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Sample records for additional resistance mechanisms

  1. 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

  2. Effect of Zr addition on the mechanical characteristics and wear resistance of Al grain refined by Ti after extrusion

    NASA Astrophysics Data System (ADS)

    Zaid, Adnan I. O.; Al-Qawabah, S. M. A.

    2016-08-01

    Aluminum and its alloys are normally grain refined by Ti or Ti+B to transfer their columnar structure during solidification into equiaxed one which improves their mechanical behavior and surface quality. In this paper, the effect of addition of Zr on the metallurgical, and mechanical aspects, hardness, ductility and wear resistance of commercially pure aluminum grain refined by Ti after extrusion is investigated. Zr was added at a level of 0.1% which corresponds to the peretectic limit at the Al-Zr phase diagram. The experimental work was carried out on the specimens after direct extrusion. It was found that addition of Ti resulted in decrease of Al grain size, whereas addition of Zr alone or in the presence of Ti, resulted in reduction of Al grain size. This led to increase of Al hardness. The effect of the addition of Ti or Zr alone resulted almost in the same enhancement of Al mechanical characteristics. As for the strain hardening index,n, increase was obtained when Zr was added alone or in the presence of Ti. Hence pronounced improvement of its formability. Regarding the effect of Zr addition on the wear resistance of aluminum; it was found that at small loads and speeds addition of Ti or Zr or both together resulted in deterioration of its wear resistance whereas at higher loads and speeds resulted in pronounced improvement of its wear resistance. Finally, the available Archard model and the other available models which consider only the mass loss failed to describe the wear mechanism of Al and its micro-alloys because they do not consider the mushrooming effect at the worn end.

  3. A novel P106L mutation in EPSPS and an unknown mechanism(s) act additively to confer resistance to glyphosate in a South African Lolium rigidum population.

    PubMed

    Kaundun, Shiv S; Dale, Richard P; Zelaya, Ian A; Dinelli, Giovanni; Marotti, Ilaria; McIndoe, Eddie; Cairns, Andrew

    2011-04-13

    Glyphosate resistance evolution in weeds is a growing problem in world agriculture. Here, we have investigated the mechanism(s) of glyphosate resistance in a Lolium rigidum population (DAG1) from South Africa. Nucleotide sequencing revealed the existence of at least three EPSPS homologues in the L. rigidum genome and identified a novel proline 106 to leucine substitution (P106L) in 52% DAG1 individuals. This mutation conferred a 1.7-fold resistance increase to glyphosate at the whole plant level. Additionally, a 3.1-fold resistance increase, not linked to metabolism or translocation, was estimated between wild-type P106-DAG1 and P106-STDS sensitive plants. Point accepted mutation analysis suggested that other amino acid substitutions at EPSPS position 106 are likely to be found in nature besides the P106/S/A/T/L point mutations reported to date. This study highlights the importance of minor mechanisms acting additively to confer significant levels of resistance to commercial field rates of glyphosate in weed populations subjected to high selection pressure.

  4. 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

  5. Mechanisms of Antibiotic Resistance

    PubMed Central

    Munita, Jose M.; Arias, Cesar A.

    2015-01-01

    Emergence of resistance among the most important bacterial pathogens is recognized as a major public health threat affecting humans worldwide. Multidrug-resistant organisms have emerged not only in the hospital environment but are now often identified in community settings, suggesting that reservoirs of antibiotic-resistant bacteria are present outside the hospital. The bacterial response to the antibiotic “attack” is the prime example of bacterial adaptation and the pinnacle of evolution. “Survival of the fittest” is a consequence of an immense genetic plasticity of bacterial pathogens that trigger specific responses that result in mutational adaptations, acquisition of genetic material or alteration of gene expression producing resistance to virtually all antibiotics currently available in clinical practice. Therefore, understanding the biochemical and genetic basis of resistance is of paramount importance to design strategies to curtail the emergence and spread of resistance and devise innovative therapeutic approaches against multidrug-resistant organisms. In this chapter, we will describe in detail the major mechanisms of antibiotic resistance encountered in clinical practice providing specific examples in relevant bacterial pathogens. PMID:27227291

  6. Mechanisms of Antibiotic Resistance.

    PubMed

    Munita, Jose M; Arias, Cesar A

    2016-04-01

    Emergence of resistance among the most important bacterial pathogens is recognized as a major public health threat affecting humans worldwide. Multidrug-resistant organisms have not only emerged in the hospital environment but are now often identified in community settings, suggesting that reservoirs of antibiotic-resistant bacteria are present outside the hospital. The bacterial response to the antibiotic "attack" is the prime example of bacterial adaptation and the pinnacle of evolution. "Survival of the fittest" is a consequence of an immense genetic plasticity of bacterial pathogens that trigger specific responses that result in mutational adaptations, acquisition of genetic material, or alteration of gene expression producing resistance to virtually all antibiotics currently available in clinical practice. Therefore, understanding the biochemical and genetic basis of resistance is of paramount importance to design strategies to curtail the emergence and spread of resistance and to devise innovative therapeutic approaches against multidrug-resistant organisms. In this chapter, we will describe in detail the major mechanisms of antibiotic resistance encountered in clinical practice, providing specific examples in relevant bacterial pathogens. PMID:27227291

  7. Resistance mechanisms in Campylobacter jejuni.

    PubMed

    Iovine, Nicole M

    2013-04-01

    Campylobacter jejuni is a major cause of food-borne gastroenteritis worldwide. While mortality is low, morbidity imparted by post-infectious sequelae such as Guillain-Barré syndrome, Reiter syndrome/reactive arthritis and irritable bowel syndrome is significant. In addition, the economic cost is high due to lost productivity. Food animals, particularly poultry, are the main reservoirs of C. jejuni. The over-use of antibiotics in the human population and in animal husbandry has led to an increase in antibiotic-resistant infections, particularly with fluoroquinolones. This is problematic because C. jejuni gastroenteritis is clinically indistinguishable from that caused by other bacterial pathogens, and such illnesses are usually treated empirically with fluoroquinolones. Since C. jejuni is naturally transformable, acquisition of additional genes imparting antibiotic resistance is likely. Therefore, an understanding of the antibiotic resistance mechanisms in C. jejuni is needed to provide proper therapy both to the veterinary and human populations.

  8. Mechanisms of Drug Resistance: Daptomycin Resistance

    PubMed Central

    Tran, Truc T.; Munita, Jose M.; Arias, Cesar A.

    2016-01-01

    Daptomycin (DAP) is a cyclic lipopeptide with in vitro activity against a variety of Gram-positive pathogens, including multidrug-resistant organisms. Since its introduction in clinical practice in 2003, DAP has become an important key front-line antibiotic for severe or deep-seated infections caused by Gram-positive organisms. Unfortunately, DAP-resistance (R) has been extensively documented in clinically important organisms such as Staphylococcus aureus, Enterococcus spp, and Streptococcus spp. Studies on the mechanisms of DAP-R in Bacillus subtilis and other Gram-positive bacteria indicate that the genetic pathways of DAP resistance are diverse and complex. However, a common phenomenon emerging from these mechanistic studies is that DAP-R is associated with important adaptive changes in cell wall and cell membrane homeostasis with critical changes in cell physiology. Findings related to these adaptive changes have offered novel insights into the genetics and molecular mechanisms of bacterial cell envelope stress response and the manner in which Gram-positive bacteria cope with the antimicrobial peptide attack and protect vital structures of the cell envelope such as the cell membrane. In this review, we will examine the most recent findings related to the molecular mechanisms of resistance to DAP in relevant Gram-positive pathogens and discuss the clinical implications for therapy against these important bacteria. PMID:26495887

  9. (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.

  10. Mechanisms of Resistance to Photodynamic Therapy

    PubMed Central

    Casas, Adriana; Di Venosa, Gabriela; Hasan, Tayyaba; Batlle, Alcira

    2013-01-01

    Photodynamic therapy (PDT) involves the administration of a photosensitizer (PS) followed by illumination with visible light, leading to generation of reactive oxygen species. The mechanisms of resistance to PDT ascribed to the PS may be shared with the general mechanisms of drug resistance, and are related to altered drug uptake and efflux rates or altered intracellular trafficking. As a second step, an increased inactivation of oxygen reactive species is also associated to PDT resistance via antioxidant detoxifying enzymes and activation of heat shock proteins. Induction of stress response genes also occurs after PDT, resulting in modulation of proliferation, cell detachment and inducing survival pathways among other multiple extracellular signalling events. In addition, an increased repair of induced damage to proteins, membranes and occasionally to DNA may happen. PDT-induced tissue hypoxia as a result of vascular damage and photochemical oxygen consumption may also contribute to the appearance of resistant cells. The structure of the PS is believed to be a key point in the development of resistance, being probably related to its particular subcellular localization. Although most of the features have already been described for chemoresistance, in many cases, no cross-resistance between PDT and chemotherapy has been reported. These findings are in line with the enhancement of PDT efficacy by combination with chemotherapy. The study of cross resistance in cells with developed resistance against a particular PS challenged against other PS is also highly complex and comprises different mechanisms. In this review we will classify the different features observed in PDT resistance, leading to a comparison with the mechanisms most commonly found in chemo resistant cells. PMID:21568910

  11. Nitroheterocyclic drug resistance mechanisms in Trypanosoma brucei

    PubMed Central

    Wyllie, Susan; Foth, Bernardo J.; Kelner, Anna; Sokolova, Antoaneta Y.; Berriman, Matthew; Fairlamb, Alan H.

    2016-01-01

    Objectives The objective of this study was to identify the mechanisms of resistance to nifurtimox and fexinidazole in African trypanosomes. Methods Bloodstream-form Trypanosoma brucei were selected for resistance to nifurtimox and fexinidazole by stepwise exposure to increasing drug concentrations. Clones were subjected to WGS to identify putative resistance genes. Transgenic parasites modulating expression of genes of interest were generated and drug susceptibility phenotypes determined. Results Nifurtimox-resistant (NfxR) and fexinidazole-resistant (FxR) parasites shared reciprocal cross-resistance suggestive of a common mechanism of action. Previously, a type I nitroreductase (NTR) has been implicated in nitro drug activation. WGS of resistant clones revealed that NfxR parasites had lost >100 kb from one copy of chromosome 7, rendering them hemizygous for NTR as well as over 30 other genes. FxR parasites retained both copies of NTR, but lost >70 kb downstream of one NTR allele, decreasing NTR transcription by half. A single knockout line of NTR displayed 1.6- and 1.9-fold resistance to nifurtimox and fexinidazole, respectively. Since NfxR and FxR parasites are ∼6- and 20-fold resistant to nifurtimox and fexinidazole, respectively, additional factors must be involved. Overexpression and knockout studies ruled out a role for a putative oxidoreductase (Tb927.7.7410) and a hypothetical gene (Tb927.1.1050), previously identified in a genome-scale RNAi screen. Conclusions NTR was confirmed as a key resistance determinant, either by loss of one gene copy or loss of gene expression. Further work is required to identify which of the many dozens of SNPs identified in the drug-resistant cell lines contribute to the overall resistance phenotype. PMID:26581221

  12. Mechanisms of polymyxin resistance: acquired and intrinsic resistance in bacteria

    PubMed Central

    Olaitan, Abiola O.; Morand, Serge; Rolain, Jean-Marc

    2014-01-01

    Polymyxins are polycationic antimicrobial peptides that are currently the last-resort antibiotics for the treatment of multidrug-resistant, Gram-negative bacterial infections. The reintroduction of polymyxins for antimicrobial therapy has been followed by an increase in reports of resistance among Gram-negative bacteria. Some bacteria, such as Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii, develop resistance to polymyxins in a process referred to as acquired resistance, whereas other bacteria, such as Proteus spp., Serratia spp., and Burkholderia spp., are naturally resistant to these drugs. Reports of polymyxin resistance in clinical isolates have recently increased, including acquired and intrinsically resistant pathogens. This increase is considered a serious issue, prompting concern due to the low number of currently available effective antibiotics. This review summarizes current knowledge concerning the different strategies bacteria employ to resist the activities of polymyxins. Gram-negative bacteria employ several strategies to protect themselves from polymyxin antibiotics (polymyxin B and colistin), including a variety of lipopolysaccharide (LPS) modifications, such as modifications of lipid A with phosphoethanolamine and 4-amino-4-deoxy-L-arabinose, in addition to the use of efflux pumps, the formation of capsules and overexpression of the outer membrane protein OprH, which are all effectively regulated at the molecular level. The increased understanding of these mechanisms is extremely vital and timely to facilitate studies of antimicrobial peptides and find new potential drugs targeting clinically relevant Gram-negative bacteria. PMID:25505462

  13. Mechanisms of polymyxin resistance: acquired and intrinsic resistance in bacteria.

    PubMed

    Olaitan, Abiola O; Morand, Serge; Rolain, Jean-Marc

    2014-01-01

    Polymyxins are polycationic antimicrobial peptides that are currently the last-resort antibiotics for the treatment of multidrug-resistant, Gram-negative bacterial infections. The reintroduction of polymyxins for antimicrobial therapy has been followed by an increase in reports of resistance among Gram-negative bacteria. Some bacteria, such as Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii, develop resistance to polymyxins in a process referred to as acquired resistance, whereas other bacteria, such as Proteus spp., Serratia spp., and Burkholderia spp., are naturally resistant to these drugs. Reports of polymyxin resistance in clinical isolates have recently increased, including acquired and intrinsically resistant pathogens. This increase is considered a serious issue, prompting concern due to the low number of currently available effective antibiotics. This review summarizes current knowledge concerning the different strategies bacteria employ to resist the activities of polymyxins. Gram-negative bacteria employ several strategies to protect themselves from polymyxin antibiotics (polymyxin B and colistin), including a variety of lipopolysaccharide (LPS) modifications, such as modifications of lipid A with phosphoethanolamine and 4-amino-4-deoxy-L-arabinose, in addition to the use of efflux pumps, the formation of capsules and overexpression of the outer membrane protein OprH, which are all effectively regulated at the molecular level. The increased understanding of these mechanisms is extremely vital and timely to facilitate studies of antimicrobial peptides and find new potential drugs targeting clinically relevant Gram-negative bacteria.

  14. Antimicrobial Resistance Mechanisms among Campylobacter

    PubMed Central

    2013-01-01

    Campylobacter jejuni and Campylobacter coli are recognized as the most common causative agents of bacterial gastroenteritis in the world. Humans most often become infected by ingesting contaminated food, especially undercooked chicken, but also other sources of bacteria have been described. Campylobacteriosis is normally a self-limiting disease. Antimicrobial treatment is needed only in patients with more severe disease and in those who are immunologically compromised. The most common antimicrobial agents used in the treatment of Campylobacter infections are macrolides, such as erythromycin, and fluoroquinolones, such as ciprofloxacin. Tetracyclines have been suggested as an alternative choice in the treatment of clinical campylobacteriosis but in practice are not often used. However, during the past few decades an increasing number of resistant Campylobacter isolates have developed resistance to fluoroquinolones and other antimicrobials such as macrolides, aminoglycosides, and beta-lactams. Trends in antimicrobial resistance have shown a clear correlation between use of antibiotics in the veterinary medicine and animal production and resistant isolates of Campylobacter in humans. In this review, the patterns of emerging resistance to the antimicrobial agents useful in treatment of the disease are presented and the mechanisms of resistance to these drugs in Campylobacter are discussed. PMID:23865047

  15. Oxidation and sulfidation resistant alloys with silicon additions

    SciTech Connect

    Dunning, John S.; Alman, David E.; Poston, J.A., Jr.; Siriwardane, R.

    2003-01-01

    The Albany Research Center (ARC) has considerable experience in developing lean chromium, austenitic stainless steels with improved high temperature oxidation resistance. Using basic alloy design principles, a baseline composition of Fe-16Cr-16Ni-2Mn-1Mo alloys with Si and Al addition at a maximum of 5 weight percent was selected for potential application at temperatures above 700ºC for supercritical and ultra-supercritical power plant application. The alloys were fully austenitic. Cyclic oxidation tests in air for 1000 hours were carried out on alloys with Si only or combined Si and Al additions in the temperature range 700ºC to 800ºC. Oxidation resistances of alloys with Si only additions were outstanding, particularly at 800ºC (i.e., these alloys possessed weight gains 4 times less than a standard type-304 alloy). In addition, Si alloys pre-oxidized at 800ºC, showed a zero weight gain in subsequent testing for 1000 hours at 700ºC. Similar improvements were observed for Si only alloy after H2S exposure at 700ºC compared with type 304 stainless steel. SEM and ESCA analysis of the oxide films and base material at the oxide/base metal interface were conducted to study potential rate controlling mechanisms at ARC. Depth profile analysis and element concentration profiles (argon ion etching/x-ray photoelectron spectroscopy) were conducted on oxidized specimens and base material at the National Energy Technology Laboratory.

  16. Mechanisms of resistance in castration-resistant prostate cancer (CRPC)

    PubMed Central

    Chandrasekar, Thenappan; Yang, Joy C.; Gao, Allen C.

    2015-01-01

    Despite advances in prostate cancer diagnosis and management, morbidity from prostate cancer remains high. Approximately 20% of men present with advanced or metastatic disease, while 29,000 men continue to die of prostate cancer each year. Androgen deprivation therapy (ADT) has been the standard of care for initial management of advanced or metastatic prostate cancer since Huggins and Hodges first introduced the concept of androgen-dependence in 1972, but progression to castration-resistant prostate cancer (CRPC) occurs within 2-3 years of initiation of ADT. CRPC, previously defined as hormone-refractory prostate cancer, is now understood to still be androgen dependent. Multiple mechanisms of resistance help contribute to the progression to castration resistant disease, and the androgen receptor (AR) remains an important driver in this progression. These mechanisms include AR amplification and hypersensitivity, AR mutations leading to promiscuity, mutations in coactivators/corepressors, androgen-independent AR activation, and intratumoral and alternative androgen production. More recently, identification of AR variants (ARVs) has been established as another mechanism of progression to CRPC. Docetaxel chemotherapy has historically been the first-line treatment for CRPC, but in recent years, newer agents have been introduced that target some of these mechanisms of resistance, thereby providing additional survival benefit. These include AR signaling inhibitors such as enzalutamide (Xtandi, ENZA, MDV-3100) and CYP17A1 inhibitors such as abiraterone acetate (Zytiga). Ultimately, these agents will also fail to suppress CRPC. While some of the mechanisms by which these agents fail are unique, many share similarities to the mechanisms contributing to CRPC progression. Understanding these mechanisms of resistance to ADT and currently approved CRPC treatments will help guide future research into targeted therapies. PMID:26814148

  17. Mechanical properties of additively manufactured octagonal honeycombs.

    PubMed

    Hedayati, R; Sadighi, M; Mohammadi-Aghdam, M; Zadpoor, A A

    2016-12-01

    Honeycomb structures have found numerous applications as structural and biomedical materials due to their favourable properties such as low weight, high stiffness, and porosity. Application of additive manufacturing and 3D printing techniques allows for manufacturing of honeycombs with arbitrary shape and wall thickness, opening the way for optimizing the mechanical and physical properties for specific applications. In this study, the mechanical properties of honeycomb structures with a new geometry, called octagonal honeycomb, were investigated using analytical, numerical, and experimental approaches. An additive manufacturing technique, namely fused deposition modelling, was used to fabricate the honeycomb from polylactic acid (PLA). The honeycombs structures were then mechanically tested under compression and the mechanical properties of the structures were determined. In addition, the Euler-Bernoulli and Timoshenko beam theories were used for deriving analytical relationships for elastic modulus, yield stress, Poisson's ratio, and buckling stress of this new design of honeycomb structures. Finite element models were also created to analyse the mechanical behaviour of the honeycombs computationally. The analytical solutions obtained using Timoshenko beam theory were close to computational results in terms of elastic modulus, Poisson's ratio and yield stress, especially for relative densities smaller than 25%. The analytical solutions based on the Timoshenko analytical solution and the computational results were in good agreement with experimental observations. Finally, the elastic properties of the proposed honeycomb structure were compared to those of other honeycomb structures such as square, triangular, hexagonal, mixed, diamond, and Kagome. The octagonal honeycomb showed yield stress and elastic modulus values very close to those of regular hexagonal honeycombs and lower than the other considered honeycombs. PMID:27612831

  18. Mechanical properties of additively manufactured octagonal honeycombs.

    PubMed

    Hedayati, R; Sadighi, M; Mohammadi-Aghdam, M; Zadpoor, A A

    2016-12-01

    Honeycomb structures have found numerous applications as structural and biomedical materials due to their favourable properties such as low weight, high stiffness, and porosity. Application of additive manufacturing and 3D printing techniques allows for manufacturing of honeycombs with arbitrary shape and wall thickness, opening the way for optimizing the mechanical and physical properties for specific applications. In this study, the mechanical properties of honeycomb structures with a new geometry, called octagonal honeycomb, were investigated using analytical, numerical, and experimental approaches. An additive manufacturing technique, namely fused deposition modelling, was used to fabricate the honeycomb from polylactic acid (PLA). The honeycombs structures were then mechanically tested under compression and the mechanical properties of the structures were determined. In addition, the Euler-Bernoulli and Timoshenko beam theories were used for deriving analytical relationships for elastic modulus, yield stress, Poisson's ratio, and buckling stress of this new design of honeycomb structures. Finite element models were also created to analyse the mechanical behaviour of the honeycombs computationally. The analytical solutions obtained using Timoshenko beam theory were close to computational results in terms of elastic modulus, Poisson's ratio and yield stress, especially for relative densities smaller than 25%. The analytical solutions based on the Timoshenko analytical solution and the computational results were in good agreement with experimental observations. Finally, the elastic properties of the proposed honeycomb structure were compared to those of other honeycomb structures such as square, triangular, hexagonal, mixed, diamond, and Kagome. The octagonal honeycomb showed yield stress and elastic modulus values very close to those of regular hexagonal honeycombs and lower than the other considered honeycombs.

  19. The Mechanism of Fluid Resistance

    NASA Technical Reports Server (NTRS)

    Vonkarman, T.; Rubach, H.

    1979-01-01

    The mechanism of fluid resistance within the limit of the square law is presented. It was concluded that the investigations should be extended and completed in two directions, namely: by an investigation of stable vortex configurations in space, and by considering the perfect fluid as the limiting case of a viscous fluid and then limiting the law of vortex of formation with the condition that only those fluid particles which were in contact with the surface of the body can receive rotation.

  20. Mechanisms of buffer therapy resistance.

    PubMed

    Bailey, Kate M; Wojtkowiak, Jonathan W; Cornnell, Heather H; Ribeiro, Maria C; Balagurunathan, Yoganand; Hashim, Arig Ibrahim; Gillies, Robert J

    2014-04-01

    Many studies have shown that the acidity of solid tumors contributes to local invasion and metastasis. Oral pH buffers can specifically neutralize the acidic pH of tumors and reduce the incidence of local invasion and metastatic formation in multiple murine models. However, this effect is not universal as we have previously observed that metastasis is not inhibited by buffers in some tumor models, regardless of buffer used. B16-F10 (murine melanoma), LL/2 (murine lung) and HCT116 (human colon) tumors are resistant to treatment with lysine buffer therapy, whereas metastasis is potently inhibited by lysine buffers in MDA-MB-231 (human breast) and PC3M (human prostate) tumors. In the current work, we confirmed that sensitive cells utilized a pH-dependent mechanism for successful metastasis supported by a highly glycolytic phenotype that acidifies the local tumor microenvironment resulting in morphological changes. In contrast, buffer-resistant cell lines exhibited a pH-independent metastatic mechanism involving constitutive secretion of matrix degrading proteases without elevated glycolysis. These results have identified two distinct mechanisms of experimental metastasis, one of which is pH-dependent (buffer therapy sensitive cells) and one which is pH-independent (buffer therapy resistant cells). Further characterization of these models has potential for therapeutic benefit.

  1. Pronounced effects of additional resistance in Andreev reflection spectroscopy

    NASA Astrophysics Data System (ADS)

    Chen, T. Y.; Huang, S. X.; Chien, C. L.

    2010-06-01

    We present a systematic investigation of the additional resistance (RE) , which is an unavoidable consequence of pseudo-four-probe electrical measurements, on the point-contact Andreev reflection (PCAR) spectrum by both modeling and experiments. Instead of considering the total resistance between the two voltage leads across a point contact as a sum of a contact resistance (RC) and a fixed sample resistance (RS) , it is essential to treat the total resistance as a sum of the Andreev resistance RAR and the additional resistance RE , which are, respectively, the resistances affected and unaffected by the Andreev reflection process. We show a detailed formalism of taking RE into account in modeling and demonstrate that the PCAR spectrum can be drastically affected by the presence of RE . Experimentally, we have found that not only RE cannot be readily measured or even estimated, it is in fact different for each contact, depending on the contact resistance and whether the contact is near the purely ballistic regime or the purely diffusive regime. A self-consistent process is necessary to analyze the entire PCAR spectrum, properly normalize the conductance, determine RE , and other parameters including the spin polarization and the superconducting gap for each contact. We determine RE for various contacts on specimens with different resistivity and resolve the causes of RE . For contacts close to the diffusive regime, there are two sources of RE : a dominant contribution which is linearly proportional to the total resistance and a constant value from the sample resistance. We also address the effects of additional resistance when PCAR is administered in the ballistic limit and in the diffusive limit. With the proper treatment of the additional resistance, we demonstrate that PCAR can quantitatively extract essential information of spin polarization and superconducting gap.

  2. The molecular mechanisms of acquired proteasome inhibitor resistance

    PubMed Central

    Kale, Andrew J.; Moore, Bradley S.

    2012-01-01

    The development of proteasome inhibitors (PIs) has transformed the treatment of multiple myeloma and mantle cell lymphoma. To date, two PIs have been FDA approved, the boronate peptide bortezomib and, most recently, the epoxyketone peptide carfilzomib. However, intrinsic and acquired resistance to PIs, for which the underlying mechanisms are poorly understood, may limit their efficacy. In this perspective, we discuss recent advances in the molecular understanding of PI resistance through acquired bortezomib resistance in human cell lines to evolved saliniosporamide A (marizomib) resistance in nature. Resistance mechanisms discussed include the upregulation of proteasome subunits and mutations of the catalytic β-subunits. Additionally, we explore potential strategies to overcome PI resistance. PMID:22978849

  3. Reducing of internal resistance lithium ion battery using glucose addition

    NASA Astrophysics Data System (ADS)

    Salim, Andri Pratama; Hafidlullah, Noor; Purwanto, Agus

    2016-02-01

    There are two indicators of battery performance, i.e : capacity and the internal resistance of battery. In this research, the affect of glucose addition to decrease the internal resistance of lithium battery was investigated. The ratio of glucose addition were varied at weight ratio 1%, 3%, and 5% and one mixtures without glucose addition. Lithium ferri phosphate (LiFePO4), polyvinylidene fluoride (PVDF), acetylene black (AB) and glucose were materials that used in this study. Both of mixtures were mixed in the vacuum mixer until became homogeneous. The slurry was coated on an aluminium foil sheet and the coated thickness was 200 µm. The performance of battery lithium was examined by Eight Channel Battery Analyzer and the Internal resistance was examined by Internal Resistance of Battery Meter. The result from all analyzer were showed that the internal resistance reduced as well as the battery capacity. The best internal resistance value is owned by mixtures with 3wt% ratio glucose addition. It has an internal resistance value about 64 miliohm.

  4. Enhancement of Corrosion Resistance of Zinc Coatings Using Green Additives

    NASA Astrophysics Data System (ADS)

    Punith Kumar, M. K.; Srivastava, Chandan

    2014-10-01

    In the present work, morphology, microstructure, and electrochemical behavior of Zn coatings containing non-toxic additives have been investigated. Zn coatings were electrodeposited over mild steel substrates using Zn sulphate baths containing four different organic additives: sodium gluconate, dextrose, dextrin, and saccharin. All these additives are "green" and can be derived from food contents. Morphological and structural characterization using electron microscopy, x-ray diffraction, and texture co-efficient analysis revealed an appreciable alteration in the morphology and texture of the deposit depending on the type of additive used in the Zn plating bath. All the Zn coatings, however, were nano-crystalline irrespective of the type of additive used. Polarization and electrochemical impedance spectroscopic analysis, used to investigate the effect of the change in microstructure and morphology on corrosion resistance behavior, illustrated an improved corrosion resistance for Zn deposits obtained from plating bath containing additives as compared to the pure Zn coatings.

  5. Drug Resistance Mechanisms in Mycobacterium tuberculosis

    PubMed Central

    Palomino, Juan Carlos; Martin, Anandi

    2014-01-01

    Tuberculosis (TB) is a serious public health problem worldwide. Its situation is worsened by the presence of multidrug resistant (MDR) strains of Mycobacterium tuberculosis, the causative agent of the disease. In recent years, even more serious forms of drug resistance have been reported. A better knowledge of the mechanisms of drug resistance of M. tuberculosis and the relevant molecular mechanisms involved will improve the available techniques for rapid drug resistance detection and will help to explore new targets for drug activity and development. This review article discusses the mechanisms of action of anti-tuberculosis drugs and the molecular basis of drug resistance in M. tuberculosis. PMID:27025748

  6. Drug Resistance Mechanisms in Mycobacterium tuberculosis.

    PubMed

    Palomino, Juan Carlos; Martin, Anandi

    2014-01-01

    Tuberculosis (TB) is a serious public health problem worldwide. Its situation is worsened by the presence of multidrug resistant (MDR) strains of Mycobacterium tuberculosis, the causative agent of the disease. In recent years, even more serious forms of drug resistance have been reported. A better knowledge of the mechanisms of drug resistance of M. tuberculosis and the relevant molecular mechanisms involved will improve the available techniques for rapid drug resistance detection and will help to explore new targets for drug activity and development. This review article discusses the mechanisms of action of anti-tuberculosis drugs and the molecular basis of drug resistance in M. tuberculosis. PMID:27025748

  7. Antiviral Drug Resistance: Mechanisms and Clinical Implications

    PubMed Central

    Chou, Sunwen

    2010-01-01

    Summary Antiviral drug resistance is an increasing concern in immunocompromised patient populations, where ongoing viral replication and prolonged drug exposure lead to the selection of resistant strains. Rapid diagnosis of resistance can be made by associating characteristic viral mutations with resistance to various drugs as determined by phenotypic assays. Management of drug resistance includes optimization of host factors and drug delivery, selection of alternative therapies based on knowledge of mechanisms of resistance, and the development of new antivirals. This article discusses drug resistance in herpesviruses and hepatitis B. PMID:20466277

  8. Tantalum Addition to Zirconium Diboride for Improved Oxidation Resistance

    NASA Technical Reports Server (NTRS)

    Levine, Stanley R.; Opila, Eliizabeth J.

    2003-01-01

    Ultrahigh temperature ceramics have performed unreliably due to material flaws and attachment design. These deficiencies are brought to the fore by the low fracture toughness and thermal shock resistance of UHTCs. If these deficiencies are overcome, we are still faced with poor oxidation resistance as a limitation on UHTC applicability to reusable launch vehicles. We have been addressing the deficiencies of UHTCs with our focus on composite constructions and functional grading to address the mechanical issues, and on composition modification to address the oxidation issue. The approaches and progress toward the latter are reported.

  9. Molecular mechanisms of methicillin resistance in Staphylococcus aureus.

    PubMed

    Domínguez, M A; Liñares, J; Martín, R

    1997-09-01

    Methicillin-resistant Staphylococcus aureus (MRSA) strains are among the most common nosocomial pathogens. The most significant mechanism of resistance to methicillin in this-species is the acquisition of a genetic determinant (mecA gene). However, resistance seems to have a more complex molecular basis, since additional chromosomal material is involved in such resistance. Besides, overproduction of penicillinase and/or alterations in the PBPs can contribute to the formation of resistance phenotypes. Genetic and environmental factors leading to MRSA are reviewed.

  10. Mechanisms of Antimicrobial Resistance in ESKAPE Pathogens

    PubMed Central

    Santajit, Sirijan; Indrawattana, Nitaya

    2016-01-01

    The ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) are the leading cause of nosocomial infections throughout the world. Most of them are multidrug resistant isolates, which is one of the greatest challenges in clinical practice. Multidrug resistance is amongst the top three threats to global public health and is usually caused by excessive drug usage or prescription, inappropriate use of antimicrobials, and substandard pharmaceuticals. Understanding the resistance mechanisms of these bacteria is crucial for the development of novel antimicrobial agents or other alternative tools to combat these public health challenges. Greater mechanistic understanding would also aid in the prediction of underlying or even unknown mechanisms of resistance, which could be applied to other emerging multidrug resistant pathogens. In this review, we summarize the known antimicrobial resistance mechanisms of ESKAPE pathogens. PMID:27274985

  11. Disease resistance: Molecular mechanisms and biotechnological applications

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This special issue “Disease resistance: molecular mechanisms and biotechnological applications” contains 11 review articles and four original research papers. Research in the area of engineering for disease resistance continues to progress although only 10% of the transgenic plants registered for ...

  12. Mechanisms of antibiotic resistance in enterococci

    PubMed Central

    Miller, William R; Munita, Jose M; Arias, Cesar A

    2015-01-01

    Multidrug-resistant (MDR) enterococci are important nosocomial pathogens and a growing clinical challenge. These organisms have developed resistance to virtually all antimicrobials currently used in clinical practice using a diverse number of genetic strategies. Due to this ability to recruit antibiotic resistance determinants, MDR enterococci display a wide repertoire of antibiotic resistance mechanisms including modification of drug targets, inactivation of therapeutic agents, overexpression of efflux pumps and a sophisticated cell envelope adaptive response that promotes survival in the human host and the nosocomial environment. MDR enterococci are well adapted to survive in the gastrointestinal tract and can become the dominant flora under antibiotic pressure, predisposing the severely ill and immunocompromised patient to invasive infections. A thorough understanding of the mechanisms underlying antibiotic resistance in enterococci is the first step for devising strategies to control the spread of these organisms and potentially establish novel therapeutic approaches. PMID:25199988

  13. Antibiotic resistance mechanisms of Myroides sp.

    PubMed

    Hu, Shao-hua; Yuan, Shu-xing; Qu, Hai; Jiang, Tao; Zhou, Ya-jun; Wang, Ming-xi; Ming, De-song

    2016-03-01

    Bacteria of the genus Myroides (Myroides spp.) are rare opportunistic pathogens. Myroides sp. infections have been reported mainly in China. Myroides sp. is highly resistant to most available antibiotics, but the resistance mechanisms are not fully elucidated. Current strain identification methods based on biochemical traits are unable to identify strains accurately at the species level. While 16S ribosomal RNA (rRNA) gene sequencing can accurately achieve this, it fails to give information on the status and mechanisms of antibiotic resistance, because the 16S rRNA sequence contains no information on resistance genes, resistance islands or enzymes. We hypothesized that obtaining the whole genome sequence of Myroides sp., using next generation sequencing methods, would help to clarify the mechanisms of pathogenesis and antibiotic resistance, and guide antibiotic selection to treat Myroides sp. infections. As Myroides sp. can survive in hospitals and the environment, there is a risk of nosocomial infections and pandemics. For better management of Myroides sp. infections, it is imperative to apply next generation sequencing technologies to clarify the antibiotic resistance mechanisms in these bacteria.

  14. Mechanisms of Candida biofilm drug resistance

    PubMed Central

    Taff, Heather T; Mitchell, Kaitlin F; Edward, Jessica A; Andes, David R

    2013-01-01

    Candida commonly adheres to implanted medical devices, growing as a resilient biofilm capable of withstanding extraordinarily high antifungal concentrations. As currently available antifungals have minimal activity against biofilms, new drugs to treat these recalcitrant infections are urgently needed. Recent investigations have begun to shed light on the mechanisms behind the profound resistance associated with the biofilm mode of growth. This resistance appears to be multifactorial, involving both mechanisms similar to conventional, planktonic antifungal resistance, such as increased efflux pump activity, as well as mechanisms specific to the biofilm lifestyle. A unique biofilm property is the production of an extracellular matrix. Two components of this material, β-glucan and extracellular DNA, promote biofilm resistance to multiple antifungals. Biofilm formation also engages several stress response pathways that impair the activity of azole drugs. Resistance within a biofilm is often heterogeneous, with the development of a subpopulation of resistant persister cells. In this article we review the molecular mechanisms underlying Candida biofilm antifungal resistance and their relative contributions during various growth phases. PMID:24059922

  15. Antibiotic resistance mechanisms of Myroides sp.*

    PubMed Central

    Hu, Shao-hua; Yuan, Shu-xing; Qu, Hai; Jiang, Tao; Zhou, Ya-jun; Wang, Ming-xi; Ming, De-song

    2016-01-01

    Bacteria of the genus Myroides (Myroides spp.) are rare opportunistic pathogens. Myroides sp. infections have been reported mainly in China. Myroides sp. is highly resistant to most available antibiotics, but the resistance mechanisms are not fully elucidated. Current strain identification methods based on biochemical traits are unable to identify strains accurately at the species level. While 16S ribosomal RNA (rRNA) gene sequencing can accurately achieve this, it fails to give information on the status and mechanisms of antibiotic resistance, because the 16S rRNA sequence contains no information on resistance genes, resistance islands or enzymes. We hypothesized that obtaining the whole genome sequence of Myroides sp., using next generation sequencing methods, would help to clarify the mechanisms of pathogenesis and antibiotic resistance, and guide antibiotic selection to treat Myroides sp. infections. As Myroides sp. can survive in hospitals and the environment, there is a risk of nosocomial infections and pandemics. For better management of Myroides sp. infections, it is imperative to apply next generation sequencing technologies to clarify the antibiotic resistance mechanisms in these bacteria. PMID:26984839

  16. Mechanisms of echinocandin antifungal drug resistance

    PubMed Central

    Perlin, David S.

    2015-01-01

    Fungal infections due to Candida and Aspergillus species cause extensive morbidity and mortality, especially among immunosuppressed patients, and antifungal therapy is critical to patient management. Yet only a few drug classes are available to treat invasive fungal diseases, and this problem is compounded by the emergence of antifungal resistance. Echinocandin drugs are the preferred choice to treat candidiasis. They are the first cell wall–active agents and target the fungal-specific enzyme glucan synthase, which catalyzes the biosynthesis of β-1,3-glucan, a key cell wall polymer. Therapeutic failures occur rarely among common Candida species, with the exception of Candida glabrata, which are frequently multidrug resistant. Echinocandin resistance in susceptible species is always acquired during therapy. The mechanism of resistance involves amino acid changes in hot-spot regions of Fks subunits of glucan synthase, which decrease the sensitivity of the enzyme to drug. Cellular stress response pathways lead to drug adaptation, which promote the formation of resistant fks strains. Clinical factors promoting echinocandin resistance include empiric therapy, prophylaxis, gastrointestinal reservoirs, and intra-abdominal infections. A better understanding of the echinocandin resistance mechanism, along with cellular and clinical factors promoting resistance, will promote more effective strategies to overcome and prevent echinocandin resistance. PMID:26190298

  17. Molecular mechanisms for tumour resistance to chemotherapy.

    PubMed

    Pan, Shu-Ting; Li, Zhi-Ling; He, Zhi-Xu; Qiu, Jia-Xuan; Zhou, Shu-Feng

    2016-08-01

    Chemotherapy is one of the prevailing methods used to treat malignant tumours, but the outcome and prognosis of tumour patients are not optimistic. Cancer cells gradually generate resistance to almost all chemotherapeutic drugs via a variety of distinct mechanisms and pathways. Chemotherapeutic resistance, either intrinsic or acquired, is caused and sustained by reduced drug accumulation and increased drug export, alterations in drug targets and signalling transduction molecules, increased repair of drug-induced DNA damage, and evasion of apoptosis. In order to better understand the mechanisms of chemoresistance, this review highlights our current knowledge of the role of altered drug metabolism and transport and deregulation of apoptosis and autophagy in the development of tumour chemoresistance. Reduced intracellular activation of prodrugs (e.g. thiotepa and tegafur) or enhanced drug inactivation by Phase I and II enzymes contributes to the development of chemoresistance. Both primary and acquired resistance can be caused by alterations in the transport of anticancer drugs which is mediated by a variety of drug transporters such as P-glycoprotein (P-gp), multidrug resistance associated proteins, and breast cancer resistance protein. Presently there is a line of evidence indicating that deregulation of programmed cell death including apoptosis and autophagy is also an important mechanism for tumour resistance to anticancer drugs. Reversal of chemoresistance is likely via pharmacological and biological approaches. Further studies are warranted to grasp the full picture of how each type of cancer cells develop resistance to anticancer drugs and to identify novel strategies to overcome it.

  18. Molecular mechanisms for tumour resistance to chemotherapy.

    PubMed

    Pan, Shu-Ting; Li, Zhi-Ling; He, Zhi-Xu; Qiu, Jia-Xuan; Zhou, Shu-Feng

    2016-08-01

    Chemotherapy is one of the prevailing methods used to treat malignant tumours, but the outcome and prognosis of tumour patients are not optimistic. Cancer cells gradually generate resistance to almost all chemotherapeutic drugs via a variety of distinct mechanisms and pathways. Chemotherapeutic resistance, either intrinsic or acquired, is caused and sustained by reduced drug accumulation and increased drug export, alterations in drug targets and signalling transduction molecules, increased repair of drug-induced DNA damage, and evasion of apoptosis. In order to better understand the mechanisms of chemoresistance, this review highlights our current knowledge of the role of altered drug metabolism and transport and deregulation of apoptosis and autophagy in the development of tumour chemoresistance. Reduced intracellular activation of prodrugs (e.g. thiotepa and tegafur) or enhanced drug inactivation by Phase I and II enzymes contributes to the development of chemoresistance. Both primary and acquired resistance can be caused by alterations in the transport of anticancer drugs which is mediated by a variety of drug transporters such as P-glycoprotein (P-gp), multidrug resistance associated proteins, and breast cancer resistance protein. Presently there is a line of evidence indicating that deregulation of programmed cell death including apoptosis and autophagy is also an important mechanism for tumour resistance to anticancer drugs. Reversal of chemoresistance is likely via pharmacological and biological approaches. Further studies are warranted to grasp the full picture of how each type of cancer cells develop resistance to anticancer drugs and to identify novel strategies to overcome it. PMID:27097837

  19. Anthelmintic Resistance in Haemonchus contortus: History, Mechanisms and Diagnosis.

    PubMed

    Kotze, A C; Prichard, R K

    2016-01-01

    Haemonchus contortus has shown a great ability to develop resistance to anthelmintic drugs. In many instances, resistance has appeared less than 10years after the introduction of a new drug class. Field populations of this species now show resistance to all major anthelmintic drug classes, including benzimidazoles (BZs), imidazothiazoles and macrocyclic lactones. In addition, resistance to the recently introduced amino-acetonitrile derivative class (monepantel) has already been reported. The existence of field populations showing resistance to all three major drug classes, and the early appearance of resistance to monepantel, threatens the sustainability of sheep and goat production systems worldwide. This chapter reviews the history of the development of resistance to the various anthelmintics in H. contortus and examines the mechanisms utilized by this species to resist the effects of these drugs. Some of these mechanisms are well understood, particularly for BZ drugs, while our knowledge and understanding of others are increasing. Finally, we summarize methods available for the diagnosis of resistance. While such diagnosis currently relies largely on the faecal egg count reduction test, which suffers from issues of expense and sensitivity, we describe past and current efforts to utilize cheaper and less laborious phenotypic assays with free-living life stages, and then describe progress on the development of molecular assays to provide sensitive resistance-detection tests. PMID:27238009

  20. Oblique view of east side mechanical additions and south side ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Oblique view of east side mechanical additions and south side of 1955 addition, facing northwest. - Albrook Air Force Station, Dispensary, East side of Canfield Avenue, Balboa, Former Panama Canal Zone, CZ

  1. Mechanisms of resistance to paraquat in plants.

    PubMed

    Hawkes, Timothy R

    2014-09-01

    The aim of this brief review is to draw information from studies of the mechanism of evolved resistance in weeds, together with information from laboratory studies of paraquat tolerance in model plants. Plants having mutations that limit paraquat uptake into cytoplasm, that confer various stress tolerances or that have transgenes that co-express two or more of the chloroplast Halliwell-Asada cycle enzymes can all exhibit enhanced tolerance to paraquat. However, none of these mechanisms correspond to the high-level resistances that have evolved naturally in weeds. Most, but not all, of the evidence from studies of paraquat-resistant biotypes of weeds can reasonably be reconciled with the proposal of a single major gene mechanism that sequesters paraquat away from chloroplasts and into the vacuole. However, the molecular details of this putative mechanism remain ill-defined.

  2. Evaluation for Additional Resistance by Lightweight Thrust Restraint on Pressure Pipe Bend

    NASA Astrophysics Data System (ADS)

    Sawada, Yutaka; Kawabata, Toshinori; Mohri, Yoshiyuki; Uchida, Kazunori

    Thrust force acts on pipe bend due to internal pressure. In previous study, the lightweight thrust restraint with geogrid and anchor plate has proposed and the effect has been proved by conducting lateral loading model tests. In the present study, a series of model tests for changing depth of cover and length of restraint were carried out, and image analysis for the ground surface in the model tests were carried out to discuss the failure mechanism of proposed method. Furthermore, the failure mechanisms in front of the anchor plate were assumed and the additional resistances due to the proposed method were calculated based on the force equilibrium. In addition, in order to examine the accuracy for the proposed formula, calculated values were compared with experimental values. As the results, additional resistance from calculation was corresponding to experimental value.

  3. [Effective prevention through nutritional and food additives: barriers and resistance].

    PubMed

    Lux, R; Walter, U

    2006-06-01

    The population-wide and individual preventive potentials of nutritional and food additives such as vitamins and trace elements are generally accepted in the international literature. Iodisation and fluoridation were and are a main focus of activity. The enrichment of food with folic acid is also partly population-related. Until now, however, the theoretical possibilities of nutritional supplementations have not been fully exploited. Various barriers and resistances arise in programme development and implementation. Interviews with key stakeholders and community groups can clarify decade-long discussions in the literature and the media. The study on hand is based on a structural analysis. It shows the various arguments as well as beneficial and impeding factors for a population-wide prevention programme, for specific target groups and individuals. The findings of this research could also be applied to other Public Health challenges.

  4. Receiving Wear-Resistance Coverings Additives of Nanoparticles of Refractory Metals at a Laser Cladding

    NASA Astrophysics Data System (ADS)

    Murzakov, M. A.; Petrovskiy, V. N.; Bykovskiy, D. P.; Andreev, A. O.; Birukov, V. P.; Markushov, Y. V.

    2016-02-01

    Laser cladding technology was used to conduct experiments on production of wear-resistant coatings with additive nanoparticles of refractory metals (WC, TaC). Mechanical testing of coating abrasion was made using Brinell-Howarth method. The obtained data was compared with wear- resistance of commercial powder containing WC. It was found that at a concentration 10-15% coating with nanopowder additives shows a dramatic increase in wear-resistance by 4-6 times as compared to carbon steel substrate. There were conducted metallurgical studies of coatings on inverse electron reflection. There was determined elemental composition of deposited coating and substrate, and microhardness measured. It was found that structure of deposited coating with nanoparticles is fine.

  5. Processable high temperature resistant addition type polyimide laminating resins

    NASA Technical Reports Server (NTRS)

    Serafini, T. T.; Delvigs, P.

    1973-01-01

    Basic studies that were performed using model compounds to elucidate the polymerization mechanism of the so-called addition-type (A-type) polyimides are reviewed. The fabrication and properties of polyimide/graphite fiber composites using A-type polyimide prepolymers as the matrix are also reviewed. An alternate method for preparing processable A-type polyimides by means of in situ polymerization of monomer reactants (PMR) on the fiber reinforcement is described. The elevated temperature properties of A-type PMR/graphite fiber composites are also presented.

  6. Antibacterial Mechanisms of Polymyxin and Bacterial Resistance

    PubMed Central

    Qin, Wangrong; Fang, Shisong; Qiu, Juanping

    2015-01-01

    Multidrug resistance in pathogens is an increasingly significant threat for human health. Indeed, some strains are resistant to almost all currently available antibiotics, leaving very limited choices for antimicrobial clinical therapy. In many such cases, polymyxins are the last option available, although their use increases the risk of developing resistant strains. This review mainly aims to discuss advances in unraveling the mechanisms of antibacterial activity of polymyxins and bacterial tolerance together with the description of polymyxin structure, synthesis, and structural modification. These are expected to help researchers not only develop a series of new polymyxin derivatives necessary for future medical care, but also optimize the clinical use of polymyxins with minimal resistance development. PMID:25664322

  7. Topoisomerase Inhibitors: Fluoroquinolone Mechanisms of Action and Resistance.

    PubMed

    Hooper, David C; Jacoby, George A

    2016-01-01

    Quinolone antimicrobials are widely used in clinical medicine and are the only current class of agents that directly inhibit bacterial DNA synthesis. Quinolones dually target DNA gyrase and topoisomerase IV binding to specific domains and conformations so as to block DNA strand passage catalysis and stabilize DNA-enzyme complexes that block the DNA replication apparatus and generate double breaks in DNA that underlie their bactericidal activity. Resistance has emerged with clinical use of these agents and is common in some bacterial pathogens. Mechanisms of resistance include mutational alterations in drug target affinity and efflux pump expression and acquisition of resistance-conferring genes. Resistance mutations in one or both of the two drug target enzymes are commonly in a localized domain of the GyrA and ParC subunits of gyrase and topoisomerase IV, respectively, 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 other antimicrobials as well as quinolones. Mutations of both types can accumulate with selection pressure and produce highly resistant strains. Resistance genes acquired on plasmids confer low-level resistance that promotes the selection of mutational high-level resistance. Plasmid-encoded resistance is because of Qnr proteins that protect the target enzymes from quinolone action, a 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. PMID:27449972

  8. [Resistance risk, cross-resistance and biochemical resistance mechanism of Laodelphax striatellus to buprofezin].

    PubMed

    Mao, Xu-lian; Liu, Jin; Li, Xu-ke; Chi, Jia-jia; Liu, Yong-jie

    2016-01-01

    In order to investigate the resistance development law and biochemical resistance mechanism of Laodelphax striatellus to buprofezin, spraying rice seedlings was used to continuously screen resistant strains of L. striatellus and dipping rice seedlings was applied to determine the toxicity and cross-resistance of L. striatellus to insecticides. After 32-generation screening with buprofezin, L. striatellus developed 168.49 folds resistance and its reality heritability (h2) was 0.11. If the killing rate was 80%-90%, L. striatellus was expected to develop 10-fold resistance to buprofezin only after 5 to 6 generations breeding. Because the actual reality heritability of field populations was usually lower than that of the resistant strains, the production of field populations increasing with 10-fold resistance would need much longer time. The results of cross-resistance showed that resistant strain had high level cross-resistance with thiamethoxam and imidacloprid, low level cross-resistance with acetamiprid, and no cross-resistance with pymetrozine and chlorpyrifos. The activity of detoxification enzymes of different strains and the syergism of synergist were measured. The results showed that cytochrome P450 monooxygenase played a major role in the resistance of L. striatellus to buprofezin, the esterase played a minor role and the GSH-S-transferase had no effect. Therefore, L. striatellus would have high risk to develop resistance to buprofezin when used in the field and might be delayed by using pymetrozine and chlorpyrifos. PMID:27228617

  9. Mechanisms responsible for nilotinib resistance in human chronic myeloid leukemia cells and reversal of resistance.

    PubMed

    Camgoz, Aylin; Gencer, Emel Basak; Ural, Ali Ugur; Baran, Yusuf

    2013-06-01

    Multidrug resistance remains a significant obstacle to successful chemotherapy. The ability to determine the possible resistance mechanisms and surmount the resistance is likely to improve chemotherapy. Nilotinib is a very effective drug in the treatment of imatinib-sensitive or -resistant patients. Although very successful hematologic and cytogenetic responses have been obtained in nilotinib-treated patients, in recent years cases showing resistance to nilotinib have been observed. We aimed to examine the mechanisms underlying nilotinib resistance and to provide new targets for the treatment of chronic myeloid leukemia (CML). There was an up-regulation of antiapoptotic BCR/ABL, GCS and SK-1 genes and MRP1 transporter gene and down-regulation of apoptotic Bax and CerS1 genes in nilotinib-resistant cells. There was no mutation in the nilotinib-binding region of BCR/ABL in resistant cells. Inhibiton of GCS and SK-1 restored nilotinib sensitivity. Targeting the proteins that are involved in nilotinib resistance in addition to the inhibition of BCR/ABL could be a better method of treatment in CML.

  10. Mechanisms of multidrug resistance in cancer.

    PubMed

    Gillet, Jean-Pierre; Gottesman, Michael M

    2010-01-01

    The development of multidrug resistance (MDR) to chemotherapy remains a major challenge in the treatment of cancer. Resistance exists against every effective anticancer drug and can develop by numerous mechanisms including decreased drug uptake, increased drug efflux, activation of detoxifying systems, activation of DNA repair mechanisms, evasion of drug-induced apoptosis, etc. In the first part of this chapter, we briefly summarize the current knowledge on individual cellular mechanisms responsible for MDR, with a special emphasis on ATP-binding cassette transporters, perhaps the main theme of this textbook. Although extensive work has been done to characterize MDR mechanisms in vitro, the translation of this knowledge to the clinic has not been crowned with success. Therefore, identifying genes and mechanisms critical to the development of MDR in vivo and establishing a reliable method for analyzing clinical samples could help to predict the development of resistance and lead to treatments designed to circumvent it. Our thoughts about translational research needed to achieve significant progress in the understanding of this complex phenomenon are therefore discussed in a third section. The pleotropic response of cancer cells to chemotherapy is summarized in a concluding diagram. PMID:19949920

  11. Insecticide resistance in vector Chagas disease: evolution, mechanisms and management.

    PubMed

    Mougabure-Cueto, Gastón; Picollo, María Inés

    2015-09-01

    Chagas disease is a chronic parasitic infection restricted to America. The disease is caused by the protozoa Trypanosoma cruzi, which is transmitted to human through the feces of infected triatomine insects. Because no treatment is available for the chronic forms of the disease, vector chemical control represents the best way to reduce the incidence of the disease. Chemical control has been based principally on spraying dwellings with insecticide formulations and led to the reduction of triatomine distribution and consequent interruption of disease transmission in several areas from endemic region. However, in the last decade it has been repeatedly reported the presence triatomnes, mainly Triatoma infestans, after spraying with pyrethroid insecticides, which was associated to evolution to insecticide resistance. In this paper the evolution of insecticide resistance in triatomines is reviewed. The insecticide resistance was detected in 1970s in Rhodnius prolixus and 1990s in R. prolixus and T. infestans, but not until the 2000s resistance to pyrthroids in T. infestans associated to control failures was described in Argentina and Bolivia. The main resistance mechanisms (i.e. enhanced metabolism, altered site of action and reduced penetration) were described in the T. infestans resistant to pyrethrods. Different resistant profiles were demonstrated suggesting independent origin of the different resistant foci of Argentina and Bolivia. The deltamethrin resistance in T. infestans was showed to be controlled by semi-dominant, autosomally inherited factors. Reproductive and developmental costs were also demonstrated for the resistant T. infestans. A discussion about resistance and tolerance concepts and the persistence of T. infestans in Gran Chaco region are presented. In addition, theoretical concepts related to toxicological, evolutionary and ecological aspects of insecticide resistance are discussed in order to understand the particular scenario of pyrethroid

  12. Insecticide resistance in vector Chagas disease: evolution, mechanisms and management.

    PubMed

    Mougabure-Cueto, Gastón; Picollo, María Inés

    2015-09-01

    Chagas disease is a chronic parasitic infection restricted to America. The disease is caused by the protozoa Trypanosoma cruzi, which is transmitted to human through the feces of infected triatomine insects. Because no treatment is available for the chronic forms of the disease, vector chemical control represents the best way to reduce the incidence of the disease. Chemical control has been based principally on spraying dwellings with insecticide formulations and led to the reduction of triatomine distribution and consequent interruption of disease transmission in several areas from endemic region. However, in the last decade it has been repeatedly reported the presence triatomnes, mainly Triatoma infestans, after spraying with pyrethroid insecticides, which was associated to evolution to insecticide resistance. In this paper the evolution of insecticide resistance in triatomines is reviewed. The insecticide resistance was detected in 1970s in Rhodnius prolixus and 1990s in R. prolixus and T. infestans, but not until the 2000s resistance to pyrthroids in T. infestans associated to control failures was described in Argentina and Bolivia. The main resistance mechanisms (i.e. enhanced metabolism, altered site of action and reduced penetration) were described in the T. infestans resistant to pyrethrods. Different resistant profiles were demonstrated suggesting independent origin of the different resistant foci of Argentina and Bolivia. The deltamethrin resistance in T. infestans was showed to be controlled by semi-dominant, autosomally inherited factors. Reproductive and developmental costs were also demonstrated for the resistant T. infestans. A discussion about resistance and tolerance concepts and the persistence of T. infestans in Gran Chaco region are presented. In addition, theoretical concepts related to toxicological, evolutionary and ecological aspects of insecticide resistance are discussed in order to understand the particular scenario of pyrethroid

  13. Resistant mechanisms and molecular epidemiology of imipenem-resistant Acinetobacter baumannii

    PubMed Central

    Xiao, Shu-Zhen; Chu, Hai-Qing; Han, Li-Zhong; Zhang, Zhe-Min; Li, Bing; Zhao, Lan; Xu, Liyun

    2016-01-01

    The aim of the study was to investigate the resistant mechanisms and homology of imipenem-resistant Acinetobacter baumannii (A. baumannii). A total of 46 non-duplicate imipenem-resistant A. baumannii clinical isolates were collected from three tertiary hospitals between July, 2011 and June, 2012. The minimal inhibitory concentrations (MICs) of antimicrobial agents were determined using the agar dilution method. Phenylalanine-arginine β-naphthylamide was used to detect the presence of the efflux pump-mediated resistant mechanism. Polymerase chain reaction was employed to amplify genes associated with drug resistance, including β-lactamase genes, efflux pump genes and outer membrane protein gene CarO. A few amplicons were randomly selected and sequenced. Multilocus sequence analysis (MLST) was employed in typing A. baumanni. A. baumannii was resistant to imipenem, simultaneously showing resistance to several other antimicrobials. In addition, 13 A. baumannii were found to mediate drug resistance through operation of the efflux pump. Of the various drug resistance genes tested, blaOXA-51 was present in 46 isolates, blaOXA-23 gene was present in 44 isolates and blaNDM gene was found in only one strain. Other drug resistant-associated genes, including blaKPC, blaIMP, blaOXA-24, blaOXA-58, blaSHV, blaGIM and blaVIM were not detected. Mutation of adeS and outer membrane protein gene CarO were found in a few of the imipenem-resistant isolates. The MLST analysis revealed that all 46 clinical isolates were clustered into 11 genotypes and the most frequent genotype was ST208. In conclusion, β-lactamase genes, genes involved in efflux pump and mutation of outer membrane protein encoding gene may be important in mediating imipenem resistance in A. baumannii. Of the 11 different genotypes, ST11 was shared by the majority of A. baumannii, which may be due to horizontal transfer of patients from hospitals. PMID:27485638

  14. Characterization of Spectinomycin Resistance in Streptococcus suis Leads to Two Novel Insights into Drug Resistance Formation and Dissemination Mechanism.

    PubMed

    Huang, Kaisong; Zhang, Qiang; Song, Yajing; Zhang, Zhewen; Zhang, Anding; Xiao, Jingfa; Jin, Meilin

    2016-10-01

    Spectinomycin is an aminocyclitol antibiotic used clinically to treat a variety of infections in animals. Here, we characterized drug resistance prevalence in clinical Streptococcus suis isolates and discovered a novel resistance mechanism in which the s5 mutation (Gly26Asp) results in high spectinomycin resistance. Additionally, a novel integrative and conjugative element encompassing a multidrug resistance spw_like-aadE-lnu(B)-lsa(E) cluster and a cadmium resistance operon were identified, suggesting a possible cause for the wide dissemination of spectinomycin resistance in S. suis.

  15. MECHANISMS OF ACQUIRED RESISTANCE IN MOUSE TYPHOID

    PubMed Central

    Blanden, R. V.; Mackaness, G. B.; Collins, F. M.

    1966-01-01

    Experiments in vitro comparing normal mouse peritoneal macrophages with cells from Salmonella typhimurium-infected mice have shown that the "immune" macrophages have conspicuously enhanced microbicidal properties. Whereas normal macrophages could inactivate only 50 to 60% of intracellular S. typhimurium pretreated with immune serum, cells from infected animals killed virtually all ingested organisms and did so at an accelerated rate. Macrophages from Listeria monocytogenes-infected mice were shown to possess similarly enhanced microbicidal activity against S. typhimurium. Furthermore, the growth of S. typhimurium in the liver and spleen was more effectively restricted in Listeria-infected mice than in animals vaccinated with heat-killed S. typhimurium, even though the Listeria-infected animals possessed no demonstrable cross-reacting antibody to S. typhimurium. The lack of resistance in the mice vaccinated with heat-killed organisms could not be attributed to any deficiency of humoral factors, since the serum from these animals was as effective at promoting phagocytosis and killing by macrophages as serum from actively infected (and demonstrably resistant) mice. Conversely, Salmonella-infected mice were totally resistant to intravenous challenge with L. monocytogenes. The level of resistance in individual animals was related to the numbers of residual Salmonellae remaining in the tissues; mice with heavier residual infections being the more resistant. Specific antiserum from mice vaccinated with heat-killed S. typhimurium was found to be significantly protective only when the intraperitoneal route of challenge was employed. The foregoing studies have been interpreted to mean that enhancement of the microbicidal ability of macrophages is the mechanism of major importance in acquired resistance to S. typhimurium infection in mice. PMID:4958757

  16. Metal Additive Manufacturing: A Review of Mechanical Properties

    NASA Astrophysics Data System (ADS)

    Lewandowski, John J.; Seifi, Mohsen

    2016-07-01

    This article reviews published data on the mechanical properties of additively manufactured metallic materials. The additive manufacturing techniques utilized to generate samples covered in this review include powder bed fusion (e.g., EBM, SLM, DMLS) and directed energy deposition (e.g., LENS, EBF3). Although only a limited number of metallic alloy systems are currently available for additive manufacturing (e.g., Ti-6Al-4V, TiAl, stainless steel, Inconel 625/718, and Al-Si-10Mg), the bulk of the published mechanical properties information has been generated on Ti-6Al-4V. However, summary tables for published mechanical properties and/or key figures are included for each of the alloys listed above, grouped by the additive technique used to generate the data. Published values for mechanical properties obtained from hardness, tension/compression, fracture toughness, fatigue crack growth, and high cycle fatigue are included for as-built, heat-treated, and/or HIP conditions, when available. The effects of test orientation/build direction on properties, when available, are also provided, along with discussion of the potential source(s) (e.g., texture, microstructure changes, defects) of anisotropy in properties. Recommendations for additional work are also provided.

  17. Mechanical Properties of Austenitic Stainless Steel Made by Additive Manufacturing.

    PubMed

    Luecke, William E; Slotwinski, John A

    2014-01-01

    Using uniaxial tensile and hardness testing, we evaluated the variability and anisotropy of the mechanical properties of an austenitic stainless steel, UNS S17400, manufactured by an additive process, selective laser melting. Like wrought materials, the mechanical properties depend on the orientation introduced by the processing. The recommended stress-relief heat treatment increases the tensile strength, reduces the yield strength, and decreases the extent of the discontinuous yielding. The mechanical properties, assessed by hardness, are very uniform across the build plate, but the stress-relief heat treatment introduced a small non-uniformity that had no correlation to position on the build plate. Analysis of the mechanical property behavior resulted in four conclusions. (1) The within-build and build-to-build tensile properties of the UNS S17400 stainless steel are less repeatable than mature engineering structural alloys, but similar to other structural alloys made by additive manufacturing. (2) The anisotropy of the mechanical properties of the UNS S17400 material of this study is larger than that of mature structural alloys, but is similar to other structural alloys made by additive manufacturing. (3) The tensile mechanical properties of the UNS S17400 material fabricated by selective laser melting are very different from those of wrought, heat-treated 17-4PH stainless steel. (4) The large discontinuous yielding strain in all tests resulted from the formation and propagation of Lüders bands.

  18. Mechanical Properties of Austenitic Stainless Steel Made by Additive Manufacturing

    PubMed Central

    Luecke, William E; Slotwinski, John A

    2014-01-01

    Using uniaxial tensile and hardness testing, we evaluated the variability and anisotropy of the mechanical properties of an austenitic stainless steel, UNS S17400, manufactured by an additive process, selective laser melting. Like wrought materials, the mechanical properties depend on the orientation introduced by the processing. The recommended stress-relief heat treatment increases the tensile strength, reduces the yield strength, and decreases the extent of the discontinuous yielding. The mechanical properties, assessed by hardness, are very uniform across the build plate, but the stress-relief heat treatment introduced a small non-uniformity that had no correlation to position on the build plate. Analysis of the mechanical property behavior resulted in four conclusions. (1) The within-build and build-to-build tensile properties of the UNS S17400 stainless steel are less repeatable than mature engineering structural alloys, but similar to other structural alloys made by additive manufacturing. (2) The anisotropy of the mechanical properties of the UNS S17400 material of this study is larger than that of mature structural alloys, but is similar to other structural alloys made by additive manufacturing. (3) The tensile mechanical properties of the UNS S17400 material fabricated by selective laser melting are very different from those of wrought, heat-treated 17-4PH stainless steel. (4) The large discontinuous yielding strain in all tests resulted from the formation and propagation of Lüders bands. PMID:26601037

  19. Mechanical Properties of Austenitic Stainless Steel Made by Additive Manufacturing.

    PubMed

    Luecke, William E; Slotwinski, John A

    2014-01-01

    Using uniaxial tensile and hardness testing, we evaluated the variability and anisotropy of the mechanical properties of an austenitic stainless steel, UNS S17400, manufactured by an additive process, selective laser melting. Like wrought materials, the mechanical properties depend on the orientation introduced by the processing. The recommended stress-relief heat treatment increases the tensile strength, reduces the yield strength, and decreases the extent of the discontinuous yielding. The mechanical properties, assessed by hardness, are very uniform across the build plate, but the stress-relief heat treatment introduced a small non-uniformity that had no correlation to position on the build plate. Analysis of the mechanical property behavior resulted in four conclusions. (1) The within-build and build-to-build tensile properties of the UNS S17400 stainless steel are less repeatable than mature engineering structural alloys, but similar to other structural alloys made by additive manufacturing. (2) The anisotropy of the mechanical properties of the UNS S17400 material of this study is larger than that of mature structural alloys, but is similar to other structural alloys made by additive manufacturing. (3) The tensile mechanical properties of the UNS S17400 material fabricated by selective laser melting are very different from those of wrought, heat-treated 17-4PH stainless steel. (4) The large discontinuous yielding strain in all tests resulted from the formation and propagation of Lüders bands. PMID:26601037

  20. Resistant mechanisms to BRAF inhibitors in melanoma

    PubMed Central

    Layos, Laura; Bugés, Cristina; de los Llanos Gil, María; Vila, Laia; Martínez-Balibrea, Eva; Martínez-Cardús, Anna

    2016-01-01

    Patients with advanced melanoma have traditionally had very poor prognosis. However, since 2011 better understanding of the biology and epidemiology of this disease has revolutionized its treatment, with newer therapies becoming available. These newer therapies can be classified into immunotherapy and targeted therapy. The immunotherapy arsenal includes inhibitors of CTLA4, PD-1 and PDL-1, while targeted therapy focuses on BRAF and MEK. BRAF inhibitors (vemurafenib, dabrafenib) have shown benefit in terms of overall survival (OS) compared to chemotherapy, and their combination with MEK inhibitors has recently been shown to improve progression-free survival (PFS), compared with monotherapy with BRAF inhibitors. However, almost 20% of patients initially do not respond, due to intrinsic resistance to therapy and, of those who do, most eventually develop mechanisms of acquired resistance, including reactivation of the MAP kinase pathway, persistent activation of receptor tyrosine kinase (RTKS) receptor, activation of phosphatidyinositol-3OH kinase, overexpression of epidermal growth factor receptor (EGFR), and interactions with the tumor microenvironment. Herein we comment in detail on mechanisms of resistance to targeted therapy and discuss the strategies to overcome them. PMID:27429963

  1. The Effect of Silicon and Aluminum Additions on the Oxidation Resistance of Lean Chromium Stainless Steels

    SciTech Connect

    Dunning, J.S.; Alman, D.E.; Rawers, J.C.

    2001-09-01

    The effect of Si and Al additions on the oxidation of lean chromium austenitic stainless steels has been studied. A baseline composition of Fe-16Cr-16Ni-2Mn-1Mo was selected to allow combined Si and Al additions of up to 5 wt. pct. in a fully austenitic alloy. The baseline composition was selected using a net Cr equivalent equation to predict the onset of G-ferrite formation in austenite. Cyclic oxidation tests in air for 1000 hours were carried out on alloys with Si only or combined Si and Al additions in the temperature range 700 C to 800 C. Oxidation resistance of alloys with Si only additions were outstanding, particularly at 800 C. It was evident that different rate controlling mechanisms for oxidation were operative at 700 C and 800 C in the Si alloys. In addition, Si alloys pre-oxidized at 800 C, showed a zero weight gain in subsequent testing for 1000 hours at 700 C. The rate controlling mechanism in alloys with combined Si and Al addition for oxidation at 800 C was also different than alloys with Si only. SEM and ESCA analysis of the oxide films and base material at the oxide/base metal interface were conducted to study potential rate controlling mechanisms.

  2. Recognition of mechanisms involved in bile resistance important to halting antimicrobial resistance in nontyphoidal Salmonella.

    PubMed

    Tsai, Ming-Han; Wu, Sih-Ru; Lee, Hao-Yuan; Chen, Chyi-Liang; Lin, Tzou-Yien; Huang, Yhu-Chering; Chiu, Cheng-Hsun

    2012-08-01

    Increasing antimicrobial resistance in nontyphoidal Salmonella (NTS) is a global public health problem that complicates antimicrobial therapy. As an enteric pathogen, Salmonella must endure the presence of bile in the intestinal tract during the course of infection. In this study, we sought to identify Salmonella genes necessary for bile resistance and to investigate their association with antimicrobial resistance. Four genes related to bile resistance were identified, namely rfaP, rfbK, dam and tolC. The first three genes are involved in lipopolysaccharide synthesis, and tolC is associated with an efflux pump. Antimicrobial susceptibility testing showed increased susceptibility to polymyxin B and ciprofloxacin in rfaP and tolC mutants of Salmonella, respectively. Genetic analysis of 45 clinical isolates of NTS revealed that all isolates with reduced susceptibility to fluoroquinolones (minimum inhibitory concentration ≥0.125 mg/L) were associated with point mutations in the quinolone resistance-determining regions of the gyrA and parC genes. The efflux pump also played a role, as evidenced by the reduction in fluoroquinolone resistance when the TolC efflux pump was inhibited by Phe-Arg-β-naphthylamide, a competitive efflux pump inhibitor. Based on these results, we conclude that an intact membrane structure and the efflux pump system provide mechanisms enabling NTS to resist bile. Caution should be taken when using ciprofloxacin and polymyxin B to treat Salmonella enteric infection, as resistance to these agents involves the same mechanisms. Addition of an efflux pump inhibitor to fluoroquinolones may be an effective strategy to deal with the increasing resistance in NTS.

  3. Analysis and modeling of resistive switching mechanisms oriented to resistive random-access memory

    NASA Astrophysics Data System (ADS)

    Huang, Da; Wu, Jun-Jie; Tang, Yu-Hua

    2013-03-01

    With the progress of the semiconductor industry, the resistive random-access memory (RAM) has drawn increasing attention. The discovery of the memristor has brought much attention to this study. Research has focused on the resistive switching characteristics of different materials and the analysis of resistive switching mechanisms. We discuss the resistive switching mechanisms of different materials in this paper and analyze the differences of those mechanisms from the view point of circuitry to establish their respective circuit models. Finally, simulations are presented. We give the prospect of using different materials in resistive RAM on account of their resistive switching mechanisms, which are applied to explain their resistive switchings.

  4. The multixenobiotic resistance mechanism in aquatic organisms

    SciTech Connect

    Kurelec, B. )

    1992-01-01

    Many aquatic organisms thrive and reproduce in polluted waters. This fact indicates that they are well equipped with a defense system(s) against several toxic xenobiotics simultaneously because water pollution is typically caused by a mixture of a number of pollutants. We have found that the biochemical mechanism underlying such multixenobiotic' resistance in freshwater and marine mussel, in several marine sponges, and in freshwater fish is similar to the mechanism of multidrug resistance (MDR) found in tumor cells that became refractory to treatment with a variety of chemotherapeutic agents. All these organisms possess a verapamil-sensitive potential to bind 2-acetylaminofluorene and vincristine onto membrane vesicles. They all express mRNA for mdr1 gene, and mdr1 protein product, the glycoprotein P170. Finally, in in vivo experiments, the accumulation of xenobiotics is enhanced in all investigated organisms in the presence of verapamil, the inhibitor of the P170 extrusion pump. The knowledge that the presence of one xenobiotic may block the pumping out, and hence accelerating accumulation, of others, may help us to understand and interpret our present and past data on different environmental parameters obtained using indicator organisms.99 references.

