for a routine primary resistance monitoring tool to screen a large number of louse populations as an alternative to conventional bioassay. As a secondary monitoring method, real-time PASA (rtPASA) has been devised for a more precise determination of low resistance allele frequencies. To obtain more detailed information on resistance allele zygosity, as well as allele frequency, serial invasive signal amplification reaction (SISAR) has been developed as an individual genotyping method. Our approach of using three tiers of molecular resistance detection should facilitate large-scale routine resistance monitoring of permethrin resistance in head lice using field-collected samples. PMID:20161186

Novel sources of leaf rust resistance in winter wheat

USDA-ARS?s Scientific Manuscript database

Leaf rust is one of the most widespread diseases of wheat, causing significant yield losses. More than 70 leaf rust resistance genes have been reported, but most of them have lost their effectiveness in the southern Great Plains of the USA. Thus continuous search for new sources of resistance is e...

Beet curly top resistance in USDA-ARS Kimberly sugar beet germplasm lines, 2016

USDA-ARS?s Scientific Manuscript database

Curly top caused by Beet curly top virus is a widespread disease problem vectored by the beet leafhopper in semiarid sugar beet production areas. Host resistance is the primary defense against this problem, but resistance in commercial cultivars is only low to intermediate. In order to identify no...

Enhanced Molecular Typing of Treponema pallidum subspecies pallidum Strains From 4 Italian Hospitals Shows Geographical Differences in Strain Type Heterogeneity, Widespread Resistance to Macrolides, and Lack of Mutations Associated With Doxycycline Resistance.

PubMed

Giacani, Lorenzo; Ciccarese, Giulia; Puga-Salazar, Christian; Dal Conte, Ivano; Colli, Laura; Cusini, Marco; Ramoni, Stefano; Delmonte, Sergio; DʼAntuono, Antonietta; Gaspari, Valeria; Drago, Francesco

2018-04-01

Although syphilis rates have been relatively high in Italy for more than 15 years, no data on the molecular types of Treponema pallidum subspecies pallidum circulating in this country are yet available. Likewise, no data on how widespread is resistance to macrolide or tetracycline antibiotics in these strains exist. Such data would, however, promote comprehensive studies on the molecular epidemiology of syphilis infections in Italy and inform future interventions aiming at syphilis control in this and other European countries. Swabs from oral, genital, cutaneous, or anal lesions were obtained from 60 syphilis patients attending dermatology clinics in Milan, Turin, Genoa, and Bologna. Molecular typing of T. pallidum DNA was performed to provide a snapshot of the genetic diversity of strains circulating in Northern Italy. Samples were also screened for mutations conferring resistance to macrolides and tetracyclines. T. pallidum DNA was detected in 88.3% (53/60) of the specimens analyzed. Complete and partial T. pallidum typing data were obtained for 77.3% (41/53) and 15.0% (8/53) of samples, respectively, whereas 4 samples could not be typed despite T. pallidum DNA being detected. The highest strain type heterogeneity was seen in samples from Bologna and Milan, followed by Genoa. Minimal diversity was detected in samples from Turin, despite the highest number of typeable samples collected there. Resistance to macrolides was detected in 94.3% (50/53) of the strains, but no known mutations associated with tetracycline resistance were found. Genetic diversity among T. pallidum strains circulating in Northern Italy varies significantly among geographical areas regardless of physical distance. Resistance to macrolides is widespread.

Cuticle Thickening in a Pyrethroid-Resistant Strain of the Common Bed Bug, Cimex lectularius L. (Hemiptera: Cimicidae)

PubMed Central

Lilly, David G.; Latham, Sharissa L.; Webb, Cameron E.; Doggett, Stephen L.

2016-01-01

Thickening of the integument as a mechanism of resistance to insecticides is a well recognised phenomenon in the insect world and, in recent times, has been found in insects exhibiting pyrethroid-resistance. Resistance to pyrethroid insecticides in the common bed bug, Cimex lectularius L., is widespread and has been frequently inferred as a reason for the pest’s resurgence. Overexpression of cuticle depositing proteins has been demonstrated in pyrethroid-resistant bed bugs although, to date, no morphological analysis of the cuticle has been undertaken in order to confirm a phenotypic link. This paper describes examination of the cuticle thickness of a highly pyrethroid-resistant field strain collected in Sydney, Australia, in response to time-to-knockdown upon forced exposure to a pyrethroid insecticide. Mean cuticle thickness was positively correlated to time-to-knockdown, with significant differences observed between bugs knocked-down at 2 hours, 4 hours, and those still unaffected at 24 hours. Further analysis also demonstrated that the 24 hours survivors possessed a statistically significantly thicker cuticle when compared to a pyrethroid-susceptible strain of C. lectularius. This study demonstrates that cuticle thickening is present within a pyrethroid-resistant strain of C. lectularius and that, even within a stable resistant strain, cuticle thickness will vary according to time-to-knockdown upon exposure to an insecticide. This response should thus be considered in future studies on the cuticle of insecticide-resistant bed bugs and, potentially, other insects. PMID:27073871

Cuticle Thickening in a Pyrethroid-Resistant Strain of the Common Bed Bug, Cimex lectularius L. (Hemiptera: Cimicidae).

PubMed

Lilly, David G; Latham, Sharissa L; Webb, Cameron E; Doggett, Stephen L

2016-01-01

Thickening of the integument as a mechanism of resistance to insecticides is a well recognised phenomenon in the insect world and, in recent times, has been found in insects exhibiting pyrethroid-resistance. Resistance to pyrethroid insecticides in the common bed bug, Cimex lectularius L., is widespread and has been frequently inferred as a reason for the pest's resurgence. Overexpression of cuticle depositing proteins has been demonstrated in pyrethroid-resistant bed bugs although, to date, no morphological analysis of the cuticle has been undertaken in order to confirm a phenotypic link. This paper describes examination of the cuticle thickness of a highly pyrethroid-resistant field strain collected in Sydney, Australia, in response to time-to-knockdown upon forced exposure to a pyrethroid insecticide. Mean cuticle thickness was positively correlated to time-to-knockdown, with significant differences observed between bugs knocked-down at 2 hours, 4 hours, and those still unaffected at 24 hours. Further analysis also demonstrated that the 24 hours survivors possessed a statistically significantly thicker cuticle when compared to a pyrethroid-susceptible strain of C. lectularius. This study demonstrates that cuticle thickening is present within a pyrethroid-resistant strain of C. lectularius and that, even within a stable resistant strain, cuticle thickness will vary according to time-to-knockdown upon exposure to an insecticide. This response should thus be considered in future studies on the cuticle of insecticide-resistant bed bugs and, potentially, other insects.

Insecticide resistance may enhance the response to a host-plant volatile kairomone for the codling moth, Cydia pomonella (L.)

NASA Astrophysics Data System (ADS)

Sauphanor, Benoît; Franck, Pierre; Lasnier, Thérèse; Toubon, Jean-François; Beslay, Dominique; Boivin, Thomas; Bouvier, Jean-Charles; Renou, Michel

2007-06-01

The behavioral and electroantennographic responses of Cydia pomonella (L.) to the ripe pear volatile ethyl (2 E,4 Z)-2,4-decadienoate (Et- E, Z-DD), were compared in insecticide-susceptible and -resistant populations originating from southern France. A dose-response relationship to this kairomonal attractant was established for antennal activity and did not reveal differences between susceptible and resistant strains. Conversely, males of the laboratory strains expressing metabolic [cytochrome P450-dependent mixed-function oxidases (mfo)] or physiological (kdr-type mutation of the sodium-channel gene) resistance mechanisms exhibited a significantly higher response to Et- E, Z-DD than those of the susceptible strain in a wind tunnel experiment. No response of the females to this kairomone could be obtained in our wind-tunnel conditions. In apple orchards, mfo-resistant male moths were captured at significantly higher rates in kairomone-baited traps than in traps baited with the sex pheromone of C. pomonella. Such a differential phenomenon was not verified for the kdr-resistant insects, which exhibited a similar response to both the sex pheromone and the kairomonal attractant in apple orchards. Considering the widespread distribution of metabolic resistance in European populations of C. pomonella and the enhanced behavioral response to Et- E, Z-DD in resistant moths, the development of control measures based on this kairomonal compound would be of great interest for the management of insecticide resistance in this species.

Efficacy of triclosan as an antimicrobial hand soap and its potential impact on antimicrobial resistance: a focused review.

PubMed

Giuliano, Christopher A; Rybak, Michael J

2015-03-01

Triclosan is a synthetic biocide found in many household products, including antimicrobial hand soap. Levels of triclosan have been found throughout the environment and in human urine, blood, and even breast milk. Increasing levels of exposure to triclosan have led to concerns over the development of resistance to triclosan and cross-resistance to other antimicrobials. We performed a literature search to assess whether the widespread use of triclosan displays a favorable benefit: risk ratio, defined by evaluation of triclosan's efficacy as an antimicrobial hand soap and its potential effect on the development of antimicrobial resistance. Data from laboratory-based studies regarding the efficacy of triclosan are conflicting, although well-designed studies suggest no significant difference in efficacy over nonantimicrobial soap. In addition, when triclosan was introduced in a community setting, no beneficial effects were observed on the reduction of infections over nonantimicrobial soap. Resistance to triclosan and cross-resistance to antimicrobials have been consistently demonstrated in laboratory settings, although overall resistance rates and cross-resistance rates in the community setting are low. Based on the available evidence, the risk of potential antimicrobial resistance outweighs the benefit of widespread triclosan use in antimicrobial soaps. © 2015 Pharmacotherapy Publications, Inc.

Bacterial genome engineering and synthetic biology: combating pathogens.

PubMed

Krishnamurthy, Malathy; Moore, Richard T; Rajamani, Sathish; Panchal, Rekha G

2016-11-04

The emergence and prevalence of multidrug resistant (MDR) pathogenic bacteria poses a serious threat to human and animal health globally. Nosocomial infections and common ailments such as pneumonia, wound, urinary tract, and bloodstream infections are becoming more challenging to treat due to the rapid spread of MDR pathogenic bacteria. According to recent reports by the World Health Organization (WHO) and Centers for Disease Control and Prevention (CDC), there is an unprecedented increase in the occurrence of MDR infections worldwide. The rise in these infections has generated an economic strain worldwide, prompting the WHO to endorse a global action plan to improve awareness and understanding of antimicrobial resistance. This health crisis necessitates an immediate action to target the underlying mechanisms of drug resistance in bacteria. The advent of new bacterial genome engineering and synthetic biology (SB) tools is providing promising diagnostic and treatment plans to monitor and treat widespread recalcitrant bacterial infections. Key advances in genetic engineering approaches can successfully aid in targeting and editing pathogenic bacterial genomes for understanding and mitigating drug resistance mechanisms. In this review, we discuss the application of specific genome engineering and SB methods such as recombineering, clustered regularly interspaced short palindromic repeats (CRISPR), and bacterial cell-cell signaling mechanisms for pathogen targeting. The utility of these tools in developing antibacterial strategies such as novel antibiotic production, phage therapy, diagnostics and vaccine production to name a few, are also highlighted. The prevalent use of antibiotics and the spread of MDR bacteria raise the prospect of a post-antibiotic era, which underscores the need for developing novel therapeutics to target MDR pathogens. The development of enabling SB technologies offers promising solutions to deliver safe and effective antibacterial therapies.

Failure mechanisms of single-crystal silicon electrodes in lithium-ion batteries

PubMed Central

Shi, Feifei; Song, Zhichao; Ross, Philip N.; Somorjai, Gabor A.; Ritchie, Robert O.; Komvopoulos, Kyriakos

2016-01-01

Long-term durability is a major obstacle limiting the widespread use of lithium-ion batteries in heavy-duty applications and others demanding extended lifetime. As one of the root causes of the degradation of battery performance, the electrode failure mechanisms are still unknown. In this paper, we reveal the fundamental fracture mechanisms of single-crystal silicon electrodes over extended lithiation/delithiation cycles, using electrochemical testing, microstructure characterization, fracture mechanics and finite element analysis. Anisotropic lithium invasion causes crack initiation perpendicular to the electrode surface, followed by growth through the electrode thickness. The low fracture energy of the lithiated/unlithiated silicon interface provides a weak microstructural path for crack deflection, accounting for the crack patterns and delamination observed after repeated cycling. On the basis of this physical understanding, we demonstrate how electrolyte additives can heal electrode cracks and provide strategies to enhance the fracture resistance in future lithium-ion batteries from surface chemical, electrochemical and material science perspectives. PMID:27297565

Failure mechanisms of single-crystal silicon electrodes in lithium-ion batteries

DOE PAGES

Shi, Feifei; Song, Zhichao; Ross, Philip N.; ...

2016-06-14

Long-term durability is a major obstacle limiting the widespread use of lithium-ion batteries in heavy-duty applications and others demanding extended lifetime. As one of the root causes of the degradation of battery performance, the electrode failure mechanisms are still unknown. In this paper, we reveal the fundamental fracture mechanisms of single-crystal silicon electrodes over extended lithiation/delithiation cycles, using electrochemical testing, microstructure characterization, fracture mechanics and finite element analysis. Anisotropic lithium invasion causes crack initiation perpendicular to the electrode surface, followed by growth through the electrode thickness. The low fracture energy of the lithiated/unlithiated silicon interface provides a weak microstructural pathmore » for crack deflection, accounting for the crack patterns and delamination observed after repeated cycling. On the basis of this physical understanding, we demonstrate how electrolyte additives can heal electrode cracks and provide strategies to enhance the fracture resistance in future lithium-ion batteries from surface chemical, electrochemical and material science perspectives.« less

Failure mechanisms of single-crystal silicon electrodes in lithium-ion batteries

NASA Astrophysics Data System (ADS)

Shi, Feifei; Song, Zhichao; Ross, Philip N.; Somorjai, Gabor A.; Ritchie, Robert O.; Komvopoulos, Kyriakos

2016-06-01

Long-term durability is a major obstacle limiting the widespread use of lithium-ion batteries in heavy-duty applications and others demanding extended lifetime. As one of the root causes of the degradation of battery performance, the electrode failure mechanisms are still unknown. In this paper, we reveal the fundamental fracture mechanisms of single-crystal silicon electrodes over extended lithiation/delithiation cycles, using electrochemical testing, microstructure characterization, fracture mechanics and finite element analysis. Anisotropic lithium invasion causes crack initiation perpendicular to the electrode surface, followed by growth through the electrode thickness. The low fracture energy of the lithiated/unlithiated silicon interface provides a weak microstructural path for crack deflection, accounting for the crack patterns and delamination observed after repeated cycling. On the basis of this physical understanding, we demonstrate how electrolyte additives can heal electrode cracks and provide strategies to enhance the fracture resistance in future lithium-ion batteries from surface chemical, electrochemical and material science perspectives.

A Comparison of Inbreeding Depression in Tropical and Widespread Drosophila Species

PubMed Central

Bechsgaard, Jesper S.; Hoffmann, Ary A.; Sgró, Carla; Loeschcke, Volker; Bilde, Trine; Kristensen, Torsten N.

2013-01-01

The evolutionary history of widespread and specialized species is likely to cause a different genetic architecture of key ecological traits in the two species groups. This may affect how these two groups respond to inbreeding. Here we investigate inbreeding effects in traits related to performance in 5 widespread and 5 tropical restricted species of Drosophila with the aim of testing whether the two species groups suffered differently from inbreeding depression. The traits investigated were egg-to-adult viability, developmental time and resistance to heat, cold and desiccation. Our results showed that levels of inbreeding depression were species and trait specific and did not differ between the species groups for stress resistance traits. However, for the life history traits developmental time and egg-to adult viability, more inbreeding depression was observed in the tropical species. The results reported suggest that for life history traits tropical species of Drosophila will suffer more from inbreeding depression than widespread species in case of increases in the rate of inbreeding e.g. due to declines in population sizes. PMID:23460779

Second generation peanut genotypes resistant to thrips-transmitted tomato spotted wilt virus exhibit tolerance rather than true resistance and differentially affect thrips fitness.

PubMed

Shrestha, Anita; Srinivasan, Rajagopalbabu; Sundaraj, Sivamani; Culbreath, Albert K; Riley, David G

2013-04-01

Spotted wilt disease caused by Tomato spotted wilt virus (TSWV) (family Bunyaviridae; genus Tospovirus) is a major constraint to peanut (Arachis hypogaea L.) production in the southeastern United States. Reducing yield losses to TSWV has heavily relied on planting genotypes that reduce the incidence of spotted wilt disease. However, mechanisms conferring resistance to TSWV have not been identified in these genotypes. Furthermore, no information is available on how these genotypes influence thrips fitness. In this study, we investigated the effects of newly released peanut genotypes (Georganic, GA-06G, Tifguard, and NC94022) with field resistance to TSWV and a susceptible genotype (Georgia Green) on tobacco thrips, Frankliniella fusca (Hinds), fitness, and TSWV incidence. Thrips-mediated transmission resulted in TSWV infection in both TSWV-resistant and susceptible genotypes and they exhibited typical TSWV symptoms. However, some resistant genotypes had reduced viral loads (fewer TSWV N-gene copies) than the susceptible genotype. F. fusca larvae acquired TSWV from resistant and susceptible genotypes indicating that resistant genotypes also can serve as inoculum sources. Unlike resistant genotypes in other crops that produce local lesions (hypersensitive reaction) upon TSWV infection, widespread symptom development was noticed in peanut genotypes. Results indicated that the observed field resistance in peanut genotypes could be because of tolerance. Further, fitness studies revealed some, but not substantial, differences in thrips adult emergence rates and developmental time between resistant and susceptible genotypes. Thrips head capsule length and width were not different when reared on different genotypes.

Pyrethroid resistance in Iranian field populations of Rhipicephalus (Boophilus) annulatus.

PubMed

Ziapour, Seyyed Payman; Kheiri, Sadegh; Fazeli-Dinan, Mahmoud; Sahraei-Rostami, Farzaneh; Mohammadpour, Reza Ali; Aarabi, Mohsen; Nikookar, Seyed Hassan; Sarafrazi, Mohammad; Asgarian, Fatemeh; Enayati, Ahmadali; Hemingway, Janet

2017-03-01

Resistance to acaricides in ticks is becoming increasingly widespread throughout the world; therefore, tick control requires resistance monitoring for each tick species. The aims of this study were to monitor the susceptibility status of the cattle tick, Rhipicephalus (Boophilus) annulatus (Acari: Ixodidae), against pyrethroid acaricides from Mazandaran Province, northern Iran, and where resistance was evident, and establish the possible underlying mechanisms. Fully engorged adult R. (B.) annulatus females collected on cattle from Mazandaran Province. Twenty-nine tick populations produced 10-18days old larvae and bioassayed with cypermethrin and λ-cyhalothrin by larval packet test and the levels of detoxification enzymes were measured. Population AM-29 had a maximum resistance ratio (RR 99 ) of 20.21 to cypermethrin and 53.57% of the tick populations were resistant at LC 99 level. With λ-cyhalothrin, 17.86% of the tick populations were resistant and AM-29 was the most resistant population with RR 99 =4.54. AM-29 also showed significant elevation of cytochrome P450 monooxygenase (P450) and glutathione S-transferase (GST) (2.76- and 2.39-fold, respectively) (P<0.001). Rhipicephalus (Boophilus) annulatus showed resistance to pyrethroid insecticides with elevated levels of P450, GST and para-nitrophenyl acetate (p-NPA) in resistant populations. Operational failure was noted in controlling R. (B.) annulatus by pyrethroid insecticides, therefore alternative pest management measures should be adopted in Iran. For the first time, a new estimate of insecticide resistance based on effective dose recommended by the pesticide manufacturer termed Operational Dose Ratio (ODR) is defined and discussed. Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.

Complicated urinary tract infections: practical solutions for the treatment of multiresistant Gram-negative bacteria.

PubMed

Pallett, Ann; Hand, Kieran

2010-11-01

Resistance in Gram-negative bacteria has been increasing, particularly over the last 6 years. This is mainly due to the spread of strains producing extended-spectrum β-lactamases (ESBLs) such as CTX-M enzymes or AmpC β-lactamases. Many of the isolates producing these enzymes are also resistant to trimethoprim, quinolones and aminoglycosides, often due to plasmid co-expression of other resistance mechanisms. CTX-M-producing Escherichia coli often occurs in the community and as E. coli is one of the commonest organisms causing urinary tract infections (UTIs) the choice of agents to treat these infections is diminishing. Novel combinations of antibiotics are being used in the community and broad-spectrum agents such as carbapenems are being used increasingly as empirical treatment for severe infections. Of particular concern therefore are reports in the UK of organisms that produce carbapenemases. As resistance is becoming more widespread, prudent use of antimicrobials is imperative and, as asymptomatic bacteriuria is typically benign in the elderly, antibiotics should not be prescribed without clinical signs of UTI. The use of antibiotics as suppressive therapy or long-term prophylaxis may no longer be defensible.

Quantifying the Evolutionary Conservation of Genes Encoding Multidrug Efflux Pumps in the ESKAPE Pathogens To Identify Antimicrobial Drug Targets

PubMed Central

Ul-Hasan, Sabah; Chan, Benjamin K.; Sistrom, Mark J.

2018-01-01

ABSTRACT Increasing rates of antibiotic-resistant bacterial infection are one of the most pressing contemporary global health concerns. The ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) have been identified as the leading global cause of multidrug-resistant bacterial infections, and overexpression of multidrug efflux (MEX) transport systems has been identified as one of the most critical mechanisms facilitating the evolution of multidrug resistance in ESKAPE pathogens. Despite efforts to develop efflux pump inhibitors to combat antibiotic resistance, the need persists to identify additional targets for future investigations. We evaluated evolutionary pressures on 110 MEX-encoding genes from all annotated ESKAPE organism genomes. We identify several MEX genes under stabilizing selection—representing targets which can facilitate broad-spectrum treatments with evolutionary constraints limiting the potential emergence of escape mutants. We also examine MEX systems being evaluated as drug targets, demonstrating that divergent selection may underlie some of the problems encountered in the development of effective treatments—specifically in relation to the NorA system in S. aureus. This study provides a comprehensive evolutionary context to efflux in the ESKAPE pathogens, which will provide critical context to the evaluation of efflux systems as antibiotic targets. IMPORTANCE Increasing rates of antibiotic-resistant bacterial infection are one of the most pressing contemporary global health concerns. The ESKAPE pathogen group represents the leading cause of these infections, and upregulation of efflux pump expression is a significant mechanism of resistance in these pathogens. This has resulted in substantial interest in the development of efflux pump inhibitors to combat antibiotic-resistant infections; however, no widespread treatments have been developed to date. Our study evaluates an often-underappreciated aspect of resistance—the impact of evolutionary selection. We evaluate selection on all annotated efflux genes in all sequenced ESKAPE pathogens, providing critical context for and insight into current and future development of efflux-targeting treatments for resistant bacterial infections. PMID:29719870

SWEET sugar transporters for phloem transport and pathogen nutrition.

PubMed

Chen, Li-Qing

2014-03-01

Many intercellular solute transport processes require an apoplasmic step, that is, efflux from one cell and subsequent uptake by an adjacent cell. Cellular uptake transporters have been identified for many solutes, including sucrose; however, efflux transporters have remained elusive for a long time. Cellular efflux of sugars plays essential roles in many processes, such as sugar efflux as the first step in phloem loading, sugar efflux for nectar secretion, and sugar efflux for supplying symbionts such as mycorrhiza, and maternal efflux for filial tissue development. Furthermore, sugar efflux systems can be hijacked by pathogens for access to nutrition from hosts. Mutations that block recruitment of the efflux mechanism by the pathogen thus cause pathogen resistance. Until recently, little was known regarding the underlying mechanism of sugar efflux. The identification of sugar efflux carriers, SWEETs (Sugars Will Eventually be Exported Transporters), has shed light on cellular sugar efflux. SWEETs appear to function as uniporters, facilitating diffusion of sugars across cell membranes. Indeed, SWEETs probably mediate sucrose efflux from putative phloem parenchyma into the phloem apoplasm, a key step proceeding phloem loading. Engineering of SWEET mutants using transcriptional activator-like effector nuclease (TALEN)-based genomic editing allowed the engineering of pathogen resistance. The widespread expression of the SWEET family promises to provide insights into many other cellular efflux mechanisms.

Chlorfenapyr, a Potent Alternative Insecticide of Phoxim To Control Bradysia odoriphaga (Diptera: Sciaridae).

PubMed

Zhao, Yunhe; Wang, Qiuhong; Wang, Yao; Zhang, Zhengqun; Wei, Yan; Liu, Feng; Zhou, Chenggang; Mu, Wei

2017-07-26

Bradysia odoriphaga is the major pest affecting Chinese chive production, and in China, it has developed widespread resistance to organophosphorus insecticides. Chlorfenapyr is a promising pyrrole insecticide with a unique mechanism of action that does not confer cross-resistance to neurotoxic insecticides. However, the effect of chlorfenapyr on organophosphate-resistant B. odoriphaga is not well understood. The present study evaluated the potential of chlorfenapyr for the control of phoxim-resistant B. odoriphaga. The results showed that chlorfenapyr had significant insecticidal activity to B. odoriphaga in multiple developmental stages, and there were no significant differences in susceptibility between the field (phoxim-resistant) and laboratory (phoxim-susceptible) populations. The pot experiment and field trials confirmed the results of our laboratory bioassays. In the field trial, chlorfenapyr applied at 3.0, 6.0, or 12.0 kg of active ingredient (a.i.)/ha significantly decreased the number of B. odoriphaga and improved the yield compared to phoxim at 6.0 kg of a.i./ha and the control conditions. Moreover, the final residues of chlorfenapyr on plants were below the maximum residue limits (MRLs) as a result of its non-systemic activity. These results demonstrate that chlorfenapyr has potential as a potent alternative to phoxim for controlling B. odoriphaga.

Managing the evolution of herbicide resistance

USDA-ARS?s Scientific Manuscript database

Herbicide-resistant (HR) weeds are widespread threats to the sustainability, productivity, and profitability of many cropping systems. Efforts to combat their spread through herbicide rotation schedules have been marginally effective at best. Despite the scope of the problem, we lack sound empirical...

Highest drought sensitivity and lowest resistance to growth suppression are found in the range core of the tree Fagus sylvatica L. not the equatorial range edge.

PubMed

Cavin, Liam; Jump, Alistair S

2017-01-01

Biogeographical and ecological theory suggests that species distributions should be driven to higher altitudes and latitudes as global temperatures rise. Such changes occur as growth improves at the poleward edge of a species distribution and declines at the range edge in the opposite or equatorial direction, mirrored by changes in the establishment of new individuals. A substantial body of evidence demonstrates that such processes are underway for a wide variety of species. Case studies from populations at the equatorial range edge of a variety of woody species have led us to understand that widespread growth decline and distributional shifts are underway. However, in apparent contrast, other studies report high productivity and reproduction in some range edge populations. We sought to assess temporal trends in the growth of the widespread European beech tree (Fagus sylvatica) across its latitudinal range. We explored the stability of populations to major drought events and the implications for predicted widespread growth decline at its equatorial range edge. In contrast to expectations, we found greatest sensitivity and low resistance to drought in the core of the species range, whilst dry range edge populations showed particularly high resistance to drought and little evidence of drought-linked growth decline. We hypothesize that this high range edge resistance to drought is driven primarily by local environmental factors that allow relict populations to persist despite regionally unfavourable climate. The persistence of such populations demonstrates that range-edge decline is not ubiquitous and is likely to be driven by declining population density at the landscape scale rather than sudden and widespread range retraction. © 2016 The Authors. Global Change Biology Published by John Wiley & Sons Ltd.

Identification of Yr59 conferring high-temperature adult-plant resistance to stripe rust in wheat germplasm PI 178759

USDA-ARS?s Scientific Manuscript database

Stripe rust, caused by Puccinia striiformis f. sp. tritici, is one of the most widespread and destructive wheat diseases worldwide. Resistant cultivars are the preferred means of control. The spring wheat germplasm ‘PI 178759’ originating from Iraq showed effective resistance to stripe rust in fie...

First report of field evolved resistance to agrochemicals in dengue mosquito, Aedes albopictus (Diptera: Culicidae), from Pakistan

PubMed Central

2011-01-01

Background Agrochemicals have been widely used in Pakistan for several years. This exposes mosquito populations, particularly those present around agricultural settings, to an intense selection pressure for insecticide resistance. The aim of the present study was to investigate the toxicity of representative agrochemicals against various populations of Aedes albopictus (Skuse) collected from three different regions from 2008-2010. Results For organophosphates and pyrethroids, the resistance ratios compared with susceptible Lab-PK were in the range of 157-266 fold for chlorpyrifos, 24-52 fold for profenofos, 41-71 fold for triazofos, and 15-26 fold for cypermethrin, 15-53 fold for deltamethrin and 21-58 fold for lambdacyhalothrin. The resistance ratios for carbamates and new insecticides were in the range of 13-22 fold for methomyl, 24-30 fold for thiodicarb, and 41-101 fold for indoxacarb, 14-27 fold for emamectin benzoate and 23-50 fold for spinosad. Pair wise comparisons of the log LC50s of insecticides revealed correlation among several insecticides, suggesting a possible cross resistance mechanism. Moreover, resistance remained stable across 3 years, suggesting field selection for general fitness had also taken place for various populations of Ae. albopictus. Conclusion Moderate to high level of resistance to agrochemicals in Pakistani field populations of Ae. albopictus is reported here first time. The geographic extent of resistance is unknown but, if widespread, may lead to problems in future vector control. PMID:21781290

Does the wide use of quaternary ammonium compounds enhance the selection and spread of antimicrobial resistance and thus threaten our health?

PubMed

Hegstad, Kristin; Langsrud, Solveig; Lunestad, Bjørn Tore; Scheie, Anne Aamdal; Sunde, Marianne; Yazdankhah, Siamak P

2010-06-01

Quaternary ammonium compounds (QACs) are widely used biocides that possess antimicrobial effect against a broad range of microorganisms. These compounds are used for numerous industrial purposes, water treatment, antifungal treatment in horticulture, as well as in pharmaceutical and everyday consumer products as preserving agents, foam boosters, and detergents. Resistance toward QACs is widespread among a diverse range of microorganisms and is facilitated by several mechanisms such as modifications in the membrane composition, expression of stress response and repair systems, or expression of efflux pump genes. Development of resistance in both pathogenic and nonpathogenic bacteria has been related to application in human medicine and the food industry. QACs in cosmetic products will inevitably come into intimate contact with the skin or mucosal linings in the mouth and thus are likely to add to the selection pressure toward more QAC-resistant microorganisms among the skin or mouth flora. There is increasing evidence of coresistance and cross-resistance between QACs and a range of other clinically important antibiotics and disinfectants. Use of QACs may have driven the fixation and spread of certain resistance cassette collectors (class 1 integrons), currently responsible for a major part of antimicrobial resistance in gram-negative bacteria. More indiscriminate use of QACs such as in cosmetic products may drive the selection of further new genetic elements that will aid in the persistence and spread of antimicrobial resistance and thus in limiting our treatment options for microbial infections.

A Linkage Map and QTL Analysis for Pyrethroid Resistance in the Bed Bug Cimex lectularius.

PubMed

Fountain, Toby; Ravinet, Mark; Naylor, Richard; Reinhardt, Klaus; Butlin, Roger K

2016-12-07

The rapid evolution of insecticide resistance remains one of the biggest challenges in the control of medically and economically important pests. Insects have evolved a diverse range of mechanisms to reduce the efficacy of the commonly used classes of insecticides, and finding the genetic basis of resistance is a major aid to management. In a previously unstudied population, we performed an F 2 resistance mapping cross for the common bed bug, Cimex lectularius, for which insecticide resistance is increasingly widespread. Using 334 SNP markers obtained through RAD-sequencing, we constructed the first linkage map for the species, consisting of 14 putative linkage groups (LG), with a length of 407 cM and an average marker spacing of 1.3 cM. The linkage map was used to reassemble the recently published reference genome, facilitating refinement and validation of the current genome assembly. We detected a major QTL on LG12 associated with insecticide resistance, occurring in close proximity (1.2 Mb) to a carboxylesterase encoding candidate gene for pyrethroid resistance. This provides another example of this candidate gene playing a major role in determining survival in a bed bug population following pesticide resistance evolution. The recent availability of the bed bug genome, complete with a full list of potential candidate genes related to insecticide resistance, in addition to the linkage map generated here, provides an excellent resource for future research on the development and spread of insecticide resistance in this resurging pest species. Copyright © 2016 Fountain et al.

Phenotypic changes associated with the fitness cost in antibiotic resistant Escherichia coli strains.

PubMed

Suzuki, Shingo; Horinouchi, Takaaki; Furusawa, Chikara

2016-02-01

the acquisition of antibiotic resistance in bacterial cells is often accompanied with a reduction of fitness in the absence of antibiotics, known as the "fitness cost". The magnitude of this fitness cost is an important biological parameter that influences the degree to which antibiotic resistant strains become widespread. However, the relationship between the fitness cost and comprehensive phenotypic and genotypic changes remains unclear. Here, we quantified the fitness cost of resistant strains obtained by experimental evolution in the presence of various antibiotics, and analyzed how the cost correlated to phenotypic and genotypic changes in the resistant strains. we measured the specific growth rate of the resistant strains in the presence of various concentrations of drugs or in their absence. In the absence of drugs, the resistant strains showed reductions of approximately 20% to 50% in growth rate compared with the parent strain, which corresponded to the fitness cost. We found that the decrease of the specific growth rate was correlated with overall expression changes between the parent and resistant strains, measured by the Euclid distance between expression profiles. We also found that there are a number of genes whose changes in expression levels were significantly correlated with the growth rate, which may account for the observed correlation between the fitness cost and overall expression changes. our analysis provides a basis for quantitative understanding of the mechanism of the fitness cost. This understanding may provide clues on how to influence the fitness cost that accompanies resistance acquisition and consequently how to limit the spread of antibiotic resistant strains.

Fluoroquinolone-Resistant Enteric Bacteria in Sub-Saharan Africa: Clones, Implications and Research Needs

PubMed Central

Chattaway, Marie A.; Aboderin, Aaron O.; Fashae, Kayode; Okoro, Chinyere K.; Opintan, Japheth A.; Okeke, Iruka N.

2016-01-01

Fluoroquinolones came into widespread use in African countries in the early 2000s, after patents for the first generation of these drugs expired. By that time, quinolone antibacterial agents had been used intensively worldwide and resistant lineages of many bacterial species had evolved. We sought to understand which Gram negative enteric pandemic lineages have been reported from Africa, as well as the nature and transmission of any indigenous resistant clones. A systematic review of articles indexed in the Medline and AJOL literature databases was conducted. We report on the findings of 43 eligible studies documenting local or pandemic fluoroquinolone-resistant enteric clones in sub-Sahara African countries. Most reports are of invasive non-typhoidal Salmonella and Escherichia coli lineages and there have been three reports of cholera outbreaks caused by fluoroquinolone-resistant Vibrio cholerae O1. Fluoroquinolone-resistant clones have also been reported from commensals and animal isolates but there are few data for non-Enterobacteriaceae and almost none for difficult-to-culture Campylobacter spp. Fluoroquinolone-resistant lineages identified in African countries were universally resistant to multiple other classes of antibacterial agents. Although as many as 972 non-duplicate articles refer to fluoroquinolone resistance in enteric bacteria from Africa, most do not report on subtypes and therefore information on the epidemiology of fluoroquinolone-resistant clones is available from only a handful of countries in the subcontinent. When resistance is reported, resistance mechanisms and lineage information is rarely investigated. Insufficient attention has been given to molecular and sequence-based methods necessary for identifying and tracking resistant clones in Africa and more research is needed in this area. PMID:27148238

Educational Effectiveness, Target, and Content for Prudent Antibiotic Use

PubMed Central

Lee, Chang-Ro; Lee, Jung Hun; Kang, Lin-Woo; Jeong, Byeong Chul; Lee, Sang Hee

2015-01-01

Widespread antimicrobial use and concomitant resistance have led to a significant threat to public health. Because inappropriate use and overuse of antibiotics based on insufficient knowledge are one of the major drivers of antibiotic resistance, education about prudent antibiotic use aimed at both the prescribers and the public is important. This review investigates recent studies on the effect of interventions for promoting prudent antibiotics prescribing. Up to now, most educational efforts have been targeted to medical professionals, and many studies showed that these educational efforts are significantly effective in reducing antibiotic prescribing. Recently, the development of educational programs to reduce antibiotic use is expanding into other groups, such as the adult public and children. The investigation of the contents of educational programs for prescribers and the public demonstrates that it is important to develop effective educational programs suitable for each group. In particular, it seems now to be crucial to develop appropriate curricula for teaching medical and nonmedical (pharmacy, dentistry, nursing, veterinary medicine, and midwifery) undergraduate students about general medicine, microbial virulence, mechanism of antibiotic resistance, and judicious antibiotic prescribing. PMID:25945327

Progress and gaps in understanding mechanisms of ash tree resistance to emerald ash borer, a model for wood-boring insects that kill angiosperms.

PubMed

Villari, Caterina; Herms, Daniel A; Whitehill, Justin G A; Cipollini, Don; Bonello, Pierluigi

2016-01-01

We review the literature on host resistance of ash to emerald ash borer (EAB, Agrilus planipennis), an invasive species that causes widespread mortality of ash. Manchurian ash (Fraxinus mandshurica), which coevolved with EAB, is more resistant than evolutionarily naïve North American and European congeners. Manchurian ash was less preferred for adult feeding and oviposition than susceptible hosts, more resistant to larval feeding, had higher constitutive concentrations of bark lignans, coumarins, proline, tyramine and defensive proteins, and was characterized by faster oxidation of phenolics. Consistent with EAB being a secondary colonizer of coevolved hosts, drought stress decreased the resistance of Manchurian ash, but had no effect on constitutive bark phenolics, suggesting that they do not contribute to increased susceptibility in response to drought stress. The induced resistance of North American species to EAB in response to the exogenous application of methyl jasmonate was associated with increased bark concentrations of verbascoside, lignin and/or trypsin inhibitors, which decreased larval survival and/or growth in bioassays. This finding suggests that these inherently susceptible species possess latent defenses that are not induced naturally by larval colonization, perhaps because they fail to recognize larval cues or respond quickly enough. Finally, we propose future research directions that would address some critical knowledge gaps. © 2015 The Authors. New Phytologist © 2015 New Phytologist Trust.

A chemical arms race at sea mediates algal host-virus interactions.

PubMed

Bidle, Kay D; Vardi, Assaf

2011-08-01

Despite the critical importance of viruses in shaping marine microbial ecosystems and lubricating upper ocean biogeochemical cycles, relatively little is known about the molecular mechanisms mediating phytoplankton host-virus interactions. Recent work in algal host-virus systems has begun to shed novel insight into the elegant strategies of viral infection and subcellular regulation of cell fate, which not only reveal tantalizing aspects of viral replication and host resistance strategies but also provide new diagnostic tools toward elucidating the impact of virus-mediated processes in the ocean. Widespread lateral gene transfer between viruses and their hosts plays a prominent role in host-virus diversification and in the regulation of host-virus infection mechanisms by allowing viruses to manipulate and 'rewire' host metabolic pathways to facilitate infection. Copyright © 2011 Elsevier Ltd. All rights reserved.

Killing me un-softly: Causes and mechanisms of arterial stiffness Recent Highlights of ATVB: Early Career Committee Contribution

PubMed Central

Lyle, Alicia N.; Raaz, Uwe

2017-01-01

The aorta is a blood vessel that provides a low resistance path for blood flow directed from the heart to peripheral organs and tissues. However, the aorta has another central hemodynamic function whereby the elastic nature of the aortic wall provides a significant biomechanical buffering capacity complementing the pulsatile cardiac blood flow and this is often referred to as Windkessel function. Stiffening of the arterial wall leads to fundamental alterations in central hemodynamics with widespread detrimental implications for organ function. In this review article, we aim to provide a short general overview of some of the most common mechanisms that contribute to increased arterial stiffness, the consequences of arterial stiffening, and the clinical conditions in which arterial stiffness occurs with a focus on recent advancements in the field. PMID:28122777

Intermittent treatment to prevent pregnancy malaria does not confer benefit in an area of widespread drug resistance.

PubMed

Harrington, Whitney E; Mutabingwa, Theonest K; Kabyemela, Edward; Fried, Michal; Duffy, Patrick E

2011-08-01

Millions of African women receive sulfadoxine-pyrimethamine (SP) as intermittent preventive treatment during pregnancy (IPTp) to avoid poor outcomes that result from malaria. However, parasites resistant to SP are widespread in parts of Africa, and IPTp may perversely exacerbate placental infections that contain SP-resistant parasites. The study used a cross-sectional design. We determined IPTp use in a delivery cohort of 880 pregnant women in Muheza, Tanzania, by report and by plasma sulfa measurements, and we examined its effects on maternal and fetal delivery outcomes. In the overall cohort, IPTp was not associated with decreased odds of placental malaria or with increased mean maternal hemoglobin or mean birth weight. Unexpectedly, IPTp was associated with decreased cord hemoglobin level and increased risk of fetal anemia, which may be related to in utero SP exposure. IPTp does not improve overall pregnancy outcomes in Muheza, Tanzania, where SP-resistant parasites predominate and may increase the odds of fetal anemia. As parasite resistance increases in a community, the overall effect of IPTp may transition from net benefit to neutral or net harm.

Clinical implications of globally emerging azole resistance in Aspergillus fumigatus

PubMed Central

Verweij, Paul E.

2016-01-01

Aspergillus fungi are the cause of an array of diseases affecting humans, animals and plants. The triazole antifungal agents itraconazole, voriconazole, isavuconazole and posaconazole are treatment options against diseases caused by Aspergillus. However, resistance to azoles has recently emerged as a new therapeutic challenge in six continents. Although de novo azole resistance occurs occasionally in patients during azole therapy, the main burden is the aquisition of resistance through the environment. In this setting, the evolution of resistance is attributed to the widespread use of azole-based fungicides. Although ubiquitously distributed, A. fumigatus is not a phytopathogen. However, agricultural fungicides deployed against plant pathogenic moulds such as Fusarium, Mycospaerella and A. flavus also show activity against A. fumigatus in the environment and exposure of non-target fungi is inevitable. Further, similarity in molecule structure between azole fungicides and antifungal drugs results in cross-resistance of A. fumigatus to medical azoles. Clinical studies have shown that two-thirds of patients with azole-resistant infections had no previous history of azole therapy and high mortality rates between 50% and 100% are reported in azole-resistant invasive aspergillosis. The resistance phenotype is associated with key mutations in the cyp51A gene, including TR34/L98H, TR53 and TR46/Y121F/T289A resistance mechanisms. Early detection of resistance is of paramount importance and if demonstrated, either with susceptibility testing or through molecular analysis, azole monotherapy should be avoided. Liposomal amphotericin B or a combination of voriconazole and an echinocandin are recomended for azole-resistant aspergillosis. This article is part of the themed issue ‘Tackling emerging fungal threats to animal health, food security and ecosystem resilience’. PMID:28080986

Feasibility of Screening for Antibiotic Resistance-Part II

DTIC Science & Technology

2005-08-01

fluoroquinolones were introduced on the market. The first two generations are not widely used anymore, because of widespread resistance or ineffectiveness...Mutations that confer resistance against ciprofloxacin have been found in all four genes encoding subunits of Topoisomerase H and IV, and also in an entirely...aerogenes, Erwinia carotovora, Escherichia coli K12, Francisella tularensis, Klebsiella pneumoniae , Neisseria gonorrhoeae, Providencia stuartii

Understanding the contribution of environmental factors in the spread of antimicrobial resistance.

PubMed

Fletcher, Stephanie

2015-07-01

The overuse and abuse of antibiotics have contributed to the global epidemic of antibiotic resistance. Current evidence suggests that widespread dependency on antibiotics and complex interactions between human health, animal husbandry and veterinary medicine, have contributed to the propagation and spread of resistant organisms. The lack of information on pathogens of major public health importance, limited surveillance, and paucity of standards for a harmonised and coordinated approach, further complicates the issue. Despite the widespread nature of antimicrobial resistance, limited focus has been placed on the role of environmental factors in propagating resistance. There are limited studies that examine the role of the environment, specifically water, sanitation and hygiene factors that contribute to the development of resistant pathogens. Understanding these elements is necessary to identify any modifiable interactions to reduce or interrupt the spread of resistance from the environment into clinical settings. This paper discusses some environmental issues that contribute to antimicrobial resistance, including soil related factors, animal husbandry and waste management, potable and wastewater, and food safety, with examples drawn mainly from the Asian region. The discussion concludes that some of the common issues are often overlooked and whilst there are numerous opportunities for environmental factors to contribute to the growing burden of antimicrobial resistance, a renewed focus on innovative and traditional environmental approaches is needed to tackle the problem.

[Insulin resistance--a physiopathological condition with numerous sequelae: non-insulin-dependent diabetes mellitus (NIDDM), android obesity, essential hypertension, dyslipidemia and atherosclerosis].

PubMed

Pedersen, O

1992-05-11

Recent research has demonstrated that reduced insulin-stimulated glucose metabolism in skeletal muscle (insulin resistance) and hyperinsulinism are common features in widespread diseases such as essential hypertension, android obesity, non-insulin dependent diabetes mellitus, dyslipidemia (in the form of raised serum triglyceride and reduced serum high-density lipoprotein (HDL) cholesterol) and arteriosclerosis. Simultaneously, investigations in a comprehensive group of healthy middle-aged men have revealed insulin resistance in one fourth. On the basis of these observations, a working hypothesis is suggested which postulates that genetic abnormalities in one or more of the candidate genes in the modes of action of insulin occur in a great proportion of the population. These may result in insulin resistance (primary genetic insulin resistance). Primary insulin resistance may be potentiated by a series of circumstances such as ageing, high-fat diet, lack of physical activity, hormonal and metabolic abnormalities or drugs (secondary insulin resistance). As a consequence of the reduced effect of insulin on muscle tissue, compensatory hyperinsulinism develops. Depending on the remaining vulnerability of the individual the hyperinsulinism is presumed to result in development of one or more phenotypes. For example if the beta-cells of the pancreas are unable to secrete sufficient insulin to compensate the insulin resistance on account of genetic defects, glucose intolerance will develop. In a similar manner, hyperinsulinism in insulin-resistant individuals who are predisposed to essential hypertension is presumed to reveal genetic defects in the blood pressure regulating mechanisms and thus contribute to development of the disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Resistance diagnosis and the changing epidemiology of antibiotic resistance.

PubMed

McAdams, David

2017-01-01

Widespread adoption of point-of-care resistance diagnostics (POCRD) reduces ineffective antibiotic use but could increase overall antibiotic use. Indeed, in the context of a standard susceptible-infected epidemiological model with a single antibiotic, POCRD accelerates the rise of resistance in the disease-causing bacterial population. When multiple antibiotics are available, however, POCRD may slow the rise of resistance even as more patients receive antibiotic treatment, belying the conventional wisdom that antibiotics are "exhaustible resources" whose increased use necessarily promotes the rise of resistance. © 2017 New York Academy of Sciences.

Resistance-surface-based wildlife conservation connectivity modeling: Summary of efforts in the United States and guide for practitioners

Treesearch

Alisa A. Wade; Kevin S. McKelvey; Michael K. Schwartz

2015-01-01

Resistance-surface-based connectivity modeling has become a widespread tool for conservation planning. The current ease with which connectivity models can be created, however, masks the numerous untested assumptions underlying both the rules that produce the resistance surface and the algorithms used to locate low-cost paths across the target landscape. Here we present...

Changes in protease activity and Cry3Aa toxin binding in the Colorado potato beetle: implications for insect resistance to Bacillus thuringiensis toxins

Treesearch

Olga Loseva; Mohamed Ibrahim; Mehmet Candas; C. Noah Koller; Leah S. Bauer; Lee A. Jr. Bulla

2002-01-01

Widespread commercial use of Bacillus thuringiensis Cry toxins to control pest insects has increased the likelihood for development of insect resistance to this entomopathogen. In this study, we investigated protease activity profiles and toxin-binding capacities in the midgut of a strain of Colorado potato beetle (CPB) that has developed resistance...

Fungal biosynthesis of gold nanoparticles: mechanism and scale up

PubMed Central

Kitching, Michael; Ramani, Meghana; Marsili, Enrico

2015-01-01

Gold nanoparticles (AuNPs) are a widespread research tool because of their oxidation resistance, biocompatibility and stability. Chemical methods for AuNP synthesis often produce toxic residues that raise environmental concern. On the other hand, the biological synthesis of AuNPs in viable microorganisms and their cell-free extracts is an environmentally friendly and low-cost process. In general, fungi tolerate higher metal concentrations than bacteria and secrete abundant extracellular redox proteins to reduce soluble metal ions to their insoluble form and eventually to nanocrystals. Fungi harbour untapped biological diversity and may provide novel metal reductases for metal detoxification and bioreduction. A thorough understanding of the biosynthetic mechanism of AuNPs in fungi is needed to reduce the time of biosynthesis and to scale up the AuNP production process. In this review, we describe the known mechanisms for AuNP biosynthesis in viable fungi and fungal protein extracts and discuss the most suitable bioreactors for industrial AuNP biosynthesis. PMID:25154648

Gene-specific mechanisms direct glucocorticoid-receptor-driven repression of inflammatory response genes in macrophages

PubMed Central

Sacta, Maria A; Tharmalingam, Bowranigan; Coppo, Maddalena; Rollins, David A; Deochand, Dinesh K; Benjamin, Bradley; Yu, Li; Zhang, Bin; Hu, Xiaoyu; Li, Rong; Chinenov, Yurii

2018-01-01

The glucocorticoid receptor (GR) potently represses macrophage-elicited inflammation, however, the underlying mechanisms remain obscure. Our genome-wide analysis in mouse macrophages reveals that pro-inflammatory paused genes, activated via global negative elongation factor (NELF) dissociation and RNA Polymerase (Pol)2 release from early elongation arrest, and non-paused genes, induced by de novo Pol2 recruitment, are equally susceptible to acute glucocorticoid repression. Moreover, in both cases the dominant mechanism involves rapid GR tethering to p65 at NF-kB-binding sites. Yet, specifically at paused genes, GR activation triggers widespread promoter accumulation of NELF, with myeloid cell-specific NELF deletion conferring glucocorticoid resistance. Conversely, at non-paused genes, GR attenuates the recruitment of p300 and histone acetylation, leading to a failure to assemble BRD4 and Mediator at promoters and enhancers, ultimately blocking Pol2 initiation. Thus, GR displays no preference for a specific pro-inflammatory gene class; however, it effects repression by targeting distinct temporal events and components of transcriptional machinery. PMID:29424686

CHEMICAL AND BIOLOGICAL STABILITY OF ARTEMISININ IN COW RUMEN FLUID AND ITS KINETICS IN GOATS (CAPRA HIRCUS)

USDA-ARS?s Scientific Manuscript database

There is a pressing need to develop alternative, natural anthelmintics to control widespread drug-resistant gastrointestinal nematodes in ruminants, such as Haemonchus contortus. Artemisinin and its semi-synthetic derivatives are widely used against drug-resistant Plasmodium falciparum, but their r...

Foliar insecticides for the control of curly top in Idaho sugar beet, 2017

USDA-ARS?s Scientific Manuscript database

Curly top caused by Beet curly top virus (BCTV) is a widespread disease problem vectored by the beet leafhopper in semiarid sugar beet production areas. Host resistance is the primary defense against this problem, but resistance in commercial cultivars is only low to intermediate. The neonicotiono...

Pyrethroid resistance is widespread among Florida populations of Aedes aegypti

USDA-ARS?s Scientific Manuscript database

Aedes aegypti is an efficient vector of a number of diseases that affect man and is of increasing concern because of the reemergence of dengue and recent identification of locally acquired chikungunya in Florida. Pesticide resistance in this species has been demonstrated in several neighboring coun...

Geographical distribution of pyrethroid resistance allele frequency in head lice (Phthiraptera: Pediculidae) from Argentina.

PubMed

Toloza, Ariel Ceferino; Ascunce, Marina S; Reed, David; Picollo, María Inés

2014-01-01

The human head louse, Pediculus humanus capitis De Geer (Phthiraptera: Pediculidae), is an obligate ectoparasite that causes pediculosis capitis and has parasitized humans since the beginning of humankind. Head louse infestations are widespread throughout the world and have been increasing since the early 1990s partially because of ineffective pediculicides. In Argentina, the overuse of products containing pyrethroids has led to the development of resistant louse populations. Pyrethroid insecticides act on the nervous system affecting voltage-sensitive sodium channels. Three point mutations at the corresponding amino acid sequence positions M815I, T917I, and L920F in the voltage-gated sodium channel gene are responsible for contributing to knockdown resistance (kdr). The management of pyrethroid resistance requires either early detection or the characterization of the mechanisms involved in head louse populations. In the current study, we estimated the distribution of kdr alleles in 154 head lice from six geographical regions of Argentina. Pyrethroid resistance kdr alleles were found in high frequencies ranging from 67 to 100%. Of these, 131 (85.1%) were homozygous resistant, 13 (8.4%) were homozygous susceptible, and 10 (6.5%) were heterozygous. Exact tests for the Hardy-Weinberg equilibrium for each location showed that genotype frequencies differed significantly from expectation in four of the six sites studied. These results show that pyrethroid resistance is well established reaching an overall frequency of 88%, thus close to fixation. With 30 yr of pyrethroid-based pediculicides use in Argentina, kdr resistance has evolved rapidly among these head louse populations.

Presence and mechanisms of acquired antimicrobial resistance in Belgian Brachyspira hyodysenteriae isolates belonging to different clonal complexes.

PubMed

Mahu, M; Pasmans, F; Vranckx, K; De Pauw, N; Vande Maele, L; Vyt, Philip; Vandersmissen, Tamara; Martel, A; Haesebrouck, F; Boyen, F

2017-08-01

Swine dysentery (SD) is an economically important disease for which antimicrobial treatment still occupies an important place to control outbreaks. However, acquired antimicrobial resistance is increasingly observed in Brachyspira hyodysenteriae. In this study, the Minimal Inhibitory Concentrations (MIC) of six antimicrobial compounds for 30 recent Belgian B. hyodysenteriae isolates were determined using a broth microdilution method. In addition, relevant regions of the 16S rRNA, 23S rRNA and the L3 protein encoding genes were sequenced to reveal mutations associated with acquired resistance. Finally, a phylogeny was reconstructed using minimal spanning tree analysis of multi locus sequence typing of the isolates. For lincomycin, doxycycline, tylosin and tylvalosin, at least 70% of the isolates did not belong to the wild-type population and were considered to have acquired resistance. For valnemulin and tiamulin, this was over 50%. In all isolates with acquired resistance to doxycycline, the G1058C mutation was present in their 16S rRNA gene. All isolates showing acquired resistance to lincomycin and both macrolides displayed the A2058T mutation in their 23S rRNA gene. Other mutations in this gene and the N148S mutation in the L3 protein were present in both wild-type isolates and isolates considered to have acquired resistance. Multi locus sequence analysis revealed a previously undescribed clonal complex, with 4 novel sequence types in which the majority of isolates showed acquired resistance to all tested antimicrobial products. In conclusion, acquired antimicrobial resistance is widespread among Belgian B. hyodysenteriae isolates. The emergence of multi-resistant clonal complexes can pose a threat to swine industry. Copyright © 2017 Elsevier B.V. All rights reserved.

BTK inhibitors in chronic lymphocytic leukemia: a glimpse to the future.

PubMed

Spaargaren, M; de Rooij, M F M; Kater, A P; Eldering, E

2015-05-07

The treatment of chronic lymphocytic leukemia (CLL) with inhibitors targeting B cell receptor signaling and other survival mechanisms holds great promise. Especially the early clinical success of Ibrutinib, an irreversible inhibitor of Bruton's tyrosine kinase (BTK), has received widespread attention. In this review we will focus on the fundamental and clinical aspects of BTK inhibitors in CLL, with emphasis on Ibrutinib as the best studied of this class of drugs. Furthermore, we summarize recent laboratory as well as clinical findings relating to the first cases of Ibrutinib resistance. Finally, we address combination strategies with Ibrutinib, and attempt to extrapolate its current status to the near future in the clinic.

Development of new drugs for an old target: the penicillin binding proteins.

PubMed

Zervosen, Astrid; Sauvage, Eric; Frère, Jean-Marie; Charlier, Paulette; Luxen, André

2012-10-24

The widespread use of β-lactam antibiotics has led to the worldwide appearance of drug-resistant strains. Bacteria have developed resistance to β-lactams by two main mechanisms: the production of β-lactamases, sometimes accompanied by a decrease of outer membrane permeability, and the production of low-affinity, drug resistant Penicillin Binding Proteins (PBPs). PBPs remain attractive targets for developing new antibiotic agents because they catalyse the last steps of the biosynthesis of peptidoglycan, which is unique to bacteria, and lies outside the cytoplasmic membrane. Here we summarize the “current state of the art” of non-β-lactam inhibitors of PBPs, which have being developed in an attempt to counter the emergence of β-lactam resistance. These molecules are not susceptible to hydrolysis by β-lactamases and thus present a real alternative to β-lactams. We present transition state analogs such as boronic acids, which can covalently bind to the active serine residue in the catalytic site. Molecules containing ring structures different from the β-lactam-ring like lactivicin are able to acylate the active serine residue. High throughput screening methods, in combination with virtual screening methods and structure based design, have allowed the development of new molecules. Some of these novel inhibitors are active against major pathogens, including methicillin-resistant Staphylococcus aureus (MRSA) and thus open avenues new for the discovery of novel antibiotics.

Cladding Attachment Over Thick Exterior Insulating Sheathing (Fact Sheet)

DOE Office of Scientific and Technical Information (OSTI.GOV)

None, None

The addition of insulation to the exterior of buildings is an effective means of increasing the thermal resistance of wood-framed walls and mass masonry wall assemblies. The location of the insulation on the exterior of the structure has many direct benefits, including better effective R-value from reduced thermal bridging, better condensation resistance, reduced thermal stress on the structure, as well as other commonly associated improvements such as increased airtightness and improved water management. For thick layers of exterior insulation (more than 1.5 in.), the use of wood furring strips attached through the insulation back to the structure has been usedmore » by many contractors and designers as a means to provide a convenient cladding attachment location. Although the approach has proven effective, there is significant resistance to its widespread implementation due to a lack of research and understanding of the mechanisms involved in the development of the vertical displacement resistance capacity. In addition, the long-term in-service performance of the system has been questioned due to potential creep effects of the assembly under the sustained dead load of the cladding and effects of varying environmental conditions. In addition, the current International Building Code (IBC) and International Residential Code (IRC) do not have a provision that specifically allows this assembly.« less

Base isolation: Fresh insight

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shustov, V.

1993-07-15

The objective of the research is a further development of the engineering concept of seismic isolation. Neglecting the transient stage of seismic loading results in a widespread misjudgement: The force of resistance associated with velocity is mostly conceived as a source of damping vibrations, though it is an active force at the same time, during an earthquake type excitation. For very pliant systems such as base isolated structures with relatively low bearing stiffness and with artificially added heavy damping mechanism, the so called `damping`` force may occur even the main pushing force at an earthquake. Thus, one of the twomore » basic pillars of the common seismic isolation philosophy, namely, the doctrine of usefulness and necessity of a strong damping mechanism, is turning out to be a self-deception, sometimes even jeopardizing the safety of structures and discrediting the very idea of seismic isolation. There is a way out: breaking with damping dependancy.« less

Microstructural and Mechanical Aspects of Reinforcement Welds for Lightweight Components Produced by Friction Hydro Pillar Processing

NASA Astrophysics Data System (ADS)

Pinheiro, Gustavo; dos Santos, Jorge; Hort, Norbert; Kainer, Karl Ulrich

The development of new creep resistant and cost effective die casting magnesium alloys such as AE, MRI, MEZ, ACM, AXJ, AJ, WE have emerged as an alternative to fulfil the actual demands in structural relevant applications as engines blocks, gear and converter boxes. However, magnesium components are in most of the cases screwed with aluminium and steel bolts, which lead the screwed joint to lose the preload force due to relaxation. This barrier limits thus the broad use of magnesium within this segment and should somehow find an adequate solution to be implemented and to help overcoming this limitation. In this context Friction Welding (FW) and particularly Friction Hydro Pillar Processing (FHPP), which can be described as a drill and fill process, appears as an alternative to widespread the use of magnesium. In this context, FHPP is intended to be used to locally reinforce mechanical fastened magnesium components.

