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Sample records for biological resistance

  1. Systems biology of diuretic resistance

    PubMed Central

    Knepper, Mark A.

    2015-01-01

    Diuretics are commonly used to treat hypertension and extracellular fluid volume expansion. However, the development of compensatory responses in the kidney limits the benefit of this class of drugs. In this issue of the JCI, Grimm and colleagues use a systems biology approach in mice lacking the kinase SPAK and unravel a complex mechanism that explains thiazide diuretic resistance. The overall process involves interactions among six different cell types in the kidney. PMID:25893597

  2. Antibiotic Resistance and the Biology of History.

    PubMed

    Landecker, Hannah

    2016-12-01

    Beginning in the 1940s, mass production of antibiotics involved the industrial-scale growth of microorganisms to harvest their metabolic products. Unfortunately, the use of antibiotics selects for resistance at answering scale. The turn to the study of antibiotic resistance in microbiology and medicine is examined, focusing on the realization that individual therapies targeted at single pathogens in individual bodies are environmental events affecting bacterial evolution far beyond bodies. In turning to biological manifestations of antibiotic use, sciences fathom material outcomes of their own previous concepts. Archival work with stored soil and clinical samples produces a record described here as 'the biology of history': the physical registration of human history in bacterial life. This account thus foregrounds the importance of understanding both the materiality of history and the historicity of matter in theories and concepts of life today.

  3. Antibiotic Resistance and the Biology of History

    PubMed Central

    2015-01-01

    Beginning in the 1940s, mass production of antibiotics involved the industrial-scale growth of microorganisms to harvest their metabolic products. Unfortunately, the use of antibiotics selects for resistance at answering scale. The turn to the study of antibiotic resistance in microbiology and medicine is examined, focusing on the realization that individual therapies targeted at single pathogens in individual bodies are environmental events affecting bacterial evolution far beyond bodies. In turning to biological manifestations of antibiotic use, sciences fathom material outcomes of their own previous concepts. Archival work with stored soil and clinical samples produces a record described here as ‘the biology of history’: the physical registration of human history in bacterial life. This account thus foregrounds the importance of understanding both the materiality of history and the historicity of matter in theories and concepts of life today. PMID:28458609

  4. Biology of tartrate-resistant acid phosphatase.

    PubMed

    Lamp, E C; Drexler, H G

    2000-11-01

    Tartrate-resistant acid phosphatase (TRAP) is a member of the ubiquitously expressed enzyme family of the acid phosphatases. Nearly 30 years ago, TRAP became known to hematologists as cytochemical marker enzyme of hairy cell leukemia. Physiologically, TRAP is primarily a cytochemical marker of macrophages, osteoclasts and dendritic cells. TRAP is localized intracellularly in the lysosomal compartment. Recent data suggest also secretion of TRAP by some cell types, in particular by osteoclasts. Human, mouse and rat TRAP are biochemically well characterized. While the complete genomic sequence of TRAP has been elucidated, only limited information on the genetic details of the gene and its regulation is available. It appears that the intracellular iron content is involved in the regulation of the enzyme. The physiological substrates for this enzyme have not been identified yet and consequently the functional role of TRAP remains completely unknown, though some hypotheses have been forwarded, e.g. involvement in bone resorption and iron homeostasis (transport, metabolism). Taken together, research on the biology of TRAP has been intensive and has led to considerable progress on a number of fronts, including the cloning of the gene. Further studies are, however, still required to determine the role of TRAP in vivo.

  5. Biology of Extreme Radiation Resistance: The Way of Deinococcus radiodurans

    PubMed Central

    Krisko, Anita; Radman, Miroslav

    2013-01-01

    The bacterium Deinococcus radiodurans is a champion of extreme radiation resistance that is accounted for by a highly efficient protection against proteome, but not genome, damage. A well-protected functional proteome ensures cell recovery from extensive radiation damage to other cellular constituents by molecular repair and turnover processes, including an efficient repair of disintegrated DNA. Therefore, cell death correlates with radiation-induced protein damage, rather than DNA damage, in both robust and standard species. From the reviewed biology of resistance to radiation and other sources of oxidative damage, we conclude that the impact of protein damage on the maintenance of life has been largely underestimated in biology and medicine. PMID:23818498

  6. Antiestrogen Resistance and the Application of Systems Biology

    PubMed Central

    Bouker, Kerrie B.; Wang, Yue; Xuan, Jianhua; Clarke, Robert

    2012-01-01

    Understanding the molecular changes that drive an acquired antiestrogen resistance phenotype is of major clinical relevance. Previous methodologies for addressing this question have taken a single gene/pathway approach and the resulting gains have been limited in terms of their clinical impact. Recent systems biology approaches allow for the integration of data from high throughput “-omics” technologies. We highlight recent advances in the field of antiestrogen resistance with a focus on transcriptomics, proteomics and methylomics. PMID:23539064

  7. Antibiotic resistance shaping multi-level population biology of bacteria

    PubMed Central

    Baquero, Fernando; Tedim, Ana P.; Coque, Teresa M.

    2013-01-01

    Antibiotics have natural functions, mostly involving cell-to-cell signaling networks. The anthropogenic production of antibiotics, and its release in the microbiosphere results in a disturbance of these networks, antibiotic resistance tending to preserve its integrity. The cost of such adaptation is the emergence and dissemination of antibiotic resistance genes, and of all genetic and cellular vehicles in which these genes are located. Selection of the combinations of the different evolutionary units (genes, integrons, transposons, plasmids, cells, communities and microbiomes, hosts) is highly asymmetrical. Each unit of selection is a self-interested entity, exploiting the higher hierarchical unit for its own benefit, but in doing so the higher hierarchical unit might acquire critical traits for its spread because of the exploitation of the lower hierarchical unit. This interactive trade-off shapes the population biology of antibiotic resistance, a composed-complex array of the independent “population biologies.” Antibiotics modify the abundance and the interactive field of each of these units. Antibiotics increase the number and evolvability of “clinical” antibiotic resistance genes, but probably also many other genes with different primary functions but with a resistance phenotype present in the environmental resistome. Antibiotics influence the abundance, modularity, and spread of integrons, transposons, and plasmids, mostly acting on structures present before the antibiotic era. Antibiotics enrich particular bacterial lineages and clones and contribute to local clonalization processes. Antibiotics amplify particular genetic exchange communities sharing antibiotic resistance genes and platforms within microbiomes. In particular human or animal hosts, the microbiomic composition might facilitate the interactions between evolutionary units involved in antibiotic resistance. The understanding of antibiotic resistance implies expanding our knowledge on multi

  8. Antibiotic resistance shaping multi-level population biology of bacteria.

    PubMed

    Baquero, Fernando; Tedim, Ana P; Coque, Teresa M

    2013-01-01

    Antibiotics have natural functions, mostly involving cell-to-cell signaling networks. The anthropogenic production of antibiotics, and its release in the microbiosphere results in a disturbance of these networks, antibiotic resistance tending to preserve its integrity. The cost of such adaptation is the emergence and dissemination of antibiotic resistance genes, and of all genetic and cellular vehicles in which these genes are located. Selection of the combinations of the different evolutionary units (genes, integrons, transposons, plasmids, cells, communities and microbiomes, hosts) is highly asymmetrical. Each unit of selection is a self-interested entity, exploiting the higher hierarchical unit for its own benefit, but in doing so the higher hierarchical unit might acquire critical traits for its spread because of the exploitation of the lower hierarchical unit. This interactive trade-off shapes the population biology of antibiotic resistance, a composed-complex array of the independent "population biologies." Antibiotics modify the abundance and the interactive field of each of these units. Antibiotics increase the number and evolvability of "clinical" antibiotic resistance genes, but probably also many other genes with different primary functions but with a resistance phenotype present in the environmental resistome. Antibiotics influence the abundance, modularity, and spread of integrons, transposons, and plasmids, mostly acting on structures present before the antibiotic era. Antibiotics enrich particular bacterial lineages and clones and contribute to local clonalization processes. Antibiotics amplify particular genetic exchange communities sharing antibiotic resistance genes and platforms within microbiomes. In particular human or animal hosts, the microbiomic composition might facilitate the interactions between evolutionary units involved in antibiotic resistance. The understanding of antibiotic resistance implies expanding our knowledge on multi

  9. Linking mitochondrial bioenergetics to insulin resistance via redox biology.

    PubMed

    Fisher-Wellman, Kelsey H; Neufer, P Darrell

    2012-03-01

    Chronic overnutrition and physical inactivity are major risk factors for insulin resistance and type 2 diabetes. Recent research indicates that overnutrition generates an increase in hydrogen peroxide (H(2)O(2)) emission from mitochondria, serving as a release valve to relieve the reducing pressure created by fuel overload, as well as a primary signal that ultimately decreases insulin sensitivity. H(2)O(2) is a major input to cellular redox circuits that link to cysteine residues throughout the entire proteome to regulate cell function. Here we review the principles of mitochondrial bioenergetics and redox systems biology and offer new insight into how H(2)O(2) emission may be linked via redox biology to the etiology of insulin resistance. Copyright © 2011 Elsevier Ltd. All rights reserved.

  10. Linking mitochondrial bioenergetics to insulin resistance via redox biology

    PubMed Central

    Fisher-Wellman, Kelsey H.; Neufer, P. Darrell

    2012-01-01

    Chronic overnutrition and physical inactivity are major risk factors for insulin resistance and type 2 diabetes. Recent research indicates that overnutrition generates an increase in hydrogen peroxide (H2O2) emission from mitochondria, serving as a release valve to relieve the reducing pressure created by fuel overload, as well as a primary signal to ultimately decrease insulin sensitivity. H2O2 is a major input to cellular redox circuits that link to cysteine residues throughout the entire proteome to regulate cell function. Here we review the principles of mitochondrial bioenergetics and redox systems biology and offer new insight as to how H2O2 emission may be linked via redox biology to the etiology of insulin resistance. PMID:22305519

  11. Bridging Physics and Biology Using Resistance and Axons

    NASA Astrophysics Data System (ADS)

    Dyer, Joshua M.

    2014-11-01

    When teaching physics, it is often difficult to get biology-oriented students to see the relevance of physics.1 A complaint often heard is that biology students are required to take physics for the Medical College Admission Test (MCAT) as part of a "weeding out" process, but that they don't feel like they need physics for biology. Despite this impression held by students, there have been calls for better physics education for future physicians and life scientists.2,3 Research is being performed to improve physics classes and labs by linking topics in biology and physics.4,5 Described here is a laboratory experiment covering the topics of resistance of materials and circuits/Kirchhoff's laws in a biology context with their direct application to neurons, axons, and electrical impulse transmission within animals. This experiment will also demonstrate the mechanism believed to cause multiple sclerosis. The apparatus was designed with low-cost and readily available materials in mind.

  12. Acinetobacter baumannii: biology and drug resistance - role of carbapenemases.

    PubMed

    Nowak, Pawel; Paluchowska, Paulina

    2016-01-01

    Acinetobacter baumannii is a Gram-negative, glucose-non-fermenting, oxidase-negative coccobacillus, most commonly associated with the hospital settings. The ability to survive in adverse environmental conditions as well as high level of natural and acquired antimicrobial resistance make A. baumannii one of the most important nosocomial pathogens. While carbapenems have long been considered as antimicrobials of last-resort, the rates of clinical A. baumannii strains resistant to these antibiotics are increasing worldwide. Carbapenem resistance among A. baumannii is conferred by coexisting mechanisms including: decrease in permeability of the outer membrane, efflux pumps, production of beta-lactamases, and modification of penicillin-binding proteins. The most prevalent mechanism of carbapenem resistance among A. baumannii is associated with carbapenem-hydro-lysing enzymes that belong to Ambler class D and B beta-lactamases. In addition, there have also been reports of resistance mediated by selected Ambler class A carbapenemases among A. baumannii strains. Resistance determinants in A. baumannii are located on chromosome and plasmids, while acquisition of new mechanisms can be mediated by insertion sequences, integrons, transposons, and plasmids. Clinical relevance of carbapen-em resistance among strains isolated from infected patients, carriers and hospital environment underlines the need for carbapenemase screening. Currently available methods vary in principle, accuracy and efficiency. The techniques that deserve particular attention belong to both easily accessible unsophisticated methods as well as advanced techniques based on mass spectrometry or molecular biology. While carbapenemases limit the therapeutic options in A. baumannii infections, studies concerning novel beta-lactamase inhibitors offer a new insight into effective therapy.

  13. Intensified agriculture favors evolved resistance to biological control.

    PubMed

    Tomasetto, Federico; Tylianakis, Jason M; Reale, Marco; Wratten, Steve; Goldson, Stephen L

    2017-03-13

    Increased regulation of chemical pesticides and rapid evolution of pesticide resistance have increased calls for sustainable pest management. Biological control offers sustainable pest suppression, partly because evolution of resistance to predators and parasitoids is prevented by several factors (e.g., spatial or temporal refuges from attacks, reciprocal evolution by control agents, and contrasting selection pressures from other enemy species). However, evolution of resistance may become more probable as agricultural intensification reduces the availability of refuges and diversity of enemy species, or if control agents have genetic barriers to evolution. Here we use 21 y of field data from 196 sites across New Zealand to show that parasitism of a key pasture pest (Listronotus bonariensis; Argentine stem weevil) by an introduced parasitoid (Microctonus hyperodae) was initially nationally successful but then declined by 44% (leading to pasture damage of c. 160 million New Zealand dollars per annum). This decline was not attributable to parasitoid numbers released, elevation, or local climatic variables at sample locations. Rather, in all locations the decline began 7 y (14 host generations) following parasitoid introduction, despite releases being staggered across locations in different years. Finally, we demonstrate experimentally that declining parasitism rates occurred in ryegrass Lolium perenne, which is grown nationwide in high-intensity was significantly less than in adjacent plots of a less-common pasture grass (Lolium multiflorum), indicating that resistance to parasitism is host plant-dependent. We conclude that low plant and enemy biodiversity in intensive large-scale agriculture may facilitate the evolution of host resistance by pests and threaten the long-term viability of biological control.

  14. Joining the club: Conforming to and resisting biology in practice

    NASA Astrophysics Data System (ADS)

    Buxton, Cory Alexander

    2000-10-01

    This study explores how science and scientists were produced and reproduced within the setting of a university biology department. It builds upon recent work in anthropology of education and feminist science studies. My purpose was to look at both the contextual and constitutive values of science as they were negotiated and played out in the training of scientists in a setting where: (1) women were well represented in leadership positions; and (2) "mainstream" science was being both taught and practiced. Findings included the organization of a status hierarchy within the department, the meanings of science and scientists that students constructed within the social spaces they occupied, examples of individual resistance to certain norms of biology practice, and examples of institutional opposition to that resistance. There was some evidence that the unusually high representation of women in positions of leadership in the biology department did result in changes in both the contextual and constitutive values of how science was conceptualized, practiced and taught in this setting. Contextually, social spaces controlled by women were likely to emphasize: (1) teamwork bringing together participants with varied backgrounds and perspectives; (2) flexible and collaborative use of physical space; and (3) willingness to do work for which they went unacknowledged or to share rewards equally even when the work distribution was not equitable. Constitutively, these social spaces were prone to: (1) interdisciplinary synthesis and comprehensive approaches; (2) the study of topics that reconsidered beliefs about gender roles in plant and animal reproduction; (3) work that would be slower and take longer to produce (and publish) but might make a large contribution (be a high quality product) eventually; and (4) an awareness by women that their practices were different in some ways than the practices of their male colleagues.

  15. Molecular biology of insect sodium channels and pyrethroid resistance.

    PubMed

    Dong, Ke; Du, Yuzhe; Rinkevich, Frank; Nomura, Yoshiko; Xu, Peng; Wang, Lingxin; Silver, Kristopher; Zhorov, Boris S

    2014-07-01

    Voltage-gated sodium channels are essential for the initiation and propagation of the action potential in neurons and other excitable cells. Because of their critical roles in electrical signaling, sodium channels are targets of a variety of naturally occurring and synthetic neurotoxins, including several classes of insecticides. This review is intended to provide an update on the molecular biology of insect sodium channels and the molecular mechanism of pyrethroid resistance. Although mammalian and insect sodium channels share fundamental topological and functional properties, most insect species carry only one sodium channel gene, compared to multiple sodium channel genes found in each mammalian species. Recent studies showed that two posttranscriptional mechanisms, alternative splicing and RNA editing, are involved in generating functional diversity of sodium channels in insects. More than 50 sodium channel mutations have been identified to be responsible for or associated with knockdown resistance (kdr) to pyrethroids in various arthropod pests and disease vectors. Elucidation of molecular mechanism of kdr led to the identification of dual receptor sites of pyrethroids on insect sodium channels. Many of the kdr mutations appear to be located within or close to the two receptor sites. The accumulating knowledge of insect sodium channels and their interactions with insecticides provides a foundation for understanding the neurophysiology of sodium channels in vivo and the development of new and safer insecticides for effective control of arthropod pests and human disease vectors.

  16. Molecular Biology of Insect Sodium Channels and Pyrethroid Resistance

    PubMed Central

    Dong, Ke; Du, Yuzhe; Rinkevich, Frank; Nomura, Yoshiko; Xu, Peng; Wang, Lingxin; Silver, Kristopher; Zhorov, Boris S.

    2015-01-01

    Voltage-gated sodium channels are essential for the initiation and propagation of the action potential in neurons and other excitable cells. Because of their critical roles in electrical signaling, sodium channels are targets of a variety of naturally occurring and synthetic neurotoxins, including several classes of insecticides. This review is intended to provide an update on the molecular biology of insect sodium channels and the molecular mechanism of pyrethroid resistance. Although mammalian and insect sodium channels share fundamental topological and functional properties, most insect species carry only one sodium channel gene, compared to multiple sodium channel genes found in each mammalian species. Recent studies showed that two posttranscriptional mechanisms, alternative splicing and RNA editing, are involved in generating functional diversity of sodium channels in insects. More than 50 sodium channel mutations have been identified to be responsible for or associated with knockdown resistance (kdr) to pyrethroids in various arthropod pests and disease vectors. Elucidation of molecular mechanism of kdr led to the identification of dual receptor sites of pyrethroids on insect sodium channels. Most of the kdr mutations appear to be located within or close to the two receptor sites. The accumulating knowledge of insect sodium channels and their interactions with insecticides provides a foundation for understanding the neurophysiology of sodium channels in vivo and the development of new and safer insecticides for effective control of arthropod pests and human disease vectors. PMID:24704279

  17. Antimicrobial resistance and biological governance: explanations for policy failure.

    PubMed

    Wallinga, D; Rayner, G; Lang, T

    2015-10-01

    The paper reviews the state of policy on antimicrobial use and the growth of antimicrobial resistance (AMR). AMR was anticipated at the time of the first use of antibiotics by their originators. For decades, reports and scientific papers have expressed concern about AMR at global and national policy levels, yet the problem, first exposed a half-century ago, worsened. The paper considers the explanations for this policy failure and the state of arguments about ways forward. These include: a deficit of economic incentivisation; complex interventions in behavioural dynamics; joint and separate shifts in medical and animal health regimes; consumerism; belief in technology; and a narrative that in a 'war on bugs' nature can be beaten by human ingenuity. The paper suggests that these narratives underplay the biological realities of the human-animal-biosphere being in constant flux, an understanding which requires an ecological public health analysis of AMR policy development and failure. The paper suggests that effective policy change requires simultaneous actions across policy levels. No single solution is possible, since AMR is the result of long-term human intervention which has accelerated certain trends in the evolution of a microbial ecosystem shared by humans, animals and other biological organisms inhabiting that ecosystem. Viewing the AMR crisis today through an ecological public health lens has the advantage of reuniting the social-ecological and bio-ecological perspectives which have been separated within public health. Copyright © 2015 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.

  18. Biological degradation of wood-plastic composites (WPC) and strategies for improving the resistance of WPC against biological decay

    Treesearch

    Anke Schirp; Rebecca E. Ibach; David E. Pendleton; Michael P. Wolcott

    2008-01-01

    Much of the research on wood-plastic composites (WPC) has focused on formulation development and processing while high biological durability of the material was assumed. The gap between assumption and knowledge in biodeterioration of WPC needs to be reduced. Although some information on the short-term resistance of WPC against biological degradation is available, long-...

  19. Systems biology of cisplatin resistance: past, present and future

    PubMed Central

    Galluzzi, L; Vitale, I; Michels, J; Brenner, C; Szabadkai, G; Harel-Bellan, A; Castedo, M; Kroemer, G

    2014-01-01

    The platinum derivative cis-diamminedichloroplatinum(II), best known as cisplatin, is currently employed for the clinical management of patients affected by testicular, ovarian, head and neck, colorectal, bladder and lung cancers. For a long time, the antineoplastic effects of cisplatin have been fully ascribed to its ability to generate unrepairable DNA lesions, hence inducing either a permanent proliferative arrest known as cellular senescence or the mitochondrial pathway of apoptosis. Accumulating evidence now suggests that the cytostatic and cytotoxic activity of cisplatin involves both a nuclear and a cytoplasmic component. Despite the unresolved issues regarding its mechanism of action, the administration of cisplatin is generally associated with high rates of clinical responses. However, in the vast majority of cases, malignant cells exposed to cisplatin activate a multipronged adaptive response that renders them less susceptible to the antiproliferative and cytotoxic effects of the drug, and eventually resume proliferation. Thus, a large fraction of cisplatin-treated patients is destined to experience therapeutic failure and tumor recurrence. Throughout the last four decades great efforts have been devoted to the characterization of the molecular mechanisms whereby neoplastic cells progressively lose their sensitivity to cisplatin. The advent of high-content and high-throughput screening technologies has accelerated the discovery of cell-intrinsic and cell-extrinsic pathways that may be targeted to prevent or reverse cisplatin resistance in cancer patients. Still, the multifactorial and redundant nature of this phenomenon poses a significant barrier against the identification of effective chemosensitization strategies. Here, we discuss recent systems biology studies aimed at deconvoluting the complex circuitries that underpin cisplatin resistance, and how their findings might drive the development of rational approaches to tackle this clinically relevant

  20. Biology of Triatoma sherlocki (Hemiptera: Reduviidae) Under Laboratory Conditions: Biological Cycle and Resistance to Starvation.

    PubMed

    Lima-Neiva, Vanessa; Gonçalves, Teresa C M; Bastos, Leonardo S; Gumiel, Marcia; Correia, Nathália C; Silva, Catia C; Almeida, Carlos E; Costa, Jane

    2017-07-01

    Triatoma sherlocki Papa, Jurberg, Carcavallo, Cerqueira & Barata was described in 2002, based on specimens caught in the wild in the municipality of Gentio do Ouro, Bahia, Brazil. In 2009, nymphs and adults were detected inside homes and sylvatic specimens were positive for Trypanosoma cruzi (Chagas). No information on the bionomics of T. sherlocki exists, although such data are considered essential to estimate its vector and colonization potential in domestic environments. Herein, the biological cycle of T. sherlocki was studied based on 123 eggs, with nymphs and adults fed on Mus musculus (Linnaeus). Nymphal development time phases, number of meals consumed, and stage-specific mortality rates were analyzed. Survival time under starvation conditions was measured between ecdysis and death among 50 nymphs (first to fifth instar) and 50 male and female adults. The median development time from egg to adult was 621.0 (CI: 489-656) d. The number of meals consumed ranged from 1 to 20 for nymphs of the first to fifth instar. The fifth instar showed the greatest resistance to starvation, with a mean of 156.5 d. The high number of meals consumed by T. sherlocki favored infection with and transmission of T. cruzi. The full development of this species under laboratory conditions with a low mortality rate indicates that this vector presents biological characteristics that may contribute to its adaptation to artificial human ecotopes. Its high resistance to starvation emphasizes the importance of entomological surveillance for this species. © The Authors 2017. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  1. Bridging Physics and Biology Using Resistance and Axons

    ERIC Educational Resources Information Center

    Dyer, Joshua M.

    2014-01-01

    When teaching physics, it is often difficult to get biology-oriented students to see the relevance of physics. A complaint often heard is that biology students are required to take physics for the Medical College Admission Test (MCAT) as part of a "weeding out" process, but that they don't feel like they need physics for biology. Despite…

  2. Bridging Physics and Biology Using Resistance and Axons

    ERIC Educational Resources Information Center

    Dyer, Joshua M.

    2014-01-01

    When teaching physics, it is often difficult to get biology-oriented students to see the relevance of physics. A complaint often heard is that biology students are required to take physics for the Medical College Admission Test (MCAT) as part of a "weeding out" process, but that they don't feel like they need physics for biology. Despite…

  3. Biological cost of fluoroquinolone resistance in Escherichia coli implicated in polyclonal infection.

    PubMed

    Bémer, P; Corvec, S; Guitton, C; Giraudeau, C; Le Gargasson, G; Espaze, E; Drugeon, H

    2007-07-01

    Polyclonal Escherichia coli strains were isolated in a transplanted patient who experienced successive septic shocks. Fluoroquinolone susceptible and resistant strains were corresponding to different PFGE fragment profiles. The gyrA S83L mutation was associated with a reduction in biological fitness. Resistant strain was selected by a long-term single use of ofloxacin.

  4. Molecular Biology of Drug Resistance in Mycobacterium tuberculosis

    PubMed Central

    Smith, Tasha; Wolff, Kerstin A.; Nguyen, Liem

    2014-01-01

    Tuberculosis (TB) has become a curable disease thanks to the discovery of antibiotics. However, it has remained one of the most difficult infections to treat. Most current TB regimens consist of six to nine months of daily doses of four drugs that are highly toxic to patients. The purpose of these lengthy treatments is to completely eradicate Mycobacterium tuberculosis, notorious for its ability to resist most antibacterial agents, thereby preventing the formation of drug resistant mutants. On the contrary, the prolonged therapies have led to poor patient adherence. This, together with a severe limit of drug choices, has resulted in the emergence of strains that are increasingly resistant to the few available antibiotics. Here we review our current understanding of molecular mechanisms underlying the profound drug resistance of M. tuberculosis. This knowledge is essential for the development of more effective antibiotics that not only are potent against drug resistant M. tuberculosis strains but also help shorten the current treatment courses required for drug susceptible TB. PMID:23179675

  5. Public health evolutionary biology of antimicrobial resistance: priorities for intervention.

    PubMed

    Baquero, Fernando; Lanza, Val F; Cantón, Rafael; Coque, Teresa M

    2015-03-01

    The three main processes shaping the evolutionary ecology of antibiotic resistance (AbR) involve the emergence, invasion and occupation by antibiotic-resistant genes of significant environments for human health. The process of emergence in complex bacterial populations is a high-frequency, continuous swarming of ephemeral combinatory genetic and epigenetic explorations inside cells and among cells, populations and communities, expanding in different environments (migration), creating the stochastic variation required for evolutionary progress. Invasion refers to the process by which AbR significantly increases in frequency in a given (invaded) environment, led by external invaders local multiplication and spread, or by endogenous conversion. Conversion occurs because of the spread of AbR genes from an exogenous resistant clone into an established (endogenous) bacterial clone(s) colonizing the environment; and/or because of dissemination of particular resistant genetic variants that emerged within an endogenous clonal population. Occupation of a given environment by a resistant variant means a permanent establishment of this organism in this environment, even in the absence of antibiotic selection. Specific interventions on emergence influence invasion, those acting on invasion also influence occupation and interventions on occupation determine emergence. Such interventions should be simultaneously applied, as they are not simple solutions to the complex problem of AbR.

  6. Public health evolutionary biology of antimicrobial resistance: priorities for intervention

    PubMed Central

    Baquero, Fernando; Lanza, Val F; Cantón, Rafael; Coque, Teresa M

    2015-01-01

    The three main processes shaping the evolutionary ecology of antibiotic resistance (AbR) involve the emergence, invasion and occupation by antibiotic-resistant genes of significant environments for human health. The process of emergence in complex bacterial populations is a high-frequency, continuous swarming of ephemeral combinatory genetic and epigenetic explorations inside cells and among cells, populations and communities, expanding in different environments (migration), creating the stochastic variation required for evolutionary progress. Invasion refers to the process by which AbR significantly increases in frequency in a given (invaded) environment, led by external invaders local multiplication and spread, or by endogenous conversion. Conversion occurs because of the spread of AbR genes from an exogenous resistant clone into an established (endogenous) bacterial clone(s) colonizing the environment; and/or because of dissemination of particular resistant genetic variants that emerged within an endogenous clonal population. Occupation of a given environment by a resistant variant means a permanent establishment of this organism in this environment, even in the absence of antibiotic selection. Specific interventions on emergence influence invasion, those acting on invasion also influence occupation and interventions on occupation determine emergence. Such interventions should be simultaneously applied, as they are not simple solutions to the complex problem of AbR. PMID:25861381

  7. Realistic species losses disproportionately reduce grassland resistance to biological invaders.

    PubMed

    Zavaleta, Erika S; Hulvey, Kristin B

    2004-11-12

    Consequences of progressive biodiversity declines depend on the functional roles of individual species and the order in which species are lost. Most studies of the biodiversity-ecosystem functioning relation tackle only the first of these factors. We used observed variation in grassland diversity to design an experimental test of how realistic species losses affect invasion resistance. Because entire plant functional groups disappeared faster than expected by chance, resistance declined dramatically with progressive species losses. Realistic biodiversity losses, even of rare species, can thus affect ecosystem processes far more than indicated by randomized-loss experiments.

  8. Characterization of the corrosion resistance of biologically active solutions: The effects of anodizing and welding

    NASA Technical Reports Server (NTRS)

    Walsh, Daniel W.

    1991-01-01

    An understanding of fabrication processes, metallurgy, electrochemistry, and microbiology is crucial to the resolution of microbiologically influenced corrosion (MIC) problems. The object of this effort was to use AC impedance spectroscopy to characterize the corrosion resistance of Type II anodized aluminum alloy 2219-T87 in sterile and biologically active media and to examine the corrosion resistance of 316L, alloy 2219-T87, and titanium alloy 6-4 in the welded and unwelded conditions. The latter materials were immersed in sterile and biologically active media and corrosion currents were measured using the polarization resistance (DC) technique.

  9. Cell biological mechanisms of multidrug resistance in tumors.

    PubMed

    Simon, S M; Schindler, M

    1994-04-26

    Multidrug resistance (MDR) is a generic term for the variety of strategies tumor cells use to evade the cytotoxic effects of anticancer drugs. MDR is characterized by a decreased sensitivity of tumor cells not only to the drug employed for chemotherapy but also to a broad spectrum of drugs with neither obvious structural homology nor common targets. This pleiotropic resistance is one of the major obstacles to the successful treatment of tumors. MDR may result from structural or functional changes at the plasma membrane or within the cytoplasm, cellular compartments, or nucleus. Molecular mechanisms of MDR are discussed in terms of modifications in detoxification and DNA repair pathways, changes in cellular sites of drug sequestration, decreases in drug-target affinity, synthesis of specific drug inhibitors within cells, altered or inappropriate targeting of proteins, and accelerated removal or secretion of drugs.

  10. Cell biological mechanisms of multidrug resistance in tumors.

    PubMed Central

    Simon, S M; Schindler, M

    1994-01-01

    Multidrug resistance (MDR) is a generic term for the variety of strategies tumor cells use to evade the cytotoxic effects of anticancer drugs. MDR is characterized by a decreased sensitivity of tumor cells not only to the drug employed for chemotherapy but also to a broad spectrum of drugs with neither obvious structural homology nor common targets. This pleiotropic resistance is one of the major obstacles to the successful treatment of tumors. MDR may result from structural or functional changes at the plasma membrane or within the cytoplasm, cellular compartments, or nucleus. Molecular mechanisms of MDR are discussed in terms of modifications in detoxification and DNA repair pathways, changes in cellular sites of drug sequestration, decreases in drug-target affinity, synthesis of specific drug inhibitors within cells, altered or inappropriate targeting of proteins, and accelerated removal or secretion of drugs. PMID:7909602

  11. Radiation resistance of biological reagents for in situ life detection.

    PubMed

    Carr, Christopher E; Rowedder, Holli; Vafadari, Cyrus; Lui, Clarissa S; Cascio, Ethan; Zuber, Maria T; Ruvkun, Gary

    2013-01-01

    Life on Mars, if it exists, may share a common ancestry with life on Earth derived from meteoritic transfer of microbes between the planets. One means to test this hypothesis is to isolate, detect, and sequence nucleic acids in situ on Mars, then search for similarities to known common features of life on Earth. Such an instrument would require biological and chemical components, such as polymerase and fluorescent dye molecules. We show that reagents necessary for detection and sequencing of DNA survive several analogues of the radiation expected during a 2-year mission to Mars, including proton (H-1), heavy ion (Fe-56, O-18), and neutron bombardment. Some reagents have reduced performance or fail at higher doses. Overall, our findings suggest it is feasible to utilize space instruments with biological components, particularly for mission durations of up to several years in environments without large accumulations of charged particles, such as the surface of Mars, and have implications for the meteoritic transfer of microbes between planets.

  12. Molecular and biological diagnostic tests for monitoring benzimidazole resistance in human soil-transmitted helminths.

    PubMed

    Diawara, Aïssatou; Schwenkenbecher, Jan M; Kaplan, Ray M; Prichard, Roger K

    2013-06-01

    In endemic countries with soil-transmitted helminths mass drug administration with albendazole or mebendazole are being implemented as a control strategy. However, it is well known in veterinary helminths that the use of the same benzimidazole drugs can place selection on the β-tubulin gene, leading to resistance. Given the concern that resistance could arise in human soil-transmitted helminths, there is an urgent need to develop accurate diagnostic tools for monitoring resistance. In this study, we developed molecular assays to detect putative resistance genetic changes in Ascaris lumbricoides, Trichuris trichiura, and hookworms, and we optimized an egg hatch assay for the canine hookworm Ancylostoma caninum and applied it to Necator americanus. Both assays were tested on field samples. The molecular assays demonstrated their reproducibility and capacity to detect the presence of worms carrying putative resistance-associated genetic changes. However, further investigations are needed to validate our molecular and biological tests on additional field isolates.

  13. Resistance and stability of a new method for bonding biological materials using sutures and biological adhesives.

    PubMed

    Paéz, J M García; Sanmartín, A Carrera; Herrero, E Jorge; Millan, I; Cordon, A; Rocha, A; Maestro, M A; Téllez, G; Castillo-Olivares, J L

    2005-01-01

    The valve leaflets of cardiac bioprostheses are secured and shaped by sutures which, given their high degree of resistance and poor elasticity, have been implicated in the generation of stresses within the leaflets, contributing to the failure of the bioprostheses. Bioadhesives are bonding materials that have begun to be utilized in surgery, although there is a lack of experience in their use with inert tissues or bioprostheses. Tensile testing is performed until rupture in samples of calf pericardium, a biomaterial employed in the manufacture of bioprosthetic heart valve leaflets. One hundred and thirty-two trials are carried out in three types of samples: intact or control tissue (n = 12); samples transected and glued in an overlapping manner with a cyanoacrylate (n = 60); and samples transected, sewn with a commercially available suture material and reinforced at the suture holes with the same cyanoacrylate (n = 60). Seven days after their preparation, 12 samples from each group, including the controls, are subjected to tensile testing until rupture and the findings are compared. In the stability study, groups of 12 each of the remaining 48 glued and 48 sutured and glued samples underwent tensile testing until rupture on days 30, 60, 90, and 120, after their preparation. The results show that bonding with the adhesive provided a resistance ranging between 1.04 and 1.87 kg, probably insufficient for use in valve leaflets, but also afforded a high degree of elasticity. After 120 days, both the glued and the sutured and glued series show excellent elastic behavior, with no rigidity or hardening of the pericardium. These samples present reversible elongation, or strain, when they surpass their elastic limit at rupture. This finding may be due to a load concentration that is damaging to the pericardium, to the behavior of the tissue as an amorphous material, or perhaps to both circumstances. These results need to be confirmed in future studies as they may be of value

  14. Biologic and Clinical Significance of Androgen Receptor Variants in Castration Resistant Prostate Cancer

    PubMed Central

    Ware, Kathryn E; Garcia-Blanco, Mariano A; Armstrong, Andrew J; Dehm, Scott M.

    2014-01-01

    As prostate cancer progresses to the lethal castration resistant and metastatic form, genetic and epigenetic adaptation, clonal selection, and evolution of the tumor microenvironment contribute to the emergence of unique biologic characteristics under the selective pressure of external stresses. These stresses include the therapies applied in the clinic or laboratory and the exposures of cancers to hormonal, paracrine, or autocrine stimuli in the context of the tumor micro- and macro-environment. The androgen receptor (AR) is a key gene involved in prostate cancer etiology and oncogenesis, including disease development, progression, response to initial hormonal therapies, and subsequent resistance to hormonal therapies. Alterations in the AR signaling pathway have been observed in certain selection contexts and contribute to the resistance to agents that target hormonal regulation of the AR, including standard androgen deprivation therapy (ADT), anti-androgens such as enzalutamide, and androgen synthesis inhibition with abiraterone acetate. One such resistance mechanism is the synthesis of constitutively active AR variants lacking the canonical ligand binding domain. This review focuses on the etiology, characterization, biologic properties, and emerging data contributing to the clinical characteristics of AR variants, and suggests approaches to full-length AR and AR variant biomarker validation, assessment, and systemic targeting in the clinic. PMID:24859991

  15. Perturbation biology nominates upstream-downstream drug combinations in RAF inhibitor resistant melanoma cells.

    PubMed

    Korkut, Anil; Wang, Weiqing; Demir, Emek; Aksoy, Bülent Arman; Jing, Xiaohong; Molinelli, Evan J; Babur, Özgün; Bemis, Debra L; Onur Sumer, Selcuk; Solit, David B; Pratilas, Christine A; Sander, Chris

    2015-08-18

    Resistance to targeted cancer therapies is an important clinical problem. The discovery of anti-resistance drug combinations is challenging as resistance can arise by diverse escape mechanisms. To address this challenge, we improved and applied the experimental-computational perturbation biology method. Using statistical inference, we build network models from high-throughput measurements of molecular and phenotypic responses to combinatorial targeted perturbations. The models are computationally executed to predict the effects of thousands of untested perturbations. In RAF-inhibitor resistant melanoma cells, we measured 143 proteomic/phenotypic entities under 89 perturbation conditions and predicted c-Myc as an effective therapeutic co-target with BRAF or MEK. Experiments using the BET bromodomain inhibitor JQ1 affecting the level of c-Myc protein and protein kinase inhibitors targeting the ERK pathway confirmed the prediction. In conclusion, we propose an anti-cancer strategy of co-targeting a specific upstream alteration and a general downstream point of vulnerability to prevent or overcome resistance to targeted drugs.

  16. Perturbation biology nominates upstream–downstream drug combinations in RAF inhibitor resistant melanoma cells

    PubMed Central

    Korkut, Anil; Wang, Weiqing; Demir, Emek; Aksoy, Bülent Arman; Jing, Xiaohong; Molinelli, Evan J; Babur, Özgün; Bemis, Debra L; Onur Sumer, Selcuk; Solit, David B; Pratilas, Christine A; Sander, Chris

    2015-01-01

    Resistance to targeted cancer therapies is an important clinical problem. The discovery of anti-resistance drug combinations is challenging as resistance can arise by diverse escape mechanisms. To address this challenge, we improved and applied the experimental-computational perturbation biology method. Using statistical inference, we build network models from high-throughput measurements of molecular and phenotypic responses to combinatorial targeted perturbations. The models are computationally executed to predict the effects of thousands of untested perturbations. In RAF-inhibitor resistant melanoma cells, we measured 143 proteomic/phenotypic entities under 89 perturbation conditions and predicted c-Myc as an effective therapeutic co-target with BRAF or MEK. Experiments using the BET bromodomain inhibitor JQ1 affecting the level of c-Myc protein and protein kinase inhibitors targeting the ERK pathway confirmed the prediction. In conclusion, we propose an anti-cancer strategy of co-targeting a specific upstream alteration and a general downstream point of vulnerability to prevent or overcome resistance to targeted drugs. DOI: http://dx.doi.org/10.7554/eLife.04640.001 PMID:26284497

  17. [Establishment and biological characteristics of a multi-drug resistant cell line A549/Gem.].

    PubMed

    Wang, Weixia; Liu, Xiaoqing; Liu, Guangxian; Lin, Li; Zheng, Xiaoling; Zhu, Yunfeng; Li, Xiaobing

    2008-02-20

    Multi-drug resistance is one of the most important reason why the survival time of non-small cell lung cancer patients is so short. The aim of this study is to establish multi-drug resistant cell line A549/Gem and discuss its biological characters so as to elaborate the possible mechanisms of gemcitabine resistance. Human gemcitabine-resistant non-small cell lung cancer cell line A549/Gem was established by repeated clinical serous peak concentration then low but gradually increasing concentration of gemcitabine from its parental cell human lung adenocarcinoma cell line A549 which is sensitive to gemcitabine. During the course of inducement, monitored its morphology, checked its resistance index and resistant pedigree by MTT method, gathered its growth curve and calculated its doubling time, examined its DNA contents and cell cycles by flow cytometry; at the same time, measured its expression of P53, EGFR, c-erb-B-2, PTEN, PCNA, c-myc, VEGF, MDR-1, Bcl-2, nm23, MMP-9, TIMP-1, CD44v6 Proteins, and RRM1 mRNA. The resistance index of A549/Gem' to gemcitabine was 163.228, and the cell line also exhibited cross-resistance to vinorelbine, taxotere, fluorouraci, etoposide and cisplatin, but kept sensitivity to paclitaxol and oxaliplatin. The doubling time of it was shorter and figures in G0-G1 phase were increased than A549. Compared with A549, A549/Gem' achieved EGFR and c-myc protein expression, nm23 protein expression enhanced, p53, Cerb-B-2 and bcl-2 protein expression reduced, PTEN, PCNA and MDR-1 protein expression vanished, but that of MMP-9, VEGF, CD44v6 and TIMP-1 protein changed trivially. Meanwhile, the expression of RRM1 mRNA was augmented markedly. The resistance index of A549/Gem to gemcitabine was 129.783, and the cell line also held cross-resistance to vinorelbine, taxotere, etoposide, cisplatin and sensitivity to paclitaxol. But the resistance to fluorouracil and sensitivity to oxaliplatin vanished. And the expression of RRM1 mRNA decreased visibly. The

  18. Characterization of p38 MAPK isoforms for drug resistance study using systems biology approach

    PubMed Central

    Engler, David A.; Matsunami, Risë K.; Su, Jing; Zhang, Le; Chang, Chung-Che (Jeff); Zhou, Xiaobo

    2014-01-01

    Motivation: p38 mitogen-activated protein kinase activation plays an important role in resistance to chemotherapeutic cytotoxic drugs in treating multiple myeloma (MM). However, how the p38 mitogen-activated protein kinase signaling pathway is involved in drug resistance, in particular the roles that the various p38 isoforms play, remains largely unknown. Method: To explore the underlying mechanisms, we developed a novel systems biology approach by integrating liquid chromatography–mass spectrometry and reverse phase protein array data from human MM cell lines with computational pathway models in which the unknown parameters were inferred using a proposed novel algorithm called modularized factor graph. Results: New mechanisms predicted by our models suggest that combined activation of various p38 isoforms may result in drug resistance in MM via regulating the related pathways including extracellular signal-regulated kinase (ERK) pathway and NFкB pathway. ERK pathway regulating cell growth is synergistically regulated by p38δ isoform, whereas nuclear factor kappa B (NFкB) pathway regulating cell apoptosis is synergistically regulated by p38α isoform. This finding that p38δ isoform promotes the phosphorylation of ERK1/2 in MM cells treated with bortezomib was validated by western blotting. Based on the predicted mechanisms, we further screened drug combinations in silico and found that a promising drug combination targeting ERK1/2 and NFκB might reduce the effects of drug resistance in MM cells. This study provides a framework of a systems biology approach to studying drug resistance and drug combination selection. Availability and implementation: RPPA experimental Data and Matlab source codes of modularized factor graph for parameter estimation are freely available online at http://ctsb.is.wfubmc.edu/publications/modularized-factor-graph.php Contact: xizhou@wakehealth.edu or zhanglcq@swu.edu.cn Supplementary information: Supplementary data are available at

  19. [Biological characteristics of defensin and its disease-resistance genetic engineering].

    PubMed

    Fu, Lan-Bao; Yu, Jia-Lin; Liu, Wei-Hua

    2011-05-01

    Defensin is a kind of cysteine-rich small peptide, which has a broad spectrum of resistance to bacteria with a special resistance mechanism. So far, a large number of studies on defensins have been reported, and the different types of defensins have been isolated from various organisms. A broad prospect of application on defensins has been displayed both in genetic engineering and medicine field. This article reviewed the classification and the biological characteristics of defensins, including mammalian α-, β-, θ-defensins, insect defensins, and plant defensins. The molecular structures, antibacterial activities, and antibacterial mechanisms of these definsins were summarized. The two mechanisms of de-fensin, including independent membrane mechanism and targeting of intracellular compounds by defensins, are ex-pounded. This paper also summarized the researches on isolation and expression of defensin genes and disease resistance genetic engineering of mammal and plant defensins. A prospect of the future applications of defensin both in biophar-maceutical sciences and plant disease resistance genetic engineering was discussed.

  20. Synthetic and Biological Studies of Sesquiterpene Polygodial: Activity of 9-Epipolygodial Against Drug Resistant Cancer Cells

    PubMed Central

    Dasari, Ramesh; De Carvalho, Annelise; Medellin, Derek C.; Middleton, Kelsey N.; Hague, Frédéric; Volmar, Marie N. M.; Frolova, Liliya V.; Rossato, Mateus F.; De La Chapa, Jorge J.; Dybdal-Hargreaves, Nicholas F.; Pillai, Akshita; Mathieu, Véronique; Rogelj, Snezna; Gonzales, Cara B.; Calixto, João B.; Evidente, Antonio; Gautier, Mathieu; Munirathinam, Gnanasekar; Glass, Rainer; Burth, Patricia; Pelly, Stephen C.; van Otterlo, Willem A. L.; Kiss, Robert; Kornienko, Alexander

    2015-01-01

    Polygodial, a terpenenoid dialdehyde isolated from Polygonum hydropiper L., is a known TRPV1 agonist. In this investigation a series of polygodial analogues were prepared and investigated for TRPV1 agonistic and anticancer activities. These experiments led to the identification of 9-epipolygodial, possessing antiproliferative potency significantly exceeding that of polygodial. Epipolygodial maintained potency against apoptosis-resistant cancer cells as well as those displaying the MDR phenotype. In addition, a chemical feasibility for the previously proposed mechanism of action of polygodial, involving the Paal-Knorr pyrrole formation with a lysine residue on the target protein, was demonstrated through the synthesis of a stable polygodial pyrrole derivative. These studies reveal rich chemical and biological properties associated with polygodial and its direct derivatives. They should inspire further work in this area aimed at the development of new pharmacological agents or exploration of novel mechanisms of covalent modification of biological molecules with natural products. PMID:26434977

  1. Without the Light of Evolution: A Case Study of Resistance and Avoidance in Learning to Teach High School Biology

    ERIC Educational Resources Information Center

    Larkin, Douglas B.; Perry-Ryder, Gail M.

    2015-01-01

    We present the case of Michael, a prospective high school biology teacher, to explore the implications of teacher resistance and avoidance to the topic of evolution. This case is drawn from a year-long qualitative research study that examined Michael's process of learning to teach high school biology and describes how his avoidance of evolution in…

  2. Without the Light of Evolution: A Case Study of Resistance and Avoidance in Learning to Teach High School Biology

    ERIC Educational Resources Information Center

    Larkin, Douglas B.; Perry-Ryder, Gail M.

    2015-01-01

    We present the case of Michael, a prospective high school biology teacher, to explore the implications of teacher resistance and avoidance to the topic of evolution. This case is drawn from a year-long qualitative research study that examined Michael's process of learning to teach high school biology and describes how his avoidance of evolution in…

  3. On the relationship between indentation hardness and modulus, and the damage resistance of biological materials.

    PubMed

    Labonte, David; Lenz, Anne-Kristin; Oyen, Michelle L

    2017-07-15

    The remarkable mechanical performance of biological materials is based on intricate structure-function relationships. Nanoindentation has become the primary tool for characterising biological materials, as it allows to relate structural changes to variations in mechanical properties on small scales. However, the respective theoretical background and associated interpretation of the parameters measured via indentation derives largely from research on 'traditional' engineering materials such as metals or ceramics. Here, we discuss the functional relevance of indentation hardness in biological materials by presenting a meta-analysis of its relationship with indentation modulus. Across seven orders of magnitude, indentation hardness was directly proportional to indentation modulus. Using a lumped parameter model to deconvolute indentation hardness into components arising from reversible and irreversible deformation, we establish criteria which allow to interpret differences in indentation hardness across or within biological materials. The ratio between hardness and modulus arises as a key parameter, which is related to the ratio between irreversible and reversible deformation during indentation, the material's yield strength, and the resistance to irreversible deformation, a material property which represents the energy required to create a unit volume of purely irreversible deformation. Indentation hardness generally increases upon material dehydration, however to a larger extent than expected from accompanying changes in indentation modulus, indicating that water acts as a 'plasticiser'. A detailed discussion of the role of indentation hardness, modulus and toughness in damage control during sharp or blunt indentation yields comprehensive guidelines for a performance-based ranking of biological materials, and suggests that quasi-plastic deformation is a frequent yet poorly understood damage mode, highlighting an important area of future research. Instrumented

  4. Nonstarter lactobacilli isolated from soft and semihard Argentinean cheeses: genetic characterization and resistance to biological barriers.

    PubMed

    Ugarte, Mariana Bude; Guglielmotti, Daniela; Giraffa, Giorgio; Reinheimer, Jorge; Hynes, Erica

    2006-12-01

    Nonstarter lactic acid bacteria isolated from Argentinean cheeses were identified and characterized by focusing on their resistance to biological barriers, along with other physiological features of potential interest, in the search for future probiotic organisms. Lactobacilli were enumerated and isolated from semihard and soft cheeses made with multistrain Streptococcus thermophilus starters. Lactobacilli counts in 1-week-old cheeses were between 10(5) and 10(7) CFU/g and then reached 10(7) CFU/ g in all 1-month samples, while streptococci were always above 10(9) CFU/g. A total number of 22 lactobacilli isolates were retained, identified, and characterized by in vitro tests. Species identity was determined by carbohydrate metabolism and species-specific PCR assays. Genetic diversity was explored by random amplified polymorphic DNA (RAPD) PCR analysis. The Lactobacillus strains were assigned to the species L. casei, L. plantarum, L. rhamnosus, L. curvatus, L. fermentum, and L. perolens. All the strains studied tolerated 25 ppm of lysozyme, and most of them showed resistance to 0.3% bile. After incubation in gastric solution (pH 2.0), counts decreased by several log units, ranging from 3.2 to 7.0. The strains were able to grow in the presence of bile salts, but only three isolates were capable of deconjugation. The nonstarter lactobacilli that were assayed fermented the prebiotic substrates (especially lactulose and inulin). Some strains showed high cell hydrophobicity and beta-galactosidase activity, as well as inhibitory activity against pathogenic bacteria. It was concluded that most of the lactobacilli isolated in this study demonstrated resistance to biological barriers and physiological characteristics compatible with probiotic properties, which make them suitable for further research in in vivo studies aimed at identifying new probiotic organisms.

  5. Molecular effects of resistance elicitors from biological origin and their potential for crop protection

    PubMed Central

    Wiesel, Lea; Newton, Adrian C.; Elliott, Ian; Booty, David; Gilroy, Eleanor M.; Birch, Paul R. J.; Hein, Ingo

    2014-01-01

    Plants contain a sophisticated innate immune network to prevent pathogenic microbes from gaining access to nutrients and from colonizing internal structures. The first layer of inducible response is governed by the plant following the perception of microbe- or modified plant-derived molecules. As the perception of these molecules results in a plant response that can provide efficient resistance toward non-adapted pathogens they can also be described as “defense elicitors.” In compatible plant/microbe interactions, adapted microorganisms have means to avoid or disable this resistance response and promote virulence. However, this requires a detailed spatial and temporal response from the invading pathogens. In agricultural practice, treating plants with isolated defense elicitors in the absence of pathogens can promote plant resistance by uncoupling defense activation from the effects of pathogen virulence determinants. The plant responses to plant, bacterial, oomycete, or fungal-derived elicitors are not, in all cases, universal and need elucidating prior to the application in agriculture. This review provides an overview of currently known elicitors of biological rather than synthetic origin and places their activity into a molecular context. PMID:25484886

  6. Uncovering three-dimensional gradients in fibrillar orientation in an impact-resistant biological armour

    PubMed Central

    Zhang, Y.; Paris, O.; Terrill, N. J.; Gupta, H. S.

    2016-01-01

    The complex hierarchical structure in biological and synthetic fibrous nanocomposites entails considerable difficulties in the interpretation of the crystallographic texture from diffraction data. Here, we present a novel reconstruction method to obtain the 3D distribution of fibres in such systems. An analytical expression is derived for the diffraction intensity from fibres, explaining the azimuthal intensity distribution in terms of the angles of the three dimensional fibre orientation distributions. The telson of stomatopod (mantis shrimp) serves as an example of natural biological armour whose high impact resistance property is believed to arise from the hierarchical organization of alpha chitin nanofibrils into fibres and twisted plywood (Bouligand) structures at the sub-micron and micron scale. Synchrotron microfocus scanning X-ray diffraction data on stomatopod telson were used as a test case to map the 3D fibre orientation across the entire tissue section. The method is applicable to a range of biological and biomimetic structures with graded 3D fibre texture at the sub-micron and micron length scales. PMID:27211574

  7. Uncovering three-dimensional gradients in fibrillar orientation in an impact-resistant biological armour

    NASA Astrophysics Data System (ADS)

    Zhang, Y.; Paris, O.; Terrill, N. J.; Gupta, H. S.

    2016-05-01

    The complex hierarchical structure in biological and synthetic fibrous nanocomposites entails considerable difficulties in the interpretation of the crystallographic texture from diffraction data. Here, we present a novel reconstruction method to obtain the 3D distribution of fibres in such systems. An analytical expression is derived for the diffraction intensity from fibres, explaining the azimuthal intensity distribution in terms of the angles of the three dimensional fibre orientation distributions. The telson of stomatopod (mantis shrimp) serves as an example of natural biological armour whose high impact resistance property is believed to arise from the hierarchical organization of alpha chitin nanofibrils into fibres and twisted plywood (Bouligand) structures at the sub-micron and micron scale. Synchrotron microfocus scanning X-ray diffraction data on stomatopod telson were used as a test case to map the 3D fibre orientation across the entire tissue section. The method is applicable to a range of biological and biomimetic structures with graded 3D fibre texture at the sub-micron and micron length scales.

  8. Uncovering three-dimensional gradients in fibrillar orientation in an impact-resistant biological armour.

    PubMed

    Zhang, Y; Paris, O; Terrill, N J; Gupta, H S

    2016-05-23

    The complex hierarchical structure in biological and synthetic fibrous nanocomposites entails considerable difficulties in the interpretation of the crystallographic texture from diffraction data. Here, we present a novel reconstruction method to obtain the 3D distribution of fibres in such systems. An analytical expression is derived for the diffraction intensity from fibres, explaining the azimuthal intensity distribution in terms of the angles of the three dimensional fibre orientation distributions. The telson of stomatopod (mantis shrimp) serves as an example of natural biological armour whose high impact resistance property is believed to arise from the hierarchical organization of alpha chitin nanofibrils into fibres and twisted plywood (Bouligand) structures at the sub-micron and micron scale. Synchrotron microfocus scanning X-ray diffraction data on stomatopod telson were used as a test case to map the 3D fibre orientation across the entire tissue section. The method is applicable to a range of biological and biomimetic structures with graded 3D fibre texture at the sub-micron and micron length scales.

  9. Hybridization of an invasive shrub affects tolerance and resistance to defoliation by a biological control agent

    USGS Publications Warehouse

    Williams, Wyatt I.; Friedman, Jonathan M.; Gaskin, John F.; Norton, Andrew P.

    2014-01-01

    Evolution has contributed to the successful invasion of exotic plant species in their introduced ranges, but how evolution affects particular control strategies is still under evaluation. For instance, classical biological control, a common strategy involving the utilization of highly specific natural enemies to control exotic pests, may be negatively affected by host hybridization because of shifts in plant traits, such as root allocation or chemical constituents. We investigated introgression between two parent species of the invasive shrub tamarisk (Tamarix spp.) in the western United States, and how differences in plant traits affect interactions with a biological control agent. Introgression varied strongly with latitude of origin and was highly correlated with plant performance. Increased levels of T. ramosissima introgression resulted in both higher investment in roots and tolerance to defoliation and less resistance to insect attack. Because tamarisk hybridization occurs predictably on the western U.S. landscape, managers may be able to exploit this information to maximize control efforts. Genetic differentiation in plant traits in this system underpins the importance of plant hybridization and may explain why some biological control releases are more successful than others.

  10. Analyzing fission yeast multidrug resistance mechanisms to develop a genetically tractable model system for chemical biology.

    PubMed

    Kawashima, Shigehiro A; Takemoto, Ai; Nurse, Paul; Kapoor, Tarun M

    2012-07-27

    Chemical inhibitors can help analyze dynamic cellular processes, particularly when probes are active in genetically tractable model systems. Although fission yeast has served as an important model system, which shares more cellular processes (e.g., RNAi) with humans than budding yeast, its use for chemical biology has been limited by its multidrug resistance (MDR) response. Using genomics and genetics approaches, we identified the key transcription factors and drug-efflux transporters responsible for fission yeast MDR and designed strains sensitive to a wide-range of chemical inhibitors, including commonly used probes. We used this strain, along with acute chemical inhibition and high-resolution imaging, to examine metaphase spindle organization in a "closed" mitosis. Together, our findings suggest that our fission yeast strains will allow the use of several inhibitors as probes, discovery of new inhibitors, and analysis of drug action. Copyright © 2012 Elsevier Ltd. All rights reserved.

  11. Barcodes of marine invertebrates from north Iberian ports: Native diversity and resistance to biological invasions.

    PubMed

    Miralles, L; Ardura, A; Arias, A; Borrell, Y J; Clusa, L; Dopico, E; de Rojas, A Hernandez; Lopez, B; Muñoz-Colmenero, M; Roca, A; Valiente, A G; Zaiko, A; Garcia-Vazquez, E

    2016-11-15

    Ports are gateways for many marine organisms transported by ships worldwide, especially non-indigenous species (NIS). In this study carried out in North Iberian ports (Cantabrian Sea, Bay of Biscay) we have observed 38% of exotic macroinvertebrates. Four species, namely the barnacle Austrominius modestus, the tubeworm Ficopomatus enigmaticus, the Pacific oyster Crassostrea gigas and the pygmy mussel Xenostrobus securis, exhibited clear signs of invasiveness. A total of 671 barcode (cytochrome oxidase subunit I or 18S rRNA) genes were obtained and confirmed the species status of some cryptic NIS. Negative and significant correlation between diversity estimators of native biota and proportion of NIS suggests biotic resistance in ports. This could be applied to management of port biota for contributing to prevent the settlement of biopollutants in these areas which are very sensitive to biological invasions.

  12. [Biology of Triatoma vitticeps (Stal, 1859) under laboratory conditions (Hemiptera: Reduviidae: Triatominae). II. Resistance to fasting].

    PubMed

    Gonçalves, T C; Victório, V M; Jurberg, J; Cunha, V

    1989-01-01

    Following the study on the biology of Triatoma vitticeps (Gonçalves et al., 1988) observations have been made on its resistance to starvation. Of the 286 eggs obtained only 201 hatched and reached the intended stage for observation. The others did not eclode, neither reached the ecdisis nor died, without explanation. The nymphs were kept, separately, in Borrel flasks and properly listed. The blood-meal was performed in mice, although the insects were kept without feeding as soon as moulted. The starvation was evaluated in two ways: the time-lapse in days between the last meal/death and between moult/death. The starvation was directly related with the developmental stage. In relation to the parameters last meal/death and moult/death, both sexes were less resistant than 3rd and 2nd stage, respectively. The experiment have been carried out for 15 months and by this time the average minimum and maximum temperatures and the humidity were 25 +/- 2 degrees C - 28 +/- 2 degrees C and 81 +/- 3% UR, respectively. The material spent belongs to the triatomine colony of the Oswaldo Cruz Institute Department of Entomology.

  13. Antibiotic-resistant Escherichia coli in karstic systems: a biological indicator of the origin of fecal contamination?