  5. Antimicrobial Peptide Resistance Mechanisms of Gram-Positive Bacteria

    PubMed Central

    Nawrocki, Kathryn L.; Crispell, Emily K.; McBride, Shonna M.

    2014-01-01

    Antimicrobial peptides, or AMPs, play a significant role in many environments as a tool to remove competing organisms. In response, many bacteria have evolved mechanisms to resist these peptides and prevent AMP-mediated killing. The development of AMP resistance mechanisms is driven by direct competition between bacterial species, as well as host and pathogen interactions. Akin to the number of different AMPs found in nature, resistance mechanisms that have evolved are just as varied and may confer broad-range resistance or specific resistance to AMPs. Specific mechanisms of AMP resistance prevent AMP-mediated killing against a single type of AMP, while broad resistance mechanisms often lead to a global change in the bacterial cell surface and protect the bacterium from a large group of AMPs that have similar characteristics. AMP resistance mechanisms can be found in many species of bacteria and can provide a competitive edge against other bacterial species or a host immune response. Gram-positive bacteria are one of the largest AMP producing groups, but characterization of Gram-positive AMP resistance mechanisms lags behind that of Gram-negative species. In this review we present a summary of the AMP resistance mechanisms that have been identified and characterized in Gram-positive bacteria. Understanding the mechanisms of AMP resistance in Gram-positive species can provide guidelines in developing and applying AMPs as therapeutics, and offer insight into the role of resistance in bacterial pathogenesis. PMID:25419466

  6. A molecular mechanism of artemisinin resistance in Plasmodium falciparum malaria.

    PubMed

    Mbengue, Alassane; Bhattacharjee, Souvik; Pandharkar, Trupti; Liu, Haining; Estiu, Guillermina; Stahelin, Robert V; Rizk, Shahir S; Njimoh, Dieudonne L; Ryan, Yana; Chotivanich, Kesinee; Nguon, Chea; Ghorbal, Mehdi; Lopez-Rubio, Jose-Juan; Pfrender, Michael; Emrich, Scott; Mohandas, Narla; Dondorp, Arjen M; Wiest, Olaf; Haldar, Kasturi

    2015-04-30

    Artemisinins are the cornerstone of anti-malarial drugs. Emergence and spread of resistance to them raises risk of wiping out recent gains achieved in reducing worldwide malaria burden and threatens future malaria control and elimination on a global level. Genome-wide association studies (GWAS) have revealed parasite genetic loci associated with artemisinin resistance. However, there is no consensus on biochemical targets of artemisinin. Whether and how these targets interact with genes identified by GWAS, remains unknown. Here we provide biochemical and cellular evidence that artemisinins are potent inhibitors of Plasmodium falciparum phosphatidylinositol-3-kinase (PfPI3K), revealing an unexpected mechanism of action. In resistant clinical strains, increased PfPI3K was associated with the C580Y mutation in P. falciparum Kelch13 (PfKelch13), a primary marker of artemisinin resistance. Polyubiquitination of PfPI3K and its binding to PfKelch13 were reduced by the PfKelch13 mutation, which limited proteolysis of PfPI3K and thus increased levels of the kinase, as well as its lipid product phosphatidylinositol-3-phosphate (PI3P). We find PI3P levels to be predictive of artemisinin resistance in both clinical and engineered laboratory parasites as well as across non-isogenic strains. Elevated PI3P induced artemisinin resistance in absence of PfKelch13 mutations, but remained responsive to regulation by PfKelch13. Evidence is presented for PI3P-dependent signalling in which transgenic expression of an additional kinase confers resistance. Together these data present PI3P as the key mediator of artemisinin resistance and the sole PfPI3K as an important target for malaria elimination.

  7. A molecular mechanism of artemisinin resistance in Plasmodium falciparum malaria

    PubMed Central

    Mbengue, Alassane; Bhattacharjee, Souvik; Pandharkar, Trupti; Liu, Haining; Estiu, Guillermina; Stahelin, Robert V.; Rizk, Shahir; Njimoh, Dieudonne L.; Ryan, Yana; Chotivanich, Kesinee; Nguon, Chea; Ghorbal, Mehdi; Lopez-Rubio, Jose-Juan; Pfrender, Michael; Emrich, Scott; Mohandas, Narla; Dondorp, Arjen M.; Wiest, Olaf; Haldar, Kasturi

    2015-01-01

    Artemisinins are the corner stone of anti-malarial drugs1. Emergence and spread of resistance to them2–4 raises risk of wiping out recent gains achieved in reducing world-wide malaria burden and threatens future malaria control and elimination on a global level. Genome wide association studies (GWAS) have revealed parasite genetic loci associated with artemisinin resistance5–10. However, there is no consensus on biochemical targets of artemisinin. Whether and how these targets interact with genes identified by GWAS, remains unknown. Here we provide biochemical and cellular evidence that artemisinins are potent inhibitors of Plasmodium falciparum phosphatidylinositol-3-kinase (PfPI3K), revealing an unexpected mechanism of action. In resistant clinical strains, increased PfPI3K was associated with the C580Y mutation in P. falciparum Kelch13 (PfKelch13), a primary marker of artemisinin resistance. Polyubiquitination of PfPI3K and its binding to PfKelch13 were reduced by PfKelch13 mutation, which limited proteolysis of PfPI3K and thus increased levels of the kinase as well as its lipid product phosphatidylinositol 3-phosphate (PI3P). We find PI3P levels to be predictive of artemisinin resistance in both clinical and engineered laboratory parasites as well as across non-isogenic strains. Elevated PI3P induced artemisinin resistance in absence of PfKelch13 mutations, but remained responsive to regulation by PfKelch13. Evidence is presented for PI3P-dependent signaling, where transgenic expression of an additional kinase confers resistance. Together these data present PI3P as the key mediator of artemisinin resistance and the sole PfPI3K as an important target for malaria elimination. PMID:25874676

  8. Bile resistance mechanisms in Lactobacillus and Bifidobacterium

    PubMed Central

    Ruiz, Lorena; Margolles, Abelardo; Sánchez, Borja

    2013-01-01

    Probiotics are live microorganisms which when administered in adequate amounts confer a health benefit on the host. Most of the probiotic bacteria currently available in the market belong to the genera Lactobacillus and Bifidobacterium, and specific health-promoting activities, such as treatment of diarrhea or amelioration of gastrointestinal discomfort, have been attributed to them. In order to be able to survive the gastrointestinal transit and transiently colonize our gut, these bacteria must be able to counteract the deleterious action of bile salts, which are the main components of bile. Bile salts are detergent-like biological substances synthesized in the liver from cholesterol. Host enzymes conjugate the newly synthesized free bile acids in the liver with the amino acids glycine or taurine, generating conjugated bile salts. These compounds are stored in the gall bladder and they are released into the duodenum during digestion to perform their physiological function, which is the solubilization of fat coming from diet. These bile salts possess strong antimicrobial activity, since they are able to disorganize the structure of the cell membrane, as well as trigger DNA damage. This means that bacteria inhabiting our intestinal tract must have intrinsic resistance mechanisms to cope with bile salts. To do that, Lactobacillus and Bifidobacterium display a variety of proteins devoted to the efflux of bile salts or protons, to modify sugar metabolism or to prevent protein misfolding. In this manuscript, we review and discuss specific bile resistance mechanisms, as well as the processes responsible for the adaptation of bifidobacteria and lactobacilli to bile. PMID:24399996

  9. Characterization of resistance mechanisms to powdery mildew (Erysiphe betae) in beet (Beta vulgaris).

    PubMed

    Fernández-Aparicio, Mónica; Prats, Elena; Emeran, Amero A; Rubiales, Diego

    2009-04-01

    Beet powdery mildew incited by Erysiphe betae is a serious foliar fungal disease of worldwide distribution causing losses of up to 30%. In the present work, we searched for resistance in a germplasm collection of 184 genotypes of Beta vulgaris including fodder (51 genotypes), garden (60 genotypes), leaf (51 genotypes), and sugar (22 genotypes) beet types. Resistant genotypes were identified in the four beet types under study. In addition, mechanisms underlying resistance were dissected through histological studies. These revealed different resistance mechanisms acting at different fungal developmental stages, i.e., penetration resistance, early and late cell death, or posthaustorial resistance. Most genotypes were able to hamper fungal development at several stages. The later are interesting for breeding aiming to resistance durability. Furthermore, characterization of defense mechanisms will be useful for further cellular and molecular studies to unravel the bases of resistance in this species.

  10. Oxidation resistance of selected mechanical carbons at 650 deg C in dry flowing air

    NASA Technical Reports Server (NTRS)

    Allen, G. P.; Wisander, D. W.

    1973-01-01

    Oxidation experiments were conducted with several experimental mechanical carbons at 650 C in air flowing at 28 cu cm/sec (STP). Experiments indicate that boron carbide addition and zinc phosphate treatment definitely improved oxidation resistance. Impregnation with coal tar pitch before final graphitization had some beneficial effect on oxidation resistance and it markedly improved flexure strength and hardness. Graphitization temperature alone did not affect oxidation resistance, but with enough added boron carbide the oxidation resistance was increased although the hardness greatly decreased.

  11. Insecticides resistance in the Culex quinquefasciatus populations from northern Thailand and possible resistance mechanisms.

    PubMed

    Yanola, Jintana; Chamnanya, Saowanee; Lumjuan, Nongkran; Somboon, Pradya

    2015-09-01

    The mosquito vector Culex quinquefasciatus is known to be resistant to insecticides worldwide, including Thailand. This study was the first investigation of the insecticide resistance mechanisms, involving metabolic detoxification and target site insensitivity in C. quinquefasciatus from Thailand. Adult females reared from field-caught larvae from six provinces of northern Thailand were determined for resistant status by exposing to 0.05% deltamethrin, 0.75% permethrin and 5% malathion papers using the standard WHO susceptibility test. The overall mortality rates were 45.8%, 11.4% and 80.2%, respectively. A fragment of voltage-gated sodium channel gene was amplified and sequenced to identify the knock down resistance (kdr) mutation. The ace-1 gene mutation was determined by using PCR-RFLP. The L1014F kdr mutation was observed in all populations, but the homozygous mutant F/F1014 genotype was found only in two of the six provinces where the kdr mutation was significantly correlated with deltamethrin resistance. However, none of mosquitoes had the G119S mutation in the ace-1 gene. A laboratory deltamethrin resistant strain, Cq_CM_R, has been established showing a highly resistant level after selection for a few generations. The mutant F1014 allele frequency was significantly increased after one generation of selection. A synergist assay was performed to assess the metabolic detoxifying enzymes. Addition of bis(4-nitrophenyl)-phosphate (BNPP) and diethyl maleate (DEM), inhibitors of esterases and glutathione S-transferases (GST), respectively, into the larval bioassay of the Cq_CM strain with deltamethrin showed no significant reduction. By contrast, addition of piperonyl butoxide (PBO), an inhibitor of cytochrome P450 monooxygenases, showed a 9-fold reduction of resistance. Resistance to pyrethroids in C. quinquefasciatus is widely distributed in northern Thailand. This study reports for the first time for the detection of the L1014F kdr mutation in wild populations

  12. Corrosion resistance and mechanical properties of alloy 803 for heat resisting applications

    SciTech Connect

    Ganesan, P.; Tassen, C.S.

    1997-08-01

    Alloy 803 was developed for applications as straight and twisted ID finned tubing in the petrochemical and chemical process industries, such as ethylene pyrolysis, that require enhanced resistance to oxidation and carburization in addition to adequate stress rupture strength. This paper presents the mechanical properties characterized for the alloy produced in other forms, such as plate, sheet and bar products, for applications in the heat treatment, chemical and petrochemical industries. The mechanical properties covered include room and high temperature tensile test results, impact strength, creep and stress rupture data for temperatures up to 2,000 F (1,093 C) at various stress levels. The preliminary results of the room and high temperature tensile and impact properties after long term exposures at intermediate temperatures are also presented. In addition to mechanical properties, the corrosion performance of alloy 803 in oxidation, sulfidation and carburization environments are presented.

  13. Mechanical and Thermal Characterization of Ultrasonic Additive Manufacturing

    NASA Astrophysics Data System (ADS)

    Foster, Daniel R.

    Additive manufacturing is an emerging production technology used to create net shaped 3-D objects from a digital model. Ultrasonic Additive Manufacturing (UAM) is a relatively new type of additive manufacturing that uses ultrasonic energy to sequentially bond layers of metal foils at temperatures much lower than the melting temperature of the material. Constructing metal structures without melting allows UAM to have distinct advantages over beam based additive manufacturing and other traditional manufacturing processes. This is because solidification defects can be avoided, structures can be composed of dissimilar material and secondary materials (both metallic and non-metallic) can be successfully embedded into the metal matrix. These advantages allow UAM to have tremendous potential to create metal matrix composite structures that cannot be built using any other manufacturing technique. Although UAM has tremendous engineering potential, the effect of interfacial bonding defects on the mechanical and thermal properties have not be characterized. Incomplete interfacial bonding at the laminar surfaces due to insufficient welding energy can result in interfacial voids. Voids create discontinuities in the structure which change the mechanical and thermal properties of the component, resulting in a structure that has different properties than the monolithic material used to create it. In-situ thermal experiments and thermal modeling demonstrates that voids at partially bonded interfaces significantly affected heat generation and thermal conductivity in. UAM parts during consolidation as well as in the final components. Using ultrasonic testing, elastic properties of UAM structures were found to be significantly reduced due to the presence of voids, with the reduction being the most severe in the transverse (foil staking) direction. Elastic constants in all three material directions decreased linearly with a reduction in the interfacial bonded area. The linear trend

  14. Embryo mechanics: balancing force production with elastic resistance during morphogenesis.

    PubMed

    Davidson, Lance A

    2011-01-01

    Morphogenesis requires the spatial and temporal control of embryo mechanics, including force production and mechanical resistance to those forces, to coordinate tissue deformation and large-scale movements. Thus, biomechanical processes play a key role in directly shaping the embryo. Additional roles for embryo mechanics during development may include the patterning of positional information and to provide feedback to ensure the success of morphogenetic movements in shaping the larval body and organs. To understand the multiple roles of mechanics during development requires familiarity with engineering principles of the mechanics of structures, the viscoelastic properties of biomaterials, and the integration of force and stress within embryonic structures as morphogenesis progresses. In this chapter, we review the basic engineering principles of biomechanics as they relate to morphogenesis, introduce methods for quantifying embryo mechanics and the limitations of these methods, and outline a formalism for investigating the role of embryo mechanics in birth defects. We encourage the nascent field of embryo mechanics to adopt standard engineering terms and test methods so that studies of diverse organisms can be compared and universal biomechanical principles can be revealed.

  15. Mechanical characterisation of additively manufactured material having lattice microstructure

    NASA Astrophysics Data System (ADS)

    Cuan-Urquizo, E.; Yang, S.; Bhaskar, A.

    2015-02-01

    Many natural and engineered structures possess cellular and porous architecture. This paper is focused on the mechanical characterisation of additively manufactured lattice structures. The lattice consists of a stack of polylactic acid (PLA) filaments in a woodpile arrangement fabricated using a fused deposition modelling 3D printer. Some of the most promising applications of this 3D lattice material of this type include scaffolds for tissue engineering and the core for sandwich panels. While there is a significant body of work concerning the manufacture of such lattice materials, attempts to understand their mechanical properties are very limited. This paper brings together manufacturing with the need to understand the structure-property relationship for this class of materials. In order to understand the elastic response of the PLA-based lattice structures obtained from the fused deposition modelling process, single filaments manufactured using the same process were experimentally characterised first. The single PLA filaments were manufactured under different temperatures. These filaments were then characterised by using tensile testing. The stress-strain curves are presented. The variability of the measured results is discussed. The measured properties are then taken as input to a finite element model of the lattice material. This model uses simple one-dimensional elements in conjunction with a novel method achieving computational economy which precludes the use of fine meshes. Using this novel model, the apparent elastic modulus of lattice along the filaments has been obtained and is presented in this paper.

  16. Bioinspired Cellular Structures: Additive Manufacturing and Mechanical Properties

    NASA Astrophysics Data System (ADS)

    Stampfl, J.; Pettermann, H. E.; Liska, R.

    Biological materials (e.g., wood, trabecular bone, marine skeletons) rely heavily on the use of cellular architecture, which provides several advantages. (1) The resulting structures can bear the variety of "real life" load spectra using a minimum of a given bulk material, featuring engineering lightweight design principles. (2) The inside of the structures is accessible to body fluids which deliver the required nutrients. (3) Furthermore, cellular architectures can grow organically by adding or removing individual struts or by changing the shape of the constituting elements. All these facts make the use of cellular architectures a reasonable choice for nature. Using additive manufacturing technologies (AMT), it is now possible to fabricate such structures for applications in engineering and biomedicine. In this chapter, we present methods that allow the 3D computational analysis of the mechanical properties of cellular structures with open porosity. Various different cellular architectures including disorder are studied. In order to quantify the influence of architecture, the apparent density is always kept constant. Furthermore, it is shown that how new advanced photopolymers can be used to tailor the mechanical and functional properties of the fabricated structures.

  17. Mechanism of suppression of piperacillin resistance in enterobacteria by tazobactam.

    PubMed Central

    Kadima, T A; Weiner, J H

    1997-01-01

    Resistance to piperacillin in several isolates of Citrobacter freundii and Enterobacter cloacae was investigated and confirmed to occur at a frequency of 10(-7) to 10(-6). Development of resistance to piperacillin was significantly suppressed by tazobactam but not by clavulanic acid. To elucidate the mechanism by which resistance suppression occurs, the effect of piperacillin plus tazobactam on the induction of AmpC beta-lactamase was analyzed by monitoring the beta-galactosidase activity of an inducible ampC-lacZ gene fusion in Escherichia coli. The combination exerted no inhibitory effect on AmpC beta-lactamase induction. Tazobactam also had no effect on the accumulation of a key intermediate in the AmpC beta-lactamase induction pathway, 1,6-anhydromurotripeptide, in an ampD mutant strain of E. coli. However, the addition of tazobactam to liquid cultures of E. cloacae 40001 in the presence of piperacillin at four times the MIC caused a delay in the recovery of the culture to piperacillin-induced stress. At 16 times the MIC, a complete suppression of regrowth occurred. Analysis of culture viability on piperacillin plates showed that the culture recovery was due to growth by moderately resistant mutants preexisting in the cell population, which at 16 times the MIC became susceptible to the combination. Evidence from the kinetics of inhibition of the E. cloacae 40001 AmpC beta-lactamase by clavulanic acid, sulbactam, and tazobactam and from the effects of these drugs on the frequency of resistance to piperacillin suggests that the suppressive effect of tazobactam on the appearance of resistance is primarily mediated by the beta-lactamase inhibitory activity. PMID:9333044

  18. Mechanisms of Resistance to Aminoglycoside Antibiotics: Overview and Perspectives

    PubMed Central

    Garneau-Tsodikova, Sylvie

    2015-01-01

    Aminoglycoside (AG) antibiotics are used to treat many Gram-negative and some Gram-positive infections and, importantly, multidrug-resistant tuberculosis. Among various bacterial species, resistance to AGs arises through a variety of intrinsic and acquired mechanisms. The bacterial cell wall serves as a natural barrier for small molecules such as AGs and may be further fortified via acquired mutations. Efflux pumps work to expel AGs from bacterial cells, and modifications here too may cause further resistance to AGs. Mutations in the ribosomal target of AGs, while rare, also contribute to resistance. Of growing clinical prominence is resistance caused by ribosome methyltransferases. By far the most widespread mechanism of resistance to AGs is the inactivation of these antibiotics by AG-modifying enzymes. We provide here an overview of these mechanisms by which bacteria become resistant to AGs and discuss their prevalence and potential for clinical relevance. PMID:26877861

  19. Experimental Induction of Bacterial Resistance to the Antimicrobial Peptide Tachyplesin I and Investigation of the Resistance Mechanisms.

    PubMed

    Hong, Jun; Hu, Jianye; Ke, Fei

    2016-10-01

    Tachyplesin I is a 17-amino-acid cationic antimicrobial peptide (AMP) with a typical cyclic antiparallel β-sheet structure that is a promising therapeutic for infections, tumors, and viruses. To date, no bacterial resistance to tachyplesin I has been reported. To explore the safety of tachyplesin I as an antibacterial drug for wide clinical application, we experimentally induced bacterial resistance to tachyplesin I by using two selection procedures and studied the preliminary resistance mechanisms. Aeromonas hydrophila XS91-4-1, Pseudomonas aeruginosa CGMCC1.2620, and Escherichia coli ATCC 25922 and F41 showed resistance to tachyplesin I under long-term selection pressure with continuously increasing concentrations of tachyplesin I. In addition, P. aeruginosa and E. coli exhibited resistance to tachyplesin I under UV mutagenesis selection conditions. Cell growth and colony morphology were slightly different between control strains and strains with induced resistance. Cross-resistance to tachyplesin I and antimicrobial agents (cefoperazone and amikacin) or other AMPs (pexiganan, tachyplesin III, and polyphemusin I) was observed in some resistant mutants. Previous studies showed that extracellular protease-mediated degradation of AMPs induced bacterial resistance to AMPs. Our results indicated that the resistance mechanism of P. aeruginosa was not entirely dependent on extracellular proteolytic degradation of tachyplesin I; however, tachyplesin I could induce increased proteolytic activity in P. aeruginosa Most importantly, our findings raise serious concerns about the long-term risks associated with the development and clinical use of tachyplesin I.

  20. 75 FR 44881 - Black Stem Rust; Additions of Rust-Resistant Varieties

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-30

    .... (See 75 FR 29191-29193.) The direct final rule notified the public of our intention to amend the black stem rust quarantine and regulations by adding 21 varieties to the list of rust-resistant Berberis... Inspection Service 7 CFR Part 301 Black Stem Rust; Additions of Rust-Resistant Varieties AGENCY: Animal...

  1. What have the mechanisms of resistance to glyphosate taught us?

    PubMed

    Shaner, Dale L; Lindenmeyer, Richard Bradley; Ostlie, Michael H

    2012-01-01

    The intensive use of glyphosate alone to manage weeds has selected populations that are glyphosate resistant. The three mechanisms of glyphosate resistance that have been elucidated are (1) target-site mutations, (2) gene amplification and (3) altered translocation due to sequestration. What have we learned from the selection of these mechanisms, and how can we apply those lessons to future herbicide-resistant crops and new mechanisms of action? First, the diversity of glyphosate resistance mechanisms has helped further our understanding of the mechanism of action of glyphosate and advanced our knowledge of plant physiology. Second, the relatively rapid evolution of glyphosate-resistant weed populations provides further evidence that no herbicide is invulnerable to resistance. Third, as new herbicide-resistant crops are developed and new mechanisms of action are discovered, the weed science community needs to ensure that we apply the lessons we have learned on resistance management from the experience with glyphosate. Every new weed management system must be evaluated during development for its potential to select for resistance, and stewardship programs should be in place when the new program is introduced.

  2. Process for improving moisture resistance of epoxy resins by addition of chromium ions

    NASA Technical Reports Server (NTRS)

    St.clair, A. K.; Stoakley, D. M.; St.clair, T. L.; Singh, J. J. (Inventor)

    1985-01-01

    A process for improving the moisture resistance properties of epoxidized TGMDA and DGEBA resin system by chemically incorporating chromium ions is described. The addition of chromium ions is believed to prevent the absorption of water molecules.

  3. Effect of chlorine purification on oxidation resistance of some mechanical carbons

    NASA Technical Reports Server (NTRS)

    Wisander, D. W.; Allen, G. P.

    1974-01-01

    Oxidation experiments were conducted with some experimental and commercial mechanical carbons at 650 C in dry air flowing at 28 cc/sec (STP). In general, purification of these carbon-graphites with chlorine at 2800 C improved oxidation resistance. Additional improvements in oxidation resistance were obtained from purification followed by an antioxidant (zinc phosphate) treatment. For the commercial materials, purification alone gave greater oxidation resistance than the antioxidant treatment alone. The reverse, however, was the case for the experimental materials.

  4. Understanding the mechanisms and drivers of antimicrobial resistance.

    PubMed

    Holmes, Alison H; Moore, Luke S P; Sundsfjord, Arnfinn; Steinbakk, Martin; Regmi, Sadie; Karkey, Abhilasha; Guerin, Philippe J; Piddock, Laura J V

    2016-01-01

    To combat the threat to human health and biosecurity from antimicrobial resistance, an understanding of its mechanisms and drivers is needed. Emergence of antimicrobial resistance in microorganisms is a natural phenomenon, yet antimicrobial resistance selection has been driven by antimicrobial exposure in health care, agriculture, and the environment. Onward transmission is affected by standards of infection control, sanitation, access to clean water, access to assured quality antimicrobials and diagnostics, travel, and migration. Strategies to reduce antimicrobial resistance by removing antimicrobial selective pressure alone rely upon resistance imparting a fitness cost, an effect not always apparent. Minimising resistance should therefore be considered comprehensively, by resistance mechanism, microorganism, antimicrobial drug, host, and context; parallel to new drug discovery, broad ranging, multidisciplinary research is needed across these five levels, interlinked across the health-care, agriculture, and environment sectors. Intelligent, integrated approaches, mindful of potential unintended results, are needed to ensure sustained, worldwide access to effective antimicrobials. PMID:26603922

  5. Molecular and biochemical mechanisms of drug resistance in fungi.

    PubMed

    Yamaguchi, H

    1999-01-01

    This paper reviews the current status of our understanding of resistance mechanisms of three major classes of antifungal drugs for systemic use, amphotericin B (AMPH), flucytosine (5-FC) and several azole antifungals, in particular fluconazole (FLCZ), at the molecular and cellular levels. Although the number of reports of AMPH- or 5-FC-resistant fungal species and strains is limited, several mechanisms of resistance have been described. AMPH-resistant Candida have a marked decrease in ergosterol content compared with AMPH-susceptible control isolates. A lesion in the UMP-pyrophosphorylase is the most frequent determinant of 5-FC resistance in C. albicans. Recently resistance of C. albicans to azoles has become an increasing problem. Extensive biochemical studies have highlighted a significant diversity in mechanisms conferring resistance to FLCZ and other azoles, which include alterations in sterol biosynthesis, target site, uptake and efflux. Among them, the most important mechanism clinically is reduced access of the drug to the intracellular P450 14 DM target, probably because of the action of a multidrug resistance efflux pump, and overproduction of that target. However, other possible resistance mechanisms for azoles remain to be identified.

  6. Detecting mechanisms of acquired BRAF inhibitor resistance in melanoma.

    PubMed

    Lo, Roger S; Shi, Hubing

    2014-01-01

    (V600)BRAF mutation was identified as an ideal target for clinical therapy due to its indispensable roles in supporting melanoma initiation and progression. Despite the fact that BRAF inhibitors (BRAFi) can elicit anti-tumor responses in the majority of treated patients and confer overall survival benefits, acquired drug resistance is a formidable obstacle to long-term management of the disease. Several aberrant events including RTK upregulation, NRAS mutation, mutant BRAF amplification or alternative splicing, and MEK mutation have been reported as acquired BRAFi resistance mechanisms. Clinially, detection of these resistance mechanisms help understand drug response patterns and help guide combinatorial therapeutic strategies. Therefore, quick and accurate diagnosis of the resistant mechanisms in tumor biopsies has become an important starting point for personalized therapy. In this chapter, we review the major acquired BRAFi resistance mechanisms, highlight their therapeutic implications, and provide the diagnostic methods from clinical samples.

  7. Mechanisms Linking Inflammation to Insulin Resistance.

    PubMed

    Chen, Li; Chen, Rui; Wang, Hua; Liang, Fengxia

    2015-01-01

    Obesity is now widespread around the world. Obesity-associated chronic low-grade inflammation is responsible for the decrease of insulin sensitivity, which makes obesity a major risk factor for insulin resistance and related diseases such as type 2 diabetes mellitus and metabolic syndromes. The state of low-grade inflammation is caused by overnutrition which leads to lipid accumulation in adipocytes. Obesity might increase the expression of some inflammatory cytokines and activate several signaling pathways, both of which are involved in the pathogenesis of insulin resistance by interfering with insulin signaling and action. It has been suggested that specific factors and signaling pathways are often correlated with each other; therefore, both of the fluctuation of cytokines and the status of relevant signaling pathways should be considered during studies analyzing inflammation-related insulin resistance. In this paper, we discuss how these factors and signaling pathways contribute to insulin resistance and the therapeutic promise targeting inflammation in insulin resistance based on the latest experimental studies. PMID:26136779

  8. Additional Drug Resistance of Multidrug-Resistant Tuberculosis in Patients in 9 Countries

    PubMed Central

    Dalton, Tracy; Ershova, Julia; Tupasi, Thelma; Caoili, Janice Campos; Van Der Walt, Martie; Kvasnovsky, Charlotte; Yagui, Martin; Bayona, Jaime; Contreras, Carmen; Leimane, Vaira; Via, Laura E.; Kim, HeeJin; Akksilp, Somsak; Kazennyy, Boris Y.; Volchenkov, Grigory V.; Jou, Ruwen; Kliiman, Kai; Demikhova, Olga V.; Cegielski, J. Peter

    2015-01-01

    Data from a large multicenter observational study of patients with multidrug-resistant tuberculosis (MDR TB) were analyzed to simulate the possible use of 2 new approaches to treatment of MDR TB: a short (9-month) regimen and a bedaquiline-containing regimen. Of 1,254 patients, 952 (75.9%) had no resistance to fluoroquinolones and second-line injectable drugs and thus would qualify as candidates for the 9-month regimen; 302 (24.1%) patients with resistance to a fluoroquinolone or second-line injectable drug would qualify as candidates for a bedaquiline-containing regimen in accordance with published guidelines. Among candidates for the 9-month regimen, standardized drug-susceptibility tests demonstrated susceptibility to a median of 5 (interquartile range 5–6) drugs. Among candidates for bedaquiline, drug-susceptibility tests demonstrated susceptibility to a median of 3 (interquartile range 2–4) drugs; 26% retained susceptibility to <2 drugs. These data may assist national TB programs in planning to implement new drugs and drug regimens. PMID:25988299

  9. Mechanism of Escherichia coli Resistance to Pyrrhocoricin

    PubMed Central

    Narayanan, Shalini; Modak, Joyanta K.; Ryan, Catherine S.; Garcia-Bustos, Jose; Davies, John K.

    2014-01-01

    Due to their lack of toxicity to mammalian cells and good serum stability, proline-rich antimicrobial peptides (PR-AMPs) have been proposed as promising candidates for the treatment of infections caused by antimicrobial-resistant bacterial pathogens. It has been hypothesized that these peptides act on multiple targets within bacterial cells, and therefore the likelihood of the emergence of resistance was considered to be low. Here, we show that spontaneous Escherichia coli mutants resistant to pyrrhocoricin arise at a frequency of approximately 6 × 10−7. Multiple independently derived mutants all contained a deletion in a nonessential gene that encodes the putative peptide uptake permease SbmA. Sensitivity could be restored to the mutants by complementation with an intact copy of the sbmA gene. These findings question the viability of the development of insect PR-AMPs as antimicrobials. PMID:24590485

  10. 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

  11. Mechanisms of Pyrazinamide Action and Resistance

    PubMed Central

    Zhang, Ying; Shi, Wanliang; Zhang, Wenhong; Mitchison, Denis

    2014-01-01

    PZA is a unique anti-tuberculosis drug that plays a key role in shortening the TB therapy. PZA kills non-replicating persisters that other TB drugs fail to kill, and thus making it an essential drug for inclusion in any drug combinations for treating drug susceptible and drug-resistant TB such as MDR-TB. PZA acts differently from common antibiotics by inhibiting multiple targets such as energy production, trans-translation and perhaps pantothenate /coenzyme A required for persister survival. Resistance to PZA is mostly caused by mutations in the pncA gene encoding pyrazinamidase involved in conversion of the prodrug PZA to the active form POA. Mutations in the drug target RpsA are also found in some PZA-resistant strains. The recent finding that panD mutations are found in some PZA-resistant strains without pncA or rpsA mutations may suggest a third PZA resistance gene and a potential new target of PZA. Current phenotype based PZA susceptibility testing is not reliable due to false resistance, and sequencing of the pncA gene represents a more rapid, cost-effective and more reliable molecular test for PZA susceptibility testing and should be used for guiding improved treatment of MDR/XDR-TB. Finally, the story of PZA has important implications for not only TB therapy but also chemotherapy in general. PZA serves as a model prototype persister drug and hopefully a ‘tipping point’ that inspires new efforts at developing a new type of antibiotics or drugs that target non-replicating persisters for improved treatment of not only TB but also other persistent bacterial infections. PMID:25530919

  12. Additives

    NASA Technical Reports Server (NTRS)

    Smalheer, C. V.

    1973-01-01

    The chemistry of lubricant additives is discussed to show what the additives are chemically and what functions they perform in the lubrication of various kinds of equipment. Current theories regarding the mode of action of lubricant additives are presented. The additive groups discussed include the following: (1) detergents and dispersants, (2) corrosion inhibitors, (3) antioxidants, (4) viscosity index improvers, (5) pour point depressants, and (6) antifouling agents.

  13. Effect of V or Zr addition on the mechanical properties of the mechanically alloyed Al-8wt%Ti alloys

    SciTech Connect

    Moon, I.H.; Lee, J.H.; Lee, K.M. . Dept. of Materials Engineering); Kim, Y.D. . Div. of Metals)

    1995-01-01

    Mechanical alloying (MA) of Al-Ti alloy, being a solid state process, offers the unique advantage of producing homogeneous and fine dispersions of thermally stable Al[sub 3]Ti phase, where the formation of the fine Al[sub 3]Ti phase by the other method is restricted from the thermodynamic viewpoint. The MA Al-Ti alloys show substantially higher strength than the conventional Al alloys at the elevated temperature due to the presence of Al[sub 3]Ti as well as Al[sub 4]C[sub 3] and Al[sub 2]O[sub 3], of which the last two phases were introduced during MA process. The addition of V or Zr to Al-Ti alloy was known to decrease the lattice mismatch between the intermetallic compound and the aluminum matrix, and such decrease in lattice mismatching can influence positively the high temperature mechanical strength of the MA Al-Ti by increasing the resistance to dispersoid coarsening at the elevated temperature. In the present study, therefore, the mechanical behavior of the MA Al-Ti-V and Al-Ti-Zr alloys were investigated in order to evaluate the effect of V or Zr addition on the mechanical properties of the MA Al-8Ti alloy at high temperature.

  14. Polymyxin Resistance of Pseudomonas aeruginosa phoQ Mutants Is Dependent on Additional Two-Component Regulatory Systems

    PubMed Central

    Gutu, Alina D.; Sgambati, Nicole; Strasbourger, Pnina; Brannon, Mark K.; Jacobs, Michael A.; Haugen, Eric; Kaul, Rajinder K.; Johansen, Helle Krogh; Høiby, Niels

    2013-01-01

    Pseudomonas aeruginosa can develop resistance to polymyxin as a consequence of mutations in the PhoPQ regulatory system, mediated by covalent lipid A modification. Transposon mutagenesis of a polymyxin-resistant phoQ mutant defined 41 novel loci required for resistance, including two regulatory systems, ColRS and CprRS. Deletion of the colRS genes, individually or in tandem, abrogated the polymyxin resistance of a ΔphoQ mutant, as did individual or tandem deletion of cprRS. Individual deletion of colR or colS in a ΔphoQ mutant also suppressed 4-amino-l-arabinose addition to lipid A, consistent with the known role of this modification in polymyxin resistance. Surprisingly, tandem deletion of colRS or cprRS in the ΔphoQ mutant or individual deletion of cprR or cprS failed to suppress 4-amino-l-arabinose addition to lipid A, indicating that this modification alone is not sufficient for PhoPQ-mediated polymyxin resistance in P. aeruginosa. Episomal expression of colRS or cprRS in tandem or of cprR individually complemented the Pm resistance phenotype in the ΔphoQ mutant, while episomal expression of colR, colS, or cprS individually did not. Highly polymyxin-resistant phoQ mutants of P. aeruginosa isolated from polymyxin-treated cystic fibrosis patients harbored mutant alleles of colRS and cprS; when expressed in a ΔphoQ background, these mutant alleles enhanced polymyxin resistance. These results define ColRS and CprRS as two-component systems regulating polymyxin resistance in P. aeruginosa, indicate that addition of 4-amino-l-arabinose to lipid A is not the only PhoPQ-regulated biochemical mechanism required for resistance, and demonstrate that colRS and cprS mutations can contribute to high-level clinical resistance. PMID:23459479

  15. Microbial resistance to disinfectants: mechanisms and significance

    SciTech Connect

    Hoff, J.C.; Akin, E.W.

    1986-11-01

    Drinking water disinfection provides the final barrier to transmission of a wide variety of potentially waterborne infectious agents including pathogenic bacteria, viruses, and protozoa. These agents differ greatly in their innate resistance to inactivation by disinfectants, ranging from extremely sensitive bacteria to highly resistant protozoan cysts. The close similarity between microorganism inactivation rates and the kinetics of chemical reactions has long been recognized. Ideally, under carefully controlled conditions, microorganism inactivation rates simulate first-order chemical reaction rates, making it possible to predict the effectiveness of disinfection under specific conditions. In practice, changes in relative resistance and deviations from first-order kinetics are caused by a number of factors, including microbial growth conditions, aggregation, and association with particulate materials. The net effect of all these factors is a reduction in the effectiveness and predictability of disinfection processes. To ensure effective pathogen control, disinfectant concentrations and contact times greater than experimentally determined values may be required. Of the factors causing enhanced disinfection resistance, protection by association with particulate matter is the most significant. Therefore, removal of particulate matter is an important step in increasing the effectiveness of disinfection processes.

  16. Mechanism of Insect Resistance to the Microbial Insecticide Bacillus thuringiensis

    NASA Astrophysics Data System (ADS)

    van Rie, J.; McGaughey, W. H.; Johnson, D. E.; Barnett, B. D.; van Mellaert, H.

    1990-01-01

    Receptor binding studies show that resistance of a laboratory-selected Plodia interpunctella strain to a Bacillus thuringiensis insecticidal crystal protein (ICP) is correlated with a 50-fold reduction in affinity of the membrane receptor for this protein. The strain is sensitive to a second type of ICP that apparently recognizes a different receptor. Understanding the mechanism of resistance will provide strategies to prevent or delay resistance and hence prolong the usefulness of B. thuringiensis ICPs as environmentally safe insecticides.

  17. Evolution of herbicide resistance mechanisms in grass weeds.

    PubMed

    Matzrafi, Maor; Gadri, Yaron; Frenkel, Eyal; Rubin, Baruch; Peleg, Zvi

    2014-12-01

    Herbicide resistant weeds are becoming increasingly common, threatening global food security. Here, we present BrIFAR: a new model system for the functional study of mechanisms of herbicide resistance in grass weeds. We have developed a large collection of Brachypodium accessions, the BrI collection, representing a wide range of habitats. Wide screening of the responses of the accessions to four major herbicide groups (PSII, ACCase, ALS/AHAS and EPSPS inhibitors) identified 28 herbicide-resistance candidate accessions. Target-site resistance to PSII inhibitors was found in accessions collected from habitats with a known history of herbicide applications. An amino acid substitution in the psbA gene (serine264 to glycine) conferred resistance and also significantly affected the flowering and shoot dry weight of the resistant accession, as compared to the sensitive accession. Non-target site resistance to ACCase inhibitors was found in accessions collected from habitats with a history of herbicide application and from a nature reserve. In-vitro enzyme activity tests and responses following pre-treatment with malathion (a cytochrome-P450 inhibitor) indicated sensitivity at the enzyme level, and give strong support to diclofop-methyl and pinoxaden enhanced detoxification as NTS resistance mechanism. BrIFAR can promote better understanding of the evolution of mechanisms of herbicide resistance and aid the implementation of integrative management approaches for sustainable agriculture.

  18. Evolution of herbicide resistance mechanisms in grass weeds.

    PubMed

    Matzrafi, Maor; Gadri, Yaron; Frenkel, Eyal; Rubin, Baruch; Peleg, Zvi

    2014-12-01

    Herbicide resistant weeds are becoming increasingly common, threatening global food security. Here, we present BrIFAR: a new model system for the functional study of mechanisms of herbicide resistance in grass weeds. We have developed a large collection of Brachypodium accessions, the BrI collection, representing a wide range of habitats. Wide screening of the responses of the accessions to four major herbicide groups (PSII, ACCase, ALS/AHAS and EPSPS inhibitors) identified 28 herbicide-resistance candidate accessions. Target-site resistance to PSII inhibitors was found in accessions collected from habitats with a known history of herbicide applications. An amino acid substitution in the psbA gene (serine264 to glycine) conferred resistance and also significantly affected the flowering and shoot dry weight of the resistant accession, as compared to the sensitive accession. Non-target site resistance to ACCase inhibitors was found in accessions collected from habitats with a history of herbicide application and from a nature reserve. In-vitro enzyme activity tests and responses following pre-treatment with malathion (a cytochrome-P450 inhibitor) indicated sensitivity at the enzyme level, and give strong support to diclofop-methyl and pinoxaden enhanced detoxification as NTS resistance mechanism. BrIFAR can promote better understanding of the evolution of mechanisms of herbicide resistance and aid the implementation of integrative management approaches for sustainable agriculture. PMID:25443832

  19. What have the mechanisms of resistance to glyphosate taught us?

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The intensive use of glyphosate alone to manage weeds has selected populations that are glyphosate resistant. The three mechanisms of glyphosate resistance that have been elucidated are 1) target site mutations; 2) gene amplification; and 3) altered translocation due to sequestration. What have we...

  20. Herbicide resistance in weeds: Survey, characterization, and mechanisms

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The goal of this paper is to present a systematic diagnostic approach towards the characterization of herbicide resistance in a given weed population with regards to profile (single, multiple, cross resistance), magnitude (fold level), mechanism, and related bio-physiological aspects. Diagnosing her...

  1. Mutational and acquired carbapenem resistance mechanisms in multidrug resistant Pseudomonas aeruginosa clinical isolates from Recife, Brazil.

    PubMed

    Cavalcanti, Felipe Lira de Sá; Mirones, Cristina Rodríguez; Paucar, Elena Román; Montes, Laura Álvarez; Leal-Balbino, Tereza Cristina; Morais, Marcia Maria Camargo de; Martínez-Martínez, Luis; Ocampo-Sosa, Alain Antonio

    2015-12-01

    An investigation was carried out into the genetic mechanisms responsible for multidrug resistance in nine carbapenem-resistant Pseudomonas aeruginosa isolates from different hospitals in Recife, Brazil. Susceptibility to antimicrobial agents was determined by broth microdilution. Polymerase chain reaction (PCR) was employed to detect the presence of genes encoding β-lactamases, aminoglycoside-modifying enzymes (AMEs), 16S rRNA methylases, integron-related genes and OprD. Expression of genes coding for efflux pumps and AmpC cephalosporinase were assessed by quantitative PCR. The outer membrane proteins were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The blaSPM-1, blaKPC-2 and blaGES-1 genes were detected in P. aeruginosa isolates in addition to different AME genes. The loss of OprD in nine isolates was mainly due to frameshift mutations, premature stop codons and point mutations. An association of loss of OprD with the overexpression of MexAB-OprM and MexXY-OprM was observed in most isolates. Hyper-production of AmpC was also observed in three isolates. Clonal relationship of the isolates was determined by repetitive element palindromic-PCR and multilocus sequence typing. Our results show that the loss of OprD along with overexpression of efflux pumps and β-lactamase production were responsible for the multidrug resistance in the isolates analysed.

  2. Mutational and acquired carbapenem resistance mechanisms in multidrug resistant Pseudomonas aeruginosa clinical isolates from Recife, Brazil

    PubMed Central

    Cavalcanti, Felipe Lira de Sá; Mirones, Cristina Rodríguez; Paucar, Elena Román; Montes, Laura Álvarez; Leal-Balbino, Tereza Cristina; de Morais, Marcia Maria Camargo; Martínez-Martínez, Luis; Ocampo-Sosa, Alain Antonio

    2015-01-01

    An investigation was carried out into the genetic mechanisms responsible for multidrug resistance in nine carbapenem-resistant Pseudomonas aeruginosaisolates from different hospitals in Recife, Brazil. Susceptibility to antimicrobial agents was determined by broth microdilution. Polymerase chain reaction (PCR) was employed to detect the presence of genes encoding β-lactamases, aminoglycoside-modifying enzymes (AMEs), 16S rRNA methylases, integron-related genes and OprD. Expression of genes coding for efflux pumps and AmpC cephalosporinase were assessed by quantitative PCR. The outer membrane proteins were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The blaSPM-1, blaKPC-2 and blaGES-1 genes were detected in P. aeruginosaisolates in addition to different AME genes. The loss of OprD in nine isolates was mainly due to frameshift mutations, premature stop codons and point mutations. An association of loss of OprD with the overexpression of MexAB-OprM and MexXY-OprM was observed in most isolates. Hyper-production of AmpC was also observed in three isolates. Clonal relationship of the isolates was determined by repetitive element palindromic-PCR and multilocus sequence typing. Our results show that the loss of OprD along with overexpression of efflux pumps and β-lactamase production were responsible for the multidrug resistance in the isolates analysed. PMID:26676375

  3. Defense mechanisms involved in disease resistance of grafted vegetables

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Vegetable grafting with resistant rootstocks is an effective strategy to control a variety of soil-borne diseases and root-knot nematodes in the Cucurbitaceae and Solanaceae. In addition, improved resistance to some foliar diseases and viruses has also been reported in grafted plants. Hence, graft...

  4. Mechanisms of resistance to DDT and pyrethroids in Patagonian populations of Simulium blackflies.

    PubMed

    Montagna, C M; Anguiano, O L; Gauna, L E; Pechen de d-Angelo, A M

    2003-03-01

    Mixed populations of the pest blackflies Simulium bonaerense Coscarón & Wygodzinsky, S. wolffhuegeli (Enderlein) and S. nigristrigatum Wygodzinsky & Coscarón (Diptera: Simuliidae) are highly resistant to DDT and pyrethroids in the Neuquén Valley, a fruit-growing area of northern Patagonia, Argentina. As these insecticides have not been used for blackfly control, resistance is attributed to exposure to agricultural insecticides. Pre-treatment with the synergist piperonyl butoxide (PBO) reduced both DDT and fenvalerate resistance, indicating that resistance was partly due to monooxygenase inhibition. Pre-treatment with the synergist tribufos to inhibit esterases slightly increased fenvalerate toxicity in the resistant population. Even so, biochemical studies indicated almost three-fold higher esterase activity in the resistant population, compared to the susceptible. Starch gel electrophoresis confirmed higher frequency and staining intensity of esterase electromorphs in the resistant population. Incomplete synergism against metabolic resistance indicates additional involvement of a non-metabolic resistance mechanism, such as target site insensitivity, assumed to be kdr-like in this case. Glutathione S-transferase activities were low and inconsistent, indicating no role in Simulium resistance. Knowing these spectra of insecticide activity and resistance mechanisms facilitates the choice of more effective products for Simulium control and permits better coordination with agrochemical operations.

  5. A review on the mechanisms of blood-flow restriction resistance training-induced muscle hypertrophy.

    PubMed

    Pearson, Stephen John; Hussain, Syed Robiul

    2015-02-01

    It has traditionally been believed that resistance training can only induce muscle growth when the exercise intensity is greater than 65% of the 1-repetition maximum (RM). However, more recently, the use of low-intensity resistance exercise with blood-flow restriction (BFR) has challenged this theory and consistently shown that hypertrophic adaptations can be induced with much lower exercise intensities (<50% 1-RM). Despite the potent hypertrophic effects of BFR resistance training being demonstrated by numerous studies, the underlying mechanisms responsible for such effects are not well defined. Metabolic stress has been suggested to be a primary factor responsible, and this is theorised to activate numerous other mechanisms, all of which are thought to induce muscle growth via autocrine and/or paracrine actions. However, it is noteworthy that some of these mechanisms do not appear to be mediated to any great extent by metabolic stress but rather by mechanical tension (another primary factor of muscle hypertrophy). Given that the level of mechanical tension is typically low with BFR resistance exercise (<50% 1-RM), one may question the magnitude of involvement of these mechanisms aligned to the adaptations reported with BFR resistance training. However, despite the low level of mechanical tension, it is plausible that the effects induced by the primary factors (mechanical tension and metabolic stress) are, in fact, additive, which ultimately contributes to the adaptations seen with BFR resistance training. Exercise-induced mechanical tension and metabolic stress are theorised to signal a number of mechanisms for the induction of muscle growth, including increased fast-twitch fibre recruitment, mechanotransduction, muscle damage, systemic and localised hormone production, cell swelling, and the production of reactive oxygen species and its variants, including nitric oxide and heat shock proteins. However, the relative extent to which these specific mechanisms are

  6. Rapid vacuolar sequestration: the horseweed glyphosate resistance mechanism

    PubMed Central

    Ge, Xia; Avignon, D André d’; Ackerman, Joseph JH; Sammons, R Douglas

    2010-01-01

    BACKGROUND Glyphosate-resistant (GR) weed species are now found with increasing frequency and threaten the critically importantGR weed management system. RESULTS The reported 31P NMR experiments on glyphosate-sensitive (S) and glyphosate-resistant (R) horseweed, Conyza canadensis (L.) Cronq., show significantly more accumulation of glyphosate within the R biotype vacuole. CONCLUSIONS Selective sequestration of glyphosate into the vacuole confers the observed horseweed resistance to glyphosate. This observation represents the first clear evidence for the glyphosate resistance mechanism in C. canadensis. PMID:20063320

  7. Mechanisms of Drug Resistance in Relapse and Refractory Multiple Myeloma.

    PubMed

    Yang, Wen-Chi; Lin, Sheng-Fung

    2015-01-01

    Multiple myeloma (MM) is a hematological malignancy that remains incurable because most patients eventually relapse or become refractory to current treatments. Although the treatments have improved, the major problem in MM is resistance to therapy. Clonal evolution of MM cells and bone marrow microenvironment changes contribute to drug resistance. Some mechanisms affect both MM cells and microenvironment, including the up- and downregulation of microRNAs and programmed death factor 1 (PD-1)/PD-L1 interaction. Here, we review the pathogenesis of MM cells and bone marrow microenvironment and highlight possible drug resistance mechanisms. We also review a potential molecular targeting treatment and immunotherapy for patients with refractory or relapse MM.

  8. Targeting bacterial topoisomerases: how to counter mechanisms of resistance.

    PubMed

    Tse-Dinh, Yuk-Ching

    2016-06-01

    DNA gyrase and topoisomerase IV are type IIA bacterial topoisomerases that are targeted by highly effective antibiotics. However, resistance via multiple mechanisms arises to limit the efficacies of these drugs. Continued research on type IIA bacterial topoisomerases has provided novel approaches to counter the most common resistance mechanism for utilization of these proven targets in antibacterial therapy. Bacterial topoisomerase I is being explored as an alternative target that is not expected to show cross-resistance. Dual targeting or combination therapy could be strategies for circumventing the development of resistance to topoisomerase-targeting antibiotics. Bacterial topoisomerases are high-value bactericidal targets that could continue to be exploited for antibacterial therapy, if new tactics to counter resistance can be adopted. PMID:27285067

  9. Targeting bacterial topoisomerases: how to counter mechanisms of resistance.

    PubMed

    Tse-Dinh, Yuk-Ching

    2016-06-01

    DNA gyrase and topoisomerase IV are type IIA bacterial topoisomerases that are targeted by highly effective antibiotics. However, resistance via multiple mechanisms arises to limit the efficacies of these drugs. Continued research on type IIA bacterial topoisomerases has provided novel approaches to counter the most common resistance mechanism for utilization of these proven targets in antibacterial therapy. Bacterial topoisomerase I is being explored as an alternative target that is not expected to show cross-resistance. Dual targeting or combination therapy could be strategies for circumventing the development of resistance to topoisomerase-targeting antibiotics. Bacterial topoisomerases are high-value bactericidal targets that could continue to be exploited for antibacterial therapy, if new tactics to counter resistance can be adopted.

  10. Antibiotic resistance mechanisms in M. tuberculosis: an update.

    PubMed

    Nguyen, Liem

    2016-07-01

    Treatment of tuberculosis (TB) has been a therapeutic challenge because of not only the naturally high resistance level of Mycobacterium tuberculosis to antibiotics but also the newly acquired mutations that confer further resistance. Currently standardized regimens require patients to daily ingest up to four drugs under direct observation of a healthcare worker for a period of 6-9 months. Although they are quite effective in treating drug susceptible TB, these lengthy treatments often lead to patient non-adherence, which catalyzes for the emergence of M. tuberculosis strains that are increasingly resistant to the few available anti-TB drugs. The rapid evolution of M. tuberculosis, from mono-drug-resistant to multiple drug-resistant, extensively drug-resistant and most recently totally drug-resistant strains, is threatening to make TB once again an untreatable disease if new therapeutic options do not soon become available. Here, I discuss the molecular mechanisms by which M. tuberculosis confers its profound resistance to antibiotics. This knowledge may help in developing novel strategies for weakening drug resistance, thus enhancing the potency of available antibiotics against both drug susceptible and resistant M. tuberculosis strains. PMID:27161440

  11. Thiamethoxam Resistance in the House Fly, Musca domestica L.: Current Status, Resistance Selection, Cross-Resistance Potential and Possible Biochemical Mechanisms

    PubMed Central

    Khan, Hafiz Azhar Ali; Akram, Waseem; Iqbal, Javaid; Naeem-Ullah, Unsar

    2015-01-01

    The house fly, Musca domestica L., is an important ectoparasite with the ability to develop resistance to insecticides used for their control. Thiamethoxam, a neonicotinoid, is a relatively new insecticide and effectively used against house flies with a few reports of resistance around the globe. To understand the status of resistance to thiamethoxam, eight adult house fly strains were evaluated under laboratory conditions. In addition, to assess the risks of resistance development, cross-resistance potential and possible biochemical mechanisms, a field strain of house flies was selected with thiamethoxam in the laboratory. The results revealed that the field strains showed varying level of resistance to thiamethoxam with resistance ratios (RR) at LC50 ranged from 7.66-20.13 folds. Continuous selection of the field strain (Thia-SEL) for five generations increased the RR from initial 7.66 fold to 33.59 fold. However, resistance declined significantly when the Thia-SEL strain reared for the next five generations without exposure to thiamethoxam. Compared to the laboratory susceptible reference strain (Lab-susceptible), the Thia-SEL strain showed cross-resistance to imidacloprid. Synergism tests revealed that S,S,S-tributylphosphorotrithioate (DEF) and piperonyl butoxide (PBO) produced synergism of thiamethoxam effects in the Thia-SEL strain (2.94 and 5.00 fold, respectively). In addition, biochemical analyses revealed that the activities of carboxylesterase (CarE) and mixed function oxidase (MFO) in the Thia-SEL strain were significantly higher than the Lab-susceptible strain. It seems that metabolic detoxification by CarE and MFO was a major mechanism for thiamethoxam resistance in the Thia-SEL strain of house flies. The results could be helpful in the future to develop an improved control strategy against house flies. PMID:25938578

  12. Thiamethoxam Resistance in the House Fly, Musca domestica L.: Current Status, Resistance Selection, Cross-Resistance Potential and Possible Biochemical Mechanisms.

    PubMed

    Khan, Hafiz Azhar Ali; Akram, Waseem; Iqbal, Javaid; Naeem-Ullah, Unsar

    2015-01-01

    The house fly, Musca domestica L., is an important ectoparasite with the ability to develop resistance to insecticides used for their control. Thiamethoxam, a neonicotinoid, is a relatively new insecticide and effectively used against house flies with a few reports of resistance around the globe. To understand the status of resistance to thiamethoxam, eight adult house fly strains were evaluated under laboratory conditions. In addition, to assess the risks of resistance development, cross-resistance potential and possible biochemical mechanisms, a field strain of house flies was selected with thiamethoxam in the laboratory. The results revealed that the field strains showed varying level of resistance to thiamethoxam with resistance ratios (RR) at LC50 ranged from 7.66-20.13 folds. Continuous selection of the field strain (Thia-SEL) for five generations increased the RR from initial 7.66 fold to 33.59 fold. However, resistance declined significantly when the Thia-SEL strain reared for the next five generations without exposure to thiamethoxam. Compared to the laboratory susceptible reference strain (Lab-susceptible), the Thia-SEL strain showed cross-resistance to imidacloprid. Synergism tests revealed that S,S,S-tributylphosphorotrithioate (DEF) and piperonyl butoxide (PBO) produced synergism of thiamethoxam effects in the Thia-SEL strain (2.94 and 5.00 fold, respectively). In addition, biochemical analyses revealed that the activities of carboxylesterase (CarE) and mixed function oxidase (MFO) in the Thia-SEL strain were significantly higher than the Lab-susceptible strain. It seems that metabolic detoxification by CarE and MFO was a major mechanism for thiamethoxam resistance in the Thia-SEL strain of house flies. The results could be helpful in the future to develop an improved control strategy against house flies.

  13. Resistance to antivirals in human cytomegalovirus: mechanisms and clinical significance.

    PubMed

    Pérez, J L

    1997-09-01

    Long term therapies needed for managing human cytomegalovirus (HCMV) infections in immunosupressed patients provided the background for the emergence of the resistance to antivirals active against HCMV. In addition, laboratory selected mutants have also been readily achieved. Both clinical and laboratory resistant strains share the same determinants of resistance. Ganciclovir resistance may be due to a few mutations in the HCMV UL97 gene and/or viral DNA pol gene, the former being responsible for about 70% of clinical resistant isolates. Among them, V464, V594, S595 and F595 are the most frequent mutations. Because of their less extensive clinical use, much less is known about resistance to foscarnet and cidofovir (formerly, HPMPC) but in both cases, it has been associated to mutations in the DNA pol. Ganciclovir resistant strains showing DNA pol mutations are cross-resistant to cidofovir and their corresponding IC50 are normally higher than those from strains harboring only mutations at the UL97 gene. To date, foscarnet resistance seems to be independent of both ganciclovir and cidofovir resistance.

  14. 76 FR 3011 - Black Stem Rust; Additions of Rust-Resistant Varieties

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-19

    ... final rule published September 8, 2010, at 75 FR 54461, is confirmed as November 8, 2010. FOR FURTHER... Health Inspection Service 7 CFR Part 301 Black Stem Rust; Additions of Rust-Resistant Varieties AGENCY... final rule. The direct final rule notified the public of our intention to amend the black stem...

  15. The tokamak density limit: A thermo-resistive disruption mechanism

    NASA Astrophysics Data System (ADS)

    Gates, David

    2015-11-01

    A magnetic island growth mechanism based on radiative cooling of the internal island flux surfaces is shown to produce the correct physical scaling to explain one of the long standing mysteries of tokamak physics - the empirical Greenwald density limit. In this presentation we will review the phenomenology of the density limit and the correlation between the Greenwald limit and the onset threshold for radiation-driven tearing modes. The behavior of magnetic islands with a 3D electron temperature distribution which is consistent with a large ratio of radial to parallel heat conductivity - and a corresponding 3D resistivity profile - is examined for islands with near-zero net heating in the island interior. The effect of varying impurity mix on the local island onset threshold is consistent with the established experimental scalings for tokamaks at the density limit. A simple analytic theory is developed which reveals the effect of heating and cooling in the island interior as well as the effect of island asymmetry. It is shown that a new term accounting for the thermal effects of island asymmetry is a crucial addition to the Modified Rutherford Equation. The resultant model exhibits a robust onset of a rapidly growing tearing mode - consistent with the disruption mechanism observed at the density limit in tokamaks. Additionally, a fully non-linear 3D cylindrical calculation is performed that simulates the effect of net island heating / cooling by raising / suppressing the temperature in the core of the island. In both the analytic theory and the numerical simulation a sudden threshold for explosive growth is found to be due to the interaction between three distinct thermal non-linearities, which affect the island resistivity, thereby modifying the growth dynamics. Expanding on the model presented, we speculate that the mechanism described may be applicable to a much wider range of tokamak disruptions than just those near the Greenwald limit. This work is supported

  16. Different mechanisms of resistance modulate sulfite tolerance in wine yeasts.

    PubMed

    Nadai, Chiara; Treu, Laura; Campanaro, Stefano; Giacomini, Alessio; Corich, Viviana

    2016-01-01

    From a technological point of view, yeast resistance to sulfite is of great interest and represents an important technological character for winemaking. Several mechanisms are involved, and strain-dependent strategies to obtain SO2 resistance can deeply influence wine quality, although this choice is less relevant in determining the technological performance of the strain during fermentation. In this study, to better understand the strain-specific mechanisms of resistance, 11 Saccharomyces cerevisiae strains, whose genomes have been previously sequenced, were selected. Their attitude towards sulfites, in terms of resistance and production, was evaluated, and RNA-sequencing of four selected strains was performed during fermentation process in synthetic grape must in the presence of SO2. Results demonstrated that at molecular level, the physical effect of SO2 triggered multiple stress responses in the cell and high tolerance to general enological stressing condition increased SO2 resistance. Adaptation mechanism due to high basal gene expression level rather than specific gene induction in the presence of sulfite seemed to be responsible in modulating strain resistance. This mechanism involved higher basal gene expression level of specific cell wall proteins, enzymes for lipid biosynthesis, and enzymes directly involved in SO2 assimilation pathway and efflux. PMID:26615396

  17. Different mechanisms of resistance modulate sulfite tolerance in wine yeasts.

    PubMed

    Nadai, Chiara; Treu, Laura; Campanaro, Stefano; Giacomini, Alessio; Corich, Viviana

    2016-01-01

    From a technological point of view, yeast resistance to sulfite is of great interest and represents an important technological character for winemaking. Several mechanisms are involved, and strain-dependent strategies to obtain SO2 resistance can deeply influence wine quality, although this choice is less relevant in determining the technological performance of the strain during fermentation. In this study, to better understand the strain-specific mechanisms of resistance, 11 Saccharomyces cerevisiae strains, whose genomes have been previously sequenced, were selected. Their attitude towards sulfites, in terms of resistance and production, was evaluated, and RNA-sequencing of four selected strains was performed during fermentation process in synthetic grape must in the presence of SO2. Results demonstrated that at molecular level, the physical effect of SO2 triggered multiple stress responses in the cell and high tolerance to general enological stressing condition increased SO2 resistance. Adaptation mechanism due to high basal gene expression level rather than specific gene induction in the presence of sulfite seemed to be responsible in modulating strain resistance. This mechanism involved higher basal gene expression level of specific cell wall proteins, enzymes for lipid biosynthesis, and enzymes directly involved in SO2 assimilation pathway and efflux.

  18. Mechanisms of lichen resistance to metallic pollution

    SciTech Connect

    Sarret, C.; Manceau, A.; Eybert-Berard, L.; Cuny, D.; Haluwyn, C. van; Deruelle, S.; Hazemann, J.L.; Menthonnex, J.J. |; Soldo, Y.

    1998-11-01

    Some lichens have a unique ability to grow in heavily contaminated areas due to the development of adaptative mechanisms allowing a high tolerance to metals. Here the authors report on the chemical forms of Pb and Zn in the metal hyperaccumulator Diploschistes muscorum and of Pb in the metal tolerant lichen Xanthoria parietina. The speciation of Zn and Pb has been investigated by powder X-ray diffraction (XRD) and extended X-ray absorption fine structure (EXAFS) spectroscopy using the advanced third-generation synchrotron radiation source of the European synchrotron radiation facility (ESRF in Grenoble). This study reveals that in both lichens cells are protected from toxicity by complexation of heavy metals, but the strategies differ: in D. muscorum, Pb and Zn are accumulated through an enhanced synthesis of oxalate, which precipitates toxic elements as insoluble salts, whereas in X. parietina, Pb is complexed to carboxylic groups of the fungal cell walls. The authors conclude that hyperaccumulation of metals results from a reactive mechanism of organic acid production, whereas metallo-tolerance is achieved by a passive complexation to existing functional groups.

  19. Mechanical properties and corrosion resistance of Inconel alloy 617 for refinery service

    SciTech Connect

    Lipscomb, W.G.; Crum, J.R.; Ganesan, P. )

    1989-01-01

    Various factors affecting the performance of Inconel alloy 617 in refinery service are evaluated. The influence of long-term exposure at 1000-1400{degrees}F (538- 760{degrees}C) on mechanical properties and high-temperature low-cycle fatigue studies are reported. In addition the effects of various heat treatments and resulting microstructure on polythionic acid stress corrosion cracking resistance and intergranular attack resistance are determined.

  20. Effects of V addition on recrystallization resistance of 7150 aluminum alloy after simulative hot deformation

    SciTech Connect

    Lai, Jing; Shi, Cangji; Chen, X.-Grant

    2014-10-15

    The effects of different V contents (0.01 to 0.19 wt.%) on the recrystallization resistance of 7150 aluminum alloys during post-deformation heat treatment were investigated. The microstructural evolutions at as-cast, as-homogenized conditions and after post-deformation annealing were studied using optical, scanning electron and transmission electron microscopes and using the electron backscattered diffraction technique. The precipitation of Al{sub 21}V{sub 2} dispersoids was observed in alloys containing 0.11 to 0.19 wt.% V after homogenization. The dispersoids were mainly distributed in the dendrite cells, and the precipitate-free zones occurred in the interdendritic regions and near grain boundaries. V addition could significantly enhance the recrystallization resistance during post-deformation annealing, particularly in the presence of a great number of Al{sub 21}V{sub 2} dispersoids. Recrystallized grain growth was effectively restricted because of the dispersoid pinning effect. The alloy containing 0.15 wt.% V exhibited the highest recrystallization resistance amongst all V-containing alloys studied. - Highlights: • Investigated the effect of V level on microstructure and flow stress of 7150 alloys • Characterized microstructures using optical microscopy, SEM, TEM and EBSD • Described the precipitation behavior of V-dispersoids in the dendritic structure • Studied the V effect on recrystallization resistance during post heat treatment • V addition greatly enhanced the recrystallization resistance during annealing.

  1. Drug Resistance Mechanisms in Bacteria Causing Sexually Transmitted Diseases and Associated with Vaginosis.

    PubMed

    Shaskolskiy, Boris; Dementieva, Ekaterina; Leinsoo, Arvo; Runina, Anastassia; Vorobyev, Denis; Plakhova, Xenia; Kubanov, Alexey; Deryabin, Dmitrii; Gryadunov, Dmitry

    2016-01-01

    Here, we review sexually transmitted diseases (STDs) caused by pathogenic bacteria and vaginal infections which result from an overgrowth of opportunistic bacterial microflora. First, we describe the STDs, the corresponding pathogens and the antimicrobials used for their treatment. In addition to the well-known diseases caused by single pathogens (i.e., syphilis, gonococcal infections, and chlamydiosis), we consider polymicrobial reproductive tract infections (especially those that are difficult to effectively clinically manage). Then, we summarize the biochemical mechanisms that lead to antimicrobial resistance and the most recent data on the emergence of drug resistance in STD pathogens and bacteria associated with vaginosis. A large amount of research performed in the last 10-15 years has shed light on the enormous diversity of mechanisms of resistance developed by bacteria. A detailed understanding of the mechanisms of antimicrobials action and the emergence of resistance is necessary to modify existing drugs and to develop new ones directed against new targets.

  2. Drug Resistance Mechanisms in Bacteria Causing Sexually Transmitted Diseases and Associated with Vaginosis

    PubMed Central

    Shaskolskiy, Boris; Dementieva, Ekaterina; Leinsoo, Arvo; Runina, Anastassia; Vorobyev, Denis; Plakhova, Xenia; Kubanov, Alexey; Deryabin, Dmitrii; Gryadunov, Dmitry

    2016-01-01

    Here, we review sexually transmitted diseases (STDs) caused by pathogenic bacteria and vaginal infections which result from an overgrowth of opportunistic bacterial microflora. First, we describe the STDs, the corresponding pathogens and the antimicrobials used for their treatment. In addition to the well-known diseases caused by single pathogens (i.e., syphilis, gonococcal infections, and chlamydiosis), we consider polymicrobial reproductive tract infections (especially those that are difficult to effectively clinically manage). Then, we summarize the biochemical mechanisms that lead to antimicrobial resistance and the most recent data on the emergence of drug resistance in STD pathogens and bacteria associated with vaginosis. A large amount of research performed in the last 10–15 years has shed light on the enormous diversity of mechanisms of resistance developed by bacteria. A detailed understanding of the mechanisms of antimicrobials action and the emergence of resistance is necessary to modify existing drugs and to develop new ones directed against new targets. PMID:27242760

  3. Drug Resistance Mechanisms in Bacteria Causing Sexually Transmitted Diseases and Associated with Vaginosis.

    PubMed

    Shaskolskiy, Boris; Dementieva, Ekaterina; Leinsoo, Arvo; Runina, Anastassia; Vorobyev, Denis; Plakhova, Xenia; Kubanov, Alexey; Deryabin, Dmitrii; Gryadunov, Dmitry

    2016-01-01

    Here, we review sexually transmitted diseases (STDs) caused by pathogenic bacteria and vaginal infections which result from an overgrowth of opportunistic bacterial microflora. First, we describe the STDs, the corresponding pathogens and the antimicrobials used for their treatment. In addition to the well-known diseases caused by single pathogens (i.e., syphilis, gonococcal infections, and chlamydiosis), we consider polymicrobial reproductive tract infections (especially those that are difficult to effectively clinically manage). Then, we summarize the biochemical mechanisms that lead to antimicrobial resistance and the most recent data on the emergence of drug resistance in STD pathogens and bacteria associated with vaginosis. A large amount of research performed in the last 10-15 years has shed light on the enormous diversity of mechanisms of resistance developed by bacteria. A detailed understanding of the mechanisms of antimicrobials action and the emergence of resistance is necessary to modify existing drugs and to develop new ones directed against new targets. PMID:27242760

  4. New insights in leptin resistance mechanisms in mice.

    PubMed

    Balland, Eglantine; Cowley, Michael A

    2015-10-01

    Leptin resistance is one of the main challenges of obesity. To date, two levels of resistance have been identified, first a decreased rate of leptin uptake into the brain and secondly a diminished central response to leptin. New findings have identified the mechanisms of leptin transport and demonstrated that it can be rescued in obesity, but it did not overcome the problem of central resistance. Alteration in the actions of leptin following diet-induced obesity (DIO) appears to be a multifactorial condition. Several phosphatases are inhibiting leptin signaling pathways in a pathological way. Besides, hypothalamic inflammation alters the neuronal circuits that control metabolism. Recent studies describing both mechanisms (inhibition of leptin signaling and inflammation), have provided key insights to potential new targets for treatment. However, recent data showing that DIO mice may conserve a cellular and physiological response to endogenous leptin, highlights the need to redefine the concept of "leptin resistance".

  5. The mechanism of resistance to sulfa drugs in Plasmodium falciparum.

    PubMed

    Triglia, Tony; Cowman, Alan F.

    1999-02-01

    The sulfonamide and sulfone (sulfa) group of antimalarials has been used extensively throughout malaria endemic regions of the world to control this important infectious disease of humans. Sulfadoxine is the most extensively used drug of this group of drugs and is usually combined with pyrimethamine (Fansidar), particularly for the control of Plasmodium falciparum, the causative agent of the most lethal form of malaria. Resistance to the sulfadoxine/pyrimethamine combination is widespread. Analysis using molecular, genetic and biochemical approaches has shown that the mechanism of resistance to sulfadoxine involves mutation of dihydropteroate synthase, the enzyme target of this group of drugs. Understanding the mechanism of resistance of P. falciparum to sulfa drugs has allowed detailed analysis of the epidemiology of the spread of drug resistance alleles in the field(1)and, in the future, opens the way to the development of novel antimalarials to this target enzyme. Copyright 1999 Harcourt Publishers Ltd.

  6. [Macrolides, lincosamides, streptogramines (MLS): mechanisms of action and resistance].

    PubMed

    Ungureanu, Vasilica

    2010-01-01

    Macrolides, lincosamides and streptogramines are distinct antibiotic (AB) families, with different chemical structure, but with similar antibacterial spectre and mechanisms. Macrolides are natural products of secondary metabolism of several species of actynomyces; they represent a group of compounds with a lactonic ring of variable dimensions (12-22 atoms of C) that can bind, by means of glycosidic bonds, sacharridic and/or amino-sacharridic structures. Most of the MLS antibiotics are bacteriostatic. Their mechanisms consist in inhibiting protein synthesis. the target being 50 S subunit of the bacterial ribosome, the binding sites being different for the different MLS classes. Erythromycin (E) was introduced in therapy in 1952; quickly, several bacterial genera started developing resistance to E. Strains resistant to E were as well resistant to all macrolides and other antibiotics with different structures--lincosamides and streptogramines B--resistance phenotype called MLSB. The main molecular mechanisms for bacterial resistance to MLS are: (1) Target modification, coded by erm genes (>12 classes). In Gram-positive cocii MLSB resistance, regardless of erm gene, can be: inducible (i MLSB)--when the presence of the inductor AB is necessary for methylation enzyme production; constitutive (c MLSB)--when the methylation enzyme is continuously produced Distinction between iMLSB and cMLSB can be easily appreciated based on the phenotypic expression of bacteria. In streptococci--all MLSB antibiotics can act as methylase inductors. (2) The decrease of AB intracellular concentration by active efflux, coded by mef genes--also called M resistance phenotype, low level resistance (LLR). (3) AB inactivation (enzymatic modification of AB); there are different resistance phenotypes: MLSB +SA and L phenotype (in staphyilococci) or SA4 phenotype and L phenotype (in enterococci).