Mutation as a Stress Response and the Regulation of Evolvability

PubMed Central

Galhardo, Rodrigo S.; Hastings, P. J.; Rosenberg, Susan M.

2010-01-01

Our concept of a stable genome is evolving to one in which genomes are plastic and responsive to environmental changes. Growing evidence shows that a variety of environmental stresses induce genomic instability in bacteria, yeast, and human cancer cells, generating occasional fitter mutants and potentially accelerating adaptive evolution. The emerging molecular mechanisms of stress-induced mutagenesis vary but share telling common components that underscore two common themes. The first is the regulation of mutagenesis in time by cellular stress responses, which promote random mutations specifically when cells are poorly adapted to their environments, i.e., when they are stressed. A second theme is the possible restriction of random mutagenesis in genomic space, achieved via coupling of mutation-generating machinery to local events such as DNA-break repair or transcription. Such localization may minimize accumulation of deleterious mutations in the genomes of rare fitter mutants, and promote local concerted evolution. Although mutagenesis induced by stresses other than direct damage to DNA was previously controversial, evidence for the existence of various stress-induced mutagenesis programs is now overwhelming and widespread. Such mechanisms probably fuel evolution of microbial pathogenesis and antibiotic-resistance, and tumor progression and chemotherapy resistance, all of which occur under stress, driven by mutations. The emerging commonalities in stress-induced-mutation mechanisms provide hope for new therapeutic interventions for all of these processes. PMID:17917874

Multiple-Herbicide Resistance Is Widespread in Roadside Palmer Amaranth Populations.

PubMed

Bagavathiannan, Muthukumar V; Norsworthy, Jason K

2016-01-01

Herbicide-resistant Palmer amaranth is a widespread issue in row-crop production in the Midsouthern US. Palmer amaranth is commonly found on roadside habitats in this region, but little is known on the degree of herbicide resistance in these populations. Herbicide resistance in roadside Palmer amaranth populations can represent the spread of an adaptive trait across a selective landscape. A large-scale survey was carried out in the Mississippi Delta region of eastern Arkansas to document the level of resistance in roadside Palmer amaranth populations to pyrithiobac and glyphosate, two important herbicides with broad history of use in the region. A total of 215 Palmer amaranth populations collected across 500 random survey sites were used in the evaluations. About 89 and 73% of the surveyed populations showed >90% survival to pyrithiobac and glyphosate, respectively. Further, only 3% of the populations were completely susceptible to glyphosate, while none of the populations was completely controlled by pyrithiobac. Among the 215 populations evaluated, 209 populations showed multiple resistance to both pyrithiobac and glyphosate at varying degrees. Dose-response assays confirmed the presence of high levels of herbicide resistance in the five selected populations (≥ 25-fold compared to a susceptible standard). Results demonstrate the prevalence of multiple-herbicide resistance in roadside Palmer amaranth populations in this region. Growers should be vigilant of Palmer amaranth infestation in roadsides adjacent to their fields and implement appropriate control measures to prevent likely spread of herbicide resistance into their fields.

Studying modification of aminoglycoside antibiotics by resistance-causing enzymes via microarray.

PubMed

Disney, Matthew D

2012-01-01

Widespread bacterial resistance to antibiotics is a significant public health concern. To remain a step ahead of evolving bacteria, new methods to study resistance to antibacterials and to uncover novel antibiotics that evade resistance are urgently needed. Herein, microarray-based methods that have been developed to study aminoglycoside modification by resistance-causing enzymes are reviewed. These arrays can also be used to study the binding of aminoglycoside antibiotics to a mimic of their therapeutic target, the rRNA aminoacyl site (A-site), and how modification by resistance-causing enzymes affects their abilities to bind RNA.

The within-host population dynamics of Mycobacterium tuberculosis vary with treatment efficacy.

PubMed

Trauner, Andrej; Liu, Qingyun; Via, Laura E; Liu, Xin; Ruan, Xianglin; Liang, Lili; Shi, Huimin; Chen, Ying; Wang, Ziling; Liang, Ruixia; Zhang, Wei; Wei, Wang; Gao, Jingcai; Sun, Gang; Brites, Daniela; England, Kathleen; Zhang, Guolong; Gagneux, Sebastien; Barry, Clifton E; Gao, Qian

2017-04-19

Combination therapy is one of the most effective tools for limiting the emergence of drug resistance in pathogens. Despite the widespread adoption of combination therapy across diseases, drug resistance rates continue to rise, leading to failing treatment regimens. The mechanisms underlying treatment failure are well studied, but the processes governing successful combination therapy are poorly understood. We address this question by studying the population dynamics of Mycobacterium tuberculosis within tuberculosis patients undergoing treatment with different combinations of antibiotics. By combining very deep whole genome sequencing (~1000-fold genome-wide coverage) with sequential sputum sampling, we were able to detect transient genetic diversity driven by the apparently continuous turnover of minor alleles, which could serve as the source of drug-resistant bacteria. However, we report that treatment efficacy has a clear impact on the population dynamics: sufficient drug pressure bears a clear signature of purifying selection leading to apparent genetic stability. In contrast, M. tuberculosis populations subject to less drug pressure show markedly different dynamics, including cases of acquisition of additional drug resistance. Our findings show that for a pathogen like M. tuberculosis, which is well adapted to the human host, purifying selection constrains the evolutionary trajectory to resistance in effectively treated individuals. Nonetheless, we also report a continuous turnover of minor variants, which could give rise to the emergence of drug resistance in cases of drug pressure weakening. Monitoring bacterial population dynamics could therefore provide an informative metric for assessing the efficacy of novel drug combinations.

Recent insights into plant-virus interactions through proteomic analysis.

PubMed

Di Carli, Mariasole; Benvenuto, Eugenio; Donini, Marcello

2012-10-05

Plant viruses represent a major threat for a wide range of host species causing severe losses in agricultural practices. The full comprehension of mechanisms underlying events of virus-host plant interaction is crucial to devise novel plant resistance strategies. Until now, functional genomics studies in plant-virus interaction have been limited mainly on transcriptomic analysis. Only recently are proteomic approaches starting to provide important contributions to this area of research. Classical two-dimensional electrophoresis (2-DE) coupled to mass spectrometry (MS) is still the most widely used platform in plant proteome analysis, although in the last years the application of quantitative "second generation" proteomic techniques (such as differential in gel electrophoresis, DIGE, and gel-free protein separation methods) are emerging as more powerful analytical approaches. Apparently simple, plant-virus interactions reveal a really complex pathophysiological context, in which resistance, defense and susceptibility, and direct virus-induced reactions interplay to trigger expression responses of hundreds of genes. Given that, this review is specifically focused on comparative proteome-based studies on pathogenesis of several viral genera, including some of the most important and widespread plant viruses of the genus Tobamovirus, Sobemovirus, Cucumovirus and Potyvirus. In all, this overview reveals a widespread repression of proteins associated with the photosynthetic apparatus, while energy metabolism/protein synthesis and turnover are typically up-regulated, indicating a major redirection of cell metabolism. Other common features include the modulation of metabolisms concerning sugars, cell wall, and reactive oxigen species as well as pathogenesis-related (PR) proteins. The fine-tuning between plant development and antiviral defense mechanisms determines new patterns of regulation of common metabolic pathways. By offering a 360-degree view of protein modulation, all proteomic tools reveal the extraordinary intricacy of mechanisms with which a simple viral genome perturbs the plant cell molecular networks. This "omic" approach, while providing a global perspective and useful information to the understanding of the plant host-virus interactome, may possibly reveal protein targets/markers useful in the design of future diagnosis and/or plant protection strategies.

Multidrug Resistance in Breast Cancer: From In Vitro Models to Clinical Studies

PubMed Central

Wind, N. S.; Holen, I.

2011-01-01

The development of multidrug resistance (MDR) and subsequent relapse on therapy is a widespread problem in breast cancer, but our understanding of the underlying molecular mechanisms is incomplete. Numerous studies have aimed to establish the role of drug transporter pumps in MDR and to link their expression to response to chemotherapy. The ATP-binding cassette (ABC) transporters are central to breast cancer MDR, and increases in ABC expression levels have been shown to correlate with decreases in response to various chemotherapy drugs and a reduction in overall survival. But as there is a large degree of redundancy between different ABC transporters, this correlation has not been seen in all studies. This paper provides an introduction to the key molecules associated with breast cancer MDR and summarises evidence of their potential roles reported from model systems and clinical studies. We provide possible explanations for why despite several decades of research, the precise role of ABC transporters in breast cancer MDR remains elusive. PMID:22332018

Mutational patterns in chemotherapy resistant muscle-invasive bladder cancer.

PubMed

Liu, David; Abbosh, Philip; Keliher, Daniel; Reardon, Brendan; Miao, Diana; Mouw, Kent; Weiner-Taylor, Amaro; Wankowicz, Stephanie; Han, Garam; Teo, Min Yuen; Cipolla, Catharine; Kim, Jaegil; Iyer, Gopa; Al-Ahmadie, Hikmat; Dulaimi, Essel; Chen, David Y T; Alpaugh, R Katherine; Hoffman-Censits, Jean; Garraway, Levi A; Getz, Gad; Carter, Scott L; Bellmunt, Joaquim; Plimack, Elizabeth R; Rosenberg, Jonathan E; Van Allen, Eliezer M

2017-12-19

Despite continued widespread use, the genomic effects of cisplatin-based chemotherapy and implications for subsequent treatment are incompletely characterized. Here, we analyze whole exome sequencing of matched pre- and post-neoadjuvant cisplatin-based chemotherapy primary bladder tumor samples from 30 muscle-invasive bladder cancer patients. We observe no overall increase in tumor mutational burden post-chemotherapy, though a significant proportion of subclonal mutations are unique to the matched pre- or post-treatment tumor, suggesting chemotherapy-induced and/or spatial heterogeneity. We subsequently identify and validate a novel mutational signature in post-treatment tumors consistent with known characteristics of cisplatin damage and repair. We find that post-treatment tumor heterogeneity predicts worse overall survival, and further observe alterations in cell-cycle and immune checkpoint regulation genes in post-treatment tumors. These results provide insight into the clinical and genomic dynamics of tumor evolution with cisplatin-based chemotherapy, suggest mechanisms of clinical resistance, and inform development of clinically relevant biomarkers and trials of combination therapies.

Trichomonicidal and parasite membrane damaging activity of bidesmosic saponins from Manilkara rufula.

PubMed

de Brum Vieira, Patrícia; Silva, Nícolas Luiz Feijó; Menezes, Camila Braz; da Silva, Márcia Vanusa; Silva, Denise Brentan; Lopes, Norberto Peporine; Macedo, Alexandre José; Bastida, Jaume; Tasca, Tiana

2017-01-01

The infection caused by Trichomonas vaginalis is the most common but overlooked non-viral sexually transmitted disease worldwide. Treatment relies on one class of drugs, the 5-nitroimidazoles, but resistance is widespread. New drugs are urgently needed. We reported the effect of crude and purified saponin fractions of Manilkara rufula against Trichomonas vaginalis. The compound responsible for antitrichomonal activity was isolated and identified as an uncommon bidesmosic saponin, Mi-saponin C. This saponin eliminated parasite viability without toxicity against the human vaginal epithelial line (HMVII). In addition, the isolated saponin fraction improved the metronidazole effect against a metronidazole-resistant isolate and dramatically reduced the cytoadherence of T. vaginalis to human cells. Investigation of the mechanism of death showed that the saponin fraction induced the parasite death due to profound membrane damage, inducing a disturbance of intracellular content without nuclear damage. To the best of our knowledge, this is the first report of antitrichomonal activity in the bidesmosic saponins of Manilkara rufula.

Trichomonicidal and parasite membrane damaging activity of bidesmosic saponins from Manilkara rufula

PubMed Central

Silva, Nícolas Luiz Feijó; Menezes, Camila Braz; da Silva, Márcia Vanusa; Silva, Denise Brentan; Lopes, Norberto Peporine; Macedo, Alexandre José; Bastida, Jaume; Tasca, Tiana

2017-01-01

The infection caused by Trichomonas vaginalis is the most common but overlooked non-viral sexually transmitted disease worldwide. Treatment relies on one class of drugs, the 5-nitroimidazoles, but resistance is widespread. New drugs are urgently needed. We reported the effect of crude and purified saponin fractions of Manilkara rufula against Trichomonas vaginalis. The compound responsible for antitrichomonal activity was isolated and identified as an uncommon bidesmosic saponin, Mi-saponin C. This saponin eliminated parasite viability without toxicity against the human vaginal epithelial line (HMVII). In addition, the isolated saponin fraction improved the metronidazole effect against a metronidazole-resistant isolate and dramatically reduced the cytoadherence of T. vaginalis to human cells. Investigation of the mechanism of death showed that the saponin fraction induced the parasite death due to profound membrane damage, inducing a disturbance of intracellular content without nuclear damage. To the best of our knowledge, this is the first report of antitrichomonal activity in the bidesmosic saponins of Manilkara rufula. PMID:29190689

Spatially uniform resistance switching of low current, high endurance titanium–niobium-oxide memristors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kumar, Suhas; Davila, Noraica; Wang, Ziwen

2016-11-24

Here we analyzed micrometer-scale titanium-niobium-oxide prototype memristors, which exhibited low write-power (< 3 μW) and energy (< 200 fJ per bit per μm 2), low read-power (~nW), and high endurance ( > millions of cycles). To understand their physico-chemical operating mechanisms, we performed in operando synchrotron X-ray transmission nanoscale spectromicroscopy using an ultra-sensitive time-multiplexed technique. We observed only spatially uniform material changes during cell operation, in sharp contrast to the frequently detected formation of a localized conduction channel in transition-metal-oxide memristors. We also associated the response of assigned spectral features distinctly to non-volatile storage (resistance change) and writing of informationmore » (application of voltage and Joule heating). Lastly, these results provide critical insights into high-performance memristors that will aid in device design, scaling and predictive circuit-modeling, all of which are essential for the widespread deployment of successful memristor applications.« less

Phytophthora capsici - Loss of Heterozygosity (LOH): A Widespread Mechanism for Rapid Adaptation (7th Annual SFAF Meeting, 2012)

ScienceCinema

Mudge, Joanne

2018-01-15

Joanne Mudge on "Phytophthora capsici - Loss of Heterozygosity (LOH): A Widespread Mechanism for Rapid Mutation" at the 2012 Sequencing, Finishing, Analysis in the Future Meeting held June 5-7, 2012 in Santa Fe, New Mexico.

Aphanomyces root rot of alfalfa: widespread distribution of race 2

USDA-ARS?s Scientific Manuscript database

The early spring of 2012 with prolonged wet soil conditions in many parts of the country resulted in reports of poor performance of alfalfa due to Aphanomyces root rot (ARR). Varieties with resistance to ARR are available, although fewer varieties have resistance to both race 1 and race 2 of the pat...

Resistance to "Developmentally Appropriate Practice": Teachers, Graduate Students, and Parents Speak Out.

ERIC Educational Resources Information Center

O'Brien, Leigh M.

Although developmentally appropriate practice (DAP) has gained widespread acceptance within early childhood education, it is not accepted by all. This study examined resistance to the DAP concept among: (1) Head Start and other early childhood teachers; (2) child caregivers; (3) African-American mothers; and (4) masters students in early childhood…

Evaluation of hemlock (Tsuga) species and hybrids for resistance to Adelges tsugae (Hemiptera: Adelgidae) using artificial infestation

Treesearch

Michael E. Montgomery; S.E. Bentz; Richard T. Olsen

2009-01-01

Hemlock (Tsuga) species and hybrids were evaluated for resistance to the hemlock woolly adelgid, Adelges tsugae Annand (Hemiptera: Adelgidae). The adelgid was accidentally introduced from Asia to the eastern United States, where it is causing widespread mortality of the native hemlocks, Tsuga canadensis (L.)...

Azithromycin Resistance and Decreased Ceftriaxone Susceptibility in Neisseria gonorrhoeae, Hawaii, USA.

PubMed

Papp, John R; Abrams, A Jeanine; Nash, Evelyn; Katz, Alan R; Kirkcaldy, Robert D; O'Connor, Norman P; O'Brien, Pamela S; Harauchi, Derek H; Maningas, Eloisa V; Soge, Olusegun O; Kersh, Ellen N; Komeya, Alan; Tomas, Juval E; Wasserman, Glenn M; Kunimoto, Gail Y; Trees, David L; Whelen, A Christian

2017-05-01

During 2016, eight Neisseria gonorrhoeae isolates from 7 patients in Hawaii were resistant to azithromycin; 5 had decreased in vitro susceptibility to ceftriaxone. Genomic analysis demonstrated a distinct phylogenetic clade when compared with local contemporary strains. Continued evolution and widespread transmission of these strains might challenge the effectiveness of current therapeutic options.

Antimicrobial stewardship: the role of scientists?

PubMed

Bowater, Laura

2015-07-01

We continue to be warned about the risk of antibiotic resistance. This campaign has targeted medicine and agriculture, asking these industries to pay attention to the risks of widespread resistance and to cut the use of antibiotics wherever possible. However, there has been little to no mention of the widespread use of antibiotics in the scientific research community. As scientists we use antibiotics and antibiotic resistance as fundamental tools for our research; almost all conventional plasmids use an antibiotic resistance gene as a selectable marker, offering us an easy method of screening. With molecular biology and genetics at the heart of many research disciplines, these tools are ubiquitous. Scientists have a responsibility to monitor and reduce our use of antibiotics. With the growth and fast advancement of synthetic biology, it is timely for us to consider other options and to teach the next generation of researchers by example how to truly value antibiotics by using them more responsibly. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Multiple insecticide resistance mechanisms in Anopheles gambiae s.l. populations from Cameroon, Central Africa.

PubMed

Nwane, Philippe; Etang, Josiane; Chouaїbou, Mouhamadou; Toto, Jean Claude; Koffi, Alphonsine; Mimpfoundi, Rémy; Simard, Frédéric

2013-02-22

Increasing incidence of DDT and pyrethroid resistance in Anopheles mosquitoes is seen as a limiting factor for malaria vector control. The current study aimed at an in-depth characterization of An. gambiae s.l. resistance to insecticides in Cameroon, in order to guide malaria vector control interventions. Anopheles gambiae s.l. mosquitoes were collected as larvae and pupae from six localities spread throughout the four main biogeographical domains of Cameroon and reared to adults in insectaries. Standard WHO insecticide susceptibility tests were carried out with 4% DDT, 0.75% permethrin and 0.05% deltamethrin. Mortality rates and knockdown times (kdt50 and kdt95) were determined and the effect of pre-exposure to the synergists DEF, DEM and PBO was assessed. Tested mosquitoes were identified to species and molecular forms (M or S) using PCR-RFLP. The hot ligation method was used to depict kdr mutations and biochemical assays were conducted to assess detoxifying enzyme activities. The An. arabiensis population from Pitoa was fully susceptible to DDT and permethrin (mortality rates>98%) and showed reduced susceptibility to deltamethrin. Resistance to DDT was widespread in An. gambiae s.s. populations and heterogeneous levels of susceptibility to permethrin and deltamethrin were observed. In many cases, prior exposure to synergists partially restored insecticide knockdown effect and increased mortality rates, suggesting a role of detoxifying enzymes in increasing mosquito survival upon challenge by pyrethroids and, to a lower extent DDT. The distribution of kdr alleles suggested a major role of kdr-based resistance in the S form of An. gambiae. In biochemical tests, all but one mosquito population overexpressed P450 activity, whereas baseline GST activity was low and similar in all field mosquito populations and in the control. In Cameroon, multiple resistance mechanisms segregate in the S form of An. gambiae resulting in heterogeneous resistance profiles, whereas in the M form and An. arabiensis insecticide tolerance seems to be essentially mediated by enzyme-based detoxification. Synergists partially restored susceptibility to pyrethroid insecticides, and might help mitigate the impact of vector resistance in the field. However, additional vector control tools are needed to further impact on malaria transmission in such settings.

Inducible repair of alkylated DNA in microorganisms.

PubMed

Mielecki, Damian; Wrzesiński, Michał; Grzesiuk, Elżbieta

2015-01-01

Alkylating agents, which are widespread in the environment, also occur endogenously as primary and secondary metabolites. Such compounds have intrinsically extremely cytotoxic and frequently mutagenic effects, to which organisms have developed resistance by evolving multiple repair mechanisms to protect cellular DNA. One such defense against alkylation lesions is an inducible Adaptive (Ada) response. In Escherichia coli, the Ada response enhances cell resistance by the biosynthesis of four proteins: Ada, AlkA, AlkB, and AidB. The glycosidic bonds of the most cytotoxic lesion, N3-methyladenine (3meA), together with N3-methylguanine (3meG), O(2)-methylthymine (O(2)-meT), and O(2)-methylcytosine (O(2)-meC), are cleaved by AlkA DNA glycosylase. Lesions such as N1-methyladenine (1meA) and N3-methylcytosine (3meC) are removed from DNA and RNA by AlkB dioxygenase. Cytotoxic and mutagenic O(6)-methylguanine (O(6)meG) is repaired by Ada DNA methyltransferase, which transfers the methyl group onto its own cysteine residue from the methylated oxygen. We review (i) the individual Ada proteins Ada, AlkA, AlkB, AidB, and COG3826, with emphasis on the ubiquitous and versatile AlkB and its prokaryotic and eukaryotic homologs; (ii) the organization of the Ada regulon in several bacterial species; (iii) the mechanisms underlying activation of Ada transcription. In vivo and in silico analysis of various microorganisms shows the widespread existence and versatile organization of Ada regulon genes, including not only ada, alkA, alkB, and aidB but also COG3826, alkD, and other genes whose roles in repair of alkylated DNA remain to be elucidated. This review explores the comparative organization of Ada response and protein functions among bacterial species beyond the classical E. coli model. Copyright © 2014 Elsevier B.V. All rights reserved.

Fluoroquinolone Resistance Mechanisms and population structure of Enterobacter cloacae non-susceptible to Ertapenem in North-Eastern France

PubMed Central

Guillard, Thomas; Cholley, Pascal; Limelette, Anne; Hocquet, Didier; Matton, Lucie; Guyeux, Christophe; Lebreil, Anne-Laure; Bajolet, Odile; Brasme, Lucien; Madoux, Janick; Vernet-Garnier, Véronique; Barbe, Coralie; Bertrand, Xavier; de Champs on behalf of CarbaFrEst Group, Christophe

2015-01-01

Fluoroquinolone (FQ) agents are a potential resort to treat infection due to Enterobacteriaceae producing extended spectrum β-lactamase and susceptible to FQ. In a context of increase of non-susceptibility to carbapenems among Enterobacteriaceae, we characterized FQ resistance mechanisms in 75 Enterobacter cloacae isolates non-susceptible to ertapenem in North-Eastern France in 2012 and describe the population structure by pulsed field gel electrophoresis (PFGE) and multi-locus sequence typing (MLST). Among them, 14.7% (12/75) carried a carbapenemase-encoding gene. Except one isolate producing VIM-1, the carbapenemase-producing isolates carried the well-known IncL/M pOXA48a plasmid. Most of the isolates (59/75) harbored at least a FQ-R determinant. qnr genes were predominant (40%, 30/75). The MLST study revealed that E. cloacae isolates’ clonality was wide [24 different sequence types (STs)]. The more widespread STs were ST74, ST101, ST110, ST114, and ST133. Carbapenem MICs were higher for E. cloacae ST74 than for other E. cloacae isolates. Plasmid-mediated quinolone resistance determinants were more often observed in E. cloacae ST74 isolates. These findings showed that (i) pOXA-48a is spreading in North-Eastern France, (ii) qnr is preponderant in E. cloacae, (iii) E. cloacae comprised a large amount of lineages spreading in North-Eastern France, and (iv) FQ as an alternative to β-lactams to treat ertapenem non-susceptible Enterobacteriaceae are compromised. PMID:26557115

Pyrolytic-carbon coating in carbon nanotube foams for better performance in supercapacitors

NASA Astrophysics Data System (ADS)

He, Nanfei; Yildiz, Ozkan; Pan, Qin; Zhu, Jiadeng; Zhang, Xiangwu; Bradford, Philip D.; Gao, Wei

2017-03-01

Nowadays, the wide-spread adoption of supercapacitors has been hindered by their inferior energy density to that of batteries. Here we report the use of our pyrolytic-carbon-coated carbon nanotube foams as lightweight, compressible, porous, and highly conductive current collectors in supercapacitors, which are infiltrated with chemically-reduced graphene oxide and later compressed via mechanical and capillary forces to generate the active electrodes. The pyrolytic carbon coatings, introduced by chemical vapor infiltration, wrap around the CNT junctions and increase the surface roughness. When active materials are infiltrated, the pyrolytic-carbon coatings help prevent the π-stacking, enlarge the accessible surface area, and increase the electrical conductivity of the scaffold. Our best-performing device offers 48% and 57% higher gravimetric energy and power density, 14% and 23% higher volumetric energy and power density, respectively, and two times higher knee frequency, than the device with commercial current collectors, while the "true-performance metrics" are strictly followed in our measurements. We have further clarified the solution resistance, charge transfer resistance/capacitance, double-layer capacitance, and Warburg resistance in our system via comprehensive impedance analysis, which will shed light on the design and optimization of similar systems.

Laser Nitriding of the Newly Developed Ti-20Nb-13Zr at.% Biomaterial Alloy to Enhance Its Mechanical and Corrosion Properties in Simulated Body Fluid

NASA Astrophysics Data System (ADS)

Hussein, M. A.; Kumar, A. Madhan; Yilbas, Bekir S.; Al-Aqeeli, N.

2017-11-01

Despite the widespread application of Ti alloy in the biomedical field, surface treatments are typically applied to improve its resistance to corrosion and wear. A newly developed biomedical Ti-20Nb-13Zr at.% alloy (TNZ) was laser-treated in nitrogen environment to improve its surface characteristics with corrosion protection performance. Surface modification of the alloy by laser was performed through a Nd:YAG laser. The structural and surface morphological alterations in the laser nitrided layer were investigated by XRD and a FE-SEM. The mechanical properties have been evaluated using nanoindentation for laser nitride and as-received samples. The corrosion protection behavior was estimated using electrochemical corrosion analysis in a physiological medium (SBF). The obtained results revealed the production of a dense and compact film of TiN fine grains (micro-/nanosize) with 9.1 µm below the surface. The mechanical assessment results indicated an improvement in the modulus of elasticity, hardness, and resistance of the formed TiN layer to plastic deformation. The electrochemical analysis exhibited that the surface protection performance of the laser nitrided TNZ substrates in the SBF could be considerably enhanced compared to that of the as-received alloy due to the presence of fine grains in the TiN layer resulting from laser nitriding. Furthermore, the untreated and treated Ti-20Nb-13Zr alloy exhibited higher corrosion resistance than the CpTi and Ti6Al4V commercial alloys. The improvements in the surface hardness and corrosion properties of Ti alloy in a simulated body obtained using laser nitriding make this approach a suitable candidate for enhancing the properties of biomaterials.

Different efficiencies of the same mechanisms result in distinct Cd tolerance within Rhizobium.

PubMed

Cardoso, Paulo; Corticeiro, Sofia; Freitas, Rosa; Figueira, Etelvina

2018-04-15

Soil contamination with metals is a widespread problem posing risks to humans and ecosystems. Metal contaminated soils often hold poor microbial density and biodiversity. Among soil bacteria, rhizobia have a great agronomic and environmental significance and are major contributors to a sustainable maintenance of soil fertility. This group of microorganisms are severely affected by metals, such as cadmium (Cd), but information about metal resistance mechanisms in rhizobia is still limited. A concerted approach of the different mechanisms conferring Cd tolerance to rhizobia was conducted using two Rhizobium strains with contrasting tolerances to Cd. Results show that both strains resort to the same mechanisms (extracellular immobilization, periplasmic allocation, cytoplasmic sequestration and biotransformation of toxic products) to overcome stress, but differences in the efficiencies of some mechanisms were noticed. The ability of Rhizobium to increase glutathione in the presence of Cd emerges as a central factor in the tolerance to Cd and is as a feature to be looked for when screening or transforming microorganisms to integrate plant-microbe consortia. These could promote plant growth at contaminated sites, being more efficient for the cleanup of metals from contaminated sites and the restoration of soil quality. Copyright © 2017 Elsevier Inc. All rights reserved.

Surviving bacterial sibling rivalry: inducible and reversible phenotypic switching in Paenibacillus dendritiformis.

PubMed

Be'er, Avraham; Florin, E-L; Fisher, Carolyn R; Swinney, Harry L; Payne, Shelley M

2011-01-01

Natural habitats vary in available nutrients and room for bacteria to grow, but successful colonization can lead to overcrowding and stress. Here we show that competing sibling colonies of Paenibacillus dendritiformis bacteria survive overcrowding by switching between two distinct vegetative phenotypes, motile rods and immotile cocci. Growing colonies of the rod-shaped bacteria produce a toxic protein, Slf, which kills cells of encroaching sibling colonies. However, sublethal concentrations of Slf induce some of the rods to switch to Slf-resistant cocci, which have distinct metabolic and resistance profiles, including resistance to cell wall antibiotics. Unlike dormant spores of P. dendritiformis, the cocci replicate. If cocci encounter conditions that favor rods, they secrete a signaling molecule that induces a switch to rods. Thus, in contrast to persister cells, P. dendritiformis bacteria adapt to changing environmental conditions by inducible and reversible phenotypic switching. In favorable environments, species may face space and nutrient limits due to overcrowding. Bacteria provide an excellent model for analyzing principles underlying overcrowding and regulation of density in nature, since their population dynamics can be easily and accurately assessed under controlled conditions. We describe a newly discovered mechanism for survival of a bacterial population during overcrowding. When competing with sibling colonies, Paenibacillus dendritiformis produces a lethal protein (Slf) that kills cells at the interface of encroaching colonies. Slf also induces a small proportion of the cells to switch from motile, rod-shaped cells to nonmotile, Slf-resistant, vegetative cocci. When crowding is reduced and nutrients are no longer limiting, the bacteria produce a signal that induces cocci to switch back to motile rods, allowing the population to spread. Genes encoding components of this phenotypic switching pathway are widespread among bacterial species, suggesting that this survival mechanism is not unique to P. dendritiformis.

Chronic exposure to arsenic in drinking water can lead to resistance to antimonial drugs in a mouse model of visceral leishmaniasis

PubMed Central

Perry, Meghan R.; Wyllie, Susan; Raab, Andrea; Feldmann, Joerg; Fairlamb, Alan H.

2013-01-01

The Indian subcontinent is the only region where arsenic contamination of drinking water coexists with widespread resistance to antimonial drugs that are used to treat the parasitic disease visceral leishmaniasis. We have previously proposed that selection for parasite resistance within visceral leishmaniasis patients who have been exposed to trivalent arsenic results in cross-resistance to the related metalloid antimony, present in the pentavalent state as a complex in drugs such as sodium stibogluconate (Pentostam) and meglumine antimonate (Glucantime). To test this hypothesis, Leishmania donovani was serially passaged in mice exposed to arsenic in drinking water at environmentally relevant levels (10 or 100 ppm). Arsenic accumulation in organs and other tissues was proportional to the level of exposure and similar to that previously reported in human liver biopsies. After five monthly passages in mice exposed to arsenic, isolated parasites were found to be completely refractory to 500 μg⋅mL−1 Pentostam compared with the control passage group (38.5 μg⋅mL−1) cultured in vitro in mouse peritoneal macrophages. Reassessment of resistant parasites following further passage for 4 mo in mice without arsenic exposure showed that resistance was stable. Treatment of infected mice with Pentostam confirmed that resistance observed in vitro also occurred in vivo. We conclude that arsenic contamination may have played a significant role in the development of Leishmania antimonial resistance in Bihar because inadequate treatment with antimonial drugs is not exclusive to India, whereas widespread antimonial resistance is. PMID:24167266

Chronic exposure to arsenic in drinking water can lead to resistance to antimonial drugs in a mouse model of visceral leishmaniasis.

PubMed

Perry, Meghan R; Wyllie, Susan; Raab, Andrea; Feldmann, Joerg; Fairlamb, Alan H

2013-12-03

The Indian subcontinent is the only region where arsenic contamination of drinking water coexists with widespread resistance to antimonial drugs that are used to treat the parasitic disease visceral leishmaniasis. We have previously proposed that selection for parasite resistance within visceral leishmaniasis patients who have been exposed to trivalent arsenic results in cross-resistance to the related metalloid antimony, present in the pentavalent state as a complex in drugs such as sodium stibogluconate (Pentostam) and meglumine antimonate (Glucantime). To test this hypothesis, Leishmania donovani was serially passaged in mice exposed to arsenic in drinking water at environmentally relevant levels (10 or 100 ppm). Arsenic accumulation in organs and other tissues was proportional to the level of exposure and similar to that previously reported in human liver biopsies. After five monthly passages in mice exposed to arsenic, isolated parasites were found to be completely refractory to 500 μg · mL(-1) Pentostam compared with the control passage group (38.5 μg · mL(-1)) cultured in vitro in mouse peritoneal macrophages. Reassessment of resistant parasites following further passage for 4 mo in mice without arsenic exposure showed that resistance was stable. Treatment of infected mice with Pentostam confirmed that resistance observed in vitro also occurred in vivo. We conclude that arsenic contamination may have played a significant role in the development of Leishmania antimonial resistance in Bihar because inadequate treatment with antimonial drugs is not exclusive to India, whereas widespread antimonial resistance is.

Ectopic activation of the rice NLR heteropair RGA4/RGA5 confers resistance to bacterial blight and bacterial leaf streak diseases.

PubMed

Hutin, Mathilde; Césari, Stella; Chalvon, Véronique; Michel, Corinne; Tran, Tuan Tu; Boch, Jens; Koebnik, Ralf; Szurek, Boris; Kroj, Thomas

2016-10-01

Bacterial blight (BB) and bacterial leaf streak (BLS) are important diseases in Oryza sativa caused by Xanthomonas oryzae pv. oryzae (Xoo) and Xanthomonas oryzae pv. oryzicola (Xoc), respectively. In both bacteria, transcription activator-like (TAL) effectors are major virulence determinants that act by transactivating host genes downstream of effector-binding elements (EBEs) bound in a sequence-specific manner. Resistance to Xoo is mostly related to the action of TAL effectors, either by polymorphisms that prevent the induction of susceptibility (S) genes or by executor (R) genes with EBEs embedded in their promoter, and that induce cell death and resistance. For Xoc, no resistance sources are known in rice. Here, we investigated whether the recognition of effectors by nucleotide binding and leucine-rich repeat domain immune receptors (NLRs), the most widespread resistance mechanism in plants, is also able to stop BB and BLS. In one instance, transgenic rice lines harboring the AVR1-CO39 effector gene from the rice blast fungus Magnaporthe oryzae, under the control of an inducible promoter, were challenged with transgenic Xoo and Xoc strains carrying a TAL effector designed to transactivate the inducible promoter. This induced AVR1-CO39 expression and triggered BB and BLS resistance when the corresponding Pi-CO39 resistance locus was present. In a second example, the transactivation of an auto-active NLR by Xoo-delivered designer TAL effectors resulted in BB resistance, demonstrating that NLR-triggered immune responses efficiently control Xoo. This forms the foundation for future BB and BLS disease control strategies, whereupon endogenous TAL effectors will target synthetic promoter regions of Avr or NLR executor genes. © 2016 The Authors The Plant Journal © 2016 John Wiley & Sons Ltd.

Moxidectin and the avermectins: Consanguinity but not identity

PubMed Central

Prichard, Roger; Ménez, Cécile; Lespine, Anne

2012-01-01

The avermectins and milbemycins contain a common macrocyclic lactone (ML) ring, but are fermentation products of different organisms. The principal structural difference is that avermectins have sugar groups at C13 of the macrocyclic ring, whereas the milbemycins are protonated at C13. Moxidectin (MOX), belonging to the milbemycin family, has other differences, including a methoxime at C23. The avermectins and MOX have broad-spectrum activity against nematodes and arthropods. They have similar but not identical, spectral ranges of activity and some avermectins and MOX have diverse formulations for great user flexibility. The longer half-life of MOX and its safety profile, allow MOX to be used in long-acting formulations. Some important differences between MOX and avermectins in interaction with various invertebrate ligand-gated ion channels are known and could be the basis of different efficacy and safety profiles. Modelling of IVM interaction with glutamate-gated ion channels suggest different interactions will occur with MOX. Similarly, profound differences between MOX and the avermectins are seen in interactions with ABC transporters in mammals and nematodes. These differences are important for pharmacokinetics, toxicity in animals with defective transporter expression, and probable mechanisms of resistance. Resistance to the avermectins has become widespread in parasites of some hosts and MOX resistance also exists and is increasing. There is some degree of cross-resistance between the avermectins and MOX, but avermectin resistance and MOX resistance are not identical. In many cases when resistance to avermectins is noticed, MOX produces a higher efficacy and quite often is fully effective at recommended dose rates. These similarities and differences should be appreciated for optimal decisions about parasite control, delaying, managing or reversing resistances, and also for appropriate anthelmintic combination. PMID:24533275

Evasion of Neutrophil Extracellular Traps by Respiratory Pathogens.

PubMed

Storisteanu, Daniel M L; Pocock, Joanna M; Cowburn, Andrew S; Juss, Jatinder K; Nadesalingam, Angalee; Nizet, Victor; Chilvers, Edwin R

2017-04-01

The release of neutrophil extracellular traps (NETs) is a major immune mechanism intended to capture pathogens. These histone- and protease-coated DNA structures are released by neutrophils in response to a variety of stimuli, including respiratory pathogens, and have been identified in the airways of patients with respiratory infection, cystic fibrosis, acute lung injury, primary graft dysfunction, and chronic obstructive pulmonary disease. NET production has been demonstrated in the lungs of mice infected with Staphylococcus aureus, Klebsiella pneumoniae, and Aspergillus fumigatus. Since the discovery of NETs over a decade ago, evidence that "NET evasion" might act as an immune protection strategy among respiratory pathogens, including group A Streptococcus, Bordetella pertussis, and Haemophilus influenzae, has been growing, with the majority of these studies being published in the past 2 years. Evasion strategies fall into three main categories: inhibition of NET release by down-regulating host inflammatory responses; degradation of NETs using pathogen-derived DNases; and resistance to the microbicidal components of NETs, which involves a variety of mechanisms, including encapsulation. Hence, the evasion of NETs appears to be a widespread strategy to allow pathogen proliferation and dissemination, and is currently a topic of intense research interest. This article outlines the evidence supporting the three main strategies of NET evasion-inhibition, degradation, and resistance-with particular reference to common respiratory pathogens.

Azithromycin Resistance and Decreased Ceftriaxone Susceptibility in Neisseria gonorrhoeae, Hawaii, USA

PubMed Central

Papp, John R.; Abrams, A. Jeanine; Nash, Evelyn; Katz, Alan R.; Kirkcaldy, Robert D.; O’Connor, Norman P.; O’Brien, Pamela S.; Harauchi, Derek H.; Maningas, Eloisa V.; Soge, Olusegun O.; Kersh, Ellen N.; Komeya, Alan; Tomas, Juval E.; Wasserman, Glenn M.; Kunimoto, Gail Y.; Trees, David L.

2017-01-01

During 2016, eight Neisseria gonorrhoeae isolates from 7 patients in Hawaii were resistant to azithromycin; 5 had decreased in vitro susceptibility to ceftriaxone. Genomic analysis demonstrated a distinct phylogenetic clade when compared with local contemporary strains. Continued evolution and widespread transmission of these strains might challenge the effectiveness of current therapeutic options. PMID:28418303

Molecular Characterization of two Potato Virus S Isolates from Late Blight Resistant Genotypes of Potato (Solanum tuberosum)

USDA-ARS?s Scientific Manuscript database

Potato virus S (PVS) has a widespread distribution in the U.S. However, only two complete nucleotide sequences have been published. A recent survey of potato fields in the state of Washington confirms that PVS is widely prevalent. Late blight resistant (LBR) potato cultivars and genotypes were sho...

An economic evaluation of fusiform rust protection research

Treesearch

F.W. Cubbage; John M. Pye; T.P. Holmes; J.E. Wagner

2000-01-01

Fusiform rust is a widespread and damaging disease of loblolly pine (P. taeda) and slash pine (P. elliottii) in the South. Research has identified families of these pines with improved genetic resistance to the disease, allowing production and planting of resistant seedlings in areas at risk. This study compared the cost of fusiform rust research to the simulated...

High residue cover crops alone or with strategic tillage to manage glyphosate-resistant palmer amaranth (amaranthus palmeri) in Southeastern cotton (gossypium hirsutum)

USDA-ARS?s Scientific Manuscript database

Glyphosate-resistant (GR) Palmer amaranth (Amaranthus palmeri S. Wats) is redefining row crop weed management in the Southeast due to its widespread distribution, high competitive ability, copious seed production, and resilience to standard weed management programs. Herbicides alone are failing to p...

Collective Landmarks for Deep Time: A New Tool for Evolution Education

ERIC Educational Resources Information Center

Delgado, Cesar

2014-01-01

Evolution is a fundamental, organising concept in biology, yet there is widespread resistance to evolution among US students and there are rising creationist challenges in Europe. Resistance to evolution is linked to lack of understanding of the age of the Earth. An understanding of deep time is thus essential for effective biology education.…

Chemistry of coast live oak response to Phytophthora ramorum infection

Treesearch

Frances S. Ockels; Alieta Eyles; Brice A. McPherson; David L. Wood; Pierluigi Bonello

2008-01-01

Since the mid 1990s, Phytophthora ramorum has been responsible for the widespread mortality of tanoaks, as well as several oak species throughout California and Oregon forests. However, not all trees die, even in areas with high disease pressure, suggesting that some trees may be resistant to the pathogen. The apparent resistance to P....

Potato common scab: a review of the causal pathogens, management practices, varietal resistance screening methods, and host resistance

USDA-ARS?s Scientific Manuscript database

Potato common scab is a widespread disease in which scab-like lesions develop on tubers. The disease is caused by pathogenic Streptomyces species, which synthesize the phytotoxin thaxtomin. The txtAB operon, responsible for thaxtomin production, can be used as a marker to identify strains of the bac...

Carbapenem Resistance: A Review

PubMed Central

Codjoe, Francis S.; Donkor, Eric S.

2017-01-01

Carbapenem resistance is a major and an on-going public health problem globally. It occurs mainly among Gram-negative pathogens such as Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter baumannii, and may be intrinsic or mediated by transferable carbapenemase-encoding genes. This type of resistance genes are already widespread in certain parts of the world, particularly Europe, Asia and South America, while the situation in other places such as sub-Saharan Africa is not well documented. In this paper, we provide an in-depth review of carbapenem resistance providing up-to-date information on the subject. PMID:29267233

Association between Three Mutations, F1565C, V1023G and S996P, in the Voltage-Sensitive Sodium Channel Gene and Knockdown Resistance in Aedes aegypti from Yogyakarta, Indonesia

PubMed Central

Rochmijati Wuliandari, Juli; Lee, Siu Fai; White, Vanessa Linley; Tantowijoyo, Warsito; Hoffmann, Ary Anthony; Endersby-Harshman, Nancy Margaret

2015-01-01

Mutations in the voltage-sensitive sodium channel gene (Vssc) have been identified in Aedes aegypti and some have been associated with pyrethroid insecticide resistance. Whether these mutations cause resistance, alone or in combination with other alleles, remains unclear, but must be understood if mutations are to become markers for resistance monitoring. We describe High Resolution Melt (HRM) genotyping assays for assessing mutations found in Ae. aegypti in Indonesia (F1565C, V1023G, S996P) and use them to test for associations with pyrethroid resistance in mosquitoes from Yogyakarta, a city where insecticide use is widespread. Such knowledge is important because Yogyakarta is a target area for releases of Wolbachia-infected mosquitoes with virus-blocking traits for dengue suppression. We identify three alleles across Yogyakarta putatively linked to resistance in previous research. By comparing resistant and susceptible mosquitoes from bioassays, we show that the 1023G allele is associated with resistance to type I and type II pyrethroids. In contrast, F1565C homozygotes were rare and there was only a weak association between individuals heterozygous for the mutation and resistance to a type I pyrethroid. As the heterozygote is expected to be incompletely recessive, it is likely that this association was due to a different resistance mechanism being present. A resistance advantage conferred to V1023G homozygotes through addition of the S996P allele in the homozygous form was suggested for the Type II pyrethroid, deltamethrin. Screening of V1023G and S996P should assist resistance monitoring in Ae. aegypti from Yogyakarta, and these mutations should be maintained in Wolbachia strains destined for release in this city to ensure that these virus-blocking strains of mosquitoes are not disadvantaged, relative to resident populations. PMID:26463408

Association between Three Mutations, F1565C, V1023G and S996P, in the Voltage-Sensitive Sodium Channel Gene and Knockdown Resistance in Aedes aegypti from Yogyakarta, Indonesia.

PubMed

Wuliandari, Juli Rochmijati; Lee, Siu Fai; White, Vanessa Linley; Tantowijoyo, Warsito; Hoffmann, Ary Anthony; Endersby-Harshman, Nancy Margaret

2015-07-23

Mutations in the voltage-sensitive sodium channel gene (Vssc) have been identified in Aedes aegypti and some have been associated with pyrethroid insecticide resistance. Whether these mutations cause resistance, alone or in combination with other alleles, remains unclear, but must be understood if mutations are to become markers for resistance monitoring. We describe High Resolution Melt (HRM) genotyping assays for assessing mutations found in Ae. aegypti in Indonesia (F1565C, V1023G, S996P) and use them to test for associations with pyrethroid resistance in mosquitoes from Yogyakarta, a city where insecticide use is widespread. Such knowledge is important because Yogyakarta is a target area for releases of Wolbachia-infected mosquitoes with virus-blocking traits for dengue suppression. We identify three alleles across Yogyakarta putatively linked to resistance in previous research. By comparing resistant and susceptible mosquitoes from bioassays, we show that the 1023G allele is associated with resistance to type I and type II pyrethroids. In contrast, F1565C homozygotes were rare and there was only a weak association between individuals heterozygous for the mutation and resistance to a type I pyrethroid. As the heterozygote is expected to be incompletely recessive, it is likely that this association was due to a different resistance mechanism being present. A resistance advantage conferred to V1023G homozygotes through addition of the S996P allele in the homozygous form was suggested for the Type II pyrethroid, deltamethrin. Screening of V1023G and S996P should assist resistance monitoring in Ae. aegypti from Yogyakarta, and these mutations should be maintained in Wolbachia strains destined for release in this city to ensure that these virus-blocking strains of mosquitoes are not disadvantaged, relative to resident populations.

Local Changes in Rates of Group A Streptococcus Disease and Antibiotic Resistance are Associated with Geographically Widespread Strain Turnover Events

DTIC Science & Technology

2010-08-01

253 14. ABSTRACT (maximum 200 words) Group A Streptococcus pyogenes is a primary agent of respiratory disease in military environments...COVERED (from - to) January 2007–December 2008 4. TITLE AND SUBTITLE Local Changes in Rates of Group A Streptococcus Disease and Antibiotic Resistance...antibiotic resistance of 802 Streptococcus isolates from 10 US military facilities collected from 2002 through 2007. Most of these sites provided

Current Status and Challenges in Identifying Disease Resistance Genes in Brassica napus

PubMed Central

Neik, Ting Xiang; Barbetti, Martin J.; Batley, Jacqueline

2017-01-01

Brassica napus is an economically important crop across different continents including temperate and subtropical regions in Europe, Canada, South Asia, China and Australia. Its widespread cultivation also brings setbacks as it plays host to fungal, oomycete and chytrid pathogens that can lead to serious yield loss. For sustainable crop production, identification of resistance (R) genes in B. napus has become of critical importance. In this review, we discuss four key pathogens affecting Brassica crops: Clubroot (Plasmodiophora brassicae), Blackleg (Leptosphaeria maculans and L. biglobosa), Sclerotinia Stem Rot (Sclerotinia sclerotiorum), and Downy Mildew (Hyaloperonospora parasitica). We first review current studies covering prevalence of these pathogens on Brassica crops and highlight the R genes and QTL that have been identified from Brassica species against these pathogens. Insights into the relationships between the pathogen and its Brassica host, the unique host resistance mechanisms and how these affect resistance outcomes is also presented. We discuss challenges in identification and deployment of R genes in B. napus in relation to highly specific genetic interactions between host subpopulations and pathogen pathotypes and emphasize the need for common or shared techniques and research materials or tighter collaboration between researchers to reconcile the inconsistencies in the research outcomes. Using current genomics tools, we provide examples of how characterization and cloning of R genes in B. napus can be carried out more effectively. Lastly, we put forward strategies to breed resistant cultivars through introgressions supported by genomic approaches and suggest prospects that can be implemented in the future for a better, pathogen-resistant B. napus. PMID:29163558

A half-truth is a whole lie: on the necessity of investigating sex influences on the brain.

PubMed

Cahill, Larry

2012-06-01

Sex influences are proving to be extremely widespread on brain function, including the human brain. Ample evidence now proves that the sex of subjects can influence, ever reverse, findings, hence conclusions, at all levels of brain science, down to the molecular level, often in completely unanticipated ways. Thus the still-prominent assumption that sex influences may be safely ignored by neurobiologists is invalid and must be abandoned. The failure to properly consider the issue fills the literature with conclusions tenuous at best, false at worst. The continuing, widespread resistance to investigating sex influences among brain scientists, a resistance largely rooted in deeply entrenched biases against the topic, is becoming increasingly scientifically indefensible and strongly retards progress in our field.

Maternal obesity and diabetes induces latent metabolic defects and widespread epigenetic changes in isogenic mice

PubMed Central

Li, Cheryl C.Y.; Young, Paul E.; Maloney, Christopher A.; Eaton, Sally A.; Cowley, Mark J.; Buckland, Michael E; Preiss, Thomas; Henstridge, Darren C.; Cooney, Gregory J.; Febbraio, Mark A.; Martin, David I.K.; Cropley, Jennifer E.; Suter, Catherine M.

2013-01-01

Intrauterine nutrition can program metabolism, creating stable changes in physiology that may have significant health consequences. The mechanism underlying these changes is widely assumed to involve epigenetic changes to the expression of metabolic genes, but evidence supporting this idea is limited. Here we have performed the first study of the epigenomic consequences of exposure to maternal obesity and diabetes. We used a mouse model of natural-onset obesity that allows comparison of genetically identical mice whose mothers were either obese and diabetic or lean with a normal metabolism. We find that the offspring of obese mothers have a latent metabolic phenotype that is unmasked by exposure to a Western-style diet, resulting in glucose intolerance, insulin resistance and hepatic steatosis. The offspring show changes in hepatic gene expression and widespread but subtle alterations in cytosine methylation. Contrary to expectation, these molecular changes do not point to metabolic pathways but instead reside in broadly developmental ontologies. We propose that, rather than being adaptive, these changes may simply produce an inappropriate response to suboptimal environments; maladaptive phenotypes may be avoidable if postnatal nutrition is carefully controlled. PMID:23764993

Microstructure, Fatigue Behavior, and Failure Mechanisms of Direct Laser-Deposited Inconel 718

NASA Astrophysics Data System (ADS)

Johnson, Alex S.; Shao, Shuai; Shamsaei, Nima; Thompson, Scott M.; Bian, Linkan

2017-03-01

Inconel 718 is considered to be a superalloy with a series of superior properties such as high strength, creep resistance, and corrosion resistance at room and elevated temperatures. Additive manufacturing (AM) is particularly appealing to Inconel 718 because of its near-net-shape production capability for circumventing the poor machinability of this superalloy. Nevertheless, AM parts are prone to porosity, which is detrimental to their fatigue resistance. Thus, further understanding of their fatigue behavior is required before their widespread use in load-bearing applications. In this work, the microstructure and fatigue properties of AM Inconel 718, produced in a Laser Engineered Net Shaping (LENS™) system and heat treated with a standard heat treatment schedule, are evaluated at room temperature. Fully reversed strain controlled fatigue tests were performed on cylindrical specimens with straight gage sections at strain amplitudes ranging from 0.001 mm/mm to 0.01 mm/mm. The fracture surfaces of fatigue specimens were inspected with a scanning electron microscope. The results indicate that the employed heat treatment allowed the large, elongated grains and dendritic structure of the as-built material to break down into smaller, equiaxed grains, with some dendritic structures remaining between layers. The AM specimens were found to possess lower fatigue resistance than wrought Inconel 718, and this is primarily attributed to the presence of brittle metal-carbide/oxide inclusions or pores near their surface.

DNA damage responsive miR-33b-3p promoted lung cancer cells survival and cisplatin resistance by targeting p21WAF1/CIP1.

PubMed

Xu, Shun; Huang, Haijiao; Chen, Yu-Ning; Deng, Yun-Ting; Zhang, Bing; Xiong, Xing-Dong; Yuan, Yuan; Zhu, Yanmei; Huang, Haiyong; Xie, Luoyijun; Liu, Xinguang

2016-11-01

Cisplatin is the most potent and widespread used chemotherapy drug for lung cancer treatment. However, the development of resistance to cisplatin is a major obstacle in clinical therapy. The principal mechanism of cisplatin is the induction of DNA damage, thus the capability of DNA damage response (DDR) is a key factor that influences the cisplatin sensitivity of cancer cells. Recent advances have demonstrated that miRNAs (microRNAs) exerted critical roles in DNA damage response; nonetheless, the association between DNA damage responsive miRNAs and cisplatin resistance and its underlying molecular mechanism still require further investigation. The present study has attempted to identify differentially expressed miRNAs in cisplatin induced DNA damage response in lung cancer cells, and probe into the effects of the misexpressed miRNAs on cisplatin sensitivity. Deep sequencing showed that miR-33b-3p was dramatically down-regulated in cisplatin-induced DNA damage response in A549 cells; and ectopic expression of miR-33b-3p endowed the lung cancer cells with enhanced survival and decreased γH2A.X expression level under cisplatin treatment. Consistently, silencing of miR-33b-3p in the cisplatin-resistant A549/DDP cells evidently sensitized the cells to cisplatin. Furthermore, we identified CDKN1A (p21) as a functional target of miR-33b-3p, a critical regulator of G1/S checkpoint, which potentially mediated the protection effects of miR-33b-3p against cisplatin. In aggregate, our results suggested that miR-33b-3p modulated the cisplatin sensitivity of cancer cells might probably through impairing the DNA damage response. And the knowledge of the drug resistance conferred by miR-33b-3p has great clinical implications for improving the efficacy of chemotherapies for treating lung cancers.

Climate-driven reduction in soil loss due to the dynamic role of vegetation

NASA Astrophysics Data System (ADS)

Constantine, J. A.; Ciampalini, R.; Walker-Springett, K.; Hales, T. C.; Ormerod, S.; Gabet, E. J.; Hall, I. R.

2016-12-01

Simulations of 21st century climate change predict increases in seasonal precipitation that may lead to widespread soil loss and reduced soil carbon stores by increasing the likelihood of surface runoff. Vegetation may counteract this increase through its dynamic response to climate change, possibly mitigating any impact on soil erosion. Here, we document for the first time the potential for vegetation to prevent widespread soil loss by surface-runoff mechanisms (i.e., rill and inter-rill erosion) by implementing a process-based soil erosion model across catchments of Great Britain with varying land-cover, topographic, and soil characteristics. Our model results reveal that, even under a significantly wetter climate, warmer air temperatures can limit soil erosion across areas with permanent vegetation cover because of its role in enhancing primary productivity, which improves leaf interception, soil infiltration-capacity, and the erosive resistance of soil. Consequently, any increase in air temperature associated with climate change will increase the threshold change in rainfall required to accelerate soil loss, and rates of soil erosion could therefore decline by up to 50% from 2070-2099 compared to baseline values under the IPCC-defined medium-emissions scenario SRES A1B. We conclude that enhanced primary productivity due to climate change can introduce a negative-feedback mechanism that limits soil loss by surface runoff as vegetation-induced impacts on soil hydrology and erodibility offset precipitation increases, highlighting the need to expand areas of permanent vegetation cover to reduce the potential for climate-driven soil loss.

Distribution Patterns of Three Sodium Channel Mutations Associated with Pyrethroid Resistance in Rhipicephalus (Boophilus) Microplus Populations from North and South America, South Africa and Australia

USDA-ARS?s Scientific Manuscript database

Resistance to synthetic pyrethroids (SP) in the cattle tick Rhipicephalus (Boophilus) microplus is widespread throughout its distribution area. Three single nucleotide substitutions identified in the Domains II and III of the sodium channel gene of R. (B.) microplus are known to be associated with t...

Fungal biosynthesis of gold nanoparticles: mechanism and scale up.

PubMed

Kitching, Michael; Ramani, Meghana; Marsili, Enrico

2015-11-01

Gold nanoparticles (AuNPs) are a widespread research tool because of their oxidation resistance, biocompatibility and stability. Chemical methods for AuNP synthesis often produce toxic residues that raise environmental concern. On the other hand, the biological synthesis of AuNPs in viable microorganisms and their cell-free extracts is an environmentally friendly and low-cost process. In general, fungi tolerate higher metal concentrations than bacteria and secrete abundant extracellular redox proteins to reduce soluble metal ions to their insoluble form and eventually to nanocrystals. Fungi harbour untapped biological diversity and may provide novel metal reductases for metal detoxification and bioreduction. A thorough understanding of the biosynthetic mechanism of AuNPs in fungi is needed to reduce the time of biosynthesis and to scale up the AuNP production process. In this review, we describe the known mechanisms for AuNP biosynthesis in viable fungi and fungal protein extracts and discuss the most suitable bioreactors for industrial AuNP biosynthesis. © 2014 The Authors. Microbial Biotechnology published by John Wiley & Sons Ltd and Society for Applied Microbiology.

Epigenetics and type II diabetes mellitus: underlying mechanisms of prenatal predisposition

PubMed Central

Sterns, J. David; Smith, Colin B.; Steele, John R.; Stevenson, Kimberly L.; Gallicano, G. Ian

2014-01-01

Type II diabetes mellitus (T2DM) is a widespread metabolic disorder characterized by insulin resistance precipitating abnormally high blood glucose levels. While the onset of T2DM is known to be the consequence of a multifactorial interplay with a strong genetic component, emerging research has demonstrated the additional role of a variety of epigenetic mechanisms in the development of this disorder. Heritable epigenetic modifications, such as DNA methylation and histone modifications, play a vital role in many important cellular processes, including pancreatic cellular differentiation and maintenance of normal β-cell function. Recent studies have found possible epigenetic mechanisms to explain observed risk factors, such as altered atherogenic lipid profiles, elevated body mass index (BMI), and impaired glucose tolerance (IGT), for later development of T2DM in children born to mothers experiencing both famine and hyperglycemic conditions. It is suggested that these epigenetic influences happen early during gestation and are less susceptible to the effects of postnatal environmental modification as was previously thought, highlighting the importance of early preventative measures in minimizing the global burden of T2DM. PMID:25364722

Thermo-mechanical modeling of laser treatment on titanium cold-spray coatings

NASA Astrophysics Data System (ADS)

Paradiso, V.; Rubino, F.; Tucci, F.; Astarita, A.; Carlone, P.