    PubMed

    Ribeiro, Angela Flores; Laroche, Emilie; Hanin, Guillaume; Fournier, Matthieu; Quillet, Laurent; Dupont, Jean-Paul; Pawlak, Barbara

    2012-07-01

    Occurrences of antibiotic-resistant Escherichia coli in two springs of a karstic system (NW France) providing drinking water were determined to study the role of aquifers in the dissemination of the resistance genes. Water samples were collected during wet and dry periods and after a heavy rainfall event to investigate E. coli density, antibiotic resistance patterns, and occurrences of class 1, 2, and 3 integrons. By observing patterns of the resistant isolates (i.e. number and type of resistances) and their occurrences, we were able to define two resistant subpopulations, introduced in the aquifer via surface water: (1) R1-2, characterized by one or two resistance(s), essentially to chloramphenicol and/or tetracycline (96.5%), was always found during the heavy rainfall event; (2) R3-10, characterized by three or more resistances, mostly resistant to tetracycline (94.1%) and beta-lactams (86%), was found transiently. Class 1 and 2 integrons were detected, mostly in the R3-10 subpopulation for class 1 integrons. The characteristics of these two subpopulations strongly suggest that the contamination originates from pasture runoff for the R1-2 subpopulation and from wastewater treatment plant effluents for the R3-10 subpopulation. These two subpopulations of E. coli could be used as biological indicators to determine the origin of groundwater contamination.

  14. An insight into the key genes and biological functions associated with insulin resistance in adipose tissue with microarray technology.

    PubMed

    Zhang, Li; Cui, Ying; Fu, Fangming; Li, Zhenzuo; Pan, Xiaoxia; Li, Hongzhuan; Li, Lin

    2015-03-01

    In the present study, the key genes and biological functions associated with insulin resistance were investigated by comparing the gene expression profiles of adipose tissue obtained from insulin‑sensitive and insulin‑resistant patients. The gene expression data set GSE20950 was downloaded from the Gene Expression Omnibus, including 39 adipose tissue samples obtained from insulin‑sensitive and insulin‑resistant patients undergoing gastric bypass surgery. Adipose samples were divided into two groups (the insulin‑sensitive and insulin‑resistant groups) and the differentially expressed genes (DEGs) were screened out with packages of R. The interactions among DEGs were retrieved with Osprey and functional enrichment analysis was performed with the WebGestalt system. Information regarding the interaction network and enriched biological functions was combined to construct a functional interaction network. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis was then conducted using the Database for Annotation, Visualization and Integrated Discovery. A total of 170 DEGs were detected in the insulin‑sensitive group, 8 downregulated and 162 upregulated. Response to glucose stimulus was the most significantly over‑represented functional term. The focal adhesion pathway was identified to be significant in the genes of the functional interaction network. The present study revealed key biological functions and DEGs in adipose tissues associated with insulin resistance, which may facilitate the development of novel therapies for insulin resistance and diabetes.

  15. Biologically-initiated rock crust on sandstone: Mechanical and hydraulic properties and resistance to erosion

    NASA Astrophysics Data System (ADS)

    Slavík, Martin; Bruthans, Jiří; Filippi, Michal; Schweigstillová, Jana; Falteisek, Lukáš; Řihošek, Jaroslav

    2017-02-01

    Biocolonization on sandstone surfaces is known to play an important role in rock disintegration, yet it sometimes also aids in the protection of the underlying materials from rapid erosion. There have been few studies comparing the mechanical and/or hydraulic properties of the BIRC (Biologically-Initiated Rock Crust) with its subsurface. As a result, the overall effects of the BIRC are not yet well understood. The objective of the present study was to briefly characterize the BIRC from both the mineralogical and biological points of view, and especially to quantify the effect of the BIRC upon the mechanical and hydraulic properties of friable sandstone. The mineralogical investigation of a well-developed BIRC showed that its surface is enriched in kaolinite and clay- to silt-sized quartz particles. Total organic carbon increases with the age of the BIRC. Based on DNA sequencing and microscopy, the BIRC is formed by various fungi, including components of lichens and green algae. Using the method of drilling resistance, by measuring tensile strength, and based on water jet testing, it was determined that a BIRC is up to 12 times less erodible and has 3-35 times higher tensile strength than the subsurface friable sandstone. Saturated hydraulic conductivity of the studied BIRC is 15-300 times lower than the subsurface, and was measured to also decrease in capillary water absorption (2-33 times). Water-vapor diffusion is not significantly influenced by the presence of the BIRC. The BIRC thus forms a hardened surface which protects the underlying material from rain and flowing water erosion, and considerably modifies the sandstone's hydraulic properties. Exposing the material to calcination (550 °C), and experiments with the enzyme zymolyase indicated that a major contribution to the surface hardening is provided by organic matter. In firmer sandstones, the BIRC may still considerably decrease the rate of weathering, as it is capable of providing cohesion to strongly

  16. Systems Biology Strategy Reveals PKCδ is Key for Sensitizing TRAIL-Resistant Human Fibrosarcoma

    PubMed Central

    Hayashi, Kentaro; Tabata, Sho; Piras, Vincent; Tomita, Masaru; Selvarajoo, Kumar

    2015-01-01

    Cancer cells are highly variable and largely resistant to therapeutic intervention. Recently, the use of the tumor necrosis factor related apoptosis-inducing ligand (TRAIL) induced treatment is gaining momentum due to TRAIL’s ability to specifically target cancers with limited effect on normal cells. Nevertheless, several malignant cancer types still remain non-sensitive to TRAIL. Previously, we developed a dynamic computational model, based on perturbation-response differential equations approach, and predicted protein kinase C (PKC) as the most effective target, with over 95% capacity to kill human fibrosarcoma (HT1080) in TRAIL stimulation (1). Here, to validate the model prediction, which has significant implications for cancer treatment, we conducted experiments on two TRAIL-resistant cancer cell lines (HT1080 and HT29). Using PKC inhibitor bisindolylmaleimide I, we demonstrated that cell viability is significantly impaired with over 95% death of both cancer types, in consistency with our previous model. Next, we measured caspase-3, Poly (ADP-ribose) polymerase (PARP), p38, and JNK activations in HT1080, and confirmed cell death occurs through apoptosis with significant increment in caspase-3 and PARP activations. Finally, to identify a crucial PKC isoform, from 10 known members, we analyzed each isoform mRNA expressions in HT1080 cells and shortlisted the highest 4 for further siRNA knock-down (KD) experiments. From these KDs, PKCδ produced the most cancer cell death in conjunction with TRAIL. Overall, our approach combining model predictions with experimental validation holds promise for systems biology based cancer therapy. PMID:25601862

  17. Inheritance of Cry1Ac resistance and associated biological traits in the cotton bollworm, Helicoverpa armigera (Lepidoptera: Noctuidae).

    PubMed

    Nair, Rupa; Kalia, Vinay; Aggarwal, K K; Gujar, Govind T

    2010-05-01

    The analysis of reciprocal genetic crosses between resistant Helicoverpa armigera strain (BH-R) (227.9-fold) with susceptible Vadodara (VA-S) strain showed dominance (h) of 0.65-0.89 and degree of dominance (D) of 0.299-0.782 suggesting Cry1Ac resistance as a semi-dominant trait. The D and h values of F(1) hybrids of female resistant parent were higher than female susceptible parent, showing maternally enhanced dominance of Cry1Ac resistance. The progeny of F(2) crosses, backcrosses of F(1) hybrid with resistant BH-R parent did not differ significantly in respect of mortality response with resistant parent except for backcross with female BH-R and male of F(1) (BH-RxVA-S) cross, suggesting dominant inheritance of Cry1Ac resistance. Evaluation of some biological attributes showed that larval and pupal periods of progenies of reciprocal F(1) crosses, backcrosses and F(2) crosses were either at par with resistant parent or lower than susceptible parent on treated diet (0.01 microg/g). The susceptible strain performed better in terms of pupation and adult formation than the resistant strain on untreated diet. In many backcrosses and F(2) crosses, Cry1Ac resistance favored emergence of more females than males on untreated diet. The normal larval period and the body weight (normal larval growth) were the dominant traits associated with susceptible strain as contrast to longer larval period and the lower body weight (slow growth) associated with resistance trait. Further, inheritance of larval period in F(2) and backcross progeny suggested existence of a major resistant gene or a set of tightly linked loci associated with Cry1Ac sensitivity. (c) 2010 Elsevier Inc. All rights reserved.

  18. Biological fitness and natural selection of amantadine resistant variants of avian influenza H5N1 viruses.

    PubMed

    Abdelwhab, E M; Veits, Jutta; Mettenleiter, Thomas C

    2017-01-15

    Outbreaks caused by the highly pathogenic H5N1 avian influenza virus (A/H5N1) devastated the poultry industry in several countries and posed a significant pandemic threat. In addition to culling of infected poultry and vaccination, amantadine has been applied in poultry in some countries to control the spread of the virus. The prevalence of the amantadine resistance marker at position 31 (Ser31Asn) of the M2 protein increased over time. However, little is known about the biological fitness and selection of H5N1 amantadine resistant strains over their sensitive counterparts. Here, using reverse genetics we investigated the biological impact of Ser31Asn in M2 commonly seen in viruses in clade 2.2.1.1 in farmed poultry in Egypt. Findings of the current study indicated that the resistance to amantadine conferred by Asn31 evolved rapidly after the application of amantadine in commercial poultry. Both the resistant and sensitive strains replicated at similar levels in avian cell culture. Asn31 increased virus entry into the cells and cell-to-cell spread and was genetically stable for several passages in cell culture. Moreover, upon co-infection of cell culture resistant strains dominated sensitive viruses even in the absence of selection by amantadine. Together, rapid emergence, stability and domination of amantadine-resistant variants over sensitive strains limit the efficacy of amantadine in poultry.

  19. A systems biology approach to overcome TRAIL resistance in cancer treatment.

    PubMed

    Selvarajoo, Kumar

    2017-09-01

    Over the last decade, our research team has investigated the dynamic responses and global properties of living cells using systems biology approaches. More specifically, we have developed computational models and statistical techniques to interpret instructive cell signaling and high-throughput transcriptome-wide behaviors of immune, cancer, and embryonic development cells. Here, I will focus on our recent works in overcoming cancer resistance. TRAIL (tumor necrosis factor related apoptosis-inducing ligand), a proinflammatory cytokine, has shown promising success in controlling cancer threat due to its ability to induce apoptosis in cancers specifically, while having limited effect on normal cells. Nevertheless, several malignant cancer types, such as fibrosarcoma (HT1080) or colorectal adenocarcinoma (HT29), remain non-sensitive to TRAIL. To sensitize HT1080 to TRAIL treatment, we first developed a dynamic computational model based on perturbation-response approach, to predict a crucial co-target to enhance cell death. The model simulations suggested that PKC inhibition together with TRAIL induce 95% cell death. Subsequently, we confirmed this result experimentally utilizing the PKC inhibitor, bisindolylmaleimide (BIM) I, and PKC siRNAs in HT1080. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Biological interactions both facilitate and resist climate-related functional change in temperate reef communities.

    PubMed

    Bates, Amanda E; Stuart-Smith, Rick D; Barrett, Neville S; Edgar, Graham J

    2017-06-14

    Shifts in the abundance and location of species are restructuring life on the Earth, presenting the need to build resilience into our natural systems. Here, we tested if protection from fishing promotes community resilience in temperate reef communities undergoing rapid warming in Tasmania. Regardless of protection status, we detected a signature of warming in the brown macroalgae, invertebrates and fishes, through increases in the local richness and abundance of warm-affinity species. Even so, responses in protected communities diverged from exploited communities. At the local scale, the number of cool-affinity fishes and canopy-forming algal species increased following protection, even though the observation window fell within a period of warming. At the same time, exploited communities gained turf algal and sessile invertebrate species. We further found that the recovery of predator populations following protection leads to marked declines in mobile invertebrates-this trend could be incorrectly attributed to warming without contextual data quantifying community change across trophic levels. By comparing long-term change in exploited and protected reefs, we empirically demonstrate the role of biological interactions in both facilitating and resisting climate-related biodiversity change. We further highlight the potential for trophic interactions to alter the progression of both range expansions and contractions. © 2017 The Author(s).

  1. Antimalarial drug resistance: a review of the biology and strategies to delay emergence and spread

    PubMed Central

    Klein, E.Y.

    2013-01-01

    The emergence of resistance to former first-line antimalarial drugs has been an unmitigated disaster. In recent years, artemisinin class drugs have become standard and they are considered an essential tool for helping to eradicate the disease. However, their ability to reduce morbidity and mortality and to slow transmission requires the maintenance of effectiveness. Recently, an artemisinin delayed-clearance phenotype was described. This is believed to be the precursor to resistance and threatens local elimination and global eradication plans. Understanding how resistance emerges and spreads is important for developing strategies to contain its spread. Resistance is the result of two processes: (i) drug selection of resistant parasites; and (ii) the spread of resistance. In this review, we examine the factors that lead to both drug selection and the spread of resistance. We then examine strategies for controlling the spread of resistance, pointing out the complexities and deficiencies in predicting how resistance will spread. PMID:23394809

  2. A systems biology approach to identify microRNAs contributing to cisplatin resistance in human ovarian cancer cells.

    PubMed

    Liu, Weisha; Wang, Shuyuan; Zhou, Shunheng; Yang, Feng; Jiang, Wei; Zhang, Qingyuan; Wang, Lihong

    2017-09-01

    Cisplatin (CDDP)-based chemotherapy is a standard first-line therapy for ovarian cancer. However, drug resistance remains a major obstacle to its efficacy. Recently, increasing evidence suggested that the aberrant expression of microRNAs (miRNAs) may contribute to drug resistance. Here, we proposed a systems biology analysis strategy to identify the novel miRNAs potentially involved in CDDP resistance in human ovarian cancer cells. Firstly, we identified the candidate miRNAs associated with CDDP resistance using NCI-60 data. Next, the differentially expressed genes (DEGs) in the CDDP-resistant ovarian cancer cell line OVCAR-8R were obtained. After mapping the DEGs to a human protein-protein interaction network, a CDDP resistance-related sub-network for ovarian cancer was constructed, and subsequently the functional gene modules were identified. Then, based on the experimentally validated miRNA regulations to target genes, 4 candidate miRNAs (miR-24-3p, miR-192-5p, miR-139-5p and miR-155-5p) were identified to potentially contribute to ovarian cancer cell chemoresistance to CDDP through mediating OVCAR-8R cell CDDP resistance-related gene modules, which participated in functions that were closely related to "apoptosis", "cell cycle" and "adhesion". In addition, we predicted the therapeutic drugs that might reduce or reverse CDDP resistance by targeting these 4 identified miRNAs. This study revealed the underlying mechanism of CDDP resistance, and provided novel potential drug targets and therapeutics for CDDP-resistant ovarian cancer patients.

  3. Mechanical resistance of peripheral nerve repair with biological glue and with conventional suture at different postoperative times.

    PubMed

    Nishimura, Marcelo Tadashi; Mazzer, Nilton; Barbieri, Cláudio Henrique; Moro, Carlos Alberto

    2008-07-01

    Regardless of its type, the repair of a peripheral nerve must ideally permit early motion of the affected limb and resist disruption by the tensile forces generated throughout the healing process and regeneration. A comparative study of the mechanical resistance of the repair of the sciatic nerve with biological glue and conventional microsurgical suture over time was undertaken in 48 rats. Both right and left sciatic nerves were exposed simultaneously and repaired at random with the glue on one side and conventional suture on the opposite side. Mechanical resistance of the repair was evaluated in situ with a universal testing machine using a hooklike accessory applied proximally to the repair site, immediately and at 7, 14, and 28 days postoperatively. A load was applied at the rate of 2 mm/min till rupture. The resistance of both types of repair significantly increased up to day 14 ( P < 0.001), and the repair with the glue was significantly less resistant than repair with conventional suture immediately postoperatively ( P < 0.001) and on day 7 ( P = 0.03). Resistance became equivalent for the two types of repair on days 14 ( P = 0.67) and 28 ( P = 0.34). The change in resistance of both types of repair with time was in accordance with the power function numeric formula.

  4. Genomes, structural biology and drug discovery: combating the impacts of mutations in genetic disease and antibiotic resistance.

    PubMed

    Pandurangan, Arun Prasad; Ascher, David B; Thomas, Sherine E; Blundell, Tom L

    2017-04-15

    For over four decades structural biology has been used to understand the mechanisms of disease, and structure-guided approaches have demonstrated clearly that they can contribute to many aspects of early drug discovery, both computationally and experimentally. Structure can also inform our understanding of impacts of mutations in human genetic diseases and drug resistance in cancers and infectious diseases. We discuss the ways that structural insights might be useful in both repurposing off-licence drugs and guide the design of new molecules that might be less susceptible to drug resistance in the future.

  5. Evolutionary Explanations for Antibiotic Resistance in Daily Press, Online Websites and Biology Textbooks in Sweden

    ERIC Educational Resources Information Center

    Bohlin, Gustav; Höst, Gunnar E.

    2015-01-01

    The present study explores the extent and precision of evolutionary explanations for antibiotic resistance in communication directed toward the Swedish public. Bacterial resistance develops through evolutionary mechanisms and knowledge of these helps to explain causes underlying the growing prevalence of resistant strains, as well as important…

  6. Activation of Photosynthesis and Resistance to Photoinhibition in Cyanobacteria within Biological Desert Crust1[w

    PubMed Central

    Harel, Yariv; Ohad, Itzhak; Kaplan, Aaron

    2004-01-01

    Filamentous cyanobacteria are the main primary producers in biological desert sand crusts. The cells are exposed to extreme environmental conditions including temperature, light, and diurnal desiccation/rehydration cycles. We have studied the kinetics of activation of photosynthesis during rehydration of the cyanobacteria, primarily Microcoleus sp., within crust samples collected in the Negev desert, Israel. We also investigated their susceptibility to photoinhibition. Activation of the photosynthetic apparatus, measured by fluorescence kinetics, thermoluminescence, and low temperature fluorescence emission spectra, did not require de novo protein synthesis. Over 50% of the photosystem II (PSII) activity, assembled phycobilisomes, and photosystem I (PSI) antennae were detected within less than 5 min of rehydration. Energy transfer to PSII and PSI by the respective antennae was fully established within 10 to 20 min of rehydration. The activation of a fraction of PSII population (about 20%–30%) was light and temperature-dependent but did not require electron flow to plastoquinone [was not inhibited by 3-(3,4-dichlorophenyl)-1,1-dimethylurea]. The cyanobacteria within the crusts are remarkably resistant to photoinhibition even in the absence of protein synthesis. The rate of PSII repair increased with light intensity and with time of exposure. Consequently, the extent of photoinhibition in high-light-exposed crusts reached a constant, relatively low, level. This is in contrast to model organisms such as Synechocystis sp. strain PCC 6803 where PSII activity declined continuously over the entire exposure to high illumination. Ability of the crust's organisms to rapidly activate photosynthesis upon rehydration and withstand photoinhibition under high light intensity may partly explain their ability to survive in this ecosystem. PMID:15466226

  7. Impact of the ahas transgene for herbicides resistance on biological nitrogen fixation and yield of soybean.

    PubMed

    Hungria, Mariangela; Nakatani, André Shigueyoshi; Souza, Rosinei Aparecida; Sei, Fernando Bonafé; de Oliveira Chueire, Ligia Maria; Arias, Carlos Arrabal

    2015-02-01

    Studies on the effects of transgenes in soybean [Glycine max (L.) Merr.] and the associated use of specific herbicides on biological nitrogen fixation (BNF) are still few, although it is important to ensure minimal impacts on benefits provided by the root-nodule symbiosis. Cultivance CV127 transgenic soybean is a cultivar containing the ahas gene, which confers resistance to herbicides of the imidazolinone group. The aim of this study was to assess the effects of the ahas transgene and of imidazolinone herbicide on BNF parameters and soybean yield. A large-scale set of field experiments was conducted, for three cropping seasons, at nine sites in Brazil, with a total of 20 trials. The experiment was designed as a completely randomized block with four replicates and the following treatments: (T1) near isogenic transgenic soybean (Cultivance CV127) + herbicide of the imidazolinone group (imazapyr); (T2) near isogenic transgenic soybean + conventional herbicides; and (T3) parental conventional soybean (Conquista) + conventional herbicides; in addition, two commercial cultivars were included, Monsoy 8001 (M-SOY 8001) (T4), and Coodetec 217 (CD 217) (T5). At the R2 growth stage, plants were collected and BNF parameters evaluated. In general, there were no effects on BNF parameters due to the transgenic trait or associated with the specific herbicide. Similarly, at the final harvest, no grain-yield effects were detected related to the ahas gene or to the specific herbicide. However, clear effects on BNF and grain yield were attributed to location and cropping season.

  8. Combined efficacy of biologically synthesized silver nanoparticles and different antibiotics against multidrug-resistant bacteria

    PubMed Central

    Naqvi, Syed Zeeshan Haider; Kiran, Urooj; Ali, Muhammad Ishtiaq; Jamal, Asif; Hameed, Abdul; Ahmed, Safia; Ali, Naeem

    2013-01-01

    Biological synthesis of nanoparticles is a growing innovative approach that is relatively cheaper and more environmentally friendly than current physicochemical processes. Among various microorganisms, fungi have been found to be comparatively more efficient in the synthesis of nanomaterials. In this research work, extracellular mycosynthesis of silver nanoparticles (AgNPs) was probed by reacting the precursor salt of silver nitrate (AgNO3) with culture filtrate of Aspergillus flavus. Initially, the mycosynthesis was regularly monitored by ultraviolet-visible spectroscopy, which showed AgNP peaks of around 400–470 nm. X-ray diffraction spectra revealed peaks of different intensities with respect to angle of diffractions (2θ) corresponding to varying configurations of AgNPs. Transmission electron micrographs further confirmed the formation of AgNPs in size ranging from 5–30 nm. Combined and individual antibacterial activities of the five conventional antibiotics and AgNPs were investigated against eight different multidrug-resistant bacterial species using the Kirby–Bauer disk-diffusion method. The decreasing order of antibacterial activity (zone of inhibition in mm) of antibiotics, AgNPs, and their conjugates against bacterial group (average) was; ciprofloxacin + AgNPs (23) . imipenem + AgNPs (21) > gentamycin + AgNPs (19) > vancomycin + AgNPs (16) > AgNPs (15) . imipenem (14) > trimethoprim + AgNPs (14) > ciprofloxacin (13) > gentamycin (11) > vancomycin (4) > trimethoprim (0). Overall, the synergistic effect of antibiotics and nanoparticles resulted in a 0.2–7.0 (average, 2.8) fold-area increase in antibacterial activity, which clearly revealed that nanoparticles can be effectively used in combination with antibiotics in order to improve their efficacy against various pathogenic microbes. PMID:23986635

  9. Fighting microbial drug resistance: a primer on the role of evolutionary biology in public health

    PubMed Central

    Perron, Gabriel G; Inglis, R Fredrik; Pennings, Pleuni S; Cobey, Sarah

    2015-01-01

    Although microbes have been evolving resistance to antimicrobials for millennia, the spread of resistance in pathogen populations calls for the development of new drugs and treatment strategies. We propose that successful, long-term resistance management requires a better understanding of how resistance evolves in the first place. This is an opportunity for evolutionary biologists to engage in public health, a collaboration that has substantial precedent. Resistance evolution has been an important tool for developing and testing evolutionary theory, especially theory related to the genetic basis of new traits and constraints on adaptation. The present era is no exception. The articles in this issue highlight the breadth of current research on resistance evolution and also its challenges. In this introduction, we review the conceptual advances that have been achieved from studying resistance evolution and describe a path forward. PMID:25861380

  10. Biological effects of emissions from resistance spot welding of zinc-coated material after controlled exposure of healthy human subjects.

    PubMed

    Gube, Monika; Kraus, Thomas; Lenz, Klaus; Reisgen, Uwe; Brand, Peter

    2014-06-01

    Do emissions from a resistance spot welding process of zinc-coated materials induce systemic inflammation in healthy subjects after exposure for 6 hours? Twelve healthy male subjects were exposed once for 6 hours either to filtered ambient air or to welding fume from resistance spot welding of zinc-coated material (mass concentration approximately 100 μg m). Biological effects were measured before, after, and 24 hours after exposure. At the concentrations used in this study, however, the suspected properties of ultrafine particles did not lead to systemic inflammation as reflected by high-sensitivity C-reactive protein or other endpoint parameters under consideration. Ultrafine particles from a resistance spot welding process of zinc-covered materials with a number concentration of about 10 cm and a mass concentration of about 100 μg m did not induce systemic inflammation.

  11. Transcriptomics and systems biology analysis in identification of specific pathways involved in cacao resistance and susceptibility to witches' broom disease.

    PubMed

    da Hora Junior, Braz Tavares; Poloni, Joice de Faria; Lopes, Maíza Alves; Dias, Cristiano Villela; Gramacho, Karina Peres; Schuster, Ivan; Sabau, Xavier; Cascardo, Júlio Cézar De Mattos; Mauro, Sônia Marli Zingaretti Di; Gesteira, Abelmon da Silva; Bonatto, Diego; Micheli, Fabienne

    2012-04-01

    This study reports on expression analysis associated with molecular systems biology of cacao-Moniliophthora perniciosa interaction. Gene expression data were obtained for two cacao genotypes (TSH1188, resistant; Catongo, susceptible) challenged or not with the fungus M. perniciosa and collected at three time points through disease. Using expression analysis, we identified 154 and 227 genes that are differentially expressed in TSH1188 and Catongo, respectively. The expression of some of these genes was confirmed by RT-qPCR. Physical protein-protein interaction (PPPI) networks of Arabidopsis thaliana orthologous proteins corresponding to resistant and susceptible interactions were obtained followed by cluster and gene ontology analyses. The integrated analysis of gene expression and systems biology allowed designing a general scheme of major mechanisms associated with witches' broom disease resistance/susceptibility. In this sense, the TSH1188 cultivar shows strong production of ROS and elicitors at the beginning of the interaction with M. perniciosa followed by resistance signal propagation and ROS detoxification. On the other hand, the Catongo genotype displays defense mechanisms that include the synthesis of some defense molecules but without success in regards to elimination of the fungus. This phase is followed by the activation of protein metabolism which is achieved with the production of proteasome associated with autophagy as a precursor mechanism of PCD. This work also identifies candidate genes for further functional studies and for genetic mapping and marker assisted selection.

  12. Genome Analysis of the First Extensively Drug-Resistant (XDR) Mycobacterium tuberculosis in Malaysia Provides Insights into the Genetic Basis of Its Biology and Drug Resistance

    PubMed Central

    Kuan, Chee Sian; Chan, Chai Ling; Yew, Su Mei; Toh, Yue Fen; Khoo, Jia-Shiun; Chong, Jennifer; Lee, Kok Wei; Tan, Yung-Chie; Yee, Wai-Yan; Ngeow, Yun Fong; Ng, Kee Peng

    2015-01-01

    The outbreak of extensively drug-resistant tuberculosis (XDR-TB) has become an increasing problem in many TB-burdened countries. The underlying drug resistance mechanisms, including the genetic variation favored by selective pressure in the resistant population, are partially understood. Recently, the first case of XDR-TB was reported in Malaysia. However, the detailed genotype family and mechanisms of the formation of multiple drugs resistance are unknown. We sequenced the whole genome of the UM 1072388579 strain with a 2-kb insert-size library and combined with that from previously sequenced 500-bp-insert paired-end reads to produce an improved sequence with maximal sequencing coverage across the genome. In silico spoligotyping and phylogenetic analyses demonstrated that UM 1072388579 strain belongs to an ancestral-like, non-Beijing clade of East Asia lineage. This is supported by the presence of a number of lineage-specific markers, including fadD28, embA, nuoD and pks7. Polymorphism analysis showed that the drug-susceptibility profile is correlated with the pattern of resistance mutations. Mutations in drug-efflux pumps and the cell wall biogenesis pathway such as mmpL, pks and fadD genes may play an important role in survival and adaptation of this strain to its surrounding environment. In this work, fifty-seven putative promoter SNPs were identified. Among them, we identified a novel SNP located at -4 T allele of TetR/acrR promoter as an informative marker to recognize strains of East Asian lineage. Our work indicates that the UM 1072388579 harbors both classical and uncommon SNPs that allow it to escape from inhibition by many antibiotics. This study provides a strong foundation to dissect the biology and underlying resistance mechanisms of the first reported XDR M. tuberculosis in Malaysia. PMID:26110649

  13. Genome Analysis of the First Extensively Drug-Resistant (XDR) Mycobacterium tuberculosis in Malaysia Provides Insights into the Genetic Basis of Its Biology and Drug Resistance.

    PubMed

    Kuan, Chee Sian; Chan, Chai Ling; Yew, Su Mei; Toh, Yue Fen; Khoo, Jia-Shiun; Chong, Jennifer; Lee, Kok Wei; Tan, Yung-Chie; Yee, Wai-Yan; Ngeow, Yun Fong; Ng, Kee Peng

    2015-01-01

    The outbreak of extensively drug-resistant tuberculosis (XDR-TB) has become an increasing problem in many TB-burdened countries. The underlying drug resistance mechanisms, including the genetic variation favored by selective pressure in the resistant population, are partially understood. Recently, the first case of XDR-TB was reported in Malaysia. However, the detailed genotype family and mechanisms of the formation of multiple drugs resistance are unknown. We sequenced the whole genome of the UM 1072388579 strain with a 2-kb insert-size library and combined with that from previously sequenced 500-bp-insert paired-end reads to produce an improved sequence with maximal sequencing coverage across the genome. In silico spoligotyping and phylogenetic analyses demonstrated that UM 1072388579 strain belongs to an ancestral-like, non-Beijing clade of East Asia lineage. This is supported by the presence of a number of lineage-specific markers, including fadD28, embA, nuoD and pks7. Polymorphism analysis showed that the drug-susceptibility profile is correlated with the pattern of resistance mutations. Mutations in drug-efflux pumps and the cell wall biogenesis pathway such as mmpL, pks and fadD genes may play an important role in survival and adaptation of this strain to its surrounding environment. In this work, fifty-seven putative promoter SNPs were identified. Among them, we identified a novel SNP located at -4 T allele of TetR/acrR promoter as an informative marker to recognize strains of East Asian lineage. Our work indicates that the UM 1072388579 harbors both classical and uncommon SNPs that allow it to escape from inhibition by many antibiotics. This study provides a strong foundation to dissect the biology and underlying resistance mechanisms of the first reported XDR M. tuberculosis in Malaysia.

  14. Clinical and biologic aspects of human cytomegalovirus resistance to antiviral drugs.

    PubMed

    Baldanti, Fausto; Lurain, Nell; Gerna, Giuseppe

    2004-05-01

    The emergence of human cytomegalovirus (HCMV) drug resistant strains is a life-threatening condition in immunocompromised individuals with active HCMV infection. HCMV drug resistance represented a major problem in patients with acquired immunodeficiency syndrome until the recent introduction of highly active antiretroviral combination therapy, which dramatically decreased the incidence in this clinical setting. However, HCMV resistance to antiviral drugs is now an emerging problem in the transplantation setting. The molecular mechanisms of HCMV drug resistance have been elucidated and rely on the selection during treatment of HCMV strains harboring mutations in two key viral genes: UL97 coding for a viral phosphotransferase and UL54 coding for the viral DNA polymerase.

  15. Silence of Long Noncoding RNA NEAT1 Inhibits Malignant Biological Behaviors and Chemotherapy Resistance in Gastric Cancer.

    PubMed

    Zhang, Jiale; Zhao, Bochao; Chen, Xiuxiu; Wang, Zhenning; Xu, Huimian; Huang, Baojun

    2017-04-11

    Gastric cancer (GC) is the most common solid tumor in digestive system. Nuclear-enriched abundant transcript 1 (NEAT1) gene is a lncRNA, and reveal potential oncogene role in several malignant tumors. The aim of this study is to investigate the expression and clinical significance of Nuclear Paraspeckle Assembly Transcript 1 (NEAT1) gene and its influence to malignant biologic behaviors and chemotherapy resistance to adriamycin in GC. This study found NEAT1 was up-regulated in GC tissues and cells, especially in in GC adriamycin-resistant cells. NEAT1 silence in SGC7901 cells could inhibit proliferation and invasion ability, and promote cell apoptosis significantly. NEAT1 silence in adriamycin-resistant SGC7901/ADR cells also depressed the half maximal inhibitory concentration (IC50) for adriamycin, chemotherapy resistance to adriamycin was inhibited significantly. NEAT1 knockdown promoted apoptosis in SGC7901/ADR cells induced by adriamycin. In summary, lncRNA NEAT1 is high-expressed in GC and functions as an oncogene to modulate apoptosis, invasion, proliferation and chemotherapy resistance of GC cells, which might be a novel potential therapeutic target for GC.

  16. On the multiscale origins of fracture resistance in human bone and its biological degradation

    SciTech Connect

    Zimmermann, Elizabeth A.; Barth, Holly D.; Ritchie, Robert O.

    2012-03-09

    Akin to other mineralized tissues, human cortical bone can resist deformation and fracture due to the nature of its hierarchical structure, which spans the molecular to macroscopic length-scales. Deformation at the smallest scales, mainly through the composite action of the mineral and collagen, contributes to bone?s strength or intrinsic fracture resistance, while crack-tip shielding mechanisms active on the microstructural scale contribute to the extrinsic fracture resistance once cracking begins. The efficiency with which these structural features can resist fracture at both small and large length-scales becomes severely degraded with such factors as aging, irradiation and disease. Indeed aging and irradiation can cause changes to the cross-link profile at fibrillar length-scales as well as changes at the three orders of magnitude larger scale of the osteonal structures, both of which combine to inhibit the bone's overall resistance to the initiation and growth of cracks.

  17. Biological Cost of Single and Multiple Norfloxacin Resistance Mutations in Escherichia coli Implicated in Urinary Tract Infections

    PubMed Central

    Lindgren, Patricia Komp; Marcusson, Linda L.; Sandvang, Dorthe; Frimodt-Møller, Niels; Hughes, Diarmaid

    2005-01-01

    Resistance to fluoroquinolones in urinary tract infection (UTIs) caused by Escherichia coli is associated with multiple mutations, typically those that alter DNA gyrase and DNA topoisomerase IV and those that regulate AcrAB-TolC-mediated efflux. We asked whether a fitness cost is associated with the accumulation of these multiple mutations. Mutants of the susceptible E. coli UTI isolate Nu14 were selected through three to five successive steps with norfloxacin. Each selection was performed with the MIC of the selected strain. After each selection the MIC was measured; and the regions of gyrA, gyrB, parC, and parE, previously associated with resistance mutations, and all of marOR and acrR were sequenced. The first selection step yielded mutations in gyrA, gyrB, and marOR. Subsequent selection steps yielded mutations in gyrA, parE, and marOR but not in gyrB, parC, or acrR. Resistance-associated mutations were identified in almost all isolates after selection steps 1 and 2 but in less than 50% of isolates after subsequent selection steps. Selected strains were competed in vitro, in urine, and in a mouse UTI infection model against the starting strain, Nu14. First-step mutations were not associated with significant fitness costs. However, the accumulation of three or more resistance-associated mutations was usually associated with a large reduction in biological fitness, both in vitro and in vivo. Interestingly, in some lineages a partial restoration of fitness was associated with the accumulation of additional mutations in late selection steps. We suggest that the relative biological costs of multiple mutations may influence the evolution of E. coli strains that develop resistance to fluoroquinolones. PMID:15917531

  18. [Effects of biological regulated measures on active organic carbon and erosion-resistance in the Three Gorges Reservoir region soil].

    PubMed

    Huang, Ru; Huang, Lin; He, Bing-Hui; Zhou, Li-Jiang; Yu, Chuan; Wang, Feng

    2013-07-01

    To gain a better knowledge of characteristics of soils and provide a scientific basis for soil erosion control in the Three Gorges Reservoir Area, contents of aggregates and total soil organic carbon (SOC), as well as soil active organic carbon fractions including particulate organic carbon (POC), readily oxidized organic carbon (ROC), dissolved organic carbon (DOC), microbial biomass carbon (MBC) in the 0-30 cm soil layer under seven different biological regulated measures were studied by the field investigation combined with the laboratory analysis. Results showed that the content of the SOC and active organic carbon fractions decreased with the increasing soil depth; the content of the SOC and active organic carbon fractions in 0-10 cm was significantly higher than that in 20-30 cm. The stability of soil aggregates were also significantly influenced by biological regulated measures, the content of > 0.25 mm water-stable aggregates in seven types of biological regulated measures was in the order of Koelreuteria bipinnata + Cassia suffruticasa > hedgerows > closed forest > natural restoration > economic forest > traditional planting > control plot, moreover, the content of 0.25 mm water-stable aggregates correlated positively with the content of SOC. Soils under different biological regulated measures all demonstrated fractal features, and soil under the measure of Koelreuteria bipinnata + Cassia suffruticasa was found to have the lowest value of fractal dimension and soil erodiable K, indicating a relatively strong structure stability and erosion-resistant capacity. Negative correlation was observed when compared the content of active organic carbon fractions with the soil erodiable K. It can be concluded that properties of soil can be managed through biological regulated measures; thence had an influence on the soil erosion-resistant capacity.

  19. Corrosion resistance and biological activity of TiO2 implant coatings produced in oxygen-rich environments.

    PubMed

    Zhang, Rui; Wan, Yi; Ai, Xing; Liu, Zhanqiang; Zhang, Dong

    2017-01-01

    The physical and chemical properties of bio-titanium alloy implant surfaces play an important role in their corrosion resistance and biological activity. New turning and turning-rolling processes are presented, employing an oxygen-rich environment in order to obtain titanium dioxide layers that can both protect implants from corrosion and also promote cell adhesion. The surface topographies, surface roughnesses and chemical compositions of the sample surfaces were obtained using scanning electron microscopy, a white light interferometer, and the Auger electron spectroscopy, respectively. The corrosion resistance of the samples in a simulated body fluid was determined using electrochemical testing. Biological activity on the samples was also analyzed, using a vitro cell culture system. The results show that compared with titanium oxide layers formed using a turning process in air, the thickness of the titanium oxide layers formed using turning and turning-rolling processes in an oxygen-rich environment increased by 4.6 and 7.3 times, respectively. Using an oxygen-rich atmosphere in the rolling process greatly improves the corrosion resistance of the resulting samples in a simulated body fluid. On samples produced using the turning-rolling process, cells spread quickly and exhibited the best adhesion characteristics.

  20. Anti-Microbial Dendrimers against Multidrug-Resistant P. aeruginosa Enhance the Angiogenic Effect of Biological Burn-wound Bandages

    PubMed Central

    Abdel-Sayed, Philippe; Kaeppli, Ariane; Siriwardena, Thissa; Darbre, Tamis; Perron, Karl; Jafari, Paris; Reymond, Jean-Louis; Pioletti, Dominique P.; Applegate, Lee Ann

    2016-01-01

    Multi-drug resistant Pseudomonas aeruginosa has increased progressively and impedes further regression in mortality in burn patients. Such wound infections serve as bacterial reservoir for nosocomial infections and are associated with significant morbidity and costs. Anti-microbial polycationic dendrimers G3KL and G3RL, able to kill multi-drug resistant P. aeruginosa, have been previously developed. The combination of these dendrimers with a class of biological bandages made of progenitor skin cells, which secrete growth factors, could positively impact wound-healing processes. However, polycations are known to be used as anti-angiogenic agents for tumor suppression. Since, neovascularization is pivotal in the healing of deep burn-wounds, the use of anti-microbial dendrimers may thus hinder the healing processes. Surprisingly, we have seen in this study that G3KL and G3RL dendrimers can have angiogenic effects. Moreover, we have shown that a dendrimer concentration ranging between 50 and 100 μg/mL in combination with the biological bandages can suppress bacterial growth without altering cell viability up to 5 days. These results show that antimicrobial dendrimers can be used in combination with biological bandages and could potentially improve the healing process with an enhanced angiogenesis. PMID:26912450

  1. Biology of Acinetobacter baumannii: Pathogenesis, Antibiotic Resistance Mechanisms, and Prospective Treatment Options.

    PubMed

    Lee, Chang-Ro; Lee, Jung Hun; Park, Moonhee; Park, Kwang Seung; Bae, Il Kwon; Kim, Young Bae; Cha, Chang-Jun; Jeong, Byeong Chul; Lee, Sang Hee

    2017-01-01

    Acinetobacter baumannii is undoubtedly one of the most successful pathogens responsible for hospital-acquired nosocomial infections in the modern healthcare system. Due to the prevalence of infections and outbreaks caused by multi-drug resistant A. baumannii, few antibiotics are effective for treating infections caused by this pathogen. To overcome this problem, knowledge of the pathogenesis and antibiotic resistance mechanisms of A. baumannii is important. In this review, we summarize current studies on the virulence factors that contribute to A. baumannii pathogenesis, including porins, capsular polysaccharides, lipopolysaccharides, phospholipases, outer membrane vesicles, metal acquisition systems, and protein secretion systems. Mechanisms of antibiotic resistance of this organism, including acquirement of β-lactamases, up-regulation of multidrug efflux pumps, modification of aminoglycosides, permeability defects, and alteration of target sites, are also discussed. Lastly, novel prospective treatment options for infections caused by multi-drug resistant A. baumannii are summarized.

  2. Biology of Acinetobacter baumannii: Pathogenesis, Antibiotic Resistance Mechanisms, and Prospective Treatment Options

    PubMed Central

    Lee, Chang-Ro; Lee, Jung Hun; Park, Moonhee; Park, Kwang Seung; Bae, Il Kwon; Kim, Young Bae; Cha, Chang-Jun; Jeong, Byeong Chul; Lee, Sang Hee

    2017-01-01

    Acinetobacter baumannii is undoubtedly one of the most successful pathogens responsible for hospital-acquired nosocomial infections in the modern healthcare system. Due to the prevalence of infections and outbreaks caused by multi-drug resistant A. baumannii, few antibiotics are effective for treating infections caused by this pathogen. To overcome this problem, knowledge of the pathogenesis and antibiotic resistance mechanisms of A. baumannii is important. In this review, we summarize current studies on the virulence factors that contribute to A. baumannii pathogenesis, including porins, capsular polysaccharides, lipopolysaccharides, phospholipases, outer membrane vesicles, metal acquisition systems, and protein secretion systems. Mechanisms of antibiotic resistance of this organism, including acquirement of β-lactamases, up-regulation of multidrug efflux pumps, modification of aminoglycosides, permeability defects, and alteration of target sites, are also discussed. Lastly, novel prospective treatment options for infections caused by multi-drug resistant A. baumannii are summarized. PMID:28348979

  3. Investigation of the Biological Characteristics of Amantadine-Resistant Influenza A Virus.

    DTIC Science & Technology

    1997-06-18

    Since the first report of amantadine -resistant strains of influenza in 1981 there has been much speculation about the epidemiological impact of these...strains should the use of amantadine and rimantadine become widespread during an influenza pandemic. To date, there have been only two reports of...with either rimantadine or amantadine . Because naturally-occurring resistant strains are not isolated more often in the absence of drug therapy, it has

  4. [Resistant starches. Part II. Physico-chemical and technological aspects solution medico-biological problems].

    PubMed

    Iur'ev, V P; Gapparov, M M; Vasserman, L A; Genkina, N K

    2006-01-01

    This paper is a review of the recent literature data related to structure, composition and physico-chemical properties of starches as well as the special methods of processing of the starch containing raw sources producing the food products with increasing content of resistant starches. The prognosis is made about usefulness of such resistant starches for control of some metabolic disorder in human organism and for prophylactic aims.

  5. A genomic approach to understanding Heliothis and Helicoverpa resistance to chemical and biological insecticides

    PubMed Central

    Heckel, D. G.

    1998-01-01

    Genomics is the comparative study of the structure and function of entire genomes. Although the complete sequencing of the genome of any insect pest is far in the future, a genomic approach can be useful in the study of mechanisms of insecticide resistance. We describe this strategy for Heliothis and Helicoverpa, two of the most destructive genera of pest moths (Lepidoptera) worldwide. Genome-wide linkage mapping provides the location of major and minor resistance genes. Positional cloning identifies novel resistance genes, even when the mechanisms are poorly understood, as with resistance to Bacillus thuringiensis toxins. Anchor loci provide the reference points for comparing the genomes and the genetic architecture of resistance mechanisms among related species. Collectively, these tools enable the description of the evolutionary response of related, but independent, genomes to the common selective pressure of insecticides in the environment. They also provide information that is useful for targeted management of specific resistance genes, and may even speed the search for families of novel insecticidal targets in Lepidoptera.

  6. Antibiotics and heavy metals resistance and other biological characters in enterococci isolated from surface water of Monte Cotugno Lake (Italy).

    PubMed

    De Niederhäusern, Simona; Bondi, Moreno; Anacarso, Immacolata; Iseppi, Ramona; Sabia, Carla; Bitonte, Fabiano; Messi, Patrizia

    2013-01-01

    Considering the limited knowledge about the biological characters in enterococci isolated from surface waters, we investigated antibiotic and heavy-metal resistance, bacteriocin production, and some important virulence traits of 165 enterococci collected in water samples from Monte Cotugno Lake, the largest artificial basin built with earth in Europe. The species distribution of isolates was as follows: Enterococcus faecium (80%), Enterococcus faecalis (12.7%), Enterococcus casseliflavus (3%), Enterococcus mundtii (1.8%), Enterococcus hirae (1.8%), Enterococcus durans (0.6%). All enterococci showed heavy metal resistance toward Cu, Ni, Pb and Zn, were susceptible to Ag and Hg, and at the same time exhibited in large percentage (83.7%) resistance to one or more of the antibiotics tested. Relatively to virulence factor genes, 50.9% enterococci were positive for gelatinase (gelE), 10.9% for aggregation substance (agg), 12.7% and 66.6% for the cell wall adhesins (efaAfs and efaAfm), respectively. No amplicons were detected after PCR for cytolysin production (cylA, cylB and cylM) and enterococcal surface protein (esp) genes. Bacteriocin production was found in most of the isolates. Given that the waters of the Monte Cotugno Lake are used for different purposes, among which farming and recreational activities, they can contribute to spread enterococci endowed with virulence factors, and antibiotics and heavy metals resistance to humans.

  7. Beyond Antimicrobial Resistance: Evidence for a Distinct Role of the AcrD Efflux Pump in Salmonella Biology

    PubMed Central

    Buckner, Michelle M. C.; La Ragione, Roberto M.; Newcombe, Jane; Dwyer, Daniel J.; Ivens, Alasdair

    2016-01-01

    ABSTRACT For over 20 years, bacterial multidrug resistance (MDR) efflux pumps have been studied because of their impact on resistance to antimicrobials. However, critical questions remain, including why produce efflux pumps under non-antimicrobial treatment conditions, and why have multiple pumps if their only purpose is antimicrobial efflux? Salmonella spp. possess five efflux pump families, including the resistance-nodulation-division (RND) efflux pumps. Notably, the RND efflux pump AcrD has a unique substrate profile, distinct from other Salmonella efflux pumps. Here we show that inactivation of acrD results in a profoundly altered transcriptome and modulation of pathways integral to Salmonella biology. The most significant transcriptome changes were central metabolism related, with additional changes observed in pathogenicity, environmental sensing, and stress response pathway expression. The extent of tricarboxylic acid cycle and fumarate metabolism expression changes led us to hypothesize that acrD inactivation may result in motility defects due to perturbation of metabolite concentrations, such as fumarate, for which a role in motility has been established. Despite minimal detectable changes in flagellar gene expression, we found that an acrD mutant Salmonella enterica serovar Typhimurium isolate was significantly impaired for swarming motility, which was restored by addition of fumarate. The acrD mutant outcompeted the wild type in fitness experiments. The results of these diverse experiments provide strong evidence that the AcrD efflux pump is not simply a redundant system providing response resilience, but also has distinct physiological functions. Together, these data indicate that the AcrD efflux pump has a significant and previously underappreciated impact on bacterial biology, despite only minor perturbations of antibiotic resistance profiles. PMID:27879336

  8. Beyond Antimicrobial Resistance: Evidence for a Distinct Role of the AcrD Efflux Pump in Salmonella Biology.

    PubMed

    Buckner, Michelle M C; Blair, Jessica M A; La Ragione, Roberto M; Newcombe, Jane; Dwyer, Daniel J; Ivens, Alasdair; Piddock, Laura J V

    2016-11-22

    For over 20 years, bacterial multidrug resistance (MDR) efflux pumps have been studied because of their impact on resistance to antimicrobials. However, critical questions remain, including why produce efflux pumps under non-antimicrobial treatment conditions, and why have multiple pumps if their only purpose is antimicrobial efflux? Salmonella spp. possess five efflux pump families, including the resistance-nodulation-division (RND) efflux pumps. Notably, the RND efflux pump AcrD has a unique substrate profile, distinct from other Salmonella efflux pumps. Here we show that inactivation of acrD results in a profoundly altered transcriptome and modulation of pathways integral to Salmonella biology. The most significant transcriptome changes were central metabolism related, with additional changes observed in pathogenicity, environmental sensing, and stress response pathway expression. The extent of tricarboxylic acid cycle and fumarate metabolism expression changes led us to hypothesize that acrD inactivation may result in motility defects due to perturbation of metabolite concentrations, such as fumarate, for which a role in motility has been established. Despite minimal detectable changes in flagellar gene expression, we found that an acrD mutant Salmonella enterica serovar Typhimurium isolate was significantly impaired for swarming motility, which was restored by addition of fumarate. The acrD mutant outcompeted the wild type in fitness experiments. The results of these diverse experiments provide strong evidence that the AcrD efflux pump is not simply a redundant system providing response resilience, but also has distinct physiological functions. Together, these data indicate that the AcrD efflux pump has a significant and previously underappreciated impact on bacterial biology, despite only minor perturbations of antibiotic resistance profiles.

  9. Efflux pump-mediated antibiotics resistance: insights from computational structural biology.

    PubMed

    Fischer, Nadine; Raunest, Martin; Schmidt, Thomas H; Koch, Dennis C; Kandt, Christian

    2014-03-01

    The continuous rise of bacterial resistance against formerly effective pharmaceuticals is a major challenge for biomedical research. Since the first computational studies published seven years ago the simulation-based investigation of antibiotics resistance mediated by multidrug efflux pumps of the resistance nodulation division (RND) protein super family has grown into a vivid field of research. Here we review the employment of molecular dynamics computer simulations to investigate RND efflux pumps focusing on our group's recent contributions to this field studying questions of energy conversion and substrate transport in the inner membrane antiporter AcrB in Escherichia coli as well as access regulation and gating mechanism in the outer membrane efflux ducts TolC and OprM in E. coli and Pseudomonas aeruginosa.

  10. Molecular biology of amitraz resistance in cattle ticks of the genus Rhipicephalus.

    PubMed

    Jonsson, Nicholas N; Klafke, Guilherme; Corley, Sean W; Tidwell, Jason; Berry, Christina M; Koh-Tan, Hh Caline

    2018-01-01

    Amitraz is an important product for the control of cattle ticks around the world. In comparison with other products for the control of ticks, it is quite affordable and it has a rapid knock-down effect. It binds with and activates adrenergic neuro-receptors of animals and it inhibits the action of monoamine oxidases (MAO). Resistance to amitraz has been documented in Rhipicephalus microplus, R. decoloratus and R. appendiculatus. Four mechanisms of resistance have been proposed, each of which is supported by evidence but none of which has been definitively confirmed as the cause of resistance in the field. The proposed mechanisms include genetic target site insensitivity in two G protein-coupled receptors, the beta-adrenergic octopamine receptor (BAOR) and the octopamine/tyramine receptor (OCT/Tyr), increased expression or activity of monoamine oxidases and increased expression or activity of the ATP binding cassette transporter.

  11. Oestrogen alters adipocyte biology and protects female mice from adipocyte inflammation and insulin resistance.

    PubMed

    Stubbins, R E; Najjar, K; Holcomb, V B; Hong, J; Núñez, N P

    2012-01-01

    Obesity is associated with insulin resistance, liver steatosis and low-grade inflammation. The role of oestrogen in sex differences in the above co-morbidities is not fully understood. Our aim was to assess the role oestrogen has in modulating adipocyte size, adipose tissue oxidative stress, inflammation, insulin resistance and liver steatosis. To determine the role oestrogen has in the above co-morbidities related to obesity, we randomized C57BL/6J mice into four groups (15 mice per group): (i) male, (ii) non-ovariectomized female (novx), (iii) ovariectomized female (ovx) and (iv) ovariectomized female mice supplemented with 17β estradiol (ovx-E). Mice received either a low-fat (LF) or a high-fat (HF) diet for 10 weeks. Outcomes measured were bodyweight, body fat, adipocyte diameter, adipose tissue lipolysis markers, adipose tissue oxidative stress, inflammation, insulin resistance and liver steatosis. Male and ovx-female mice consuming the HF diet had a higher propensity of gaining weight, specifically in the form of body fat. Oestrogen protected female mice from adipocyte hypertrophy and from developing adipose tissue oxidative stress and inflammation. Moreover, novx-female and ovx-female+E mice had higher phosphorylated levels of protein kinase A and hormone sensitive lipase, markers associated with lipolysis. Additionally, male and ovx female mice had a higher propensity of developing liver steatosis and insulin resistance. In contrast, oestrogen protected female mice from developing liver steatosis and from becoming insulin resistant. We show that oestrogen protects female mice from adipocyte hypertrophy and adipose tissue oxidative stress and inflammation. Furthermore, oestrogen prevented female mice from developing liver steatosis and from becoming insulin resistant. © 2011 Blackwell Publishing Ltd.

  12. Proteomics of Skeletal Muscle: Focus on Insulin Resistance and Exercise Biology

    PubMed Central

    Deshmukh, Atul S.

    2016-01-01

    Skeletal muscle is the largest tissue in the human body and plays an important role in locomotion and whole body metabolism. It accounts for ~80% of insulin stimulated glucose disposal. Skeletal muscle insulin resistance, a primary feature of Type 2 diabetes, is caused by a decreased ability of muscle to respond to circulating insulin. Physical exercise improves insulin sensitivity and whole body metabolism and remains one of the most promising interventions for the prevention of Type 2 diabetes. Insulin resistance and exercise adaptations in skeletal muscle might be a cause, or consequence, of altered protein expressions profiles and/or their posttranslational modifications (PTMs). Mass spectrometry (MS)-based proteomics offer enormous promise for investigating the molecular mechanisms underlying skeletal muscle insulin resistance and exercise-induced adaptation; however, skeletal muscle proteomics are challenging. This review describes the technical limitations of skeletal muscle proteomics as well as emerging developments in proteomics workflow with respect to samples preparation, liquid chromatography (LC), MS and computational analysis. These technologies have not yet been fully exploited in the field of skeletal muscle proteomics. Future studies that involve state-of-the-art proteomics technology will broaden our understanding of exercise-induced adaptations as well as molecular pathogenesis of insulin resistance. This could lead to the identification of new therapeutic targets. PMID:28248217

  13. Preliminary investigation of biological resistance, water absorption and swelling of thermally compressed pine wood panels

    Treesearch

    Oner Unsal; S. Nami Kartal; Zeki Candan; Rachel Arango; Carol A. Clausen; Frederick Green

    2008-01-01

    Wood can be modified by compressive, thermal and chemical treatments. Compression of wood under thermal conditions is resulted in densification of wood. This study evaluated decay and termite resistance of thermally compressed pine wood panels at either 5 or 7 MPa and at either 120 or 150°C for one hour. The process caused increases in density and decreases in...

  14. Synthetic and Biological Studies of Sesquiterpene Polygodial: Activity of 9-Epipolygodial against Drug-Resistant Cancer Cells.

    PubMed

    Dasari, Ramesh; De Carvalho, Annelise; Medellin, Derek C; Middleton, Kelsey N; Hague, Frédéric; Volmar, Marie N M; Frolova, Liliya V; Rossato, Mateus F; De La Chapa, Jorge J; Dybdal-Hargreaves, Nicholas F; Pillai, Akshita; Mathieu, Véronique; Rogelj, Snezna; Gonzales, Cara B; Calixto, João B; Evidente, Antonio; Gautier, Mathieu; Munirathinam, Gnanasekar; Glass, Rainer; Burth, Patricia; Pelly, Stephen C; van Otterlo, Willem A L; Kiss, Robert; Kornienko, Alexander

    2015-12-01

    Polygodial, a terpenoid dialdehyde isolated from Polygonum hydropiper L., is a known agonist of the transient receptor potential vanilloid 1 (TRPV1). In this investigation a series of polygodial analogues were prepared and investigated for TRPV1-agonist and anticancer activities. These experiments led to the identification of 9-epipolygodial, which has antiproliferative potency significantly exceeding that of polygodial. 9-Epipolygodial was found to maintain potency against apoptosis-resistant cancer cells as well as those displaying the multidrug-resistant (MDR) phenotype. In addition, the chemical feasibility for the previously proposed mechanism of action of polygodial, involving the formation of a Paal-Knorr pyrrole with a lysine residue on the target protein, was demonstrated by the synthesis of a stable polygodial pyrrole derivative. These studies reveal rich chemical and biological properties associated with polygodial and its direct derivatives. These compounds should inspire further work in this area aimed at the development of new pharmacological agents, or the exploration of novel mechanisms of covalent modification of biological molecules with natural products.

  15. Tetracycline Antibiotics: Mode of Action, Applications, Molecular Biology, and Epidemiology of Bacterial Resistance

    PubMed Central

    Chopra, Ian; Roberts, Marilyn

    2001-01-01

    Tetracyclines were discovered in the 1940s and exhibited activity against a wide range of microorganisms including gram-positive and gram-negative bacteria, chlamydiae, mycoplasmas, rickettsiae, and protozoan parasites. They are inexpensive antibiotics, which have been used extensively in the prophlylaxis and therapy of human and animal infections and also at subtherapeutic levels in animal feed as growth promoters. The first tetracycline-resistant bacterium, Shigella dysenteriae, was isolated in 1953. Tetracycline resistance now occurs in an increasing number of pathogenic, opportunistic, and commensal bacteria. The presence of tetracycline-resistant pathogens limits the use of these agents in treatment of disease. Tetracycline resistance is often due to the acquisition of new genes, which code for energy-dependent efflux of tetracyclines or for a protein that protects bacterial ribosomes from the action of tetracyclines. Many of these genes are associated with mobile plasmids or transposons and can be distinguished from each other using molecular methods including DNA-DNA hybridization with oligonucleotide probes and DNA sequencing. A limited number of bacteria acquire resistance by mutations, which alter the permeability of the outer membrane porins and/or lipopolysaccharides in the outer membrane, change the regulation of innate efflux systems, or alter the 16S rRNA. New tetracycline derivatives are being examined, although their role in treatment is not clear. Changing the use of tetracyclines in human and animal health as well as in food production is needed if we are to continue to use this class of broad-spectrum antimicrobials through the present century. PMID:11381101

  16. Biological resistance of polyethylene composites made with chemically modified fiber or flour

    Treesearch

    Rebecca E. Ibach; Craig M. Clemons

    2002-01-01

    The role of moisture in the biological decay of wood-plastic composites was investigated. Southern pine wood fiber and ponderosa pine wood flour were chemically modified using either acetic anhydride (AA), butylene oxide (BO), or propylene oxide (PO). A 50:50 mixture of high density polyethylene and either chemically modified fiber or flour, or untreated fiber or flour...

  17. The effect on biological and moisture resistance of epichlorohydrin chemically modified wood

    Treesearch

    Rebecca E. Ibach; Beom-Goo Lee

    2002-01-01

    Southern pine solid wood and fiber were chemically modified with epichlorohydrin to help in understanding the role of moisture in the mechanism of biological effectiveness of chemically modified wood. The solid wood had weight gains from 11% to 34%, while the fiber had weight gains from 9% to 75%. After modification, part of the specimens were water leached for 2 weeks...

  18. EPIDEMIOLOGICAL AND GENETICAL STUDIES ON THE DRUG-RESISTANCE OF SHIGELLAE AND STAPHYLOCOCCI.

    DTIC Science & Technology

    ANTIBIOTICS , RESISTANCE (BIOLOGY)), (*SHIGELLA, RESISTANCE(BIOLOGY)), (*STAPHYLOCOCCUS, RESISTANCE(BIOLOGY)), EPIDEMIOLOGY, GENETICS, DRUGS, BACTERIOPHAGES, TETRACYCLINES, PENICILLINS, ESCHERICHIA COLI, JAPAN

  19. Biological activity of Pityrosporum. I. Enhancement of resistance in mice stimulated by Pityrosporum against Salmonella typhimurium.