  7. Drug resistance. Population transcriptomics of human malaria parasites reveals the mechanism of artemisinin resistance.

    PubMed

    Mok, Sachel; Ashley, Elizabeth A; Ferreira, Pedro E; Zhu, Lei; Lin, Zhaoting; Yeo, Tomas; Chotivanich, Kesinee; Imwong, Mallika; Pukrittayakamee, Sasithon; Dhorda, Mehul; Nguon, Chea; Lim, Pharath; Amaratunga, Chanaki; Suon, Seila; Hien, Tran Tinh; Htut, Ye; Faiz, M Abul; Onyamboko, Marie A; Mayxay, Mayfong; Newton, Paul N; Tripura, Rupam; Woodrow, Charles J; Miotto, Olivo; Kwiatkowski, Dominic P; Nosten, François; Day, Nicholas P J; Preiser, Peter R; White, Nicholas J; Dondorp, Arjen M; Fairhurst, Rick M; Bozdech, Zbynek

    2015-01-23

    Artemisinin resistance in Plasmodium falciparum threatens global efforts to control and eliminate malaria. Polymorphisms in the kelch domain-carrying protein K13 are associated with artemisinin resistance, but the underlying molecular mechanisms are unknown. We analyzed the in vivo transcriptomes of 1043 P. falciparum isolates from patients with acute malaria and found that artemisinin resistance is associated with increased expression of unfolded protein response (UPR) pathways involving the major PROSC and TRiC chaperone complexes. Artemisinin-resistant parasites also exhibit decelerated progression through the first part of the asexual intraerythrocytic development cycle. These findings suggest that artemisinin-resistant parasites remain in a state of decelerated development at the young ring stage, whereas their up-regulated UPR pathways mitigate protein damage caused by artemisinin. The expression profiles of UPR-related genes also associate with the geographical origin of parasite isolates, further suggesting their role in emerging artemisinin resistance in the Greater Mekong Subregion.

  8. Drug resistance. Population transcriptomics of human malaria parasites reveals the mechanism of artemisinin resistance.

    PubMed

    Mok, Sachel; Ashley, Elizabeth A; Ferreira, Pedro E; Zhu, Lei; Lin, Zhaoting; Yeo, Tomas; Chotivanich, Kesinee; Imwong, Mallika; Pukrittayakamee, Sasithon; Dhorda, Mehul; Nguon, Chea; Lim, Pharath; Amaratunga, Chanaki; Suon, Seila; Hien, Tran Tinh; Htut, Ye; Faiz, M Abul; Onyamboko, Marie A; Mayxay, Mayfong; Newton, Paul N; Tripura, Rupam; Woodrow, Charles J; Miotto, Olivo; Kwiatkowski, Dominic P; Nosten, François; Day, Nicholas P J; Preiser, Peter R; White, Nicholas J; Dondorp, Arjen M; Fairhurst, Rick M; Bozdech, Zbynek

    2015-01-23

    Artemisinin resistance in Plasmodium falciparum threatens global efforts to control and eliminate malaria. Polymorphisms in the kelch domain-carrying protein K13 are associated with artemisinin resistance, but the underlying molecular mechanisms are unknown. We analyzed the in vivo transcriptomes of 1043 P. falciparum isolates from patients with acute malaria and found that artemisinin resistance is associated with increased expression of unfolded protein response (UPR) pathways involving the major PROSC and TRiC chaperone complexes. Artemisinin-resistant parasites also exhibit decelerated progression through the first part of the asexual intraerythrocytic development cycle. These findings suggest that artemisinin-resistant parasites remain in a state of decelerated development at the young ring stage, whereas their up-regulated UPR pathways mitigate protein damage caused by artemisinin. The expression profiles of UPR-related genes also associate with the geographical origin of parasite isolates, further suggesting their role in emerging artemisinin resistance in the Greater Mekong Subregion. PMID:25502316

  9. Effects of Al/sub 2/O/sub 3/ additions on resistivity and microstructure of yttria-stabilized zirconia

    SciTech Connect

    Miyayama, M.; Yanagida, A.; Asada, A.

    1986-04-01

    Stabilized zirconia is a well-known oxygen ionic conductor which acts over a wide range of oxygen partial pressure. Hence the material has been developed for use in a variety of electrical applications such as oxygen sensors, oxygen pumps, and fuel cells. Since zirconia has a high melting point (approx. =2680/sup 0/C), temperatures in excess of 1600/sup 0/C are generally required for traditional fabrication techniques. Sintering agents and/or fine zirconia powders are required for producing dense, impermeable and mechanically strong stabilized zirconia ceramics. However, in most cases, sintering agents have a negative effect on the conduction behavior of stabilized zirconia. Small additions of SiO/sub 2/ are particularly effective for the densification of CaO-stabilized ZrO/sub 2/ (CSZ), but they cause a large increase in resistivity of Y/sub 2/O/sub 3/-stabilized ZrO/sub 2/ (YSZ) at low temperatures. Additions of TiO/sub 2/ to CSZ, and of Fe/sub 2/O/sub 3/ and Bi/sub 2/O/sub 3/ to YSZ, are also reported to aid densification and cause moderate increases in resistivity. The effect of Al/sub 2/O/sub 3/ additions on the resistivity of stabilized zirconia is rather complicated.

  10. Development of trastuzumab-resistant human gastric carcinoma cell lines and mechanisms of drug resistance

    PubMed Central

    Zuo, Qiang; Liu, Jing; Zhang, Jingwen; Wu, Mengwan; Guo, Lihong; Liao, Wangjun

    2015-01-01

    Trastuzumab has been successfully employed for the treatment of Her-2-positive gastric cancer. However, there are problems with both primary and secondary resistance to trastuzumab. In this study, we employed the human gastric carcinoma cell line NCI-N87 with high Her-2 expression to create trastuzumab-resistant NCI-N87/TR cells by stepwise exposure to increasing doses of trastuzumab. Western blotting and Real-time PCR were conducted to detect protein and gene levels. Compared with NCI-N87 cells, the expression of P-IGF-1R and P-AKT proteins was significantly increased in NCI-N87/TR cells (both P = 0.000), while PTEN gene and protein expression showed a significant decrease (both P = 0.000). In addition, mutations of the PTEN gene were detected at exons 5, 7, and 8. The sensitivity of NCI-N87/TR cells to trastuzumab was increased by transfection with the PTEN gene, or by incubation with a PI3K inhibitor (LY294002) or an IGF-IR inhibitor (AG1024), as well as siRNA targeting PI3K p110 or IGF-1R. Taken together, our findings showed that activation of the PI3K-AKT signaling pathway was one of the major mechanisms leading to resistance of NCI-N87/TR gastric cancer cells to trastuzumab, which was probably associated with PTEN gene down-regulation and mutation, as well as with over-activity of the IGF-1R signaling pathway. PMID:26108989

  11. Pathophysiological mechanisms of death resistance in colorectal carcinoma

    PubMed Central

    Huang, Ching-Ying; Yu, Linda Chia-Hui

    2015-01-01

    Colon cancers develop adaptive mechanisms to survive under extreme conditions and display hallmarks of unlimited proliferation and resistance to cell death. The deregulation of cell death is a key factor that contributes to chemoresistance in tumors. In a physiological context, balance between cell proliferation and death, and protection against cell damage are fundamental processes for maintaining gut epithelial homeostasis. The mechanisms underlying anti-death cytoprotection and tumor resistance often bear common pathways, and although distinguishing them would be a challenge, it would also provide an opportunity to develop advanced anti-cancer therapeutics. This review will outline cell death pathways (i.e., apoptosis, necrosis, and necroptosis), and discuss cytoprotective strategies in normal intestinal epithelium and death resistance mechanisms of colon tumor. In colorectal cancers, the intracellular mechanisms of death resistance include the direct alteration of apoptotic and necroptotic machinery and the upstream events modulating death effectors such as tumor suppressor gene inactivation and pro-survival signaling pathways. The autocrine, paracrine and exogenous factors within a tumor microenvironment can also instigate resistance against apoptotic and necroptotic cell death in colon cancers through changes in receptor signaling or transporter uptake. The roles of cyclooxygenase-2/prostaglandin E2, growth factors, glucose, and bacterial lipopolysaccharides in colorectal cancer will be highlighted. Targeting anti-death pathways in the colon cancer tissue might be a promising approach outside of anti-proliferation and anti-angiogenesis strategies for developing novel drugs to treat refractory tumors. PMID:26557002

  12. Biochemical Mechanism of HIV-1 Resistance to Rilpivirine*

    PubMed Central

    Singh, Kamalendra; Marchand, Bruno; Rai, Devendra K.; Sharma, Bechan; Michailidis, Eleftherios; Ryan, Emily M.; Matzek, Kayla B.; Leslie, Maxwell D.; Hagedorn, Ariel N.; Li, Zhe; Norden, Pieter R.; Hachiya, Atsuko; Parniak, Michael A.; Xu, Hong-Tao; Wainberg, Mark A.; Sarafianos, Stefan G.

    2012-01-01

    Rilpivirine (RPV) is a second generation nonnucleoside reverse transcriptase (RT) inhibitor (NNRTI) that efficiently inhibits HIV-1 resistant to first generation NNRTIs. Virological failure during therapy with RPV and emtricitabine is associated with the appearance of E138K and M184I mutations in RT. Here we investigate the biochemical mechanism of RT inhibition and resistance to RPV. We used two transient kinetics approaches (quench-flow and stopped-flow) to determine how subunit-specific mutations in RT p66 or p51 affect association and dissociation of RPV to RT as well as their impact on binding of dNTP and DNA and the catalytic incorporation of nucleotide. We compared WT with four subunit-specific RT mutants, p66M184I/p51WT, p66E138K/p51E138K, p66E138K/M184I/p51E138K, and p66M184I/p51E138K. Ile-184 in p66 (p66184I) decreased the catalytic efficiency of RT (kpol/Kd.dNTP), primarily through a decrease in dNTP binding (Kd.dNTP). Lys-138 either in both subunits or in p51 alone abrogated the negative effect of p66184I by restoring dNTP binding. Furthermore, p51138K reduced RPV susceptibility by altering the ratio of RPV dissociation to RPV association, resulting in a net reduction in RPV equilibrium binding affinity (Kd.RPV = koff.RPV/kon.RPV). Quantum mechanics/molecular mechanics hybrid molecular modeling revealed that p51E138K affects access to the RPV binding site by disrupting the salt bridge between p51E138 and p66K101. p66184I caused repositioning of the Tyr-183 active site residue and decreased the efficiency of RT, whereas the addition of p51138K restored Tyr-183 to a WT-like conformation, thus abrogating the Ile-184-induced functional defects. PMID:22955279

  13. Biochemical mechanism of HIV-1 resistance to rilpivirine.

    PubMed

    Singh, Kamalendra; Marchand, Bruno; Rai, Devendra K; Sharma, Bechan; Michailidis, Eleftherios; Ryan, Emily M; Matzek, Kayla B; Leslie, Maxwell D; Hagedorn, Ariel N; Li, Zhe; Norden, Pieter R; Hachiya, Atsuko; Parniak, Michael A; Xu, Hong-Tao; Wainberg, Mark A; Sarafianos, Stefan G

    2012-11-01

    Rilpivirine (RPV) is a second generation nonnucleoside reverse transcriptase (RT) inhibitor (NNRTI) that efficiently inhibits HIV-1 resistant to first generation NNRTIs. Virological failure during therapy with RPV and emtricitabine is associated with the appearance of E138K and M184I mutations in RT. Here we investigate the biochemical mechanism of RT inhibition and resistance to RPV. We used two transient kinetics approaches (quench-flow and stopped-flow) to determine how subunit-specific mutations in RT p66 or p51 affect association and dissociation of RPV to RT as well as their impact on binding of dNTP and DNA and the catalytic incorporation of nucleotide. We compared WT with four subunit-specific RT mutants, p66(M184I)/p51(WT), p66(E138K)/p51(E138K), p66(E138K/M184I)/p51(E138K), and p66(M184I)/p51(E138K). Ile-184 in p66 (p66(184I)) decreased the catalytic efficiency of RT (k(pol)/K(d)(.dNTP)), primarily through a decrease in dNTP binding (K(d)(.dNTP)). Lys-138 either in both subunits or in p51 alone abrogated the negative effect of p66(184I) by restoring dNTP binding. Furthermore, p51(138K) reduced RPV susceptibility by altering the ratio of RPV dissociation to RPV association, resulting in a net reduction in RPV equilibrium binding affinity (K(d)(.RPV) = k(off.RPV)/k(on.RPV)). Quantum mechanics/molecular mechanics hybrid molecular modeling revealed that p51(E138K) affects access to the RPV binding site by disrupting the salt bridge between p51(E138) and p66(K101). p66(184I) caused repositioning of the Tyr-183 active site residue and decreased the efficiency of RT, whereas the addition of p51(138K) restored Tyr-183 to a WT-like conformation, thus abrogating the Ile-184-induced functional defects. PMID:22955279

  14. Mechanism of resistance of evolved glyphosate-resistant Palmer amaranth (Amaranthus palmeri).

    PubMed

    Gaines, Todd A; Shaner, Dale L; Ward, Sarah M; Leach, Jan E; Preston, Christopher; Westra, Philip

    2011-06-01

    Evolved glyphosate resistance in weedy species represents a challenge for the continued success and utility of glyphosate-resistant crops. Glyphosate functions by inhibiting the plant enzyme 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS). The resistance mechanism was determined in a population of glyphosate-resistant Palmer amaranth from Georgia (U.S.). Within this population, glyphosate resistance correlates with increases in (a) genomic copy number of EPSPS, (b) expression of the EPSPS transcript, (c) EPSPS protein level, and (d) EPSPS enzymatic activity. Dose response results from the resistant and an F(2) population suggest that between 30 and 50 EPSPS genomic copies are necessary to survive glyphosate rates between 0.5 and 1.0 kg ha(-1). These results further confirm the role of EPSPS gene amplification in conferring glyphosate resistance in this population of Palmer amaranth. Questions remain related to how the EPSPS amplification initially occurred and the occurrence of this mechanism in other Palmer amaranth populations and other glyphosate-resistant species.

  15. Creep Resistance of Disk Alloy CH98 with Tungsten and Niobium Additions

    NASA Technical Reports Server (NTRS)

    Gayda, John

    2003-01-01

    Gas turbine engines for future subsonic transports will likely have higher pressure ratios which will require nickel-base superalloy disks with temperature capability up to 1400 F, an increase of about 200 F over current engines. Several advanced disk alloys are being developed to fill this need. One of these, CH98, is a promising candidate for gas turbine engines and is being studied in NASA's AST Program. Additions of the refractory elements tungsten and niobium have been shown to improve tensile and creep properties while maintaining good high temperature fatigue crack growth resistance. Further improvements in creep and crack growth resistance can be achieved with a coarse grain microstructure. The purpose of the present study is aimed at providing a detailed assessment of 0.2 percent creep rates for coarse grain CH98 with tungsten and niobium additions over a range of temperatures and stresses of interest to disk applications.

  16. Monitoring and identifying antibiotic resistance mechanisms in bacteria.

    PubMed

    Roe, M T; Pillai, S D

    2003-04-01

    Sub-therapeutic administration of antibiotics to animals is under intense scrutiny because they contribute to the dissemination of antibiotic-resistant bacteria into the food chain. Studies suggest that there is a link between the agricultural use of antibiotics and antibiotic-resistant human infections. Antibiotic-resistant organisms from animal and human wastes reenter the human and animal populations through a number of pathways including natural waters, irrigation water, drinking water, and vegetables and foods. Antibiotic usage in the United States for animal production (disease prevention and growth promotion) is estimated to be 18 million pounds annually. As much as 25 to 75% of the antibiotics administered to feedlot animals are excreted unaltered in feces. Because about 180 million dry tons of livestock and poultry waste is generated annually in the United States, it is not surprising that animal-derived antibiotic-resistant organisms are found contaminating groundwater, surface water, and food crops. It is extremely important to clearly understand the molecular mechanisms that could potentially cause lateral or horizontal gene transfer of antibiotic resistance genes among bacteria. Once the mechanisms and magnitude of resistance gene transfer are clearly understood and quantified, strategies can be instituted to reduce the potential for dissemination of these genes.

  17. Effect of mechanical surface and heat treatments on erosion resistance

    NASA Technical Reports Server (NTRS)

    Salik, J.; Buckley, D. H.

    1980-01-01

    The effects of mechanical surface treatments as well as heat treatments on the erosion resistance of 6061 aluminum alloy and 1045 steel were studied. Mechanical surface treatments were found to have little or no effect on the erosion resistance. This is due to the formation by particle impact of a work hardened surface layer regardless of the initial surface condition. The erosion resistance of Al single crystals is found to be independent of orientation. This is due to destruction of the surface microstructure and formation of a polycrystalline surface layer by the impact of erodant particles as observed by X-ray diffraction. While upon solution treatment of annealed 6061 aluminum the increase in hardness is accompanied by an increase in erosion resistance, precipitation treatment which causes a further increase in hardness results in slightly lower erosion resistance. Using two types of erodant particles, glass beads and crushed glass, the erosion rate is found to be strongly dependent on erodant particle shape, being an order of magnitude higher for erosion with crushed glass as compared to glass beads. While for erosion with glass beads heat treatment of 1045 steel had a profound effect on its erosion resistance, little or no such effect was observed for erosion with crushed glass.

  18. Resistive switching characteristics and mechanisms in silicon oxide memory devices

    NASA Astrophysics Data System (ADS)

    Chang, Yao-Feng; Fowler, Burt; Chen, Ying-Chen; Zhou, Fei; Wu, Xiaohan; Chen, Yen-Ting; Wang, Yanzhen; Xue, Fei; Lee, Jack C.

    2016-05-01

    Intrinsic unipolar SiOx-based resistance random access memories (ReRAM) characterization, switching mechanisms, and applications have been investigated. Device structures, material compositions, and electrical characteristics are identified that enable ReRAM cells with high ON/OFF ratio, low static power consumption, low switching power, and high readout-margin using complementary metal-oxide semiconductor transistor (CMOS)-compatible SiOx-based materials. These ideas are combined with the use of horizontal and vertical device structure designs, composition optimization, electrical control, and external factors to help understand resistive switching (RS) mechanisms. Measured temperature effects, pulse response, and carrier transport behaviors lead to compact models of RS mechanisms and energy band diagrams in order to aid the development of computer-aided design for ultralarge-v scale integration. This chapter presents a comprehensive investigation of SiOx-based RS characteristics and mechanisms for the post-CMOS device era.

  19. Screening and incorporation of rust resistance from Allium cepa into bunching onion (Allium fistulosum) via alien chromosome addition.

    PubMed

    Wako, Tadayuki; Yamashita, Ken-ichiro; Tsukazaki, Hikaru; Ohara, Takayoshi; Kojima, Akio; Yaguchi, Shigenori; Shimazaki, Satoshi; Midorikawa, Naoko; Sakai, Takako; Yamauchi, Naoki; Shigyo, Masayoshi

    2015-04-01

    Bunching onion (Allium fistulosum L.; 2n = 16), bulb onion (Allium cepa L. Common onion group), and shallot (Allium cepa L. Aggregatum group) cultivars were inoculated with rust fungus, Puccinia allii, isolated from bunching onion. Bulb onions and shallots are highly resistant to rust, suggesting they would serve as useful resources for breeding rust resistant bunching onions. To identify the A. cepa chromosome(s) related to rust resistance, a complete set of eight A. fistulosum - shallot monosomic alien addition lines (MAALs) were inoculated with P. allii. At the seedling stage, FF+1A showed a high level of resistance in controlled-environment experiments, suggesting that the genes related to rust resistance could be located on shallot chromosome 1A. While MAAL, multi-chromosome addition line, and hypoallotriploid adult plants did not exhibit strong resistance to rust. In contrast to the high resistance of shallot, the addition line FF+1A+5A showed reproducibly high levels of rust resistance.

  20. Tumor resistance to vascular disrupting agents: mechanisms, imaging, and solutions

    PubMed Central

    Liang, Wenjie; Ni, Yicheng; Chen, Feng

    2016-01-01

    The emergence of vascular disrupting agents (VDAs) is a significant advance in the treatment of solid tumors. VDAs induce rapid and selective shutdown of tumor blood flow resulting in massive necrosis. However, a viable marginal tumor rim always remains after VDA treatment and is a major cause of recurrence. In this review, we discuss the mechanisms involved in the resistance of solid tumors to VDAs. Hypoxia, tumor-associated macrophages, and bone marrow-derived circulating endothelial progenitor cells all may contribute to resistance. Resistance can be monitored using magnetic resonance imaging markers. The various solutions proposed to manage tumor resistance to VDAs emphasize combining these agents with other approaches including antiangiogenic agents, chemotherapy, radiotherapy, radioimmunotherapy, and sequential dual-targeting internal radiotherapy. PMID:26812886

  1. Effect of mechanical surface and heat treatments on erosion resistance

    NASA Technical Reports Server (NTRS)

    Salik, J.; Buckley, D. H.

    1981-01-01

    The effect of erosion by glass beads and crushed glass and by heat treatments on the erosional resistance of 6061 aluminum alloy and 1045 steel were studied. The aluminum alloy's erosion resistance was found to be insensitive to mechanical surface treatment applied before testing, and was determined to depend on the properties of the work-hardened surface layer; this was also demonstrated for aluminum alloy single crystals. The aluminum alloy heat treatments included annealing, solution, and precipitation. Solution was found to increase erosion resistance but precipitation had the opposite effect. Hardness showed no correlation with erosion resistance for either aluminum alloy steel. The steel tests showed that crushed glass provides an order of magnitude more erosion than glass beads.

  2. Antifungal drug resistance among Candida species: mechanisms and clinical impact.

    PubMed

    Sanguinetti, Maurizio; Posteraro, Brunella; Lass-Flörl, Cornelia

    2015-06-01

    The epidemiology of Candida infections has changed in recent years. Although Candida albicans is still the main cause of invasive candidiasis in most clinical settings, a substantial proportion of patients is now infected with non-albicans Candida species. The various Candida species vary in their susceptibility to the most commonly used antifungal agents, and the intrinsic resistance to antifungal therapy seen in some species, along with the development of acquired resistance during treatment in others, is becoming a major problem in the management of Candida infection. A better understanding of the mechanisms and clinical impact of antifungal drug resistance is essential for the efficient treatment of patients with Candida infection and for improving treatment outcomes. Herein, we report resistance to the azoles and echinocandins among Candida species.

  3. Mechanisms of Linezolid Resistance among Staphylococci in a Tertiary Hospital

    PubMed Central

    Quiles-Melero, Inmaculada; Gómez-Gil, Rosa; Romero-Gómez, María Pilar; Sánchez-Díaz, Ana María; de Pablos, Manuela; García-Rodriguez, Julio; Gutiérrez, Avelino

    2013-01-01

    The mechanisms of linezolid resistance among 86 staphylococcal isolates from two intensive care units were investigated. The most frequent was the G2576T mutation in the 23S rRNA (82%). The cfr gene was found in 17% of the isolates, seven S. aureus and eight S. epidermidis isolates. Four of the S. epidermidis isolates had the G2576T mutation and the cfr gene. In four S. haemolyticus isolates, the mechanism could not be identified. PMID:23269737

  4. Pool of resistance mechanisms to glyphosate in Digitaria insularis.

    PubMed

    de Carvalho, Leonardo Bianco; Alves, Pedro Luis da Costa Aguiar; González-Torralva, Fidel; Cruz-Hipolito, Hugo Enrique; Rojano-Delgado, Antonia María; De Prado, Rafael; Gil-Humanes, Javier; Barro, Francisco; de Castro, María Dolores Luque

    2012-01-18

    Digitaria insularis biotypes resistant to glyphosate have been detected in Brazil. Studies were carried out in controlled conditions to determine the role of absorption, translocation, metabolism, and gene mutation as mechanisms of glyphosate resistance in D. insularis. The susceptible biotype absorbed at least 12% more (14)C-glyphosate up to 48 h after treatment (HAT) than resistant biotypes. High differential (14)C-glyphosate translocation was observed at 12 HAT, so that >70% of the absorbed herbicide remained in the treated leaf in resistant biotypes, whereas 42% remained in the susceptible biotype at 96 HAT. Glyphosate was degraded to aminomethylphosphonic acid (AMPA), glyoxylate, and sarcosine by >90% in resistant biotypes, whereas a small amount of herbicide (up to 11%) was degraded by the susceptible biotype up to 168 HAT. Two amino acid changes were found at positions 182 and 310 in EPSPS, consisting of a proline to threonine and a tyrosine to cysteine substitution, respectively, in resistant biotypes. Therefore, absorption, translocation, metabolism, and gene mutation play an important role in the D. insularis glyphosate resistance.

  5. Mechanisms of resistance to HER2 target therapy.

    PubMed

    Tortora, Giampaolo

    2011-01-01

    In the past years, several agents targeting signaling proteins critical for breast cancer growth and dissemination entered clinical evaluation. They include drugs directed against the HER/ErbB family of receptor tyrosine kinases, especially HER2; several downstream signal transducers; and proteins involved in tumor angiogenesis and dissemination. Unfortunately, resistance to targeted agents is a quite common feature, and understanding of the molecular mechanisms predicting response or failure has become a crucial issue to optimize treatment and select patients who are the best candidates to respond. The neoadjuvant setting offers unique opportunities allowing tumor sampling and search for molecular determinants of response. A variety of tumor and host factors may account for the onset of resistance. Major progress has been made in the understanding of the mechanisms involved in the primary and acquired resistance to targeted agents, especially the anti-HER2 drugs, which play a pivotal role in the weaponry against breast cancer.

  6. Mechanisms of Drug Resistance in Relapse and Refractory Multiple Myeloma

    PubMed Central

    Yang, Wen-Chi; Lin, Sheng-Fung

    2015-01-01

    Multiple myeloma (MM) is a hematological malignancy that remains incurable because most patients eventually relapse or become refractory to current treatments. Although the treatments have improved, the major problem in MM is resistance to therapy. Clonal evolution of MM cells and bone marrow microenvironment changes contribute to drug resistance. Some mechanisms affect both MM cells and microenvironment, including the up- and downregulation of microRNAs and programmed death factor 1 (PD-1)/PD-L1 interaction. Here, we review the pathogenesis of MM cells and bone marrow microenvironment and highlight possible drug resistance mechanisms. We also review a potential molecular targeting treatment and immunotherapy for patients with refractory or relapse MM. PMID:26649299

  7. Mechanisms of resistance to EGFR tyrosine kinase inhibitors.

    PubMed

    Huang, Lihua; Fu, Liwu

    2015-09-01

    Since the discovery that non-small cell lung cancer (NSCLC) is driven by epidermal growth factor receptor (EGFR) mutations, the EGFR tyrosine kinase inhibitors (EGFR-TKIs, e.g., gefitinib and elrotinib) have been effectively used for clinical treatment. However, patients eventually develop drug resistance. Resistance to EGFR-TKIs is inevitable due to various mechanisms, such as the secondary mutation (T790M), activation of alternative pathways (c-Met, HGF, AXL), aberrance of the downstream pathways (K-RAS mutations, loss of PTEN), impairment of the EGFR-TKIs-mediated apoptosis pathway (BCL2-like 11/BIM deletion polymorphism), histologic transformation, ATP binding cassette (ABC) transporter effusion, etc. Here we review and summarize the known resistant mechanisms to EGFR-TKIs and provide potential targets for development of new therapeutic strategies.

  8. Mechanisms and consequences of bacterial resistance to antimicrobial peptides.

    PubMed

    Andersson, D I; Hughes, D; Kubicek-Sutherland, J Z

    2016-05-01

    Cationic antimicrobial peptides (AMPs) are an intrinsic part of the human innate immune system. Over 100 different human AMPs are known to exhibit broad-spectrum antibacterial activity. Because of the increased frequency of resistance to conventional antibiotics there is an interest in developing AMPs as an alternative antibacterial therapy. Several cationic peptides that are derivatives of AMPs from the human innate immune system are currently in clinical development. There are also ongoing clinical studies aimed at modulating the expression of AMPs to boost the human innate immune response. In this review we discuss the potential problems associated with these therapeutic approaches. There is considerable experimental data describing mechanisms by which bacteria can develop resistance to AMPs. As for any type of drug resistance, the rate by which AMP resistance would emerge and spread in a population of bacteria in a natural setting will be determined by a complex interplay of several different factors, including the mutation supply rate, the fitness of the resistant mutant at different AMP concentrations, and the strength of the selective pressure. Several studies have already shown that AMP-resistant bacterial mutants display broad cross-resistance to a variety of AMPs with different structures and modes of action. Therefore, routine clinical administration of AMPs to treat bacterial infections may select for resistant bacterial pathogens capable of better evading the innate immune system. The ramifications of therapeutic levels of exposure on the development of AMP resistance and bacterial pathogenesis are not yet understood. This is something that needs to be carefully studied and monitored if AMPs are used in clinical settings. PMID:27180309

  9. Mechanisms and consequences of bacterial resistance to antimicrobial peptides.

    PubMed

    Andersson, D I; Hughes, D; Kubicek-Sutherland, J Z

    2016-05-01

    Cationic antimicrobial peptides (AMPs) are an intrinsic part of the human innate immune system. Over 100 different human AMPs are known to exhibit broad-spectrum antibacterial activity. Because of the increased frequency of resistance to conventional antibiotics there is an interest in developing AMPs as an alternative antibacterial therapy. Several cationic peptides that are derivatives of AMPs from the human innate immune system are currently in clinical development. There are also ongoing clinical studies aimed at modulating the expression of AMPs to boost the human innate immune response. In this review we discuss the potential problems associated with these therapeutic approaches. There is considerable experimental data describing mechanisms by which bacteria can develop resistance to AMPs. As for any type of drug resistance, the rate by which AMP resistance would emerge and spread in a population of bacteria in a natural setting will be determined by a complex interplay of several different factors, including the mutation supply rate, the fitness of the resistant mutant at different AMP concentrations, and the strength of the selective pressure. Several studies have already shown that AMP-resistant bacterial mutants display broad cross-resistance to a variety of AMPs with different structures and modes of action. Therefore, routine clinical administration of AMPs to treat bacterial infections may select for resistant bacterial pathogens capable of better evading the innate immune system. The ramifications of therapeutic levels of exposure on the development of AMP resistance and bacterial pathogenesis are not yet understood. This is something that needs to be carefully studied and monitored if AMPs are used in clinical settings.

  10. Surveillance of Travellers: An Additional Tool for Tracking Antimalarial Drug Resistance in Endemic Countries

    PubMed Central

    Gharbi, Myriam; Flegg, Jennifer A.; Pradines, Bruno; Berenger, Ako; Ndiaye, Magatte; Djimdé, Abdoulaye A.; Roper, Cally; Hubert, Véronique; Kendjo, Eric; Venkatesan, Meera; Brasseur, Philippe; Gaye, Oumar; Offianan, André T.; Penali, Louis; Le Bras, Jacques; Guérin, Philippe J.; Study, Members of the French National Reference Center for Imported Malaria

    2013-01-01

    Introduction There are growing concerns about the emergence of resistance to artemisinin-based combination therapies (ACTs). Since the widespread adoption of ACTs, there has been a decrease in the systematic surveillance of antimalarial drug resistance in many malaria-endemic countries. The aim of this work was to test whether data on travellers returning from Africa with malaria could serve as an additional surveillance system of local information sources for the emergence of drug resistance in endemic-countries. Methodology Data were collected from travellers with symptomatic Plasmodium falciparum malaria returning from Senegal (n = 1,993), Mali (n = 2,372), Cote d’Ivoire (n = 4,778) or Cameroon (n = 3,272) and recorded in the French Malaria Reference Centre during the period 1996–2011. Temporal trends of the proportion of parasite isolates that carried the mutant genotype, pfcrt 76T, a marker of resistance to chloroquine (CQ) and pfdhfr 108N, a marker of resistance to pyrimethamine, were compared for travellers and within-country surveys that were identified through a literature review in PubMed. The in vitro response to CQ was also compared between these two groups for parasites from Senegal. Results The trends in the proportion of parasites that carried pfcrt 76T, and pfdhfr 108N, were compared for parasites from travellers and patients within-country using the slopes of the curves over time; no significant differences in the trends were found for any of the 4 countries. These results were supported by in vitro analysis of parasites from the field in Senegal and travellers returning to France, where the trends were also not significantly different. Conclusion The results have not shown different trends in resistance between parasites derived from travellers or from parasites within-country. This work highlights the value of an international database of drug responses in travellers as an additional tool to assess the emergence of drug

  11. Preparation and ageing-resistant properties of polyester composites modified with functional nanoscale additives.

    PubMed

    Guo, Gang; Shi, Qiwu; Luo, Yanbing; Fan, Rangrang; Zhou, Liangxue; Qian, Zhiyong; Yu, Jie

    2014-01-01

    This study investigated ageing-resistant properties of carboxyl-terminated polyester (polyethylene glycol terephthalate) composites modified with nanoscale titanium dioxide particles (nano-TiO2). The nano-TiO2 was pretreated by a dry coating method, with aluminate coupling agent as a functional grafting additive. The agglomeration resistance was evaluated, which exhibited significant improvement for the modified nanoparticles. Then, the effects of the modified nano-TiO2 on the crosslinking and ageing-resistant properties of the composites were studied. With a real-time Fourier transform infrared (FT-IR) measurement, the nano-TiO2 displayed promoting effect on the crosslinking of polyester resin with triglycidyl isocyanurate (TGIC) as crosslinking agent. Moreover, the gloss retention, colour aberration and the surface morphologies of the composites during accelerated UV ageing (1500 hours) were investigated. The results demonstrated much less degree of ageing degradation for the nanocomposites, indicating an important role of the nano-TiO2 in improving the ageing-resistant properties of synthetic polymer composites. PMID:24872802

  12. Preparation and ageing-resistant properties of polyester composites modified with functional nanoscale additives.

    PubMed

    Guo, Gang; Shi, Qiwu; Luo, Yanbing; Fan, Rangrang; Zhou, Liangxue; Qian, Zhiyong; Yu, Jie

    2014-01-01

    This study investigated ageing-resistant properties of carboxyl-terminated polyester (polyethylene glycol terephthalate) composites modified with nanoscale titanium dioxide particles (nano-TiO2). The nano-TiO2 was pretreated by a dry coating method, with aluminate coupling agent as a functional grafting additive. The agglomeration resistance was evaluated, which exhibited significant improvement for the modified nanoparticles. Then, the effects of the modified nano-TiO2 on the crosslinking and ageing-resistant properties of the composites were studied. With a real-time Fourier transform infrared (FT-IR) measurement, the nano-TiO2 displayed promoting effect on the crosslinking of polyester resin with triglycidyl isocyanurate (TGIC) as crosslinking agent. Moreover, the gloss retention, colour aberration and the surface morphologies of the composites during accelerated UV ageing (1500 hours) were investigated. The results demonstrated much less degree of ageing degradation for the nanocomposites, indicating an important role of the nano-TiO2 in improving the ageing-resistant properties of synthetic polymer composites.

  13. Preparation and ageing-resistant properties of polyester composites modified with functional nanoscale additives

    NASA Astrophysics Data System (ADS)

    Guo, Gang; Shi, Qiwu; Luo, Yanbing; Fan, Rangrang; Zhou, Liangxue; Qian, Zhiyong; Yu, Jie

    2014-05-01

    This study investigated ageing-resistant properties of carboxyl-terminated polyester (polyethylene glycol terephthalate) composites modified with nanoscale titanium dioxide particles (nano-TiO2). The nano-TiO2 was pretreated by a dry coating method, with aluminate coupling agent as a functional grafting additive. The agglomeration resistance was evaluated, which exhibited significant improvement for the modified nanoparticles. Then, the effects of the modified nano-TiO2 on the crosslinking and ageing-resistant properties of the composites were studied. With a real-time Fourier transform infrared (FT-IR) measurement, the nano-TiO2 displayed promoting effect on the crosslinking of polyester resin with triglycidyl isocyanurate (TGIC) as crosslinking agent. Moreover, the gloss retention, colour aberration and the surface morphologies of the composites during accelerated UV ageing (1500 hours) were investigated. The results demonstrated much less degree of ageing degradation for the nanocomposites, indicating an important role of the nano-TiO2 in improving the ageing-resistant properties of synthetic polymer composites.

  14. Preparation and ageing-resistant properties of polyester composites modified with functional nanoscale additives

    PubMed Central

    2014-01-01

    This study investigated ageing-resistant properties of carboxyl-terminated polyester (polyethylene glycol terephthalate) composites modified with nanoscale titanium dioxide particles (nano-TiO2). The nano-TiO2 was pretreated by a dry coating method, with aluminate coupling agent as a functional grafting additive. The agglomeration resistance was evaluated, which exhibited significant improvement for the modified nanoparticles. Then, the effects of the modified nano-TiO2 on the crosslinking and ageing-resistant properties of the composites were studied. With a real-time Fourier transform infrared (FT-IR) measurement, the nano-TiO2 displayed promoting effect on the crosslinking of polyester resin with triglycidyl isocyanurate (TGIC) as crosslinking agent. Moreover, the gloss retention, colour aberration and the surface morphologies of the composites during accelerated UV ageing (1500 hours) were investigated. The results demonstrated much less degree of ageing degradation for the nanocomposites, indicating an important role of the nano-TiO2 in improving the ageing-resistant properties of synthetic polymer composites. PMID:24872802

  15. Antibacterial-Resistant Pseudomonas aeruginosa: Clinical Impact and Complex Regulation of Chromosomally Encoded Resistance Mechanisms

    PubMed Central

    Lister, Philip D.; Wolter, Daniel J.; Hanson, Nancy D.

    2009-01-01

    Summary: Treatment of infectious diseases becomes more challenging with each passing year. This is especially true for infections caused by the opportunistic pathogen Pseudomonas aeruginosa, with its ability to rapidly develop resistance to multiple classes of antibiotics. Although the import of resistance mechanisms on mobile genetic elements is always a concern, the most difficult challenge we face with P. aeruginosa is its ability to rapidly develop resistance during the course of treating an infection. The chromosomally encoded AmpC cephalosporinase, the outer membrane porin OprD, and the multidrug efflux pumps are particularly relevant to this therapeutic challenge. The discussion presented in this review highlights the clinical significance of these chromosomally encoded resistance mechanisms, as well as the complex mechanisms/pathways by which P. aeruginosa regulates their expression. Although a great deal of knowledge has been gained toward understanding the regulation of AmpC, OprD, and efflux pumps in P. aeruginosa, it is clear that we have much to learn about how this resourceful pathogen coregulates different resistance mechanisms to overcome the antibacterial challenges it faces. PMID:19822890

  16. Effects of Sn addition on the microstructure, mechanical properties and corrosion behavior of Ti–Nb–Sn alloys

    SciTech Connect

    Moraes, Paulo E.L.; Contieri, Rodrigo J.; Lopes, Eder S.N.; Robin, Alain; Caram, Rubens

    2014-10-15

    Ti and Ti alloys are widely used in restorative surgery because of their good biocompatibility, enhanced mechanical behavior and high corrosion resistance in physiological media. The corrosion resistance of Ti-based materials is due to the spontaneous formation of the TiO{sub 2} oxide film on their surface, which exhibits elevated stability in biological fluids. Ti–Nb alloys, depending on the composition and the processing routes to which the alloys are subjected, have high mechanical strength combined with low elastic modulus. The addition of Sn to Ti–Nb alloys allows the phase transformations to be controlled, particularly the precipitation of ω phase. The aim of this study is to discuss the microstructure, mechanical properties and corrosion behavior of cast Ti–Nb alloys to which Sn has been added. Samples were centrifugally cast in a copper mold, and the microstructure was characterized using optical microscopy, scanning electron microscopy and X-ray diffractometry. Mechanical behavior evaluation was performed using Berkovich nanoindentation, Vickers hardness and compression tests. The corrosion behavior was evaluated in Ringer's solution at room temperature using electrochemical techniques. The results obtained suggested that the physical, mechanical and chemical behaviors of the Ti–Nb–Sn alloys are directly dependent on the Sn content. - Graphical abstract: Effects of Sn addition to the Ti–30Nb alloy on the elastic modulus. - Highlights: • Sn addition causes reduction of the ω phase precipitation. • Minimum Vickers hardness and elastic modulus occurred for 6 wt.% Sn content. • Addition of 6 wt.% Sn resulted in maximum ductility and minimum compression strength. • All Ti–30Nb–XSn (X = 0, 2, 4, 6, 8 and 10%) alloys are passive in Ringer's solution. • Highest corrosion resistance was observed for 6 wt.% Sn content.

  17. Molecular mechanism of resistance of Fusarium fujikuroi to benzimidazole fungicides.

    PubMed

    Chen, Zihao; Gao, Tao; Liang, Shuping; Liu, Kexue; Zhou, Mingguo; Chen, Changjun

    2014-08-01

    Although carbendazim (MBC) and other benzimidazole fungicides have effectively controlled bakanae disease of rice (which is caused by Fusarium fujikuroi, F. proliferatum, and F. verticillioides) in the past, MBC resistance has become common. Previous research has shown that MBC resistance results from a mutation in the β1 -tubulin (β1 tub) gene in F. verticillioides. However, MBC resistance in F. fujikuroi, a predominant species in China, does not result from a mutation in the β1 tub. The molecular mechanism of F. fujikuroi resistance against benzimidazole fungicides is poorly understood. In this study, we determined that although β1 tub and β2 -tubulin (β2 tub) in F. fujikuroi have high homology with β1 tub and β2 tub in F. verticillioides, MBC resistance in F. fujikuroi results from mutations in β2 tub [GAG(Glu)→GTG(Val) at codon 198, TTC(Phe)→TAC(Tyr) at codon 200, and GGC(Gly)→GGT(Gly) at codon 235] but not in β1 tub. Δβ2 tub (β2 tub deletion) mutants were highly sensitive to MBC, produced fewer conidia and were less virulent than parental strains. Complementation of the Δβ2 tub mutants with a copy of the whole β2 tub locus from their parental strains restored the level of MBC resistance (or sensitivity) to that of the parental strain.

  18. Influenza neuraminidase inhibitors: antiviral action and mechanisms of resistance

    PubMed Central

    McKimm‐Breschkin, Jennifer L.

    2012-01-01

    Please cite this paper as: McKimm‐Breschkin (2012) Influenza neuraminidase inhibitors: Antiviral action and mechanisms of resistance. Influenza and Other Respiratory Viruses 7(Suppl. 1), 25–36. There are two major classes of antivirals available for the treatment and prevention of influenza, the M2 inhibitors and the neuraminidase inhibitors (NAIs). The M2 inhibitors are cheap, but they are only effective against influenza A viruses, and resistance arises rapidly. The current influenza A H3N2 and pandemic A(H1N1)pdm09 viruses are already resistant to the M2 inhibitors as are many H5N1 viruses. There are four NAIs licensed in some parts of the world, zanamivir, oseltamivir, peramivir, and a long‐acting NAI, laninamivir. This review focuses on resistance to the NAIs. Because of differences in their chemistry and subtle differences in NA structures, resistance can be both NAI‐ and subtype specific. This results in different drug resistance profiles, for example, the H274Y mutation confers resistance to oseltamivir and peramivir, but not to zanamivir, and only in N1 NAs. Mutations at E119, D198, I222, R292, and N294 can also reduce NAI sensitivity. In the winter of 2007–2008, an oseltamivir‐resistant seasonal influenza A(H1N1) strain with an H274Y mutation emerged in the northern hemisphere and spread rapidly around the world. In contrast to earlier evidence of such resistant viruses being unfit, this mutant virus remained fully transmissible and pathogenic and became the major seasonal A(H1N1) virus globally within a year. This resistant A(H1N1) virus was displaced by the sensitive A(H1N1)pdm09 virus. Approximately 0·5–1·0% of community A(H1N1)pdm09 isolates are currently resistant to oseltamivir. It is now apparent that variation in non‐active site amino acids can affect the fitness of the enzyme and compensate for mutations that confer high‐level oseltamivir resistance resulting in minimal impact on enzyme function. PMID:23279894

  19. The Landscape of Pancreatic Cancer Therapeutic Resistance Mechanisms.

    PubMed

    Chand, Saswati; O'Hayer, Kevin; Blanco, Fernando F; Winter, Jordan M; Brody, Jonathan R

    2016-01-01

    Pancreatic cancer (pancreatic ductal adenocarcinoma, PDA) is infamously moving to the top of the list as one of the most lethal cancers with an overall 5 year survival rate of 7%. Multiple genomic-based and molecular characterization studies of PDA specimens and established animal models have provided the field with multiple targets and a progression model of this disease. Still, to date, the best therapeutic options are surgery and combination cytotoxic therapies. In general, even in the best case scenario (i.e., an early stage diagnosis and a response to a specific therapy), most of these fortunate patients' PDA cells acquire or exert resistance mechanisms and eventually kill the patient. Herein, we touch on a growing field of investigation that focuses on PDA cell therapeutic resistance mechanisms. We examine extrinsic elements (i.e., the tumor microenvironment, hypoxia) to the intrinsic processes within the cell (i.e., post-transcriptional gene regulation and somatic mutations) that are important for therapeutic efficacy and resistance. Even as better targeted and personalized approaches move through the clinical trial pipeline the discussed resistance mechanisms will most likely play a role in the management of this deadly disease.

  20. The Landscape of Pancreatic Cancer Therapeutic Resistance Mechanisms

    PubMed Central

    Chand, Saswati; O'Hayer, Kevin; Blanco, Fernando F.; Winter, Jordan M.; Brody, Jonathan R.

    2016-01-01

    Pancreatic cancer (pancreatic ductal adenocarcinoma, PDA) is infamously moving to the top of the list as one of the most lethal cancers with an overall 5 year survival rate of 7%. Multiple genomic-based and molecular characterization studies of PDA specimens and established animal models have provided the field with multiple targets and a progression model of this disease. Still, to date, the best therapeutic options are surgery and combination cytotoxic therapies. In general, even in the best case scenario (i.e., an early stage diagnosis and a response to a specific therapy), most of these fortunate patients' PDA cells acquire or exert resistance mechanisms and eventually kill the patient. Herein, we touch on a growing field of investigation that focuses on PDA cell therapeutic resistance mechanisms. We examine extrinsic elements (i.e., the tumor microenvironment, hypoxia) to the intrinsic processes within the cell (i.e., post-transcriptional gene regulation and somatic mutations) that are important for therapeutic efficacy and resistance. Even as better targeted and personalized approaches move through the clinical trial pipeline the discussed resistance mechanisms will most likely play a role in the management of this deadly disease. PMID:26929734

  1. Glycation & Insulin Resistance: Novel Mechanisms and Unique Targets?

    PubMed Central

    Song, Fei; Schmidt, Ann Marie

    2012-01-01

    Objectives Multiple biochemical, metabolic and signal transduction pathways contribute to insulin resistance. In this review, we present the evidence that the post-translational process of protein glycation may play role in insulin resistance. The post-translational modifications, the advanced glycation endproducts (AGEs), are formed and accumulate by endogenous and exogenous mechanisms. Methods and Results AGEs may contribute to insulin resistance by a variety of mechanisms, including generation of tumor necrosis factor-alpha, direct modification of the insulin molecule thereby leading to its impaired action, generation of oxidative stress, and impairment of mitochondrial function, as examples. AGEs may stimulate signal transduction via engagement of cellular receptors, such as RAGE, or receptor for AGE. AGE-RAGE interaction perpetuates AGE formation and cellular stress via induction of inflammation, oxidative stress and reduction in the expression and activity of the enzyme, glyoxalase I that detoxifies the AGE precursor, methylglyoxal, or MG. Conclusions Once set in motion, glycation-promoting mechanisms may stimulate ongoing AGE production and target tissue stresses that reduce insulin responsiveness. Strategies to limit AGE accumulation and action may contribute to prevention of insulin resistance and its consequences. PMID:22815341

  2. Etoxazole resistance in predatory mite Phytoseiulus persimilis A.-H. (Acari: Phytoseiidae): Cross-resistance, inheritance and biochemical resistance mechanisms.

    PubMed

    Yorulmaz Salman, Sibel; Aydınlı, Fatma; Ay, Recep

    2015-07-01

    Phytoseiulus persimilis of the family Phytoseiidae is an effective predatory mite species that is used to control pest mites. The LC50 and LC60 values of etoxazole were determined on P. persimilis using a leaf-disc method and spraying tower. A laboratory selection population designated ETO6 was found to have a 111.63-fold resistance to etoxazole following 6 selection cycles. This population developed low cross-resistance to spinosad, spiromesifen, acetamiprid, indoxacarb, chlorantraniliprole, milbemectin and moderate cross-resistance to deltamethrin. PBO, IBP and DEM synergised resistance 3.17-, 2.85- and 3.60-fold respectively. Crossing experiments revealed that etoxazole resistance in the ETO6 population was an intermediately dominant and polygenic. In addition, detoxifying enzyme activities were increased 2.71-fold for esterase, 3.09-fold for glutathione S-transferase (GST) and 2.76-fold for cytochrome P450 monooxygenase (P450) in the ETO6 population. Selection for etoxazole under laboratory conditions resulted in the development of etoxazole resistance in the predatory mite P. persimilis that are resistant to pesticides are considered valuable for use in resistance management programmes within integrated pest control strategies. PMID:26071813

  3. Molecular mechanisms of cisplatin resistance in cervical cancer

    PubMed Central

    Zhu, Haiyan; Luo, Hui; Zhang, Wenwen; Shen, Zhaojun; Hu, Xiaoli; Zhu, Xueqiong

    2016-01-01

    Patients with advanced or recurrent cervical cancer have poor prognosis, and their 1-year survival is only 10%–20%. Chemotherapy is considered as the standard treatment for patients with advanced or recurrent cervical cancer, and cisplatin appears to treat the disease effectively. However, resistance to cisplatin may develop, thus substantially compromising the efficacy of cisplatin to treat advanced or recurrent cervical cancer. In this article, we systematically review the recent literature and summarize the recent advances in our understanding of the molecular mechanisms underlying cisplatin resistance in cervical cancer. PMID:27354763

  4. Mechanisms of powdery mildew resistance in the Vitaceae family.

    PubMed

    Feechan, Angela; Kabbara, Samuela; Dry, Ian B

    2011-04-01

    The cultivated grapevine, Vitis vinifera, is a member of the Vitaceae family, which comprises over 700 species in 14 genera. Vitis vinifera is highly susceptible to the powdery mildew pathogen Erysiphe necator. However, other species within the Vitaceae family have been reported to show resistance to this fungal pathogen, but little is known about the mechanistic basis of this resistance. Therefore, the frequency of successful E. necator penetration events, in addition to programmed cell death (PCD) responses, were investigated in a representative genotype from a range of different species within the Vitaceae family. The results revealed that penetration resistance and PCD-associated responses, or combinations of both, are employed by the different Vitaceae genera to limit E. necator infection. In order to further characterize the cellular processes involved in the observed penetration resistance, specific inhibitors of the actin cytoskeleton and secretory/endocytic vesicle trafficking function were employed. These inhibitors were demonstrated to successfully break the penetration resistance in V. vinifera against the nonadapted powdery mildew E. cichoracearum. However, the use of these inhibitors with the adapted powdery mildew E. necator unexpectedly revealed that, although secretory and endocytic vesicle trafficking pathways play a crucial role in nonhost penetration resistance, the adapted powdery mildew species may actually require these pathways to successfully penetrate the plant host. PMID:21355998

  5. Microstructure and Corrosion Resistance of Laser Additively Manufactured 316L Stainless Steel

    NASA Astrophysics Data System (ADS)

    Trelewicz, Jason R.; Halada, Gary P.; Donaldson, Olivia K.; Manogharan, Guha

    2016-03-01

    Additive manufacturing (AM) of metal alloys to produce complex part designs via powder bed fusion methods such as laser melting promises to be a transformative technology for advanced materials processing. However, effective implementation of AM processes requires a clear understanding of the processing-structure-properties-performance relationships in fabricated components. In this study, we report on the formation of micro and nanoscale structures in 316L stainless steel samples printed by laser AM and their implications for general corrosion resistance. A variety of techniques including x-ray diffraction, optical, scanning and transmission electron microscopy, x-ray fluorescence, and energy dispersive x-ray spectroscopy were employed to characterize the microstructure and chemistry of the laser additively manufactured 316L stainless steel, which are compared with wrought 316L coupons via electrochemical polarization. Apparent segregation of Mo has been found to contribute to a loss of passivity and an increased anodic current density. While porosity will also likely impact the environmental performance (e.g., facilitating crevice corrosion) of AM alloys, this work demonstrates the critical influence of microstructure and heterogeneous solute distributions on the corrosion resistance of laser additively manufactured 316L stainless steel.

  6. Towards the understanding of resistance mechanisms in clinically isolated trimethoprim-resistant, methicillin-resistant Staphylococcus aureus dihydrofolate reductase.

    PubMed

    Frey, Kathleen M; Lombardo, Michael N; Wright, Dennis L; Anderson, Amy C

    2010-04-01

    Resistance to therapeutics such as trimethoprim-sulfamethoxazole has become an increasing problem in strains of methicillin-resistant Staphylococcus aureus (MRSA). Clinically isolated trimethoprim-resistant strains reveal a double mutation, H30N/F98Y, in dihydrofolate reductase (DHFR). In order to develop novel and effective therapeutics against these resistant strains, we evaluated a series of propargyl-linked antifolate lead compounds for inhibition of the mutant enzyme. For the propargyl-linked antifolates, the F98Y mutation generates minimal (between 1.2- and 6-fold) losses of affinity and the H30N mutation generates greater losses (between 2.4- and 48-fold). Conversely, trimethoprim affinity is largely diminished by the F98Y mutation (36-fold) and is not affected by the H30N mutation. In order to elucidate a mechanism of resistance, we determined a crystal structure of a complex of this double mutant with a lead propargyl-linked antifolate. This structure suggests a resistance mechanism consistent both for the propargyl-linked class of antifolates and for trimethoprim that is based on the loss of a conserved water-mediated hydrogen bond.

  7. Towards the Understanding of Resistance Mechanisms in Clinically Isolated Trimethoprim-resistant, Methicillin-resistant Staphylococcus aureus Dihydrofolate Reductase

    SciTech Connect

    Frey, K.; Lombardo, M; Wright, D; Anderson, A

    2010-01-01

    Resistance to therapeutics such as trimethoprim-sulfamethoxazole has become an increasing problem in strains of methicillin-resistant Staphylococcus aureus (MRSA). Clinically isolated trimethoprim-resistant strains reveal a double mutation, H30N/F98Y, in dihydrofolate reductase (DHFR). In order to develop novel and effective therapeutics against these resistant strains, we evaluated a series of propargyl-linked antifolate lead compounds for inhibition of the mutant enzyme. For the propargyl-linked antifolates, the F98Y mutation generates minimal (between 1.2- and 6-fold) losses of affinity and the H30N mutation generates greater losses (between 2.4- and 48-fold). Conversely, trimethoprim affinity is largely diminished by the F98Y mutation (36-fold) and is not affected by the H30N mutation. In order to elucidate a mechanism of resistance, we determined a crystal structure of a complex of this double mutant with a lead propargyl-linked antifolate. This structure suggests a resistance mechanism consistent both for the propargyl-linked class of antifolates and for trimethoprim that is based on the loss of a conserved water-mediated hydrogen bond.

  8. Mechanisms and evolution of plant resistance to aphids.

    PubMed

    Züst, Tobias; Agrawal, Anurag A

    2016-01-01

    Aphids are important herbivores of both wild and cultivated plants. Plants rely on unique mechanisms of recognition, signalling and defence to cope with the specialized mode of phloem feeding by aphids. Aspects of the molecular mechanisms underlying aphid-plant interactions are beginning to be understood. Recent advances include the identification of aphid salivary proteins involved in host plant manipulation, and plant receptors involved in aphid recognition. However, a complete picture of aphid-plant interactions requires consideration of the ecological outcome of these mechanisms in nature, and the evolutionary processes that shaped them. Here we identify general patterns of resistance, with a special focus on recognition, phytohormonal signalling, secondary metabolites and induction of plant resistance. We discuss how host specialization can enable aphids to co-opt both the phytohormonal responses and defensive compounds of plants for their own benefit at a local scale. In response, systemically induced resistance in plants is common and often involves targeted responses to specific aphid species or even genotypes. As co-evolutionary adaptation between plants and aphids is ongoing, the stealthy nature of aphid feeding makes both the mechanisms and outcomes of these interactions highly distinct from those of other herbivore-plant interactions. PMID:27250753

  9. Mechanisms of Klebsiella pneumoniae resistance to complement-mediated killing.

    PubMed Central

    Merino, S; Camprubí, S; Albertí, S; Benedí, V J; Tomás, J M

    1992-01-01

    The different mechanisms of Klebsiella pneumoniae resistance to complement-mediated killing were investigated by using different strains and isogenic mutants previously characterized for their surface components. We found that strains from serotypes whose K antigen masks the lipopolysaccharide (LPS) molecules (such as serotypes K1, K10, and K16) fail to activate complement, while strains with smooth LPS exposed at the cell surface (with or without K antigen) activate complement but are resistant to complement-mediated killing. The reasons for this resistance are that C3b binds far from the cell membrane and that the lytic final complex C5b-9 (membrane attack complex) is not formed. Isogenic rough mutants (K+ or K-) are serum sensitive because they bind C3b close to the cell membrane and the lytic complex (C5b-9) is formed. Images PMID:1587619

  10. Mechanisms of drug resistance that target the androgen axis in castration resistant prostate cancer (CRPC).

    PubMed

    Penning, Trevor M

    2015-09-01

    Castrate resistant prostate cancer (CRPC) is the fatal-form of prostate cancer and remains androgen dependent. The reactivation of the androgen axis occurs due to adaptive intratumoral androgen biosynthesis which can be driven by adrenal androgens and/or by changes in the androgen receptor (AR) including AR gene amplification. These mechanisms are targeted with P450c17 inhibitors e.g., abiraterone acetate and AR super-antagonists e.g., enzalutamide, respectively. Clinical experience indicates that with either agent an initial response is followed by drug resistance and the patient clinically progresses on these agents. This article reviews the mechanisms of intrinsic and acquired drug resistance that target the androgen axis and how this might be surmounted.

  11. Trastuzumab emtansine: mechanisms of action and drug resistance

    PubMed Central

    2014-01-01

    Trastuzumab emtansine (T-DM1) is an antibody-drug conjugate that is effective and generally well tolerated when administered as a single agent to treat advanced breast cancer. Efficacy has now been demonstrated in randomized trials as first line, second line, and later than the second line treatment of advanced breast cancer. T-DM1 is currently being evaluated as adjuvant treatment for early breast cancer. It has several mechanisms of action consisting of the anti-tumor effects of trastuzumab and those of DM1, a cytotoxic anti-microtubule agent released within the target cells upon degradation of the human epidermal growth factor receptor-2 (HER2)-T-DM1 complex in lysosomes. The cytotoxic effect of T-DM1 likely varies depending on the intracellular concentration of DM1 accumulated in cancer cells, high intracellular levels resulting in rapid apoptosis, somewhat lower levels in impaired cellular trafficking and mitotic catastrophe, while the lowest levels lead to poor response to T-DM1. Primary resistance of HER2-positive metastatic breast cancer to T-DM1 appears to be relatively infrequent, but most patients treated with T-DM1 develop acquired drug resistance. The mechanisms of resistance are incompletely understood, but mechanisms limiting the binding of trastuzumab to cancer cells may be involved. The cytotoxic effect of T-DM1 may be impaired by inefficient internalization or enhanced recycling of the HER2-T-DM1 complex in cancer cells, or impaired lysosomal degradation of trastuzumab or intracellular trafficking of HER2. The effect of T-DM1 may also be compromised by multidrug resistance proteins that pump DM1 out of cancer cells. In this review we discuss the mechanism of action of T-DM1 and the key clinical results obtained with it, the combinations of T-DM1 with other cytotoxic agents and anti-HER drugs, and the potential resistance mechanisms and the strategies to overcome resistance to T-DM1. PMID:24887180

  12. Insulin resistance: an additional risk factor in the pathogenesis of cardiovascular disease in type 2 diabetes.

    PubMed

    Patel, Tushar P; Rawal, Komal; Bagchi, Ashim K; Akolkar, Gauri; Bernardes, Nathalia; Dias, Danielle da Silva; Gupta, Sarita; Singal, Pawan K

    2016-01-01

    Sedentary life style and high calorie dietary habits are prominent leading cause of metabolic syndrome in modern world. Obesity plays a central role in occurrence of various diseases like hyperinsulinemia, hyperglycemia and hyperlipidemia, which lead to insulin resistance and metabolic derangements like cardiovascular diseases (CVDs) mediated by oxidative stress. The mortality rate due to CVDs is on the rise in developing countries. Insulin resistance (IR) leads to micro or macro angiopathy, peripheral arterial dysfunction, hampered blood flow, hypertension, as well as the cardiomyocyte and the endothelial cell dysfunctions, thus increasing risk factors for coronary artery blockage, stroke and heart failure suggesting that there is a strong association between IR and CVDs. The plausible linkages between these two pathophysiological conditions are altered levels of insulin signaling proteins such as IR-β, IRS-1, PI3K, Akt, Glut4 and PGC-1α that hamper insulin-mediated glucose uptake as well as other functions of insulin in the cardiomyocytes and the endothelial cells of the heart. Reduced AMPK, PFK-2 and elevated levels of NADP(H)-dependent oxidases produced by activated M1 macrophages of the adipose tissue and elevated levels of circulating angiotensin are also cause of CVD in diabetes mellitus condition. Insulin sensitizers, angiotensin blockers, superoxide scavengers are used as therapeutics in the amelioration of CVD. It evidently becomes important to unravel the mechanisms of the association between IR and CVDs in order to formulate novel efficient drugs to treat patients suffering from insulin resistance-mediated cardiovascular diseases. The possible associations between insulin resistance and cardiovascular diseases are reviewed here. PMID:26542377

  13. [MOLECULAR MECHANISMS OF DRUG RESISTANCE NEISSERIA GONORRHOEAE HISTORY AND PROSPECTS].

    PubMed

    Bodoev, I N; Il'ina, E N

    2015-01-01

    Neisseria gonorrhoeae (gonococcus) is a strict human pathogen, which causes gonorrhea--an infectious disease, whose origin dates back to more than two thousand years. Due to the unique plasticity of the genetic material, these bacteria have acquired the capacity to adapt to the host immune system, cause repeated infections, as well as withstand antimicrobials. Since the introduction of antibiotics in 1930s, gonococcus has displayed its propensity to develop resistance to all clinically useful antibiotics. It is important to note that the known resistance determinants of N. gonorrhoeae were acquired through horizontal gene transfer, recombination and spontaneous mutagenesis, and may be located both in the chromosome and on the plasmid. After introduction of a new antimicrobial drug, gonococcus becomes resistant within two decades and replaces sensitive bacterial population. Currently Ceftriaxone is the last remaining antibiotic for first-line treatment of gonorrhea. However, the first gonococcus displaying high-level resistance to Ceftriaxone was isolated in Japan a few years ago. Therefore, in the near future, gonorrhea may become untreatable. In the present review, we discuss the chronology of the anti-gonorrhea drugs (antibiotics) replacement, the evolution of resistance mechanisms emergence and future perspectives of N. gonorrhoeae treatment.

  14. Mechanisms of resistance to HER family targeting antibodies

    SciTech Connect

    Kruser, Tim J.; Wheeler, Deric L.

    2010-04-15

    The epidermal growth factor (EGF) family of receptor tyrosine kinases consists of four members: EGFR (HER1/ErbB1), HER2/neu (ErbB2), HER3 (ErbB3) and HER4 (ErbB4). Receptor activation via ligand binding leads to downstream signaling that influence cell proliferation, angiogenesis, invasion and metastasis. Aberrant expression or activity of EGFR and HER2 have been strongly linked to the etiology of several human epithelial cancers including but not limited to head and neck squamous cell carcinoma (HNSCC), non-small cell lung cancer (NSCLC), colorectal cancer (CRC), and breast cancer. With this, intense efforts have been made to inhibit the activity of the EGFR and HER2 by designing antibodies against the ligand binding domains (cetuximab, panitumumab and trastuzumab) or small molecules against the tyrosine kinase domains (erlotinib, gefitinib, and lapatinib). Both approaches have shown considerable clinical promise. However, increasing evidence suggests that the majority of patients do not respond to these therapies, and those who show initial response ultimately become refractory to treatment. While mechanisms of resistance to tyrosine kinase inhibitors have been extensively studied, resistance to monoclonal antibodies is less well understood, both in the laboratory and in the clinical setting. In this review, we discuss resistance to antibody-based therapies against the EGFR and HER2, similarities between these resistance profiles, and strategies to overcome resistance to HER family targeting monoclonal antibody therapy.

  15. Mechanisms of Resistance in Bacteria: An Evolutionary Approach

    PubMed Central

    Martins, Ana; Hunyadi, Attila; Amaral, Leonard

    2013-01-01

    Acquisition of resistance is one of the major causes of failure in therapy of bacterial infections. According to the World Health Organization (WHO), thousands of deaths caused by Salmonella sp., Escherichia coli, Staphylococcus aureus or Mycobacteria tuberculosis are due to failure in therapy caused by resistance to the chemotherapeutic agents. Understanding the mechanisms of resistance acquisition by the bacterial strains is therefore essential to prevent and overcome resistance. However, it is very difficult to extrapolate from in vitro studies, where the variables are far less and under constant control, as compared to what happens in vivo where the chosen chemotherapeutic, its effective dose, and the patient’s immune system are variables that differ substantially case-by-case. The aim of this review is to provide a new perspective on the possible ways by which resistance is acquired by the bacterial strains within the patient, with a special emphasis on the adaptive response of the infecting bacteria to the administered antibiotic. PMID:23560029

  16. Mechanisms of antimicrobial resistance in finfish aquaculture environments.

    PubMed

    Miranda, Claudio D; Tello, Alfredo; Keen, Patricia L

    2013-01-01

    Consumer demand for affordable fish drives the ever-growing global aquaculture industry. The intensification and expansion of culture conditions in the production of several finfish species has been coupled with an increase in bacterial fish disease and the need for treatment with antimicrobials. Understanding the molecular mechanisms of antimicrobial resistance prevalent in aquaculture environments is important to design effective disease treatment strategies, to prioritize the use and registration of antimicrobials for aquaculture use, and to assess and minimize potential risks to public health. In this brief article we provide an overview of the molecular mechanisms of antimicrobial resistance in genes found in finfish aquaculture environments and highlight specific research that should provide the basis of sound, science-based policies for the use of antimicrobials in aquaculture.

  17. Current perspectives on tigecycline resistance in Enterobacteriaceae: susceptibility testing issues and mechanisms of resistance.

    PubMed

    Pournaras, Spyros; Koumaki, Vasiliki; Spanakis, Nicholas; Gennimata, Vasiliki; Tsakris, Athanassios

    2016-07-01

    During the past decades, rates of multidrug-resistant (MDR) and carbapenem-resistant (CR) Enterobacteriaceae clinical isolates, mainly Klebsiella spp., Escherichia coli, Enterobacter spp., Proteus spp. and Serratia marcescens, have increased, considerably restricting effective antimicrobial treatments. Tigecycline, the first member of the glycylcyclines, has been approved by the US Food and Drug Administration (FDA) for the treatment of complicated skin and soft-tissue, complicated intra-abdominal and community-acquired bacterial respiratory infections and is increasingly administered against MDR Enterobacteriaceae. Although resistance has gradually appeared, tigecycline still remains relatively active among Enterobacteriaceae, with resistance rates largely <10% in most wide-scale surveillance studies. Tigecycline resistance has been reported in some studies to be elevated among extended-spectrum β-lactamase (ESBL)-producing, MDR, extensively drug-resistant and CR isolates. Broth microdilution (BMD) is the reference method for tigecycline susceptibility testing, but disagreements have been reported between the methods applied for routine tigecycline susceptibility testing. Therefore, confirmation of daily tigecycline susceptibility testing with BMD appears important in order to avoid misclassification of isolates. Various mechanisms have been reported to confer tigecycline resistance, with RND-type transporters, mainly the AcrAB efflux pump, playing an important role. Other pumps and various control pathways are also implicated in tigecycline resistance. Overall, tigecycline is a potent therapeutic option for enterobacterial infections. Accurate detection of tigecycline susceptibility status and surveillance of resistant organisms in the hospital environment is necessary in order to optimise its use and to preserve tigecycline in our therapeutic arsenal.

  18. An insight into the drug resistance profile & mechanism of drug resistance in Neisseria gonorrhoeae.

    PubMed

    Patel, Achchhe Lal; Chaudhry, Uma; Sachdev, Divya; Sachdeva, Poonam Nagpal; Bala, Manju; Saluja, Daman

    2011-10-01

    Among the aetiological agents of treatable sexually transmitted diseases (STDs), Neissseria gonorrhoeae is considered to be most important because of emerging antibiotic resistant strains that compromise the effectiveness of treatment of the disease - gonorrhoea. In most of the developing countries, treatment of gonorrhoea relies mainly on syndromic management rather than the aetiological based therapy. Gonococcal infections are usually treated with single-dose therapy with an agent found to cure > 95 per cent of cases. Unfortunately during the last few decades, N. gonorrhoeae has developed resistance not only to less expensive antimicrobials such as sulphonamides, penicillin and tetracyclines but also to fluoroquinolones. The resistance trend of N. gonorrhoeae towards these antimicrobials can be categorised into pre-quinolone, quinolone and post-quinolone era. Among the antimicrobials available so far, only the third-generation cephalosporins could be safely recommended as first-line therapy for gonorrhoea globally. However, resistance to oral third-generation cephalosporins has also started emerging in some countries. Therefore, it has become imperative to initiate sustained national and international efforts to reduce infection and misuse of antibiotics so as to prevent further emergence and spread of antimicrobial resistance. It is necessary not only to monitor drug resistance and optimise treatment regimens, but also to gain insight into how gonococcus develops drug resistance. Knowledge of mechanism of resistance would help us to devise methods to prevent the occurrence of drug resistance against existing and new drugs. Such studies could also help in finding out new drug targets in N. gonorrhoeae and also a possibility of identification of new drugs for treating gonorrhoea. PMID:22089602

  19. Drug Resistance Characteristics and Macrolide-Resistant Mechanisms of Streptococcus pneumoniae in Wenzhou City, China

    PubMed Central

    Hu, Dakang; Sun, Zheng; Luo, Xinhua; Liu, Shuangchun; Yu, Lianhua; Qu, Ying; Yang, Jinhong; Yu, Jian; Li, Xiangyang; Zhang, Jin

    2016-01-01

    Background Streptococcus pneumoniae (SP) is a Gram-positive, alpha-hemolytic, facultative anaerobic member of the genus Streptococcus. The erythromycin-resistant methylase (erm) gene and macrolide efflux (mef) gene are the 2 main genes that can mediate SP. Transposon (Tn) also plays an important role in the collection and metastasis of the gene. In the present study we investigated the drug resistance characteristics and the macrolide-resistant mechanisms of SP in Wenzhou City, China. Material/Methods Sixty-eight strains of SP were isolated from sputum samples of hospitalized children in the Second Affiliated Hospital of Wenzhou Medical University. These strains were analyzed using antimicrobial susceptibility tests to determine their drug resistance to 10 kinds of antibacterials. Macrolide-resistant phenotypes were identified using K-B method. PCR method was used to analyze the erm B gene, mef A gene, and int Tn gene. Results Drug resistance rates of 68 strains of SP were 98.5%, 100.0%, 63.2%, 52.9%, 94.1%, 89.7%, 0.0%, 0.0%, 16.2%, and 14.7% for clindamycin, erythromycin, penicillin G, cefotaxime, tetracycline, sulfamethoxazole/trimethoprim, levofloxacin, vancomycin, chloramphenicol, and amoxicillin, respectively. Total detection rates of the erm B gene, mef A gene, and int Tn gene were 98.5%, 91.2%, and 100.0%, respectively. Conclusions SP shows significant multi-drug resistance in Wenzhou City, whereas there is no clinical value of macrolides antibiotics for SP. cMLSB mediated by erm B gene is the most predominant phenotype among macrolide-resistant SP. The int Tn gene may play an important role in horizontal transfer and clonal dissemination of SP drug resistance genes in Wenzhou City. PMID:27483416

  20. Drug Resistance Characteristics and Macrolide-Resistant Mechanisms of Streptococcus pneumoniae in Wenzhou City, China.