2018-05-01

Titanium coatings are very attractive to several industrial fields, especially aeronautics, due to the enhanced corrosion resistance and wear properties as well as improved compatibility with carbon fiber reinforced plastic (CFRP) materials. Cold sprayed titanium coatings, among the others deposition processes, are finding a widespread use in high performance applications, whereas post-deposition treatments are often used to modify the microstructure of the cold-sprayed layer. Laser treatments allow one to noticeably increase the superficial properties of titanium coatings when the process parameters are properly set. On the other hand, the high heat input required to melt titanium particles may result in excessive temperature increase even in the substrate. This paper introduces a thermo-mechanical model to simulate the laser treatment effects on a cold sprayed titanium coating as well as the aluminium substrate. The proposed thermo-mechanical finite element model considers the transient temperature field due to the laser source and applied boundary conditions using them as input loads for the subsequent stress-strain analysis. Numerical outcomes highlighted the relevance of thermal gradients and thermally induced stresses and strains in promoting the damage of the coating.

Overview of Poisoning

MedlinePlus

... Soap and soap products (including hand soap) Spermaceti Starch and sizing Stearic acid Sunscreens Talc (except when ... In the United States, widespread use of child-resistant containers with safety caps has greatly reduced the ...

Dinitroaniline herbicide resistance and the microtubule cytoskeleton.

PubMed

Anthony; Hussey

1999-03-01

Dinitroaniline herbicides have been used for pre-emergence weed control for the past 25 years in cotton, soybean, wheat and oilseed crops. Considering their long persistence and extensive use, resistance to dinitroanilines is fairly rare. However, the most widespread dinitroaniline-resistant weeds, the highly resistant (R) and the intermediate (I) biotypes of the invasive goosegrass Eleusine indica, are now infesting more than 1000 cotton fields in the southern states of the USA. The molecular basis of this resistance has been identified, and found to be a point mutation in a major microtubule cytoskeletal protein, alpha-tubulin. These studies have served both to explain the establishment of resistance and to reveal fundamental properties of tubulin gene expression and microtubule structure.

The development of genetic resistance to myxomatosis in wild rabbits in Britain.

PubMed

Ross, J; Sanders, M F

1984-06-01

The presence of genetic resistance to myxomatosis in a sample of wild rabbits from one area in England was reported in 1977. Rabbits from three other areas in Great Britain have been tested subsequently, and all cases showed similar resistance to a moderately virulent strain of myxoma virus. Rabbits from one area also showed a significant degree of resistance to a fully virulent strain of virus. It is concluded that genetic resistance to myxomatosis is widespread in wild rabbit populations in Britain. The implications of the results are discussed in relation to the co-evolution of the disease and its host.

The development of genetic resistance to myxomatosis in wild rabbits in Britain.

PubMed Central

Ross, J.; Sanders, M. F.

1984-01-01

The presence of genetic resistance to myxomatosis in a sample of wild rabbits from one area in England was reported in 1977. Rabbits from three other areas in Great Britain have been tested subsequently, and all cases showed similar resistance to a moderately virulent strain of myxoma virus. Rabbits from one area also showed a significant degree of resistance to a fully virulent strain of virus. It is concluded that genetic resistance to myxomatosis is widespread in wild rabbit populations in Britain. The implications of the results are discussed in relation to the co-evolution of the disease and its host. PMID:6736637

Insecticidal and sterilizing effect of Olyset Duo®, a permethrin and pyriproxyfen mixture net against pyrethroid-susceptible and -resistant strains of Anopheles gambiae s.s.: a release-recapture assay in experimental huts.

PubMed

Djènontin, Armel; Ahoua Alou, Ludovic P; Koffi, Alphonsine; Zogo, Barnabas; Duarte, Elves; N'Guessan, Raphael; Moiroux, Nicolas; Pennetier, Cédric

2015-01-01

In the context of the widespread distribution of pyrethroid resistance among malaria vectors, we did a release-recapture trial in experimental huts to investigate the insecticidal and sterilizing effects of a novel long-lasting net (LN), Olyset® Duo, incorporating a mixture of permethrin (PER) and the insect growth regulator (IGR), pyri-proxyfen (PPF). An LN containing PPF alone and a classic Olyset® Net were tested in parallel as positive controls. The effect of progressive number of holes (6, 30, or 150) that may accrue in nets over time was simulated. We used two laboratory Anopheles gambiae s.s. strains: the susceptible Kisumu strain and the pyrethroid-resistant VK-Per strain having solely kdr as resistance mechanism. The effect of these nets on the reproductive success of blood-fed females that survived the different LNs conditions was recorded. Regardless of the mosquito strain, the LNs containing PPF alone with as many as 30 holes drastically reduced the number of eggs laid by females succeeding in feeding, i.e. fecundity by 98% and egg hatching rate (fertility) by 93% relative to untreated control net. Very few of the resistant females blood fed and survived under the Olyset® Duo with similar number of holes (up to 30) but of these few, the inhibition of reproductive success was 100%. There was no evidence that the Olyset® Duo LN with 150 holes impacted fecundity or fertility of the resistant colony. The efficacy of Olyset® Duo is encouraging and clearly illustrates that this new net might be a promising tool for malaria transmission control and resistance management. © A. Djènontin et al., published by EDP Sciences, 2015.

Clayey Landslide Initiation and Acceleration Strongly Modulated by Soil Swelling

NASA Astrophysics Data System (ADS)

Schulz, William H.; Smith, Joel B.; Wang, Gonghui; Jiang, Yao; Roering, Joshua J.

2018-02-01

Largely unknown mechanisms restrain motion of clay-rich, slow-moving landslides that are widespread worldwide and rarely accelerate catastrophically. We studied a clayey, slow-moving landslide typical of thousands in Northern California, USA, to decipher hydrologic-mechanical interactions that modulate landslide dynamics. Similar to some other studies, observed pore-water pressures correlated poorly with landslide reactivation and speed. In situ and laboratory measurements strongly suggested that variable pressure along the landslide's lateral shear boundaries resulting from seasonal soil expansion and contraction modulated its reactivation and speed. Slope-stability modeling suggested that the landslide's observed behavior could be predicted by including transient swell pressure as a resistance term, whereas modeling considering only transient hydrologic conditions predicted movement five to six months prior to when it was observed. All clayey soils swell to some degree; hence, our findings suggest that swell pressure likely modulates motion of many landslides and should be considered to improve forecasts of clayey landslide initiation and mobility.

Clayey landslide initiation and acceleration strongly modulated by soil swelling

USGS Publications Warehouse

Schulz, William; Smith, Joel B.; Wang, Gonghui; Jiang, Yao; Roering, Joshua J.

2018-01-01

Largely unknown mechanisms restrain motion of clay-rich, slow-moving landslides that are widespread worldwide and rarely accelerate catastrophically. We studied a clayey, slow-moving landslide typical of thousands in northern California, USA, to decipher hydrologic-mechanical interactions that modulate landslide dynamics. Similar to some other studies, observed pore-water pressures correlated poorly with landslide reactivation and speed. In situ and laboratory measurements strongly suggested that variable pressure along the landslide's lateral shear boundaries resulting from seasonal soil expansion and contraction modulated its reactivation and speed. Slope-stability modeling suggested that the landslide's observed behavior could be predicted by including transient swell pressure as a resistance term, whereas modeling considering only transient hydrologic conditions predicted movement 5–6 months prior to when it was observed. All clayey soils swell to some degree; hence, our findings suggest that swell pressure likely modulates motion of many landslides and should be considered to improve forecasts of clayey landslide initiation and mobility.

Interspecific comparison of constitutive ash phloem phenolic chemistry reveals compounds unique to Manchurian ash, a species resistant to emerald ash borer

Treesearch

Justin G.A. Whitehill; Stephen O. Opiyo; Jennifer L. Koch; Daniel A. Herms; Donald F. Cipollini; Pierluigi Bonello

2012-01-01

The emerald ash borer (Agrilus planipennis, EAB) is an invasive wood-borer indigenous to Asia and is responsible for widespread ash (Fraxinus spp.) mortality in the U.S. and Canada. Resistance and susceptibility to EAB varies among Fraxinus spp., which is a result of their co-evolutionary history with the pest....

Endophytic bacteria and their potential to enhance heavy metal phytoextraction.

PubMed

Rajkumar, Mani; Ae, Noriharu; Freitas, Helena

2009-09-01

Pollution of soils with heavy metals is becoming one of the most severe environmental and human health hazards. Due to its widespread contamination finding innovative ways to clean metal pollutant has become a priority in the remediation field. Phytoremediation, the use of plants for the restoration of environments contaminated with pollutants is a relatively new technology that is more benign than current engineering solutions to treat contaminated sites. Recently, the benefits of combining endophytic bacteria with plants for increased remediation of pollutants have been successfully tried for toxic metal removal from contaminated soils. Endophytic bacteria reside within plant hosts without causing disease symptoms. Further, the metal resistant endophytes are reported to be present in various hyperaccumulator plants growing on heavy metal contaminated soils and play an important role in successful survival and growth of plants. Moreover, the metal resistant endophytes are reported to promote plant growth by various mechanisms such as nitrogen fixation, solubilization of minerals, production of phytohormones, siderophores, utilization of 1-aminocyclopropane-1-carboxylic acid as a sole N source and transformation of nutrient elements. In this review we highlight the diversity and plant growth promoting features of metal resistant endophytic bacteria and discuss their potential in phytoextraction of heavy metals from contaminated soils.

Molecular Cloning and Characterization of a P-Glycoprotein from the Diamondback Moth, Plutella xylostella (Lepidoptera: Plutellidae)

PubMed Central

Tian, Lixia; Yang, Jiaqiang; Hou, Wenjie; Xu, Baoyun; Xie, Wen; Wang, Shaoli; Zhang, Youjun; Zhou, Xuguo; Wu, Qingjun

2013-01-01

Macrocyclic lactones such as abamectin and ivermectin constitute an important class of broad-spectrum insecticides. Widespread resistance to synthetic insecticides, including abamectin and ivermectin, poses a serious threat to the management of diamondback moth, Plutella xylostella (L.) (Lepidoptera: Plutellidae), a major pest of cruciferous plants worldwide. P-glycoprotein (Pgp), a member of the ABC transporter superfamily, plays a crucial role in the removal of amphiphilic xenobiotics, suggesting a mechanism for drug resistance in target organisms. In this study, PxPgp1, a putative Pgp gene from P. xylostella, was cloned and characterized. The open reading frame (ORF) of PxPgp1 consists of 3774 nucleotides, which encodes a 1257-amino acid peptide. The deduced PxPgp1 protein possesses structural characteristics of a typical Pgp, and clusters within the insect ABCB1. PxPgp1 was expressed throughout all developmental stages, and showed the highest expression level in adult males. PxPgp1 was highly expressed in midgut, malpighian tubules and testes. Elevated expression of PxPgp1 was observed in P. xylostella strains after they were exposed to the abamectin treatment. In addition, the constitutive expressions of PxPgp1 were significantly higher in laboratory-selected and field-collected resistant strains in comparison to their susceptible counterpart. PMID:24264038

Crystal structure of the avilamycin resistance-conferring methyltransferase AviRa from Streptomyces viridochromogenes.

PubMed

Mosbacher, Tanja G; Bechthold, Andreas; Schulz, Georg E

2003-05-23

The emergence of antibiotic-resistant bacterial strains is a widespread problem in contemporary medical practice and drug design. It is therefore important to elucidate the underlying mechanism in each case. The methyltransferase AviRa from Streptomyces viridochromogenes mediates resistance to the antibiotic avilamycin, which is closely related to evernimicin, an oligosaccharide antibiotic that has been used in medical studies. The structure of AviRa was determined by X-ray diffraction at 1.5A resolution. Phases were obtained from one selenomethionine residue introduced by site-directed mutagenesis. The chain-fold is similar to that of most methyltransferases, although AviRa contains two additional helices as a specific feature. A putative-binding site for the cofactor S-adenosyl-L-methionine was derived from homologous structures. It agrees with the conserved pattern of interacting amino acid residues. AviRa methylates a specific guanine base within the peptidyltransferase loop of the 23S ribosomal RNA. Guided by the target, the enzyme was docked to the cognate ribosomal surface, where it fit well into a deep cleft without contacting any ribosomal protein. The two additional alpha-helices of AviRa filled a depression in the surface. Since the transferred methyl group of the cofactor is in a pocket beneath the enzyme surface, the targeted guanine base has to flip out for methylation.

Silver nanoparticles as potential antibacterial agents.

PubMed

Franci, Gianluigi; Falanga, Annarita; Galdiero, Stefania; Palomba, Luciana; Rai, Mahendra; Morelli, Giancarlo; Galdiero, Massimiliano

2015-05-18

Multi-drug resistance is a growing problem in the treatment of infectious diseases and the widespread use of broad-spectrum antibiotics has produced antibiotic resistance for many human bacterial pathogens. Advances in nanotechnology have opened new horizons in nanomedicine, allowing the synthesis of nanoparticles that can be assembled into complex architectures. Novel studies and technologies are devoted to understanding the mechanisms of disease for the design of new drugs, but unfortunately infectious diseases continue to be a major health burden worldwide. Since ancient times, silver was known for its anti-bacterial effects and for centuries it has been used for prevention and control of disparate infections. Currently nanotechnology and nanomaterials are fully integrated in common applications and objects that we use every day. In addition, the silver nanoparticles are attracting much interest because of their potent antibacterial activity. Many studies have also shown an important activity of silver nanoparticles against bacterial biofilms. This review aims to summarize the emerging efforts to address current challenges and solutions in the treatment of infectious diseases, particularly the use of nanosilver antimicrobials.

Draft genome sequence of field isolate Brucella melitensis strain 2007BM/1 from India.

PubMed

Singh, D K; Kumar, Bablu; Shrinet, Garima; Singh, R P; Das, Aparajita; Mantur, B G; Abhishek; Pandey, Aruna; Mondal, Piyali; Sajjanar, B K; Doimari, Soni; Singh, Vijayata; Kumari, Reena; Tiwari, A K; Gandham, Ravi Kumar

2018-04-21

Brucellosis is among one of the most widespread important global zoonotic diseases that is endemic in many parts of India. Brucella melitensis is supposed to be the most pathogenic species for humans. Here we report the draft genome sequence of B. melitensis strain 2007BM/1 isolated from a human in India. Genomic DNA was extracted from Brucella culture and was sequenced using an Illumina MiSeq platform. The generated reads were assembled using three de novo assemblers and the draft genome was annotated. This monoisolate, with a genome length of 3268756bp, was found to be resistant to azithromycin and trimethoprim/sulfamethoxazole but susceptible to tetracycline, ofloxacin, rifampicin, ciprofloxacin and doxycycline. The presence of virulence genes in the strain was identified. The results obtained will help in understanding drug resistance mechanisms and virulence factors in highly zoonotic B. melitensis and suggest the need for judicious use of antibiotics in livestock health and management practices. Copyright © 2018 International Society for Chemotherapy of Infection and Cancer. Published by Elsevier Ltd. All rights reserved.

Adolescent Obesity and Insulin Resistance: Roles of Ectopic Fat Accumulation and Adipose Inflammation.

PubMed

Caprio, Sonia; Perry, Rachel; Kursawe, Romy

2017-05-01

As a consequence of the global rise in the prevalence of adolescent obesity, an unprecedented phenomenon of type 2 diabetes has emerged in pediatrics. At the heart of the development of type 2 diabetes lies a key metabolic derangement: insulin resistance (IR). Despite the widespread occurrence of IR affecting an unmeasurable number of youths worldwide, its pathogenesis remains elusive. IR in obese youth is a complex phenomenon that defies explanation by a single pathway. In this review we first describe recent data on the prevalence, severity, and racial/ethnic differences in pediatric obesity. We follow by elucidating the initiating events associated with the onset of IR, and describe a distinct "endophenotype" in obese adolescents characterized by a thin superficial layer of abdominal subcutaneous adipose tissue, increased visceral adipose tissue, marked IR, dyslipidemia, and fatty liver. Further, we provide evidence for the cellular and molecular mechanisms associated with this peculiar endophenotype and its relations to IR in the obese adolescent. Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.

[Bacterial meningitis caused by beta-lactamase-negative, ampicillin-resistant nontypeable Haemophilus influenzae in a 1-year-old girl: a case report].

PubMed

Abe, Katsuaki; Hoshino, Tadashi; Imuta, Naoko; Nishi, Junichiro; Ishiwada, Naruhiko

2014-05-01

We present herein the case report of bacterial meningitis caused by nontypeable Haemophilus influenzae (NTHi) in a 1-year-7-month-old girl with no medically significant history. NTHi from cerebrospinal fluid (CSF) was the beta-lactamase non-producing ampicillin resistant strain (BLNAR). Some beta-lactams were administrated, but fever was prolonged. Finally, rifampicin seemed to be effective. In NTHi, compared with H. influenzae type b (Hib), the prevalence of BLNAR is high. Hence, complicated cases may increase in the near future if the use of the Hib vaccine becomes widespread, and meningitis caused by NTHi increases. It may be necessary to consider combination therapy or use of non-beta-lactams that have a different antimicrobial mechanism from beta-lactams. PCR analysis revealed the possibility that the CSF isolate lacked the P5 protein gene. Though deficiency of P5 fimbriae is known to reduce the affinity of NTHi for the human respiratory epithelium, determining whether P5 deficient NTHi induced meningitis will require further study.

An enhanced password authentication scheme for session initiation protocol with perfect forward secrecy.

PubMed

Qiu, Shuming; Xu, Guoai; Ahmad, Haseeb; Guo, Yanhui

2018-01-01

The Session Initiation Protocol (SIP) is an extensive and esteemed communication protocol employed to regulate signaling as well as for controlling multimedia communication sessions. Recently, Kumari et al. proposed an improved smart card based authentication scheme for SIP based on Farash's scheme. Farash claimed that his protocol is resistant against various known attacks. But, we observe some accountable flaws in Farash's protocol. We point out that Farash's protocol is prone to key-compromise impersonation attack and is unable to provide pre-verification in the smart card, efficient password change and perfect forward secrecy. To overcome these limitations, in this paper we present an enhanced authentication mechanism based on Kumari et al.'s scheme. We prove that the proposed protocol not only overcomes the issues in Farash's scheme, but it can also resist against all known attacks. We also provide the security analysis of the proposed scheme with the help of widespread AVISPA (Automated Validation of Internet Security Protocols and Applications) software. At last, comparing with the earlier proposals in terms of security and efficiency, we conclude that the proposed protocol is efficient and more secure.

The Janus transcription factor HapX controls fungal adaptation to both iron starvation and iron excess

PubMed Central

Gsaller, Fabio; Hortschansky, Peter; Beattie, Sarah R; Klammer, Veronika; Tuppatsch, Katja; Lechner, Beatrix E; Rietzschel, Nicole; Werner, Ernst R; Vogan, Aaron A; Chung, Dawoon; Mühlenhoff, Ulrich; Kato, Masashi; Cramer, Robert A; Brakhage, Axel A; Haas, Hubertus

2014-01-01

Balance of physiological levels of iron is essential for every organism. In Aspergillus fumigatus and other fungal pathogens, the transcription factor HapX mediates adaptation to iron limitation and consequently virulence by repressing iron consumption and activating iron uptake. Here, we demonstrate that HapX is also essential for iron resistance via activating vacuolar iron storage. We identified HapX protein domains that are essential for HapX functions during either iron starvation or high-iron conditions. The evolutionary conservation of these domains indicates their wide-spread role in iron sensing. We further demonstrate that a HapX homodimer and the CCAAT-binding complex (CBC) cooperatively bind an evolutionary conserved DNA motif in a target promoter. The latter reveals the mode of discrimination between general CBC and specific HapX/CBC target genes. Collectively, our study uncovers a novel regulatory mechanism mediating both iron resistance and adaptation to iron starvation by the same transcription factor complex with activating and repressing functions depending on ambient iron availability. PMID:25092765

Antibiotic use and resistance in animals: Belgian initiatives.

PubMed

Daeseleire, Els; De Graef, Evelyne; Rasschaert, Geertrui; De Mulder, Thijs; Van den Meersche, Tina; Van Coillie, Els; Dewulf, Jeroen; Heyndrickx, Marc

2016-05-01

The widespread use of antibiotics in animals is causing concerns about the growing risk for development and the spread of antibiotic-resistant bacteria. Antibiotic consumption is higher in animals than in humans as reported in a joint publication of EFSA (European Food Safety Agency), ECDC (European Centre for Disease Prevention and Control), and EMA (European Medicines Agency) using data from 2011 and 2012. Both in humans and animals, positive associations between the consumption of antibiotics and resistant bacteria are observed. Responsible use of antibiotics in humans and animals should therefore be promoted. In this paper some general aspects of antibiotic resistance such as microbiological versus clinical resistance, intrinsic versus acquired resistance, resistance mechanisms, and transfer of resistance are briefly introduced. In 2012, the Belgian Center of Expertise on Antimicrobial Consumption and Resistance in Animals (AMCRA) was founded. Its mission is to collect and analyze all data related to antibiotic use and resistance in animals in Belgium and to communicate these findings in a neutral and objective manner. One of AMCRA's 10 objectives is a 50% reduction in antibiotic consumption in veterinary medicine in Belgium by 2020. The aim of this paper is to report on the achievements of this national project. The Institute for Agricultural and Fisheries Research (ILVO, Merelbeke-Melle), in collaboration with Ghent University, is currently working on three nationally funded projects on antibiotic resistance in animal husbandry. In the first project, an in vitro model is used to study the influence of low antibiotic concentrations due to carry-over after production and usage of medicated feed on the development of resistance in the pig gut. Part of that project is to develop a quantitative risk assessment model. A second project focuses on tracking excreted antibiotics used in pig rearing and their influence on the development of antibiotic resistance in pig manure and the environment. In the last project, the relation between the use of biocides in animal husbandry and antibiotic resistance development are being studied. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Nudges in a post-truth world

PubMed Central

2017-01-01

Nudges—policy proposals informed by work in behavioural economics and psychology that are designed to lead to better decision-making or better behaviour—are controversial. Critics allege that they bypass our deliberative capacities, thereby undermining autonomy and responsible agency. In this paper, I identify a kind of nudge I call a nudge to reason, which make us more responsive to genuine evidence. I argue that at least some nudges to reason do not bypass our deliberative capacities. Instead, use of these nudges should be seen as appeals to mechanisms partially constitutive of these capacities, and therefore as benign (so far as autonomy and responsible agency are concerned). I sketch some concrete proposals for nudges to reason which are especially important given the apparent widespread resistance to evidence seen in recent political events. PMID:28526778

Gastroprotective role of glucocorticoids during NSAID-induced gastropathy.

PubMed

Filaretova, Ludmila

2013-01-01

Nonsteroidal anti-inflammatory drugs (NSAIDs) make significant contributions to gastric ulcer disease which remains widespread. Although several factors have been postulated as pathogenic elements of the gastric injury induced by NSAIDs, it is, however believed that prostaglandin deficiency plays a critical role in the pathogenesis of this injury. During prostaglandin deficiency, other defensive mechanisms might operate to attenuate NSAID-induced gastropathy. According to our results, NSAIDs, similar to stress, induce an increase in glucocorticoid production that in turn helps the gastric mucosa to resist the harmful actions of these drugs. In this article, we review our experimental data suggesting that glucocorticoids may play a role as natural defensive factors in maintaining the integrity of the gastric mucosa during NSAID therapy and might operate to attenuate NSAID-induced gastropathy.

Genomic analysis of bifunctional Class C-Class D β-lactamases in environmental bacteria.

PubMed

Silveira, Melise Chaves; Catanho, Marcos; Miranda, Antônio Basílio de

2018-01-01

β-lactamases, which are found in several bacterial species and environments, are the main cause of resistance to β-lactams in Gram-negative bacteria. In 2009, a protein (LRA-13) with two β-lactamase domains (one class C domain and one class D domain) was experimentally characterised, and an extended action spectrum against β-lactams consistent with two functional domains was found. Here, we present the results of searches in the non-redundant NCBI protein database that revealed the existence of a group of homologous bifunctional β-lactamases in the genomes of environmental bacteria. These findings suggest that bifunctional β-lactamases are widespread in nature; these findings also raise concern that bifunctional β-lactamases may be transferred to bacteria of clinical importance through lateral gene transfer mechanisms.

A case of generalized bromhidrosis following whole-body depilatory laser.

PubMed

Helou, Josiane; Haber, Roger; Kechichian, Elio; Tomb, Roland

2015-01-01

Laser treatment is a widespread method for hair removal. Despite its very common use, side effects remain relatively rare and transient. Axillary hyperhidrosis and bromhidrosis have already been reported in the literature after depilatory lasers. We report here a novel side effect of total body bromhidrosis following hair removal laser. A 27-year-old man, phototype 3 underwent four sessions of total body depilatory laser, combining pulsed alexandrite and pulsed diode lasers. A few days afterwards, a generalized foul odor was noted and was resistant to regular deodorants and Aluminum chloride based antiperspirants. Possible mechanisms include the activation of dormant bacteria in the skin flora, sweat gland dysfunction, altered skin flora, sweat gland hormone receptor disturbances, and genetic factors. Total body bromhidrosis and hyperhidrosis are potential complications of total body laser hair removal.

The DAF-16 FOXO Transcription Factor Regulates natc-1 to Modulate Stress Resistance in Caenorhabditis elegans, Linking Insulin/IGF-1 Signaling to Protein N-Terminal Acetylation

PubMed Central

Warnhoff, Kurt; Murphy, John T.; Kumar, Sandeep; Schneider, Daniel L.; Peterson, Michelle; Hsu, Simon; Guthrie, James; Robertson, J. David; Kornfeld, Kerry

2014-01-01

The insulin/IGF-1 signaling pathway plays a critical role in stress resistance and longevity, but the mechanisms are not fully characterized. To identify genes that mediate stress resistance, we screened for C. elegans mutants that can tolerate high levels of dietary zinc. We identified natc-1, which encodes an evolutionarily conserved subunit of the N-terminal acetyltransferase C (NAT) complex. N-terminal acetylation is a widespread modification of eukaryotic proteins; however, relatively little is known about the biological functions of NATs. We demonstrated that loss-of-function mutations in natc-1 cause resistance to a broad-spectrum of physiologic stressors, including multiple metals, heat, and oxidation. The C. elegans FOXO transcription factor DAF-16 is a critical target of the insulin/IGF-1 signaling pathway that mediates stress resistance, and DAF-16 is predicted to directly bind the natc-1 promoter. To characterize the regulation of natc-1 by DAF-16 and the function of natc-1 in insulin/IGF-1 signaling, we analyzed molecular and genetic interactions with key components of the insulin/IGF-1 pathway. natc-1 mRNA levels were repressed by DAF-16 activity, indicating natc-1 is a physiological target of DAF-16. Genetic studies suggested that natc-1 functions downstream of daf-16 to mediate stress resistance and dauer formation. Based on these findings, we hypothesize that natc-1 is directly regulated by the DAF-16 transcription factor, and natc-1 is a physiologically significant effector of the insulin/IGF-1 signaling pathway that mediates stress resistance and dauer formation. These studies identify a novel biological function for natc-1 as a modulator of stress resistance and dauer formation and define a functionally significant downstream effector of the insulin/IGF-1 signaling pathway. Protein N-terminal acetylation mediated by the NatC complex may play an evolutionarily conserved role in regulating stress resistance. PMID:25330323

Prevalence of antibiotic-resistant Gram-negative bacteria associated with the red-eared slider (Trachemys scripta elegans).

PubMed

Liu, Dandan; Wilson, Cailin; Hearlson, Jodie; Singleton, Jennifer; Thomas, R Brent; Crupper, Scott S

2013-09-01

Free-ranging Red-eared Sliders (Trachemys scripta elegans) were captured from farm ponds located in the Flint Hills of Kansas and a zoo pond in Emporia, Kansas, USA, to evaluate their enteric bacterial flora and associated antibiotic resistance. Bacteria obtained from cloacal swabs were composed of six different Gram-negative genera. Although antibiotic resistance was present in turtles captured from both locations, 40 and 49% of bacteria demonstrated multiple antibiotic resistance to four of the antibiotics tested from the zoo captured and Flint Hills ponds turtles, respectively. These data illustrate environmental antibiotic resistance is widespread in the bacterial flora obtained from Red-eared Sliders in east central Kansas.

Symbionts Commonly Provide Broad Spectrum Resistance to Viruses in Insects: A Comparative Analysis of Wolbachia Strains

PubMed Central

Martinez, Julien; Longdon, Ben; Bauer, Simone; Chan, Yuk-Sang; Miller, Wolfgang J.; Bourtzis, Kostas; Teixeira, Luis; Jiggins, Francis M.

2014-01-01

In the last decade, bacterial symbionts have been shown to play an important role in protecting hosts against pathogens. Wolbachia, a widespread symbiont in arthropods, can protect Drosophila and mosquito species against viral infections. We have investigated antiviral protection in 19 Wolbachia strains originating from 16 Drosophila species after transfer into the same genotype of Drosophila simulans. We found that approximately half of the strains protected against two RNA viruses. Given that 40% of terrestrial arthropod species are estimated to harbour Wolbachia, as many as a fifth of all arthropods species may benefit from Wolbachia-mediated protection. The level of protection against two distantly related RNA viruses – DCV and FHV – was strongly genetically correlated, which suggests that there is a single mechanism of protection with broad specificity. Furthermore, Wolbachia is making flies resistant to viruses, as increases in survival can be largely explained by reductions in viral titer. Variation in the level of antiviral protection provided by different Wolbachia strains is strongly genetically correlated to the density of the bacteria strains in host tissues. We found no support for two previously proposed mechanisms of Wolbachia-mediated protection — activation of the immune system and upregulation of the methyltransferase Dnmt2. The large variation in Wolbachia's antiviral properties highlights the need to carefully select Wolbachia strains introduced into mosquito populations to prevent the transmission of arboviruses. PMID:25233341

Increased corrosion resistance of the AZ80 magnesium alloy by rapid solidification.

PubMed

Aghion, E; Jan, L; Meshi, L; Goldman, J

2015-11-01

Magnesium (Mg) and Mg-alloys are being considered as implantable biometals. Despite their excellent biocompatibility and good mechanical properties, their rapid corrosion is a major impediment precluding their widespread acceptance as implantable biomaterials. Here, we investigate the potential for rapid solidification to increase the corrosion resistance of Mg alloys. To this end, the effect of rapid solidification on the environmental and stress corrosion behavior of the AZ80 Mg alloy vs. its conventionally cast counterpart was evaluated in simulated physiological electrolytes. The microstructural characteristics were examined by optical microscopy, SEM, TEM, and X-ray diffraction analysis. The corrosion behavior was evaluated by immersion, salt spraying, and potentiodynamic polarization. Stress corrosion resistance was assessed by Slow Strain Rate Testing. The results indicate that the corrosion resistance of rapidly solidified ribbons is significantly improved relative to the conventional cast alloy due to the increased Al content dissolved in the α-Mg matrix and the correspondingly reduced presence of the β-phase (Mg17 Al12 ). Unfortunately, extrusion consolidated solidified ribbons exhibited a substantial reduction in the environmental performance and stress corrosion resistance. This was mainly attributed to the detrimental effect of the extrusion process, which enriched the iron impurities and increased the internal stresses by imposing a higher dislocation density. In terms of immersion tests, the average corrosion rate of the rapidly solidified ribbons was <0.4 mm/year compared with ∼2 mm/year for the conventionally cast alloy and 26 mm/year for the rapidly solidified extruded ribbons. © 2014 Wiley Periodicals, Inc.

Pyocyanin Production by Pseudomonas aeruginosa Confers Resistance to Ionic Silver

PubMed Central

Merrett, Neil D.

2014-01-01

Silver in its ionic form (Ag+), but not the bulk metal (Ag0), is toxic to microbial life forms and has been used for many years in the treatment of wound infections. The prevalence of bacterial resistance to silver is considered low due to the nonspecific nature of its toxicity. However, the recent increased use of silver as an antimicrobial agent for medical, consumer, and industrial products has raised concern that widespread silver resistance may emerge. Pseudomonas aeruginosa is a common pathogen that produces pyocyanin, a redox toxin and a reductant for molecular oxygen and ferric (Fe3+) ions. The objective of this study was to determine whether pyocyanin reduces Ag+ to Ag0, which may contribute to silver resistance due to lower bioavailability of the cation. Using surface plasmon resonance spectroscopy and scanning electron microscopy, pyocyanin was confirmed to be a reductant for Ag+, forming Ag0 nanoparticles and reducing the bioavailability of free Ag+ by >95% within minutes. Similarly, a pyocyanin-producing strain of P. aeruginosa (PA14) reduced Ag+ but not a pyocyanin-deficient (ΔphzM) strain of the bacterium. Challenge of each strain with Ag+ (as AgNO3) gave MICs of 20 and 5 μg/ml for the PA14 and ΔphzM strains, respectively. Removal of pyocyanin from the medium strain PA14 was grown in or its addition to the medium that ΔphzM mutant was grown in gave MICs of 5 and 20 μg/ml, respectively. Clinical isolates demonstrated similar pyocyanin-dependent resistance to Ag+. We conclude that pseudomonal silver resistance exists independently of previously recognized intracellular mechanisms and may be more prevalent than previously considered. PMID:25001302

Inhibition of disheveled-2 resensitizes cisplatin-resistant lung cancer cells through down-regulating Wnt/β-catenin signaling.

PubMed

Luo, Ke; Gu, Xiuhui; Liu, Jing; Zeng, Guodan; Peng, Liaotian; Huang, Houyi; Jiang, Mengju; Yang, Ping; Li, Minhui; Yang, Yuhan; Wang, Yuanyuan; Peng, Quekun; Zhu, Li; Zhang, Kun

2016-09-10

Cisplatin (CDDP) is currently recommended as the front-line chemotherapeutic agent for lung cancer. However, the resistance to cisplatin is widespread in patients with advanced lung cancer, and the molecular mechanism of such resistance remains incompletely understood. Disheveled (DVL), a key mediator of Wnt/β-catenin, has been linked to cancer progression, while the role of DVL in cancer drug resistance is not clear. Here, we found that DVL2 was over-expressed in cisplatin-resistant human lung cancer cells A549/CDDP compared to the parental A549 cells. Inhibition of DVL2 by its inhibitor (3289-8625) or shDVL2 resensitized A549/CDDP cells to cisplatin. In addition, over-expression of DVL2 in A549 cells increased the protein levels of BCRP, MRP4, and Survivin, which are known to be associated with chemoresistance, while inhibition of DVL2 in A549/CDDP cells decreased these protein levels, and reduced the accumulation and nuclear translocation of β-catenin. In addition, shβ-catenin abolished the DVL2-induced the expression of BCRP, MRP4, and Survivin. Furthermore, our data showed that GSK3β/β-catenin signals were aberrantly activated by DVL2, and inactivation of GSK3β reversed the shDVL2-induced down-regulation of β-catenin. Taken together, these results suggested that inhibition of DVL2 can sensitize cisplatin-resistant lung cancer cells through down-regulating Wnt/β-catenin signaling and inhibiting BCRP, MRP4, and Survivin expression. It promises a new strategy to chemosensitize cisplatin-induced cytotoxicity in lung cancer. Copyright © 2016 Elsevier Inc. All rights reserved.

Radiation resistance of asporogenous bacteria in frozen beef. Final report, Sep 1974--Feb 1975

DOE Office of Scientific and Technical Information (OSTI.GOV)

Maxcy, R.B.; Rowley, D.B.; Annellis, A.

1976-03-01

A scheme was developed to isolate the most radiation resistant vegetative microbial cells occurring in beef. Selection of pure cultures and enrichment provided 16 apparently different isolates with higher radiation resistance than spores of Clostridium botulinum. Most of these bacteria were found to be Moraxella or Acinetobacter. They grew over a temperature range of 2 - 50 C. Preliminary data indicated the isolates to be relatively sensitive to heat and to limited oxygen. It would appear these organisms are rather widespread and frequent in nature. (GRA)

A new sulfonamide resistance gene (sul3) in Escherichia coli is widespread in the pig population of Switzerland.

PubMed

Perreten, Vincent; Boerlin, Patrick

2003-03-01

A new gene, sul3, which specifies a 263-amino-acid protein similar to a dihydropteroate synthase encoded by the 54-kb conjugative plasmid pVP440 from Escherichia coli was characterized. Expression of the cloned sul3 gene conferred resistance to sulfamethoxazole on E. coli. Two copies of the insertion element IS15Delta/26 flanked the region containing sul3. The sul3 gene was detected in one-third of the sulfonamide-resistant pathogenic E. coli isolates from pigs in Switzerland.

A New Sulfonamide Resistance Gene (sul3) in Escherichia coli Is Widespread in the Pig Population of Switzerland

PubMed Central

Perreten, Vincent; Boerlin, Patrick

2003-01-01

A new gene, sul3, which specifies a 263-amino-acid protein similar to a dihydropteroate synthase encoded by the 54-kb conjugative plasmid pVP440 from Escherichia coli was characterized. Expression of the cloned sul3 gene conferred resistance to sulfamethoxazole on E. coli. Two copies of the insertion element IS15Δ/26 flanked the region containing sul3. The sul3 gene was detected in one-third of the sulfonamide-resistant pathogenic E. coli isolates from pigs in Switzerland. PMID:12604565

The current insecticide resistance status of Anopheles gambiae (s.l.) (Culicidae) in rural and urban areas of Bouaké, Côte d'Ivoire.

PubMed

Zoh, Dounin Danielle; Ahoua Alou, Ludovic Phamien; Toure, Mahama; Pennetier, Cédric; Camara, Soromane; Traore, Dipomin François; Koffi, Alphonsine Amanan; Adja, Akré Maurice; Yapi, Ahoua; Chandre, Fabrice

2018-03-02

Several studies were carried out in experimental hut station in areas surrounding the city of Bouaké, after the crisis in Côte d'Ivoire. They reported increasing resistance levels to insecticide for malaria transmiting mosquitoes. The present work aims to evaluate the current resistance level of An. gambiae (s.l.) in rural and urban areas in the city of Bouaké. Larvae of Anopheles gambiae (s.l.) were collected from five different study sites and reared to adult stages. The resistance status was assessed using the WHO bioassay test kits for adult mosquitoes, with eight insecticides belonging to pyrethroids, organochlorines, carbamates and organophosphates classes. Molecular assays were performed to identify the molecular forms of An. gambiae (s.l.), the L1014F kdr and the ace-1R alleles in individual mosquitoes. The synergist PBO was used to investigate the role of enzymes in resistance. Biochemical assays were performed to detect potential increased activities in mixed function oxidase (MFO) levels, non-specific esterases (NSE) and glutathione S-transferases (GST). High resistance levels to pyrethroids, organochlorines, and carbamates were observed in Anopheles gambiae (s.l.) from Bouaké. Mortalities ranged between 0 and 73% for the eight tested insecticides. The pre-exposure to PBO restored full or partial susceptibility to pyrethroids in the different sites. The same trend was observed with the carbamates in five sites, but to a lesser extent. With DDT, pre-exposure to PBO did not increase the mortality rate of An. gambiae (s.l.) from the same sites. Tolerance to organophosphates was observed. An increased activity of NSE and higher level of MFO were found compared to the Kisumu susceptible reference strain. Two molecular forms, S form [(An. gambiae (s.s)] and M form (An. coluzzi) were identified. The kdr allele frequencies vary from 85.9 to 99.8% for An. gambiae (s.s.) and from 81.7 to 99.6% for An. coluzzii. The ace-1R frequencies vary between 25.6 and 38.8% for An. gambiae (s.s.) and from 28.6 to 36.7% for An. coluzzii. Resistance to insecticides is widespread within both An. gambiae (s.s.) and An. coluzzii. Two mechanisms of resistance, i.e. metabolic and target-site mutation seemed to largely explain the high resistance level of mosquitoes in Bouaké. Pyrethroid resistance was found exclusively due to the metabolic mechanism.

Induction of Systemic Resistance against Aphids by Endophytic Bacillus velezensis YC7010 via Expressing PHYTOALEXIN DEFICIENT4 in Arabidopsis

PubMed Central

Rashid, Md. Harun-Or-; Khan, Ajmal; Hossain, Mohammad T.; Chung, Young R.

2017-01-01

Aphids are the most destructive insect pests. They suck the sap and transmit plant viruses, causing widespread yield loss of many crops. A multifunctional endophytic bacterial strain Bacillus velezensis YC7010 has been found to induce systemic resistance against bacterial and fungal pathogens of rice. However, its activity against insects attack and underlying cellular and molecular defense mechanisms are not elucidated yet. Here, we show that root drenching of Arabidopsis seedlings with B. velezensis YC7010 can induce systemic resistance against green peach aphid (GPA), Myzus persicae. Treatment of bacterial suspension of B. velezensis YC7010 at 2 × 107 CFU/ml to Arabidopsis rhizosphere induced higher accumulation of hydrogen peroxide, cell death, and callose deposition in leaves compared to untreated plants at 6 days after infestation of GPA. Salicylic acid, jasmonic acid, ethylene, and abscisic acid were not required to confer defense against GPA in Arabidopsis plants treated by B. velezensis YC7010. Bacterial treatment with B. velezensis YC7010 significantly reduced settling, feeding and reproduction of GPA on Arabidopsis leaves via strongly expressing senescence-promoting gene PHYTOALEXIN DEFICIENT4 (PAD4) while suppressing BOTRYTIS-INDUCED KINASE1 (BIK1). These results indicate that B. velezensis YC7010-induced systemic resistance to the GPA is a hypersensitive response mainly dependent on higher expression of PAD4 with suppression of BIK1, resulting in more accumulation of hydrogen peroxide, cell death, and callose deposition in Arabidopsis. PMID:28261260

Intrinsic Resistance of Burkholderia cepacia Complex to Benzalkonium Chloride

PubMed Central

Ahn, Youngbeom; Kim, Jeong Myeong; Kweon, Ohgew; Kim, Seong-Jae; Jones, Richard C.; Woodling, Kellie; Gamboa da Costa, Gonçalo; LiPuma, John J.; Hussong, David; Marasa, Bernard S.

2016-01-01

ABSTRACT Pharmaceutical products that are contaminated with Burkholderia cepacia complex (BCC) bacteria may pose serious consequences to vulnerable patients. Benzyldimethylalkylammonium chloride (BZK) cationic surfactants are extensively used in medical applications and have been implicated in the coselection of antimicrobial resistance. The ability of BCC to degrade BZK, tetradecyldimethylbenzylammonium chloride (C14BDMA-Cl), dodecyldimethylbenzylammonium chloride (C12BDMA-Cl), decyldimethylbenzylammonium chloride (C10BDMA-Cl), hexyldimethylbenzylammonium chloride, and benzyltrimethylammonium chloride was determined by incubation in 1/10-diluted tryptic soy broth (TSB) to determine if BCC bacteria have the ability to survive and inactivate these disinfectants. With BZK, C14BDMA-Cl, and C12BDMA-Cl, inhibition of the growth of 20 BCC strains was observed in disinfectant solutions that ranged from 64 to 256 µg/ml. The efflux pump inhibitor carbonyl cyanide m-chlorophenylhydrazone increased the sensitivity of bacteria to 64 µg/ml BZK. The 20 BCC strains grew well in 1/10-diluted TSB medium with BZK, C12BDMA-Cl, and C10BDMA-Cl; they absorbed and degraded the compounds in 7 days. Formation of benzyldimethylamine and benzylmethylamine as the initial metabolites suggested that the cleavage of the C alkyl-N bond occurred as the first step of BZK degradation by BCC bacteria. Proteomic data confirmed the observed efflux activity and metabolic inactivation via biodegradation in terms of BZK resistance of BCC bacteria, which suggests that the two main resistance mechanisms are intrinsic and widespread. PMID:27879334

Global Fitness Profiling Identifies Arsenic and Cadmium Tolerance Mechanisms in Fission Yeast.

PubMed

Guo, Lan; Ganguly, Abantika; Sun, Lingling; Suo, Fang; Du, Li-Lin; Russell, Paul

2016-10-13

Heavy metals and metalloids such as cadmium [Cd(II)] and arsenic [As(III)] are widespread environmental toxicants responsible for multiple adverse health effects in humans. However, the molecular mechanisms underlying metal-induced cytotoxicity and carcinogenesis, as well as the detoxification and tolerance pathways, are incompletely understood. Here, we use global fitness profiling by barcode sequencing to quantitatively survey the Schizosaccharomyces pombe haploid deletome for genes that confer tolerance of cadmium or arsenic. We identified 106 genes required for cadmium resistance and 110 genes required for arsenic resistance, with a highly significant overlap of 36 genes. A subset of these 36 genes account for almost all proteins required for incorporating sulfur into the cysteine-rich glutathione and phytochelatin peptides that chelate cadmium and arsenic. A requirement for Mms19 is explained by its role in directing iron-sulfur cluster assembly into sulfite reductase as opposed to promoting DNA repair, as DNA damage response genes were not enriched among those required for cadmium or arsenic tolerance. Ubiquinone, siroheme, and pyridoxal 5'-phosphate biosynthesis were also identified as critical for Cd/As tolerance. Arsenic-specific pathways included prefoldin-mediated assembly of unfolded proteins and protein targeting to the peroxisome, whereas cadmium-specific pathways included plasma membrane and vacuolar transporters, as well as Spt-Ada-Gcn5-acetyltransferase (SAGA) transcriptional coactivator that controls expression of key genes required for cadmium tolerance. Notable differences are apparent with corresponding screens in the budding yeast Saccharomyces cerevisiae, underscoring the utility of analyzing toxic metal defense mechanisms in both organisms. Copyright © 2016 Guo et al.

Sound stress-induced long-term enhancement of mechanical hyperalgesia in rats is maintained by sympathoadrenal catecholamines.

PubMed

Khasar, Sachia G; Dina, Olayinka A; Green, Paul G; Levine, Jon D

2009-10-01

Although stress plays an important role in chronic widespread pain syndromes, such as fibromyalgia, the underlying mechanism has remained elusive. We have recently demonstrated, in a model of chronic widespread pain, that prolonged enhancement of immune mediator hyperalgesia, induced by unpredictable sound stress, requires a contribution of both the sympathoadrenal (epinephrine) and the hypothalamic-pituitary adrenal (corticosterone) neuroendocrine stress axes. Because this stress protocol produced sustained elevation of plasma epinephrine, in the current study we tested the hypothesis that the sympathoadrenal axis also plays a role in maintenance of symptoms in this model of chronic widespread pain. After establishment, adrenal medullectomy abolished the enhancement of epinephrine-induced cutaneous and muscle hyperalgesia. Administration of stress levels of epinephrine to adrenal medullectomized rats reconstituted the pain phenotype. These observations suggest that the sympathoadrenal stress axis plays a major role in the induction as well as maintenance of stress-induced enhancement of mechanical hyperalgesia, mediated by prolonged elevation of circulating epinephrine. We present data showing mechanical hyperalgesia persisting for up to 28 days after exposure to sound stress, with evidence that the sympathoadrenal axis mediator epinephrine plays a major role. These findings could have clinical implications with regard to novel potential treatments for chronic widespread pain syndromes, such as fibromyalgia.

Effects of over-expressing a native gene encoding 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) on glyphosate resistance in Arabidopsis thaliana.

PubMed

Yang, Xiao; Beres, Zachery T; Jin, Lin; Parrish, Jason T; Zhao, Wanying; Mackey, David; Snow, Allison A

2017-01-01

Widespread overuse of the herbicide glyphosate, the active ingredient in RoundUp®, has led to the evolution of glyphosate-resistant weed biotypes, some of which persist by overproducing the herbicide's target enzyme, 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS). EPSPS is a key enzyme in the shikimic acid pathway for biosynthesis of aromatic amino acids, lignin, and defensive compounds, but little is known about how overproducing EPSPS affects downstream metabolites, growth, or lifetime fitness in the absence of glyphosate. We are using Arabidopsis as a model system for investigating phenotypic effects of overproducing EPSPS, thereby avoiding confounding effects of genetic background or other mechanisms of herbicide resistance in agricultural weeds. Here, we report results from the first stage of this project. We designed a binary vector expressing a native EPSPS gene from Arabidopsis under control of the CaMV35S promoter (labelled OX, for over-expression). For both OX and the empty vector (labelled EV), we obtained nine independent T3 lines. Subsets of these lines were used to characterize glyphosate resistance in greenhouse experiments. Seven of the nine OX lines exhibited enhanced glyphosate resistance when compared to EV and wild-type control lines, and one of these was discarded due to severe deformities. The remaining six OX lines exhibited enhanced EPSPS gene expression and glyphosate resistance compared to controls. Glyphosate resistance was correlated with the degree of EPSPS over-expression for both vegetative and flowering plants, indicating that glyphosate resistance can be used as a surrogate for EPSPS expression levels in this system. These findings set the stage for examination of the effects of EPSPS over-expression on fitness-related traits in the absence of glyphosate. We invite other investigators to contact us if they wish to study gene expression, downstream metabolic effects, and other questions with these particular lines.

Effects of over-expressing a native gene encoding 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) on glyphosate resistance in Arabidopsis thaliana

PubMed Central

Beres, Zachery T.; Jin, Lin; Parrish, Jason T.; Zhao, Wanying; Mackey, David; Snow, Allison A.

2017-01-01

Widespread overuse of the herbicide glyphosate, the active ingredient in RoundUp®, has led to the evolution of glyphosate-resistant weed biotypes, some of which persist by overproducing the herbicide’s target enzyme, 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS). EPSPS is a key enzyme in the shikimic acid pathway for biosynthesis of aromatic amino acids, lignin, and defensive compounds, but little is known about how overproducing EPSPS affects downstream metabolites, growth, or lifetime fitness in the absence of glyphosate. We are using Arabidopsis as a model system for investigating phenotypic effects of overproducing EPSPS, thereby avoiding confounding effects of genetic background or other mechanisms of herbicide resistance in agricultural weeds. Here, we report results from the first stage of this project. We designed a binary vector expressing a native EPSPS gene from Arabidopsis under control of the CaMV35S promoter (labelled OX, for over-expression). For both OX and the empty vector (labelled EV), we obtained nine independent T3 lines. Subsets of these lines were used to characterize glyphosate resistance in greenhouse experiments. Seven of the nine OX lines exhibited enhanced glyphosate resistance when compared to EV and wild-type control lines, and one of these was discarded due to severe deformities. The remaining six OX lines exhibited enhanced EPSPS gene expression and glyphosate resistance compared to controls. Glyphosate resistance was correlated with the degree of EPSPS over-expression for both vegetative and flowering plants, indicating that glyphosate resistance can be used as a surrogate for EPSPS expression levels in this system. These findings set the stage for examination of the effects of EPSPS over-expression on fitness-related traits in the absence of glyphosate. We invite other investigators to contact us if they wish to study gene expression, downstream metabolic effects, and other questions with these particular lines. PMID:28426703

The Obscure World of Integrative and Mobilizable Elements, Highly Widespread Elements that Pirate Bacterial Conjugative Systems

PubMed Central

Guédon, Gérard; Libante, Virginie; Coluzzi, Charles; Payot, Sophie

2017-01-01

Conjugation is a key mechanism of bacterial evolution that involves mobile genetic elements. Recent findings indicated that the main actors of conjugative transfer are not the well-known conjugative or mobilizable plasmids but are the integrated elements. This paper reviews current knowledge on “integrative and mobilizable elements” (IMEs) that have recently been shown to be highly diverse and highly widespread but are still rarely described. IMEs encode their own excision and integration and use the conjugation machinery of unrelated co-resident conjugative element for their own transfer. Recent studies revealed a much more complex and much more diverse lifecycle than initially thought. Besides their main transmission as integrated elements, IMEs probably use plasmid-like strategies to ensure their maintenance after excision. Their interaction with conjugative elements reveals not only harmless hitchhikers but also hunters that use conjugative elements as target for their integration or harmful parasites that subvert the conjugative apparatus of incoming elements to invade cells that harbor them. IMEs carry genes conferring various functions, such as resistance to antibiotics, that can enhance the fitness of their hosts and that contribute to their maintenance in bacterial populations. Taken as a whole, IMEs are probably major contributors to bacterial evolution. PMID:29165361

Widespread Natural Occurrence of Hydroxyurea in Animals.

PubMed

Fraser, David I; Liu, Kyle T; Reid, Bryan J; Hawkins, Emily; Sevier, Andrew; Pyle, Michelle; Robinson, Jacob W; Ouellette, Pierre H R; Ballantyne, James S

2015-01-01

Here we report the widespread natural occurrence of a known antibiotic and antineoplastic compound, hydroxyurea in animals from many taxonomic groups. Hydroxyurea occurs in all the organisms we have examined including invertebrates (molluscs and crustaceans), fishes from several major groups, amphibians and mammals. The species with highest concentrations was an elasmobranch (sharks, skates and rays), the little skate Leucoraja erinacea with levels up to 250 μM, high enough to have antiviral, antimicrobial and antineoplastic effects based on in vitro studies. Embryos of L. erinacea showed increasing levels of hydroxyurea with development, indicating the capacity for hydroxyurea synthesis. Certain tissues of other organisms (e.g. skin of the frog (64 μM), intestine of lobster (138 μM) gills of the surf clam (100 μM)) had levels high enough to have antiviral effects based on in vitro studies. Hydroxyurea is widely used clinically in the treatment of certain human cancers, sickle cell anemia, psoriasis, myeloproliferative diseases, and has been investigated as a potential treatment of HIV infection and its presence at high levels in tissues of elasmobranchs and other organisms suggests a novel mechanism for fighting disease that may explain the disease resistance of some groups. In light of the known production of nitric oxide from exogenously applied hydroxyurea, endogenous hydoxyurea may play a hitherto unknown role in nitric oxide dynamics.

Widespread Natural Occurrence of Hydroxyurea in Animals

PubMed Central

Fraser, David I.; Liu, Kyle T.; Reid, Bryan J.; Hawkins, Emily; Sevier, Andrew; Pyle, Michelle; Robinson, Jacob W.; Ouellette, Pierre H. R.; Ballantyne, James S.

2015-01-01

Here we report the widespread natural occurrence of a known antibiotic and antineoplastic compound, hydroxyurea in animals from many taxonomic groups. Hydroxyurea occurs in all the organisms we have examined including invertebrates (molluscs and crustaceans), fishes from several major groups, amphibians and mammals. The species with highest concentrations was an elasmobranch (sharks, skates and rays), the little skate Leucoraja erinacea with levels up to 250 μM, high enough to have antiviral, antimicrobial and antineoplastic effects based on in vitro studies. Embryos of L. erinacea showed increasing levels of hydroxyurea with development, indicating the capacity for hydroxyurea synthesis. Certain tissues of other organisms (e.g. skin of the frog (64 μM), intestine of lobster (138 μM) gills of the surf clam (100 μM)) had levels high enough to have antiviral effects based on in vitro studies. Hydroxyurea is widely used clinically in the treatment of certain human cancers, sickle cell anemia, psoriasis, myeloproliferative diseases, and has been investigated as a potential treatment of HIV infection and its presence at high levels in tissues of elasmobranchs and other organisms suggests a novel mechanism for fighting disease that may explain the disease resistance of some groups. In light of the known production of nitric oxide from exogenously applied hydroxyurea, endogenous hydoxyurea may play a hitherto unknown role in nitric oxide dynamics. PMID:26600157

The Arsenic Detoxification System in Corynebacteria: Basis and Application for Bioremediation and Redox Control.

PubMed

Mateos, Luis M; Villadangos, Almudena F; de la Rubia, Alfonso G; Mourenza, Alvaro; Marcos-Pascual, Laura; Letek, Michal; Pedre, Brandán; Messens, Joris; Gil, Jose A

2017-01-01

Arsenic (As) is widespread in the environment and highly toxic. It has been released by volcanic and anthropogenic activities and causes serious health problems worldwide. To survive arsenic-rich environments, soil and saprophytic microorganisms have developed molecular detoxification mechanisms to survive arsenic-rich environments, mainly by the enzymatic conversion of inorganic arsenate (As V ) to arsenite (As III ) by arsenate reductases, which is then extruded by arsenite permeases. One of these Gram-positive bacteria, Corynebacterium glutamicum, the workhorse of biotechnological research, is also resistant to arsenic. To sanitize contaminated soils and waters, C. glutamicum strains were modified to work as arsenic "biocontainers." Two chromosomally encoded ars operons (ars1 and ars2) are responsible for As resistance. The genes within these operons encode for metalloregulatory proteins (ArsR1/R2), arsenite permeases (Acr3-1/-2), and arsenate reductases (ArsC1/C2/C1'). ArsC1/C2 arsenate reductases are coupled to the low molecular weight thiol mycothiol (MSH) and to the recently discovered mycoredoxin-1 (Mrx-1) present in most Actinobacteria. This MSH/Mrx-1 redox system protects cells against different forms of stress, including reactive oxygen species (ROS), metals, and antibiotics. ROS can modify functional sulfur cysteines by oxidizing the thiol (-SH) to a sulfenic acid (-SOH). These oxidation-sensitive protein cysteine thiols are redox regulated by the MSH/Mrx-1 couple in Corynebacterium and Mycobacterium. In summary, the molecular mechanisms involved in arsenic resistance system in C. glutamicum have paved the way for understanding the cellular response against oxidative stress in Actinobacteria. Copyright © 2017 Elsevier Inc. All rights reserved.

Tantalum-based thin film coatings for wear resistant arthroprostheses.

PubMed

Balagna, C; Faga, M G; Spriano, S

2011-10-01

Cobalt-chromium-molybdenum alloys with high carbon content (HC-CoCrMo) are widely used as materials for arthroprosthesis, in particular in metal-on-metal (MoM) hip joints. In spite of their good wear and corrosion resistance, production of metallic wear particles and metal ion release will occur on a large time-scale. An enhancement of the metal ion level in the patient's blood and urine is often reported in clinical data. Hypersensitivity, inflammatory response and cell necrosis can occur as consequence. So implants on young patients and women on childbearing age are not so widespread. The aim of this research is the realization of a thin film coating in order to improve the biocompatibility of Co-based alloys and to reduce debris production, ion release and citotoxicity. The innovative process consists of a thermal treatment in molten salts, in order to obtain a tantalum enriched thin film coating. Tantalum is chosen because it is considered a biocompatible metal with high corrosion resistance and low ion release. Three HC-CoCrMo alloys, produced by different manufacturing processes, are tested as substrates. The coating is a thin film of TaC or it can be composed by a multilayer of two tantalum carbides and metallic tantalum, depending on the temperature of the treatment and on the carbon content of the substrate. The thin films as well the substrates are characterized from the structural, chemical and morphological point of view. Moreover mechanical behaviour of treated and untreated materials is analyzed by means of nanohardness, scratch and ball-on-disc wear tests. The coating increases the mechanical and tribological properties of HC-CoCrMo.

Calcium-mediated apoptosis in a plant hypersensitive disease resistance response.