    PubMed Central

    Takahashi, M; Ushijima, T; Ozaki, Y

    1984-01-01

    The effect of administration with Pityrosporum (P. orbiculare, P. ovale, P. pachydermatis and Pityrosporum sp.) on susceptibility of mice to Salmonella typhimurium infection was studied. Pretreatment of mice with 50 mg (wet weight) of killed Pityrosporum 4 days prior to the intraperitoneal (i.p.) challenge of 4 X 10(5) (10 LD50) S. typhimurium elicited resistance comparable to that induced by 500 micrograms (dry weight) of killed Propionibacterium acnes and over 30% of the infected mice survived. Among the species tested, P. pachydermatis was slightly less effective. The challenged organisms were not detected from the blood of mice treated with Pityrosporum but were present in the liver and spleen in approximately level amounts (10(4)-10(5)/organ) during the course of testing. These results suggest that the increased resistance in mice is the result of stimulation of the reticuloendothelial system by Pityrosporum. PMID:6368372

  20. Synthesis and Biological Evaluation of Muraymycin Analogues Active against Anti-Drug-Resistant Bacteria

    PubMed Central

    2010-01-01

    Muraymycin analogues with a lipophilic substituent were synthesized using an Ugi four-component assemblage. This approach provides ready access to a range of analogues simply by altering the aldehyde component. The impact of the lipophilic substituent on the antibacterial activity was very large, and analogues 7b−e and 8b−e exhibited good activity against a range of Gram-positive bacterial pathogens including methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus faecium. This study also showed that the accessory urea-dipeptide motif contributes to MraY inhibitory and antibacterial activity. The knowledge obtained from our structure−activity relationship study of muraymycins provides further direction toward the design of potent MraY inhibitors. This study has set the stage for the generation of novel antibacterial “lead” compounds based on muraymycins. PMID:24900205

  1. Synthesis and Biological Evaluation of Muraymycin Analogues Active against Anti-Drug-Resistant Bacteria.

    PubMed

    Tanino, Tetsuya; Ichikawa, Satoshi; Al-Dabbagh, Bayan; Bouhss, Ahmed; Oyama, Hiroshi; Matsuda, Akira

    2010-09-09

    Muraymycin analogues with a lipophilic substituent were synthesized using an Ugi four-component assemblage. This approach provides ready access to a range of analogues simply by altering the aldehyde component. The impact of the lipophilic substituent on the antibacterial activity was very large, and analogues 7b-e and 8b-e exhibited good activity against a range of Gram-positive bacterial pathogens including methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus faecium. This study also showed that the accessory urea-dipeptide motif contributes to MraY inhibitory and antibacterial activity. The knowledge obtained from our structure-activity relationship study of muraymycins provides further direction toward the design of potent MraY inhibitors. This study has set the stage for the generation of novel antibacterial "lead" compounds based on muraymycins.

  2. Nanotextured stainless steel for improved corrosion resistance and biological response in coronary stenting

    NASA Astrophysics Data System (ADS)

    Mohan, Chandini C.; Prabhath, Anupama; Cherian, Aleena Mary; Vadukumpully, Sajini; Nair, Shantikumar V.; Chennazhi, Krishnaprasad; Menon, Deepthy

    2014-12-01

    Nanosurface engineering of metallic substrates for improved cellular response is a persistent theme in biomaterials research. The need to improve the long term prognosis of commercially available stents has led us to adopt a `polymer-free' approach which is cost effective and industrially scalable. In this study, 316L stainless steel substrates were surface modified by hydrothermal treatment in alkaline pH, with and without the addition of a chromium precursor, to generate a well adherent uniform nanotopography. The modified surfaces showed improved hemocompatibility and augmented endothelialization, while hindering the proliferation of smooth muscle cells. Moreover, they also exhibited superior material properties like corrosion resistance, surface integrity and reduced metal ion leaching. The combination of improved corrosion resistance and selective vascular cell viability provided by nanomodification can be successfully utilized to offer a cell-friendly solution to the inherent limitations pertinent to bare metallic stents.

  3. Nanotextured stainless steel for improved corrosion resistance and biological response in coronary stenting.

    PubMed

    Mohan, Chandini C; Prabhath, Anupama; Cherian, Aleena Mary; Vadukumpully, Sajini; Nair, Shantikumar V; Chennazhi, Krishnaprasad; Menon, Deepthy

    2015-01-14

    Nanosurface engineering of metallic substrates for improved cellular response is a persistent theme in biomaterials research. The need to improve the long term prognosis of commercially available stents has led us to adopt a 'polymer-free' approach which is cost effective and industrially scalable. In this study, 316L stainless steel substrates were surface modified by hydrothermal treatment in alkaline pH, with and without the addition of a chromium precursor, to generate a well adherent uniform nanotopography. The modified surfaces showed improved hemocompatibility and augmented endothelialization, while hindering the proliferation of smooth muscle cells. Moreover, they also exhibited superior material properties like corrosion resistance, surface integrity and reduced metal ion leaching. The combination of improved corrosion resistance and selective vascular cell viability provided by nanomodification can be successfully utilized to offer a cell-friendly solution to the inherent limitations pertinent to bare metallic stents.

  4. Biological activity of Pityrosporum. I. Enhancement of resistance in mice stimulated by Pityrosporum against Salmonella typhimurium.

    PubMed

    Takahashi, M; Ushijima, T; Ozaki, Y

    1984-04-01

    The effect of administration with Pityrosporum (P. orbiculare, P. ovale, P. pachydermatis and Pityrosporum sp.) on susceptibility of mice to Salmonella typhimurium infection was studied. Pretreatment of mice with 50 mg (wet weight) of killed Pityrosporum 4 days prior to the intraperitoneal (i.p.) challenge of 4 X 10(5) (10 LD50) S. typhimurium elicited resistance comparable to that induced by 500 micrograms (dry weight) of killed Propionibacterium acnes and over 30% of the infected mice survived. Among the species tested, P. pachydermatis was slightly less effective. The challenged organisms were not detected from the blood of mice treated with Pityrosporum but were present in the liver and spleen in approximately level amounts (10(4)-10(5)/organ) during the course of testing. These results suggest that the increased resistance in mice is the result of stimulation of the reticuloendothelial system by Pityrosporum.

  5. Epithelial Plasticity in Castration-Resistant Prostate Cancer: Biology of the Lethal Phenotype

    DTIC Science & Technology

    2014-07-01

    included either abiraterone (n=8), enzalutamide (n=7), nilutamide (n=6), or ketoconazole (n=2). The remainder of the men received protocol-directed...Prior therapies ADT or orchiectomy Bicalutamide, nilutamide, or flutamide, n (%) Ketoconazole , n (%) Abiraterone, enzalutamide, or TAK700, n...Efficacy of docetaxel-based chemotherapy following ketoconazole in metastatic castration-resistant prostate cancer. Urol Oncol 2012 (epub ahead of print

  6. Biological Cost of Different Mechanisms of Colistin Resistance and Their Impact on Virulence in Acinetobacter baumannii

    PubMed Central

    Moreno, Antonio; Fernández, Nathalie; Vallejo, Juán A.; Aranda, Jesús; Adler, Ben; Harper, Marina; Boyce, John D.

    2014-01-01

    Two mechanisms of resistance to colistin have been described in Acinetobacter baumannii. One involves complete loss of lipopolysaccharide (LPS), resulting from mutations in lpxA, lpxC, or lpxD, and the second is associated with phosphoethanolamine addition to LPS, mediated through mutations in pmrAB. In order to assess the clinical impacts of both resistance mechanisms, A. baumannii ATCC 19606 and its isogenic derivatives, AL1851 ΔlpxA, AL1852 ΔlpxD, AL1842 ΔlpxC, and ATCC 19606 pmrB, were analyzed for in vitro growth rate, in vitro and in vivo competitive growth, infection of A549 respiratory alveolar epithelial cells, virulence in the Caenorhabditis elegans model, and virulence in a systemic mouse infection model. The in vitro growth rate of the lpx mutants was clearly diminished; furthermore, in vitro and in vivo competitive-growth experiments revealed a reduction in fitness for both mutant types. Infection of A549 cells with ATCC 19606 or the pmrB mutant resulted in greater loss of viability than with lpx mutants. Finally, the lpx mutants were highly attenuated in both the C. elegans and mouse infection models, while the pmrB mutant was attenuated only in the C. elegans model. In summary, while colistin resistance in A. baumannii confers a clear selective advantage in the presence of colistin treatment, it causes a noticeable cost in terms of overall fitness and virulence, with a more striking reduction associated with LPS loss than with phosphoethanolamine addition. Therefore, we hypothesize that colistin resistance mediated by changes in pmrAB will be more likely to arise in clinical settings in patients treated with colistin. PMID:24189257

  7. [Study on difference of biological characteristics and resistance to powdery mildew of different Astragalus populations].

    PubMed

    Cao, Jian-Jun; Liang, Zong-Suo; Wang, Wei-Ling; Duan, Qi-Mei

    2008-05-01

    To study difference among populations which belong to Astragalus membranaceus and A. membranaceus var. mongholicus on morphology, habit, characteristics of physiology and resistance to powdery mildew, and classify them in order to provide theoretical basis for breeding and improving varieties. Morphology, habits, isozyme and soluble protein electrophoretograms were compared among the populations. They were categorized by cluster analysis based on those electrophoretograms. Different ability of resistance to powdery mildew was also studied through comparing disease indices among six populations. The results showed A. membranaceus var. mongholicus was distinctly different from A. membranaceus. There was a special type in colonies of A. membranaceus, which showed hairy upper epidermis of leaflets and later florescence. Astragalus for medicine could be categorized in three types A. membranaceus var. mongholicus, A. membranaceus early florescence type and A. membranaceus late florescence type. Among them A. membranaceus var. mongholicus is most resistant to powdery mildew, while A. membranaceus is easily infected, and the early florescence type is even more easily infected.

  8. Population biology of Gram-positive pathogens: high-risk clones for dissemination of antibiotic resistance

    PubMed Central

    Willems, Rob J. L.; Hanage, William P; Bessen, Debra E.; Feil, Edward J.

    2011-01-01

    Infections caused by multi-resistant Gram positive bacteria represent a major health burden in the community as well as in hospitalized patients. Staphylococcus aureus, Enterococcus faecalis and Enterococcus faecium are well-known pathogens of hospitalized patients, frequently linked with resistance against multiple antibiotics, compromising effective therapy. Streptococcus pneumoniae and Streptococcus pyogenes are important pathogens in the community and S. aureus has recently emerged as an important community-acquired pathogen. Population genetic studies reveal that recombination prevails as a driving force of genetic diversity in E. faecium, E. faecalis, S. pneumoniae, and S. pyogenes and thus, these species are weakly clonal. Although recombination has a relatively modest role driving the genetic variation of the core genome of S. aureus, the horizontal acquistion of resistance and virulence genes plays a key role in the emergence of new clinically relevant clones in this species. In this review we discuss the population genetics of E. faecium, E. faecalis, S. pneumoniae, S. pyogenes, and S. aureus. Knowledge of the population structure of these pathogens is not only highly relevant for (molecular) epidemiological research but also for identifying the genetic variation that underlies changes in clinical behaviour, to improve our understanding of the pathogenic behaviour of particular clones and to identify novel targets for vaccines or immunotherapy. PMID:21658083

  9. Environmental and biological factors influencing the UV-C resistance of Listeria monocytogenes.

    PubMed

    Gayán, E; Serrano, M J; Pagán, R; Álvarez, I; Condón, S

    2015-04-01

    In this investigation, the effect of microbiological factors (strain, growth phase, exposition to sublethal stresses, and photorepair ability), treatment medium characteristics (pH, water activity, and absorption coefficient), and processing parameters (dose and temperature) on the UV resistance of Listeria monocytogenes was studied. The dose to inactivate 99.99% of the initial population of the five strains tested ranged from 21.84 J/mL (STCC 5672) to 14.66 J/mL (STCC 4031). The UV inactivation of the most resistant strain did not change in different growth phases and after exposure to sublethal heat, acid, basic, and oxidative shocks. The pH and water activity of the treatment medium did not affect the UV resistance of L. monocytogenes, whereas the inactivation rate decreased exponentially with the absorption coefficient. The lethal effect of UV radiation increased synergistically with temperature between 50 and 60 °C (UV-H treatment). A UV-H treatment of 27.10 J/mL at 55 °C reached 2.99 and 3.69 Log10 inactivation cycles of L. monocytogenes in orange juice and vegetable broth, and more than 5 Log10 cycles in apple juice and chicken broth. This synergistic effect opens the possibility to design UV combined processes for the pasteurization of liquid foods with high absorptivity. Copyright © 2014 Elsevier Ltd. All rights reserved.

  10. Molecular biology of castration-resistant prostate cancer: basis for the novel therapeutic targets.

    PubMed

    Mellado, Begoña; Marin Aguilera, Mercedes; Pereira, Maria Veronica

    2013-06-01

    Prostate cancer cells express the androgen receptor (AR) and need the presence of androgens to survive. Androgen suppression is the gold standard first-line therapy for metastatic disease. Almost all prostate cancer patients initially respond to hormonal therapy, but most of them gradually develop castration-resistant progression. Recent evidence has shown that progression at the castration resistant prostate cancer (CRPC) stage is often mediated by AR signalling. Importantly, subsequent AR androgen inhibition, by abiraterone acetate or enzalutamide, has shown to improve patients' survival. Several mechanisms that enhance AR signalling in an androgen-depleted environment have been elucidated:(1) AR mutations that allow activation by low androgen levels or by other endogenous steroids, (2) AR amplification and/or overexpression,(3)increased local intracrine synthesis of androgens, (4) changes in AR cofactors and (5) cross-talk with cytokines and growth factors. Today, there are under development a number of novel agents targeting the AR signaling pathway. This article reviews the postulated mechanisms of AR-driven resistance to androgen suppression that have contributed to the development of new hormonal therapeutic strategies in prostate cancer.

  11. Characterization of the corrosion resistance of several alloys to dilute biologically active solutions

    NASA Technical Reports Server (NTRS)

    Walsh, Daniel W.

    1990-01-01

    Sulfate reducing bacteria and acid producing bacteria/fungi detected in hygiene waters increased the corrosion rate in aluminum alloy. Biologically active media enhanced the formation of pits on metal coupons. Direct observation of gas evolved at the corrosion sample, coupled with scanning electron microscopy (SEM) and energy dispersive x-ray analysis of the corrosion products indicates that the corrosion rate is increased because the presence of bacteria favor the reduction of hydrogen as the cathodic reaction through the reaction of oxygen and water. SEM verifies the presence of microbes in a biofilm on the surface of corroding samples. The bacterial consortia are associated with anodic sites on the metal surface, aggressive pitting occurs adjacent to biofilms. Many pits are associated with triple points and inclusions in the aluminum alloy microstructure. Similar bacterial colonization was found on the stainless steel samples. Fourier transform Infrared Spectroscopy confirmed the presence of carbonyl groups in pitted areas of samples exposed to biologically active waters.

  12. Synergistic and Additive Effect of Oregano Essential Oil and Biological Silver Nanoparticles against Multidrug-Resistant Bacterial Strains

    PubMed Central

    Scandorieiro, Sara; de Camargo, Larissa C.; Lancheros, Cesar A. C.; Yamada-Ogatta, Sueli F.; Nakamura, Celso V.; de Oliveira, Admilton G.; Andrade, Célia G. T. J.; Duran, Nelson; Nakazato, Gerson; Kobayashi, Renata K. T.

    2016-01-01

    Bacterial resistance to conventional antibiotics has become a clinical and public health problem, making therapeutic decisions more challenging. Plant compounds and nanodrugs have been proposed as potential antimicrobial alternatives. Studies have shown that oregano (Origanum vulgare) essential oil (OEO) and silver nanoparticles have potent antibacterial activity, also against multidrug-resistant strains; however, the strong organoleptic characteristics of OEO and the development of resistance to these metal nanoparticles can limit their use. This study evaluated the antibacterial effect of a two-drug combination of biologically synthesized silver nanoparticles (bio-AgNP), produced by Fusarium oxysporum, and OEO against Gram-positive and Gram-negative bacteria, including multidrug-resistant strains. OEO and bio-AgNP showed bactericidal effects against all 17 strains tested, with minimal inhibitory concentrations (MIC) ranging from 0.298 to 1.193 mg/mL and 62.5 to 250 μM, respectively. Time-kill curves indicated that OEO acted rapidly (within 10 min), while the metallic nanoparticles took 4 h to kill Gram-negative bacteria and 24 h to kill Gram-positive bacteria. The combination of the two compounds resulted in a synergistic or additive effect, reducing their MIC values and reducing the time of action compared to bio-AgNP used alone, i.e., 20 min for Gram-negative bacteria and 7 h for Gram-positive bacteria. Scanning electron microscopy (SEM) revealed similar morphological alterations in Staphylococcus aureus (non-methicillin-resistant S. aureus, non-MRSA) cells exposed to three different treatments (OEO, bio-AgNP and combination of the two), which appeared cell surface blebbing. Individual and combined treatments showed reduction in cell density and decrease in exopolysaccharide matrix compared to untreated bacterial cells. It indicated that this composition have an antimicrobial activity against S. aureus by disrupting cells. Both compounds showed very low

  13. Bacterial silver resistance: molecular biology and uses and misuses of silver compounds.

    PubMed

    Silver, Simon

    2003-06-01

    Resistance to silver compounds as determined by bacterial plasmids and genes has been defined by molecular genetics. Silver resistance conferred by the Salmonella plasmid pMGH100 involves nine genes in three transcription units. A sensor/responder (SilRS) two-component transcriptional regulatory system governs synthesis of a periplasmic Ag(I)-binding protein (SilE) and two efflux pumps (a P-type ATPase (SilP) plus a three-protein chemiosmotic RND Ag(I)/H+ exchange system (SilCBA)). The same genes were identified on five of 19 additional IncH incompatibility class plasmids but thus far not on other plasmids. Of 70 random enteric isolates from a local hospital, isolates from catheters and other Ag-exposed sites, and total genomes of enteric bacteria, 10 have recognizable sil genes. The centrally located six genes are found and functional in the chromosome of Escherichia coli K-12, and also occur on the genome of E. coli O157:H7. The use of molecular epidemiological tools will establish the range and diversity of such resistance systems in clinical and non-clinical sources. Silver compounds are used widely as effective antimicrobial agents to combat pathogens (bacteria, viruses and eukaryotic microorganisms) in the clinic and for public health hygiene. Silver cations (Ag+) are microcidal at low concentrations and used to treat burns, wounds and ulcers. Ag is used to coat catheters to retard microbial biofilm development. Ag is used in hygiene products including face creams, "alternative medicine" health supplements, supermarket products for washing vegetables, and water filtration cartridges. Ag is generally without adverse effects for humans, and argyria (irreversible discoloration of the skin resulting from subepithelial silver deposits) is rare and mostly of cosmetic concern.

  14. Characterising the biology of novel lytic bacteriophages infecting multidrug resistant Klebsiella pneumoniae.

    PubMed

    Kęsik-Szeloch, Agata; Drulis-Kawa, Zuzanna; Weber-Dąbrowska, Beata; Kassner, Jerzy; Majkowska-Skrobek, Grażyna; Augustyniak, Daria; Lusiak-Szelachowska, Marzanna; Zaczek, Maciej; Górski, Andrzej; Kropinski, Andrew M

    2013-03-28

    Members of the genus Klebsiella are among the leading microbial pathogens associated with nosocomial infection. The increased incidence of antimicrobial resistance in these species has propelled the need for alternate/combination therapeutic regimens to aid clinical treatment. Bacteriophage therapy forms one of these alternate strategies. Electron microscopy, burst size, host range, sensitivity of phage particles to temperature, chloroform, pH, and restriction digestion of phage DNA were used to characterize Klebsiella phages. Of the 32 isolated phages eight belonged to the family Myoviridae, eight to the Siphoviridae whilst the remaining 16 belonged to the Podoviridae. The host range of these phages was characterised against 254 clinical Enterobacteriaceae strains including multidrug resistant Klebsiella isolates producing extended-spectrum beta-lactamases (ESBLs). Based on their lytic potential, six of the phages were further characterised for burst size, physicochemical properties and sensitivity to restriction endonuclease digestion. In addition, five were fully sequenced. Multiple phage-encoded host resistance mechanisms were identified. The Siphoviridae phage genomes (KP16 and KP36) contained low numbers of host restriction sites similar to the strategy found in T7-like phages (KP32). In addition, phage KP36 encoded its own DNA adenine methyltransferase. The φKMV-like KP34 phage was sensitive to all endonucleases used in this study. Dam methylation of KP34 DNA was detected although this was in the absence of an identifiable phage encoded methyltransferase. The Myoviridae phages KP15 and KP27 both carried Dam and Dcm methyltransferase genes and other anti-restriction mechanisms elucidated in previous studies. No other anti-restriction mechanisms were found, e.g. atypical nucleotides (hmC or glucosyl hmC), although Myoviridae phage KP27 encodes an unknown anti-restriction mechanism that needs further investigation.

  15. Study of the influence of sporulation conditions on heat resistance of Geobacillus stearothermophilus used in the development of biological indicators for steam sterilization.

    PubMed

    Guizelini, Belquis P; Vandenberghe, Luciana P S; Sella, Sandra Regina B R; Soccol, Carlos Ricardo

    2012-12-01

    Biological indicators are important tools in infection control via sterilization process monitoring. The use of a standardized spore crop with a well-defined heat resistance will guarantee the quality of a biological indicator. Ambient factors during sporulation can affect spore characteristics and properties, including heat resistance. The aim of this study is to evaluate the main sporulation factors responsible for heat resistance in Geobacillus stearothermophilus, a useful biological indicator for steam sterilization. A sequence of a three-step optimization of variables (initial pH, nutrient concentration, tryptone, peptone, beef extract, yeast extract, manganese sulfate, magnesium sulfate, calcium chloride and potassium phosphate) was carried out to screen those that have a significant influence on heat resistance of produced spores. The variable exerting greatest influence on G. stearothermophilus heat resistance during sporulation was found to be the initial pH. Lower nutrient concentration and alkaline pH around 8.5 tended to enhance decimal reduction time at 121 °C (D(121°C)). A central composite design enabled a fourfold enhancement in heat resistance, and the model obtained accurately describes positive pH and negative manganese sulfate concentration influence on spore heat resistance.

  16. Biological protein-resistance layer construction of recombinant hirudin on polymethyl methacrylate IOL surface.

    PubMed

    Zheng, Zhiwen; Jiao, Yan; Ren, Li; Wang, Yingjun

    2015-03-01

    In this article, the surface of intraocular len material PMMA was first aminated for activation on which some polar groups generated such as C-N, COO(-), -OH, NH3(+), etc. Then the anticoagulant drugs recombinant hirudin (rH) was grafted with amido bonds to look forward to resist the adsorption of nonspecific protein or cells in tear, even the cataract. The detailed analysis and discussion about the grafting quantity, molography, wettability, electric charges, chemical structure, and the dynamic adsorption of protein Fn on the material surface were carried on by the technology of ultraviolet photometric, contact angle, solid Zeta potential, X-ray photoelectron spectroscopy, and quartz crystal microbalance. The surface with a certain amount of rH modification existed more hydrophilic due to the amphiphilic structure than before, on which the protein adsorption was the most unstable. The results indicated that the rH modification improved the resistance of PMMA to nonspecific adsorption of protein Fn to achieve the expectative effect.

  17. Ultrasensitive detection of drug resistant cancer cells in biological matrixes using an amperometric nanobiosensor.

    PubMed

    Chandra, Pranjal; Noh, Hui-Bog; Pallela, Ramjee; Shim, Yoon-Bo

    2015-08-15

    Multidrug resistance (MDR) is a key issue in the failure of cancer chemotherapy and its detection will be helpful to develop suitable therapeutic strategies for cancer patients and overcome the death rates. In this direction, we designed a new amperometric sensor (a medical device prototype) to detect drug resistant cancer cells by sensing "Permeability glycoprotein (P-gp)". The sensor probe is fabricated by immobilizing monoclonal P-gp antibody on the gold nanoparticles (AuNPs) conducting polymer composite. The detection relies on a sandwich-type approach using a bioconjugate, where the aminophenyl boronic acid (APBA) served as a recognition molecule which binds with the cell surface glycans and hydrazine (Hyd) served as an electrocatalyst for the reduction of H2O2 which are attached on multi-wall carbon nanotube (MWCNT) (APBA-MWCNT-Hyd). A linear range for the cancer cell detection is obtained between 50 and 100,000 cells/mL with the detection limit of 23±2 cells/mL. The proposed immunosensor is successfully applied to detect MDR cancer cells (MDRCC) in serum and mixed cell samples. Interferences by drug sensitive (SKBr-3 and HeLa), noncancerous cells (HEK-293 and OSE), and other chemical molecules present in the real sample matrix are examined. The sensitivity of the proposed immunosensor is excellent compared with the conventional reporter antibody based assay. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. Empirical resistive-force theory for slender biological filaments in shear-thinning fluids.

    PubMed

    Riley, Emily E; Lauga, Eric

    2017-06-01

    Many cells exploit the bending or rotation of flagellar filaments in order to self-propel in viscous fluids. While appropriate theoretical modeling is available to capture flagella locomotion in simple, Newtonian fluids, formidable computations are required to address theoretically their locomotion in complex, nonlinear fluids, e.g., mucus. Based on experimental measurements for the motion of rigid rods in non-Newtonian fluids and on the classical Carreau fluid model, we propose empirical extensions of the classical Newtonian resistive-force theory to model the waving of slender filaments in non-Newtonian fluids. By assuming the flow near the flagellum to be locally Newtonian, we propose a self-consistent way to estimate the typical shear rate in the fluid, which we then use to construct correction factors to the Newtonian local drag coefficients. The resulting non-Newtonian resistive-force theory, while empirical, is consistent with the Newtonian limit, and with the experiments. We then use our models to address waving locomotion in non-Newtonian fluids and show that the resulting swimming speeds are systematically lowered, a result which we are able to capture asymptotically and to interpret physically. An application of the models to recent experimental results on the locomotion of Caenorhabditis elegans in polymeric solutions shows reasonable agreement and thus captures the main physics of swimming in shear-thinning fluids.

  19. Empirical resistive-force theory for slender biological filaments in shear-thinning fluids

    NASA Astrophysics Data System (ADS)

    Riley, Emily E.; Lauga, Eric

    2017-06-01

    Many cells exploit the bending or rotation of flagellar filaments in order to self-propel in viscous fluids. While appropriate theoretical modeling is available to capture flagella locomotion in simple, Newtonian fluids, formidable computations are required to address theoretically their locomotion in complex, nonlinear fluids, e.g., mucus. Based on experimental measurements for the motion of rigid rods in non-Newtonian fluids and on the classical Carreau fluid model, we propose empirical extensions of the classical Newtonian resistive-force theory to model the waving of slender filaments in non-Newtonian fluids. By assuming the flow near the flagellum to be locally Newtonian, we propose a self-consistent way to estimate the typical shear rate in the fluid, which we then use to construct correction factors to the Newtonian local drag coefficients. The resulting non-Newtonian resistive-force theory, while empirical, is consistent with the Newtonian limit, and with the experiments. We then use our models to address waving locomotion in non-Newtonian fluids and show that the resulting swimming speeds are systematically lowered, a result which we are able to capture asymptotically and to interpret physically. An application of the models to recent experimental results on the locomotion of Caenorhabditis elegans in polymeric solutions shows reasonable agreement and thus captures the main physics of swimming in shear-thinning fluids.

  20. Profiles of miRNAs matched to biology in aromatase inhibitor resistant breast cancer

    PubMed Central

    Hoppe, Reiner; Fan, Ping; Büttner, Florian; Winter, Stefan; Tyagi, Amit K.; Cunliffe, Heather; Jordan, V. Craig; Brauch, Hiltrud

    2016-01-01

    Aromatase inhibitor (AI) resistance during breast cancer treatment is mimicked by MCF-7:5C (5C) and MCF-7:2A (2A) cell lines that grow spontaneously. Survival signaling is reconfigured but cells are vulnerable to estradiol (E2)-inducible apoptosis. These model systems have alterations of stress related pathways including the accumulation of endoplasmic reticulum, oxidative, and inflammatory stress that occur prior to E2-induced apoptosis. We investigated miRNA expression profiles of 5C and 2A to characterize their AI resistance phenotypes. Affymetrix GeneChip miRNA2.0 arrays identified 184 miRNAs differentially expressed in 2A and 5C compared to E2-free wild-type MCF-7:WS8. In 5C, 34 miRNAs of the DLK1-DIO3 locus and miR-31 were overexpressed, whereas miR-222 was low. TCGA data revealed poor and favorable overall survival for low miR-31 and miR-222 levels, respectively (HR=3.0, 95% CI:1.9-4.8; HR=0.3, 95% CI:0.1-0.6). Targets of deregulated miRNAs were identified using CLIP-confirmed TargetScan predictions. KEGG enrichment analyses for 5C- and 2A-specific target gene sets revealed pathways associated with cell proliferation including insulin, mTOR, and ErbB signaling as well as immune response and metabolism. Key genes overrepresented in 5C- and 2A-specific pathway interaction networks including EGFR, IGF1R and PIK3R1 had lower protein levels in 5C compared to 2A and were found to be differentially modulated by respective miRNA sets. Distinct up-regulated miRNAs from the DLK1-DIO3 locus may cause these attenuative effects as they are predicted to interact with corresponding 3′ untranslated regions. These new miRNA profiles become an important regulatory database to explore E2-induced apoptotic mechanisms of clinical relevance for the treatment of resistant breast cancer. PMID:27659519

  1. Integrated management of fusarium wilt of chickpea with sowing date, host resistance, and biological control.

    PubMed

    Landa, Blanca B; Navas-Cortés, Juan A; Jiménez-Díaz, Rafael M

    2004-09-01

    ABSTRACT A 3-year experiment was conducted in field microplots infested with Fusarium oxysporum f. sp. ciceris race 5 at Córdoba, Spain, in order to assess efficacy of an integrated management strategy for Fusarium wilt of chickpea that combined the choice of sowing date, use of partially resistant chickpea genotypes, and seed and soil treatments with biocontrol agents Bacillus megaterium RGAF 51, B. subtilis GB03, nonpathogenic F. oxysporum Fo 90105, and Pseudomonas fluorescens RG 26. Advancing the sowing date from early spring to winter significantly delayed disease onset, reduced the final disease intensity (amount of disease in a microplot that combines disease incidence and severity, expressed as a percentage of the maximum possible amount of disease in that microplot), and increased chickpea seed yield. A significant linear relationship was found between disease development over time and weather variables at the experimental site, with epidemics developing earlier and faster as mean temperature increased and accumulated rainfall decreased. Under conditions highly conducive for Fusarium wilt development, the degree of disease control depended primarily on choice of sowing date, and to a lesser extent on level of resistance of chickpea genotypes to F. oxysporum f. sp. ciceris race 5, and the biocontrol treatments. The main effects of sowing date, partially resistant genotypes, and biocontrol agents were a reduction in the rate of epidemic development over time, a reduction of disease intensity, and an increase in chickpea seedling emergence, respectively. Chickpea seed yield was influenced by all three factors in the study. The increase in chickpea seed yield was the most consistent effect of the biocontrol agents. However, that effect was primarily influenced by sowing date, which also determined disease development. Effectiveness of biocontrol treatments in disease management was lowest in January sowings, which were least favorable for Fusarium wilt. Sowing

  2. Altered biological and biochemical properties of a phosphonoacetate-resistant mutant of herpesvirus of turkeys.

    PubMed

    Lee, L F; Nazerian, K; Witter, R L; Leinbach, S S; Boezi, J A

    1978-01-01

    A phosphonoacetate (PA)-resistant mutant of the herpesvirus of turkeys (HVT) was isolated and characterized. The mutant (HVTpa) replicates in growth medium containing 300 microgram/ml of PA and shows in vitro temperature sensitivity at 41 degrees C (its 37 degrees C/41 degrees C efficiency of replication is about 5). HVTpa replicates poorly in chickens and fails to provide complete protection against MDV challenge. The HVTpa-induced DNA polymerase has an apparent inhibition constant for PA 10 times as great, an apparent inhibition constant for pyrophosphate, twice as great, and an apparent Michaelis constant for dCTP 2.5 times as great as the respective figures for the HVTwt-induced enzyme. The HVTpa-induced enzyme is also more thermolabile.

  3. Local recording of biological magnetic fields using Giant Magneto Resistance-based micro-probes

    PubMed Central

    Barbieri, Francesca; Trauchessec, Vincent; Caruso, Laure; Trejo-Rosillo, Josué; Telenczuk, Bartosz; Paul, Elodie; Bal, Thierry; Destexhe, Alain; Fermon, Claude; Pannetier-Lecoeur, Myriam; Ouanounou, Gilles

    2016-01-01

    The electrical activity of brain, heart and skeletal muscles generates magnetic fields but these are recordable only macroscopically, such as in magnetoencephalography, which is used to map neuronal activity at the brain scale. At the local scale, magnetic fields recordings are still pending because of the lack of tools that can come in contact with living tissues. Here we present bio-compatible sensors based on Giant Magneto-Resistance (GMR) spin electronics. We show on a mouse muscle in vitro, using electrophysiology and computational modeling, that this technology permits simultaneous local recordings of the magnetic fields from action potentials. The sensitivity of this type of sensor is almost size independent, allowing the miniaturization and shaping required for in vivo/vitro magnetophysiology. GMR-based technology can constitute the magnetic counterpart of microelectrodes in electrophysiology, and might represent a new fundamental tool to investigate the local sources of neuronal magnetic activity. PMID:27991562

  4. Local recording of biological magnetic fields using Giant Magneto Resistance-based micro-probes.

    PubMed

    Barbieri, Francesca; Trauchessec, Vincent; Caruso, Laure; Trejo-Rosillo, Josué; Telenczuk, Bartosz; Paul, Elodie; Bal, Thierry; Destexhe, Alain; Fermon, Claude; Pannetier-Lecoeur, Myriam; Ouanounou, Gilles

    2016-12-19

    The electrical activity of brain, heart and skeletal muscles generates magnetic fields but these are recordable only macroscopically, such as in magnetoencephalography, which is used to map neuronal activity at the brain scale. At the local scale, magnetic fields recordings are still pending because of the lack of tools that can come in contact with living tissues. Here we present bio-compatible sensors based on Giant Magneto-Resistance (GMR) spin electronics. We show on a mouse muscle in vitro, using electrophysiology and computational modeling, that this technology permits simultaneous local recordings of the magnetic fields from action potentials. The sensitivity of this type of sensor is almost size independent, allowing the miniaturization and shaping required for in vivo/vitro magnetophysiology. GMR-based technology can constitute the magnetic counterpart of microelectrodes in electrophysiology, and might represent a new fundamental tool to investigate the local sources of neuronal magnetic activity.

  5. A peptide-based biological coating for enhanced corrosion resistance of titanium alloy biomaterials in chloride-containing fluids.

    PubMed

    Muruve, Noah; Feng, Yuanchao; Platnich, Jaye; Hassett, Daniel; Irvin, Randall; Muruve, Daniel; Cheng, Frank

    2017-03-01

    Titanium alloys are common materials in the manufacturing of dental and orthopedic implants. Although these materials exhibit excellent biocompatibility, corrosion in response to biological fluids can impact prosthesis performance and longevity. In this work, a PEGylated metal binding peptide (D-K122-4-PEG), derived from bacteria Pseudomonas aeruginosa, was applied on a titanium (Ti) alloy, and the corrosion resistance of the coated alloy specimen was investigated in simulated chloride-containing physiological fluids by electrochemical impedance spectroscopy and micro-electrochemical measurements, surface characterization, and biocompatibility testing. Compared to uncoated specimen, the D-K122-4-PEG-coated Ti alloy demonstrates decreased corrosion current density without affecting the natural passivity. Morphological analysis using atomic force microscopy and scanning electron microscopy confirms a reduction in surface roughness of the coated specimens in the fluids. The D-K122-4-PEG does not affect the binding of HEK-293T cells to the surface of unpolished Ti alloy, nor does it increase the leukocyte activation properties of the metal. D-K122-4-PEG represents a promising coating to enhance the corrosion resistance of Ti alloys in physiological fluids, while maintaining an excellent biocompatibility.

  6. Cancer systems biology in the genome sequencing era: part 2, evolutionary dynamics of tumor clonal networks and drug resistance.

    PubMed

    Wang, Edwin; Zou, Jinfeng; Zaman, Naif; Beitel, Lenore K; Trifiro, Mark; Paliouras, Miltiadis

    2013-08-01

    A tumor often consists of multiple cell subpopulations (clones). Current chemo-treatments often target one clone of a tumor. Although the drug kills that clone, other clones overtake it and the tumor recurs. Genome sequencing and computational analysis allows to computational dissection of clones from tumors, while singe-cell genome sequencing including RNA-Seq allows profiling of these clones. This opens a new window for treating a tumor as a system in which clones are evolving. Future cancer systems biology studies should consider a tumor as an evolving system with multiple clones. Therefore, topics discussed in Part 2 of this review include evolutionary dynamics of clonal networks, early-warning signals (e.g., genome duplication events) for formation of fast-growing clones, dissecting tumor heterogeneity, and modeling of clone-clone-stroma interactions for drug resistance. The ultimate goal of the future systems biology analysis is to obtain a 'whole-system' understanding of a tumor and therefore provides a more efficient and personalized management strategies for cancer patients.

  7. Envenoming bites by kraits: the biological basis of treatment-resistant neuromuscular paralysis.

    PubMed

    Prasarnpun, S; Walsh, J; Awad, S S; Harris, J B

    2005-12-01

    Beta-bungarotoxin, a neurotoxic phospholipase A2 is a major fraction of the venom of kraits. The toxin was inoculated into one hind limb of young adult rats. The inoculated hind limb was paralysed within 3 h, and remained paralysed for 2 days. The paralysis was associated with the loss of synaptic vesicles from motor nerve terminal boutons, a decline in immunoreactivity of synaptophysin, SNAP-25 and syntaxin, a loss of muscle mass and the upregulation of NaV(1.5) mRNA and protein. Between 3 and 6 h after the inoculation of toxin, some nerve terminal boutons exhibited clear signs of degeneration. Others appeared to be in the process of withdrawing from the synaptic cleft and some boutons were fully enwrapped in terminal Schwann cell processes. By 12 h all muscle fibres were denervated. Re-innervation began at 3 days with the appearance of regenerating nerve terminals, a return of neuromuscular function in some muscles and a progressive increase in the immunoreactivity of synaptophysin, SNAP-25 and syntaxin. Full recovery occurred at 7 days. The data were compared with recently published clinical data on envenoming bites by kraits and by extrapolation we suggest that the acute, reversible denervation caused by beta-bungarotoxin is a credible explanation for the clinically important, profound treatment-resistant neuromuscular paralysis seen in human subjects bitten by these animals.

  8. Applications of supervised learning to biological signals: ECG signal quality and systemic vascular resistance.

    PubMed

    Redmond, Stephen J; Lee, Qim Yi; Xie, Yang; Lovell, Nigel H

    2012-01-01

    Discovering information encoded in non-invasively recorded biosignals which belies an individual's well-being can help facilitate the development of low-cost unobtrusive medical device technologies, or enable the unsupervised performance of physiological assessments without excessive oversight from trained clinical personnel. Although the unobtrusive or unsupervised nature of such technologies often results in less accurate measures than their invasive or supervised counterparts, this disadvantage is typically outweighed by the ability to monitor larger populations than ever before. The expected consequential benefit will be an improvement in healthcare provision and health outcomes for all. The process of discovering indicators of health in unsupervised or unobtrusive biosignal recordings, or automatically ensuring the validity and quality of such signals, is best realized when following a proven systematic methodology. This paper provides a brief tutorial review of supervised learning, which is a sub-discipline of machine learning, and discusses its application in the development of algorithms to interpret biosignals acquired in unsupervised or semi-supervised environments, with the aim of estimating well-being. Some specific examples in the disparate application areas of telehealth electrocardiogram recording and calculating post-operative systemic vascular resistance are discussed in the context of this systematic approach for information discovery.

  9. Design, Synthesis, Biological and Structural Evaluations of Novel HIV-1 Protease Inhibitors to Combat Drug Resistance

    PubMed Central

    Parai, Maloy Kumar; Huggins, David J.; Cao, Hong; Nalam, Madhavi N. L.; Ali, Akbar; Schiffer, Celia A.; Tidor, Bruce; Rana, Tariq M.

    2012-01-01

    A series of new HIV-1 protease inhibitors (PIs) were designed using a general strategy that combines computational structure-based design with substrate-envelope constraints. The PIs incorporate various alcohol-derived P2 carbamates with acyclic and cyclic heteroatomic functionalities into the (R)-hydroxyethylamine isostere. Most of the new PIs show potent binding affinities against wild-type HIV-1 protease and three multidrug resistant (MDR) variants, in particular inhibitors containing 2,2-dichloroacetamide, pyrrolidinone, imidazolidinone, and oxazolidinone moieties at P2 are the most potent with Ki values in the picomolar range. Several new PIs exhibit nanomolar antiviral potencies against patient-derived wild-type viruses from HIV-1 clades A, B, and C and two MDR variants. Crystal structure analyses of four potent inhibitors revealed that carbonyl groups of the new P2 moieties promote extensive hydrogen bond interactions with the invariant Asp-29 residue of the protease. These structure-activity relationship findings can be utilized to design new PIs with enhanced enzyme inhibitory and antiviral potencies. PMID:22708897

  10. Applying electrical resistivity tomography and biological methods to assess the surface-groundwater interaction in two Mediterranean rivers (central Spain)

    NASA Astrophysics Data System (ADS)

    Iepure, Sanda; Gómez Ortiz, David; Lillo Ramos, Javier; Rasines Ladero, Ruben; Persoiu, Aurel

    2014-05-01

    Delineation of the extent of hyporheic zone (HZ) in river ecosystems is problematic due to the scarcity of spatial information about the structure of riverbed sediments and the magnitude and extent of stream interactions with the parafluvial and riparian zones. The several existing methods vary in both quality and quantity of information and imply the use of hydrogeological and biological methods. In the last decades, various non-invasive geophysical techniques were developed to characterise the streambed architecture and also to provide detailed spatial information on its vertical and horizontal continuity. All classes of techniques have their strengths and limitations; therefore, in order to assess their potential in delineating the lateral and vertical spatial extents of alluvial sediments, we have combined the near-surface images obtained by electrical resistivity tomography (ERT) with biological assessment of invertebrates in two Mediterranean lowland rivers from central Spain. We performed in situ imaging of the thickness and continuity of alluvial sediments under the riverbed and parafluvial zone during base-flow conditions (summer 2013 and winter 2014) at two different sites with distinct lithology along the Tajuña and Henares Rivers. ERT was performed by installing the electrodes (1 m spacing) on a 47 m long transect normal to the river channel using a Wener-Schlumberger array, across both the riparian zones and the river bed. Invertebrates were collected in the streambed from a depth of 20-40 cm, using the Bou-Rouch method, and from boreholes drilled to a depth of 1.5 m in the riparian zone. The ERT images obtained at site 1 (medium and coarse sand dominated lithology) shows resistivity values ranging from ~20 to 80 ohm•m for the in-stream sediments, indicating a permeable zone up to ~ 0.5 m thick and extending laterally for ca. 5 m from the channel. These sediments contribute to active surface/hyporheic water exchanges and to low water retention in

  11. Do Offspring of Insects Feeding on Defoliation-Resistant Trees Have Better Biological Performance When Exposed to Nutritionally-Imbalanced Food?

    PubMed Central

    Quezada-Garcia, Roberto; Fuentealba, Alvaro; Nguyen, Ngoc; Bauce, Éric

    2015-01-01

    White spruce (Picea glauca (Moench) Voss) trees that are resistant or susceptible to spruce budworm (Choristoneura fumiferana (Clem.)) attack were identified in a southern Quebec plantation. Due to high mortality-induced selective pressures imposed by resistant trees on spruce budworm larvae, insects that survive on resistant trees exhibited greater biological performance than those on susceptible trees. We tested the hypothesis that this better biological performance is maintained across generations when progeny were subjected to nutritional stress. We collected pupae from resistant and susceptible trees (phenotype). Adults were reared under controlled laboratory conditions. Progeny were subsequently reared on two types of artificial diet (high vs. low quality). Low quality diet simulated food quality deterioration during outbreak conditions. Results confirmed that surviving insects collected from resistant trees have better performance than those from susceptible trees. Offspring performance (pupal mass, developmental time) was affected only by diet quality. These results suggest that adaptive advantages that would be acquired from parents fed on resistant trees are lost when progeny are exposed to nutritionally-imbalanced food, but the effects persist when larvae are fed a balanced diet. Offspring mortality, fecundity and fertility were positively influenced by parental origin (tree phenotype). PMID:26463069

  12. Do Offspring of Insects Feeding on Defoliation-Resistant Trees Have Better Biological Performance When Exposed to Nutritionally-Imbalanced Food?

    PubMed

    Quezada-Garcia, Roberto; Fuentealba, Alvaro; Nguyen, Ngoc; Bauce, Éric

    2015-01-12

    White spruce (Picea glauca (Moench) Voss) trees that are resistant or susceptible to spruce budworm (Choristoneura fumiferana (Clem.)) attack were identified in a southern Quebec plantation. Due to high mortality-induced selective pressures imposed by resistant trees on spruce budworm larvae, insects that survive on resistant trees exhibited greater biological performance than those on susceptible trees. We tested the hypothesis that this better biological performance is maintained across generations when progeny were subjected to nutritional stress. We collected pupae from resistant and susceptible trees (phenotype). Adults were reared under controlled laboratory conditions. Progeny were subsequently reared on two types of artificial diet (high vs. low quality). Low quality diet simulated food quality deterioration during outbreak conditions. Results confirmed that surviving insects collected from resistant trees have better performance than those from susceptible trees. Offspring performance (pupal mass, developmental time) was affected only by diet quality. These results suggest that adaptive advantages that would be acquired from parents fed on resistant trees are lost when progeny are exposed to nutritionally-imbalanced food, but the effects persist when larvae are fed a balanced diet. Offspring mortality, fecundity and fertility were positively influenced by parental origin (tree phenotype).

  13. Br-rich tips of calcified crab claws are less hard but more fracture resistant: a comparison of mineralized and heavy-element biological materials.

    PubMed

    Schofield, Robert M S; Niedbala, Jack C; Nesson, Michael H; Tao, Ye; Shokes, Jacob E; Scott, Robert A; Latimer, Matthew J

    2009-06-01

    We find that the spoon-like tips of the chelipeds (large claws) of the crab Pachygrapsus crassipes differ from the rest of the claw in that they are not calcified, but instead contain about 1% bromine--thus they represent a new example of a class of structural biological materials that contain heavy elements such as Zn, Mn, Fe, Cu, and Br bound in an organic matrix. X-ray absorption spectroscopy data suggest that the bromine is bound to phenyl rings, possibly in tyrosine. We measure a broad array of mechanical properties of a heavy-element biological material for the first time (abrasion resistance, coefficient of kinetic friction, energy of fracture, hardness, modulus of elasticity and dynamic mechanical properties), and we make a direct comparison with a mineralized tissue. Our results suggest that the greatest advantage of bromine-rich cuticle over calcified cuticle is resistance to fracture (the energy of fracture is about an order of magnitude greater than for calcified cuticle). The greatest advantage relative to unenriched cuticle, represented by ant mandible cuticle, is a factor of about 1.5 greater hardness and modulus of elasticity.The spoon-like tips gain additional fracture resistance from the orientation of the constituent laminae and from the viscoelasticity of the material. We suggest that fracture resistance is of greater importance in smaller organisms, and we speculate that one function of heavy elements in structural biological materials is to reduce molecular resonant frequencies and thereby increase absorption of energy from impacts.

  14. Biological Characteristics of Experimental Genotype Mixtures of Cydia Pomonella Granulovirus (CpGV): Ability to Control Susceptible and Resistant Pest Populations

    PubMed Central

    Graillot, Benoit; Bayle, Sandrine; Blachere-Lopez, Christine; Besse, Samantha; Siegwart, Myriam; Lopez-Ferber, Miguel

    2016-01-01

    The detection of resistance in codling moth (Cydia pomonella) populations against the Mexican isolate of its granulovirus (CpGV-M), raised questions on the sustainability of the use of this biological insecticide. In resistant host cells, CpGV-M is not able to complete its replication cycle because replication is blocked at an early step. Virus isolates able to overcome this resistance have been characterized—among them, the CpGV-R5 isolate. In mixed infections on resistant insects, both CpGV-M and CpGV-R5 viruses replicate, while CpGV-M alone does not induce mortality. Genetically heterogeneous virus populations, containing 50% of each CpGV-M and CpGV-R5 appear to control resistant host populations as well as CpGV-R5 alone at the same final concentration, even if the concentration of CpGV-R5 is only half in the former. The use of mixed genotype virus preparations instead of genotypically homogeneous populations may constitute a better approach than traditional methods for the development of baculovirus-based biological insecticides. PMID:27213431

  15. Wildfire-resistant biological soil crusts and fire-induced loss of soil stability in Palouse prairies, USA

    USGS Publications Warehouse

    Bowker, M.A.; Belnap, J.; Rosentreter, R.; Graham, B.

    2004-01-01

    Frequent low-intensity fires are a natural component of the ecology of the Palouse prairies of northwestern North America. To study the effects of fire upon biological soil crusts (BSCs) occurring in these grasslands, we sampled three burned (in 2000) sites and three unburned sites in the Hell's Canyon area (OR, USA) ???1 year post-fire. We measured vascular plant and BSC cover, soil microbe pigmentation, texture and chemistry, and soil surface physical properties (stability and rugosity). Festuca idahoensis was two times more abundant in unburned plots (P=0.0006), and vascular plant and litter cover were generally higher in unburned plots. At the community scale, there was no difference in the lichen and moss species composition, suggesting much less drastic effects of fire on BSCs than reported in other systems. Soil surface stability (measured using slake value) was significantly lower in burned sites than unburned sites (median value=5 versus 6, P=0.008), a result which is likely due to the greater density of lichens and mosses encountered in the unburned plots. Soil microbe pigmentation was lower in burned plots (P=0.03), suggesting that the biomass of photosynthetic microbes had decreased; however, the presence of intra- and extracellular pigments in burned soils indicates that microorganisms were not eradicated. Pigments most strongly associated with cyanobacteria were more abundant in unburned sites, suggesting that cyanobacteria may have been more strongly impacted by the fire than other BSC components. Composition of nutrients and surface rugosity did not differ significantly between treatments. We hypothesize that Palouse prairie soil crusts are relatively resistant to wildfire because of low fire intensity and their occupation of space away from the vascular plant fuel load.

  16. A functional biological network centered on XRCC3: a new possible marker of chemoradiotherapy resistance in rectal cancer patients

    PubMed Central

    Agostini, Marco; Zangrando, Andrea; Pastrello, Chiara; D'Angelo, Edoardo; Romano, Gabriele; Giovannoni, Roberto; Giordan, Marco; Maretto, Isacco; Bedin, Chiara; Zanon, Carlo; Digito, Maura; Esposito, Giovanni; Mescoli, Claudia; Lavitrano, Marialuisa; Rizzolio, Flavio; Jurisica, Igor; Giordano, Antonio; Pucciarelli, Salvatore; Nitti, Donato

    2015-01-01

    Preoperative chemoradiotherapy is widely used to improve local control of disease, sphincter preservation and to improve survival in patients with locally advanced rectal cancer. Patients enrolled in the present study underwent preoperative chemoradiotherapy, followed by surgical excision. Response to chemoradiotherapy was evaluated according to Mandard's Tumor Regression Grade (TRG). TRG 3, 4 and 5 were considered as partial or no response while TRG 1 and 2 as complete response. From pretherapeutic biopsies of 84 locally advanced rectal carcinomas available for the analysis, only 42 of them showed 70% cancer cellularity at least. By determining gene expression profiles, responders and non-responders showed significantly different expression levels for 19 genes (P < 0.001). We fitted a logistic model selected with a stepwise procedure optimizing the Akaike Information Criterion (AIC) and then validated by means of leave one out cross validation (LOOCV, accuracy = 95%). Four genes were retained in the achieved model: ZNF160, XRCC3, HFM1 and ASXL2. Real time PCR confirmed that XRCC3 is overexpressed in responders group and HFM1 and ASXL2 showed a positive trend. In vitro test on colon cancer resistant/susceptible to chemoradioterapy cells, finally prove that XRCC3 deregulation is extensively involved in the chemoresistance mechanisms. Protein-protein interactions (PPI) analysis involving the predictive classifier revealed a network of 45 interacting nodes (proteins) with TRAF6 gene playing a keystone role in the network. The present study confirmed the possibility that gene expression profiling combined with integrative computational biology is useful to predict complete responses to preoperative chemoradiotherapy in patients with advanced rectal cancer. PMID:26023803

  17. A functional biological network centered on XRCC3: a new possible marker of chemoradiotherapy resistance in rectal cancer patients.

    PubMed

    Agostini, Marco; Zangrando, Andrea; Pastrello, Chiara; D'Angelo, Edoardo; Romano, Gabriele; Giovannoni, Roberto; Giordan, Marco; Maretto, Isacco; Bedin, Chiara; Zanon, Carlo; Digito, Maura; Esposito, Giovanni; Mescoli, Claudia; Lavitrano, Marialuisa; Rizzolio, Flavio; Jurisica, Igor; Giordano, Antonio; Pucciarelli, Salvatore; Nitti, Donato

    2015-01-01

    Preoperative chemoradiotherapy is widely used to improve local control of disease, sphincter preservation and to improve survival in patients with locally advanced rectal cancer. Patients enrolled in the present study underwent preoperative chemoradiotherapy, followed by surgical excision. Response to chemoradiotherapy was evaluated according to Mandard's Tumor Regression Grade (TRG). TRG 3, 4 and 5 were considered as partial or no response while TRG 1 and 2 as complete response. From pretherapeutic biopsies of 84 locally advanced rectal carcinomas available for the analysis, only 42 of them showed 70% cancer cellularity at least. By determining gene expression profiles, responders and non-responders showed significantly different expression levels for 19 genes (P < 0.001). We fitted a logistic model selected with a stepwise procedure optimizing the Akaike Information Criterion (AIC) and then validated by means of leave one out cross validation (LOOCV, accuracy = 95%). Four genes were retained in the achieved model: ZNF160, XRCC3, HFM1 and ASXL2. Real time PCR confirmed that XRCC3 is overexpressed in responders group and HFM1 and ASXL2 showed a positive trend. In vitro test on colon cancer resistant/susceptible to chemoradioterapy cells, finally prove that XRCC3 deregulation is extensively involved in the chemoresistance mechanisms. Protein-protein interactions (PPI) analysis involving the predictive classifier revealed a network of 45 interacting nodes (proteins) with TRAF6 gene playing a keystone role in the network. The present study confirmed the possibility that gene expression profiling combined with integrative computational biology is useful to predict complete responses to preoperative chemoradiotherapy in patients with advanced rectal cancer.

  18. Establishment and biological characteristics of acquired gefitinib resistance in cell line NCI-H1975/gefinitib-resistant with epidermal growth factor receptor T790M mutation.

    PubMed

    Zhao, Bao-Xia; Wang, Jing; Song, Bo; Wei, Hong; Lv, Wei-Peng; Tian, Li-Min; Li, Mei; Lv, Shen

    2015-04-01

    Non‑small cell lung cancer (NSCLC) cells harboring mutations in the epidermal growth factor receptor (EGFR) gene initially respond well to EGFR tyrosine kinase inhibitors (TKI), including gefitinib. However the tumor cells will invariably develop acquired resistance to the drug. The EGFR T790M mutation is generally considered to be the molecular genetic basis of acquired TKI resistance. The present study aimed to explore how the T790M mutation induces tumor cells to escape inhibition by TKI treatment. An acquired gefitinib‑resistant cell line (NCI‑H1975/GR) was generated from the NCI‑H1975 human NSCLC cell line, which harbors the sensitive L858R and resistant T790M mutations of EGFR. The resistant cell line was established by exposing the cells intermittently to increasing concentrations of gefitinib. The mechanisms by which NSCLC acquires resistance to TKIs based on the T790M mutation, were investigated by detecting the protein expression levels of the EGFR/Kirsten rat sarcoma viral oncogene homolog (KRAS)/v‑Raf murine sarcoma viral oncogene homolog B (BRAF) transduction pathway, and epithelial‑mesenchymal transition (EMT) with immunocytochemistry. The resistance of the NCI‑H1975/GR cells to gefitinib was 2.009‑fold, as compared with the parent cells; however, the protein expression levels of EGFR, KRAS and BRAF were lower in the resistant cells. Some mesenchymal morphology was observed in the NCI‑H1975/GR cells, alongside a decreasing E‑cadherin expression and increasing vimentin expression. These results suggest that the reactivation of the EGFR/KRAS/BRAF transduction pathway was not detected in the NCI‑H1975/GR cells. EMT may have an important role in the development of acquired resistance to EGFR‑TKIs in NSCLC cells with sensitivity and resistance mutations.

  19. Durable resistance to the wheat rusts: Integrating systems biology and traditional phenotype-based research methods to guide the deployment of resistance genes

    PubMed Central

    Lowe, Iago; Cantu, Dario; Dubcovsky, Jorge

    2016-01-01

    Genes which confer partial resistance to the rusts in wheat figure prominently in discussions of potential durable resistance strategies. The positional cloning of the first of these genes, Lr34/Yr18 and Yr36, has revealed different protein structures, suggesting that the category of partial resistance genes, as defined by phenotype, likely groups together suites of functionally heterogenous genes. With the number of mapped partial rust resistance genes increasing rapidly as a result of ongoing advances in marker and sequencing technologies, breeding programs needing to select and prioritize genes for deployment confront a fundamental question: which genes or gene combinations are more likely to provide durable protection against these evolving pathogens? We argue that a refined classification of partial rust resistance genes is required to start answering this question, one based not merely on disease phenotype but also on gene cloning, molecular functional characterization, and interactions with other host and pathogen proteins. Combined with accurate and detailed disease phenotyping and standard genetic studies, an integrated wheat-rust interactome promises to provide the basis for a functional classification of partial resistance genes and thus a conceptual framework for their rational deployment. PMID:26900170

  20. Resistance of vectors of disease to pesticides. Fifth report of the WHO Expert Committee in Vector Biology and Control.

    PubMed

    1980-01-01

    The resistance of vectors (the term includes primary and intermediate vertebrate and invertebrate hosts and animal reservoirs of human and animal diseases) of disease to pesticides is a major problem faced by WHO member states in the control of vectorborne diseases. Since the meeting of the WHO Expert Committee on Insecticides in 1975, resistance has continued to increase and to affect disease control programs in many countries. The appearance of multiresistance in several important vectors has been the most significant development since the 1975 meeting. The sandfly Phlebotomus papatasi in Bihar, India has been found to be resistant to DDT, leaving the tsetse fly the only important vector species in which resistance has not been reported. This book discusses 1) pesticide resistance in arthropod vectors, malaria vectors, vectors of other diseases and disease reservoirs (rodents); 2) present status of research on resistance of vectors to pesticides, including the biochemistry and genetics of resistance; 3) measures to counteract resistance; 4) detection and monitoring of vector resistance to pesticides; 5) disseminatin of information and training; and 6) recommendations for future research and courses of action.

  1. MYC functions are specific in biological subtypes of breast cancer and confers resistance to endocrine therapy in luminal tumours

    PubMed Central

    Green, Andrew R; Aleskandarany, Mohammed A; Agarwal, Devika; Elsheikh, Somaia; Nolan, Christopher C; Diez-Rodriguez, Maria; Macmillan, R Douglas; Ball, Graham R; Caldas, Carlos; Madhusudan, Srinivasan; Ellis, Ian O; Rakha, Emad A

    2016-01-01

    Background: MYC is amplified in approximately 15% of breast cancers (BCs) and is associated with poor outcome. c-MYC protein is multi-faceted and participates in many aspects of cellular function and is linked with therapeutic response in BCs. We hypothesised that the functional role of c-MYC differs between molecular subtypes of BCs. Methods: We therefore investigated the correlation between c-MYC protein expression and other proteins involved in different cellular functions together with clinicopathological parameters, patients' outcome and treatments in a large early-stage molecularly characterised series of primary invasive BCs (n=1106) using immunuohistochemistry. The METABRIC BC cohort (n=1980) was evaluated for MYC mRNA expression and a systems biology approach utilised to identify genes associated with MYC in the different BC molecular subtypes. Results: High MYC and c-MYC expression was significantly associated with poor prognostic factors, including grade and basal-like BCs. In luminal A tumours, c-MYC was associated with ATM (P=0.005), Cyclin B1 (P=0.002), PIK3CA (P=0.009) and Ki67 (P<0.001). In contrast, in basal-like tumours, c-MYC showed positive association with Cyclin E (P=0.003) and p16 (P=0.042) expression only. c-MYC was an independent predictor of a shorter distant metastases-free survival in luminal A LN+ tumours treated with endocrine therapy (ET; P=0.013). In luminal tumours treated with ET, MYC mRNA expression was associated with BC-specific survival (P=0.001). In ER-positive tumours, MYC was associated with expression of translational genes while in ER-negative tumours it was associated with upregulation of glucose metabolism genes. Conclusions: c-MYC function is associated with specific molecular subtypes of BCs and its overexpression confers resistance to ET. The diverse mechanisms of c-MYC function in the different molecular classes of BCs warrants further investigation particularly as potential therapeutic targets. PMID:26954716

  2. Biological comparison of wild-type and zidovudine-resistant isolates of human immunodeficiency virus type 1 from the same subjects: susceptibility and resistance to other drugs.