    PubMed

    Hu, Dakang; Sun, Zheng; Luo, Xinhua; Liu, Shuangchun; Yu, Lianhua; Qu, Ying; Yang, Jinhong; Yu, Jian; Li, Xiangyang; Zhang, Jin

    2016-01-01

    BACKGROUND Streptococcus pneumoniae (SP) is a Gram-positive, alpha-hemolytic, facultative anaerobic member of the genus Streptococcus. The erythromycin-resistant methylase (erm) gene and macrolide efflux (mef) gene are the 2 main genes that can mediate SP. Transposon (Tn) also plays an important role in the collection and metastasis of the gene. In the present study we investigated the drug resistance characteristics and the macrolide-resistant mechanisms of SP in Wenzhou City, China. MATERIAL AND METHODS Sixty-eight strains of SP were isolated from sputum samples of hospitalized children in the Second Affiliated Hospital of Wenzhou Medical University. These strains were analyzed using antimicrobial susceptibility tests to determine their drug resistance to 10 kinds of antibacterials. Macrolide-resistant phenotypes were identified using K-B method. PCR method was used to analyze the erm B gene, mef A gene, and int Tn gene. RESULTS Drug resistance rates of 68 strains of SP were 98.5%, 100.0%, 63.2%, 52.9%, 94.1%, 89.7%, 0.0%, 0.0%, 16.2%, and 14.7% for clindamycin, erythromycin, penicillin G, cefotaxime, tetracycline, sulfamethoxazole/trimethoprim, levofloxacin, vancomycin, chloramphenicol, and amoxicillin, respectively. Total detection rates of the erm B gene, mef A gene, and int Tn gene were 98.5%, 91.2%, and 100.0%, respectively. CONCLUSIONS SP shows significant multi-drug resistance in Wenzhou City, whereas there is no clinical value of macrolides antibiotics for SP. cMLSB mediated by erm B gene is the most predominant phenotype among macrolide-resistant SP. The int Tn gene may play an important role in horizontal transfer and clonal dissemination of SP drug resistance genes in Wenzhou City. PMID:27483416

  1. Mechanisms of Linezolid Resistance among Coagulase-Negative Staphylococci Determined by Whole-Genome Sequencing

    PubMed Central

    Tewhey, Ryan; Gu, Bing; Kelesidis, Theodoros; Charlton, Carmen; Bobenchik, April; Hindler, Janet; Schork, Nicholas J.

    2014-01-01

    ABSTRACT Linezolid resistance is uncommon among staphylococci, but approximately 2% of clinical isolates of coagulase-negative staphylococci (CoNS) may exhibit resistance to linezolid (MIC, ≥8 µg/ml). We performed whole-genome sequencing (WGS) to characterize the resistance mechanisms and genetic backgrounds of 28 linezolid-resistant CoNS (21 Staphylococcus epidermidis isolates and 7 Staphylococcus haemolyticus isolates) obtained from blood cultures at a large teaching health system in California between 2007 and 2012. The following well-characterized mutations associated with linezolid resistance were identified in the 23S rRNA: G2576U, G2447U, and U2504A, along with the mutation C2534U. Mutations in the L3 and L4 riboproteins, at sites previously associated with linezolid resistance, were also identified in 20 isolates. The majority of isolates harbored more than one mutation in the 23S rRNA and L3 and L4 genes. In addition, the cfr methylase gene was found in almost half (48%) of S. epidermidis isolates. cfr had been only rarely identified in staphylococci in the United States prior to this study. Isolates of the same sequence type were identified with unique mutations associated with linezolid resistance, suggesting independent acquisition of linezolid resistance in each isolate. PMID:24915435

  2. Modification of silicone sealant to improve gamma radiation resistance, by addition of protective agents

    NASA Astrophysics Data System (ADS)

    González-Pérez, Giovanni; Burillo, Guillermina

    2013-09-01

    Poly (dimethylsiloxane) (PDMS) sealant (SS) was modified with the addition of different protective compounds to conserve its physical-chemical properties during gamma irradiation. 2-Vinyl naphthalene (2-VN), bisphenol-A (BPA) and poly (vinyl carbazole) (PVK) were used to evaluate radiation protection through the crosslinking effect of radiation. The samples were irradiated with doses from 100 kGy to 500 kGy at room temperature in air, with a 60Co gamma source, and the changes in molecular weight, thermal behavior, elastic properties and infrared spectra (FTIR-ATR) absorbance analysis were determined. The molecular weight of unmodified silicone sealant increases with the absorbed dose because of crosslinking as predominant effect. However, the crosslinking effect was inhibited with the addition of protective agent due to the aromatic compounds present. Modified silicone sealant films present better radiation resistance than unmodified system.

  3. Implementation of In Vitro Drug Resistance Assays: Maximizing the Potential for Uncovering Clinically Relevant Resistance Mechanisms

    PubMed Central

    Korpal, Manav; Feala, Jacob; Puyang, Xiaoling; Zou, Jian; Ramos, Alex H.; Wu, Jeremy; Baumeister, Timm; Yu, Lihua; Warmuth, Markus; Zhu, Ping

    2015-01-01

    Although targeted therapies are initially effective, resistance inevitably emerges. Several methods, such as genetic analysis of resistant clinical specimens, have been applied to uncover these resistance mechanisms to facilitate follow-up care. Although these approaches have led to clinically relevant discoveries, difficulties in attaining the relevant patient material or in deconvoluting the genomic data collected from these specimens have severely hampered the path towards a cure. To this end, we here describe a tool for expeditious discovery that may guide improvement in first-line therapies and alternative clinical management strategies. By coupling preclinical in vitro or in vivo drug selection with next-generation sequencing, it is possible to identify genomic structural variations and/or gene expression alterations that may serve as functional drivers of resistance. This approach facilitates the spontaneous emergence of alterations, enhancing the probability that these mechanisms may be observed in the patients. In this protocol we provide guidelines to maximize the potential for uncovering single nucleotide variants that drive resistance using adherent lines. PMID:26710000

  4. Evidence for a reserpine-affected mechanism of resistance to tetracycline in Neisseria gonorrhoeae.

    PubMed

    Ruiz, Joaquim; Ribera, Anna; Jurado, Angels; Marco, Francesc; Vila, Jordi

    2005-10-01

    The presence of a reserpine-affected mechanism of tetracycline resistance was investigated in 17 Neisseria gonorrhoeae clinical isolates. To establish this fact the MIC of tetracycline in the presence and absence of reserpine was determined, and, in addition, mechanisms of tetracycline resistance were analyzed by PCR. The results showed that reserpine affects the MIC of tetracycline at least 4-fold in all isolates, including those containing the tetM gene. An inhibitory effect of reserpine against the MtrCDE efflux system was ruled out by using strains either with an inactive or with an unrepressed MtrCDE system. The results suggest the presence of a constitutive system of resistance to tetracycline, by a possible efflux pump, which may be inhibited by reserpine. Further studies are required to determine the exact nature of the action of reserpine on the MIC of tetracycline. PMID:16309425

  5. Molecular mechanism of glucocorticoid resistance in inflammatory bowel disease

    PubMed Central

    De Iudicibus, Sara; Franca, Raffaella; Martelossi, Stefano; Ventura, Alessandro; Decorti, Giuliana

    2011-01-01

    Natural and synthetic glucocorticoids (GCs) are widely employed in a number of inflammatory, autoimmune and neoplastic diseases, and, despite the introduction of novel therapies, remain the first-line treatment for inducing remission in moderate to severe active Crohn’s disease and ulcerative colitis. Despite their extensive therapeutic use and the proven effectiveness, considerable clinical evidence of wide inter-individual differences in GC efficacy among patients has been reported, in particular when these agents are used in inflammatory diseases. In recent years, a detailed knowledge of the GC mechanism of action and of the genetic variants affecting GC activity at the molecular level has arisen from several studies. GCs interact with their cytoplasmic receptor, and are able to repress inflammatory gene expression through several distinct mechanisms. The glucocorticoid receptor (GR) is therefore crucial for the effects of these agents: mutations in the GR gene (NR3C1, nuclear receptor subfamily 3, group C, member 1) are the primary cause of a rare, inherited form of GC resistance; in addition, several polymorphisms of this gene have been described and associated with GC response and toxicity. However, the GR is not self-standing in the cell and the receptor-mediated functions are the result of a complex interplay of GR and many other cellular partners. The latter comprise several chaperonins of the large cooperative hetero-oligomeric complex that binds the hormone-free GR in the cytosol, and several factors involved in the transcriptional machinery and chromatin remodeling, that are critical for the hormonal control of target genes transcription in the nucleus. Furthermore, variants in the principal effectors of GCs (e.g. cytokines and their regulators) have also to be taken into account for a comprehensive evaluation of the variability in GC response. Polymorphisms in genes involved in the transport and/or metabolism of these hormones have also been

  6. In vitro additive effect of imipenem combined with vancomycin against multiple-drug resistant, coagulase-negative Staphylococci.

    PubMed

    Traub, W H; Spohr, M; Bauer, D

    1986-09-01

    Imipenem combined with vancomycin resulted in a marked additive effect in vitro against 9 clinical isolates of multiple-drug resistant (MDR), coagulase-negative staphylococci, including strains resistant against imipenem. The additive effect was documented with the aid of checkerboard MIC determinations and with time kill curve experiments. In contrast, imipenem combined with vancomycin merely yielded weak additive or indifferent effects against 10 MDR isolates of Staphylococcus aureus, all of which were susceptible to imipenem.

  7. Novel mechanism of resistance to glycopeptide antibiotics in Enterococcus faecium

    PubMed Central

    Cremniter, Julie; Mainardi, Jean-Luc; Josseaume, Nathalie; Quincampoix, Jean-Charles; Dubost, Lionel; Hugonnet, Jean-Emmanuel; Marie, Arul; Gutmann, Laurent; Rice, Louis B.; Arthur, Michel

    2006-01-01

    Glycopeptides and β-lactams are the major antibiotics available for the treatment of infections due to Gram-positive bacteria. Emergence of cross-resistance to these drugs by a single mechanism has been considered as unlikely since they inhibit peptidoglycan polymerization by different mechanisms. The glycopeptides bind to the peptidyl-D-Ala4-D-Ala5 extremity of peptidoglycan precursors and block by steric hindrance the essential glycosyltransferase and D,D-transpeptidase activities of the penicillin-binding proteins (PBPs). The β-lactams are structural analogues of D-Ala4-D-Ala5 and act as suicide substrates of the D,D-transpeptidase module of the PBPs. Here we show that bypass of the PBPs by the recently described β-lactam-insensitive L,D-transpeptidase from Enterococcus faecium (Ldtfm) can lead to high-level resistance to glycopeptides and β-lactams. Cross-resistance was selected by glycopeptides alone or serially by β-lactams and glycopeptides. In the corresponding mutants, UDP-MurNAc-pentapeptide was extensively converted to UDP-MurNAc-tetrapeptide following hydrolysis of D-Ala5, thereby providing the substrate of Ldtfm. Complete elimination of D-Ala5, a residue essential for glycopeptide binding, was possible since Ldtfm uses the energy of the L-Lys3-D-Ala4 peptide bond for cross-link formation in contrast to PBPs which use the energy of the D-Ala4-D-Ala5 bond. This novel mechanism of glycopeptide resistance was unrelated to the previously identified replacement of D-Ala5 by D-Ser or D-lactate. PMID:16943188

  8. Mechanisms of Nuclear Export in Cancer and Resistance to Chemotherapy.

    PubMed

    El-Tanani, Mohamed; Dakir, El-Habib; Raynor, Bethany; Morgan, Richard

    2016-03-14

    Tumour suppressor proteins, such as p53, BRCA1, and ABC, play key roles in preventing the development of a malignant phenotype, but those that function as transcriptional regulators need to enter the nucleus in order to function. The export of proteins between the nucleus and cytoplasm is complex. It occurs through nuclear pores and exported proteins need a nuclear export signal (NES) to bind to nuclear exportin proteins, including CRM1 (Chromosomal Region Maintenance protein 1), and the energy for this process is provided by the RanGTP/RanGDP gradient. Due to the loss of DNA repair and cell cycle checkpoints, drug resistance is a major problem in cancer treatment, and often an initially successful treatment will fail due to the development of resistance. An important mechanism underlying resistance is nuclear export, and a number of strategies that can prevent nuclear export may reverse resistance. Examples include inhibitors of CRM1, antibodies to the nuclear export signal, and alteration of nuclear pore structure. Each of these are considered in this review.

  9. Neurobiological Mechanisms Supporting Experience-Dependent Resistance to Social Stress

    PubMed Central

    Cooper, Matthew A.; Clinard, Catherine T.; Morrison, Kathleen E.

    2015-01-01

    Humans and other animals show a remarkable capacity for resilience following traumatic, stressful events. Resilience is thought to be an active process related to coping with stress, although the cellular and molecular mechanisms that support active coping and stress resistance remain poorly understood. In this review, we focus on the neurobiological mechanisms by which environmental and social experiences promote stress resistance. In male Syrian hamsters, exposure to a brief social defeat stressor leads to increased avoidance of novel opponents, which we call conditioned defeat. Also, hamsters that have achieved dominant social status show reduced conditioned defeat as well as cellular and molecular changes in the neural circuits controlling the conditioned defeat response. We propose that experience-dependent neural plasticity occurs in the prelimbic (PL) cortex, infralimbic (IL) cortex, and ventral medial amygdala (vMeA) during the maintenance of dominance relationships, and that adaptions in these neural circuits support stress resistance in dominant individuals. Overall, behavioral treatments that promote success in competitive interactions may represent valuable interventions for instilling resilience. PMID:25677096

  10. Mechanisms underlying the antidepressant response and treatment resistance

    PubMed Central

    Levinstein, Marjorie R.; Samuels, Benjamin A.

    2014-01-01

    Depression is a complex and heterogeneous disorder affecting millions of Americans. There are several different medications and other treatments that are available and effective for many patients with depression. However, a substantial percentage of patients fail to achieve remission with these currently available interventions, and relapse rates are high. Therefore, it is necessary to determine both the mechanisms underlying the antidepressant response and the differences between responders and non-responders to treatment. Delineation of these mechanisms largely relies on experiments that utilize animal models. Therefore, this review provides an overview of the various mouse models that are currently used to assess the antidepressant response, such as chronic mild stress, social defeat, and chronic corticosterone. We discuss how these mouse models can be used to advance our understanding of the differences between responders and non-responders to antidepressant treatment. We also provide an overview of experimental treatment modalities that are used for treatment-resistant depression, such as deep brain stimulation and ketamine administration. We will then review the various genetic polymorphisms and transgenic mice that display resistance to antidepressant treatment. Finally, we synthesize the published data to describe a potential neural circuit underlying the antidepressant response and treatment resistance. PMID:25018708

  11. Mechanisms of Induced Resistance in Barley Against Drechslera teres.

    PubMed

    Lyngs Jørgensen, H J; Lübeck, P S; Thordal-Christensen, H; de Neergaard, E; Smedegaard-Petersen, V

    1998-07-01

    ABSTRACT Quantitative and qualitative histopathological methods and molecular analyses were used to study the mechanisms by which preinoculation with either of the nonbarley pathogens, Bipolaris maydis and Septoria nodorum, inhibited growth of Drechslera teres. Collectively, our data suggest that induced resistance is the principal mechanism responsible for impeding the pathogen. The enhancement of resistance in the host was primarily manifested during penetration by D. teres, and after penetration, where growth of D. teres ceased soon after development of infection vesicles. Thus, 24 h after pretreatment with B. maydis or S. nodorum, the penetration frequency from D. teres appressoria was reduced from 42.7% in the controls to 9.5 and 14.8%, respectively. The reductions were associated with increased formation of fluorescent papillae in induced cells (early defense reaction). The postpenetrational inhibition of D. teres completely stopped fungal growth and was apparently linked to an enhancement of multicellular hypersensitive responses in inducer-treated leaves (late defense reaction). Papillae formation and multicellular hypersensitive reactions were also observed in fully susceptible, noninduced control leaves, but they were inadequate to stop fungal progress. Northern blots from leaves treated with either inducer alone support the conclusion that induced resistance is involved in suppression of D. teres by increased formation of papillae and hypersensitive reactions. Thus, the blots showed strong expression of several defense response genes that are involved in these reactions in barley attacked by Erysiphe graminis f. sp. hordei.

  12. Insulin resistance and alterations in angiogenesis: additive insults that may lead to preeclampsia.

    PubMed

    Thadhani, Ravi; Ecker, Jeffrey L; Mutter, Walter P; Wolf, Myles; Smirnakis, Karen V; Sukhatme, Vikas P; Levine, Richard J; Karumanchi, S Ananth

    2004-05-01

    Altered angiogenesis and insulin resistance, which are intimately related at a molecular level, characterize preeclampsia. To test if an epidemiological interaction exists between these two alterations, we performed a nested case-control study of 28 women who developed preeclampsia and 57 contemporaneous controls. Serum samples at 12 weeks of gestation were measured for sex hormone binding globulin (SHBG; low levels correlate with insulin resistance) and placental growth factor (PlGF; a proangiogenic molecule). Compared with controls, women who developed preeclampsia had lower serum levels of SHBG (208+/-116 versus 256+/-101 nmol/L, P=0.05) and PlGF (16+/-14 versus 67+/-150 pg/mL, P<0.001), and in multivariable analysis, women with serum levels of PlGF < or =20 pg/mL had an increased risk of developing preeclampsia (odds ratio [OR] 7.6, 95% CI 1.4 to 38.4). Stratified by levels of serum SHBG (< or =175 versus >175 mg/dL), women with low levels of SHBG and PlGF had a 25.5-fold increased risk of developing preeclampsia (P=0.10), compared with 1.8 (P=0.38) among women with high levels of SHBG and low levels of PlGF. Formal testing for interaction (PlGFxSHBG) was significant (P=0.02). In a model with 3 (n-1) interaction terms (high PlGF and high SHBG, reference), the risk for developing preeclampsia was as follows: low PlGF and low SHBG, OR 15.1, 95% CI 1.7 to 134.9; high PlGF and low SHBG, OR 4.1, 95% CI 0.45 to 38.2; low PlGF and high SHBG, OR 8.7, 95% CI 1.2 to 60.3. Altered angiogenesis and insulin resistance are additive insults that lead to preeclampsia.

  13. Antimicrobial Combinations against Pan-Resistant Acinetobacter baumannii Isolates with Different Resistance Mechanisms

    PubMed Central

    Leite, Gleice Cristina; Oliveira, Maura Salaroli; Perdigão-Neto, Lauro Vieira; Rocha, Cristiana Kamia Dias; Guimarães, Thais; Rizek, Camila; Levin, Anna Sara; Costa, Silvia Figueiredo

    2016-01-01

    The study investigated the effect of antibiotic combinations against 20 clinical isolates of A. baumannii (seven colistin-resistant and 13 colistin-susceptible) with different resistance mechanisms. Clinical data, treatment, and patient mortality were evaluated. The following methods were used: MIC, PCRs, and outer membrane protein (OMP) analysis. Synergy was investigated using the checkerboard and time-kill methods. Clonality was evaluated by PFGE. Based on clonality, the whole genome sequence of six A. baumannii isolates was analyzed. All isolates were resistant to meropenem, rifampicin, and fosfomycin. OXA-23 and OXA-143 were the most frequent carbapenemases found. Four isolates showed loss of a 43kDa OMP. The colistin-susceptible isolates belonged to different clones and showed the highest synergistic effect with fosfomycin-amikacin. Among colistin-resistant isolates, the highest synergistic effect was observed with the combinations of colistin-rifampicin followed by colistin-vancomycin. All colistin-resistant isolates harbored blaOXA-23-like and belonged to CC113. Clinical and demographic data were available for 18 of 20 patients. Fourteen received treatment and eight patients died during treatment. The most frequent site of infection was the blood in 13 of 14 patients. Seven patients received vancomycin plus an active drug against A. baumannii; however, mortality did not differ in this group. The synergistic effect was similar for colistin-susceptible isolates of distinct clonal origin presenting with the same resistance mechanism. Overall mortality and death during treatment was high, and despite the high synergism in vitro with vancomycin, death did not differ comparing the use or not of vancomycin plus an active drug against A. baumannii. PMID:26998609

  14. The Effect of Carbon Additions on the Creep Resistance of Fe-25Al-5Zr Alloy

    NASA Astrophysics Data System (ADS)

    Dobeš, Ferdinand; Vodičková, Věra; Veselý, Jozef; Kratochvíl, Petr

    2016-09-01

    Creep experiments were conducted on Fe-25 at. pct Al-5 at. pct Zr alloy with carbon additions at the temperatures of 973 K and 1173 K (700 °C and 900 °C). The alloys were tested in two different states: (i) cast and (ii) annealed at 1273 K (1000 °C) for 50 hours. Stress exponents and activation energies were estimated. The values of the stress exponent n could be explained by the dislocation motion controlled by climb. The increased values of n in the high-carbon alloy at the temperature of 1173 K (900 °C) can be described by means of the threshold stress concept. The creep resistance at 973 K (700 °C) decreased with the increasing content of carbon. This result is discussed in terms of the ratio of zirconium to carbon in the alloy. An increase of the creep resistance with increasing ratio Zr:C is in agreement with the behavior observed previously in alloys with substantially lower concentrations of zirconium.

  15. 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.

  16. Mechanisms of reef coral resistance to future climate change.

    PubMed

    Palumbi, Stephen R; Barshis, Daniel J; Traylor-Knowles, Nikki; Bay, Rachael A

    2014-05-23

    Reef corals are highly sensitive to heat, yet populations resistant to climate change have recently been identified. To determine the mechanisms of temperature tolerance, we reciprocally transplanted corals between reef sites experiencing distinct temperature regimes and tested subsequent physiological and gene expression profiles. Local acclimatization and fixed effects, such as adaptation, contributed about equally to heat tolerance and are reflected in patterns of gene expression. In less than 2 years, acclimatization achieves the same heat tolerance that we would expect from strong natural selection over many generations for these long-lived organisms. Our results show both short-term acclimatory and longer-term adaptive acquisition of climate resistance. Adding these adaptive abilities to ecosystem models is likely to slow predictions of demise for coral reef ecosystems.

  17. Cell Biological Mechanisms of Multidrug Resistance in Tumors

    NASA Astrophysics Data System (ADS)

    Simon, Sanford M.; Schindler, Melvin

    1994-04-01

    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 pleotropic 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.

  18. Mycoplasma bovis: Mechanisms of Resistance and Trends in Antimicrobial Susceptibility

    PubMed Central

    Lysnyansky, Inna; Ayling, Roger D.

    2016-01-01

    Mycoplasma bovis is a cell-wall-less bacterium and belongs to the class Mollicutes. It is the most important etiological agent of bovine mycoplasmoses in North America and Europe, causing respiratory disease, mastitis, otitis media, arthritis, and reproductive disease. Clinical disease associated with M. bovis is often chronic, debilitating, and poorly responsive to antimicrobial therapy, resulting in significant economic loss, the full extent of which is difficult to estimate. Until M. bovis vaccines are universally available, sanitary control measures and antimicrobial treatment are the only approaches that can be used in attempts to control M. bovis infections. However, in vitro studies show that many of the current M. bovis isolates circulating in Europe have high minimum inhibitory concentrations (MIC) for many of the commercially available antimicrobials. In this review we summarize the current MIC trends indicating the development of antimicrobial resistance in M. bovis as well as the known molecular mechanisms by which resistance is acquired. PMID:27199926

  19. Nanoparticle mechanics: deformation detection via nanopore resistive pulse sensing

    NASA Astrophysics Data System (ADS)

    Darvish, Armin; Goyal, Gaurav; Aneja, Rachna; Sundaram, Ramalingam V. K.; Lee, Kidan; Ahn, Chi Won; Kim, Ki-Bum; Vlahovska, Petia M.; Kim, Min Jun

    2016-07-01

    Solid-state nanopores have been widely used in the past for single-particle analysis of nanoparticles, liposomes, exosomes and viruses. The shape of soft particles, particularly liposomes with a bilayer membrane, can greatly differ inside the nanopore compared to bulk solution as the electric field inside the nanopores can cause liposome electrodeformation. Such deformations can compromise size measurement and characterization of particles, but are often neglected in nanopore resistive pulse sensing. In this paper, we investigated the deformation of various liposomes inside nanopores. We observed a significant difference in resistive pulse characteristics between soft liposomes and rigid polystyrene nanoparticles especially at higher applied voltages. We used theoretical simulations to demonstrate that the difference can be explained by shape deformation of liposomes as they translocate through the nanopores. Comparing our results with the findings from electrodeformation experiments, we demonstrated that the rigidity of liposomes can be qualitatively compared using resistive pulse characteristics. This application of nanopores can provide new opportunities to study the mechanics at the nanoscale, to investigate properties of great value in fundamental biophysics and cellular mechanobiology, such as virus deformability and fusogenicity, and in applied sciences for designing novel drug/gene delivery systems.Solid-state nanopores have been widely used in the past for single-particle analysis of nanoparticles, liposomes, exosomes and viruses. The shape of soft particles, particularly liposomes with a bilayer membrane, can greatly differ inside the nanopore compared to bulk solution as the electric field inside the nanopores can cause liposome electrodeformation. Such deformations can compromise size measurement and characterization of particles, but are often neglected in nanopore resistive pulse sensing. In this paper, we investigated the deformation of various

  20. [Evolution as resistance to entropy. I. Mechanisms of species homeostasis].

    PubMed

    Shcherbakov, V P

    2005-01-01

    The idea is discussed that the common output of any evolution is creation of the entities that are increasingly resistant to further evolution. The moving force of evolution is entropy, the tendency to disorder. This general aspiration for chaos is a cause of the mortality of organisms and species, however, being prerequisite for any movement, it creates (by chance) novelties, which may occur (by chance) more resistant to further decay and thus survive. The surviving of those who survive is the most general principle of evolution discovered by Darwin for particular case of biological evolution. The second law of thermodynamics states that our Universe is perishing but its ontology is such that it creates resistance to destruction. The evolution is a history of this resistance. Not only those who die do not survive but also those who evolve. The entities that change (evolve) rapidly disappear rapidly and by this reason they are not observed among both the fossils and now-living organisms. We know only about long-living species. All the existing organisms are endowed with an ability to resist other changing. The following main achievements of the species homeostasis are discussed: high fidelity of DNA replication and effective mechanisms of DNA repair; diploidy; normalizing selection; truncated selection; heterozygote superiority; ability to change phenotype adaptively without changing genotype; parental care and the K-strategy of reproduction; behavior that provides independence of the environment. The global resistance of the living systems to entropy is provided the state that all the essential in biology is determined not by physical-chemical interactions but could semantic rules. A conception of "potential zygotic information" that determines the rules of ontogenesis is proposed. A zygote does not contain this information in explicit form. It is created de novo step by step during ontogenesis and it could not be decoded beforehand. The experimental data on the

  1. Resistance Mechanisms for the Bruton’s Tyrosine Kinase Inhibitor Ibrutinib

    PubMed Central

    Woyach, Jennifer A.; Furman, Richard R.; Liu, Ta-Ming; Ozer, Hatice Gulcin; Zapatka, Marc; Ruppert, Amy S.; Xue, Ling; Li, Daniel Hsieh-Hsin; Steggerda, Susanne M.; Versele, Matthias; Dave, Sandeep S.; Zhang, Jenny; Yilmaz, Ayse Selen; Jaglowski, Samantha M.; Blum, Kristie A.; Lozanski, Arletta; Lozanski, Gerard; James, Danelle F.; Barrientos, Jacqueline C.; Lichter, Peter; Stilgenbauer, Stephan; Buggy, Joseph J.; Chang, Betty Y.; Johnson, Amy J.; Byrd, John C.

    2014-01-01

    BACKGROUND Ibrutinib is an irreversible inhibitor of Bruton’s tyrosine kinase (BTK) and is effective in chronic lymphocytic leukemia (CLL). Resistance to irreversible kinase inhibitors and resistance associated with BTK inhibition have not been characterized. Although only a small proportion of patients have had a relapse during ibrutinib therapy, an understanding of resistance mechanisms is important. We evaluated patients with relapsed disease to identify mutations that may mediate ibrutinib resistance. METHODS We performed whole-exome sequencing at baseline and the time of relapse on samples from six patients with acquired resistance to ibrutinib therapy. We then performed functional analysis of identified mutations. In addition, we performed Ion Torrent sequencing for identified resistance mutations on samples from nine patients with prolonged lymphocytosis. RESULTS We identified a cysteine-to-serine mutation in BTK at the binding site of ibrutinib in five patients and identified three distinct mutations in PLCγ2 in two patients. Functional analysis showed that the C481S mutation of BTK results in a protein that is only reversibly inhibited by ibrutinib. The R665W and L845F mutations in PLCγ2 are both potentially gain-of-function mutations that lead to autonomous B-cell–receptor activity. These mutations were not found in any of the patients with prolonged lymphocytosis who were taking ibrutinib. CONCLUSIONS Resistance to the irreversible BTK inhibitor ibrutinib often involves mutation of a cysteine residue where ibrutinib binding occurs. This finding, combined with two additional mutations in PLCγ2 that are immediately downstream of BTK, underscores the importance of the B-cell–receptor pathway in the mechanism of action of ibrutinib in CLL. (Funded by the National Cancer Institute and others.) PMID:24869598

  2. Susceptibility to insecticides and resistance mechanisms in Aedes aegypti from the Colombian Caribbean Region.

    PubMed

    Maestre-Serrano, Ronald; Gomez-Camargo, Doris; Ponce-Garcia, Gustavo; Flores, Adriana E

    2014-11-01

    We determined the susceptibility to insecticides and the biochemical and molecular mechanisms involved in resistance in nine populations of Aedes aegypti (L.) of the Colombian Caribbean region. Bioassays were performed on larvae for susceptibility to temephos and on adults to the insecticides malathion, fenitrothion, pirimiphos-methyl, permethrin, deltamethrin, λ-cyhalothrin and cyfluthrin. The resistance ratio (RR) for each insecticide in the populations was determined, using the susceptible Rockefeller strain as a susceptible control. Additionally, we evaluated the response of the populations to the diagnostic dose (DD) of the organochlorine pesticide DDT. The following biochemical mechanisms associated with resistance were studied: α-esterases, β-esterases, mixed-function oxidases (MFO), glutathione s-transferases (GST) and insensitive acetylcholinesterase (iAChE) as well as the presence of kdr I1,016 mutation and its frequency. All populations studied showed susceptibility to the organophosphates evaluated (RR < 5-fold), except for the Puerto Colombia and Soledad populations which showed high resistance (RR 15-fold) and moderate resistance (RR 5-fold) to temephos, respectively, and Sincelejo (Sucre) with moderate resistance to pirimiphos-methyl (RR 5-fold). All populations evaluated with DD of DDT were found to be resistant with 2-28% of mortality. Variability was observed in the resistance to pyrethroids: permethrin (RR 1.2- to 30.8-fold), deltamethrin RR 0.9- to 37.8-fold), λ-cyalothrin (RR 3.4- to 83-fold) and cyfluthrin (RR 0.3- to 33.8-fold). Incipiently α-esterases and MFO levels were found in the Valledupar population; MFO showed the same profile in Cienaga and GST in the Sincelejo population, all other populations showed unaltered profiles of the enzymes evaluated. The kdr I1,016 mutation was found in all populations evaluated with variability in its allelic and genotypic frequencies. PMID:25454522

  3. Susceptibility to insecticides and resistance mechanisms in Aedes aegypti from the Colombian Caribbean Region.

    PubMed

    Maestre-Serrano, Ronald; Gomez-Camargo, Doris; Ponce-Garcia, Gustavo; Flores, Adriana E

    2014-11-01

    We determined the susceptibility to insecticides and the biochemical and molecular mechanisms involved in resistance in nine populations of Aedes aegypti (L.) of the Colombian Caribbean region. Bioassays were performed on larvae for susceptibility to temephos and on adults to the insecticides malathion, fenitrothion, pirimiphos-methyl, permethrin, deltamethrin, λ-cyhalothrin and cyfluthrin. The resistance ratio (RR) for each insecticide in the populations was determined, using the susceptible Rockefeller strain as a susceptible control. Additionally, we evaluated the response of the populations to the diagnostic dose (DD) of the organochlorine pesticide DDT. The following biochemical mechanisms associated with resistance were studied: α-esterases, β-esterases, mixed-function oxidases (MFO), glutathione s-transferases (GST) and insensitive acetylcholinesterase (iAChE) as well as the presence of kdr I1,016 mutation and its frequency. All populations studied showed susceptibility to the organophosphates evaluated (RR < 5-fold), except for the Puerto Colombia and Soledad populations which showed high resistance (RR 15-fold) and moderate resistance (RR 5-fold) to temephos, respectively, and Sincelejo (Sucre) with moderate resistance to pirimiphos-methyl (RR 5-fold). All populations evaluated with DD of DDT were found to be resistant with 2-28% of mortality. Variability was observed in the resistance to pyrethroids: permethrin (RR 1.2- to 30.8-fold), deltamethrin RR 0.9- to 37.8-fold), λ-cyalothrin (RR 3.4- to 83-fold) and cyfluthrin (RR 0.3- to 33.8-fold). Incipiently α-esterases and MFO levels were found in the Valledupar population; MFO showed the same profile in Cienaga and GST in the Sincelejo population, all other populations showed unaltered profiles of the enzymes evaluated. The kdr I1,016 mutation was found in all populations evaluated with variability in its allelic and genotypic frequencies.

  4. Mechanisms of resistance to organophosphorus insecticides in populations of the obliquebanded leafroller Choristoneura rosaceana (Harris) (Lepidoptera: Tortricidae) from southern Ontario.

    PubMed

    Pree, David J; Whitty, Karen J; Bittner, Lori A; Pogoda, Mitchell K

    2003-01-01

    Populations of Choristoneura rosaceana (Harris) from orchards in Ontario were shown to be resistant to azinphos-methyl and to other types of organophosphorus insecticides. Resistance extended to methyl carbamates and to methomyl. The laboratory population used for these assays and selected with azinphosmethyl was also resistant to the pyrethroid, cypermethrin. Resistance was associated with increased esterase activity and was reduced by the addition of the synergist DEF. IEF studies of esterases also indicated increased activity in resistant populations, but did not identify any unique esterases associated with the resistance. Resistance was highly correlated (r = 0.78) with elevated esterases but not with increased glutathione-S transferase activity (r = 0.13). Other mechanisms did not appear to be related.

  5. The Effect of Zirconium Addition on the Oxidation Resistance of Aluminide Coatings

    NASA Astrophysics Data System (ADS)

    Zagula-Yavorska, Maryana; Pytel, Maciej; Romanowska, Jolanta; Sieniawski, Jan

    2015-04-01

    Nickel, Mar M247, and Mar M200 superalloys were coated with zirconium-doped aluminide deposited by the chemical vapor deposition method. All coatings consisted of two layers: an additive one, comprising of the β-NiAl phase and the interdiffusion one. The interdiffusion layer on pure nickel consisted of the γ'-Ni3Al phase and β-NiAl phase on superalloys. Precipitations of zirconium-rich particles were found near the coating's surface and at the interface between the additive and the interdiffusion layer. Zirconium doping of aluminide coating improved the oxidation resistance of aluminide coatings deposited both on the nickel substrate and on the Mar M200 superalloy. Precipitations of ZrO2 embedded by the Al2O3 oxide were formed during oxidation. It seems that the ZrO2 oxide increases adhesion of the Al2O3 oxide to the coating and decreases the propensity of the Al2O3 oxide rumpling and spalling.

  6. Resistance mechanisms and drug susceptibility testing of nontuberculous mycobacteria.

    PubMed

    van Ingen, Jakko; Boeree, Martin J; van Soolingen, Dick; Mouton, Johan W

    2012-06-01

    Nontuberculous mycobacteria (NTM) are increasingly recognized as causative agents of opportunistic infections in humans. For most NTM infections the therapy of choice is drug treatment, but treatment regimens differ by species, in particular between slow (e.g. Mycobacterium avium complex, Mycobacterium kansasii) and rapid growers (e.g. Mycobacterium abscessus, Mycobacterium fortuitum). In general, drug treatment is long, costly, and often associated with drug-related toxicities; outcome of drug treatment is poor and is likely related to the high levels of natural antibiotic resistance in NTM. The role of drug susceptibility testing (DST) in the choice of agents for antimicrobial treatment of NTM disease, mainly that by slow growers, remains subject of debate. There are important discrepancies between drug susceptibility measured in vitro and the activity of the drug observed in vivo. In part, these discrepancies derive from laboratory technical issues. There is still no consensus on a standardized method. With the increasing clinical importance of NTM disease, DST of NTM is again in the spotlight. This review provides a comprehensive overview of the mechanisms of drug resistance in NTM, phenotypic methods for testing susceptibility in past and current use for DST of NTM, as well as molecular approaches to assess drug resistance.

  7. The tokamak density limit: A thermo-resistive disruption mechanism

    SciTech Connect

    Gates, D. A.; Brennan, D. P.; Delgado-Aparicio, L.; White, R. B.

    2015-06-15

    The behavior of magnetic islands with 3D electron temperature and the corresponding 3D resistivity effects on growth are examined for islands with near-zero net heating in the island interior. We refer to the resulting class of non-linearities as thermo-resistive effects. In particular, the effects of varying impurity mix on the previously proposed local island onset threshold [Gates and Delgado-Aparicio, Phys. Rev. Lett. 108, 165004 (2012)] are examined and shown to be consistent with the well established experimental scalings for tokamaks at the density limit. A surprisingly simple semi-analytic theory is developed which imposes the effects of heating/cooling in the island interior as well as the effects of island geometry. For the class of current profiles considered, it is found that a new term that accounts for the thermal effects of island asymmetry is required in the modified Rutherford equation. The resultant model is shown to exhibit a robust onset of a rapidly growing tearing mode—consistent with the disruption mechanism observed at the density limit in tokamaks. A fully non-linear 3D cylindrical calculation is performed that simulates the effect of net island heating/cooling by raising/suppressing the temperature in the core of the island. In both the analytic theory and the numerical simulation, the sudden threshold for rapid growth is found to be due to an interaction between three distinct thermal non-linearities which affect the island resistivity, thereby modifying the growth dynamics.

  8. Intestinal regeneration as an insect resistance mechanism to entomopathogenic bacteria.

    PubMed

    Castagnola, Anaïs; Jurat-Fuentes, Juan Luis

    2016-06-01

    The intestinal epithelium of insects is exposed to xenobiotics and entomopathogens during the feeding developmental stages. In these conditions, an effective enterocyte turnover mechanism is highly desirable to maintain integrity of the gut epithelial wall. As in other insects, the gut of lepidopteran larvae have stem cells that are capable of proliferation, which occurs during molting and pathogenic episodes. While much is known on the regulation of gut stem cell division during molting, there is a current knowledge gap on the molecular regulation of gut healing processes after entomopathogen exposure. Relevant information on this subject is emerging from studies of the response to exposure to insecticidal proteins from the bacterium Bacillus thuringiensis (Bt) as model intoxicants. In this work we discuss currently available data on the molecular cues involved in gut stem cell proliferation, insect gut healing, and the implications of enhanced healing as a potential mechanism of resistance against Bt toxins. PMID:27436739

  9. Process for improving mechanical properties of epoxy resins by addition of cobalt ions

    NASA Technical Reports Server (NTRS)

    Stoakley, D. M.; St.clair, A. K. (Inventor)

    1984-01-01

    A resin product useful as an adhesive, composite or casting resin is described as well as the process used in its preparation to improve its flexural strength mechanical property characteristics. Improved flexural strength is attained with little or no change in density, thermal stability or moisture resistance by chemically incorporating 1.2% to 10.6% by weight Co(3) ions in an epoxidized resin system.

  10. Screening and incorporation of rust resistance from Allium cepa into bunching onion (Allium fistulosum) via alien chromosome addition.

    PubMed

    Wako, Tadayuki; Yamashita, Ken-ichiro; Tsukazaki, Hikaru; Ohara, Takayoshi; Kojima, Akio; Yaguchi, Shigenori; Shimazaki, Satoshi; Midorikawa, Naoko; Sakai, Takako; Yamauchi, Naoki; Shigyo, Masayoshi

    2015-04-01

    Bunching onion (Allium fistulosum L.; 2n = 16), bulb onion (Allium cepa L. Common onion group), and shallot (Allium cepa L. Aggregatum group) cultivars were inoculated with rust fungus, Puccinia allii, isolated from bunching onion. Bulb onions and shallots are highly resistant to rust, suggesting they would serve as useful resources for breeding rust resistant bunching onions. To identify the A. cepa chromosome(s) related to rust resistance, a complete set of eight A. fistulosum - shallot monosomic alien addition lines (MAALs) were inoculated with P. allii. At the seedling stage, FF+1A showed a high level of resistance in controlled-environment experiments, suggesting that the genes related to rust resistance could be located on shallot chromosome 1A. While MAAL, multi-chromosome addition line, and hypoallotriploid adult plants did not exhibit strong resistance to rust. In contrast to the high resistance of shallot, the addition line FF+1A+5A showed reproducibly high levels of rust resistance. PMID:26218854

  11. Molecular Gymnastics: Mechanisms of HIV-1 Resistance to CCR5 Antagonists and Impact on Virus Phenotypes.

    PubMed

    Roche, Michael; Borm, Katharina; Flynn, Jacqueline K; Lewin, Sharon R; Churchill, Melissa J; Gorry, Paul R

    2016-01-01

    Human immunodeficiency virus type 1 (HIV-1) enters host cells through the binding of its envelope glycoproteins (Env) to the host cell receptor CD4 and then subsequent binding to a chemokine coreceptor, either CCR5 or CXCR4. CCR5 antagonists are a relatively recent class addition to the armamentarium of anti-HIV-1 drugs. These compounds act by binding to a hydrophobic pocket formed by the transmembrane helices of CCR5 and altering the conformation of the extracellular domains, such that they are no longer recognized by Env. Maraviroc is the first drug within this class to be licenced for use in HIV-1 therapy regimens. HIV resistance to CCR5 antagonists occurs either through outgrowth of pre-existing CXCR4-using viruses, or through acquisition of the ability of CCR5-using HIV-1 to use the antagonist bound form of CCR5. In the latter scenario, the mechanism underlying resistance is through complex alterations in the way that resistant Envs engage CCR5. These significant changes are unlikely to occur without consequence to the viral entry phenotype and may also open up new avenues to target CCR5 antagonist resistant viruses. This review discusses the mechanism of action of CCR5 antagonists, how HIV resistance to CCR5 antagonists occurs, and the subsequent effects on Env function. PMID:26324043

  12. Molecular Gymnastics: Mechanisms of HIV-1 Resistance to CCR5 Antagonists and Impact on Virus Phenotypes.

    PubMed

    Roche, Michael; Borm, Katharina; Flynn, Jacqueline K; Lewin, Sharon R; Churchill, Melissa J; Gorry, Paul R

    2016-01-01

    Human immunodeficiency virus type 1 (HIV-1) enters host cells through the binding of its envelope glycoproteins (Env) to the host cell receptor CD4 and then subsequent binding to a chemokine coreceptor, either CCR5 or CXCR4. CCR5 antagonists are a relatively recent class addition to the armamentarium of anti-HIV-1 drugs. These compounds act by binding to a hydrophobic pocket formed by the transmembrane helices of CCR5 and altering the conformation of the extracellular domains, such that they are no longer recognized by Env. Maraviroc is the first drug within this class to be licenced for use in HIV-1 therapy regimens. HIV resistance to CCR5 antagonists occurs either through outgrowth of pre-existing CXCR4-using viruses, or through acquisition of the ability of CCR5-using HIV-1 to use the antagonist bound form of CCR5. In the latter scenario, the mechanism underlying resistance is through complex alterations in the way that resistant Envs engage CCR5. These significant changes are unlikely to occur without consequence to the viral entry phenotype and may also open up new avenues to target CCR5 antagonist resistant viruses. This review discusses the mechanism of action of CCR5 antagonists, how HIV resistance to CCR5 antagonists occurs, and the subsequent effects on Env function.

  13. Insecticide Resistance Status of United States Populations of Aedes albopictus and Mechanisms Involved

    PubMed Central

    Marcombe, Sébastien; Farajollahi, Ary; Healy, Sean P.; Clark, Gary G.; Fonseca, Dina M.

    2014-01-01

    Aedes albopictus (Skuse) is an invasive mosquito that has become an important vector of chikungunya and dengue viruses. Immature Ae. albopictus thrive in backyard household containers that require treatment with larvicides and when adult populations reach pest levels or disease transmission is ongoing, adulticiding is often required. To assess the feasibility of control of USA populations, we tested the susceptibility of Ae. albopictus to chemicals representing the main insecticide classes with different modes of action: organochlorines, organophosphates, carbamates, pyrethroids, insect growth regulators (IGR), naturalytes, and biolarvicides. We characterized a susceptible reference strain of Ae. albopictus, ATM95, and tested the susceptibility of eight USA populations to five adulticides and six larvicides. We found that USA populations are broadly susceptible to currently available larvicides and adulticides. Unexpectedly, however, we found significant resistance to dichlorodiphenyltrichloroethane (DDT) in two Florida populations and in a New Jersey population. We also found resistance to malathion, an organophosphate, in Florida and New Jersey and reduced susceptibility to the IGRs pyriproxyfen and methoprene. All populations tested were fully susceptible to pyrethroids. Biochemical assays revealed a significant up-regulation of GSTs in DDT-resistant populations in both larval and adult stages. Also, β-esterases were up-regulated in the populations with suspected resistance to malathion. Of note, we identified a previously unknown amino acid polymorphism (Phe → Leu) in domain III of the VGSC, in a location known to be associated with pyrethroid resistance in another container-inhabiting mosquito, Aedes aegypti L. The observed DDT resistance in populations from Florida may indicate multiple introductions of this species into the USA, possibly from tropical populations. In addition, the mechanisms underlying DDT resistance often result in pyrethroid resistance

  14. Insecticide resistance status of United States populations of Aedes albopictus and mechanisms involved.

    PubMed

    Marcombe, Sébastien; Farajollahi, Ary; Healy, Sean P; Clark, Gary G; Fonseca, Dina M

    2014-01-01

    Aedes albopictus (Skuse) is an invasive mosquito that has become an important vector of chikungunya and dengue viruses. Immature Ae. albopictus thrive in backyard household containers that require treatment with larvicides and when adult populations reach pest levels or disease transmission is ongoing, adulticiding is often required. To assess the feasibility of control of USA populations, we tested the susceptibility of Ae. albopictus to chemicals representing the main insecticide classes with different modes of action: organochlorines, organophosphates, carbamates, pyrethroids, insect growth regulators (IGR), naturalytes, and biolarvicides. We characterized a susceptible reference strain of Ae. albopictus, ATM95, and tested the susceptibility of eight USA populations to five adulticides and six larvicides. We found that USA populations are broadly susceptible to currently available larvicides and adulticides. Unexpectedly, however, we found significant resistance to dichlorodiphenyltrichloroethane (DDT) in two Florida populations and in a New Jersey population. We also found resistance to malathion, an organophosphate, in Florida and New Jersey and reduced susceptibility to the IGRs pyriproxyfen and methoprene. All populations tested were fully susceptible to pyrethroids. Biochemical assays revealed a significant up-regulation of GSTs in DDT-resistant populations in both larval and adult stages. Also, β-esterases were up-regulated in the populations with suspected resistance to malathion. Of note, we identified a previously unknown amino acid polymorphism (Phe → Leu) in domain III of the VGSC, in a location known to be associated with pyrethroid resistance in another container-inhabiting mosquito, Aedes aegypti L. The observed DDT resistance in populations from Florida may indicate multiple introductions of this species into the USA, possibly from tropical populations. In addition, the mechanisms underlying DDT resistance often result in pyrethroid resistance

  15. Strengthening mechanisms and mechanical properties of high interstitial stainless steel for drill collar and its corrosion resistance

    NASA Astrophysics Data System (ADS)

    Lee, Eunkyung

    Two types (CN66, CN71) of high interstitial stainless steels (HISSs) were investigated for down-hole application in sour gas well environments. Experiments were designed to identify factors that have a significant effect on mechanical properties. The three factors examined in the study were carbon + nitrogen content (0.66 or 0.71 mass %), cooling rate in quenching (air or water), and heat treatment time (2 or 4 hours). The results showed that the cooling rate, C+N content, and the two-factor interaction of these variables have a significant effect on the mechanical properties of HISSs. Based on the statistical analysis results on mechanical properties, extensive analyses were undertaken to understand the strengthening mechanisms of HISSs. Microstructure analysis revealed that a pearlite phase with a high carbide and/or nitride content is dissolved in the matrix by heat treatment at 1,200 ºC which is considered the dissolution to increase the concentration of interstitial elements in steels. The distribution of elements in HISSs was investigated by quantitative mapping using EPMA, which showed that the high carbon concentration (carbide/cementite) area was decreased by increases in both the cooling rate and C+N content. The ferrite volume fraction of each specimen is increased by an increase in cooling rate, because there is insufficient time to form austenite from retained ferrite. The lattice expansion of HISS was investigated by the calculation of lattice parameters under various conditions, and these investigations confirm the solid solution strengthening effect on HISSs. CN66 with heat treatment at fast cooling has the highest wear resistance; a finding that was consistent with hardening mechanisms that occur due to an increased ferrite volume fraction. In addition, precipitates on the surface and the chemical bonding of chromium were investigated. As the amount of CrN bonding increased, the wear resistance also increased. This study also assessed the

  16. Resistance to antiplatelet drugs: molecular mechanisms and laboratory detection.

    PubMed

    Cattaneo, M

    2007-07-01

    The definition 'resistance to antiplatelet drugs' should be limited to situations in which failure of the drug to hit its pharmacological target has been documented by specific laboratory tests. Aspirin resistance, as determined by specific tests (e.g. serum thromboxane B(2)), appears to be rare (1-2%) and, in most instances, is caused by poor compliance. In contrast to aspirin, studies that used specific tests to measure the pharmacological effect of thienopyridines [e.g. vasodilator-stimulated phosphoprotein (VASP)] showed a wide variability of responses to these drugs, with significant proportions of subjects (15-30%) who are very poor responders. Inter-individual differences in the extent of metabolism of thienopyridines to their active metabolites is the most plausible mechanism for the observed inter-individual variability in platelet inhibition. The demonstration that some patients may be 'resistant' or 'poor responders' to the pharmacological effect of antiplatelet drugs, has prompted the need of laboratory monitoring of antiplatelet therapy. However, many published studies have been performed using unspecific tests of platelet function, which identify patients on antiplatelet treatment with high residual platelet reactivity, which is not necessarily because of resistance to antiplatelet drugs. Despite this drawback, identification of patients with high residual platelet reactivity may be useful to predict their risk of atherothrombotic events. However, many studies still need to be carried out to identify the ideal laboratory test and to answer basic questions on its clinical utility and cost-effectiveness, before monitoring antiplatelet therapy can be recommended in the clinical practise. Until then, monitoring of antiplatelet therapy should be considered for investigational purposes only. PMID:17635731

  17. [Insulin resistance as a mechanism of adaptation during human evolution].

    PubMed

    Ricart, W; Fernández-Real, J M

    2010-10-01

    The recent application of concepts of evolution to human disease is proving useful to understand certain pathophysiological mechanisms of different entities that span genomic alterations of immunity, respiratory and hormone function, and the circulatory and neural systems. However, effort has concentrated on explaining the keys to adaptation that define human metabolism and, since the early 1960s, several theories have been developed. This article reviews some of the hypotheses postulated in recent years on the potential benefit of insulin resistance and discusses the most recent knowledge. The concept of the thrifty gene seems to have been definitively refuted by current knowledge. The current paradigm describes an interaction between the metabolic and the immune systems resulting from their coevolution, promoted by evolutionary pressures triggered by fasting, infection and intake of different foods. The activation and regulation of these ancient mechanisms in integrated and interdependent areas defines insulin resistance as a survival strategy that is critical during fasting and in the fight against infection. The relationship with some components of the diet and, particularly, with the symbiotic intestinal microflora points to new paradigms in understanding the pathophysiology of obesity, metabolic syndrome and type 2 diabetes mellitus.

  18. [Insulin resistance as a mechanism of adaptation during human evolution].

    PubMed

    Ricart, W; Fernández-Real, J M

    2010-10-01

    The recent application of concepts of evolution to human disease is proving useful to understand certain pathophysiological mechanisms of different entities that span genomic alterations of immunity, respiratory and hormone function, and the circulatory and neural systems. However, effort has concentrated on explaining the keys to adaptation that define human metabolism and, since the early 1960s, several theories have been developed. This article reviews some of the hypotheses postulated in recent years on the potential benefit of insulin resistance and discusses the most recent knowledge. The concept of the thrifty gene seems to have been definitively refuted by current knowledge. The current paradigm describes an interaction between the metabolic and the immune systems resulting from their coevolution, promoted by evolutionary pressures triggered by fasting, infection and intake of different foods. The activation and regulation of these ancient mechanisms in integrated and interdependent areas defines insulin resistance as a survival strategy that is critical during fasting and in the fight against infection. The relationship with some components of the diet and, particularly, with the symbiotic intestinal microflora points to new paradigms in understanding the pathophysiology of obesity, metabolic syndrome and type 2 diabetes mellitus. PMID:20675202

  19. Hypergravity experiments to evaluate gravity resistance mechanisms in plants.

    PubMed

    Soga, Kouichi; Yano, Sachiko; Matsumoto, Shouhei; Hoson, Takayuki

    2015-01-01

    Hypergravity generated by centrifugal acceleration is the only practical method to modify the magnitude of gravitational acceleration for a sufficient duration on Earth and has been used to analyze the nature and mechanism of graviresponse, particularly gravity resistance, in plants. Plant organs are generally resistant to gravitational acceleration. Hypergravity produced from centrifugation speeds in the range of 10-300 × g, which is easily produced by a benchtop centrifuge, is often used during plant experiments. After centrifugation, the plant material is fixed with suitable fixatives in appropriate sample storage containers such as the Chemical Fixation Bag. The material is then analyzed with a variety of methods, depending on the purpose of the experiment. Plant material fixed with the RNAlater(®) solution can be sequentially used for determining the mechanical properties of the cell wall, for RNA extraction (which is necessary for gene expression analysis), for estimating the enzyme activity of the cell wall proteins, and for determining the levels as well as the compositions of cell wall polysaccharides. The plant material can also be used directly for microscopic observation of cellular components such as cortical microtubules.

  20. Aspirin and clopidogrel resistance: possible mechanisms and clinical relevance. Part II: Potential causes and laboratory tests.

    PubMed

    Vadász, Dávid; Sztriha, László K; Sas, Katalin; Vécsei, László

    2013-01-30

    Recent meta-analyses have indicated that patients with vascular disease demonstrated by laboratory tests to be aspirin or clopidogrel-resistant are at an increased risk of major vascular events. The suggested mechanisms of aspirin resistance include genetic polymorphism, alternative pathways of platelet activation, aspirin-insensitive thromboxane biosynthesis, drug interactions, or a low aspirin dose. Clopidogrel resistance is likely to develop as a result of a decreased bioavailability of the active metabolite, due to genetic variation or concomitant drug treatment. Additional work is required to improve and validate laboratory tests of platelet function, so that they may become useful tools for selection of the most appropriate antiplatelet therapy for an individual patient. Improvements in antiplatelet treatment strategies in the future should lead to a reduction in premature vascular events. PMID:23607225

  1. Both epistatic and additive effects of QTLs are involved in polygenic induced resistance to disease: a case study, the interaction pepper - Phytophthora capsici Leonian.

    PubMed

    Lefebvre, V; Palloix, A

    1996-09-01

    To study the resistance of pepper to Phytophthora capsici, we analyzed 94 doubled-haploid (DH) lines derived from the intraspecific F1 hybrid obtained from a cross between Perennial, an Indian pungent resistant line, and Yolo Wonder, an American bell-pepper susceptible line, with 119 DNA markers. Four different criteria were used to evaluate the resistance, corresponding to different steps or mechanisms of the host-pathogen interaction: root-rot index, receptivity, inducibility and stability. Three distinct ANOVA models between DNA marker genotypes and the four disease criteria identified 13 genomic regions, distributed across several linkage groups or unlinked markers, affecting the resistance of pepper to P. capsici. Some QTLs were criterion specific, whereas others affect several criteria, so that the four resistance criteria were controlled by different combinations of QTLs. The QTLs were very different in their quantitative effect (R(2) values), including major QTLs which explained 41-55% of the phenotypic variance, intermediate QTLs with additive or/and epistatic action (17-28% of the variance explained) and minor QTLs. Favourable alleles of some minor QTLs were carried in the susceptible parent. The total phenotypic variation accounted for by QTLs reached up to 90% for receptivity, with an important part due to epistasis effects between QTLs (with or without additive effects). The relative impact of resistance QTLs in disease response is discussed. PMID:24162341

  2. Multiple resistance mechanisms among Aspergillus fumigatus mutants with high-level resistance to itraconazole.

    PubMed

    Nascimento, Adriana M; Goldman, Gustavo H; Park, Steven; Marras, Salvatore A E; Delmas, Guillaume; Oza, Uma; Lolans, Karen; Dudley, Michael N; Mann, Paul A; Perlin, David S

    2003-05-01

    A collection of Aspergillus fumigatus mutants highly resistant to itraconazole (RIT) at 100 micro g ml(-1) were selected in vitro (following UV irradiation as a preliminary step) to investigate mechanisms of drug resistance in this clinically important pathogen. Eight of the RIT mutants were found to have a mutation at Gly54 (G54E, -K, or -R) in the azole target gene CYP51A. Primers designed for highly conserved regions of multidrug resistance (MDR) pumps were used in reverse transcriptase PCR amplification reactions to identify novel genes encoding potential MDR efflux pumps in A. fumigatus. Two genes, AfuMDR3 and AfuMDR4, showed prominent changes in expression levels in many RIT mutants and were characterized in more detail. Analysis of the deduced amino acid sequence encoded by AfuMDR3 revealed high similarity to major facilitator superfamily transporters, while AfuMDR4 was a typical member of the ATP-binding cassette superfamily. Real-time quantitative PCR with molecular beacon probes was used to assess expression levels of AfuMDR3 and AfuMDR4. Most RIT mutants showed either constitutive high-level expression of both genes or induction of expression upon exposure to itraconazole. Our results suggest that overexpression of one or both of these newly identified drug efflux pump genes of A. fumigatus and/or selection of drug target site mutations are linked to high-level itraconazole resistance and are mechanistic considerations for the emergence of clinical resistance to itraconazole.

  3. Incidence and mechanisms of resistance to the combination of amoxicillin and clavulanic acid in Escherichia coli.

    PubMed Central

    Stapleton, P; Wu, P J; King, A; Shannon, K; French, G; Phillips, I

    1995-01-01

    Among Escherichia coli organisms isolated at St. Thomas's Hospital during the years 1990 to 1994, the frequency of resistance to amoxicillin-clavulanic acid (tested by disk diffusion in a ratio of 2:1) remained constant at about 5% of patient isolates (10 to 15% of the 41 to 45% that were amoxicillin resistant). Mechanisms of increased resistance were determined for 72 consecutively collected such amoxicillin-clavulanic acid-resistant isolates. MICs of the combination were 16-8 micrograms/ml for 51 (71%) of these and > or = 32-16 micrograms/ml for the remainder. The predominant mechanism was hyperproduction of enzymes isoelectrically cofocusing with TEM-1 (beta-lactamase activities, > 200 nmol of nitrocefin hydrolyzed per min per mg of protein) which was found in 44 isolates (61%); two isolates produced smaller amounts (approximately 150 nmol/min/mg) of such enzymes, and two isolates hyperproduced enzymes cofocusing with TEM-2. Eleven isolates produced enzymes cofocusing with OXA-1 beta-lactamase, which has previously been associated with resistance to amoxicillin-clavulanic acid. Ten isolates produced increased amounts of chromosomal beta-lactamase, and four of these additionally produced TEM-1 or TEM-2. Three isolates produced inhibitor-resistant TEM-group enzymes. In one of the enzymes (pI, 5.4), the amino acid sequence change was Met-67-->Val, and thus the enzyme is identical to TEM-34. Another (pI, 5.4) had the substitution Met-67-->Ile and is identical to IRT-I67, which we propose now be given the designation TEM-40. The third (pI, 5.2) had the substitution Arg-241-->Thr; this enzyme has not been reported previously and should be called TEM-41. The rarity and diversity of inhibitor-resistant TEM-group enzymes suggest that they are the result of spontaneous mutations that have not yet spread. PMID:8585729

  4. Pokeweed antiviral protein: its cytotoxicity mechanism and applications in plant disease resistance.

    PubMed

    Di, Rong; Tumer, Nilgun E

    2015-03-06

    Pokeweed antiviral protein (PAP) is a 29 kDa type I ribosome inactivating protein (RIP) found in pokeweed plants. Pokeweed produces different forms of PAP. This review focuses on the spring form of PAP isolated from Phytolacca americana leaves. PAP exerts its cytotoxicity by removing a specific adenine from the α-sarcin/ricin loop of the large ribosomal RNA. Besides depurination of the rRNA, PAP has additional activities that contribute to its cytotoxicity. The mechanism of PAP cytotoxicity is summarized based on evidence from the analysis of transgenic plants and the yeast model system. PAP was initially found to be anti-viral when it was co-inoculated with plant viruses onto plants. Transgenic plants expressing PAP and non-toxic PAP mutants have displayed broad-spectrum resistance to both viral and fungal infection. The mechanism of PAP-induced disease resistance in transgenic plants is summarized.

  5. Insertion torque versus mechanical resistance of mini-implants inserted in different cortical thickness

    PubMed Central

    Santos, Renata de Faria; Ruellas, Antonio Carlos de Oliveira; Fernandes, Daniel Jogaib; Elias, Carlos Nelson

    2014-01-01

    Objective This study aimed to measure insertion torque, tip mechanical resistance to fracture and transmucosal neck of mini-implants (MI) (Conexão Sistemas de PróteseT), as well as to analyze surface morphology. Methods Mechanical tests were carried out to measure the insertion torque of MIs in different cortical thicknesses, and tip mechanical resistance to fracture as well as transmucosal neck of MIs. Surface morphology was assessed by scanning electron microscopy (SEM) before and after the mechanical tests. Results Values of mechanical resistance to fracture (22.14 N.cm and 54.95 N.cm) were higher and statistically different (P < 0.05) from values of insertion torque for 1-mm (7.60 N.cm) and 2-mm (13.27 N.cm) cortical thicknesses. Insertion torque was statistically similar (P > 0.05) to torsional fracture in the tip of MI (22.14 N.cm) when 3 mm cortical thickness (16.11 N.cm) and dense bone (23.95 N.cm) were used. Torsional fracture of the transmucosal neck (54.95 N.cm) was higher and statistically different (P < 0.05) from insertion torsional strength in all tested situations. SEM analysis showed that the MIs had the same smooth surface when received from the manufacturer and after the mechanical tests were performed. Additionally, no significant marks resulting from the manufacturing process were observed. Conclusion All mini-implants tested presented adequate surface morphology. The resistance of mini-implants to fracture safely allows placement in 1 and 2-mm cortical thickness. However, in 3-mm cortical thickness and dense bones, pre-drilling with a bur is recommended before insertion. PMID:25162571

  6. Influence of Tin Additions on the Phase-Transformation Characteristics of Mechanical Alloyed Cu-Al-Ni Shape-Memory Alloy

    NASA Astrophysics Data System (ADS)

    Saud, Safaa N.; Hamzah, E.; Abubakar, T.; Bakhsheshi-Rad, H. R.; Mohammed, M. N.

    2016-07-01

    The influence of the addition of Sn to Cu-Al-Ni alloy as a fourth element with different percentages of 0.5, 1.0, and 1.5 wt pct on the microstructure, phase-transformation temperatures, mechanical properties, and corrosion behaviors was investigated. The modified and unmodified alloys were fabricated by mechanical alloying followed by microwave sintering. The sintered and homogenized alloys of Cu-Al-Ni-xSn shape-memory alloys had a refined particle structure with an average particle size of 40 to 50 µm associated with an improvement in the mechanical properties and corrosion resistance. With the addition of Sn, the porosity density tends to decrease, which can also lead to improvements in the properties of the modified alloys. The minimum porosity percentage was observed in the Cu-Al-Ni-1.0 wt pct Sn alloy, which resulted in enhancing the ductility, strain recovery, and corrosion resistance. Further increasing the Sn addition to 1.5 wt pct, the strength of the alloy increased because the highest volume fraction of precipitates was formed. Regarding the corrosion behavior, addition of Sn up to 1 wt pct increased the corrosion resistance of the base SMA from 2.97 to 19.20 kΩ cm2 because of formation of a protective film that contains hydrated tin oxyhydroxide, aluminum dihydroxychloride, and copper chloride on the alloy. However, further addition of Sn reduced the corrosion resistance.

  7. Influence of Tin Additions on the Phase-Transformation Characteristics of Mechanical Alloyed Cu-Al-Ni Shape-Memory Alloy

    NASA Astrophysics Data System (ADS)

    Saud, Safaa N.; Hamzah, E.; Abubakar, T.; Bakhsheshi-Rad, H. R.; Mohammed, M. N.

    2016-10-01

    The influence of the addition of Sn to Cu-Al-Ni alloy as a fourth element with different percentages of 0.5, 1.0, and 1.5 wt pct on the microstructure, phase-transformation temperatures, mechanical properties, and corrosion behaviors was investigated. The modified and unmodified alloys were fabricated by mechanical alloying followed by microwave sintering. The sintered and homogenized alloys of Cu-Al-Ni- xSn shape-memory alloys had a refined particle structure with an average particle size of 40 to 50 µm associated with an improvement in the mechanical properties and corrosion resistance. With the addition of Sn, the porosity density tends to decrease, which can also lead to improvements in the properties of the modified alloys. The minimum porosity percentage was observed in the Cu-Al-Ni-1.0 wt pct Sn alloy, which resulted in enhancing the ductility, strain recovery, and corrosion resistance. Further increasing the Sn addition to 1.5 wt pct, the strength of the alloy increased because the highest volume fraction of precipitates was formed. Regarding the corrosion behavior, addition of Sn up to 1 wt pct increased the corrosion resistance of the base SMA from 2.97 to 19.20 kΩ cm2 because of formation of a protective film that contains hydrated tin oxyhydroxide, aluminum dihydroxychloride, and copper chloride on the alloy. However, further addition of Sn reduced the corrosion resistance.

  8. Nutrient enrichment affects the mechanical resistance of aquatic plants

    PubMed Central

    Puijalon, Sara

    2012-01-01

    For many plant species, nutrient availability induces important anatomical responses, particularly the production of low-density tissues to the detriment of supporting tissues. Due to the contrasting biomechanical properties of plant tissues, these anatomical responses may induce important modifications in the biomechanical properties of plant organs. The aim of this study was to determine the effects of nutrient enrichment on the anatomical traits of two freshwater plant species and its consequences on plant biomechanical performance. Two plant species were grown under controlled conditions in low versus high nutrient levels. The anatomical and biomechanical traits of the plant stems were measured. Both species produced tissues with lower densities under nutrient-rich conditions, accompanied by modifications in the structure of the aerenchyma for one species. As expected, nutrient enrichment also led to important modifications in the biomechanical properties of the stem for both species. In particular, mechanical resistance (breaking force and strength) and stiffness of stems were significantly reduced under nutrient rich conditions. The production of weaker stem tissues as a result of nutrient enrichment may increase the risk of plants to mechanical failure, thus challenging plant maintenance in mechanically stressful or disturbed habitats. PMID:23028018

  9. Nutrient enrichment affects the mechanical resistance of aquatic plants.

    PubMed

    Lamberti-Raverot, Barbara; Puijalon, Sara

    2012-10-01

    For many plant species, nutrient availability induces important anatomical responses, particularly the production of low-density tissues to the detriment of supporting tissues. Due to the contrasting biomechanical properties of plant tissues, these anatomical responses may induce important modifications in the biomechanical properties of plant organs. The aim of this study was to determine the effects of nutrient enrichment on the anatomical traits of two freshwater plant species and its consequences on plant biomechanical performance. Two plant species were grown under controlled conditions in low versus high nutrient levels. The anatomical and biomechanical traits of the plant stems were measured. Both species produced tissues with lower densities under nutrient-rich conditions, accompanied by modifications in the structure of the aerenchyma for one species. As expected, nutrient enrichment also led to important modifications in the biomechanical properties of the stem for both species. In particular, mechanical resistance (breaking force and strength) and stiffness of stems were significantly reduced under nutrient rich conditions. The production of weaker stem tissues as a result of nutrient enrichment may increase the risk of plants to mechanical failure, thus challenging plant maintenance in mechanically stressful or disturbed habitats. PMID:23028018

  10. Mechanisms underlying obesity resistance associated with high spontaneous physical activity.

    PubMed

    Teske, J A; Billington, C J; Kotz, C M

    2014-01-01

    Obesity resistance due to elevated orexin signaling is accompanied by high levels of spontaneous physical activity (SPA). The behavioral and neural mechanisms underlying this observation have not been fully worked out. We determined the contribution of hypothalamic orexin receptors (OXRs) to SPA stimulated by orexin A (OXA), whether OXA-stimulated SPA was secondary to arousal and whether voluntary wheel running led to compensations in 24-h SPA. We further tested whether orexin action on dopamine one receptors (DA1R) in the substantia nigra (SN) plays an important role in the generation of SPA. To test this, SPA response was determined in lean and obese rats with cannulae targeted toward the rostral lateral hypothalamus (rLH) or SN. Sleep/wake states were also measured in rats with rLH cannula and electroencephalogram/electromyogram radiotelemetry transmitters. SPA in lean rats was more sensitive to antagonism of the OX1R and in the early response to the orexin 2 agonist. OXA increased arousal equally in lean and obese rodents, which is discordant from the greater SPA response in lean rats. Obesity-resistant rats ran more and wheel running was directly related to 24-h SPA levels. The OX1R antagonist, SB-334867-A, and the DA1R antagonist, SCH3390, in SN more effectively reduced SPA stimulated by OXA in obesity-resistant rats. These data suggest OXA-stimulated SPA is not secondary to enhanced arousal, propensity for SPA parallels inclination to run and that orexin action on dopaminergic neurons in SN may participate in the mediation of SPA and running wheel activity.

  11. [Molecular mechanisms of plant resistance to cadmium toxicity].

    PubMed

    Xu, Zhenghao; Shen, Guojun; Zhu, Changqing; Xu, Linjuan; He, Yong; Yu, Gusong

    2006-06-01

    Cadmium (Cd) is a non-essential trace element for plants, and has strong toxicity at low concentrations. It can suppress the elongation growth of plant cell, inhibit oxidative mitochondrial phosphorylation, induce oxidative stress, inhibit the activities of several antioxidative enzymes, affect photosynthesis by inhibiting ferrous reductase or damaging photosynthesis apparatus, and cause the alteration of chromatin and the change of plasma membrane ATPase activity. In response to Cd stress, the cells of cadmium-resistant plant species can produce a number of proteins such as phytochelatins, metallothioneins and stress proteins to detoxify Cd ions, and efficiently repair Cd damage. The plant cells can also resort to other defense systems to detoxify Cd ions, e.g., the immobilization of Cd by cell wall, exclusion of Cd through the action of plasma membrane, compartmentalization of Cd by vacuolar, and release of plant glands. The phytochelatin synthase (PCS) genes of Arabidopsin, wheat and Schizosaccharomyces pombe had been identified by using different approaches, and the metallothioneins (MT) in plants was also identified recently. By introducing animal MT genes, transgenic plants could increase the resistant ability to Cd toxicity. Subjected to Cd, plant cells often start to synthesize stress proteins such as heat shock proteins, and the plants having been transformed the stress protein genes could enhance their resistant capacity to Cd ions. It was reported that zinc (Zn) ion-transporting proteins could also transport Cd ion. Some minor genes not conferring tolerance on their own could modify the major gene (s), and enhance Cd tolerance. Cd detoxification in wild type plants could be a complex phenomenon, probably under polygenic control to Cd, while acute Cd stress seemed to be a simpler mechanism, apparently involving only one or a few specific major genes.

  12. Insecticide Resistance and Malaria Vector Control: The Importance of Fitness Cost Mechanisms in Determining Economically Optimal Control Trajectories

    PubMed Central

    Brown, Zachary S.; Dickinson, Katherine L.; Kramer, Randall A.

    2014-01-01

    The evolutionary dynamics of insecticide resistance in harmful arthropods has economic implications, not only for the control of agricultural pests (as has been well studied), but also for the control of disease vectors, such as malaria-transmitting Anopheles mosquitoes. Previous economic work on insecticide resistance illustrates the policy relevance of knowing whether insecticide resistance mutations involve fitness costs. Using a theoretical model, this article investigates economically optimal strategies for controlling malaria-transmitting mosquitoes when there is the potential for mosquitoes to evolve resistance to insecticides. Consistent with previous literature, we find that fitness costs are a key element in the computation of economically optimal resistance management strategies. Additionally, our models indicate that different biological mechanisms underlying these fitness costs (e.g., increased adult mortality and/or decreased fecundity) can significantly alter economically optimal resistance management strategies. PMID:23448053

  13. Mechanically-induced resistive switching in ferroelectric tunnel junctions.

    PubMed

    Lu, H; Kim, D J; Bark, C-W; Ryu, S; Eom, C B; Tsymbal, E Y; Gruverman, A

    2012-12-12

    Recent advances in atomic-precision processing of oxide ferroelectrics-materials with a stable polarization that can be switched by an external electric field-have generated considerable interest due to rich physics associated with their fundamental properties and high potential for application in devices with enhanced functionality. One of the particularly promising phenomena is the tunneling electroresistance (TER) effect-polarization-dependent bistable resistance behavior of ferroelectric tunnel junctions (FTJ). Conventionally, the application of an electric field above the coercive field of the ferroelectric barrier is required to observe this phenomenon. Here, we report a mechanically induced TER effect in ultrathin ferroelectric films of BaTiO(3) facilitated by a large strain gradient induced by a tip of a scanning probe microscope (SPM). The obtained results represent a new paradigm for voltage-free control of electronic properties of nanoscale ferroelectrics and, more generally, complex oxide materials. PMID:23181389

  14. Clarithromycin Resistance Mechanisms of Epidemic β-Lactamase-Nonproducing Ampicillin-Resistant Haemophilus influenzae Strains in Japan.