PubMed

Levine, A; Pennell, R I; Alvarez, M E; Palmer, R; Lamb, C

1996-04-01

Avirulent pathogens elicit a battery of plant defenses, often accompanied by collapse of the challenged cells. In soybean cells, sustained accumulation of H2O2 from an oxidative burst cues localized host cell death. Such hypersensitive cell death appears to be an active process, but little is known about the mechanisms underlying cellular collapse. We show that H2O2 stimulates a rapid influx of Ca2+ into soybean cells, which activates a physiological cell death program resulting in the generation of large (approximately 50 kb) DNA fragments and cell corpse morphology--including cell shrinkage, plasma membrane blebbing and nuclear condensation--characteristic of apoptosis. In contrast, H2O2 induction of the cellular protectant gene glutathione S-transferase is Ca(2+)-independent. Apoptosis in soybean cells and leaf tissue was induced by avirulent Pseudomonas syringae pv. glycinea but was not observed at comparable stages of the compatible interaction with the isogenic virulent strain, which fails to elicit a hypersensitive response. Apoptosis was also observed at the onset of the hypersensitive response in Arabidopsis leaves inoculated with avirulent P. syringae pv. tomato and in tobacco cells treated with the fungal peptide cryptogein, which is involved in the induction of non-host resistance to Phytophthora cryptogea. These observations establish a signal function for Ca2+ downstream of the oxidative burst in the activation of a physiological cell death program in soybean cells that is similar to apoptosis in animals. That the characteristic cell corpse morphology is also induced in Arabidopsis and tobacco by different avirulence signals suggests that apoptosis may prove to be a common, but not necessarily ubiquitous, feature of incompatible plant-pathogen interactions. Emerging similarities between facets of hypersensitive disease resistance and the mammalian native immune system indicate that apoptosis is a widespread defence mechanism in eukaryotes.

Antimicrobial bacteriophage-derived proteins and therapeutic applications

USDA-ARS?s Scientific Manuscript database

Antibiotics have the remarkable power to control bacterial infections. Unfortunately, widespread use, whether regarded as prudent or not, has favored the emergence and persistence of antibiotic resistant strains of human pathogenic bacteria, resulting in a global health threat. Bacteriophages (pha...

Entrapment of bed bugs by leaf trichomes inspires microfabrication of biomimetic surfaces

PubMed Central

Szyndler, Megan W.; Haynes, Kenneth F.; Potter, Michael F.; Corn, Robert M.; Loudon, Catherine

2013-01-01

Resurgence in bed bug infestations and widespread pesticide resistance have greatly renewed interest in the development of more sustainable, environmentally friendly methods to manage bed bugs. Historically, in Eastern Europe, bed bugs were entrapped by leaves from bean plants, which were then destroyed; this purely physical entrapment was related to microscopic hooked hairs (trichomes) on the leaf surfaces. Using scanning electron microscopy and videography, we documented the capture mechanism: the physical impaling of bed bug feet (tarsi) by these trichomes. This is distinct from a Velcro-like mechanism of non-piercing entanglement, which only momentarily holds the bug without sustained capture. Struggling, trapped bed bugs are impaled by trichomes on several legs and are unable to free themselves. Only specific, mechanically vulnerable locations on the bug tarsi are pierced by the trichomes, which are located at effective heights and orientations for bed bug entrapment despite a lack of any evolutionary association. Using bean leaves as templates, we microfabricated surfaces indistinguishable in geometry from the real leaves, including the trichomes, using polymers with material properties similar to plant cell walls. These synthetic surfaces snag the bed bugs temporarily but do not hinder their locomotion as effectively as real leaves. PMID:23576783

Malaria Theranostics using Hemozoin-Generated Vapor Nanobubbles

PubMed Central

Hleb, Ekaterina Y. Lukianova-; Lapotko, Dmitri O.

2014-01-01

Malaria remains a widespread and deadly infectious human disease, with increasing diagnostic and therapeutic challenges due to the drug resistance and aggressiveness of malaria infection. Early detection and innovative approaches for parasite destruction are needed. The high optical absorbance and nano-size of hemozoin crystals have been exploited to detect and mechanically destroy the malaria parasite in a single theranostic procedure. Transient vapor nanobubbles are generated around hemozoin crystals in malaria parasites in infected erythrocytes in response to a single short laser pulse. Optical scattering signals of the nanobubble report the presence of the malaria parasite. The mechanical impact of the same nanobubble physically destroys the parasite in nanoseconds in a drug-free manner. Laser-induced nanobubble treatment of human blood in vitro results in destruction of up to 95% of parasites after a single procedure, and delivers an 8-fold better parasiticidal efficacy compared to standard chloroquine drug treatment. The mechanism of destruction is highly selective for malaria infected red cells and does not harm neighboring, uninfected erythrocytes. Thus, laser pulse-induced vapor nanobubble generation around hemozoin supports both rapid and highly specific detection and destruction of malaria parasites in one theranostic procedure. PMID:24883125

Malaria theranostics using hemozoin-generated vapor nanobubbles.

PubMed

Lukianova-Hleb, Ekaterina Y; Lapotko, Dmitri O

2014-01-01

Malaria remains a widespread and deadly infectious human disease, with increasing diagnostic and therapeutic challenges due to the drug resistance and aggressiveness of malaria infection. Early detection and innovative approaches for parasite destruction are needed. The high optical absorbance and nano-size of hemozoin crystals have been exploited to detect and mechanically destroy the malaria parasite in a single theranostic procedure. Transient vapor nanobubbles are generated around hemozoin crystals in malaria parasites in infected erythrocytes in response to a single short laser pulse. Optical scattering signals of the nanobubble report the presence of the malaria parasite. The mechanical impact of the same nanobubble physically destroys the parasite in nanoseconds in a drug-free manner. Laser-induced nanobubble treatment of human blood in vitro results in destruction of up to 95% of parasites after a single procedure, and delivers an 8-fold better parasiticidal efficacy compared to standard chloroquine drug treatment. The mechanism of destruction is highly selective for malaria infected red cells and does not harm neighboring, uninfected erythrocytes. Thus, laser pulse-induced vapor nanobubble generation around hemozoin supports both rapid and highly specific detection and destruction of malaria parasites in one theranostic procedure.

[Pre- and post-conditioning phenomena: the protective physiological mechanisms in the aspect of pathogenesis and the theory of treatment of ENT pathology].

PubMed

Zhuravskiĭ, S G; Galagudza, M M; Ivanov, S A

2013-01-01

The objective of the present work was to expose the universal general biological significance of the protective pre- and postconditioning phenomena and to provide an insight into the possibility of application of therapeutic modalities based on these effects in current otorhinolaryngological practice. Pre- and postconditioning phenomena (Pre-C and Post-C respectively) began to be studied as protective physiological mechanisms since the 1980s, first in cardiology and thereafter in other fields of experimental medicine. At the same time, their protective properties had been known and intuitively used much earlier among the established human cultural and social stereotypes, psychophysical training techniques, and methods of traditional and empirical medicine. The widespread application of these phenomena gives evidence of their universal biological nature as factors involved in the interactions between the organism and pathogens (including co-morbidity), the process leading to the enhancement of non-specific resistance, mechanisms underlying realization of pharmacodynamic effects of a number of pharmaceutical products,etc. The understanding of the protective potential of PreC and PostC dictates the necessity to revise and further elaborate the present-day strategy of prophylaxis and treatment of the most serious chronic ENT diseases.

Combating Global Antibiotic Resistance: Emerging One Health Concerns in Lower- and Middle-Income Countries.

PubMed

Nadimpalli, Maya; Delarocque-Astagneau, Elisabeth; Love, David C; Price, Lance B; Huynh, Bich-Tram; Collard, Jean-Marc; Lay, Kruy Sun; Borand, Laurence; Ndir, Awa; Walsh, Timothy R; Guillemot, Didier

2018-03-05

Antibiotic misuse in lower- and middle-income countries (LMICs) contributes to the development of antibiotic resistance that can disseminate globally. Strategies specific to LMICs that seek to reduce antibiotic misuse by humans, but simultaneously improve antibiotic access, have been proposed. However, most approaches to date have not considered the growing impact of animal and environmental reservoirs of antibiotic resistance, which threaten to exacerbate the antibiotic resistance crisis in LMICs. In particular, current strategies do not prioritize the impacts of increased antibiotic use for terrestrial food-animal and aquaculture production, inadequate food safety, and widespread environmental pollution. Here, we propose new approaches that address emerging, One Health challenges.

Stainless and stainless-clad reinforcement for highway bridge use.

DOT National Transportation Integrated Search

2011-12-01

Stainless steel as concrete reinforcement has been in use for several decades. Although highly resistant to corrosion, and able to provide greater than 100 years maintenance-free service life, the main drawback to widespread use has been the cost of ...

Sublethal exposure, insecticide resistance, and community stress

USDA-ARS?s Scientific Manuscript database

Although a prevalent pest management tool and anthropogenic stressors of widespread occurrence, insecticides are subject to biased perceptions and research demands largely guided by their use, market value, and regulatory requirements. As a result, short-term and simplistic efforts focusing on letha...

Evaluation of light attraction for the stored-product psocid, Liposcelis bostrychophila

USDA-ARS?s Scientific Manuscript database

The psocid, Liposcelis bostrychophila Badonnel (Psocoptera: Liposcelididae), is the most widespread psocid pest of stored-products. Because L. bostrychophila has developed resistance to several chemical insecticides it is important to investigate other integrated pest management (IPM) approaches, an...

Levofloxacin for the treatment of pyelonephritis.

PubMed

Rafat, Cédric; Debrix, Isabelle; Hertig, Alexandre

2013-06-01

Levofloxacin , the l-isomer of ofloxacin has become one of the cornerstones of antibiotic therapy of pyelonephritis since its introduction in the 1990s, thanks to its exceptional pharmacokinetic (PK) and pharmacodynamic (PD) profile, broad-spectrum antibacterial action and satisfactory tolerance. However, the emergence of widespread fluoroquinolone resistance over the past decade, has prompted to re-examine its place in the treatment of urinary tract infection. This review covers the medical literature in any language through December 2012, on 'levofloxacin'. To identify relevant articles, the search terms 'pyelonephritis', 'urinary tract infections', 'levofloxacin', 'levaquin' and 'ofloxacin' were obtained through PubMed, MEDLINE and Clinicaltrials.gov queries. The authors focus on clinical trials, articles related to the PK and PD properties of levofloxacin as well as recent development in the mechanisms and prevalence of levofloxacin resistance. Major points stemming from international guidelines are also reviewed. Levofloxacin has achieved satisfactory bacterial eradication rates and clinical success across all available trials, similar to the antibiotic comparator. High-dose (750 mg) orally administrated levofloxacin over a short 5-day course is a reasonable option for patients eligible for outpatient management. Levofloxacin is no longer a suitable option for first-line empirical treatment of pyelonephritis in areas where resistance rates are high (> 10%) when pyelonephritis is hospital-acquired. Efforts to promote fluoroquinolone-sparing agents should be encouraged and its prescription should be performed in compliance with antimicrobial guidelines.

Inhibitors of the Hepatitis C Virus Polymerase; Mode of Action and Resistance.

PubMed

Eltahla, Auda A; Luciani, Fabio; White, Peter A; Lloyd, Andrew R; Bull, Rowena A

2015-09-29

The hepatitis C virus (HCV) is a pandemic human pathogen posing a substantial health and economic burden in both developing and developed countries. Controlling the spread of HCV through behavioural prevention strategies has met with limited success and vaccine development remains slow. The development of antiviral therapeutic agents has also been challenging, primarily due to the lack of efficient cell culture and animal models for all HCV genotypes, as well as the large genetic diversity between HCV strains. On the other hand, the use of interferon-α-based treatments in combination with the guanosine analogue, ribavirin, achieved limited success, and widespread use of these therapies has been hampered by prevalent side effects. For more than a decade, the HCV RNA-dependent RNA polymerase (RdRp) has been targeted for antiviral development, and direct-acting antivirals (DAA) have been identified which bind to one of at least six RdRp inhibitor-binding sites, and are now becoming a mainstay of highly effective and well tolerated antiviral treatment for HCV infection. Here we review the different classes of RdRp inhibitors and their mode of action against HCV. Furthermore, the mechanism of antiviral resistance to each class is described, including naturally occurring resistance-associated variants (RAVs) in different viral strains and genotypes. Finally, we review the impact of these RAVs on treatment outcomes with the newly developed regimens.

Development of a Molecular System for Studying Microbial Arsenate Respiration

NASA Astrophysics Data System (ADS)

Saltikov, C. W.; Newman, D. K.

2002-12-01

The toxic element arsenic is a major contaminant of many groundwaters and surface waters throughout the world. Arsenic enrichment is primarily of geological origin resulting from weathering processes and geothermal activity. Not surprisingly, microorganisms inhabiting anoxic arsenic-contaminated environments have evolved to exploit arsenate during respiration. Numerous bacteria have been isolated that use arsenate as a terminal electron acceptor for respiratory growth. The diversity of this metabolism appears to be widespread throughout the microbial tree of life, suggesting respiratory arsenate reduction is ancient in origin. Yet little is known about the molecular mechanisms for how these organisms respire arsenate. We have developed a model system in Shewanella trabarsenatis, strain ANA-3, a facultative anaerobe that respires arsenate and tolerates high concentrations of arsenite (10 mM). Through loss-of-function studies, we have identified genes involved in both arsenic resistance and arsenate respiration. The genes that confer resistance to arsenic are homologous to the well-characterized ars operon of E. coli. However, the respiratory arsenate reductase is predicted to encode a novel protein that shares homologous regions (~ 40 % similarity) to molybdopterin anaerobic reductases specific for DMSO, thiosulfate, nitrate, and polysulfide. I will discuss our emerging model for how strain ANA-3 respires arsenate and the relationship between arsenite resistance and arsenate respiration. I will also highlight the relevance of this type of analysis for biogeochemical studies.

Enterococcus faecalis Constitutes an Unusual Bacterial Model in Lysozyme Resistance▿

PubMed Central

Hébert, Laurent; Courtin, Pascal; Torelli, Riccardo; Sanguinetti, Maurizio; Chapot-Chartier, Marie-Pierre; Auffray, Yanick; Benachour, Abdellah

2007-01-01

Lysozyme is an important and widespread compound of the host constitutive defense system, and it is assumed that Enterococcus faecalis is one of the few bacteria that are almost completely lysozyme resistant. On the basis of the sequence analysis of the whole genome of E. faecalis V583 strain, we identified two genes that are potentially involved in lysozyme resistance, EF_0783 and EF_1843. Protein products of these two genes share significant homology with Staphylococcus aureus peptidoglycan O-acetyltransferase (OatA) and Streptococcus pneumoniae N-acetylglucosamine deacetylase (PgdA), respectively. In order to determine whether EF_0783 and EF_1843 are involved in lysozyme resistance, we constructed their corresponding mutants and a double mutant. The ΔEF_0783 mutant and ΔEF_0783 ΔEF_1843 double mutant were shown to be more sensitive to lysozyme than the parental E. faecalis JH2-2 strain and ΔEF_1843 mutant were. However, compared to other bacteria, such as Listeria monocytogenes or S. pneumoniae, the tolerance of ΔEF_0783 and ΔEF_0783 ΔEF_1843 mutants towards lysozyme remains very high. Peptidoglycan structure analysis showed that EF_0783 modifies the peptidoglycan by O acetylation of N-acetyl muramic acid, while the EF_1843 deletion has no obvious effect on peptidoglycan structure under the same conditions. Moreover, the EF_0783 and EF_1843 deletions seem to significantly affect the ability of E. faecalis to survive within murine macrophages. In all, while EF_0783 is currently involved in the lysozyme resistance of E. faecalis, peptidoglycan O acetylation and de-N-acetylation are not the main mechanisms conferring high levels of lysozyme resistance to E. faecalis. PMID:17785473

Inhibition of disheveled-2 resensitizes cisplatin-resistant lung cancer cells through down-regulating Wnt/β-catenin signaling

DOE Office of Scientific and Technical Information (OSTI.GOV)

Luo, Ke; Gu, Xiuhui; Liu, Jing

Cisplatin (CDDP) is currently recommended as the front-line chemotherapeutic agent for lung cancer. However, the resistance to cisplatin is widespread in patients with advanced lung cancer, and the molecular mechanism of such resistance remains incompletely understood. Disheveled (DVL), a key mediator of Wnt/β-catenin, has been linked to cancer progression, while the role of DVL in cancer drug resistance is not clear. Here, we found that DVL2 was over-expressed in cisplatin-resistant human lung cancer cells A549/CDDP compared to the parental A549 cells. Inhibition of DVL2 by its inhibitor (3289-8625) or shDVL2 resensitized A549/CDDP cells to cisplatin. In addition, over-expression of DVL2more » in A549 cells increased the protein levels of BCRP, MRP4, and Survivin, which are known to be associated with chemoresistance, while inhibition of DVL2 in A549/CDDP cells decreased these protein levels, and reduced the accumulation and nuclear translocation of β-catenin. In addition, shβ-catenin abolished the DVL2-induced the expression of BCRP, MRP4, and Survivin. Furthermore, our data showed that GSK3β/β-catenin signals were aberrantly activated by DVL2, and inactivation of GSK3β reversed the shDVL2-induced down-regulation of β-catenin. Taken together, these results suggested that inhibition of DVL2 can sensitize cisplatin-resistant lung cancer cells through down-regulating Wnt/β-catenin signaling and inhibiting BCRP, MRP4, and Survivin expression. It promises a new strategy to chemosensitize cisplatin-induced cytotoxicity in lung cancer. - Highlights: • Inhibition of DVL2 chemosensitizes resistant lung cancer to cisplatin. • DVL2 positively regulated the expression of BCRP, MRP4 and Survivin. • β-catenin mediated the DVL2-induced expression. • DVL2 increased the accumulation and nuclear translocation of β-catenin. • DVL2 up-regulated β-catenin via inhibiting GSK3β.« less

Increasing awareness about antibiotic use and resistance: a hands-on project for high school students.

PubMed

Fonseca, Maria João; Santos, Catarina L; Costa, Patrício; Lencastre, Leonor; Tavares, Fernando

2012-01-01

Health-promoting education is essential to foster an informed society able to make decisions about socio-scientific issues based on scientifically sustained criteria. Antibiotic resistance is currently a major public health issue. Considering that irrational antibiotic use has been associated with the development and widespread of antibiotic resistant bacteria, educational interventions to promote prudent antibiotic consumption are required. This study focuses on the outcomes of an interventional program implemented at the University of Porto, Portugal, to promote awareness about antibiotic resistance at high school levels (15-17 year old). The project Microbiology recipes: antibiotics à la carte articulates a set of wet and dry lab activities designed to promote the participants' understanding of concepts and processes underlying antibiotics' production and activity, such as the notion of mechanisms of action of antibiotics. Following a mix-method approach based on a pre-/post design, the effectiveness of this project was assessed by gathering data from surveys, direct observation and analysis of artifacts of 42 high school students (aged 15 and 16 years). The results indicate that the participants developed a more comprehensive picture of antibiotic resistance. The project was shown to promote more sophisticated conceptualizations of bacteria and antibiotics, increased awareness about the perils of antibiotic resistance, and enhanced consciousness towards measures that can be undertaken to mitigate the problem. The participants regarded their experiences as enjoyable and useful, and believed that the project contributed to improve their understanding and raise their interest about the issues discussed. Furthermore, there were also improvements in their procedural skills concerning the laboratory techniques performed. This study evidences the possibility of increasing high school students' awareness about the consequences of antibiotic resistance and the importance of judicious antibiotic use. The findings inform about the educational benefits of incorporating hands-on activities in science education programs.

Antibiotic-resistant bacteria show widespread collateral sensitivity to antimicrobial peptides.

PubMed

Lázár, Viktória; Martins, Ana; Spohn, Réka; Daruka, Lejla; Grézal, Gábor; Fekete, Gergely; Számel, Mónika; Jangir, Pramod K; Kintses, Bálint; Csörgő, Bálint; Nyerges, Ákos; Györkei, Ádám; Kincses, András; Dér, András; Walter, Fruzsina R; Deli, Mária A; Urbán, Edit; Hegedűs, Zsófia; Olajos, Gábor; Méhi, Orsolya; Bálint, Balázs; Nagy, István; Martinek, Tamás A; Papp, Balázs; Pál, Csaba

2018-06-01

Antimicrobial peptides are promising alternative antimicrobial agents. However, little is known about whether resistance to small-molecule antibiotics leads to cross-resistance (decreased sensitivity) or collateral sensitivity (increased sensitivity) to antimicrobial peptides. We systematically addressed this question by studying the susceptibilities of a comprehensive set of 60 antibiotic-resistant Escherichia coli strains towards 24 antimicrobial peptides. Strikingly, antibiotic-resistant bacteria show a high frequency of collateral sensitivity to antimicrobial peptides, whereas cross-resistance is relatively rare. We identify clinically relevant multidrug-resistance mutations that increase bacterial sensitivity to antimicrobial peptides. Collateral sensitivity in multidrug-resistant bacteria arises partly through regulatory changes shaping the lipopolysaccharide composition of the bacterial outer membrane. These advances allow the identification of antimicrobial peptide-antibiotic combinations that enhance antibiotic activity against multidrug-resistant bacteria and slow down de novo evolution of resistance. In particular, when co-administered as an adjuvant, the antimicrobial peptide glycine-leucine-amide caused up to 30-fold decrease in the antibiotic resistance level of resistant bacteria. Our work provides guidelines for the development of efficient peptide-based therapies of antibiotic-resistant infections.

Disrupting Mosquito Reproduction and Parasite Development for Malaria Control

PubMed Central

Gabrieli, Paolo; Buckee, Caroline O.; Catteruccia, Flaminia

2016-01-01

The control of mosquito populations with insecticide treated bed nets and indoor residual sprays remains the cornerstone of malaria reduction and elimination programs. In light of widespread insecticide resistance in mosquitoes, however, alternative strategies for reducing transmission by the mosquito vector are urgently needed, including the identification of safe compounds that affect vectorial capacity via mechanisms that differ from fast-acting insecticides. Here, we show that compounds targeting steroid hormone signaling disrupt multiple biological processes that are key to the ability of mosquitoes to transmit malaria. When an agonist of the steroid hormone 20-hydroxyecdysone (20E) is applied to Anopheles gambiae females, which are the dominant malaria mosquito vector in Sub Saharan Africa, it substantially shortens lifespan, prevents insemination and egg production, and significantly blocks Plasmodium falciparum development, three components that are crucial to malaria transmission. Modeling the impact of these effects on Anopheles population dynamics and Plasmodium transmission predicts that disrupting steroid hormone signaling using 20E agonists would affect malaria transmission to a similar extent as insecticides. Manipulating 20E pathways therefore provides a powerful new approach to tackle malaria transmission by the mosquito vector, particularly in areas affected by the spread of insecticide resistance. PMID:27977810

Synthesis, characterization, and efficacy of antimicrobial chlorhexidine hexametaphosphate nanoparticles for applications in biomedical materials and consumer products

PubMed Central

Barbour, Michele E; Maddocks, Sarah E; Wood, Natalie J; Collins, Andrew M

2013-01-01

Chlorhexidine (CHX) is an antimicrobial agent that is efficacious against gram-negative and -positive bacteria and yeasts. Its mechanism of action is based on cell membrane disruption and, as such, it does not promote the development of bacterial resistance, which is associated with the widespread use of antibiotics. In this manuscript, we report the development of novel antimicrobial nanoparticles (NPs) based on a hexametaphosphate salt of CHX. These are synthesized by instantaneous reaction between equimolar aqueous solutions of CHX digluconate and sodium hexametaphosphate, under room temperature and pressure. The reaction results in a stable colloid composed of highly negatively charged NPs (−50 mV), of size 20–160 nm. The NPs adhere rapidly to specimens of glass, titanium, and an elastomeric wound dressing, in a dose-dependent manner. The functionalized materials exhibit a gradual leaching of soluble CHX over a period of at least 50 days. The NP colloid is efficacious against methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa in both planktonic and biofilm conditions. These NPs may find application in a range of biomedical and consumer materials. PMID:24092973

An enhanced password authentication scheme for session initiation protocol with perfect forward secrecy

PubMed Central

2018-01-01

The Session Initiation Protocol (SIP) is an extensive and esteemed communication protocol employed to regulate signaling as well as for controlling multimedia communication sessions. Recently, Kumari et al. proposed an improved smart card based authentication scheme for SIP based on Farash’s scheme. Farash claimed that his protocol is resistant against various known attacks. But, we observe some accountable flaws in Farash’s protocol. We point out that Farash’s protocol is prone to key-compromise impersonation attack and is unable to provide pre-verification in the smart card, efficient password change and perfect forward secrecy. To overcome these limitations, in this paper we present an enhanced authentication mechanism based on Kumari et al.’s scheme. We prove that the proposed protocol not only overcomes the issues in Farash’s scheme, but it can also resist against all known attacks. We also provide the security analysis of the proposed scheme with the help of widespread AVISPA (Automated Validation of Internet Security Protocols and Applications) software. At last, comparing with the earlier proposals in terms of security and efficiency, we conclude that the proposed protocol is efficient and more secure. PMID:29547619

Effects of Benzalkonium Chloride on Planktonic Growth and Biofilm Formation by Animal Bacterial Pathogens

PubMed Central

Ebrahimi, Azizollah; Hemati, Majid; Shabanpour, Ziba; Habibian Dehkordi, Saeed; Bahadoran, Shahab; Lotfalian, Sharareh; Khubani, Shahin

2015-01-01

Background: Resistance toward quaternary ammonium compounds (QACs) is widespread among a diverse range of microorganisms and is facilitated by several mechanisms such as biofilm formation. Objectives: In this study, the effects of benzalkonium chloride on planktonic growth and biofilm formation by some field isolates of animal bacterial pathogens were investigated. Materials and Methods: Forty clinical isolates of Escherichia coli, Salmonella serotypes, Staphylococcus aureus and Streptococcus agalactiae (10 isolates of each) were examined for effects of benzalkonium chloride on biofilm formation and planktonic growth using microtiter plates. For all the examined strains in the presence of benzalkonium chloride, biofilm development and planktonic growth were affected at the same concentrations of disinfectant. Results: The means of strains growth increase after the minimal inhibitory concentration (MIC) were significant in all the bacteria (except for E. coli in 1/32 and S. agalactiae in of 1/8 MIC). Biofilm formation increased with decrease of antiseptics concentration; a significant increase was found in all the samples. The most turbidity related to S. aureus and the least to Salmonella. Conclusions: Bacterial resistance against quaternary ammonium compounds is increasing which can increase the bacterial biofilm formation. PMID:25793094

Life in an Arsenic-Containing Gold Mine: Genome and Physiology of the Autotrophic Arsenite-Oxidizing Bacterium Rhizobium sp. NT-26

PubMed Central

Andres, Jérémy; Arsène-Ploetze, Florence; Barbe, Valérie; Brochier-Armanet, Céline; Cleiss-Arnold, Jessica; Coppée, Jean-Yves; Dillies, Marie-Agnès; Geist, Lucie; Joublin, Aurélie; Koechler, Sandrine; Lassalle, Florent; Marchal, Marie; Médigue, Claudine; Muller, Daniel; Nesme, Xavier; Plewniak, Frédéric; Proux, Caroline; Ramírez-Bahena, Martha Helena; Schenowitz, Chantal; Sismeiro, Odile; Vallenet, David; Santini, Joanne M.; Bertin, Philippe N.

2013-01-01

Arsenic is widespread in the environment and its presence is a result of natural or anthropogenic activities. Microbes have developed different mechanisms to deal with toxic compounds such as arsenic and this is to resist or metabolize the compound. Here, we present the first reference set of genomic, transcriptomic and proteomic data of an Alphaproteobacterium isolated from an arsenic-containing goldmine: Rhizobium sp. NT-26. Although phylogenetically related to the plant-associated bacteria, this organism has lost the major colonizing capabilities needed for symbiosis with legumes. In contrast, the genome of Rhizobium sp. NT-26 comprises a megaplasmid containing the various genes, which enable it to metabolize arsenite. Remarkably, although the genes required for arsenite oxidation and flagellar motility/biofilm formation are carried by the megaplasmid and the chromosome, respectively, a coordinate regulation of these two mechanisms was observed. Taken together, these processes illustrate the impact environmental pressure can have on the evolution of bacterial genomes, improving the fitness of bacterial strains by the acquisition of novel functions. PMID:23589360

THE DEVELOPMENT AND TREND OF INSECTICIDE-RESISTANCE IN ANOPHELES ACONITUS DOENITZ AND ANOPHELES SUNDAICUS RODENWALDT.

PubMed

SOERONO, M; DAVIDSON, G; MUIR, D A

1965-01-01

The spread of insecticide-resistance in the two main vectors of malaria in Java, Anopheles aconitus Dönitz and A. sundaicus Rodenwaldt, has been of concern to workers in the Indonesian malaria eradication programme since DDT-resistance was first detected, in A. sundaicus, in 1954. The history of development of resistance in these two vectors has been summarized in this paper by assembling the available records in chronological order, thus facilitating reference.The picture which emerges is that of somewhat erratic occurrence of DDT-resistance in A. sundaicus and more stable, expanding areas of DDT-resistant A. aconitus. Dieldrin-resistance is more widespread than DDT-resistance in both species and preceded the onset of DDT-resistance in A. aconitus but not in A. sundaicus. These features should not be regarded as species characteristics, however, since selection pressures on the two species have been far from uniform.Malathion appears to be a promising alternative to DDT and dieldrin for the control of the two vectors in the circumstances described.

Genetic Mimetics of Mycobacterium tuberculosis and Methicillin-Resistant Staphylococcus aureus as Verification Standards for Molecular Diagnostics.

PubMed

Machowski, Edith Erika; Kana, Bavesh Davandra

2017-12-01

Molecular diagnostics have revolutionized the management of health care through enhanced detection of disease or infection and effective enrollment into treatment. In recognition of this, the World Health Organization approved the rollout of nucleic acid amplification technologies for identification of Mycobacterium tuberculosis using platforms such as GeneXpert MTB/RIF, the GenoType MTBDR plus line probe assay, and, more recently, GeneXpert MTB/RIF Ultra. These assays can simultaneously detect tuberculosis infection and assess rifampin resistance. However, their widespread use in health systems requires verification and quality assurance programs. To enable development of these, we report the construction of genetically modified strains of Mycobacterium smegmatis that mimic the profile of Mycobacterium tuberculosis on both the GeneXpert MTB/RIF and the MTBDR plus line probe diagnostic tests. Using site-specific gene editing, we also created derivatives that faithfully mimic the diagnostic result of rifampin-resistant M. tuberculosis , with mutations at positions 513, 516, 526, 531, and 533 in the rifampin resistance-determining region of the rpoB gene. Next, we extended this approach to other diseases and demonstrated that a Staphylococcus aureus gene sequence can be introduced into M. smegmatis to generate a positive response for the SCC mec probe in the GeneXpert SA Nasal Complete molecular diagnostic cartridge, designed for identification of methicillin-resistant S. aureus These biomimetic strains are cost-effective, have low biohazard content, accurately mimic drug resistance, and can be produced with relative ease, thus illustrating their potential for widespread use as verification standards for diagnosis of a variety of diseases. Copyright © 2017 American Society for Microbiology.

Anthelmintic resistance in equine nematodes

PubMed Central

Matthews, Jacqueline B.

2014-01-01

Anthelmintics have been applied indiscriminately to control horse nematodes for over 40 years. Three broad-spectrum anthelmintic classes are currently registered for nematode control in horses: benzimidazoles (fenbendazole, oxibendazole), tetrahydropyrimidines (pyrantel) and macrocyclic lactones (ivermectin, moxidectin). Generally, control strategies have focused on nematode egg suppression regimens that involve the frequent application of anthelmintics to all horses at intervals based on strongyle egg reappearance periods after treatment. The widespread use of such programmes has substantially reduced clinical disease, especially that associated with large strongyle species; however, high treatment frequency has led to considerable selection pressure for anthelmintic resistance, particularly in cyathostomin species. Field studies published over the last decade indicate that benzimidazole resistance is widespread globally in cyathostomins and there are also many reports of resistance to pyrantel in these worms. Cyathostomin resistance to macrocyclic lactone compounds is emerging, principally measured as a reduction in strongyle egg reappearance time observed after treatment. Ivermectin resistance is a further concern in the small intestinal nematode, Parascaris equorum, an important pathogen of foals. These issues indicate that horse nematodes must now be controlled using methods less dependent on anthelmintic use and more reliant on management practices designed to reduce the force of infection in the environment. Such strategies include improved grazing management integrated with targeted anthelmintic administration involving faecal egg count (FEC)-directed treatments. The latter require that the supporting diagnostic tests available are robust and practically applicable. Recent research has focused on maximising the value of FEC analysis in horses and on optimizing protocols for anthelmintic efficacy testing. Other studies have sought to develop diagnostics that will help define levels of pre-patent infection. This review describes recent advances in each of these areas of research. PMID:25516842

Aerobic, resistance or combined training: A systematic review and meta-analysis of exercise to reduce cardiovascular risk in adults with metabolic syndrome.

PubMed

Wewege, Michael A; Thom, Jeanette M; Rye, Kerry-Anne; Parmenter, Belinda J

2018-05-03

Exercise is beneficial to individuals with metabolic syndrome (MetS). An understudied group, who represent the majority of the MetS population, are individuals who have not developed diabetes. This review examined aerobic, resistance and combined (aerobic + resistance) exercise for cardiovascular risk factors in MetS without diabetes. Eight electronic databases were searched up to September 2017 for randomised controlled trials >4 weeks in duration that compared an exercise intervention to the non-exercise control in MetS without diabetes. MetS criteria, cardiorespiratory fitness and cardiovascular risk factors were meta-analysed in a random effects model. Eleven studies with 16 interventions were included (12 aerobic, 4 resistance). Aerobic exercise significantly improved waist circumference -3.4 cm (p < 0.01), fasting glucose -0.15 mmol/L (p = 0.03), high-density cholesterol 0.05 mmol/L (p = 0.02), triglycerides -0.29 mmol/L (p < 0.01), diastolic blood pressure -1.6 mmHg (p = 0.01), and cardiorespiratory fitness 4.2 ml/kg/min (p < 0.01), among other outcomes. No significant effects were determined following resistance exercise possibly due to limited data. Sub-analyses suggested that aerobic exercise progressed to vigorous intensity, and conducted 3 days/week for ≥12 weeks offered larger and more widespread improvements. Aerobic exercise following current guidelines offers widespread benefits to individuals with MetS without diabetes. More studies on resistance/combined exercise programs in MetS are required to improve the quality of evidence. Copyright © 2018 Elsevier B.V. All rights reserved.

Brave New World: The Information Management Revolution.

ERIC Educational Resources Information Center

McIntyre, Jim

1995-01-01

Indiana University and the University of Delaware have begun to expand the notion of financial information management by the innovative use of computer and Internet applications. Widespread access to institutional information has advantages and disadvantages. At both institutions, information managers addressed administrative resistance but…

The development of pathogen resistance in Daphnia magna: implications for disease spread in age-structured populations.

PubMed

Garbutt, Jennie S; O'Donoghue, Anna J P; McTaggart, Seanna J; Wilson, Philip J; Little, Tom J

2014-11-01

Immunity in vertebrates is well established to develop with time, but the ontogeny of defence in invertebrates is markedly less studied. Yet, age-specific capacity for defence against pathogens, coupled with age structure in populations, has widespread implications for disease spread. Thus, we sought to determine the susceptibility of hosts of different ages in an experimental invertebrate host-pathogen system. In a series of experiments, we show that the ability of Daphnia magna to resist its natural bacterial pathogen Pasteuria ramosa changes with host age. Clonal differences make it difficult to draw general conclusions, but the majority of observations indicate that resistance increases early in the life of D. magna, consistent with the idea that the defence system develops with time. Immediately following this, at about the time when a daphnid would be most heavily investing in reproduction, resistance tends to decline. Because many ecological factors influence the age structure of Daphnia populations, our results highlight a broad mechanism by which ecological context can affect disease epidemiology. We also show that a previously observed protective effect of restricted maternal food persists throughout the entire juvenile period, and that the protective effect of prior treatment with a small dose of the pathogen ('priming') persists for 7 days, observations that reinforce the idea that immunity in D. magna can change over time. Together, our experiments lead us to conclude that invertebrate defence capabilities have an ontogeny that merits consideration with respect to both their immune systems and the epidemic spread of infection. © 2014. Published by The Company of Biologists Ltd.

The development of pathogen resistance in Daphnia magna: implications for disease spread in age-structured populations

PubMed Central

Garbutt, Jennie S.; O'Donoghue, Anna J. P.; McTaggart, Seanna J.; Wilson, Philip J.; Little, Tom J.

2014-01-01

Immunity in vertebrates is well established to develop with time, but the ontogeny of defence in invertebrates is markedly less studied. Yet, age-specific capacity for defence against pathogens, coupled with age structure in populations, has widespread implications for disease spread. Thus, we sought to determine the susceptibility of hosts of different ages in an experimental invertebrate host–pathogen system. In a series of experiments, we show that the ability of Daphnia magna to resist its natural bacterial pathogen Pasteuria ramosa changes with host age. Clonal differences make it difficult to draw general conclusions, but the majority of observations indicate that resistance increases early in the life of D. magna, consistent with the idea that the defence system develops with time. Immediately following this, at about the time when a daphnid would be most heavily investing in reproduction, resistance tends to decline. Because many ecological factors influence the age structure of Daphnia populations, our results highlight a broad mechanism by which ecological context can affect disease epidemiology. We also show that a previously observed protective effect of restricted maternal food persists throughout the entire juvenile period, and that the protective effect of prior treatment with a small dose of the pathogen (‘priming’) persists for 7 days, observations that reinforce the idea that immunity in D. magna can change over time. Together, our experiments lead us to conclude that invertebrate defence capabilities have an ontogeny that merits consideration with respect to both their immune systems and the epidemic spread of infection. PMID:25214486

Detection of the V1016G mutation in the voltage-gated sodium channel gene of Aedes aegypti (Diptera: Culicidae) by allele-specific PCR assay, and its distribution and effect on deltamethrin resistance in Thailand.

PubMed

Stenhouse, Steven A; Plernsub, Suriya; Yanola, Jintana; Lumjuan, Nongkran; Dantrakool, Anchalee; Choochote, Wej; Somboon, Pradya

2013-08-30

Resistance to pyrethroid insecticides is widespread among populations of Aedes aegypti, the main vector for the dengue virus. Several different point mutations within the voltage-gated sodium channel (VGSC) gene contribute to such resistance. A mutation at position 1016 in domain II, segment 6 of the VGSC gene in Ae. aegypti leads to a valine to glycine substitution (V1016G) that confers resistance to deltamethrin. This study developed and utilized an allele-specific PCR (AS-PCR) assay that could be used to detect the V1016G mutation. The assay was validated against a number of sequenced DNA samples of known genotype and was determined to be in complete agreement. Larvae and pupae were collected from various localities throughout Thailand. Samples were reared to adulthood and their resistance status against deltamethrin was determined by standard WHO susceptibility bioassays. Deltamethrin-resistant and susceptible insects were then genotyped for the V1016G mutation. Additionally, some samples were genotyped for a second mutation at position 1534 in domain III (F1534C) which is also known to confer pyrethroid resistance. The bioassay results revealed an overall mortality of 77.6%. Homozygous 1016G individuals survived at higher rates than either heterozygous or wild-type (1016 V) mosquitoes. The 1016G mutation was significantly and positively associated with deltamethrin resistance and was widely distributed throughout Thailand. Interestingly, wild-type 1016 V mosquitoes tested were homozygous for the 1534C mutation, and all heterozygous mosquitoes were also heterozygous for 1534C. Mutant homozygous (G/G) mosquitoes expressed the wild-type (F/F) at position 1534. However, the presence of the 1534C mutation was not associated with deltamethrin resistance. Our bioassay results indicate that all populations sampled display some degree of resistance to deltamethrin. Homozygous 1016G mosquitoes were far likelier to survive such exposure. However, resistance in some populations cannot be explained due to kdr mutations and indicates that other resistance mechanisms are operating. The presence of this mutation alone does not fully explain the resistance phenotype we see among Thai Ae. aegypti populations.

Spontaneous mutation rate is a plastic trait associated with population density across domains of life.

PubMed

Krašovec, Rok; Richards, Huw; Gifford, Danna R; Hatcher, Charlie; Faulkner, Katy J; Belavkin, Roman V; Channon, Alastair; Aston, Elizabeth; McBain, Andrew J; Knight, Christopher G

2017-08-01

Rates of random, spontaneous mutation can vary plastically, dependent upon the environment. Such plasticity affects evolutionary trajectories and may be adaptive. We recently identified an inverse plastic association between mutation rate and population density at 1 locus in 1 species of bacterium. It is unknown how widespread this association is, whether it varies among organisms, and what molecular mechanisms of mutagenesis or repair are required for this mutation-rate plasticity. Here, we address all 3 questions. We identify a strong negative association between mutation rate and population density across 70 years of published literature, comprising hundreds of mutation rates estimated using phenotypic markers of mutation (fluctuation tests) from all domains of life and viruses. We test this relationship experimentally, determining that there is indeed density-associated mutation-rate plasticity (DAMP) at multiple loci in both eukaryotes and bacteria, with up to 23-fold lower mutation rates at higher population densities. We find that the degree of plasticity varies, even among closely related organisms. Nonetheless, in each domain tested, DAMP requires proteins scavenging the mutagenic oxidised nucleotide 8-oxo-dGTP. This implies that phenotypic markers give a more precise view of mutation rate than previously believed: having accounted for other known factors affecting mutation rate, controlling for population density can reduce variation in mutation-rate estimates by 93%. Widespread DAMP, which we manipulate genetically in disparate organisms, also provides a novel trait to use in the fight against the evolution of antimicrobial resistance. Such a prevalent environmental association and conserved mechanism suggest that mutation has varied plastically with population density since the early origins of life.

Spontaneous mutation rate is a plastic trait associated with population density across domains of life

PubMed Central

Gifford, Danna R.; Hatcher, Charlie; Faulkner, Katy J.; Belavkin, Roman V.; Channon, Alastair; Aston, Elizabeth; McBain, Andrew J.

2017-01-01

Rates of random, spontaneous mutation can vary plastically, dependent upon the environment. Such plasticity affects evolutionary trajectories and may be adaptive. We recently identified an inverse plastic association between mutation rate and population density at 1 locus in 1 species of bacterium. It is unknown how widespread this association is, whether it varies among organisms, and what molecular mechanisms of mutagenesis or repair are required for this mutation-rate plasticity. Here, we address all 3 questions. We identify a strong negative association between mutation rate and population density across 70 years of published literature, comprising hundreds of mutation rates estimated using phenotypic markers of mutation (fluctuation tests) from all domains of life and viruses. We test this relationship experimentally, determining that there is indeed density-associated mutation-rate plasticity (DAMP) at multiple loci in both eukaryotes and bacteria, with up to 23-fold lower mutation rates at higher population densities. We find that the degree of plasticity varies, even among closely related organisms. Nonetheless, in each domain tested, DAMP requires proteins scavenging the mutagenic oxidised nucleotide 8-oxo-dGTP. This implies that phenotypic markers give a more precise view of mutation rate than previously believed: having accounted for other known factors affecting mutation rate, controlling for population density can reduce variation in mutation-rate estimates by 93%. Widespread DAMP, which we manipulate genetically in disparate organisms, also provides a novel trait to use in the fight against the evolution of antimicrobial resistance. Such a prevalent environmental association and conserved mechanism suggest that mutation has varied plastically with population density since the early origins of life. PMID:28837573

Experiential Training for Empowerment of the Workforce.

ERIC Educational Resources Information Center

Cook, John A.

As downsizing of government and business organizations has become widespread, many managers are seeking to increase productivity by empowering the workforce. When effectively and appropriately implemented, empowered workforce structures can cut costs and improve quality and safety. Yet resistance to such changes arises from a patriarchal…

Public transport as a reservoir of methicillin-resistant staphylococci.

PubMed

Stepanović, S; Cirković, I; Djukić, S; Vuković, D; Svabić-Vlahović, M

2008-10-01

The aim of this study was to explore the occurrence of methicillin-resistant staphylococci in a large urban public transport system. Samples were taken from hand rails, which passengers hold onto when they are standing. In total, 1400 swabs taken from 55 vehicles (trolleybuses, trams and buses) were examined. As many as 30.1% samples were positive for the presence of methicillin-resistant coagulase-negative staphylococci (MRCoNS), but none for methicillin-resistant Staphylococcus aureus (MRSA). MRCoNS were isolated from all 55 vehicles. Nearly 50% of MRCoNS isolates displayed resistance not only to beta-lactams, but at least to two or more other classes of antimicrobials as well. This study demonstrated widespread occurrence of MRCoNS on hand rails in public transport vehicles. MRSA was not detected. The recovery of methicillin-resistant staphylococci from public transport system implies a potential risk for transmission of these bacteria in an out-hospital environment.

Increasing incidence of fluoroquinolone-resistant Mycobacterium tuberculosis in Mumbai, India.

PubMed

Agrawal, D; Udwadia, Z F; Rodriguez, C; Mehta, A

2009-01-01

Tertiary referral centre, private hospital, Mumbai, India. To analyse the incidence of fluoroquinolone (FQ) resistant Mycobacterium tuberculosis (TB) in our laboratory from 1995 to 2004. Retrospective review and analysis of the drug susceptibility test records of all M. tuberculosis culture-positive samples from our Microbiology Department from 1995 to 2004. FQ resistance has increased exponentially in our laboratory, from 3% in 1996 to 35% in 2004. The incidence of multidrug-resistant tuberculosis has also increased during the same period, from 33% in 1995 to 56% in 2004. The incidence of FQ-resistant M. tuberculosis is gradually increasing to alarming levels. This may be due to widespread use of this vital group of drugs in the treatment of community-acquired infections. We urge that these broad spectrum antibiotics be used judiciously, and ideally be reserved for treatment of resistant TB in TB-endemic areas.

Chloroquine-resistant falciparum malaria in East Kalimantan, Indonesia.

PubMed

Verdrager, J; Arwati; Simanjuntak, C H; Saroso, J S

1976-03-01

Following the discovery of four imported chloroquine-resistant P. falciparum infections in the Province of Yogyakarta (Island of Java) sensitivity tests were carried out in the Province of East Kalimantan Island of Borneo). Twenty subjects were given 25 mg. of chloroquine base per kilogram of body weight over three days. Two infections were found resistant at the RII level and a third at the RI level with early recrudescence on day 7. In the other 17 cases followed up to day 21, six were found again with asexual parasites between day 9 and day 14 and a seventh on day 21. These results confirm the presence of chloroquine resistance in P. falciparum in East Kalimantan and, together with previous findings, suggest a widespread distribution of chloroquine-resistant falciparum malaria in this Province of Indonesia. It is particularly interesting to note that chloroquine-resistant falciparum malaria has now been detected in almost all the area of dispersion of A. balabacensis.

Increased resistance to ciprofloxacin and ofloxacin in multidrug-resistant mycobacterium tuberculosis isolates from patients seen at a tertiary hospital in the Philippines.

PubMed

Grimaldo, E R; Tupasi, T E; Rivera, A B; Quelapio, M I; Cardaño, R C; Derilo, J O; Belen, V A

2001-06-01

A hospital-based study at the Makati Medical Center, Makati City, Philippines, a hyperendemic area for tuberculosis (TB). To determine the susceptibility of Mycobacterium tuberculosis to ciprofloxacin and ofloxacin. Retrospective analysis of drug susceptibility tests (DST) of M. tuberculosis isolated from 1995-2000. Resistance to ciprofloxacin was 26.8%, ofloxacin 35.3%, and multidrug resistance (MDR) was 17.2%. Of the MDR strains, 51.4% were resistant to ciprofloxacin and ofloxacin. Acquired resistance was significantly higher for all first-line drugs and for ciprofloxacin, but not for ofloxacin. A significant increase in resistance to ciprofloxacin and ofloxacin was noted compared to 1989-1994, while resistance to the firstline drugs was not significantly different. Ciprofloxacin and ofloxacin are now a significantly less effective alternative therapy in tuberculosis, particularly MDR-TB, due to a selection pressure from their widespread use in the treatment of TB and possibly other infections in the community, which is hyperendemic for tuberculosis.

Internal strain drives spontaneous periodic buckling in collagen and regulates remodeling.

PubMed

Dittmore, Andrew; Silver, Jonathan; Sarkar, Susanta K; Marmer, Barry; Goldberg, Gregory I; Neuman, Keir C

2016-07-26

Fibrillar collagen, an essential structural component of the extracellular matrix, is remarkably resistant to proteolysis, requiring specialized matrix metalloproteinases (MMPs) to initiate its remodeling. In the context of native fibrils, remodeling is poorly understood; MMPs have limited access to cleavage sites and are inhibited by tension on the fibril. Here, single-molecule recordings of fluorescently labeled MMPs reveal cleavage-vulnerable binding regions arrayed periodically at ∼1-µm intervals along collagen fibrils. Binding regions remain periodic even as they migrate on the fibril, indicating a collective process of thermally activated and self-healing defect formation. An internal strain relief model involving reversible structural rearrangements quantitatively reproduces the observed spatial patterning and fluctuations of defects and provides a mechanism for tension-dependent stabilization of fibrillar collagen. This work identifies internal-strain-driven defects that may have general and widespread regulatory functions in self-assembled biological filaments.

Natural Products: An Alternative to Conventional Therapy for Dermatophytosis?

PubMed

Lopes, Graciliana; Pinto, Eugénia; Salgueiro, Lígia

2017-02-01

The increased incidence of fungal infections, associated with the widespread use of antifungal drugs, has resulted in the development of resistance, making it necessary to discover new therapeutic alternatives. Among fungal infections, dermatophytoses constitute a serious public health problem, affecting 20-25 % of the world population. Medicinal plants represent an endless source of bioactive molecules, and their volatile and non-volatile extracts are clearly recognized for being the historical basis of therapeutic health care. Because of this, the research on natural products with antifungal activity against dermatophytes has considerably increased in recent years. However, despite the recognized anti-dermatophytic potential of natural products, often advantageous face to commercial drugs, there is still a long way to go until their use in therapeutics. This review attempts to summarize the current status of anti-dermatophytic natural products, focusing on their mechanism of action, the developed pharmaceutical formulations and their effectiveness in human and animal models of infection.

Specification and misspecification of theoretical foundations and logic models for health communication campaigns.

PubMed

Slater, Michael D

2006-01-01

While increasingly widespread use of behavior change theory is an advance for communication campaigns and their evaluation, such theories provide a necessary but not sufficient condition for theory-based communication interventions. Such interventions and their evaluations need to incorporate theoretical thinking about plausible mechanisms of message effect on health-related attitudes and behavior. Otherwise, strategic errors in message design and dissemination, and misspecified campaign logic models, insensitive to campaign effects, are likely to result. Implications of the elaboration likelihood model, attitude accessibility, attitude to the ad theory, exemplification, and framing are explored, and implications for campaign strategy and evaluation designs are briefly discussed. Initial propositions are advanced regarding a theory of campaign affect generalization derived from attitude to ad theory, and regarding a theory of reframing targeted health behaviors in those difficult contexts in which intended audiences are resistant to the advocated behavior or message.

Internal strain drives spontaneous periodic buckling in collagen and regulates remodeling

PubMed Central

Dittmore, Andrew; Silver, Jonathan; Sarkar, Susanta K.; Marmer, Barry; Goldberg, Gregory I.; Neuman, Keir C.

2016-01-01

Fibrillar collagen, an essential structural component of the extracellular matrix, is remarkably resistant to proteolysis, requiring specialized matrix metalloproteinases (MMPs) to initiate its remodeling. In the context of native fibrils, remodeling is poorly understood; MMPs have limited access to cleavage sites and are inhibited by tension on the fibril. Here, single-molecule recordings of fluorescently labeled MMPs reveal cleavage-vulnerable binding regions arrayed periodically at ∼1-µm intervals along collagen fibrils. Binding regions remain periodic even as they migrate on the fibril, indicating a collective process of thermally activated and self-healing defect formation. An internal strain relief model involving reversible structural rearrangements quantitatively reproduces the observed spatial patterning and fluctuations of defects and provides a mechanism for tension-dependent stabilization of fibrillar collagen. This work identifies internal–strain-driven defects that may have general and widespread regulatory functions in self-assembled biological filaments. PMID:27402741

Synergistic antimicrobial therapy using nanoparticles and antibiotics for the treatment of multidrug-resistant bacterial infection

NASA Astrophysics Data System (ADS)

Gupta, Akash; Saleh, Neveen M.; Das, Riddha; Landis, Ryan F.; Bigdeli, Arafeh; Motamedchaboki, Khatereh; Rosa Campos, Alexandre; Pomeroy, Kenneth; Mahmoudi, Morteza; Rotello, Vincent M.

2017-06-01

Infections caused by multidrug-resistant (MDR) bacteria pose a serious global burden of mortality, causing thousands of deaths each year. Antibiotic treatment of resistant infections further contributes to the rapidly increasing number of antibiotic-resistant species and strains. Synthetic macromolecules such as nanoparticles (NPs) exhibit broad-spectrum activity against MDR species, however lack of specificity towards bacteria relative to their mammalian hosts limits their widespread therapeutic application. Here, we demonstrate synergistic antimicrobial therapy using hydrophobically functionalized NPs and fluoroquinolone antibiotics for treatment of MDR bacterial strains. An 8-16-fold decrease in antibiotic dosage is achieved in presence of engineered NPs to combat MDR strains. This strategy demonstrates the potential of using NPs to ‘revive’ antibiotics that have been rendered ineffective due to the development of resistance by pathogenic bacteria.

Blood flow restriction training and the exercise pressor reflex: a call for concern.

PubMed

Spranger, Marty D; Krishnan, Abhinav C; Levy, Phillip D; O'Leary, Donal S; Smith, Scott A

2015-11-01

Blood flow restriction (BFR) training (also known as Kaatsu training) is an increasingly common practice employed during resistance exercise by athletes attempting to enhance skeletal muscle mass and strength. During BFR training, blood flow to the exercising muscle is mechanically restricted by placing flexible pressurizing cuffs around the active limb proximal to the working muscle. This maneuver results in the accumulation of metabolites (e.g., protons and lactic acid) in the muscle interstitium that increase muscle force and promote muscle growth. Therefore, the premise of BFR training is to simulate and receive the benefits of high-intensity resistance exercise while merely performing low-intensity resistance exercise. This technique has also been purported to provide health benefits to the elderly, individuals recovering from joint injuries, and patients undergoing cardiac rehabilitation. Since the seminal work of Alam and Smirk in the 1930s, it has been well established that reductions in blood flow to exercising muscle engage the exercise pressor reflex (EPR), a reflex that significantly contributes to the autonomic cardiovascular response to exercise. However, the EPR and its likely contribution to the BFR-mediated cardiovascular response to exercise is glaringly missing from the scientific literature. Inasmuch as the EPR has been shown to generate exaggerated increases in sympathetic nerve activity in disease states such as hypertension (HTN), heart failure (HF), and peripheral artery disease (PAD), concerns are raised that BFR training can be used safely for the rehabilitation of patients with cardiovascular disease, as has been suggested. Abnormal BFR-induced and EPR-mediated cardiovascular complications generated during exercise could precipitate adverse cardiovascular or cerebrovascular events (e.g., cardiac arrhythmia, myocardial infarction, stroke and sudden cardiac death). Moreover, although altered EPR function in HTN, HF, and PAD underlies our concern for the widespread implementation of BFR, use of this training mechanism may also have negative consequences in the absence of disease. That is, even normal, healthy individuals performing resistance training exercise with BFR are potentially at increased risk for deleterious cardiovascular events. This review provides a brief yet detailed overview of the mechanisms underlying the autonomic cardiovascular response to exercise with BFR. A more complete understanding of the consequences of BFR training is needed before this technique is passively explored by the layman athlete or prescribed by a health care professional. Copyright © 2015 the American Physiological Society.

Einstein and the "Crucial" Experiment

ERIC Educational Resources Information Center

Holton, Gerald

1969-01-01

Examines the widespread view that it was the crucial Michelson-Morley experiment that led Einstein to formulate the special relativity theory. From Einstein's writings, evidence is presented that no such direct genetic connection exists. The author suggests that the historian of science must resist the experimenticist's fallacy of imposing a…

Northwest forest plants defeat pests and diseases!

Treesearch

Natasha Vizcarra; Rick Kelsey; Joe Karchesy

2017-01-01

Societies use biologically active chemicals as medicines and pesticides to protect human and agricultural health. But widespread use of synthetic compounds raises concerns about their safety, and resistance development in targeted pests.To find safer alternatives, scientists turned to native plants and trees in Pacific Northwest forests...

Making the Hidden Curriculum Visible: Sustainability Literacy in Higher Education

ERIC Educational Resources Information Center

Winter, Jennie; Cotton, Debby

2012-01-01

Despite strong political support for the development of sustainability literacy amongst the UK graduates, embedding sustainability in the higher education curriculum has met with widespread indifference, and in some cases, active resistance. However, opportunities exist beyond the formal curriculum for engaging students in learning about…

Windrow burning eliminates Italian Ryegrass (Lolium perenne ssp. multiflorum) seed viability

USDA-ARS?s Scientific Manuscript database

Burning of crop residues that have been concentrated behind the harvest combine (windrowed) is one of several harvest weed seed control strategies that have been developed and evaluated in Australia to address the widespread evolution of multiple herbicide resistance in annual weeds. Herbicide-resis...

Metagenomic recovery of phage genomes of uncultured freshwater actinobacteria.

PubMed

Ghai, Rohit; Mehrshad, Maliheh; Mizuno, Carolina Megumi; Rodriguez-Valera, Francisco

2017-01-01

Low-GC Actinobacteria are among the most abundant and widespread microbes in freshwaters and have largely resisted all cultivation efforts. Consequently, their phages have remained totally unknown. In this work, we have used deep metagenomic sequencing to assemble eight complete genomes of the first tailed phages that infect freshwater Actinobacteria. Their genomes encode the actinobacterial-specific transcription factor whiB, frequently found in mycobacteriophages and also in phages infecting marine pelagic Actinobacteria. Its presence suggests a common and widespread strategy of modulation of host transcriptional machinery upon infection via this transcriptional switch. We present evidence that some whiB-carrying phages infect the acI lineage of Actinobacteria. At least one of them encodes the ADP-ribosylating component of the widespread bacterial AB toxins family (for example, clostridial toxin). We posit that the presence of this toxin reflects a 'trojan horse' strategy, providing protection at the population level to the abundant host microbes against eukaryotic predators.

Isoniazid Preventive Therapy and Risk for Resistant Tuberculosis

PubMed Central

Balcells, Maria Elvira; Thomas, Sara L.; Godfrey-Faussett, Peter

2006-01-01

In the context of tuberculosis (TB) resurgence, isoniazid preventive therapy (IPT) is increasingly promoted, but concerns about the risk for development of isoniazid-resistant tuberculosis may hinder its widespread implementation. We conducted a systematic review of data published since 1951 to assess the effect of primary IPT on the risk for isoniazid-resistant TB. Different definitions of isoniazid resistance were used, which affected summary effect estimates; we report the most consistent results. When all 13 studies (N = 18,095 persons in isoniazid groups and N = 17,985 persons in control groups) were combined, the summary relative risk for resistance was 1.45 (95% confidence interval 0.85–2.47). Results were similar when studies of HIV-uninfected and HIV-infected persons were considered separately. Analyses were limited by small numbers and incomplete testing of isolates, but findings do not exclude an increased risk for isoniazid-resistant TB after IPT. The diagnosis of active TB should be excluded before IPT. Continued surveillance for isoniazid resistance is essential. PMID:16704830

Out of sight, out of mind: why doesn't widespread clinical quality failure command our attention?

PubMed

Milstein, Arnold; Adler, Nancy E

2003-01-01

This paper examines the tolerance by all stakeholders of increasingly well documented evidence of serious and widespread clinical quality failure in the United States. Using research evidence from psychology, it describes specific cognitive and motivational impediments to the perception of quality failure-those shared by all stakeholders and those particularly relevant to patients and their families and to health care professionals. The authors endorse efforts by the National Quality Forum and others to make quality failure more publicly visible. They also point to the pivotal role of health care industry leaders in sustaining focus on a problem that inherently resists visibility.