    PubMed Central

    Rooke, R; Parniak, M A; Tremblay, M; Soudeyns, H; Li, X G; Gao, Q; Yao, X J; Wainberg, M A

    1991-01-01

    We used a viral endpoint dilution assay to show changes in the proportion of zidovudine (azidothymidine; AZT)-resistant viruses within a heterogeneous mixture of human immunodeficiency virus type 1 (HIV-1) quasispecies isolated from patients on long-term AZT therapy. Several HIV-1 isolates, which could replicate in 10 microM AZT, were susceptible to both 2',3'-dideoxycytidine and a novel cytosine analog BCH-189, in which a sulfur atom replaces the 3' carbon of the pentose ring. In certain instances, cross-resistance was seen with 3'-didehydro-2',3'-dideoxythymidine. Although most strains of AZT-resistant HIV-1 displayed reduced susceptibility to 3'-azido-2',3'-dideoxyuridine, two strains were identified for which this was not the case. PMID:1649576

  3. World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for Biological Treatment of Schizophrenia, part 1: update 2012 on the acute treatment of schizophrenia and the management of treatment resistance.

    PubMed

    Hasan, Alkomiet; Falkai, Peter; Wobrock, Thomas; Lieberman, Jeffrey; Glenthoj, Birte; Gattaz, Wagner F; Thibaut, Florence; Möller, Hans-Jürgen

    2012-07-01

    These updated guidelines are based on a first edition of the World Federation of Societies of Biological Psychiatry Guidelines for Biological Treatment of Schizophrenia published in 2005. For this 2012 revision, all available publications pertaining to the biological treatment of schizophrenia were reviewed systematically to allow for an evidence-based update. These guidelines provide evidence-based practice recommendations that are clinically and scientifically meaningful and these guidelines are intended to be used by all physicians diagnosing and treating people suffering from schizophrenia. Based on the first version of these guidelines, a systematic review of the MEDLINE/PUBMED database and the Cochrane Library, in addition to data extraction from national treatment guidelines, has been performed for this update. The identified literature was evaluated with respect to the strength of evidence for its efficacy and then categorised into six levels of evidence (A-F; Bandelow et al. 2008b, World J Biol Psychiatry 9:242). This first part of the updated guidelines covers the general descriptions of antipsychotics and their side effects, the biological treatment of acute schizophrenia and the management of treatment-resistant schizophrenia.

  4. InFlo: a novel systems biology framework identifies cAMP-CREB1 axis as a key modulator of platinum resistance in ovarian cancer.

    PubMed

    Dimitrova, N; Nagaraj, A B; Razi, A; Singh, S; Kamalakaran, S; Banerjee, N; Joseph, P; Mankovich, A; Mittal, P; DiFeo, A; Varadan, V

    2017-04-27

    Characterizing the complex interplay of cellular processes in cancer would enable the discovery of key mechanisms underlying its development and progression. Published approaches to decipher driver mechanisms do not explicitly model tissue-specific changes in pathway networks and the regulatory disruptions related to genomic aberrations in cancers. We therefore developed InFlo, a novel systems biology approach for characterizing complex biological processes using a unique multidimensional framework integrating transcriptomic, genomic and/or epigenomic profiles for any given cancer sample. We show that InFlo robustly characterizes tissue-specific differences in activities of signalling networks on a genome scale using unique probabilistic models of molecular interactions on a per-sample basis. Using large-scale multi-omics cancer datasets, we show that InFlo exhibits higher sensitivity and specificity in detecting pathway networks associated with specific disease states when compared to published pathway network modelling approaches. Furthermore, InFlo's ability to infer the activity of unmeasured signalling network components was also validated using orthogonal gene expression signatures. We then evaluated multi-omics profiles of primary high-grade serous ovarian cancer tumours (N=357) to delineate mechanisms underlying resistance to frontline platinum-based chemotherapy. InFlo was the only algorithm to identify hyperactivation of the cAMP-CREB1 axis as a key mechanism associated with resistance to platinum-based therapy, a finding that we subsequently experimentally validated. We confirmed that inhibition of CREB1 phosphorylation potently sensitized resistant cells to platinum therapy and was effective in killing ovarian cancer stem cells that contribute to both platinum-resistance and tumour recurrence. Thus, we propose InFlo to be a scalable and widely applicable and robust integrative network modelling framework for the discovery of evidence-based biomarkers

  5. Synthesis and biological evaluation of levofloxacin core-based derivatives with potent antibacterial activity against resistant Gram-positive pathogens.

    PubMed

    Huang, Xiaoguang; Bao, Yingxia; Zhu, Shaoxuan; Zhang, Xiaona; Lan, Shilong; Wang, Ting

    2015-09-15

    A series of C10 non-basic building block-substituted, levofloxacin core-based derivatives were synthesized in 43-86% yield. The antibacterial activity of these new fluoroquinolones was evaluated using a standard broth microdilution technique. The quinolone (S)-9-fluoro-10-(4-hydroxypiperidin-1-yl)-3-methyl-7-oxo-3,7-dihydro-2H-[1,4]oxazino[2,3,4-ij]quinoline-6-carboxylic acid L-arginine tetrahydrate exhibited superior antibacterial activity against quinolone-susceptible and resistant strains compared with the clinically used fluoroquinolones ciprofloxacin, levofloxacin, moxifloxacin, penicillin, and vancomycin, especially to the methicillin-resistant Staphylococcus aureus clinical isolates, penicillin-resistant Streptococcus pneumoniae clinical isolates, and Streptococcus pyogenes. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. Effects of siRNA-mediated silencing of myeloid cell leukelia-1 on the biological behaviors and drug resistance of gastric cancer cells

    PubMed Central

    Li, Bo-Pei; Liu, Jin-Lu; Chen, Jun-Qiang; Wang, Zhen; Mao, Yuan-Tian; Chen, Ye-Yang

    2015-01-01

    Objective: This study was to investigate the effects of siRNA mediated silencing of myeloid cell leukelia-1 (Mcl-1) on the biological behaviors and drug resistance of human drug-resistant gastric cancer (GC) cell lines, and to explore the potential mechanisms. Methods: siRNA targeting Mcl-1 mRNA were designed and independently transfected into SGC-7901/VCR and SGC-7901/DDP. Cell proliferation and drug sensitivity were examined by MTT assay. Cell apoptosis and cell cycle were detected by flow cytometry. Cell Invasion and migration abilities were detected by transwell chamber assays. The expressions of drug-resistance-related genes and apoptosis-related proteins were detected by quantitative real-time PCR and Western blot assay, respectively. Results: siRNA effectively inhibited the Mcl-1 expression, lowered the proliferation rate (P<0.05), raised the apoptosis rate (P<0.05), and arrested cells in S-phase (P<0.05). After inhibiting Mcl-1, the cell migration and invasion decreased (P<0.05), the resistance to VCR, DDP and 5-Fu was reversed to different extents (P<0.05), TS mRNA expression increased significantly (P<0.05), MDR1 remained unchanged (P>0.05), but DPD and TOP2A decreased significantly (P<0.05). Following Mcl-1 silencing, Bcl-2 was over-expressed in VCR-siRNA group, but the expressions of Fas and survivin reduced markedly (P<0.05); Bcl-2 and Fas expressions decreased significantly in DDP-siRNA group (P<0.05), but survivin expression remained unchanged. Conclusion: Mcl-1 is implicated in the proliferation, invasion, apoptosis and drug resistance of GC cells, and may be a promising target for the therapy of GC. PMID:26807186

  7. Design, synthesis of methotrexate-diosgenin conjugates and biological evaluation of their effect on methotrexate transport-resistant cells.

    PubMed

    Cai, Bangrong; Liao, Aimei; Lee, Kyung-Ku; Ban, Jae-Sam; Yang, Hyun-Sam; Im, Young Jun; Chun, ChangJu

    2016-12-01

    A series of methotrexate-diosgenin conjugates was designed and synthesized to enhance the passive internalization of methotrexate (MTX) into transport-resistant cells. The inhibitory effects of these conjugates on dihydrofolate reductase (DHFR), and their anti-proliferation behaviors against a transport-resistant breast cancer cell line, MDA-MB-231, were investigated. All of the synthesized conjugates retained an ability to inhibit DHFR after the diosgenin substitution. The MTX conjugates were much more potent against methotrexate-resistant MDA-MB-231 cells than MTX. Conjugate 18, containing a disulfide bond, exhibited the most potent anti-proliferative and DHFR inhibitory effects (IC50=4.1μM and 17.21nM, respectively). Anti-proliferative activity was higher in the conjugate with a longer space linker (conjugate 21) than those with shorter linkers (conjugates 19 and 20). These results suggest that diosgenin conjugation of MTX may be an effective way to overcome its transport resistance in cancer cells. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Biological characterization of lead-enhanced exopolysaccharide produced by a lead resistant Enterobacter cloacae strain P2B.

    PubMed

    Naik, Milind Mohan; Pandey, Anju; Dubey, Santosh Kumar

    2012-09-01

    A lead resistant bacterial strain isolated from effluent of lead battery manufacturing company of Goa, India has been identified as Enterobacter cloacae strain P2B based on morphological, biochemical characters, FAME profile and 16S rDNA sequence data. This bacterial strain could resist lead nitrate up to 1.6 mM. Significant increase in exopolysaccharide (EPS) production was observed as the production increased from 28 to 108 mg/L dry weight when exposed to 1.6 mM lead nitrate in Tris buffered minimal medium. Fourier-transformed infrared spectroscopy of this EPS revealed presence of several functional groups involved in metal binding viz. carboxyl, hydroxyl and amide groups along with glucuronic acid. Gas chromatography coupled with mass spectrometry analysis of alditol-acetate derivatives of acid hydrolysed EPS produced in presence of 1.6 mM lead nitrate demonstrated presence of several neutral sugars such as rhamnose, arabinose, xylose, mannose, galactose and glucose, which contribute to lead binding hydroxyl groups. Scanning electron microscope coupled with energy dispersive X-ray spectrometric analysis of this lead resistant strain exposed to 1.6 mM lead nitrate interestingly revealed mucous EPS surrounding bacterial cells which sequestered 17 % lead (as weight %) extracellularly and protected the bacterial cells from toxic effects of lead. This lead resistant strain also showed multidrug resistance. Thus these results significantly contribute to better understanding of structure, function and environmental application of lead-enhanced EPSs produced by bacteria. This lead-enhanced biopolymer can play a very important role in bioremediation of several heavy metals including lead.

  9. Three-way interaction between biological control insects, a congener and their shared parasitoid: Evidence of biotic resistance

    USDA-ARS?s Scientific Manuscript database

    Invasive plants are one of the strongest drivers of species extinctions. Weed biological control offers a sustainable and safe means of long-term population reduction of their target. Herbivores introduced for the control of invasive plants interact with the native community in addition to the top-d...

  10. Metabolomic Profiling of the Effects of Melittin on Cisplatin Resistant and Cisplatin Sensitive Ovarian Cancer Cells Using Mass Spectrometry and Biolog Microarray Technology

    PubMed Central

    Alonezi, Sanad; Tusiimire, Jonans; Wallace, Jennifer; Dufton, Mark J.; Parkinson, John A.; Young, Louise C.; Clements, Carol J.; Park, Jin Kyu; Jeon, Jong Woon; Ferro, Valerie A.; Watson, David G.

    2016-01-01

    In the present study, liquid chromatography-mass spectrometry (LC-MS) was employed to characterise the metabolic profiles of two human ovarian cancer cell lines A2780 (cisplatin-sensitive) and A2780CR (cisplatin-resistant) in response to their exposure to melittin, a cytotoxic peptide from bee venom. In addition, the metabolomics data were supported by application of Biolog microarray technology to examine the utilisation of carbon sources by the two cell lines. Data extraction with MZmine 2.14 and database searching were applied to provide metabolite lists. Principal component analysis (PCA) gave clear separation between the cisplatin-sensitive and resistant strains and their respective controls. The cisplatin-resistant cells were slightly more sensitive to melittin than the sensitive cells with IC50 values of 4.5 and 6.8 μg/mL respectively, although the latter cell line exhibited the greatest metabolic perturbation upon treatment. The changes induced by melittin in the cisplatin-sensitive cells led mostly to reduced levels of amino acids in the proline/glutamine/arginine pathway, as well as to decreased levels of carnitines, polyamines, adenosine triphosphate (ATP) and nicotinamide adenine dinucleotide (NAD+). The effects on energy metabolism were supported by the data from the Biolog assays. The lipid compositions of the two cell lines were quite different with the A2780 cells having higher levels of several ether lipids than the A2780CR cells. Melittin also had some effect on the lipid composition of the cells. Overall, this study suggests that melittin might have some potential as an adjuvant therapy in cancer treatment. PMID:27754384

  11. Using biological and physico-chemical test methods to assess the role of concrete mixture design in resistance to microbially induced corrosion

    NASA Astrophysics Data System (ADS)

    House, Mitchell Wayne

    Concrete is the most widely used material for construction of wastewater collection, storage, and treatment infrastructure. The chemical and physical characteristics of hydrated portland cement make it susceptible to degradation under highly acidic conditions. As a result, some concrete wastewater infrastructure may be susceptible to a multi-stage degradation process known as microbially induced corrosion, or MIC. MIC begins with the production of aqueous hydrogen sulfide (H2S(aq)) by anaerobic sulfate reducing bacteria present below the waterline. H2S(aq) partitions to the gas phase where it is oxidized to sulfuric acid by the aerobic sulfur oxidizing bacteria Thiobacillus that resides on concrete surfaces above the waterline. Sulfuric acid then attacks the cement paste portion of the concrete matrix through decalcification of calcium hydroxide and calcium silica hydrate coupled with the formation of expansive corrosion products. The attack proceeds inward resulting in reduced service life and potential failure of the concrete structure. There are several challenges associated with assessing a concrete's susceptibility to MIC. First, no standard laboratory tests exist to assess concrete resistance to MIC. Straightforward reproduction of MIC in the laboratory is complicated by the use of microorganisms and hydrogen sulfide gas. Physico-chemical tests simulating MIC by immersing concrete specimens in sulfuric acid offer a convenient alternative, but do not accurately capture the damage mechanisms associated with biological corrosion. Comparison of results between research studies is difficult due to discrepancies that can arise in experimental methods even if current ASTM standards are followed. This thesis presents two experimental methods to evaluate concrete resistance to MIC: one biological and one physico-chemical. Efforts are made to address the critical aspects of each testing method currently absent in the literature. The first method presented is a new test

  12. Comparison of Chemical Sensitivity of Fresh and Long-Stored Heat Resistant Neosartorya fischeri Environmental Isolates Using BIOLOG Phenotype MicroArray System

    PubMed Central

    Panek, Jacek; Frąc, Magdalena; Bilińska-Wielgus, Nina

    2016-01-01

    Spoilage of heat processed food and beverage by heat resistant fungi (HRF) is a major problem for food industry in many countries. Neosartorya fischeri is the leading source of spoilage in thermally processed products. Its resistance to heat processing and toxigenicity makes studies about Neosartorya fischeri metabolism and chemical sensitivity essential. In this study chemical sensitivity of two environmental Neosartorya fischeri isolates were compared. One was isolated from canned apples in 1923 (DSM3700), the other from thermal processed strawberry product in 2012 (KC179765), used as long-stored and fresh isolate, respectively. The study was conducted using Biolog Phenotype MicroArray platforms of chemical sensitivity panel and traditional hole-plate method. The study allowed for obtaining data about Neosartorya fischeri growth inhibitors. The fresh isolate appeared to be much more resistant to chemical agents than the long-stored isolate. Based on phenotype microarray assay nitrogen compounds, toxic cations and membrane function compounds were the most effective in growth inhibition of N. fischeri isolates. According to the study zaragozic acid A, thallium(I) acetate and sodium selenate were potent and promising N. fischeri oriented fungicides which was confirmed by both chemical sensitivity microplates panel and traditional hole-plate methods. PMID:26815302

  13. Comparison of Chemical Sensitivity of Fresh and Long-Stored Heat Resistant Neosartorya fischeri Environmental Isolates Using BIOLOG Phenotype MicroArray System.

    PubMed

    Panek, Jacek; Frąc, Magdalena; Bilińska-Wielgus, Nina

    2016-01-01

    Spoilage of heat processed food and beverage by heat resistant fungi (HRF) is a major problem for food industry in many countries. Neosartorya fischeri is the leading source of spoilage in thermally processed products. Its resistance to heat processing and toxigenicity makes studies about Neosartorya fischeri metabolism and chemical sensitivity essential. In this study chemical sensitivity of two environmental Neosartorya fischeri isolates were compared. One was isolated from canned apples in 1923 (DSM3700), the other from thermal processed strawberry product in 2012 (KC179765), used as long-stored and fresh isolate, respectively. The study was conducted using Biolog Phenotype MicroArray platforms of chemical sensitivity panel and traditional hole-plate method. The study allowed for obtaining data about Neosartorya fischeri growth inhibitors. The fresh isolate appeared to be much more resistant to chemical agents than the long-stored isolate. Based on phenotype microarray assay nitrogen compounds, toxic cations and membrane function compounds were the most effective in growth inhibition of N. fischeri isolates. According to the study zaragozic acid A, thallium(I) acetate and sodium selenate were potent and promising N. fischeri oriented fungicides which was confirmed by both chemical sensitivity microplates panel and traditional hole-plate methods.

  14. Biological rational for sequential targeting of Bruton tyrosine kinase and Bcl-2 to overcome CD40-induced ABT-199 resistance in mantle cell lymphoma

    PubMed Central

    Chiron, David; Touzeau, Cyrille; Maïga, Sophie; Moreau, Philippe; Pellat-Deceunynck, Catherine; Le Gouill, Steven; Amiot, Martine

    2015-01-01

    The aggressive biological behavior of mantle cell lymphoma (MCL) and its short response to current treatment highlight a great need for better rational therapy. Herein, we investigate the ability of ABT-199, the Bcl-2-selective BH3 mimetic, to kill MCL cells. Among MCL cell lines tested (n = 8), only three were sensitive (LD50 < 200 nM). In contrast, all primary MCL samples tested (n = 11) were highly sensitive to ABT-199 (LD50 < 10 nM). Mcl-1 and Bcl-xL both confer resistance to ABT-199-specific killing and BCL2/(BCLXL + MCL1) mRNA ratio is a strong predictor of sensitivity. By mimicking the microenvironment through CD40 stimulation, we show that ABT-199 sensitivity is impaired through activation of NF-kB pathway and Bcl-xL up-regulation. We further demonstrate that resistance is rapidly lost when MCL cells detach from CD40L-expressing fibroblasts. It has been reported that ibrutinib induces lymphocytosis in vivo holding off malignant cells from their protective microenvironment. We show here for two patients undergoing ibrutinib therapy that mobilized MCL cells are highly sensitive to ABT-199. These results provide evidence that in situ ABT-199 resistance can be overcome when MCL cells escape from the lymph nodes. Altogether, our data support the clinical application of ABT-199 therapy both as a single agent and in sequential combination with BTK inhibitors. PMID:25797245

  15. Synthesis and biological activities of novel pleuromutilin derivatives with a substituted thiadiazole moiety as potent drug-resistant bacteria inhibitors.

    PubMed

    Shang, Ruofeng; Pu, Xiuying; Xu, Ximing; Xin, Zhijun; Zhang, Chao; Guo, Wenzhu; Liu, Yu; Liang, Jianping

    2014-07-10

    A series of novel pleuromutilin derivatives possessing thiadiazole moieties were synthesized via acylation reactions under mild conditions. The in vitro antibacterial activities of the derivatives against methicillin-resistant Staphylococcus aureus, methicillin-resistant Staphylococcus epidermidis, Escherichia coli, and Streptococcus agalactiae were tested by the agar dilution method and Oxford cup assay. The majority of the tested compounds displayed moderate antibacterial activities. Importantly, the three compounds with amino or tertiary amine groups in their side chains, 11, 13b, and 15c, were the most active antibacterial agents. Docking experiments carried out on the peptidyl transferase center (PTC) of 23S rRNA proved that there is a reasonable direct correlation between the binding free energy (ΔGb, kcal/mol) and the antibacterial activity. Moreover, the pharmacokinetic profiles of 11 and 15c in rat were characterized by moderate clearance and oral bioavailability.

  16. Biological effects of THC and a lipophilic cannabis extract on normal and insulin resistant 3T3-L1 adipocytes.

    PubMed

    Gallant, M; Odei-Addo, F; Frost, C L; Levendal, R-A

    2009-10-01

    Type 2 diabetes, a chronic disease, affects about 150 million people world wide. It is characterized by insulin resistance of peripheral tissues such as liver, skeletal muscle, and fat. Insulin resistance is associated with elevated levels of tumor necrosis factor alpha (TNF-alpha), which in turn inhibits insulin receptor tyrosine kinase autophosphorylation. It has been reported that cannabis is used in the treatment of diabetes. A few reports indicate that smoking cannabis can lower blood glucose in diabetics. Delta(9)-tetrahydrocannabinol (THC) is the primary psychoactive component of cannabis. This study aimed to determine the effect of a lipophilic cannabis extract on adipogenesis, using 3T3-L1 cells, and to measure its effect on insulin sensitivity in insulin resistant adipocytes. Cells were cultured in Dulbecco's modified eagle medium (DMEM) with 10% fetal bovine serum (FBS) and differentiated over a 3 day period for all studies. In the adipogenesis studies, differentiated cells were exposed to the extract in the presence and absence of insulin. Lipid content and glucose uptake was subsequently measured. Insulin-induced glucose uptake increased, while the rate of adipogenesis decreased with increasing THC concentration. Insulin-resistance was induced using TNF-alpha, exposed to the extract and insulin-induced glucose uptake measured. Insulin-induced glucose was increased in these cells after exposure to the extract. Semiquantitative real time polymerase chain reaction (RT-PCR) was performed after ribonucleic acid (RNA) extraction to evaluate the effects of the extract on glucose transporter isotype 4 (GLUT-4), insulin receptor substrate-1 (IRS-1) and IRS-2 gene expression.

  17. Polyether ionophores: broad-spectrum and promising biologically active molecules for the control of drug-resistant bacteria and parasites

    PubMed Central

    Kevin, Dion A; Meujo, Damaris AF; Hamann, Mark T

    2016-01-01

    Background As multidrug-resistant (MDR) pathogens continue to emerge, there is a substantial amount of pressure to identify new drug candidates. Carboxyl polyethers, also referred to as polyether antibiotics, are a unique class of compounds with outstanding potency against a variety of critical infectious disease targets including protozoa, bacteria and viruses. The characteristics of these molecules that are of key interest are their selectivity and high potency against several MDR etiological agents. Objective Although many studies have been published about carboxyl polyether antibiotics, there are no recent reviews of this class of drugs. The purpose of this review is to provide the reader with an overview of the spectrum of activity of polyether antibiotics, their mechanism of action, toxicity and potential as drug candidates to combat drug-resistant infectious diseases. Conclusion Polyether ionophores show a high degree of promise for the potential control of drug-resistant bacterial and parasitic infections. Despite the long history of use of this class of drugs, very limited medicinal chemistry and drug optimization studies have been reported, thus leaving the door open to these opportunities in the future. Scifinder and PubMed were the main search engines used to locate articles relevant to the topic presented in the present review. Keywords used in our search were specific names of each of the 88 compounds presented in the review as well as more general terms such as polyethers, ionophores, carboxylic polyethers and polyether antibiotics. PMID:23480512

  18. Biological evaluation of cryptophycin 52 fragment A analogues: effect of the multidrug resistance ATP binding cassette transporters on antitumor activity.

    PubMed

    Al-Awar, Rima S; Corbett, Thomas H; Ray, James E; Polin, Lisa; Kennedy, Joseph H; Wagner, Margaret M; Williams, Daniel C

    2004-09-01

    Cryptophycin 52 (LY355703) is a potent antiproliferative analogue of the marine natural product cryptophycin 1. It has been shown to have a broad range of antitumor activity against human tumor xenografts and murine tumors including tumors resistant to Taxol and Adriamycin. Its mechanism of action involves arresting cells in the G2-M phase of the cell cycle by binding to microtubules and suppressing their dynamics. This 16-membered depsipeptide can be divided into four major subunits or fragments (A-D). We reported previously on our synthetic efforts around fragment A and discovered that this region of the molecule was amenable to a structure-activity relationship study that resulted in highly active antiproliferative agents when evaluated in the CEM leukemia cell line. The synthetic analogues were designed to help improve the efficacy and aqueous solubility of the parent compound; therefore, many in this series contained ionizable functional groups such as an amino group, a hydroxy group, or a carboxylic acid. Although several of these analogues showed improvements in potency over cryptophycin 52 in drug-sensitive tumor xenograft models, many lost their activity against Adriamycin-resistant tumor lines. It was discovered on additional in vitro evaluation that these analogues became good substrates of the multidrug resistance transporter P-glycoprotein.

  19. Physical and biological characteristics of multi drug resistance (MDR): An integral approach considering pH and drug resistance in cancer.

    PubMed

    Omran, Ziad; Scaife, Paula; Stewart, Simon; Rauch, Cyril

    2017-04-01

    The role of the Warburg effect in cancer remains to be elucidated with a resurgence in research efforts over the past decade. Why a cancer cell would prefer to use energy inefficient glycolysis, leading to an alteration of pH both inside and outside of the cell, remains to be uncovered. The development of MDR represents a major challenge in the treatment of cancer and it is explained, so far, by the over expression of drug transporters such as the well-known and archetypal P-glycoprotein (Pgp). However, controversies exist regarding the function of Pgp in multi-drug resistance. We suggest here that Pgp-mediated MDR relies fundamentally on pH alterations mediated by the Warburg effect. Furthermore, we propose that the use of proton pump and/or transporters inhibitors (PPIs/PTIs) in cancer are key to controlling both MDR, i.e. sensitize tumors to antineoplastic agents, and drug-related adverse effects. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

  20. Impacts of off-road vehicles on nitrogen cycles in biological soil crusts: Resistance in different U.S. deserts

    USGS Publications Warehouse

    Belnap, J.

    2002-01-01

    Biological soil crusts are an important component of desert ecosystems, as they influence soil stability and fertility. This study examined and compared the short-term vehicular impacts on lichen cover and nitrogenase activity (NA) of biological soil crusts. Experimental disturbance was applied to different types of soil in regions throughout the western U.S. (Great Basin, Colorado Plateau, Sonoran, Chihuahuan, and Mojave deserts). Results show that pre-disturbance cover of soil lichens is significantly correlated with the silt content of soils, and negatively correlated with sand and clay. While disturbance appeared to reduce NA at all sites, differences were statistically significant at only 12 of the 26 sites. Cool desert sites showed a greater decline than hot desert sites, which may indicate non-heterocystic cyanobacterial species are more susceptible to disturbance than non-heterocystic species. Sandy soils showed greater reduction of NA as sand content increased, while fine-textured soils showed a greater decline as sand content increased. At all sites, higher NA before the disturbance resulted in less impact to NA post-disturbance. These results may be useful in predicting the impacts of off-road vehicles in different regions and different soils. ?? 2002 Published by Elsevier Science Ltd.

  1. Treatment of Amaranthus cruentus with chemical and biological inducers of resistance has contrasting effects on fitness and protection against compatible Gram positive and Gram negative bacterial pathogens.

    PubMed

    Casarrubias-Castillo, Kena; Martínez-Gallardo, Norma A; Délano-Frier, John P

    2014-07-01

    Amaranthus cruentus (Ac) plants were treated with the synthetic systemic acquired resistance (SAR) inducer benzothiadiazole (BTH), methyl jasmonate (MeJA) and the incompatible pathogen, Pseudomonas syringae pv. syringae (Pss), under greenhouse conditions. The treatments induced a set of marker genes in the absence of pathogen infection: BTH and Pss similarly induced genes coding for pathogenesis-related and antioxidant proteins, whereas MeJA induced the arginase, LOX2 and amarandin 1 genes. BTH and Pss were effective when tested against the Gram negative pathogen Ps pv. tabaci (Pst), which was found to have a compatible interaction with grain amaranth. The resistance response appeared to be salicylic acid-independent. However, resistance against Clavibacter michiganensis subsp. michiganensis (Cmm), a Gram positive tomato pathogen also found to infect Ac, was only conferred by Pss, while BTH increased susceptibility. Conversely, MeJA was ineffective against both pathogens. Induced resistance against Pst correlated with the rapid and sustained stimulation of the above genes, including the AhPAL2 gene, which were expressed both locally and distally. The lack of protection against Cmm provided by BTH, coincided with a generalized down-regulation of defense gene expression and chitinase activity. On the other hand, Pss-treated Ac plants showed augmented expression levels of an anti-microbial peptide gene and, surprisingly, of AhACCO, an ethylene biosynthetic gene associated with susceptibility to Cmm in tomato, its main host. Pss treatment had no effect on productivity, but compromised growth, whereas MeJA reduced yield and harvest index. Conversely, BTH treatments led to smaller plants, but produced significantly increased yields. These results suggest essential differences in the mechanisms employed by biological and chemical agents to induce SAR in Ac against bacterial pathogens having different infection strategies. This may determine the outcome of a particular

  2. Multifunctional commercially pure titanium for the improvement of bone integration: Multiscale topography, wettability, corrosion resistance and biological functionalization.

    PubMed

    Ferraris, Sara; Vitale, Alessandra; Bertone, Elisa; Guastella, Salvatore; Cassinelli, Clara; Pan, Jinshan; Spriano, Silvia

    2016-03-01

    The objects of this research are commercially pure titanium surfaces, with multifunctional behavior, obtained through a chemical treatment and biological functionalization. The explored surfaces are of interest for dental implants, in contact with bone, where several simultaneous and synergistic actions are needed, in order to get a fast and effective osseointegration. The here described modified surfaces present a layer of titanium oxide, thicker than the native one, with a multi-scale surface topography (a surface roughness on the nano scale, which can be overlapped to a micro or macro roughness of the substrate) and a high density of OH groups, that increase surface wettability, induce a bioactive behavior (hydroxyapatite precipitation in simulated body fluid) and make possible the grafting of biomolecules (alkaline phosphatase, ALP, in the present research). The surface oxide is an efficient barrier against corrosion, with passive behavior both with and without application of an external voltage. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. Development of a novel, hemolysis-resistant reagent for assessment of α-amylase in biological fluids.

    PubMed

    Ronda, Luca; Mozzarelli, Andrea; Aloe, Rosalia; Lippi, Giuseppe

    2013-07-01

    Although the assessment of α-amylase is an essential part of the diagnostic workout of several pancreatic and extra-pancreatic disorders, its enzymatic activity is significantly reduced in the presence of cell-free hemoglobin such as in samples with spurious hemolysis, due to chemical and spectrophotometric interference. We developed a new reagent that provides reliable results on hemolyzed biological specimens. All tests were performed on Beckman Coulter AU5822. Intra-assay imprecision was assessed on three serum samples with low, intermediate and high α-amylase concentration. Linearity was assessed by serially diluting two samples with low and high values of α-amylase. The comparison with commercial reagent was performed on 40 serum samples. Hemolysis studies were carried out by mechanically hemolysis of 20 lithium-heparin samples. The intra-assay imprecision was comprised between 1.3% and 2.2%. The linearity was excellent (r=0.998), and highly significant agreement was observed with the commercial assay (r=1.00; mean bias -3.8%). Although a significant correlation between non-hemolyzed and hemolyzed specimens was found with both assays (p<0.001), a much greater agreement was observed with the experimental method (r=0.997 vs. 0.818). No measurement exceeded the total allowable error with the experimental assay, whereas the threshold was exceeded in 85% of samples using the commercial method. The clinical applications of the experimental reagent include α-amylase assessment in hemolyzed samples, in urine and other biological fluids contaminated with lysed erythrocytes, or in patients under frequent transfusions and hemoglobin-based blood substitutes therapy. The formulation of this reagent could be adapted for other clinical chemistry or immunochemistry assays.

  4. Evidence of early alterations in adipose tissue biology and function and its association with obesity-related inflammation and insulin resistance in children.

    PubMed

    Landgraf, Kathrin; Rockstroh, Denise; Wagner, Isabel V; Weise, Sebastian; Tauscher, Roy; Schwartze, Julian T; Löffler, Dennis; Bühligen, Ulf; Wojan, Magdalena; Till, Holger; Kratzsch, Jürgen; Kiess, Wieland; Blüher, Matthias; Körner, Antje

    2015-04-01

    Accumulation of fat mass in obesity may result from hypertrophy and/or hyperplasia and is frequently associated with adipose tissue (AT) dysfunction in adults. Here we assessed early alterations in AT biology and function by comprehensive experimental and clinical characterization of 171 AT samples from lean and obese children aged 0 to 18 years. We show an increase in adipocyte size and number in obese compared with lean children beginning in early childhood. These alterations in AT composition in obese children were accompanied by decreased basal lipolytic activity and significantly enhanced stromal vascular cell proliferation in vitro, potentially underlying the hypertrophy and hyperplasia seen in obese children, respectively. Furthermore, macrophage infiltration, including the formation of crown-like structures, was increased in AT of obese children from 6 years on and was associated with higher hs-CRP serum levels. Clinically, adipocyte hypertrophy was not only associated with leptin serum levels but was highly and independently correlated with HOMA-IR as a marker of insulin resistance in children. In summary, we show that adipocyte hypertrophy is linked to increased inflammation in AT in obese children, thereby providing evidence that obesity-associated AT dysfunction develops in early childhood and is related to insulin resistance. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  5. MgF2-coated porous magnesium/alumina scaffolds with improved strength, corrosion resistance, and biological performance for biomedical applications.

    PubMed

    Kang, Min-Ho; Jang, Tae-Sik; Kim, Sung Won; Park, Hui-Sun; Song, Juha; Kim, Hyoun-Ee; Jung, Kyung-Hwan; Jung, Hyun-Do

    2016-05-01

    Porous magnesium (Mg) has recently emerged as a promising biodegradable alternative to biometal for bone ingrowth; however, its low mechanical properties and high corrosion rate in biological environments remain problematic. In this study, porous magnesium was implemented in a scaffold that closely mimics the mechanical properties of human bones with a controlled degradation rate and shows good biocompatibility to match the regeneration rate of bone tissue at the affected site. The alumina-reinforced Mg scaffold was produced by spark plasma sintering and coated with magnesium fluoride (MgF2) using a hydrofluoric acid solution to regulate the corrosion rate under physiological conditions. Sodium chloride granules (NaCl), acting as space holders, were leached out to achieve porous samples (60%) presenting an average pore size of 240 μm with complete pore interconnectivity. When the alumina content increased from 0 to 5 vol%, compressive strength and stiffness rose considerably from 9.5 to 13.8 MPa and from 0.24 to 0.40 GPa, respectively. Moreover, the biological response evaluated by in vitro cell test and blood test of the MgF2-coated porous Mg composite was enhanced with better corrosion resistance compared with that of uncoated counterparts. Consequently, MgF2-coated porous Mg/alumina composites may be applied in load-bearing biodegradable implants.

  6. Biological and molecular characterization of an ECV-304-derived cell line resistant to p53-mediated apoptosis.

    PubMed

    Maxwell, S A; Davis, G E

    2000-06-01

    Upregulation of the p53 tumor suppressor protein by infection with a recombinant p53 adenovirus resulted in extensive apoptosis in ECV-304 cells and the eventual death of almost all the cells. To establish a system to elucidate the molecular mechanisms involved in p53-mediated apoptosis of these cells, we established a variant of ECV-304 that is resistant to p53-induced apoptosis by repeated infections with a recombinant p53 adenovirus. We have designated this variant as the DECV cell line (Differentiated ECV-304). DECV cells expressed similar amounts of nuclear-localized p53 as ECV-304 cells when infected with recombinant p53 adenovirus, but in contrast to ECV-304 cells, greater than 95% of DECV cells survived and remained viable after 24 hours of infection. In further contrast to ECV-304 cells, DECV cells grew less efficiently in soft agar and exhibited contact inhibition in growth assays. Moreover, DECV cells formed unusual lattice or cyst-like structures in culture and formed lumenal structures indicative of epithelial differentiation in three-dimensional collagen matrices, while parental ECV-304 cells showed minimal evidence of these cellular behaviors. A comparative molecular analysis of gene expression in DECV and ECV-304 cells was conducted by cDNA microarray technology. Protocadherin-1 was found to be expressed in DECV cells but not in ECV-304 cells, while the Id-3 gene was observed expressed in ECV-304 cells but not in DECV cells. Moreover, upregulated expression of p53 in ECV-304 cells induced the EPHB2 (Ephrin) receptor tyrosine kinase and the ephrin-B1 ligand mRNAs compared to DECV cells treated in the same manner. These data demonstrate that a new variant of the ECV-304 cell line, which is resistant to p53-mediated apoptosis, exhibits differential gene expression as well as distinct cell behaviors as compared to the parental ECV-304 cell line. DECV cells should prove to be a useful tool in future studies to elucidate mechanisms of p53-mediated

  7. Design, synthesis and biological evaluation of LBM-A5 derivatives as potent P-glycoprotein-mediated multidrug resistance inhibitors.

    PubMed

    Wu, Yuxiang; Pan, Miaobo; Dai, Yuxuan; Liu, Baomin; Cui, Jian; Shi, Wei; Qiu, Qianqian; Huang, Wenlong; Qian, Hai

    2016-05-15

    A novel series of P-glycoprotein (P-gp)-mediated multidrug resistance (MDR) inhibitors with triazol-N-phenethyl-tetrahydroisoquinoline or triazol-N-ethyl-tetrahydroisoquinoline scaffold were designed and synthesized via click chemistry. Most of the synthesized compounds showed higher reversal activity than verapamil (VRP). Among them, the most potent compound 4 showed a comparable activity with the known potent P-gp inhibitor WK-X-34 with lower cytotoxicity toward K562 cells (IC50>100μM). Compared with VRP, compound 4 exhibited more potency in increasing drug accumulation in K562/A02 MDR cells. Moreover, compound 4 could significantly reverse MDR in a dose-dependent manner and also persist longer chemo-sensitizing effect than VRP with reversibility. Further mechanism studies revealed that compound 4 could remarkably increase the intracellular accumulation of Adriamycin (ADM) in K562/A02 cells as well as inhibit rhodamine-123 (Rh123) efflux from the cells. These results suggested that compound 4 may represent a promising candidate for developing P-gp-mediated MDR inhibitors. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. Synthesis and Biological Evaluation of 4-Anilino-quinazolines and -quinolines as Inhibitors of Breast Cancer Resistance Protein (ABCG2).

    PubMed

    Krapf, Michael K; Wiese, Michael

    2016-06-09

    Chemotherapeutic treatment of cancer often fails due to overexpression of the ATP-binding cassette (ABC) transport proteins, like ABCG2, triggering active efflux of various structurally unrelated drugs. This so-called multidrug resistance (MDR) may be reversed by selective, potent, and nontoxic inhibitors of ABCG2. As only a few potent inhibitors are known, new compounds based on a 4-substituted-2-phenylquinazoline scaffold were investigated. Substitution with hydroxy, cyano, nitro, acetamido, and fluoro led to high inhibitory activities toward ABCG2. The ability to reverse MDR of the most active compounds was confirmed in a MTT efficacy assay. Moreover, a negligibly low intrinsic cytotoxicity was found resulting in a high therapeutic ratio. Investigations of the inhibitory activity toward ABCB1 and ABCC1 yielded a high selectivity toward ABCG2 for the quinazoline compounds. Quinoline-based analogues showed lower inhibitory activity and selectivity. The study yielded a variety of promising compounds, some with superior properties compared to those of the standard inhibitor Ko143.

  9. Design, Synthesis, and Biological and Structural Evaluations of Novel HIV-1 Protease Inhibitors To Combat Drug Resistance

    SciTech Connect

    Parai, Maloy Kumar; Huggins, David J.; Cao, Hong; Nalam, Madhavi N.L.; Ali, Akbar; Schiffer, Celia A.; Tidor, Bruce; Rana, Tariq M.

    2012-09-11

    A series of new HIV-1 protease inhibitors (PIs) were designed using a general strategy that combines computational structure-based design with substrate-envelope constraints. The PIs incorporate various alcohol-derived P2 carbamates with acyclic and cyclic heteroatomic functionalities into the (R)-hydroxyethylamine isostere. Most of the new PIs show potent binding affinities against wild-type HIV-1 protease and three multidrug resistant (MDR) variants. In particular, inhibitors containing the 2,2-dichloroacetamide, pyrrolidinone, imidazolidinone, and oxazolidinone moieties at P2 are the most potent with Ki values in the picomolar range. Several new PIs exhibit nanomolar antiviral potencies against patient-derived wild-type viruses from HIV-1 clades A, B, and C and two MDR variants. Crystal structure analyses of four potent inhibitors revealed that carbonyl groups of the new P2 moieties promote extensive hydrogen bond interactions with the invariant Asp29 residue of the protease. These structure-activity relationship findings can be utilized to design new PIs with enhanced enzyme inhibitory and antiviral potencies.

  10. Biological features of core networks that result from a high-fat diet in hepatic and pulmonary tissues in mammary tumour-bearing, obesity-resistant mice.

    PubMed

    Kim, Eun Ji; Oh, Hea Young; Heo, Hyoung-Sam; Hong, Ji Eun; Jung, Sung-Jae; Lee, Ki Won; Park, Jong Hoon; Hur, Cheol-Goo; Park, Jung Han Yoon

    2013-07-28

    We previously demonstrated that the chronic consumption of a high-fat diet (HFD) promotes lung and liver metastases of 4T1 mammary carcinoma cells in obesity-resistant BALB/c mice. To examine early transcriptional responses to tumour progression in the liver and lungs of HFD-fed mice, 4-week-old female BALB/c mice were divided into four groups: sham-injected, control diet (CD)-fed; sham-injected, HFD-fed (SH); 4T1 cell-injected, CD-fed (TC); 4T1 cell-injected, HFD-fed (TH). Following 16 weeks of either a CD or HFD, 4T1 cells were injected into the mammary fat pads of mice in the TC and TH groups and all mice were continuously fed identical diets. At 14 d post-injection, RNA was isolated from hepatic and pulmonary tissues for microarray analysis of mRNA expression. Functional annotation and core network analyses were conducted for the TH/SH Unique gene set. Inflammation in hepatic tissues and cell mitosis in pulmonary tissues were the most significant biological functions in the TH/SH Unique gene set. The biological core networks of the hepatic TH/SH Unique gene set were characterised as those genes involved in the activation of acute inflammatory responses (Orm1, Lbp, Hp and Cfb), disordered lipid metabolism and deregulated cell cycle progression. Networks of the pulmonary Unique gene set displayed the deregulation of cell cycle progression (Cdc20, Cdk1 and Bub1b). These HFD-influenced alterations may have led to favourable conditions for the formation of both pro-inflammatory and pro-mitotic microenvironments in the target organs that promote immune cell infiltration and differentiation, as well as the infiltration and proliferation of metastatic tumour cells.

  11. Biological preconcentrator

    DOEpatents

    Manginell, Ronald P.; Bunker, Bruce C.; Huber, Dale L.

    2008-09-09

    A biological preconcentrator comprises a stimulus-responsive active film on a stimulus-producing microfabricated platform. The active film can comprise a thermally switchable polymer film that can be used to selectively absorb and desorb proteins from a protein mixture. The biological microfabricated platform can comprise a thin membrane suspended on a substrate with an integral resistive heater and/or thermoelectric cooler for thermal switching of the active polymer film disposed on the membrane. The active polymer film can comprise hydrogel-like polymers, such as poly(ethylene oxide) or poly(n-isopropylacrylamide), that are tethered to the membrane. The biological preconcentrator can be fabricated with semiconductor materials and technologies.

  12. Design, Synthesis, Protein−Ligand X-ray Structure, and Biological Evaluation of a Series of Novel Macrocyclic Human Immunodeficiency Virus-1 Protease Inhibitors to Combat Drug Resistance

    SciTech Connect

    Ghosh, Arun K.; Kulkarni, Sarang; Anderson, David D.; Hong, Lin; Baldridge, Abigail; Wang, Yuan-Fang; Chumanevich, Alexander A.; Kovalevsky, Andrey Y.; Tojo, Yasushi; Amano, Masayuki; Koh, Yasuhiro; Tang, Jordan; Weber, Irene T.; Mitsuya, Hiroaki

    2010-04-05

    The structure-based design, synthesis, and biological evaluation of a series of nonpeptidic macrocyclic HIV protease inhibitors are described. The inhibitors are designed to effectively fill in the hydrophobic pocket in the S1'-S2' subsites and retain all major hydrogen bonding interactions with the protein backbone similar to darunavir (1) or inhibitor 2. The ring size, the effect of methyl substitution, and unsaturation within the macrocyclic ring structure were assessed. In general, cyclic inhibitors were significantly more potent than their acyclic homologues, saturated rings were less active than their unsaturated analogues and a preference for 10- and 13-membered macrocylic rings was revealed. The addition of methyl substituents resulted in a reduction of potency. Both inhibitors 14b and 14c exhibited marked enzyme inhibitory and antiviral activity, and they exerted potent activity against multidrug-resistant HIV-1 variants. Protein-ligand X-ray structures of inhibitors 2 and 14c provided critical molecular insights into the ligand-binding site interactions.

  13. Antimicrobial (Drug) Resistance

    MedlinePlus

    ... NIAID invests in basic research to understand the biology of microbes, their behavior, and how drug resistance ... Nucleotide Polymorphism Phylogenetics & Ontology Proteomics & Protein Analysis Systems Biology Data Portals Software Applications BCBB Mobyle Interface Designer ( ...

  14. Effects of 6-Weeks High-Intensity Interval Training in Schoolchildren with Insulin Resistance: Influence of Biological Maturation on Metabolic, Body Composition, Cardiovascular and Performance Non-responses

    PubMed Central

    Alvarez, Cristian; Ramírez-Campillo, Rodrigo; Ramírez-Vélez, Robinson; Izquierdo, Mikel

    2017-01-01

    Background: Previous studies have observed significant heterogeneity in the magnitude of change in measures of metabolic response to exercise training. There are a lack of studies examining the prevalence of non-responders (NRs) in children while considering other potential environmental factors involved such as biological maturation. Aim: To compare the effects and prevalence of NRs to improve the insulin resistance level (by HOMA-IR), as well as to other anthropometric, cardiovascular, and performance co-variables, between early (EM) and normal maturation (NM) in insulin-resistance schoolchildren after 6-weeks of HIIT. Methods: Sedentary children (age 11.4 ± 1.7 years) were randomized to either HIIT-EM group (n = 12) or HIIT-NM group (n = 17). Fasting glucose (FGL), fasting insulin (FINS) and homeostasis model assessment of insulin resistant (HOMA-IR) were assessed as the main outcomes, as well as the body composition [body mass, body mass index (BMI), waist circumference (WC), and tricipital (TSF), suprailiac (SSF) and abdominal skinfold (AbdSF)], cardiovascular systolic (SBP) and diastolic blood pressure (DBP), and muscular performance [one-repetition maximum strength leg-extension (1RMLE) and upper row (1RMUR) tests] co-variables were assessed before and after intervention. Responders or NRs to training were defined as a change in the typical error method from baseline to follow-up for the main outcomes and co-variables. Results: There were no significant differences between groups in the prevalence of NRs based on FGL, FINS, and HOMA-IR. There were significant differences in NRs prevalence to decrease co-variables body mass (HIIT-EM 66.6% vs. HIIT-NM 35.2%) and SBP (HIIT-EM 41.6% vs. HIIT-NM 70.5%). A high risk [based on odds ratios (OR)] of NRs cases was detected for FGL, OR = 3.2 (0.2 to 5.6), and HOMA-IR, OR = 3.2 (0.2 to 6.0). Additionally, both HIIT-EM and HIIT-NM groups showed significant decreases (P < 0.05) in TSF, SSF, and AbdSF skinfold, and

  15. Effects of 6-Weeks High-Intensity Interval Training in Schoolchildren with Insulin Resistance: Influence of Biological Maturation on Metabolic, Body Composition, Cardiovascular and Performance Non-responses.

    PubMed

    Alvarez, Cristian; Ramírez-Campillo, Rodrigo; Ramírez-Vélez, Robinson; Izquierdo, Mikel

    2017-01-01

    Background: Previous studies have observed significant heterogeneity in the magnitude of change in measures of metabolic response to exercise training. There are a lack of studies examining the prevalence of non-responders (NRs) in children while considering other potential environmental factors involved such as biological maturation. Aim: To compare the effects and prevalence of NRs to improve the insulin resistance level (by HOMA-IR), as well as to other anthropometric, cardiovascular, and performance co-variables, between early (EM) and normal maturation (NM) in insulin-resistance schoolchildren after 6-weeks of HIIT. Methods: Sedentary children (age 11.4 ± 1.7 years) were randomized to either HIIT-EM group (n = 12) or HIIT-NM group (n = 17). Fasting glucose (FGL), fasting insulin (FINS) and homeostasis model assessment of insulin resistant (HOMA-IR) were assessed as the main outcomes, as well as the body composition [body mass, body mass index (BMI), waist circumference (WC), and tricipital (TSF), suprailiac (SSF) and abdominal skinfold (AbdSF)], cardiovascular systolic (SBP) and diastolic blood pressure (DBP), and muscular performance [one-repetition maximum strength leg-extension (1RMLE) and upper row (1RMUR) tests] co-variables were assessed before and after intervention. Responders or NRs to training were defined as a change in the typical error method from baseline to follow-up for the main outcomes and co-variables. Results: There were no significant differences between groups in the prevalence of NRs based on FGL, FINS, and HOMA-IR. There were significant differences in NRs prevalence to decrease co-variables body mass (HIIT-EM 66.6% vs. HIIT-NM 35.2%) and SBP (HIIT-EM 41.6% vs. HIIT-NM 70.5%). A high risk [based on odds ratios (OR)] of NRs cases was detected for FGL, OR = 3.2 (0.2 to 5.6), and HOMA-IR, OR = 3.2 (0.2 to 6.0). Additionally, both HIIT-EM and HIIT-NM groups showed significant decreases (P < 0.05) in TSF, SSF, and AbdSF skinfold, and

  16. Chemical and Biological Resistant Clothing

    DTIC Science & Technology

    2013-04-01

    tributyl phosphate (TBP) and methyl salicylate (MS) at room temperature, high temperature and co-feeding mixture settings. To evaluate the...ISO International Organization for Standardization MS methyl salicylate MVTR moisture vapor transport rate NFPA National Fire Protection...methylpropene-co-2- methyl -1,3-butadiene)), working on the principle of total blockage. 2 The lack of breathability of butyl rubber, however, results in

  17. Cellular Signaling Pathways in Insulin Resistance-Systems Biology Analyses of Microarray Dataset Reveals New Drug Target Gene Signatures of Type 2 Diabetes Mellitus.

    PubMed

    Muhammad, Syed Aun; Raza, Waseem; Nguyen, Thanh; Bai, Baogang; Wu, Xiaogang; Chen, Jake

    2017-01-01

    Purpose: Type 2 diabetes mellitus (T2DM) is a chronic and metabolic disorder affecting large set of population of the world. To widen the scope of understanding of genetic causes of this disease, we performed interactive and toxicogenomic based systems biology study to find potential T2DM related genes after cDNA differential analysis. Methods: From the list of 50-differential expressed genes (p < 0.05), we found 9-T2DM related genes using extensive data mapping. In our constructed gene-network, T2DM-related differentially expressed seeder genes (9-genes) are found to interact with functionally related gene signatures (31-genes). The genetic interaction network of both T2DM-associated seeder as well as signature genes generally relates well with the disease condition based on toxicogenomic and data curation. Results: These networks showed significant enrichment of insulin signaling, insulin secretion and other T2DM-related pathways including JAK-STAT, MAPK, TGF, Toll-like receptor, p53 and mTOR, adipocytokine, FOXO, PPAR, P13-AKT, and triglyceride metabolic pathways. We found some enriched pathways that are common in different conditions. We recognized 11-signaling pathways as a connecting link between gene signatures in insulin resistance and T2DM. Notably, in the drug-gene network, the interacting genes showed significant overlap with 13-FDA approved and few non-approved drugs. This study demonstrates the value of systems genetics for identifying 18 potential genes associated with T2DM that are probable drug targets. Conclusions: This integrative and network based approaches for finding variants in genomic data expect to accelerate identification of new drug target molecules for different diseases and can speed up drug discovery outcomes.

  18. Cellular Signaling Pathways in Insulin Resistance-Systems Biology Analyses of Microarray Dataset Reveals New Drug Target Gene Signatures of Type 2 Diabetes Mellitus

    PubMed Central

    Muhammad, Syed Aun; Raza, Waseem; Nguyen, Thanh; Bai, Baogang; Wu, Xiaogang; Chen, Jake

    2017-01-01

    Purpose: Type 2 diabetes mellitus (T2DM) is a chronic and metabolic disorder affecting large set of population of the world. To widen the scope of understanding of genetic causes of this disease, we performed interactive and toxicogenomic based systems biology study to find potential T2DM related genes after cDNA differential analysis. Methods: From the list of 50-differential expressed genes (p < 0.05), we found 9-T2DM related genes using extensive data mapping. In our constructed gene-network, T2DM-related differentially expressed seeder genes (9-genes) are found to interact with functionally related gene signatures (31-genes). The genetic interaction network of both T2DM-associated seeder as well as signature genes generally relates well with the disease condition based on toxicogenomic and data curation. Results: These networks showed significant enrichment of insulin signaling, insulin secretion and other T2DM-related pathways including JAK-STAT, MAPK, TGF, Toll-like receptor, p53 and mTOR, adipocytokine, FOXO, PPAR, P13-AKT, and triglyceride metabolic pathways. We found some enriched pathways that are common in different conditions. We recognized 11-signaling pathways as a connecting link between gene signatures in insulin resistance and T2DM. Notably, in the drug-gene network, the interacting genes showed significant overlap with 13-FDA approved and few non-approved drugs. This study demonstrates the value of systems genetics for identifying 18 potential genes associated with T2DM that are probable drug targets. Conclusions: This integrative and network based approaches for finding variants in genomic data expect to accelerate identification of new drug target molecules for different diseases and can speed up drug discovery outcomes. PMID:28179884

  19. Precision engineering for PRRSV resistance in pigs: Macrophages from genome edited pigs lacking CD163 SRCR5 domain are fully resistant to both PRRSV genotypes while maintaining biological function

    PubMed Central

    Jackson, Ben; Mileham, Alan J.; Ait-Ali, Tahar; Whitelaw, C. Bruce A.

    2017-01-01

    Porcine Reproductive and Respiratory Syndrome (PRRS) is a panzootic infectious disease of pigs, causing major economic losses to the world-wide pig industry. PRRS manifests differently in pigs of all ages but primarily causes late-term abortions and stillbirths in sows and respiratory disease in piglets. The causative agent of the disease is the positive-strand RNA PRRS virus (PRRSV). PRRSV has a narrow host cell tropism, limited to cells of the monocyte/macrophage lineage. CD163 has been described as a fusion receptor for PRRSV, whereby the scavenger receptor cysteine-rich domain 5 (SRCR5) region was shown to be an interaction site for the virus in vitro. CD163 is expressed at high levels on the surface of macrophages, particularly in the respiratory system. Here we describe the application of CRISPR/Cas9 to pig zygotes, resulting in the generation of pigs with a deletion of Exon 7 of the CD163 gene, encoding SRCR5. Deletion of SRCR5 showed no adverse effects in pigs maintained under standard husbandry conditions with normal growth rates and complete blood counts observed. Pulmonary alveolar macrophages (PAMs) and peripheral blood monocytes (PBMCs) were isolated from the animals and assessed in vitro. Both PAMs and macrophages obtained from PBMCs by CSF1 stimulation (PMMs) show the characteristic differentiation and cell surface marker expression of macrophages of the respective origin. Expression and correct folding of the SRCR5 deletion CD163 on the surface of macrophages and biological activity of the protein as hemoglobin-haptoglobin scavenger was confirmed. Challenge of both PAMs and PMMs with PRRSV genotype 1, subtypes 1, 2, and 3 and PMMs with PRRSV genotype 2 showed complete resistance to viral infections assessed by replication. Confocal microscopy revealed the absence of replication structures in the SRCR5 CD163 deletion macrophages, indicating an inhibition of infection prior to gene expression, i.e. at entry/fusion or unpacking stages. PMID:28231264

  20. Precision engineering for PRRSV resistance in pigs: Macrophages from genome edited pigs lacking CD163 SRCR5 domain are fully resistant to both PRRSV genotypes while maintaining biological function.

    PubMed

    Burkard, Christine; Lillico, Simon G; Reid, Elizabeth; Jackson, Ben; Mileham, Alan J; Ait-Ali, Tahar; Whitelaw, C Bruce A; Archibald, Alan L

    2017-02-01

    Porcine Reproductive and Respiratory Syndrome (PRRS) is a panzootic infectious disease of pigs, causing major economic losses to the world-wide pig industry. PRRS manifests differently in pigs of all ages but primarily causes late-term abortions and stillbirths in sows and respiratory disease in piglets. The causative agent of the disease is the positive-strand RNA PRRS virus (PRRSV). PRRSV has a narrow host cell tropism, limited to cells of the monocyte/macrophage lineage. CD163 has been described as a fusion receptor for PRRSV, whereby the scavenger receptor cysteine-rich domain 5 (SRCR5) region was shown to be an interaction site for the virus in vitro. CD163 is expressed at high levels on the surface of macrophages, particularly in the respiratory system. Here we describe the application of CRISPR/Cas9 to pig zygotes, resulting in the generation of pigs with a deletion of Exon 7 of the CD163 gene, encoding SRCR5. Deletion of SRCR5 showed no adverse effects in pigs maintained under standard husbandry conditions with normal growth rates and complete blood counts observed. Pulmonary alveolar macrophages (PAMs) and peripheral blood monocytes (PBMCs) were isolated from the animals and assessed in vitro. Both PAMs and macrophages obtained from PBMCs by CSF1 stimulation (PMMs) show the characteristic differentiation and cell surface marker expression of macrophages of the respective origin. Expression and correct folding of the SRCR5 deletion CD163 on the surface of macrophages and biological activity of the protein as hemoglobin-haptoglobin scavenger was confirmed. Challenge of both PAMs and PMMs with PRRSV genotype 1, subtypes 1, 2, and 3 and PMMs with PRRSV genotype 2 showed complete resistance to viral infections assessed by replication. Confocal microscopy revealed the absence of replication structures in the SRCR5 CD163 deletion macrophages, indicating an inhibition of infection prior to gene expression, i.e. at entry/fusion or unpacking stages.

  1. Design, Synthesis and Biological Evaluation of 1-[(2-benzyloxyl/alkoxyl) methyl]-5-halo-6-aryluracils as Potent HIV-1 Non-Nucleoside Reverse Transcriptase Inhibitors with Improved Drug Resistance Profile

    PubMed Central

    Wang, Xiaowei; Zhang, Jianfang; Huang, Yang; Wang, Ruiping; Zhang, Liang; Qiao, Kang; Li, Li; Liu, Chang; Ouyang, Yabo; Xu, Weisi; Zhang, Zhili; Zhang, Liangren; Shao, Yiming; Jiang, Shibo; Ma, Liying; Liu, Junyi

    2012-01-01

    Since the emergence of drug-resistant mutants has limited the efficacy of non-nucleoside reverse transcriptase inhibitors (NNRTIs), it is essential to develop new antivirals with better drug-resistance and pharmacokinetic profiles. Here we designed and synthesized a series of 1-[(2-benzyloxyl/alkoxyl)methyl]-5-halo-6-aryluracils, the HEPT analogues, and evaluated their biological activity using Nevirapine and 18 (TNK-651) as reference compounds. Most of these compounds, especially 6b, 7b, 9b, 11b and 7c, exhibited highly potent anti-HIV-1 activity against both wild-type and NNRTI-resistant HIV-1 strains. The compound 7b, that had the highest selectivity index (SI = 38,215), is more potent than Nevirapine and 18. These results suggest that introduction of halogen at the C-5 position may contribute to the effectiveness of these compounds against RTI-resistant variants. In addition, m-substituents on the C-6 aromatic moiety could significantly enhance activity against NNRTI-resistant HIV-1 strains. These compounds can be further developed as next-generation NNRTIs with improved antiviral efficacy and drug-resistance profile. PMID:22283377

  2. [French Society for Biological Psychiatry and Neuropsychopharmacology and Fondation FondaMental task force: Formal Consensus for the management of treatment-resistant depression].