    PubMed

    Seyama, Shoji; Wajima, Takeaki; Nakaminami, Hidemasa; Noguchi, Norihisa

    2016-05-01

    The aim of this study was to clarify the clarithromycin resistance mechanisms of β-lactamase-nonproducing ampicillin-resistant Haemophilus influenzae strains. In all clarithromycin-resistant strains, the transcript level of acrB was significantly elevated, and these strains had a frameshift mutation in acrR Introduction of the acrR mutation into H. influenzae Rd generated a clarithromycin-resistant transformant with the same MIC as the donor strain. Our results indicate that the acrR mutation confers clarithromycin resistance by the increasing the transcription of acrB.

  15. Molecular and cellular mechanisms of cadmium resistance in cultured cells

    SciTech Connect

    Grady, D.L.; Moyzis, R.K.; Hildebrand, C.E.

    1985-01-01

    Heavy metal induction of the synthesis of metallothioneins (MTs) provides an ideal model system for basic mechanistic studies of gene expression. Cell lines varying in their resistance to heavy metals have been isolated through a regime of exposure to serially increasing levels of Cd followed by clonal isolation. These cell lines have been used to examine the role of methylation and amplification in the Cd-resistant (Cd/sup r/) phenotype. It is suggested that regulation of expression of the MT genes in Cd/sup r/ Chinese hamster cells is modulated at both the transcriptional and translational levels. An analysis of the MT2 gene sequence has uncovered a potential alternative splice site in the first intron. Usage of this site would insert 3 or 12 additional amino acids between amino acids 9 and 10. Analysis of the splicing pattern of the MT2 gene transcript in cultured cells has indicated that the second intron is preferentially removed prior to first intron excision. 34 refs., 2 figs., 1 tab.

  16. Candida parapsilosis Resistance to Fluconazole: Molecular Mechanisms and In Vivo Impact in Infected Galleria mellonella Larvae

    PubMed Central

    Souza, Ana Carolina R.; Fuchs, Beth Burgwyn; Pinhati, Henrique M. S.; Siqueira, Ricardo A.; Hagen, Ferry; Meis, Jacques F.

    2015-01-01

    Candida parapsilosis is the main non-albicans Candida species isolated from patients in Latin America. Mutations in the ERG11 gene and overexpression of membrane transporter proteins have been linked to fluconazole resistance. The aim of this study was to evaluate the molecular mechanisms in fluconazole-resistant strains of C. parapsilosis isolated from critically ill patients. The identities of the nine collected C. parapsilosis isolates at the species level were confirmed through molecular identification with a TaqMan qPCR assay. The clonal origin of the strains was checked by microsatellite typing. The Galleria mellonella infection model was used to confirm in vitro resistance. We assessed the presence of ERG11 mutations, as well as the expression of ERG11 and two additional genes that contribute to antifungal resistance (CDR1 and MDR1), by using real-time quantitative PCR. All of the C. parapsilosis (sensu stricto) isolates tested exhibited fluconazole MICs between 8 and 16 μg/ml. The in vitro data were confirmed by the failure of fluconazole in the treatment of G. mellonella infected with fluconazole-resistant strains of C. parapsilosis. Sequencing of the ERG11 gene revealed a common mutation leading to a Y132F amino acid substitution in all of the isolates, a finding consistent with their clonal origin. After fluconazole exposure, overexpression was noted for ERG11, CDR1, and MDR1 in 9/9, 9/9, and 2/9 strains, respectively. We demonstrated that a combination of molecular mechanisms, including the presence of point mutations in the ERG11 gene, overexpression of ERG11, and genes encoding efflux pumps, are involved in fluconazole resistance in C. parapsilosis. PMID:26259795

  17. Candida parapsilosis Resistance to Fluconazole: Molecular Mechanisms and In Vivo Impact in Infected Galleria mellonella Larvae.

    PubMed

    Souza, Ana Carolina R; Fuchs, Beth Burgwyn; Pinhati, Henrique M S; Siqueira, Ricardo A; Hagen, Ferry; Meis, Jacques F; Mylonakis, Eleftherios; Colombo, Arnaldo L

    2015-10-01

    Candida parapsilosis is the main non-albicans Candida species isolated from patients in Latin America. Mutations in the ERG11 gene and overexpression of membrane transporter proteins have been linked to fluconazole resistance. The aim of this study was to evaluate the molecular mechanisms in fluconazole-resistant strains of C. parapsilosis isolated from critically ill patients. The identities of the nine collected C. parapsilosis isolates at the species level were confirmed through molecular identification with a TaqMan qPCR assay. The clonal origin of the strains was checked by microsatellite typing. The Galleria mellonella infection model was used to confirm in vitro resistance. We assessed the presence of ERG11 mutations, as well as the expression of ERG11 and two additional genes that contribute to antifungal resistance (CDR1 and MDR1), by using real-time quantitative PCR. All of the C. parapsilosis (sensu stricto) isolates tested exhibited fluconazole MICs between 8 and 16 μg/ml. The in vitro data were confirmed by the failure of fluconazole in the treatment of G. mellonella infected with fluconazole-resistant strains of C. parapsilosis. Sequencing of the ERG11 gene revealed a common mutation leading to a Y132F amino acid substitution in all of the isolates, a finding consistent with their clonal origin. After fluconazole exposure, overexpression was noted for ERG11, CDR1, and MDR1 in 9/9, 9/9, and 2/9 strains, respectively. We demonstrated that a combination of molecular mechanisms, including the presence of point mutations in the ERG11 gene, overexpression of ERG11, and genes encoding efflux pumps, are involved in fluconazole resistance in C. parapsilosis.

  18. Effect of Operating Parameters and Chemical Additives on Crystal Habit and Specific Cake Resistance of Zinc Hydroxide Precipitates

    SciTech Connect

    Alwin, Jennifer Louise

    1999-08-01

    The effect of process parameters and chemical additives on the specific cake resistance of zinc hydroxide precipitates was investigated. The ability of a slurry to be filtered is dependent upon the particle habit of the solid and the particle habit is influenced by certain process variables. The process variables studied include neutralization temperature, agitation type, and alkalinity source used for neutralization. Several commercially available chemical additives advertised to aid in solid/liquid separation were also examined in conjunction with hydroxide precipitation. A statistical analysis revealed that the neutralization temperature and the source of alkalinity were statistically significant in influencing the specific cake resistance of zinc hydroxide precipitates in this study. The type of agitation did not significantly effect the specific cake resistance of zinc hydroxide precipitates. The use of chemical additives in conjunction with hydroxide precipitation had a favorable effect on the filterability. The morphology of the hydroxide precipitates was analyzed using scanning electron microscopy.

  19. Mechanism of resistance to macrolide-lincosamide-streptogramin antibiotics in Streptococcus thermophilus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Resistance to macrolide-lincosamide-streptogramin (MLS) group antibiotics in the dairy bacterium Streptococcus thermophilus (ST) is documented but the mechanism of resistance has not been elucidated. MIC values for erythromycin (Erm), azithromycin (Azm), tylosin (Tyl), spiramycin (Spm), pristinamyci...

  20. Development of High-Antifouling PPSU Ultrafiltration Membrane by Using Compound Additives: Preparation, Morphologies, and Filtration Resistant Properties.

    PubMed

    Liu, Jie; Zhong, Zhencheng; Ma, Rui; Zhang, Weichen; Li, Jiding

    2016-01-01

    In this study, flat sheet asymmetric polyphenylsulfone (PPSU) ultrafiltration membranes with enhanced antifouling properties were prepared with a non-solvent induced phase separation (NIPS) method through compound additives containing a polymeric pore-forming agent, a small molecular non-solvent and a surfactant. The formation processes of the porous asymmetric membranes with different kinds of additives were studied in detail, and the microstructure controllable preparation of membrane was achieved by establishing a bridge between the membrane preparation parameters and separation performances. All prepared membranes were characterized by using a scanning electron microscope (SEM), contact angle analysis, porosity, maximum pore size, water and BSA solution permeability studies. The performance efficiency of the membrane was evaluated by using BSA as a model foulant in terms of permeability, solute rejection (R), Rm (membrane inherent resistance), Rc (cake layer resistance), and Rp (pore plugging resistance). The results showed that when the compound additives were used, the inter-connected pores were observed, maximum pore size, contact angle and membrane filtration resistance decreased, while the porosity increased. When PVP compound additives were added, the water flux increased from 80.4 to 148.1 L/(m²·h), the BSA rejection increased from 53.2% to 81.5%. A similar trend was observed for membranes with added PEG compound additives; the water flux and BSA rejection simultaneously increased. The filtration resistance decreased as a result of compound additives. The uniformity of membrane and the number of effective pores could be enhanced by adding compound additives through the cooperation of different additives.

  1. Development of High-Antifouling PPSU Ultrafiltration Membrane by Using Compound Additives: Preparation, Morphologies, and Filtration Resistant Properties.

    PubMed

    Liu, Jie; Zhong, Zhencheng; Ma, Rui; Zhang, Weichen; Li, Jiding

    2016-01-01

    In this study, flat sheet asymmetric polyphenylsulfone (PPSU) ultrafiltration membranes with enhanced antifouling properties were prepared with a non-solvent induced phase separation (NIPS) method through compound additives containing a polymeric pore-forming agent, a small molecular non-solvent and a surfactant. The formation processes of the porous asymmetric membranes with different kinds of additives were studied in detail, and the microstructure controllable preparation of membrane was achieved by establishing a bridge between the membrane preparation parameters and separation performances. All prepared membranes were characterized by using a scanning electron microscope (SEM), contact angle analysis, porosity, maximum pore size, water and BSA solution permeability studies. The performance efficiency of the membrane was evaluated by using BSA as a model foulant in terms of permeability, solute rejection (R), Rm (membrane inherent resistance), Rc (cake layer resistance), and Rp (pore plugging resistance). The results showed that when the compound additives were used, the inter-connected pores were observed, maximum pore size, contact angle and membrane filtration resistance decreased, while the porosity increased. When PVP compound additives were added, the water flux increased from 80.4 to 148.1 L/(m²·h), the BSA rejection increased from 53.2% to 81.5%. A similar trend was observed for membranes with added PEG compound additives; the water flux and BSA rejection simultaneously increased. The filtration resistance decreased as a result of compound additives. The uniformity of membrane and the number of effective pores could be enhanced by adding compound additives through the cooperation of different additives. PMID:27338487

  2. Development of High-Antifouling PPSU Ultrafiltration Membrane by Using Compound Additives: Preparation, Morphologies, and Filtration Resistant Properties

    PubMed Central

    Liu, Jie; Zhong, Zhencheng; Ma, Rui; Zhang, Weichen; Li, Jiding

    2016-01-01

    In this study, flat sheet asymmetric polyphenylsulfone (PPSU) ultrafiltration membranes with enhanced antifouling properties were prepared with a non-solvent induced phase separation (NIPS) method through compound additives containing a polymeric pore-forming agent, a small molecular non-solvent and a surfactant. The formation processes of the porous asymmetric membranes with different kinds of additives were studied in detail, and the microstructure controllable preparation of membrane was achieved by establishing a bridge between the membrane preparation parameters and separation performances. All prepared membranes were characterized by using a scanning electron microscope (SEM), contact angle analysis, porosity, maximum pore size, water and BSA solution permeability studies. The performance efficiency of the membrane was evaluated by using BSA as a model foulant in terms of permeability, solute rejection (R), Rm (membrane inherent resistance), Rc (cake layer resistance), and Rp (pore plugging resistance). The results showed that when the compound additives were used, the inter-connected pores were observed, maximum pore size, contact angle and membrane filtration resistance decreased, while the porosity increased. When PVP compound additives were added, the water flux increased from 80.4 to 148.1 L/(m2·h), the BSA rejection increased from 53.2% to 81.5%. A similar trend was observed for membranes with added PEG compound additives; the water flux and BSA rejection simultaneously increased. The filtration resistance decreased as a result of compound additives. The uniformity of membrane and the number of effective pores could be enhanced by adding compound additives through the cooperation of different additives. PMID:27338487

  3. Improving Student Understanding of Addition of Angular Momentum in Quantum Mechanics

    ERIC Educational Resources Information Center

    Zhu, Guangtian; Singh, Chandralekha

    2013-01-01

    We describe the difficulties advanced undergraduate and graduate students have with concepts related to addition of angular momentum in quantum mechanics. We also describe the development and implementation of a research-based learning tool, Quantum Interactive Learning Tutorial (QuILT), to reduce these difficulties. The preliminary evaluation…

  4. Mechanisms of antibiotic resistance to enrofloxacin in uropathogenic Escherichia coli in dog.

    PubMed

    Piras, Cristian; Soggiu, Alessio; Greco, Viviana; Martino, Piera Anna; Del Chierico, Federica; Putignani, Lorenza; Urbani, Andrea; Nally, Jarlath E; Bonizzi, Luigi; Roncada, Paola

    2015-09-01

    Escherichia coli (E. coli) urinary tract infections (UTIs) are becoming a serious problem both for pets and humans (zoonosis) due to the close contact and to the increasing resistance to antibiotics. This study has been performed in order to unravel the mechanism of induced enrofloxacin resistance in canine E. coli isolates that represent a good tool to study this pathology. The isolated E. coli has been induced with enrofloxacin and studied through 2D DIGE and shotgun MS. Discovered differentially expressed proteins are principally involved in antibiotic resistance and linked to oxidative stress response, to DNA protection and to membrane permeability. Moreover, since enrofloxacin is an inhibitor of DNA gyrase, the overexpression of DNA starvation/stationary phase protection protein (Dsp) could be a central point to discover the mechanism of this clone to counteract the effects of enrofloxacin. In parallel, the dramatic decrease of the synthesis of the outer membrane protein W, which represents one of the main gates for enrofloxacin entrance, could explain additional mechanism of E. coli defense against this antibiotic. All 2D DIGE and MS data have been deposited into the ProteomeXchange Consortium with identifier PXD002000 and DOI http://dx.doi.org/10.6019/PXD002000. This article is part of a Special Issue entitled: HUPO 2014. PMID:26066767

  5. Effect of Ti additive on (Cr, Fe)7C3 carbide in arc surfacing layer and its refined mechanism

    NASA Astrophysics Data System (ADS)

    Zhou, Yefei; Yang, Yulin; Yang, Jian; Hao, Feifei; Li, Da; Ren, Xuejun; Yang, Qingxiang

    2012-06-01

    Arc surfacing layer of hypoeutectic high chromium cast iron (HCCI) expects refiner carbides in the microstructure to improve its mechanical properties. In this paper, Ti additive as a strong carbide forming element was added in the hypoeutectic HCCI arc surfacing layer. Microstructure of titaniferous hypoeutectic HCCI was studied by optical microscopy, X-ray diffraction and field emission scanning electronic microscopy with energy dispersive spectrometer. Furthermore, the M(M = Cr, Fe)7C3 carbide refinement mechanism was explained by the phase diagram calculation and lattice misfit theory. The results show that, the M7C3 carbide in arc surfacing microstructure of hypoeutectic HCCI has been refined with 2 wt.% Ti additive, and TiC carbide can be observed in/around the M7C3 carbide. With Ti addictive increasing, the micro-hardness along the depth in profile section of layer becomes more uniform, and the wear resistance has been improved. According to the phase diagram calculation, MC carbide precipitates prior to M7C3 carbide in Fe-Cr-C-Ti alloy. In addition, the lattice misfit between (1 1 0)TiC and (0C is 9.257%, which indicates that the TiC as heterogeneous nuclei of the M7C3 is medium effective. Therefore, the M7C3 carbide can be refined.

  6. Mechanism behind Resistance against the Organophosphate Azamethiphos in Salmon Lice (Lepeophtheirus salmonis).

    PubMed

    Kaur, Kiranpreet; Helgesen, Kari Olli; Bakke, Marit Jørgensen; Horsberg, Tor Einar

    2015-01-01

    Acetylcholinesterase (AChE) is the primary target for organophosphates (OP). Several mutations have been reported in AChE to be associated with the reduced sensitivity against OP in various arthropods. However, to the best of our knowledge, no such reports are available for Lepeophtheirus salmonis. Hence, in the present study, we aimed to determine the association of AChE(s) gene(s) with resistance against OP. We screened the AChE genes (L. salmonis ace1a and ace1b) in two salmon lice populations: one sensitive (n=5) and the other resistant (n=5) for azamethiphos, a commonly used OP in salmon farming. The screening led to the identification of a missense mutation Phe362Tyr in L. salmonis ace1a, (corresponding to Phe331 in Torpedo californica AChE) in all the samples of the resistant population. We confirmed the potential role of the mutation, with reduced sensitivity against azamethiphos in L. salmonis, by screening for Phe362Tyr in 2 sensitive and 5 resistant strains. The significantly higher frequency of the mutant allele (362Tyr) in the resistant strains clearly indicated the possible association of Phe362Tyr mutation in L. salmonis ace1a with resistance towards azamethiphos. The 3D modelling, short term survival experiments and enzymatic assays further supported the imperative role of Phe362Tyr in reduced sensitivity of L. salmonis for azamethiphos. Based on all these observations, the present study, for the first time, presents the mechanism of resistance in L. salmonis against azamethiphos. In addition, we developed a rapid diagnostic tool for the high throughput screening of Phe362Tyr mutation using High Resolution Melt analysis. PMID:25893248

  7. Mechanism behind Resistance against the Organophosphate Azamethiphos in Salmon Lice (Lepeophtheirus salmonis)

    PubMed Central

    Kaur, Kiranpreet; Helgesen, Kari Olli; Bakke, Marit Jørgensen; Horsberg, Tor Einar

    2015-01-01

    Acetylcholinesterase (AChE) is the primary target for organophosphates (OP). Several mutations have been reported in AChE to be associated with the reduced sensitivity against OP in various arthropods. However, to the best of our knowledge, no such reports are available for Lepeophtheirus salmonis. Hence, in the present study, we aimed to determine the association of AChE(s) gene(s) with resistance against OP. We screened the AChE genes (L. salmonis ace1a and ace1b) in two salmon lice populations: one sensitive (n=5) and the other resistant (n=5) for azamethiphos, a commonly used OP in salmon farming. The screening led to the identification of a missense mutation Phe362Tyr in L. salmonis ace1a, (corresponding to Phe331 in Torpedo californica AChE) in all the samples of the resistant population. We confirmed the potential role of the mutation, with reduced sensitivity against azamethiphos in L. salmonis, by screening for Phe362Tyr in 2 sensitive and 5 resistant strains. The significantly higher frequency of the mutant allele (362Tyr) in the resistant strains clearly indicated the possible association of Phe362Tyr mutation in L. salmonis ace1a with resistance towards azamethiphos. The 3D modelling, short term survival experiments and enzymatic assays further supported the imperative role of Phe362Tyr in reduced sensitivity of L. salmonis for azamethiphos. Based on all these observations, the present study, for the first time, presents the mechanism of resistance in L. salmonis against azamethiphos. In addition, we developed a rapid diagnostic tool for the high throughput screening of Phe362Tyr mutation using High Resolution Melt analysis. PMID:25893248

  8. Improvement of mechanical properties by additive assisted laser sintering of PEEK

    SciTech Connect

    Kroh, M. Bonten, C.; Eyerer, P.

    2014-05-15

    The additive assisted laser sintering was recently developed at IKT: A carbon black (CB) additive is used to adjust the polymer's laser absorption behavior with the aim to improve the interconnection of sintered powder layers. In this paper a parameter study, Polyetheretherketone (PEEK) samples were prepared with different contents of carbon black and were laser sintered with varying thermal treatment. The samples were mechanically tested and investigated by optical light and transmission electron microscopy. An influence on the morphology at the border areas of particles and intersections of laser sintered layers was found. Depending on the viscosity of the raw material and CB content, different shapes of lamellae were observed. These (trans-) crystalline or polymorph structures, respectively, influence the thermal and mechanical behavior of the virgin PEEK. Moreover, the thermal treatment during the sintering process caused an improvement of mechanical properties like tensile strength and elongation at break.

  9. Improvement of mechanical properties by additive assisted laser sintering of PEEK

    NASA Astrophysics Data System (ADS)

    Kroh, M.; Bonten, C.; Eyerer, P.

    2014-05-01

    The additive assisted laser sintering was recently developed at IKT: A carbon black (CB) additive is used to adjust the polymer's laser absorption behavior with the aim to improve the interconnection of sintered powder layers. In this paper a parameter study, Polyetheretherketone (PEEK) samples were prepared with different contents of carbon black and were laser sintered with varying thermal treatment. The samples were mechanically tested and investigated by optical light and transmission electron microscopy. An influence on the morphology at the border areas of particles and intersections of laser sintered layers was found. Depending on the viscosity of the raw material and CB content, different shapes of lamellae were observed. These (trans-) crystalline or polymorph structures, respectively, influence the thermal and mechanical behavior of the virgin PEEK. Moreover, the thermal treatment during the sintering process caused an improvement of mechanical properties like tensile strength and elongation at break.

  10. Exploring the host transcriptome for mechanisms underlying protective immunity and resistance to nematode infections in ruminants.

    PubMed

    Li, Robert W; Choudhary, Ratan K; Capuco, Anthony V; Urban, Joseph F

    2012-11-23

    Nematode infections in ruminants are a major impediment to the profitable production of meat and dairy products, especially for small farms. Gastrointestinal parasitism not only negatively impacts weight gain and milk yield, but is also a major cause of mortality in small ruminants. The current parasite control strategy involves heavy use of anthelmintics that has resulted in the emergence of drug-resistant parasite strains. This, in addition to increasing consumer demand for animal products that are free of drug residues has stimulated development of alternative strategies, including selective breeding of parasite resistant ruminants. The development of protective immunity and manifestations of resistance to nematode infections relies upon the precise expression of the host genome that is often confounded by mechanisms simultaneously required to control multiple nematode species as well as ecto- and protozoan parasites, and microbial and viral pathogens. Understanding the molecular mechanisms underlying these processes represents a key step toward development of effective new parasite control strategies. Recent progress in characterizing the transcriptome of both hosts and parasites, utilizing high-throughput microarrays and RNA-seq technology, has led to the recognition of unique interactions and the identification of genes and biological pathways involved in the response to parasitism. Innovative use of the knowledge gained by these technologies should provide a basis for enhancing innate immunity while limiting the polarization of acquired immunity can negatively affect optimal responses to co-infection. Strategies for parasite control that use diet and vaccine/adjuvant combination could be evaluated by monitoring the host transcriptome for induction of appropriate mechanisms for imparting parasite resistance. Knowledge of different mechanisms of host immunity and the critical regulation of parasite development, physiology, and virulence can also selectively

  11. Clinical epidemiology and resistance mechanisms of carbapenem-resistant Acinetobacter baumannii, French Guiana, 2008-2014.

    PubMed

    Mahamat, Aba; Bertrand, Xavier; Moreau, Brigitte; Hommel, Didier; Couppie, Pierre; Simonnet, Christine; Kallel, Hatem; Demar, Magalie; Djossou, Felix; Nacher, Mathieu

    2016-07-01

    This study investigated the clinical epidemiology and resistance mechanisms of Acinetobacter baumannii and characterised the clonal diversity of carbapenem-resistant A. baumannii (CRAB) during an ICU-associated outbreak at Cayenne Hospital, French Guiana. All non-duplicate A. baumannii isolates from 2008 to 2014 were tested for antibiotic susceptibility by disk diffusion. Multilocus sequence typing, pulsed-field gel electrophoresis (PFGE) and characterisation of carbapenemase-encoding genes were performed on CRAB. Of the 441 A. baumannii isolates, most were from males (54.0%) and were detected mainly from the ICU (30.8%) and medicine wards (21.8%). In the ICU, strains were mainly isolated from the respiratory tract (44.1%) and bloodstream (14.0%), whereas in medicine wards they mainly were from wound/drainage (36.5%) and bloodstream (25.0%). A. baumannii showed the greatest susceptibility to piperacillin/tazobactam (92.7%), imipenem (92.5%), colistin (95.6%) and amikacin (97.2%), being lower in the ICU and medicine wards compared with other wards. An outbreak of OXA-23-producing CRAB occurred in the 13-bed ICU in 2010. CRAB strains were more co-resistant to other antimicrobials compared with non-CRAB. Molecular genetics analysis revealed five sequence types [ST78, ST107 and ST642 and two new STs (ST830 and ST831)]. Analysis of PFGE profiles indicated cross-transmissions of CRAB within the ICU, between the ICU and one medicine ward during transfer of patients, and within that medicine ward. This study provides the first clinical and molecular data of A. baumannii from French Guiana and the Amazon basin. The ICU was the highest risk unit of this nosocomial outbreak of OXA-23-producing CRAB, which could subsequently disseminate within the hospital.

  12. Effects of sarA inactivation on the intrinsic multidrug resistance mechanism of Staphylococcus aureus.

    PubMed

    O'Leary, Jessica O; Langevin, Mark J; Price, Christopher T D; Blevins, Jon S; Smeltzer, Mark S; Gustafson, John E

    2004-08-15

    The sarA locus of Staphylococccus aureus regulates the synthesis of over 100 genes on the S. aureus chromosome. We now report the effects of sarA inactivation on intrinsic multidrug resistance expression by S. aureus. In a strain-dependent fashion, sarA::kan mutants of three unrelated strains of S. aureus demonstrated significantly increased susceptibility to five or more of the following substances: the antibiotics ciprofloxacin, fusidic acid, and vancomycin; the DNA-intercalating agent ethidium; and four common household cleaner formulations. In addition, all three sarA::kan mutants demonstrated significantly increased accumulation of ciprofloxacin and one sarA::kan mutant demonstrated increased ethidium accumulation. Our data therefore indicate that sarA plays a role in the intrinsic multidrug resistance mechanism expressed by S. aureus, in part by regulating drug accumulation.

  13. Role of extracellular vesicles in de novo mineralization: an additional novel mechanism of cardiovascular calcification.

    PubMed

    New, Sophie E P; Aikawa, Elena

    2013-08-01

    Extracellular vesicles are membrane micro/nanovesicles secreted by many cell types into the circulation and the extracellular milieu in physiological and pathological conditions. Evidence suggests that extracellular vesicles, known as matrix vesicles, play a role in the mineralization of skeletal tissue, but emerging ultrastructural and in vitro studies have demonstrated their contribution to cardiovascular calcification as well. Cells involved in the progression of cardiovascular calcification release active vesicles capable of nucleating hydroxyapatite on their membranes. This review discusses the role of extracellular vesicles in cardiovascular calcification and elaborates on this additional mechanism of calcification as an alternative pathway to the currently accepted mechanism of biomineralization via osteogenic differentiation.

  14. Quantum mechanics/molecular mechanics modeling of covalent addition between EGFR-cysteine 797 and N-(4-anilinoquinazolin-6-yl) acrylamide.

    PubMed

    Capoferri, Luigi; Lodola, Alessio; Rivara, Silvia; Mor, Marco

    2015-03-23

    Irreversible epidermal growth factor receptor (EGFR) inhibitors can circumvent resistance to first-generation ATP-competitive inhibitors in the treatment of nonsmall-cell lung cancer. They covalently bind a noncatalytic cysteine (Cys797) at the surface of EGFR active site by an acrylamide warhead. Herein, we used a hybrid quantum mechanics/molecular mechanics (QM/MM) potential in combination with umbrella sampling in the path-collective variable space to investigate the mechanism of alkylation of Cys797 by the prototypical covalent inhibitor N-(4-anilinoquinazolin-6-yl) acrylamide. Calculations show that Cys797 reacts with the acrylamide group of the inhibitor through a direct addition mechanism, with Asp800 acting as a general base/general acid in distinct steps of the reaction. The obtained reaction free energy is negative (ΔA = -12 kcal/mol) consistent with the spontaneous and irreversible alkylation of Cys797 by N-(4-anilinoquinazolin-6-yl) acrylamide. Our calculations identify desolvation of Cys797 thiolate anion as a key step of the alkylation process, indicating that changes in the intrinsic reactivity of the acrylamide would have only a minor impact on the inhibitor potency.

  15. A target-protection mechanism of antibiotic resistance at atomic resolution: insights into FusB-type fusidic acid resistance

    PubMed Central

    Tomlinson, Jennifer H.; Thompson, Gary S.; Kalverda, Arnout P.; Zhuravleva, Anastasia; O’Neill, Alex J.

    2016-01-01

    Antibiotic resistance in clinically important bacteria can be mediated by proteins that physically associate with the drug target and act to protect it from the inhibitory effects of an antibiotic. We present here the first detailed structural characterization of such a target protection mechanism mediated through a protein-protein interaction, revealing the architecture of the complex formed between the FusB fusidic acid resistance protein and the drug target (EF-G) it acts to protect. Binding of FusB to EF-G induces conformational and dynamic changes in the latter, shedding light on the molecular mechanism of fusidic acid resistance. PMID:26781961

  16. Effect of Organic Additive on Surface Roughness of Polycrystalline Silicon Film after Chemical Mechanical Polishing

    NASA Astrophysics Data System (ADS)

    Hwang, Hee-Sub; Park, Jin-Hyung; Yi, Sok-Ho; Paik, Ungyu; Park, Jea-Gun

    2010-01-01

    The effect of an organic additive on the surface roughness of a polycrystalline silicon (poly-Si) film was investigated by chemical mechanical polishing (CMP). The surface roughness of the polished poly-Si film was markedly reduced by adding 0.001 wt % hydroxyl ethyl cellulose (HEC) and then decreased slightly with further addition of HEC. We concluded that the reduction of surface roughness was attributed to the formation of a hydroplane layer on the poly-Si surface. Evidence of the hydroplane layer was verified by contact angle and X-ray photoelectron spectroscopy (XPS) measurements.

  17. Obesity, insulin resistance and comorbidities – Mechanisms of association

    PubMed Central

    Castro, Ana Valeria B.; Kolka, Cathryn M.; Kim, Stella P.; Bergman, Richard N.

    2015-01-01

    Overall excess of fat, usually defined by the body mass index, is associated with metabolic (e.g. glucose intolerance, type 2 diabetes mellitus (T2DM), dyslipidemia) and non-metabolic disorders (e.g. neoplasias, polycystic ovary syndrome, non-alcoholic fat liver disease, glomerulopathy, bone fragility etc.). However, more than its total amount, the distribution of adipose tissue throughout the body is a better predictor of the risk to the development of those disorders. Fat accumulation in the abdominal area and in non-adipose tissue (ectopic fat), for example, is associated with increased risk to develop metabolic and non-metabolic derangements. On the other hand, observations suggest that individuals who present peripheral adiposity, characterized by large hip and thigh circumferences, have better glucose tolerance, reduced incidence of T2DM and of metabolic syndrome. Insulin resistance (IR) is one of the main culprits in the association between obesity, particularly visceral, and metabolic as well as non-metabolic diseases. In this review we will highlight the current pathophysiological and molecular mechanisms possibly involved in the link between increased VAT, ectopic fat, IR and comorbidities. We will also provide some insights in the identification of these abnormalities. PMID:25211442

  18. Effective Mechanical Properties of Lattice Material Fabricated by Material Extrusion Additive Manufacturing

    SciTech Connect

    Park, Sang-In; Choi, Seung-kyum; Rosen, David W; Duty, Chad E

    2014-01-01

    In this paper, a two-step homogenization method is proposed and implemented for evaluating effective mechanical properties of lattice structured material fabricated by the material extrusion additive manufacturing process. In order to consider the characteristics of the additive manufacturing process in estimation procedures, the levels of scale for homogenization are divided into three stages the levels of layer deposition, structural element, and lattice structure. The method consists of two transformations among stages. In the first step, the transformation between layer deposition and structural element levels is proposed to find the geometrical and material effective properties of structural elements in the lattice structure. In the second step, the method to estimate effective mechanical properties of lattice material is presented, which uses a unit cell and is based on the discretized homogenization method for periodic structure. The method is implemented for cubic lattice structure and compared to experimental results for validation purposes.

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

    PubMed

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

    2016-01-01

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

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  2. Inheritance, Realized Heritability, and Biochemical Mechanisms of Malathion Resistance in Bactrocera dorsalis (Diptera: Tephritidae).

    PubMed

    Wang, Luo-Luo; Feng, Zi-Jiao; Li, Ting; Lu, Xue-Ping; Zhao, Jia-Jia; Niu, Jin-Zhi; Smagghe, Guy; Wang, Jin-Jun

    2016-02-01

    To better characterize the resistance development and therefore establish effective pest management strategies, this study was undertaken to investigate the inheritance mode and biochemical mechanisms of malathion resistance in the oriental fruit fly, Bactrocera dorsalis (Hendel), which is one of the most notorious pests in the world. After 22 generations of selection with malathion, the malathion-resistant (MR) strain of B. dorsalis developed a 34-fold resistance compared with a laboratory susceptible strain [malathion-susceptible (MS)]. Bioassay results showed that there was no significant difference between the LD50 values of malathion against the progenies from both reciprocal crosses (F(1)-SR and F(1)-RS). The degree of dominance values (D) was calculated as 0.39 and 0.32 for F(1)-RS and F(1)-SR, respectively. The logarithm dosage-probit mortality lines of the F(2) generation and progeny from the backcross showed no clear plateaus of mortality across a range of doses. In addition, Chi-square analysis revealed significant differences between the mortality data and the theoretical expectations. The realized heritability (h(2)) value was 0.16 in the laboratory-selected resistant strain of B. dorsalis. Enzymatic activities identified significant changes of carboxylesterases, cytochrome P450 (general oxidases), and glutathione S-transferases in MR compared with the MS strain of B. dorsalis. Taken together, this study revealed for the first time that malathion resistance in B. dorsalis follows an autosomal, incompletely dominant, and polygenic mode of inheritance and is closely associated with significantly elevated activities of three major detoxification enzymes. PMID:26362988

  3. Inheritance, Realized Heritability, and Biochemical Mechanisms of Malathion Resistance in Bactrocera dorsalis (Diptera: Tephritidae).

    PubMed

    Wang, Luo-Luo; Feng, Zi-Jiao; Li, Ting; Lu, Xue-Ping; Zhao, Jia-Jia; Niu, Jin-Zhi; Smagghe, Guy; Wang, Jin-Jun

    2016-02-01

    To better characterize the resistance development and therefore establish effective pest management strategies, this study was undertaken to investigate the inheritance mode and biochemical mechanisms of malathion resistance in the oriental fruit fly, Bactrocera dorsalis (Hendel), which is one of the most notorious pests in the world. After 22 generations of selection with malathion, the malathion-resistant (MR) strain of B. dorsalis developed a 34-fold resistance compared with a laboratory susceptible strain [malathion-susceptible (MS)]. Bioassay results showed that there was no significant difference between the LD50 values of malathion against the progenies from both reciprocal crosses (F(1)-SR and F(1)-RS). The degree of dominance values (D) was calculated as 0.39 and 0.32 for F(1)-RS and F(1)-SR, respectively. The logarithm dosage-probit mortality lines of the F(2) generation and progeny from the backcross showed no clear plateaus of mortality across a range of doses. In addition, Chi-square analysis revealed significant differences between the mortality data and the theoretical expectations. The realized heritability (h(2)) value was 0.16 in the laboratory-selected resistant strain of B. dorsalis. Enzymatic activities identified significant changes of carboxylesterases, cytochrome P450 (general oxidases), and glutathione S-transferases in MR compared with the MS strain of B. dorsalis. Taken together, this study revealed for the first time that malathion resistance in B. dorsalis follows an autosomal, incompletely dominant, and polygenic mode of inheritance and is closely associated with significantly elevated activities of three major detoxification enzymes.

  4. The effect of fermentation and addition of vegetable oil on resistant starch formation in wholegrain breads.

    PubMed

    Buddrick, Oliver; Jones, Oliver A H; Hughes, Jeff G; Kong, Ing; Small, Darryl M

    2015-08-01

    Resistant starch has potential health benefits but the factors affecting its formation in bread and baked products are not well studied. Here, the formation of resistant starch in wholemeal bread products was evaluated in relation to the processing conditions including fermentation time, temperature and the inclusion of palm oil as a vitamin source. The effects of each the factor were assessed using a full factorial design. The impact on final starch content of traditional sourdough fermentation of wholemeal rye bread, as well as the bulk fermentation process of wheat and wheat/oat blends of wholemeal bread, was also assessed by enzyme assay. Palm oil content was found to have a significant effect on the formation of resistant starch in all of the breads while fermentation time and temperature had no significant impact. Sourdough fermentation of rye bread was found to have a greater impact on resistant starch formation than bulk fermentation of wheat and wheat blend breads, most likely due the increased organic acid content of the sourdough process. PMID:25766816

  5. Confirming QTLs and finding additional loci responsible for resistance to rice sheath blight disease

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Rice sheath blight disease (Rhizoctonia solani AG1-1AKühn) is one of the most destructive rice diseases worldwide. Utilization of host resistance is the most economical and environmentally sound strategy in managing sheath blight (ShB). Ten ShB-QTLs were previously mapped in a LJRIL population using...

  6. The effect of fermentation and addition of vegetable oil on resistant starch formation in wholegrain breads.

    PubMed

    Buddrick, Oliver; Jones, Oliver A H; Hughes, Jeff G; Kong, Ing; Small, Darryl M

    2015-08-01

    Resistant starch has potential health benefits but the factors affecting its formation in bread and baked products are not well studied. Here, the formation of resistant starch in wholemeal bread products was evaluated in relation to the processing conditions including fermentation time, temperature and the inclusion of palm oil as a vitamin source. The effects of each the factor were assessed using a full factorial design. The impact on final starch content of traditional sourdough fermentation of wholemeal rye bread, as well as the bulk fermentation process of wheat and wheat/oat blends of wholemeal bread, was also assessed by enzyme assay. Palm oil content was found to have a significant effect on the formation of resistant starch in all of the breads while fermentation time and temperature had no significant impact. Sourdough fermentation of rye bread was found to have a greater impact on resistant starch formation than bulk fermentation of wheat and wheat blend breads, most likely due the increased organic acid content of the sourdough process.

  7. Improvement of corrosion resistance of high-velocity oxyfuel-sprayed stainless steel coatings by addition of molybdenum

    NASA Astrophysics Data System (ADS)

    Kawakita, Jin; Kuroda, Seiji; Fukushima, Takeshi; Kodama, Toshiaki

    2005-06-01

    To improve the marine corrosion resistance of stainless steel coatings fabricated by high-velocity oxyfuel (HVOF) spraying with a gas shroud attachment, the molybdenum (Mo) content of stainless steel was increased to form coatings with a chemical composition of Fe balance-18mass%Cr-22mass%Ni-2˜8mass%Mo. These coatings were highly dense, with <0.1 vol.% in porosity, and less oxidized, with 0.5 mass% in oxygen content at most. The corrosion mechanism and resistance of the coatings were investigated by electrochemical measurement, chemical analysis, and statistical processing. The general corrosion resistance of the coatings in 0.5 mol/dm3 sulfuric acid was improved with increases in Mo content, and the corrosion rate could be decreased to 8.8 × 10-2 mg/cm2 per hour (˜1 mm/year) at 8 mass% Mo. The pitting corrosion resistance of the coatings in artificial seawater was improved with increases in Mo content and was superior to that of the 316L stainless steel coating. The crevice corrosion resistance of the coatings in artificial seawater was improved and the number of rust spots at 4 mass% Mo was decreased to 38% of that for the 316L coating. Accordingly, Mo is highly effective in improving the corrosion resistance of the stainless steel coatings by HVOF spraying.

  8. Additive genetic variation in resistance traits of an exotic pine species: little evidence for constraints on evolution of resistance against native herbivores

    PubMed Central

    Moreira, X; Zas, R; Sampedro, L

    2013-01-01

    The apparent failure of invasions by alien pines in Europe has been explained by the co-occurrence of native pine congeners supporting herbivores that might easily recognize the new plants as hosts. Previous studies have reported that exotic pines show reduced tolerance and capacity to induce resistance to those native herbivores. We hypothesize that limited genetic variation in resistance to native herbivores and the existence of evolutionary trade-offs between growth and resistance could represent additional potential constraints on the evolution of invasiveness of exotic pines outside their natural range. In this paper, we examined genetic variation for constitutive and induced chemical defences (measured as non-volatile resin in the stem and total phenolics in the needles) and resistance to two major native generalist herbivores of pines in cafeteria bioassays (the phloem-feeder Hylobius abietis and the defoliator Thaumetopoea pityocampa) using half-sib families drawn from a sample of the population of Pinus radiata introduced to Spain in the mid-19th century. We found (i) significant genetic variation, with moderate-to-high narrow-sense heritabilities for both the production of constitutive non-volatile resin and induced total phenolics, and for constitutive resistance against T. pityocampa in bioassays, (ii) no evolutionary trade-offs between plant resistance and growth traits or between the production of different quantitative chemical defences and (iii) a positive genetic correlation between constitutive resistance to the two studied herbivores. Overall, results of our study indicate that the exotic pine P. radiata has limited genetic constraints on the evolution of resistance against herbivores in its introduced range, suggesting that, at least in terms of interactions with these enemies, this pine species has potential to become invasive in the future. PMID:23232833

  9. Toward a mechanism for biliprotein lyases: revisiting nucleophilic addition to phycocyanobilin.

    PubMed

    Tu, Jun-Ming; Zhou, Ming; Haessner, Rainer; Plöscher, Matthias; Eichacker, Lutz; Scheer, Hugo; Zhao, Kai-Hong

    2009-04-22

    Biliprotein lyases attach linear-tetrapyrrolic bilins covalently to apoproteins, which is a prerequisite for the assembly of phycobiliproteins into phycobilisomes, the light-harvesting complexes of cyanobacteria. On the basis of the addition of thiol and imidazole to phycocyanobilin, we propose a generalized lyase reaction mechanism. The adducts contain isomerized phycocyanobilin that can be transferred by the lyase to apoproteins by either back-isomerization, generating phycocyanobilin-containing proteins, or direct transfer, generating phycoviolobilin-containing proteins.

  10. Swarming populations of Salmonella represent a unique physiological state coupled to multiple mechanisms of antibiotic resistance

    PubMed Central

    Kim, Wook

    2003-01-01

    Salmonella enterica serovar Typhimurium is capable of swarming over semi-solid surfaces. Although its swarming behavior shares many readily observable similarities with other swarming bacteria, the phenomenon remains somewhat of an enigma in this bacterium since some attributes skew away from the better characterized systems. Swarming is quite distinct from the classic swimming motility, as there is a prerequisite for cells to first undergo a morphological transformation into swarmer cells. In some organisms, swarming is controlled by quorum sensing, and in others, swarming has been shown to be coupled to increased expression of important virulence factors. Swarming in serovar Typhimurium is coupled to elevated resistance to a wide variety of structurally and functionally distinct classes of antimicrobial compounds. As serovar Typhimurium differentiates into swarm cells, the pmrHFIJKLM operon is up-regulated, resulting in a more positively charged LPS core. Furthermore, as swarm cells begin to de-differentiate, the pmr operon expression is down-regulated, rapidly reaching the levels observed in swim cells. This is one potential mechanism which confers swarm cells increased resistance to antibiotics such as the cationic antimicrobial peptides. However, additional mechanisms are likely associated with the cells in the swarm state that confer elevated resistance to such a broad spectrum of antimicrobial agents. PMID:14615815

  11. Mechanisms Of The Dissolution Inhibition Effect And Their Application To Designing Novel Deep-UV Resists

    NASA Astrophysics Data System (ADS)

    Murata, Makoto; Koshiba, Mitsunobu; Harita, Yoshiyuki

    1989-08-01

    The dissolution inhibition effect and alkaline solubility were investigated for naphthoquinone diazides like 1,2-naphthoquinone diazide (NQD), its 5-sulfonylchloride (NQD-C) and 5-sulfonyloxybenzene (DAM), and for other compounds like sulfonylchlorides, sulfonyl esters, sulfones and a ketone which do not contain a naphthoquinone diazide moiety. As a result, it has turned out that the dissolution inhibition effect does not depend on the specific structure; namely, the naphthoquinone diazide moiety itself, but largely on the alkaline solubility of the compounds added to a novolak resin. An XPS study for the films consisting of a novolak resin and a dissolution inhibitor indicates a formation of an inhibitor-rich protective thin layer on the film surface after immersion of the film in an alkaline developer. In this paper is proposed a new third dissolution inhibition mechanism in addition to the previously reported chemical crosslinking and dipolar interaction; i.e., the alkaline insoluble protective layer inhibits the dissolution of novolak resin at the interface between the film and the developer. A new three-component type deep-UV resist has been also developed as an application of the new mechanism. The resist consists of a novolak resin, 5-diazo Meldrum's acid and a new dissolution inhibitors like phenyltosylate and p-phenylene ditosylate, which successfully improve the residual resist thickness.

  12. Genetic resistance in experimental autoimmune encephalomyelitis. I. Analysis of the mechanism of LeR resistance using radiation chimeras

    SciTech Connect

    Pelfrey, C.M.; Waxman, F.J.; Whitacre, C.C. )

    1989-09-01

    Experimental autoimmune encephalomyelitis (EAE) is a cell-mediated autoimmune disease of the central nervous system that has been extensively studied in the rat. The Lewis rat is highly susceptible to the induction of EAE, while the Lewis resistant (LeR) rat is known to be resistant. In this paper, we demonstrate that the LeR rat, which was derived from the Lewis strain by inbreeding of fully resistant animals, is histocompatible with the Lewis strain. Radiation chimeras, a tool for distinguishing between immunologic and nonimmunologic resistance mechanisms, were utilized to analyze the cellular mechanisms involved in genetic resistance to EAE. By transplanting bone marrow cells from LeR rats into irradiated Lewis recipients, Lewis rats were rendered resistant to EAE induction. Likewise, transplanting Lewis bone marrow cells into irradiated LeR recipients rendered LeR rats susceptible. Mixed lymphoid cell chimeras using bone marrow, spleen, and thymus cells in Lewis recipient rats revealed individual lymphoid cell types and cell interactions that significantly affected the incidence and severity of EAE. Our results suggest that LeR resistance is mediated by hematopoietic/immune cells, and that cells located in the spleen appear to play a critical role in the resistance/susceptibility to EAE induction. Depletion of splenic adherent cells did not change the patterns of EAE resistance. In vivo cell mixing studies suggested the presence of a suppressor cell population in the LeR spleen preparations which exerted an inhibitory effect on Lewis autoimmune responses. Thus, the mechanism of LeR resistance appears to be different from that in other EAE-resistant animals.

  13. Characterization of Pseudomonas aeruginosa isolates from dogs and cats in Japan: current status of antimicrobial resistance and prevailing resistance mechanisms.

    PubMed

    Harada, Kazuki; Arima, Sayuri; Niina, Ayaka; Kataoka, Yasushi; Takahashi, Toshio

    2012-02-01

    Seventy-three Pseudomonas aeruginosa isolates were collected from dogs and cats in Japan to investigate antimicrobial susceptibility and resistance mechanisms to anti-pseudomonal agents. Resistance rates against orbifloxacin, enrofloxacin, ciprofloxacin, cefotaxime, aztreonam and gentamicin were 34.2, 31.5, 20.5, 17.8, 12.3 and 4.1%, respectively. The degree of resistance to cefotaxime, orbifloxacin, and enrofloxacin was greatly affected by efflux pump inhibitors, indicating overexpression of efflux pump contributes to these resistances. Notably, orbifloxacin and enrofloxacin resistance was observed even in isolates without mutations in the target sites. This is the first report on cephalosporin- and fluoroquinolone-resistant isolates of P. aeruginosa from Japanese companion animals.

  14. Increased Mechanical Properties Through the Addition of Zr to GRCop-84

    NASA Technical Reports Server (NTRS)

    Ellis, David L.; Lerch, Bradley A.

    2011-01-01

    GRCop-84 (Cu-8 at.% Cr-4 at.% Nb) has shown exceptional mechanical properties above 932 F (773 K). However, its properties below 932 F (773 K) are inferior to precipitation strengthened alloys such as Cu-Cr, Cu-Zr and Cu-Cr-Zr when they are in the fully aged, hard-drawn condition. It has been noted that the addition of small amounts of Zr, typically 0.1 wt.% to 0.5 wt.%, can greatly enhance the mechanical properties of copper-based alloys. Limited testing was conducted upon GRCop-84 with an addition of 0.4 wt.% Zr to determine its tensile, creep and low cycle fatigue (LCF) properties. Very large increases in strength (up to 68%) and ductility (up to 123%) were observed at both room temperature and 932 F (773 K). Creep properties at 932 F (773 K) demonstrated more than an order of magnitude decrease in the creep rate relative to unmodified GRCop-84 with a corresponding order of magnitude increase in creep life. Limited LCF testing showed that the modified alloy had a comparable LCF life at room temperature, but it was capable of sustaining a much higher load. While more testing and composition optimization are required, the addition of Zr to GRCop-84 has shown clear benefits to mechanical properties.

  15. Evaluation of Camellia sinensis catechins as a swine antimicrobial feed additive that does not cause antibiotic resistance.

    PubMed

    Ohno, Akira; Kataoka, Shinichiro; Ishii, Yoshikazu; Terasaki, Toshiaki; Kiso, Masaaki; Okubo, Mitsuyuki; Yamaguchi, Keizo; Tateda, Kazuhiro

    2013-01-01

    Antimicrobial growth promoters (AGPs) have been banned and phased out because their use has been linked to the emergence and spread of antibiotic-resistant pathogens; however, the ban has had a marked impact on livestock production, and feed additive alternatives to AGPs are required. We focused on green tea leaves as potential alternatives to AGPs because they contain significant amounts of polyphenol catechins, which have antivirus and antimicrobial effects. We examined cross-resistance between epigallocatechin gallate (EGCG), which is the most abundant catechin of green tea leaves, and commercially available antimicrobials in clinically problematic antimicrobial-resistant bacteria, and whether bacteria have the ability to acquire resistance by consecutive passage in sub-inhibitory concentrations of EGCG. EGCG did not display any cross-resistance with reference antimicrobials and the bacteria did not acquire EGCG resistance. Further, we examined the growth-promoting effects of dried green tea leaves on the breeding of a new Japanese breed, Tokyo-X pigs. While the mortality rates of the green tea leaf (GTL) and AGP groups were both 11.1% (one in nine piglets), the mortality rate was 50% for the control group with an additive-free diet (four in eight piglets). The rate of body weight increase in both the GTL and AGP groups was approximately the same. The growth-promoting effects of green tea leaves and AGPs were similar, and there was no possibility that the antimicrobial properties of catechins caused the same problem as AGPs. Thus, it can be concluded that green tea leaves are a safe feed additive alternative to AGPs.

  16. Evaluation of Camellia sinensis catechins as a swine antimicrobial feed additive that does not cause antibiotic resistance.

    PubMed

    Ohno, Akira; Kataoka, Shinichiro; Ishii, Yoshikazu; Terasaki, Toshiaki; Kiso, Masaaki; Okubo, Mitsuyuki; Yamaguchi, Keizo; Tateda, Kazuhiro

    2013-01-01

    Antimicrobial growth promoters (AGPs) have been banned and phased out because their use has been linked to the emergence and spread of antibiotic-resistant pathogens; however, the ban has had a marked impact on livestock production, and feed additive alternatives to AGPs are required. We focused on green tea leaves as potential alternatives to AGPs because they contain significant amounts of polyphenol catechins, which have antivirus and antimicrobial effects. We examined cross-resistance between epigallocatechin gallate (EGCG), which is the most abundant catechin of green tea leaves, and commercially available antimicrobials in clinically problematic antimicrobial-resistant bacteria, and whether bacteria have the ability to acquire resistance by consecutive passage in sub-inhibitory concentrations of EGCG. EGCG did not display any cross-resistance with reference antimicrobials and the bacteria did not acquire EGCG resistance. Further, we examined the growth-promoting effects of dried green tea leaves on the breeding of a new Japanese breed, Tokyo-X pigs. While the mortality rates of the green tea leaf (GTL) and AGP groups were both 11.1% (one in nine piglets), the mortality rate was 50% for the control group with an additive-free diet (four in eight piglets). The rate of body weight increase in both the GTL and AGP groups was approximately the same. The growth-promoting effects of green tea leaves and AGPs were similar, and there was no possibility that the antimicrobial properties of catechins caused the same problem as AGPs. Thus, it can be concluded that green tea leaves are a safe feed additive alternative to AGPs. PMID:23138151

  17. Mechanisms and modeling of the effects of additives on the nitrogen oxides emission

    NASA Technical Reports Server (NTRS)

    Kundu, Krishna P.; Nguyen, H. Lee; Kang, M. Paul

    1991-01-01

    A theoretical study on the emission of the oxides of nitrogen in the combustion of hydrocarbons is presented. The current understanding of the mechanisms and the rate parameters for gas phase reactions were used to calculate the NO(x) emission. The possible effects of different chemical species on thermal NO(x), on a long time scale were discussed. The mixing of these additives at various stages of combustion were considered and NO(x) concentrations were calculated; effects of temperatures were also considered. The chemicals such as hydrocarbons, H2, CH3OH, NH3, and other nitrogen species were chosen as additives in this discussion. Results of these calculations can be used to evaluate the effects of these additives on the NO(x) emission in the industrial combustion system.

  18. Influence of oxide-based sintering additives on densification and mechanical behavior of tricalcium phosphate (TCP).

    PubMed

    Bhatt, Himesh A; Kalita, Samar J

    2007-05-01

    In this research, we studied and analyzed the effects of four different oxide-based sintering additives on densification, mechanical behavior, biodegradation and biocompatibility of tricalcium phosphate (TCP) bioceramics. Selective sintering additives were introduced into pure TCP ceramics, in small quantities, through homogeneous mixing, using a mortar and pestle. The consequent powders of different compositions were pressed into cylindrical compacts, uniaxially and sintered at elevated temperatures, 1150 degrees C and 1250 degrees C, separately in a muffle furnace. X-ray powder diffraction technique was used to analyze the phase-purity of TCP after sintering. Hardness of these sintered specimens was evaluated using a Vickers hardness tester. Sintered cylindrical samples were tested under uniaxial compressive loading, as a function of composition to determine their failure strength. Biodegradation studies conducted using simulated body fluid under dynamic environment, revealed that these additives could control the rate of resorption and hardness degradation of TCP ceramics. PMID:17211718

  19. Mechanism, stability and fitness cost of resistance to pyriproxyfen in the house fly, Musca domestica L. (Diptera: Muscidae).

    PubMed

    Shah, Rizwan Mustafa; Shad, Sarfraz Ali; Abbas, Naeem

    2015-03-01

    Pyriproxyfen, a bio-rational insecticide, used worldwide for the management of many insect pests including the house fly, Musca domestica. To devise a retrospective resistance management strategy, biological parameters of pyriproxyfen resistant (Pyri-SEL), unselected (UNSEL), Cross1 and Cross2M. domestica strains were studied in the laboratory. Additionally, the stability and mechanism of resistance was also investigated. After 30 generations of pyriproxyfen selection, a field-collected strain developed 206-fold resistance compared with susceptible strain. Synergists such as piperonyl butoxide and S,S,S-tributylphosphorotrithioate did not alter the LC50 values, suggesting another cause of target site resistance to pyriproxyfen in the Pyri-SEL strain. The resistance to all tested insecticides was unstable in Pyri-SEL strain. The relative fitness of 0.51 with lower fecundity, hatchability, lower number of next generation larvae, reduced mean population growth rate and net reproductive rate were observed in the Pyri-SEL strain compared with the UNSEL strain. The cost of fitness associated with pyriproxyfen resistance was evident in Pyri-SEL strain. The present study provides useful information for making pro-active resistance management strategies to delay resistance development.

  20. Systemic Acquired Resistance in Moss: Further Evidence for Conserved Defense Mechanisms in Plants

    PubMed Central

    Winter, Peter S.; Bowman, Collin E.; Villani, Philip J.; Dolan, Thomas E.; Hauck, Nathanael R.

    2014-01-01

    Vascular plants possess multiple mechanisms for defending themselves against pathogens. One well-characterized defense mechanism is systemic acquired resistance (SAR). In SAR, a plant detects the presence of a pathogen and transmits a signal throughout the plant, inducing changes in the expression of various pathogenesis-related (PR) genes. Once SAR is established, the plant is capable of mounting rapid responses to subsequent pathogen attacks. SAR has been characterized in numerous angiosperm and gymnosperm species; however, despite several pieces of evidence suggesting SAR may also exist in non-vascular plants6–8, its presence in non-vascular plants has not been conclusively demonstrated, in part due to the lack of an appropriate culture system. Here, we describe and use a novel culture system to demonstrate that the moss species Amblystegium serpens does initiate a SAR-like reaction upon inoculation with Pythium irregulare, a common soil-borne oomycete. Infection of A. serpens gametophores by P. irregulare is characterized by localized cytoplasmic shrinkage within 34 h and chlorosis and necrosis within 7 d of inoculation. Within 24 h of a primary inoculation (induction), moss gametophores grown in culture became highly resistant to infection following subsequent inoculation (challenge) by the same pathogen. This increased resistance was a response to the pathogen itself and not to physical wounding. Treatment with β-1,3 glucan, a structural component of oomycete cell walls, was equally effective at triggering SAR. Our results demonstrate, for the first time, that this important defense mechanism exists in a non-vascular plant, and, together with previous studies, suggest that SAR arose prior to the divergence of vascular and non-vascular plants. In addition, this novel moss – pathogen culture system will be valuable for future characterization of the mechanism of SAR in moss, which is necessary for a better understanding of the evolutionary history of SAR

  1. Creatine Loading, Resistance Exercise Performance, and Muscle Mechanics.

    ERIC Educational Resources Information Center

    Stevenson, Scott W.; Dudley, Gary A.

    2001-01-01

    Examined whether creatine (CR) monohydrate loading would alter resistance exercise performance, isometric strength, or in vivo contractile properties of the quadriceps femoris muscle compared with placebo loading in resistance-trained athletes. Overall, CR loading did not provide an ergogenic benefit for the unilateral dynamic knee extension…

  2. Mechanisms of naturally evolved ethanol resistance in Drosophila melanogaster.

    PubMed

    Fry, James D

    2014-11-15

    The decaying fruit in which Drosophila melanogaster feed and breed can contain ethanol in concentrations as high as 6-7%. In this cosmopolitan species, populations from temperate regions are consistently more resistant to ethanol poisoning than populations from the tropics, but little is known about the physiological basis of this difference. I show that when exposed to low levels of ethanol vapor, flies from a tropical African population accumulated 2-3 times more internal ethanol than flies from a European population, giving evidence that faster ethanol catabolism by European flies contributes to the resistance difference. Using lines differing only in the origin of their third chromosome, however, I show that faster ethanol elimination cannot fully explain the resistance difference, because relative to African third chromosomes, European third chromosomes confer substantially higher ethanol resistance, while having little effect on internal ethanol concentrations. European third chromosomes also confer higher resistance to acetic acid, a metabolic product of ethanol, than African third chromosomes, suggesting that the higher ethanol resistance conferred by the former might be due to increased resistance to deleterious effects of ethanol-derived acetic acid. In support of this hypothesis, when ethanol catabolism was blocked with an Alcohol dehydrogenase mutant, there was no difference in ethanol resistance between flies with European and African third chromosomes. PMID:25392459

  3. Hypoglycemic effects and mechanisms of electroacupuncture on insulin resistance.

    PubMed

    Yin, Jieyun; Kuang, Jian; Chandalia, Manisha; Tuvdendorj, Demidmaa; Tumurbaatar, Batbayar; Abate, Nicola; Chen, Jiande D Z

    2014-08-01

    The aim of this study was to investigate effects and mechanisms of electroacupuncture (EA) on blood glucose and insulin sensitivity in mice fed a high-fat diet. Both wild-type (WT) and adipose ectonucleotide pyrophosphate phosphodiesterase (ENPP1) transgenic (TG) mice were fed a high-fat diet for 12 wk; for each mouse, an intraperitoneal glucose tolerance test (IPGTT) and insulin tolerance test (ITT) were performed with or without EA at abdomen or auricular areas. A high-fat diet-induced insulin resistance in both WT and TG mice. In the WT mice, EA at 3 Hz and 15 Hz, but not at 1 Hz or 100 Hz, via CV4+CV12 significantly reduced postprandial glucose levels; EA at 3 Hz was most potent. The glucose level was reduced by 61.7% at 60 min and 74.5% at 120 min with EA at 3 Hz (all P < 0.001 vs. control). Similar hypoglycemic effect was noted in the TG mice. On the contrary, EA at auricular points increased postprandial glucose level (P < 0.03). 4). EA at 3 Hz via CV4+CV12 significantly enhanced the decrease of blood glucose after insulin injection, suggesting improvement of insulin sensitivity. Plasma free fatty acid was significantly suppressed by 42.5% at 15 min and 50.8% at 30 min with EA (P < 0.01) in both WT and TG mice. EA improves glucose tolerance in both WT and TG mice fed a high-fat diet, and the effect is associated with stimulation parameters and acupoints and is probably attributed to the reduction of free fatty acid. PMID:24848362

  4. Mechanism Of Resistance Of Evolved Glyphosate-Resistant Palmer Amaranth (Amaranthus Palmeri L.)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Evolved glyphosate resistance in weedy species represents a challenge for the continued success and utility of glyphosate-resistant crops. The first case of evolved glyphosate resistance in Palmer amaranth was a population from the U.S. state of Georgia, which was previously reported to have amplif...

  5. A brief review on the mechanisms of aspirin resistance.

    PubMed

    Du, Gang; Lin, Qiang; Wang, Jinhua

    2016-10-01

    Aspirin is the most widely prescribed drug for the primary and secondary prevention of cardiovascular and cerebrovascular diseases. However, a large number of patients continue to experience thromboembolic events despite aspirin therapy, a phenomenon referred to as aspirin resistance or treatment failure. Aspirin resistance is often observed along with a high incidence of unstable plaque, cardiovascular events and cerebrovascular accident. Studies have shown that aspirin reduces the production of TXA2, but not totally inhibits the activation of platelets. In this review, we analyze current and past research on aspirin resistance, presenting important summaries of results regarding the potential contributive roles of single nucleotide polymorphisms, inflammation, metabolic syndrome and miRNAs. The aim of this article is to provide a brief review on aspirin resistance and platelet function, which will provide important insights into the research of aspirin resistance. PMID:27372038

  6. Mechanical properties and phase composition of potential biodegradable Mg-Zn-Mn-base alloys with addition of rare earth elements

    SciTech Connect

    Stulikova, Ivana; Smola, Bohumil

    2010-10-15

    Mechanical properties and creep resistance of the MgY4Zn1Mn1 alloy in the as cast as well as in the T5 condition were compared to those of the MgCe4Zn1Mn1 alloy in the same conditions. Yield tensile stress and ultimate tensile strength of the MgY4Zn1Mn1 alloy are slightly better in the temperature range 20 deg. C-400 deg. C than these of the MgCe4Zn1Mn1 alloy. Better thermal stability of ultimate tensile strength was observed in the T5 treated MgCe4Zn1Mn1 alloy than in this material in the as cast condition. An outstanding creep resistance at 225 deg. C-350 deg. C found in the MgY4Zn1Mn1 alloy is due to the existence of the 18R long period stacking structure persisting in this alloy even a long heat treatment of 500 deg. C/32 h. No similar stacking effects happen when Ce substitutes Y in approximately the same concentration. The creep resistance deteriorates considerably in the MgCe4Zn1Mn1 alloy. Rectangular particles of the equilibrium Mg{sub 12}Ce phase dominate in the microstructure of as cast as well as of high temperature heat-treated MgCe4Zn1Mn1 alloy. A population of small oval particles containing Mg and Zn develops additionally during annealing of this alloy. These particles pin effectively dislocations and can be responsible for the better thermal stability of the T5 treated material.

  7. Common Mechanism of Cross-Resistance Development in Pathogenic Bacteria Bacillus cereus Against Alamethicin and Pediocin Involves Alteration in Lipid Composition.

    PubMed

    Meena, Sunita; Mehla, Jitender; Kumar, Raj; Sood, S K

    2016-10-01

    To understand the mechanism of development of cross-resistance in food pathogen Bacillus cereus against an antimicrobial peptide pediocin and antibiotic alamethicin, the present study was designed. Pediococcus pentosaceus was taken as a source of pediocin, and it was purified by ammonium sulphate precipitation followed by cation exchange chromatography with 14.01-fold purity and 14.4 % recovery. B. cereus strains alamethicin-resistant strains (IC50 3.23 µg/ml) were selected from sensitive population with IC50 2.37 µg/ml. The development of resistance in B. cereus against alamethicin was associated with decrease in alamethicin-membrane interaction observed by in vitro assay. Resistant strain of B. cereus was found to harbour one additional general lipid as compared to sensitive strain, one amino group lacking phospholipid and one amino group containing phospholipid (ACP). In addition, ACP content was increased in resistant mutant (29.7 %) as compared to sensitive strain (14.56 %). The alamethicin-resistant mutant B. cereus also showed increased IC50 (58.8 AU/ml) for pediocin as compared to sensitive strain (IC50 47.8 AU/ml). Cross-resistance to pediocin and alamethicin in resistant mutant of B. cereus suggested a common mechanism of resistance. Therefore, this understanding could result in the development of peptide which will be effective against the resistant strains that share same mechanism of resistance.

  8. Acetolactate Synthase-Inhibiting Herbicide-Resistant Rice Flatsedge (Cyperus iria): Cross Resistance and Molecular Mechanism of Resistance

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Overuse of acetolactate synthase (ALS) –inhibiting herbicides in rice has led to evolution of halosulfuron-resistant rice flatsedge (Cyperus iria L.) in Arkansas (AR) and Mississippi (MS), USA. Resistant accessions were cross-resistant to labeled field rates of ALS-inhibiting herbicides from four d...

  9. Mechanical properties of potato starch modified by moisture content and addition of lubricant

    NASA Astrophysics Data System (ADS)

    Stasiak, Mateusz; Molenda, Marek; Horabik, Józef; Mueller, Peter; Opaliński, Ireneusz

    2014-10-01

    Laboratory testing was conducted to deliver a set of characteristics of structure and mechanical properties of pure starch and starch with an addition of a lubricant - magnesium stearate. Considerable influence of moisture content of potato starch was found in the case of density, parameters of internal friction, coefficients of wall friction and flowability. Elasticity was found to be strongly influenced by water content of the material. Addition of magnesium stearate affected density and parameters of flowability, internal friction and elasticity. Bulk density increased from 604 to 774 kg m-3 with decrease in moisture content of potato starch from 17 to for 6%. Addition of magnesium stearate resulted in approximately 10% decrease in bulk density. Angle of internal friction obtained for 10 kPa of consolidation stress decreased from 33 to 24º with increase in moisture content, and to approximately 22º with addition of the lubricant. With an increase of moisture content from 6 to 18% and with addition of the lubricant, the modulus of elasticity during loading decreased from approximately 1.0 to 0.1 MPa. Modulus of elasticity during unloading was found in the range from 19 to 42 MPa and increased with increase of moisture content and amount of lubricant.

  10. Effect of ternary additions on the oxidation resistance of Ti{sub 5}Si{sub 3}

    SciTech Connect

    Thom, A.J.; Akinc, M. |

    1995-10-01

    Refractory intermetallic silicides are receiving increasing consideration for use as high temperature structural materials. Ti{sub 5}Si{sub 3}-based compositions are attractive due to their ability to incorporate a variety of interstitial ternary additions. These ternary additions present a unique opportunity to potentially tailor physical properties. Previous experimental work has shown that these additions significantly increase the otherwise poor oxidation resistance of undoped Ti{sub 5}Si{sub 3} above 700 C. Recent experimental work by the authors on the oxidation of small atom doped Ti{sub 5}Si{sub 3} is discussed. Interstitial additions of boron, carbon, and oxygen substantially improve the isothermal oxidation resistance of Ti{sub 5}Si{sub 3} at 1,000 C. In contrast, added nitrogen does not provide significant improvement. Even up to 1,306 C, interstitial oxygen imparts excellent oxidation resistance with a mass gain of 1.1 mg/cm{sup 2} after 240 hours.

  11. Antibacterial activity of oxyresveratrol against methicillin-resistant Staphylococcus aureus and its mechanism

    PubMed Central

    Joung, Dae-Ki; Mun, Su-Hyun; Choi, Sung-Hoon; Kang, Ok-Hwa; Kim, Sung-Bae; Lee, Young-Seob; Zhou, Tian; Kong, Ryong; Choi, Jang-Gi; Shin, Dong-Won; Kim, Youn-Chul; Lee, Dong-Sung; Kwon, Dong-Yeul

    2016-01-01

    Oxyresveratrol (ORV) is a naturally occurring compound found in mulberries that exhibits a wide spectrum of biological activities. However, the underlying mechanism of the action of ORV against the methicillin-resistant S. aureus (MRSA) pathogen has not yet been reported. MRSA is multidrug-resistant, causing skin and other types of infections. The aim of the present study was to examine the antimicrobial activity of ORV and the underlying mechanism of its action on MRSA. The antibacterial activity of ORV was evaluated using a minimum inhibitory concentration (MIC) assay, and the mechanism of its antibacterial action on S. aureus was investigated using a combination of ORV with detergent, ATPase inhibitors and peptidoglycan (PGN). In addition, the survival characteristics and changes in MRSA morphology were monitored using transmission electron microscopy (TEM). The MIC value of ORV against all S. aureus strains was found to be 125 µg/ml. The optical density at 600 nm of each suspension treated using a combination of ORV with Triton X-100, N,N'-dicyclohexylcarbodiimide or sodium azide was reduced by 68.9–89.8% compared with the value upon treatment with ORV alone. In the ORV and PGN combination assay, direct binding of ORV with PGN from S. aureus was evident. Furthermore, TEM examination of MRSA treated with ORV showed alterations in septa formation. In conclusion, these results showed that ORV has a strong antibacterial effect against S. aureus, mainly by increasing membrane permeability and inhibiting ATPase when combined with other drugs. PMID:27588079

  12. Rolling Resistance and Mechanical Properties of Grinded Copper Surfaces Using Molecular Dynamics Simulation.

    PubMed

    Liang, Shih-Wei; Wang, Chih-Hao; Fang, Te-Hua

    2016-12-01

    Mechanical properties of copper (Cu) film under grinding process were accomplished by molecular dynamics simulation. A numerical calculation was carried out to understand the distributions of atomic and slip vector inside the Cu films. In this study, the roller rotation velocity, temperature, and roller rotation direction change are investigated to clarify their effect on the deformation mechanism. The simulation results showed that the destruction of materials was increased proportionally to the roller rotation velocity. The machining process at higher temperature results in larger kinetic energy of atoms than lower temperature during the grinding process of the Cu films. The result also shows that the roller rotation in the counterclockwise direction had the better stability than the roller rotation in the clockwise direction due to significantly increased backfill atoms in the groove of the Cu film surface. Additionally, the effects of the rolling resistances on the Cu film surfaces during the grinding process are studied by the molecular dynamics simulation method. PMID:27637893

  13. Rolling Resistance and Mechanical Properties of Grinded Copper Surfaces Using Molecular Dynamics Simulation.

    PubMed

    Liang, Shih-Wei; Wang, Chih-Hao; Fang, Te-Hua

    2016-12-01

    Mechanical properties of copper (Cu) film under grinding process were accomplished by molecular dynamics simulation. A numerical calculation was carried out to understand the distributions of atomic and slip vector inside the Cu films. In this study, the roller rotation velocity, temperature, and roller rotation direction change are investigated to clarify their effect on the deformation mechanism. The simulation results showed that the destruction of materials was increased proportionally to the roller rotation velocity. The machining process at higher temperature results in larger kinetic energy of atoms than lower temperature during the grinding process of the Cu films. The result also shows that the roller rotation in the counterclockwise direction had the better stability than the roller rotation in the clockwise direction due to significantly increased backfill atoms in the groove of the Cu film surface. Additionally, the effects of the rolling resistances on the Cu film surfaces during the grinding process are studied by the molecular dynamics simulation method.

  14. Rolling Resistance and Mechanical Properties of Grinded Copper Surfaces Using Molecular Dynamics Simulation

    NASA Astrophysics Data System (ADS)

    Liang, Shih-Wei; Wang, Chih-Hao; Fang, Te-Hua

    2016-09-01

    Mechanical properties of copper (Cu) film under grinding process were accomplished by molecular dynamics simulation. A numerical calculation was carried out to understand the distributions of atomic and slip vector inside the Cu films. In this study, the roller rotation velocity, temperature, and roller rotation direction change are investigated to clarify their effect on the deformation mechanism. The simulation results showed that the destruction of materials was increased proportionally to the roller rotation velocity. The machining process at higher temperature results in larger kinetic energy of atoms than lower temperature during the grinding process of the Cu films. The result also shows that the roller rotation in the counterclockwise direction had the better stability than the roller rotation in the clockwise direction due to significantly increased backfill atoms in the groove of the Cu film surface. Additionally, the effects of the rolling resistances on the Cu film surfaces during the grinding process are studied by the molecular dynamics simulation method.