Is the Computer Revolution About to Happen in the Classroom?

ERIC Educational Resources Information Center

Smith, S.

1984-01-01

Both practical and irrational factors will substantially delay the widespread use of computer-assisted instruction (CAI) in Australia's schools, including the following: lack of suitable software, insufficient hardware, ignorance of what CAI offers, lack of expert advice, computer anxiety, reaction against computer zealots, and resistance to…

Application of WWTP Biosolids and Resulting Perfluorinated Compound Contamination of Surface and Well Water in Decatur, Alabama, USA

EPA Science Inventory

Perfluorinated chemicals (PFCs) such as perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) have been produced and used in a wide range of industrial and consumer products for many decades. Their resistance to degradation has led to their widespread distribution in...

Efficacy of sericea lespedeza hay as a natural dewormer in goats: Dose titration study

USDA-ARS?s Scientific Manuscript database

Gastrointestinal nematode (GIN) parasitism is the greatest threat to economic sheep and goat production in the southern USA, and there is widespread prevalence of GIN resistance to broad-spectrum anthelmintics in this region. A natural alternative for controlling GIN in small ruminants is feeding h...

DIYA: A Bacterial Annotation Pipeline for any Genomics Lab

DTIC Science & Technology

2009-02-12

make more modules available. Functions we are looking to add to the DIYA pipeline include software for detection of prophages, CRISPR elements (Sorek...R. et al. (2008) CRISPR –a widespread system that provides acquired resistance against phages in bacteria and archaea. Nat. Rev. Microbiol., 6, 181

Potential geographic distribution of Palmer amaranth under current and future climates

USDA-ARS?s Scientific Manuscript database

Herbicide resistant weeds are increasingly becoming a major challenge for agricultural production worldwide. Palmer amaranth is an invasive annual forb that has recently emerged as one of the most widespread and severe agronomic weeds in the US, due in part to its facility for evolving herbicide res...

Mapping resistance to Phytophthora cinnamomi in chestnut (Castanea sp.)

Treesearch

Bode A. Olukolu; C. Dana Nelson; Albert G. Abbott

2012-01-01

Phytophthora cinnamomi (Phytophthora crown and root rot, or ink disease) is now known to infect several hundred plant species in the world and is especially linked to the widespread death of mature chestnut (Castanea) and evergreen oak (Quercus ilex L.) trees in southeast United States. With an expanding...

Detection of permethrin resistance and fipronil tolerance in Rhipicephalus sanguineus (Acari: Ixodidae) in the United States

USDA-ARS?s Scientific Manuscript database

Permethrin is a commonly used acaricide for tick control on domestic animals and in residential environments, while fipronil use is restricted to on-animal treatment. Following widespread reports of permethrin and fipronil application failures to control indoor infestations of Rhipicephalus sanguin...

Synergistic Effect of Dietary Curcuma, Capsicum, and Lentinus on enhancing local immunity against Eimeria acervulina infection

USDA-ARS?s Scientific Manuscript database

Traditionally, the application of prophylactic antibiotics has been successful in reducing infection-related morbidity and mortality in animal production. However, with increasing concerns over the widespread use of feed-added chemicals in animal production and the emergence of antibiotic resistant ...

Nicotinoid and pyrethroid insecticide resistance in houseflies (Diptera: Muscidae) collected from Florida dairies.

PubMed

Kaufman, Phillip E; Nunez, Sonia C; Mann, Rajinder S; Geden, Christopher J; Scharf, Michael E

2010-03-01

The housefly, Musca domestica L., continues to be a major pest of confined livestock operations. Houseflies have developed resistance to most chemical classes, and new chemistries for use in animal agriculture are increasingly slow to emerge. Five adult housefly strains from four Florida dairy farms were evaluated for resistance to four insecticides (beta-cyfluthrin, permethrin, imidacloprid and nithiazine). Significant levels of tolerance were found in most field strains to all insecticides, and in some cases substantial resistance was apparent (as deduced from comparison with prior published results). At the LC(90) level, greater than 20-fold resistance was found in two of the fly strains for permethrin and one fly strain for imidacloprid. Beta-cyfluthrin LC(90) resistance ratios exceeded tenfold resistance in three fly strains. The relatively underutilized insecticide nithiazine had the lowest resistance ratios; however, fourfold LC(90) resistance was observed in one southern Florida fly strain. Farm insecticide use and its impact on resistance selection in Florida housefly populations are discussed. Housefly resistance to pyrethroids is widespread in Florida. Imidacloprid resistance is emerging, and tolerance was observed to both imidacloprid and nithiazine. If these insecticides are to retain efficacy, producer use must be restrained.

Rapamycin Exerts Antifungal Activity In Vitro and In Vivo against Mucor circinelloides via FKBP12-Dependent Inhibition of Tor

PubMed Central

Bastidas, Robert J.; Shertz, Cecelia A.; Lee, Soo Chan; Heitman, Joseph

2012-01-01

The zygomycete Mucor circinelloides is an opportunistic fungal pathogen that commonly infects patients with malignancies, diabetes mellitus, and solid organ transplants. Despite the widespread use of antifungal therapy in the management of zygomycosis, the incidence of infections continues to rise among immunocompromised individuals. In this study, we established that the target and mechanism of antifungal action of the immunosuppressant rapamycin in M. circinelloides are mediated via conserved complexes with FKBP12 and a Tor homolog. We found that spontaneous mutations that disrupted conserved residues in FKBP12 conferred rapamycin and FK506 resistance. Disruption of the FKBP12-encoding gene, fkbA, also conferred rapamycin and FK506 resistance. Expression of M. circinelloides FKBP12 (McFKBP12) complemented a Saccharomyces cerevisiae mutant strain lacking FKBP12 to restore rapamycin sensitivity. Expression of the McTor FKBP12-rapamycin binding (FRB) domain conferred rapamycin resistance in S. cerevisiae, and McFKBP12 interacted in a rapamycin-dependent fashion with the McTor FRB domain in a yeast two-hybrid assay, validating McFKBP12 and McTor as conserved targets of rapamycin. We showed that in vitro, rapamycin exhibited potent growth inhibitory activity against M. circinelloides. In a Galleria mellonella model of systemic mucormycosis, rapamycin improved survival by 50%, suggesting that rapamycin and nonimmunosuppressive analogs have the potential to be developed as novel antifungal therapies for treatment of patients with mucormycosis. PMID:22210828

Correlation between Conjugated Bisphenol A Concentrations and Efflux Transporter Expression in Human Fetal Livers

PubMed Central

Moscovitz, Jamie E.; Nahar, Muna S.; Shalat, Stuart L.; Slitt, Angela L.; Dolinoy, Dana C.

2016-01-01

Because of its widespread use in the manufacturing of consumer products over several decades, human exposure to bisphenol A (BPA) has been pervasive. Fetuses are particularly sensitive to BPA exposure, with a number of negative developmental and reproductive outcomes observed in rodent perinatal models. Xenobiotic transporters are one mechanism to extrude conjugated and unconjugated BPA from the liver. In this study, the mRNA expression of xenobiotic transporters and relationships with total, conjugated, and free BPA levels were explored utilizing human fetal liver samples. The mRNA expression of breast cancer resistance protein (BCRP) and multidrug resistance-associated transporter (MRP)4, as well as BCRP and multidrug resistance transporter 1 exhibited the highest degree of correlation, with r2 values of 0.941 and 0.816 (P < 0.001 for both), respectively. Increasing concentrations of conjugated BPA significantly correlated with high expression of MRP1 (P < 0.001), MRP2 (P < 0.05), and MRP3 (P < 0.05) transporters, in addition to the NF-E2–related factor 2 transcription factor (P < 0.001) and its prototypical target gene, NAD(P)H quinone oxidoreductase 1 (P < 0.001). These data demonstrate that xenobiotic transporters may be coordinately expressed in the human fetal liver. This is also the first report of a relationship between environmentally relevant fetal BPA levels and differences in the expression of transporters that can excrete the parent compound and its metabolites. PMID:26851240

Rapamycin exerts antifungal activity in vitro and in vivo against Mucor circinelloides via FKBP12-dependent inhibition of Tor.

PubMed

Bastidas, Robert J; Shertz, Cecelia A; Lee, Soo Chan; Heitman, Joseph; Cardenas, Maria E

2012-03-01

The zygomycete Mucor circinelloides is an opportunistic fungal pathogen that commonly infects patients with malignancies, diabetes mellitus, and solid organ transplants. Despite the widespread use of antifungal therapy in the management of zygomycosis, the incidence of infections continues to rise among immunocompromised individuals. In this study, we established that the target and mechanism of antifungal action of the immunosuppressant rapamycin in M. circinelloides are mediated via conserved complexes with FKBP12 and a Tor homolog. We found that spontaneous mutations that disrupted conserved residues in FKBP12 conferred rapamycin and FK506 resistance. Disruption of the FKBP12-encoding gene, fkbA, also conferred rapamycin and FK506 resistance. Expression of M. circinelloides FKBP12 (McFKBP12) complemented a Saccharomyces cerevisiae mutant strain lacking FKBP12 to restore rapamycin sensitivity. Expression of the McTor FKBP12-rapamycin binding (FRB) domain conferred rapamycin resistance in S. cerevisiae, and McFKBP12 interacted in a rapamycin-dependent fashion with the McTor FRB domain in a yeast two-hybrid assay, validating McFKBP12 and McTor as conserved targets of rapamycin. We showed that in vitro, rapamycin exhibited potent growth inhibitory activity against M. circinelloides. In a Galleria mellonella model of systemic mucormycosis, rapamycin improved survival by 50%, suggesting that rapamycin and nonimmunosuppressive analogs have the potential to be developed as novel antifungal therapies for treatment of patients with mucormycosis.

Zero temperature coefficient of resistance of the electrical-breakdown path in ultrathin hafnia

NASA Astrophysics Data System (ADS)

Zhang, H. Z.; Ang, D. S.

2017-09-01

The recent widespread attention on the use of the non-volatile resistance switching property of a microscopic oxide region after electrical breakdown for memory applications has prompted basic interest in the conduction properties of the breakdown region. Here, we report an interesting crossover from a negative to a positive temperature dependence of the resistance of a breakdown region in ultrathin hafnia as the applied voltage is increased. As a consequence, a near-zero temperature coefficient of resistance is obtained at the crossover voltage. The behavior may be modeled by (1) a tunneling-limited transport involving two farthest-spaced defects along the conduction path at low voltage and (2) a subsequent transition to a scattering-limited transport after the barrier is overcome by a larger applied voltage.

Virulence traits and antibiotic resistance among enterococci isolated from dogs with periodontal disease.

PubMed

Oliveira, Manuela; Tavares, Marta; Gomes, Diana; Touret, Tiago; São Braz, Berta; Tavares, Luís; Semedo-Lemsaddek, Teresa

2016-06-01

Periodontal disease - PD - is one of the most widespread diseases in dogs, but the role of this odontogenic infection in the dissemination of pathogenic bacteria present in the oral mucosa to other animals or pet owners is understudied. Trying to unveil the putative pathogenicity of enterococci present in the gums of dogs diagnosed with PD, thirty-two animals were investigated during routine visits to a private veterinary clinic. Seventy-one enterococci were recovered and characterized regarding species, genomic variability, virulence traits, antimicrobial resistance and biofilm-forming ability. Isolates were mainly identified as Enterococcus faecalis, with the large majority (95%) being able to produce biofilm. Regarding antibiotic resistance, all dog-enterococci were susceptible to ampicillin, amoxicillin/clavulanate, gentamicin-120, imipenem and vancomycin; while distinct levels of resistance were observed for chloramphenicol (10%), erythromycin (20%), streptomycin-300 (35%) and tetracycline (95%). For virulence traits incidence levels of 35% were observed for β-hemolysis and 25% for cylA, 25% for gelatinase and 35% for gelE; 85% harbor efaAfs and ebpABC; while ace, agg and esp are present respectively in 50, 30 and 10% of the dog-enterococci; efaAfm and acm were detected in all the Enterococcus faecium. Overall, the widespread prevalence of PD in dogs, associated with the close contact between companion animals, other animals and humans, may act as source for the dissemination of opportunistic pathogenic bacteria. Hence, aforementioned data on virulence and resistance features, emphasizes the need for active surveillance measures, such as the diagnose of PD in companion animals during routine visits to the veterinary clinic. Copyright © 2016 Elsevier Ltd. All rights reserved.

Insecticide resistance and resistance mechanisms in bed bugs, Cimex spp. (Hemiptera: Cimicidae).

PubMed

Dang, Kai; Doggett, Stephen L; Veera Singham, G; Lee, Chow-Yang

2017-06-29

The worldwide resurgence of bed bugs [both Cimex lectularius L. and Cimex hemipterus (F.)] over the past two decades is believed in large part to be due to the development of insecticide resistance. The transcriptomic and genomic studies since 2010, as well as morphological, biochemical and behavioral studies, have helped insecticide resistance research on bed bugs. Multiple resistance mechanisms, including penetration resistance through thickening or remodelling of the cuticle, metabolic resistance by increased activities of detoxification enzymes (e.g. cytochrome P450 monooxygenases and esterases), and knockdown resistance by kdr mutations, have been experimentally identified as conferring insecticide resistance in bed bugs. Other candidate resistance mechanisms, including behavioral resistance, some types of physiological resistance (e.g. increasing activities of esterases by point mutations, glutathione S-transferase, target site insensitivity including altered AChEs, GABA receptor insensitivity and altered nAChRs), symbiont-mediated resistance and other potential, yet undiscovered mechanisms may exist. This article reviews recent studies of resistance mechanisms and the genes governing insecticide resistance, potential candidate resistance mechanisms, and methods of monitoring insecticide resistance in bed bugs. This article provides an insight into the knowledge essential for the development of both insecticide resistance management (IRM) and integrated pest management (IPM) strategies for successful bed bug management.

Bfr1p is responsible for tributyltin resistance in Schizosaccharomyces pombe.

PubMed

Akiyama, Koichi; Iwaki, Tomoko; Sugimoto, Naoko; Chardwiriyapreecha, Soracom; Kawano, Miyuki; Nishimoto, Sogo; Sugahara, Takuya; Sekito, Takayuki; Kakinuma, Yoshimi

2011-01-01

ATP-binding cassette (ABC) transporter plays an important role for resistance against xenobiotics. There are eleven ABC transporter genes in the genome of fission yeast Schizosaccharomyces pombe. We examined the role of ABC transporter against the toxicity of tributyltin chloride (TBT), a widespread environmental pollutant, in cell growth. Among individual ABC transporter mutants, the growth of a mutant deficient in Bfr1p, a plasma membrane-embedded transporter, was extremely sensitive to TBT. The lethal TBT concentration inducing 50% of cell death (LC(50)) was 25 µM for the parent strain and 10.2 µM for the bfr1∆ mutant. Thus, Bfr1p was responsible for TBT resistance in S. pombe.

Bacterial cheating limits antibiotic resistance

NASA Astrophysics Data System (ADS)

Xiao Chao, Hui; Yurtsev, Eugene; Datta, Manoshi; Artemova, Tanya; Gore, Jeff

2012-02-01

The widespread use of antibiotics has led to the evolution of resistance in bacteria. Bacteria can gain resistance to the antibiotic ampicillin by acquiring a plasmid carrying the gene beta-lactamase, which inactivates the antibiotic. This inactivation may represent a cooperative behavior, as the entire bacterial population benefits from removing the antibiotic. The cooperative nature of this growth suggests that a cheater strain---which does not contribute to breaking down the antibiotic---may be able to take advantage of cells cooperatively inactivating the antibiotic. Here we find experimentally that a ``sensitive'' bacterial strain lacking the plasmid conferring resistance can invade a population of resistant bacteria, even in antibiotic concentrations that should kill the sensitive strain. We observe stable coexistence between the two strains and find that a simple model successfully explains the behavior as a function of antibiotic concentration and cell density. We anticipate that our results will provide insight into the evolutionary origin of phenotypic diversity and cooperative behaviors.

Counterfeit anti-infective drugs.

PubMed

Newton, Paul N; Green, Michael D; Fernández, Facundo M; Day, Nicholas P J; White, Nicholas J

2006-09-01

The production of counterfeit or substandard anti-infective drugs is a widespread and under-recognised problem that contributes to morbidity, mortality, and drug resistance, and leads to spurious reporting of resistance and toxicity and loss of confidence in health-care systems. Counterfeit drugs particularly affect the most disadvantaged people in poor countries. Although advances in forensic chemical analysis and simple field tests will enhance drug quality monitoring, improved access to inexpensive genuine medicines, support of drug regulatory authorities, more open reporting, vigorous law enforcement, and more international cooperation with determined political leadership will be essential to counter this threat.

Pyrochemical and Dry Processing Methods Program. A selected bibliography

DOE Office of Scientific and Technical Information (OSTI.GOV)

McDuffie, H.F.; Smith, D.H.; Owen, P.T.

1979-03-01

This selected bibliography with abstracts was compiled to provide information support to the Pyrochemical and Dry Processing Methods (PDPM) Program sponsored by DOE and administered by the Argonne National Laboratory. Objectives of the PDPM Program are to evaluate nonaqueous methods of reprocessing spent fuel as a route to the development of proliferation-resistant and diversion-resistant methods for widespread use in the nuclear industry. Emphasis was placed on the literature indexed in the ERDA--DOE Energy Data Base (EDB). The bibliography includes indexes to authors, subject descriptors, EDB subject categories, and titles.

Quantitative proteomic view associated with resistance to clinically important antibiotics in Gram-positive bacteria: a systematic review

PubMed Central

Lee, Chang-Ro; Lee, Jung Hun; Park, Kwang Seung; Jeong, Byeong Chul; Lee, Sang Hee

2015-01-01

The increase of methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE) poses a worldwide and serious health threat. Although new antibiotics, such as daptomycin and linezolid, have been developed for the treatment of infections of Gram-positive pathogens, the emergence of daptomycin-resistant and linezolid-resistant strains during therapy has now increased clinical treatment failures. In the past few years, studies using quantitative proteomic methods have provided a considerable progress in understanding antibiotic resistance mechanisms. In this review, to understand the resistance mechanisms to four clinically important antibiotics (methicillin, vancomycin, linezolid, and daptomycin) used in the treatment of Gram-positive pathogens, we summarize recent advances in studies on resistance mechanisms using quantitative proteomic methods, and also examine proteins playing an important role in the bacterial mechanisms of resistance to the four antibiotics. Proteomic researches can identify proteins whose expression levels are changed in the resistance mechanism to only one antibiotic, such as LiaH in daptomycin resistance and PrsA in vancomycin resistance, and many proteins simultaneously involved in resistance mechanisms to various antibiotics. Most of resistance-related proteins, which are simultaneously associated with resistance mechanisms to several antibiotics, play important roles in regulating bacterial envelope biogenesis, or compensating for the fitness cost of antibiotic resistance. Therefore, proteomic data confirm that antibiotic resistance requires the fitness cost and the bacterial envelope is an important factor in antibiotic resistance. PMID:26322035

A high-fat, ketogenic diet causes hepatic insulin resistance in mice, despite increasing energy expenditure and preventing weight gain.

PubMed

Jornayvaz, François R; Jurczak, Michael J; Lee, Hui-Young; Birkenfeld, Andreas L; Frederick, David W; Zhang, Dongyang; Zhang, Xian-Man; Samuel, Varman T; Shulman, Gerald I

2010-11-01

Low-carbohydrate, high-fat ketogenic diets (KD) have been suggested to be more effective in promoting weight loss than conventional caloric restriction, whereas their effect on hepatic glucose and lipid metabolism and the mechanisms by which they may promote weight loss remain controversial. The aim of this study was to explore the role of KD on liver and muscle insulin sensitivity, hepatic lipid metabolism, energy expenditure, and food intake. Using hyperinsulinemic-euglycemic clamps, we studied insulin action in mice fed a KD or regular chow (RC). Body composition was assessed by ¹H magnetic resonance spectroscopy. Despite being 15% lighter (P < 0.001) than RC-fed mice because of a 17% increase in energy expenditure (P < 0.001), KD-fed mice manifested severe hepatic insulin resistance, as reflected by decreased suppression (0% vs. 100% in RC-fed mice, P < 0.01) of endogenous glucose production during the clamp. Hepatic insulin resistance could be attributed to a 350% increase in hepatic diacylglycerol content (P < 0.001), resulting in increased activation of PKCε (P < 0.05) and decreased insulin receptor substrate-2 tyrosine phosphorylation (P < 0.01). Food intake was 56% (P < 0.001) lower in KD-fed mice, despite similar caloric intake, and could partly be attributed to a more than threefold increase (P < 0.05) in plasma N-acylphosphatidylethanolamine concentrations. In conclusion, despite preventing weight gain in mice, KD induces hepatic insulin resistance secondary to increased hepatic diacylglycerol content. Given the key role of nonalcoholic fatty liver disease in the development of type 2 diabetes and the widespread use of KD for the treatment of obesity, these results may have potentially important clinical implications.

Nanocrystalline Nb-Al-Ge mixtures fabricated using wet mechanical milling

NASA Astrophysics Data System (ADS)

Pusceddu, E.; Charlton, S.; Hampshire, D. P.

2008-02-01

An investigation into Nb-Al-Ge mixtures is presented with special attention to the superconducting compounds Nb3(Al1-xGex) with x = 0, 0.3 and 1, which are reported to provide the highest upper critical field values for Nb-based compounds. Wet mechanical milling using copper milling media and distilled water as a process control agent (PCA) was used with the intention of improving the yield, properties and the performance of these materials. Very high yields of nanocrystalline material were achieved but significant copper contamination occurred - confirmed using inductively-coupled-plasma atomic-emission-spectroscopy. Simultaneous thermogravimetric measurements and differential scanning calorimetry were performed on powders milled for up to 20 h with different PCA content, to quantify the work done on the powders. A typical grain size of a few nm was obtained for the Nb-Al-Ge mixtures after several hours milling. Powder ground for 20 h with 5% PCA was processed using a hot isostatic press (HIP) operating at 2000 atm and temperatures up to 750 °C. The room temperature resistivity decreased as the temperature of the HIPing increased. Unfortunately, despite the nanocrystalline microstructure of the powders and the high HIP temperatures, if superconducting material was formed it was below the detection level of resistivity, Ac. susceptibility and SQUID measurements. We conclude that during milling there was widespread contamination of the powders by the PCA so that milling with distilled water as a PCA is not to be recommended for fabricating nanocrystalline Nb3(Al1-xGex) A15 superconducting compounds.

Prophylactic Antibiotic Use in COPD and the Potential Anti-Inflammatory Activities of Antibiotics.

PubMed

Huckle, Anthony W; Fairclough, Lucy C; Todd, Ian

2018-05-01

Antibiotics have previously demonstrated anti-inflammatory properties, and they have been linked to therapeutic benefit in several pulmonary conditions that feature inflammation. Previous research suggests that these anti-inflammatory properties may be beneficial in the treatment of COPD. This review assesses the potential benefit of prophylactic, long-term, and low-dose antibiotic therapy in COPD, and whether any effects seen are anti-inflammatory in nature. Randomized, controlled trials comparing antibiotic therapy with placebo in subjects with stable COPD were evaluated. Twelve trials involving 3,784 participants and a range of antibiotics were included: azithromycin (6 studies, 1,972 participants), clarithromycin (1 study, 67 participants), erythromycin (3 studies, 254 participants), roxithromycin (1 study, 191 participants), and moxifloxacin (2 studies, 1,198 participants). In vitro, in vivo, and ex vivo experimental study designs exploring the mechanisms via which antibiotics may act in subjects with stable COPD were evaluated. Azithromycin and erythromycin showed the greatest effect in subjects with COPD, with evidence suggesting improvement in exacerbation-related outcomes and health status, as measured by the St George Respiratory Questionnaire. An increase in antibiotic resistance was reported in 2 studies. The macrolide class of antibiotics exhibited convincing anti-inflammatory properties with relevance to COPD, implicating several pathways as potential mechanisms of action. In conclusion, the therapeutic benefit of macrolide antibiotics in subjects with stable COPD is consistent with anti-inflammatory properties, and macrolides should be considered as a potential therapy in COPD. Safety concerns regarding antibiotic resistance need to be addressed before widespread use in clinical practice. Copyright © 2018 by Daedalus Enterprises.

Asynchrony between Host Plant and Insects-Defoliator within a Tritrophic System: The Role of Herbivore Innate Immunity

PubMed Central

Martemyanov, Vyacheslav V.; Pavlushin, Sergey V.; Dubovskiy, Ivan M.; Yushkova, Yuliya V.; Morosov, Sergey V.; Chernyak, Elena I.; Efimov, Vadim M.; Ruuhola, Teija; Glupov, Victor V.

2015-01-01

The effects of asynchrony in the phenology of spring-feeding insect-defoliators and their host plants on insects’ fitness, as well as the importance of this effect for the population dynamics of outbreaking species of insects, is a widespread and well-documented phenomenon. However, the spreading of this phenomenon through the food chain, and especially those mechanisms operating this spreading, are still unclear. In this paper, we study the effect of seasonally declined leafquality (estimated in terms of phenolics and nitrogen content) on herbivore fitness, immune parameters and resistance against pathogen by using the silver birch Betula pendula—gypsy moth Lymantria dispar—nucleopolyhedrovirus as the tritrophic system. We show that a phenological mismatch induced by the delay in the emergence of gypsy moth larvae and following feeding on mature leaves has negative effects on the female pupal weight, on the rate of larval development and on the activity of phenoloxidase in the plasma of haemolymph. In addition, the larval susceptibility to exogenous nucleopolyhydrovirus infection as well as covert virus activation were both enhanced due to the phenological mismatch. The observed effects of phenological mismatch on insect-baculovirus interaction may partially explain the strong and fast fluctuations in the population dynamics of the gypsy moth that is often observed in the studied part of the defoliator area. This study also reveals some indirect mechanisms of effect related to host plant quality, which operate through the insect innate immune status and affect resistance to both exogenous and endogenous virus. PMID:26115118

Antimicrobials in small-scale urban pig farming in a lower middle-income country - arbitrary use and high resistance levels.

PubMed

Ström, G; Boqvist, S; Albihn, A; Fernström, L-L; Andersson Djurfeldt, A; Sokerya, S; Sothyra, T; Magnusson, U

2018-01-01

Administration of antimicrobials to food-producing animals is regarded as a major contributor to the overall emergence of resistance in bacteria worldwide. However, few data are available on global antimicrobial use and resistance (AMR) in livestock, especially from low- and middle-income countries. We conducted a structured survey of 91 small-scale pig farms in the urban and peri-urban areas of Phnom Penh, Cambodia, to assess the farmers' knowledge, attitudes and practices related to antimicrobial use in their pig production. Commensal Escherichia coli was isolated from three healthy pigs from each farm ( n  = 261) and susceptibility testing was performed against 14 antimicrobials, using broth microdilution. Univariable logistic regression and generalized linear mixed models were used to investigate potential associations between farm characteristics, management factors and resistance to different types of antimicrobials. We found a widespread and arbitrary use of antimicrobials, often based on the farmer's own judgment. Around 66% of the farmers reported frequently self-adjusting treatment duration and dosage, and 45% had not heard about the term 'antimicrobial resistance'. The antimicrobials most commonly mentioned or kept by the farmers were amoxicillin, tylosin, gentamicin and colistin. Around 37% used a feed concentrate that contained antimicrobials, while antimicrobials for humans were used as a last-line treatment by 10% of the farmers. Commensal E. coli exhibited high prevalence of resistance to several antimicrobials considered to be of critical importance for human medicine, including ampicillin, ciprofloxacin and colistin, and multidrug-resistance was found in 79% of the samples. Higher prevalence of resistance was observed on farms that administered prophylactic antimicrobials and on farms that treated the entire group or herd in the event of disease. The widespread and arbitrary use of antimicrobials in pig farming in Cambodia is highly worrisome. Overall, farmers had a low awareness of the risks and consequences related to antimicrobial use and AMR. The results presented in this study confirm the hypothesis that non-rational use of antimicrobials results in higher prevalence of AMR and highlight the need for professional animal health systems that involve medically rational use of antimicrobials in emerging economies such as Cambodia.

Molecular epidemiology of drug-resistant Neisseria gonorrhoeae in Russia (Current Status, 2015).

PubMed

Kubanov, Alexey; Vorobyev, Denis; Chestkov, Aleksandr; Leinsoo, Arvo; Shaskolskiy, Boris; Dementieva, Ekaterina; Solomka, Viktoria; Plakhova, Xenia; Gryadunov, Dmitry; Deryabin, Dmitriy

2016-08-09

The widespread distribution of Neisseria gonorrhoeae strains that are resistant to previously used and clinically implemented antibiotics is a significant global public health problem. In line with WHO standards, the national Gonococcal Antimicrobial Surveillance Programme (RU-GASP) has been in existence in Russia since 2004; herein, the current status (2015) is described, including associations between N. gonorrhoeae antimicrobial susceptibility, primary genetic resistance determinants and specific strain sequence types. A total of 124 N. gonorrhoeae strains obtained from 9 regions in Russia in 2015 were examined using N. gonorrhoeae Multi-Antigen Sequence Typing (NG-MAST), an antimicrobial susceptibility test according to European Committee on Antimicrobial Susceptibility Testing (EUCAST) criteria and an oligonucleotide microarray for the identification of mutations in the penA, ponA, rpsJ, gyrA and parC genes responsible for penicillin G, tetracycline, and fluoroquinolone resistance. Genogroup (G) isolates were evaluated based on their porB and tbpB sequence types (STs). NG-MAST analysis showed a diversified population of N. gonorrhoeae in Russia with 58 sequence types, 35 of which were described for the first time. The STs 807, 1544, 1993, 5714, 9476 and 12531, which were typical for some Russian Federation regions and several countries of the former Soviet Union, were represented by five or more isolates. The internationally widespread ST 1407 was represented by a single strain in the present study. Division into genogroups facilitated an exploration of the associations between N. gonorrhoeae sequence type, antimicrobial resistance spectra and genetic resistance determinant contents. Preliminarily susceptible (G-807, G-12531) and resistant (G-5714, G-9476) genogroups were revealed. The variability in the most frequently observed STs and genogroups in each participating region indicated geographically restricted antimicrobial susceptibility in N. gonorrhoeae populations. Resistance or intermediate susceptibility to previously recommended antimicrobials, such as penicillin G (60.5 %), ciprofloxacin (41.1 %) and tetracycline (25 %), is common in the N. gonorrhoeae population. Based on previous reports and current data, ceftriaxone and spectinomycin should be recommended for first-line empiric antimicrobial monotherapy for gonorrhoea in Russia.

Thermal conductivity and thermal boundary resistance of atomic layer deposited high-k dielectric aluminum oxide, hafnium oxide, and titanium oxide thin films on silicon

NASA Astrophysics Data System (ADS)

Scott, Ethan A.; Gaskins, John T.; King, Sean W.; Hopkins, Patrick E.

2018-05-01

The need for increased control of layer thickness and uniformity as device dimensions shrink has spurred increased use of atomic layer deposition (ALD) for thin film growth. The ability to deposit high dielectric constant (high-k) films via ALD has allowed for their widespread use in a swath of optical, optoelectronic, and electronic devices, including integration into CMOS compatible platforms. As the thickness of these dielectric layers is reduced, the interfacial thermal resistance can dictate the overall thermal resistance of the material stack compared to the resistance due to the finite dielectric layer thickness. Time domain thermoreflectance is used to interrogate both the thermal conductivity and the thermal boundary resistance of aluminum oxide, hafnium oxide, and titanium oxide films on silicon. We calculate a representative design map of effective thermal resistances, including those of the dielectric layers and boundary resistances, as a function of dielectric layer thickness, which will be of great importance in predicting the thermal resistances of current and future devices.

Successes and challenges of managing resistance in Helicoverpa armigera to Bt cotton in Australia.

PubMed

Downes, Sharon; Mahon, Rod

2012-01-01

Bt cotton has been gradually released and adopted by Australian growers since 1996. It was initially deployed in Australia primarily to control the polyphagous pest Helicoverpa armigera (Hübner), which in the 1990s became increasingly difficult to control due to widespread resistance to synthetic chemical insecticides. Bt-cotton has become a key tool in a program of integrated pest management for the production system that reduces pesticide dependence and the problems associated with its use. Herein we overview the deployment of Bt cotton in Australia including its performance and the approaches used to prolong the evolution of resistance to it by H. armigera. An integral component of this approach is monitoring resistance in this pest. We outline resistance screening methods, as well as the characteristics of resistant strains of H. armigera that have been isolated from field populations, or selected in the laboratory. We then highlight the successes and challenges for Bt cotton in Australia by way of discussing adaptive resistance management in light of potential changes in resistance.

Widespread movement of invasive cattle fever ticks (Rhipicephalus microplus) in southern Texas leads to shared local infestations on cattle and deer.

PubMed

Busch, Joseph D; Stone, Nathan E; Nottingham, Roxanne; Araya-Anchetta, Ana; Lewis, Jillian; Hochhalter, Christian; Giles, John R; Gruendike, Jeffrey; Freeman, Jeanne; Buckmeier, Greta; Bodine, Deanna; Duhaime, Roberta; Miller, Robert J; Davey, Ronald B; Olafson, Pia U; Scoles, Glen A; Wagner, David M

2014-04-17

Rhipicephalus (Boophilus) microplus is a highly-invasive tick that transmits the cattle parasites (Babesia bovis and B. bigemina) that cause cattle fever. R. microplus and Babesia are endemic in Mexico and ticks persist in the United States inside a narrow tick eradication quarantine area (TEQA) along the Rio Grande. This containment area is threatened by unregulated movements of illegal cattle and wildlife like white-tailed deer (WTD; Odocoileus virginianus). Using 11 microsatellite loci we genotyped 1,247 R. microplus from 63 Texas collections, including outbreak infestations from outside the TEQA. We used population genetic analyses to test hypotheses about ecological persistence, tick movement, and impacts of the eradication program in southern Texas. We tested acaricide resistance with larval packet tests (LPTs) on 47 collections. LPTs revealed acaricide resistance in 15/47 collections (32%); 11 were outside the TEQA and three were resistant to multiple acaricides. Some collections highly resistant to permethrin were found on cattle and WTD. Analysis of genetic differentiation over time at seven properties revealed local gene pools with very low levels of differentiation (FST 0.00-0.05), indicating persistence over timespans of up to 29 months. However, in one neighborhood differentiation varied greatly over a 12-month period (FST 0.03-0.13), suggesting recurring immigration from distinct sources as another persistence mechanism. Ticks collected from cattle and WTD at the same location are not differentiated (FST = 0), implicating ticks from WTD as a source of ticks on cattle (and vice versa) and emphasizing the importance of WTD to tick control strategies. We identified four major genetic groups (K = 4) using Bayesian population assignment, suggesting multiple introductions to Texas. Two dispersal mechanisms give rise to new tick infestations: 1) frequent short-distance dispersal from the TEQA; and 2) rare long-distance, human-mediated dispersal from populations outside our study area, probably Mexico. The threat of cattle fever tick transport into Texas is increased by acaricide resistance and the ability of R. microplus to utilize WTD as an alternate host. Population genetic analyses may provide a powerful tool for tracking invasions in other parts of the world where these ticks are established.

Widespread movement of invasive cattle fever ticks (Rhipicephalus microplus) in southern Texas leads to shared local infestations on cattle and deer

PubMed Central

2014-01-01

Background Rhipicephalus (Boophilus) microplus is a highly-invasive tick that transmits the cattle parasites (Babesia bovis and B. bigemina) that cause cattle fever. R. microplus and Babesia are endemic in Mexico and ticks persist in the United States inside a narrow tick eradication quarantine area (TEQA) along the Rio Grande. This containment area is threatened by unregulated movements of illegal cattle and wildlife like white-tailed deer (WTD; Odocoileus virginianus). Methods Using 11 microsatellite loci we genotyped 1,247 R. microplus from 63 Texas collections, including outbreak infestations from outside the TEQA. We used population genetic analyses to test hypotheses about ecological persistence, tick movement, and impacts of the eradication program in southern Texas. We tested acaricide resistance with larval packet tests (LPTs) on 47 collections. Results LPTs revealed acaricide resistance in 15/47 collections (32%); 11 were outside the TEQA and three were resistant to multiple acaricides. Some collections highly resistant to permethrin were found on cattle and WTD. Analysis of genetic differentiation over time at seven properties revealed local gene pools with very low levels of differentiation (FST 0.00-0.05), indicating persistence over timespans of up to 29 months. However, in one neighborhood differentiation varied greatly over a 12-month period (FST 0.03-0.13), suggesting recurring immigration from distinct sources as another persistence mechanism. Ticks collected from cattle and WTD at the same location are not differentiated (FST = 0), implicating ticks from WTD as a source of ticks on cattle (and vice versa) and emphasizing the importance of WTD to tick control strategies. We identified four major genetic groups (K = 4) using Bayesian population assignment, suggesting multiple introductions to Texas. Conclusions Two dispersal mechanisms give rise to new tick infestations: 1) frequent short-distance dispersal from the TEQA; and 2) rare long-distance, human-mediated dispersal from populations outside our study area, probably Mexico. The threat of cattle fever tick transport into Texas is increased by acaricide resistance and the ability of R. microplus to utilize WTD as an alternate host. Population genetic analyses may provide a powerful tool for tracking invasions in other parts of the world where these ticks are established. PMID:24742041

BMI1 induces an invasive signature in melanoma that promotes metastasis and chemoresistance

PubMed Central

Ferretti, Roberta; Bhutkar, Arjun; McNamara, Molly C.; Lees, Jacqueline A.

2016-01-01

Melanoma can switch between proliferative and invasive states, which have identifying gene expression signatures that correlate with good and poor prognosis, respectively. However, the mechanisms controlling these signatures are poorly understood. In this study, we identify BMI1 as a key determinant of melanoma metastasis by which its overexpression enhanced and its deletion impaired dissemination. Remarkably, in this tumor type, BMI1 had no effect on proliferation or primary tumor growth but enhanced every step of the metastatic cascade. Consistent with the broad spectrum of effects, BMI1 activated widespread gene expression changes, which are characteristic of melanoma progression and also chemoresistance. Accordingly, we showed that up-regulation or down-regulation of BMI1 induced resistance or sensitivity to BRAF inhibitor treatment and that induction of noncanonical Wnt by BMI1 is required for this resistance. Finally, we showed that our BMI1-induced gene signature encompasses all of the hallmarks of the previously described melanoma invasive signature. Moreover, our signature is predictive of poor prognosis in human melanoma and is able to identify primary tumors that are likely to become metastatic. These data yield key insights into melanoma biology and establish BMI1 as a compelling drug target whose inhibition would suppress both metastasis and chemoresistance of melanoma. PMID:26679841

Eukaryotic resistance to fluoride toxicity mediated by a widespread family of fluoride export proteins.

PubMed

Li, Sanshu; Smith, Kathryn D; Davis, Jared H; Gordon, Patricia B; Breaker, Ronald R; Strobel, Scott A

2013-11-19

Fluorine is an abundant element and is toxic to organisms from bacteria to humans, but the mechanisms by which eukaryotes resist fluoride toxicity are unknown. The Escherichia coli gene crcB was recently shown to be regulated by a fluoride-responsive riboswitch, implicating it in fluoride response. There are >8,000 crcB homologs across all domains of life, indicating that it has an important role in biology. Here we demonstrate that eukaryotic homologs [renamed FEX (fluoride exporter)] function in fluoride export. FEX KOs in three eukaryotic model organisms, Neurospora crassa, Saccharomyces cerevisiae, and Candida albicans, are highly sensitized to fluoride (>200-fold) but not to other halides. Some of these KO strains are unable to grow in fluoride concentrations found in tap water. Using the radioactive isotope of fluoride, (18)F, we developed an assay to measure the intracellular fluoride concentration and show that the FEX deletion strains accumulate fluoride in excess of the external concentration, providing direct evidence of FEX function in fluoride efflux. In addition, they are more sensitive to lower pH in the presence of fluoride. These results demonstrate that eukaryotic FEX genes encode a previously unrecognized class of fluoride exporter necessary for survival in standard environmental conditions.

Eukaryotic resistance to fluoride toxicity mediated by a widespread family of fluoride export proteins

PubMed Central

Li, Sanshu; Smith, Kathryn D.; Davis, Jared H.; Gordon, Patricia B.; Breaker, Ronald R.; Strobel, Scott A.

2013-01-01

Fluorine is an abundant element and is toxic to organisms from bacteria to humans, but the mechanisms by which eukaryotes resist fluoride toxicity are unknown. The Escherichia coli gene crcB was recently shown to be regulated by a fluoride-responsive riboswitch, implicating it in fluoride response. There are >8,000 crcB homologs across all domains of life, indicating that it has an important role in biology. Here we demonstrate that eukaryotic homologs [renamed FEX (fluoride exporter)] function in fluoride export. FEX KOs in three eukaryotic model organisms, Neurospora crassa, Saccharomyces cerevisiae, and Candida albicans, are highly sensitized to fluoride (>200-fold) but not to other halides. Some of these KO strains are unable to grow in fluoride concentrations found in tap water. Using the radioactive isotope of fluoride, 18F, we developed an assay to measure the intracellular fluoride concentration and show that the FEX deletion strains accumulate fluoride in excess of the external concentration, providing direct evidence of FEX function in fluoride efflux. In addition, they are more sensitive to lower pH in the presence of fluoride. These results demonstrate that eukaryotic FEX genes encode a previously unrecognized class of fluoride exporter necessary for survival in standard environmental conditions. PMID:24173035

PPARγ coactivator-1α contributes to exercise-induced regulation of intramuscular lipid droplet programming in mice and humans.

PubMed

Koves, Timothy R; Sparks, Lauren M; Kovalik, J P; Mosedale, Merrie; Arumugam, Ramamani; DeBalsi, Karen L; Everingham, Karen; Thorne, Leigh; Phielix, Esther; Meex, Ruth C; Kien, C Lawrence; Hesselink, Matthijs K C; Schrauwen, Patrick; Muoio, Deborah M

2013-02-01

Intramuscular accumulation of triacylglycerol, in the form of lipid droplets (LD), has gained widespread attention as a hallmark of metabolic disease and insulin resistance. Paradoxically, LDs also amass in muscles of highly trained endurance athletes who are exquisitely insulin sensitive. Understanding the molecular mechanisms that mediate the expansion and appropriate metabolic control of LDs in the context of habitual physical activity could lead to new therapeutic opportunities. Herein, we show that acute exercise elicits robust upregulation of a broad program of genes involved in regulating LD assembly, morphology, localization, and mobilization. Prominent among these was perilipin-5, a scaffolding protein that affects the spatial and metabolic interactions between LD and their surrounding mitochondrial reticulum. Studies in transgenic mice and primary human skeletal myocytes established a key role for the exercise-responsive transcriptional coactivator PGC-1α in coordinating intramuscular LD programming with mitochondrial remodeling. Moreover, translational studies comparing physically active versus inactive humans identified a remarkably strong association between expression of intramuscular LD genes and enhanced insulin action in exercise-trained subjects. These results reveal an intimate molecular connection between intramuscular LD biology and mitochondrial metabolism that could prove relevant to the etiology and treatment of insulin resistance and other disorders of lipid imbalance.

PPARγ coactivator-1α contributes to exercise-induced regulation of intramuscular lipid droplet programming in mice and humans

PubMed Central

Koves, Timothy R.; Sparks, Lauren M.; Kovalik, J. P.; Mosedale, Merrie; Arumugam, Ramamani; DeBalsi, Karen L.; Everingham, Karen; Thorne, Leigh; Phielix, Esther; Meex, Ruth C.; Kien, C. Lawrence; Hesselink, Matthijs K. C.; Schrauwen, Patrick; Muoio, Deborah M.

2013-01-01

Intramuscular accumulation of triacylglycerol, in the form of lipid droplets (LD), has gained widespread attention as a hallmark of metabolic disease and insulin resistance. Paradoxically, LDs also amass in muscles of highly trained endurance athletes who are exquisitely insulin sensitive. Understanding the molecular mechanisms that mediate the expansion and appropriate metabolic control of LDs in the context of habitual physical activity could lead to new therapeutic opportunities. Herein, we show that acute exercise elicits robust upregulation of a broad program of genes involved in regulating LD assembly, morphology, localization, and mobilization. Prominent among these was perilipin-5, a scaffolding protein that affects the spatial and metabolic interactions between LD and their surrounding mitochondrial reticulum. Studies in transgenic mice and primary human skeletal myocytes established a key role for the exercise-responsive transcriptional coactivator PGC-1α in coordinating intramuscular LD programming with mitochondrial remodeling. Moreover, translational studies comparing physically active versus inactive humans identified a remarkably strong association between expression of intramuscular LD genes and enhanced insulin action in exercise-trained subjects. These results reveal an intimate molecular connection between intramuscular LD biology and mitochondrial metabolism that could prove relevant to the etiology and treatment of insulin resistance and other disorders of lipid imbalance. PMID:23175776

Insight into the Meligethes aeneus voltage-sensitive sodium channel structure and an attempt to select the best pyrethroid ligands.

PubMed

Obrępalska-Stęplowska, Aleksandra; Czerwoniec, Anna; Wieczorek, Przemysław; Wrzesińska, Barbara

2016-01-01

The voltage-sensitive sodium channel (VSSC) is a target for the pharmacological action of pyrethroids which are used in controlling pests, including those of agricultural importance. Among these is the pollen beetle (Meligethes aeneus F.) - the most serious pest of Brassica napus. Owing to the heavy use of pyrethroids, a widespread build-up of resistance has occurred. The main cause of pyrethroid insensitivity in M. aeneus is considered to be an increased oxidative metabolism; however, the additional mechanism of resistance associated with mutations in the VSSC might contribute to this phenomenon. We generated a VSSC 3D model to study the docking affinities of pyrethroids to their target site within the channel. Our goal was to identify the pyrethroids for which docking affinity scores were high and not affected by potential mutations in the VSSC. We found that the docking scores of cypermethrin are hardly influenced by the appearance of point mutations. Additionally, tau-fluvalinate, deltamethrin and bifenthrin are VSSC ligands with high affinity scores. Our docking models suggest that point mutations in the VSSC binding pocket might affect the stability of ligand interactions and change the pattern of ligand docking locations, which might have a potential effect on VSSC gating properties. © 2015 Society of Chemical Industry.

The role of polycarbonate monomer bisphenol-A in insulin resistance

PubMed Central

2017-01-01

Bisphenol A (BPA) is a synthetic unit of polycarbonate polymers and epoxy resins, the types of plastics that could be found in essentially every human population and incorporated into almost every aspect of the modern human society. BPA polymers appear in a wide range of products, from liquid storages (plastic bottles, can and glass linings, water pipes and tanks) and food storages (plastics wraps and containers), to medical and dental devices. BPA polymers could be hydrolyzed spontaneously or in a photo- or temperature-catalyzed process, providing widespread environmental distribution and chronic exposure to the BPA monomer in contemporary human populations. Bisphenol A is also a xenoestrogen, an endocrine-disrupting chemical (EDC) that interferes with the endocrine system mimicking the effects of an estrogen and could potentially keep our endocrine system in a constant perturbation that parallels endocrine disruption arising during pregnancy, such as insulin resistance (IR). Gestational insulin resistance represents a natural biological phenomenon of higher insulin resistance in peripheral tissues of the pregnant females, when nutrients are increasingly being directed to the embryo instead of being stored in peripheral tissues. Gestational diabetes mellitus may appear in healthy non-diabetic females, due to gestational insulin resistance that leads to increased blood sugar levels and hyperinsulinemia (increased insulin production from the pancreatic beta cells). The hypothesis states that unnoticed and constant exposure to this environmental chemical might potentially lead to the formation of chronic low-level endocrine disruptive state that resembles gestational insulin resistance, which might contribute to the development of diabetes. The increasing body of evidence supports the major premises of this hypothesis, as exemplified by the numerous publications examining the association of BPA and insulin resistance, both epidemiological and mechanistic. However, to what extent BPA might contribute to the development of diabetes in the modern societies still remains unknown. In this review, I discuss the chemical properties of BPA and the sources of BPA contamination found in the environment and in human tissues. I provide an overview of mechanisms for the proposed role of bisphenol A in insulin resistance and diabetes, as well as other related diseases, such as cardiovascular diseases. I describe the transmission of BPA effects to the offspring and postulate that gender related differences might originate from differences in liver enzyme levels, such as UDP-glucuronosyltransferase, which is involved in BPA processing and its elimination from the organism. I discuss the molecular mechanisms of BPA action through nuclear and membrane-bound ER receptors, non-monotonic dose response, epigenetic modifications of the DNA and propose that chronic exposure to weak binders, such as BPA, may mimic the effects of strong binders, such as estrogens. PMID:28929027

The role of polycarbonate monomer bisphenol-A in insulin resistance.

PubMed

Pjanic, Milos

2017-01-01

Bisphenol A (BPA) is a synthetic unit of polycarbonate polymers and epoxy resins, the types of plastics that could be found in essentially every human population and incorporated into almost every aspect of the modern human society. BPA polymers appear in a wide range of products, from liquid storages (plastic bottles, can and glass linings, water pipes and tanks) and food storages (plastics wraps and containers), to medical and dental devices. BPA polymers could be hydrolyzed spontaneously or in a photo- or temperature-catalyzed process, providing widespread environmental distribution and chronic exposure to the BPA monomer in contemporary human populations. Bisphenol A is also a xenoestrogen, an endocrine-disrupting chemical (EDC) that interferes with the endocrine system mimicking the effects of an estrogen and could potentially keep our endocrine system in a constant perturbation that parallels endocrine disruption arising during pregnancy, such as insulin resistance (IR). Gestational insulin resistance represents a natural biological phenomenon of higher insulin resistance in peripheral tissues of the pregnant females, when nutrients are increasingly being directed to the embryo instead of being stored in peripheral tissues. Gestational diabetes mellitus may appear in healthy non-diabetic females, due to gestational insulin resistance that leads to increased blood sugar levels and hyperinsulinemia (increased insulin production from the pancreatic beta cells). The hypothesis states that unnoticed and constant exposure to this environmental chemical might potentially lead to the formation of chronic low-level endocrine disruptive state that resembles gestational insulin resistance, which might contribute to the development of diabetes. The increasing body of evidence supports the major premises of this hypothesis, as exemplified by the numerous publications examining the association of BPA and insulin resistance, both epidemiological and mechanistic. However, to what extent BPA might contribute to the development of diabetes in the modern societies still remains unknown. In this review, I discuss the chemical properties of BPA and the sources of BPA contamination found in the environment and in human tissues. I provide an overview of mechanisms for the proposed role of bisphenol A in insulin resistance and diabetes, as well as other related diseases, such as cardiovascular diseases. I describe the transmission of BPA effects to the offspring and postulate that gender related differences might originate from differences in liver enzyme levels, such as UDP-glucuronosyltransferase, which is involved in BPA processing and its elimination from the organism. I discuss the molecular mechanisms of BPA action through nuclear and membrane-bound ER receptors, non-monotonic dose response, epigenetic modifications of the DNA and propose that chronic exposure to weak binders, such as BPA, may mimic the effects of strong binders, such as estrogens.

An ace-1 gene duplication resorbs the fitness cost associated with resistance in Anopheles gambiae, the main malaria mosquito.

PubMed

Assogba, Benoît S; Djogbénou, Luc S; Milesi, Pascal; Berthomieu, Arnaud; Perez, Julie; Ayala, Diego; Chandre, Fabrice; Makoutodé, Michel; Labbé, Pierrick; Weill, Mylène

2015-10-05

Widespread resistance to pyrethroids threatens malaria control in Africa. Consequently, several countries switched to carbamates and organophophates insecticides for indoor residual spraying. However, a mutation in the ace-1 gene conferring resistance to these compounds (ace-1(R) allele), is already present. Furthermore, a duplicated allele (ace-1(D)) recently appeared; characterizing its selective advantage is mandatory to evaluate the threat. Our data revealed that a unique duplication event, pairing a susceptible and a resistant copy of the ace-1 gene spread through West Africa. Further investigations revealed that, while ace-1(D) confers less resistance than ace-1(R), the high fitness cost associated with ace-1(R) is almost completely suppressed by the duplication for all traits studied. ace-1 duplication thus represents a permanent heterozygote phenotype, selected, and thus spreading, due to the mosaic nature of mosquito control. It provides malaria mosquito with a new evolutionary path that could hamper resistance management.

An ace-1 gene duplication resorbs the fitness cost associated with resistance in Anopheles gambiae, the main malaria mosquito

PubMed Central

Assogba, Benoît S.; Djogbénou, Luc S.; Milesi, Pascal; Berthomieu, Arnaud; Perez, Julie; Ayala, Diego; Chandre, Fabrice; Makoutodé, Michel; Labbé, Pierrick; Weill, Mylène

2015-01-01

Widespread resistance to pyrethroids threatens malaria control in Africa. Consequently, several countries switched to carbamates and organophophates insecticides for indoor residual spraying. However, a mutation in the ace-1 gene conferring resistance to these compounds (ace-1R allele), is already present. Furthermore, a duplicated allele (ace-1D) recently appeared; characterizing its selective advantage is mandatory to evaluate the threat. Our data revealed that a unique duplication event, pairing a susceptible and a resistant copy of the ace-1 gene spread through West Africa. Further investigations revealed that, while ace-1D confers less resistance than ace-1R, the high fitness cost associated with ace-1R is almost completely suppressed by the duplication for all traits studied. ace-1 duplication thus represents a permanent heterozygote phenotype, selected, and thus spreading, due to the mosaic nature of mosquito control. It provides malaria mosquito with a new evolutionary path that could hamper resistance management. PMID:26434951

Collateral damage: rapid exposure-induced evolution of pesticide resistance leads to increased susceptibility to parasites.

PubMed

Jansen, Mieke; Stoks, Robby; Coors, Anja; van Doorslaer, Wendy; de Meester, Luc

2011-09-01

Although natural populations may evolve resistance to anthropogenic stressors such as pollutants, this evolved resistance may carry costs. Using an experimental evolution approach, we exposed different Daphnia magna populations in outdoor containers to the carbamate pesticide carbaryl and control conditions, and assessed the resulting populations for both their resistance to carbaryl as well as their susceptibility to infection by the widespread bacterial microparasite Pasteuria ramosa. Our results show that carbaryl selection led to rapid evolution of carbaryl resistance with seemingly no cost when assessed in a benign environment. However, carbaryl-resistant populations were more susceptible to parasite infection than control populations. Exposure to both stressors reveals a synergistic effect on sterilization rate by P. ramosa, but this synergism did not evolve under pesticide selection. Assessing costs of rapid adaptive evolution to anthropogenic stress in a semi-natural context may be crucial to avoid too optimistic predictions for the fitness of the evolving populations. © 2011 The Author(s).

Molecular characterization of the amplified carboxylesterase gene associated with organophosphorus insecticide resistance in the brown planthopper, Nilaparvata lugens.

PubMed

Small, G J; Hemingway, J

2000-12-01

Widespread resistance to organophosphorus insecticides (OPs) in Nilaparvata lugens is associated with elevation of carboxylesterase activity. A cDNA encoding a carboxylesterase, Nl-EST1, has been isolated from an OP-resistant Sri Lankan strain of N. lugens. The full-length cDNA codes for a 547-amino acid protein with high homology to other esterases/lipases. Nl-EST1 has an N-terminal hydrophobic signal peptide sequence of 24 amino acids which suggests that the mature protein is secreted from cells expressing it. The nucleotide sequence of the homologue of Nl-EST1 in an OP-susceptible, low esterase Sri Lankan strain of N. lugens is identical to Nl-EST1. Southern analysis of genomic DNA from the Sri Lankan OP-resistant and susceptible strains suggests that Nl-EST1 is amplified in the resistant strain. Therefore, resistance to OPs in the Sri Lankan strain is through amplification of a gene identical to that found in the susceptible strain.

Change in Biotypic Diversity of Russian Wheat Aphid (Hemiptera: Aphididae) Populations in the United States.

PubMed

Puterka, G J; Giles, K L; Brown, M J; Nicholson, S J; Hammon, R W; Peairs, F B; Randolph, T L; Michaels, G J; Bynum, E D; Springer, T L; Armstrong, J S; Mornhinweg, D W

2015-04-01

A key component of Russian wheat aphid, Diuraphis noxia (Kurdjumov), management has been through planting resistant wheat cultivars. A new biotype, RWA2, appeared in 2003 which caused widespread damage to wheat cultivars containing the Dn4 gene. Biotypic diversity in Russian wheat aphid populations has not been addressed since 2005 when RWA2 dominated the biotype complex. Our objectives were to determine the biotypic diversity in the Central Great Plains and Colorado Plateau at regional (2010, 2011, 2013) and local (2012) levels and detect the presence of new Russian wheat aphid biotypes. Regional and within-field aphid collections were screened against Russian wheat aphid-resistant wheat genotypes containing genes Dn3, Dn4, Dn6, Dn7, Dn9, CI2401; and resistant barley STARS 9301B. In 2010, all aphid collections from Texas were avirulent to the Dn4 resistance gene in wheat. Regional results revealed Dn4 avirulent RWA6 was widespread (55-84%) in populations infesting wheat in both regions. Biotypes RWA1, 2, and 3/7 were equally represented with percentages<20% each while RWA8 was rarely detected. Combining percentages of RWA1, 6, and 8 across regions to estimate avirulence to Dn4 gene revealed high percentages for both 2011 (64-80%) and 2013 (69-90%). In contrast, the biotype structure at the local level differed where biotype percentages varied up to ≥2-fold between fields. No new biotypes were detected; therefore, Dn7, CI2401, and STARS9301B remained resistant to all known Russian wheat aphid biotypes. This study documents a shift to Dn4 avirulent biotypes and serves as a valuable baseline for biotypic diversity in Russian wheat aphid populations prior to the deployment of new Russian wheat aphid-resistant wheat cultivars. Published by Oxford University Press on behalf of Entomological Society of America 2015. This work is written by US Government employees and is in the public domain in the US.

Interplay among Resistance Profiles, High-Risk Clones, and Virulence in the Caenorhabditis elegans Pseudomonas aeruginosa Infection Model.

PubMed

Sánchez-Diener, Irina; Zamorano, Laura; López-Causapé, Carla; Cabot, Gabriel; Mulet, Xavier; Peña, Carmen; Del Campo, Rosa; Cantón, Rafael; Doménech-Sánchez, Antonio; Martínez-Martínez, Luis; Arcos, Susana C; Navas, Alfonso; Oliver, Antonio

2017-12-01

The increasing prevalence of nosocomial infections produced by multidrug-resistant (MDR) or extensively drug-resistant (XDR) Pseudomonas aeruginosa is frequently linked to widespread international strains designated high-risk clones. In this work, we attempted to decipher the interplay between resistance profiles, high-risk clones, and virulence, testing a large ( n = 140) collection of well-characterized P. aeruginosa isolates from different sources (bloodstream infections, nosocomial outbreaks, cystic fibrosis, and the environment) in a Caenorhabditis elegans infection model. Consistent with previous data, we documented a clear inverse correlation between antimicrobial resistance and virulence in the C. elegans model. Indeed, the lowest virulence was linked to XDR profiles, which were typically linked to defined high-risk clones. However, virulence varied broadly depending on the involved high-risk clone; it was high for sequence type 111 (ST111) and ST235 but very low for ST175. The highest virulence of ST235 could be attributed to its exoU + type III secretion system (TTSS) genotype, which was found to be linked with higher virulence in our C. elegans model. Other markers, such as motility or pigment production, were not essential for virulence in the C. elegans model but seemed to be related with the higher values of the statistical normalized data. In contrast to ST235, the ST175 high-risk clone, which is widespread in Spain and France, seems to be associated with a particularly low virulence in the C. elegans model. Moreover, the previously described G154R AmpR mutation, prevalent in ST175, was found to contribute to the reduced virulence, although it was not the only factor involved. Altogether, our results provide a major step forward for understanding the interplay between P. aeruginosa resistance profiles, high-risk clones, and virulence. Copyright © 2017 American Society for Microbiology.