    PubMed

    Charpeaud, T; Genty, J-B; Destouches, S; Yrondi, A; Lancrenon, S; Alaïli, N; Bellivier, F; Bennabi, D; Bougerol, T; Camus, V; D'amato, T; Doumy, O; Haesebaert, F; Holtzmann, J; Lançon, C; Lefebvre, M; Moliere, F; Nieto, I; Richieri, R; Schmitt, L; Stephan, F; Vaiva, G; Walter, M; Leboyer, M; El-Hage, W; Haffen, E; Llorca, P-M; Courtet, P; Aouizerate, B

    2017-09-01

    Major depression represents among the most frequent psychiatric disorders in the general population with an estimated lifetime prevalence of 16-17%. It is characterized by high levels of comorbidities with other psychiatric conditions or somatic diseases as well as a recurrent or chronic course in 50 to 80% of the cases leading to negative repercussions on the daily functioning, with an impaired quality of life, and to severe direct/indirect costs. Large cohort studies have supported that failure of a first-line antidepressant treatment is observed in more than 60% of patients. In this case, several treatment strategies have been proposed by classical evidence-based guidelines from internationally recognized scientific societies, referring primarily on: I) the switch to another antidepressant of the same or different class; II) the combination with another antidepressant of complementary pharmacological profile; III) the addition of a wide range of pharmacological agents intending to potentiate the therapeutic effects of the ongoing antidepressant medication; IV) the association with appropriate psychological therapies; and, V) the use of non-invasive brain stimulation techniques. However, although based on the most recently available data and rigorous methodology, standard guidelines have the significant disadvantage of not covering a large variety of clinical conditions, while currently observed in everyday clinical practice. From these considerations, formalized recommendations by a large panel of French experts in the management of depressed patients have been developed under the shared sponsorship of the French Association of Biological Psychiatry and Neuropsychopharmacology (AFPBN) and the Fondation FondaMental. These French recommendations are presented in this special issue in order to provide relevant information about the treatment choices to make, depending particularly on the clinical response to previous treatment lines or the complexity of clinical

  3. Wild birds as biological indicators of environmental pollution: antimicrobial resistance patterns of Escherichia coli and enterococci isolated from common buzzards (Buteo buteo).

    PubMed

    Radhouani, Hajer; Poeta, Patrícia; Gonçalves, Alexandre; Pacheco, Rui; Sargo, Roberto; Igrejas, Gilberto

    2012-06-01

    A total of 36 Escherichia coli and 31 enterococci isolates were recovered from 42 common buzzard faecal samples. The E. coli isolates showed high levels of resistance to streptomycin and tetracycline. The following resistance genes were detected: bla(TEM) (20 of 22 ampicillin-resistant isolates), tet(A) and/or tet(B) (16 of 27 tetracycline-resistant isolates), aadA1 (eight of 27 streptomycin-resistant isolates), cmlA (three of 15 chloramphenicol-resistant isolates), aac(3)-II with/without aac(3)-IV (all seven gentamicin-resistant isolates) and sul1 and/or sul2 and/or sul3 [all eight sulfamethoxazole/trimethoprim-resistant (SXT) isolates]. intI1 and intI2 genes were detected in four SXT-resistant isolates. The virulence-associated genes fimA (type 1 fimbriae), papC (P fimbriae) and aer (aerobactin) were detected in 61.1, 13.8 and 11.1% of the isolates, respectively. The isolates belonged to phylogroups A (47.2%), B1 (8.3%), B2 (13.9%) and D (30.5%). For the enterococci isolates, Enterococcus faecium was the most prevalent species (48.4%). High levels of tetracycline and erythromycin resistance were found among our isolates (87 and 81%, respectively). Most of the tetracycline-resistant strains carried the tet(M) and/or tet(L) genes. The erm(B) gene was detected in 80% of erythromycin-resistant isolates. The vat(D) and/or vat(E) genes were found in nine of the 17 quinupristin-dalfopristin-resistant isolates. The enterococcal isolates showing high-level resistance for kanamycin, gentamicin and streptomycin contained the aph(3')-IIIa, aac(6')-aph(2″) and ant(6)-Ia genes, respectively. This report reveals that common buzzards seem to represent an important reservoir, or at least a source, of multi-resistant E. coli and enterococci isolates, and consequently may represent a considerable hazard to human and animal health by transmission of these isolates to waterways and other environmental sources via their faecal deposits.

  4. Biological and Epidemiological Features of Antibiotic-Resistant Streptococcus pneumoniae in Pre- and Post-Conjugate Vaccine Eras: a United States Perspective

    PubMed Central

    Kim, Lindsay; McGee, Lesley; Tomczyk, Sara

    2016-01-01

    SUMMARY Streptococcus pneumoniae inflicts a huge disease burden as the leading cause of community-acquired pneumonia and meningitis. Soon after mainstream antibiotic usage, multiresistant pneumococcal clones emerged and disseminated worldwide. Resistant clones are generated through adaptation to antibiotic pressures imposed while naturally residing within the human upper respiratory tract. Here, a huge array of related commensal streptococcal strains transfers core genomic and accessory resistance determinants to the highly transformable pneumococcus. β-Lactam resistance is the hallmark of pneumococcal adaptability, requiring multiple independent recombination events that are traceable to nonpneumococcal origins and stably perpetuated in multiresistant clonal complexes. Pneumococcal strains with elevated MICs of β-lactams are most often resistant to additional antibiotics. Basic underlying mechanisms of most pneumococcal resistances have been identified, although new insights that increase our understanding are continually provided. Although all pneumococcal infections can be successfully treated with antibiotics, the available choices are limited for some strains. Invasive pneumococcal disease data compiled during 1998 to 2013 through the population-based Active Bacterial Core surveillance program (U.S. population base of 30,600,000) demonstrate that targeting prevalent capsular serotypes with conjugate vaccines (7-valent and 13-valent vaccines implemented in 2000 and 2010, respectively) is extremely effective in reducing resistant infections. Nonetheless, resistant non-vaccine-serotype clones continue to emerge and expand. PMID:27076637

  5. Alanine 501 Mutations in Penicillin-Binding Protein 2 from Neisseria gonorrhoeae: Structure, Mechanism, and Effects on Cephalosporin Resistance and Biological Fitness.

    PubMed

    Tomberg, Joshua; Fedarovich, Alena; Vincent, Leah R; Jerse, Ann E; Unemo, Magnus; Davies, Christopher; Nicholas, Robert A

    2017-02-28

    Resistance of Neisseria gonorrhoeae to expanded-spectrum cephalosporins such as ceftriaxone and cefixime has increased markedly in the past decade. The primary cephalosporin resistance determinant is a mutated penA gene, which encodes the essential peptidoglycan transpeptidase, penicillin-binding protein 2 (PBP2). Decreased susceptibility and resistance can be conferred by mosaic penA alleles containing upward of 60 amino acid changes relative to wild-type PBP2, or by nonmosaic alleles with relatively few mutations, the most important of which occurs at Ala501 located near the active site of PBP2. Recently, fully cefixime- and ceftriaxone-resistant clinical isolates that harbored a mosaic penA allele with an A501P mutation were identified. To examine the potential of mutations at Ala501 to increase resistance to expanded-spectrum cephalosporins, we randomized codon 501 in a mosaic penA allele and transformed N. gonorrhoeae to increased cefixime resistance. Interestingly, only five substitutions of Ala501 (A501V, A501T, A501P, A501R, and A501S) that increased resistance and preserved essential transpeptidase function were isolated. To understand their structural implications, these mutations were introduced into the nonmosaic PBP2-6140CT, which contains four C-terminal mutations present in PBP2 from the penicillin-resistant strain FA6140. The crystal structure of PBP2-6140CT-A501T was determined and revealed ordering of a loop near the active site and a new hydrogen bond involving Thr501 that connects the loop and the SxxK conserved active site motif. The structure suggests that increased rigidity in the active site region is a mechanism for cephalosporin resistance mediated by Ala501 mutations in PBP2.

  6. Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China: a microbiological and molecular biological study.

    PubMed

    Liu, Yi-Yun; Wang, Yang; Walsh, Timothy R; Yi, Ling-Xian; Zhang, Rong; Spencer, James; Doi, Yohei; Tian, Guobao; Dong, Baolei; Huang, Xianhui; Yu, Lin-Feng; Gu, Danxia; Ren, Hongwei; Chen, Xiaojie; Lv, Luchao; He, Dandan; Zhou, Hongwei; Liang, Zisen; Liu, Jian-Hua; Shen, Jianzhong

    2016-02-01

    Until now, polymyxin resistance has involved chromosomal mutations but has never been reported via horizontal gene transfer. During a routine surveillance project on antimicrobial resistance in commensal Escherichia coli from food animals in China, a major increase of colistin resistance was observed. When an E coli strain, SHP45, possessing colistin resistance that could be transferred to another strain, was isolated from a pig, we conducted further analysis of possible plasmid-mediated polymyxin resistance. Herein, we report the emergence of the first plasmid-mediated polymyxin resistance mechanism, MCR-1, in Enterobacteriaceae. The mcr-1 gene in E coli strain SHP45 was identified by whole plasmid sequencing and subcloning. MCR-1 mechanistic studies were done with sequence comparisons, homology modelling, and electrospray ionisation mass spectrometry. The prevalence of mcr-1 was investigated in E coli and Klebsiella pneumoniae strains collected from five provinces between April, 2011, and November, 2014. The ability of MCR-1 to confer polymyxin resistance in vivo was examined in a murine thigh model. Polymyxin resistance was shown to be singularly due to the plasmid-mediated mcr-1 gene. The plasmid carrying mcr-1 was mobilised to an E coli recipient at a frequency of 10(-1) to 10(-3) cells per recipient cell by conjugation, and maintained in K pneumoniae and Pseudomonas aeruginosa. In an in-vivo model, production of MCR-1 negated the efficacy of colistin. MCR-1 is a member of the phosphoethanolamine transferase enzyme family, with expression in E coli resulting in the addition of phosphoethanolamine to lipid A. We observed mcr-1 carriage in E coli isolates collected from 78 (15%) of 523 samples of raw meat and 166 (21%) of 804 animals during 2011-14, and 16 (1%) of 1322 samples from inpatients with infection. The emergence of MCR-1 heralds the breach of the last group of antibiotics, polymyxins, by plasmid-mediated resistance. Although currently confined to China

  7. Resisting Resistance: Targeted Therapies in Lung Cancer

    PubMed Central

    Lin, Jessica J.; Shaw, Alice T.

    2016-01-01

    Drug resistance inevitably limits the efficacy of all targeted therapies including tyrosine kinase inhibitors (TKIs). Understanding the biological underpinnings of TKI resistance is key to the successful development of future therapeutic strategies. Traditionally, mechanisms of TKI resistance have been viewed under a dichotomous lens. Tumor cells are TKI-sensitive or TKI-refractory, exhibit intrinsic or acquired resistance, and accumulate alterations within or outside the target to promote their survival. Such classifications facilitate our comprehension of an otherwise complex biology, but are likely an oversimplification. Recent studies underscore the multifaceted, genetically heterogeneous nature of TKI resistance, which evolves dynamically with changes in therapy. In this Review, we provide a broad framework for understanding the diverse mechanisms of resistance at play in oncogene-driven lung cancers. PMID:27819059

  8. Synthesis and biological evaluation of novel pyrido[2,3-b]pyrazines inhibiting both erlotinib-sensitive and erlotinib-resistant cell lines.

    PubMed

    Kékesi, László; Sipos, Anna; Németh, Gábor; Pató, János; Breza, Nóra; Baska, Ferenc; Őrfi, László; Kéri, György

    2013-11-15

    A series of novel pyrido[2,3-b]pyrazines were synthesized as potential antitumor agents for erlotinib-resistant tumors. Known signal inhibitor compounds from our Nested Chemical Library were tested in phenotypic assays on erlotinib-sensitive PC9 and erlotinib-resistant PC9-ER cell lines to find a compound class to be active on erlotinib resistant cell lines. Based on the screening data, novel pyrido[2,3-b]pyrazines were designed and synthesized. The effect of the substituent position of the heteroaromatic moiety in position 7 and the importance of unsubstituted position 2 of the pyridopyrazine core were explored. Compound 7n had an IC50 value of 0.09 μM for the inhibition of PC9 and 0.15 μM for the inhibition of PC9-ER. We found that some lead compounds of these structures overcome erlotinib-resistance which might become promising drug candidates to fight against NSCLC with EGFR T790M mutation. The signaling network(s) involved in the mechanism(s) of action of these novel compounds in overcoming erlotinib resistance remain to be elucidated. Copyright © 2013 Elsevier Ltd. All rights reserved.

  9. Biological and sequence analysis of a novel European isolate of Barley mild mosaic virus that overcomes the barley rym5 resistance gene.

    PubMed

    Kanyuka, K; McGrann, G; Alhudaib, K; Hariri, D; Adams, M J

    2004-08-01

    A Barley mild mosaic virus (BaMMV) isolate from France (BaMMV-Sil) capable of overcoming rym5-controlled resistance was inoculated to barley genotypes carrying various genes for resistance to the barley mosaic viruses. BaMMV-Sil was unable to infect genotypes carrying rym1, rym4, rym8, rym9, or rym11 but genotypes carrying rym3, rym5, rym6 or no known bymovirus resistance gene were susceptible. Plants carrying rym7 or rym10 showed partial resistance with delayed virus accumulation. The two genomic RNAs of BaMMV-Sil were sequenced and compared to published sequences and those of a further common strain isolate from the UK. Four amino acid differences were observed between BaMMV-Sil and European common strain isolates in the polypeptide encoded by RNA1, the RNA species which determines pathogenicity on the rym5 genotypes. Only two of these differences are likely to be functionally important (His rather than Gln at position1217 in the VPg cistron; His rather than Asp at position 1776 in the NIb cistron). Comparisons with related viruses in the genera Bymovirus and Potyvirus suggest that the change in the VPg, which occurs within a motif conserved amongst all viruses within the family Potyviridae, is the more likely cause of rym5 resistance-breaking.

  10. Androgen resistance.

    PubMed

    Hughes, Ieuan A; Deeb, Asma

    2006-12-01

    Androgen resistance causes the androgen insensitivity syndrome in its variant forms and is a paradigm of clinical syndromes associated with hormone resistance. In its complete form, the syndrome causes XY sex reversal and a female phenotype. Partial resistance to androgens is a common cause of ambiguous genitalia of the newborn, but a similar phenotype may result from several other conditions, including defects in testis determination and androgen biosynthesis. The biological actions of androgens are mediated by a single intracellular androgen receptor encoded by a gene on the long arm of the X chromosome. Mutations in this gene result in varying degrees of androgen receptor dysfunction and phenotypes that often show poor concordance with the genotype. Functional characterization and three-dimensional modelling of novel mutant receptors has been informative in understanding the mechanism of androgen action. Management issues in syndromes of androgen insensitivity include decisions on sex assignment, timing of gonadectomy in relation to tumour risk, and genetic and psychological counselling.

  11. Avoiding the Perfect Storm: The Biologic and Clinical Case for Reevaluating the 7-Day Expectation for Methicillin-Resistant Staphylococcus aureus Bacteremia Before Switching Therapy

    PubMed Central

    Goldstein, Ellie J. C.; Kullar, Ravina; McKinnell, James A.; Sakoulas, George

    2014-01-01

    Persistent methicillin-resistant Staphylococcus aureus (MRSA) bacteremia (MRSAB) is associated with poor outcomes and serious complications. The MRSA guidelines define treatment failure and persistent bacteremia as lasting ≥7 days; however, this definition requires reevaluation. Aggressively reducing the bacterial inoculum promptly is critical because factors already in place before clinical presentation are driving resistance to the few antibiotics that are available to treat MRSAB. Alternative approaches to treat MRSAB should be considered within 3–4 days of persistent MRSAB. With rapid molecular diagnostics emerging in clinical microbiology laboratories and biomarkers as a potential for early patient risk stratification, a future shorter threshold may become possible. PMID:25048852

  12. Complete Genome Sequence of Klebsiella pneumoniae Strain ATCC 43816 KPPR1, a Rifampin-Resistant Mutant Commonly Used in Animal, Genetic, and Molecular Biology Studies

    PubMed Central

    Broberg, Christopher A.; Wu, Weisheng; Cavalcoli, James D.; Miller, Virginia L.

    2014-01-01

    Klebsiella pneumoniae is an urgent public health threat due to the spread of carbapenem-resistant strains causing serious, and frequently fatal, infections. To facilitate genetic, molecular, and immunological studies of this pathogen, we report the complete chromosomal sequence of a genetically tractable, prototypical strain used in animal models. PMID:25291761

  13. Hidden Treasures in “Ancient” Microarrays: Gene-Expression Portrays Biology and Potential Resistance Pathways of Major Lung Cancer Subtypes and Normal Tissue

    PubMed Central

    Kerkentzes, Konstantinos; Lagani, Vincenzo; Tsamardinos, Ioannis; Vyberg, Mogens; Røe, Oluf Dimitri

    2014-01-01

    Objective: Novel statistical methods and increasingly more accurate gene annotations can transform “old” biological data into a renewed source of knowledge with potential clinical relevance. Here, we provide an in silico proof-of-concept by extracting novel information from a high-quality mRNA expression dataset, originally published in 2001, using state-of-the-art bioinformatics approaches. Methods: The dataset consists of histologically defined cases of lung adenocarcinoma (AD), squamous (SQ) cell carcinoma, small-cell lung cancer, carcinoid, metastasis (breast and colon AD), and normal lung specimens (203 samples in total). A battery of statistical tests was used for identifying differential gene expressions, diagnostic and prognostic genes, enriched gene ontologies, and signaling pathways. Results: Our results showed that gene expressions faithfully recapitulate immunohistochemical subtype markers, as chromogranin A in carcinoids, cytokeratin 5, p63 in SQ, and TTF1 in non-squamous types. Moreover, biological information with putative clinical relevance was revealed as potentially novel diagnostic genes for each subtype with specificity 93–100% (AUC = 0.93–1.00). Cancer subtypes were characterized by (a) differential expression of treatment target genes as TYMS, HER2, and HER3 and (b) overrepresentation of treatment-related pathways like cell cycle, DNA repair, and ERBB pathways. The vascular smooth muscle contraction, leukocyte trans-endothelial migration, and actin cytoskeleton pathways were overexpressed in normal tissue. Conclusion: Reanalysis of this public dataset displayed the known biological features of lung cancer subtypes and revealed novel pathways of potentially clinical importance. The findings also support our hypothesis that even old omics data of high quality can be a source of significant biological information when appropriate bioinformatics methods are used. PMID:25325012

  14. All biology is computational biology.

    PubMed

    Markowetz, Florian

    2017-03-01

    Here, I argue that computational thinking and techniques are so central to the quest of understanding life that today all biology is computational biology. Computational biology brings order into our understanding of life, it makes biological concepts rigorous and testable, and it provides a reference map that holds together individual insights. The next modern synthesis in biology will be driven by mathematical, statistical, and computational methods being absorbed into mainstream biological training, turning biology into a quantitative science.

  15. All biology is computational biology

    PubMed Central

    2017-01-01

    Here, I argue that computational thinking and techniques are so central to the quest of understanding life that today all biology is computational biology. Computational biology brings order into our understanding of life, it makes biological concepts rigorous and testable, and it provides a reference map that holds together individual insights. The next modern synthesis in biology will be driven by mathematical, statistical, and computational methods being absorbed into mainstream biological training, turning biology into a quantitative science. PMID:28278152

  16. Synthesis and biological investigation of 2,4-substituted quinazolines as highly potent inhibitors of breast cancer resistance protein (ABCG2).

    PubMed

    Krapf, Michael K; Gallus, Jennifer; Wiese, Michael

    2017-08-10

    Expression of ABCG2, a member of the ABC transporter superfamily, has been correlated to the clinical outcome of multiple cancers and is often associated with the occurrence of multidrug resistance (MDR) in chemotherapy. Inhibition of the transport protein by potent and selective inhibitors might be a way to treat cancer more efficiently and improve the therapy of cancer patients. Recently we reported the synthesis of new inhibitors based on a quinazoline scaffold. In the present study more structural variations were explored. Compounds with 3,4-dimethoxy groups and meta or para nitro substituents were found to be highly potent inhibitors of ABCG2. The most potent compound was more than five-fold more potent than Ko143, one of the best inhibitors of ABCG2. To determine the new compounds selectivity toward ABCG2 their inhibitory effects on ABCB1 and ABCC1 were also investigated identifying selective as well as broadspectrum inhibitors. Furthermore, intrinsic cytotoxicity and efficacy regarding the reversal of multidrug resistance toward SN-38 and mitoxantrone were explored. The most potent compounds were able to reverse the resistance toward the cytostatic agents with EC50 values below 20 nM. Additionally, the type of interaction between inhibitors and the ABCG2 substrate Hoechst 33342 was investigated yielding competitive and non-competitive interactions suggesting different modes of binding. Finally the effect of the derivatives on vanadate-sensitive ATPase activity of ABCG2 was determined. According to the different effects on ATPase activity we conclude the existence of different binding sites. This study provides the structural requirements for high potency inhibition and elucidates the interaction with ABCG2 setting the basis for further studies. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  17. Variations in grain lipophilic phytochemicals, proteins and resistance to Fusarium spp. growth during grain storage as affected by biological plant protection with Aureobasidium pullulans (de Bary).

    PubMed

    Wachowska, Urszula; Tańska, Małgorzata; Konopka, Iwona

    2016-06-16

    Modern agriculture relies on an integrated approach, where chemical treatment is reduced to a minimum and replaced by biological control that involves the use of active microorganisms. The effect of the antagonistic yeast-like fungus Aureobasidium pullulans on proteins and bioactive compounds (alkylresorcinols, sterols, tocols and carotenoids) in winter wheat grain and on the colonization of wheat kernels by fungal microbiota, mainly Fusarium spp. pathogens, was investigated. Biological treatment contributed to a slight increase contents of tocols, alkylresorcinols and sterols in grain. At the same time, the variation of wheat grain proteins was low and not significant. Application of A. pullulans enhanced the natural yeast colonization after six months of grain storage and inhibited growth of F. culmorum pathogens penetrating wheat kernel. This study demonstrated that an integrated approach of wheat grain protection with the use of the yeast-like fungus A. pullulans reduced kernel colonization by Fusarium spp. pathogens and increased the content of nutritionally beneficial phytochemicals in wheat grain without a loss of gluten proteins responsible for baking value.

  18. Study of plasma modified-PTFE for biological applications: relationship between protein resistant properties, plasma treatment, surface composition and surface roughness.

    PubMed

    Vandencasteele, Nicolas; Nisol, Bernard; Viville, Pascal; Lazzaroni, Roberto; Castner, David G; Reniers, François

    2008-09-15

    PTFE samples were treated by low-pressure, O2 RF plasmas. The adsorption of BSA was used as a probe for the protein resistant properties. The exposure of PTFE to an O2 plasma leads to an increase in the chamber pressure. OES reveals the presence of CO, CO2 and F in the gas phase, indicating a strong etching of the PTFE surface by the O2 plasma. Furthermore, the high resolution C1s spectrum shows the appearance of CF3, CF and C-CF components in addition to the CF2 component, which is consistent with etching of the PTFE surface. WCA as high as 160° were observed, indicating a superhydrophobic behaviour. AFM Images of surfaces treated at high plasma power showed a increase in roughness. Lower amounts of BSA adsorption were detected on high power, O2 plasma-modified PTFE samples compared to low power, oxygen plasma-modified ones.

  19. Cross-Institute Evaluations of Inhibitor-Resistant PCR Reagents for Direct Testing of Aerosol and Blood Samples Containing Biological Warfare Agent DNA

    PubMed Central

    Minogue, Timothy D.; Rachwal, Phillip A.; Trombley Hall, Adrienne; Koehler, Jeffery W.

    2014-01-01

    Rapid pathogen detection is crucial for the timely introduction of therapeutics. Two groups (one in the United Kingdom and one in the United States) independently evaluated inhibitor-resistant PCR reagents for the direct testing of substrates. In the United Kingdom, a multiplexed Bacillus anthracis (target) and Bacillus subtilis (internal-control) PCR was used to evaluate 4 reagents against 5 PCR inhibitors and down-selected the TaqMan Fast Virus 1-Step master mix (Life Technologies Inc.). In the United States, four real-time PCR assays (targeting B. anthracis, Brucella melitensis, Venezuelan equine encephalitis virus [VEEV], and Orthopoxvirus spp.) were used to evaluate 5 reagents (plus the Fast Virus master mix) against buffer, blood, and soil samples and down-selected the KAPA Blood Direct master mix (KAPA Biosystems Inc.) with added Platinum Taq (Life Technologies). The down-selected reagents underwent further testing. In the United Kingdom experiments, both reagents were tested against seven contrived aerosol collector samples containing B. anthracis Ames DNA and B. subtilis spores from a commercial formulation (BioBall). In PCR assays with reaction mixtures containing 40% crude sample, an airfield-collected sample induced inhibition of the B. subtilis PCR with the KAPA reagent and complete failure of both PCRs with the Fast Virus reagent. However, both reagents allowed successful PCR for all other samples—which inhibited PCRs with a non-inhibitor-resistant reagent. In the United States, a cross-assay limit-of-detection (LoD) study in blood was conducted. The KAPA Blood Direct reagent allowed the detection of agent DNA (by four PCRs) at higher concentrations of blood in the reaction mixture (2.5%) than the Fast Virus reagent (0.5%), although LoDs differed between assays and reagent combinations. Across both groups, the KAPA Blood Direct reagent was determined to be the optimal reagent for inhibition relief in PCR. PMID:24334660

  20. Cross-institute evaluations of inhibitor-resistant PCR reagents for direct testing of aerosol and blood samples containing biological warfare agent DNA.

    PubMed

    Minogue, Timothy D; Rachwal, Phillip A; Trombley Hall, Adrienne; Koehler, Jeffery W; Weller, Simon A

    2014-02-01

    Rapid pathogen detection is crucial for the timely introduction of therapeutics. Two groups (one in the United Kingdom and one in the United States) independently evaluated inhibitor-resistant PCR reagents for the direct testing of substrates. In the United Kingdom, a multiplexed Bacillus anthracis (target) and Bacillus subtilis (internal-control) PCR was used to evaluate 4 reagents against 5 PCR inhibitors and down-selected the TaqMan Fast Virus 1-Step master mix (Life Technologies Inc.). In the United States, four real-time PCR assays (targeting B. anthracis, Brucella melitensis, Venezuelan equine encephalitis virus [VEEV], and Orthopoxvirus spp.) were used to evaluate 5 reagents (plus the Fast Virus master mix) against buffer, blood, and soil samples and down-selected the KAPA Blood Direct master mix (KAPA Biosystems Inc.) with added Platinum Taq (Life Technologies). The down-selected reagents underwent further testing. In the United Kingdom experiments, both reagents were tested against seven contrived aerosol collector samples containing B. anthracis Ames DNA and B. subtilis spores from a commercial formulation (BioBall). In PCR assays with reaction mixtures containing 40% crude sample, an airfield-collected sample induced inhibition of the B. subtilis PCR with the KAPA reagent and complete failure of both PCRs with the Fast Virus reagent. However, both reagents allowed successful PCR for all other samples-which inhibited PCRs with a non-inhibitor-resistant reagent. In the United States, a cross-assay limit-of-detection (LoD) study in blood was conducted. The KAPA Blood Direct reagent allowed the detection of agent DNA (by four PCRs) at higher concentrations of blood in the reaction mixture (2.5%) than the Fast Virus reagent (0.5%), although LoDs differed between assays and reagent combinations. Across both groups, the KAPA Blood Direct reagent was determined to be the optimal reagent for inhibition relief in PCR.

  1. Hofmeister effects in biology: effect of choline addition on the salt-induced super activity of horseradish peroxidase and its implication for salt resistance of plants.

    PubMed

    Pinna, M C; Bauduin, P; Touraud, D; Monduzzi, M; Ninham, B W; Kunz, W

    2005-09-01

    The effect of choline addition on the salt-induced super activity of horseradish peroxidase (HRP) is investigated. HRP is presented in the literature as an efficient H(2)O(2) scavenger, and choline is the precursor of glycine betaine, a strong osmoprotectant molecule. Both the regulations of H(2)O(2) and of osmoprotectant concentrations are implicated in plants in order to counteract salt-induced cell damage. For the oxidation of 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS), sulfate anions were found to play a crucial role in the increase of HRP activity. This induced super activity can be strongly reduced by adding choline chloride. The phenomena provide an example of physicochemical Hofmeister effects playing a central regulatory role in an important biological system.

  2. Synthetic biology

    PubMed Central

    Bower, Adam G; McClintock, Maria K

    2010-01-01

    The field of synthetic biology has made rapid progress in a number of areas including method development, novel applications and community building. In seeking to make biology “engineerable,” synthetic biology is increasing the accessibility of biological research to researchers of all experience levels and backgrounds. One of the underlying strengths of synthetic biology is that it may establish the framework for a rigorous bottom-up approach to studying biology starting at the DNA level. Building upon the existing framework established largely by the Registry of Standard Biological Parts, careful consideration of future goals may lead to integrated multi- scale approaches to biology. Here we describe some of the current challenges that need to be addressed or considered in detail to continue the development of synthetic biology. Specifically, discussion on the areas of elucidating biological principles, computational methods and experimental construction methodologies are presented. PMID:21326830

  3. Preliminary structure-activity relationships and biological evaluation of novel antitubercular indolecarboxamide derivatives against drug-susceptible and drug-resistant Mycobacterium tuberculosis strains.

    PubMed

    Onajole, Oluseye K; Pieroni, Marco; Tipparaju, Suresh K; Lun, Shichun; Stec, Jozef; Chen, Gang; Gunosewoyo, Hendra; Guo, Haidan; Ammerman, Nicole C; Bishai, William R; Kozikowski, Alan P

    2013-05-23

    Tuberculosis (TB) remains one of the leading causes of mortality and morbidity worldwide, with approximately one-third of the world's population infected with latent TB. This is further aggravated by HIV coinfection and the emergence of multidrug- and extensively drug-resistant (MDR and XDR, respectively) TB; hence the quest for highly effective antitubercular drugs with novel modes of action is imperative. We report herein the discovery of an indole-2-carboxamide analogue, 3, as a highly potent antitubercular agent, and the subsequent chemical modifications aimed at establishing a preliminary body of structure-activity relationships (SARs). These efforts led to the identification of three molecules (12-14) possessing an exceptional activity in the low nanomolar range against actively replicating Mycobacterium tuberculosis , with minimum inhibitory concentration (MIC) values lower than those of the most prominent antitubercular agents currently in use. These compounds were also devoid of apparent toxicity to Vero cells. Importantly, compound 12 was found to be active against the tested XDR-TB strains and orally active in the serum inhibition titration assay.

  4. Enhancing growth, phytochemical constituents and aphid resistance capacity in cabbage with foliar application of eckol--a biologically active phenolic molecule from brown seaweed.

    PubMed

    Rengasamy, Kannan R R; Kulkarni, Manoj G; Pendota, Srinivasa C; Van Staden, Johannes

    2016-03-25

    Although foliar application of seaweed extracts on plant growth and development has and is extensively studied, reliable knowledge and understanding of the mode of action of particular compound(s) responsible for enhancing plant growth is lacking. A brown seaweed Ecklonia maxima is widely used commercially as a biostimulant to improve plant growth and crop protection. Eckol, a phenolic compound isolated from E. maxima has recently shown stimulatory effects in maize, indicating its potential use as a plant biostimulant. Cabbage is a widely cultivated vegetable crop throughout the world, which requires high input of fertilizers and is susceptible to several aphid borne diseases. This study was conducted to evaluate the effect of foliar application of eckol on the growth, phytochemical constituents and myrosinase activity (aphid resistance capacity) of commercially cultivated cabbage. Foliar application of eckol (10(-6) M) significantly enhanced shoot and root length, shoot and root fresh and dry weight, leaf area and leaf number. This treatment also showed a significant increase in photosynthetic pigments (chlorophyll 'a', chlorophyll 'b', total chlorophyll and carotenoid) compared to the untreated plants. The levels of protein, proline and iridoid glycosides were significantly higher in cabbage leaves with eckol treatment. All the control plants were severely infested with cabbage aphid (Brevicoryne brassicae) but no infestation was observed on the eckol-sprayed plants, which can be attributed to an increase in myrosinase activity. This study reveals dual effects (plant growth promoting and insect repelling) of eckol on cabbage plants that need further investigations both under field conditions and in other brassicaceous species.

  5. Biological Filters.

    ERIC Educational Resources Information Center

    Klemetson, S. L.

    1978-01-01

    Presents the 1978 literature review of wastewater treatment. The review is concerned with biological filters, and it covers: (1) trickling filters; (2) rotating biological contractors; and (3) miscellaneous reactors. A list of 14 references is also presented. (HM)

  6. Biological Filters.

    ERIC Educational Resources Information Center

    Klemetson, S. L.

    1978-01-01

    Presents the 1978 literature review of wastewater treatment. The review is concerned with biological filters, and it covers: (1) trickling filters; (2) rotating biological contractors; and (3) miscellaneous reactors. A list of 14 references is also presented. (HM)

  7. Resistance-resistant antibiotics.

    PubMed

    Oldfield, Eric; Feng, Xinxin

    2014-12-01

    New antibiotics are needed because drug resistance is increasing while the introduction of new antibiotics is decreasing. We discuss here six possible approaches to develop 'resistance-resistant' antibiotics. First, multitarget inhibitors in which a single compound inhibits more than one target may be easier to develop than conventional combination therapies with two new drugs. Second, inhibiting multiple targets in the same metabolic pathway is expected to be an effective strategy owing to synergy. Third, discovering multiple-target inhibitors should be possible by using sequential virtual screening. Fourth, repurposing existing drugs can lead to combinations of multitarget therapeutics. Fifth, targets need not be proteins. Sixth, inhibiting virulence factor formation and boosting innate immunity may also lead to decreased susceptibility to resistance. Although it is not possible to eliminate resistance, the approaches reviewed here offer several possibilities for reducing the effects of mutations and, in some cases, suggest that sensitivity to existing antibiotics may be restored in otherwise drug-resistant organisms.

  8. Biological properties

    Treesearch

    Rebecca E. Ibach

    2005-01-01

    There are numerous biological degradations that wood is exposed to in various environments. Biological damage occurs when a log, sawn product, or final product is not stored, handled, or designed properly. Biological organisms, such as bacteria, mold, stain, decay fungi, insects, and marine borers, depend heavily on temperature and moisture conditions to grow. A higher...

  9. [Biological weapons].

    PubMed

    Kerwat, K; Becker, S; Wulf, H; Densow, D

    2010-08-01

    Biological weapons are weapons of mass destruction that use pathogens (bacteria, viruses) or the toxins produced by them to target living organisms or to contaminate non-living substances. In the past, biological warfare has been repeatedly used. Anthrax, plague and smallpox are regarded as the most dangerous biological weapons by various institutions. Nowadays it seems quite unlikely that biological warfare will be employed in any military campaigns. However, the possibility remains that biological weapons may be used in acts of bioterrorism. In addition all diseases caused by biological weapons may also occur naturally or as a result of a laboratory accident. Risk assessment with regard to biological danger often proves to be difficult. In this context, an early identification of a potentially dangerous situation through experts is essential to limit the degree of damage. Georg Thieme Verlag KG Stuttgart * New York.

  10. Synthetic biology for therapeutic applications.

    PubMed

    Abil, Zhanar; Xiong, Xiong; Zhao, Huimin

    2015-02-02

    Synthetic biology is a relatively new field with the key aim of designing and constructing biological systems with novel functionalities. Today, synthetic biology devices are making their first steps in contributing new solutions to a number of biomedical challenges, such as emerging bacterial antibiotic resistance and cancer therapy. This review discusses some synthetic biology approaches and applications that were recently used in disease mechanism investigation and disease modeling, drug discovery and production, as well as vaccine development and treatment of infectious diseases, cancer, and metabolic disorders.

  11. Synthetic Biology for Therapeutic Applications

    PubMed Central

    2015-01-01

    Synthetic biology is a relatively new field with the key aim of designing and constructing biological systems with novel functionalities. Today, synthetic biology devices are making their first steps in contributing new solutions to a number of biomedical challenges, such as emerging bacterial antibiotic resistance and cancer therapy. This review discusses some synthetic biology approaches and applications that were recently used in disease mechanism investigation and disease modeling, drug discovery and production, as well as vaccine development and treatment of infectious diseases, cancer, and metabolic disorders. PMID:25098838

  12. Antimicrobial Resistance

    MedlinePlus

    ... spread of antimicrobial resistance. Present situation Resistance in bacteria Antibiotic resistance is present in every country. Patients with infections caused by drug-resistant bacteria are at increased risk of worse clinical outcomes ...

  13. Anthelmintic resistance.

    PubMed

    Waller, P J

    1997-11-01

    simple commercial fact that by far the greatest anthelmintic sales are associated with the cattle industry. However, this market is specific and sectoral, with by far the greatest sales in North America and Western Europe, where the prevalence of resistance is likely to be low and remain so, more-or-less indefinitely. So the chances of the above scenario occurring must be considered low. Remarkable developments have recently occurred in non-chemotherapeutic parasite control options, for example worm vaccines, host selection and biological control. Also, there seems to be greater acceptance of various grazing management practices designed to reduce the frequency of anthelmintic treatment. However, they collectively cannot be expected to offer immediate salvation to farmers now faced with chemotherapeutic failure to control nematode parasites in their flocks. The future for these farmers must be considered bleak, because compounded with these problems are the poor commodity prices for sheep and goat meat and fibre, resulting in relentless reductions in funding for research to support these industries. Perhaps the major social issues associated with re-structuring and possibly abandonment of sheep and goat farming in affected areas may precipitate action? As veterinary parasitologists, who in general have an interest and expertise in parasite control, we must promote the importance of the problem of anthelmintic resistance and ways to tackle it.

  14. Endless Resistance. Endless Antibiotics?

    PubMed Central

    Fisher, Jed F.; Mobashery, Shahriar

    2016-01-01

    The practice of medicine was profoundly transformed by the introduction of the antibiotics (compounds isolated from Nature) and the antibacterials (compounds prepared by synthesis) for the control of bacterial infection. As a result of the extraordinary success of these compounds over decades of time, a timeless biological activity for these compounds has been presumed. This presumption is no longer. The inexorable acquisition of resistance mechanisms by bacteria is retransforming medical practice. Credible answers to this dilemma are far better recognized than they are being implemented. In this perspective we examine (and in key respects, reiterate) the chemical and biological strategies being used to address the challenge of bacterial resistance. PMID:27746889

  15. A high area, porous and resistant platinized stainless steel fiber coated by nanostructured polypyrrole for direct HS-SPME of nicotine in biological samples prior to GC-FID quantification.

    PubMed

    Abdolhosseini, Sana; Ghiasvand, Alireza; Heidari, Nahid

    2017-09-01

    The surface of a stainless steel fiber was made porous, resistant and cohesive using electrophoretic deposition and coated by the nanostructured polypyrrole using an amended in-situ electropolymerization method. The coated fiber was applied for direct extraction of nicotine in biological samples through a headspace solid-phase microextraction (HS-SPME) method followed by GC-FID determination. The effects of the important experimental variables on the efficiency of the developed HS-SPME-GC-FID method, including pH of sample solution, extraction temperature and time, stirring rate, and ionic strength were evaluated and optimized. Under the optimal experimental conditions, the calibration curve was linear over the range of 0.1-20μgmL(-1) and the detection limit was obtained 20ngmL(-1). Relative standard deviation (RSD, n=6) was calculated 7.6%. The results demonstrated the superiority of the proposed fiber compared with the most used commercial types. The proposed HS-SPME-GC-FID method was successfully used for the analysis of nicotine in urine and human plasma samples. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. [Reduction of livestock-associated methicillin-resistant staphylococcus aureus (LA-MRSA) in the exhaust air of two piggeries by a bio-trickling filter and a biological three-step air cleaning system].

    PubMed

    Clauss, Marcus; Schulz, Jochen; Stratmann-Selke, Janin; Decius, Maja; Hartung, Jörg

    2013-01-01

    "Livestock-associated" Methicillin-resistent Staphylococcus aureus (LA-MRSA) are frequently found in the air of piggeries, are emitted into the ambient air of the piggeries and may also drift into residential areas or surrounding animal husbandries.. In order to reduce emissions from animal houses such as odour, gases and dust different biological air cleaning systems are commercially available. In this study the retention efficiencies for the culturable LA-MRSA of a bio-trickling filter and a combined three step system, both installed at two different piggeries, were investigated. Raw gas concentrations for LA-MRSA of 2.1 x 10(2) cfu/m3 (biotrickling filter) and 3.9 x 10(2) cfu/m3 (three step system) were found. The clean gas concentrations were in each case approximately one power of ten lower. Both systems were able to reduce the number of investigated bacteria in the air of piggeries on average about 90%. The investigated systems can contribute to protect nearby residents. However, considerable fluctuations of the emissions can occur.

  17. Biological indeterminacy.

    PubMed

    Greenspan, Ralph J

    2012-09-01

    Reductionist explanations in biology generally assume that biological mechanisms are highly deterministic and basically similar between individuals. A contrasting view has emerged recently that takes into account the degeneracy of biological processes--the ability to arrive at a given endpoint by a variety of available paths, even within the same individual. This perspective casts significant doubt on the prospects for the ability to predict behavior accurately based on brain imaging or genotyping, and on the ability of neuroscience to stipulate ethics.

  18. Is synthetic biology mechanical biology?

    PubMed

    Holm, Sune

    2015-12-01

    A widespread and influential characterization of synthetic biology emphasizes that synthetic biology is the application of engineering principles to living systems. Furthermore, there is a strong tendency to express the engineering approach to organisms in terms of what seems to be an ontological claim: organisms are machines. In the paper I investigate the ontological and heuristic significance of the machine analogy in synthetic biology. I argue that the use of the machine analogy and the aim of producing rationally designed organisms does not necessarily imply a commitment to mechanical biology. The ideal of applying engineering principles to biology is best understood as expressing recognition of the machine-unlikeness of natural organisms and the limits of human cognition. The paper suggests an interpretation of the identification of organisms with machines in synthetic biology according to which it expresses a strategy for representing, understanding, and constructing living systems that are more machine-like than natural organisms.

  19. Biology Notes.

    ERIC Educational Resources Information Center

    School Science Review, 1983

    1983-01-01

    Describes laboratory procedures, demonstrations, and classroom activities/materials, including chi-square tests on a microcomputer, an integrated biology game, microscope slides of leaf stomata, culturing soil nematodes, technique for watering locust egg-laying tubes, hazards of biological chemicals (such as benzene, benzidene, calchicine,…

  20. Biology Notes.

    ERIC Educational Resources Information Center

    School Science Review, 1982

    1982-01-01

    Presents procedures, exercises, demonstrations, and information on a variety of biology topics including labeling systems, biological indicators of stream pollution, growth of lichens, reproductive capacity of bulbous buttercups, a straw balance to measure transpiration, interaction of fungi, osmosis, and nitrogen fixation and crop production. (DC)

  1. Biology Notes.

    ERIC Educational Resources Information Center

    School Science Review, 1982

    1982-01-01

    Presents procedures, exercises, demonstrations, and information on a variety of biology topics including labeling systems, biological indicators of stream pollution, growth of lichens, reproductive capacity of bulbous buttercups, a straw balance to measure transpiration, interaction of fungi, osmosis, and nitrogen fixation and crop production. (DC)

  2. Biology Notes.

    ERIC Educational Resources Information Center

    School Science Review, 1982

    1982-01-01

    Describes laboratory procedures, demonstrations, and classroom activities/materials, including use of dwarf cichlids (fishes) in secondary school biology, teaching edge effects on stomatal diffusion, computer program on effects of selection on gene frequencies, biological oxidation/reduction reactions, short cuts with Drosophila, computer program…

  3. Biology Notes.

    ERIC Educational Resources Information Center

    School Science Review, 1982

    1982-01-01

    Describes laboratory procedures, demonstrations, and classroom activities/materials, including use of dwarf cichlids (fishes) in secondary school biology, teaching edge effects on stomatal diffusion, computer program on effects of selection on gene frequencies, biological oxidation/reduction reactions, short cuts with Drosophila, computer program…

  4. Biology Notes.

    ERIC Educational Resources Information Center

    School Science Review, 1978

    1978-01-01

    Presents experiments, demonstrations, activities and ideas relating to various fields of biology to be used in biology courses in secondary schools. Among those experiments presented are demonstrating the early stages of ferns and mosses and simple culture methods for fern prothalli. (HM)

  5. Biology Notes.

    ERIC Educational Resources Information Center

    School Science Review, 1983

    1983-01-01

    Describes laboratory procedures, demonstrations, and classroom activities/materials, including chi-square tests on a microcomputer, an integrated biology game, microscope slides of leaf stomata, culturing soil nematodes, technique for watering locust egg-laying tubes, hazards of biological chemicals (such as benzene, benzidene, calchicine,…

  6. Biology Notes.

    ERIC Educational Resources Information Center

    School Science Review, 1978

    1978-01-01

    Presents experiments, demonstrations, activities and ideas relating to various fields of biology to be used in biology courses in secondary schools. Among those experiments presented are demonstrating the early stages of ferns and mosses and simple culture methods for fern prothalli. (HM)

  7. Biological Oceanography

    NASA Astrophysics Data System (ADS)

    Dyhrman, Sonya

    2004-10-01

    The ocean is arguably the largest habitat on the planet, and it houses an astounding array of life, from microbes to whales. As a testament to this diversity and its importance, the discipline of biological oceanography spans studies of all levels of biological organization, from that of single genes, to organisms, to their population dynamics. Biological oceanography also includes studies on how organisms interact with, and contribute to, essential global processes. Students of biological oceanography are often as comfortable looking at satellite images as they are electron micrographs. This diversity of perspective begins the textbook Biological Oceanography, with cover graphics including a Coastal Zone Color Scanner image representing chlorophyll concentration, an electron micrograph of a dinoflagellate, and a photograph of a copepod. These images instantly capture the reader's attention and illustrate some of the different scales on which budding oceanographers are required to think. Having taught a core graduate course in biological oceanography for many years, Charlie Miller has used his lecture notes as the genesis for this book. The text covers the subject of biological oceanography in a manner that is targeted to introductory graduate students, but it would also be appropriate for advanced undergraduates.

  8. Biological warfare agents.

    PubMed

    Thavaselvam, Duraipandian; Vijayaraghavan, Rajagopalan

    2010-07-01

    The recent bioterrorist attacks using anthrax spores have emphasized the need to detect and decontaminate critical facilities in the shortest possible time. There has been a remarkable progress in the detection, protection and decontamination of biological warfare agents as many instrumentation platforms and detection methodologies are developed and commissioned. Even then the threat of biological warfare agents and their use in bioterrorist attacks still remain a leading cause of global concern. Furthermore in the past decade there have been threats due to the emerging new diseases and also the re-emergence of old diseases and development of antimicrobial resistance and spread to new geographical regions. The preparedness against these agents need complete knowledge about the disease, better research and training facilities, diagnostic facilities and improved public health system. This review on the biological warfare agents will provide information on the biological warfare agents, their mode of transmission and spread and also the detection systems available to detect them. In addition the current information on the availability of commercially available and developing technologies against biological warfare agents has also been discussed. The risk that arise due to the use of these agents in warfare or bioterrorism related scenario can be mitigated with the availability of improved detection technologies.

  9. Biological warfare agents

    PubMed Central

    Thavaselvam, Duraipandian; Vijayaraghavan, Rajagopalan

    2010-01-01

    The recent bioterrorist attacks using anthrax spores have emphasized the need to detect and decontaminate critical facilities in the shortest possible time. There has been a remarkable progress in the detection, protection and decontamination of biological warfare agents as many instrumentation platforms and detection methodologies are developed and commissioned. Even then the threat of biological warfare agents and their use in bioterrorist attacks still remain a leading cause of global concern. Furthermore in the past decade there have been threats due to the emerging new diseases and also the re-emergence of old diseases and development of antimicrobial resistance and spread to new geographical regions. The preparedness against these agents need complete knowledge about the disease, better research and training facilities, diagnostic facilities and improved public health system. This review on the biological warfare agents will provide information on the biological warfare agents, their mode of transmission and spread and also the detection systems available to detect them. In addition the current information on the availability of commercially available and developing technologies against biological warfare agents has also been discussed. The risk that arise due to the use of these agents in warfare or bioterrorism related scenario can be mitigated with the availability of improved detection technologies. PMID:21829313

  10. Resistance-Resistant Antibiotics

    PubMed Central

    Oldfield, Eric; Feng, Xinxin

    2014-01-01

    New antibiotics are needed because as drug resistance is increasing, the introduction of new antibiotics is decreasing. Here, we discuss six possible approaches to develop ‘resistance-resistant’ antibiotics. First, multi-target inhibitors in which a single compound inhibits more than one target may be easier to develop than conventional combination therapies with two new drugs. Second, inhibiting multiple targets in the same metabolic pathway is expected to be an effective strategy due to synergy. Third, discovering multiple-target inhibitors should be possible by using sequential virtual screening. Fourth, re-purposing existing drugs can lead to combinations of multi-target therapeutics. Fifth, targets need not be proteins. Sixth, inhibiting virulence factor formation and boosting innate immunity may also lead to decreased susceptibility to resistance. Although it is not possible to eliminate resistance, the approaches reviewed here offer several possibilities for reducing the effects of mutations and in some cases suggest that sensitivity to existing antibiotics may be restored, in otherwise drug resistant organisms. PMID:25458541

  11. Electron transfer in biology

    NASA Astrophysics Data System (ADS)

    Williams, R. J. P.

    Electron transfer is one of the key reactions of biology not just in catalysis of oxidation/reduction reactions but in the conversion of sources of energy such as light to usable form for chemical transformations. There are then two intriguing problems. What is the nature of the matrix in which electrons flow in a biological cell after the initial charge separation due for example to the absorption of light. Here we are examining biological structures similar to man's electronic wires and the construction must be of low resistance in what are apparently insulators - organic polymers. It has been found that the electronic conduction system is largely made from metallo-proteins associated with lipid membranes. We understand much about these biological wires today. The second problem concerns the conversion of the energy captured from the light into usable chemical form. The major synthetic step in the production of biological polymers, including proteins, DNA, RNA, polysaccharides and fats, is condensation, i.e. the removal of water in the formation of amides, esters and so on. Now these condensation reactions are driven in biology by using a drying agent in water, namely the anhydride, pyrophosphate, in a special compound ATP, adenosine triphosphate. The central problem is to discover exactly how the flow of electrons can be related to the synthesis of (bound) pyrophosphate. (In a thermodynamic sense pyrophosphate is a water soluble kinetically stable drying agent comparable with solid P2O5.) In the biological systems the connection between these different classes of reaction, electron transfer and condensation, is known to be via the production of an energized gradient of protons across the biological membrane which arises from the flow of electrons across the same membrane in the electron transport wires of biology. However we do not understand thoroughly the steps which lead from electron flow in a membrane to proton gradients in that membrane, i.e. electron

  12. BIOLOGICAL WARFARE

    PubMed Central

    Beeston, John

    1953-01-01

    The use of biological agents as controlled weapons of war is practical although uncertain. Three types of agents are feasible, including pathogenic organisms and biological pests, toxins, and synthetic hormones regulating plant growth. These agents may be chosen for selective effects varying from prolonged incipient illness to death of plants, man and domestic animals. For specific preventive and control measures required to combat these situations, there must be careful and detailed planning. The nucleus of such a program is available within the existing framework of public health activities. Additional research and expansion of established activities in time of attack are necessary parts of biological warfare defense. PMID:13059641

  13. Bottle Biology.

    ERIC Educational Resources Information Center

    CSTA Journal, 1995

    1995-01-01

    Provides hands-on biology activities using plastic bottles that allow students to become engaged in asking questions, creating experiments, testing hypotheses, and generating answers. Activities explore terrestrial and aquatic systems. (MKR)

  14. Biological Agents

    MedlinePlus

    ... is required. Biological Agents Menu Overview In Focus: Ebola Frederick A. Murphy/CDC OSHA's Ebola webpage provides ... OSHA offers, visit OSHA's Workers' page. In Focus: Ebola Frederick A. Murphy/CDC OSHA's Ebola webpage provides ...

  15. Biology Notes

    ERIC Educational Resources Information Center

    School Science Review, 1972

    1972-01-01

    Twelve new experiments in biology are described by teachers for use in classrooms. Broad areas covered include enzyme action, growth regulation, microscopy, respiration, germination, plant succession, leaf structure and blood structure. Explanations are detailed. (PS)

  16. Bottle Biology.

    ERIC Educational Resources Information Center

    CSTA Journal, 1995

    1995-01-01

    Provides hands-on biology activities using plastic bottles that allow students to become engaged in asking questions, creating experiments, testing hypotheses, and generating answers. Activities explore terrestrial and aquatic systems. (MKR)

  17. Biology Notes

    ERIC Educational Resources Information Center

    School Science Review, 1972

    1972-01-01

    Ten ideas that have been tried out by the authors in schools are presented for biology teachers. The areas covered include genetics, dispersal of seeds, habituation in earthworms, respiration, sensory neurons, fats and oils. A reading list is provided. (PS)

  18. Biological monitoring

    SciTech Connect

    Ho, M.H.; Dillon, H.K.

    1986-02-01

    Biological monitoring is defined as the measurement and assessment of workplace agents or their metabolites in tissues, secreta, excreta, expired air, or any combination of these to evaluate exposure and health risk compared to an appropriate reference. Biological monitoring offers several advantages: it takes into account individual variability in biological activity resulting from a chemical insult. It takes into account the effects of personal physical activity and individual life styles. It is a valuable adjunct to ambient monitoring and health surveillance. The importance of chemical speciation in the toxicity of pollutants is discussed. Basic protocols for lead, aluminum, cadmium, mercury, selenium, and nickel are presented. Basic criteria for biological monitoring methods are presented. 11 references, 1 table.

  19. Biology Notes

    ERIC Educational Resources Information Center

    School Science Review, 1972

    1972-01-01

    Ten ideas that have been tried out by the authors in schools are presented for biology teachers. The areas covered include genetics, dispersal of seeds, habituation in earthworms, respiration, sensory neurons, fats and oils. A reading list is provided. (PS)

  20. Biology Notes

    ERIC Educational Resources Information Center

    School Science Review, 1973

    1973-01-01

    Some helpful ideas are proposed for use by biology teachers. Topics included are Food Webs,'' Key to Identification of Families,'' Viruses,'' Sieve Tube,'' Woodlice,'' Ecology of Oak Leaf Roller Moth,'' and Model Making.'' (PS)

  1. Biology Notes

    ERIC Educational Resources Information Center

    School Science Review, 1972

    1972-01-01

    Twelve new experiments in biology are described by teachers for use in classrooms. Broad areas covered include enzyme action, growth regulation, microscopy, respiration, germination, plant succession, leaf structure and blood structure. Explanations are detailed. (PS)

  2. Biology Notes

    ERIC Educational Resources Information Center

    School Science Review, 1973

    1973-01-01

    Some helpful ideas are proposed for use by biology teachers. Topics included are Food Webs,'' Key to Identification of Families,'' Viruses,'' Sieve Tube,'' Woodlice,'' Ecology of Oak Leaf Roller Moth,'' and Model Making.'' (PS)

  3. Drug Resistance

    MedlinePlus

    HIV Treatment Drug Resistance (Last updated 3/2/2017; last reviewed 3/2/2017) Key Points As HIV multiplies in the ... the risk of drug resistance. What is HIV drug resistance? Once a person becomes infected with HIV, ...

  4. Ecological Compatibility of GM Crops and Biological Control

    USDA-ARS?s Scientific Manuscript database

    Insect-resistant and herbicide-tolerant genetically modified (GM) crops pervade many modern cropping systems, and present challenges and opportunities for developing biologically-based pest management programs. Interactions between biological control agents (insect predators, parasitoids, and pathog...

  5. Biological Oceanography

    NASA Technical Reports Server (NTRS)

    Abbott, M. R.

    1984-01-01

    Within the framework of global biogeochemical cycles and ocean productivity, there are two areas that will be of particular interest to biological oceanography in the 1990s. The first is the mapping in space time of the biomass and productivity of phytoplankton in the world ocean. The second area is the coupling of biological and physical processes as it affects the distribution and growth rate of phytoplankton biomass. Certainly other areas will be of interest to biological oceanographers, but these two areas are amenable to observations from satellites. Temporal and spatial variability is a regular feature of marine ecosystems. The temporal and spatial variability of phytoplankton biomass and productivity which is ubiquitous at all time and space scales in the ocean must be characterized. Remote sensing from satellites addresses these problems with global observations of mesocale (2 to 20 days, 10 to 200 km) features over a long period of time.

  6. (Biological dosimetry)

    SciTech Connect

    Sega, G.A.

    1990-11-06

    The traveler participated in an International Symposium on Trends in Biological Dosimetry and presented an invited paper entitled, Adducts in sperm protamine and DNA vs mutation frequency.'' The purpose of the Symposium was to examine the applicability of new methods to study quantitatively the effects of xenobiotic agents (radiation and chemicals) on molecular, cellular and organ systems, with special emphasis on human biological dosimetry. The general areas covered at the meeting included studies on parent compounds and metabolites; protein adducts; DNA adducts; gene mutations; cytogenetic end-points and reproductive methods.

  7. Biotic resistance in marine environments.

    PubMed

    Kimbro, David L; Cheng, Brian S; Grosholz, Edwin D

    2013-06-01

    Biological invasions depend in part on the resistance of native communities. Meta-analyses of terrestrial experiments demonstrate that native primary producers and herbivores generally resist invasions of primary producers, and that resistance through competition strengthens with native producer diversity. To test the generality of these findings, we conducted a meta-analysis of marine experiments. We found that native marine producers generally failed to resist producer invasions through competition unless the native community was diverse, and this diversity effect was weaker in marine than in terrestrial systems. In contrast, native consumers equally resisted invasive producers in both ecosystems. Most marine experiments, however, tested invasive consumers and these invasions were resisted more strongly than were producer invasions. Given these differences between ecosystems and between marine trophic levels, we used a model-selection approach to assess if factors other than the resistance mechanism (i.e. competition vs. consumption) are more important for predicting marine biotic resistance. These results suggest that understanding marine biotic resistance depends on latitude, habitat and invader taxon, in addition to distinguishing between competition with and consumption by native species. By examining biotic resistance within and across ecosystems, our work provides a more complete understanding of the factors that underlie biological invasions. © 2013 John Wiley & Sons Ltd/CNRS.

  8. Biological Control of Nematodes with Bacteria

    USDA-ARS?s Scientific Manuscript database

    Biological control of nematodes is receiving increased attention as environmental considerations with the use of nematicides have increased in importance and their high cost prohibits use on many crops. In addition, nematode resistant cultivars are not available for many crops and resistance that i...

  9. Sverdrup's Biology

    NASA Astrophysics Data System (ADS)

    McGowan, J.

    2002-12-01

    Sverdrup's contribution to Biological Oceanography were more than merely substantial, they were of fundamental importance. His plan for the training of graduate students at Scripps did not recognize the traditional division of the basic disciplines into separate categories of physics, chemistry, biology and geology. He insisted that Oceanography was a multi-disciplinary subject and that all entering students should study all four subjects. Today this is not very unusual but it was in the early 50s when I took those courses. We biologists carried away from those courses an appreciation of the importance of both spatial and temporal scale. It was of clear relevance to problems of oceanic population and community biology. But there was still more to his biology. He is responsible for a very simple, but very elegant model of the regulation of oceanic primary productivity. The elements of this model are found today in the ten or so highly derivative models. He also published a map predicting global ocean productivity based on the ideas in the model plus some wonderfully intuitive thinking. This map does not differ strongly from those glorious false color ones being published today.

  10. Biology Notes.

    ERIC Educational Resources Information Center

    School Science Review, 1981

    1981-01-01

    Outlines a variety of laboratory procedures, techniques, and materials including construction of a survey frame for field biology, a simple tidal system, isolation and applications of plant protoplasts, tropisms, teaching lung structure, and a key to statistical methods for biologists. (DS)

  11. Biology Notes.

    ERIC Educational Resources Information Center

    School Science Review, 1983

    1983-01-01

    Describes laboratory procedures, demonstrations, and classroom activities/materials, including water relation exercise on auxin-treated artichoke tuber tissue; aerobic respiration in yeast; an improved potometer; use of mobiles in biological classification, and experiments on powdery mildews and banana polyphenol oxidase. Includes reading lists…

  12. Scaffolded biology.

    PubMed

    Minelli, Alessandro

    2016-09-01

    Descriptions and interpretations of the natural world are dominated by dichotomies such as organism vs. environment, nature vs. nurture, genetic vs. epigenetic, but in the last couple of decades strong dissatisfaction with those partitions has been repeatedly voiced and a number of alternative perspectives have been suggested, from perspectives such as Dawkins' extended phenotype, Turner's extended organism, Oyama's Developmental Systems Theory and Odling-Smee's niche construction theory. Last in time is the description of biological phenomena in terms of hybrids between an organism (scaffolded system) and a living or non-living scaffold, forming unit systems to study processes such as reproduction and development. As scaffold, eventually, we can define any resource used by the biological system, especially in development and reproduction, without incorporating it as happens in the case of resources fueling metabolism. Addressing biological systems as functionally scaffolded systems may help pointing to functional relationships that can impart temporal marking to the developmental process and thus explain its irreversibility; revisiting the boundary between development and metabolism and also regeneration phenomena, by suggesting a conceptual framework within which to investigate phenomena of regular hypermorphic regeneration such as characteristic of deer antlers; fixing a periodization of development in terms of the times at which a scaffolding relationship begins or is terminated; and promoting plant galls to legitimate study objects of developmental biology.