  15. Transfer of resistance against the beet cyst nematode from radish (Raphanus sativus) to rape (Brassica napus) by monosomic chromosome addition.

    PubMed

    Peterka, H; Budahn, H; Schrader, O; Ahne, R; Schütze, W

    2004-06-01

    In rape ( Brassica napus), no resistance to the beet cyst nematode (BCN) Heterodera schachtii is available. This study was carried out to determine the specific chromosome(s) of resistant radish ( Raphanus sativus) carrying the gene(s) for nematode resistance as a prequisite to convert rape from a host into a trap crop for this pest. A Raphanobrassica progeny of 25 plants was analyzed which segregated for all nine chromosomes of the Raphanus genome in a genetic background of synthetic rape. The number of radish chromosomes was determined by fluorescence in situ hybridization, using the Raphanus-specific DNA probe pURsN; and their type was identified by chromosome-specific randomly amplified polymorphic DNA markers. Five different multiple rape-radish chromosome additions (comprising the whole set of nine radish chromosomes, a-i) were selected and crossed to rape. For each cross-progeny, the number of cysts on plant roots was counted 42 days after inoculation with a L2 larvae suspension. Simultaneously, the plants were characterized for the presence or absence of individual radish chromosomes, using sets of chromosome-specific markers. Thus, the effect of each radish chromosome on cyst number was tested. Chromosome d had a major resistance effect, whereas the presence/absence of the other radish chromosomes had nearly no influence on cyst number. Plants with added chromosome d showed a resistance level comparable with that of the radish donor parent. The analysis in the cross to rape of a plant monosomic only for chromosome d confirmed the strong effect of this chromosome on nematode resistance. A further experiment comprising seven crosses using winter rape breeding lines and monosomic addition line d as pollen parent provided the same results on a broader genetic basis. In each case, the added chromosome d in a single dosage caused nearly the full resistance of the radish donor. Resistance was independent of the glucosinolate content in the roots. The

  16. Toxicodynamic mechanisms and monitoring of acaricide resistance in the two-spotted spider mite.

    PubMed

    Kwon, Deok Ho; Clark, J Marshall; Lee, Si Hyeock

    2015-06-01

    The two-spotted spider (Tetranychus urticae) is one of the most serious pests world-wide and has developed resistance to many types of acaricides. Various mutations on acaricide target site genes have been determined to be responsible for toxicodynamic resistance, and the genotyping and frequency prediction of these mutations can be employed as an alternative resistance monitoring strategy. A quantitative sequencing (QS) protocol was reported as a population-based genotyping technique, and applied for the determination of resistance allele frequencies in T. urticae field populations. In addition, a modified glass vial bioassay method (residual contact vial bioassay, RCV) was implemented as a rapid on-site resistance monitoring tool. The QS protocol, together with the RCV, would greatly facilitate monitoring of T. urticae resistance. Recent completion of T. urticae genome analysis should facilitate the identification of additional resistance genetic markers that can be employed for molecular resistance monitoring. PMID:26047116

  17. Toxicodynamic mechanisms and monitoring of acaricide resistance in the two-spotted spider mite.

    PubMed

    Kwon, Deok Ho; Clark, J Marshall; Lee, Si Hyeock

    2015-06-01

    The two-spotted spider (Tetranychus urticae) is one of the most serious pests world-wide and has developed resistance to many types of acaricides. Various mutations on acaricide target site genes have been determined to be responsible for toxicodynamic resistance, and the genotyping and frequency prediction of these mutations can be employed as an alternative resistance monitoring strategy. A quantitative sequencing (QS) protocol was reported as a population-based genotyping technique, and applied for the determination of resistance allele frequencies in T. urticae field populations. In addition, a modified glass vial bioassay method (residual contact vial bioassay, RCV) was implemented as a rapid on-site resistance monitoring tool. The QS protocol, together with the RCV, would greatly facilitate monitoring of T. urticae resistance. Recent completion of T. urticae genome analysis should facilitate the identification of additional resistance genetic markers that can be employed for molecular resistance monitoring.

  18. Development and characterization of a Psathyrostachys huashanica Keng 7Ns chromosome addition line with leaf rust resistance.

    PubMed

    Du, Wanli; Wang, Jing; Wang, Liangming; Zhang, Jun; Chen, Xinhong; Zhao, Jixin; Yang, Qunhui; Wu, Jun

    2013-01-01

    The aim of this study was to characterize a Triticum aestivum-Psathyrostachys huashanica Keng (2n = 2x = 14, NsNs) disomic addition line 2-1-6-3. Individual line 2-1-6-3 plants were analyzed using cytological, genomic in situ hybridization (GISH), EST-SSR, and EST-STS techniques. The alien addition line 2-1-6-3 was shown to have two P. huashanica chromosomes, with a meiotic configuration of 2n = 44 = 22 II. We tested 55 EST-SSR and 336 EST-STS primer pairs that mapped onto seven different wheat chromosomes using DNA from parents and the P. huashanica addition line. One EST-SSR and nine EST-STS primer pairs indicated that the additional chromosome of P. huashanica belonged to homoeologous group 7, the diagnostic fragments of five EST-STS markers (BE404955, BE591127, BE637663, BF482781 and CD452422) were cloned, sequenced and compared. The results showed that the amplified polymorphic bands of P. huashanica and disomic addition line 2-1-6-3 shared 100% sequence identity, which was designated as the 7Ns disomic addition line. Disomic addition line 2-1-6-3 was evaluated to test the leaf rust resistance of adult stages in the field. We found that one pair of the 7Ns genome chromosomes carried new leaf rust resistance gene(s). Moreover, wheat line 2-1-6-3 had a superior numbers of florets and grains per spike, which were associated with the introgression of the paired P. huashanica chromosomes. These high levels of disease resistance and stable, excellent agronomic traits suggest that this line could be utilized as a novel donor in wheat breeding programs.

  19. Molecular cytogenetic identification of a wheat-rye 1R addition line with multiple spikelets and resistance to powdery mildew.

    PubMed

    Yang, Wujuan; Wang, Changyou; Chen, Chunhuan; Wang, Yajuan; Zhang, Hong; Liu, Xinlun; Ji, Wanquan

    2016-04-01

    Alien addition lines are important for transferring useful genes from alien species into common wheat. Rye is an important and valuable gene resource for improving wheat disease resistance, yield, and environment adaptation. A new wheat-rye addition line, N9436B, was developed from the progeny of the cross of common wheat (Triticum aestivum L., 2n = 6x = 42, AABBDD) cultivar Shaanmai 611 and rye (Secale cereal L., 2n = 2x = 14, RR) accession Austrian rye. We characterized this new line by cytology, genomic in situ hybridization (GISH), fluorescence in situ hybridization (FISH), molecular markers, and disease resistance screening. N9436B was stable in morphology and cytology, with a chromosome composition of 2n = 42 + 2t = 22II. GISH investigations showed that this line contained two rye chromosomes. GISH, FISH, and molecular maker identification suggested that the introduced R chromosome and the missing wheat chromosome arms were 1R chromosome and 2DL chromosome arm, respectively. N9436B exhibited 30-37 spikelets per spike and a high level of resistance to powdery mildew (Blumeria graminis f. sp. tritici, Bgt) isolate E09 at the seedling stage. N9436B was cytologically stable, had the trait of multiple spikelets, and was resistant to powdery mildew; this line should thus be useful in wheat improvement.

  20. Mechanisms of Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Resistance and Strategies to Overcome Resistance in Lung Adenocarcinoma

    PubMed Central

    Chang, Yoon Soo; Choi, Chang-Min

    2016-01-01

    Somatic mutations that lead to hyperactivation of epidermal growth factor receptor (EGFR) signaling are detected in approximately 50% of lung adenocarcinoma in people from the Far East population and tyrosine kinase inhibitors are now the standard first line treatment for advanced disease. They have led to a doubling of progression-free survival and an increase in overall survival by more than 2 years. However, emergence of resistant clones has become the primary cause for treatment failure, and has created a new challenge in the daily management of patients with EGFR mutations. Identification of mechanisms leading to inhibitor resistance has led to new therapeutic modalities, some of which have now been adapted for patients with unsuccessful tyrosine kinase inhibitor treatment. In this review, we describe mechanisms of tyrosine kinase inhibitor resistance and the available strategies to overcoming resistance. PMID:27790276

  1. A novel mechanism of insect resistance engineered into tobacco

    NASA Astrophysics Data System (ADS)

    Hilder, Vaughan A.; Gatehouse, Angharad M. R.; Sheerman, Suzanne E.; Barker, Richard F.; Boulter, Donald

    1987-11-01

    A major goal of plant genetic engineering is the introduction of agronomically desirable phenotypic traits into crop plants in situations where conventional breeding methods have been unsuccessful. One such target is enhanced resistance to insect pests which, in view of the estimated production losses world-wide and the heavy costs of protective treatments, is very important. We report here that a gene encoding a cowpea trypsin inhibitor, which has been shown to give some measure of field resistance to insect pests1, confers, when transferred to tobacco, enhanced resistance to this species' own herbivorous insect pests.

  2. Induced Resistance as a Mechanism of Biological Control by Lysobacter enzymogenes Strain C3.

    PubMed

    Kilic-Ekici, Ozlem; Yuen, Gary Y

    2003-09-01

    ABSTRACT Induced resistance was found to be a mechanism for biological control of leaf spot, caused by Bipolaris sorokiniana, in tall fescue (Festuca arundinacea) using the bacterium Lysobacter enzymogenes strain C3. Resistance elicited by C3 suppressed germination of B. sorokiniana conidia on the phylloplane in addition to reducing the severity of leaf spot. The pathogen-inhibitory effect could be separated from antibiosis by using heat-inactivated cells of C3 that retained no antifungal activity. Application of live or heat-killed cells to tall fescue leaves resulted only in localized resistance confined to the treated leaf, whereas treatment of roots resulted in systemic resistance expressed in the foliage. The effects of foliar and root applications of C3 were long lasting, as evidenced by suppression of conidial germination and leaf spot development even when pathogen inoculation was delayed 15 days after bacterial treatment. When C3 population levels and germination of pathogen conidia was examined on leaf segments, germination percentage was reduced on all segments from C3-treated leaves compared with segments from non-treated leaves, but no dose-response relationship typical of antagonism was found. Induced resistance by C3 was not host or pathogen specific; foliar application of heat-killed C3 cells controlled B. sorokiniana on wheat and also was effective in reducing the severity of brown patch, caused by Rhizoctonia solani, on tall fescue. Treatments of tall fescue foliage or roots with C3 resulted in significantly elevated peroxidase activity compared with the control.

  3. Gelation Behaviors and Mechanism of Silk Fibroin According to the Addition of Nitrate Salts

    PubMed Central

    Im, Dong Su; Kim, Min Hee; Yoon, Young Il; Park, Won Ho

    2016-01-01

    Silk fibroin (SF) is a typical fibrous protein that is secreted by silkworms and spiders. It has been used in a variety of areas, and especially for tissue-engineering scaffolds, due to its sound processability, mechanical properties, biodegradability, and biocompatibility. With respect to gelation, the SF gelation time is long in aqueous solutions, so a novel approach is needed to shorten this time. The solubility of regenerated SF is sound in formic acid (FA), which is a carboxylic acid of the simplest structure. In this study, SF was dissolved in formic acid, and the addition of salts then induced a rapid gelation that accompanied a solution-color change. Based on the gelation behaviors of the SF solution according to different SF and salt concentrations, the gelation mechanism was investigated. PMID:27735861

  4. Liraglutide, leptin, and their combined effects on feeding: additive intake reduction through common intracellular signaling mechanisms

    PubMed Central

    Kanoski, Scott E.; Ong, Zhi Yi; Fortin, Samantha M.; Schlessinger, Elizabeth S.; Grill, Harvey J.

    2014-01-01

    Aims Glucagon like peptide-1 receptor (GLP-1R) agonists and leptin each exert anorexigenic effects. In combination, the intake inhibitory and weight loss effects are greater than either treatment alone, however the mechanisms unclear. Materials and methods Effects of liraglutide (a long-acting GLP-1 analogue) and leptin co-treatment, delivered in low or moderate doses subcutaneously (SC) or to the 3rd ventricle respectively, on cumulative intake, meal patterns, and hypothalamic expression of intracellular signaling proteins [phosphorylated signal transducer and activator of transcription-3 (pSTAT3) and protein tyrosine phosphatase-1B (PTP1B)] were examined in lean rats. Results A low-dose combination of liraglutide (25μg/kg) and leptin (0.75μg) additively reduced cumulative food intake and body weight, a result mediated predominantly through a significant reduction in meal frequency that was not present with either drug alone. Liraglutide treatment alone also reduced meal size; an effect not enhanced with leptin co-administration. Moderate doses of liraglutide (75μg/kg) and leptin (4μg) examined separately each reduced meal frequency, cumulative food intake, and body weight; only liraglutide reduced meal size. In combination these doses did not further enhance the anorexigenic effects of either treatment alone. Ex vivo immunoblot showed elevated pSTAT3 in hypothalamic tissue following liraglutide-leptin co-treatment, an effect greater than leptin treatment alone. In addition, SC liraglutide reduced expression of PTP1B (a negative regulator of leptin receptor signaling), revealing a potential mechanism for the enhanced pSTAT3 response following liraglutide-leptin co-administration. Conclusions Collectively, these results provide novel behavioral and molecular mechanisms underlying the additive reduction in food intake and body weight following liraglutide-leptin combination treatment. PMID:25475828

  5. Use of additives to improve microstructures and fracture resistance of silicon nitride ceramics

    DOEpatents

    Becher, Paul F.; Lin, Hua-Tay

    2011-06-28

    A high-strength, fracture-resistant silicon nitride ceramic material that includes about 5 to about 75 wt-% of elongated reinforcing grains of beta-silicon nitride, about 20 to about 95 wt-% of fine grains of beta-silicon nitride, wherein the fine grains have a major axis of less than about 1 micron; and about 1 to about 15 wt-% of an amorphous intergranular phase comprising Si, N, O, a rare earth element and a secondary densification element. The elongated reinforcing grains have an aspect ratio of 2:1 or greater and a major axis measuring about 1 micron or greater. The elongated reinforcing grains are essentially isotropically oriented within the ceramic microstructure. The silicon nitride ceramic exhibits a room temperature flexure strength of 1,000 MPa or greater and a fracture toughness of 9 MPa-m.sup.(1/2) or greater. The silicon nitride ceramic exhibits a peak strength of 800 MPa or greater at 1200 degrees C. Also included are methods of making silicon nitride ceramic materials which exhibit the described high flexure strength and fracture-resistant values.

  6. Additional Electrochemical Treatment Effects on the Switching Characteristics of Anodic Porous Alumina Resistive Switching Memory

    NASA Astrophysics Data System (ADS)

    Otsuka, Shintaro; Takeda, Ryouta; Furuya, Saeko; Shimizu, Tomohiro; Shingubara, Shouso; Iwata, Nobuyuki; Watanabe, Tadataka; Takano, Yoshiki; Takase, Kouichi

    2012-06-01

    We have investigated the current-voltage characteristics of a resistive switching memory (ReRAM), especially the reproducibility of the switching voltage between an insulating state and a metallic state. The poor reproducibility hinders the practical use of this memory. According to a filament model, the variation of the switching voltage may be understood in terms of the random choice of filaments with different conductivities and lengths at each switching. A limitation of the number of conductive paths is expected to lead to the suppression of the variation of switching voltage. In this study, two strategies for the limitation have been proposed using an anodic porous alumina (APA). The first is the reduction of the number of conductive paths by restriction of the contact area between the top electrodes and the insulator. The second is the lowering of the resistivity of the insulator, which makes it possible to grow filaments with the same characteristics by electrochemical treatments using a pulse-electroplating technique.

  7. Fasting and other mild stresses with hormetic effects in Drosophila melanogaster can additively increase resistance to cold.

    PubMed

    Le Bourg, Éric

    2015-08-01

    Mild stresses can have various positive effects in animal models and human beings. Previous studies have shown that fasting, i.e. a short starvation period with water ad lib, increases resistance to a severe cold stress in flies (percentage of survivors 3 days after being kept at 0 °C). Only a few studies have combined two mild stresses with hormetic effects in an attempt to obtain additive effects. Fasting was combined in the same flies with either a hypergravity, cold or heat stress and resistance to cold was observed. When each mild stress had positive effects on this trait (fasting, cold, and hypergravity in males only), their combination had additive effects. However, when one of the mild stresses had no positive effect or even a negative effect (heat), combining it with fasting did not increase the positive effect of fasting or even decreased it.

  8. Fabrication and thermal shock resistance of HfB2-SiC composite with B4C additives

    NASA Astrophysics Data System (ADS)

    Weng, L.; Han, W.; Hong, Ch.

    2011-12-01

    A HfB2 based ceramic matrix composite containing 20 vol.% SiC particles with 2 vol.% B4C as sintering additives was fabricated by hot-pressed sintering. The microstructure and properties, especially the thermal shock resistance of the composite were investigated. Results showed that the addition of B4C improved the powder sinterability and led to obtaining nearly full dense composite. The flexural strength and fracture toughness of the composite were 771 MPa and 7.06 MPam1/2, respectively. The thermal shock resistance tests indicated that the residual strength decreased significantly when the thermal shock temperature difference was higher than 600 °C. The large number of microcracks on the sample surface was the main reason for the catastrophic failure.

  9. Failure mechanisms of additively manufactured porous biomaterials: Effects of porosity and type of unit cell.

    PubMed

    Kadkhodapour, J; Montazerian, H; Darabi, A Ch; Anaraki, A P; Ahmadi, S M; Zadpoor, A A; Schmauder, S

    2015-10-01

    Since the advent of additive manufacturing techniques, regular porous biomaterials have emerged as promising candidates for tissue engineering scaffolds owing to their controllable pore architecture and feasibility in producing scaffolds from a variety of biomaterials. The architecture of scaffolds could be designed to achieve similar mechanical properties as in the host bone tissue, thereby avoiding issues such as stress shielding in bone replacement procedure. In this paper, the deformation and failure mechanisms of porous titanium (Ti6Al4V) biomaterials manufactured by selective laser melting from two different types of repeating unit cells, namely cubic and diamond lattice structures, with four different porosities are studied. The mechanical behavior of the above-mentioned porous biomaterials was studied using finite element models. The computational results were compared with the experimental findings from a previous study of ours. The Johnson-Cook plasticity and damage model was implemented in the finite element models to simulate the failure of the additively manufactured scaffolds under compression. The computationally predicted stress-strain curves were compared with the experimental ones. The computational models incorporating the Johnson-Cook damage model could predict the plateau stress and maximum stress at the first peak with less than 18% error. Moreover, the computationally predicted deformation modes were in good agreement with the results of scaling law analysis. A layer-by-layer failure mechanism was found for the stretch-dominated structures, i.e. structures made from the cubic unit cell, while the failure of the bending-dominated structures, i.e. structures made from the diamond unit cells, was accompanied by the shearing bands of 45°.

  10. Failure mechanisms of additively manufactured porous biomaterials: Effects of porosity and type of unit cell.

    PubMed

    Kadkhodapour, J; Montazerian, H; Darabi, A Ch; Anaraki, A P; Ahmadi, S M; Zadpoor, A A; Schmauder, S

    2015-10-01

    Since the advent of additive manufacturing techniques, regular porous biomaterials have emerged as promising candidates for tissue engineering scaffolds owing to their controllable pore architecture and feasibility in producing scaffolds from a variety of biomaterials. The architecture of scaffolds could be designed to achieve similar mechanical properties as in the host bone tissue, thereby avoiding issues such as stress shielding in bone replacement procedure. In this paper, the deformation and failure mechanisms of porous titanium (Ti6Al4V) biomaterials manufactured by selective laser melting from two different types of repeating unit cells, namely cubic and diamond lattice structures, with four different porosities are studied. The mechanical behavior of the above-mentioned porous biomaterials was studied using finite element models. The computational results were compared with the experimental findings from a previous study of ours. The Johnson-Cook plasticity and damage model was implemented in the finite element models to simulate the failure of the additively manufactured scaffolds under compression. The computationally predicted stress-strain curves were compared with the experimental ones. The computational models incorporating the Johnson-Cook damage model could predict the plateau stress and maximum stress at the first peak with less than 18% error. Moreover, the computationally predicted deformation modes were in good agreement with the results of scaling law analysis. A layer-by-layer failure mechanism was found for the stretch-dominated structures, i.e. structures made from the cubic unit cell, while the failure of the bending-dominated structures, i.e. structures made from the diamond unit cells, was accompanied by the shearing bands of 45°. PMID:26143351

  11. Investigation of mechanical properties of masterbatches and composites with small additions of CNTs

    NASA Astrophysics Data System (ADS)

    Burmistrov, I. N.; Yudintseva, T. I.; Ilinykh, I. A.; Khaydarov, B. B.; Mazov, I. N.; Anshin, S. M.; Kuznetsov, D. V.

    2016-01-01

    The present paper investigated physical and mechanical properties of the nanotube masterbatches and the polymer composites with low contents of carbon nanotubes (CNTs), which were obtained by diluting masterbatches. Ethylene-octene copolymer was used as the binder for the masterbatches, which provides the elasticity of the material at a content 20 wt% of CNT. Masterbatches were obtained with a 2-roller mixer, and their additive to polypropylene was carried out on a single screw injection molding machine. Strength properties of ethylene-octene copolymer increased when additing CNTs in an amount of 5-20 wt%. When the concentration of CNT in masterbatches is reduced to 0.01-0.1 wt% its strength characteristics increased up to 4-18%. The most effective strengthening of polypropylene was observed with the content of CNTs 0.1 wt%.

  12. Ultrasound-Induced New Cellular Mechanism Involved in Drug Resistance

    PubMed Central

    Hassan, Mariame A.; Furusawa, Yukihiro; Minemura, Masami; Rapoport, Natalya; Sugiyama, Toshiro; Kondo, Takashi

    2012-01-01

    The acoustic effects in a biological milieu offer several scenarios for the reversal of multidrug resistance. In this study, we have observed higher sensitivity of doxorubicin-resistant uterine sarcoma MES-SA/DX5 cells to ultrasound exposure compared to its parent counterpart MES-SA cells; however, the results showed that the acoustic irradiation was genotoxic and could promote neotic division in exposed cells that was more pronounced in the resistant variant. The neotic progeny, imaged microscopically 24 hr post sonication, could contribute in modulating the final cell survival when an apoptotic dose of doxorubicin was combined with ultrasound applied either simultaneously or sequentially in dual-treatment protocols. Depending on the time and order of application of ultrasound and doxorubicin in combination treatments, there was either desensitization of the parent cells or sensitization of the resistant cells to doxorubicin action. PMID:23284614

  13. Antibiotic Methylation: A New Mechanism of Antimicrobial Resistance.

    PubMed

    Malone, Kerri M; Gordon, Stephen V

    2016-10-01

    In new research on Mycobacterium tuberculosis, the causative agent of tuberculosis, Warrier and colleagues have discovered a novel mode of bacterial drug resistance, namely antibiotic inactivation via N-methylation.

  14. Antibiotic Methylation: A New Mechanism of Antimicrobial Resistance.

    PubMed

    Malone, Kerri M; Gordon, Stephen V

    2016-10-01

    In new research on Mycobacterium tuberculosis, the causative agent of tuberculosis, Warrier and colleagues have discovered a novel mode of bacterial drug resistance, namely antibiotic inactivation via N-methylation. PMID:27593675

  15. Distinct Detoxification Mechanisms Confer Resistance to Mesotrione and Atrazine in a Population of Waterhemp1[C][W][OPEN

    PubMed Central

    Ma, Rong; Kaundun, Shiv S.; Tranel, Patrick J.; Riggins, Chance W.; McGinness, Daniel L.; Hager, Aaron G.; Hawkes, Tim; McIndoe, Eddie; Riechers, Dean E.

    2013-01-01

    Previous research reported the first case of resistance to mesotrione and other 4-hydroxyphenylpyruvate dioxygenase (HPPD) herbicides in a waterhemp (Amaranthus tuberculatus) population designated MCR (for McLean County mesotrione- and atrazine-resistant). Herein, experiments were conducted to determine if target site or nontarget site mechanisms confer mesotrione resistance in MCR. Additionally, the basis for atrazine resistance was investigated in MCR and an atrazine-resistant but mesotrione-sensitive population (ACR for Adams County mesotrione-sensitive but atrazine-resistant). A standard sensitive population (WCS for Wayne County herbicide-sensitive) was also used for comparison. Mesotrione resistance was not due to an alteration in HPPD sequence, HPPD expression, or reduced herbicide absorption. Metabolism studies using whole plants and excised leaves revealed that the time for 50% of absorbed mesotrione to degrade in MCR was significantly shorter than in ACR and WCS, which correlated with previous phenotypic responses to mesotrione and the quantity of the metabolite 4-hydroxy-mesotrione in excised leaves. The cytochrome P450 monooxygenase inhibitors malathion and tetcyclacis significantly reduced mesotrione metabolism in MCR and corn (Zea mays) excised leaves but not in ACR. Furthermore, malathion increased mesotrione activity in MCR seedlings in greenhouse studies. These results indicate that enhanced oxidative metabolism contributes significantly to mesotrione resistance in MCR. Sequence analysis of atrazine-resistant (MCR and ACR) and atrazine-sensitive (WCS) waterhemp populations detected no differences in the psbA gene. The times for 50% of absorbed atrazine to degrade in corn, MCR, and ACR leaves were shorter than in WCS, and a polar metabolite of atrazine was detected in corn, MCR, and ACR that cochromatographed with a synthetic atrazine-glutathione conjugate. Thus, elevated rates of metabolism via distinct detoxification mechanisms contribute to

  16. Exploring Mechanisms of Resistance to Respiratory Inhibitors in Field Strains of Botrytis cinerea, the Causal Agent of Gray Mold ▿ †

    PubMed Central

    Leroux, Pierre; Gredt, Michel; Leroch, Michaela; Walker, Anne-Sophie

    2010-01-01

    Respiratory inhibitors are among the fungicides most widely used for disease control on crops. Most are strobilurins and carboxamides, inhibiting the cytochrome b of mitochondrial complex III and the succinate dehydrogenase of mitochondrial complex II, respectively. A few years after the approval of these inhibitors for use on grapevines, field isolates of Botrytis cinerea, the causal agent of gray mold, resistant to one or both of these classes of fungicide were recovered in France and Germany. However, little was known about the mechanisms underlying this resistance in field populations of this fungus. Such knowledge could facilitate resistance risk assessment. The aim of this study was to investigate the mechanisms of resistance occurring in B. cinerea populations. Highly specific resistance to strobilurins was correlated with a single mutation of the cytb target gene. Changes in its intronic structure may also have occurred due to an evolutionary process controlling selection for resistance. Specific resistance to carboxamides was identified for six phenotypes, with various patterns of resistance levels and cross-resistance. Several mutations specific to B. cinerea were identified within the sdhB and sdhD genes encoding the iron-sulfur protein and an anchor protein of the succinate dehydrogenase complex. Another as-yet-uncharacterized mechanism of resistance was also recorded. In addition to target site resistance mechanisms, multidrug resistance, linked to the overexpression of membrane transporters, was identified in strains with low to moderate resistance to several respiratory inhibitors. This diversity of resistance mechanisms makes resistance management difficult and must be taken into account when developing strategies for Botrytis control. PMID:20693447

  17. Colistin and tigecycline resistance in carbapenemase-producing Gram-negative bacteria: emerging resistance mechanisms and detection methods.

    PubMed

    Osei Sekyere, J; Govinden, U; Bester, L A; Essack, S Y

    2016-09-01

    A literature review was undertaken to ascertain the molecular basis for tigecycline and colistin resistance mechanisms and the experimental basis for the detection and delineation of this resistance particularly in carbapenemase-producing Gram-negative bacteria. Pubmed, Google Scholar and Science Direct were searched with the keywords colistin, tigecycline, resistance mechanisms and detection methods. Trans-complementation and comparative MIC studies, mass spectrometry, chromatography, spectrofluorometry, PCR, qRT-PCR and whole genome sequencing (WGS) were commonly used to determine tigecycline and colistin resistance mechanisms, specifically modifications in the structural and regulatory efflux (acrAB, OqxAB, kpgABC adeABC-FGH-IJK, mexAB-XY-oprJM and soxS, rarA robA, ramRAB marRABC, adeLRS, mexRZ and nfxb) and lipid A (pmrHFIJFKLM, lpxA, lpxC lpxD and mgrB, pmrAB, phoPQ,) genes respectively. Mutations in the ribosomal 16S rRNA operon rrnBC, also yielded resistance to tigecycline through target site modifications. The mcr-1 gene conferring resistance to colistin was identified via WGS, trans-complementation and a murine thigh infection model studies. Common detection methods are mainly antibiotic sensitivity testing with broth microdilution while molecular identification tools are mostly PCR and WGS. Spectrofluorometry, MALDI-TOF MS, micro-array and real-time multiplex PCR hold much promise for the future as new detection tools.

  18. Functional Genome Screening to Elucidate the Colistin Resistance Mechanism

    PubMed Central

    Kumar, Mohit; Gupta, Ashutosh; Sahoo, Rajesh Kumar; Jena, Jayanti; Debata, Nagen Kumar; Subudhi, Enketeswara

    2016-01-01

    Antibiogram profile of 1590 clinical bacterial isolates based on thirteen different antimicrobial compounds showed that 1.6% of the bacterial isolates are multidrug resistant. Distribution pattern based on 16S rRNA sequence analysis showed that Pseudomonas aeruginosa constituted the largest group (83.6%) followed by Burkholderia pseudomallei sp. A191 (5.17%), Staphylococcus sp. A261 (3.45%). Among the various antibiotics used, colistin appeared to be the most effective against the Gram negative bacteria. Burkholderia pseudomallei sp. A191 and Pseudomonas aeruginosa sp. A111 showed resistance to 1500 μg/ml and 750 μg/ml of colistin respectively which constitutes 7.7% of the bacterial population. A functional genomics strategy was employed to discover the molecular support for colistin resistance in Burkholderia pseudomallei sp. A191. A pUC plasmid-based genomic expression library was constructed with an estimated library size of 2.1 × 107bp. Five colistin resistant clones were obtained after functional screening of the library. Analysis of DNA sequence of five colistin resistant clones showed homology to two component regularity systems (TCRS) encoding for a histidine kinase (mrgS) and its regulatory component (mrgR). Cross complementation assay showed that mutations in mrgS were sufficient enough to confer colistin resistant phenotype in a sensitive strain. PMID:26988670

  19. Antibiotic resistance in Enterobacteriaceae: mechanisms and clinical implications.

    PubMed

    Iredell, Jon; Brown, Jeremy; Tagg, Kaitlin

    2016-02-08

    Resistance of the Enterobacteriaceae to antibiotics, especially of the β lactam type, is increasingly dominated by the mobilization of continuously expressed single genes that encode efficient drug modifying enzymes. Strong and ubiquitous selection pressure has seemingly been accompanied by a shift from "natural" resistance, such as inducible chromosomal enzymes, membrane impermeability, and drug efflux, to the modern paradigm of mobile gene pools that largely determine the epidemiology of modern antibiotic resistance. In this way, antibiotic resistance is more available than ever before to organisms such as Escherichia coli and Klebsiella pneumoniae that are important causes of major sepsis. Modulation of the phenotype by host bacteria makes gene transmission less obvious and may in part explain why tracking and control of carbapenem resistance has been particularly problematic in the Enterobacteriaceae. This review discusses the underlying principles and clinical implications of the mobility and fixation of resistance genes and the exploitable opportunities and potential threats arising from apparent limitations on diversity in these mobile gene pools. It also provides some illustrative paradoxes and clinical corollaries, as well as a summary of future options.

  20. Functional Genome Screening to Elucidate the Colistin Resistance Mechanism.

    PubMed

    Kumar, Mohit; Gupta, Ashutosh; Sahoo, Rajesh Kumar; Jena, Jayanti; Debata, Nagen Kumar; Subudhi, Enketeswara

    2016-01-01

    Antibiogram profile of 1590 clinical bacterial isolates based on thirteen different antimicrobial compounds showed that 1.6% of the bacterial isolates are multidrug resistant. Distribution pattern based on 16S rRNA sequence analysis showed that Pseudomonas aeruginosa constituted the largest group (83.6%) followed by Burkholderia pseudomallei sp. A191 (5.17%), Staphylococcus sp. A261 (3.45%). Among the various antibiotics used, colistin appeared to be the most effective against the Gram negative bacteria. Burkholderia pseudomallei sp. A191 and Pseudomonas aeruginosa sp. A111 showed resistance to 1500 μg/ml and 750 μg/ml of colistin respectively which constitutes 7.7% of the bacterial population. A functional genomics strategy was employed to discover the molecular support for colistin resistance in Burkholderia pseudomallei sp. A191. A pUC plasmid-based genomic expression library was constructed with an estimated library size of 2.1 × 10(7)bp. Five colistin resistant clones were obtained after functional screening of the library. Analysis of DNA sequence of five colistin resistant clones showed homology to two component regularity systems (TCRS) encoding for a histidine kinase (mrgS) and its regulatory component (mrgR). Cross complementation assay showed that mutations in mrgS were sufficient enough to confer colistin resistant phenotype in a sensitive strain. PMID:26988670

  1. Transcriptome analysis of genes related to resistance against powdery mildew in wheat-Thinopyrum alien addition disomic line germplasm SN6306.

    PubMed

    Li, Quanquan; Niu, Zubiao; Bao, Yinguang; Tian, Qiuju; Wang, Honggang; Kong, Lingrang; Feng, Deshun

    2016-09-15

    Wheat powdery mildew, which is mainly caused by Blumeria graminis f. sp. tritici (Bgt), seriously damages wheat production. The wheat-Thinopyrum intermedium alien addition disomic line germplasm SN6306, being one of the important sources of genes for wheat resistance, is highly resistant to Bgt E09 and to many other powdery mildew physiological races. However, knowledge on the resistance mechanism of SN6306 remains limited. Our study employed high-throughput RNA sequencing based on next-generation sequencing technology (Illumina) to obtain an overview of the transcriptome characteristics of SN6306 and its parent wheat Yannong 15 (YN15) during Bgt infection. The sequencing generated 104,773 unigenes, 9909 of which showed varied expression levels. Among the 9909 unigenes, 1678 unigenes showed 0 reads in YN15. The expression levels in Bgt-inoculated SN6306 and YN15 of exactly 39 unigenes that showed 0 or considerably low reads in YN15 were validated to identify the genes involved in Bgt resistance. Among the 39 unigenes, 12 unigenes were upregulated in SN6306 by 3-45 times. These unigenes mainly encoded kinase, synthase, proteases, and signal transduction proteins, which may play an important role in the resistance against Bgt. To confirm whether the unigenes that showed 0 reads in YN15 are really unique to SN6306, 8 unigenes were cloned and sequenced. Results showed that the selected unigenes are more similar to SN6306 and Th. intermedium than to the wheat cultivar YN15. The sequencing results further confirmed that the unigenes showing 0 reads in YN15 are unique to SN6306 and are most likely derived from Th. intermedium (Host) Nevski. Thus, the genes from Th. intermedium most probably conferred the resistance of SN6306 to Bgt. PMID:27265028

  2. Mechanism of Resistance and Novel Targets Mediating Resistance to EGFR and c-Met Tyrosine Kinase Inhibitors in Non-Small Cell Lung Cancer

    PubMed Central

    Chhabra, Gagan; Nlend, Marie

    2015-01-01

    Tyrosine kinase inhibitors (TKIs) against EGFR and c-Met are initially effective when administered individually or in combination to non-small cell lung cancer (NSCLC) patients. However, the overall efficacies of TKIs are limited due to the development of drug resistance. Therefore, it is important to elucidate mechanisms of EGFR and c-Met TKI resistance in order to develop more effective therapies. Model NSCLC cell lines H1975 and H2170 were used to study the similarities and differences in mechanisms of EGFR/c-Met TKI resistance. H1975 cells are positive for the T790M EGFR mutation, which confers resistance to current EGFR TKI therapies, while H2170 cells are EGFR wild-type. Previously, H2170 cells were made resistant to the EGFR TKI erlotinib and the c-Met TKI SU11274 by exposure to progressively increasing concentrations of TKIs. In H2170 and H1975 TKI-resistant cells, key Wnt and mTOR proteins were found to be differentially modulated. Wnt signaling transducer, active β-catenin was upregulated in TKI-resistant H2170 cells when compared to parental cells. GATA-6, a transcriptional activator of Wnt, was also found to be upregulated in resistant H2170 cells. In H2170 erlotinib resistant cells, upregulation of inactive GSK3β (p-GSK3β) was observed, indicating activation of Wnt and mTOR pathways which are otherwise inhibited by its active form. However, in H1975 cells, Wnt modulators such as active β-catenin, GATA-6 and p-GSK3β were downregulated. Additional results from MTT cell viability assays demonstrated that H1975 cell proliferation was not significantly decreased after Wnt inhibition by XAV939, but combination treatment with everolimus (mTOR inhibitor) and erlotinib resulted in synergistic cell growth inhibition. Thus, in H2170 cells and H1975 cells, simultaneous inhibition of key Wnt or mTOR pathway proteins in addition to EGFR and c-Met may be a promising strategy for overcoming EGFR and c-Met TKI resistance in NSCLC patients. PMID:26301867

  3. A review of control methods and resistance mechanisms in stored-product insects.

    PubMed

    Boyer, S; Zhang, H; Lempérière, G

    2012-04-01

    This review describes the major stored-product insect species and their resistance to insecticides. The economic importance of the control of those pests is highlighted with a loss of more than one billion US dollars per year worldwide. A detailed common description of species resistance throughout the world has been developed, and we observed 28 recurrent studied species involved in resistance cases disseminated on the five continents. The different mechanisms, including behavioral resistance, were studied particularly on Oryzaephilus surinamensis. The role of detoxifying enzymes and studies on the genetic resistance, involving the kdr mutation mechanisms and the transmission of the genes of resistance, are also described. A chapter clarifying definitions on cross and multiple resistance is enclosed.

  4. A review of control methods and resistance mechanisms in stored-product insects.

    PubMed

    Boyer, S; Zhang, H; Lempérière, G

    2012-04-01

    This review describes the major stored-product insect species and their resistance to insecticides. The economic importance of the control of those pests is highlighted with a loss of more than one billion US dollars per year worldwide. A detailed common description of species resistance throughout the world has been developed, and we observed 28 recurrent studied species involved in resistance cases disseminated on the five continents. The different mechanisms, including behavioral resistance, were studied particularly on Oryzaephilus surinamensis. The role of detoxifying enzymes and studies on the genetic resistance, involving the kdr mutation mechanisms and the transmission of the genes of resistance, are also described. A chapter clarifying definitions on cross and multiple resistance is enclosed. PMID:22126937

  5. Research Progress on the Role of ABC Transporters in the Drug Resistance Mechanism of Intractable Epilepsy

    PubMed Central

    Xiong, Jie; Mao, Ding-an; Liu, Li-qun

    2015-01-01

    The pathogenesis of intractable epilepsy is not fully clear. In recent years, both animal and clinical trials have shown that the expression of ATP-binding cassette (ABC) transporters is increased in patients with intractable epilepsy; additionally, epileptic seizures can lead to an increase in the number of sites that express ABC transporters. These findings suggest that ABC transporters play an important role in the drug resistance mechanism of epilepsy. ABC transporters can perform the funcions of a drug efflux pump, which can reduce the effective drug concentration at epilepsy lesions by reducing the permeability of the blood brain barrier to antiepileptic drugs, thus causing resistance to antiepileptic drugs. Given the important role of ABC transporters in refractory epilepsy drug resistance, antiepileptic drugs that are not substrates of ABC transporters were used to obtain ABC transporter inhibitors with strong specificity, high safety, and few side effects, making them suitable for long-term use; therefore, these drugs can be used for future clinical treatment of intractable epilepsy. PMID:26491660

  6. Mechanisms of daptomycin resistance in Staphylococcus aureus: role of the cell membrane and cell wall

    PubMed Central

    Bayer, Arnold S.; Schneider, Tanja; Sahl, Hans-Georg

    2012-01-01

    The bactericidal, cell membrane-targeting lipopeptide antibiotic daptomycin (DAP) is an important agent in treating invasive Staphylococcus aureus infections. However, there have been numerous recent reports of development of daptomycin-resistance (DAP-R) during therapy with this agent. The mechanisms of DAP-R in S. aureus appear to be quite diverse. DAP-R strains often exhibit progressive accumulation of single nucleotide polymorphisms in the multipeptide resistance factor gene (mprF) and the yycFG components of the yycFGHI operon. Both loci are involved in key cell membrane (CM) events, with mprF being responsible for the synthesis and outer CM translocation of the positively-charged phospholipid, lysyl-phosphotidylglycerol (L-PG), while the yyc operon is involved in the generalized response to stressors such as antimicrobials. In addition, other perturbations of the CM have been identified in DAP-R strains including: extremes in CM order; resistance to CM depolarization and permeabilization; and reduced surface binding of DAP. Moreover, modifications of the cell wall (CW) appear to also contribute to DAP-R, including enhanced expression of the dlt operon (involved in D-alanylation of CW teichoic acids) and progressive CW thickening. PMID:23215859

  7. Molecular Cytogenetic Identification of a New Wheat-Rye 6R Chromosome Disomic Addition Line with Powdery Mildew Resistance.

    PubMed

    An, Diaoguo; Zheng, Qi; Luo, Qiaoling; Ma, Pengtao; Zhang, Hongxia; Li, Lihui; Han, Fangpu; Xu, Hongxing; Xu, Yunfeng; Zhang, Xiaotian; Zhou, Yilin

    2015-01-01

    Rye (Secale cereale L.) possesses many valuable genes that can be used for improving disease resistance, yield and environment adaptation of wheat (Triticum aestivum L.). However, the documented resistance stocks derived from rye is faced severe challenge due to the variation of virulent isolates in the pathogen populations. Therefore, it is necessary to develop desirable germplasm and search for novel resistance gene sources against constantly accumulated variation of the virulent isolates. In the present study, a new wheat-rye line designated as WR49-1 was produced through distant hybridization and chromosome engineering protocols between common wheat cultivar Xiaoyan 6 and rye cultivar German White. Using sequential GISH (genomic in situ hybridization), mc-FISH (multicolor fluorescence in situ hybridization), mc-GISH (multicolor GISH) and EST (expressed sequence tag)-based marker analysis, WR49-1 was proved to be a new wheat-rye 6R disomic addition line. As expected, WR49-1 showed high levels of resistance to wheat powdery mildew (Blumeria graminis f. sp. tritici, Bgt) pathogens prevalent in China at the adult growth stage and 19 of 23 Bgt isolates tested at the seedling stage. According to its reaction pattern to different Bgt isolates, WR49-1 may possess new resistance gene(s) for powdery mildew, which differed from the documented powdery mildew gene, including Pm20 on chromosome arm 6RL of rye. Additionally, WR49-1 was cytologically stable, had improved agronomic characteristics and therefore could serve as an important bridge for wheat breeding and chromosome engineering.

  8. Origin and Evolution of Antibiotic Resistance: The Common Mechanisms of Emergence and Spread in Water Bodies

    PubMed Central

    Lupo, Agnese; Coyne, Sébastien; Berendonk, Thomas Ulrich

    2011-01-01

    The environment, and especially freshwater, constitutes a reactor where the evolution and the rise of new resistances occur. In water bodies such as waste water effluents, lakes, and rivers or streams, bacteria from different sources, e.g., urban, industrial, and agricultural waste, probably selected by intensive antibiotic usage, are collected and mixed with environmental species. This may cause two effects on the development of antibiotic resistances: first, the contamination of water by antibiotics or other pollutants lead to the rise of resistances due to selection processes, for instance, of strains over-expressing broad range defensive mechanisms, such as efflux pumps. Second, since environmental species are provided with intrinsic antibiotic resistance mechanisms, the mixture with allochthonous species is likely to cause genetic exchange. In this context, the role of phages and integrons for the spread of resistance mechanisms appears significant. Allochthonous species could acquire new resistances from environmental donors and introduce the newly acquired resistance mechanisms into the clinics. This is illustrated by clinically relevant resistance mechanisms, such as the fluoroquinolones resistance genes qnr. Freshwater appears to play an important role in the emergence and in the spread of antibiotic resistances, highlighting the necessity for strategies of water quality improvement. We assume that further knowledge is needed to better understand the role of the environment as reservoir of antibiotic resistances and to elucidate the link between environmental pollution by anthropogenic pressures and emergence of antibiotic resistances. Only an integrated vision of these two aspects can provide elements to assess the risk of spread of antibiotic resistances via water bodies and suggest, in this context, solutions for this urgent health issue. PMID:22303296

  9. Insecticide Resistance Mechanisms in the Green Peach Aphid Myzus persicae (Hemiptera: Aphididae) I: A Transcriptomic Survey

    PubMed Central

    Silva, Andrea X.; Jander, Georg; Samaniego, Horacio; Ramsey, John S; Figueroa, Christian C.

    2012-01-01

    Background Insecticide resistance is one of the best examples of rapid micro-evolution found in nature. Since the development of the first synthetic insecticide in 1939, humans have invested considerable effort to stay ahead of resistance phenotypes that repeatedly develop in insects. Aphids are a group of insects that have become global pests in agriculture and frequently exhibit insecticide resistance. The green peach aphid, Myzus persicae, has developed resistance to at least seventy different synthetic compounds, and different insecticide resistance mechanisms have been reported worldwide. Methodology/Principal Findings To further characterize this resistance, we analyzed genome-wide transcriptional responses in three genotypes of M. persicae, each exhibiting different resistance mechanisms, in response to an anti-cholinesterase insecticide. The sensitive genotype (exhibiting no resistance mechanism) responded to the insecticide by up-regulating 183 genes primarily ones related to energy metabolism, detoxifying enzymes, proteins of extracellular transport, peptidases and cuticular proteins. The second genotype (resistant through a kdr sodium channel mutation), up-regulated 17 genes coding for detoxifying enzymes, peptidase and cuticular proteins. Finally, a multiply resistant genotype (carrying kdr and a modified acetylcholinesterase), up-regulated only 7 genes, appears not to require induced insecticide detoxification, and instead down-regulated many genes. Conclusions/Significance This study suggests strongly that insecticide resistance in M. persicae is more complex that has been described, with the participation of a broad array of resistance mechanisms. The sensitive genotype exhibited the highest transcriptional plasticity, accounting for the wide range of potential adaptations to insecticides that this species can evolve. In contrast, the multiply resistant genotype exhibited a low transcriptional plasticity, even for the expression of genes encoding

  10. Differential Costs of Two Distinct Resistance Mechanisms Induced by Different Herbivore Species in Arabidopsis.

    PubMed

    Onkokesung, Nawaporn; Reichelt, Michael; van Doorn, Arjen; Schuurink, Robert C; Dicke, Marcel

    2016-02-01

    Plants respond to herbivory with the induction of resistance, mediated by distinct phytohormonal signaling pathways and their interactions. Phloem feeders are known to induce plant resistance via the salicylic acid pathway, whereas biting-chewing herbivores induce plant resistance mainly via the jasmonate pathway. Here, we show that a specialist caterpillar (biting-chewing herbivore) and a specialist aphid (phloem feeder) differentially induce resistance against Pieris brassicae caterpillars in Arabidopsis (Arabidopsis thaliana) plants. Caterpillar feeding induces resistance through the jasmonate signaling pathway that is associated with the induction of kaempferol 3,7-dirhamnoside, whereas aphid feeding induces resistance via a novel mechanism involving sinapoyl malate. The role of sinapoyl malate is confirmed through the use of a mutant compromised in the biosynthesis of this compound. Caterpillar-induced resistance is associated with a lower cost in terms of plant growth reduction than aphid-induced resistance. A strong constitutive resistance against P. brassicae caterpillars in combination with a strong growth attenuation in plants of a transfer DNA (T-DNA) insertion mutant of WRKY70 (wrky70) suggest that the WRKY70 transcription factor, a regulator of downstream responses mediated by jasmonate-salicylic acid signaling cross talk, is involved in the negative regulation of caterpillar resistance and in the tradeoff between growth and defense. In conclusion, different mechanisms of herbivore-induced resistance come with different costs, and a functional WRKY70 transcription factor is required for the induction of low-cost resistance. PMID:26603653

  11. Activity of Isavuconazole and Other Azoles against Candida Clinical Isolates and Yeast Model Systems with Known Azole Resistance Mechanisms

    PubMed Central

    Coste, Alix T.

    2015-01-01

    Isavuconazole is a novel, broad-spectrum, antifungal azole. In order to evaluate its interactions with known azole resistance mechanisms, isavuconazole susceptibility among different yeast models and clinical isolates expressing characterized azole resistance mechanisms was tested and compared to those of fluconazole, itraconazole, posaconazole, and voriconazole. Saccharomyces cerevisiae expressing the Candida albicans and C. glabrata ATP binding cassette (ABC) transporters (CDR1, CDR2, and CgCDR1), major facilitator (MDR1), and lanosterol 14-α-sterol-demethylase (ERG11) alleles with mutations were used. In addition, pairs of C. albicans and C. glabrata strains from matched clinical isolates with known azole resistance mechanisms were investigated. The expression of ABC transporters increased all azole MICs, suggesting that all azoles tested were substrates of ABC transporters. The expression of MDR1 did not increase posaconazole, itraconazole, and isavuconazole MICs. Relative increases of azole MICs (from 4- to 32-fold) were observed for fluconazole, voriconazole, and isavuconazole when at least two mutations were present in the same ERG11 allele. Upon MIC testing of azoles with clinical C. albicans and C. glabrata isolates with known resistance mechanisms, the MIC90s of C. albicans for fluconazole, voriconazole, itraconazole, posaconazole, and isavuconazole were 128, 2, 1, 0.5, and 2 μg/ml, respectively, while in C. glabrata they were 128, 2, 4, 4, and 16 μg/ml, respectively. In conclusion, the effects of azole resistance mechanisms on isavuconazole did not differ significantly from those of other azoles. Resistance mechanisms in yeasts involving ABC transporters and ERG11 decreased the activity of isavuconazole, while MDR1 had limited effect. PMID:26482310

  12. Bypassing Mechanisms of Mitochondria-Mediated Cancer Stem Cells Resistance to Chemo- and Radiotherapy

    PubMed Central

    Lyakhovich, Alex; Lleonart, Matilde E.

    2016-01-01

    Cancer stem cells (CSCs) are highly resistant to conventional chemo- and radiotherapeutic regimes. Therefore, the multiple drug resistance (MDR) of cancer is most likely due to the resistance of CSCs. Such resistance can be attributed to some bypassing pathways including detoxification mechanisms of reactive oxygen and nitrogen species (RO/NS) formation or enhanced autophagy. Unlike in normal cells, where RO/NS concentration is maintained at certain threshold required for signal transduction or immune response mechanisms, CSCs may develop alternative pathways to diminish RO/NS levels leading to cancer survival. In this minireview, we will focus on elaborated mechanisms developed by CSCs to attenuate high RO/NS levels. Gaining a better insight into the mechanisms of stem cell resistance to chemo- or radiotherapy may lead to new therapeutic targets thus serving for better anticancer strategies. PMID:26697128

  13. Understanding the Genetic Mechanisms of Cancer Drug Resistance Using Genomic Approaches.

    PubMed

    Hu, Xueda; Zhang, Zemin

    2016-02-01

    A major obstacle in precision cancer medicine is the inevitable resistance to targeted therapies. Tremendous effort and progress has been made over the past few years to understand the biochemical and genetic mechanisms underlying drug resistance, with the goal to eventually overcome such daunting challenges. Diverse mechanisms, such as secondary mutations, oncogene bypass, and epigenetic alterations, can all lead to drug resistance, and the number of known involved genes is growing rapidly, thus providing many possibilities to overcome resistance. The finding of these mechanisms and genes invariably requires the application of genomic and functional genomic approaches to tumors or cancer models. In this review, we briefly highlight the major drug-resistance mechanisms known today, and then focus primarily on the technological approaches leading to the advancement of this field. PMID:26689126

  14. Understanding the Genetic Mechanisms of Cancer Drug Resistance Using Genomic Approaches.

    PubMed

    Hu, Xueda; Zhang, Zemin

    2016-02-01

    A major obstacle in precision cancer medicine is the inevitable resistance to targeted therapies. Tremendous effort and progress has been made over the past few years to understand the biochemical and genetic mechanisms underlying drug resistance, with the goal to eventually overcome such daunting challenges. Diverse mechanisms, such as secondary mutations, oncogene bypass, and epigenetic alterations, can all lead to drug resistance, and the number of known involved genes is growing rapidly, thus providing many possibilities to overcome resistance. The finding of these mechanisms and genes invariably requires the application of genomic and functional genomic approaches to tumors or cancer models. In this review, we briefly highlight the major drug-resistance mechanisms known today, and then focus primarily on the technological approaches leading to the advancement of this field.

  15. 75 FR 29191 - Black Stem Rust; Additions of Rust-Resistant Varieties

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-25

    ... by a fungus that reduces the quality and yield of infected wheat, oat, barley, and rye crops. In addition to infecting small grains, the fungus lives on a variety of alternate host plants that are species of ] the genera Berberis, Mahoberberis, and Mahonia. The fungus is spread from host to host...

  16. 75 FR 54461 - Black Stem Rust; Additions of Rust-Resistant Varieties

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-08

    ... States. The disease is caused by a fungus that reduces the quality and yield of infected wheat, oat, barley, and rye crops. In addition to infecting small grains, the fungus lives on a variety of alternate host plants that are species of the genera Berberis, Mahoberberis, and Mahonia. The fungus is...

  17. 78 FR 27855 - Black Stem Rust; Additions of Rust-Resistant Species and Varieties

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-13

    ... the United States. The disease is caused by a fungus (Puccinia graminis) that reduces the quality and yield of infected wheat, oat, barley, and rye crops. In addition to infecting small grains, the fungus... Mahonia. The fungus is spread from host to host by windborne spores. The black stem rust quarantine...

  18. Effect of Y Addition on the Mechanical Properties and Microstructure of Zn-Al Alloys

    NASA Astrophysics Data System (ADS)

    Li, Mingyang; Lu, Shujing; Long, Fang; Sheng, Meng; Geng, Haoran; Liu, Wendi

    2015-05-01

    This article will discuss the influence of the rare earth Y on the microstructure and mechanical properties of Zn-Al alloys (ZA27, ZA35, and ZA40), and it will provide reference to rare-earth microalloying through the cast ingot metallurgy process. The results also suggest that the microstructure can be refined and mechanical properties can be improved obviously when adding the right amount of Y, and its tensile strength and brinell hardness increased by 9.1% and 11.7% compared with the unmodified ZA27 alloys, respectively. Compared with non-Y addition, the alloys will form dispersed YZn12 phase, which can strongly pin dislocations and subgrain boundary, inhibiting further recrystallization. On this basis, the impacts of Y on the microstructure and mechanical properties of ZA27, ZA35, and ZA40 have been explored. After adding Y, the microstructures of as-cast Zn-Al alloys are refined at different degree. However, with the increase of Al content, the microstructure shows a certain coarsening and the segregation and shrinkage porosity occur. The most effective refining appears in ZA27-0.4%Y.

  19. Modeling and additive manufacturing of bio-inspired composites with tunable fracture mechanical properties.

    PubMed

    Dimas, Leon S; Buehler, Markus J

    2014-07-01

    Flaws, imperfections and cracks are ubiquitous in material systems and are commonly the catalysts of catastrophic material failure. As stresses and strains tend to concentrate around cracks and imperfections, structures tend to fail far before large regions of material have ever been subjected to significant loading. Therefore, a major challenge in material design is to engineer systems that perform on par with pristine structures despite the presence of imperfections. In this work we integrate knowledge of biological systems with computational modeling and state of the art additive manufacturing to synthesize advanced composites with tunable fracture mechanical properties. Supported by extensive mesoscale computer simulations, we demonstrate the design and manufacturing of composites that exhibit deformation mechanisms characteristic of pristine systems, featuring flaw-tolerant properties. We analyze the results by directly comparing strain fields for the synthesized composites, obtained through digital image correlation (DIC), and the computationally tested composites. Moreover, we plot Ashby diagrams for the range of simulated and experimental composites. Our findings show good agreement between simulation and experiment, confirming that the proposed mechanisms have a significant potential for vastly improving the fracture response of composite materials. We elucidate the role of stiffness ratio variations of composite constituents as an important feature in determining the composite properties. Moreover, our work validates the predictive ability of our models, presenting them as useful tools for guiding further material design. This work enables the tailored design and manufacturing of composites assembled from inferior building blocks, that obtain optimal combinations of stiffness and toughness. PMID:24700202

  20. Design of a mechanical system in gait rehabilitation with progressive addition of weight

    NASA Astrophysics Data System (ADS)

    Braidot, Ariel A. A.; Aleman, Guillermo L.

    2011-12-01

    In this paper we designed and developed a mechanical device for gait rehabilitation based on the application of "partial body weight reduction therapy". An evaluation of the characteristics of devices based on this therapy currently available on the market was carried out obtaining information of the different mechanisms used in it. The device was designed to adapt to different height and weight of patients and to be used with additional equipment in gait rehabilitation, for example, treadmills, elliptical trainers and vertical scalers. It was envisaged to be used by patients with asymmetry in the lower extremities capabilities. We developed a stable structure in steel ASTM A36 which does not depend on the building conditions of the installation site. RamAdvanse software was used to calculate structural stability. A winch with automatic brake mechanism was used to raise/lower the patient, who was tied to a comfortable harness which provided safety to the patient and therapist. It was possible to quantify precisely, using counterweights, the weight borne by the patient during therapy. We obtained a small-sized and ergonomic low-cost prototype, with similar features to those currently considered cutting-edge devices.

  1. The effects of tantalum addition on the microtexture and mechanical behaviour of tungsten for ITER applications

    NASA Astrophysics Data System (ADS)

    Tejado, E.; Carvalho, P. A.; Munoz, A.; Dias, M.; Correia, J. B.; Mardolcar, U. V.; Pastor, J. Y.

    2015-12-01

    Tungsten (W) and its alloys are very promising materials for producing plasma-facing components (PFCs) in the fusion power reactors of the near future, even as a structural part in them. However, whereas the properties of pure tungsten are suitable for a PFC, its structural applications are still limited due to its low toughness, ductile to brittle transition temperature and recrystallization behaviour. Therefore, many efforts have been made to improve its performance by alloying tungsten with other elements. Hence, in this investigation, the thermo-mechanical performance of two new tungsten-tantalum materials has been evaluated. Materials with W-5wt.%Ta and W-15wt.%Ta were processed by mechanical alloying (MA) and later consolidation by hot isostatic pressing (HIP), with distinct settings for each composition. Thus, it was possible to determine the relationship between the microstructure and the addition of Ta with the macroscopic mechanical properties. These were measured by means of hardness, flexural strength and fracture toughness, in the temperature range of 300-1473 K. The microstructure and the fracture surfaces features of the tested materials were analysed by Field Emission Scanning Electron Microscopy (FESEM).

  2. Modeling and additive manufacturing of bio-inspired composites with tunable fracture mechanical properties.

    PubMed

    Dimas, Leon S; Buehler, Markus J

    2014-07-01

    Flaws, imperfections and cracks are ubiquitous in material systems and are commonly the catalysts of catastrophic material failure. As stresses and strains tend to concentrate around cracks and imperfections, structures tend to fail far before large regions of material have ever been subjected to significant loading. Therefore, a major challenge in material design is to engineer systems that perform on par with pristine structures despite the presence of imperfections. In this work we integrate knowledge of biological systems with computational modeling and state of the art additive manufacturing to synthesize advanced composites with tunable fracture mechanical properties. Supported by extensive mesoscale computer simulations, we demonstrate the design and manufacturing of composites that exhibit deformation mechanisms characteristic of pristine systems, featuring flaw-tolerant properties. We analyze the results by directly comparing strain fields for the synthesized composites, obtained through digital image correlation (DIC), and the computationally tested composites. Moreover, we plot Ashby diagrams for the range of simulated and experimental composites. Our findings show good agreement between simulation and experiment, confirming that the proposed mechanisms have a significant potential for vastly improving the fracture response of composite materials. We elucidate the role of stiffness ratio variations of composite constituents as an important feature in determining the composite properties. Moreover, our work validates the predictive ability of our models, presenting them as useful tools for guiding further material design. This work enables the tailored design and manufacturing of composites assembled from inferior building blocks, that obtain optimal combinations of stiffness and toughness.

  3. Gene expression profiling of the androgen independent prostate cancer cells demonstrates complex mechanisms mediating resistance to docetaxel

    PubMed Central

    Desarnaud, Frank; Geck, Peter; Parkin, Christopher; Carpinito, Gino

    2011-01-01

    The molecular mechanisms conferring resistance to docetaxel in prostate cancer patients remain partially understood. We generated docetaxel resistant derivatives of the androgen independent prostate cancer cell lines PC-3 and DU-145. Docetaxel rapidly induces DU-145 cell death via apoptosis and the drug resistant cells were produced by periodically exposing proliferating DU-145 cultures to small doses of docetaxel. In PC-3 cells docetaxel induces delayed cell death via mitotic catastrophe evident by profound multinucleation and formation of giant cells. Mononucleated progeny of the giant PC-3 cells shows significant resistance to docetaxel. Gene expression profiling of these docetaxel resistant PC-3 cells revealed sets of docetaxel inducible and constitutively expressed genes associated with major cancer pathways. A contradictory overlap with DU-145 docetaxel resistant cells was also found. Analyses suggested significant changes associated with apoptotic function, DNA repair, cell growth, survival and proliferation, metabolism, maintenance of cytoskeleton and extracellular matrix formation. These cellular processes often contribute to drug resistance and our study identified a set of genes managing this phenotype. Additional analyses of the drug resistant PC-3 cells using shRNA constructs determined direct relevance of Cyclin G2 to docetaxel resistance as well as prevention of multinucleation, whereas the knockdown of upregulated CYP1B1 showed no effect on either of these processes. Downregulated GBP1 was explored by ectopic overexpression and even though GBP1 has a potential to mediate resistance to docetaxel, it was not utilized in PC-3 cells. The results suggest complex combination of gene expression pattern changes that enables resistance to docetaxel while preventing death via multinucleation. PMID:21057205

  4. A new detection method for a newly revealed mechanism of pyrethroid resistance development in Varroa destructor.

    PubMed

    Strachecka, Aneta; Borsuk, Grzegorz; Olszewski, Krzysztof; Paleolog, Jerzy

    2015-11-01

    The Varroa destructor mite has recently displayed an ever increasing resistance to new drugs, contributing to CCD proliferation. This work was aimed at determining new viable methods for identifying the pyrethroid resistance of V. destructor and DNA methylation in resistant and sensitive mites. DNA was extracted from Varroa mites. Nucleotide changes in the DNA of pyrethroid-resistant, pyrethroid-sensitive, and control mites were identified with polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) in the case of five mitochondrial gene fragments. More bands were observed in the drug-resistant mites than in the other two groups. Sequencing confirmed these observations. Decreased global DNA methylation levels were observed in the pyrethroid-resistant mites. There exists a previously undescribed mechanism of pyrethroid resistance development in Varroa mites. The PCR-SSCP methods can be considered and further developed as useful tools for detecting V. destructor resistance. PMID:26210302

  5. Counterintuitive mechanisms of the addition of hydrogen and simple olefins to heavy group 13 alkene analogues.

    PubMed

    Caputo, Christine A; Koivistoinen, Juha; Moilanen, Jani; Boynton, Jessica N; Tuononen, Heikki M; Power, Philip P

    2013-02-01

    The mechanism of the reaction of olefins and hydrogen with dimetallenes ArMMAr (Ar = aromatic group; M = Al or Ga) was studied by density functional theory calculations and experimental methods. The digallenes, for which the most experimental data are available, are extensively dissociated to gallanediyl monomers, :GaAr, in hydrocarbon solution, but the calculations and experimental data showed also that they react with simple olefins, such as ethylene, as intact ArGaGaAr dimers via stepwise [2 + 2 + 2] cycloadditions due to their considerably lower activation barriers vis-à-vis the gallanediyl monomers, :GaAr. This pathway was preferred over the [2 + 2] cycloaddition of olefin to monomeric :GaAr to form a gallacyclopropane ring with subsequent dimerization to yield the 1,2-digallacyclobutane intermediate and, subsequently, the 1,4-digallacyclohexane product. The calculations showed also that the addition of H(2) to digallene proceeds by a different mechanism involving the initial addition of one equivalent of H(2) to form a 1,2-dihydride intermediate. This reacts with a second equivalent of H(2) to give two ArGaH(2) fragments which recombine to give the observed product with terminal and bridging H-atoms, Ar(H)Ga(μ-H)(2)Ga(H)Ar. The computations agree with the experimental observation that the :GaAr(iPr(8)) (Ar(iPr(8)) = C(6)H-2,6-(C(6)H(3)-2,4,6-(i)Pr(3))(2)-3,5-(i)Pr(2)), which does not associate even in the solid state, does not react with ethylene or hydrogen. Calculations on the reaction of propene with ArAlAlAr show that, in contrast to the digallenes, addition involves an open-shell transition state consistent with the higher singlet diradical character of dialuminenes.

  6. Mechanisms of antimicrobial resistance and genetic relatedness among enterococci isolated from dogs and cats in the United States

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Aims: In this study, mechanisms of antimicrobial resistance and genetic relatedness among resistant enterococci from dogs and cats in the United States were determined. Methods and Results: Enterococci resistant to chloramphenicol, ciprofloxacin, erythromycin, gentamicin, kanamycin, streptomycin,...

  7. Membrane fouling in a membrane bioreactor: High filtration resistance of gel layer and its underlying mechanism.

    PubMed

    Chen, Jianrong; Zhang, Meijia; Li, Fengquan; Qian, Lei; Lin, Hongjun; Yang, Lining; Wu, Xilin; Zhou, Xiaoling; He, Yiming; Liao, Bao-Qiang

    2016-10-01

    A membrane bioreactor (MBR) was continuously operated to investigate mechanisms of fouling caused by the gel layer in this study. Agar was used as a model foulant for gel layer formation, and filtration resistance of gel layers was systematically assessed. The results showed that gel layer possessed unusually high specific filtration resistance (SFR) and high measured porosity as compared with cake layer. Current knowledge cannot explain the contradiction between high filtration resistance and high porosity of gel layer. A new fouling mechanism based on Flory-Huggins theory was then proposed. Filtration resistance of agar gel layer was found to be independent of pH and ionic strength, but linearly increase with gel thickness. The results are accordant with the mechanism deductions. Simulation of the mechanism model showed that the filtration resistance induced by mixing chemical potential variation was comparable to the experimental data of filtration resistance of agar gel layer, indicating that the proposed mechanism is the predominant mechanism responsible for the high filtration resistance of gel layer. The proposed mechanism was further verified from the bound water viewpoint.

  8. Similar and Additive Effects of Ovariectomy and Diabetes on Insulin Resistance and Lipid Metabolism

    PubMed Central

    Tawfik, Shady H.; Mahmoud, Bothaina F.; Saad, Mohamed I.; Shehata, Mona; Kamel, Maher A.; Helmy, Madiha H.

    2015-01-01

    Type 2 diabetes mellitus (T2DM) is among the leading causes of death in postmenopausal women. The disruption of ovarian function may contribute to the incidence of T2DM. The purpose of this study was to investigate the effects of ovariectomy and T2DM on glucose and lipid homeostasis, perilipin levels in adipose tissues, as a lipolytic regulator, and levels of certain adipokines. Ovariectomized (OVX) rats were used as a model for postmenopausal women. The study was performed on sham, OVX, sham diabetic, and OVX diabetic female rats. The results indicated that ovariectomy alters adipose tissue metabolism through reducing perilipin content in white adipose tissue (WAT); however it has no effect on perilipin level in brown adipose tissue (BAT). OVX diabetic females suffer from serious metabolic disturbances, suggested by exacerbation of insulin resistance in terms of disrupted lipid profile, higher HOMA-IR, hyperinsulinemia, higher leptin, and lower adiponectin concentrations. These metabolic derangements may underlie the predisposition for cardiovascular disease in women after menopause. Therefore, for efficient treatment, the menopausal status of diabetic female should be addressed, and the order of events is of great importance because ovariectomy following development of diabetes has more serious complications compared to development of diabetes as result of menopause. PMID:25834745

  9. Methicillin resistance in Staphylococcus epidermidis. Relationship between the additional penicillin-binding protein and an attachment transpeptidase.

    PubMed

    Gaisford, W C; Reynolds, P E

    1989-10-20

    The penicillin-binding proteins (PBP) of a methicillin-resistant strain of Staphylococcus epidermidis, 100,604 p+m+ and a non-isogenic sensitive strain, p-m- were characterised. The presence of a novel PBP, produced by the methicillin-resistant strain of S. epidermidis, with an Mr identical to that of PBP2' in Staphylococcus aureus 13,136 p-m+, was revealed by sodium dodecyl sulphate/polyacrylamide gel electrophoresis and subsequent fluorography of solubilised membrane proteins isolated from cells labelled with [3H]benzylpenicillin. This novel PBP was only detected in cells which had been grown at 30 degrees C, in media containing beta-lactam antibiotic and 5% NaCl. The sensitivity of an attachment transpeptidation reaction measured under non-growing conditions in the sensitive and resistant strains indicated that the novel PBP catalysed this reaction. The similarity of radiolabelled peptides resulting from partial proteolytic digestion of the novel PBP in S. epidermidis 100,604 p+m+ and from PBP2' in S. aureus 13,136 p+m+ lends support to the theory that the additional DNA encoding PBP2' in S. aureus and the same protein in S. epidermidis has been passed to both species from an unknown source. Studies of the development and loss of resistance of attachment transpeptidase activity, and the appearance and disappearance of the novel protein when cultures of the resistant strain were transferred from conditions allowing the expression of resistance to those not allowing such expression and vice-versa, indicated that there was a strong correlation between the presence of PBP2' and the degree of resistance of the attachment transpeptidation reaction and that the production of this protein was affected by temperature at a regulatory or genetic level. Studies on the induction and loss of beta-lactamase activity and of the novel PBP when the resistant strain was grown in the presence or absence of beta-lactam antibiotics at either 40 degrees C or 30 degrees C suggests that

  10. Methicillin resistance in Staphylococcus epidermidis. Relationship between the additional penicillin-binding protein and an attachment transpeptidase.