Interplay among Resistance Profiles, High-Risk Clones, and Virulence in the Caenorhabditis elegans Pseudomonas aeruginosa Infection Model

PubMed Central

Sánchez-Diener, Irina; López-Causapé, Carla; Mulet, Xavier; Cantón, Rafael; Doménech-Sánchez, Antonio; Martínez-Martínez, Luis; Arcos, Susana C.; Navas, Alfonso

2017-01-01

ABSTRACT The increasing prevalence of nosocomial infections produced by multidrug-resistant (MDR) or extensively drug-resistant (XDR) Pseudomonas aeruginosa is frequently linked to widespread international strains designated high-risk clones. In this work, we attempted to decipher the interplay between resistance profiles, high-risk clones, and virulence, testing a large (n = 140) collection of well-characterized P. aeruginosa isolates from different sources (bloodstream infections, nosocomial outbreaks, cystic fibrosis, and the environment) in a Caenorhabditis elegans infection model. Consistent with previous data, we documented a clear inverse correlation between antimicrobial resistance and virulence in the C. elegans model. Indeed, the lowest virulence was linked to XDR profiles, which were typically linked to defined high-risk clones. However, virulence varied broadly depending on the involved high-risk clone; it was high for sequence type 111 (ST111) and ST235 but very low for ST175. The highest virulence of ST235 could be attributed to its exoU+ type III secretion system (TTSS) genotype, which was found to be linked with higher virulence in our C. elegans model. Other markers, such as motility or pigment production, were not essential for virulence in the C. elegans model but seemed to be related with the higher values of the statistical normalized data. In contrast to ST235, the ST175 high-risk clone, which is widespread in Spain and France, seems to be associated with a particularly low virulence in the C. elegans model. Moreover, the previously described G154R AmpR mutation, prevalent in ST175, was found to contribute to the reduced virulence, although it was not the only factor involved. Altogether, our results provide a major step forward for understanding the interplay between P. aeruginosa resistance profiles, high-risk clones, and virulence. PMID:28923877

Regulation of DNA methylation turnover at LTR retrotransposons and imprinted loci by the histone methyltransferase Setdb1.

PubMed

Leung, Danny; Du, Tingting; Wagner, Ulrich; Xie, Wei; Lee, Ah Young; Goyal, Preeti; Li, Yujing; Szulwach, Keith E; Jin, Peng; Lorincz, Matthew C; Ren, Bing

2014-05-06

During mammalian development, DNA methylation patterns need to be reset in primordial germ cells (PGCs) and preimplantation embryos. However, many LTR retrotransposons and imprinted genes are impervious to such global epigenetic reprogramming via hitherto undefined mechanisms. Here, we report that a subset of such genomic regions are resistant to widespread erasure of DNA methylation in mouse embryonic stem cells (mESCs) lacking the de novo DNA methyltransferases (Dnmts) Dnmt3a and Dnmt3b. Intriguingly, these loci are enriched for H3K9me3 in mESCs, implicating this mark in DNA methylation homeostasis. Indeed, deletion of the H3K9 methyltransferase SET domain bifurcated 1 (Setdb1) results in reduced H3K9me3 and DNA methylation levels at specific loci, concomitant with increased 5-hydroxymethylation (5hmC) and ten-eleven translocation 1 binding. Taken together, these data reveal that Setdb1 promotes the persistence of DNA methylation in mESCs, likely reflecting one mechanism by which DNA methylation is maintained at LTR retrotransposons and imprinted genes during developmental stages when DNA methylation is reprogrammed.

Unique features of a global human ectoparasite identified through sequencing of the bed bug genome

USDA-ARS?s Scientific Manuscript database

The bed bug, Cimex lectularius, has re-established itself as a ubiquitous human ectoparasite throughout much of the world during the last two decades. This global resurgence is likely linked to increased international travel and commerce and widespread insecticide resistance. Analyses of the C. le...

Positive Returns from Investment in Fusiform Rust Research

Treesearch

John M. Pye; John E. Wagner; Thomas P. Holmes; Frederick W. Cubbage

1997-01-01

Fusiform rust [Cronartium quercuum (Berk.) Miy. ex Shirai f. sp. fusiforme Burdsall et Snow] is a widespread and damaging disease of loblolly and slash pine across much of the Southern United States. Research by government and university scientists has identified families of these species with improved genetic resistance to infection by the disease, allowing production...

Disease Vector Ecology Profile: Colombia

DTIC Science & Technology

1998-12-01

the Amazon Basin. Unknown. Unknown. Culex gnomatus VEE (Ecuador, Peru ) Many mammals and birds, but equines are key reservoirs with high...Arboviruses other than Dengue or Yellow Fever in the Amazon Basin and Associated Northwestern Regions of South America...widespread (Amazonia, Orinoquia, Cauca Valley, Caribbean regions), and to mefloquine and amodiaquine ( Amazon Basin). Plasmodium vivax resistance

Rose parental characterization and population development for the identification of novel rose black spot resistance genes [abstract

USDA-ARS?s Scientific Manuscript database

Rose black spot disease, caused by the pathogen Diplocarpon rosae Wolf, is one of the most widespread and serious diseases of outdoor-grown roses worldwide. Defoliation caused by the disease compromises ornamental value, and repeated defoliation events weakens plants and can lead to plant death. Bot...

Soil wettability and wetting agents . . . our current knowledge of the problem

Treesearch

Leonard F. DeBano; Joseph F. Osborn; Jay S. Krammes; John Letey

1967-01-01

Soils that resist wetting are a widespread phenomenon on chaparral areas of southern California watersheds. On burned watersheds, non-wettable soils markedly reduce moisture movement during both evaporation and infiltration. The reduced infiltration rate probably contributes significantly to the high debris production from the watersheds. Factors involved in the...

Change in biotypic diversity of Russian wheat aphid (Hemiptera: Aphididae) populations in the United States

USDA-ARS?s Scientific Manuscript database

A key component of Russian wheat aphid (RWA), Diuraphis noxia (Kurdjumov), management has been through planting resistant wheat cultivars. A new biotype, RWA2, appeared in 2003 which caused widespread damage to wheat cultivars containing Dn4 gene. Biotypic diversity in RWA populations has not been...

Characterization of antibiotic resistant (AR) fecal indicators in runoff from fields amended with swine manure

USDA-ARS?s Scientific Manuscript database

The application of animal manures to agricultural soil is a widespread practice. One concern associated with food animal manures is the introduction of antibiotic drugs, AR bacteria, and AR genes that may be spread through and across agroecosystems, with the potential to adversely impact the treatm...

Synthesis and insecticidal activity of novel pyrimidine derivatives containing urea pharmacophore against Aedes aegypti

USDA-ARS?s Scientific Manuscript database

Aedes aegypti is a major mosquito vector for the transmission of serious diseases, especially dengue and yellow fever. More than one billion people in developing countries are at risk. The widespread and continual use of pesticides can lead to resistant mosquitoes. In order to maintain mosquito cont...

Young People and Alcohol--Where's the Risk? Changing the Focus of School-Based Prevention Initiatives

ERIC Educational Resources Information Center

Petrie, Margaret

2017-01-01

Research statistics highlighting the social costs of widespread excessive alcohol consumption have led to a proliferation of school-based prevention programmes that aim to give young people the skills and knowledge necessary to resist social pressure to drink alcohol and avoid potentially "risky" consumption. Such interventions offer,…

Gender Equity in Science and Engineering: Advancing Change in Higher Education. Routledge Studies in Management, Organizations and Society

ERIC Educational Resources Information Center

Bilimoria, Diana; Liang, Xiangfen

2011-01-01

Women faculty's participation in academic science and engineering is critical for future US global competitiveness, yet their underrepresentation particularly in senior positions remains a widespread problem. To overcome persistent institutional resistance and barriers to change, the "NSF ADVANCE" institutional transformation initiative,…

RNA-Sequencing of Cercospora beticola DMI-sensitive and -resistant isolates after treatment with tetraconazole identifies common and contrasting pathway induction

USDA-ARS?s Scientific Manuscript database

Cercospora beticola causes Cercospora leaf spot of sugarbeet. Cercospora leaf spot management measures often include application of the sterol demethylation inhibitor (DMI) class of fungicides. The reliance on DMIs and the consequent selection pressures imposed by their widespread use has led to th...

A Risk Assessment of Antibiotic Pan-Drug-Resistance in the UK: Bayesian Analysis of an Expert Elicitation Study

PubMed Central

Carter, Daniel; Charlett, André; Conti, Stefano; Robotham, Julie V.; Johnson, Alan P.; Livermore, David M.; Fowler, Tom; Sharland, Mike; Hopkins, Susan; Woodford, Neil; Burgess, Philip; Dobra, Stephen

2017-01-01

To inform the UK antimicrobial resistance strategy, a risk assessment was undertaken of the likelihood, over a five-year time-frame, of the emergence and widespread dissemination of pan-drug-resistant (PDR) Gram-negative bacteria that would pose a major public health threat by compromising effective healthcare delivery. Subsequent impact over five- and 20-year time-frames was assessed in terms of morbidity and mortality attributable to PDR Gram-negative bacteraemia. A Bayesian approach, combining available data with expert prior opinion, was used to determine the probability of the emergence, persistence and spread of PDR bacteria. Overall probability was modelled using Monte Carlo simulation. Estimates of impact were also obtained using Bayesian methods. The estimated probability of widespread occurrence of PDR pathogens within five years was 0.2 (95% credibility interval (CrI): 0.07–0.37). Estimated annual numbers of PDR Gram-negative bacteraemias at five and 20 years were 6800 (95% CrI: 400–58,600) and 22,800 (95% CrI: 1500–160,000), respectively; corresponding estimates of excess deaths were 1900 (95% CrI: 0–23,000) and 6400 (95% CrI: 0–64,000). Over 20 years, cumulative estimates indicate 284,000 (95% CrI: 17,000–1,990,000) cases of PDR Gram-negative bacteraemia, leading to an estimated 79,000 (95% CrI: 0–821,000) deaths. This risk assessment reinforces the need for urgent national and international action to tackle antibiotic resistance. PMID:28272350

A low-cost contact system to assess load displacement velocity in a resistance training machine.

PubMed

Buscà, Bernat; Font, Anna

2011-01-01

This study sought to determine the validity of a new system for assessing the displacement and average velocity within machine-based resistance training exercise using the Chronojump System. The new design is based on a contact bar and a simple, low-cost mechanism that detects the conductivity of electrical potentials with a precision chronograph. This system allows coaches to assess velocity to control the strength training process. A validation study was performed by assessing the concentric phase parameters of a leg press exercise. Output time data from the Chronojump System in combination with the pre-established range of movement was compared with data from a position sensor connected to a Biopac System. A subset of 87 actions from 11 professional tennis players was recorded and, using the two methods, average velocity and displacement variables in the same action were compared. A t-test for dependent samples and a correlation analysis were undertaken. The r value derived from the correlation between the Biopac System and the contact Chronojump System was >0.94 for all measures of displacement and velocity on all loads (p < 0.01). The Effect Size (ES) was 0.18 in displacement and 0.14 in velocity and ranged from 0.09 to 0.31 and from 0.07 to 0.34, respectively. The magnitude of the difference between the two methods in all parameters and the correlation values provided certain evidence of validity of the Chronojump System to assess the average displacement velocity of loads in a resistance training machine. Key pointsThe assessment of speed in resistance machines is a valuable source of information for strength training.Many commercial systems used to assess velocity, power and force are expensive thereby preventing widespread use by coaches and athletes.The system is intended to be a low-cost device for assessing and controlling the velocity exerted on each repetition in any resistance training machine.The system could be easily adapted in any vertical displacement barbell exercise.

Detection of antimicrobial resistance genes associated with the International Space Station environmental surfaces

DOE Office of Scientific and Technical Information (OSTI.GOV)

Urbaniak, C.; Sielaff, A. Checinska; Frey, K. G.

Antimicrobial resistance (AMR) is a global health issue. In an effort to minimize this threat to astronauts, who may be immunocompromised and thus at a greater risk of infection from antimicrobial resistant pathogens, a comprehensive study of the ISS “resistome’ was conducted. Using whole genome sequencing (WGS) and disc diffusion antibiotic resistance assays, 9 biosafety level 2 organisms isolated from the ISS were assessed for their antibiotic resistance. Molecular analysis of AMR genes from 24 surface samples collected from the ISS during 3 different sampling events over a span of a year were analyzed with Ion AmpliSeq™ and metagenomics. Discmore » diffusion assays showed that Enterobacter bugandensis strains were resistant to all 9 antibiotics tested and Staphylococcus haemolyticus being resistant to none. Ion AmpliSeq™ revealed that 123 AMR genes were found, with those responsible for beta-lactam and trimethoprim resistance being the most abundant and widespread. Using a variety of methods, the genes involved in antimicrobial resistance have been examined for the first time from the ISS. Lastly, this information could lead to mitigation strategies to maintain astronaut health during long duration space missions when return to Earth for treatment is not possible.« less

Detection of antimicrobial resistance genes associated with the International Space Station environmental surfaces

DOE PAGES

Urbaniak, C.; Sielaff, A. Checinska; Frey, K. G.; ...

2018-01-16

Antimicrobial resistance (AMR) is a global health issue. In an effort to minimize this threat to astronauts, who may be immunocompromised and thus at a greater risk of infection from antimicrobial resistant pathogens, a comprehensive study of the ISS “resistome’ was conducted. Using whole genome sequencing (WGS) and disc diffusion antibiotic resistance assays, 9 biosafety level 2 organisms isolated from the ISS were assessed for their antibiotic resistance. Molecular analysis of AMR genes from 24 surface samples collected from the ISS during 3 different sampling events over a span of a year were analyzed with Ion AmpliSeq™ and metagenomics. Discmore » diffusion assays showed that Enterobacter bugandensis strains were resistant to all 9 antibiotics tested and Staphylococcus haemolyticus being resistant to none. Ion AmpliSeq™ revealed that 123 AMR genes were found, with those responsible for beta-lactam and trimethoprim resistance being the most abundant and widespread. Using a variety of methods, the genes involved in antimicrobial resistance have been examined for the first time from the ISS. Lastly, this information could lead to mitigation strategies to maintain astronaut health during long duration space missions when return to Earth for treatment is not possible.« less

Detection of antimicrobial resistance genes associated with the International Space Station environmental surfaces.

PubMed

Urbaniak, C; Sielaff, A Checinska; Frey, K G; Allen, J E; Singh, N; Jaing, C; Wheeler, K; Venkateswaran, K

2018-01-16

Antimicrobial resistance (AMR) is a global health issue. In an effort to minimize this threat to astronauts, who may be immunocompromised and thus at a greater risk of infection from antimicrobial resistant pathogens, a comprehensive study of the ISS "resistome' was conducted. Using whole genome sequencing (WGS) and disc diffusion antibiotic resistance assays, 9 biosafety level 2 organisms isolated from the ISS were assessed for their antibiotic resistance. Molecular analysis of AMR genes from 24 surface samples collected from the ISS during 3 different sampling events over a span of a year were analyzed with Ion AmpliSeq ™ and metagenomics. Disc diffusion assays showed that Enterobacter bugandensis strains were resistant to all 9 antibiotics tested and Staphylococcus haemolyticus being resistant to none. Ion AmpliSeq ™ revealed that 123 AMR genes were found, with those responsible for beta-lactam and trimethoprim resistance being the most abundant and widespread. Using a variety of methods, the genes involved in antimicrobial resistance have been examined for the first time from the ISS. This information could lead to mitigation strategies to maintain astronaut health during long duration space missions when return to Earth for treatment is not possible.

Widespread distribution of a tet W determinant among tetracycline-resistant isolates of the animal pathogen Arcanobacterium pyogenes.

PubMed

Billington, Stephen J; Songer, J Glenn; Jost, B Helen

2002-05-01

Tetracycline resistance is common among isolates of the animal commensal and opportunistic pathogen Arcanobacterium pyogenes. The tetracycline resistance determinant cloned from two bovine isolates of A. pyogenes was highly similar at the DNA level (92% identity) to the tet(W) gene, encoding a ribosomal protection tetracycline resistance protein, from the rumen bacterium Butyrivibrio fibrisolvens. The tet(W) gene was found in all 20 tetracycline-resistant isolates tested, indicating that it is a widely distributed determinant of tetracycline resistance in this organism. In 25% of tetracycline-resistant isolates, the tet(W) gene was associated with a mob gene, encoding a functional mobilization protein, and an origin of transfer, suggesting that the determinant may be transferable to other bacteria. In fact, low-frequency transfer of tet(W) was detected from mob+ A. pyogenes isolates to a tetracycline-sensitive A. pyogenes recipient. The mobile nature of this determinant and the presence of A. pyogenes in the gastrointestinal tract of cattle and pigs suggest that A. pyogenes may have inherited this determinant within the gastrointestinal tracts of these animals.

Intrinsic, adaptive and acquired antimicrobial resistance in Gram-negative bacteria.

PubMed

Arzanlou, Mohsen; Chai, Wern Chern; Venter, Henrietta

2017-02-28

Gram-negative bacteria are responsible for a large proportion of antimicrobial-resistant infections in humans and animals. Among this class of bacteria are also some of the most successful environmental organisms. Part of this success is their adaptability to a variety of different niches, their intrinsic resistance to antimicrobial drugs and their ability to rapidly acquire resistance mechanisms. These mechanisms of resistance are not exclusive and the interplay of several mechanisms causes high levels of resistance. In this review, we explore the molecular mechanisms underlying resistance in Gram-negative organisms and how these different mechanisms enable them to survive many different stress conditions. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

[Benefits of spironolactone as the optimal treatment for drug resistant hypertension. Pathway-2 trial review].

PubMed

Prado, J C; Ruilope, L M; Segura, J

Pathway-2 is the first randomised, double-blind and crossover trial that compares spironolactone as a fourth drug with alfa-blocker, beta-blocker and placebo. This study shows that spironolactone is the drug with more possibilities of success for the management of patients with difficult-to-treat hypertension in patients with a combination of three drugs and poor control. The results validate the widespread treatment with mineralocorticoid receptor antagonists in resistant hypertension. Copyright © 2016 SEH-LELHA. Publicado por Elsevier España, S.L.U. All rights reserved.

Transforming Wartime Contracting: Controlling Costs, Reducing Risks

DTIC Science & Technology

2011-08-01

reduce the risk of awarding contracts to companies with questionable capability to perform. Expansion of investigative authority and jurisdiction ...A forcing function is needed to ensure widespread and effective adoption of contingency-contracting reform. Otherwise, agency inertia , resistance to...inflamed because jurisdiction over contractors is ambiguous, legal accountability is uncertain, and a clear command-and-control structure is absent. A

Biotic resistance via granivory: Establishment by invasive, naturalized, and native asters reflects generalist preference

Treesearch

Dean E. Pearson; Ragan M. Callaway; John L. Maron

2011-01-01

Escape from specialist natural enemies is frequently invoked to explain exotic plant invasions, but little attention has been paid to how generalist consumers in the recipient range may influence invasion. We examined how seed preferences of the widespread generalist granivore Peromyscus maniculatus related to recruitment of the strongly invasive exotic Centaurea...

Learning about Phases of the Moon and Eclipses: A Guide for Teachers and Curriculum Developers

ERIC Educational Resources Information Center

Kavanagh, Claudine; Agan, Lori; Sneider, Cary

2005-01-01

"National Science Education Standards" (1996), published by the National Research Council, recommends that students learn to explain Moon phases and eclipses by the time they graduate from eighth grade. It is clear from the research literature, however, that misconceptions about Moon phases and eclipses are widespread and resistant to change, even…

Evidence of cellulose digestion in the wood boring isopod Sphaeroma terebrans

Treesearch

Lori K. Benson; Stanley A. Rice; Bruce R. Johnson

1999-01-01

Sphaeroma terebrans Bate is a widespread estuarine, wood-boring, isopod found in red mangrove (Rhizophora mangle) forests of tropical and subtropical estuarine waters. Because it causes extensive damage to man-made structures in marine coastal zones and is resistant to common methods of wood preservation it is important to understand fully how S. terebrans uses the...

Amplification of DNA from preserved specimens shows blowflies were preadapted for the rapid evolution of insecticide resistance

PubMed Central

Hartley, C. J.; Newcomb, R. D.; Russell, R. J.; Yong, C. G.; Stevens, J. R.; Yeates, D. K.; La Salle, J.; Oakeshott, J. G.

2006-01-01

Mutations of esterase 3 confer two forms of organophosphate resistance on contemporary Australasian Lucilia cuprina. One form, called diazinon resistance, is slightly more effective against commonly used insecticides and is now more prevalent than the other form, called malathion resistance. We report here that the single amino acid replacement associated with diazinon resistance and two replacements associated with malathion resistance also occur in esterase 3 in the sibling species Lucilia sericata, suggesting convergent evolution around a finite set of resistance options. We also find parallels between the species in the geographic distributions of the polymorphisms: In both cases, the diazinon-resistance change is absent or rare outside Australasia where insecticide pressure is lower, whereas the changes associated with malathion resistance are widespread. Furthermore, PCR analysis of pinned specimens of Australasian L. cuprina collected before the release of organophosphate insecticides reveals no cases of the diazinon-resistance change but several cases of those associated with malathion resistance. Thus, the early outbreak of resistance in this species can be explained by the preexistence of mutant alleles encoding malathion resistance. The pinned specimen analysis also shows much higher genetic diversity at the locus before organophosphate use, suggesting that the subsequent sweep of diazinon resistance in Australasia has compromised the scope for the locus to respond further to the ongoing challenge of the insecticides. PMID:16723400

diskImageR: quantification of resistance and tolerance to antimicrobial drugs using disk diffusion assays.

PubMed

Gerstein, Aleeza C; Rosenberg, Alexander; Hecht, Inbal; Berman, Judith

2016-07-01

Microbial pathogens represent an increasing threat to human health. Although many infections can be successfully treated and cleared, drug resistance is a widespread problem. The existence of subpopulations of 'tolerant' cells (where a fraction of the population is able to grow above the population resistance level) may increase the rate of treatment failure; yet, existing methods to measure subpopulation effects are cumbersome. Here we describe diskImageR, a computational pipeline that analyses photographs of disk diffusion assays to determine the degree of drug susceptibility [the radius of inhibition, (RAD)], and two aspects of subpopulation growth [the fraction of growth (FoG) within the zone of inhibition, (ZOI), and the rate of change in growth from no drug to inhibitory drug concentrations, (SLOPE)]. diskImageR was used to examine the response of the human fungal pathogen Candida albicans to the antifungal drug fluconazole across different strain backgrounds and growth conditions. Disk diffusion assays performed under Clinical and Laboratory Standards Institute (CLSI) conditions led to more susceptibility and less tolerance than assays performed using rich medium conditions. We also used diskImageR to quantify the effects of three drugs in combination with fluconazole, finding that all three combinations affected tolerance, with the effect of one drug (doxycycline) being very strain dependent. The three drugs had different effects on susceptibility, with doxycycline generally having no effect, chloroquine generally increasing susceptibility and pyrvinium pamoate generally reducing susceptibility. The ability to simultaneously quantitate different aspects of microbial drug responses will facilitate the study of mechanisms of subpopulation responses in the presence of antimicrobial drugs.

Pyrethroid-Resistance Level Affects Performance of Larvicides and Adulticides From Different Insecticide Classes in Populations of Listronotus maculicollis (Coleoptera: Curculionidae).

PubMed

Koppenhöfer, Albrecht M; Kostromytska, Olga S; Wu, Shaohui

2018-05-25

The annual bluegrass weevil, Listronotus maculicollis Kirby (Coleoptera: Curculionidae), is a major pest of golf course turf in eastern North America with widespread insecticide resistance. This study examined the effect of pyrethroid-resistance level on the efficacy of adulticides and larvicides from different insecticide classes commonly used for L. maculicollis management through greenhouse and field studies. The tested populations had previously been determined to be susceptible, moderately resistant, resistant, and highly resistant to the pyrethroid bifenthrin. Targeting adults, efficacy was significantly reduced for bifenthrin against the highly resistant population and for the spinosyn spinosad and the oxadizine indoxacarb against the resistant and highly resistant populations. Efficacy of the organophosphate chlorpyrifos was not significantly reduced. No adulticide provided significant control of resistant and highly resistant populations. Targeting larvae, the efficacy of spinosad and the anthranilic diamide cyantraniliprole was marginally reduced against the highly resistant population. Significant reductions in efficacy and no significant control were observed for indoxacarb against the highly resistant population and for the neonicotinoid clothianidin, the anthranilic diamide chlorantraniliprole, and the organophosphate trichlorfon against the resistant and highly resistant populations. Our findings lay the groundwork for management recommendations for populations with different resistance levels. Generally, synthetic insecticide applications should be minimized with greater use of larvicides supplemented with nonchemical control alternatives. The remaining effective larvicides should be rotated using cyantraniliprole, spinosad, and indoxacarb against resistant and cyantraniliprole and spinosad against highly resistant populations.

Statins: antimicrobial resistance breakers or makers?

PubMed Central

Lareu, Ricky R.; Dix, Brett R.; Hughes, Jeffery D.

2017-01-01

Introduction The repurposing of non-antibiotic drugs as adjuvant antibiotics may help break antimicrobial resistance (AMR). Statins are commonly prescribed worldwide to lower cholesterol. They also possess qualities of AMR “breakers”, namely direct antibacterial activity, synergism with antibiotics, and ability to stimulate the host immune system. However, statins’ role as AMR breakers may be limited. Their current extensive use for cardiovascular protection might result in selective pressures for resistance, ironically causing statins to be AMR “makers” instead. This review examines statins’ potential as AMR breakers, probable AMR makers, and identifies knowledge gaps in a statin-bacteria-human-environment continuum. The most suitable statin for repurposing is identified, and a mechanism of antibacterial action is postulated based on structure-activity relationship analysis. Methods A literature search using keywords “statin” or “statins” combined with “minimum inhibitory concentration” (MIC) was performed in six databases on 7th April 2017. After screening 793 abstracts, 16 relevant studies were identified. Unrelated studies on drug interactions; antifungal or antiviral properties of statins; and antibacterial properties of mevastatin, cerivastatin, antibiotics, or natural products were excluded. Studies involving only statins currently registered for human use were included. Results Against Gram-positive bacteria, simvastatin generally exerted the greatest antibacterial activity (lowest MIC) compared to atorvastatin, rosuvastatin, and fluvastatin. Against Gram-negative bacteria, atorvastatin generally exhibited similar or slightly better activity compared to simvastatin, but both were more potent than rosuvastatin and fluvastatin. Discussion Statins may serve as AMR breakers by working synergistically with existing topical antibiotics, attenuating virulence factors, boosting human immunity, or aiding in wound healing. It is probable that statins’ mechanism of antibacterial activity involves interference of bacterial cell regulatory functions via binding and disrupting cell surface structures such as wall teichoic acids, lipoteichoic acids, lipopolysaccharides, and/or surface proteins. The widespread use of statins for cardiovascular protection may favor selective pressures or co-selection for resistance, including dysbiosis of the human gut microbiota, sublethal plasma concentrations in bacteremic patients, and statin persistence in the environment, all possibly culminating in AMR. Conclusion Simvastatin appears to be the most suitable statin for repurposing as a novel adjuvant antibiotic. Current evidence better supports statins as potential AMR breakers, but their role as plausible AMR makers cannot be excluded. Elucidating the mechanism of statins’ antibacterial activity is perhaps the most important knowledge gap to address as this will likely clarify statins’ role as AMR breakers or makers. PMID:29085751

Next step in the ongoing arms race between myxoma virus and wild rabbits in Australia is a novel disease phenotype

PubMed Central

Kerr, Peter J.; Cattadori, Isabella M.; Liu, June; Sim, Derek G.; Dodds, Jeff W.; Brooks, Jason W.; Kennett, Mary J.; Holmes, Edward C.

2017-01-01

In host–pathogen arms races, increases in host resistance prompt counteradaptation by pathogens, but the nature of that counteradaptation is seldom directly observed outside of laboratory models. The best-documented field example is the coevolution of myxoma virus (MYXV) in European rabbits. To understand how MYXV in Australia has continued to evolve in wild rabbits under intense selection for genetic resistance to myxomatosis, we compared the phenotypes of the progenitor MYXV and viral isolates from the 1950s and the 1990s in laboratory rabbits with no resistance. Strikingly, and unlike their 1950s counterparts, most virus isolates from the 1990s induced a highly lethal immune collapse syndrome similar to septic shock. Thus, the next step in this canonical case of coevolution after a species jump has been further escalation by the virus in the face of widespread host resistance. PMID:28808019

Glycol porphyrin derivatives and temoporfin elicit resistance to photodynamic therapy by different mechanisms

PubMed Central

Kralova, Jarmila; Kolar, Michal; Kahle, Michal; Truksa, Jaroslav; Lettlova, Sandra; Balusikova, Kamila; Bartunek, Petr

2017-01-01

The development of drug resistance is a major problem which often occurs during anticancer chemotherapies. Photodynamic therapy (PDT) has been studied as an alternative treatment modality for drug-resistant tumors, however the question of resistance to PDT and potential cross-resistance with chemotherapy has yet to be fully answered. To investigate the mechanism of resistance to PDT, we developed an in vitro experimental model system in a mouse mammary carcinoma cell line 4T1. We used two ethylene glycol derivatives of tetraphenylporphyrin, and tetraphenylchlorin derivative, temoporfin, as photosensitizers (PS). PDT-resistant clones were obtained by exposure to a set concentration of PS followed by irradiation with increasing light doses. PDT resistance to soluble glycol porphyrins was mediated mainly by increased drug efflux through ABCB1 (P-glycoprotein) as we demonstrated by specific ABCB1 knockdown experiments, which in turn rescued the sensitivity of resistant cells to PDT. In contrast, resistance raised to temoporfin, which is generally more lipophilic than glycol porphyrins, elicited mechanism based on sequestration of the drug to lysosomes. The resistance that is acquired from a particular PS could be overcome by using a different PS, which is not susceptible to the same mechanism(s) of resistance. Elucidation of the underlying mechanisms in various types of resistance might facilitate improvements in PDT treatment design. PMID:28295025

Nudges in a post-truth world.

PubMed

Levy, Neil

2017-08-01

Nudges-policy proposals informed by work in behavioural economics and psychology that are designed to lead to better decision-making or better behaviour-are controversial. Critics allege that they bypass our deliberative capacities, thereby undermining autonomy and responsible agency. In this paper, I identify a kind of nudge I call a nudge to reason, which make us more responsive to genuine evidence. I argue that at least some nudges to reason do not bypass our deliberative capacities. Instead, use of these nudges should be seen as appeals to mechanisms partially constitutive of these capacities, and therefore as benign (so far as autonomy and responsible agency are concerned). I sketch some concrete proposals for nudges to reason which are especially important given the apparent widespread resistance to evidence seen in recent political events. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Promising Hard Carbon Coatings on Cu Substrates: Corrosion and Tribological Performance with Theoretical Aspect

NASA Astrophysics Data System (ADS)

Kumar, A. Madhan; Babu, R. Suresh; Obot, I. B.; Adesina, Akeem Yusuf; Ibrahim, Ahmed; de Barros, A. L. F.

2018-05-01

Protecting the surface of metals and alloys against corrosion and wear is of abundant importance owing to their widespread applications. In the present work, we report the improved anticorrosion and tribo-mechanical performance of copper (Cu) by a hard carbon (HC) coating synthesized in different pyrolysis temperature. Structural and surface characterization with roughness measurements was systematically investigated using various techniques. Effect of pyrolysis temperature on the corrosion behavior of coated Cu substrates in 0.6 M NaCl solution was evaluated via electrochemical impedance spectroscopy, potentiodynamic polarization. Pin-on-disk wear test of coated Cu substrate showed the influence of the pyrolysis temperature on the wear resistance performance of the HC coatings. According to the obtained results, it could be concluded that the HC coatings synthesized at 1100 °C revealed an enhanced comprehensive performance, revealing their possible utilization as a protective coating for Cu substrates in chloride environment. Monte Carlo simulations have been utilized to elucidate the interaction between the Cu surface and HC coatings.

Promising Hard Carbon Coatings on Cu Substrates: Corrosion and Tribological Performance with Theoretical Aspect

NASA Astrophysics Data System (ADS)

Kumar, A. Madhan; Babu, R. Suresh; Obot, I. B.; Adesina, Akeem Yusuf; Ibrahim, Ahmed; de Barros, A. L. F.

2018-01-01

Protecting the surface of metals and alloys against corrosion and wear is of abundant importance owing to their widespread applications. In the present work, we report the improved anticorrosion and tribo-mechanical performance of copper (Cu) by a hard carbon (HC) coating synthesized in different pyrolysis temperature. Structural and surface characterization with roughness measurements was systematically investigated using various techniques. Effect of pyrolysis temperature on the corrosion behavior of coated Cu substrates in 0.6 M NaCl solution was evaluated via electrochemical impedance spectroscopy, potentiodynamic polarization. Pin-on-disk wear test of coated Cu substrate showed the influence of the pyrolysis temperature on the wear resistance performance of the HC coatings. According to the obtained results, it could be concluded that the HC coatings synthesized at 1100 °C revealed an enhanced comprehensive performance, revealing their possible utilization as a protective coating for Cu substrates in chloride environment. Monte Carlo simulations have been utilized to elucidate the interaction between the Cu surface and HC coatings.

Immunology, epidemiology and mathematical modelling towards a better understanding of invasive non-typhoidal Salmonella disease and rational vaccination approaches.

PubMed

Mastroeni, Pietro; Rossi, Omar

2016-12-01

Invasive non-typhoidal Salmonella (iNTS) infections cause a high burden of lethal sepsis in young children and HIV patients, often associated with malaria, anaemia, malnutrition and sickle-cell disease. Vaccines against iNTS are urgently needed but none are licensed yet. Areas covered: This review illustrates how immunology, epidemiology and within-host pathogen behaviour affect invasive Salmonella infections and highlights how this knowledge can assist the improvement and choice of vaccines. Expert Commentary: Control of iNTS disease requires approaches that reduce transmission and improve diagnosis and treatment. These are often difficult to implement due to the fragile ecology and economies in endemic countries. Vaccines will be key tools in the fight against iNTS disease. To optimise vaccine design, we need to better define protective antigens and mechanisms of resistance to disease in susceptible populations even in those individuals where innate immunity may be impaired by widespread comorbidities.

Bulk antimony sulfide with excellent cycle stability as next-generation anode for lithium-ion batteries

PubMed Central

Yu, Denis Y. W.; Hoster, Harry E.; Batabyal, Sudip K.

2014-01-01

Nanomaterials as anode for lithium-ion batteries (LIB) have gained widespread interest in the research community. However, scaling up and processibility are bottlenecks to further commercialization of these materials. Here, we report that bulk antimony sulfide with a size of 10–20 μm exhibits a high capacity and stable cycling of 800 mAh g−1. Mechanical and chemical stabilities of the electrodes are ensured by an optimal electrode-electrolyte system design, with a polyimide-based binder together with fluoroethylene carbonate in the electrolyte. The polyimide binder accommodates the volume expansion during alloying process and fluoroethylene carbonate suppresses the increase in charge transfer resistance of the electrodes. We observed that particle size is not a major factor affecting the charge-discharge capacities, rate capability and stability of the material. Despite the large particle size, bulk antimony sulfide shows excellent rate performance with a capacity of 580 mAh g−1 at a rate of 2000 mA g−1. PMID:24691396

UVR2 ensures transgenerational genome stability under simulated natural UV-B in Arabidopsis thaliana

PubMed Central

Willing, Eva-Maria; Piofczyk, Thomas; Albert, Andreas; Winkler, J. Barbro; Schneeberger, Korbinian; Pecinka, Ales

2016-01-01

Ground levels of solar UV-B radiation induce DNA damage. Sessile phototrophic organisms such as vascular plants are recurrently exposed to sunlight and require UV-B photoreception, flavonols shielding, direct reversal of pyrimidine dimers and nucleotide excision repair for resistance against UV-B radiation. However, the frequency of UV-B-induced mutations is unknown in plants. Here we quantify the amount and types of mutations in the offspring of Arabidopsis thaliana wild-type and UV-B-hypersensitive mutants exposed to simulated natural UV-B over their entire life cycle. We show that reversal of pyrimidine dimers by UVR2 photolyase is the major mechanism required for sustaining plant genome stability across generations under UV-B. In addition to widespread somatic expression, germline-specific UVR2 activity occurs during late flower development, and is important for ensuring low mutation rates in male and female cell lineages. This allows plants to maintain genome integrity in the germline despite exposure to UV-B. PMID:27905394

A versatile technique for fabrication of SiC SPM probes

NASA Astrophysics Data System (ADS)

Therrien, Joel; Schmidt, Daniel; Barrot, Sheetal; Patel, Bhavin

2008-03-01

To date SPM probes have largely been fabricated via methods borrowed from the semiconductor industry for fabricating Micro Electro Mechanical Systems. Although these techniques have enabled SPM to see widespread use, the processes put significant limitations on what structures can be made. We report our progress on fabricating SPM cantilevers composed of Silicon Carbide using polymer molding techniques. A pre-ceramic polymer is molded into the desired probe shape and then converted to SiC via pyrolisys. We will also report on progress in using photo-sterolithography for fabrication of even more complex geometries. In addition to opening up a much larger set of probe structures, the use of SiC leads to improved wear resistance of the resulting probes. Among the potential applications, this method enables the fabrication of low spring constant, high resonant frequency cantilevers via cross sectional geometries not accessible to standard fabrication techniques. Such probes are required for high speed tapping and non-contact imaging.

Clinical, economic and societal impact of antibiotic resistance.

PubMed

Barriere, Steven L

2015-02-01

The concern over antibiotic resistance has been voiced since the discovery of modern antibiotics > 75 years ago. The concerns have only increased with time, with efforts to control resistance caused by widespread overuse of antibiotics in human medicine and far more than appreciated use in the feeding of animals for human consumption to promote growth. The problem is worldwide, but certain regions and selected health care institutions report far more resistance, including strains of Gram-negative bacteria that are susceptible only to the once discarded drugs polymyxin B or colistin, and pan-resistant strains are on the rise. One of the central efforts to control resistance, apart from antimicrobial stewardship, is the development of new antimicrobial agents. This has lagged significantly over the past 10 - 15 years, for a variety of reasons; but promising new agents are being developed, unfortunately none thus far addressing all potentially resistant strains. There is the unlikely, but not unreal, possibility that we could return to a pre-antibiotic era, where morbidity and mortality rates have risen dramatically and routine surgical procedures are not performed for fear of post-operative infections. The onus of control of resistance is a moral imperative that falls on the shoulders of all.

Bacterial cheating limits the evolution of antibiotic resistance

NASA Astrophysics Data System (ADS)

Chao, Hui Xiao; Datta, Manoshi; Yurtsev, Eugene; Gore, Jeff

2011-03-01

The widespread use of antibiotics has led to the evolution of resistance in bacteria. Bacteria can gain resistance to the antibiotic ampicillin by acquiring a plasmid carrying the gene beta-lactamase, which inactivates the antibiotic. This inactivation may represent a cooperative behavior, as the entire bacterial population benefits from removing the antibiotic. The cooperative nature of this growth suggests that a cheater strain--which does not contribute to breaking down the antibiotic--may be able to take advantage of cells cooperatively inactivating the antibiotic. Here we experimentally find that a ``sensitive'' bacterial strain lacking the plasmid conferring resistance can invade a population of resistant bacteria, even in antibiotic concentrations that should kill the sensitive strain. We observe stable coexistence between the two strains and find that a simple model successfully explains the behavior as a function of antibiotic concentration and cell density. We anticipate that our results will provide insight into the evolutionary origin of phenotypic diversity and cooperative behaviors found in nature.

Clinical Relevance of Type II Fatty Acid Synthesis Bypass in Staphylococcus aureus

PubMed Central

Guillemet, Mélanie; Soler, Charles; Morvan, Claire; Halpern, David; Pourcel, Christine; Vu Thien, Hoang; Lamberet, Gilles

2017-01-01

ABSTRACT The need for new antimicrobials to treat bacterial infections has led to the use of type II fatty acid synthesis (FASII) enzymes as front-line targets. However, recent studies suggest that FASII inhibitors may not work against the opportunist pathogen Staphylococcus aureus, as environmental fatty acids favor emergence of multi-anti-FASII resistance. As fatty acids are abundant in the host and one FASII inhibitor, triclosan, is widespread, we investigated whether fatty acid pools impact resistance in clinical and veterinary S. aureus isolates. Simple addition of fatty acids to the screening medium led to a 50% increase in triclosan resistance, as tested in 700 isolates. Moreover, nonculturable triclosan-resistant fatty acid auxotrophs, which escape detection under routine conditions, were uncovered in primary patient samples. FASII bypass in selected isolates correlated with polymorphisms in the acc and fabD loci. We conclude that fatty-acid-dependent strategies to escape FASII inhibition are common among S. aureus isolates and correlate with anti-FASII resistance and emergence of nonculturable variants. PMID:28193654

Factors promoting survival of bacteria in chlorinated water supplies.

PubMed Central

LeChevallier, M W; Cawthon, C D; Lee, R G

1988-01-01

Results of our experiments showed that the attachment of bacteria to surfaces provided the greatest increase in disinfection resistance. Attachment of unencapsulated Klebsiella pneumoniae grown in medium with high levels of nutrients to glass microscope slides afforded the microorganisms as much as a 150-fold increase in disinfection resistance. Other mechanisms which increased disinfection resistance included the age of the biofilm, bacterial encapsulation, and previous growth conditions (e.g., growth medium and growth temperature). These factors increased resistance to chlorine from 2- to 10-fold. The choice of disinfectant residual was shown to influence the type of resistance mechanism observed. Disinfection by free chlorine was affected by surfaces, age of the biofilm, encapsulation, and nutrient effects. Disinfection by monochloramine, however, was only affected by surfaces. Importantly, results showed that these resistance mechanisms were multiplicative (i.e., the resistance provided by one mechanism could be multiplied by the resistance provided by a second mechanism). PMID:3288119

Quorum sensing and microbial drug resistance.

PubMed

Chen, Yu-fan; Liu, Shi-yin; Liang, Zhi-bin; Lv, Ming-fa; Zhou, Jia-nuan; Zhang, Lian-hui

2016-10-20

Microbial drug resistance has become a serious problem of global concern, and the evolution and regulatory mechanisms of microbial drug resistance has become a hotspot of research in recent years. Recent studies showed that certain microbial resistance mechanisms are regulated by quorum sensing system. Quorum sensing is a ubiquitous cell-cell communication system in the microbial world, which associates with cell density. High-density microbial cells produce sufficient amount of small signal molecules, activating a range of downstream cellular processes including virulence and drug resistance mechanisms, which increases bacterial drug tolerance and causes infections on host organisms. In this review, the general mechanisms of microbial drug resistance and quorum-sensing systems are summarized with a focus on the association of quorum sensing and chemical signaling systems with microbial drug resistance mechanisms, including biofilm formation and drug efflux pump. The potential use of quorum quenching as a new strategy to control microbial resistance is also discussed.

Antibiotic-resistant bacteria in the Hudson River Estuary linked to wet weather sewage contamination.

PubMed

Young, Suzanne; Juhl, Andrew; O'Mullan, Gregory D

2013-06-01

Heterotrophic bacteria resistant to tetracycline and ampicillin were assessed in waterways of the New York City metropolitan area using culture-dependent approaches and 16S rRNA gene sequence analysis of resultant isolates. Resistant microbes were detected at all 10 sampling sites in monthly research cruises on the lower Hudson River Estuary (HRE), with highest concentrations detected at nearshore sites. Higher frequency sampling was conducted in Flushing Bay, to enumerate resistant microbes under both dry and wet weather conditions. Concentrations of ampicillin- and tetracycline-resistant bacteria, in paired samples, were positively correlated with one another and increased following precipitation. Counts of the fecal indicator, Enterococcus, were positively correlated with levels of resistant bacteria, suggesting a shared sewage-associated source. Analysis of 16S rRNA from isolates identified a phylogenetically diverse group of resistant bacteria, including genera containing opportunistic pathogens. The occurrence of Enterobacteriaceae, a family of enteric bacteria, was found to be significantly higher in resistant isolates compared to total heterotrophic bacteria and increased following precipitation. This study is the first to document the widespread distribution of antibiotic-resistant bacteria in the HRE and to demonstrate clearly a link between the abundance of antibiotic-resistant bacteria and levels of sewage-associated bacteria in an estuary.

Quantitative Resistance: More Than Just Perception of a Pathogen

PubMed Central

2017-01-01

Molecular plant pathology has focused on studying large-effect qualitative resistance loci that predominantly function in detecting pathogens and/or transmitting signals resulting from pathogen detection. By contrast, less is known about quantitative resistance loci, particularly the molecular mechanisms controlling variation in quantitative resistance. Recent studies have provided insight into these mechanisms, showing that genetic variation at hundreds of causal genes may underpin quantitative resistance. Loci controlling quantitative resistance contain some of the same causal genes that mediate qualitative resistance, but the predominant mechanisms of quantitative resistance extend beyond pathogen recognition. Indeed, most causal genes for quantitative resistance encode specific defense-related outputs such as strengthening of the cell wall or defense compound biosynthesis. Extending previous work on qualitative resistance to focus on the mechanisms of quantitative resistance, such as the link between perception of microbe-associated molecular patterns and growth, has shown that the mechanisms underlying these defense outputs are also highly polygenic. Studies that include genetic variation in the pathogen have begun to highlight a potential need to rethink how the field considers broad-spectrum resistance and how it is affected by genetic variation within pathogen species and between pathogen species. These studies are broadening our understanding of quantitative resistance and highlighting the potentially vast scale of the genetic basis of quantitative resistance. PMID:28302676

Ichthyosis associated with widespread tinea corporis: report of three cases.

PubMed

Freitas, Camila Fernanda Novak Pinheiro de; Mulinari-Brenner, Fabiane; Fontana, Hanae Rafaela; Gentili, Arthur Conelian; Hammerschmidt, Mariana

2013-01-01

Ichthyoses are a common group of keratinization disorders. A non-inflammatory generalized persistent skin desquamation is observed. It is characterized by increased cell turnover, thickening of the stratum corneum and functional changes of sebaceous and sweat glands. All of these favor fungal proliferation. Dermatophytes may infect skin, hair and nails causing ringworm or tinea. They have the ability to obtain nutrients from keratinized material. One of its most prevalent genera is Trichophyton rubrum. Although tineas and ichthyoses are quite common, the association of the two entities is rarely reported in the literature. Three cases of ichthyosis associated with widespread infection by T. rubrum are presented. Resistance to several antifungal treatments was responsible for worsening of ichthyosis signs and symptoms.

Ichthyosis associated with widespread tinea corporis: report of three cases*

PubMed Central

de Freitas, Camila Fernanda Novak Pinheiro; Mulinari-Brenner, Fabiane; Fontana, Hanae Rafaela; Gentili, Arthur Conelian; Hammerschmidt, Mariana

2013-01-01

Ichthyoses are a common group of keratinization disorders. A non-inflammatory generalized persistent skin desquamation is observed. It is characterized by increased cell turnover, thickening of the stratum corneum and functional changes of sebaceous and sweat glands. All of these favor fungal proliferation. Dermatophytes may infect skin, hair and nails causing ringworm or tinea. They have the ability to obtain nutrients from keratinized material. One of its most prevalent genera is Trichophyton rubrum. Although tineas and ichthyoses are quite common, the association of the two entities is rarely reported in the literature. Three cases of ichthyosis associated with widespread infection by T. rubrum are presented. Resistance to several antifungal treatments was responsible for worsening of ichthyosis signs and symptoms. PMID:24068140

PCR-based methods for the detection of L1014 kdr mutation in Anopheles culicifacies sensu lato

PubMed Central

Singh, Om P; Bali, Prerna; Hemingway, Janet; Subbarao, Sarala K; Dash, Aditya P; Adak, Tridibes

2009-01-01

Background Anopheles culicifacies s.l., a major malaria vector in India, has developed widespread resistance to DDT and is becoming resistant to pyrethroids–the only insecticide class recommended for the impregnation of bed nets. Knock-down resistance due to a point mutation in the voltage gated sodium channel at L1014 residue (kdr) is a common mechanism of resistance to DDT and pyrethroids. The selection of this resistance may pose a serious threat to the success of the pyrethroid-impregnated bed net programme. This study reports the presence of kdr mutation (L1014F) in a field population of An. culicifacies s.l. and three new PCR-based methods for kdr genotyping. Methods The IIS4-IIS5 linker to IIS6 segments of the para type voltage gated sodium channel gene of DDT and pyrethroid resistant An. culicifacies s.l. population from the Surat district of India was sequenced. This revealed the presence of an A-to-T substitution at position 1014 leading to a leucine-phenylalanine mutation (L1014F) in a few individuals. Three molecular methods viz. Allele Specific PCR (AS-PCR), an Amplification Refractory Mutation System (ARMS) and Primer Introduced Restriction Analysis-PCR (PIRA-PCR) were developed and tested for kdr genotyping. The specificity of the three assays was validated following DNA sequencing of the samples genotyped. Results The genotyping of this An. culicifacies s.l. population by the three PCR based assays provided consistent result and were in agreement with DNA sequencing result. A low frequency of the kdr allele mostly in heterozygous condition was observed in the resistant population. Frequencies of the different genotypes were in Hardy-Weinberg equilibrium. Conclusion The Leu-Phe mutation, which generates the kdr phenotype in many insects, was detected in a pyrethroid and DDT resistant An. culicifacies s.l. population. Three PCR-based methods were developed for kdr genotyping. All the three assays were specific. The ARMS method was refractory to non-specific amplification in non-stringent amplification conditions. The PIRA-PCR assay is able to detect both the codons for the phenylalanine mutation at kdr locus, i.e., TTT and TTC, in a single assay, although the latter codon was not found in the population genotyped. PMID:19594947

A transcriptomic analysis of bermudagrass (Cynodon dactylon) provides novel insights into the basis of low temperature tolerance.

PubMed

Chen, Liang; Fan, Jibiao; Hu, Longxing; Hu, Zhengrong; Xie, Yan; Zhang, Yingzi; Lou, Yanhong; Nevo, Eviatar; Fu, Jinmin

2015-09-11

Cold stress is regarded as a key factor limiting widespread use for bermudagrass (Cynodon dactylon). Therefore, to improve cold tolerance for bermudagrass, it is urgent to understand molecular mechanisms of bermudagrass response to cold stress. However, our knowledge about the molecular responses of this species to cold stress is largely unknown. The objective of this study was to characterize the transcriptomic response to low temperature in bermudagrass by using RNA-Seq platform. Ten cDNA libraries were generated from RNA samples of leaves from five different treatments in the cold-resistant (R) and the cold-sensitive (S) genotypes, including 4 °C cold acclimation (CA) for 24 h and 48 h, freezing (-5 °C) treatments for 4 h with or without prior CA, and controls. When subjected to cold acclimation, global gene expressions were initiated more quickly in the R genotype than those in the S genotype. The R genotype activated gene expression more effectively in response to freezing temperature after 48 h CA than the S genotype. The differentially expressed genes were identified as low temperature sensing and signaling-related genes, functional proteins and transcription factors, many of which were specifically or predominantly expressed in the R genotype under cold treatments, implying that these genes play important roles in the enhanced cold hardiness of bermudagrass. KEGG pathway enrichment analysis for DEGs revealed that photosynthesis, nitrogen metabolism and carbon fixation pathways play key roles in bermudagrass response to cold stress. The results of this study may contribute to our understanding the molecular mechanism underlying the responses of bermudagrass to cold stress, and also provide important clues for further study and in-depth characterization of cold-resistance breeding candidate genes in bermudagrass.

Antiplasmodial dihetarylthioethers target the coenzyme A synthesis pathway in Plasmodium falciparum erythrocytic stages.

PubMed

Weidner, Thomas; Lucantoni, Leonardo; Nasereddin, Abed; Preu, Lutz; Jones, Peter G; Dzikowski, Ron; Avery, Vicky M; Kunick, Conrad

2017-05-15

Malaria is a widespread infectious disease that threatens a large proportion of the population in tropical and subtropical areas. Given the emerging resistance against the current standard anti-malaria chemotherapeutics, the development of alternative drugs is urgently needed. New anti-malarials representing chemotypes unrelated to currently used drugs have an increased potential for displaying novel mechanisms of action and thus exhibit low risk of cross-resistance against established drugs. Phenotypic screening of a small library (32 kinase-inhibitor analogs) against Plasmodium falciparum NF54-luc asexual erythrocytic stage parasites identified a diarylthioether structurally unrelated to registered drugs. Hit expansion led to a series in which the most potent congener displayed nanomolar antiparasitic activity (IC 50  = 39 nM, 3D7 strain). Structure-activity relationship analysis revealed a thieno[2,3-d]pyrimidine on one side of the thioether linkage as a prerequisite for antiplasmodial activity. Within the series, the oxazole derivative KuWei173 showed high potency (IC 50  = 75 nM; 3D7 strain), good solubility in aqueous solvents (1.33 mM), and >100-fold selectivity toward human cell lines. Rescue experiments identified inhibition of the plasmodial coenzyme A synthesis as a possible mode of action for this compound class. The class of antiplasmodial bishetarylthioethers reported here has been shown to interfere with plasmodial coenzyme A synthesis, a mechanism of action not yet exploited for registered anti-malarial drugs. The oxazole congener KuWei173 displays double-digit nanomolar antiplasmodial activity, selectivity against human cell lines, high drug likeness, and thus represents a promising chemical starting point for further drug development.

Glyphosate Resistance of C3 and C4 Weeds under Rising Atmospheric CO2

PubMed Central

Fernando, Nimesha; Manalil, Sudheesh; Florentine, Singarayer K.; Chauhan, Bhagirath S.; Seneweera, Saman

2016-01-01

The present paper reviews current knowledge on how changes of plant metabolism under elevated CO2 concentrations (e[CO2]) can affect the development of the glyphosate resistance of C3 and C4 weeds. Among the chemical herbicides, glyphosate, which is a non-selective and post-emergence herbicide, is currently the most widely used herbicide in global agriculture. As a consequence, glyphosate resistant weeds, particularly in major field crops, are a widespread problem and are becoming a significant challenge to future global food production. Of particular interest here it is known that the biochemical processes involved in photosynthetic pathways of C3 and C4 plants are different, which may have relevance to their competitive development under changing environmental conditions. It has already been shown that plant anatomical, morphological, and physiological changes under e[CO2] can be different, based on (i) the plant’s functional group, (ii) the available soil nutrients, and (iii) the governing water status. In this respect, C3 species are likely to have a major developmental advantage under a CO2 rich atmosphere, by being able to capitalize on the overall stimulatory effect of e[CO2]. For example, many tropical weed grass species fix CO2 from the atmosphere via the C4 photosynthetic pathway, which is a complex anatomical and biochemical variant of the C3 pathway. Thus, based on our current knowledge of CO2 fixing, it would appear obvious that the development of a glyphosate-resistant mechanism would be easier under an e[CO2] in C3 weeds which have a simpler photosynthetic pathway, than for C4 weeds. However, notwithstanding this logical argument, a better understanding of the biochemical, genetic, and molecular measures by which plants develop glyphosate resistance and how e[CO2] affects these measures will be important before attempting to innovate sustainable technology to manage the glyphosate-resistant evolution of weeds under e[CO2]. Such information will be of essential in managing weed control by herbicide use, and to thus ensure an increase in global food production in the event of increased atmospheric [CO2] levels. PMID:27446140

Glyphosate Resistance of C3 and C4 Weeds under Rising Atmospheric CO2.

PubMed

Fernando, Nimesha; Manalil, Sudheesh; Florentine, Singarayer K; Chauhan, Bhagirath S; Seneweera, Saman

2016-01-01

The present paper reviews current knowledge on how changes of plant metabolism under elevated CO2 concentrations (e[CO2]) can affect the development of the glyphosate resistance of C3 and C4 weeds. Among the chemical herbicides, glyphosate, which is a non-selective and post-emergence herbicide, is currently the most widely used herbicide in global agriculture. As a consequence, glyphosate resistant weeds, particularly in major field crops, are a widespread problem and are becoming a significant challenge to future global food production. Of particular interest here it is known that the biochemical processes involved in photosynthetic pathways of C3 and C4 plants are different, which may have relevance to their competitive development under changing environmental conditions. It has already been shown that plant anatomical, morphological, and physiological changes under e[CO2] can be different, based on (i) the plant's functional group, (ii) the available soil nutrients, and (iii) the governing water status. In this respect, C3 species are likely to have a major developmental advantage under a CO2 rich atmosphere, by being able to capitalize on the overall stimulatory effect of e[CO2]. For example, many tropical weed grass species fix CO2 from the atmosphere via the C4 photosynthetic pathway, which is a complex anatomical and biochemical variant of the C3 pathway. Thus, based on our current knowledge of CO2 fixing, it would appear obvious that the development of a glyphosate-resistant mechanism would be easier under an e[CO2] in C3 weeds which have a simpler photosynthetic pathway, than for C4 weeds. However, notwithstanding this logical argument, a better understanding of the biochemical, genetic, and molecular measures by which plants develop glyphosate resistance and how e[CO2] affects these measures will be important before attempting to innovate sustainable technology to manage the glyphosate-resistant evolution of weeds under e[CO2]. Such information will be of essential in managing weed control by herbicide use, and to thus ensure an increase in global food production in the event of increased atmospheric [CO2] levels.

Potential Risks Associated with the Proposed Widespread Use of Tamiflu

PubMed Central

Singer, Andrew C.; Nunn, Miles A.; Gould, Ernest A.; Johnson, Andrew C.

2007-01-01

Background The threat of pandemic influenza has focused attention and resources on virus surveillance, prevention, and containment. The World Health Organization has strongly recommended the use of the antiviral drug Tamiflu both to treat and prevent pandemic influenza infection. A major concern for the long-term efficacy of this strategy is to limit the development of Tamiflu-resistant influenza strains. However, in the event of a pandemic, hundreds of millions of courses of Tamiflu, stockpiled globally, will be rapidly deployed. Given its apparent resistance to biodegradation and hydrophilicity, oseltamivir carboxylate (OC), the active antiviral and metabolite of Tamiflu, is predicted to enter receiving riverwater from sewage treatment works in its active form. Objective Our objective in this study was to determine the likely concentrations of OC released into U.S. and U.K. river catchments using hydrologic modeling and current assumptions about the course and management of an influenza pandemic. Discussion We predict that high concentrations of OC (micrograms per liter) capable of inhibiting influenza virus replication would be sustained for periods of several weeks, presenting an increased risk for the generation of antiviral resistance and genetic exchange between influenza viruses in wildfowl. Owing to the apparent recalcitrance of OC in sewage treatment works, widespread use of Tamiflu during an influenza pandemic also poses a potentially significant, uncharacterized, ecotoxicologic risk in each affected nation’s waterways. Conclusion To gauge the hazard presented by Tamiflu use during a pandemic, we recommend a) direct measurement of Tamiflu persistence, biodegradation, and transformation in the environment; b) further modeling of likely drug concentrations in the catchments of countries where humans and waterfowl come into frequent close contact, and where significant Tamiflu deployment is envisaged; and c) further characterization of the risks of generating Tamiflu-resistant viruses in OC-exposed wildfowl. PMID:17366827

Mathematical modeling and computational prediction of cancer drug resistance.