  13. Biology Notes.

    ERIC Educational Resources Information Center

    School Science Review, 1979

    1979-01-01

    Organized by topic is a reading list for A- and S-level biology. Described are experiments for measuring rate of water uptake in a shoot; questions to aid students in designing experiments; rise of overhead projection to demonstrate osmosis and blood cell counting; and microbial manufacture of vinegar. (CS)

  14. Biology Notes

    ERIC Educational Resources Information Center

    School Science Review, 1976

    1976-01-01

    Describes nine biology experiments, including osmosis, genetics; oxygen content of blood, enzymes in bean seedlings, preparation of bird skins, vascularization in bean seedlings, a game called "sequences" (applied to review situations), crossword puzzle for human respiration, and physiology of the woodlouse. (CS)

  15. Biology Notes

    ERIC Educational Resources Information Center

    School Science Review, 1976

    1976-01-01

    Describes nine biology experiments, including osmosis, genetics; oxygen content of blood, enzymes in bean seedlings, preparation of bird skins, vascularization in bean seedlings, a game called "sequences" (applied to review situations), crossword puzzle for human respiration, and physiology of the woodlouse. (CS)

  16. Bottle Biology.

    ERIC Educational Resources Information Center

    Jager, Peter

    1993-01-01

    Describes activities which utilize plastic drink bottles and are designed to foster the development of a wide range of biological and ecological concepts. Includes instructions for making a model compost column and presents a model that illustrates open versus closed ecosystems. (DDR)

  17. Biology Notes.

    ERIC Educational Resources Information Center

    School Science Review, 1984

    1984-01-01

    Presents information on the teaching of nutrition (including new information relating to many current O-level syllabi) and part 16 of a reading list for A- and S-level biology. Also includes a note on using earthworms as a source of material for teaching meiosis. (JN)

  18. Cancer Biology

    ERIC Educational Resources Information Center

    Dominiecki, Mary E.

    2004-01-01

    University of Colorado's Virtual Student Fellowship available at and developed by Bakemeier, Richard F. This website is designed to give students applying for a fellowship an overview of basic topics in biology and how they are used by cancer researchers to develop new treatments.

  19. Biology Notes.

    ERIC Educational Resources Information Center

    School Science Review, 1980

    1980-01-01

    Describes equipment, activities, and experiments useful in biology and environmental education instruction, including, among others, sampling in ecology using an overhead projector, the slide finder as an aid to microscopy, teaching kidney function, and teaching wildlife conservation-sand dune systems. (SK)

  20. Biology Notes.

    ERIC Educational Resources Information Center

    School Science Review, 1981

    1981-01-01

    Outlines a variety of laboratory procedures, techniques, and materials including construction of a survey frame for field biology, a simple tidal system, isolation and applications of plant protoplasts, tropisms, teaching lung structure, and a key to statistical methods for biologists. (DS)

  1. Biology Notes.

    ERIC Educational Resources Information Center

    School Science Review, 1984

    1984-01-01

    Presents information on the teaching of nutrition (including new information relating to many current O-level syllabi) and part 16 of a reading list for A- and S-level biology. Also includes a note on using earthworms as a source of material for teaching meiosis. (JN)

  2. Biology Excursions

    ERIC Educational Resources Information Center

    Baldock, R. N.

    1973-01-01

    Provides many useful suggestions and cautions for planning and executing a biology field excursion. Specific procedures are outlined for investigating land communities and coastal areas, and a number of follow-up laboratory activities are described. The appendix provides an extensive bibliography with useful comments on the literature. (JR)

  3. Marine Biology

    ERIC Educational Resources Information Center

    Dewees, Christopher M.; Hooper, Jon K.

    1976-01-01

    A variety of informational material for a course in marine biology or oceanology at the secondary level is presented. Among the topics discussed are: food webs and pyramids, planktonic blooms, marine life, plankton nets, food chains, phytoplankton, zooplankton, larval plankton and filter feeders. (BT)

  4. Marine Biology

    ERIC Educational Resources Information Center

    Dewees, Christopher M.; Hooper, Jon K.

    1976-01-01

    A variety of informational material for a course in marine biology or oceanology at the secondary level is presented. Among the topics discussed are: food webs and pyramids, planktonic blooms, marine life, plankton nets, food chains, phytoplankton, zooplankton, larval plankton and filter feeders. (BT)

  5. Biology Notes.

    ERIC Educational Resources Information Center

    School Science Review, 1983

    1983-01-01

    Describes laboratory procedures, demonstrations, and classroom activities/materials, including water relation exercise on auxin-treated artichoke tuber tissue; aerobic respiration in yeast; an improved potometer; use of mobiles in biological classification, and experiments on powdery mildews and banana polyphenol oxidase. Includes reading lists…

  6. Biology Notes.

    ERIC Educational Resources Information Center

    School Science Review, 1979

    1979-01-01

    Organized by topic is a reading list for A- and S-level biology. Described are experiments for measuring rate of water uptake in a shoot; questions to aid students in designing experiments; rise of overhead projection to demonstrate osmosis and blood cell counting; and microbial manufacture of vinegar. (CS)

  7. Biologic Vaccines

    PubMed Central

    ADAMS, KATHERINE T.

    2009-01-01

    The threat of new disease pandemics has spurred the development of biologic vaccines, which promise tremendous improvements in global and local health. Several lend themselves to the prevention or treatment of chronic diseases. But the uncertainties of whom to vaccinate raise the question of whether the health care system can make these promising products viable. PMID:22478749

  8. Biology Notes.

    ERIC Educational Resources Information Center

    School Science Review, 1980

    1980-01-01

    Describes equipment, activities, and experiments useful in biology and environmental education instruction, including, among others, sampling in ecology using an overhead projector, the slide finder as an aid to microscopy, teaching kidney function, and teaching wildlife conservation-sand dune systems. (SK)

  9. Cancer Biology

    ERIC Educational Resources Information Center

    Dominiecki, Mary E.

    2004-01-01

    University of Colorado's Virtual Student Fellowship available at and developed by Bakemeier, Richard F. This website is designed to give students applying for a fellowship an overview of basic topics in biology and how they are used by cancer researchers to develop new treatments.

  10. Biology Notes.

    ERIC Educational Resources Information Center

    School Science Review, 1981

    1981-01-01

    Presents content information and/or laboratory procedures and experiments on different biology topics including small-scale cultivation of watercress and its use in water-culture experiments, microbiology of the phylloplane, use of mouthbrooders in science class, and the gene. (DC)

  11. Bottle Biology.

    ERIC Educational Resources Information Center

    Jager, Peter

    1993-01-01

    Describes activities which utilize plastic drink bottles and are designed to foster the development of a wide range of biological and ecological concepts. Includes instructions for making a model compost column and presents a model that illustrates open versus closed ecosystems. (DDR)

  12. (Biological dosimetry)

    SciTech Connect

    Preston, R.J.

    1990-12-17

    The traveler attended the 1st International Conference on Biological Dosimetry in Madrid, Spain. This conference was organized to provide information to a general audience of biologists, physicists, radiotherapists, industrial hygiene personnel and individuals from related fields on the current ability of cytogenetic analysis to provide estimates of radiation dose in cases of occupational or environmental exposure. There is a growing interest in Spain in biological dosimetry because of the increased use of radiation sources for medical and occupational uses, and with this the anticipated and actual increase in numbers of overexposure. The traveler delivered the introductory lecture on Biological Dosimetry: Mechanistic Concepts'' that was intended to provide a framework by which the more applied lectures could be interpreted in a mechanistic way. A second component of the trip was to provide advice with regard to several recent cases of overexposure that had been or were being assessed by the Radiopathology and Radiotherapy Department of the Hospital General Gregorio Maranon'' in Madrid. The traveler had provided information on several of these, and had analyzed cells from some exposed or purportedly exposed individuals. The members of the biological dosimetry group were referred to individuals at REACTS at Oak Ridge Associated Universities for advice on follow-up treatment.

  13. Biology Notes.

    ERIC Educational Resources Information Center

    School Science Review, 1981

    1981-01-01

    Presents content information and/or laboratory procedures and experiments on different biology topics including small-scale cultivation of watercress and its use in water-culture experiments, microbiology of the phylloplane, use of mouthbrooders in science class, and the gene. (DC)

  14. Insulin and Insulin Resistance

    PubMed Central

    2005-01-01

    As obesity and diabetes reach epidemic proportions in the developed world, the role of insulin resistance and its consequences are gaining prominence. Understanding the role of insulin in wide-ranging physiological processes and the influences on its synthesis and secretion, alongside its actions from the molecular to the whole body level, has significant implications for much chronic disease seen in Westernised populations today. This review provides an overview of insulin, its history, structure, synthesis, secretion, actions and interactions followed by a discussion of insulin resistance and its associated clinical manifestations. Specific areas of focus include the actions of insulin and manifestations of insulin resistance in specific organs and tissues, physiological, environmental and pharmacological influences on insulin action and insulin resistance as well as clinical syndromes associated with insulin resistance. Clinical and functional measures of insulin resistance are also covered. Despite our incomplete understanding of the complex biological mechanisms of insulin action and insulin resistance, we need to consider the dramatic social changes of the past century with respect to physical activity, diet, work, socialisation and sleep patterns. Rapid globalisation, urbanisation and industrialisation have spawned epidemics of obesity, diabetes and their attendant co-morbidities, as physical inactivity and dietary imbalance unmask latent predisposing genetic traits. PMID:16278749

  15. Systems biology of innate immunity

    PubMed Central

    Zak, Daniel E.; Aderem, Alan

    2009-01-01

    Summary Systems biology is the comprehensive and quantitative analysis of the interactions between all of the components of biological systems over time. Systems biology involves an iterative cycle, in which emerging biological problems drive the development of new technologies and computational tools. These technologies and tools then open new frontiers that revolutionize biology. Innate immunity is well suited for systems analysis, because the relevant cells can be isolated in various functional states and their interactions can be reconstituted in a biologically meaningful manner. Application of the tools of systems biology to the innate immune system will enable comprehensive analysis of the complex interactions that maintain the difficult balance between host defense and inflammatory disease. In this review, we discuss innate immunity in the context of the systems biology concepts, emergence, robustness, and modularity, and we describe emerging technologies we are applying in our systems-level analyses. These technologies include genomics, proteomics, computational analysis, forward genetics screens, and analyses that link human genetic polymorphisms to disease resistance. PMID:19120490

  16. Crusts: biological

    USGS Publications Warehouse

    Belnap, Jayne; Elias, Scott A.

    2013-01-01

    Biological soil crusts, a community of cyanobacteria, lichens, mosses, and fungi, are an essential part of dryland ecosystems. They are critical in the stabilization of soils, protecting them from wind and water erosion. Similarly, these soil surface communities also stabilized soils on early Earth, allowing vascular plants to establish. They contribute nitrogen and carbon to otherwise relatively infertile dryland soils, and have a strong influence on hydrologic cycles. Their presence can also influence vascular plant establishment and nutrition.

  17. Foldit Biology

    DTIC Science & Technology

    2015-07-31

    and widely used talking points in the biology curriculum: Hemoglobin, Lysozyme and Lactase . Hemoglobin is our first example and is currently used to...its ability to succinctly capture into one package all of the important aspects of a protein interacting with other molecules. Lactase is the...third example, in which we introduce interactive gameplay to show how enzymes work. Like the Lysozyme example, the Lactase example is a multi-state

  18. Marine biology

    SciTech Connect

    Thurman, H.V.; Webber, H.H.

    1984-01-01

    This book discusses both taxonomic and ecological topics on marine biology. Full coverage of marine organisms of all five kingdoms is provided, along with interesting and thorough discussion of all major marine habitats. Organization into six major parts allows flexibility. It also provides insight into important topics such as disposal of nuclear waste at sea, the idea that life began on the ocean floor, and how whales, krill, and people interact. A full-color photo chapter reviews questions, and exercises. The contents are: an overview marine biology: fundamental concepts/investigating life in the ocean; the physical ocean, the ocean floor, the nature of water, the nature and motion of ocean water; general ecology, conditions for life in the sea, biological productivity and energy transfer; marine organisms; monera, protista, mycota and metaphyta; the smaller marine animals, the large animals marine habitats, the intertidal zone/benthos of the continental shelf, the photic zone, the deep ocean, the ocean under stress, marine pollution, appendix a: the metric system and conversion factors/ appendix b: prefixes and suffixes/ appendix c: taxonomic classification of common marine organisms, and glossary, and index.

  19. 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...

  20. Whence Resistance?

    PubMed Central

    Davies, Stephen W.; Metzger, Rosemarie; Swenson, Brian R.; Sawyer, Robert G.

    2015-01-01

    Abstract Background: Antimicrobial resistance results from a complex interaction between pathogenic and non-pathogenic bacteria, antimicrobial pressure, and genes, which together comprise the total body of potential resistance elements. The purpose of this study is to review and evaluate the importance of antimicrobial pressure on the development of resistance in a single surgical intensive care unit. Methods: We reviewed a prospectively collected dataset of all intensive care unit (ICU)-acquired infections in surgical and trauma patients over a 6-y period at a single hospital. Resistant gram-negative pathogens (rGNR) included those resistant to all aminoglycosides, quinolones, penicillins, cephalosporins, or carbapenems; resistant gram-positive infections (rGPC) included methicillin-resistant Staphylococcus aureus (MRSA) or vancomycin-resistant enterococci (VRE). Each resistant infection was evaluated for prior or concomitant antibiotic use, previous treatment for the same (non-resistant) organism, and concurrent infection with the same organism (genus and species, although not necessarily resistant) in another ICU patient. Results: Three hundred and thirty resistant infections were identified: 237 rGNR and 93 rGPC. Infections with rGNR occurred frequently while receiving antibiotic therapy (65%), including the sensitive form of the subsequent resistant pathogen (42.2%). Infections with rGPC were also likely to occur on antimicrobial therapy (50.6%). Treatment of a different patient for an infection with the same resistant pathogen in the ICU at the time of diagnosis, implying potential patient-to-patient transmission occurred more frequently with rGNR infections (38.8%). Conclusion: Antimicrobial pressure exerts a substantial effect on the development of subsequent infection. Our data demonstrate a high estimated rate of de novo emergence of resistance after treatment, which appears to be more common than patient-to-patient transmission. These data support

  1. RESISTIVITY METHODS

    USDA-ARS?s Scientific Manuscript database

    Resistivity methods were among the first geophysical techniques developed. The basic concept originated with Conrad Schlumberger, who conducted the initial resistivity field tests in Normandy, France during 1912. The resistivity method, employed in its earliest and most conventional form, uses an ex...

  2. Biological membranes

    PubMed Central

    Watson, Helen

    2015-01-01

    Biological membranes allow life as we know it to exist. They form cells and enable separation between the inside and outside of an organism, controlling by means of their selective permeability which substances enter and leave. By allowing gradients of ions to be created across them, membranes also enable living organisms to generate energy. In addition, they control the flow of messages between cells by sending, receiving and processing information in the form of chemical and electrical signals. This essay summarizes the structure and function of membranes and the proteins within them, and describes their role in trafficking and transport, and their involvement in health and disease. Techniques for studying membranes are also discussed. PMID:26504250

  3. Biological Weapons and Modern Warfare

    DTIC Science & Technology

    1991-04-01

    for Agents 45 C. Resistance Coding 46 D. Delivery Systems 46 E. New BW Agents 47 F. Toxins 47 G. New Agents and the Biological Weapons Convention...10]. Open air vulnerability testing and contamination of public water systems with live organisms, such as Serratia marcescens . Covert programs were...conducted in San Francisco Bay, using two bacteria (Bacillus globigli and Seratia marcescens ) and fluorescent particles. Various 1Bacillus species were used

  4. Creating biological nanomaterials using synthetic biology

    NASA Astrophysics Data System (ADS)

    Rice, MaryJoe K.; Ruder, Warren C.

    2014-02-01

    Synthetic biology is a new discipline that combines science and engineering approaches to precisely control biological networks. These signaling networks are especially important in fields such as biomedicine and biochemical engineering. Additionally, biological networks can also be critical to the production of naturally occurring biological nanomaterials, and as a result, synthetic biology holds tremendous potential in creating new materials. This review introduces the field of synthetic biology, discusses how biological systems naturally produce materials, and then presents examples and strategies for incorporating synthetic biology approaches in the development of new materials. In particular, strategies for using synthetic biology to produce both organic and inorganic nanomaterials are discussed. Ultimately, synthetic biology holds the potential to dramatically impact biological materials science with significant potential applications in medical systems.

  5. Creating biological nanomaterials using synthetic biology.

    PubMed

    Rice, MaryJoe K; Ruder, Warren C

    2014-02-01

    Synthetic biology is a new discipline that combines science and engineering approaches to precisely control biological networks. These signaling networks are especially important in fields such as biomedicine and biochemical engineering. Additionally, biological networks can also be critical to the production of naturally occurring biological nanomaterials, and as a result, synthetic biology holds tremendous potential in creating new materials. This review introduces the field of synthetic biology, discusses how biological systems naturally produce materials, and then presents examples and strategies for incorporating synthetic biology approaches in the development of new materials. In particular, strategies for using synthetic biology to produce both organic and inorganic nanomaterials are discussed. Ultimately, synthetic biology holds the potential to dramatically impact biological materials science with significant potential applications in medical systems.

  6. Active Biological Materials

    NASA Astrophysics Data System (ADS)

    Fletcher, Daniel A.; Geissler, Phillip L.

    2009-05-01

    Cells make use of dynamic internal structures to control shape and create movement. By consuming energy to assemble into highly organized systems of interacting parts, these structures can generate force and resist compression, as well as adaptively change in response to their environment. Recent progress in reconstituting cytoskeletal structures in vitro has provided an opportunity to characterize the mechanics and dynamics of filament networks formed from purified proteins. Results indicate that a complex interplay between length scales and timescales underlies the mechanical responses of these systems and that energy consumption, as manifested in molecular motor activity and cytoskeletal filament growth, can drive transitions between distinct material states. This review discusses the basic characteristics of these active biological materials that set them apart from conventional materials and that create a rich array of unique behaviors.

  7. Resistance mechanisms

    PubMed Central

    Cag, Yasemin; Caskurlu, Hulya; Fan, Yanyan; Cao, Bin

    2016-01-01

    By definition, the terms sepsis and septic shock refer to a potentially fatal infectious state in which the early administration of an effective antibiotic is the most significant determinant of the outcome. Because of the global spread of resistant bacteria, the efficacy of antibiotics has been severely compromised. S. pneumonia, Escherichia coli (E. coli), Klebsiella, Acinetobacter, and Pseudomonas are the predominant pathogens of sepsis and septic shock. It is common for E. coli, Klebsiella, Acinetobacter and Pseudomonas to be resistant to multiple drugs. Multiple drug resistance is caused by the interplay of multiple resistance mechanisms those emerge via the acquisition of extraneous resistance determinants or spontaneous mutations. Extended-spectrum beta-lactamases (ESBLs), carbapenemases, aminoglycoside-modifying enzymes (AMEs) and quinolone resistance determinants are typically external and disseminate on mobile genetic elements, while porin-efflux mechanisms are activated by spontaneous modifications of inherited structures. Porin and efflux mechanisms are frequent companions of multiple drug resistance in Acinetobacter and P. aeruginosa, but only occasionally detected among E. coli and Klebsiella. Antibiotic resistance became a global health threat. This review examines the major resistance mechanisms of the leading microorganisms of sepsis. PMID:27713884

  8. Structural Biology Fact Sheet

    MedlinePlus

    ... Home > Science Education > Structural Biology Fact Sheet Structural Biology Fact Sheet Tagline (Optional) Middle/Main Content Area What is structural biology? Structural biology is a field of science focused ...

  9. Overcoming drug resistance through in silico prediction.

    PubMed

    Carbonell, Pablo; Trosset, Jean-Yves

    2014-03-01

    Prediction tools are commonly used in pre-clinical research to assist target selection, to optimize drug potency or to predict the pharmacological profile of drug candidates. In silico prediction and overcoming drug resistance is a new opportunity that creates a high interest in pharmaceutical research. This review presents two main in silico strategies to meet this challenge: a structure-based approach to study the influence of mutations on the drug-target interaction and a system-biology approach to identify resistance pathways for a given drug. In silico screening of synergies between therapeutic and resistant pathways through biological network analysis is an example of technique to escape drug resistance. Structure-based drug design and in silico system biology are complementary approaches to reach few objectives at once: increase efficiency, reduce toxicity and overcoming drug resistance.

  10. Simulating Biological and Non-Biological Motion

    ERIC Educational Resources Information Center

    Bruzzo, Angela; Gesierich, Benno; Wohlschlager, Andreas

    2008-01-01

    It is widely accepted that the brain processes biological and non-biological movements in distinct neural circuits. Biological motion, in contrast to non-biological motion, refers to active movements of living beings. Aim of our experiment was to investigate the mechanisms underlying mental simulation of these two movement types. Subjects had to…

  11. Simulating Biological and Non-Biological Motion

    ERIC Educational Resources Information Center

    Bruzzo, Angela; Gesierich, Benno; Wohlschlager, Andreas

    2008-01-01

    It is widely accepted that the brain processes biological and non-biological movements in distinct neural circuits. Biological motion, in contrast to non-biological motion, refers to active movements of living beings. Aim of our experiment was to investigate the mechanisms underlying mental simulation of these two movement types. Subjects had to…

  12. Comments on biological asymmetry.

    PubMed

    Opitz, J M; Utkus, A

    2001-07-15

    , there are additional forms of biological asymmetry which have other biological bases such as Lyonization, somatic/clonal mosaicism, mosaic aneuploidy/polyploidy, chimaerism, and developmental "resistance" seen with especial clarity in virtually every hereditary limb malformation. In this paper we will attempt to enumerate the causal forms and bases of biological asymmetry. Copyright 2001 Wiley-Liss, Inc.

  13. [Biological activity of Spirulina].

    PubMed

    Blinkova, L P; Gorobets, O B; Baturo, A P

    2001-01-01

    In this review information of Spirulina platensis (SP), a blue-green alga (photosynthesizing cyanobacterium) having diverse biological activity is presented. Due to high content of highly valuable proteins, indispensable amino acids, vitamins, beta-carotene and other pigments, mineral substances, indispensable fatty acids and polysaccharides, PS has been found suitable for use as bioactive additive. SP produces an immunostimulating effect by enhancing the resistance of humans, mammals, chickens and fish to infections, the capacity of influencing hemopoiesis, stimulating the production of antibodies and cytokines. Under the influence of SP macrophages, T and B cells are activated. SP sulfolipids have proved to be effective against HIV. Preparations obtained from SP biomass have also been found active against herpesvirus, cytomegalovirus, influenza virus, etc. SP extracts are capable in inhibiting cancerogenesis. SP preparations are regarded as functional products contributing to the preservation of the resident intestinal microflora, especially lactic acid bacilli and bifidobacteria, and to a decrease in the level of Candida albicans. The biological activity of SP with respect to microorganisms holds good promise for using these microalgae as components of culture media.

  14. Biological hydrogen photoproduction

    SciTech Connect

    Nemoto, Y.

    1995-09-01

    Following are the major accomplishments of the 6th year`s study of biological hydrogen photoproduction which were supported by DOE/NREL. (1) We have been characterizing a biological hydrogen production system using synchronously growing aerobically nitrogen-fixing unicellular cyanobacterium, Synechococcus sp. Miami BG 043511. So far it was necessary to irradiate the cells to produce hydrogen. Under darkness they did not produce hydrogen. However, we found that, if the cells are incubated with oxygen, they produce hydrogen under the dark. Under 80% argon + 20% oxygen condition, the hydrogen production activity under the dark was about one third of that under the light + argon condition. (2) Also it was necessary so far to incubate the cells under argon atmosphere to produce hydrogen in this system. Argon treatment is very expensive and should be avoided in an actual hydrogen production system. We found that, if the cells are incubated at a high cell density and in a container with minimum headspace, it is not necessary to use argon for the hydrogen production. (3) Calcium ion was found to play an important role in the mechanisms of protection of nitrogenase from external oxygen. This will be a clue to understand the reason why the hydrogen production is so resistant to oxygen in this strain. (4) In this strain, sulfide can be used as electron donor for the hydrogen production. This result shows that waste water can be used for the hydrogen production system using this strain.

  15. Role of Chemotherapy and Mechanisms of Resistance to Chemotherapy in Metastatic Castration-Resistant Prostate Cancer

    PubMed Central

    Lohiya, Vipin; Aragon-Ching, Jeanny B.; Sonpavde, Guru

    2016-01-01

    Chemotherapy using the taxanes, docetaxel and cabazitaxel, remains an important therapeutic option in metastatic castration-resistant prostate cancer (CRPC). However, despite the survival benefits afforded by these agents, the survival increments are modest and resistance occurs universally. Efforts to overcome resistance to docetaxel by combining with biologic agents have heretofore been unsuccessful. Indeed, resistance to these taxanes is also associated with cross-resistance to the antiandrogen drugs, abiraterone and enzalutamide. Here, we discuss the various mechanisms of resistance to chemotherapy in metastatic CRPC and the potential role of emerging regimens and agents in varying clinical phases of development. PMID:27773999

  16. Antibiotic Resistance

    MedlinePlus

    ... are even stronger. Bacteria and Viruses Questions about Antibiotic Resistance Bacteria and Viruses Bacteria and viruses are the two ... even help us to digest food. But other bacteria cause bad diseases like TB and lyme disease. Questions about Antibiotic Resistance Does this affect me? If you have a ...

  17. Macrolide resistance.

    PubMed

    Weisblum, B

    1998-03-01

    The macrolides have evolved through four chemical generations since erythromycin became available for clinical use in 1952. The first generation, the 14-membered ring macrolide erythromycin, induced resistance and was replaced by the second generation 16-membered ring macrolides which did not. The inability to induce came at the price of mutation, in the pathogenic target strain, to constitutive expression of resistance. A third generation of macrolides improved the acid-stability, and therefore the pharmacokinetics of erythromycin, extending the clinical use of macrolides to Helicobacter pylori and Mycobacterium tuberculosis. Improved pharmacokinetics resulted in the selection of intrinsically resistant mutant strains with rRNA structural alterations. Expression of resistance in these strains was unexpected, explainable by low rRNA gene copy number which made resistance dominant. A fourth generation of macrolides, the 14-membered ring ketolides are the most recent development. Members of this generation are reported to be effective against inducibly resistant strains, and ketolide resistant strains have not yet been reported. In this review we discuss details of the ways in which bacteria have become resistant to the first three generations of macrolides, both with respect to their biochemistry, and the genetic mechanisms by which their expression is regulated.

  18. Managing Resistance.

    ERIC Educational Resources Information Center

    Maag, John W.

    2000-01-01

    This article presents some considerations and ideas for managing students' resistance. They are organized around four topics: the impact of context on behavior, the importance of being comprehensive and nonrestrictive in behavior, the adaptive function of resistant behavior, and the benefit of joining children in their frame of reference.…

  19. Genetic resistances

    USDA-ARS?s Scientific Manuscript database

    Genetic resistance often has been recognized as the most viable mean for limiting soil-borne diseases. In sugar beet, it is only for Beet necrotic yellow vein virus, i.e., rhizomania that a set of fairly different and effective, single-gene resistance is currently available, while for other soil-bor...

  20. Managing Resistance.

    ERIC Educational Resources Information Center

    Maag, John W.

    2000-01-01

    This article presents some considerations and ideas for managing students' resistance. They are organized around four topics: the impact of context on behavior, the importance of being comprehensive and nonrestrictive in behavior, the adaptive function of resistant behavior, and the benefit of joining children in their frame of reference.…

  1. Synthetic biology platform technologies for antimicrobial applications.

    PubMed

    Braff, Dana; Shis, David; Collins, James J

    2016-10-01

    The growing prevalence of antibiotic resistance calls for new approaches in the development of antimicrobial therapeutics. Likewise, improved diagnostic measures are essential in guiding the application of targeted therapies and preventing the evolution of therapeutic resistance. Discovery platforms are also needed to form new treatment strategies and identify novel antimicrobial agents. By applying engineering principles to molecular biology, synthetic biologists have developed platforms that improve upon, supplement, and will perhaps supplant traditional broad-spectrum antibiotics. Efforts in engineering bacteriophages and synthetic probiotics demonstrate targeted antimicrobial approaches that can be fine-tuned using synthetic biology-derived principles. Further, the development of paper-based, cell-free expression systems holds promise in promoting the clinical translation of molecular biology tools for diagnostic purposes. In this review, we highlight emerging synthetic biology platform technologies that are geared toward the generation of new antimicrobial therapies, diagnostics, and discovery channels.

  2. Resisting HRD's Resistance to Diversity

    ERIC Educational Resources Information Center

    Bierema, Laura L.

    2010-01-01

    Purpose: The purpose of this paper is to empirically illustrate how human resource development (HRD) resists and omits issues of diversity in academic programs, textbooks, and research; analyze the research on HRD and diversity over a ten-year period; discuss HRD's resistance to diversity; and offer some recommendations for a more authentic…

  3. Resistivity analysis

    DOEpatents

    Bruce, Michael R.; Bruce, Victoria J.; Ring, Rosalinda M.; Cole, Edward Jr. I.; Hawkins, Charles F.; Tangyungong, Paiboon

    2006-06-13

    According to an example embodiment of the present invention a semiconductor die having a resistive electrical connection is analyzed. Heat is directed to the die as the die is undergoing a state-changing operation to cause a failure due to suspect circuitry. The die is monitored, and a circuit path that electrically changes in response to the heat is detected and used to detect that a particular portion therein of the circuit is resistive. In this manner, the detection and localization of a semiconductor die defect that includes a resistive portion of a circuit path is enhanced.

  4. Interface resistance

    NASA Astrophysics Data System (ADS)

    Sinkkonen, Juha

    1983-11-01

    Interface resistance is studied by using the Landauer formula which relates the resistance to the quantum mechanical transmission coefficient. A simple rederivation of the Landauer formula is given. Using a step-like potential barrier as a model for the metal-semiconductor contact an analytical expression for the effective Richardson constant is derived. As an other application the grain boundary resistance in polycrystalline semiconductors is studied. The short-range potential fluctuation associated with the grain boundary is described by a rectangular potential barrier. The results for the grain boundary limited mobility cover both the strong and weak scattering regimes.

  5. Circadian systems biology in Metazoa.

    PubMed

    Lin, Li-Ling; Huang, Hsuan-Cheng; Juan, Hsueh-Fen

    2015-11-01

    Systems biology, which can be defined as integrative biology, comprises multistage processes that can be used to understand components of complex biological systems of living organisms and provides hierarchical information to decoding life. Using systems biology approaches such as genomics, transcriptomics and proteomics, it is now possible to delineate more complicated interactions between circadian control systems and diseases. The circadian rhythm is a multiscale phenomenon existing within the body that influences numerous physiological activities such as changes in gene expression, protein turnover, metabolism and human behavior. In this review, we describe the relationships between the circadian control system and its related genes or proteins, and circadian rhythm disorders in systems biology studies. To maintain and modulate circadian oscillation, cells possess elaborative feedback loops composed of circadian core proteins that regulate the expression of other genes through their transcriptional activities. The disruption of these rhythms has been reported to be associated with diseases such as arrhythmia, obesity, insulin resistance, carcinogenesis and disruptions in natural oscillations in the control of cell growth. This review demonstrates that lifestyle is considered as a fundamental factor that modifies circadian rhythm, and the development of dysfunctions and diseases could be regulated by an underlying expression network with multiple circadian-associated signals.

  6. Lantibiotic resistance.

    PubMed

    Draper, Lorraine A; Cotter, Paul D; Hill, Colin; Ross, R Paul

    2015-06-01

    The dramatic rise in the incidence of antibiotic resistance demands that new therapeutic options will have to be developed. One potentially interesting class of antimicrobials are the modified bacteriocins termed lantibiotics, which are bacterially produced, posttranslationally modified, lanthionine/methyllanthionine-containing peptides. It is interesting that low levels of resistance have been reported for lantibiotics compared with commercial antibiotics. Given that there are very few examples of naturally occurring lantibiotic resistance, attempts have been made to deliberately induce resistance phenotypes in order to investigate this phenomenon. Mechanisms that hinder the action of lantibiotics are often innate systems that react to the presence of any cationic peptides/proteins or ones which result from cell well damage, rather than being lantibiotic specific. Such resistance mechanisms often arise due to altered gene regulation following detection of antimicrobials/cell wall damage by sensory proteins at the membrane. This facilitates alterations to the cell wall or changes in the composition of the membrane. Other general forms of resistance include the formation of spores or biofilms, which are a common mechanistic response to many classes of antimicrobials. In rare cases, bacteria have been shown to possess specific antilantibiotic mechanisms. These are often species specific and include the nisin lytic protein nisinase and the phenomenon of immune mimicry.

  7. Lantibiotic Resistance

    PubMed Central

    Draper, Lorraine A.; Ross, R. Paul

    2015-01-01

    SUMMARY The dramatic rise in the incidence of antibiotic resistance demands that new therapeutic options will have to be developed. One potentially interesting class of antimicrobials are the modified bacteriocins termed lantibiotics, which are bacterially produced, posttranslationally modified, lanthionine/methyllanthionine-containing peptides. It is interesting that low levels of resistance have been reported for lantibiotics compared with commercial antibiotics. Given that there are very few examples of naturally occurring lantibiotic resistance, attempts have been made to deliberately induce resistance phenotypes in order to investigate this phenomenon. Mechanisms that hinder the action of lantibiotics are often innate systems that react to the presence of any cationic peptides/proteins or ones which result from cell well damage, rather than being lantibiotic specific. Such resistance mechanisms often arise due to altered gene regulation following detection of antimicrobials/cell wall damage by sensory proteins at the membrane. This facilitates alterations to the cell wall or changes in the composition of the membrane. Other general forms of resistance include the formation of spores or biofilms, which are a common mechanistic response to many classes of antimicrobials. In rare cases, bacteria have been shown to possess specific antilantibiotic mechanisms. These are often species specific and include the nisin lytic protein nisinase and the phenomenon of immune mimicry. PMID:25787977

  8. Allicin: chemistry and biological properties.

    PubMed

    Borlinghaus, Jan; Albrecht, Frank; Gruhlke, Martin C H; Nwachukwu, Ifeanyi D; Slusarenko, Alan J

    2014-08-19

    Allicin (diallylthiosulfinate) is a defence molecule from garlic (Allium sativum L.) with a broad range of biological activities. Allicin is produced upon tissue damage from the non-proteinogenic amino acid alliin (S-allylcysteine sulfoxide) in a reaction that is catalyzed by the enzyme alliinase. Current understanding of the allicin biosynthetic pathway will be presented in this review. Being a thiosulfinate, allicin is a reactive sulfur species (RSS) and undergoes a redox-reaction with thiol groups in glutathione and proteins that is thought to be essential for its biological activity. Allicin is physiologically active in microbial, plant and mammalian cells. In a dose-dependent manner allicin can inhibit the proliferation of both bacteria and fungi or kill cells outright, including antibiotic-resistant strains like methicillin-resistant Staphylococcus aureus (MRSA). Furthermore, in mammalian cell lines, including cancer cells, allicin induces cell-death and inhibits cell proliferation. In plants allicin inhibits seed germination and attenuates root-development. The majority of allicin's effects are believed to be mediated via redox-dependent mechanisms. In sub-lethal concentrations, allicin has a variety of health-promoting properties, for example cholesterol- and blood pressure-lowering effects that are advantageous for the cardio-vascular system. Clearly, allicin has wide-ranging and interesting applications in medicine and (green) agriculture, hence the detailed discussion of its enormous potential in this review. Taken together, allicin is a fascinating biologically active compound whose properties are a direct consequence of the molecule's chemistry.

  9. Therapeutic strategies to combat antibiotic resistance.

    PubMed

    Brooks, Benjamin D; Brooks, Amanda E

    2014-11-30

    With multidrug resistant bacteria on the rise, new antibiotic approaches are required. Although a number of new small molecule antibiotics are currently in the development pipeline with many more in preclinical development, the clinical options and practices for infection control must be expanded. Biologics and non-antibiotic adjuvants offer this opportunity for expansion. Nevertheless, to avoid known mechanisms of resistance, intelligent combination approaches for multiple simultaneous and complimentary therapies must be designed. Combination approaches should extend beyond biologically active molecules to include smart controlled delivery strategies. Infection control must integrate antimicrobial stewardship, new antibiotic molecules, biologics, and delivery strategies into effective combination therapies designed to 1) fight the infection, 2) avoid resistance, and 3) protect the natural microbiome. This review explores these developing strategies in the context of circumventing current mechanisms of resistance.

  10. Biological Evaluation of Potent Triclosan-Derived Inhibitors of the Enoyl-Acyl Carrier Protein Reductase InhA in Drug-sensitive and Drug-resistant Strains of Mycobacterium tuberculosis

    PubMed Central

    Vilchèze, Catherine; Lun, Shichun; Perryman, Alexander L.; Wang, Xin; Freundlich, Joel S.; Bishai, William; Jacobs, William R.

    2014-01-01

    New triclosan (TRC) analogs were evaluated for their activity against the enoyl-acyl carrier protein reductase InhA in Mycobacterium tuberculosis (Mtb). TRC is a well-known inhibitor of InhA and specific modifications to its positions 5 and 4′ afforded twenty-seven derivatives; of these compounds seven derivatives showed an improved potency in comparison to TRC. These analogs were active against both drug-susceptible and drug-resistant Mtb strains. The most active compound in this series, 3, had an MIC value of 0.6 μg/mL (1.5 μM) against wild-type Mtb. At a concentration equal to its MIC, this molecule inhibited the purified InhA enzyme to the extent of 98%, and it showed an IC50 value of 90 nM. Compounds 3 and 14 were able to inhibit the biosynthesis of mycolic acids. Furthermore, mc24914, an Mtb strain overexpressing inhA, was resistant to the compounds 3 and 14, supporting the notion that InhA is the likely molecular target of the TRC derivatives presented herein. PMID:25165007

  11. [Biology of size and gravity].

    PubMed

    Yamashita, Masamichi; Baba, Shoji A

    2004-03-01

    Gravity is a force that acts on mass. Biological effects of gravity and their magnitude depend on scale of mass and difference in density. One significant contribution of space biology is confirmation of direct action of gravity even at the cellular level. Since cell is the elementary unit of life, existence of primary effects of gravity on cells leads to establish the firm basis of gravitational biology. However, gravity is not limited to produce its biological effects on molecules and their reaction networks that compose living cells. Biological system has hierarchical structure with layers of organism, group, and ecological system, which emerge from the system one layer down. Influence of gravity is higher at larger mass. In addition to this, actions of gravity in each layer are caused by process and mechanism that is subjected and different in each layer of the hierarchy. Because of this feature, summing up gravitational action on cells does not explain gravity for biological system at upper layers. Gravity at ecological system or organismal level can not reduced to cellular mechanism. Size of cells and organisms is one of fundamental characters of them and a determinant in their design of form and function. Size closely relates to other physical quantities, such as mass, volume, and surface area. Gravity produces weight of mass. Organisms are required to equip components to support weight and to resist against force that arise at movement of body or a part of it. Volume and surface area associate with mass and heat transport process at body. Gravity dominates those processes by inducing natural convection around organisms. This review covers various elements and process, with which gravity make influence on living systems, chosen on the basis of biology of size. Cells and biochemical networks are under the control of organism to integrate a consolidated form. How cells adjust metabolic rate to meet to the size of the composed organism, whether is gravity

  12. [Detection of Staphylococcus aureus resistant to methicillin (MRSA) by molecular biology (Cepheid GeneXpert IL, GeneOhm BD, Roche LightCycler, Hyplex Evigene I2A) versus screening by culture: Economic and practical strategy for the laboratory].

    PubMed

    Laudat, P; Demondion, E; Jouannet, C; Charron, J; Chillou, C; Salaun, V; Mankikian, B

    2012-06-01

    Patients admitted in cardiac surgery and cardiac ICU at the Clinic Saint-Gatien (Tours) are screened for MRSA at the entrance by nasal swab and culture on blood agar and selective chromogenic medium made by addition of cefoxitin: BBL CHROMagar MRSA-II BD (result obtained at Day +1). We wanted to assess the molecular biology techniques available to obtain a result at day 0 for the majority of patients and to define an economic and practical strategy for the laboratory. We studied four molecular biology techniques: Cepheid GeneXpert (Cepheid) GeneOhm (BD), LightCycler (Roche) and Hyplex (I2A). Upon reception, nasal swabs were treated by culture, considered as reference, and one of the techniques of molecular biology, according to the manufacturer's notice. We conducted four studies between April 2008 and February 2009 to obtain a significant sample for each of them. By screening we mean a method that allows us to exclude MRSA carriage for patients waiting for surgery, and not to change patient management: for example, lack of isolation measures specific to entrance, no modification of antibiotic prophylaxis during surgery and no isolation measures in the immediate postoperative period. The criteria we considered for this evaluation were: (1) technician time: time to perform one or a series of sample(s) n=10 or more (about 2h for all techniques except GeneXpert 75min), level of skilled competences (no specific training for GeneXpert); (2) results: turnaround time (all molecular biology techniques), ease of reading and results interpretations (no specialized training required for GeneXpert), failure or not (12% of failure of internal controls for GeneOhm); (3) economic: cost for one or a series of sample(s) (n=10 or more), if we considered X as the reference culture cost (10 X Hyplex and LightCycler, 20 X and 40 X for GeneXpert GeneOhm); (4) NPV: 100% for GeneXpert and LightCycler. At same sensitivity, no technique, including culture, can solve alone our problem, which

  13. (Mechanisms of tolerance and resistance)

    SciTech Connect

    Waters, L.C.

    1990-08-28

    The traveler participated in the Seventh International Congress of Pesticide Chemistry by presenting a poster entitled Studies on the Expression of Insecticide Resistance-Associated Cytochrome P450 in Drosophila Using Cloned DNA'' and as an invited speaker in the Workshop Session on Insecticide Resistance. The Congress covered a wide range of topics, including studies of new syntheic compounds and natural products with crop protecting properties, modes of action of pesticides, mechanisms of pesticide resistance, environmental fate of pesticides and estimates of risk to pesticide exposure. Several presentations on the potential role of cytochrome P450 in resistance to insecticides and herbicides were relevant to our work at ORNL's Biology Division on molecular mechanisms of P450 expression.

  14. Drug resistance in eukaryotic microorganisms.

    PubMed

    Fairlamb, Alan H; Gow, Neil A R; Matthews, Keith R; Waters, Andrew P

    2016-06-24

    Eukaryotic microbial pathogens are major contributors to illness and death globally. Although much of their impact can be controlled by drug therapy as with prokaryotic microorganisms, the emergence of drug resistance has threatened these treatment efforts. Here, we discuss the challenges posed by eukaryotic microbial pathogens and how these are similar to, or differ from, the challenges of prokaryotic antibiotic resistance. The therapies used for several major eukaryotic microorganisms are then detailed, and the mechanisms that they have evolved to overcome these therapies are described. The rapid emergence of resistance and the restricted pipeline of new drug therapies pose considerable risks to global health and are particularly acute in the developing world. Nonetheless, we detail how the integration of new technology, biological understanding, epidemiology and evolutionary analysis can help sustain existing therapies, anticipate the emergence of resistance or optimize the deployment of new therapies.

  15. Drug resistance in eukaryotic microorganisms

    PubMed Central

    Fairlamb, Alan H.; Gow, Neil A. R.; Matthews, Keith R.; Waters, Andrew P.

    2016-01-01

    Eukaryotic microbial pathogens are major contributors to illness and death globally. Although much of their impact can be controlled by drug therapy as with prokaryotic microorganisms, the emergence of drug resistance has threatened these treatment efforts. Here, we discuss the challenges posed by eukaryotic microbial pathogens and how these are similar to, or differ from, the challenges of prokaryotic antibiotic resistance. The therapies used for several major eukaryotic microorganisms are then detailed, and the mechanisms that they have evolved to overcome these therapies are described. The rapid emergence of resistance and the restricted pipeline of new drug therapies pose considerable risks to global health and are particularly acute in the developing world. Nonetheless, we detail how the integration of new technology, biological understanding, epidemiology and evolutionary analysis can help sustain existing therapies, anticipate the emergence of resistance or optimize the deployment of new therapies. PMID:27572976

  16. Biological warfare agents.

    PubMed

    Pohanka, Miroslav; Kuca, Kamil

    2010-01-01

    Biological warfare agents are a group of pathogens and toxins of biological origin that can be potentially misused for military or criminal purposes. The present review attempts to summarize necessary knowledge about biological warfare agents. The historical aspects, examples of applications of these agents such as anthrax letters, biological weapons impact, a summary of biological warfare agents and epidemiology of infections are described. The last section tries to estimate future trends in research on biological warfare agents.

  17. Resident resistance.

    PubMed

    Price, J L; Cleary, B

    1999-01-01

    Clearly, faculty must work hard with residents to explore the nature of their resistance to a program's learning and growth opportunities. Initial steps to a deeper, more effective, and longer-lasting change process must be pursued. If resident resistance is mishandled or misunderstood, then learning and professional growth may be sidetracked and the purposes of residency training defeated. Listening to the whole person of the resident and avoiding the trap of getting caught up in merely responding to select resident behaviors that irritate us is critical. Every faculty member in the family practice residency program must recognize resistance as a form of defense that cannot immediately be torn down or taken away. Resident defenses have important purposes to play in stress reduction even if they are not always healthy. Residents, especially interns, use resistance to avoid a deeper and more truthful look at themselves as physicians. A family practice residency program that sees whole persons in their residents and that respects resident defenses will effectively manage the stress and disharmony inherent to the resistant resident.

  18. Student Teachers' Approaches to Teaching Biological Evolution

    ERIC Educational Resources Information Center

    Borgerding, Lisa A.; Klein, Vanessa A.; Ghosh, Rajlakshmi; Eibel, Albert

    2015-01-01

    Evolution is fundamental to biology and scientific literacy, but teaching high school evolution is often difficult. Evolution teachers face several challenges including limited content knowledge, personal conflicts with evolution, expectations of resistance, concerns about students' conflicts with religion, and curricular constraints. Evolution…

  19. Student Teachers' Approaches to Teaching Biological Evolution

    ERIC Educational Resources Information Center

    Borgerding, Lisa A.; Klein, Vanessa A.; Ghosh, Rajlakshmi; Eibel, Albert

    2015-01-01

    Evolution is fundamental to biology and scientific literacy, but teaching high school evolution is often difficult. Evolution teachers face several challenges including limited content knowledge, personal conflicts with evolution, expectations of resistance, concerns about students' conflicts with religion, and curricular constraints. Evolution…

  20. Evolutionary Biology: Its Value to Society

    ERIC Educational Resources Information Center

    Carson, Hampton L.

    1972-01-01

    Cites examples of the contribution of basic research in evolutionary biology to the solution of problems facing society (1) by dispelling myths about human origins, the nature of the individual, and the nature of race (2) by providing basic data concerning the effects of overpopulation, the production of improved sources of food, resistance of…

  1. Evolutionary Biology: Its Value to Society

    ERIC Educational Resources Information Center

    Carson, Hampton L.

    1972-01-01

    Cites examples of the contribution of basic research in evolutionary biology to the solution of problems facing society (1) by dispelling myths about human origins, the nature of the individual, and the nature of race (2) by providing basic data concerning the effects of overpopulation, the production of improved sources of food, resistance of…

  2. Synthetic biology of antimicrobial discovery

    PubMed Central

    Zakeri, Bijan; Lu, Timothy K.

    2012-01-01

    Antibiotic discovery has a storied history. From the discovery of penicillin by Sir Alexander Fleming to the relentless quest for antibiotics by Selman Waksman, the stories have become like folklore, used to inspire future generations of scientists. However, recent discovery pipelines have run dry at a time when multidrug resistant pathogens are on the rise. Nature has proven to be a valuable reservoir of antimicrobial agents, which are primarily produced by modularized biochemical pathways. Such modularization is well suited to remodeling by an interdisciplinary approach that spans science and engineering. Herein, we discuss the biological engineering of small molecules, peptides, and non-traditional antimicrobials and provide an overview of the growing applicability of synthetic biology to antimicrobials discovery. PMID:23654251

  3. Biological Regulation of Bone Quality

    PubMed Central

    Alliston, Tamara

    2014-01-01

    The ability of bone to resist fracture is determined by the combination of bone mass and bone quality. Like bone mass, bone quality is carefully regulated. Of the many aspects of bone quality, this review focuses on biological mechanisms that control the material quality of the bone extracellular matrix (ECM). Bone ECM quality depends upon ECM composition and organization. Proteins and signaling pathways that affect the mineral or organic constituents of bone ECM impact bone ECM material properties, such as elastic modulus and hardness. These properties are also sensitive to pathways that regulate bone remodeling by osteoblasts, osteoclasts, and osteocytes. Several extracellular proteins, signaling pathways, intracellular effectors, and transcription regulatory networks have been implicated in the control of bone ECM quality. A molecular understanding of these mechanisms will elucidate the biological control of bone quality and suggest new targets for the development of therapies to prevent bone fragility. PMID:24894149

  4. Drug resistance in Giardia duodenalis.

    PubMed

    Ansell, Brendan R E; McConville, Malcolm J; Ma'ayeh, Showgy Y; Dagley, Michael J; Gasser, Robin B; Svärd, Staffan G; Jex, Aaron R

    2015-11-01

    Giardia duodenalis is a microaerophilic parasite of the human gastrointestinal tract and a major contributor to diarrheal and post-infectious chronic gastrointestinal disease world-wide. Treatment of G. duodenalis infection currently relies on a small number of drug classes. Nitroheterocyclics, in particular metronidazole, have represented the front line treatment for the last 40 years. Nitroheterocyclic-resistant G. duodenalis have been isolated from patients and created in vitro, prompting considerable research into the biomolecular mechanisms of resistance. These compounds are redox-active and are believed to damage proteins and DNA after being activated by oxidoreductase enzymes in metabolically active cells. In this review, we explore the molecular phenotypes of nitroheterocyclic-resistant G. duodenalis described to date in the context of the protist's unusual glycolytic and antioxidant systems. We propose that resistance mechanisms are likely to extend well beyond currently described resistance-associated enzymes (i.e., pyruvate ferredoxin oxidoreductases and nitroreductases), to include NAD(P)H- and flavin-generating pathways, and possibly redox-sensitive epigenetic regulation. Mechanisms that allow G. duodenalis to tolerate oxidative stress may lead to resistance against both oxygen and nitroheterocyclics, with implications for clinical control. The present review highlights the potential for systems biology tools and advanced bioinformatics to further investigate the multifaceted mechanisms of nitroheterocyclic resistance in this important pathogen.

  5. Antibacterial drug discovery in the resistance era.

    PubMed

    Brown, Eric D; Wright, Gerard D

    2016-01-21

    The looming antibiotic-resistance crisis has penetrated the consciousness of clinicians, researchers, policymakers, politicians and the public at large. The evolution and widespread distribution of antibiotic-resistance elements in bacterial pathogens has made diseases that were once easily treatable deadly again. Unfortunately, accompanying the rise in global resistance is a failure in antibacterial drug discovery. Lessons from the history of antibiotic discovery and fresh understanding of antibiotic action and the cell biology of microorganisms have the potential to deliver twenty-first century medicines that are able to control infection in the resistance era.

  6. Transglutaminases: nature's biological glues.

    PubMed Central

    Griffin, Martin; Casadio, Rita; Bergamini, Carlo M

    2002-01-01

    Transglutaminases (Tgases) are a widely distributed group of enzymes that catalyse the post-translational modification of proteins by the formation of isopeptide bonds. This occurs either through protein cross-linking via epsilon-(gamma-glutamyl)lysine bonds or through incorporation of primary amines at selected peptide-bound glutamine residues. The cross-linked products, often of high molecular mass, are highly resistant to mechanical challenge and proteolytic degradation, and their accumulation is found in a number of tissues and processes where such properties are important, including skin, hair, blood clotting and wound healing. However, deregulation of enzyme activity generally associated with major disruptions in cellular homoeostatic mechanisms has resulted in these enzymes contributing to a number of human diseases, including chronic neurodegeneration, neoplastic diseases, autoimmune diseases, diseases involving progressive tissue fibrosis and diseases related to the epidermis of the skin. In the present review we detail the structural and regulatory features important in mammalian Tgases, with particular focus on the ubiquitous type 2 tissue enzyme. Physiological roles and substrates are discussed with a view to increasing and understanding the pathogenesis of the diseases associated with transglutaminases. Moreover the ability of these enzymes to modify proteins and act as biological glues has not gone unnoticed by the commercial sector. As a consequence, we have included some of the present and future biotechnological applications of this increasingly important group of enzymes. PMID:12366374

  7. The determinants of the antibiotic resistance process

    PubMed Central

    Franco, Beatriz Espinosa; Altagracia Martínez, Marina; Sánchez Rodríguez, Martha A; Wertheimer, Albert I

    2009-01-01

    Background: The use of antibiotic drugs triggers a complex interaction involving many biological, sociological, and psychological determinants. Resistance to antibiotics is a serious worldwide problem which is increasing and has implications for morbidity, mortality, and health care both in hospitals and in the community. Objectives: To analyze current research on the determinants of antibiotic resistance and comprehensively review the main factors in the process of resistance in order to aid our understanding and assessment of this problem. Methods: We conducted a MedLine search using the key words “determinants”, “antibiotic”, and “antibiotic resistance” to identify publications between 1995 and 2007 on the determinants of antibiotic resistance. Publications that did not address the determinants of antibiotic resistance were excluded. Results: The process and determinants of antibiotic resistance are described, beginning with the development of antibiotics, resistance and the mechanisms of resistance, sociocultural determinants of resistance, the consequences of antibiotic resistance, and alternative measures proposed to combat antibiotic resistance. Conclusions: Analysis of the published literature identified the main determinants of antibiotic resistance as irrational use of antibiotics in humans and animal species, insufficient patient education when antibiotics are prescribed, lack of guidelines for treatment and control of infections, lack of scientific information for physicians on the rational use of antibiotics, and lack of official government policy on the rational use of antibiotics in public and private hospitals. PMID:21694883

  8. Computing motion using resistive networks

    NASA Technical Reports Server (NTRS)

    Koch, Christof; Luo, Jin; Mead, Carver; Hutchinson, James

    1988-01-01

    Recent developments in the theory of early vision are described which lead from the formulation of the motion problem as an ill-posed one to its solution by minimizing certain 'cost' functions. These cost or energy functions can be mapped onto simple analog and digital resistive networks. It is shown how the optical flow can be computed by injecting currents into resistive networks and recording the resulting stationary voltage distribution at each node. These networks can be implemented in cMOS VLSI circuits and represent plausible candidates for biological vision systems.

  9. Systems Chemical Biology

    PubMed Central

    Oprea, Tudor I.; Tropsha, Alexander; Faulon, Jean-Loup; Rintoul, Mark D.

    2009-01-01

    The increasing availability of data related to genes, proteins and their modulation by small molecules, paralleled by the emergence of simulation tools in systems biology, has provided a vast amount of biological information. However, there is a critical need to develop cheminformatics tools that can integrate chemical knowledge with these biological databases, with the goal of creating systems chemical biology. PMID:17637771

  10. CAREERS IN BIOLOGY EDUCATION.

    ERIC Educational Resources Information Center

    KLINGE, PAUL

    THIS ENTIRE JOURNAL IS DEVOTED TO ARTICLES WHICH DESCRIBE VARIOUS CAREERS IN BIOLOGY EDUCATION. PART 1 CONTAINS ARTICLES ON CLASSROOM CAREERS IN BIOLOGY EDUCATION. THE ARTICLES DISCUSS (1) BIOLOGY TEACHING AT VARIOUS EDUCATIONAL LEVELS, (2) THE BIOLOGY TEACHER AS A RESEARCHER, AND (3) TEACHER AIDES FOR SCIENCE PROGRAMS. PART 2 PRESENTS ARTICLES ON…

  11. [Biogeography: geography or biology?].

    PubMed

    Kafanov, A I

    2009-01-01

    General biogeography is an interdisciplinary science, which combines geographic and biological aspects constituting two distinct research fields: biological geography and geographic biology. These fields differ in the nature of their objects of study, employ different methods and represent Earth sciences and biological sciences, respectively. It is suggested therefore that the classification codes for research fields and the state professional education standard should be revised.

  12. Learning Biology by Designing

    ERIC Educational Resources Information Center

    Janssen, Fred; Waarlo, Arend Jan

    2010-01-01

    According to a century-old tradition in biological thinking, organisms can be considered as being optimally designed. In modern biology this idea still has great heuristic value. In evolutionary biology a so-called design heuristic has been formulated which provides guidance to researchers in the generation of knowledge about biological systems.…

  13. Biological conversion system

    DOEpatents

    Scott, C.D.

    A system for bioconversion of organic material comprises a primary bioreactor column wherein a biological active agent (zymomonas mobilis) converts the organic material (sugar) to a product (alcohol), a rejuvenator column wherein the biological activity of said biological active agent is enhanced, and means for circulating said biological active agent between said primary bioreactor column and said rejuvenator column.

  14. Synthetic biology: insights into biological computation.

    PubMed

    Manzoni, Romilde; Urrios, Arturo; Velazquez-Garcia, Silvia; de Nadal, Eulàlia; Posas, Francesc

    2016-04-18

    Organisms have evolved a broad array of complex signaling mechanisms that allow them to survive in a wide range of environmental conditions. They are able to sense external inputs and produce an output response by computing the information. Synthetic biology attempts to rationally engineer biological systems in order to perform desired functions. Our increasing understanding of biological systems guides this rational design, while the huge background in electronics for building circuits defines the methodology. In this context, biocomputation is the branch of synthetic biology aimed at implementing artificial computational devices using engineered biological motifs as building blocks. Biocomputational devices are defined as biological systems that are able to integrate inputs and return outputs following pre-determined rules. Over the last decade the number of available synthetic engineered devices has increased exponentially; simple and complex circuits have been built in bacteria, yeast and mammalian cells. These devices can manage and store information, take decisions based on past and present inputs, and even convert a transient signal into a sustained response. The field is experiencing a fast growth and every day it is easier to implement more complex biological functions. This is mainly due to advances in in vitro DNA synthesis, new genome editing tools, novel molecular cloning techniques, continuously growing part libraries as well as other technological advances. This allows that digital computation can now be engineered and implemented in biological systems. Simple logic gates can be implemented and connected to perform novel desired functions or to better understand and redesign biological processes. Synthetic biological digital circuits could lead to new therapeutic approaches, as well as new and efficient ways to produce complex molecules such as antibiotics, bioplastics or biofuels. Biological computation not only provides possible biomedical and

  15. Biosecurity and Open-Source Biology: The Promise and Peril of Distributed Synthetic Biological Technologies.

    PubMed

    Evans, Nicholas G; Selgelid, Michael J

    2015-08-01

    In this article, we raise ethical concerns about the potential misuse of open-source biology (OSB): biological research and development that progresses through an organisational model of radical openness, deskilling, and innovation. We compare this organisational structure to that of the open-source software model, and detail salient ethical implications of this model. We demonstrate that OSB, in virtue of its commitment to openness, may be resistant to governance attempts.

  16. Drug Resistance

    USDA-ARS?s Scientific Manuscript database

    Drug resistance refers to both intrinsic and acquired abilities of cells or organisms to become insensitive or refractory to chemotherapeutic intervention. The advent of antibiotics is considered one of the most important medicinal developments in human history, which has led to significantly reduce...

  17. Resistive Networks.

    ERIC Educational Resources Information Center

    Balabanian, Norman

    This programed text on resistive networks was developed under contract with the United States Office of Education as part of a series of materials for use in an electrical engineering sequence. It is to be used in conjunction with other materials and with other short texts in the series, this one being Number 3. (DH)

  18. Resistant hypertension and chronotherapy.

    PubMed

    Prkacin, Ingrid; Balenovic, Diana; Djermanovic-Dobrota, Vesna; Lukac, Iva; Drazic, Petra; Pranjic, Iva-Klara

    2015-04-01

    Resistant hypertension is defined as blood pressure that remains above 140/90 mmHg in spite of the continuous use of three antihypertensive agents in optimal dose, including diuretic, and lifestyle changes. According to data from United States of America and Europe, the prevalence ranges from 10 up to 30% in patients with hypertension. Numerous biological and lifestyle factors can contribute to the development of resistant hypertension: medications, volume overload, obesity, diabetes mellitus, older age, renal parenchymal and renovascular disease, primary aldosteronism, obstructive sleep apnea, pheochormocytoma, Cushing's syndrome, thyroid diseases, aortic coarctation. For diagnosing patient's history is important, assessing compliance, regular blood pressure measurement, physical examination, biochemical evaluation and noninvasive imaging. The evaluation including 24h ambulatory monitoring of blood pressure (ABPM) in the identification of "non-dipper" hypertension. Non-dipper has particular importance and the prevalence of abnormally high sleep blood pressure is very often in chronic kidney patients. Therapeutic restoration of normal physiologic blood pressure reduction during night-time sleep (circadial variation) is the most significant independent predictor of decreased risk and the basis for the chronotherapy. The resistant hypertension treatment is achieved with nonpharmacological and pharmacological approach, treating secondary hypertension causes and invasive procedures.