    PubMed

    Gaisford, W C; Reynolds, P E

    1989-10-20

    The penicillin-binding proteins (PBP) of a methicillin-resistant strain of Staphylococcus epidermidis, 100,604 p+m+ and a non-isogenic sensitive strain, p-m- were characterised. The presence of a novel PBP, produced by the methicillin-resistant strain of S. epidermidis, with an Mr identical to that of PBP2' in Staphylococcus aureus 13,136 p-m+, was revealed by sodium dodecyl sulphate/polyacrylamide gel electrophoresis and subsequent fluorography of solubilised membrane proteins isolated from cells labelled with [3H]benzylpenicillin. This novel PBP was only detected in cells which had been grown at 30 degrees C, in media containing beta-lactam antibiotic and 5% NaCl. The sensitivity of an attachment transpeptidation reaction measured under non-growing conditions in the sensitive and resistant strains indicated that the novel PBP catalysed this reaction. The similarity of radiolabelled peptides resulting from partial proteolytic digestion of the novel PBP in S. epidermidis 100,604 p+m+ and from PBP2' in S. aureus 13,136 p+m+ lends support to the theory that the additional DNA encoding PBP2' in S. aureus and the same protein in S. epidermidis has been passed to both species from an unknown source. Studies of the development and loss of resistance of attachment transpeptidase activity, and the appearance and disappearance of the novel protein when cultures of the resistant strain were transferred from conditions allowing the expression of resistance to those not allowing such expression and vice-versa, indicated that there was a strong correlation between the presence of PBP2' and the degree of resistance of the attachment transpeptidation reaction and that the production of this protein was affected by temperature at a regulatory or genetic level. Studies on the induction and loss of beta-lactamase activity and of the novel PBP when the resistant strain was grown in the presence or absence of beta-lactam antibiotics at either 40 degrees C or 30 degrees C suggests that

  11. Multiple Mechanisms Increase Levels of Resistance in Rapistrum rugosum to ALS Herbicides

    PubMed Central

    Hatami, Zahra M.; Gherekhloo, Javid; Rojano-Delgado, Antonia M.; Osuna, Maria D.; Alcántara, Ricardo; Fernández, Pablo; Sadeghipour, Hamid R.; De Prado, Rafael

    2016-01-01

    Rapistrum rugosum (turnip weed) is a common weed of wheat fields in Iran, which is most often controlled by tribenuron-methyl (TM), a sulfonylurea (SU) belonging to the acetolactate synthase (ALS) inhibiting herbicides group. Several cases of unexplained control failure of R. rugosum by TM have been seen, especially in Golestan province-Iran. Hence, there is lack of research in evaluation of the level of resistance of the R. rugosum populations to TM, using whole plant dose-response and enzyme assays, then investigating some potential resistance mechanisms Results revealed that the resistance factor (RF) for resistant (R) populations was 2.5–6.6 fold higher than susceptible (S) plant. Neither foliar retention, nor 14C-TM absorption and translocation were the mechanisms responsible for resistance in turnip weed. Metabolism of TM was the second resistant mechanism in two populations (Ag-R5 and G-1), in which three metabolites were found. The concentration of TM for 50% inhibition of ALS enzyme activity in vitro showed a high level of resistance to the herbicide (RFs were from 28 to 38) and cross-resistance to sulfonyl-aminocarbonyl-triazolinone (SCT), pyrimidinyl-thiobenzoate (PTB) and triazolopyrimidine (TP), with no cross-resistance to imidazolinone (IMI). Substitution Pro 197 to Ser 197 provided resistance to four of five ALS-inhibiting herbicides including SU, TP, PTB, and SCT with no resistance to IMI. These results documented the first case of R. rugosum resistant population worldwide and demonstrated that both RST and NRST mechanisms are involved to the resistance level to TM. PMID:26941749

  12. ADDITIONAL STRESS AND FRACTURE MECHANICS ANALYSES OF PRESSURIZED WATER REACTOR PRESSURE VESSEL NOZZLES

    SciTech Connect

    Walter, Matthew; Yin, Shengjun; Stevens, Gary; Sommerville, Daniel; Palm, Nathan; Heinecke, Carol

    2012-01-01

    In past years, the authors have undertaken various studies of nozzles in both boiling water reactors (BWRs) and pressurized water reactors (PWRs) located in the reactor pressure vessel (RPV) adjacent to the core beltline region. Those studies described stress and fracture mechanics analyses performed to assess various RPV nozzle geometries, which were selected based on their proximity to the core beltline region, i.e., those nozzle configurations that are located close enough to the core region such that they may receive sufficient fluence prior to end-of-life (EOL) to require evaluation of embrittlement as part of the RPV analyses associated with pressure-temperature (P-T) limits. In this paper, additional stress and fracture analyses are summarized that were performed for additional PWR nozzles with the following objectives: To expand the population of PWR nozzle configurations evaluated, which was limited in the previous work to just two nozzles (one inlet and one outlet nozzle). To model and understand differences in stress results obtained for an internal pressure load case using a two-dimensional (2-D) axi-symmetric finite element model (FEM) vs. a three-dimensional (3-D) FEM for these PWR nozzles. In particular, the ovalization (stress concentration) effect of two intersecting cylinders, which is typical of RPV nozzle configurations, was investigated. To investigate the applicability of previously recommended linear elastic fracture mechanics (LEFM) hand solutions for calculating the Mode I stress intensity factor for a postulated nozzle corner crack for pressure loading for these PWR nozzles. These analyses were performed to further expand earlier work completed to support potential revision and refinement of Title 10 to the U.S. Code of Federal Regulations (CFR), Part 50, Appendix G, Fracture Toughness Requirements, and are intended to supplement similar evaluation of nozzles presented at the 2008, 2009, and 2011 Pressure Vessels and Piping (PVP

  13. The combination of trastuzumab and pertuzumab administered at approved doses may delay development of trastuzumab resistance by additively enhancing antibody-dependent cell-mediated cytotoxicity

    PubMed Central

    Tóth, Gábor; Szöőr, Árpád; Simon, László; Yarden, Yosef; Szöllősi, János; Vereb, György

    2016-01-01

    ABSTRACT Although the recently concluded CLEOPATRA trial showed clinical benefits of combining trastuzumab and pertuzumab for treating HER2-positive metastatic breast cancer, trastuzumab monotherapy is still the mainstay in adjuvant settings. Since trastuzumab resistance occurs in over half of these cancers, we examined the mechanisms by which treatment of intrinsically trastuzumab-resistant and -sensitive tumors can benefit from the combination of these antibodies. F(ab′)2 of both trastuzumab and pertuzumab were generated and validated in order to separately analyze antibody-dependent cell-mediated cytotoxicity (ADCC)-based and direct biological effects of the antibodies. Compared to monotherapy, combination of the two antibodies at clinically permitted doses enhanced the recruitment of natural killer cells responsible for ADCC, and significantly delayed the outgrowth of xenografts from intrinsically trastuzumab-resistant JIMT-1 cells. Antibody dose-response curves of in vitro ADCC showed that antibody-mediated killing can be saturated, and the two antibodies exert an additive effect at sub-saturation doses. Thus, the additive effect in vivo indicates that therapeutic tissue levels likely do not saturate ADCC. Additionally, isobole studies with the in vitro trastuzumab-sensitive BT-474 cells showed that the direct biological effect of combined treatment is additive, and surpasses the maximum effect of either monotherapy. Our results suggest the combined therapy is expected to give results that are superior to monotherapy, whatever the type of HER2-positive tumor may be. The combination of both antibodies at maximum clinically approved doses should thus be administered to patients to recruit maximum ADCC and cause maximum direct biological growth inhibition. PMID:27380003

  14. Mechanism of DMI resistance in field isolates of Cercospora beticola

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Leaf spot, caused by the fungus Cercospora beticola, is an endemic disease of sugarbeets in the North Dakota and Minnesota growing regions. Control measures against the fungus include resistant sugarbeet varieties and crop rotation, but the disease is managed effectively only when combined with tim...

  15. Autoimmune mechanisms in antibiotic treatment-resistant lyme arthritis.

    PubMed

    Steere, A C; Gross, D; Meyer, A L; Huber, B T

    2001-05-01

    In about 10% of patients with Lyme arthritis in the United States, joint inflammation persists for months or even several years after the apparent eradication of the spirochete, Borrelia burgdorferi, from the joint with antibiotic treatment. We propose a model of molecular mimicry affecting genetically susceptible individuals to explain this treatment-resistant course. The majority of patients with treatment-resistant Lyme arthritis have HLA-DRB1*0401 or related alleles, and the severity and duration of their arthritis correlate with cellular and humoral immune responses to outer-surface protein A OspA) of the spirochete. Using an algorithm, the immunodominant epitope of OspA presented by the DRB1*0401 molecule was predicted to be located at aa 165-173. In a search of the Genetics Computer Group gene bank, only one human protein was identified, lymphocyte function associated antigen-1 (hLFA-1), that had sequence homology with OspA(165-173)and predicted binding in the DRB1*0401 molecule. Synovial fluid T cells from most patients with treatment-resistant arthritis responded to both OspA and hLFA-1, whereas those from patients with other forms of chronic inflammatory arthritis did not. Molecular mimicry between a dominant T cell epitope of OspA and hLFA-1 may be an important factor in the persistence of joint inflammation in genetically susceptible patients with treatment-resistant Lyme arthritis.

  16. Insights into molecular mechanism of blast resistance in weedy rice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Weedy rice is a serious pest in direct-seeded rice fields in the U.S. and worldwide. Under suitable conditions, weedy rice can reduce crop yields up to 70%. However, weedy rice may carry novel disease resistance genes. Rice blast disease caused by the fungus Magnaporthe oryzae is a major disease wo...

  17. Molecular mechanisms of primary resistance to flucytosine in Candida albicans.

    PubMed

    Hope, William W; Tabernero, Lydia; Denning, David W; Anderson, Michael J

    2004-11-01

    Primary resistance in Candida albicans to flucytosine (5-FC) was investigated in 25 strains by identifying and sequencing the genes FCA1, FUR1, FCY21, and FCY22, which code for cytosine deaminase, uracil phosphoribosyltransferase (UPRT), and two purine-cytosine permeases, respectively. These proteins are involved in pyrimidine salvage and 5-FC metabolism. An association between a polymorphic nucleotide and resistance to 5-FC was found within FUR1 where the substitution of cytidylate for thymidylate at nucleotide position 301 results in the replacement of arginine with cysteine at amino acid position 101 in UPRT. Isolates that are homozygous for this mutation display increased levels of resistance to 5-FC, whereas heterozygous isolates have reduced susceptibility. Three-dimensional protein modeling of UPRT suggests that the Arg101Cys mutation disturbs the quaternary structure of the enzyme, which is postulated to compromise optimal enzyme activity. A single resistant isolate, lacking the above polymorphism in FUR1, has a homozygous polymorphism in FCA1 that results in a glycine-to-aspartate substitution at position 28 in cytosine deaminase.

  18. Evolution of amoxicillin resistance of Helicobacter pylori in vitro: characterization of resistance mechanisms.

    PubMed

    Qureshi, Nadia N; Gallaher, Brandon; Schiller, Neal L

    2014-12-01

    Helicobacter pylori is the major cause of peptic ulcers and gastric cancer in humans. Treatment involves a two or three drug cocktail, typically including amoxicillin. Increasing levels of resistance to amoxicillin contribute to treatment failures, and higher levels of resistance are believed to be due to multiple genetic mutations. In this study, we examined the progression of spontaneous genetic mutations that contribute to amoxicillin resistance in H. pylori when exposed to increasing concentrations of amoxicillin in vitro. During the selection process, we isolated five strains each of which had progressively higher levels of resistance. Using a whole genome sequencing approach, we identified mutations in a number of genes, notably pbp1, pbp2, hefC, hopC, and hofH, and by sequencing these genes in each isolate we were able to map the order and gradual accumulation of mutations in these isolates. These five isolates, each expressing multiple mutated genes and four transformed strains expressing individually mutated pbp1, hefC, or hofH, were characterized using minimum inhibitory concentrations, amoxicillin uptake, and efflux studies. Our results indicate that mutations in pbp1, hefC, hopC, hofH, and possibly pbp2 contribute to H. pylori high-level amoxicillin resistance. The data also provide evidence for the complexity of the evolution of amoxicillin resistance in H. pylori and indicate that certain families of genes might be more susceptible to amoxicillin resistance mutations than others. PMID:24901497

  19. Cisplatin Resistant Spheroids Model Clinically Relevant Survival Mechanisms in Ovarian Tumors

    PubMed Central

    Miller, Daniel H.; Medina, Jamie E.; Hamilton, Joshua W.; Messerli, Mark A.; Brodsky, Alexander S.

    2016-01-01

    The majority of ovarian tumors eventually recur in a drug resistant form. Using cisplatin sensitive and resistant cell lines assembled into 3D spheroids we profiled gene expression and identified candidate mechanisms and biological pathways associated with cisplatin resistance. OVCAR-8 human ovarian carcinoma cells were exposed to sub-lethal concentrations of cisplatin to create a matched cisplatin-resistant cell line, OVCAR-8R. Genome-wide gene expression profiling of sensitive and resistant ovarian cancer spheroids identified 3,331 significantly differentially expressed probesets coding for 3,139 distinct protein-coding genes (Fc >2, FDR < 0.05) (S2 Table). Despite significant expression changes in some transporters including MDR1, cisplatin resistance was not associated with differences in intracellular cisplatin concentration. Cisplatin resistant cells were significantly enriched for a mesenchymal gene expression signature. OVCAR-8R resistance derived gene sets were significantly more biased to patients with shorter survival. From the most differentially expressed genes, we derived a 17-gene expression signature that identifies ovarian cancer patients with shorter overall survival in three independent datasets. We propose that the use of cisplatin resistant cell lines in 3D spheroid models is a viable approach to gain insight into resistance mechanisms relevant to ovarian tumors in patients. Our data support the emerging concept that ovarian cancers can acquire drug resistance through an epithelial-to-mesenchymal transition. PMID:26986722

  20. Effect of yttrium addition on the microstructure and mechanical properties of ODS RAF steels

    NASA Astrophysics Data System (ADS)

    Auger, M. A.; de Castro, V.; Leguey, T.; Tarcísio-Costa, J.; Monge, M. A.; Muñoz, A.; Pareja, R.

    2014-12-01

    An oxide dispersion strengthened (ODS) alloy with nominal composition Fe-14Cr-2W-0.3Ti-0.24Y (wt.%) was produced by mechanical alloying using elemental powders, and subsequent hot isostatic pressing. The microstructure of the material and characteristics of the oxide particle dispersion were investigated by electron microscopy. The effect of heat treatments on the microhardness and tensile properties at room temperature was also studied. The results show that a fine dispersion of Y-O-rich nanoparticles is achieved, together with larger (Cr, Ti)-rich precipitates. The absence of Ti is apparent in the majority of these nanoparticles, in contrast with reported results for ODS Ti-modified steels processed with Y2O3 addition.

  1. Additive effect of alcohol and nicotine on lipid peroxidation and antioxidant defence mechanism in rats.

    PubMed

    Ashakumary, L; Vijayammal, P L

    1996-01-01

    Cigarette smoking has been established as a major risk factor for atherosclerosis and also for lung cancer. Nicotine is one of the major toxic components of cigarette smoke that is believed to be partly responsible for the deleterious effect of cigarette smoke. Alcohol intake is another major risk factor for the development of cardiovascular disease. Lipid peroxidation is a process associated with the pathogenesis of atherosclerosis. The concentration of lipid peroxides is found to be increased in alcohol-treated rats. On nicotine administration along with alcohol, an additive effect was observed in lipid peroxidation and the antioxidant defence mechanism. The activity of scavenging enzymes superoxide dismutase, catalase and glutathione reductase was found to be decreased, while the activity of glutathione peroxidase and the concentration of glutathione were increased. PMID:8854216

  2. Allium fistulosum as a novel system to investigate mechanisms of freezing resistance.

    PubMed

    Tanino, Karen K; Kobayashi, Shion; Hyett, Craig; Hamilton, Kaila; Liu, Jun; Li, Bin; Borondics, Ferenc; Pedersen, Tor; Tse, John; Ellis, Tom; Kawamura, Yukio; Uemura, Matsuo

    2013-01-01

    Allium fistulosum was investigated as a novel model system to examine the mechanism of freezing resistance in cold hardy plants. The 250 × 50 × 90 µm average cell size and single epidermal cell layer system allowed direct observation of endoplasmic reticulum (ER), functional group localization during acclimation, freezing and thawing on an individual cell basis in live intact tissues. Cells increased freezing resistance from an LT50 of -11°C (non-acclimated) to -25°C under 2 weeks of cold acclimation. Samples were processed using Fourier transform infrared technology (FTIR) on a synchrotron light source and a focal plane array detector. In addition, confocal fluorescent microscopy combined with a cryostage using ER selective dye of ER-Tracker allowed more detailed examination of membrane responses during freezing. Cold acclimation increased the ER volume per cell, and the freeze-induced cell deformation stopped ER streaming and ER vesiculation subsequently occurred through the breakdown in the ER network. Freeze-induced ER vesicles in cold-acclimated cells were larger and more abundant than those in non-acclimated cells. According to FTIR, the carbohydrate/ester fraction and α-helical/β-sheet secondary structure localized in the apoplast/plasma membrane region were most visibly increased during cold acclimation. Results suggest the mechanism of cold acclimation and freezing resistance in very hardy cells may be associated with both alterations in the apoplast/plasma membrane region and the ER cryodynamics. Allium fistulosum appears to be a useful system to obtain direct evidence at both intra and extracellular levels during cold acclimation and the freezing process. PMID:23078395

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

    PubMed

    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

  4. 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

  5. Resistance to sunitinib in renal cell carcinoma: From molecular mechanisms to predictive markers and future perspectives.

    PubMed

    Joosten, S C; Hamming, L; Soetekouw, P M; Aarts, M J; Veeck, J; van Engeland, M; Tjan-Heijnen, V C

    2015-01-01

    The introduction of agents that inhibit tumor angiogenesis by targeting vascular endothelial growth factor (VEGF) signaling has made a significant impact on the survival of patients with metastasized renal cell carcinoma (RCC). Sunitinib, a tyrosine kinase inhibitor of the VEGF receptor, has become the mainstay of treatment for these patients. Although treatment with sunitinib substantially improved patient outcome, the initial success is overshadowed by the occurrence of resistance. The mechanisms of resistance are poorly understood. Insight into the molecular mechanisms of resistance will help to better understand the biology of RCC and can ultimately aid the development of more effective therapies for patients with this infaust disease. In this review we comprehensively discuss molecular mechanisms of resistance to sunitinib and the involved biological processes, summarize potential biomarkers that predict response and resistance to treatment with sunitinib, and elaborate on future perspectives in the treatment of metastasized RCC. PMID:25446042

  6. Mechanically tunable aspheric lenses via additive manufacture of hanging elastomeric droplets for microscopic applications

    NASA Astrophysics Data System (ADS)

    Fuh, Yiin-Kuen; Chen, Pin-Wen; Lai, Zheng-Hong

    2016-07-01

    Mechanically deformable lenses with dynamically tunable focal lengths have been developed in this work. The fabricated five types of aspheric polydimethylsiloxane (PDMS) lenses presented here have an initial focal length of 7.0, 7.8, 9.0, 10.0 and 10.2 mm. Incorporating two modes of operation in biconvex and concave-convex configurations, the focal lengths can be tuned dynamically as 5.2-10.2, 5.5-9.9, 6.6-11.9, 6.1-13.5 and 6.6-13.5 mm respectively. Additive manufacturing was utilized to fabricate these five types of aspheric lenses (APLs) via sequential layering of PDMS materials. Complex structures with three-dimensional features and shorter focal lengths can be successfully produced by repeatedly depositing, inverting and curing controlled PDMS volume onto previously cured PDMS droplets. From our experiments, we empirically found a direct dependence of the focal length of the lenses with the amount (volume) of deposited PDMS droplets. This new mouldless, low-cost, and flexible lens fabrication method is able to transform an ordinary commercial smartphone camera into a low-cost portable microscope. A few microscopic features can be readily visualized, such as wrinkles of ladybird pupa and printed circuit board. The fabrication technique by successively applying hanging droplet and facile mechanical focal-length-tuning set-up can be easily adopted in the development of high-performance optical lenses.

  7. Effect of addition of semi refined carrageenan on mechanical characteristics of gum arabic edible film

    NASA Astrophysics Data System (ADS)

    Setyorini, D.; Nurcahyani, P. R.

    2016-04-01

    Currently the seaweed is processed flour and Semi Refined Carraagenan (SRC). However, total production is small, but both of these products have a high value and are used in a wide variety of products such as cosmetics, processed foods, medicines, and edible film. The aim of this study were (1) to determine the effect of SRC on mechanical characteristics of edible film, (2) to determine the best edible film which added by SRC with different concentration. The edible film added by SRC flour which divided into three concentrations of SRC. There are 1.5%; 3%; and 4.5% of SRC, then added 3% glycerol and 0.6% arabic gum. The mechanical properties of the film measured by a universal testing machine Orientec Co. Ltd., while the water vapor permeability measured by the gravimetric method dessicant modified. The experimental design used was completely randomized design with a further test of Duncan. The result show SRC concentration differences affect the elongation breaking point and tensile strength. But not significant effect on the thickness, yield strength and the modulus of elasticity. The best edible film is edible film with the addition of SRC 4.5%.

  8. Mechanical characterization of an additively manufactured Inconel 718 theta-shaped specimen

    SciTech Connect

    Cakmak, Ercan; Watkins, Thomas R.; Bunn, Jeffrey R.; Cornwell, Paris A.; Wang, Yanli; Dehoff, Ryan R.; Babu, Sudarsanam Suresh; Sochalski-Kolbus, Lindsay M.

    2015-11-20

    Two sets of “theta”-shaped specimens were additively manufactured with Inconel 718 powders using an electron beam melting technique with two distinct scan strategies. Light optical microscopy, mechanical testing coupled with a digital image correlation (DIC) technique, finite element modeling, and neutron diffraction with in situ loading characterizations were conducted. The cross-members of the specimens were the focus. Light optical micrographs revealed that different microstructures were formed with different scan strategies. Ex situ mechanical testing revealed each build to be stable under load until ductility was observed on the cross-members before failure. The elastic moduli were determined by forming a correlation between the elastic tensile stresses determined from FEM, and the elastic strains obtained from DIC. The lattice strains were mapped with neutron diffraction during in situ elastic loading; and a good correlation between the average axial lattice strains on the cross-member and those determined from the DIC analysis was found. Lastly, the spatially resolved stresses in the elastic deformation regime are derived from the lattice strains and increased with applied load, showing a consistent distribution along the cross-member.

  9. Mechanical characterization of an additively manufactured Inconel 718 theta-shaped specimen

    DOE PAGES

    Cakmak, Ercan; Watkins, Thomas R.; Bunn, Jeffrey R.; Cornwell, Paris A.; Wang, Yanli; Dehoff, Ryan R.; Babu, Sudarsanam Suresh; Sochalski-Kolbus, Lindsay M.

    2015-11-20

    Two sets of “theta”-shaped specimens were additively manufactured with Inconel 718 powders using an electron beam melting technique with two distinct scan strategies. Light optical microscopy, mechanical testing coupled with a digital image correlation (DIC) technique, finite element modeling, and neutron diffraction with in situ loading characterizations were conducted. The cross-members of the specimens were the focus. Light optical micrographs revealed that different microstructures were formed with different scan strategies. Ex situ mechanical testing revealed each build to be stable under load until ductility was observed on the cross-members before failure. The elastic moduli were determined by forming a correlationmore » between the elastic tensile stresses determined from FEM, and the elastic strains obtained from DIC. The lattice strains were mapped with neutron diffraction during in situ elastic loading; and a good correlation between the average axial lattice strains on the cross-member and those determined from the DIC analysis was found. Lastly, the spatially resolved stresses in the elastic deformation regime are derived from the lattice strains and increased with applied load, showing a consistent distribution along the cross-member.« less

  10. Microstructures, mechanical properties and corrosion resistances of extruded Mg-Zn-Ca-xCe/La alloys.

    PubMed

    Tong, L B; Zhang, Q X; Jiang, Z H; Zhang, J B; Meng, J; Cheng, L R; Zhang, H J

    2016-09-01

    Magnesium alloys are considered as good candidates for biomedical applications, the influence of Ce/La microalloying on the microstructure, mechanical property and corrosion performance of extruded Mg-5.3Zn-0.6Ca (wt%) alloy has been investigated in the current study. After Ce/La addition, the conventional Ca2Mg6Zn3 phases are gradually replaced by new Mg-Zn-Ce/La-(Ca) phases (T1'), which can effectively divide the Ca2Mg6Zn3 phase. The Ca2Mg6Zn3/T1' structure in Mg-Zn-Ca-0.5Ce/La alloy is favorably broken into small particles during the extrusion, resulting in an obvious refinement of secondary phase. The dynamic recrystallized grain size is dramatically decreased after 0.5Ce/La addition, and the tensile yield strength is improved, while further addition reverses the effect, due to the grain coarsening. However, the corrosion resistance of extruded Mg-Zn-Ca alloy deteriorates after Ce/La addition, because the diameter of secondary phase particle is remarkably decreased, which increases the amount of cathodic sites and accelerates the galvanic corrosion process. PMID:27179307

  11. Microstructures, mechanical properties and corrosion resistances of extruded Mg-Zn-Ca-xCe/La alloys.

    PubMed

    Tong, L B; Zhang, Q X; Jiang, Z H; Zhang, J B; Meng, J; Cheng, L R; Zhang, H J

    2016-09-01

    Magnesium alloys are considered as good candidates for biomedical applications, the influence of Ce/La microalloying on the microstructure, mechanical property and corrosion performance of extruded Mg-5.3Zn-0.6Ca (wt%) alloy has been investigated in the current study. After Ce/La addition, the conventional Ca2Mg6Zn3 phases are gradually replaced by new Mg-Zn-Ce/La-(Ca) phases (T1'), which can effectively divide the Ca2Mg6Zn3 phase. The Ca2Mg6Zn3/T1' structure in Mg-Zn-Ca-0.5Ce/La alloy is favorably broken into small particles during the extrusion, resulting in an obvious refinement of secondary phase. The dynamic recrystallized grain size is dramatically decreased after 0.5Ce/La addition, and the tensile yield strength is improved, while further addition reverses the effect, due to the grain coarsening. However, the corrosion resistance of extruded Mg-Zn-Ca alloy deteriorates after Ce/La addition, because the diameter of secondary phase particle is remarkably decreased, which increases the amount of cathodic sites and accelerates the galvanic corrosion process.

  12. Systematic investigation of the synthesis, characterization and switching mechanism of metal oxide nanoparticle resists

    NASA Astrophysics Data System (ADS)

    Siauw, Meiliana; Du, Ke; Valade, David; Trefonas, Peter; Thackeray, James W.; Whittaker, Andrew; Blakey, Idriss

    2016-03-01

    Metal oxide nanoparticle resists have recently emerged as next generation photoresist materials which exhibit promising performance for extreme ultraviolet lithography. In this present work, we are able to show our ability to synthesize and well characterize small uniform metal oxide nanoparticles, to present stability study of the nanoparticles in the resist solvent over time, to pattern ~20 nm features by electron beam lithography, and to provide an insight into the insolubilization mechanism of the resist system.

  13. Effects of nitrogen addition on microstructure and mechanical behavior of biomedical Co-Cr-Mo alloys.

    PubMed

    Yamanaka, Kenta; Mori, Manami; Chiba, Akihiko

    2014-01-01

    In the present study, the microstructures and tensile deformation behaviors of biomedical Co-29Cr-6Mo (wt%) alloys containing different concentrations of nitrogen (0-0.24wt%) were systematically investigated. As the nitrogen concentration increased, the volume fraction of athermal ε martensite decreased, because nanoprecipitates hindered the formation of stacking faults (SFs) by acting as obstacles to Shockley partial dislocation formation, and athermal ε martensite usually forms through the regular overlapping of SFs. The formation of the athermal ε martensite was completely suppressed when the nitrogen concentration exceeded 0.10wt%, resulting in a simultaneous improvement in the strength and ductility of the alloys. It was found that the glide of the Shockley partial dislocations and the strain-induced γ (fcc)→ε (hcp) martensitic transformation (SIMT) operated as the primary deformation mechanisms. However, adding nitrogen reduced the work hardening by suppressing the formation of the SFs and preventing the SIMT from taking place. This resulted in an intrinsic decrease in the tensile ductility of the alloys. It is also shown that all the alloys exhibited premature fractures owing to the SIMT. The formation of annealing twins in the γ grains is found to be enhanced by nitrogen addition and to promote the SIMT, resulting in a reduction in the elongation-to-failure due to nitrogen addition. These results should aid in the design of alloys that contain nitrogen.

  14. Mechanisms on electrical breakdown strength increment of polyethylene by aromatic carbonyl compounds addition: a theoretical study.

    PubMed

    Zhang, Hui; Shang, Yan; Wang, Xuan; Zhao, Hong; Han, Baozhong; Li, Zesheng

    2013-12-01

    A theoretical investigation is accomplished on the mechanisms of electrical breakdown strength increment of polyethylene at the atomic and molecular levels. It is found that the addition of aromatic carbonyl compounds as voltage stabilizers is one of the important factors for increasing electrical breakdown strength of polyethylene, as the additives can trap hot electrons, obtain energy of hot electrons, and transform the aliphatic cation to relatively stable aromatic cation to prevent the degradation of the polyethylene matrix. The HOMO-LUMO energy gaps (E(g)), the ionization potentials (IPs), and electron affinities (EAs) at the ground states of a series of aromatic carbonyl compounds are obtained at the B3LYP/6-311+G(d,p) level. The theoretical results are in good agreement with the available experimental findings, show that 2,4-dioctyloxybenzophenone (Bzo) and 4,4'-didodecyloxybenzil (Bd) molecules can effectively increase the electrical breakdown strength when they are doped into polyethylene because of their much smaller E g values than all the other studied aromatic carbonyl molecules and excellent compatibility with polymers matrix.

  15. Effects of Ga and Sn Additions on the Creep Strength and Oxidation Resistance of Near-α Ti Alloys

    NASA Astrophysics Data System (ADS)

    Kitashima, Tomonori; Yamabe-Mitarai, Yoko; Iwasaki, Satoshi; Kuroda, Shuji

    2016-09-01

    The effects of Ga and Sn additions, with an almost constant value regarding Al equivalence, on the creep properties and oxidation resistance of the near-α Ti alloy Ti-5Al-4Zr-1Mo were investigated. The creep strain rate increased due to the replacement of Sn with Ga, which was accompanied by an increase in the volume fraction of primary equiaxed α phase. In addition, the replacement of Sn with Ga decreased the activation energy of the steady-state creep rate for the similar volume fraction of the equiaxed α phase. Ga addition improved the oxidation resistance without Ga segregation at the TiO2/substrate interface, whereas Sn promoted oxide spallation with metallic Sn segregation at the interface. Ga uniformly dissolved into the internal TiO2 and into the external Al2O3 as a result of solid solution formation between Ga2O3 and the aforementioned oxides, which suppressed oxide growth. The formation of (GaAl)2TiO5 in TiO2 and Al2O3 was also discussed on the basis of the phase relationships in the TiO2-Al2O3-Ga2O3 system.

  16. Mechanisms of action of systemic antibiotics used in periodontal treatment and mechanisms of bacterial resistance to these drugs

    PubMed Central

    SOARES, Geisla Mary Silva; FIGUEIREDO, Luciene Cristina; FAVERI, Marcelo; CORTELLI, Sheila Cavalca; DUARTE, Poliana Mendes; FERES, Magda

    2012-01-01

    Antibiotics are important adjuncts in the treatment of infectious diseases, including periodontitis. The most severe criticisms to the indiscriminate use of these drugs are their side effects and, especially, the development of bacterial resistance. The knowledge of the biological mechanisms involved with the antibiotic usage would help the medical and dental communities to overcome these two problems. Therefore, the aim of this manuscript was to review the mechanisms of action of the antibiotics most commonly used in the periodontal treatment (i.e. penicillin, tetracycline, macrolide and metronidazole) and the main mechanisms of bacterial resistance to these drugs. Antimicrobial resistance can be classified into three groups: intrinsic, mutational and acquired. Penicillin, tetracycline and erythromycin are broad-spectrum drugs, effective against gram-positive and gram-negative microorganisms. Bacterial resistance to penicillin may occur due to diminished permeability of the bacterial cell to the antibiotic; alteration of the penicillin-binding proteins, or production of β-lactamases. However, a very small proportion of the subgingival microbiota is resistant to penicillins. Bacteria become resistant to tetracyclines or macrolides by limiting their access to the cell, by altering the ribosome in order to prevent effective binding of the drug, or by producing tetracycline/macrolide-inactivating enzymes. Periodontal pathogens may become resistant to these drugs. Finally, metronidazole can be considered a prodrug in the sense that it requires metabolic activation by strict anaerobe microorganisms. Acquired resistance to this drug has rarely been reported. Due to these low rates of resistance and to its high activity against the gram-negative anaerobic bacterial species, metronidazole is a promising drug for treating periodontal infections. PMID:22858695

  17. Chronic Myeloid Leukemia – Mechanisms of Resistance and Treatment

    PubMed Central

    Jabbour, Elias; Parikh, Sameer A.; Kantarjian, Hagop; Cortes, Jorge

    2015-01-01

    Imatinib mesylate has revolutionized the treatment landscape for patients with newly diagnosed chronic myeloid leukemia (CML). Imatinib at a dose of 400 mg/day is considered the standard treatment for all newly diagnosed chronic phase CML. Follow-up on the pivotal International Randomized Study of Interfreron versus STI571 (IRIS) study has shown excellent response rates, progression-free survival and overall survival after 8 years of follow-up. However, some patients will develop resistance to imatinib treatment due to a multitude of reasons. Numerous strategies to overcome resistance are available including dose escalation of imatinib, switching to a second generation tyrosine kinase inhibitor or to one of the newer non-tyrosine kinase inhibitors. This review guides the treating physician with a rational approach in the management of CML patients who fail initial treatment with imatinib or lose response while on therapy with imatinib. PMID:22054730

  18. Effectiveness of Antipseudomonal Antibiotics and Mechanisms of Multidrug Resistance in Pseudomonas aeruginosa.

    PubMed

    El ZOWALATYl, Mohamed E; Gyetvaii, Bpla

    2016-01-01

    Pseudomonas aeruginosa is a leading human pathogen that causes serious infections at various tissues and organs leading to life threatening health problems and possible deadly outcomes. Resistance patterns vary widely whether it is from hospitals or community acquired infections. Reporting resistance profiles to a certain antibiotics provide valuable information in a given setting, but may be extrapolated outside the sampling location. In the present study, P. aeruginosa isolates were screened to determine their susceptibilities against anti-pseudomonal antimicrobial agents and possible existing mechanisms of resistance were determined. Eighty-six isolates of P. aeruginosa were recovered. Isolates representing different resistance profiles were screened for the existence of three different resistance mechanisms including drug inactivation due to metallo-β-lactamases, drug impermeability by outer membrane proteins and drug efflux. All tested isolates showed uniform susceptibility (100%, n = 86/86) to piperacillin, meropenem, amikacin, and polymyxin B. A single isolate was found to be imipenem resistant (99%, n = 85/86). The possible mechanisms of resistance of P. aeruginosa to imipenem involve active drug efflux pumps, outer membrane impermeability as well as drug inactivating enzymes. These findings demonstrate the fundamental importance of the in vitro susceptibility testing of antibiotics prior to antipseudomonal therapy and highlight the need for a continuous antimicrobial resistance surveillance programs to monitor the changing resistance patterns so that clinicians and health care officials are updated as to the most effective therapeutic agents to combat the serious outcomes of P. aeruginosa infections.

  19. Burn-resistant behavior and mechanism of Ti14 alloy

    NASA Astrophysics Data System (ADS)

    Chen, Yong-nan; Huo, Ya-zhou; Song, Xu-ding; Bi, Zhao-zhao; Gao, Yang; Zhao, Yong-qing

    2016-02-01

    The direct-current simulation burning method was used to investigate the burn-resistant behavior of Ti14 titanium alloy. The results show that Ti14 alloy exhibits a better burn resistance than TC4 alloy (Ti-6Al-4V). Cu is observed to preferentially migrate to the surface of Ti14 alloy during the burning reaction, and the burned product contains Cu, Cu2O, and TiO2. An oxide layer mainly comprising loose TiO2 is observed beneath the burned product. Meanwhile, Ti2Cu precipitates at grain boundaries near the interface of the oxide layer, preventing the contact between O2 and Ti and forming a rapid diffusion layer near the matrix interface. Consequently, a multiple-layer structure with a Cu-enriched layer (burned product)/Cu-lean layer (oxide layer)/Cu-enriched layer (rapid diffusion layer) configuration is formed in the burn heat-affected zone of Ti14 alloy; this multiple-layer structure is beneficial for preventing O2 diffusion. Furthermore, although Al can migrate to form Al2O3 on the surface of TC4 alloy, the burn-resistant ability of TC4 is unimproved because the Al2O3 is discontinuous and not present in sufficient quantity.

  20. [Antithrombin resistance: a new mechanism of inherited thrombophilia].

    PubMed

    Kojima, Tetsuhito; Takagi, Akira; Murata, Moe; Takagi, Yuki

    2015-06-01

    Venous thromboembolism is a multifactorial disease resulting from complex interactions among genetic and environmental factors. To date, numerous genetic defects have been found in families with hereditary thrombophilia, but there may still be many undiscovered causative gene mutations. We investigated a possible causative gene defect in a large Japanese family with inherited thrombophilia, and found a novel missense mutation in the prothrombin gene (p.Arg596Leu) resulting in a variant prothrombin (prothrombin Yukuhashi). The mutant prothrombin had moderately lower activity than wild type prothrombin in clotting assays, but formation of the thrombin-antithrombin (TAT) complex was substantially impaired resulting in prolonged thrombin activity. A thrombin generation assay revealed that the peak activity of the mutant prothrombin was fairly low, but its inactivation was extremely slow in reconstituted plasma. The Leu596 substitution caused a gain-of-function mutation in the prothrombin gene, resulting in resistance to antithrombin and susceptibility to thrombosis. We also showed the effects of the prothrombin Yukuhashi mutation on the thrombomodulin-protein C anticoagulation system, recent development of a laboratory test detecting antithrombin resistance in plasma, and another antithrombin resistant mutation found in other thrombophilia families. PMID:26256872

  1. Antimicrobial susceptibility and mechanisms of resistance to quinolones and beta-lactams in Acinetobacter genospecies 3.

    PubMed

    Ribera, A; Fernández-Cuenca, F; Beceiro, A; Bou, G; Martínez-Martínez, L; Pascual, A; Cisneros, J M; Rodríguez-Baño, J; Pachón, J; Vila, J

    2004-04-01

    Antimicrobial susceptibility was determined in 15 epidemiologically unrelated clinical isolates of Acinetobacter genospecies 3. Moreover, the mechanisms of resistance to some beta-lactam antibiotics may be associated with the presence of a chromosomal cephalosporinase, AmpC, and the resistance to quinolones related to mutations in the gyrA and parC genes.

  2. Antimicrobial Susceptibility and Mechanisms of Resistance to Quinolones and β-Lactams in Acinetobacter Genospecies 3

    PubMed Central

    Ribera, A.; Fernández-Cuenca, F.; Beceiro, A.; Bou, G.; Martínez-Martínez, L.; Pascual, A.; Cisneros, J. M.; Rodríguez-Baño, J.; Pachón, J.; Vila, J.

    2004-01-01

    Antimicrobial susceptibility was determined in 15 epidemiologically unrelated clinical isolates of Acinetobacter genospecies 3. Moreover, the mechanisms of resistance to some β-lactam antibiotics may be associated with the presence of a chromosomal cephalosporinase, AmpC, and the resistance to quinolones related to mutations in the gyrA and parC genes. PMID:15047561

  3. The Role of Translocation as a Mechanism of Resistance to Glyphosate

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The continuous use of glyphosate has resulted in the selection of resistant biotypes in 13 different weed species. Three different mechanisms of resistance have been proposed for these biotypes: 1) Decreased translocation to meristems; 2) Mutation of target site 5-enol-pyruvylshikimate-3-phosphate ...

  4. Mechanisms of Stress Resistance and Gene Regulation in the Radioresistant Bacterium Deinococcus radiodurans.

    PubMed

    Agapov, A A; Kulbachinskiy, A V

    2015-10-01

    The bacterium Deinococcus radiodurans reveals extraordinary resistance to ionizing radiation, oxidative stress, desiccation, and other damaging conditions. In this review, we consider the main molecular mechanisms underlying such resistance, including the action of specific DNA repair and antioxidation systems, and transcription regulation during the anti-stress response.

  5. An additional set of phages to characterize epidemic methicillin-resistant Staphylococcus aureus strains from Spain (1989-92).

    PubMed

    Vindel, A; Trincado, P; Gomez, E; Aparicio, P; Martin de Nicolas, M; Boquete, T; Saez Nieto, J A

    1994-04-01

    In recent years, methicillin-resistant Staphylococcus aureus (MRSA) isolates in Spain have increased dramatically; in 1986 there were only 1.2% MRSA amongst all nosocomial Staphylococcus aureus (SA) isolates, by 1989 this percentage had risen to 44% in some hospital causing a very serious epidemic situation in the country. We have characterized these isolates by direct, reverse and Fisk phage typing and we have also looked for an additional local set of phages to help us to differentiate these strains. We have been able to differentiate an epidemic strain from other MRSA strains which cause sporadic hospital outbreaks, and we have also distinguished between some variants of the epidemic strain.

  6. Beyond Mutations: Additional Mechanisms and Implications of SWI/SNF Complex Inactivation

    PubMed Central

    Marquez, Stefanie B.; Thompson, Kenneth W.; Lu, Li; Reisman, David

    2015-01-01

    SWI/SNF is a major regulator of gene expression. Its role is to facilitate the shifting and exposure of DNA segments within the promoter and other key domains to transcription factors and other essential cellular proteins. This complex interacts with a wide range of proteins and does not function within a single, specific pathway; thus, it is involved in a multitude of cellular processes, including DNA repair, differentiation, development, cell adhesion, and growth control. Given SWI/SNF’s prominent role in these processes, many of which are important for blocking cancer development, it is not surprising that the SWI/SNF complex is targeted during cancer initiation and progression both by mutations and by non-mutational mechanisms. Currently, the understanding of the types of alterations, their frequency, and their impact on the SWI/SNF subunits is an area of intense research that has been bolstered by a recent cadre of NextGen sequencing studies. These studies have revealed mutations in SWI/SNF subunits, indicating that this complex is thus important for cancer development. The purpose of this review is to put into perspective the role of mutations versus other mechanisms in the silencing of SWI/SNF subunits, in particular, BRG1 and BRM. In addition, this review explores the recent development of synthetic lethality and how it applies to this complex, as well as how BRM polymorphisms are becoming recognized as potential clinical biomarkers for cancer risk. Significance: Recent reviews have detailed the occurrence of mutations in nearly all SWI/SNF subunits, which indicates that this complex is an important target for cancer. However, when the frequency of mutations in a given tumor type is compared to the frequency of subunit loss, it becomes clear that other non-mutational mechanisms must play a role in the inactivation of SWI/SNF subunits. Such data indicate that epigenetic mechanisms that are known to regulate BRM may also be involved in the loss of

  7. Molecular epidemiology and mechanisms of carbapenem resistance in Pseudomonas aeruginosa isolates from Chinese hospitals.

    PubMed

    Wang, Jie; Zhou, Jian-ying; Qu, Ting-ting; Shen, Ping; Wei, Ze-qing; Yu, Yun-song; Li, Lan-juan

    2010-05-01

    We investigated the molecular epidemiology and carbapenem resistance mechanisms of 258 non-duplicate carbapenem-resistant clinical isolates of Pseudomonas aeruginosa collected from 2006 to 2007 at 28 hospitals in China. Up to 88% of the carbapenem-resistant isolates were multidrug-resistant. Pulsed-field gel electrophoresis (PFGE) revealed that levels of intrahospital and interhospital dissemination of clones were low. To assess the mechanisms leading to resistance, all 258 carbapenem-resistant isolates were analysed for expression of the chromosomal beta-lactamase (AmpC), the porin important for entry of carbapenems (OprD) and an efflux system (MexAB-OprM) known to extrude some beta-lactams. Carbapenem resistance was driven mainly by mutational inactivation of OprD, accompanied or not by hyperexpression of AmpC or MexAB-OprM. Metallo-beta-lactamase genes were detected in 22 carbapenem-resistant isolates in China, belonging to eight pulsotypes. The bla(OXA-50) gene was detected among all of the carbapenem-resistant isolates, whereas the bla(GES-5) gene was detected in only one carbapenem-resistant isolate.

  8. Investigation of vibroshock stability of a mechanical contact by measurement of its resistance

    NASA Technical Reports Server (NTRS)

    Butsevichyus, S. G.; Zaretskas, V. S. S.

    1973-01-01

    Experimental results on the vibration and impact strength of a contact junction are presented, using contact resistance measurement. The contact pressure, condition, and cleanliness of surfaces are also considered, as well as the type and intensity of mechanical action.

  9. Brittle Fracture Resistance of Chinga Ataxite at Different Mechanical Loading Conditions

    NASA Astrophysics Data System (ADS)

    Grokhovsky, V. I.; Gladkovsky, S. V.

    2016-08-01

    In this study comparative results of Chinga meteorite material fracture resistance evaluation at different test temperatures and loading conditions using fracture mechanics approach as well as fractographic data analysis are presented.

  10. Diverse drug-resistance mechanisms can emerge from drug-tolerant cancer persister cells

    PubMed Central

    Ramirez, Michael; Rajaram, Satwik; Steininger, Robert J.; Osipchuk, Daria; Roth, Maike A.; Morinishi, Leanna S.; Evans, Louise; Ji, Weiyue; Hsu, Chien-Hsiang; Thurley, Kevin; Wei, Shuguang; Zhou, Anwu; Koduru, Prasad R.; Posner, Bruce A.; Wu, Lani F.; Altschuler, Steven J.

    2016-01-01

    Cancer therapy has traditionally focused on eliminating fast-growing populations of cells. Yet, an increasing body of evidence suggests that small subpopulations of cancer cells can evade strong selective drug pressure by entering a ‘persister' state of negligible growth. This drug-tolerant state has been hypothesized to be part of an initial strategy towards eventual acquisition of bona fide drug-resistance mechanisms. However, the diversity of drug-resistance mechanisms that can expand from a persister bottleneck is unknown. Here we compare persister-derived, erlotinib-resistant colonies that arose from a single, EGFR-addicted lung cancer cell. We find, using a combination of large-scale drug screening and whole-exome sequencing, that our erlotinib-resistant colonies acquired diverse resistance mechanisms, including the most commonly observed clinical resistance mechanisms. Thus, the drug-tolerant persister state does not limit—and may even provide a latent reservoir of cells for—the emergence of heterogeneous drug-resistance mechanisms. PMID:26891683

  11. Investigation into the hydrogen gas sensing mechanism of cubic silicon carbide resistive gas sensors

    NASA Astrophysics Data System (ADS)

    Fawcett, Timothy J.

    The hydrogen (H2) gas sensing mechanism driving 3C-SiC resistive gas sensors is investigated in this work in which two hypotheses are proposed. One hypothesis involves the surface adsorption of H2 on the sensor surface with the adsorbed molecules influencing the flow of current in a resistive gas sensor, termed the surface adsorption detection mechanism. The second hypothesis includes the transfer of heat from the sensor to the gas, producing a change in the temperature of the device when the heat transfer characteristics of the gas change, termed the thermal detection mechanism. The heat transfer characteristics of the gas are dependent on the thermal conductivity of the gas, a property which is a strong function of gas composition. Thus, the thermal detection mechanism mainly detects changes in the thermal conductivity of a gas or gas mixture. Initial experiments suggested the surface adsorption mechanism as the detection mechanism of resistive 3C-SiC gas sensors. However, these experiments were performed in the absence of device temperature measurements. Recent experiments in which the device temperature was measured with a resistance temperature detector (RTD) in thermal contact with the device strongly support the thermal detection mechanism as being responsible for hydrogen gas detection. Experimental observations show the temperature of the resistive 3C-SiC hydrogen gas sensors changes greatly with changing hydrogen gas composition. For example, a 3C-SiC/SOI resistive sensor biased at 10 Vdc displayed a change in temperature from ˜400°C to ˜216°C, correlating to a change in current from ˜41 mA to ˜6mA, upon the introduction of 100% H2. The this 3C-SiC/SOI resistive sensor, this large decrease in temperature caused a large increase in resistance which is detected as a decrease in current. Several different experiments have also been performed to confirm the thermal detection mechanism hypothesis.

  12. Detection of a second mechanism of resistance to gentamicin in animal strains of Escherichia coli.

    PubMed Central

    Chaslus-Dancla, E; Gerbaud, G; Martel, J L; Lagorce, M; Lafont, J P; Courvalin, P

    1987-01-01

    One mechanism of plasmid-mediated resistance to gentamicin in Escherichia coli strains isolated from animals is due to the synthesis of the aminoglycoside 3-N-acetyltransferase type IV. A second mechanism of plasmid-mediated resistance to gentamicin was detected in animal strains of E. coli in France and is due to the production of the aminoglycoside 3-N-acetyltransferase type II. The molecular relationships among plasmids encoding this enzyme were studied. Images PMID:3307622

  13. Casein films: effects of formulation, environmental conditions, and addition of citric pectin on the structure and mechanical properties

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Thin casein films for food packaging applications reportedly possess good strength and low oxygen permeability, but low water-resistance and elasticity. Modifying and customizing the mechanical properties of the films to target specific behaviors depending on environmental conditions would enable a...

  14. Azole-resistant Aspergillus fumigatus in Denmark: a laboratory-based study on resistance mechanisms and genotypes.

    PubMed

    Jensen, R H; Hagen, F; Astvad, K M T; Tyron, A; Meis, J F; Arendrup, M C

    2016-06-01

    Azole-resistant Aspergillus fumigatus originating from the environment as well as induced during therapy are continuously emerging in Danish clinical settings. We performed a laboratory-based retrospective study (2010-2014) of azole resistance and genetic relationship of A. fumigatus at the national mycology reference laboratory of Denmark. A total of 1162 clinical and 133 environmental A. fumigatus isolates were identified by morphology, thermotolerance and/or β-tubulin sequencing. Screening for azole resistance was carried out using azole agar, and resistant isolates were susceptibility tested by the EUCAST (European Committee on Antimicrobial Susceptibility Testing) E.Def 9.2 reference method and CYP51A sequenced. Genotyping was performed for outbreak investigation and, when appropriate, short tandem repeat Aspergillus fumigatus microsatellite assay. All 133 environmental A. fumigatus isolates were azole susceptible. However, from 2010 to 2014, there was an increasing prevalence of azole resistance (from 1.4 to 6% isolates (p <0.001) and 1.8 to 4% patients (p <0.05)) among the clinical isolates, with the well-known environmental CYP51A variant TR34/L98H responsible for >50% of the azole resistance mechanisms. Among 184 Danish A. fumigatus isolates, 120 unique genotypes were identified and compared to a collection of 1822 international genotypes. Seven (5.8%) Danish genotypes were shared between isolates within Denmark but with different origin, 19 (15.8%) were shared with foreign genotypes, and two (11.8%) of 17 genotypes of isolates carrying the TR34/L98H resistance mechanisms were identical to two Dutch TR34/L98H isolates. Our findings underlines the demand for correct identification and susceptibility testing of clinical mould isolates. Furthermore, although complex, genotyping supported the hypotheses regarding clonal expansion and the potential of a single origin for the TR34/L98H clone. PMID:27091095

  15. Progression from high insulin resistance to type 2 diabetes does not entail additional visceral adipose tissue inflammation.

    PubMed

    Barbarroja, Nuria; Lopez-Pedrera, Chary; Garrido-Sanchez, Lourdes; Mayas, Maria Dolores; Oliva-Olivera, Wilfredo; Bernal-Lopez, Maria Rosa; El Bekay, Rajaa; Tinahones, Francisco Jose

    2012-01-01

    Obesity is associated with a low-grade chronic inflammation state. As a consequence, adipose tissue expresses pro-inflammatory cytokines that propagate inflammatory responses systemically elsewhere, promoting whole-body insulin resistance and consequential islet β-cell exhaustation. Thus, insulin resistance is considered the early stage of type 2 diabetes. However, there is evidence of obese individuals that never develop diabetes indicating that the mechanisms governing the association between the increase of inflammatory factors and type 2 diabetes are much more complex and deserve further investigation. We studied for the first time the differences in insulin signalling and inflammatory pathways in blood and visceral adipose tissue (VAT) of 20 lean healthy donors and 40 equal morbidly obese (MO) patients classified in high insulin resistance (high IR) degree and diabetes state. We studied the changes in proinflammatory markers and lipid content from serum; macrophage infiltration, mRNA expression of inflammatory cytokines and transcription factors, activation of kinases involved in inflammation and expression of insulin signalling molecules in VAT. VAT comparison of these experimental groups revealed that type 2 diabetic-MO subjects exhibit the same pro-inflammatory profile than the high IR-MO patients, characterized by elevated levels of IL-1β, IL-6, TNFα, JNK1/2, ERK1/2, STAT3 and NFκB. Our work rules out the assumption that the inflammation should be increased in obese people with type 2 diabetes compared to high IR obese. These findings indicate that some mechanisms, other than systemic and VAT inflammation must be involved in the development of type 2 diabetes in obesity.

  16. Progression from High Insulin Resistance to Type 2 Diabetes Does Not Entail Additional Visceral Adipose Tissue Inflammation

    PubMed Central

    Barbarroja, Nuria; Lopez-Pedrera, Chary; Garrido-Sanchez, Lourdes; Mayas, Maria Dolores; Oliva-Olivera, Wilfredo; Bernal-Lopez, Maria Rosa; El Bekay, Rajaa; Tinahones, Francisco Jose

    2012-01-01

    Obesity is associated with a low-grade chronic inflammation state. As a consequence, adipose tissue expresses pro-inflammatory cytokines that propagate inflammatory responses systemically elsewhere, promoting whole-body insulin resistance and consequential islet β-cell exhaustation. Thus, insulin resistance is considered the early stage of type 2 diabetes. However, there is evidence of obese individuals that never develop diabetes indicating that the mechanisms governing the association between the increase of inflammatory factors and type 2 diabetes are much more complex and deserve further investigation. We studied for the first time the differences in insulin signalling and inflammatory pathways in blood and visceral adipose tissue (VAT) of 20 lean healthy donors and 40 equal morbidly obese (MO) patients classified in high insulin resistance (high IR) degree and diabetes state. We studied the changes in proinflammatory markers and lipid content from serum; macrophage infiltration, mRNA expression of inflammatory cytokines and transcription factors, activation of kinases involved in inflammation and expression of insulin signalling molecules in VAT. VAT comparison of these experimental groups revealed that type 2 diabetic-MO subjects exhibit the same pro-inflammatory profile than the high IR-MO patients, characterized by elevated levels of IL-1β, IL-6, TNFα, JNK1/2, ERK1/2, STAT3 and NFκB. Our work rules out the assumption that the inflammation should be increased in obese people with type 2 diabetes compared to high IR obese. These findings indicate that some mechanisms, other than systemic and VAT inflammation must be involved in the development of type 2 diabetes in obesity. PMID:23110196

  17. Towards new mechanisms: an update on therapeutics for treatment-resistant major depressive disorder.

    PubMed

    Papakostas, G I; Ionescu, D F

    2015-10-01

    Depression is a devastating disorder that places a significant burden on both the individual and society. As such, the discovery of novel therapeutics and innovative treatments--especially for treatment-resistant depression (TRD)--are essential. Research into antidepressant therapies for TRD has evolved from explorations of antidepressants with primary mechanisms of action on the monoaminergic neurotransmitter system to augmentation agents with primary mechanisms both within and outside of the serotonin/norepinephrine system. Now the field of antidepressant research has changed trajectories yet again; this time, compounds with primary mechanisms of action on the glutamatergic, cholinergic and opioid systems are in the forefront of antidepressant exploration. In this review, we will discuss the most recent research surrounding these novel compounds. In addition, we will discuss novel device-based therapeutics, with a particular focus on transcranial magnetic stimulation. In many cases of antidepressant drug discovery, the role of serendipity coupled with meticulous clinical observation in drug development in medicine was crucial. Moving forward, we must look toward the combination of innovation plus improvements on the remarkable discoveries thus far to advance the field of antidepressant research. PMID:26148812

  18. Towards new mechanisms: an update on therapeutics for treatment-resistant major depressive disorder.

    PubMed

    Papakostas, G I; Ionescu, D F

    2015-10-01

    Depression is a devastating disorder that places a significant burden on both the individual and society. As such, the discovery of novel therapeutics and innovative treatments--especially for treatment-resistant depression (TRD)--are essential. Research into antidepressant therapies for TRD has evolved from explorations of antidepressants with primary mechanisms of action on the monoaminergic neurotransmitter system to augmentation agents with primary mechanisms both within and outside of the serotonin/norepinephrine system. Now the field of antidepressant research has changed trajectories yet again; this time, compounds with primary mechanisms of action on the glutamatergic, cholinergic and opioid systems are in the forefront of antidepressant exploration. In this review, we will discuss the most recent research surrounding these novel compounds. In addition, we will discuss novel device-based therapeutics, with a particular focus on transcranial magnetic stimulation. In many cases of antidepressant drug discovery, the role of serendipity coupled with meticulous clinical observation in drug development in medicine was crucial. Moving forward, we must look toward the combination of innovation plus improvements on the remarkable discoveries thus far to advance the field of antidepressant research.

  19. CRISPR-Cas and Restriction-Modification Act Additively against Conjugative Antibiotic Resistance Plasmid Transfer in Enterococcus faecalis.

    PubMed

    Price, Valerie J; Huo, Wenwen; Sharifi, Ardalan; Palmer, Kelli L

    2016-01-01

    Enterococcus faecalis is an opportunistic pathogen and a leading cause of nosocomial infections. Conjugative pheromone-responsive plasmids are narrow-host-range mobile genetic elements (MGEs) that are rapid disseminators of antibiotic resistance in the faecalis species. Clustered regularly interspaced short palindromic repeat (CRISPR)-Cas and restriction-modification confer acquired and innate immunity, respectively, against MGE acquisition in bacteria. Most multidrug-resistant E. faecalis isolates lack CRISPR-Cas and possess an orphan locus lacking cas genes, CRISPR2, that is of unknown function. Little is known about restriction-modification defense in E. faecalis. Here, we explore the hypothesis that multidrug-resistant E. faecalis strains are immunocompromised. We assessed MGE acquisition by E. faecalis T11, a strain closely related to the multidrug-resistant hospital isolate V583 but which lacks the ~620 kb of horizontally acquired genome content that characterizes V583. T11 possesses the E. faecalis CRISPR3-cas locus and a predicted restriction-modification system, neither of which occurs in V583. We demonstrate that CRISPR-Cas and restriction-modification together confer a 4-log reduction in acquisition of the pheromone-responsive plasmid pAM714 in biofilm matings. Additionally, we show that the orphan CRISPR2 locus is functional for genome defense against another pheromone-responsive plasmid, pCF10, only in the presence of cas9 derived from the E. faecalis CRISPR1-cas locus, which most multidrug-resistant E. faecalis isolates lack. Overall, our work demonstrated that the loss of only two loci led to a dramatic reduction in genome defense against a clinically relevant MGE, highlighting the critical importance of the E. faecalis accessory genome in modulating horizontal gene transfer. Our results rationalize the development of antimicrobial strategies that capitalize upon the immunocompromised status of multidrug-resistant E. faecalis. IMPORTANCE

  20. CRISPR-Cas and Restriction-Modification Act Additively against Conjugative Antibiotic Resistance Plasmid Transfer in Enterococcus faecalis.

    PubMed

    Price, Valerie J; Huo, Wenwen; Sharifi, Ardalan; Palmer, Kelli L

    2016-01-01

    Enterococcus faecalis is an opportunistic pathogen and a leading cause of nosocomial infections. Conjugative pheromone-responsive plasmids are narrow-host-range mobile genetic elements (MGEs) that are rapid disseminators of antibiotic resistance in the faecalis species. Clustered regularly interspaced short palindromic repeat (CRISPR)-Cas and restriction-modification confer acquired and innate immunity, respectively, against MGE acquisition in bacteria. Most multidrug-resistant E. faecalis isolates lack CRISPR-Cas and possess an orphan locus lacking cas genes, CRISPR2, that is of unknown function. Little is known about restriction-modification defense in E. faecalis. Here, we explore the hypothesis that multidrug-resistant E. faecalis strains are immunocompromised. We assessed MGE acquisition by E. faecalis T11, a strain closely related to the multidrug-resistant hospital isolate V583 but which lacks the ~620 kb of horizontally acquired genome content that characterizes V583. T11 possesses the E. faecalis CRISPR3-cas locus and a predicted restriction-modification system, neither of which occurs in V583. We demonstrate that CRISPR-Cas and restriction-modification together confer a 4-log reduction in acquisition of the pheromone-responsive plasmid pAM714 in biofilm matings. Additionally, we show that the orphan CRISPR2 locus is functional for genome defense against another pheromone-responsive plasmid, pCF10, only in the presence of cas9 derived from the E. faecalis CRISPR1-cas locus, which most multidrug-resistant E. faecalis isolates lack. Overall, our work demonstrated that the loss of only two loci led to a dramatic reduction in genome defense against a clinically relevant MGE, highlighting the critical importance of the E. faecalis accessory genome in modulating horizontal gene transfer. Our results rationalize the development of antimicrobial strategies that capitalize upon the immunocompromised status of multidrug-resistant E. faecalis. IMPORTANCE

  1. CRISPR-Cas and Restriction-Modification Act Additively against Conjugative Antibiotic Resistance Plasmid Transfer in Enterococcus faecalis

    PubMed Central

    Price, Valerie J.; Huo, Wenwen; Sharifi, Ardalan

    2016-01-01

    ABSTRACT Enterococcus faecalis is an opportunistic pathogen and a leading cause of nosocomial infections. Conjugative pheromone-responsive plasmids are narrow-host-range mobile genetic elements (MGEs) that are rapid disseminators of antibiotic resistance in the faecalis species. Clustered regularly interspaced short palindromic repeat (CRISPR)-Cas and restriction-modification confer acquired and innate immunity, respectively, against MGE acquisition in bacteria. Most multidrug-resistant E. faecalis isolates lack CRISPR-Cas and possess an orphan locus lacking cas genes, CRISPR2, that is of unknown function. Little is known about restriction-modification defense in E. faecalis. Here, we explore the hypothesis that multidrug-resistant E. faecalis strains are immunocompromised. We assessed MGE acquisition by E. faecalis T11, a strain closely related to the multidrug-resistant hospital isolate V583 but which lacks the ~620 kb of horizontally acquired genome content that characterizes V583. T11 possesses the E. faecalis CRISPR3-cas locus and a predicted restriction-modification system, neither of which occurs in V583. We demonstrate that CRISPR-Cas and restriction-modification together confer a 4-log reduction in acquisition of the pheromone-responsive plasmid pAM714 in biofilm matings. Additionally, we show that the orphan CRISPR2 locus is functional for genome defense against another pheromone-responsive plasmid, pCF10, only in the presence of cas9 derived from the E. faecalis CRISPR1-cas locus, which most multidrug-resistant E. faecalis isolates lack. Overall, our work demonstrated that the loss of only two loci led to a dramatic reduction in genome defense against a clinically relevant MGE, highlighting the critical importance of the E. faecalis accessory genome in modulating horizontal gene transfer. Our results rationalize the development of antimicrobial strategies that capitalize upon the immunocompromised status of multidrug-resistant E

  2. Genetics and preliminary mechanism of chlorpyrifos resistance in Phenacoccus solenopsis Tinsley (Homoptera: Pseudococcidae).

    PubMed

    Afzal, Muhammad Babar Shahzad; Ijaz, Mamuna; Farooq, Zahra; Shad, Sarfraz Ali; Abbas, Naeem

    2015-03-01

    Cotton mealybug, Phenacoccus solenopsis Tinsley, is a serious pest of cotton and other crops and infestation by this pest results in yield losses that affect the economy of Pakistan. Various groups of insecticides have been used to control this pest but resistance development is a major factor that inhibits its control in the field. Chlorpyrifos is a common insecticide used against many pests including P. solenopsis. The present experiment was designed to assess the genetics and mechanism of chlorpyrifos resistance and to develop a better resistance management strategy and assess the genetics and mechanism of chlorpyrifos resistance. Before selection, the field strain showed 3.1-fold resistance compared to the susceptible strain (CSS). After 8 rounds of selection with chlorpyrifos, a selected population developed a 191.0-fold resistance compared to the CSS. The LC50 values of F1 (CRR ♀ × CSS ♂) and F1(†) (CRR ♂ × CSS ♀) strains were not significantly different and dominance (DLC) values were 0.42 and 0.55. Reciprocal crosses between chlorpyrifos susceptible and resistant strains indicated that resistance was autosomal and incompletely recessive. The monogenic model of fit test and calculation of number of genes segregating in the chlorpyrifos resistant strain demonstrated that resistance is controlled by multiple genes. A value of 0.59 was calculated for realized heritability for chlorpyrifos resistance. Synergism bioassays with piperonyl butoxide and S, S, S-butyl phosphorotrithioate showed that chlorpyrifos resistance was associated with microsomal oxidases and esterases. It was concluded that chlorpyrifos resistance in P. solenopsis was autosomally inherited, incompletely recessive and polygenic. These findings would be helpful to improve the management of P. solenopsis.

  3. Microbial modeling of thermal resistance of Alicyclobacillus acidoterrestris CRA7152 spores in concentrated orange juice with nisin addition

    PubMed Central

    Peña, Wilmer Edgard Luera; de Massaguer, Pilar Rodriguez; Teixeira, Luciano Quintão

    2009-01-01

    The nisin effect on thermal death of Alicyclobacillus acidoterrestris CRA 7152 spores in concentrated orange juice (64°Brix) was studied. Concentrations of 0, 50, 75 and 100 IU of nisin/ml juice, at temperatures of 92, 95, 98 and 102°C were evaluated. The quadratic polynomial model was used to analyze the effects of the factors and their interaction. Verification of surviving spores was carried out through plating in K medium (pH 3.7). The results showed that the D values without nisin addition were 25.5, 12.9, 6.1 and 2.3 min for 92, 95, 98 and 102°C respectively. With addition of nisin into the juice there was a drop of heat resistance as the concentration was increased at a same temperature. With 30, 50, 75, 100 and 150 IU/ml at 95°C, the D values were 12.34, 11.38, 10.49, 9.49 and 9.42 min respectively, showing that a decrease in the D value up to 27% can be obtained. The second order polynomial model established with r2 = 0.995 showed that the microorganism resistance was affected by the action of temperature followed by the nisin concentration. Nisin therefore is an alternative for reducing the rigor of the A. acidoterrestris CRA 7152 thermal treatment. PMID:24031405

  4. Mechanical Properties of Metal Nitrides for Radiation Resistant Coating Applications: A DFT Study

    NASA Astrophysics Data System (ADS)

    Mota, Oscar U. Ojeda; Araujo, Roy A.; Wang, Haiyan; Çağın, Tahir

    Metal nitrides compounds like aluminum nitride (AlN), titanium nitride (TiN), tantalum nitride (TaN), hafnium nitride (HfN) and zirconium nitride (ZrN) are of great interesting because of their chemical and physical properties such as: high melting point, resistivity, thermal conductivity and extremely high hardness. They are the materials of choice for various applications like protective coating for tools, diffusion barriers or metal gate contact in microelectronics, and lately their potential applications as radiation-resistive shields. In order to assess their use for radiation tolerance we have studied the structural, mechanical and electronic properties. We have evaluated the anisotropic elastic constants and their pressure dependence for three different crystalline phases: B1-NaCl, B2-CsCl, and B3-ZnS crystal structures. In addition to these cubic polymorphs, we also have studied potential hexagonal structures of some of the same metal nitrides. All computations are carried out using first principles Density Functional Theory (DFT) approach.

  5. Resistance Training for Diabetes Prevention and Therapy: Experimental Findings and Molecular Mechanisms

    PubMed Central

    2013-01-01

    Type 2 diabetes mellitus (T2D) is characterized by insulin resistance, impaired glycogen synthesis, lipid accumulation, and impaired mitochondrial function. Exercise training has received increasing recognition as a cornerstone in the prevention and treatment of T2D. Emerging research suggests that resistance training (RT) has the power to combat metabolic dysfunction in patients with T2D and seems to be an effective measure to improve overall metabolic health and reduce metabolic risk factors in diabetic patients. However, there is limited mechanistic insight into how these adaptations occur. This review provides an overview of the intervention data on the impact of RT on glucose metabolism. In addition, the molecular mechanisms that lead to adaptation in skeletal muscle in response to RT and that are associated with possible beneficial metabolic responses are discussed. Some of the beneficial adaptations exerted by RT include increased GLUT4 translocation in skeletal muscle, increased insulin sensitivity and hence restored metabolic flexibility. Increased energy expenditure and excess postexercise oxygen consumption in response to RT may be other beneficial effects. RT is increasingly establishing itself as an effective measure to improve overall metabolic health and reduce metabolic risk factors in diabetic patients. PMID:24455726

  6. The potential impact of antifungal drug resistance mechanisms on the host immune response to Candida

    PubMed Central

    Lewis, Russell E.; Viale, Pierluigi; Kontoyiannis, Dimitrios P.

    2012-01-01

    A large number of studies have been published over the last two decades examining molecular mechanisms of antifungal resistance in Candida species. However, few of these studies have explored how such mechanisms influence the host immune response to this opportunistic pathogen. With recent advances in our understanding of host immunity to Candida, a body of emerging literature has begun to explore how intrinsic and adaptive resistance mechanisms in Candida alter host immune system evasion and detection, which could have important implications for understanding (1) why certain resistance mechanisms and Candida species predominate in certain patient populations, (2) the biological context for understanding why high in vitro levels of resistance in may not necessarily correlate with risk of drug failure in vivo and (3) insight into effective immunotherapeutic strategies for combatting Candida resistance. Although this area of research is still in its infancy, two themes are emerging: First, the immunoevasion and intracellular persistence of C. glabrata may be a key factor in the capability of this species to persist in the course of multiple antifungal treatments and develop multidrug resistance. Second, changes in the cell wall associated with antifungal resistance often favor evasion for the host immune response. PMID:22722245

  7. Additional funding mechanisms for Public Hospitals in Greece: the case of Chania Mental Health Hospital

    PubMed Central

    2010-01-01

    Objectives To investigate whether the long term lease of public hospital owned land could be an additional financing mechanism for Greek public (mental) health hospitals. Methods We performed a financial analysis of the official 2008 data of a case - study hospital (Mental Health Hospital of Chania). We used a capital budgeting approach to investigate whether value is created for the public hospital by engaging its assets in a project for the development of a private renal dialysis Unit. Results The development of the private unit in hospital owned land is a good investment decision, as it generates high project Net Present Value and Internal Rate of Return. When the project commences generating operating cash flows, nearly €400.000 will be paid annually to the Mental Health Hospital of Chania as rent, thereby gradually decreasing the annual deficit of the hospital. Conclusions Revenue generated from the long term lease of public hospital land is crucial to gradually eliminate hospital deficit. The Ministry of Health should encourage similar forms of Public Private Partnerships in order to ensure the sustainability of public (mental) hospitals. PMID:21067580

  8. Mechanical properties of SiB6 addition of carbon sintered body

    NASA Astrophysics Data System (ADS)

    Tanaka, Samon; Fukushima, Noriyuki; Matsushita, Jun-ichi; Akatsu, T.; Niihara, K.; Yasuda, E.

    2001-04-01

    Boride material is said as the useful material, which has high melting point and high strength. B4C in carbide is very hard at the next of the diamond and cubic-BN in the Mohs hardness and B4C has excellent chemical stability and high strength. B4C is being used as the polishing material from the hardness. However, it is difficult to make sintered body from high melting point (2623 K). Several silicon boride phases such as SiB4, SiB6, SiB6-x, SiB6+x, and Si11B31, were previously reported. Silicon hexaboride (SiB6) has proved to be a potentially useful material because of its high degree of hardness, moderate melting point (2123 K), and low specific gravity. We studied the preparation of SiB6-B4C-SiC sintered body in this report. We knew experientially that SiB6 reacts with carbon at the high temperature, and forms B4C or SiC. Carbon addition SiB6 sintered body produced by hot pressing and reaction sintering that sintering condition was 1973 K for 3.6 ks in vacuum under a pressure of 25 MPa. The relative density of sintered bodies (SiB6-0,5,10,15 wt%C) was approximately 100%. Characterization of mechanical properties was used indentation, Vickers hardness and thermal

  9. Effect of green propolis addition to physical-mechanical properties of glass ionomer cements

    PubMed Central

    TROCA, Valéria Barros Pereira Barbosa; FERNANDES, Karen Barros Parron; TERRILE, Amélia Elena; MARCUCCI, Maria Cristina; de ANDRADE, Flaviana Bombarda; WANG, Linda

    2011-01-01

    Objective This study investigated the mechanical properties of glass ionomer cements (GICs) combined with propolis as a natural antimicrobial substance Material and Methods Typified green propolis, as an ethanolic extract (EEP) or in the lyophilized form (powder), was incorporated to specimens of Ketac Fil Plus, ChemFlex and Ketac Molar Easymix GICs. For each test, 8 specimens of each material were prepared. For water sorption and solubility tests, specimens were subjected to dehydration, hydration and re-dehydration cycles until a constant mass was obtained for each step. Measurements were recorded using a digital balance of 10-4 g precision. For the diametral tensile strength test, specimens were tested in a universal test machine at 0.5 mm/min crosshead speed after 24 h storage in deionized water. Data were evaluated by one-way ANOVA and Tukey’s tests (p<0.05). Results The addition of propolis to GIC clearly increased water sorption compared to pure material. Solubility was material-dependent and was not clearly evident. For the diametral tensile strength test, association with propolis altered negatively only Chemflex. Conclusion It may be concluded that incorporation of propolis to GICs alters some properties in a material-dependent condition. PMID:21552709

  10. Effect of Ag and Pb Addition on Microstructural and Mechanical Properties of SAC 105 Solders

    NASA Astrophysics Data System (ADS)

    Molnar, Aliz; Janovszky, Dora; Kardos, Ibolya; Molnar, Istvan; Gacsi, Zoltan

    2015-10-01

    Melting and crystallization processes of lead-free and lead-contaminated alloys in near-equilibrium state were investigated. In addition, the effect of silver content up to 4 wt.% on the microstructure of Sn-Ag-Cu alloys was studied. The volume fraction of β-Sn decreased by half owing to 4 wt.% Ag content. Furthermore, contamination by lead strongly influences the properties of the solidified microstructure. The Pb grains appear as a result of two processes when the Pb content is equal to 0.5 wt.% or higher: Pb phase solidifies in the quaternary eutectic at 176°C, and Pb grains precipitate from the primary β-Sn solid solution grain during a solid state reaction. The freezing range enlarges to 51°C due to 2 wt.% Pb content owing to quaternary eutectic. Above 1 wt.% Pb content, the mechanical properties also improve due to grains of quaternary eutectic Pb and precipitated Pb grains with a size <1 μm.

  11. Resistance to Gastrointestinal nematodse of cattle: Identification of genomic regions affecting resistance and potential mechanisms

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Gastrointestinal nematode infections remain a major economic drain on the efficient raising of cattle throughout the world. The recent demonstrations of the appearance of drug resistance in these parasites underscores the problems associated with a complete reliance on anthelmintics to control econ...

  12. Additional Routes to Staphylococcus aureus Daptomycin Resistance as Revealed by Comparative Genome Sequencing, Transcriptional Profiling, and Phenotypic Studies

    PubMed Central

    Song, Yang; Rubio, Aileen; Jayaswal, Radheshyam K.; Silverman, Jared A.; Wilkinson, Brian J.