PubMed

Sun, Xiaoqiang; Hu, Bin

2017-06-23

Diverse forms of resistance to anticancer drugs can lead to the failure of chemotherapy. Drug resistance is one of the most intractable issues for successfully treating cancer in current clinical practice. Effective clinical approaches that could counter drug resistance by restoring the sensitivity of tumors to the targeted agents are urgently needed. As numerous experimental results on resistance mechanisms have been obtained and a mass of high-throughput data has been accumulated, mathematical modeling and computational predictions using systematic and quantitative approaches have become increasingly important, as they can potentially provide deeper insights into resistance mechanisms, generate novel hypotheses or suggest promising treatment strategies for future testing. In this review, we first briefly summarize the current progress of experimentally revealed resistance mechanisms of targeted therapy, including genetic mechanisms, epigenetic mechanisms, posttranslational mechanisms, cellular mechanisms, microenvironmental mechanisms and pharmacokinetic mechanisms. Subsequently, we list several currently available databases and Web-based tools related to drug sensitivity and resistance. Then, we focus primarily on introducing some state-of-the-art computational methods used in drug resistance studies, including mechanism-based mathematical modeling approaches (e.g. molecular dynamics simulation, kinetic model of molecular networks, ordinary differential equation model of cellular dynamics, stochastic model, partial differential equation model, agent-based model, pharmacokinetic-pharmacodynamic model, etc.) and data-driven prediction methods (e.g. omics data-based conventional screening approach for node biomarkers, static network approach for edge biomarkers and module biomarkers, dynamic network approach for dynamic network biomarkers and dynamic module network biomarkers, etc.). Finally, we discuss several further questions and future directions for the use of computational methods for studying drug resistance, including inferring drug-induced signaling networks, multiscale modeling, drug combinations and precision medicine. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Social Resistance Framework for Understanding High-Risk Behavior Among Nondominant Minorities: Preliminary Evidence

PubMed Central

Williams, David R.; Kawachi, Ichiro

2013-01-01

Objectives. The recently developed social resistance framework addresses a widespread pattern in which members of some nondominant minorities tend to engage in various risky and unhealthy behaviors more than the majority group. This pilot study tested the core hypotheses derived from this innovative framework. Methods. We conducted in 2011 a nationally representative Web-based survey of 200 members of a nondominant minority group (African Americans) and 200 members of a majority group (Whites). Results. The preliminary findings supported the main premises of the framework and suggested that nondominant minorities who felt discriminated and alienated from society tended also to have higher levels of social resistance. Those with higher levels of social resistance also engaged more in risky and unhealthy behaviors—smoking, drinking, and nonuse of seat belts—than did those with lower levels of social resistance. These associations were not found in the majority group. Conclusions. These preliminary results supported the framework and suggested that social resistance might play a meaningful role in risky and unhealthy behaviors of nondominant minorities, and should be taken into account when trying to reduce health disparities. PMID:23597381

A Protocol to Assess Insect Resistance to Heat Waves, Applied to Bumblebees (Bombus Latreille, 1802)

PubMed Central

Martinet, Baptiste; Lecocq, Thomas; Smet, Jérémy; Rasmont, Pierre

2015-01-01

Insect decline results from numerous interacting factors including climate change. One of the major phenomena related to climate change is the increase of the frequency of extreme events such as heat waves. Since heat waves are suspected to dramatically increase insect mortality, there is an urgent need to assess their potential impact. Here, we determined and compared the resistance to heat waves of insects under hyperthermic stress through their time before heat stupor (THS) when they are exposed to an extreme temperature (40°C). For this, we used a new experimental standardised device available in the field or in locations close to the field collecting sites. We applied this approach on different Arctic, Boreo-Alpine and Widespread bumblebee species in order to predict consequences of heat waves. Our results show a heat resistance gradient: the heat stress resistance of species with a centred arctic distribution is weaker than the heat resistance of the Boreo-Alpine species with a larger distribution which is itself lower than the heat stress resistance of the ubiquitous species. PMID:25738862

Central Mechanisms in the Maintenance of Chronic Widespread Noninflammatory Muscle Pain

PubMed Central

DeSantana, Josimari M.; Sluka, Kathleen A.

2009-01-01

Chronic widespread pain (CWP) conditions such as fibromyalgia and myofascial syndromes are characterized by generalized pain, tenderness, morning stiffness, disturbed sleep, and pronounced fatigue. However, CWP pathophysiology is still unclear. A number of hypotheses have been proposed as the underlying pathophysiology of CWP: muscular dysfunction/ischemia, central sensitization, and a deficit in endogenous pain-modulating systems. This article reviews the current and emerging literature about the pathophysiology and neurobiology of chronic widespread musculoskeletal pain. Widespread musculoskeletal pain results in changes in the central nervous system in human subjects and animal models. These changes likely reflect alterations in supraspinal modulation of nociception, and include increases in excitatory and decreases in inhibitory modulation pathways. These alterations in excitation and inhibition likely drive changes observed in the spinal cord to result in central sensitization, and the consequent pain and hyperalgesia. PMID:18765138

Sporulation properties and antimicrobial susceptibility in endemic and rare Clostridium difficile PCR ribotypes.

PubMed

Zidaric, Valerija; Rupnik, Maja

2016-06-01

Increased sporulation and antibiotic resistance have been proposed to be associated with certain Clostridium difficile epidemic strains such as PCR ribotype 027. In this study we examined these properties in another widespread PCR ribotype, 014/020, in comparison to prevalent PCR ribotype 002 and a group of rarely represented PCR ribotypes. Highest sporulation was observed in 014/020 strains at 24 h, while after 72 h PCR ribotype 002 and rare PCR ribotypes formed higher total number of spores. PCR ribotype 014/020 strains exhibited slightly higher resistance to tested antimicrobials, followed by group of rare PCR ribotypes and less common PCR ribotype 002. Neither sporulation properties nor antibiotic resistance clearly differed in endemic and rare strains. Copyright © 2016 Elsevier Ltd. All rights reserved.

Identification of subsurface brines in the McMurdo Dry Valleys, Antarctica, via an airborne EM resistivity survey

NASA Astrophysics Data System (ADS)

Foley, N.; Tulaczyk, S. M.; Auken, E.; Schamper, C.; Dugan, H. A.; Mikucki, J.; Virginia, R. A.; Doran, P. T.

2015-12-01

We used a helicopter-borne time domain electromagnetic resistivity survey to detect and map hypersaline brines beneath glaciers and permafrost in the McMurdo Dry Valleys (MDV). In the MDV, a substantially ice-free region of coastal Antarctica, liquid water is present at the surface only in summer streams, ice-covered lakes with brackish to hypersaline bottom waters, and at Blood Falls, a hypersaline discharge from Taylor Glacier. Beneath the surface, however, water can remain liquid at temperatures below 0 °C (and therefore at unexpectedly shallow depths) as a hypersaline brine. These brines, which are measured as zones of low resistivity in an otherwise high resistivity environment, are widespread in Taylor Valley, where they may connect lakes, subglacial waters, and the ocean. By using surface landscape characteristics - such as the presence of lakes, glaciers, or bare ground - we are able to compare changes in resistivity with depth. We find that in areas of surface permafrost (most of the MDV) there is a marked shift to low resistivity material around 200 m below the surface. At lakes, the stratified nature of their waters is detectable and sufficiently large lakes create taliks (unfrozen 'holes' in permafrost) that penetrate to the low resistivity zone around 200 m depth, suggesting connectivity through a regional aquifer. Underneath Taylor Glacier, we detect similar brines, which are the probable source for Blood Falls. These subglacial brines extend from the snout of Taylor Glacier (where they appear to connect to the hypersaline waters of West Lake Bonney) to the limit of our detection ability several kilometers up glacier where the ice became too thick for measurements. Our measurements are consistent with limited drilling done in the MDV during the 1970s and radar measurements taken more recently on Taylor Glacier. The transition to low resistivity at ~200 m depth occurs over a temperature range measured in boreholes of about -10 to -5 °C, which is consistent with predictions of temperatures at the base of Taylor Glacier. The widespread nature of these brines may require reassessment of our understanding of Taylor Glacier's movement and the geochemistry of MDV lakes, which have historically been considered isolated from a regional aquifer.

Is biotic resistance enhanced by natural variation in diversity?

USGS Publications Warehouse

Grace, James B.; Harrison, Susan P.; Cornell, Howard

2017-01-01

Theories linking diversity to ecosystem function have been challenged by the widespread observation of more exotic species in more diverse native communities. Few studies have addressed the underlying processes by dissecting how biotic resistance to new invaders may be shaped by the same environmental influences that determine diversity and other community properties.In grasslands with heterogeneous soils, we added invaders and removed competitors to analyze the causes of invasion resistance. Abiotic resistance was measured using invader success in the absence of the resident community. Biotic resistance was measured as the reduction in invader success in the presence of the resident community.Invaders were most successful where biotic resistance was lowest and abiotic resistance was highest, confirming the dominant role of biotic resistance. Contrary to theory, though, biotic resistance was highest where both species richness and functional diversity were lowest. In the multivariate framework of a structural equation model, biotic resistance was independent of community diversity, and was highest where fertile soils led to high community biomass.Seed predation slightly augmented biotic resistance without qualitatively changing the results. Soil-related genotypic variation in the invader also did not affect the results.We conclude that in natural systems, diversity may be correlated with invasibility and yet have little effect on biotic resistance to invasion. More generally, the environmental causes of variation in diversity should be considered when examining the potential functional consequences of diversity.

An emergent multiple predator effect may enhance biotic resistance in a stream fish assemblage

Treesearch

Bret C. Harvey; Jason L. White; Rodney J. Nakamoto

2004-01-01

While two cyprinid fishes introduced from nearby drainages have become widespread and abundant in the Eel River of northwestern California, a third nonindigenous cyprinid has remained largely confined to <25 km of one major tributary (the Van Duzen River) for at least 15 years. The downstream limit of this species, speckled dace, does not appear to correspond...

Mechanisms of Antimicrobial Peptide Resistance in Gram-Negative Bacteria

PubMed Central

Band, Victor I.; Weiss, David S.

2014-01-01

Cationic antimicrobial peptides (CAMPs) are important innate immune defenses that inhibit colonization by pathogens and contribute to clearance of infections. Gram-negative bacterial pathogens are a major target, yet many of them have evolved mechanisms to resist these antimicrobials. These resistance mechanisms can be critical contributors to bacterial virulence and are often crucial for survival within the host. Here, we summarize methods used by Gram-negative bacteria to resist CAMPs. Understanding these mechanisms may lead to new therapeutic strategies against pathogens with extensive CAMP resistance. PMID:25927010

Historic perspective: prebiotics, probiotics, and other alternatives to antibiotics.

PubMed

Hume, M E

2011-11-01

Applications of antimicrobials in food production and human health have found favor throughout human history. Antibiotic applications in agricultural and human medical arenas have resulted in tremendous increases in food animal production and historically unprecedented gains in human health protection. Successes attributed to widespread antibiotic use have been accompanied by the inadvertent emergence of antibiotic-resistant bacteria. A major problem associated with this emerging resistance is the crossover use of some antibiotics in agricultural settings as well as in the prevention and treatment of human disease. This outcome led to calls to restrict the use of human health-related antibiotics in food animal production. Calls for restricted antibiotic use have heightened existing searches for alternatives to antibiotics that give similar or enhanced production qualities as highly reliable as the antibiotics currently provided to food animals. Agricultural and scientific advances, mainly within the last 100 yr, have given us insights into sources, structures, and actions of materials that have found widespread application in our modern world. The purpose of this presentation is to provide a historic perspective on the search for what are generally known as antibiotics and alternative antimicrobials, probiotics, prebiotics, bacteriophages, bacteriocins, and phytotherapeutics.

Integration of decoy domains derived from protein targets of pathogen effectors into plant immune receptors is widespread.

PubMed

Kroj, Thomas; Chanclud, Emilie; Michel-Romiti, Corinne; Grand, Xavier; Morel, Jean-Benoit

2016-04-01

Plant immune receptors of the class of nucleotide-binding and leucine-rich repeat domain (NLR) proteins can contain additional domains besides canonical NB-ARC (nucleotide-binding adaptor shared by APAF-1, R proteins, and CED-4 (NB-ARC)) and leucine-rich repeat (LRR) domains. Recent research suggests that these additional domains act as integrated decoys recognizing effectors from pathogens. Proteins homologous to integrated decoys are suspected to be effector targets and involved in disease or resistance. Here, we scrutinized 31 entire plant genomes to identify putative integrated decoy domains in NLR proteins using the Interpro search. The involvement of the Zinc Finger-BED type (ZBED) protein containing a putative decoy domain, called BED, in rice (Oryza sativa) resistance was investigated by evaluating susceptibility to the blast fungus Magnaporthe oryzae in rice over-expression and knock-out mutants. This analysis showed that all plants tested had integrated various atypical protein domains into their NLR proteins (on average 3.5% of all NLR proteins). We also demonstrated that modifying the expression of the ZBED gene modified disease susceptibility. This study suggests that integration of decoy domains in NLR immune receptors is widespread and frequent in plants. The integrated decoy model is therefore a powerful concept to identify new proteins involved in disease resistance. Further in-depth examination of additional domains in NLR proteins promises to unravel many new proteins of the plant immune system. © 2016 The Authors. New Phytologist © 2016 New Phytologist Trust.

Biology and management of Avena fatua and Avena ludoviciana: two noxious weed species of agro-ecosystems.

PubMed

Bajwa, Ali Ahsan; Akhter, Muhammad Javaid; Iqbal, Nadeem; Peerzada, Arslan Masood; Hanif, Zarka; Manalil, Sudheesh; Hashim, Saima; Ali, Hafiz Haider; Kebaso, Lynda; Frimpong, David; Namubiru, Halima; Chauhan, Bhagirath Singh

2017-08-01

Avena fatua and Avena ludoviciana are closely related grass weed species infesting a large number of crops around the world. These species are widely distributed in diverse agro-ecosystems from temperate to sub-tropical regions due to their unique seed traits, successful germination ecology, high competitive ability, and allelopathic potential. A. fatua is more widespread, adaptable, and problematic than A. ludoviciana. Both these species infest major winter and spring crops, including wheat, oat, barley, canola, maize, alfalfa, and sunflower, causing up to 70% yield losses depending on crop species and weed density. Chemical control has been challenged by large-scale herbicide resistance evolution in these weed species. A. fatua is the most widespread herbicide-resistant weed in the world, infesting about 5 million hectares in 13 countries. The use of alternative herbicides with different modes of action has proved effective. Several cultural practices, including diverse crop rotations, cover crops, improved crop competition (using competitive cultivars, high seed rates, narrow row spacing, altered crop geometry), and allelopathic suppression, have shown promise for controlling A. fatua and A. ludoviciana. The integrated use of these cultural methods can reduce the herbicide dose required, and lower dependency on herbicides to control these grasses. Moreover, integrated management may successfully control herbicide-resistant populations of these weed species. The use of integrated approaches based on the knowledge of biology and ecology of A. fatua and A. ludoviciana may help to manage them sustainably in the future.

Antimicrobial Chemicals Are Associated with Elevated Antibiotic Resistance Genes in the Indoor Dust Microbiome.

PubMed

Hartmann, Erica M; Hickey, Roxana; Hsu, Tiffany; Betancourt Román, Clarisse M; Chen, Jing; Schwager, Randall; Kline, Jeff; Brown, G Z; Halden, Rolf U; Huttenhower, Curtis; Green, Jessica L

2016-09-20

Antibiotic resistance is increasingly widespread, largely due to human influence. Here, we explore the relationship between antibiotic resistance genes and the antimicrobial chemicals triclosan, triclocarban, and methyl-, ethyl-, propyl-, and butylparaben in the dust microbiome. Dust samples from a mixed-use athletic and educational facility were subjected to microbial and chemical analyses using a combination of 16S rRNA amplicon sequencing, shotgun metagenome sequencing, and liquid chromatography tandem mass spectrometry. The dust resistome was characterized by identifying antibiotic resistance genes annotated in the Comprehensive Antibiotic Resistance Database (CARD) from the metagenomes of each sample using the Short, Better Representative Extract Data set (ShortBRED). The three most highly abundant antibiotic resistance genes were tet(W), blaSRT-1, and erm(B). The complete dust resistome was then compared against the measured concentrations of antimicrobial chemicals, which for triclosan ranged from 0.5 to 1970 ng/g dust. We observed six significant positive associations between the concentration of an antimicrobial chemical and the relative abundance of an antibiotic resistance gene, including one between the ubiquitous antimicrobial triclosan and erm(X), a 23S rRNA methyltransferase implicated in resistance to several antibiotics. This study is the first to look for an association between antibiotic resistance genes and antimicrobial chemicals in dust.

Comparative cephalopod shell strength and the role of septum morphology on stress distribution

PubMed Central

Zachow, Stefan; Hoffmann, René

2016-01-01

The evolution of complexly folded septa in ammonoids has long been a controversial topic. Explanations of the function of these folded septa can be divided into physiological and mechanical hypotheses with the mechanical functions tending to find widespread support. The complexity of the cephalopod shell has made it difficult to directly test the mechanical properties of these structures without oversimplification of the septal morphology or extraction of a small sub-domain. However, the power of modern finite element analysis now permits direct testing of mechanical hypothesis on complete, empirical models of the shells taken from computed tomographic data. Here we compare, for the first time using empirical models, the capability of the shells of extant Nautilus pompilius, Spirula spirula, and the extinct ammonite Cadoceras sp. to withstand hydrostatic pressure and point loads. Results show hydrostatic pressure imparts highest stress on the final septum with the rest of the shell showing minimal compression. S. spirula shows the lowest stress under hydrostatic pressure while N. pompilius shows the highest stress. Cadoceras sp. shows the development of high stress along the attachment of the septal saddles with the shell wall. Stress due to point loads decreases when the point force is directed along the suture as opposed to the unsupported chamber wall. Cadoceras sp. shows the greatest decrease in stress between the point loads compared to all other models. Greater amplitude of septal flutes corresponds with greater stress due to hydrostatic pressure; however, greater amplitude decreases the stress magnitude of point loads directed along the suture. In our models, sutural complexity does not predict greater resistance to hydrostatic pressure but it does seem to increase resistance to point loads, such as would be from predators. This result permits discussion of palaeoecological reconstructions on the basis of septal morphology. We further suggest that the ratio used to characterize septal morphology in the septal strength index and in calculations of tensile strength of nacre are likely insufficient. A better understanding of the material properties of cephalopod nacre may allow the estimation of maximum depth limits of shelled cephalopods through finite element analysis. PMID:27672501

Quantitative Resistance: More Than Just Perception of a Pathogen.

PubMed

Corwin, Jason A; Kliebenstein, Daniel J

2017-04-01

Molecular plant pathology has focused on studying large-effect qualitative resistance loci that predominantly function in detecting pathogens and/or transmitting signals resulting from pathogen detection. By contrast, less is known about quantitative resistance loci, particularly the molecular mechanisms controlling variation in quantitative resistance. Recent studies have provided insight into these mechanisms, showing that genetic variation at hundreds of causal genes may underpin quantitative resistance. Loci controlling quantitative resistance contain some of the same causal genes that mediate qualitative resistance, but the predominant mechanisms of quantitative resistance extend beyond pathogen recognition. Indeed, most causal genes for quantitative resistance encode specific defense-related outputs such as strengthening of the cell wall or defense compound biosynthesis. Extending previous work on qualitative resistance to focus on the mechanisms of quantitative resistance, such as the link between perception of microbe-associated molecular patterns and growth, has shown that the mechanisms underlying these defense outputs are also highly polygenic. Studies that include genetic variation in the pathogen have begun to highlight a potential need to rethink how the field considers broad-spectrum resistance and how it is affected by genetic variation within pathogen species and between pathogen species. These studies are broadening our understanding of quantitative resistance and highlighting the potentially vast scale of the genetic basis of quantitative resistance. © 2017 American Society of Plant Biologists. All rights reserved.

Polycystic Ovary Syndrome: Insights into the Therapeutic Approach with Inositols

PubMed Central

Sortino, Maria A.; Salomone, Salvatore; Carruba, Michele O.; Drago, Filippo

2017-01-01

Polycystic ovary syndrome (PCOS) is characterized by hormonal abnormalities that cause menstrual irregularity and reduce ovulation rate and fertility, associated to insulin resistance. Myo-inositol (cis-1,2,3,5-trans-4,6-cyclohexanehexol, MI) and D-chiro-inositol (cis-1,2,4-trans-3,5,6-cyclohexanehexol, DCI) represent promising treatments for PCOS, having shown some therapeutic benefits without substantial side effects. Because the use of inositols for treating PCOS is widespread, a deep understanding of this treatment option is needed, both in terms of potential mechanisms and efficacy. This review summarizes the current knowledge on the biological effects of MI and DCI and the results obtained from relevant intervention studies with inositols in PCOS. Based on the published results, both MI and DCI represent potential valid therapeutic approaches for the treatment of insulin resistance and its associated metabolic and reproductive disorders, such as those occurring in women affected by PCOS. Furthermore, the combination MI/DCI seems also effective and might be even superior to either inositol species alone. However, based on available data, a particular MI:DCI ratio to be administered to PCOS patients cannot be established. Further studies are then necessary to understand the real contents of MI or DCI uptaken by the ovary following oral administration in order to identify optimal doses and/or combination ratios. PMID:28642705

Facts and fiction about sulfur metabolism in relation to plant-pathogen interactions.

PubMed

Bloem, E; Haneklaus, S; Salac, I; Wickenhäuser, P; Schnug, E

2007-09-01

Sulfur deficiency developed into a widespread nutrient disorder in the 1980s because of the drastic decrease of SO(2) emissions in western Europe after Clean Air Acts came into force. It was observed that not only the yield and quality of agricultural crops were negatively affected by sulfur deficiency but also their health status. Since the mid 1990s the physiological background of this latter phenomenon in the sulfur metabolism has been studied by different researchers. From 2001 until 2006, field trials with different varieties of oilseed rape were conducted in Germany, and also from 2001 until 2003 in Scotland, to investigate the underlying mechanisms of sulfur-induced resistance and to develop fertiliser strategies which increase the health status of crops and minimise the requirement for chemical fungicides. A comprehensive disease assessment was conducted and a range of different sulfur-containing metabolites and enzymes were analysed in relation to sulfur nutrition and fungal diseases. H2S emissions from field-grown crops under different sulfur nutritional status were studied for the first time and a positive relationship was observed. Besides S fertilisation, fungal infection increased H2S emissions, too. The studies deliver new insight into the complex of sulfur-induced resistance but many questions still remain open. This contribution will show different possible strategies to solve some of the open questions.

Mechanisms of Candida biofilm drug resistance

PubMed Central

Taff, Heather T; Mitchell, Kaitlin F; Edward, Jessica A; Andes, David R

2013-01-01

Candida commonly adheres to implanted medical devices, growing as a resilient biofilm capable of withstanding extraordinarily high antifungal concentrations. As currently available antifungals have minimal activity against biofilms, new drugs to treat these recalcitrant infections are urgently needed. Recent investigations have begun to shed light on the mechanisms behind the profound resistance associated with the biofilm mode of growth. This resistance appears to be multifactorial, involving both mechanisms similar to conventional, planktonic antifungal resistance, such as increased efflux pump activity, as well as mechanisms specific to the biofilm lifestyle. A unique biofilm property is the production of an extracellular matrix. Two components of this material, β-glucan and extracellular DNA, promote biofilm resistance to multiple antifungals. Biofilm formation also engages several stress response pathways that impair the activity of azole drugs. Resistance within a biofilm is often heterogeneous, with the development of a subpopulation of resistant persister cells. In this article we review the molecular mechanisms underlying Candida biofilm antifungal resistance and their relative contributions during various growth phases. PMID:24059922

Glyphosate resistance: state of knowledge

PubMed Central

Sammons, Robert Douglas; Gaines, Todd A

2014-01-01

Studies of mechanisms of resistance to glyphosate have increased current understanding of herbicide resistance mechanisms. Thus far, single-codon non-synonymous mutations of EPSPS (5-enolypyruvylshikimate-3-phosphate synthase) have been rare and, relative to other herbicide mode of action target-site mutations, unconventionally weak in magnitude for resistance to glyphosate. However, it is possible that weeds will emerge with non-synonymous mutations of two codons of EPSPS to produce an enzyme endowing greater resistance to glyphosate. Today, target-gene duplication is a common glyphosate resistance mechanism and could become a fundamental process for developing any resistance trait. Based on competition and substrate selectivity studies in several species, rapid vacuole sequestration of glyphosate occurs via a transporter mechanism. Conversely, as the chloroplast requires transporters for uptake of important metabolites, transporters associated with the two plastid membranes may separately, or together, successfully block glyphosate delivery. A model based on finite glyphosate dose and limiting time required for chloroplast loading sets the stage for understanding how uniquely different mechanisms can contribute to overall glyphosate resistance. PMID:25180399

Hermeneutics, Underdetermination and Quantum Mechanics.

ERIC Educational Resources Information Center

Cushing, James T.

1995-01-01

States that the existence of an essential underdetermination in the interpretation of the formalism of quantum mechanics, in spite of the widespread belief that logic and empirical considerations alone demand an indeterministic world view in physics, legitimizes the analysis of hermeneutics in science education. (LZ)

Characterization of Methicillin Resistant Staphylococcus aureus isolated from human and animal samples in Egypt.

PubMed

Bendary, M M; Solyman, S M; Azab, M M; Mahmoud, N F; Hanora, A M

2016-02-29

Staphylococcus aureus (S. aureus) has been one of the most problematic pathogens. Methicillin Resistant S. aureus (MRSA) has emerged as a major concern for both human and animal. Antibiotic resistance genes dissemination might be possible between human and animal bacteria. The aim of this study is to show phenotypic and genotypic diversity of human and animal MRSA isolates. Antibiogram typing and biofilm production were used as a primary phenotypic typing tool for the characterization of (40) animal and (38) human MRSA isolates. Genetic typing based on sequencing of 16S rRNA gene and virulence gene profiles were done. Antimicrobial resistance profiles of the animal isolates showed little evidence of widespread of resistance, although this was seen in many human isolates. The biofilm production was detected in higher percentage among animal isolates. Based on the genetic typing and multiple antibiotic resistance (MAR) index, the majority of animal isolates clustered into lineages that were not found in human isolates. Animal and human MRSA isolates showed diversity in antibiotic resistance and virulence gene profiles may be due to host adaptation or chances for contamination between the two hosts were not present in our study.

Genetics of resistance to the geminivirus, Bean dwarf mosaic virus, and the role of the hypersensitive response in common bean.

PubMed

Seo, Y-S; Gepts, P; Gilbertson, R L

2004-03-01

Bean dwarf mosaic virus (BDMV) is a single-stranded DNA virus (genus: Begomovirus, family: Geminiviridae) that infects common bean ( Phaseolus vulgaris L.) and causes stunted plant growth, and mosaic and mottle symptoms in leaves. BDMV shows differential pathogenicity in common bean, infecting germplasm of the Andean gene pool (e.g., the snap bean cultivar Topcrop), but not that of the Middle American gene pool (e.g., the pinto bean cultivar Othello). Resistance to BDMV in Othello is associated with development of a hypersensitive response (HR) in vascular (phloem) tissues. In this study, Middle American germplasm representing the four recognized races (i.e., Durango, Guatemala, Jalisco, and Mesoamerica) and the parents of Othello were inoculated with BDMV and a BDMV-green fluorescent protein (GFP) reporter. All genotypes showed partial or complete resistance to BDMV and BDMV-GFP, indicating the widespread distribution of resistance in the Middle American gene pool. A number of BDMV-resistant germplasm did not show the HR, indicating it is not correlated with resistance. In the F(1), F(2), and F(3) of reciprocal crosses between Othello and Topcrop, a single dominant allele, Bdm, conferred BDMV resistance.

Evolution of resistance to a multiple-herbivore community: genetic correlations, diffuse coevolution, and constraints on the plant's response to selection.

PubMed

Wise, Michael J; Rausher, Mark D

2013-06-01

Although plants are generally attacked by a community of several species of herbivores, relatively little is known about the strength of natural selection for resistance in multiple-herbivore communities-particularly how the strength of selection differs among herbivores that feed on different plant organs or how strongly genetic correlations in resistance affect the evolutionary responses of the plant. Here, we report on a field study measuring natural selection for resistance in a diverse community of herbivores of Solanum carolinense. Using linear phenotypic-selection analyses, we found that directional selection acted to increase resistance to seven species. Selection was strongest to increase resistance to fruit feeders, followed by flower feeders, then leaf feeders. Selection favored a decrease in resistance to a stem borer. Bootstrapping analyses showed that the plant population contained significant genetic variation for each of 14 measured resistance traits and significant covariances in one-third of the pairwise combinations of resistance traits. These genetic covariances reduced the plant's overall predicted evolutionary response for resistance against the herbivore community by about 60%. Diffuse (co)evolution was widespread in this community, and the diffuse interactions had an overwhelmingly constraining (rather than facilitative) effect on the plant's evolution of resistance. © 2013 The Author(s). Evolution © 2013 The Society for the Study of Evolution.

Mechanisms and significance of fungicide resistance†

PubMed Central

Deising, Holger B.; Reimann, Sven; Pascholati, Sérgio F.

2008-01-01

In this review article, we show that occurrence of fungicide resistance is one of the most important issues in modern agriculture. Fungicide resistance may be due to mutations of genes encoding fungicide targets (qualitative fungicide resistance) or to different mechanisms that are induced by sub-lethal fungicide stress. These mechanisms result in different and varying levels of resistance (quantitative fungicide resistance). We discuss whether or not extensive use of fungicides in agricultural environments is related to the occurrence of fungicide resistance in clinical environments. Furthermore, we provide recommendations of how development of fungicide resistant pathogen populations may be prevented or delayed. PMID:24031218

Primaquine in vivax malaria: an update and review on management issues

PubMed Central

2011-01-01

Primaquine was officially licensed as an anti-malarial drug by the FDA in 1952. It has remained the only FDA licensed drug capable of clearing the intra-hepatic schizonts and hypnozoites of Plasmodium vivax. This update and review focuses on five major aspects of primaquine use in treatment of vivax malaria, namely: a) evidence of efficacy of primaquine for its current indications; b) potential hazards of its widespread use, c) critical analysis of reported resistance against primaquine containing regimens; d) evidence for combining primaquine with artemisinins in areas of chloroquine resistance; and e) the potential for replacement of primaquine with newer drugs. PMID:22152065

Primaquine in vivax malaria: an update and review on management issues.

PubMed

Fernando, Deepika; Rodrigo, Chaturaka; Rajapakse, Senaka

2011-12-12

Primaquine was officially licensed as an anti-malarial drug by the FDA in 1952. It has remained the only FDA licensed drug capable of clearing the intra-hepatic schizonts and hypnozoites of Plasmodium vivax. This update and review focuses on five major aspects of primaquine use in treatment of vivax malaria, namely: a) evidence of efficacy of primaquine for its current indications; b) potential hazards of its widespread use, c) critical analysis of reported resistance against primaquine containing regimens; d) evidence for combining primaquine with artemisinins in areas of chloroquine resistance; and e) the potential for replacement of primaquine with newer drugs.

Artemisinin-Resistant Plasmodium falciparum Parasites Exhibit Altered Patterns of Development in Infected Erythrocytes

PubMed Central

Hott, Amanda; Casandra, Debora; Sparks, Kansas N.; Morton, Lindsay C.; Castanares, Geocel-Grace; Rutter, Amanda

2015-01-01

Artemisinin derivatives are used in combination with other antimalarial drugs for treatment of multidrug-resistant malaria worldwide. Clinical resistance to artemisinin recently emerged in southeast Asia, yet in vitro phenotypes for discerning mechanism(s) of resistance remain elusive. Here, we describe novel phenotypic resistance traits expressed by artemisinin-resistant Plasmodium falciparum. The resistant parasites exhibit altered patterns of development that result in reduced exposure to drug at the most susceptible stage of development in erythrocytes (trophozoites) and increased exposure in the most resistant stage (rings). In addition, a novel in vitro delayed clearance assay (DCA) that assesses drug effects on asexual stages was found to correlate with parasite clearance half-life in vivo as well as with mutations in the Kelch domain gene associated with resistance (Pf3D7_1343700). Importantly, all of the resistance phenotypes were stable in cloned parasites for more than 2 years without drug pressure. The results demonstrate artemisinin-resistant P. falciparum has evolved a novel mechanism of phenotypic resistance to artemisinin drugs linked to abnormal cell cycle regulation. These results offer insights into a novel mechanism of drug resistance in P. falciparum and new tools for monitoring the spread of artemisinin resistance. PMID:25779582

Drug resistance mechanisms and novel drug targets for tuberculosis therapy.

PubMed

Islam, Md Mahmudul; Hameed, H M Adnan; Mugweru, Julius; Chhotaray, Chiranjibi; Wang, Changwei; Tan, Yaoju; Liu, Jianxiong; Li, Xinjie; Tan, Shouyong; Ojima, Iwao; Yew, Wing Wai; Nuermberger, Eric; Lamichhane, Gyanu; Zhang, Tianyu

2017-01-20

Drug-resistant tuberculosis (TB) poses a significant challenge to the successful treatment and control of TB worldwide. Resistance to anti-TB drugs has existed since the beginning of the chemotherapy era. New insights into the resistant mechanisms of anti-TB drugs have been provided. Better understanding of drug resistance mechanisms helps in the development of new tools for the rapid diagnosis of drug-resistant TB. There is also a pressing need in the development of new drugs with novel targets to improve the current treatment of TB and to prevent the emergence of drug resistance in Mycobacterium tuberculosis. This review summarizes the anti-TB drug resistance mechanisms, furnishes some possible novel drug targets in the development of new agents for TB therapy and discusses the usefulness using known targets to develop new anti-TB drugs. Whole genome sequencing is currently an advanced technology to uncover drug resistance mechanisms in M. tuberculosis. However, further research is required to unravel the significance of some newly discovered gene mutations in their contribution to drug resistance. Copyright © 2016 Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, and Genetics Society of China. Published by Elsevier Ltd. All rights reserved.

Class act: safety comparison of approved tyrosine kinase inhibitors for non-small-cell lung carcinoma.

PubMed

Burotto, Mauricio; Ali, Syed Abbas; O'Sullivan Coyne, Geraldine

2015-01-01

The past decade has seen the development and widespread use of tyrosine kinase inhibitors (TKIs) targeting a mutated EGFR (mEGFR) for the treatment of metastatic NSCLC. We discuss the main properties of the TKIs currently recommended for the treatment of mEGFR NSCLC: gefitinib, erlotinib and afatinib. The mechanism of action, pharmacodynamics and pharmacokinetics of these drugs, with emphasis on the historical context of their preclinical and clinical development, will be covered, including potential resistance mechanisms to these first-generation TKIs that has driven the trial design for second and third generations of EGFR inhibitors. Six Phase III clinical trials comparing these three TKIs with cisplatin-based chemotherapy upfront for mEGFR NSCLC provide the basis for the comparative safety and toxicity analysis between these agents. Class-related toxicity of these EGFR inhibitors, including life-threatening effects, will be discussed. Toxicity and safety analysis from the Phase III trials of these agents in mEGFR populations suggests that afatinib has more frequent and severe side effects. Given that an efficacy advantage has not yet been demonstrated for afatinib over erlotinib and gefitinib, the consistent class toxicity profile of these agents means that gefitinib and erlotinib are a safer first-line treatment recommendation.

Evasion of Neutrophil Extracellular Traps by Respiratory Pathogens

PubMed Central

Storisteanu, Daniel M. L.; Pocock, Joanna M.; Cowburn, Andrew S.; Juss, Jatinder K.; Nadesalingam, Angalee; Nizet, Victor

2017-01-01

The release of neutrophil extracellular traps (NETs) is a major immune mechanism intended to capture pathogens. These histone- and protease-coated DNA structures are released by neutrophils in response to a variety of stimuli, including respiratory pathogens, and have been identified in the airways of patients with respiratory infection, cystic fibrosis, acute lung injury, primary graft dysfunction, and chronic obstructive pulmonary disease. NET production has been demonstrated in the lungs of mice infected with Staphylococcus aureus, Klebsiella pneumoniae, and Aspergillus fumigatus. Since the discovery of NETs over a decade ago, evidence that “NET evasion” might act as an immune protection strategy among respiratory pathogens, including group A Streptococcus, Bordetella pertussis, and Haemophilus influenzae, has been growing, with the majority of these studies being published in the past 2 years. Evasion strategies fall into three main categories: inhibition of NET release by down-regulating host inflammatory responses; degradation of NETs using pathogen-derived DNases; and resistance to the microbicidal components of NETs, which involves a variety of mechanisms, including encapsulation. Hence, the evasion of NETs appears to be a widespread strategy to allow pathogen proliferation and dissemination, and is currently a topic of intense research interest. This article outlines the evidence supporting the three main strategies of NET evasion—inhibition, degradation, and resistance—with particular reference to common respiratory pathogens. PMID:27854516

Bactericidal effects of low-intensity extremely high frequency electromagnetic field: an overview with phenomenon, mechanisms, targets and consequences.

PubMed

Torgomyan, Heghine; Trchounian, Armen

2013-02-01

Low-intensity electromagnetic field (EMF) of extremely high frequencies is a widespread environmental factor. This field is used in telecommunication systems, therapeutic practices and food protection. Particularly, in medicine and food industries EMF is used for its bactericidal effects. The significant targets of cellular mechanisms for EMF effects at resonant frequencies in bacteria could be water (H(2)O), cell membrane and genome. The changes in H(2)O cluster structure and properties might be leading to increase of chemical activity or hydration of proteins and other cellular structures. These effects are likely to be specific and long-term. Moreover, cell membrane with its surface characteristics, substance transport and energy-conversing processes is also altered. Then, the genome is affected because the conformational changes in DNA and the transition of bacterial pro-phages from lysogenic to lytic state have been detected. The consequences for EMF interaction with bacteria are the changes in their sensitivity to different chemicals, including antibiotics. These effects are important to understand distinguishing role of bacteria in environment, leading to changed metabolic pathways in bacteria and their antibiotic resistance. This EMF may also affect the cell-to-cell interactions in bacterial populations, since bacteria might interact with each other through EMF of sub-extremely high frequency range.

Role of salicylic acid in resistance to cadmium stress in plants.

PubMed

Liu, Zhouping; Ding, Yanfei; Wang, Feijuan; Ye, Yaoyao; Zhu, Cheng

2016-04-01

We review and introduce the importance of salicylic acid in plants under cadmium stress, and provide insights into potential regulatory mechanisms for alleviating cadmium toxicity. Cadmium (Cd) is a widespread and potentially toxic environmental pollutant, originating mainly from rapid industrial processes, the application of fertilizers, manures and sewage sludge, and urban activities. It is easily taken up by plants, resulting in obvious toxicity symptoms, including growth retardation, leaf chlorosis, leaf and root necrosis, altered structures and ultrastructures, inhibition of photosynthesis, and cell death. Therefore, alleviating Cd toxicity in plants is a major aim of plant research. Salicylic acid (SA) is a ubiquitous plant phenolic compound that has been used in many plant species to alleviate Cd toxicity by regulating plant growth, reducing Cd uptake and distribution in plants, protecting membrane integrity and stability, scavenging reactive oxygen species and enhancing antioxidant defense system, improving photosynthetic capacity. Furthermore, SA functions as a signaling molecule involved in the expression of several important genes. Significant amounts of research have focused on understanding SA functions and signaling in plants under Cd stress, but several questions still remain unanswered. In this article, the influence of SA on Cd-induced stress in plants and the potential regulation mechanism for alleviating Cd toxicity are reviewed.

A Mechanism for Gratitude Development in a Child

ERIC Educational Resources Information Center

Li, Shi

2016-01-01

Most scholars consider gratitude as a moral emotion, with only few seeing it as a character trait. As a result, no systematic mechanism has ever been attempted to develop gratitude in children. Given the social issue of widespread lack of gratitude in the one-child generations of China, this article attempts to outline a mechanism of parental…

Melanoma patient derived xenografts acquire distinct Vemurafenib resistance mechanisms

PubMed Central

Monsma, David J; Cherba, David M; Eugster, Emily E; Dylewski, Dawna L; Davidson, Paula T; Peterson, Chelsea A; Borgman, Andrew S; Winn, Mary E; Dykema, Karl J; Webb, Craig P; MacKeigan, Jeffrey P; Duesbery, Nicholas S; Nickoloff, Brian J; Monks, Noel R

2015-01-01

Variable clinical responses, tumor heterogeneity, and drug resistance reduce long-term survival outcomes for metastatic melanoma patients. To guide and accelerate drug development, we characterized tumor responses for five melanoma patient derived xenograft models treated with Vemurafenib. Three BRAFV600E models showed acquired drug resistance, one BRAFV600E model had a complete and durable response, and a BRAFV600V model was expectedly unresponsive. In progressing tumors, a variety of resistance mechanisms to BRAF inhibition were uncovered, including mutant BRAF alternative splicing, NRAS mutation, COT (MAP3K8) overexpression, and increased mutant BRAF gene amplification and copy number. The resistance mechanisms among the patient derived xenograft models were similar to the resistance pathways identified in clinical specimens from patients progressing on BRAF inhibitor therapy. In addition, there was both inter- and intra-patient heterogeneity in resistance mechanisms, accompanied by heterogeneous pERK expression immunostaining profiles. MEK monotherapy of Vemurafenib-resistant tumors caused toxicity and acquired drug resistance. However, tumors were eradicated when Vemurafenib was combined the MEK inhibitor. The diversity of drug responses among the xenograft models; the distinct mechanisms of resistance; and the ability to overcome resistance by the addition of a MEK inhibitor provide a scheduling rationale for clinical trials of next-generation drug combinations. PMID:26101714

Insecticide Resistance and Metabolic Mechanisms Involved in Larval and Adult Stages of Aedes aegypti Insecticide-Resistant Reference Strains from Cuba.

PubMed

Bisset, Juan Andrés; Rodríguez, María Magdalena; French, Leydis; Severson, David W; Gutiérrez, Gladys; Hurtado, Daymi; Fuentes, Ilario

2014-12-01

Studies were conducted to compare levels of insecticide resistance and to determine the metabolic resistance mechanisms in larval and adult stages of Aedes aegypti from Cuba. Three insecticide-resistant reference strains of Ae. aegypti from Cuba were examined. These strains were derived from a Santiago de Cuba strain isolated in 1997; it was previously subjected to a strong selection for resistance to temephos (SAN-F6), deltamethrin (SAN-F12), and propoxur (SAN-F13) and routinely maintained in the laboratory under selection pressure up to the present time, when the study was carried out. In addition, an insecticide-susceptible strain was used for comparison. The insecticide resistance in larvae and adults was determined using standard World Health Organization methodologies. Insecticide resistance mechanisms were determined by biochemical assays. The esterases (α EST and β EST) and mixed function oxidase (MFO) activities were significantly higher in adults than in the larvae of the three resistant strains studied. The association of resistance level with the biochemical mechanism for each insecticide was established for each stage. The observed differences between larval and adult stages of Ae. aegypti in their levels of insecticide resistance and the biochemical mechanisms involved should be included as part of monitoring and surveillance activities in Ae. aegypti vector control programs.

Cross-stress resistance in Saccharomyces cerevisiae yeast--new insight into an old phenomenon.

PubMed

Święciło, Agata

2016-03-01

Acquired stress resistance is the result of mild stress causing the acquisition of resistance to severe stress of the same or a different type. The mechanism of "same-stress" resistance (resistance to a second, strong stress after mild primary stress of the same type) probably depends on the activation of defense and repair mechanisms specific for a particular type of stress, while cross-stress resistance (i.e., resistance to a second, strong stress after a different type of mild primary stress) is the effect of activation of both a specific and general stress response program, which in Saccharomyces cerevisiae yeast is known as the environmental stress response (ESR). Advancements in research techniques have made it possible to study the mechanism of cross-stress resistance at various levels of cellular organization: stress signal transduction pathways, regulation of gene expression, and transcription or translation processes. As a result of this type of research, views on the cross-stress protection mechanism have been reconsidered. It was originally thought that cross-stress resistance, irrespective of the nature of the two stresses, was determined by universal mechanisms, i.e., the same mechanisms within the general stress response. They are now believed to be more specific and strictly dependent on the features of the first stress.

Biodegradable DNA Nanoparticles that Provide Widespread Gene Delivery in the Brain

PubMed Central

Mastorakos, Panagiotis; Song, Eric; Zhang, Clark; Berry, Sneha; Park, Hee Won; Kim, Young Eun; Park, Jong Sung; Lee, Seulki; Suk, Jung Soo; Hanes, Justin

2016-01-01

Successful gene therapy of neurological disorders is predicated on achieving widespread and uniform transgene expression throughout the affected disease area in the brain. However, conventional gene vectors preferentially travel through low-resistance perivascular spaces and/or are confined to the administration site even with the aid of a pressure-driven flow provided by convection-enhanced delivery. Biodegradable DNA nanoparticles offer a safe gene delivery platform devoid of adverse effects associated with virus-based or synthetic non-biodegradable systems. Using a state-of-the-art biodegradable polymer, poly(β-amino ester), we engineered colloidally stable sub-100 nm DNA nanoparticles coated with a non-adhesive polyethylene glycol corona that are able to avoid the adhesive and steric hindrances imposed by the extracellular matrix. Following convection enhanced delivery, these brain-penetrating nanoparticles were able to homogeneously distribute throughout the rodent striatum and mediate widespread and high-level transgene expression. These nanoparticles provide a biodegradable DNA nanoparticle platform enabling uniform transgene expression patterns in vivo and hold promise for the treatment of neurological diseases. PMID:26680637

[Capability of national reference laboratories in Latin America to detect emerging resistance mechanisms].

PubMed

Corso, Alejandra; Guerriero, Leonor; Pasterán, Fernando; Ceriana, Paola; Callejo, Raquel; Prieto, Mónica; Tuduri, Ezequiel; Lopardo, Horacio; Vay, Carlos; Smayevsky, Jorgelina; Tokumoto, Marta; Alvarez, Jorge Matheu; Pardo, Pilar Ramón; Galas, Marcelo

2011-12-01

To evaluate the capability of 17 national reference laboratories participating in the Latin American Quality Control Program in Bacteriology and Antibiotic Resistance (LA-EQAS) to detect emerging resistance mechanisms- namely: resistance of enterobacteria to carbapenems due to the presence of Klebsiella pneumoniae carbapenemase (KPC) and metallo-beta-lactamase (MBL) type IMP, and intermediate resistance of Staphylococcus aureus isolates to vancomycin (vancomycin-intermediate resistant S. aureus-VISA). The following three isolates were sent to the 17 participating LA-EQAS laboratories: KPC -producing Klebsiella pneumoniae PAHO-161, IMP-producing Enterobacter cloacae PAHO-166, and S. aureus PAHO-165 with intermediate resistance to vancomycin. Performance of each of the following operations was evaluated: interpretation of sensitivity tests, detection of the resistance mechanism, and assessment of either inhibition halo size (disk diffusion method) or minimum inhibitory concentration (MIC). Concordance in the detection of resistance mechanisms was 76.4%, 73.3%, and 66.7% for the K. pneumoniae PAHO-161, E. cloacae PAHO-166, and S. aureus PAHO-165 strains, respectively. Concordance between the inhibition areas observed by the participating laboratories and the ranges established by the coordinating laboratory was acceptable for all three isolates, at 90.8%, 92.8%, and 88.9%, respectively. Overall concordance in on the detection of KPC, MBL, and VISA resistance mechanisms was 72.1%. We consider the national reference laboratories in Latin America capable of recognizing these emerging resistance mechanisms and expect that maximum levels of concordance will be reached in the future.

Progress on mechanism of ethambutol resistance in Mycobacterium Tuberculosis.

PubMed

Wang, Ting; Jiao, Wei-wei; Shen, A-dong

2016-10-20

The occurance and prevalence of multidrug-resistant tuberculosis poses a serious threat to the global tuberculosis control. Ethambutol (EMB) is one of the first-line anti-tuberculosis drugs, which is usually used in combination with isoniazid and rifampicin for treating pan-sensitive tuberculosis, and it can also be used in drug-resistant tuberculosis. However, the situation of EMB resistance is alarmingly high, especially in multi-drug resistant tuberculosis. In China, EMB resistance rate in the previously treated cases was up to 17.2% and showed an increased tendency. What was worse, 51.3%-66.7% of multidrug-resistant tuberculosis cases were resistant to EMB. Thus, it is important to understand the drug resistance mechanism of EMB, which will help to slow down the drug resistance rate of EMB. In this review, we focus on the current status of EMB resistance, the effects of EMB and the mechanisms of EMB resistance in Mycobacterium tuberculosis.

Circulating tumour DNA profiling reveals heterogeneity of EGFR inhibitor resistance mechanisms in lung cancer patients

PubMed Central

Chabon, Jacob J.; Simmons, Andrew D.; Lovejoy, Alexander F.; Esfahani, Mohammad S.; Newman, Aaron M.; Haringsma, Henry J.; Kurtz, David M.; Stehr, Henning; Scherer, Florian; Karlovich, Chris A.; Harding, Thomas C.; Durkin, Kathleen A.; Otterson, Gregory A.; Purcell, W. Thomas; Camidge, D. Ross; Goldman, Jonathan W.; Sequist, Lecia V.; Piotrowska, Zofia; Wakelee, Heather A.; Neal, Joel W.; Alizadeh, Ash A.; Diehn, Maximilian

2016-01-01

Circulating tumour DNA (ctDNA) analysis facilitates studies of tumour heterogeneity. Here we employ CAPP-Seq ctDNA analysis to study resistance mechanisms in 43 non-small cell lung cancer (NSCLC) patients treated with the third-generation epidermal growth factor receptor (EGFR) inhibitor rociletinib. We observe multiple resistance mechanisms in 46% of patients after treatment with first-line inhibitors, indicating frequent intra-patient heterogeneity. Rociletinib resistance recurrently involves MET, EGFR, PIK3CA, ERRB2, KRAS and RB1. We describe a novel EGFR L798I mutation and find that EGFR C797S, which arises in ∼33% of patients after osimertinib treatment, occurs in <3% after rociletinib. Increased MET copy number is the most frequent rociletinib resistance mechanism in this cohort and patients with multiple pre-existing mechanisms (T790M and MET) experience inferior responses. Similarly, rociletinib-resistant xenografts develop MET amplification that can be overcome with the MET inhibitor crizotinib. These results underscore the importance of tumour heterogeneity in NSCLC and the utility of ctDNA-based resistance mechanism assessment. PMID:27283993

Mating Success, Longevity, and Fertility of Diabrotica virgifera virgifera LeConte (Chrysomelidae: Coleoptera) in Relation to Body Size and Cry3Bb1-Resistant and Cry3Bb1-Susceptible Genotypes

PubMed Central

French, Bryan Wade; Hammack, Leslie; Tallamy, Douglas W.

2015-01-01

Insect resistance to population control methodologies is a widespread problem. The development of effective resistance management programs is often dependent on detailed knowledge regarding the biology of individual species and changes in that biology associated with resistance evolution. This study examined the reproductive behavior and biology of western corn rootworm beetles of known body size from lines resistant and susceptible to the Cry3Bb1 protein toxin expressed in transgenic Bacillus thuringiensis maize. In crosses between, and within, the resistant and susceptible genotypes, no differences occurred in mating frequency, copulation duration, courtship duration, or fertility; however, females mated with resistant males showed reduced longevity. Body size did not vary with genotype. Larger males and females were not more likely to mate than smaller males and females, but larger females laid more eggs. Moderately strong, positive correlation occurred between the body sizes of successfully mated males and females; however, weak correlation also existed for pairs that did not mate. Our study provided only limited evidence for fitness costs associated with the Cry3Bb1-resistant genotype that might reduce the persistence in populations of the resistant genotype but provided additional evidence for size-based, assortative mating, which could favor the persistence of resistant genotypes affecting body size. PMID:26569315

Herbicide mixtures at high doses slow the evolution of resistance in experimentally evolving populations of Chlamydomonas reinhardtii.

PubMed

Lagator, Mato; Vogwill, Tom; Mead, Andrew; Colegrave, Nick; Neve, Paul

2013-05-01

The widespread evolution of resistance to herbicides is a pressing issue in global agriculture. Evolutionary principles and practices are key to the management of this threat to global food security. The application of mixtures of herbicides has been advocated as an anti-resistance strategy, without substantial empirical support for its validation. We evolved experimentally populations of the unicellular green chlorophyte, Chlamydomonas reinhardtii, to minimum inhibitory concentrations (MICs) of single-herbicide modes of action and to pair-wise and three-way mixtures between different herbicides at various total combined doses. Herbicide mixtures were most effective when each component was applied at or close to its MIC. When doses were high, increasing the number of mixture components was also effective in reducing the evolution of resistance. Employing mixtures at low combined doses did not retard resistance evolution, even accelerating the evolution of resistance to some components. At low doses, increasing the number of herbicides in the mixture tended to select for more generalist resistance (cross-resistance). Our results reinforce findings from the antibiotic resistance literature and confirm that herbicide mixtures can be very effective for resistance management, but that mixtures should only be employed where the economic and environmental context permits the applications of high combined doses. © 2013 The Authors. New Phytologist © 2013 New Phytologist Trust.

Bacillus subtilis vegetative isolate surviving chlorine dioxide exposure: an elusive mechanism of resistance.

PubMed

Martin, D J H; Wesgate, R L; Denyer, S P; McDonnell, G; Maillard, J-Y

2015-12-01

Oxidizing agents such as chlorine dioxide are widely used microbicides, including for disinfection of medical equipment. We isolated a Bacillus subtilis isolate from a washer-disinfector whose vegetative form demonstrated unique resistance to chlorine dioxide (0·03%) and hydrogen peroxide (7·5%). The aim of this study was to understand the mechanisms of resistance expressed by this isolate. A range of resistance mechanisms were investigated in the B. subtilis isolate and a reference B. subtilis strain (ATCC 6051) to include bacterial cell aggregation, the presence of profuse exopolysaccharide (EPS), and the expression of detoxification enzymes. The basis of resistance of the isolate to high concentrations of oxidizing agents was not linked to the presence of endospores. Although, the presence of EPS, aggregation and expression of detoxification enzymes may play a role in bacterial survival to low concentrations of chlorine dioxide, it is unlikely that the mechanisms helped tested to survive the bactericidal effect of higher oxidizer concentrations. Overall, the mechanisms conferring resistance to chlorine dioxide and hydrogen peroxide remains elusive. Based on recent advances in the mode of action of oxidizing agents and notably hydrogen peroxide, we postulate that additional efficient intracellular mechanisms may be involved to explain significant resistance to in-use concentrations of commonly used high-level disinfectants. The isolation of a highly resistant vegetative Gram-positive bacterium to a highly reactive oxidizing agent is worrying. Understanding the mechanisms conferring such resistance is essential to effectively control such bacterial isolates. Here, we postulate that there are still mechanisms of bacterial resistance that have not been fully characterized. © 2015 The Authors published by John Wiley & Sons Ltd on behalf of Society for Applied Microbiology.

How should we respond to the emergence of plasmid-mediated colistin resistance in humans and animals?

PubMed

Al-Tawfiq, Jaffar A; Laxminarayan, Ramanan; Mendelson, Marc

2017-01-01

The widespread use of antibiotics in humans and animals has contributed to growing rates of antibiotic resistance. Previously treatable bacterial infections now require the last line of antibiotics or are untreatable. The current antibiotic of last resort for carbapenem-resistant Gram-negative bacterial infections is often colistin. Evidence for the shifting pattern of colistin resistance and how the international community should respond are discussed in this review. The literature on colistin resistance was reviewed. Plasmid-mediated colistin resistance encoded by mcr-1 was first documented in China during the routine surveillance of food animals. This has been followed by similar reports across a wide geographic area, in humans, animals, and the environment. The mcr-1 gene has been reported among human isolates in 29 countries, related to environmental samples in four countries, and in food animals and other animals in 28 countries. More recently, a second gene encoding resistance, mcr-2, has been isolated from porcine and bovine Escherichia coli. The emergence and horizontal transmission of colistin resistance highlights the need for heightened stewardship efforts across the One Health platform for this antibiotic of last resort, and indeed for all antibiotics used in animals and humans. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Extended-spectrum beta-lactamase-producing Escherichia coli in common vampire bats Desmodus rotundus and livestock in Peru.

PubMed

Benavides, J A; Shiva, C; Virhuez, M; Tello, C; Appelgren, A; Vendrell, J; Solassol, J; Godreuil, S; Streicker, D G

2018-06-01

Antibiotic resistance mediated by bacterial production of extended-spectrum beta-lactamase (ESBL) is a global threat to public health. ESBL resistance is most commonly hospital-acquired; however, infections acquired outside of hospital settings have raised concerns over the role of livestock and wildlife in the zoonotic spread of ESBL-producing bacteria. Only limited data are available on the circulation of ESBL-producing bacteria in animals. Here, we report ESBL-producing Escherichia coli in wild common vampire bats Desmodus rotundus and livestock near Lima, Peru. Molecular analyses revealed that most of this resistance resulted from the expression of bla CTX-M-15 genes carried by plasmids, which are disseminating worldwide in hospital settings and have also been observed in healthy children of Peru. Multilocus sequence typing showed a diverse pool of E. coli strains carrying this resistance that were not always host species-specific, suggesting sharing of strains between species or infection from a common source. This study shows widespread ESBL resistance in wild and domestic animals, supporting animal communities as a potential source of resistance. Future work is needed to elucidate the role of bats in the dissemination of antibiotic-resistant strains of public health importance and to understand the origin of the observed resistance. © 2018 Blackwell Verlag GmbH.

An Expert Elicitation of the Proliferation Resistance of Using Small Modular Reactors (SMR) for the Expansion of Civilian Nuclear Systems.

PubMed

Siegel, Jonas; Gilmore, Elisabeth A; Gallagher, Nancy; Fetter, Steve

2018-02-01

To facilitate the use of nuclear energy globally, small modular reactors (SMRs) may represent a viable alternative or complement to large reactor designs. One potential benefit is that SMRs could allow for more proliferation resistant designs, manufacturing arrangements, and fuel-cycle practices at widespread deployment. However, there is limited work evaluating the proliferation resistance of SMRs, and existing proliferation assessment approaches are not well suited for these novel arrangements. Here, we conduct an expert elicitation of the relative proliferation resistance of scenarios for future nuclear energy deployment driven by Generation III+ light-water reactors, fast reactors, or SMRs. Specifically, we construct the scenarios to investigate relevant technical and institutional features that are postulated to enhance the proliferation resistance of SMRs. The experts do not consistently judge the scenario with SMRs to have greater overall proliferation resistance than scenarios that rely on conventional nuclear energy generation options. Further, the experts disagreed on whether incorporating a long-lifetime sealed core into an SMR design would strengthen or weaken proliferation resistance. However, regardless of the type of reactor, the experts judged that proliferation resistance would be enhanced by improving international safeguards and operating several multinational fuel-cycle facilities rather than supporting many more national facilities. © 2017 Society for Risk Analysis.

Novel genetic factors involved in resistance to Bacillus thuringiensis in Plutella xylostella.