  19. Resistant Hypertension and Chronotherapy

    PubMed Central

    Prkacin, Ingrid; Balenovic, Diana; Djermanovic-Dobrota, Vesna; Lukac, Iva; Drazic, Petra; Pranjic, Iva-Klara

    2015-01-01

    Resistant hypertension is defined as blood pressure that remains above 140/90 mmHg in spite of the continuous use of three antihypertensive agents in optimal dose, including diuretic, and lifestyle changes. According to data from United States of America and Europe, the prevalence ranges from 10 up to 30% in patients with hypertension. Numerous biological and lifestyle factors can contribute to the development of resistant hypertension: medications, volume overload, obesity, diabetes mellitus, older age, renal parenchymal and renovascular disease, primary aldosteronism, obstructive sleep apnea, pheochormocytoma, Cushing’s syndrome, thyroid diseases, aortic coarctation. For diagnosing patient’s history is important, assessing compliance, regular blood pressure measurement, physical examination, biochemical evaluation and noninvasive imaging. The evaluation including 24h ambulatory monitoring of blood pressure (ABPM) in the identification of “non-dipper” hypertension. Non-dipper has particular importance and the prevalence of abnormally high sleep blood pressure is very often in chronic kidney patients. Therapeutic restoration of normal physiologic blood pressure reduction during night-time sleep (circadial variation) is the most significant independent predictor of decreased risk and the basis for the chronotherapy. The resistant hypertension treatment is achieved with nonpharmacological and pharmacological approach, treating secondary hypertension causes and invasive procedures. PMID:26005390

  20. Synthetic Biology - The Synthesis of Biology.

    PubMed

    Ausländer, Simon; Ausländer, David; Fussenegger, Martin

    2016-12-11

    Synthetic biology envisages the engineering of man-made living biomachines from standardized components that can perform pre-defined functions in a (self-)controlled manner. Different research strategies and interdisciplinary efforts are pursued to implement engineering principles to biology. The "top-down" strategy exploits nature's incredible diversity of existing, natural parts to construct synthetic compositions of genetic, metabolic or signalling networks with predictable and controllable properties. This mainly application-driven approach results in living factories that produce drugs, biofuels, biomaterials and fine chemicals and results in living pills that are based on engineered cells with the capacity to autonomously detect and treat disease states in vivo. In contrast, the "bottom-up" strategy seeks to be independent of existing living systems by designing biological systems from scratch and synthesizing artificial biological entities not found in nature. This more knowledge-driven approach investigates the reconstruction of minimal biological systems that are capable of performing basic biological phenomena, such as self-organization, self-replication and self-sustainability. Moreover, the syntheses of artificial biological units, such as synthetic nucleotides or amino acids, and their implementation into polymers inside living cells currently set the boundaries between natural and artificial biological systems. In particular, the in vitro design, synthesis and transfer of complete genomes into host cells and the application of efficient genome-wide intervention techniques point to the future of synthetic biology: the creation of living designer cells with tailored desirable properties for biomedicine and biotechnology.

  1. [A population-genetics approach to the problem of nonspecific biological resistance of the human body. III. The ABO and rhesus blood group systems of healthy and sick children and their mothers].

    PubMed

    Kurbatova, O L; Botvin'ev, O K; Altukhov, Iu P

    1984-04-01

    ABO and Rhesus blood types have been specified in 2047 diseased newborns, diseased infants and children who died before the age of one, as well as in their mothers. 527 healthy children and their mothers were investigated as a control group. A significant difference in the ABO phenotype frequencies has been revealed between: i) healthy and dead children, ii) mothers of diseased newborns and mothers of healthy children, iii) dead children and their mothers. The significant increase in the incidence of maternal Rhesus-negative phenotype, as compared with the control group, was shown in the groups of diseased newborns, diseased infants and dead children. In the same groups, mothers differ significantly from their children with respect to the frequency of Rhesus phenotypes. The incidence of Rhesus-incompatible mother-child pairs in the groups of diseased newborns, diseased infants and dead children was shown to be two times higher than the respective frequency in the control group and the expected frequency. A certain increase in the frequency of ABO-incompatible pairs was revealed in the groups of diseased newborns and dead children, but the difference, as compared to the control group, did not prove to be statistically significant. A hypothesis was advanced to the effect that the mother-child incompatibility for Rhesus and ABO antigens may result not only in fetal wastage and haemolytic disease of newborns, but also in the decrease of child's resistance to diseases of different origin.

  2. Biological evaluation of potent triclosan-derived inhibitors of the enoyl-acyl carrier protein reductase InhA in drug-sensitive and drug-resistant strains of Mycobacterium tuberculosis.

    PubMed

    Stec, Jozef; Vilchèze, Catherine; Lun, Shichun; Perryman, Alexander L; Wang, Xin; Freundlich, Joel S; Bishai, William; Jacobs, William R; Kozikowski, Alan P

    2014-11-01

    New triclosan (TRC) analogues were evaluated for their activity against the enoyl-acyl carrier protein reductase InhA in Mycobacterium tuberculosis (Mtb). TRC is a well-known inhibitor of InhA, and specific modifications to its positions 5 and 4' afforded 27 derivatives; of these compounds, seven derivatives showed improved potency over that of TRC. These analogues were active against both drug-susceptible and drug-resistant Mtb strains. The most active compound in this series, 4-(n-butyl)-1,2,3-triazolyl TRC derivative 3, had an MIC value of 0.6 μg mL(-1) (1.5 μM) against wild-type Mtb. At a concentration equal to its MIC, this compound inhibited purified InhA by 98 %, and showed an IC50 value of 90 nM. Compound 3 and the 5-methylisoxazole-modified TRC 14 were able to inhibit the biosynthesis of mycolic acids. Furthermore, mc(2) 4914, an Mtb strain overexpressing inhA, was found to be less susceptible to compounds 3 and 14, supporting the notion that InhA is the likely molecular target of the TRC derivatives presented herein.

  3. Bacterial Genome Engineering and Synthetic Biology: Combating Pathogens

    DTIC Science & Technology

    2016-11-04

    Bacterial chromosomal modifications have greatly aided in better comprehension of bacterial mechanisms of pathogenesis and virulence. Among the genome...1 Bacterial Genome Engineering and Synthetic Biology: Combating Pathogens 1Malathy Krishnamurthy, 1Richard T. Moore, 1Sathish Rajamani, 1Rekha G...resistance in bacteria. Research The advent of new bacterial genome engineering and synthetic biology (SB) tools is providing promising diagnostic

  4. Outdoor Biology Instructional Strategies Trial Edition. Set I.

    ERIC Educational Resources Information Center

    Fairwell, Kay, Ed.; And Others

    The Outdoor Biology Instructional Strategies (OBIS) Trial Edition Set I contains 24 varied activities which make use of crafts, simulations, and basic investigative techniques to provide introductory learning experiences in outdoor biology for children aged 10 to 15. The individual water-resistant folio for each activity includes biological…

  5. Systems interface biology

    PubMed Central

    Doyle, Francis J; Stelling, Jörg

    2006-01-01

    The field of systems biology has attracted the attention of biologists, engineers, mathematicians, physicists, chemists and others in an endeavour to create systems-level understanding of complex biological networks. In particular, systems engineering methods are finding unique opportunities in characterizing the rich behaviour exhibited by biological systems. In the same manner, these new classes of biological problems are motivating novel developments in theoretical systems approaches. Hence, the interface between systems and biology is of mutual benefit to both disciplines. PMID:16971329

  6. Systems interface biology.

    PubMed

    Doyle, Francis J; Stelling, Jörg

    2006-10-22

    The field of systems biology has attracted the attention of biologists, engineers, mathematicians, physicists, chemists and others in an endeavour to create systems-level understanding of complex biological networks. In particular, systems engineering methods are finding unique opportunities in characterizing the rich behaviour exhibited by biological systems. In the same manner, these new classes of biological problems are motivating novel developments in theoretical systems approaches. Hence, the interface between systems and biology is of mutual benefit to both disciplines.

  7. Durable resistance of crops to disease: a Darwinian perspective.

    PubMed

    Brown, James K M

    2015-01-01

    This review takes an evolutionary view of breeding crops for durable resistance to disease. An understanding of coevolution between hosts and parasites leads to predictors of potentially durable resistance, such as corresponding virulence having a high fitness cost to the pathogen or resistance being common in natural populations. High partial resistance can also promote durability. Whether or not resistance is actually durable, however, depends on ecological and epidemiological processes that stabilize genetic polymorphism, many of which are absent from intensive agriculture. There continues to be no biological, genetic, or economic model for durable resistance. The analogy between plant breeding and natural selection indicates that the basic requirements are genetic variation in potentially durable resistance, effective and consistent selection for resistance, and an efficient breeding process in which trials of disease resistance are integrated with other traits. Knowledge about genetics and mechanisms can support breeding for durable resistance once these fundamentals are in place.

  8. Is Biology Boring? Student Attitudes toward Biology

    ERIC Educational Resources Information Center

    Prokop, Pavol; Prokop, Matel; Tunnicliffe, Sue Dale

    2007-01-01

    The study examines the interests and attitudes of school students toward biology: through their interest in out-of-school activities and their attitude towards lessons as measured by interest, importance and difficulty. Biology lessons were relatively popular with the greatest preference found among students learning zoology. Girls showed…

  9. Is Biology Boring? Student Attitudes toward Biology

    ERIC Educational Resources Information Center

    Prokop, Pavol; Prokop, Matel; Tunnicliffe, Sue Dale

    2007-01-01

    The study examines the interests and attitudes of school students toward biology: through their interest in out-of-school activities and their attitude towards lessons as measured by interest, importance and difficulty. Biology lessons were relatively popular with the greatest preference found among students learning zoology. Girls showed…

  10. A view from Riggs: treatment resistance and patient authority -- V. Silencing the messenger: the social dynamics of treatment resistance.

    PubMed

    Elmendorf, Donna; Parish, Margaret

    2007-01-01

    Treatment resistance has emerged as a significant issue in our era emphasizing biological treatments for psychiatric disorders. Some treatment programs utilize milieu treatment to advance work with treatment resistant patients. This article (1) explores the social factors that contribute to and exacerbate treatment resistance (2) reviews the theoretical framework and rationale of a therapeutic community milieu treatment program, and (3) illustrates therapeutic community work with two treatment resistant patients.

  11. Models for synthetic biology

    PubMed Central

    Kaznessis, Yiannis N

    2007-01-01

    Synthetic biological engineering is emerging from biology as a distinct discipline based on quantification. The technologies propelling synthetic biology are not new, nor is the concept of designing novel biological molecules. What is new is the emphasis on system behavior. The objective is the design and construction of new biological devices and systems to deliver useful applications. Numerous synthetic gene circuits have been created in the past decade, including bistable switches, oscillators, and logic gates, and possible applications abound, including biofuels, detectors for biochemical and chemical weapons, disease diagnosis, and gene therapies. More than fifty years after the discovery of the molecular structure of DNA, molecular biology is mature enough for real quantification that is useful for biological engineering applications, similar to the revolution in modeling in chemistry in the 1950s. With the excitement that synthetic biology is generating, the engineering and biological science communities appear remarkably willing to cross disciplinary boundaries toward a common goal. PMID:17986347

  12. Quantitative disease resistance and quantitative resistance Loci in breeding.

    PubMed

    St Clair, Dina A

    2010-01-01

    Quantitative disease resistance (QDR) has been observed within many crop plants but is not as well understood as qualitative (monogenic) disease resistance and has not been used as extensively in breeding. Mapping quantitative trait loci (QTLs) is a powerful tool for genetic dissection of QDR. DNA markers tightly linked to quantitative resistance loci (QRLs) controlling QDR can be used for marker-assisted selection (MAS) to incorporate these valuable traits. QDR confers a reduction, rather than lack, of disease and has diverse biological and molecular bases as revealed by cloning of QRLs and identification of the candidate gene(s) underlying QRLs. Increasing our biological knowledge of QDR and QRLs will enhance understanding of how QDR differs from qualitative resistance and provide the necessary information to better deploy these resources in breeding. Application of MAS for QRLs in breeding for QDR to diverse pathogens is illustrated by examples from wheat, barley, common bean, tomato, and pepper. Strategies for optimum deployment of QRLs require research to understand effects of QDR on pathogen populations over time.

  13. Repair-Resistant DNA Lesions

    PubMed Central

    2017-01-01

    The eukaryotic global genomic nucleotide excision repair (GG-NER) pathway is the major mechanism that removes most bulky and some nonbulky lesions from cellular DNA. There is growing evidence that certain DNA lesions are repaired slowly or are entirely resistant to repair in cells, tissues, and in cell extract model assay systems. It is well established that the eukaryotic DNA lesion-sensing proteins do not detect the damaged nucleotide, but recognize the distortions/destabilizations in the native DNA structure caused by the damaged nucleotides. In this article, the nature of the structural features of certain bulky DNA lesions that render them resistant to NER, or cause them to be repaired slowly, is compared to that of those that are good-to-excellent NER substrates. Understanding the structural features that distinguish NER-resistant DNA lesions from good NER substrates may be useful for interpreting the biological significance of biomarkers of exposure of human populations to genotoxic environmental chemicals. NER-resistant lesions can survive to replication and cause mutations that can initiate cancer and other diseases. Furthermore, NER diminishes the efficacy of certain chemotherapeutic drugs, and the design of more potent pharmaceuticals that resist repair can be advanced through a better understanding of the structural properties of DNA lesions that engender repair-resistance. PMID:28750166

  14. [Vancomycin-resistant Staphylococcus aureus].

    PubMed

    Rodríguez, Carlos Andrés; Vesga, Omar

    2005-12-01

    The evolution and molecular mechanisms of vancomycin resistance in Staphylococcus aureus were reviewed. Case reports and research studies on biochemestry, electron microscopy and molecular biology of Staphylococcus aureus were selected from Medline database and summarized in the following review. After almost 40 years of successful treatment of S. aureus with vancomycin, several cases of clinical failures have been reported (since 1997). S. aureus strains have appeared with intermediate susceptibility (MIC 8-16 microg/ml), as well as strains with heterogeneous resistance (global MIC < or =4 microg/ml), but with subpopulations of intermediate susceptibility. In these cases, resistance is mediated by cell wall thickening with reduced cross linking. This traps the antibiotic before it reaches its major target, the murein monomers in the cell membrane. In 2002, a total vancomycin resistant strain (MIC > or =32 microg/ml) was reported with vanA genes from Enterococcus spp. These genes induce the change of D-Ala-D-Ala terminus for D-Ala-D-lactate in the cell wall precursors, leading to loss of affinity for glycopeptides. Vancomycin resistance in S. aureus has appeared; it is mediated by cell wall modifications that trap the antibiotic before it reaches its action site. In strains with total resistance, Enterococcus spp. genes have been acquired that lead to modification of the glycopeptide target.

  15. Estimation of insecticide persistence, biological activity and mosquito resistance to PermaNet® 2 long-lasting insecticidal nets over three to 32 months of use in Ethiopia

    PubMed Central

    2014-01-01

    Background Information is needed on the expected durability of insecticidal nets under operational conditions. The persistence of insecticidal efficacy is important to estimate the median serviceable life of nets under field conditions and to plan for net replacement. Methods Deltamethrin residue levels were evaluated by the proxy method of X-ray fluorescence spectrometry on 189 nets used for three to six months from nine sites, 220 nets used for 14-20 months from 11 sites, and 200 nets used for 26-32 months from ten sites in Ethiopia. A random sample of 16.5-20% of nets from each time period (total 112 of 609 nets) were tested by bioassay with susceptible mosquitoes, and nets used for 14-20 months and 26-32 months were also tested with wild caught mosquitoes. Results Mean insecticide levels estimated by X-ray fluorescence declined by 25.9% from baseline of 66.2 (SD 14.6) mg/m2 at three to six months to 44.1 (SD 21.2) mg/m2 at 14-20 months and by 30.8% to 41.1 (SD 18.9) mg/m2 at 26-32 months. More than 95% of nets retained greater than 10 mg/m2 of deltamethrin and over 79% had at least 25 mg/m2 at all time periods. By bioassay with susceptible Anopheles, mortality averaged 89.0% on 28 nets tested at three to six months, 93.3% on 44 nets at 14-20 months and 94.1% on 40 nets at 26-32 months. With wild caught mosquitoes, mortality averaged 85.4% (range 79.1 to 91.7%) at 14-20 months but had dropped significantly to 47.2% (39.8 to 54.7%) at 26-32 months. Conclusions Insecticide residue level, as estimated by X-ray fluorescence, declined by about one third between three and six months and 14-20 months, but remained relatively stable and above minimum requirements thereafter up to 26-32 months. The insecticidal activity of PermaNet® 2.0 long-lasting insecticidal nets in the specified study area may be considered effective to susceptible mosquitoes at least for the duration indicated in this study (32 months). However, results indicated that resistance in

  16. Pre-resistance-welding resistance check

    DOEpatents

    Destefan, Dennis E.; Stompro, David A.

    1991-01-01

    A preweld resistance check for resistance welding machines uses an open circuited measurement to determine the welding machine resistance, a closed circuit measurement to determine the parallel resistance of a workpiece set and the machine, and a calculation to determine the resistance of the workpiece set. Any variation in workpiece set or machine resistance is an indication that the weld may be different from a control weld.

  17. Systems Biology of Embryogenesis

    PubMed Central

    Edelman, Lucas B.; Chandrasekaran, Sriram; Price, Nathan D.

    2010-01-01

    The development of a complete organism from a single cell involves extraordinarily complex orchestration of biological processes that vary intricately across space and time. Systems biology seeks to describe how all elements of a biological system interact in order to understand, model, and ultimately predict aspects of emergent biological processes. Embryogenesis represents an extraordinary opportunity – and challenge – for the application of systems biology. Systems approaches have already been used successfully to study various aspects of development, from complex intracellular networks to 4D models of organogenesis. Going forward, great advancements and discoveries can be expected from systems approaches applied to embryogenesis and developmental biology. PMID:20003850

  18. Antibiotic Resistance In Neisseria Gonorrhoeae: Impact Of Ceftriaxone Resistance On Microbial Fitness And Potential Of Resistance Determinants To Spread During Mixed Infection

    DTIC Science & Technology

    2016-03-07

    Molecular Biology Methods ............................................................................. 59 2.2 Bacterial Culture Conditions and...DNA Transfer ......................................................................... 66 2.7b Transfer of Resistance During Bacterial Co-culture...160 A.1b1 Bacterial Strains ....................................................................................... 160 A.1b2

  19. Biology of Blood

    MedlinePlus

    ... here for the Professional Version Home Blood Disorders Biology of Blood Overview of Blood Resources In This ... Version. DOCTORS: Click here for the Professional Version Biology of Blood Overview of Blood Components of Blood ...

  20. Advances in Biological Science.

    ERIC Educational Resources Information Center

    Oppenheimer, Steven B.; And Others

    1988-01-01

    Reviews major developments in areas that are at the cutting edge of biological research. Areas include: human anti-cancer gene, recombinant DNA techniques for the detection of Huntington disease carriers, and marine biology. (CW)

  1. Advances in Biological Science.

    ERIC Educational Resources Information Center

    Oppenheimer, Steven B.; And Others

    1988-01-01

    Reviews major developments in areas that are at the cutting edge of biological research. Areas include: human anti-cancer gene, recombinant DNA techniques for the detection of Huntington disease carriers, and marine biology. (CW)

  2. Resetting Biological Clocks

    ERIC Educational Resources Information Center

    Winfree, Arthur T.

    1975-01-01

    Reports on experiments conducted on two biological clocks, in organisms in the plant and animal kingdoms, which indicate that biological oscillation can be arrested by a single stimulus of a definite strength delivered at the proper time. (GS)

  3. Biology is simple.

    PubMed

    Newman, Tim

    2015-12-30

    This paper explores the potential for simplicity to reveal new biological understanding. Borrowing selectively from physics thinking, and contrasting with Crick's reductionist philosophy, the author argues that greater emphasis on simplicity is necessary to advance biology and its applications.

  4. Resetting Biological Clocks

    ERIC Educational Resources Information Center

    Winfree, Arthur T.

    1975-01-01

    Reports on experiments conducted on two biological clocks, in organisms in the plant and animal kingdoms, which indicate that biological oscillation can be arrested by a single stimulus of a definite strength delivered at the proper time. (GS)

  5. Foundations for engineering biology.

    PubMed

    Endy, Drew

    2005-11-24

    Engineered biological systems have been used to manipulate information, construct materials, process chemicals, produce energy, provide food, and help maintain or enhance human health and our environment. Unfortunately, our ability to quickly and reliably engineer biological systems that behave as expected remains quite limited. Foundational technologies that make routine the engineering of biology are needed. Vibrant, open research communities and strategic leadership are necessary to ensure that the development and application of biological technologies remains overwhelmingly constructive.

  6. Biology and the Government

    ERIC Educational Resources Information Center

    Reid, Roger D.

    1969-01-01

    Emphasizes the social implications of biological knowledge and discusses two main government roles in biology: (1) a creative and supportive role, including support of education and research, (2) control, regulation and protection related to the applications of biological knowledge. Public control is considered necessary in areas such as food and…

  7. BIOLOGICAL FOUNDATIONS OF LANGUAGE.

    ERIC Educational Resources Information Center

    LENNEBERG, ERIC H.

    THE RELATIONSHIP BETWEEN BIOLOGY AND LANGUAGE IS EXPLORED IN THIS VOLUME. THE AUTHOR BELIEVES THAT "LANGUAGE IS THE MANIFESTATION OF SPECIES-SPECIFIC COGNITIVE PROPENSITIES. IT IS THE CONSEQUENCE OF THE BIOLOGICAL PECULIARITIES THAT MAKE A HUMAN TYPE OF COGNITION POSSIBLE." IN ATTEMPTING TO "REINSTATE THE CONCEPT OF THE BIOLOGICAL BASIS OF…

  8. BIOLOGICAL FOUNDATIONS OF LANGUAGE.

    ERIC Educational Resources Information Center

    LENNEBERG, ERIC H.

    THE RELATIONSHIP BETWEEN BIOLOGY AND LANGUAGE IS EXPLORED IN THIS VOLUME. THE AUTHOR BELIEVES THAT "LANGUAGE IS THE MANIFESTATION OF SPECIES-SPECIFIC COGNITIVE PROPENSITIES. IT IS THE CONSEQUENCE OF THE BIOLOGICAL PECULIARITIES THAT MAKE A HUMAN TYPE OF COGNITION POSSIBLE." IN ATTEMPTING TO "REINSTATE THE CONCEPT OF THE BIOLOGICAL BASIS OF…

  9. Teaching and Learning Biology.

    ERIC Educational Resources Information Center

    Dowdeswell, W. H.

    Provided in this book is a critical review of modern biology curricula and teaching methods with particular reference to the advance of knowledge and changes in society. The book consists of an introduction (discussing biology as a subject, attitudes to learning, and values in biology teaching), 12 chapters, and 4 appendices. Teaching/learning…

  10. Designing synthetic biology.

    PubMed

    Agapakis, Christina M

    2014-03-21

    Synthetic biology is frequently defined as the application of engineering design principles to biology. Such principles are intended to streamline the practice of biological engineering, to shorten the time required to design, build, and test synthetic gene networks. This streamlining of iterative design cycles can facilitate the future construction of biological systems for a range of applications in the production of fuels, foods, materials, and medicines. The promise of these potential applications as well as the emphasis on design has prompted critical reflection on synthetic biology from design theorists and practicing designers from many fields, who can bring valuable perspectives to the discipline. While interdisciplinary connections between biologists and engineers have built synthetic biology via the science and the technology of biology, interdisciplinary collaboration with artists, designers, and social theorists can provide insight on the connections between technology and society. Such collaborations can open up new avenues and new principles for research and design, as well as shed new light on the challenging context-dependence-both biological and social-that face living technologies at many scales. This review is inspired by the session titled "Design and Synthetic Biology: Connecting People and Technology" at Synthetic Biology 6.0 and covers a range of literature on design practice in synthetic biology and beyond. Critical engagement with how design is used to shape the discipline opens up new possibilities for how we might design the future of synthetic biology.

  11. Teaching and Learning Biology.

    ERIC Educational Resources Information Center

    Dowdeswell, W. H.

    Provided in this book is a critical review of modern biology curricula and teaching methods with particular reference to the advance of knowledge and changes in society. The book consists of an introduction (discussing biology as a subject, attitudes to learning, and values in biology teaching), 12 chapters, and 4 appendices. Teaching/learning…

  12. General Biology Syllabus.

    ERIC Educational Resources Information Center

    Hunter, Scott; Watthews, Thomas

    This syllabus has been developed as an alternative to Regents biology and is intended for the average student who could benefit from an introductory biology course. It is divided into seven major units dealing with, respectively: (1) similarities among living things; (2) human biology (focusing on nutrition, transport, respiration, excretion, and…

  13. Biology Myth-Killers

    ERIC Educational Resources Information Center

    Lampert, Evan

    2014-01-01

    "Biology Myth-Killers" is an activity designed to identify and correct common misconceptions for high school and college introductory biology courses. Students identify common myths, which double as biology misconceptions, and use appropriate sources to share the "truth" about the myths. This learner-centered activity is a fun…

  14. Biology Myth-Killers

    ERIC Educational Resources Information Center

    Lampert, Evan

    2014-01-01

    "Biology Myth-Killers" is an activity designed to identify and correct common misconceptions for high school and college introductory biology courses. Students identify common myths, which double as biology misconceptions, and use appropriate sources to share the "truth" about the myths. This learner-centered activity is a fun…

  15. General Biology Syllabus.

    ERIC Educational Resources Information Center

    Hunter, Scott; Watthews, Thomas

    This syllabus has been developed as an alternative to Regents biology and is intended for the average student who could benefit from an introductory biology course. It is divided into seven major units dealing with, respectively: (1) similarities among living things; (2) human biology (focusing on nutrition, transport, respiration, excretion, and…

  16. Mythology in Introductory Biology.

    ERIC Educational Resources Information Center

    Vogel, Steve

    1987-01-01

    Argues that introductory courses in college biology do a poor job of encouraging students to enter a career in biology. Cites examples of poorly written textbooks and treatments of various aspects of biology including basic definitions, cells and their operations, the mechanics of life, the nervous system, evolution and sex. (TW)

  17. Biology of Elderly Suicide.

    ERIC Educational Resources Information Center

    Rifai, A. Hind; And Others

    1992-01-01

    Describes age-related changes in central nervous system pertinent to biology of suicide. Reviews postmortem biological studies of brains of suicides and suicide attempters. As suicide attempts in elderly are characterized by violence, discusses biological studies of impulsive violence. Describes data on effect of degenerative diseases on serotonin…

  18. Upgrading Undergraduate Biology Education

    ERIC Educational Resources Information Center

    Musante, Susan

    2011-01-01

    On many campuses throughout the country, undergraduate biology education is in serious need of an upgrade. During the past few decades, the body of biological knowledge has grown exponentially, and as a research endeavor, the practice of biology has evolved. Education research has also made great strides, revealing many new insights into how…

  19. Biology and the Government

    ERIC Educational Resources Information Center

    Reid, Roger D.

    1969-01-01

    Emphasizes the social implications of biological knowledge and discusses two main government roles in biology: (1) a creative and supportive role, including support of education and research, (2) control, regulation and protection related to the applications of biological knowledge. Public control is considered necessary in areas such as food and…

  20. Chemistry and Biology

    ERIC Educational Resources Information Center

    Wigston, David L.

    1970-01-01

    Discusses the relationship between chemisty and biology in the science curriculum. Points out the differences in perception of the disciplines, which the physical scientists favoring reductionism. Suggests that biology departments offer a special course for chemistry students, just as the chemistry departments have done for biology students.…

  1. Controversial Issues within Biology: Enriching Biology Teaching.

    ERIC Educational Resources Information Center

    Van Rooy, Wilhelmina

    2000-01-01

    Describes the development and implementation of a senior high school biology lesson concerned with organ transplantation. Discusses the teacher's rationale and techniques for using controversial issues in science teaching. (Contains 18 references.) (Author/WRM)

  2. Spectroscopic diagnostics for bacteria in biologic sample

    DOEpatents

    El-Sayed, Mostafa A.; El-Sayed, Ivan H.

    2002-01-01

    A method to analyze and diagnose specific bacteria in a biologic sample using spectroscopy is disclosed. The method includes obtaining the spectra of a biologic sample of a non-infected patient for use as a reference, subtracting the reference from the spectra of an infected sample, and comparing the fingerprint regions of the resulting differential spectrum with reference spectra of bacteria in saline. Using this diagnostic technique, specific bacteria can be identified sooner and without culturing, bacteria-specific antibiotics can be prescribed sooner, resulting in decreased likelihood of antibiotic resistance and an overall reduction of medical costs.

  3. Superinfection and the evolution of resistance to antimalarial drugs.

    PubMed

    Klein, Eili Y; Smith, David L; Laxminarayan, Ramanan; Levin, Simon

    2012-09-22

    A major issue in the control of malaria is the evolution of drug resistance. Ecological theory has demonstrated that pathogen superinfection and the resulting within-host competition influences the evolution of specific traits. Individuals infected with Plasmodium falciparum are consistently infected by multiple parasites; however, while this probably alters the dynamics of resistance evolution, there are few robust mathematical models examining this issue. We developed a general theory for modelling the evolution of resistance with host superinfection and examine: (i) the effect of transmission intensity on the rate of resistance evolution; (ii) the importance of different biological costs of resistance; and (iii) the best measure of the frequency of resistance. We find that within-host competition retards the ability and slows the rate at which drug-resistant parasites invade, particularly as the transmission rate increases. We also find that biological costs of resistance that reduce transmission are less important than reductions in the duration of drug-resistant infections. Lastly, we find that random sampling of the population for resistant parasites is likely to significantly underestimate the frequency of resistance. Considering superinfection in mathematical models of antimalarial drug resistance may thus be important for generating accurate predictions of interventions to contain resistance.

  4. Superinfection and the evolution of resistance to antimalarial drugs

    PubMed Central

    Klein, Eili Y.; Smith, David L.; Laxminarayan, Ramanan; Levin, Simon

    2012-01-01

    A major issue in the control of malaria is the evolution of drug resistance. Ecological theory has demonstrated that pathogen superinfection and the resulting within-host competition influences the evolution of specific traits. Individuals infected with Plasmodium falciparum are consistently infected by multiple parasites; however, while this probably alters the dynamics of resistance evolution, there are few robust mathematical models examining this issue. We developed a general theory for modelling the evolution of resistance with host superinfection and examine: (i) the effect of transmission intensity on the rate of resistance evolution; (ii) the importance of different biological costs of resistance; and (iii) the best measure of the frequency of resistance. We find that within-host competition retards the ability and slows the rate at which drug-resistant parasites invade, particularly as the transmission rate increases. We also find that biological costs of resistance that reduce transmission are less important than reductions in the duration of drug-resistant infections. Lastly, we find that random sampling of the population for resistant parasites is likely to significantly underestimate the frequency of resistance. Considering superinfection in mathematical models of antimalarial drug resistance may thus be important for generating accurate predictions of interventions to contain resistance. PMID:22787024

  5. Synthetic biology: putting synthesis into biology.

    PubMed

    Liang, Jing; Luo, Yunzi; Zhao, Huimin

    2011-01-01

    The ability to manipulate living organisms is at the heart of a range of emerging technologies that serve to address important and current problems in environment, energy, and health. However, with all its complexity and interconnectivity, biology has for many years been recalcitrant to engineering manipulations. The recent advances in synthesis, analysis, and modeling methods have finally provided the tools necessary to manipulate living systems in meaningful ways and have led to the coining of a field named synthetic biology. The scope of synthetic biology is as complicated as life itself--encompassing many branches of science and across many scales of application. New DNA synthesis and assembly techniques have made routine customization of very large DNA molecules. This in turn has allowed the incorporation of multiple genes and pathways. By coupling these with techniques that allow for the modeling and design of protein functions, scientists have now gained the tools to create completely novel biological machineries. Even the ultimate biological machinery--a self-replicating organism--is being pursued at this moment. The aim of this article is to dissect and organize these various components of synthetic biology into a coherent picture.

  6. Synthetic Biology: Putting Synthesis into Biology

    PubMed Central

    Liang, Jing; Luo, Yunzi; Zhao, Huimin

    2010-01-01

    The ability to manipulate living organisms is at the heart of a range of emerging technologies that serve to address important and current problems in environment, energy, and health. However, with all its complexity and interconnectivity, biology has for many years been recalcitrant to engineering manipulations. The recent advances in synthesis, analysis, and modeling methods have finally provided the tools necessary to manipulate living systems in meaningful ways, and have led to the coining of a field named synthetic biology. The scope of synthetic biology is as complicated as life itself – encompassing many branches of science, and across many scales of application. New DNA synthesis and assembly techniques have made routine the customization of very large DNA molecules. This in turn has allowed the incorporation of multiple genes and pathways. By coupling these with techniques that allow for the modeling and design of protein functions, scientists have now gained the tools to create completely novel biological machineries. Even the ultimate biological machinery – a self-replicating organism – is being pursued at this moment. It is the purpose of this review to dissect and organize these various components of synthetic biology into a coherent picture. PMID:21064036

  7. Synthetic biology--putting engineering into biology.

    PubMed

    Heinemann, Matthias; Panke, Sven

    2006-11-15

    Synthetic biology is interpreted as the engineering-driven building of increasingly complex biological entities for novel applications. Encouraged by progress in the design of artificial gene networks, de novo DNA synthesis and protein engineering, we review the case for this emerging discipline. Key aspects of an engineering approach are purpose-orientation, deep insight into the underlying scientific principles, a hierarchy of abstraction including suitable interfaces between and within the levels of the hierarchy, standardization and the separation of design and fabrication. Synthetic biology investigates possibilities to implement these requirements into the process of engineering biological systems. This is illustrated on the DNA level by the implementation of engineering-inspired artificial operations such as toggle switching, oscillating or production of spatial patterns. On the protein level, the functionally self-contained domain structure of a number of proteins suggests possibilities for essentially Lego-like recombination which can be exploited for reprogramming DNA binding domain specificities or signaling pathways. Alternatively, computational design emerges to rationally reprogram enzyme function. Finally, the increasing facility of de novo DNA synthesis-synthetic biology's system fabrication process-supplies the possibility to implement novel designs for ever more complex systems. Some of these elements have merged to realize the first tangible synthetic biology applications in the area of manufacturing of pharmaceutical compounds.

  8. Resistant hypertension.

    PubMed

    Armario, P; Oliveras, A; de la Sierra, A

    2013-11-01

    A 53 year old woman with hypercholesterolemia treated with statins, with no history of cardiovascular disease, was referred to the Hypertension and Vascular Risk Unit for management of hypertension resistant to 4 antihypertensive agents at full doses. The patient had obesity, with a body mass index of 36.3kg/m(2) and office blood pressure 162/102mm Hg. Physical examination showed no data of interest. glucose 120mg/dl, glycated Hb: 6.4%, albuminuria 68mg/g, kidney function and study of the renin angiotensin system and other biochemical parameters were normal. Echocardiography: left ventricular mass, 131g/m(2) (normal, <110g/m(2)). True resistant hypertension was confirmed by ambulatory monitoring of blood pressure during 24h (153/89mm Hg). Spironolactone treatment (25mg/day) was added and was well tolerated, with no change in renal function and kaliemia within normal (4.1mmol/l) following the treatment. After 8 weeks, blood pressure was well controlled: office blood pressure 132/86mm Hg and 24h-ambulatory blood pressure: 128/79mm Hg. Copyright © 2013 Elsevier España, S.L. All rights reserved.

  9. Synthetic biological networks

    NASA Astrophysics Data System (ADS)

    Archer, Eric; Süel, Gürol M.

    2013-09-01

    Despite their obvious relationship and overlap, the field of physics is blessed with many insightful laws, while such laws are sadly absent in biology. Here we aim to discuss how the rise of a more recent field known as synthetic biology may allow us to more directly test hypotheses regarding the possible design principles of natural biological networks and systems. In particular, this review focuses on synthetic gene regulatory networks engineered to perform specific functions or exhibit particular dynamic behaviors. Advances in synthetic biology may set the stage to uncover the relationship of potential biological principles to those developed in physics.

  10. Biological Control in Agroecosystems

    NASA Astrophysics Data System (ADS)

    Batra, Suzanne W. T.

    1982-01-01

    Living organisms are used as biological pest control agents in (i) classical biological control, primarily for permanent control of introduced perennial weed pests or introduced pests of perennial crops; (ii) augmentative biological control, for temporary control of native or introduced pests of annual crops grown in monoculture; and (iii) conservative or natural control, in which the agroecosystem is managed to maximize the effect of native or introduced biological control agents. The effectiveness of biological control can be improved if it is based on adequate ecological information and theory, and if it is integrated with other pest management practices.

  11. [Biological evolution and specialization].

    PubMed

    Luo, Weizhen; Wang, Deli

    2003-12-01

    There were some disputes about the concept and mechanism of biological evolution. This paper tried to give more explanations on the key concepts. The biological adaptability was distinguished into two different concepts: biological evolution and specialization. The former was defined as the process of biologically gradual evolvement, and the latter was considered as the process of species formation at horizontal development. Moreover, a new conceptual framework was applied to the popular biological theories known by people, and the previous research results or discoveries were explained over again.

  12. Clopidogrel resistance: what's new?

    PubMed

    Cuisset, Thomas; Cayla, Guillaume; Silvain, Johanne

    2010-01-01

    The concept of clopidogrel resistance emerged several years ago. Since then, many studies have been performed to elucidate the mechanisms and potential clinical impact of this biological finding. These studies identified complex mechanisms, including drug-drug interactions, genetic polymorphisms and clinical factors, and showed consistently the clinical relevance of the variability of clopidogrel response, with higher ischaemic risk in low-responders or non-responders, and higher bleeding risk in hyper-responders. Several strategies for overcoming clopidogrel resistance have been evaluated in small clinical studies, but the benefit of tailored antiplatelet therapy has yet to be validated in large randomized trials, which are currently ongoing. Upcoming antiplatelet drugs that are more potent will change the field of antiplatelet therapy in acute coronary syndromes. The future of antiplatelet therapy sounds more complex, with different drugs, and tailored therapy based on platelet tests and/or genetic testing, but it will lead us to propose a more individualized therapy, which hopefully will improve patient outcome. Copyright 2010 Elsevier Masson SAS. All rights reserved.

  13. Computational Systems Chemical Biology

    PubMed Central

    Oprea, Tudor I.; May, Elebeoba E.; Leitão, Andrei; Tropsha, Alexander

    2013-01-01

    There is a critical need for improving the level of chemistry awareness in systems biology. The data and information related to modulation of genes and proteins by small molecules continue to accumulate at the same time as simulation tools in systems biology and whole body physiologically-based pharmacokinetics (PBPK) continue to evolve. We called this emerging area at the interface between chemical biology and systems biology systems chemical biology, SCB (Oprea et al., 2007). The overarching goal of computational SCB is to develop tools for integrated chemical-biological data acquisition, filtering and processing, by taking into account relevant information related to interactions between proteins and small molecules, possible metabolic transformations of small molecules, as well as associated information related to genes, networks, small molecules and, where applicable, mutants and variants of those proteins. There is yet an unmet need to develop an integrated in silico pharmacology / systems biology continuum that embeds drug-target-clinical outcome (DTCO) triplets, a capability that is vital to the future of chemical biology, pharmacology and systems biology. Through the development of the SCB approach, scientists will be able to start addressing, in an integrated simulation environment, questions that make the best use of our ever-growing chemical and biological data repositories at the system-wide level. This chapter reviews some of the major research concepts and describes key components that constitute the emerging area of computational systems chemical biology. PMID:20838980

  14. Computational systems chemical biology.

    PubMed

    Oprea, Tudor I; May, Elebeoba E; Leitão, Andrei; Tropsha, Alexander

    2011-01-01

    There is a critical need for improving the level of chemistry awareness in systems biology. The data and information related to modulation of genes and proteins by small molecules continue to accumulate at the same time as simulation tools in systems biology and whole body physiologically based pharmacokinetics (PBPK) continue to evolve. We called this emerging area at the interface between chemical biology and systems biology systems chemical biology (SCB) (Nat Chem Biol 3: 447-450, 2007).The overarching goal of computational SCB is to develop tools for integrated chemical-biological data acquisition, filtering and processing, by taking into account relevant information related to interactions between proteins and small molecules, possible metabolic transformations of small molecules, as well as associated information related to genes, networks, small molecules, and, where applicable, mutants and variants of those proteins. There is yet an unmet need to develop an integrated in silico pharmacology/systems biology continuum that embeds drug-target-clinical outcome (DTCO) triplets, a capability that is vital to the future of chemical biology, pharmacology, and systems biology. Through the development of the SCB approach, scientists will be able to start addressing, in an integrated simulation environment, questions that make the best use of our ever-growing chemical and biological data repositories at the system-wide level. This chapter reviews some of the major research concepts and describes key components that constitute the emerging area of computational systems chemical biology.

  15. Microfluidics: reframing biological enquiry.

    PubMed

    Duncombe, Todd A; Tentori, Augusto M; Herr, Amy E

    2015-09-01

    The underlying physical properties of microfluidic tools have led to new biological insights through the development of microsystems that can manipulate, mimic and measure biology at a resolution that has not been possible with macroscale tools. Microsystems readily handle sub-microlitre volumes, precisely route predictable laminar fluid flows and match both perturbations and measurements to the length scales and timescales of biological systems. The advent of fabrication techniques that do not require highly specialized engineering facilities is fuelling the broad dissemination of microfluidic systems and their adaptation to specific biological questions. We describe how our understanding of molecular and cell biology is being and will continue to be advanced by precision microfluidic approaches and posit that microfluidic tools - in conjunction with advanced imaging, bioinformatics and molecular biology approaches - will transform biology into a precision science.

  16. Chromium and insulin resistance.

    PubMed

    Anderson, Richard A

    2003-12-01

    Insulin resistance leads to the inability of insulin to control the utilization and storage of glucose. It is associated initially with elevated levels of circulating insulin followed by glucose intolerance which may progress to type 2 diabetes, hyperlipidaemia, hypertension, obesity and cardiovascular diseases. While the causes of these diseases are multifactorial, one nutrient that is associated with all of these abnormalities is Cr. In the presence of Cr, in a biologically active form, much lower levels of insulin are required. Modern diets, which are often high in refined carbohydrates, are not only low in Cr, but lead to enhanced Cr losses. In response to the consumption of refined carbohydrates, there is a rapid rise in blood sugar leading to elevations in insulin that cause a mobilization of Cr. Once mobilized, Cr is not reabsorbed but lost via the urine leading to decreased Cr stores. Several studies involving both human subjects and experimental animals have reported improvements in insulin sensitivity, blood glucose, insulin, lipids, haemoglobin A1c, lean body mass and related variables in response to improved Cr nutrition. However, not all studies have reported beneficial effects associated with improved Cr nutrition. Well-controlled human studies are needed to document an unequivocal effect of Cr on insulin sensitivity in human subjects. Studies need to involve a significant number of subjects with insulin resistance, glucose intolerance or early stages of diabetes, who have not been taking supplements containing Cr for at least 4 months, and involve at least 400 to 600 microg supplemental Cr daily or more. Studies should be at least 4 months to document sustained effects of supplemental Cr on insulin resistance and related variables. Cr is a nutrient and not a therapeutic agent and therefore will only be of benefit to those whose problems are due to suboptimal intake of Cr.

  17. The biological control of the malaria vector.

    PubMed

    Kamareddine, Layla

    2012-09-01

    The call for malaria control, over the last century, marked a new epoch in the history of this disease. Many control strategies targeting either the Plasmodium parasite or the Anopheles vector were shown to be effective. Yet, the emergence of drug resistant parasites and insecticide resistant mosquito strains, along with numerous health, environmental, and ecological side effects of many chemical agents, highlighted the need to develop alternative tools that either complement or substitute conventional malaria control approaches. The use of biological means is considered a fundamental part of the recently launched malaria eradication program and has so far shown promising results, although this approach is still in its infancy. This review presents an overview of the most promising biological control tools for malaria eradication, namely fungi, bacteria, larvivorous fish, parasites, viruses and nematodes.

  18. The Biological Control of the Malaria Vector

    PubMed Central

    Kamareddine, Layla

    2012-01-01

    The call for malaria control, over the last century, marked a new epoch in the history of this disease. Many control strategies targeting either the Plasmodium parasite or the Anopheles vector were shown to be effective. Yet, the emergence of drug resistant parasites and insecticide resistant mosquito strains, along with numerous health, environmental, and ecological side effects of many chemical agents, highlighted the need to develop alternative tools that either complement or substitute conventional malaria control approaches. The use of biological means is considered a fundamental part of the recently launched malaria eradication program and has so far shown promising results, although this approach is still in its infancy. This review presents an overview of the most promising biological control tools for malaria eradication, namely fungi, bacteria, larvivorous fish, parasites, viruses and nematodes. PMID:23105979

  19. Biological control and sustainable food production.

    PubMed

    Bale, J S; van Lenteren, J C; Bigler, F

    2008-02-27

    The use of biological control for the management of pest insects pre-dates the modern pesticide era. The first major successes in biological control occurred with exotic pests controlled by natural enemy species collected from the country or area of origin of the pest (classical control). Augmentative control has been successfully applied against a range of open-field and greenhouse pests, and conservation biological control schemes have been developed with indigenous predators and parasitoids. The cost-benefit ratio for classical biological control is highly favourable (1:250) and for augmentative control is similar to that of insecticides (1:2-1:5), with much lower development costs. Over the past 120 years, more than 5000 introductions of approximately 2000 non-native control agents have been made against arthropod pests in 196 countries or islands with remarkably few environmental problems. Biological control is a key component of a 'systems approach' to integrated pest management, to counteract insecticide-resistant pests, withdrawal of chemicals and minimize the usage of pesticides. Current studies indicate that genetically modified insect-resistant Bt crops may have no adverse effects on the activity or function of predators or parasitoids used in biological control. The introduction of rational approaches for the environmental risk assessment of non-native control agents is an essential step in the wider application of biological control, but future success is strongly dependent on a greater level of investment in research and development by governments and related organizations that are committed to a reduced reliance on chemical control.

  20. Selective insulin resistance in adipocytes.

    PubMed

    Tan, Shi-Xiong; Fisher-Wellman, Kelsey H; Fazakerley, Daniel J; Ng, Yvonne; Pant, Himani; Li, Jia; Meoli, Christopher C; Coster, Adelle C F; Stöckli, Jacqueline; James, David E

    2015-05-01

    Aside from glucose metabolism, insulin regulates a variety of pathways in peripheral tissues. Under insulin-resistant conditions, it is well known that insulin-stimulated glucose uptake is impaired, and many studies attribute this to a defect in Akt signaling. Here we make use of several insulin resistance models, including insulin-resistant 3T3-L1 adipocytes and fat explants prepared from high fat-fed C57BL/6J and ob/ob mice, to comprehensively distinguish defective from unaffected aspects of insulin signaling and its downstream consequences in adipocytes. Defective regulation of glucose uptake was observed in all models of insulin resistance, whereas other major actions of insulin such as protein synthesis and anti-lipolysis were normal. This defect corresponded to a reduction in the maximum response to insulin. The pattern of change observed for phosphorylation in the Akt pathway was inconsistent with a simple defect at the level of Akt. The only Akt substrate that showed consistently reduced phosphorylation was the RabGAP AS160 that regulates GLUT4 translocation. We conclude that insulin resistance in adipose tissue is highly selective for glucose metabolism and likely involves a defect in one of the components regulating GLUT4 translocation to the cell surface in response to insulin. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  1. Tamoxifen Resistance: Emerging Molecular Targets

    PubMed Central

    Rondón-Lagos, Milena; Villegas, Victoria E.; Rangel, Nelson; Sánchez, Magda Carolina; Zaphiropoulos, Peter G.

    2016-01-01

    17β-Estradiol (E2) plays a pivotal role in the development and progression of breast cancer. As a result, blockade of the E2 signal through either tamoxifen (TAM) or aromatase inhibitors is an important therapeutic strategy to treat or prevent estrogen receptor (ER) positive breast cancer. However, resistance to TAM is the major obstacle in endocrine therapy. This resistance occurs either de novo or is acquired after an initial beneficial response. The underlying mechanisms for TAM resistance are probably multifactorial and remain largely unknown. Considering that breast cancer is a very heterogeneous disease and patients respond differently to treatment, the molecular analysis of TAM’s biological activity could provide the necessary framework to understand the complex effects of this drug in target cells. Moreover, this could explain, at least in part, the development of resistance and indicate an optimal therapeutic option. This review highlights the implications of TAM in breast cancer as well as the role of receptors/signal pathways recently suggested to be involved in the development of TAM resistance. G protein—coupled estrogen receptor, Androgen Receptor and Hedgehog signaling pathways are emerging as novel therapeutic targets and prognostic indicators for breast cancer, based on their ability to mediate estrogenic signaling in ERα-positive or -negative breast cancer. PMID:27548161

  2. Tamoxifen Resistance: Emerging Molecular Targets.

    PubMed

    Rondón-Lagos, Milena; Villegas, Victoria E; Rangel, Nelson; Sánchez, Magda Carolina; Zaphiropoulos, Peter G

    2016-08-19

    17β-Estradiol (E2) plays a pivotal role in the development and progression of breast cancer. As a result, blockade of the E2 signal through either tamoxifen (TAM) or aromatase inhibitors is an important therapeutic strategy to treat or prevent estrogen receptor (ER) positive breast cancer. However, resistance to TAM is the major obstacle in endocrine therapy. This resistance occurs either de novo or is acquired after an initial beneficial response. The underlying mechanisms for TAM resistance are probably multifactorial and remain largely unknown. Considering that breast cancer is a very heterogeneous disease and patients respond differently to treatment, the molecular analysis of TAM's biological activity could provide the necessary framework to understand the complex effects of this drug in target cells. Moreover, this could explain, at least in part, the development of resistance and indicate an optimal therapeutic option. This review highlights the implications of TAM in breast cancer as well as the role of receptors/signal pathways recently suggested to be involved in the development of TAM resistance. G protein-coupled estrogen receptor, Androgen Receptor and Hedgehog signaling pathways are emerging as novel therapeutic targets and prognostic indicators for breast cancer, based on their ability to mediate estrogenic signaling in ERα-positive or -negative breast cancer.

  3. Standard biological parts knowledgebase.

    PubMed

    Galdzicki, Michal; Rodriguez, Cesar; Chandran, Deepak; Sauro, Herbert M; Gennari, John H

    2011-02-24

    We have created the Knowledgebase of Standard Biological Parts (SBPkb) as a publically accessible Semantic Web resource for synthetic biology (sbolstandard.org). The SBPkb allows researchers to query and retrieve standard biological parts for research and use in synthetic biology. Its initial version includes all of the information about parts stored in the Registry of Standard Biological Parts (partsregistry.org). SBPkb transforms this information so that it is computable, using our semantic framework for synthetic biology parts. This framework, known as SBOL-semantic, was built as part of the Synthetic Biology Open Language (SBOL), a project of the Synthetic Biology Data Exchange Group. SBOL-semantic represents commonly used synthetic biology entities, and its purpose is to improve the distribution and exchange of descriptions of biological parts. In this paper, we describe the data, our methods for transformation to SBPkb, and finally, we demonstrate the value of our knowledgebase with a set of sample queries. We use RDF technology and SPARQL queries to retrieve candidate "promoter" parts that are known to be both negatively and positively regulated. This method provides new web based data access to perform searches for parts that are not currently possible.

  4. Trends and Challenges in Pesticide Resistance Detection.

    PubMed

    2016-10-01

    Pesticide resistance is a crucial factor to be considered when developing strategies for the minimal use of pesticides while maintaining pesticide efficacy. This goal requires monitoring the emergence and development of resistance to pesticides in crop pests. To this end, various methods for resistance diagnosis have been developed for different groups of pests. This review provides an overview of biological, biochemical, and molecular methods that are currently used to detect and quantify pesticide resistance. The agronomic, technical, and economic advantages and drawbacks of each method are considered. Emerging technologies are also described, with their associated challenges and their potential for the detection of resistance mechanisms likely to be selected by current and future plant protection methods.

  5. [Biological aspects of pancreatic cancer].

    PubMed

    Tonel, E; Carbone, A; Scirelli, T; Bellone, G; Emanuelli, G

    2005-04-01

    Pancreatic ductal carcinoma still is an aggressive disease with a fatal prognosis due to late diagnosis and resistance to pharmacological and surgical treatments. Molecular investigations of pancreatic cancer are complicated by the restricted accessibility of the organ for biopsies. However, recent studies have indicated that pancreatic cancer is a multi-stage process resulting from the accumulation of genetic changes in the somatic DNA of normal cells. These molecular alterations, including overexpression of receptor-ligand systems, oncogene activation and loss of tumour suppressor genes, leads to a profound disturbance in cell cycle regulation and continuous growth. The molecular findings are now integrated in a pancreatic tumour progression model, with genetically and morphological defined precursor lesions. However, it remains unclear whether the initial target cells of this cancer develop from ductal or acinar cells. This review will present recent emerging questions on the biology of pancreatic cancer with particular emphasis on the cell origin and tumour microenvironment.

  6. [Natural biological risks and military biological risks].

    PubMed

    Michel, P; Attree, O; Mage, R; Tournier, J N; Quesnel-Hellmann, A

    2000-01-01

    The Iraqi biological program, the activities of sect Aum in Japan and the extensive endemicity of plague prove the existence of military, terrorist and natural biological risks. Among the agents of natural risk (viruses, bacteria.), plague is induced by modification of the ecosystem. Present since 1921 in the high plateau of Madagaskar, the disease evolves under two modes, endemic (natural) or epidemic (urban). Since the control of endemicity is impossible, the decrease of incidence will be obtained by the control of the animal reservoir. The military risk is part of the history of armed conquests. Anthrax and botulinum toxins, are the most toxic agents, banned by the Convention of London (1972). In 1995, 4 years after the end of Gulf war, UNSCOM obtained from authorities the inventory of Iraqi biological program, with details on the militarization of toxins and spores. These furtive weapons, are produced with limited technological skills, often in dual manufactures and are difficult to control.

  7. Engineering scalable biological systems

    PubMed Central

    2010-01-01

    Synthetic biology is focused on engineering biological organisms to study natural systems and to provide new solutions for pressing medical, industrial and environmental problems. At the core of engineered organisms are synthetic biological circuits that execute the tasks of sensing inputs, processing logic and performing output functions. In the last decade, significant progress has been made in developing basic designs for a wide range of biological circuits in bacteria, yeast and mammalian systems. However, significant challenges in the construction, probing, modulation and debugging of synthetic biological systems must be addressed in order to achieve scalable higher-complexity biological circuits. Furthermore, concomitant efforts to evaluate the safety and biocontainment of engineered organisms and address public and regulatory concerns will be necessary to ensure that technological advances are translated into real-world solutions. PMID:21468204

  8. Plant synthetic biology.

    PubMed

    Liu, Wusheng; Stewart, C Neal

    2015-05-01

    Plant synthetic biology is an emerging field that combines engineering principles with plant biology toward the design and production of new devices. This emerging field should play an important role in future agriculture for traditional crop improvement, but also in enabling novel bioproduction in plants. In this review we discuss the design cycles of synthetic biology as well as key engineering principles, genetic parts, and computational tools that can be utilized in plant synthetic biology. Some pioneering examples are offered as a demonstration of how synthetic biology can be used to modify plants for specific purposes. These include synthetic sensors, synthetic metabolic pathways, and synthetic genomes. We also speculate about the future of synthetic biology of plants. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. Biological tracer method

    DOEpatents

    Strong-Gunderson, Janet M.; Palumbo, Anthony V.

    1998-01-01

    The present invention is a biological tracer method for characterizing the movement of a material through a medium, comprising the steps of: introducing a biological tracer comprising a microorganism having ice nucleating activity into a medium; collecting at least one sample of the medium from a point removed from the introduction point; and analyzing the sample for the presence of the biological tracer. The present invention is also a method for using a biological tracer as a label for material identification by introducing a biological tracer having ice nucleating activity into a material, collecting a sample of a portion of the labelled material and analyzing the sample for the presence of the biological tracer.

  10. Biological tracer method

    DOEpatents

    Strong-Gunderson, J.M.; Palumbo, A.V.

    1998-09-15

    The present invention is a biological tracer method for characterizing the movement of a material through a medium, comprising the steps of: introducing a biological tracer comprising a microorganism having ice nucleating activity into a medium; collecting at least one sample of the medium from a point removed from the introduction point; and analyzing the sample for the presence of the biological tracer. The present invention is also a method for using a biological tracer as a label for material identification by introducing a biological tracer having ice nucleating activity into a material, collecting a sample of a portion of the labelled material and analyzing the sample for the presence of the biological tracer. 2 figs.

  11. Biological detector and method

    DOEpatents

    Sillerud, Laurel; Alam, Todd M; McDowell, Andrew F

    2013-02-26

    A biological detector includes a conduit for receiving a fluid containing one or more magnetic nanoparticle-labeled, biological objects to be detected and one or more permanent magnets or electromagnet for establishing a low magnetic field in which the conduit is disposed. A microcoil is disposed proximate the conduit for energization at a frequency that permits detection by NMR spectroscopy of whether the one or more magnetically-labeled biological objects is/are present in the fluid.

  12. Biological detector and method

    DOEpatents

    Sillerud, Laurel; Alam, Todd M; McDowell, Andrew F

    2014-04-15

    A biological detector includes a conduit for receiving a fluid containing one or more magnetic nanoparticle-labeled, biological objects to be detected and one or more permanent magnets or electromagnet for establishing a low magnetic field in which the conduit is disposed. A microcoil is disposed proximate the conduit for energization at a frequency that permits detection by NMR spectroscopy of whether the one or more magnetically-labeled biological objects is/are present in the fluid.

  13. Biological detector and method

    SciTech Connect

    Sillerud, Laurel; Alam, Todd M.; McDowell, Andrew F.

    2015-11-24

    A biological detector includes a conduit for receiving a fluid containing one or more magnetic nanoparticle-labeled, biological objects to be detected and one or more permanent magnets or electromagnet for establishing a low magnetic field in which the conduit is disposed. A microcoil is disposed proximate the conduit for energization at a frequency that permits detection by NMR spectroscopy of whether the one or more magnetically-labeled biological objects is/are present in the fluid.

  14. Biological Individuality of Man

    DTIC Science & Technology

    1974-12-01

    RECIPIENT’S CAT * LOO NUMBER Biological Individuality of Man 5 TlrPE OF REPORT a PERIOD COVERED Technical « PERFORMING ORO REPORT...Variability 13 A. Background , 13 B. Slatistictl Approaches to Biological Variability 13 C. Genetic Aspects of Biological Variability . 14 III...ioiological determinants of individuality. Only recently, have genetic infaienccs been investigated and the potentialities for future control of bio

  15. Sustainable management of insect-resistant crops

    USDA-ARS?s Scientific Manuscript database

    Crop genetically engineered to provide resistance to specific groups of insect pests have been adopted by millions of growers throughout the world. Here we document the effects of transgenic crops on pest population densities, beneficial insect densities and biological control services, insecticide ...

  16. A biological semiconductor based on electrical percolation

    PubMed Central

    Yang, Minghui; Bruck, Hugh Alan; Kostov, Yordan; Rasooly, Avraham

    2010-01-01

    We have developed a novel biological semiconductor (BSC) based on electrical percolation through a multi-layer 3-D carbon nanotube-antibody network, which can measure biological interactions directly and electronically. In Electrical Percolation, the passage of current through the conductive network is dependent upon the continuity of the network. Molecular interactions, such as binding of antigens to the antibodies, disrupt the network continuity causing increased resistance of the network. A BSC is fabricated by immobilizing a pre-functionalized single-walled carbon nanotubes (SWNTs)-antibody complex directly on a Poly(methyl methacrylate) (PMMA) surface (also known as plexi-glass or Acrylic). We used the BSC for direct (label-free) electronic measurements of antibody-antigen binding, showing that, at slightly above the electrical percolation threshold of the network, binding of a specific antigen dramatically increases the electrical resistance. Using anti-Staphylococcal enterotoxin B (SEB) IgG as a “gate” and SEB as an “actuator”, we demonstrated that the BSC was able to detect SEB at concentrations of 1 ng/ml. The new BSCs may permit assembly of multiple sensors on the same chip to create “Biological Central Processing Units (CPUs)” with multiple biological elements, capable of processing and sorting out information on multiple analytes simultaneously. PMID:20361741

  17. Systems Biology of Metabolism.

    PubMed

    Nielsen, Jens

    2017-06-20

    Metabolism is highly complex and involves thousands of different connected reactions; it is therefore necessary to use mathematical models for holistic studies. The use of mathematical models in biology is referred to as systems biology. In this review, the principles of systems biology are described, and two different types of mathematical models used for studying metabolism are discussed: kinetic models and genome-scale metabolic models. The use of different omics technologies, including transcriptomics, proteomics, metabolomics, and fluxomics, for studying metabolism is presented. Finally, the application of systems biology for analyzing global regulatory structures, engineering the metabolism of cell factories, and analyzing human diseases is discussed.