PubMed

Ayra-Pardo, C; Raymond, B; Gulzar, A; Rodríguez-Cabrera, L; Morán-Bertot, I; Crickmore, N; Wright, D J

2015-12-01

The widespread and sustainable exploitation of the entomopathogen Bacillus thuringiensis (Bt) in pest control is threatened by the evolution of resistance. Although resistance is often associated with loss of binding of the Bt toxins to the insect midgut cells, other factors have been implicated. Here we used suppressive subtractive hybridization and gene expression suppression to identify additional molecular components involved in Bt-resistance in Plutella xylostella. We isolated transcripts from genes that were differentially expressed in the midgut of larvae from a resistant population, following ingestion of a Bt kurstaki HD1 strain-based commercial formulation (DiPel), and compared with a genetically similar susceptible population. Quantitative real-time polymerase-chain reaction (RT-PCR) analysis confirmed the differential basal expression of a subset of these genes. Gene expression suppression of three of these genes (P. xylostella cyclin-dependent kinase 5 regulatory subunit associated protein 1-like 1, stromal cell-derived factor 2-like 1 and hatching enzyme-like 1) significantly increased the pathogenicity of HD1 to the resistant population. In an attempt to link the multitude of factors reportedly influencing resistance to Bt with the well-characterized loss of toxin binding, we also considered Bt-resistance models in P. xylostella and other insects. © 2015 The Royal Entomological Society.

Molecular characterization and functional analysis of Eimeria tenella malate dehydrogenase.

PubMed

Chen, Ting; Huang, Bing; Zhao, Qiping; Dong, Hui; Zhu, Shunhai; Zhao, Zongping; Lv, Ling; Yan, Ming; Han, Hongyu

2018-05-08

Eimeria tenella is a serious intracellular parasite that actively invades cecal epithelial cells of chickens. The widespread use of drugs causes severe resistance to Eimeria tenella. We detected that malate dehydrogenase (MDH), one of the differentially expressed genes, was upregulated in diclazuril-resistant and maduramicin-resistant strains through transcriptome sequencing. In this study, we cloned and expressed MDH of E. tenella (EtMDH). Quantitative real-time polymerase chain reactions (qPCR) and Western blots were used to analyze the expression of EtMDH in resistant and sensitive strains, indicating EtMDH was upregulated in two resistant strains at the messenger RNA and protein levels. Enzyme activity was tested through absorbance measurement and the EtMDH activity increased in two resistant strains. Expression levels of EtMDH in four developmental stages of E. tenella were tested through qPCR and Western blot. Invasion inhibition assays explored if EtMDH was involved in invasion of DF-1 cells by E. tenella sporozoites. Indirect immunofluorescence assays investigated EtMDH distribution during parasite development in DF-1 cells invaded by E. tenella sporozoites. Experimental results showed that EtMDH may be related to drug resistance of E. tenella during its development and invasion. EtMDH may be an effective molecular marker for detection of E. tenella drug resistance.

[Fluoroquinolones and Gram-negative bacteria: antimicrobial activity and mechanisms of resistance].

PubMed

Luzzaro, F

2008-04-01

Fluoroquinolones acts by interacting with type II topoisomerases (DNA gyrase and topoisomerases IV). Related to this mechanism of action, bacteria have developed resistance mechanisms consisting in some target mutations (GyrA/GyrB for DNA gyrase and ParC/ParE for topoisomerase IV) or in a reduced access to the target itself, by either decreased permeability or augmented expression of efflux pumps, such as AcrAB and MexAB. Along with these classical mechanisms of chromosomal resistance, the presence of fluoroquinolones resistant proteins (Qnr) has been recently evidenced, codified by transmissible genes by means of plasmids, especially in Enterobacter spp., Escherichia coli and Klebsiella pneumoniae, whereas Proteus mirabilis and non fermenter Gram-negative, like Acinetobacter spp. and Pseudomonas aeruginosa, are not involved in such a kind of resistance. Qnr proteins determine a slight increase in MIC values, which often remains below the susceptibility breakpoint. More relevant is their impact on MPC values. Additionally, new specific resistance mechanisms have been described. AAC(6')-Ib-cr represents the first enzyme able to inactivate, by acetylation, antimicrobials of two different classes, aminoglycosides and fluoroquinolones. However, ciprofloxacin and norfloxacin, but not levofloxacin, are susceptible to this enzyme action. Finally, the presence of another resistance mechanism has been reported, an efflux-pump plasmid-mediated, codified by the QepA gene, which acts by a selective mechanism. Only hydrophilic fluoroquinolones, i.e. norfloxacin and ciprofloxacin, but not all the other ones, i.e. levofloxacin, moxifloxacin, etc, are affected by this mechanism. In the light of these new information, it is clear that, in terms of bacterial resistance, it is not any more possible to assimilate one fluoroquinolones to another, since different molecules can be diversely active, due to the specific resistance mechanism.

Cognitive tutoring induces widespread neuroplasticity and remediates brain function in children with mathematical learning disabilities.

PubMed

Iuculano, Teresa; Rosenberg-Lee, Miriam; Richardson, Jennifer; Tenison, Caitlin; Fuchs, Lynn; Supekar, Kaustubh; Menon, Vinod

2015-09-30

Competency with numbers is essential in today's society; yet, up to 20% of children exhibit moderate to severe mathematical learning disabilities (MLD). Behavioural intervention can be effective, but the neurobiological mechanisms underlying successful intervention are unknown. Here we demonstrate that eight weeks of 1:1 cognitive tutoring not only remediates poor performance in children with MLD, but also induces widespread changes in brain activity. Neuroplasticity manifests as normalization of aberrant functional responses in a distributed network of parietal, prefrontal and ventral temporal-occipital areas that support successful numerical problem solving, and is correlated with performance gains. Remarkably, machine learning algorithms show that brain activity patterns in children with MLD are significantly discriminable from neurotypical peers before, but not after, tutoring, suggesting that behavioural gains are not due to compensatory mechanisms. Our study identifies functional brain mechanisms underlying effective intervention in children with MLD and provides novel metrics for assessing response to intervention.

Assessment of deep dynamic mechanical sensitivity in individuals with tension-type headache: The dynamic pressure algometry.

PubMed

Palacios-Ceña, M; Wang, K; Castaldo, M; Guerrero-Peral, Á; Caminero, A B; Fernández-de-Las-Peñas, C; Arendt-Nielsen, L

2017-09-01

To explore the validity of dynamic pressure algometry for evaluating deep dynamic mechanical sensitivity by assessing its association with headache features and widespread pressure sensitivity in tension-type headache (TTH). One hundred and eighty-eight subjects with TTH (70% women) participated. Deep dynamic sensitivity was assessed with a dynamic pressure algometry set (Aalborg University, Denmark © ) consisting of 11 different rollers including fixed levels from 500 g to 5300 g. Each roller was moved at a speed of 0.5 cm/s over a 60-mm horizontal line covering the temporalis muscle. Dynamic pain threshold (DPT-level of the first painful roller) was determined and pain intensity during DPT was rated on a numerical pain rate scale (NPRS, 0-10). Headache clinical features were collected on a headache diary. As gold standard, static pressure pain thresholds (PPT) were assessed over temporalis, C5/C6 joint, second metacarpal, and tibialis anterior muscle. Side-to-side consistency between DPT (r = 0.843, p < 0.001) and pain evoked (r = 0.712; p < 0.001) by dynamic algometer was observed. DPT was moderately associated with widespread PPTs (0.526 > r > 0.656, all p < 0.001). Furthermore, pain during DPT was negatively associated with widespread PPTs (-0.370 < r < -0.162, all p < 0.05). Dynamic pressure algometry was a valid tool for assessing deep dynamic mechanical sensitivity in TTH. DPT was associated with widespread pressure sensitivity independently of the frequency of headaches supporting that deep dynamic pressure sensitivity within the trigeminal area is consistent with widespread pressure sensitivity. Assessing deep static and dynamic somatic tissue pain sensitivity may provide new opportunities for differentiated diagnostics and possibly a new tool for assessing treatment effects. The current study found that dynamic pressure algometry in the temporalis muscle was associated with widespread pressure pain sensitivity in individuals with tension-type headache. The association was independent of the frequency of headaches. Assessing deep static and dynamic somatic tissue pain sensitivity may provide new opportunities for differentiated diagnostics and possibly a tool for assessing treatment effects. © 2017 European Pain Federation - EFIC®.

High level QM/MM modeling of the formation of the tetrahedral intermediate in the acylation of wild type and K73A mutant TEM-1 class A beta-lactamase.

PubMed

Hermann, Johannes C; Pradon, Juliette; Harvey, Jeremy N; Mulholland, Adrian J

2009-10-29

The breakdown of beta-lactam antibiotics by beta-lactamases is the most important resistance mechanism of gram negative bacteria against these drugs. The reaction mechanism of class A beta-lactamases, the most widespread family of these enzymes, consists of two main steps: acylation of an active site serine by the antibiotic, followed by deacylation and release of the cleaved compound. We have investigated the first step in acylation (the formation of the tetrahedral intermediate) for the reaction of benzylpenicillin in the TEM-1 enzyme using high level combined quantum mechanics/molecular mechanics (QM/MM) methods. Structures were optimized at the B3LYP/6-31+G(d)/CHARMM27 level, with energies for key points calculated up to the ab initio SCS-MP2/aug-cc-pVTZ/CHARMM27 level. The results support a mechanism in which Glu166 removes a proton (via an intervening water molecule) from Ser70, which in turn attacks the beta-lactam of the antibiotic. Depending on the method used, the calculated barriers range from 3 to 12 kcal mol(-1) for this step, consistent with experimental data. We have also modeled this reaction step in a model of the K73A mutant enzyme. The barrier to reaction in this mutant model is found to be slightly higher: the results indicate that Lys73 stabilizes the transition state, in particular deprotonated Ser70, lowering the barrier by about 1.7 kcal mol(-1). This finding may help to explain the conservation of Lys73, in addition to the role we have previously found for it in the later stages of the reaction (Hermann et al. Org. Biomol. Chem. 2006, 4, 206-210).

High Level QM/MM Modeling of the Formation of the Tetrahedral Intermediate in the Acylation of Wild Type and K73A Mutant TEM-1 Class A β-Lactamase

NASA Astrophysics Data System (ADS)

Hermann, Johannes C.; Pradon, Juliette; Harvey, Jeremy N.; Mulholland, Adrian J.

2009-09-01

The breakdown of β-lactam antibiotics by β-lactamases is the most important resistance mechanism of Gram negative bacteria against these drugs. The reaction mechanism of class A β-lactamases, the most widespread family of these enzymes, consists of two main steps: acylation of an active site serine by the antibiotic, followed by deacylation and release of the cleaved compound. We have investigated the first step in acylation (the formation of the tetrahedral intermediate) for the reaction of benzylpenicillin in the TEM-1 enzyme using high level combined quantum mechanics/molecular mechanics (QM/MM) methods. Structures were optimized at the B3LYP/6-31+G(d)/CHARMM27 level, with energies for key points calculated up to the ab initio SCS-MP2/aug-cc-pVTZ/CHARMM27 level. The results support a mechanism in which Glu166 removes a proton (via an intervening water molecule) from Ser70, which in turn attacks the β-lactam of the antibiotic. Depending on the method used, the calculated barriers range from 3 to 12 kcal mol-1 for this step, consistent with experimental data. We have also modeled this reaction step in a model of the K73A mutant enzyme. The barrier to reaction in this mutant model is found to be slightly higher: the results indicate that Lys73 stabilizes the transition state, in particular deprotonated Ser70, lowering the barrier by about 1.7 kcal mol-1. This finding may help to explain the conservation of Lys73, in addition to the role we have previously found for it in the later stages of the reaction ( Hermann et al. Org. Biomol. Chem. 2006, 4, 206 - 210 ).

Toluene diisocyanate caused electrophysiological disturbances in the upper airways wall.

PubMed

Piskorska, Elzbieta; Hołyńska-Iwan, Iga; Kaczorowski, Piotr; Soczywko-Ciudzińska, Julita; Wiciński, Michał; Lampka, Magdalena; Smuszkiewicz, Piotr; Tyrakowski, Tomasz

2009-01-01

Toluene diisocyanate (TDI) due to its widespread use in industry is one of the most common and well-known causes of occupational asthma and Reactive Airways Dysfunction Syndrome (RADS). In this study the impact of TDI on the electrophysiological properties of the airways wall, particularly on the mechanisms of absorption of sodium ions and chloride ions secretion was evaluated. Isolated rabbit tracheal wall (from outbred stock animals) was mounted in an apparatus for electrophysiological experiments by means of Ussing method and was mechanically stimulated by the jet flux of specified fluid directed onto the mucosal surface of the tissue from a peristaltic pump. The measured parameters were: transepithelial potential difference under control conditions (PD, mV), after mechanical stimulation (dPD or physiological reaction of hyperpolarization, mV) and electric resistance (R, Omega cm2). When TDI (0.035 mM) was added to stimulation fluid, only the immediate reaction was identified and when it was added to incubation fluid and other experimental fluids, the late (post-incubation) reaction was determined. The experiments involving the inhibition of Na+ by amiloride and Cl- by bumetanide were also performed. A series of functional tests for 72 pieces of tracheal wall from 36 animals were performed. It has been shown that short-term exposure to TDI significantly changed the course of reactions to mechanical stimulation. Also after incubation in the presence of TDI, the reactions to mechanical stimulation were changed in relation to control conditions. The immediate reaction of the isolated rabbit tracheal wall after exposure to TDI depends on the duration of exposure and on the physiological condition of the tissue in respect of sodium and chloride ion transport.

Various Wolbachia genotypes differently influence host Drosophila dopamine metabolism and survival under heat stress conditions.

PubMed

Gruntenko, Nataly Е; Ilinsky, Yury Yu; Adonyeva, Natalya V; Burdina, Elena V; Bykov, Roman A; Menshanov, Petr N; Rauschenbach, Inga Yu

2017-12-28

One of the most widespread prokaryotic symbionts of invertebrates is the intracellular bacteria of Wolbachia genus which can be found in about 50% of insect species. Wolbachia causes both parasitic and mutualistic effects on its host that include manipulating the host reproductive systems in order to increase their transmission through the female germline, and increasing the host fitness. One of the mechanisms, promoting adaptation in biological organisms, is a non-specific neuroendocrine stress reaction. In insects, this reaction includes catecholamines, dopamine, serotonin and octopamine, which act as neurotransmitters, neuromodulators and neurohormones. The level of dopamine metabolism correlates with heat stress resistance in Drosophila adults. To examine Wolbachia effect on Drosophila survival under heat stress and dopamine metabolism we used five strains carrying the nuclear background of interbred Bi90 strain and cytoplasmic backgrounds with different genotype variants of Wolbachia (produced by 20 backcrosses of Bi90 males with appropriate source of Wolbachia). Non-infected Bi90 strain (treated with tetracycline for 3 generations) was used as a control group. We demonstrated that two of five investigated Wolbachia variants promote changes in Drosophila heat stress resistance and activity of enzymes that produce and degrade dopamine, alkaline phosphatase and dopamine-dependent arylalkylamine N-acetyltransferase. What is especially interesting, wMelCS genotype of Wolbachia increases stress resistance and the intensity of dopamine metabolism, whereas wMelPop strain decreases them. wMel, wMel2 and wMel4 genotypes of Wolbachia do not show any effect on the survival under heat stress or dopamine metabolism. L-DOPA treatment, known to increase the dopamine content in Drosophila, levels the difference in survival under heat stress between all studied groups. The genotype of symbiont determines the effect that the symbiont has on the stress resistance of the host insect.

Cationic antimicrobial peptide resistance mechanisms of streptococcal pathogens.

PubMed

LaRock, Christopher N; Nizet, Victor

2015-11-01

Cationic antimicrobial peptides (CAMPs) are critical front line contributors to host defense against invasive bacterial infection. These immune factors have direct killing activity toward microbes, but many pathogens are able to resist their effects. Group A Streptococcus, group B Streptococcus and Streptococcus pneumoniae are among the most common pathogens of humans and display a variety of phenotypic adaptations to resist CAMPs. Common themes of CAMP resistance mechanisms among the pathogenic streptococci are repulsion, sequestration, export, and destruction. Each pathogen has a different array of CAMP-resistant mechanisms, with invasive disease potential reflecting the utilization of several mechanisms that may act in synergy. Here we discuss recent progress in identifying the sources of CAMP resistance in the medically important Streptococcus genus. Further study of these mechanisms can contribute to our understanding of streptococcal pathogenesis, and may provide new therapeutic targets for therapy and disease prevention. This article is part of a Special Issue entitled: Bacterial Resistance to Antimicrobial Peptides. Copyright © 2015 Elsevier B.V. All rights reserved.

Identification of the Zinc Finger Protein ZRANB2 as a Novel Maternal Lipopolysaccharide-binding Protein That Protects Embryos of Zebrafish against Gram-negative Bacterial Infections*

PubMed Central

Wang, Xia; Du, Xiaoyuan; Li, Hongyan; Zhang, Shicui

2016-01-01

Zinc finger ZRANB2 proteins are widespread in animals, but their functions and mechanisms remain poorly defined. Here we clearly demonstrate that ZRANB2 is a newly identified LPS-binding protein present abundantly in the eggs/embryos of zebrafish. We also show that recombinant ZRANB2 (rZRANB2) acts as a pattern recognition receptor capable of identifying the bacterial signature molecule LPS as well as binding the Gram-negative bacteria Escherichia coli, Vibrio anguilarum, and Aeromonas hydrophila and functions as an antibacterial effector molecule capable of directly killing the bacteria. Furthermore, we reveal that N-terminal residues 11–37 consisting of the first ZnF_RBZ domain are indispensable for ZRANB2 antimicrobial activity. Importantly, microinjection of rZRANB2 into early embryos significantly enhanced the resistance of the embryos against pathogenic A. hydrophila challenge, and this enhanced bacterial resistance was markedly reduced by co-injection of anti-ZRANB2 antibody. Moreover, precipitation of ZRANB2 in the embryo extracts by preincubation with anti-ZRANB2 antibody caused a marked decrease in the antibacterial activity of the extracts against the bacteria tested. In addition, the N-terminal peptide Z1/37 or Z11/37 with in vitro antibacterial activity also promoted the resistance of embryos against A. hydrophila, but the peptide Z38/198 without in vitro antibacterial activity did not. Collectively, these results indicate that ZRANB2 is a maternal LPS-binding protein that can protect the early embryos of zebrafish against pathogenic attacks, a novel role ever assigned to ZRANB2 proteins. This work also provides new insights into the immunological function of the zinc finger proteins that are widely distributed in various animals. PMID:26740623

The effectiveness of faecal removal methods of pasture management to control the cyathostomin burden of donkeys.

PubMed

Corbett, Christopher J; Love, Sandy; Moore, Anna; Burden, Faith A; Matthews, Jacqui B; Denwood, Matthew J

2014-01-24

The level of anthelmintic resistance within some cyathostomin parasite populations has increased to the level where sole reliance on anthelmintic-based control protocols is not possible. Management-based nematode control methods, including removal of faeces from pasture, are widely recommended for use in association with a reduction in anthelmintic use to reduce selection pressure for drug resistance; however, very little work has been performed to quantitatively assess the effectiveness of such methods. We analysed data obtained from 345 donkeys at The Donkey Sanctuary (Devon, UK), managed under three different pasture management techniques, to investigate the effectiveness of faeces removal in strongyle control in equids. The management groups were as follows: no removal of faeces from pasture, manual, twice-weekly removal of faeces from pasture and automatic, twice-weekly removal of faeces from pasture (using a mechanical pasture sweeper). From turn-out onto pasture in May, monthly faecal egg counts were obtained for each donkey and the dataset subjected to an auto regressive moving average model. There was little to no difference in faecal egg counts between the two methods of faecal removal; both resulted in significantly improved cyathostomin control compared to the results obtained from the donkeys that grazed pasture from which there was no faecal removal. This study represents a valuable and unique assessment of the effectiveness of the removal of equine faeces from pasture, and provides an evidence base from which to advocate twice-weekly removal of faeces from pasture as an adjunct for equid nematode control. Widespread adoption of this practice could substantially reduce anthelmintic usage, and hence reduce selection pressure for nematode resistance to the currently effective anthelmintic products.

The effectiveness of faecal removal methods of pasture management to control the cyathostomin burden of donkeys

PubMed Central

2014-01-01

Background The level of anthelmintic resistance within some cyathostomin parasite populations has increased to the level where sole reliance on anthelmintic-based control protocols is not possible. Management-based nematode control methods, including removal of faeces from pasture, are widely recommended for use in association with a reduction in anthelmintic use to reduce selection pressure for drug resistance; however, very little work has been performed to quantitatively assess the effectiveness of such methods. Methods We analysed data obtained from 345 donkeys at The Donkey Sanctuary (Devon, UK), managed under three different pasture management techniques, to investigate the effectiveness of faeces removal in strongyle control in equids. The management groups were as follows: no removal of faeces from pasture, manual, twice-weekly removal of faeces from pasture and automatic, twice-weekly removal of faeces from pasture (using a mechanical pasture sweeper). From turn-out onto pasture in May, monthly faecal egg counts were obtained for each donkey and the dataset subjected to an auto regressive moving average model. Results There was little to no difference in faecal egg counts between the two methods of faecal removal; both resulted in significantly improved cyathostomin control compared to the results obtained from the donkeys that grazed pasture from which there was no faecal removal. Conclusions This study represents a valuable and unique assessment of the effectiveness of the removal of equine faeces from pasture, and provides an evidence base from which to advocate twice-weekly removal of faeces from pasture as an adjunct for equid nematode control. Widespread adoption of this practice could substantially reduce anthelmintic usage, and hence reduce selection pressure for nematode resistance to the currently effective anthelmintic products. PMID:24460700

Mechanisms of genome evolution of Streptococcus.

PubMed

Andam, Cheryl P; Hanage, William P

2015-07-01

The genus Streptococcus contains 104 recognized species, many of which are associated with human or animal hosts. A globally prevalent human pathogen in this group is Streptococcus pneumoniae (the pneumococcus). While being a common resident of the upper respiratory tract, it is also a major cause of otitis media, pneumonia, bacteremia and meningitis, accounting for a high burden of morbidity and mortality worldwide. Recent findings demonstrate the importance of recombination and selection in driving the population dynamics and evolution of different pneumococcal lineages, allowing them to successfully evade the impacts of selective pressures such as vaccination and antibiotic treatment. We highlight the ability of pneumococci to respond to these pressures through processes including serotype replacement, capsular switching and horizontal gene transfer (HGT) of antibiotic resistance genes. The challenge in controlling this pathogen also lies in the exceptional genetic and phenotypic variation among different pneumococcal lineages, particularly in terms of their pathogenicity and resistance to current therapeutic strategies. The widespread use of pneumococcal conjugate vaccines, which target only a small subset of the more than 90 pneumococcal serotypes, provides us with a unique opportunity to elucidate how the processes of selection and recombination interact to generate a remarkable level of plasticity and heterogeneity in the pneumococcal genome. These processes also play an important role in the emergence and spread of multi-resistant strains, which continues to pose a challenge in disease control and/or eradication. The application of population of genomic approaches at different spatial and temporal scales will help improve strategies to control this global pathogen, and potentially other pathogenic streptococci. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

Mechanisms of Antimicrobial Resistance in ESKAPE Pathogens

PubMed Central

Santajit, Sirijan; Indrawattana, Nitaya

2016-01-01

The ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) are the leading cause of nosocomial infections throughout the world. Most of them are multidrug resistant isolates, which is one of the greatest challenges in clinical practice. Multidrug resistance is amongst the top three threats to global public health and is usually caused by excessive drug usage or prescription, inappropriate use of antimicrobials, and substandard pharmaceuticals. Understanding the resistance mechanisms of these bacteria is crucial for the development of novel antimicrobial agents or other alternative tools to combat these public health challenges. Greater mechanistic understanding would also aid in the prediction of underlying or even unknown mechanisms of resistance, which could be applied to other emerging multidrug resistant pathogens. In this review, we summarize the known antimicrobial resistance mechanisms of ESKAPE pathogens. PMID:27274985

Mechanisms of Antimicrobial Resistance in ESKAPE Pathogens.

PubMed

Santajit, Sirijan; Indrawattana, Nitaya

2016-01-01

The ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) are the leading cause of nosocomial infections throughout the world. Most of them are multidrug resistant isolates, which is one of the greatest challenges in clinical practice. Multidrug resistance is amongst the top three threats to global public health and is usually caused by excessive drug usage or prescription, inappropriate use of antimicrobials, and substandard pharmaceuticals. Understanding the resistance mechanisms of these bacteria is crucial for the development of novel antimicrobial agents or other alternative tools to combat these public health challenges. Greater mechanistic understanding would also aid in the prediction of underlying or even unknown mechanisms of resistance, which could be applied to other emerging multidrug resistant pathogens. In this review, we summarize the known antimicrobial resistance mechanisms of ESKAPE pathogens.

Antimicrobial Use and Antimicrobial Resistance: A Population Perspective

PubMed Central

Samore, Matthew H.

2002-01-01

The need to stem the growing problem of antimicrobial resistance has prompted multiple, sometimes conflicting, calls for changes in the use of antimicrobial agents. One source of disagreement concerns the major mechanisms by which antibiotics select resistant strains. For infections like tuberculosis, in which resistance can emerge in treated hosts through mutation, prevention of antimicrobial resistance in individual hosts is a primary method of preventing the spread of resistant organisms in the community. By contrast, for many other important resistant pathogens, such as penicillin-resistant Streptococcus pneumoniae, methicillin-resistant Staphylococcus aureus, and vancomycin-resistant Enterococcus faecium resistance is mediated by the acquisition of genes or gene fragments by horizontal transfer; resistance in the treated host is a relatively rare event. For these organisms, indirect, population-level mechanisms of selection account for the increase in the prevalence of resistance. These mechanisms can operate even when treatment has a modest, or even negative, effect on an individual host’s colonization with resistant organisms. PMID:11971765

Pesticide durability and the evolution of resistance: A novel application of survival analysis.

PubMed

Brevik, Kristian; Schoville, Sean D; Mota-Sanchez, David; Chen, Yolanda H

2018-03-01

Arthropod pests are widely perceived to evolve resistance to insecticides at different rates. Although widespread "successful" species are assumed to evolve quickly and minor pests slowly, few studies have utilized published data on resistance events to test for differences among species. Using 532 records from the Arthropod Pesticide Resistance Database covering 20 species, we applied a survival analysis to model the number of generations from insecticide introduction to the first report of arthropod resistance, providing one of the most comprehensive analyses of this question to date. Our approach tested: 1) whether successful pests evolve resistance faster than close relatives, 2) whether species differ significantly in the time to demonstrate resistance, and 3) whether different insecticide classes differ in durability (length of time an insecticide is used before resistance arises). We found that species differed significantly in the amount of time it took for resistance to be reported. Overall, the median duration between the introduction of an insecticide and the first report of resistance was 66 generations (95% c.i. 60-78 generations), and highly-resistant arthropods did not evolve resistance faster than their relatives. Insecticide durability did not differ by the mode of action or year of introduction. Arthropod species significantly varied in how rapidly they evolve resistance to new insecticides, regardless of their chemistry. Visualization of the history of insecticide resistance provides information to be used for understanding how pesticide resistance evolved and how it can best be managed. © 2018 Society of Chemical Industry. © 2018 Society of Chemical Industry.

Ponderosa pine resin defenses and growth: metrics matter.

PubMed

Hood, Sharon; Sala, Anna

2015-11-01

Bark beetles (Coleoptera: Curculionidae, Scolytinae) cause widespread tree mortality in coniferous forests worldwide. Constitutive and induced host defenses are important factors in an individual tree's ability to survive an attack and in bottom-up regulation of bark beetle population dynamics, yet quantifying defense levels is often difficult. For example, in Pinus spp., resin flow is important for resistance to bark beetles but is extremely variable among individuals and within a season. While resin is produced and stored in resin ducts, the specific resin duct metrics that best correlate with resin flow remain unclear. The ability and timing of some pine species to produce induced resin is also not well understood. We investigated (i) the relationships between ponderosa pine (Pinus ponderosa Lawson & C. Lawson) resin flow and axial resin duct characteristics, tree growth and physiological variables, and (ii) if mechanical wounding induces ponderosa pine resin flow and resin ducts in the absence of bark beetles. Resin flow increased later in the growing season under moderate water stress and was highest in faster growing trees. The best predictors of resin flow were nonstandardized measures of resin ducts, resin duct size and total resin duct area, both of which increased with tree growth. However, while faster growing trees tended to produce more resin, models of resin flow using only tree growth were not statistically significant. Further, the standardized measures of resin ducts, density and duct area relative to xylem area, decreased with tree growth rate, indicating that slower growing trees invested more in resin duct defenses per unit area of radial growth, despite a tendency to produce less resin overall. We also found that mechanical wounding induced ponderosa pine defenses, but this response was slow. Resin flow increased after 28 days, and resin duct production did not increase until the following year. These slow induced responses may allow unsuccessfully attacked or wounded trees to resist future bark beetle attacks. Forest management that encourages healthy, vigorously growing trees will also favor larger resin ducts, thereby conferring increased constitutive resistance to bark beetle attacks. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Bilateral widespread mechanical pain hypersensitivity as sign of central sensitization in patients with cluster headache.

PubMed

Fernández-de-Las-Peñas, César; Ortega-Santiago, Ricardo; Cuadrado, María L; López-de-Silanes, Carlos; Pareja, Juan A

2011-03-01

To investigate bilateral widespread pressure pain hyperalgesia in deep tissues over symptomatic (trigemino-cervical) and nonsymptomatic (distant pain-free) regions in patients with cluster headache (CH). Central sensitization is claimed to play a relevant role in CH. No study has previously searched for widespread pressure hyperalgesia in deep tissues over both symptomatic (trigemino-cervical) and nonsymptomatic (distant pain-free) regions in patients with CH. Sixteen men (mean age: 43 ± 11 years) with CH in a remission phase and 16 matched controls were recruited. Pressure pain thresholds (PPTs) were bilaterally measured over the supra-orbital (V1), infra-orbital (V2), mental (V3), median (C5), radial (C6), and ulnar (C7) nerves, C5-C6 zygapophyseal joint, mastoid process, and tibialis anterior muscle by an assessor blinded to the subjects' condition. The results showed that PPT levels were significantly decreased bilaterally in patients with CH as compared with healthy controls (all sites, P < .001). A greater degree of sensitization over the mastoid process (P < .001) and a lower degree of sensitization over the tibialis anterior muscle (P < .01) was found. Our findings revealed bilateral widespread pressure pain hypersensitivity in patients with CH confirming the presence of central sensitization mechanisms in this headache condition. © 2010 American Headache Society.

Bilateral widespread mechanical pain sensitivity in carpal tunnel syndrome: evidence of central processing in unilateral neuropathy.

PubMed

Fernández-de-las-Peñas, César; de la Llave-Rincón, Ana Isabel; Fernández-Carnero, Josué; Cuadrado, María Luz; Arendt-Nielsen, Lars; Pareja, Juan A

2009-06-01

The aim of this study was to investigate whether bilateral widespread pressure hypersensitivity exists in patients with unilateral carpal tunnel syndrome. A total of 20 females with carpal tunnel syndrome (aged 22-60 years), and 20 healthy matched females (aged 21-60 years old) were recruited. Pressure pain thresholds were assessed bilaterally over median, ulnar, and radial nerve trunks, the C5-C6 zygapophyseal joint, the carpal tunnel and the tibialis anterior muscle in a blinded design. The results showed that pressure pain threshold levels were significantly decreased bilaterally over the median, ulnar, and radial nerve trunks, the carpal tunnel, the C5-C6 zygapophyseal joint, and the tibialis anterior muscle in patients with unilateral carpal tunnel syndrome as compared to healthy controls (all, P < 0.001). Pressure pain threshold was negatively correlated to both hand pain intensity and duration of symptoms (all, P < 0.001). Our findings revealed bilateral widespread pressure hypersensitivity in subjects with carpal tunnel syndrome, which suggest that widespread central sensitization is involved in patients with unilateral carpal tunnel syndrome. The generalized decrease in pressure pain thresholds associated with pain intensity and duration of symptoms supports a role of the peripheral drive to initiate and maintain central sensitization. Nevertheless, both central and peripheral sensitization mechanisms are probably involved at the same time in carpal tunnel syndrome.

Cationic Antimicrobial Peptide Resistance Mechanisms of Streptococcal Pathogens

PubMed Central

LaRock, Christopher N.; Nizet, Victor

2015-01-01

Cationic antimicrobial peptides (CAMPs) are critical front line contributors to host defense against invasive bacterial infection. These immune factors have direct killing activity toward microbes, but many pathogens are able to resist their effects. Group A Streptococcus, group B Streptococcus and Streptococcus pneumoniae are among the most common pathogens of humans and display a variety of phenotypic adaptations to resist CAMPs. Common themes of CAMP resistance mechanisms among the pathogenic streptococci are repulsion, sequestration, export, and destruction. Each pathogen has a different array of CAMP-resistant mechanisms, with invasive disease potential reflecting the utilization of several mechanisms that may act in synergy. Here we discuss recent progress in identifying the sources of CAMP resistance in the medically important Streptococcus genus. Further study of these mechanisms can contribute to our understanding of streptococcal pathogenesis, and may provide new therapeutic targets for therapy and disease prevention. PMID:25701232

Antimicrobial Resistance and Virulence-Associated Genes of Campylobacter spp. Isolated from Raw Milk, Fish, Poultry, and Red Meat.

PubMed

Raeisi, Mojtaba; Khoshbakht, Rahem; Ghaemi, Ezzat Allah; Bayani, Mahsan; Hashemi, Mohammad; Seyedghasemi, Navisa Sadat; Shirzad-Aski, Hesamaddin

2017-10-01

This study was designed and conducted to evaluate the frequency, antimicrobial resistance, and presence of six virulence-associated genes among thermophilic Campylobacters isolated from raw milk, poultry (chicken, turkey, and duck), fish, cattle, and sheep meat. Out of 590 samples, which were recovered from different origins, 141 (23.9%) samples were positive for Campylobacters. Campylobacter spp. was isolated in 40.8% (106/260), 14% (28/200), and 8.7% (7/80) of poultry meat, red meat, and milk samples, respectively. Antimicrobial susceptibility test indicated a high frequency of resistance to ciprofloxacin, tetracycline, and nalidixic acid among the isolates. Furthermore, prevalence of waaC, ciaB, and pldA genes were 91.7%, 86.7%, and 80.8%, respectively; and, none of the isolates harbored both wlaN and cgtB genes, simultaneously. Moreover, there was a weak correlation between antibiotics resistance and presence of the pathogen genes. However, the existence of Campylobacter spp. isolates in food animal products, with high resistance to antibiotics and several virulence gene possessions, is alarming and increases the attention to the widespread use of antibiotics.

The efficacy of a chitin synthesis inhibitor against field populations of organophosphate-resistant Aedes aegypti in Brazil.

PubMed

Fontoura, Nathalia Giglio; Bellinato, Diogo Fernandes; Valle, Denise; Lima, José Bento Pereira

2012-05-01

The mosquito Aedes aegypti is the main focus of dengue control campaigns. Because of widespread resistance against conventional chemical insecticides, chitin synthesis inhibitors (CSIs) are considered control alternatives. We evaluated the resistance status of four Brazilian Ae. aegypti populations to both the organophosphate temephos and the pyrethroid deltamethrin, which are used in Brazil to control larvae and adults, respectively. All vector populations exhibited high levels of temephos resistance and varying rates of alterations in their susceptibility to pyrethroids. The effect of the CSI novaluron on these populations was also investigated. Novaluron was effective against all populations under laboratory conditions. Field-simulated assays with partial water replacement were conducted to evaluate novaluron persistence. Bioassays were continued until an adult emergence inhibition of at least 70% was attained. We found a residual effect of eight weeks under indoor conditions and novaluron persisted for five-six weeks in assays conducted in an external area. Our data show that novaluron is effective against the Ae. aegypti populations tested, regardless of their resistance to conventional chemical insecticides.

Calcium and Magnesium Ions Are Membrane-Active against Stationary-Phase Staphylococcus aureus with High Specificity

NASA Astrophysics Data System (ADS)

Xie, Yuntao; Yang, Lihua

2016-02-01

Staphylococcus aureus (S. aureus) is notorious for its ability to acquire antibiotic-resistance, and antibiotic-resistant S. aureus has become a wide-spread cause of high mortality rate. Novel antimicrobials capable of eradicating S. aureus cells including antibiotic-resistant ones are thus highly desired. Membrane-active bactericides and species-specific antimicrobials are two promising sources of novel anti-infective agents for fighting against bacterial antibiotic-resistance. We herein show that Ca2+ and Mg2+, two alkaline-earth-metal ions physiologically essential for diverse living organisms, both disrupt model S. aureus membranes and kill stationary-phase S. aureus cells, indicative of membrane-activity. In contrast to S. aureus, Escherichia coli and Bacillus subtilis exhibit unaffected survival after similar treatment with these two cations, indicative of species-specific activity against S. aureus. Moreover, neither Ca2+ nor Mg2+ lyses mouse red blood cells, indicative of hemo-compatibility. This works suggests that Ca2+ and Mg2+ may have implications in targeted eradication of S. aureus pathogen including the antibiotic-resistant ones.

Lasers in automobile production

NASA Astrophysics Data System (ADS)

Pizzi, P.

There is a trend in mechanical equipment to replace complicated mechanical components with electronics, especially microprocessors, laser technology represents an important new tool. The effects of laser technology can be seen in production systems concerned with cutting, welding, heat treatment, and the alloying of mechanical components. Applications in the automobile industry today are not very widespread and are concerned essentially with welding and cutting.

Sensitivity study of the Storegga Slide tsunami using retrogressive and visco-plastic rheology models

NASA Astrophysics Data System (ADS)

Kim, Jihwan; Løvholt, Finn

2016-04-01

Enormous submarine landslides having volumes up to thousands of km3 and long run-out may cause tsunamis with widespread effects. Clay-rich landslides, such as Trænadjupet and Storegga offshore Norway commonly involve retrogressive mass and momentum release mechanisms that affect the tsunami generation. As a consequence, the failure mechanisms, soil parameters, and release rate of the retrogression are of importance for the tsunami generation. Previous attempts to model the tsunami generation due to retrogressive landslides are few, and limited to idealized conditions. Here, a visco-plastic model including additional effects such as remolding, time dependent mass release, and hydrodynamic resistance, is employed for simulating the Storegga Slide. As landslide strength parameters and their evolution in time are uncertain, it is necessary to conduct a sensitivity study to shed light on the tsunamigenic processes. The induced tsunami is simulated using Geoclaw. We also compare our tsunami simulations with recent analysis conducted using a pure retrogressive model for the landslide, as well as previously published results using a block model. The availability of paleotsunami run-up data and detailed slide deposits provides a suitable background for improved understanding of the slide mechanics and tsunami generation. The research leading to these results has received funding from the Research Council of Norway under grant number 231252 (Project TsunamiLand) and the European Union's Seventh Framework Programme (FP7/2007-2013) under grant agreement 603839 (Project ASTARTE).

Animal models of fibromyalgia

PubMed Central

2013-01-01

Animal models of disease states are valuable tools for developing new treatments and investigating underlying mechanisms. They should mimic the symptoms and pathology of the disease and importantly be predictive of effective treatments. Fibromyalgia is characterized by chronic widespread pain with associated co-morbid symptoms that include fatigue, depression, anxiety and sleep dysfunction. In this review, we present different animal models that mimic the signs and symptoms of fibromyalgia. These models are induced by a wide variety of methods that include repeated muscle insults, depletion of biogenic amines, and stress. All potential models produce widespread and long-lasting hyperalgesia without overt peripheral tissue damage and thus mimic the clinical presentation of fibromyalgia. We describe the methods for induction of the model, pathophysiological mechanisms for each model, and treatment profiles. PMID:24314231

Status of Insecticide Resistance in Papua New Guinea: An Update from Nation-Wide Monitoring of Anopheles Mosquitoes.

PubMed

Koimbu, Gussy; Czeher, Cyrille; Katusele, Michelle; Sakur, Muker; Kilepak, Lemen; Tandrapah, Anthony; Hetzel, Manuel W; Pulford, Justin; Robinson, Leanne; Karl, Stephan

2018-01-01

Insecticide resistance (IR) monitoring is an important component of vector-borne disease control. The last assessment of IR in Papua New Guinea (PNG) was conducted in 2010. Since then, vector populations have been exposed to higher levels of pyrethroids with the continued nation-wide distribution of insecticide-treated nets. Here, we provide an update on phenotypic IR in four highly malaria-endemic areas of PNG. IR against deltamethrin, lambda-cyhalothrin, and dichlorodiphenyltrichloroethane was assessed using World Health Organization bioassays. A total of 108 bioassays for each insecticide were conducted screening 2,290 adult female anopheline mosquitoes. No phenotypic resistance was observed. Bioassay parameters agreed well with those observed in other studies that used the same assays and insecticides. These results indicate that the three tested insecticides are still universally effective in PNG. Continued IR monitoring (every 1-2 years) in PNG is recommended to detect reduced susceptibility early and adjust guidelines to prevent widespread resistance.

Nonuniversality of the Archie exponent due to multifractality of resistivity well logs

NASA Astrophysics Data System (ADS)

Dashtian, Hassan; Yang, Yafan; Sahimi, Muhammad

2015-12-01

Archie's law expresses a relation between the formation factor F of porous media and their porosity ϕ, F∝ϕ-m, where m is the Archie or the cementation exponent. Despite widespread use of Archie's law, the value of m and whether it is universal and independent of the type of reservoir have remained controversial. We analyze various porosity and resistivity logs along 36 wells in six Iranian oil and gas reservoirs using wavelet transform coherence and multifractal detrended fluctuation analysis. m is estimated for two sets of data: one set contains the resistivity data that include those segments of the well that contain significant clay content and one without. The analysis indicates that the well logs are multifractal and that due to the multifractality the exponent m is nonuniversal. Thus, analysis of the resistivity of laboratory or outcrop samples that are not multifractal yields estimates of m that are not applicable to well logs in oil or gas reservoirs.

Recessive Resistance Derived from Tomato cv. Tyking-Limits Drastically the Spread of Tomato Yellow Leaf Curl Virus

PubMed Central

Pereira-Carvalho, Rita C.; Díaz-Pendón, Juan A.; Fonseca, Maria Esther N.; Boiteux, Leonardo S.; Fernández-Muñoz, Rafael; Moriones, Enrique; Resende, Renato O.

2015-01-01

The tomato yellow leaf curl disease (TYLCD) causes severe damage to tomato (Solanum lycopersicum L.) crops throughout tropical and subtropical regions of the world. TYLCD is associated with a complex of single-stranded circular DNA plant viruses of the genus Begomovirus (family Geminiviridae) transmitted by the whitefy Bemisia tabaci Gennadius (Hemiptera: Aleyrodidae). The tomato inbred line TX 468-RG is a source of monogenic recessive resistance to begomoviruses derived from the hybrid cv. Tyking F1. A detailed analysis of this germplasm source against tomato yellow leaf curl virus-Israel (TYLCV-IL), a widespread TYLCD-associated virus, showed a significant restriction to systemic virus accumulation even under continuous virus supply. The resistance was effective in limiting the onset of TYLCV-IL in tomato, as significantly lower primary spread of the virus occurred in resistant plants. Also, even if a limited number of resistant plants could result infected, they were less efficient virus sources for secondary spread owing to the impaired TYLCV-IL accumulation. Therefore, the incorporation of this resistance into breeding programs might help TYLCD management by drastically limiting TYLCV-IL spread. PMID:26008699

The Rising Tide of Antimicrobial Resistance in Aquaculture: Sources, Sinks and Solutions

PubMed Central

Watts, Joy E. M.; Schreier, Harold J.; Lanska, Lauma; Hale, Michelle S.

2017-01-01

As the human population increases there is an increasing reliance on aquaculture to supply a safe, reliable, and economic supply of food. Although food production is essential for a healthy population, an increasing threat to global human health is antimicrobial resistance. Extensive antibiotic resistant strains are now being detected; the spread of these strains could greatly reduce medical treatment options available and increase deaths from previously curable infections. Antibiotic resistance is widespread due in part to clinical overuse and misuse; however, the natural processes of horizontal gene transfer and mutation events that allow genetic exchange within microbial populations have been ongoing since ancient times. By their nature, aquaculture systems contain high numbers of diverse bacteria, which exist in combination with the current and past use of antibiotics, probiotics, prebiotics, and other treatment regimens—singularly or in combination. These systems have been designated as “genetic hotspots” for gene transfer. As our reliance on aquaculture grows, it is essential that we identify the sources and sinks of antimicrobial resistance, and monitor and analyse the transfer of antimicrobial resistance between the microbial community, the environment, and the farmed product, in order to better understand the implications to human and environmental health. PMID:28587172

Hepatitis C virus resistance to the new direct-acting antivirals.

PubMed

Esposito, Isabella; Trinks, Julieta; Soriano, Vicente

2016-10-01

The treatment of hepatitis C virus (HCV) infection has dramatically improved in recent years with the widespread use of interferon-free combination regimens. Despite the high sustained virological response (SVR) rates (over 90%) obtained with direct-acting antivirals (DAAs), drug resistance has emerged as a potential challenge. The high replication rate of HCV and the low fidelity of its RNA polymerase result in a high degree of genetic variability in the HCV population, which ultimately explains the rapid selection of drug resistance associated variants (RAVs). Results from clinical trials and real-world experience have both provided important information on the rate and clinical significance of RAVs. They can be present in treatment-naive patients as natural polymorphisms although more frequently they are selected upon treatment failure. In patients engaged in high-risk behaviors, RAVs can be transmitted. Although DAA failures generally occur in less than 10% of treated chronic hepatitis C patients, selection of drug resistance is the rule in most cases. HCV re-treatment options are available, but first-line therapeutic strategies should be optimized to efficiently prevent DAA failure due to baseline HCV resistance. Considerable progress is being made and next-generation DAAs are coming with pangenotypic activity and higher resistance barrier.

The Rising Tide of Antimicrobial Resistance in Aquaculture: Sources, Sinks and Solutions.

PubMed

Watts, Joy E M; Schreier, Harold J; Lanska, Lauma; Hale, Michelle S

2017-06-01

As the human population increases there is an increasing reliance on aquaculture to supply a safe, reliable, and economic supply of food. Although food production is essential for a healthy population, an increasing threat to global human health is antimicrobial resistance. Extensive antibiotic resistant strains are now being detected; the spread of these strains could greatly reduce medical treatment options available and increase deaths from previously curable infections. Antibiotic resistance is widespread due in part to clinical overuse and misuse; however, the natural processes of horizontal gene transfer and mutation events that allow genetic exchange within microbial populations have been ongoing since ancient times. By their nature, aquaculture systems contain high numbers of diverse bacteria, which exist in combination with the current and past use of antibiotics, probiotics, prebiotics, and other treatment regimens-singularly or in combination. These systems have been designated as "genetic hotspots" for gene transfer. As our reliance on aquaculture grows, it is essential that we identify the sources and sinks of antimicrobial resistance, and monitor and analyse the transfer of antimicrobial resistance between the microbial community, the environment, and the farmed product, in order to better understand the implications to human and environmental health.

The emerging profile of cross-resistance among the nonnucleoside HIV-1 reverse transcriptase inhibitors.

PubMed

Sluis-Cremer, Nicolas

2014-07-31

Nonnucleoside reverse transcriptase inhibitors (NNRTIs) are widely used to treat HIV-1-infected individuals; indeed most first-line antiretroviral therapies typically include one NNRTI in combination with two nucleoside analogs. In 2008, the next-generation NNRTI etravirine was approved for the treatment of HIV-infected antiretroviral therapy-experienced individuals, including those with prior NNRTI exposure. NNRTIs are also increasingly being included in strategies to prevent HIV-1 infection. For example: (1) nevirapine is used to prevent mother-to-child transmission; (2) the ASPIRE (MTN 020) study will test whether a vaginal ring containing dapivirine can prevent HIV-1 infection in women; (3) a microbicide gel formulation containing the urea-PETT derivative MIV-150 is in a phase I study to evaluate safety, pharmacokinetics, pharmacodynamics and acceptability; and (4) a long acting rilpivirine formulation is under-development for pre-exposure prophylaxis. Given their widespread use, particularly in resource-limited settings, as well as their low genetic barriers to resistance, there are concerns about overlapping resistance between the different NNRTIs. Consequently, a better understanding of the resistance and cross-resistance profiles among the NNRTI class is important for predicting response to treatment, and surveillance of transmitted drug-resistance.

Response to UVB radiation and oxidative stress of marine bacteria isolated from South Pacific Ocean and Mediterranean Sea.

PubMed

Matallana-Surget, S; Villette, C; Intertaglia, L; Joux, F; Bourrain, M; Lebaron, P

2012-12-05

Marine bacterial strains isolated from South Pacific and Mediterranean Sea were studied for their resistance to UVB radiation, their repair capacity under photoreactivating light, as well as their oxidative stress response using concentrated hydrogen peroxide (H(2)O(2)), as an oxidizer. A total of 30 marine bacteria were isolated from the hyper-oligotrophic waters of the South Pacific Gyre to the eutrophic waters of the Chilean coast during the BIOSOPE cruise (2004), and 10 strains from surface Mediterranean coastal waters. One third of bacteria presented a high resistance to UVB and almost all isolates presented an efficient post-irradiation recovery. Only few strains showed cell survival to high concentration of H(2)O(2). No correlation between the sampling sites and the bacterial UVB resistance was observed. Two marine bacteria, Erythrobacter flavus and Ruegeria mobilis, were of particular interest, presenting a good response to the three parameters (UVB and H(2)O(2) resistance/efficient repair). Unexpectedly, two resistant strains were again identified as Ruegeria species underlining that this geographically widespread genus, resist to UVB regardless the environment from which the isolates originate. Copyright © 2012 Elsevier B.V. All rights reserved.

The Emerging Profile of Cross-Resistance among the Nonnucleoside HIV-1 Reverse Transcriptase Inhibitors

PubMed Central

Sluis-Cremer, Nicolas

2014-01-01

Nonnucleoside reverse transcriptase inhibitors (NNRTIs) are widely used to treat HIV-1-infected individuals; indeed most first-line antiretroviral therapies typically include one NNRTI in combination with two nucleoside analogs. In 2008, the next-generation NNRTI etravirine was approved for the treatment of HIV-infected antiretroviral therapy-experienced individuals, including those with prior NNRTI exposure. NNRTIs are also increasingly being included in strategies to prevent HIV-1 infection. For example: (1) nevirapine is used to prevent mother-to-child transmission; (2) the ASPIRE (MTN 020) study will test whether a vaginal ring containing dapivirine can prevent HIV-1 infection in women; (3) a microbicide gel formulation containing the urea-PETT derivative MIV-150 is in a phase I study to evaluate safety, pharmacokinetics, pharmacodynamics and acceptability; and (4) a long acting rilpivirine formulation is under-development for pre-exposure prophylaxis. Given their widespread use, particularly in resource-limited settings, as well as their low genetic barriers to resistance, there are concerns about overlapping resistance between the different NNRTIs. Consequently, a better understanding of the resistance and cross-resistance profiles among the NNRTI class is important for predicting response to treatment, and surveillance of transmitted drug-resistance. PMID:25089538

Differential Resistance Mechanisms to Glyphosate Result in Fitness Cost for Lolium perenne and L. multiflorum

PubMed Central

Fernández-Moreno, Pablo T.; Alcántara-de la Cruz, Ricardo; Smeda, Reid J.; De Prado, Rafael

2017-01-01

Multiple mechanisms of resistance to glyphosate are exhibited by populations of Lolium spp. worldwide. Association of resistance with growth and reproductive fitness is an important predictor for long-term success of glyphosate-resistant (R) versus glyphosate-susceptible (S) biotypes. Numerous studies were conducted on R- and S-biotypes of Italian ryegrass (Lolium multiflorum) and perennial ryegrass (L. perenne) to characterize the underlying mechanism(s) of glyphosate resistance and associate this with growth and reproductive fitness. L. perenne expressed both altered uptake and translocation as well as a genetic change at 106-Pro to –Ser, This pattern for two resistance mechanisms is unique. L. multiflorum also exhibited altered uptake and translocation as well as duplication of EPSPS gene copies. Reduced plant biomass and height for R-versus S-biotypes of both species was evident over two growing seasons. This resulted in S- versus R- L. multiflorum producing up to 47 and 38% more seeds in 2014 and 2015, respectively. S- L. perenne produced up to 20 and 30% more seeds in 2014 and 2015, respectively. Both non-target site and target-site mechanisms of glyphosate resistance can render Lolium spp. at a competitive disadvantage. This has long-term implications for the success of glyphosate-resistant plants in the absence of selection pressure. PMID:29089958

Extended spectrum β-lactamases, carbapenemases and mobile genetic elements responsible for antibiotics resistance in Gram-negative bacteria.

PubMed

El Salabi, Allaaeddin; Walsh, Timothey R; Chouchani, Chedly

2013-05-01

Infectious diseases due to Gram-negative bacteria are a leading cause of morbidity and mortality worldwide. Antimicrobial agents represent one major therapeutic tools implicated to treat these infections. The misuse of antimicrobial agents has resulted in the emergence of resistant strains of Gram-negatives in particular Enterobacteriaceae and non-fermenters; they have an effect not only on a human but on the public health when bacteria use the resistance mechanisms to spread in the hospital environment and to the community outside the hospitals by means of mobile genetic elements. Gram-negative bacteria have become increasingly resistant to antimicrobial agents. They have developed several mechanisms by which they can withstand to antimicrobials, these mechanisms include the production of Extended-spectrum β-lactamases (ESBLs) and carbapenemases, furthermore, Gram-negative bacteria are now capable of spreading such resistance between members of the family Enterobacteriaceae and non-fermenters using mobile genetic elements as vehicles for such resistance mechanisms rendering antibiotics useless. Therefore, addressing the issue of mechanisms of antimicrobial resistance is considered one of most urgent priorities. This review will help to illustrate different resistance mechanisms; ESBLs, carbapenemases encoded by genes carried by mobile genetic elements, which are used by Gram-negative bacteria to escape antimicrobial effect.

Epigenetic Mechanisms of Tamoxifen Resistance in Luminal Breast Cancer.

PubMed

Abdel-Hafiz, Hany A

2017-07-06

Breast cancer is one of the most common cancers and the second leading cause of cancer death in the United States. Estrogen receptor (ER)-positive cancer is the most frequent subtype representing more than 70% of breast cancers. These tumors respond to endocrine therapy targeting the ER pathway including selective ER modulators (SERMs), selective ER downregulators (SERDs) and aromatase inhibitors (AIs). However, resistance to endocrine therapy associated with disease progression remains a significant therapeutic challenge. The precise mechanisms of endocrine resistance remain unclear. This is partly due to the complexity of the signaling pathways that influence the estrogen-mediated regulation in breast cancer. Mechanisms include ER modifications, alteration of coregulatory function and modification of growth factor signaling pathways. In this review, we provide an overview of epigenetic mechanisms of tamoxifen resistance in ER-positive luminal breast cancer. We highlight the effect of epigenetic changes on some of the key mechanisms involved in tamoxifen resistance, such as tumor-cell heterogeneity, ER signaling pathway and cancer stem cells (CSCs). It became increasingly recognized that CSCs are playing an important role in driving metastasis and tamoxifen resistance. Understanding the mechanism of tamoxifen resistance will provide insight into the design of novel strategies to overcome the resistance and make further improvements in breast cancer therapeutics.

The resistance mechanisms and treatment strategies for EGFR-mutant advanced non-small-cell lung cancer

PubMed Central

Zhong, Wen-Zhao; Zhou, Qing; Wu, Yi-Long

2017-01-01

Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKI) have been established as the standard therapy for EGFR-sensitizing mutant advanced non-small-cell lung cancer (NSCLC). However, patients ultimately develop resistance to these drugs. There are several mechanisms of both primary and secondary resistance to EGFR-TKIs. The primary resistance mechanisms include point mutations in exon 18, deletions or insertions in exon 19, insertions, duplications and point mutations in exon 20 and point mutation in exon 21 of EGFR gene. Secondary resistance to EGFR-TKIs is due to emergence of T790M mutation, activation of alternative signaling pathways, bypassing downstream signaling pathways and histological transformation. Strategies to overcome these intrinsic and acquired resistance mechanisms are complex. With the development of the precision medicine for advanced NSCLC, available systemic and local treatment options have expanded, requiring new clinical algorithms that take into account resistance mechanism. Though combination therapy is emerging as the standard of to overcome resistance mechanisms. Personalized treatment modalities based on molecular diagnosis and monitoring is essential for disease management. Emerging data from the ongoing clinical trials on combination therapy of third generation TKIs and antibodies in EGFR mutant NSCLC are promising for better survival outcomes. PMID:29050366

Neonatal infections due to multi-resistant strains: Epidemiology, current treatment, emerging therapeutic approaches and prevention.

PubMed

Tzialla, Chryssoula; Borghesi, Alessandro; Pozzi, Margherita; Stronati, Mauro

2015-12-07

Severe infections represent the main cause of neonatal mortality accounting for more than one million neonatal deaths worldwide every year. Antibiotics are the most commonly prescribed medications in neonatal intensive care units. The benefits of antibiotic therapy when indicated are clearly enormous, but the continued and widespread use of antibiotics has generated over the years a strong selective pressure on microorganisms, favoring the emergence of resistant strains. Health agencies worldwide are galvanizing attention toward antibiotic resistance in gram-positive and gram-negative bacteria. Infections in neonatal units due to multidrug and extensively multidrug resistant bacteria are rising and are already seriously challenging antibiotic treatment options. While there is a growing choice of agents against multi-resistant gram-positive bacteria, new options for multi-resistant gram-negative bacteria in the clinical practice have decreased significantly in the last 20 years making the treatment of infections caused by multidrug-resistant pathogens challenging mostly in neonates. Treatment options are currently limited and will be some years before any new treatment for neonates become available for clinical use, if ever. The aim of the review is to highlight the current knowledge on antibiotic resistance in the neonatal population, the possible therapeutic choices, and the prevention strategies to adopt in order to reduce the emergency and spread of resistant strains. Copyright © 2015 Elsevier B.V. All rights reserved.

Whole-Transcriptome and -Genome Analysis of Extensively Drug-Resistant Mycobacterium tuberculosis Clinical Isolates Identifies Downregulation of ethA as a Mechanism of Ethionamide Resistance

PubMed Central

de Welzen, Lynne; Eldholm, Vegard; Maharaj, Kashmeel; Manson, Abigail L.; Earl, Ashlee M.

2017-01-01

ABSTRACT Genetics-based drug susceptibility testing has improved the diagnosis of drug-resistant tuberculosis but is limited by our lack of knowledge of all resistance mechanisms. Next-generation sequencing has assisted in identifying the principal genetic mechanisms of resistance for many drugs, but a significant proportion of phenotypic drug resistance is unexplained genetically. Few studies have formally compared the transcriptomes of susceptible and resistant Mycobacterium tuberculosis strains. We carried out comparative whole-genome transcriptomics of extensively drug-resistant (XDR) clinical isolates using RNA sequencing (RNA-seq) to find novel transcription-mediated mechanisms of resistance. We identified a promoter mutation (t to c) at position −11 (t−11c) relative to the start codon of ethA that reduces the expression of a monooxygenase (EthA) that activates ethionamide. (In this article, nucleotide changes are lowercase and amino acid substitutions are uppercase.) Using a flow cytometry-based reporter assay, we show that the reduced transcription of ethA is not due to transcriptional repression by ethR. Clinical strains harboring this mutation were resistant to ethionamide. Other ethA promoter mutations were identified in a global genomic survey of resistant M. tuberculosis strains. These results demonstrate a new mechanism of ethionamide resistance that can cause high-level resistance when it is combined with other ethionamide resistance-conferring mutations. Our study revealed many other genes which were highly up- or downregulated in XDR strains, including a toxin-antitoxin module (mazF5 mazE5) and tRNAs (leuX and thrU). This suggests that global transcriptional modifications could contribute to resistance or the maintenance of bacterial fitness have also occurred in XDR strains. PMID:28993337