  18. Macrothermodynamics of Biological Evolution:

    NASA Astrophysics Data System (ADS)

    Gladyshev, Georgi P.

    The author sets forth general considerations pertaining to the thermodynamic theory of biological evolution and the aging of living organisms. It becomes much easier to comprehend the phenomenon of life scrutinizing the formation of structural hierarchies of biological matter applying different temporal scales. These scales are 'identified' by nature itself, and this is reflected in the law of temporal hierarchies. The author discusses some misunderstandings in thermodynamics and evolutionary biology. A simple physicochemical model of biological evolution and the development of living beings is proposed. The considered theory makes it possible to use physicochemical evaluations to develop effective anti-aging diets.

  19. Biological Water Quality Criteria

    EPA Pesticide Factsheets

    Page contains links to Technical Documents pertaining to Biological Water Quality Criteria, including, technical assistance documents for states, tribes and territories, program overviews, and case studies.

  20. Metadata Activities in Biology

    SciTech Connect

    Inigo, Gil San; HUTCHISON, VIVIAN; Frame, Mike; Palanisamy, Giri

    2010-01-01

    The National Biological Information Infrastructure program has advanced the biological sciences ability to standardize, share, integrate and synthesize data by making the metadata program a core of its activities. Through strategic partnerships, a series of crosswalks for the main biological metadata specifications have enabled data providers and international clearinghouses to aggregate and disseminate tens of thousands of metadata sets describing petabytes of data records. New efforts at the National Biological Information Infrastructure are focusing on better metadata creation and curation tools, semantic mediation for data discovery and other curious initiatives.

  1. Physical and biological properties of Bazna waters

    PubMed Central

    TRÂMBIŢAŞ, DAN

    2013-01-01

    The healing properties of Bazna waters and their therapeutic indications have been well known since the 18th century. The objective of the present study was to characterize these waters from physical and biological points of view, and to further analyze the nitrogen compounds, especially NH4+. The following physical parameters of the water were analyzed: density (g/cm3), electric resistivity (Ω·m), electric conductivity (cm−1o−1), salinity, The pH analysis of the biological component was performed on samples from 4 basins. Nitrogen compounds were dosed in the form of ammonium ion (NH4+). The physical and chemical proprieties are similar across the basins. Flora and fauna biological components were identified. Ammonium ions were identified in large quantities, but this did not lead to hygienicaly unclean waters. PMID:26527972

  2. Physical and biological properties of Bazna waters.

    PubMed

    Trâmbiţaş, Dan

    2013-01-01

    The healing properties of Bazna waters and their therapeutic indications have been well known since the 18(th) century. The objective of the present study was to characterize these waters from physical and biological points of view, and to further analyze the nitrogen compounds, especially NH4+. The following physical parameters of the water were analyzed: density (g/cm(3)), electric resistivity (Ω·m), electric conductivity (cm(-1)o(-1)), salinity, The pH analysis of the biological component was performed on samples from 4 basins. Nitrogen compounds were dosed in the form of ammonium ion (NH(4+)). The physical and chemical proprieties are similar across the basins. Flora and fauna biological components were identified. Ammonium ions were identified in large quantities, but this did not lead to hygienicaly unclean waters.

  3. Mechanisms of drug resistance: quinolone resistance

    PubMed Central

    Hooper, David C.; Jacoby, George A.

    2015-01-01

    Quinolone antimicrobials are synthetic and widely used in clinical medicine. Resistance emerged with clinical use and became common in some bacterial pathogens. Mechanisms of resistance include two categories of mutation and acquisition of resistance-conferring genes. Resistance mutations in one or both of the two drug target enzymes, DNA gyrase and DNA topoisomerase IV, are commonly in a localized domain of the GyrA and ParE subunits of the respective enzymes and reduce drug binding to the enzyme-DNA complex. Other resistance mutations occur in regulatory genes that control the expression of native efflux pumps localized in the bacterial membrane(s). These pumps have broad substrate profiles that include quinolones as well as other antimicrobials, disinfectants, and dyes. Mutations of both types can accumulate with selection pressure and produce highly resistant strains. Resistance genes acquired on plasmids can confer low-level resistance that promotes the selection of mutational high-level resistance. Plasmid-encoded resistance is due to Qnr proteins that protect the target enzymes from quinolone action, one mutant aminoglycoside-modifying enzyme that also modifies certain quinolones, and mobile efflux pumps. Plasmids with these mechanisms often encode additional antimicrobial resistances and can transfer multidrug resistance that includes quinolones. Thus, the bacterial quinolone resistance armamentarium is large. PMID:26190223

  4. Mechanisms of drug resistance: quinolone resistance.

    PubMed

    Hooper, David C; Jacoby, George A

    2015-09-01

    Quinolone antimicrobials are synthetic and widely used in clinical medicine. Resistance emerged with clinical use and became common in some bacterial pathogens. Mechanisms of resistance include two categories of mutation and acquisition of resistance-conferring genes. Resistance mutations in one or both of the two drug target enzymes, DNA gyrase and DNA topoisomerase IV, are commonly in a localized domain of the GyrA and ParE subunits of the respective enzymes and reduce drug binding to the enzyme-DNA complex. Other resistance mutations occur in regulatory genes that control the expression of native efflux pumps localized in the bacterial membrane(s). These pumps have broad substrate profiles that include quinolones as well as other antimicrobials, disinfectants, and dyes. Mutations of both types can accumulate with selection pressure and produce highly resistant strains. Resistance genes acquired on plasmids can confer low-level resistance that promotes the selection of mutational high-level resistance. Plasmid-encoded resistance is due to Qnr proteins that protect the target enzymes from quinolone action, one mutant aminoglycoside-modifying enzyme that also modifies certain quinolones, and mobile efflux pumps. Plasmids with these mechanisms often encode additional antimicrobial resistances and can transfer multidrug resistance that includes quinolones. Thus, the bacterial quinolone resistance armamentarium is large.

  5. Workshop Introduction: Systems Biology and Biological Models

    EPA Science Inventory

    As we consider the future of toxicity testing, the importance of applying biological models to this problem is clear. Modeling efforts exist along a continuum with respect to the level of organization (e.g. cell, tissue, organism) linked to the resolution of the model. Generally,...

  6. Workshop Introduction: Systems Biology and Biological Models

    EPA Science Inventory

    As we consider the future of toxicity testing, the importance of applying biological models to this problem is clear. Modeling efforts exist along a continuum with respect to the level of organization (e.g. cell, tissue, organism) linked to the resolution of the model. Generally,...

  7. Antimicrobial Peptides: Versatile Biological Properties

    PubMed Central

    Pushpanathan, Muthuirulan; Rajendhran, Jeyaprakash

    2013-01-01

    Antimicrobial peptides are diverse group of biologically active molecules with multidimensional properties. In recent past, a wide variety of AMPs with diverse structures have been reported from different sources such as plants, animals, mammals, and microorganisms. The presence of unusual amino acids and structural motifs in AMPs confers unique structural properties to the peptide that attribute for their specific mode of action. The ability of these active AMPs to act as multifunctional effector molecules such as signalling molecule, immune modulators, mitogen, antitumor, and contraceptive agent makes it an interesting candidate to study every aspect of their structural and biological properties for prophylactic and therapeutic applications. In addition, easy cloning and recombinant expression of AMPs in heterologous plant host systems provided a pipeline for production of disease resistant transgenic plants. Besides these properties, AMPs were also used as drug delivery vectors to deliver cell impermeable drugs to cell interior. The present review focuses on the diversity and broad spectrum antimicrobial activity of AMPs along with its multidimensional properties that could be exploited for the application of these bioactive peptides as a potential and promising drug candidate in pharmaceutical industries. PMID:23935642

  8. Opportunities for Synthetic Biology in Antibiotics: Expanding Glycopeptide Chemical Diversity

    PubMed Central

    2012-01-01

    Synthetic biology offers a new path for the exploitation and improvement of natural products to address the growing crisis in antibiotic resistance. All antibiotics in clinical use are facing eventual obsolesce as a result of the evolution and dissemination of resistance mechanisms, yet there are few new drug leads forthcoming from the pharmaceutical sector. Natural products of microbial origin have proven over the past 70 years to be the wellspring of antimicrobial drugs. Harnessing synthetic biology thinking and strategies can provide new molecules and expand chemical diversity of known antibiotic scaffolds to provide much needed new drug leads. The glycopeptide antibiotics offer paradigmatic scaffolds suitable for such an approach. We review these strategies here using the glycopeptides as an example and demonstrate how synthetic biology can expand antibiotic chemical diversity to help address the growing resistance crisis. PMID:23654249

  9. Opportunities for synthetic biology in antibiotics: expanding glycopeptide chemical diversity.

    PubMed

    Thaker, Maulik N; Wright, Gerard D

    2015-03-20

    Synthetic biology offers a new path for the exploitation and improvement of natural products to address the growing crisis in antibiotic resistance. All antibiotics in clinical use are facing eventual obsolesce as a result of the evolution and dissemination of resistance mechanisms, yet there are few new drug leads forthcoming from the pharmaceutical sector. Natural products of microbial origin have proven over the past 70 years to be the wellspring of antimicrobial drugs. Harnessing synthetic biology thinking and strategies can provide new molecules and expand chemical diversity of known antibiotic scaffolds to provide much needed new drug leads. The glycopeptide antibiotics offer paradigmatic scaffolds suitable for such an approach. We review these strategies here using the glycopeptides as an example and demonstrate how synthetic biology can expand antibiotic chemical diversity to help address the growing resistance crisis.

  10. Leaf rust of wheat: Pathogen biology, variation and host resistance

    USDA-ARS?s Scientific Manuscript database

    Rusts are important pathogens of angiosperms and gymnosperms. Rust fungi are among the most important pathogens of cereals. Cereal rusts are heteroecious and macrocyclic requiring two taxonomically unrelated hosts to complete a five spore stage life cycle. Cereal rust fungi are highly variable for v...

  11. Simultaneous laurel wilt disease biology and resistance research

    Treesearch

    Jason A. Smith; Randy C. Ploetz

    2012-01-01

    Laurel wilt (LW) is a devastating, emerging disease of native and non-native members of the Lauraceae family in the southeastern United States. Currently, the fungal pathogen (Raffaelea lauricola) and its vector (Xyleborus glabratus) are found in Alabama, Florida, Georgia, Mississippi, and North and South Carolina. The wilt is...

  12. M. tuberculosis Hypothetical Proteins and Proteins of Unknown Function: Hope for Exploring Novel Resistance Mechanisms as well as Future Target of Drug Resistance.

    PubMed

    Sharma, Divakar; Bisht, Deepa

    2017-01-01

    Drug resistance in tuberculosis predominantly, mono-resistance, multi drug resistance, extensively drug resistance and totally drug resistance have emerged as a major problem in the chemotherapy of tuberculosis. Failures of first and second line anti-tuberculosis drugs treatment leads to emergence of resistant Mycobacterium tuberculosis. Few genes are reported as the principal targets of the resistance and apart from the primary targets many explanations have been proposed for drug resistance but still some resistance mechanisms are unknown. As proteins involved in most of the biological processes, these are potentially explored the unknown mechanism of drug resistance and attractive targets for diagnostics/future therapeutics against drug resistance. In last decade a panel of studies on expression proteomics of drug resistant M. tuberculosis isolates reported the differential expression of uncharacterized proteins and suggested these might be involved in resistance. Here we emphasize that detailed bioinformatics analysis (like molecular docking, pupylation, and proteins-proteins interaction) of these uncharacterized and hypothetical proteins might predict their interactive partners (other proteins) which are involved in various pathways of M. tuberculosis system biology and might give a clue for novel mechanism of drug resistance or future drug targets. In future these uncharacterized targets might be open the new resistance mechanism and used as potential drug targets against drug resistant tuberculosis.

  13. M. tuberculosis Hypothetical Proteins and Proteins of Unknown Function: Hope for Exploring Novel Resistance Mechanisms as well as Future Target of Drug Resistance

    PubMed Central

    Sharma, Divakar; Bisht, Deepa

    2017-01-01

    Drug resistance in tuberculosis predominantly, mono-resistance, multi drug resistance, extensively drug resistance and totally drug resistance have emerged as a major problem in the chemotherapy of tuberculosis. Failures of first and second line anti-tuberculosis drugs treatment leads to emergence of resistant Mycobacterium tuberculosis. Few genes are reported as the principal targets of the resistance and apart from the primary targets many explanations have been proposed for drug resistance but still some resistance mechanisms are unknown. As proteins involved in most of the biological processes, these are potentially explored the unknown mechanism of drug resistance and attractive targets for diagnostics/future therapeutics against drug resistance. In last decade a panel of studies on expression proteomics of drug resistant M. tuberculosis isolates reported the differential expression of uncharacterized proteins and suggested these might be involved in resistance. Here we emphasize that detailed bioinformatics analysis (like molecular docking, pupylation, and proteins-proteins interaction) of these uncharacterized and hypothetical proteins might predict their interactive partners (other proteins) which are involved in various pathways of M. tuberculosis system biology and might give a clue for novel mechanism of drug resistance or future drug targets. In future these uncharacterized targets might be open the new resistance mechanism and used as potential drug targets against drug resistant tuberculosis. PMID:28377758

  14. A view from Riggs: treatment resistance and patient authority-II. Transmission of trauma and treatment resistance.

    PubMed

    Fromm, M Gerard

    2006-01-01

    Treatment resistance has emerged as a significant issue in our era emphasizing biological treatments for psychiatric disorders. This article suggests that some patients who carry trauma from previous generations become treatment resistant because of this burden. Advancing the treatment of these patients often requires openness to the burdens of past generations and attention to unraveling their meaning.

  15. Wrestling with Resistance.

    ERIC Educational Resources Information Center

    Hartzell, Gary

    1996-01-01

    Discusses reasons for and methods to defuse classroom teachers' resistance to change in the workplace. Suggestions include planning for resistance, acknowledging peoples' concerns and addressing them specifically, avoiding criticism of current methods, individualizing resistance reduction, and providing ongoing support. (JKP)

  16. Combating Antibiotic Resistance

    MedlinePlus

    ... For Consumers Home For Consumers Consumer Updates Combating Antibiotic Resistance Share Tweet Linkedin Pin it More sharing options ... however, have contributed to a phenomenon known as antibiotic resistance. This resistance develops when potentially harmful bacteria change ...

  17. Conserving and Enhancing Biological Control of Nematodes

    PubMed Central

    Timper, Patricia

    2014-01-01

    Conservation biological control is the modification of the environment or existing practices to protect and enhance antagonistic organisms to reduce damage from pests. This approach to biological control has received insufficient attention compared with inundative applications of microbial antagonists to control nematodes. This review provides examples of how production practices can enhance or diminish biological control of plant-parasitic nematodes and other soilborne pests. Antagonists of nematodes can be enhanced by providing supplementary food sources such as occurs when organic amendments are applied to soil. However, some organic amendments (e.g., manures and plants containing allelopathic compounds) can also be detrimental to nematode antagonists. Plant species and genotype can strongly influence the outcome of biological control. For instance, the susceptibility of the plant to the nematode can determine the effectiveness of control; good hosts will require greater levels of suppression than poor hosts. Plant genotype can also influence the degree of rhizosphere colonization and antibiotic production by antagonists, as well the expression of induced resistance by plants. Production practices such as crop rotation, fallow periods, tillage, and pesticide applications can directly disrupt populations of antagonistic organisms. These practices can also indirectly affect antagonists by reducing their primary nematode host. One of the challenges of conservation biological control is that practices intended to protect or enhance suppression of nematodes may not be effective in all field sites because they are dependent on indigenous antagonists. Ultimately, indicators will need to be identified, such as the presence of particular antagonists, which can guide decisions on where it is practical to use conservation biological control. Antagonists can also be applied to field sites in conjunction with conservation practices to improve the consistency, efficacy, and

  18. Conserving and enhancing biological control of nematodes.

    PubMed

    Timper, Patricia

    2014-06-01

    Conservation biological control is the modification of the environment or existing practices to protect and enhance antagonistic organisms to reduce damage from pests. This approach to biological control has received insufficient attention compared with inundative applications of microbial antagonists to control nematodes. This review provides examples of how production practices can enhance or diminish biological control of plant-parasitic nematodes and other soilborne pests. Antagonists of nematodes can be enhanced by providing supplementary food sources such as occurs when organic amendments are applied to soil. However, some organic amendments (e.g., manures and plants containing allelopathic compounds) can also be detrimental to nematode antagonists. Plant species and genotype can strongly influence the outcome of biological control. For instance, the susceptibility of the plant to the nematode can determine the effectiveness of control; good hosts will require greater levels of suppression than poor hosts. Plant genotype can also influence the degree of rhizosphere colonization and antibiotic production by antagonists, as well the expression of induced resistance by plants. Production practices such as crop rotation, fallow periods, tillage, and pesticide applications can directly disrupt populations of antagonistic organisms. These practices can also indirectly affect antagonists by reducing their primary nematode host. One of the challenges of conservation biological control is that practices intended to protect or enhance suppression of nematodes may not be effective in all field sites because they are dependent on indigenous antagonists. Ultimately, indicators will need to be identified, such as the presence of particular antagonists, which can guide decisions on where it is practical to use conservation biological control. Antagonists can also be applied to field sites in conjunction with conservation practices to improve the consistency, efficacy, and

  19. Recognizing the real threat of biological terror.

    PubMed Central

    Wenzel, Richard P.

    2002-01-01

    Weapons of mass destruction can be used to harm and terrorize populations. Such weapons include those with chemical, nuclear or biological properties. Obviously computer viruses can add additional barriers to a quick response. The most effective, least costly and greatest threats are biologicals. Biological terror is not new, and biological weapons have been used for centuries. However, as a result of modern technology, the risks are greater now and the outcomes more terrible. Today they include live pathogens, various toxins, and theoretically "bioregulators"--biochemicals affecting cell signaling. Altered cell signaling could be used to induce apoptosis-cell death, or a heightened outpouring of cytokines mimicking overwhelming sepsis, or even an intracellular, biochemical "strike" causing cellular paralysis. Biological weaponeers now have the frightening ability to alter the genetic makeup of pathogens, rendering them resistant not only to available antibiotic therapy but also to currently effective vaccines. In dark corners of some fringe groups, bioweaponeers are searching for the capability of designing pathogens that target specific races, by virtue of discriminating ligands (1). The resulting morbidity and mortality from use of any biological weapons will be accompanied by chaos, governmental and social instability, panic, an extraordinary utilization of available resources, and an ongoing epidemic of sleepless nights (2,3). Herein I will review some of the issues and some of the currently available biological weapons. The major goal is to highlight the clinical presentations of patients with infections that could be used as biological weapons. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 PMID:12053717

  20. Bioinformatics and School Biology

    ERIC Educational Resources Information Center

    Dalpech, Roger

    2006-01-01

    The rapidly changing field of bioinformatics is fuelling the need for suitably trained personnel with skills in relevant biological "sub-disciplines" such as proteomics, transcriptomics and metabolomics, etc. But because of the complexity--and sheer weight of data--associated with these new areas of biology, many school teachers feel…

  1. Detecting biological warfare agents.

    PubMed

    Song, Linan; Ahn, Soohyoun; Walt, David R

    2005-10-01

    We developed a fiber-optic, microsphere-based, high-density array composed of 18 species-specific probe microsensors to identify biological warfare agents. We simultaneously identified multiple biological warfare agents in environmental samples by looking at specific probe responses after hybridization and response patterns of the multiplexed array.

  2. Human Biology: Experimental.

    ERIC Educational Resources Information Center

    New York City Board of Education, Brooklyn, NY. Bureau of Curriculum Development.

    Education is a process of adapting to change, and the rate of change is especially rapid in science today. This curriculum in human biology is an alternative to the New York State courses in general and Regents biology, and it has been designed to focus on change from the standpoint of the urban student. It is designed to provide students with…

  3. Biologic Patterns of Disability.

    ERIC Educational Resources Information Center

    Granger, Carl V.; Linn, Richard T.

    2000-01-01

    Describes the use of Rasch analysis to elucidate biological patterns of disability present in the functional ability of persons undergoing medical rehabilitation. Uses two measures, one for inpatients and one for outpatients, to illustrate the approach and provides examples of some biological patterns of disability associated with specific types…

  4. Biology of Skin Color.

    ERIC Educational Resources Information Center

    Corcos, Alain

    1983-01-01

    Information from scientific journals on the biology of skin color is discussed. Major areas addressed include: (1) biology of melanin, melanocytes, and melanosomes; (2) melanosome and human diversity; (3) genetics of skin color; and (4) skin color, geography, and natural selection. (JN)

  5. Biology 100-A.

    ERIC Educational Resources Information Center

    Pensacola Junior Coll., FL.

    This publication is the course guide book for a one-semester, non-laboratory junior college course in biology. Included for each topic are lesson objectives, learning materials, and discussion ideas for seminar groups. Topics include the organization of life, heredity, reproduction, the meaning of biology to modern man, and homeostasis and…

  6. Biology and Health Education.

    ERIC Educational Resources Information Center

    Turner, Sheila; Oberg, Kristina; Unnerstad, Gunilla

    1999-01-01

    Researchers studied English and Swedish biology student teachers' perceptions of teaching health as part of biology. As part of the study, the students investigated secondary students' understanding of health. Surveys and interviews were effective in collecting student teachers' views. They indicated that student teachers' perceptions changed over…

  7. Homosexuality, biology, and ideology.

    PubMed

    Haumann, G

    1995-01-01

    This paper critically examines the complex relationships and interdependencies between biological theories on homosexuality and sociosexual ideologies. It challenges the privileged status of biology as the ultimate authority on homosexuality. This status is based on the belief that biology is a value-free science. On the contrary, this essay shows how unacknowledged assumptions and culturally bound patterns of thinking about sexuality taint biological research. Sociosexual ideologies are defined as principles that organize the ways we express our sexualities and the way we theorize about them in biology. The following ideologies are identified: (1) sexuality-as-heterosexuality, (2) sexuality-as-reproduction, (3) sexual dualism (male vs. female), and (4) the view the homosexuality is a sexual inversion. The process by which these ideologies are incorporated into biology is two-fold: (1) as a projective act from society onto nature and (2) as a reflective act from nature back into society. It is further argued that biological knowledge of homosexuality resulting from that process can be used for diverse political interests. Finally, it is proposed that since biological theories on homosexuality are inseparable from the context of their paradigmatic origin, it is possible that new theories could be derived from new ideologies.

  8. Sourcebook for Biological Sciences.

    ERIC Educational Resources Information Center

    Troyer, Donald L.; And Others

    This is a reference book of curriculum and multimedia materials, equipment and supplies, professional references, and auxiliary resource material. This sourcebook attempts to meet the needs of the classroom biology teacher and is a direct response to the many questions and concerns of both biology teachers and those preparing to become teachers.…

  9. Biological Clocks & Circadian Rhythms

    ERIC Educational Resources Information Center

    Robertson, Laura; Jones, M. Gail

    2009-01-01

    The study of biological clocks and circadian rhythms is an excellent way to address the inquiry strand in the National Science Education Standards (NSES) (NRC 1996). Students can study these everyday phenomena by designing experiments, gathering and analyzing data, and generating new experiments. As students explore biological clocks and circadian…

  10. Experimenting with Mathematical Biology

    ERIC Educational Resources Information Center

    Sanft, Rebecca; Walter, Anne

    2016-01-01

    St. Olaf College recently added a Mathematical Biology concentration to its curriculum. The core course, Mathematics of Biology, was redesigned to include a wet laboratory. The lab classes required students to collect data and implement the essential modeling techniques of formulation, implementation, validation, and analysis. The four labs…

  11. Experimenting with Mathematical Biology

    ERIC Educational Resources Information Center

    Sanft, Rebecca; Walter, Anne

    2016-01-01

    St. Olaf College recently added a Mathematical Biology concentration to its curriculum. The core course, Mathematics of Biology, was redesigned to include a wet laboratory. The lab classes required students to collect data and implement the essential modeling techniques of formulation, implementation, validation, and analysis. The four labs…

  12. Biological Macromolecule Crystallization Database

    National Institute of Standards and Technology Data Gateway

    SRD 21 Biological Macromolecule Crystallization Database (Web, free access)   The Biological Macromolecule Crystallization Database and NASA Archive for Protein Crystal Growth Data (BMCD) contains the conditions reported for the crystallization of proteins and nucleic acids used in X-ray structure determinations and archives the results of microgravity macromolecule crystallization studies.

  13. Biology Bulletins "Revisited"

    ERIC Educational Resources Information Center

    Audet, Richard H.

    2006-01-01

    In October 1981, an article appeared in "The American Biology Teacher" with the catchy title, "Bio-Bull." In it, author, Dale Carlson, described a powerful form of communication that he employed successfully in his community college classes. Each week students received what he called a "Bio-Bull" that included current biological topics,…

  14. Detecting Biological Warfare Agents

    PubMed Central

    Song, Linan; Ahn, Soohyoun

    2005-01-01

    We developed a fiber-optic, microsphere-based, high-density array composed of 18 species-specific probe microsensors to identify biological warfare agents. We simultaneously identified multiple biological warfare agents in environmental samples by looking at specific probe responses after hybridization and response patterns of the multiplexed array. PMID:16318712

  15. Human Biology: Experimental.

    ERIC Educational Resources Information Center

    New York City Board of Education, Brooklyn, NY. Bureau of Curriculum Development.

    Education is a process of adapting to change, and the rate of change is especially rapid in science today. This curriculum in human biology is an alternative to the New York State courses in general and Regents biology, and it has been designed to focus on change from the standpoint of the urban student. It is designed to provide students with…

  16. Biology of Skin Color.

    ERIC Educational Resources Information Center

    Corcos, Alain

    1983-01-01

    Information from scientific journals on the biology of skin color is discussed. Major areas addressed include: (1) biology of melanin, melanocytes, and melanosomes; (2) melanosome and human diversity; (3) genetics of skin color; and (4) skin color, geography, and natural selection. (JN)

  17. Biological Clocks & Circadian Rhythms

    ERIC Educational Resources Information Center

    Robertson, Laura; Jones, M. Gail

    2009-01-01

    The study of biological clocks and circadian rhythms is an excellent way to address the inquiry strand in the National Science Education Standards (NSES) (NRC 1996). Students can study these everyday phenomena by designing experiments, gathering and analyzing data, and generating new experiments. As students explore biological clocks and circadian…

  18. Integrated Biological Control

    SciTech Connect

    JOHNSON, A.R.

    2002-09-01

    Biological control is any activity taken to prevent, limit, clean up, or remediate potential environmental, health and safety, or workplace quality impacts from plants, animals, or microorganisms. At Hanford the principal emphasis of biological control is to prevent the transport of radioactive contamination by biological vectors (plants, animals, or microorganisms), and where necessary, control and clean up resulting contamination. Other aspects of biological control at Hanford include industrial weed control (e.g.; tumbleweeds), noxious weed control (invasive, non-native plant species), and pest control (undesirable animals such as rodents and stinging insects; and microorganisms such as molds that adversely affect the quality of the workplace environment). Biological control activities may be either preventive (apriori) or in response to existing contamination spread (aposteriori). Surveillance activities, including ground, vegetation, flying insect, and other surveys, and apriori control actions, such as herbicide spraying and placing biological barriers, are important in preventing radioactive contamination spread. If surveillance discovers that biological vectors have spread radioactive contamination, aposteriori control measures, such as fixing contamination, followed by cleanup and removal of the contamination to an approved disposal location are typical response functions. In some cases remediation following the contamination cleanup and removal is necessary. Biological control activities for industrial weeds, noxious weeds and pests have similar modes of prevention and response.

  19. Integrated Biological Control

    SciTech Connect

    JOHNSON, A.R.

    2003-10-09

    Biological control is any activity taken to prevent, limit, clean up, or remediate potential environmental, health and safety, or workplace quality impacts from plants, animals, or microorganisms. At Hanford the principal emphasis of biological control is to prevent the transport of radioactive contamination by biological vectors (plants, animals, or microorganisms), and where necessary, control and clean up resulting contamination. Other aspects of biological control at Hanford include industrial weed control (e.g.; tumbleweeds), noxious weed control (invasive, non-native plant species), and pest control (undesirable animals such as rodents and stinging insects, and microorganisms such as molds that adversely affect the quality of the workplace environment). Biological control activities may be either preventive (a priori) or in response to existing contamination spread (a posteriori). Surveillance activities, including ground, vegetation, flying insect, and other surveys, and a priori control actions, such as herbicide spraying and placing biological barriers, are important in preventing radioactive contamination spread. If surveillance discovers that biological vectors have spread radioactive contamination, a posteriori control measures, such as fixing contamination, followed by cleanup and removal of the contamination to an approved disposal location are typical response functions. In some cases remediation following the contamination cleanup and removal is necessary. Biological control activities for industrial weeds, noxious weeds and pests have similar modes of prevention and response.

  20. Biology Bulletins "Revisited"

    ERIC Educational Resources Information Center

    Audet, Richard H.

    2006-01-01

    In October 1981, an article appeared in "The American Biology Teacher" with the catchy title, "Bio-Bull." In it, author, Dale Carlson, described a powerful form of communication that he employed successfully in his community college classes. Each week students received what he called a "Bio-Bull" that included current biological topics,…

  1. Biological monitors of pollution

    SciTech Connect

    Root, M.

    1990-02-01

    This article discusses the use of biological monitors to assess the biological consequences of toxicants in the environment, such as bioavailability, synergism, and bioaccumulation through the food web. Among the organisms discussed are fly larvae, worms, bees, shellfish, fishes, birds (starlings, owls, hawks, songbirds) and mammals (rabbits, field mice, shrews).

  2. Towards a Liberal Biology

    ERIC Educational Resources Information Center

    Davies, P. M. C.

    1970-01-01

    Discusses the purpose of a university biology department and the organization of its curriculum in terms of perceived crises in British biology. Concludes that reform becomes a project of crucial importance, not only to the social and technological development of civilized societies, but to the survival of the human species. (Author/AL)

  3. Microarray analysis of gene regulations and potential association with acephate-resistance and fitness cost in Lygus lineola

    USDA-ARS?s Scientific Manuscript database

    The tarnished plant bug has become increasingly resistant to organophosphates in recent years. To better understand acephate resistance mechanisms, biological, biochemical, and molecular experiments were systematically conducted with susceptible (LLS) and acephate-selected (LLR) strains. Selection o...

  4. Biological effects of minerals

    SciTech Connect

    Guthrie, G.D. Jr.

    1991-09-01

    In general, clay materials exhibit a range of biological activities, from apparently inactive or slightly active, such as hematite, to highly fibrogenic and carcinogenic, such as fibrous brucite (nemalite). The zeolites also exhibit such as range, with some mordenite being slightly active and erionite being highly active; however, erionite is the only zeolite that has been studied extensively. The diversity of mineral species holds great potential for probing these mechanisms, especially when mineralogical data are integrated with biological data. Unfortunately, many of the studies reporting data on the biological effects of clays and zeolites fail to report detailed mineralogical information; hence, it is difficult at present to interpret the biological activities of minerals in terms of their physical and chemical properties. Important mineralogical data that are only rarely considered in biological research include exact mineralogy of the specimen (i.e., identification and abundance of contaminants), physical and chemical properties of minerals, and surface properties of minerals. 141 refs., 1 fig., 8 tabs.

  5. Biological sample collector

    DOEpatents

    Murphy, Gloria A [French Camp, CA

    2010-09-07

    A biological sample collector is adapted to a collect several biological samples in a plurality of filter wells. A biological sample collector may comprise a manifold plate for mounting a filter plate thereon, the filter plate having a plurality of filter wells therein; a hollow slider for engaging and positioning a tube that slides therethrough; and a slide case within which the hollow slider travels to allow the tube to be aligned with a selected filter well of the plurality of filter wells, wherein when the tube is aligned with the selected filter well, the tube is pushed through the hollow slider and into the selected filter well to sealingly engage the selected filter well and to allow the tube to deposit a biological sample onto a filter in the bottom of the selected filter well. The biological sample collector may be portable.

  6. Space biology research development

    NASA Technical Reports Server (NTRS)

    Bonting, Sjoerd L.

    1993-01-01

    The purpose of the Search for Extraterrestrial Intelligence (SETI) Institute is to conduct and promote research related activities regarding the search for extraterrestrial life, particularly intelligent life. Such research encompasses the broad discipline of 'Life in the Universe', including all scientific and technological aspects of astronomy and the planetary sciences, chemical evolution, the origin of life, biological evolution, and cultural evolution. The primary purpose was to provide funding for the Principal Investigator to collaborate with the personnel of the SETI Institute and the NASA-Ames Research center in order to plan and develop space biology research on and in connection with Space Station Freedom; to promote cooperation with the international partners in the space station; to conduct a study on the use of biosensors in space biology research and life support system operation; and to promote space biology research through the initiation of an annual publication 'Advances in Space Biology and Medicine'.

  7. Assessment of benzimidazole resistance in Haemonchus contortus in sheep flocks in Ontario, Canada: comparison of detection methods for drug resistance.

    PubMed

    Barrere, V; Falzon, L C; Shakya, K P; Menzies, P I; Peregrine, A S; Prichard, R K

    2013-11-15

    In 2011, a field study was conducted to assess drug resistance of gastro-intestinal nematodes in sheep flocks in Ontario, Canada. Benzimidazole resistance in Haemonchus contortus was assessed by genetic analysis of eggs; measurement of resistant allele percentages at codons 167, 198 and 200 in the β-tubulin gene was determined on pools of H. contortus eggs using pyrosequencing. Susceptibility to benzimidazoles in gastro-intestinal nematodes was also determined using a Faecal Egg Count Reduction Test (FECRT) and a Larval Development Assay (LDA). In total, 16 farms were assessed with the genetic test. Based on resistant allele frequencies, all of the farms (16/16) tested had benzimidazole resistance in H. contortus; the overall percentage of benzimidazole-resistant H. contortus (estimated prior to treatment using the Hardy-Weinberg formula) was 68.5%. The FECRT and LDA were performed on 11 and 13 farms, respectively. Resistance to fenbendazole was detected on 100% (11/11) of the farms where the FECRT was performed. The LDA revealed the presence of thiabendazole resistance in H. contortus in 92% (12/13) of the farms. Estimated percentages of resistant parasites in H. contortus populations obtained with the two biological tests and the genetic test were compared. The results of the genetic test were in agreement with the biological tests and confirmed that benzimidazole resistance in H. contortus is present in Ontario sheep flocks. Differences between the different methods of drug resistance detection are discussed in terms of cost, time and sampling.

  8. Biological Resource Centers and Systems Biology.

    PubMed

    Wang, Yufeng; Lilburn, Timothy G

    2009-02-11

    There are hundreds of Biological Resource Centers (BRCs) around the world, holding many little-studied microorganism. The proportion of bacterial strains that is well represented in the sequence and literature databases may be as low as 1%. This body of unexplored diversity represents an untapped source of useful strains and derived products. However, a modicum of phenotypic data is available for almost all the bacterial strains held by BRCs around the world. It is at the phenotypic level that our knowledge of the well-studied strains of bacteria and the many yet-to-be studied strains intersects. This suggests we might leverage the phenotypic data from the data-poor bacteria with the omics data from the data-rich bacteria, using our knowledge of their evolutionary relationships, to map the metabolic networks of the little-known bacteria. This systems biology-based approach is a new way to explore the diversity harbored in BRCs.

  9. Defense Horizons. Number 25, March 2003. Biology and the Battlefield

    DTIC Science & Technology

    2003-03-01

    biological warfare efforts. Defec- tors from the former Soviet Union told of genetically engineered “ superbugs ” that included antibiotic-resistant anthrax...cells contain the same complement of genes, cells are specialized and do not all manufacture the same proteins. Thus, the study of the full complement...the current genomic and proteomic approaches: Classical approaches to the study of biology have involved biochemistry (the study of proteins in

  10. Mammalian Synthetic Biology: Engineering Biological Systems.

    PubMed

    Black, Joshua B; Perez-Pinera, Pablo; Gersbach, Charles A

    2017-06-21

    The programming of new functions into mammalian cells has tremendous application in research and medicine. Continued improvements in the capacity to sequence and synthesize DNA have rapidly increased our understanding of mechanisms of gene function and regulation on a genome-wide scale and have expanded the set of genetic components available for programming cell biology. The invention of new research tools, including targetable DNA-binding systems such as CRISPR/Cas9 and sensor-actuator devices that can recognize and respond to diverse chemical, mechanical, and optical inputs, has enabled precise control of complex cellular behaviors at unprecedented spatial and temporal resolution. These tools have been critical for the expansion of synthetic biology techniques from prokaryotic and lower eukaryotic hosts to mammalian systems. Recent progress in the development of genome and epigenome editing tools and in the engineering of designer cells with programmable genetic circuits is expanding approaches to prevent, diagnose, and treat disease and to establish personalized theranostic strategies for next-generation medicines. This review summarizes the development of these enabling technologies and their application to transforming mammalian synthetic biology into a distinct field in research and medicine.

  11. Antibiotic resistance in Chlamydiae.

    PubMed

    Sandoz, Kelsi M; Rockey, Daniel D

    2010-09-01

    There are few documented reports of antibiotic resistance in Chlamydia and no examples of natural and stable antibiotic resistance in strains collected from humans. While there are several reports of clinical isolates exhibiting resistance to antibiotics, these strains either lost their resistance phenotype in vitro, or lost viability altogether. Differences in procedures for chlamydial culture in the laboratory, low recovery rates of clinical isolates and the unknown significance of heterotypic resistance observed in culture may interfere with the recognition and interpretation of antibiotic resistance. Although antibiotic resistance has not emerged in chlamydiae pathogenic to humans, several lines of evidence suggest they are capable of expressing significant resistant phenotypes. The adept ability of chlamydiae to evolve to antibiotic resistance in vitro is demonstrated by contemporary examples of mutagenesis, recombination and genetic transformation. The isolation of tetracycline-resistant Chlamydia suis strains from pigs also emphasizes their adaptive ability to acquire antibiotic resistance genes when exposed to significant selective pressure.

  12. Managing biological diversity

    USGS Publications Warehouse

    Samson, Fred B.; Knopf, Fritz L.

    1993-01-01

    Biological diversity is the variety of life and accompanying ecological processes (Off. Technol. Assess. 1987, Wilcove and Samson 1987, Keystone 1991). Conservation of biological diversity is a major environmental issue (Wilson 1988, Counc. Environ. Quality 1991). The health and future of the earth's ecological systems (Lubchenco et al. 1991), global climate change (Botkin 1990), and an ever-increasing rate in loss of species, communities, and ecological systems (Myers 1990) are among issues drawing biological diversity to the mainstream of conservation worldwide (Int. Union Conserv. Nat. and Nat. Resour. [IUCN] et al. 1991). The legal mandate for conserving biological diversity is now in place (Carlson 1988, Doremus 1991). More than 19 federal laws govern the use of biological resources in the United States (Rein 1991). The proposed National Biological Diversity Conservation and Environmental Research Act (H.R. 585 and S.58) notes the need for a national biological diversity policy, would create a national center for biological diversity research, and recommends a federal interagency strategy for ecosystem conservation. There are, however, hard choices ahead for the conservation of biological diversity, and biologists are grappling with how to set priorities in research and management (Roberts 1988). We sense disillusion among field biologists and managers relative to how to operationally approach the seemingly overwhelming charge of conserving biological diversity. Biologists also need to respond to critics like Hunt (1991) who suggest a tree farm has more biological diversity than an equal area of old-growth forest. At present, science has played only a minor role in the conservation of biological diversity (Weston 1992) with no unified approach available to evaluate strategies and programs that address the quality and quantity of biological diversity (Murphy 1990, Erwin 1992). Although actions to conserve biological diversity need to be clearly defined by

  13. Mechanics of Biological Nanotechnology

    NASA Astrophysics Data System (ADS)

    Phillips, Rob; Purohit, Prashant K.; Kondev, Jané

    One of the most compelling areas to be touched by nanotechnology is biological science. Indeed, we will argue that there is a fascinating interplay between these two subjects, with biology as a key beneficiary of advances in nanotechnology as a result of a new generation of single molecule experiments that complement traditional assays involving statistical assemblages of molecules. This interplay runs in both directions, with nanotechnology continually receiving inspiration from biology itself. The goal of this chapter is to highlight some representative examples of the exchange between biology and nanotechnology and to illustrate the role of nanomechanics in this field and how mechanical models have arisen in response to the emergence of this new field. Primary attention will be given to the particular example of the processes that attend the life cycle of bacterial viruses. Viruses feature many of the key lessons of biological nanotechnology, including self assembly, as evidenced in the spontaneous formation of the protein shell (capsid) within which the viral genome is packaged, and a motor-mediated biological process, namely, the packaging of DNA in this capsid by a molecular motor that pushes the DNA into the capsid. We argue that these processes in viruses are a compelling real-world example of nature's nanotechnology and reveal the nanomechanical challenges that will continue to be confronted at the nanotechnology-biology interface.

  14. Mechanics of Biological Nanotechnology

    NASA Astrophysics Data System (ADS)

    Phillips, Rob; Purohit, Prashant; Kondev, Jané

    One of the most compelling areas to be touched by nanotechnology is biological science. Indeed, we will argue that there is a fascinating interplay between these two subjects, with biology as a key beneficiary of advances in nanotechnology as a result of a new generation of single-molecule experiments that complement traditional assays involving statistical assemblages of molecules. This interplay runs in both directions, with nanotechnology continually receiving inspiration from biology itself. The goal of this chapter is to highlight some representative examples of the exchange between biology and nanotechnology and to illustrate the role of nanomechanics in this field and how mechanical models have arisen in response to the emergence of this new field. Primary attention will be given to the particular example of the processes that attend the life cycle of bacterial viruses. Viruses feature many of the key lessons of biological nanotechnology, including self assembly, as evidenced in the spontaneous formation of the protein shell (capsid) within which the viral genome is packaged, and a motor-mediated biological process, namely the packaging of DNA in this capsid by a molecular motor that pushes the DNA into the capsid. We argue that these processes in viruses are a compelling real-world example of nature's nanotechnology, and they reveal the nanomechanical challenges that will continue to be confronted at the nanotechnology-biology interface.

  15. Biological and Chemical Security

    SciTech Connect

    Fitch, P J

    2002-12-19

    The LLNL Chemical & Biological National Security Program (CBNP) provides science, technology and integrated systems for chemical and biological security. Our approach is to develop and field advanced strategies that dramatically improve the nation's capabilities to prevent, prepare for, detect, and respond to terrorist use of chemical or biological weapons. Recent events show the importance of civilian defense against terrorism. The 1995 nerve gas attack in Tokyo's subway served to catalyze and focus the early LLNL program on civilian counter terrorism. In the same year, LLNL began CBNP using Laboratory-Directed R&D investments and a focus on biodetection. The Nunn-Lugar-Domenici Defense Against Weapons of Mass Destruction Act, passed in 1996, initiated a number of U.S. nonproliferation and counter-terrorism programs including the DOE (now NNSA) Chemical and Biological Nonproliferation Program (also known as CBNP). In 2002, the Department of Homeland Security was formed. The NNSA CBNP and many of the LLNL CBNP activities are being transferred as the new Department becomes operational. LLNL has a long history in national security including nonproliferation of weapons of mass destruction. In biology, LLNL had a key role in starting and implementing the Human Genome Project and, more recently, the Microbial Genome Program. LLNL has over 1,000 scientists and engineers with relevant expertise in biology, chemistry, decontamination, instrumentation, microtechnologies, atmospheric modeling, and field experimentation. Over 150 LLNL scientists and engineers work full time on chemical and biological national security projects.

  16. Systems biology and addiction.

    PubMed

    Tretter, F; Gebicke-Haerter, P J; Albus, M; an der Heiden, U; Schwegler, H

    2009-05-01

    The onset of addiction is marked with drug induced positive experiences that keep being repeated. During that time, adaptation occurs and addiction is stabilized. Interruption of those processes induces polysymptomatic withdrawal syndromes. Abstinence is accompanied by risks of relapse. These features of addiction suggest adaptive brain dynamics with common pathways in complex neuronal networks. Addiction research has used animal models, where some of those phenomena could be reproduced, to find correlates of addictive behavior. The major thrust of those approaches has been on the involvement of genes and proteins. Recently, an enormous amount of data has been obtained by high throughput technologies in these fields. Therefore, (Computational) "Systems Biology" had to be implemented as a new approach in molecular biology and biochemistry. Conceptually, Systems Biology can be understood as a field of theoretical biology that tries to identify patterns in complex data sets and that reconstructs the cell and cellular networks as complex dynamic, self-organizing systems. This approach is embedded in systems science as an interdisciplinary effort to understand complex dynamical systems and belongs to the field of theoretical neuroscience (Computational Neuroscience). Systems biology, in a similar way as computational neuroscience is based on applied mathematics, computer-based computation and experimental simulation. In terms of addiction research, building up "computational molecular systems biology of the (addicted) neuron" could provide a better molecular biological understanding of addiction on the cellular and network level. Some key issues are addressed in this article.

  17. Noise in biological circuits

    SciTech Connect

    Simpson, Michael L.; Allen, Michael S.; Cox, Chris D.; Dar, Roy D.; Karig, David K.; McCollum, James M.; Cooke, John F.

    2009-01-13

    Noise biology focuses on the sources, processing, and biological consequences of the inherent stochastic fluctuations in molecular transitions or interactions that control cellular behavior. These fluctuations are especially pronounced in small systems where the magnitudes of the fluctuations approach or exceed the mean value of the molecular population. Noise biology is an essential component of nanomedicine where the communication of information is across a boundary that separates small synthetic and biological systems that are bound by their size to reside in environments of large fluctuations. Here we review the fundamentals of the computational, analytical, and experimental approaches to noise biology. We review results that show that the competition between the benefits of low noise and those of low population has resulted in the evolution of genetic system architectures that produce an uneven distribution of stochasticity across the molecular components of cells and, in some cases, use noise to drive biological function. We review the exact and approximate approaches to gene circuit noise analysis and simulation, and reviewmany of the key experimental results obtained using flow cytometry and time-lapse fluorescent microscopy. In addition, we consider the probative value of noise with a discussion of using measured noise properties to elucidate the structure and function of the underlying gene circuit. Lastly, we conclude with a discussion of the frontiers of and significant future challenges for noise biology.

  18. Synthetic biology era: Improving antibiotic's world.

    PubMed

    Guzmán-Trampe, Silvia; Ceapa, Corina D; Manzo-Ruiz, Monserrat; Sánchez, Sergio

    2017-01-31

    The emergence of antibiotic-resistant pathogen microorganisms is problematic in the context of the current spectrum of available medication. The poor specificity and the high toxicity of some available molecules have made imperative the search for new strategies to improve the specificity and to pursue the discovery of novel compounds with increased bioactivity. Using living cells as platforms, synthetic biology has counteracted this problem by offering novel pathways to create synthetic systems with improved and desired functions. Among many other biotechnological approaches, the advances in synthetic biology have made it possible to design and construct novel biological systems in order to look for new drugs with increased bioactivity. Advancements have also been made in the redesigning of RNA and DNA molecules in order to engineer antibiotic clusters for antibiotic overexpression. As for the production of these antibacterial compounds, yeasts and filamentous fungi as well as gene therapy are utilized to enhance protein solubility. Specific delivery is achieved by creating chimeras using plant genes into bacterial hosts. Some of these synthetic systems are currently in clinical trials, proving the proficiency of synthetic biology in terms of both pharmacological activities as well as an increase in the biosafety of treatments. It is possible that we may just be seeing the tip of the iceberg, and synthetic biology applications will overpass expectations beyond our present knowledge.

  19. [Viruses as biological weapons].

    PubMed

    Akçali, Alper

    2005-07-01

    The destruction made by nuclear, biological and chemical weapons used by governments and terrorist groups in the near history is posing anxiety and fear for human being. Rumour about the possible use of these agents leads to the development of serious negative effects on populations. Since there are no vaccine and therapy for most viral agents and cost of production as biological weapons is low, interest rate is rising for viruses. In this review, general characteristics, diagnosis, therapy and protective measures for viral agents such as variola virus, hemorrhagic fever viruses, encephalitis viruses, Hantaviruses and Nipah viruses, those can be used as biological weapon, have been summarized.

  20. Evolutionary Design in Biology

    NASA Astrophysics Data System (ADS)

    Wiese, Kay C.

    Much progress has been achieved in recent years in molecular biology and genetics. The sheer volume of data in the form of biological sequences has been enormous and efficient methods for dealing with these huge amounts of data are needed. In addition, the data alone does not provide information on the workings of biological systems; hence much research effort has focused on designing mathematical and computational models to address problems from molecular biology. Often, the terms bioinformatics and computational biology are used to refer to the research fields concerning themselves with designing solutions to molecular problems in biology. However, there is a slight distinction between bioinformatics and computational biology: the former is concerned with managing the enormous amounts of biological data and extracting information from it, while the latter is more concerned with the design and development of new algorithms to address problems such as protein or RNA folding. However, the boundary is blurry, and there is no consistent usage of the terms. We will use the term bioinformatics to encompass both fields. To cover all areas of research in bioinformatics is beyond the scope of this section and we refer the interested reader to [2] for a general introduction. A large part of what bioinformatics is concerned about is evolution and function of biological systems on a molecular level. Evolutionary computation and evolutionary design are concerned with developing computational systems that "mimic" certain aspects of natural evolution (mutation, crossover, selection, fitness). Much of the inner workings of natural evolutionary systems have been copied, sometimes in modified format into evolutionary computation systems. Artificial neural networks mimic the functioning of simple brain cell clusters. Fuzzy systems are concerned with the "fuzzyness" in decision making, similar to a human expert. These three computational paradigms fall into the category of

  1. Metabolomics and malaria biology

    PubMed Central

    Lakshmanan, Viswanathan; Rhee, Kyu Y.; Daily, Johanna P.

    2010-01-01

    Metabolomics has ushered in a novel and multi-disciplinary realm in biological research. It has provided researchers with a platform to combine powerful biochemical, statistical, computational, and bioinformatics techniques to delve into the mysteries of biology and disease. The application of metabolomics to study malaria parasites represents a major advance in our approach towards gaining a more comprehensive perspective on parasite biology and disease etiology. This review attempts to highlight some of the important aspects of the field of metabolomics, and its ongoing and potential future applications to malaria research. PMID:20970461

  2. A Hypothesis on Biological Protection from Space Radiation Through the Use of Therapeutic Gases

    NASA Technical Reports Server (NTRS)

    Schoenfeld, Michael

    2011-01-01

    This slide presentation proposes a hypothesis to use therapeutic gases in space to enhance the biological protection for astronauts from space radiation. The fundamental role in how radiation causes biological damage appears to be radiolysis, the dissociation of water by radiation. A chain of events appears to cause molecular and biological transformations that ultimately manifest into medical diseases. The hypothesis of this work is that applying medical gases may increase resistance to radiation, by possessing the chemical properties that effectively improve the radical scavenging and enhance bond repair and to induce biological processes which enhance and support natural resistance and repair mechanisms.

  3. Cisplatin resistance and opportunities for precision medicine.

    PubMed

    Amable, Lauren

    2016-04-01

    Cisplatin is one of the most commonly used chemotherapy drugs, treating a wide range of cancer types. Unfortunately, many cancers initially respond to platinum treatment but when the tumor returns, drug resistance frequently occurs. Resistance to cisplatin is attributed to three molecular mechanisms: increased DNA repair, altered cellular accumulation, and increased drug inactivation. The use of precision medicine to make informed decisions on a patient's cisplatin resistance status and predicting the tumor response would allow the clinician to tailor the chemotherapy program based on the biology of the disease. In this review, key biomarkers of each molecular mechanism will be discussed along with the current clinical research. Additionally, known polymorphisms for each biomarker will be discussed in relation to their influence on cisplatin resistance.

  4. Noncoding RNA in drug resistant sarcoma

    PubMed Central

    Li, Xiaoyang; Shen, Jacson K.; Hornicek, Francis J.; Xiao, Tao; Duan, Zhenfeng

    2017-01-01

    Sarcomas are a group of malignant tumors that arise from mesenchymal origin. Despite significant development of multidisciplinary treatments for sarcoma, survival rates have reached a plateau. Chemotherapy has been extensively used for sarcoma treatment; however, the development of drug resistance is a major obstacle limiting the success of many anticancer agents. Sarcoma biology has traditionally focused on genomic and epigenomic deregulation of protein-coding genes to identify the therapeutic potential for reversing drug resistance. New and more creative approaches have found the involvement of noncoding RNAs, including microRNAs and long noncoding RNAs in drug resistant sarcoma. In this review, we discuss the current knowledge of noncoding RNAs characteristics and the regulated genes involved in drug resistant sarcoma, and focus on their therapeutic potential in the future.

  5. Supervisee Resistance. ERIC Digest.

    ERIC Educational Resources Information Center

    Bradley, Loretta J.; Gould, L. J.

    This digest focuses on issues of supervisee resistance, defined as defensive behaviors of the supervisee that serve to reduce supervision-induced anxiety. It describes resistant behavior and identifies ways to counteract it, while noting that supervisee resistance is common. The purposes and goals of supervisee resistance, as manifested in verbal…

  6. How Cancer Cells Become Resistant to Cationic Lytic Peptides: It's the Sugar!

    PubMed

    Pierce, Joshua G

    2017-02-16

    In this issue of Cell Chemical Biology, Ishikawa et al. (2017) demonstrate that the loss of cell-surface anionic saccharides can impart resistance toward anticancer peptides. This study provides the first insight into potential resistance mechanisms toward cationic lytic peptides and highlights the important, yet previously unappreciated, role cell-surface glycans can play in cellular resistance mechanisms.

  7. Thermodynamics of Biological Processes

    PubMed Central

    Garcia, Hernan G.; Kondev, Jane; Orme, Nigel; Theriot, Julie A.; Phillips, Rob

    2012-01-01

    There is a long and rich tradition of using ideas from both equilibrium thermodynamics and its microscopic partner theory of equilibrium statistical mechanics. In this chapter, we provide some background on the origins of the seemingly unreasonable effectiveness of ideas from both thermodynamics and statistical mechanics in biology. After making a description of these foundational issues, we turn to a series of case studies primarily focused on binding that are intended to illustrate the broad biological reach of equilibrium thinking in biology. These case studies include ligand-gated ion channels, thermodynamic models of transcription, and recent applications to the problem of bacterial chemotaxis. As part of the description of these case studies, we explore a number of different uses of the famed Monod–Wyman–Changeux (MWC) model as a generic tool for providing a mathematical characterization of two-state systems. These case studies should provide a template for tailoring equilibrium ideas to other problems of biological interest. PMID:21333788

  8. Biological satellite Kosmos-936

    NASA Technical Reports Server (NTRS)

    Vedeshin, L. A.

    1978-01-01

    A description is given of physiological experiments performed on the biological satellite Kosmos-936. Other experiments to determine the electrostatic and dielectric responses to the effects of cosmic radiation are discussed.

  9. Precision Measurement in Biology

    NASA Astrophysics Data System (ADS)

    Quake, Stephen

    Is biology a quantitative science like physics? I will discuss the role of precision measurement in both physics and biology, and argue that in fact both fields can be tied together by the use and consequences of precision measurement. The elementary quanta of biology are twofold: the macromolecule and the cell. Cells are the fundamental unit of life, and macromolecules are the fundamental elements of the cell. I will describe how precision measurements have been used to explore the basic properties of these quanta, and more generally how the quest for higher precision almost inevitably leads to the development of new technologies, which in turn catalyze further scientific discovery. In the 21st century, there are no remaining experimental barriers to biology becoming a truly quantitative and mathematical science.

  10. A Challenge to Biology

    ERIC Educational Resources Information Center

    Trumbull, Richard

    1975-01-01

    Cautions biology instructors to be aware of the possible overproduction of life science scholars whose future may include unemployment or underemployment. Urges that these instructors provide their students with knowledge for employment outside the traditional educational and research fields. (MLH)

  11. ERLN Biological Focus Area

    EPA Pesticide Factsheets

    The Environmental Response Laboratory Network supports the goal to increase national capacity for biological analysis of environmental samples. This includes methods development and verification, technology transfer, and collaboration with USDA, FERN, CDC.

  12. Biologic Medications for Psoriasis

    MedlinePlus

    ... six of the biologics we evaluated have a warning on their drug label that they might increase ... long-term safety in 23 458 patients from global clinical trials in rheumatoid arthritis, juvenile idiopathic arthritis, ...

  13. Progress in space biology.

    PubMed

    Imshenetskii, A A

    1979-01-01

    Over the past two decades there has arisen a new branch of biology--space biology. This short review is devoted to a discussion of its achievements. It considers the results of research in the area of gravitation biology, and an account is made of studies in those areas of radiobiology which have relevance to the study of the cosmos. There is a brief summary of the results of the search for the upper and lower limits of the biosphere, and information is presented regarding the measures employed to maintain planetary quarantine. A great deal of attention has been given to the search for extraterrestrial life, one of the most important of problems. The results obtained with the aid of the American Viking probes on Mars are given special attention. The review presents experimental data based both upon data obtained in experiments on biological specimens during space flights of satellites and space vehicles, and also upon the results of laboratory research.

  14. EDITORIAL: Physical Biology

    NASA Astrophysics Data System (ADS)

    Roscoe, Jane

    2004-06-01

    Physical Biology is a new peer-reviewed publication from Institute of Physics Publishing. Launched in 2004, the journal will foster the integration of biology with the traditionally more quantitative fields of physics, chemistry, computer science and other math-based disciplines. Its primary aim is to further the understanding of biological systems at all levels of complexity, ranging from the role of structure and dynamics of a single molecule to cellular networks and organisms. The journal encourages the development of a new biology-driven physics based on the extraordinary and increasingly rich data arising in biology, and provides research directions for those involved in the creation of novel bio-engineered systems. Physical Biology will publish a stimulating combination of full length research articles, communications, perspectives, reviews and tutorials from a wide range of disciplines covering topics such as: Single-molecule studies and nanobiotechnology Molecular interactions and protein folding Charge transfer and photobiology Ion channels; structure, function and ion regulation Molecular motors and force generation Subcellular processes Biological networks and neural systems Modeling aspects of molecular and cell biology Cell-cell signaling and interaction Biological patterns and development Evolutionary processes Novel tools and methods in physical biology Experts in the areas encompassed by the journal's scope have been appointed to the Editorial Scientific Committee and the composition of the Committee will be updated regularly to reflect the developments in this new and exciting field. Physical Biology is free online to everyone in 2004; you are invited to take advantage of this offer by visiting the journal homepage at http://physbio.iop.org This special print edition of Physical Biology is a combination of issues 1 and 2 of this electronic-only journal and it brings together an impressive range of articles in the fields covered, including a popular

  15. The Biology of Aging.

    ERIC Educational Resources Information Center

    Sprott, Richard L.; And Others

    1992-01-01

    Thirteen articles in this special issue discuss aging theories, biomarkers of aging, aging research, disease, cancer biology, Alzheimer's disease, stress, oxidation of proteins, gene therapy, service delivery, biogerontology, and ethics and aging research. (SK)

  16. The Biology of Behaviour.

    ERIC Educational Resources Information Center

    Broom, D. M.

    1981-01-01

    Discusses topics to aid in understanding animal behavior, including the value of the biological approach to psychology, functional systems, optimality and fitness, universality of environmental effects on behavior, and evolution of social behavior. (DS)

  17. Vaccines and biologics.

    PubMed

    Ferreira, Isabel; Isenberg, David

    2014-08-01

    Patients with autoimmune rheumatic diseases are more susceptible to infectious complications during the course of their disease. The introduction of biologics has been a major achievement in treating these diseases, but an increased risk of infection associated with these therapies has become evident. Some infections can be prevented by vaccination and it is clearly worthwhile considering which immunisations would be sensible and practicable for these patients. To date no formal specific recommendations for patients on biologics have been published. A search was made of Medline (via PubMed) from 1970 to January 2014 to provide results. This review aims to provide a systematic analysis of the data about vaccines and biologics and considers recommendations for vaccination in adult patients with autoimmune rheumatic diseases treated with biologics.

  18. Insecticides and Biological Control

    ERIC Educational Resources Information Center

    Furness, G. O.

    1972-01-01

    Use of insecticides has been questioned due to their harmful effects on edible items. Biological control of insects along with other effective practices for checking spread of parasites on crops are discussed. (PS)

  19. The Biology of Aging.

    ERIC Educational Resources Information Center

    Sprott, Richard L.; And Others

    1992-01-01

    Thirteen articles in this special issue discuss aging theories, biomarkers of aging, aging research, disease, cancer biology, Alzheimer's disease, stress, oxidation of proteins, gene therapy, service delivery, biogerontology, and ethics and aging research. (SK)

  20. Insecticides and Biological Control

    ERIC Educational Resources Information Center

    Furness, G. O.

    1972-01-01

    Use of insecticides has been questioned due to their harmful effects on edible items. Biological control of insects along with other effective practices for checking spread of parasites on crops are discussed. (PS)