    2013-01-01

    Daptomycin is an extensively used anti-staphylococcal agent due to the rise in methicillin-resistant Staphylococcus aureus, but the mechanism(s) of resistance is poorly understood. Comparative genome sequencing, transcriptomics, ultrastructure, and cell envelope studies were carried out on two relatively higher level (4 and 8 µg/ml−1) laboratory-derived daptomycin-resistant strains (strains CB1541 and CB1540 respectively) compared to their parent strain (CB1118; MW2). Several mutations were found in the strains. Both strains had the same mutations in the two-component system genes walK and agrA. In strain CB1540 mutations were also detected in the ribose phosphate pyrophosphokinase (prs) and polyribonucleotide nucleotidyltransferase genes (pnpA), a hypothetical protein gene, and in an intergenic region. In strain CB1541 there were mutations in clpP, an ATP-dependent protease, and two different hypothetical protein genes. The strain CB1540 transcriptome was characterized by upregulation of cap (capsule) operon genes, genes involved in the accumulation of the compatible solute glycine betaine, ure genes of the urease operon, and mscL encoding a mechanosensitive chanel. Downregulated genes included smpB, femAB and femH involved in the formation of the pentaglycine interpeptide bridge, genes involved in protein synthesis and fermentation, and spa encoding protein A. Genes altered in their expression common to both transcriptomes included some involved in glycine betaine accumulation, mscL, ure genes, femH, spa and smpB. However, the CB1541 transcriptome was further characterized by upregulation of various heat shock chaperone and protease genes, consistent with a mutation in clpP, and lytM and sceD. Both strains showed slow growth, and strongly decreased autolytic activity that appeared to be mainly due to decreased autolysin production. In contrast to previous common findings, we did not find any mutations in phospholipid biosynthesis genes, and it appears there

  13. Viscous forces are predominant in the zona pellucida mechanical resistance

    NASA Astrophysics Data System (ADS)

    Papi, Massimiliano; Maiorana, Alessandro; Douet, Cécile; Maulucci, Giuseppe; Parasassi, Tiziana; Brunelli, Roberto; Goudet, Ghylène; De Spirito, Marco

    2013-01-01

    The zona pellucida (ZP) is a multilayer glycoprotein spherical shell surrounding mammalian eggs. The ZP's mechanical response plays a crucial role in mammalian fertilization and is a parameter commonly adopted in "in vitro fertilization" to characterize the oocytes quality. While it is assumed that ZP mechanical response is purely elastic, here we prove that dissipative forces cannot be neglected. Physiologically, this evidence implies that an increase in the spermatozoa motility can induce dramatic changes on the ZP reaction force turning ZP shell in an impenetrable barrier leading to fertility impairments.

  14. Class I Microcins: Their Structures, Activities, and Mechanisms of Resistance

    NASA Astrophysics Data System (ADS)

    Severinov, Konstantin; Semenova, Ekaterina; Kazakov, Teymur

    Microcin J25, microcin B17, and microcin C7-C51 are the three known members of class I posttranslationally modified microcins (heavily posttranslationally modified antibacterial peptides produced by Enterobacteriaceae with molecular weights of less than 5 kDa). The three microcins are unrelated to each other; they have structures that are highly atypical for ribosomally synthesized peptides and target essential molecular machines that are validated drug targets. In this chapter, available data on mechanisms of action, structure-activity relationships, and immunity mechanisms for class I microcins and related compounds are discussed.

  15. Transcriptome Analysis Reveals Mechanisms by Which Lactococcus lactis Acquires Nisin Resistance

    PubMed Central

    Kramer, Naomi E.; van Hijum, Sacha A. F. T.; Knol, Jan; Kok, Jan; Kuipers, Oscar P.

    2006-01-01

    Nisin, a posttranslationally modified antimicrobial peptide produced by Lactococcus lactis, is widely used as a food preservative. Yet, the mechanisms leading to the development of nisin resistance in bacteria are poorly understood. We used whole-genome DNA microarrays of L. lactis IL1403 to identify the factors underlying acquired nisin resistance mechanisms. The transcriptomes of L. lactis IL1403 and L. lactis IL1403 Nisr, which reached a 75-fold higher nisin resistance level, were compared. Differential expression was observed in genes encoding proteins that are involved in cell wall biosynthesis, energy metabolism, fatty acid and phospholipid metabolism, regulatory functions, and metal and/or peptide transport and binding. These results were further substantiated by showing that several knockout and overexpression mutants of these genes had strongly altered nisin resistance levels and that some knockout strains could no longer become resistant to the same level of nisin as that of the wild-type strain. The acquired nisin resistance mechanism in L. lactis is complex, involving various different mechanisms. The four major mechanisms are (i) preventing nisin from reaching the cytoplasmic membrane, (ii) reducing the acidity of the extracellular medium, thereby stimulating the binding of nisin to the cell wall, (iii) preventing the insertion of nisin into the membrane, and (iv) possibly transporting nisin across the membrane or extruding nisin out of the membrane. PMID:16641446

  16. Circulating tumour DNA profiling reveals heterogeneity of EGFR inhibitor resistance mechanisms in lung cancer patients.

    PubMed

    Chabon, Jacob J; Simmons, Andrew D; Lovejoy, Alexander F; Esfahani, Mohammad S; Newman, Aaron M; Haringsma, Henry J; Kurtz, David M; Stehr, Henning; Scherer, Florian; Karlovich, Chris A; Harding, Thomas C; Durkin, Kathleen A; Otterson, Gregory A; Purcell, W Thomas; Camidge, D Ross; Goldman, Jonathan W; Sequist, Lecia V; Piotrowska, Zofia; Wakelee, Heather A; Neal, Joel W; Alizadeh, Ash A; Diehn, Maximilian

    2016-01-01

    Circulating tumour DNA (ctDNA) analysis facilitates studies of tumour heterogeneity. Here we employ CAPP-Seq ctDNA analysis to study resistance mechanisms in 43 non-small cell lung cancer (NSCLC) patients treated with the third-generation epidermal growth factor receptor (EGFR) inhibitor rociletinib. We observe multiple resistance mechanisms in 46% of patients after treatment with first-line inhibitors, indicating frequent intra-patient heterogeneity. Rociletinib resistance recurrently involves MET, EGFR, PIK3CA, ERRB2, KRAS and RB1. We describe a novel EGFR L798I mutation and find that EGFR C797S, which arises in ∼33% of patients after osimertinib treatment, occurs in <3% after rociletinib. Increased MET copy number is the most frequent rociletinib resistance mechanism in this cohort and patients with multiple pre-existing mechanisms (T790M and MET) experience inferior responses. Similarly, rociletinib-resistant xenografts develop MET amplification that can be overcome with the MET inhibitor crizotinib. These results underscore the importance of tumour heterogeneity in NSCLC and the utility of ctDNA-based resistance mechanism assessment. PMID:27283993

  17. Circulating tumour DNA profiling reveals heterogeneity of EGFR inhibitor resistance mechanisms in lung cancer patients

    PubMed Central

    Chabon, Jacob J.; Simmons, Andrew D.; Lovejoy, Alexander F.; Esfahani, Mohammad S.; Newman, Aaron M.; Haringsma, Henry J.; Kurtz, David M.; Stehr, Henning; Scherer, Florian; Karlovich, Chris A.; Harding, Thomas C.; Durkin, Kathleen A.; Otterson, Gregory A.; Purcell, W. Thomas; Camidge, D. Ross; Goldman, Jonathan W.; Sequist, Lecia V.; Piotrowska, Zofia; Wakelee, Heather A.; Neal, Joel W.; Alizadeh, Ash A.; Diehn, Maximilian

    2016-01-01

    Circulating tumour DNA (ctDNA) analysis facilitates studies of tumour heterogeneity. Here we employ CAPP-Seq ctDNA analysis to study resistance mechanisms in 43 non-small cell lung cancer (NSCLC) patients treated with the third-generation epidermal growth factor receptor (EGFR) inhibitor rociletinib. We observe multiple resistance mechanisms in 46% of patients after treatment with first-line inhibitors, indicating frequent intra-patient heterogeneity. Rociletinib resistance recurrently involves MET, EGFR, PIK3CA, ERRB2, KRAS and RB1. We describe a novel EGFR L798I mutation and find that EGFR C797S, which arises in ∼33% of patients after osimertinib treatment, occurs in <3% after rociletinib. Increased MET copy number is the most frequent rociletinib resistance mechanism in this cohort and patients with multiple pre-existing mechanisms (T790M and MET) experience inferior responses. Similarly, rociletinib-resistant xenografts develop MET amplification that can be overcome with the MET inhibitor crizotinib. These results underscore the importance of tumour heterogeneity in NSCLC and the utility of ctDNA-based resistance mechanism assessment. PMID:27283993

  18. Turbulence and mechanism of resistance on spheres and cylinders

    NASA Technical Reports Server (NTRS)

    Ahlborn, FR

    1932-01-01

    The nature of turbulent flow through pipes and around obstacles is analyzed and illustrated by photographs of turbulence on screens and straighteners. It is shown that the reversal of flow and of the resistance law on spheres is not explainable by Prandtl's turbulence in the boundary layer. The investigation of the analogous phenomena on the cylinder yields a reversal of the total field of flow. The very pronounced changes in pressure distribution connected with it were affirmed by manometric measurements on spheres by Professor O. Krell. The reversal in a homogenous nonvortical flow is brought about by the advance of the stable arrangement of Karman's dead air vortices toward the test object and by the substitution of an alternatingly one-sided or rotating but stable vortex formation in place of the initially symmetrical formation. This also explains the marked variations of the models.

  19. Mechanism of concentration addition toxicity: they are different for nonpolar narcotic chemicals, polar narcotic chemicals and reactive chemicals.

    PubMed

    Lin, Zhifen; Du, Jianwei; Yin, Kedong; Wang, Liansheng; Yu, Hongxia

    2004-03-01

    According to the toxicity mechanism of the individual chemicals, the concentration addition toxicity mechanism is revealed for nonpolar-narcotic-chemical mixtures, polar-narcotic-chemical mixtures and reactive-chemical mixtures, respectively. For nonpolar-narcotic-chemical mixtures, the partitioning of individual chemicals from water to biophase was determined, and the result shows that their concentration additive effect results from no competitive partitioning among individual chemicals. For polar-narcotic-chemical mixtures, their toxicity are contributed by two factors (the total baseline toxicity and the hydrogen bond donor activity of individual chemicals), and it is the concentration additive effect for either of these two factors that leads to their concentration addition toxicity. In addition, the interactions between the reactive chemicals and the biological macromolecules are discussed thoroughly. The results suggest that the net effect of these interactions is zero, and it is this zero net effect that leads to the concentration addition toxicity mechanism for reactive-chemical mixtures.

  20. Molecular mechanisms associated with Fluconazole resistance in clinical Candida albicans isolates from India.

    PubMed

    Mane, Arati; Vidhate, Pallavi; Kusro, Chanchal; Waman, Vaishali; Saxena, Vandana; Kulkarni-Kale, Urmila; Risbud, Arun

    2016-02-01

    Resistance to azole antifungals is a significant problem in Candida albicans. An understanding of resistance at molecular level is essential for the development of strategies to tackle resistance and rationale design of newer antifungals and target-based molecular approaches. This study presents the first evaluation of molecular mechanisms associated with fluconazole resistance in clinical C.albicans isolates from India. Target site (ERG11) alterations were determined by DNA sequencing, whereas real-time PCRs were performed to quantify target and efflux pump genes (CDR1, CDR2, MDR1) in 87 [Fluconazole susceptible (n = 30), susceptible-dose dependent (n = 30) and resistant (n = 27)] C.albicans isolates. Cross-resistance to fluconazole, ketoconazole and itraconazole was observed in 74.1% isolates. Six amino acid substitutions were identified, including 4 (E116D, F145L, E226D, I437V) previously reported ones and 2 (P406L, Q474H) new ones. CDR1 over-expression was seen in 77.7% resistant isolates. CDR2 was exclusively expressed with CDR1 and their concomitant over-expression was associated with azole cross-resistance. MDR1 and ERG11 over-expression did not seem to be associated with resistance. Our results show that drug efflux mediated by Adenosine-5'-triphosphate (ATP)-binding cassette transporters, especially CDR1 is the predominant mechanism of fluconazole resistance and azole cross-resistance in C. albicans and indicate the need for research directed towards developing strategies to tackle efflux mediated resistance to salvage azoles.

  1. Isolation and characterization of a wheat--Psathyrostachys huashanica 'Keng' 3Ns disomic addition line with resistance to stripe rust.

    PubMed

    Du, Wanli; Wang, Jing; Pang, Yuhui; Wang, Liangming; Wu, Jun; Zhao, Jixin; Yang, Qunhui; Chen, Xinhong

    2014-01-01

    We isolated a wheat germplasm line, 22-2, which was derived from common wheat (Triticum aestivum '7182') and Psathyrostachys huashanica 'Keng' (2n = 2x = 14, NsNs). Genomic composition and homoeologous relationships of 22-2 was analyzed using cytology, genomic in situ hybridization (GISH), EST-SSR, and EST-STS to characterize the alien chromatin in the transfer line. The cytological investigations showed that the chromosome number and configuration were 2n = 44 = 22 II. Mitotic and meiotic GISH using P. huashanica genomic DNA as the probe indicated that 22-2 contained a pair of P. huashanica chromosomes. The genomic affinities of the introduced P. huashanica chromosomes were determined by EST-SSR and EST-STS using multiple-loci markers from seven wheat homoeologous groups between the parents and addition line. One EST-SSR and 17 EST-STS markers, which were located on the homoeologous group 3 chromosomes of wheat, amplified polymorphic bands in 22-2 that were unique to P. huashanica. Thus, these markers suggested that the introduced Ns chromosome pair belonged to homoeologous group 3, so we designated 22-2 as a 3Ns disomic addition line. Based on disease reaction to mixed races (CYR31, CYR32, and Shuiyuan14) of stripe rust in the adult stages, 22-2 was found to have high resistance to stripe rust, which was possibly derived from its P. huashanica parent. Consequently, the new disomic addition line 22-2 could be a valuable donor source for wheat improvement depending on the excellent agronomic traits, especially, the introduction of novel disease resistance genes into wheat during breeding programs.

  2. Isolation and characterization of a wheat--Psathyrostachys huashanica 'Keng' 3Ns disomic addition line with resistance to stripe rust.

    PubMed

    Du, Wanli; Wang, Jing; Pang, Yuhui; Wang, Liangming; Wu, Jun; Zhao, Jixin; Yang, Qunhui; Chen, Xinhong

    2014-01-01

    We isolated a wheat germplasm line, 22-2, which was derived from common wheat (Triticum aestivum '7182') and Psathyrostachys huashanica 'Keng' (2n = 2x = 14, NsNs). Genomic composition and homoeologous relationships of 22-2 was analyzed using cytology, genomic in situ hybridization (GISH), EST-SSR, and EST-STS to characterize the alien chromatin in the transfer line. The cytological investigations showed that the chromosome number and configuration were 2n = 44 = 22 II. Mitotic and meiotic GISH using P. huashanica genomic DNA as the probe indicated that 22-2 contained a pair of P. huashanica chromosomes. The genomic affinities of the introduced P. huashanica chromosomes were determined by EST-SSR and EST-STS using multiple-loci markers from seven wheat homoeologous groups between the parents and addition line. One EST-SSR and 17 EST-STS markers, which were located on the homoeologous group 3 chromosomes of wheat, amplified polymorphic bands in 22-2 that were unique to P. huashanica. Thus, these markers suggested that the introduced Ns chromosome pair belonged to homoeologous group 3, so we designated 22-2 as a 3Ns disomic addition line. Based on disease reaction to mixed races (CYR31, CYR32, and Shuiyuan14) of stripe rust in the adult stages, 22-2 was found to have high resistance to stripe rust, which was possibly derived from its P. huashanica parent. Consequently, the new disomic addition line 22-2 could be a valuable donor source for wheat improvement depending on the excellent agronomic traits, especially, the introduction of novel disease resistance genes into wheat during breeding programs. PMID:24564214

  3. Functional Characterization of Bacteria Isolated from Ancient Arctic Soil Exposes Diverse Resistance Mechanisms to Modern Antibiotics

    PubMed Central

    Perron, Gabriel G.; Whyte, Lyle; Turnbaugh, Peter J.; Goordial, Jacqueline; Hanage, William P.; Dantas, Gautam; Desai, Michael M.

    2015-01-01

    Using functional metagenomics to study the resistomes of bacterial communities isolated from different layers of the Canadian high Arctic permafrost, we show that microbial communities harbored diverse resistance mechanisms at least 5,000 years ago. Among bacteria sampled from the ancient layers of a permafrost core, we isolated eight genes conferring clinical levels of resistance against aminoglycoside, β-lactam and tetracycline antibiotics that are naturally produced by microorganisms. Among these resistance genes, four also conferred resistance against amikacin, a modern semi-synthetic antibiotic that does not naturally occur in microorganisms. In bacteria sampled from the overlaying active layer, we isolated ten different genes conferring resistance to all six antibiotics tested in this study, including aminoglycoside, β-lactam and tetracycline variants that are naturally produced by microorganisms as well as semi-synthetic variants produced in the laboratory. On average, we found that resistance genes found in permafrost bacteria conferred lower levels of resistance against clinically relevant antibiotics than resistance genes sampled from the active layer. Our results demonstrate that antibiotic resistance genes were functionally diverse prior to the anthropogenic use of antibiotics, contributing to the evolution of natural reservoirs of resistance genes. PMID:25807523

  4. Functional characterization of bacteria isolated from ancient arctic soil exposes diverse resistance mechanisms to modern antibiotics.

    PubMed

    Perron, Gabriel G; Whyte, Lyle; Turnbaugh, Peter J; Goordial, Jacqueline; Hanage, William P; Dantas, Gautam; Desai, Michael M

    2015-01-01

    Using functional metagenomics to study the resistomes of bacterial communities isolated from different layers of the Canadian high Arctic permafrost, we show that microbial communities harbored diverse resistance mechanisms at least 5,000 years ago. Among bacteria sampled from the ancient layers of a permafrost core, we isolated eight genes conferring clinical levels of resistance against aminoglycoside, β-lactam and tetracycline antibiotics that are naturally produced by microorganisms. Among these resistance genes, four also conferred resistance against amikacin, a modern semi-synthetic antibiotic that does not naturally occur in microorganisms. In bacteria sampled from the overlaying active layer, we isolated ten different genes conferring resistance to all six antibiotics tested in this study, including aminoglycoside, β-lactam and tetracycline variants that are naturally produced by microorganisms as well as semi-synthetic variants produced in the laboratory. On average, we found that resistance genes found in permafrost bacteria conferred lower levels of resistance against clinically relevant antibiotics than resistance genes sampled from the active layer. Our results demonstrate that antibiotic resistance genes were functionally diverse prior to the anthropogenic use of antibiotics, contributing to the evolution of natural reservoirs of resistance genes.

  5. Additive manufacturing of Inconel 718 using electron beam melting: Processing, post-processing, & mechanical properties

    NASA Astrophysics Data System (ADS)

    Sames, William James, V.

    Additive Manufacturing (AM) process parameters were studied for production of the high temperature alloy Inconel 718 using Electron Beam Melting (EBM) to better understand the relationship between processing, microstructure, and mechanical properties. Processing parameters were analyzed for impact on process time, process temperature, and the amount of applied energy. The applied electron beam energy was shown to be integral to the formation of swelling defects. Standard features in the microstructure were identified, including previously unidentified solidification features such as shrinkage porosity and non-equilibrium phases. The as-solidified structure does not persist in the bulk of EBM parts due to a high process hold temperature (˜1000°C), which causes in situ homogenization. The most significant variability in as-fabricated microstructure is the formation of intragranular delta-phase needles, which can form in samples produced with lower process temperatures (< 960°C). A novel approach was developed and demonstrated for controlling the temperature of cool down, thus providing a technique for in situ heat treatment of material. This technique was used to produce material with hardness of 478+/-7 HV with no post-processing, which exceeds the hardness of peak-aged Inconel 718. Traditional post-processing methods of hot isostatic pressing (HIP) and solution treatment and aging (STA) were found to result in variability in grain growth and phase solution. Recrystallization and grain structure are identified as possible mechanisms to promote grain growth. These results led to the conclusion that the first step in thermal post-processing of EBM Inconel 718 should be an optimized solution treatment to reset phase variation in the as-fabricated microstructure without incurring significant grain growth. Such an optimized solution treatment was developed (1120°C, 2hr) for application prior to aging or HIP. The majority of as-fabricated tensile properties met ASTM

  6. Galectin-1 drives lymphoma CD20 immunotherapy resistance: validation of a preclinical system to identify resistance mechanisms.

    PubMed

    Lykken, Jacquelyn M; Horikawa, Mayuka; Minard-Colin, Veronique; Kamata, Masahiro; Miyagaki, Tomomitsu; Poe, Jonathan C; Tedder, Thomas F

    2016-04-14

    Non-Hodgkin lymphoma (NHL) is the most commonly diagnosed hematologic cancer of adults in the United States, with the vast majority of NHLs deriving from malignant B lymphocytes that express cell surface CD20. CD20 immunotherapy (rituximab) is widely used to treat NHL, even though the initial effectiveness of rituximab varies widely among patients and typically wanes over time. The mechanisms through which lymphomas initially resist or gain resistance to immunotherapy are not well established. To address this, a preclinical mouse model system was developed to comprehensively identify lymphoma transcriptomic changes that confer resistance to CD20 immunotherapy. The generation of spontaneous primary and familial lymphomas revealed that sensitivity to CD20 immunotherapy was not regulated by differences in CD20 expression, prior exposure to CD20 immunotherapy, or serial in vivo passage. An unbiased forward exome screen of these primary lymphomas was used to validate the utility of this expansive lymphoma cohort, which revealed that increased lymphoma galectin-1 (Gal-1) expression strongly correlated with resistance to immunotherapy. Genetically induced lymphoma Gal-1 expression ablated antibody-dependent lymphoma phagocytosis in vitro and lymphoma sensitivity to CD20 immunotherapy in vivo. Human NHLs also express elevated Gal-1 compared with nonmalignant lymphocytes, demonstrating the ability of this preclinical model system to identify molecular targets that could be relevant to human therapy. This study therefore established a powerful preclinical model system that permits the comprehensive identification of the dynamic lymphoma molecular network that drives resistance to immunotherapy. PMID:26888257

  7. Galectin-1 drives lymphoma CD20 immunotherapy resistance: validation of a preclinical system to identify resistance mechanisms.

    PubMed

    Lykken, Jacquelyn M; Horikawa, Mayuka; Minard-Colin, Veronique; Kamata, Masahiro; Miyagaki, Tomomitsu; Poe, Jonathan C; Tedder, Thomas F

    2016-04-14

    Non-Hodgkin lymphoma (NHL) is the most commonly diagnosed hematologic cancer of adults in the United States, with the vast majority of NHLs deriving from malignant B lymphocytes that express cell surface CD20. CD20 immunotherapy (rituximab) is widely used to treat NHL, even though the initial effectiveness of rituximab varies widely among patients and typically wanes over time. The mechanisms through which lymphomas initially resist or gain resistance to immunotherapy are not well established. To address this, a preclinical mouse model system was developed to comprehensively identify lymphoma transcriptomic changes that confer resistance to CD20 immunotherapy. The generation of spontaneous primary and familial lymphomas revealed that sensitivity to CD20 immunotherapy was not regulated by differences in CD20 expression, prior exposure to CD20 immunotherapy, or serial in vivo passage. An unbiased forward exome screen of these primary lymphomas was used to validate the utility of this expansive lymphoma cohort, which revealed that increased lymphoma galectin-1 (Gal-1) expression strongly correlated with resistance to immunotherapy. Genetically induced lymphoma Gal-1 expression ablated antibody-dependent lymphoma phagocytosis in vitro and lymphoma sensitivity to CD20 immunotherapy in vivo. Human NHLs also express elevated Gal-1 compared with nonmalignant lymphocytes, demonstrating the ability of this preclinical model system to identify molecular targets that could be relevant to human therapy. This study therefore established a powerful preclinical model system that permits the comprehensive identification of the dynamic lymphoma molecular network that drives resistance to immunotherapy.

  8. Dynamic iso-resistive trunk extension simulation: contributions of the intrinsic and reflexive mechanisms to spinal stability.

    PubMed

    Davarani, S Zeinali; Shirazi-Adl, A; Hemami, H; Mousavi, S J; Parnianpour, M

    2007-01-01

    The effects of external resistance on the recruitment of trunk muscles and the role of intrinsic and reflexive mechanisms to ensure the spinal stability are significant issues in spinal biomechanics. A computational model of spine under the control of 48 anatomically oriented muscle actions was used to simulate iso-resistive trunk movements. Neural excitation of muscles was attained based on inverse dynamics approach along with the stability-based optimization. The effect of muscle spindle reflex response on the trunk movement stability was evaluated upon the application of a perturbation moment. In this study, the trunk extension movement at various resistance levels while extending from 60 degrees flexion to the upright posture was investigated. Incorporation of the stability condition as an additional constraint in the optimization algorithm increased antagonistic activities for all resistance levels demonstrating that the co-activation caused an increase in the intrinsic stiffness of the spine and its stability in a feed-forward manner. During the acceleration phase of the movement, extensors activity increased while flexors activity decreased in response to the higher resistance. The co-activation ratio noticed in the braking phase of the movement increased with higher resistance. In presence of a 30 Nm flexion perturbation moment, reflexive feed-back noticeably decreased the induced deviation of the velocity and position profiles from the desired ones at all resistance levels. The stability-generated co-activation decreased the reflexive response of muscle spindles to the perturbation demonstrating that both intrinsic and reflexive mechanisms contribute to the trunk stability. The rise in muscle co-activation can ameliorate the corruption of afferent neural sensory system at the expense of higher loading of the spine.

  9. Ruminal ionophores, mechanism of action, resistance and the future

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Ionophores are antibiotics that have an unusual mode of a action that dissipates ion gradients across the cell membranes of sensitive bacteria, and they have been used as feed additives for more than 30 years. Ionophores inhibit bacteria that produce hydrogen, a precursor of methane and bacteria th...

  10. Blast from the Past: Reassessing Forgotten Translation Inhibitors, Antibiotic Selectivity, and Resistance Mechanisms to Aid Drug Development.

    PubMed

    Arenz, Stefan; Wilson, Daniel N

    2016-01-01

    Protein synthesis is a major target within the bacterial cell for antibiotics. Investigations into ribosome-targeting antibiotics have provided much needed functional and structural insight into their mechanism of action. However, the increasing prevalence of multi-drug-resistant bacteria has limited the utility of our current arsenal of clinically relevant antibiotics, highlighting the need for the development of new classes. Recent structural studies have characterized a number of antibiotics discovered decades ago that have unique chemical scaffolds and/or utilize novel modes of action to interact with the ribosome and inhibit translation. Additionally, structures of eukaryotic cytoplasmic and mitochondrial ribosomes have provided further structural insight into the basis for specificity and toxicity of antibiotics. Together with our increased understanding of bacterial resistance mechanisms, revisiting our treasure trove of "forgotten" antibiotics could pave the way for the next generation of antimicrobial agents. PMID:26585390

  11. Blast from the Past: Reassessing Forgotten Translation Inhibitors, Antibiotic Selectivity, and Resistance Mechanisms to Aid Drug Development.

    PubMed

    Arenz, Stefan; Wilson, Daniel N

    2016-01-01

    Protein synthesis is a major target within the bacterial cell for antibiotics. Investigations into ribosome-targeting antibiotics have provided much needed functional and structural insight into their mechanism of action. However, the increasing prevalence of multi-drug-resistant bacteria has limited the utility of our current arsenal of clinically relevant antibiotics, highlighting the need for the development of new classes. Recent structural studies have characterized a number of antibiotics discovered decades ago that have unique chemical scaffolds and/or utilize novel modes of action to interact with the ribosome and inhibit translation. Additionally, structures of eukaryotic cytoplasmic and mitochondrial ribosomes have provided further structural insight into the basis for specificity and toxicity of antibiotics. Together with our increased understanding of bacterial resistance mechanisms, revisiting our treasure trove of "forgotten" antibiotics could pave the way for the next generation of antimicrobial agents.

  12. Corrosion resistant iron aluminides exhibiting improved mechanical properties and corrosion resistance

    DOEpatents

    Liu, Chain T.; McKamey, Claudette G.; Tortorelli, Peter F.; David, Stan A.

    1994-01-01

    The specification discloses a corrosion-resistant intermetallic alloy comprising, in atomic percent, an FeAl iron aluminide containing from about 30 to about 40% aluminum alloyed with from about 0.01 to 0.4% zirconium and from 0.01 to about 0.8% boron. The alloy exhibits considerably improved room temperature ductility for enhanced usefulness in structural applications. The high temperature strength and fabricability is improved by alloying with molybdenum, carbon, chromium and vanadium.

  13. Corrosion resistant iron aluminides exhibiting improved mechanical properties and corrosion resistance

    DOEpatents

    Liu, C.T.; McKamey, C.G.; Tortorelli, P.F.; David, S.A.

    1994-06-14

    The specification discloses a corrosion-resistant intermetallic alloy comprising, in atomic percent, an FeAl iron aluminide containing from about 30 to about 40% aluminum alloyed with from about 0.01 to 0.4% zirconium and from 0.01 to about 0.8% boron. The alloy exhibits considerably improved room temperature ductility for enhanced usefulness in structural applications. The high temperature strength and fabricability is improved by alloying with molybdenum, carbon, chromium and vanadium. 9 figs.

  14. Molecular mechanism of viral resistance to a potent non-nucleoside inhibitor unveiled by molecular simulations.

    PubMed

    Asthana, Shailendra; Shukla, Saumya; Ruggerone, Paolo; Vargiu, Attilio V

    2014-11-11

    Recently, we reported on a potent benzimidazole derivative (227G) that inhibits the growth of the bovine viral diarrhea virus (BVDV) in cell-based and enzyme assays at nanomolar concentrations. The target of 227G is the viral RNA-dependent RNA polymerase (RdRp), and the I261M mutation located in motif I of the RdRp finger domain was found to induce drug resistance. Here we propose a molecular mechanism for the retained functionality of the enzyme in the presence of the inhibitor, on the basis of a thorough computational study of the apo and holo forms of the BVDV RdRp either in the wild type (wt) or in the form carrying the I261M mutation. Our study shows that although the mutation affects to some extent the structure of the apoenzyme, the functional dynamics of the protein appear to be largely maintained, which is consistent with the retained functionality of this natural mutant. Despite the binding site of 227G not collapsing or undergoing drastic structural changes upon introduction of the I261M substitution, these alterations reflect crucially on the binding mode of 227G, which is significantly different from that found in wt RdRp. In particular, while in the wt system the four loops lining the template entrance site embrace 227G and close the template passageway, in the I261M variant the template entrance is only marginally occluded, allowing in principle the translocation of the template to the interior of the enzyme. In addition, the mutated enzyme in the presence of 227G retains several characteristics of the wt apoprotein. Our work provides an original molecular picture of a resistance mechanism that is consistent with published experimental data.

  15. Mechanisms of Oryza sativa (Poaceae) resistance to Tagosodes orizicolus (Homoptera: Delphacidae) under greenhouse condition in Venezuela.

    PubMed

    González, Alex; Labrín, Natalia; Alvarez, Rosa M; Jayaro, Yorman; Gamboa, Carlos; Reyes, Edicta; Barrientos, Venancio

    2012-03-01

    Tagosodes orizicolus is one of the main plagues of rice in tropical America causing two types of damages, the direct one, feeding and oviposition effect, and an indirect one, by the transmission of the "Rice hoja blanca virus". During 2006-2007 we carried out research under greenhouse conditions at Fundaci6n Danac, Venezuela, in order to determine the mechanisms of antixenosis, antibiosis and tolerance to T. orizicolus, which could be acting in commercial varieties and advanced lines of the rice genetic breeding programs of INIA and Fundaci6n Danac. The method of free feeding was used for the antixenosis evaluation, whereas the method of forced feeding was used for antibiosis evaluation (effect on survival and oviposition). Additionally, we used the indirect method based on biomass depression to estimate the tolerance. Some of the evaluated traits included: grade of damage, number of insects settling on rice plants, percentage of sogata mortality at the mature state, number of eggs in the leaf midrib and an index of tolerance. The results showed that rice genotypes possess different combinations of resistance mechanisms, as well as different grades of reactions. The susceptible control 'Bluebonnet 50' was consistently susceptible across experiments and the resistant control 'Makalioka' had high antixenosis and high antibiosis based on survival and oviposition. The rest of the genotypes presented lower or higher degrees of antixenosis and antibiosis for survival and oviposition. The genotype 'FD0241-M-17-6-1-1-1-1' was identified with possible tolerance to the direct damage of sogata. PMID:22458212

  16. Possible additional antidepressant-like mechanism of sodium butyrate: targeting the hippocampus.

    PubMed

    Han, Arum; Sung, Yu-Bin; Chung, Soo-Young; Kwon, Min-Soo

    2014-06-01

    Chromatin remodeling mediated by histone acetylation might be involved in the pathophysiology and the treatment of depression. Recently, it has been reported that the histone deacetylase (HDAC) inhibitors, such as sodium butyrate (SB), could be a potential therapeutic agent for depression treatment. In the present study, we aimed to clarify the antidepressant mechanism of SB in the hippocampus. The mice were exposed to chronic restraint stress (CRS) for 14 consecutive days (2 h/day) to induce depression-like behaviors. To assess depression-like behaviors, sucrose preference test, light dark test (LD), tail suspension test (TST), and forced swim test (FST) were performed after CRS. We observed that CRS decreased HDAC2 and 5 mRNA and protein levels in the hippocampus. In addition, SB co-treatment decreased the depression-like behaviors that are induced by CRS. SB prevented and normalized the phosphorylation of cAMP response element binding protein (pCREB), acetylation of histone H3 (AceH3), HDAC2, and brain-derived neurotrophic factor (BDNF) expression level that were decreased by CRS in the hippocampus. These results suggest that the decreased HDAC2 and 5 expressions in the hippocampus of CRS may be a type of spontaneous coping response against CRS. However, it seems to be unsuccessful to prevent depression induction since reduction of pCREB, AceH3 and BDNF were accompanied by CRS in the hippocampus. Moreover, the reduced AceH3 level may be associated with the decreased pCREB, which appears to lead to the decreased BDNF.

  17. Mechanics of additively manufactured porous biomaterials based on the rhombicuboctahedron unit cell.

    PubMed

    Hedayati, R; Sadighi, M; Mohammadi-Aghdam, M; Zadpoor, A A

    2016-01-01

    Thanks to recent developments in additive manufacturing techniques, it is now possible to fabricate porous biomaterials with arbitrarily complex micro-architectures. Micro-architectures of such biomaterials determine their physical and biological properties, meaning that one could potentially improve the performance of such biomaterials through rational design of micro-architecture. The relationship between the micro-architecture of porous biomaterials and their physical and biological properties has therefore received increasing attention recently. In this paper, we studied the mechanical properties of porous biomaterials made from a relatively unexplored unit cell, namely rhombicuboctahedron. We derived analytical relationships that relate the micro-architecture of such porous biomaterials, i.e. the dimensions of the rhombicuboctahedron unit cell, to their elastic modulus, Poisson's ratio, and yield stress. Finite element models were also developed to validate the analytical solutions. Analytical and numerical results were compared with experimental data from one of our recent studies. It was found that analytical solutions and numerical results show a very good agreement particularly for smaller values of apparent density. The elastic moduli predicted by analytical and numerical models were in very good agreement with experimental observations too. While in excellent agreement with each other, analytical and numerical models somewhat over-predicted the yield stress of the porous structures as compared to experimental data. As the ratio of the vertical struts to the inclined struts, α, approaches zero and infinity, the rhombicuboctahedron unit cell respectively approaches the octahedron (or truncated cube) and cube unit cells. For those limits, the analytical solutions presented here were found to approach the analytic solutions obtained for the octahedron, truncated cube, and cube unit cells, meaning that the presented solutions are generalizations of the

  18. Preclinical evidence of multiple mechanisms underlying trastuzumab resistance in gastric cancer

    PubMed Central

    Arienti, Chiara; Zanoni, Michele; Pignatta, Sara; Del Rio, Alberto; Carloni, Silvia; Tebaldi, Michela; Tedaldi, Gianluca; Tesei, Anna

    2016-01-01

    HER2-positive advanced gastric cancer patients frequently develop resistance to trastuzumab through mechanisms still poorly understood. In breast cancer, other members of the HER-family are known to be involved in trastuzumab-resistance, as is overexpression of the scaffold protein IQGAP1. In the present work, we investigated acquired resistance to trastuzumab in gastric cancer experimental models. Trastuzumab-resistant (HR) subclones derived from 3 HER2-overexpressing gastric cancer cells were generated and characterized for alterations in HER2-signaling mechanisms by next-generation sequencing, immunohistochemical, western blot and qRT-PCR techniques, and molecular modeling analysis. All subclones showed a reduced growth rate with respect to parental cell lines but each had a different resistance mechanism. In NCI N87 HR cells, characterized by a marked increase in HER2-signaling pathways with respect to the parental cell line, trastuzumab sensitivity was restored when IQGAP1 expression was silenced. AKG HR subclone showed higher HER3 protein expression than the parental line. High nuclear HER4 levels were observed in KKP HR cells. In conclusion, our study revealed that high IQGAP1 expression leads to resistance to trastuzumab in gastric cancer. Furthermore, 2 new mutations of the HER2 gene that may be involved in acquired resistance were identified in AKG HR and KKP HR subclones. PMID:26919099

  19. Mechanisms of drug resistance in colon cancer and its therapeutic strategies

    PubMed Central

    Hu, Tao; Li, Zhen; Gao, Chun-Ying; Cho, Chi Hin

    2016-01-01

    Drug resistance develops in nearly all patients with colon cancer, leading to a decrease in the therapeutic efficacies of anticancer agents. This review provides an up-to-date summary on over-expression of ATP-binding cassette (ABC) transporters and evasion of apoptosis, two representatives of transport-based and non-transport-based mechanisms of drug resistance, as well as their therapeutic strategies. Different ABC transporters were found to be up-regulated in colon cancer, which can facilitate the efflux of anticancer drugs out of cancer cells and decrease their therapeutic effects. Inhibition of ABC transporters by suppressing their protein expressions or co-administration of modulators has been proven as an effective approach to sensitize drug-resistant cancer cells to anticancer drugs in vitro. On the other hand, evasion of apoptosis observed in drug-resistant cancers also results in drug resistance to anticancer agents, especially to apoptosis inducers. Restoration of apoptotic signals by BH3 mimetics or epidermal growth factor receptor inhibitors and inhibition of cancer cell growth by alternative cell death pathways, such as autophagy, are effective means to treat such resistant cancer types. Given that the drug resistance mechanisms are different among colon cancer patients and may change even in a single patient at different stages, personalized and specific combination therapy is proposed to be more effective and safer for the reversal of drug resistance in clinics. PMID:27570424

  20. Genomic Insights into Intrinsic and Acquired Drug Resistance Mechanisms in Achromobacter xylosoxidans

    PubMed Central

    Hu, Yongfei; Zhu, Yuying; Ma, Yanan; Liu, Fei; Lu, Na; Yang, Xi; Luan, Chunguang; Yi, Yong

    2014-01-01

    Achromobacter xylosoxidans is an opportunistic pathogen known to be resistant to a wide range of antibiotics; however, the knowledge about the drug resistance mechanisms is limited. We used a high-throughput sequencing approach to sequence the genomes of the A. xylosoxidans type strain ATCC 27061 and a clinical isolate, A. xylosoxidans X02736, and then we used different bioinformatics tools to analyze the drug resistance genes in these bacteria. We obtained the complete genome sequence for A. xylosoxidans ATCC 27061 and the draft sequence for X02736. We predicted a total of 50 drug resistance-associated genes in the type strain, including 5 genes for β-lactamases and 17 genes for efflux pump systems; these genes are also conserved among other A. xylosoxidans genomes. In the clinical isolate, except for the conserved resistance genes, we also identified several acquired resistance genes carried by a new transposon embedded in a novel integrative and conjugative element. Our study provides new insights into the intrinsic and acquired drug resistance mechanisms in A. xylosoxidans, which will be helpful for better understanding the physiology of A. xylosoxidans and the evolution of antibiotic resistance in this bacterium. PMID:25487802

  1. Organophosphate Resistance and its Main Mechanism in Populations of Codling Moth (Lepidoptera: Tortricidae) from Central Chile.

    PubMed

    Reyes, Maritza; Barros-Parada, Wilson; Ramírez, Claudio C; Fuentes-Contreras, Eduardo

    2015-02-01

    The codling moth, Cydia pomonella (L.), is the key pest of apple production worldwide. Insecticide resistance has been reported in all producing countries, based on five different mechanisms. Codling moth in Chile has resistance to azinphos-methyl and tebufenozide in post-diapausing larvae. However, there are no studies about the susceptibility of these populations to insecticides from other chemical groups. Therefore, the efficacy of azinphos-methyl, chlorpyrifos-ethyl, esfenvalerate, methoxyfenozide, tebufenozide, and thiacloprid on neonate and post-diapausing larvae from six field populations was investigated, and identified resistance mechanisms in this species were evaluated. Neonate larvae were susceptible to all insecticides studied, but post-diapausing larvae from four populations were resistant to chlorpyrifos, one of them was also resistant to azinphos-methyl, and another one was resistant to tebufenozide. The acetylcholinesterase insensitivity mutation was not detected, and the sodium channel knockdown resistance mutation was present in a low frequency in one population. Detoxifying enzymatic activity of glutathione S-transferases, esterases, and cytochrome P-450 monooxygenases in adults differed among populations, but chlorpyrifos resistance was associated only with a decreased esterase activity as shown by a significant negative correlation between chlorpyrifos mortality and esterase activity. PMID:26470131

  2. Organophosphate Resistance and its Main Mechanism in Populations of Codling Moth (Lepidoptera: Tortricidae) from Central Chile.

    PubMed

    Reyes, Maritza; Barros-Parada, Wilson; Ramírez, Claudio C; Fuentes-Contreras, Eduardo

    2015-02-01

    The codling moth, Cydia pomonella (L.), is the key pest of apple production worldwide. Insecticide resistance has been reported in all producing countries, based on five different mechanisms. Codling moth in Chile has resistance to azinphos-methyl and tebufenozide in post-diapausing larvae. However, there are no studies about the susceptibility of these populations to insecticides from other chemical groups. Therefore, the efficacy of azinphos-methyl, chlorpyrifos-ethyl, esfenvalerate, methoxyfenozide, tebufenozide, and thiacloprid on neonate and post-diapausing larvae from six field populations was investigated, and identified resistance mechanisms in this species were evaluated. Neonate larvae were susceptible to all insecticides studied, but post-diapausing larvae from four populations were resistant to chlorpyrifos, one of them was also resistant to azinphos-methyl, and another one was resistant to tebufenozide. The acetylcholinesterase insensitivity mutation was not detected, and the sodium channel knockdown resistance mutation was present in a low frequency in one population. Detoxifying enzymatic activity of glutathione S-transferases, esterases, and cytochrome P-450 monooxygenases in adults differed among populations, but chlorpyrifos resistance was associated only with a decreased esterase activity as shown by a significant negative correlation between chlorpyrifos mortality and esterase activity.

  3. A molecular dynamics investigation on the crizotinib resistance mechanism of C1156Y mutation in ALK

    SciTech Connect

    Sun, Hui-Yong; Ji, Feng-Qin

    2012-06-29

    Highlights: Black-Right-Pointing-Pointer The study revealed the detailed resistance mechanism of the non-active mutation C1156Y in ALK. Black-Right-Pointing-Pointer C1156Y leads to crizotinib displacement and conformational changes in the binding cavity. Black-Right-Pointing-Pointer The conformations cause a decline in the vdW and electrostatic energy between crizotinib and ALK. -- Abstract: Crizotinib is an anaplastic lymphoma kinase (ALK) inhibitor that has recently been approved in the US for the treatment of non-small cell lung carcinoma (NSCLC). Despite its outstanding safety and efficacy, several resistant mutations against crizotinib have been detected in the treatment of NSCLC. However, in contrast to the widely accepted mechanism of steric hindrance by mutations at the active site, the mechanism by which the C1156Y non-active site mutation confers resistance against crizotinib remains unclear. In the present study, the resistance mechanism of C1156Y in ALK was investigated using molecular dynamics simulations. The results suggest that despite the non-active site mutation, C1156Y causes the dislocation of crizotinib as well as the indirect conformational changes in the binding cavity, which results in a marked decrease in the van der Waals and electrostatic interactions between crizotinib and ALK. The obtained results provide a detailed explanation of the resistance caused by C1156Y and may give a vital clue for the design of drugs to combat crizotinib resistance.

  4. Mechanical and morphological properties of arterial resistance vessels in young and old spontaneously hypertensive rats.

    PubMed

    Warshaw, D M; Mulvany, M J; Halpern, W

    1979-08-01

    We studied alterations in structural and mechanical properties of mesenteric arterial resistance vessels from young (6-week) and old (50-week) spontaneously hypertensive (SHR)and matched normotensive Wistar-Kyoto (WKY) rats. Emphasis was placed upon relating the active tension capabilities of these vessels to their smooth muscle cell content. Cylindrical segments, 0.7 mm long with internal diameters of 150 micrometer, were mounted in a myograph capable of recording circumferential vessel wall tension and dimensions. Comparisons of vessel morphology and mechanics were performed at a normalized internal circumference, L1,where active tension (delta T1) is near maximum. Arterial wall and medial hypertrophy were observed in young and old SHR. Since the percent smooth muscle cells within the media for SHR was similar to that of WKY, both increased smooth muscle cell and connective tissue content account for the medial hypertrophy. These differences in SHR vessels were reflected directly in their passive and active mechanical properties. Fully relaxed vessels from SHR were less compliant, and upon activation at L1 (high potassium depolarization), delta T1 was not different for young SHR and WKY, but values for old SHR were 35% greater (P less than 0.05) than for WKY. When relating the active force generation of the vessel to the actual smooth muscle cell area, values for smooth muscle cell stress (force/area) were similar for SHR and WKY at both ages. In addition, similarities were observed for active dynamic mechanical measurements of Young's modulus and half response time. Genetic hypertension in rats therefore appears to be associated with the development of increased vessel contractility determined by a greater number of smooth muscle cells which possess contractile properties similar to those of normotensive vessels.

  5. The cyclic oxidation resistance at 1200 C of beta-NiAl, FeAl, and CoAl alloys with selected third element additions

    NASA Technical Reports Server (NTRS)

    Barrett, C. A.; Titran, R. H.

    1992-01-01

    The intermetallic compounds Beta-NiAl, FeAl, and CoAl were tested in cyclic oxidation with selected third element alloy additions. Tests in static air for 200 1-hr cycles at 1200 C indicated by specific weight change/time data and x-ray diffraction analysis that the 5 at percent alloy additions did not significantly improve the oxidation resistance over the alumina forming baseline alloys without the additions. Many of the alloy additions were actually deleterious. Ta and Nb were the only alloy additions that actually altered the nature of the oxide(s) formed and still maintained the oxidation resistance of the protective alumina scale.

  6. Mechanism of single-layer 193-nm dissolution inhibition resist

    NASA Astrophysics Data System (ADS)

    Yan, Zhenglin; Houlihan, Francis M.; Reichmanis, Elsa; Nalamasu, Omkaram; Reiser, Arnost; Dabbagh, Gary; Hutton, Richard S.; Osei, Dan; Sousa, Jose; Bolan, Kevin J.

    2000-06-01

    We have found that the progress of developer base into films of terpolymers of norbornene (NB)-maleic anhydride (MA) and acrylic acid (AA) is a percolation process with a critical site concentration of x(c) equals 0.084 which suggests that every acrylic acid site in the terpolymer of norbornene-maleic anhydride-acrylic acid can make 12 monomer units of the polymer water compatible. In practice these systems are being used with various tert-butyl esters of cholic acid as dissolution inhibitors. The cholates differ very much in their dissolution inhibition factors (lowest t-butyl cholate (1.3) to highest t-butyl lithocholate glutarate dimer (7.4). The change in these factors corrected for molarity follow the hydrophobic character of the dissolution as measured by log(p). A quick screening method has also been established to evaluate dissolution inhibitors based on our observation that the cloud point (the volume % acetone in a water/acetone which gives persistent cloudiness) parallels the dissolution inhibiting power as measured by the dissolution inhibition factor. For dissolution promotion, optimal results are obtained with t-butyl 1,3,5-cyclohexanetricarboxylate (f equals -6.3) and poorest results with t-butyl lithocholate (f equals -2.8); this appears to track with the number of carboxyl groups and the hydrophobicity of the carboxylic acids. The Rmax found for resist formulations tracks well with these findings. Another factor in determining the ultimate achievable contrast is the degree of acidolytic deprotection achieved by the material. It appears that acidolyticaly cleaveable carboxylate esters with a higher concentration of electron withdrawing groups such as t-butyl 1,3,5-cyclohexanetricarboxylate are more effective.

  7. Classical and Targeted Anticancer Drugs: An Appraisal of Mechanisms of Multidrug Resistance.

    PubMed

    Baguley, Bruce C

    2016-01-01

    The mechanisms by which tumor cells resist the action of multiple anticancer drugs, often with widely different chemical structures, have been pursued for more than 30 years. The identification of P-glycoprotein (P-gp), a drug efflux transporter protein with affinity for multiple therapeutic drugs, provided an important potential mechanism and further work, which identified other members of ATP-binding cassette (ABC) family that act as drug transporters. Several observations, including results of clinical trials with pharmacological inhibitors of P-gp, have suggested that mechanisms other than efflux transporters should be considered as contributors to resistance, and in this review mechanisms of anticancer drug resistance are considered more broadly. Cells in human tumors exist is a state of continuous turnover, allowing ongoing selection and "survival of the fittest." Tumor cells die not only as a consequence of drug therapy but also by apoptosis induced by their microenvironment. Cell death can be mediated by host immune mechanisms and by nonimmune cells acting on so-called death receptors. The tumor cell proliferation rate is also important because it controls tumor regeneration. Resistance to therapy might therefore be considered to arise from a reduction of several distinct cell death mechanisms, as well as from an increased ability to regenerate. This review provides a perspective on these mechanisms, together with brief descriptions of some of the methods that can be used to investigate them in a clinical situation. PMID:26910066

  8. Using Liquid Smoke to Improve Mechanical and Water Resistance Properties of Gelatin Films.

    PubMed

    Wang, Wenwang; Li, Cong; Zhang, Hongjie; Ni, Yonghao

    2016-05-01

    Improvement of mechanical and water barrier properties is critical for gelatin films when applied to edible food packaging. A liquid smoke (LS) obtained from hawthorn nucleus was used to improve the performance of gelatin film based on its abundant compounds. Through SPME-GC-MS analysis, 86 volatile and semi-volatile chemical compounds was detected in LS, in which the total carbonyl compounds were 27.60%, with the main aldehyde as 2-furaldehyde (9.83%). For gelatin films, an observable influence of LS on film transparency was observed in gelatin films, but not for its thickness and microstructure. Desirably, adding LS into gelatin solution increased the tensile strength of the films, with a better value of 16.38 MPa as 3 wt% LS added, compared with the control (10.30 MPa). Accordingly, film elongation decreased with a LS dependent manner. Furthermore, the water resistance properties of gelatin film were improved by the LS addition, which was supported by the results of water contact angle, water vapor permeability. Moreover, the addition of LS also led to a higher insolubility for gelatin films. Also, thermal stability of the LS treated gelatin films was slightly enhanced with the DSC analysis. According to the FTIR spectra and crosslinking degree detection results, all the above enhancing of gelatin film should be attributed to the crosslinking between carbonyl groups in LS and amide functionalities in gelatin based on nucleophilic reaction. PMID:27061211

  9. Using Liquid Smoke to Improve Mechanical and Water Resistance Properties of Gelatin Films.

    PubMed

    Wang, Wenwang; Li, Cong; Zhang, Hongjie; Ni, Yonghao

    2016-05-01

    Improvement of mechanical and water barrier properties is critical for gelatin films when applied to edible food packaging. A liquid smoke (LS) obtained from hawthorn nucleus was used to improve the performance of gelatin film based on its abundant compounds. Through SPME-GC-MS analysis, 86 volatile and semi-volatile chemical compounds was detected in LS, in which the total carbonyl compounds were 27.60%, with the main aldehyde as 2-furaldehyde (9.83%). For gelatin films, an observable influence of LS on film transparency was observed in gelatin films, but not for its thickness and microstructure. Desirably, adding LS into gelatin solution increased the tensile strength of the films, with a better value of 16.38 MPa as 3 wt% LS added, compared with the control (10.30 MPa). Accordingly, film elongation decreased with a LS dependent manner. Furthermore, the water resistance properties of gelatin film were improved by the LS addition, which was supported by the results of water contact angle, water vapor permeability. Moreover, the addition of LS also led to a higher insolubility for gelatin films. Also, thermal stability of the LS treated gelatin films was slightly enhanced with the DSC analysis. According to the FTIR spectra and crosslinking degree detection results, all the above enhancing of gelatin film should be attributed to the crosslinking between carbonyl groups in LS and amide functionalities in gelatin based on nucleophilic reaction.

  10. Focus ion beam-induced mechanical stress switching in an ultra-fast resistive switching device

    NASA Astrophysics Data System (ADS)

    Yang, Xiang

    2016-06-01

    The Mo/Si3N4:Pt/Pt nanometallic resistive switching devices with ultra-fast write/erase speed (<50 ns) were fabricated. Other than conventional electrical switching, a mechanical stress-induced switching was demonstrated. Such mechanical stress was provided by momentum transfer of 30 keV Ga+ ions in a focus ion beam system, enabling a one-way high resistance state (HRS) to low resistance state (LRS) transition. The capability of mechanical stress switching provides evidence that electron trapping/detrapping mechanism is responsible for nanometallic resistive switching. It was further demonstrated that HRS (trapping state) is a meta-stable state, while LRS (detrapping state) is a stable state. Strong mechanical stress facilitates local bond distortion in dielectric films and thus lowers the energy barrier between HRS and LRS, eventually leading to a barrier-less state transition. A quantitative model based on stress-mediated parallel conduction paths were established to provide a more accurate description of the resistive switching devices.

  11. DNA markers closely linked to nematode resistance genes in sugar beet (Beta vulgaris L.) mapped using chromosome additions and translocations originating from wild beets of the Procumbentes section.

    PubMed

    Jung, C; Koch, R; Fischer, F; Brandes, A; Wricke, G; Herrmann, R G

    1992-03-01

    Genes conferring resistance to the beet cyst nematode (Heterodera schachtii Schm.) have been transferred to sugar beet (Beta vulgaris L.) from three wild species of the Procumbentes section using monosomic addition and translocation lines, because no meiotic recombination occurs between chromosomes of cultured and wild species. In the course of a project to isolate the nematode resistance genes by strategies of reverse genetics, probes were cloned from DNA of a fragmented B. procumbens chromosome carrying a resistance gene, which had been isolated by pulsed-field gel electrophoresis. One probe (pRK643) hybridized with a short dispersed repetitive DNA element, which was found only in wild beets, and thus may be used as a molecular marker for nematode resistance to progeneis of monosomic addition lines segregating resistant and susceptible individuals. Additional probes for the resistance gene region were obtained with a polymerase chain reaction (PCR)-based strategy using repetitive primers to amplify DNA located between repetitive elements. One of these probes established the existence of at least six different chromosomes from wild beet species, each conferring resistance independently of the others. A strict correlation between the length of the wild beet chromatin introduced in fragment addition and translocation lines and the repeat copy number has been used physically to map the region conferring resistance to a chromosome segment of 0.5-3 Mb.

  12. Endocrine therapy resistance in breast cancer: current status, possible mechanisms and overcoming strategies.

    PubMed

    Fan, Weimin; Chang, Jinjia; Fu, Peifeng

    2015-08-01

    Endocrine therapy has become one of most effective forms of targeted adjuvant therapy for hormone-sensitive breast cancer and may be given after surgery or radiotherapy, and also prior, or subsequent to chemotherapy. Current commonly used drugs for adjuvant endocrine therapy can be divided into following three classes: selective estrogen receptor modulators, aromatase inhibitors and selective estrogen receptor downregulators. Tumor cells can develop resistance to endocrine therapy, a major obstacle limiting the success of breast cancer treatment. The complicated crosstalk, both genomic and nongenomic, between estrogen receptors and growth factors was considered to be a crucial factor contributing to endocrine resistance. However, resistance to this therapy is thought to be a progressive, step-wise process, and the underlying mechanism remains unclear. In this review, we summarize the possible biological and molecular mechanisms that underlie endocrine resistance, and discuss some novel strategies to overcoming these issues.

  13. Desiccation resistance in tropical insects: causes and mechanisms underlying variability in a Panama ant community.

    PubMed

    Bujan, Jelena; Yanoviak, Stephen P; Kaspari, Michael

    2016-09-01

    Desiccation resistance, the ability of an organism to reduce water loss, is an essential trait in arid habitats. Drought frequency in tropical regions is predicted to increase with climate change, and small ectotherms are often under a strong desiccation risk. We tested hypotheses regarding the underexplored desiccation potential of tropical insects. We measured desiccation resistance in 82 ant species from a Panama rainforest by recording the time ants can survive desiccation stress. Species' desiccation resistance ranged from 0.7 h to 97.9 h. We tested the desiccation adaptation hypothesis, which predicts higher desiccation resistance in habitats with higher vapor pressure deficit (VPD) - the drying power of the air. In a Panama rainforest, canopy microclimates averaged a VPD of 0.43 kPa, compared to a VPD of 0.05 kPa in the understory. Canopy ants averaged desiccation resistances 2.8 times higher than the understory ants. We tested a number of mechanisms to account for desiccation resistance. Smaller insects should desiccate faster given their higher surface area to volume ratio. Desiccation resistance increased with ant mass, and canopy ants averaged 16% heavier than the understory ants. A second way to increase desiccation resistance is to carry more water. Water content was on average 2.5% higher in canopy ants, but total water content was not a good predictor of ant desiccation resistance or critical thermal maximum (CT max), a measure of an ant's thermal tolerance. In canopy ants, desiccation resistance and CT max were inversely related, suggesting a tradeoff, while the two were positively correlated in understory ants. This is the first community level test of desiccation adaptation hypothesis in tropical insects. Tropical forests do contain desiccation-resistant species, and while we cannot predict those simply based on their body size, high levels of desiccation resistance are always associated with the tropical canopy.

  14. Desiccation resistance in tropical insects: causes and mechanisms underlying variability in a Panama ant community.

    PubMed

    Bujan, Jelena; Yanoviak, Stephen P; Kaspari, Michael

    2016-09-01

    Desiccation resistance, the ability of an organism to reduce water loss, is an essential trait in arid habitats. Drought frequency in tropical regions is predicted to increase with climate change, and small ectotherms are often under a strong desiccation risk. We tested hypotheses regarding the underexplored desiccation potential of tropical insects. We measured desiccation resistance in 82 ant species from a Panama rainforest by recording the time ants can survive desiccation stress. Species' desiccation resistance ranged from 0.7 h to 97.9 h. We tested the desiccation adaptation hypothesis, which predicts higher desiccation resistance in habitats with higher vapor pressure deficit (VPD) - the drying power of the air. In a Panama rainforest, canopy microclimates averaged a VPD of 0.43 kPa, compared to a VPD of 0.05 kPa in the understory. Canopy ants averaged desiccation resistances 2.8 times higher than the understory ants. We tested a number of mechanisms to account for desiccation resistance. Smaller insects should desiccate faster given their higher surface area to volume ratio. Desiccation resistance increased with ant mass, and canopy ants averaged 16% heavier than the understory ants. A second way to increase desiccation resistance is to carry more water. Water content was on average 2.5% higher in canopy ants, but total water content was not a good predictor of ant desiccation resistance or critical thermal maximum (CT max), a measure of an ant's thermal tolerance. In canopy ants, desiccation resistance and CT max were inversely related, suggesting a tradeoff, while the two were positively correlated in understory ants. This is the first community level test of desiccation adaptation hypothesis in tropical insects. Tropical forests do contain desiccation-resistant species, and while we cannot predict those simply based on their body size, high levels of desiccation resistance are always associated with the tropical canopy. PMID:27648242

  15. Mechanically reliable surface oxides for high-temperature corrosion resistance

    SciTech Connect

    Natesan, K.; Veal, B.W.; Grimsditch, M.; Renusch, D.; Paulikas, A.P.

    1995-05-01

    Corrosion is widely recognized as being important, but an understanding of the underlying phenomena involves factors such as the chemistry and physics of early stages of oxidation, chemistry and bonding at the substrate/oxide interface, role of segregants on the strength of that bond, transport processes through scale, mechanisms of residual stress generation and relief, and fracture behavior at the oxide/substrate interface. Because of this complexity a multilaboratory program has been initiated under the auspices of the DOE Center of Excellence for the Synthesis and Processing of Advanced Materials, with strong interactions and cross-leveraging with DOE Fossil Energy and US industry. Objective is to systematically generate the knowledge required to establish a scientific basis for designing and synthesizing improved protective oxide scales/coatings (slow-growing, adherent, sound) on high-temperature materials without compromising the requisite properties of the bulk materials. The objectives of program work at Argonne are to (1) correlate actual corrosion performance with stresses, voids, segregants, interface roughness, initial stages of oxidation, and microstructures; (2) study such behavior in growing or as-grown films; and (3) define prescriptive design and synthesis routes to mechanically reliable surface oxides. Several techniques, such as Auger electron spectroscopy, X-ray diffraction, X-ray grazing incidence reflectance, grazing-angle X-ray fluorescence, optical fluorescence, and Raman spectroscopy, are used in the studies. Tne project has selected Fe-25 wt.% Cr-20 wt.% Ni and Fe-Cr-Al alloys, which are chromia- and alumina-formers respectively, for the studies. This paper presents some of the results on early stages of oxidation and on surface segregation of elements.

  16. Desiccation resistance and contamination as mechanisms of gaia.

    PubMed

    Brown, S; Margulis, L; Ibarra, S; Siqueiros, D

    1985-01-01

    The gaia hypothesis, formulated by J.E. Lovelock, asserts the composition of the reactive gases, the oxidation-reduction state and the temperature of the lower atmosphere of the planet Earth are actively regulated by the biota. Lovelock and Watson, using highly simplified mathematical models, have shown that the modulation of atmospheric temperature can be achieved by exponentially growing populations of differently colored organisms ("dark and light daisies"). It is more likely that the modulation of atmospheric gas composition is based on the colligative properties of exponentially growing mixed populations of microorganisms rather than on "daisies". Exponential growth of one population of microorganisms leads to gaseous and other metabolic products released to the environment, which favor the exponential growth of different populations, each with their own unique emissions. Extremely high densities of mixed populations of microorganisms ensue. These populations form structured microbial communities composed of members in varying states of activity. Growth potential of metabolically diverse populations most likely provides the basis for the responsiveness of the biota to changing environments. We have attempted to measure an aspect of the growth potential and diversity of one microbial community, that from a flat laminated microbial mat dominated by the cyanobacterium, Microcoleus. Microbial mat samples collected at yearly intervals between 1977 and 1982 were allowed to dry. Subsamples were revived under laboratory conditions by rewetting, and the resulting complex microbial populations were analyzed. Greater than 10(4) viable organisms per ml were estimated to be present in the desiccated samples. Only a portion of the diverse community could be characterized. There were at least 115 different types of desiccation resistant microorganisms present in these samples, primarily bacteria. However, more than a dozen types of rather uncommon fungi and protoctists were

  17. Desiccation resistance and contamination as mechanisms of gaia.

    PubMed

    Brown, S; Margulis, L; Ibarra, S; Siqueiros, D

    1985-01-01

    The gaia hypothesis, formulated by J.E. Lovelock, asserts the composition of the reactive gases, the oxidation-reduction state and the temperature of the lower atmosphere of the planet Earth are actively regulated by the biota. Lovelock and Watson, using highly simplified mathematical models, have shown that the modulation of atmospheric temperature can be achieved by exponentially growing populations of differently colored organisms ("dark and light daisies"). It is more likely that the modulation of atmospheric gas composition is based on the colligative properties of exponentially growing mixed populations of microorganisms rather than on "daisies". Exponential growth of one population of microorganisms leads to gaseous and other metabolic products released to the environment, which favor the exponential growth of different populations, each with their own unique emissions. Extremely high densities of mixed populations of microorganisms ensue. These populations form structured microbial communities composed of members in varying states of activity. Growth potential of metabolically diverse populations most likely provides the basis for the responsiveness of the biota to changing environments. We have attempted to measure an aspect of the growth potential and diversity of one microbial community, that from a flat laminated microbial mat dominated by the cyanobacterium, Microcoleus. Microbial mat samples collected at yearly intervals between 1977 and 1982 were allowed to dry. Subsamples were revived under laboratory conditions by rewetting, and the resulting complex microbial populations were analyzed. Greater than 10(4) viable organisms per ml were estimated to be present in the desiccated samples. Only a portion of the diverse community could be characterized. There were at least 115 different types of desiccation resistant microorganisms present in these samples, primarily bacteria. However, more than a dozen types of rather uncommon fungi and protoctists were

  18. Neisseria gonorrhoeae strain with high-level resistance to spectinomycin due to a novel resistance mechanism (mutated ribosomal protein S5) verified in Norway.

    PubMed

    Unemo, Magnus; Golparian, Daniel; Skogen, Vegard; Olsen, Anne Olaug; Moi, Harald; Syversen, Gaute; Hjelmevoll, Stig Ove

    2013-02-01

    Gonorrhea may become untreatable, and new treatment options are essential. Verified resistance to spectinomycin is exceedingly rare. However, we describe a high-level spectinomycin-resistant (MIC, >1,024 μg/ml) Neisseria gonorrhoeae strain from Norway with a novel resistance mechanism. The resistance determinant was a deletion of codon 27 (valine) and a K28E alteration in the ribosomal protein 5S. The traditional spectinomycin resistance gene (16S rRNA) was wild type. Despite this exceedingly rare finding, spectinomycin available for treatment of ceftriaxone-resistant urogenital gonorrhea would be very valuable. PMID:23183436

  19. Effects of silicon additions on oxidation and mechanical behavior of the nickel-base superalloy B-1900

    NASA Technical Reports Server (NTRS)

    Miner, R. V., Jr.; Lowell, C. E.

    1975-01-01

    Test specimens with nominal additions of Si were tested in oxidation, thermal fatigue, sulfidation, tension, and stress rupture, and were also extensively studied metallographically. Alloy B-1900 modified with 0.6- or 1.2-wt% Si exhibited oxidation resistance equivalent to that of aluminide-coated B-1900 during cyclic, high-gas-velocity oxidation tests. Resistances to thermal fatigue and sulfidation were improved by the Si additions, but were not superior to aluminide-coated B-1900. Stress-rupture tests at 1000 C of specimens given the standard heat treatment to simulate an aluminide coating cycle showed Si to be detrimental. However, application of another heat treatment increased the rupture life of the alloy with 0.6-wt% Si to that of the unmodified B-1900 given the standard heat treatment.

  20. Investigation of mechanism and molecular epidemiology of linezolid-resistant Enterococcus faecalis in China.

    PubMed

    Wang, Lipeng; He, Yunyan; Xia, Yun; Wang, Huijuan; Liang, Shumei

    2014-08-01

    Enterococcus is a major cause of important nosocomial infections. Linezolid, the first member of an entirely new class of antibiotics (oxazolidinones), is effective against serious infections caused by Enterococcus. However, resistance to linezolid has been discovered throughout the world rapidly. From 2011 to 2013, nine linezolid-resistant E. faecalis isolates were collected and the possible mechanisms of linezolid resistance, including mutations in domain V of 23S rRNA genes and in ribosomal proteins L3 and L4, and the multiresistance gene cfr, were investigated. Furthermore, an epidemiological survey of the nine linezolid-resistant E. faecalis isolates was performed by pulsed field gel electrophoresis (PFGE), multilocus sequence typing (MLST) and DiversiLab. The three methods were compared to evaluate their merits and demerits, respectively. We failed to find the resistance mechanisms that have been revealed in recent years by PCR and sequencing analysis in the linezolid-resistant E. faecalis. Epidemiological investigation suggested that a small-scale outbreak of linezolid-resistant E. faecalis emerged in neurosurgery ICU from March to May of 2013. DiversiLab was a reliable typing tool and a suitable alternative to PFGE because it was as discriminatory as PFGE and better than MLST.

  1. General mechanisms of drought response and their application in drought resistance improvement in plants.

    PubMed

    Fang, Yujie; Xiong, Lizhong

    2015-02-01

    Plants often encounter unfavorable environmental conditions because of their sessile lifestyle. These adverse factors greatly affect the geographic distribution of plants, as well as their growth and productivity. Drought stress is one of the premier limitations to global agricultural production due to the complexity of the water-limiting environment and changing climate. Plants have evolved a series of mechanisms at the morphological, physiological, biochemical, cellular, and molecular levels to overcome water deficit or drought stress conditions. The drought resistance of plants can be divided into four basic types-drought avoidance, drought tolerance, drought escape, and drought recovery. Various drought-related traits, including root traits, leaf traits, osmotic adjustment capabilities, water potential, ABA content, and stability of the cell membrane, have been used as indicators to evaluate the drought resistance of plants. In the last decade, scientists have investigated the genetic and molecular mechanisms of drought resistance to enhance the drought resistance of various crops, and significant progress has been made with regard to drought avoidance and drought tolerance. With increasing knowledge to comprehensively decipher the complicated mechanisms of drought resistance in model plants, it still remains an enormous challenge to develop water-saving and drought-resistant crops to cope with the water shortage and increasing demand for food production in the future. PMID:25336153

  2. Overcoming ABC transporter-mediated multidrug resistance: Molecular mechanisms and novel therapeutic drug strategies.

    PubMed

    Li, Wen; Zhang, Han; Assaraf, Yehuda G; Zhao, Kun; Xu, Xiaojun; Xie, Jinbing; Yang, Dong-Hua; Chen, Zhe-Sheng

    2016-07-01

    Multidrug resistance is a key determinant of cancer chemotherapy failure. One of the major causes of multidrug resistance is the enhanced efflux of drugs by membrane ABC transporters. Targeting ABC transporters projects a promising approach to eliminating or suppressing drug resistance in cancer treatment. To reveal the functional mechanisms of ABC transporters in drug resistance, extensive studies have been conducted from identifying drug binding sites to elucidating structural dynamics. In this review article, we examined the recent crystal structures of ABC proteins to depict the functionally important structural elements, such as domains, conserved motifs, and critical amino acids that are involved in ATP-binding and drug efflux. We inspected the drug-binding sites on ABC proteins and the molecular mechanisms of various substrate interactions with the drug binding pocket. While our continuous battle against drug resistance is far from over, new approaches and technologies have emerged to push forward our frontier. Most recent developments in anti-MDR strategies include P-gp inhibitors, RNA-interference, nano-medicines, and delivering combination strategies. With the advent of the 'Omics' era - genomics, epigenomics, transcriptomics, proteomics, and metabolomics - these disciplines play an important role in fighting the battle against chemoresistance by further unraveling the molecular mechanisms of drug resistance and shed light on medical therapies that specifically target MDR. PMID:27449595

  3. General mechanisms of drought response and their application in drought resistance improvement in plants.

    PubMed

    Fang, Yujie; Xiong, Lizhong

    2015-02-01

    Plants often encounter unfavorable environmental conditions because of their sessile lifestyle. These adverse factors greatly affect the geographic distribution of plants, as well as their growth and productivity. Drought stress is one of the premier limitations to global agricultural production due to the complexity of the water-limiting environment and changing climate. Plants have evolved a series of mechanisms at the morphological, physiological, biochemical, cellular, and molecular levels to overcome water deficit or drought stress conditions. The drought resistance of plants can be divided into four basic types-drought avoidance, drought tolerance, drought escape, and drought recovery. Various drought-related traits, including root traits, leaf traits, osmotic adjustment capabilities, water potential, ABA content, and stability of the cell membrane, have been used as indicators to evaluate the drought resistance of plants. In the last decade, scientists have investigated the genetic and molecular mechanisms of drought resistance to enhance the drought resistance of various crops, and significant progress has been made with regard to drought avoidance and drought tolerance. With increasing knowledge to comprehensively decipher the complicated mechanisms of drought resistance in model plants, it still remains an enormous challenge to develop water-saving and drought-resistant crops to cope with the water shortage and increasing demand for food production in the future.

  4. Dynamical Network of HIV-1 Protease Mutants Reveals the Mechanism of Drug Resistance and Unhindered Activity.

    PubMed

    Appadurai, Rajeswari; Senapati, Sanjib

    2016-03-15

    HIV-1 protease variants resist drugs by active and non-active-site mutations. The active-site mutations, which are the primary or first set of mutations, hamper the stability of the enzyme and resist the drugs minimally. As a result, secondary mutations that not only increase protein stability for unhindered catalytic activity but also resist drugs very effectively arise. While the mechanism of drug resistance of the active-site mutations is through modulating the active-site pocket volume, the mechanism of drug resistance of the non-active-site mutations is unclear. Moreover, how these allosteric mutations, which are 8-21 Å distant, communicate to the active site for drug efflux is completely unexplored. Results from molecular dynamics simulations suggest that the primary mechanism of drug resistance of the secondary mutations involves opening of the flexible protease flaps. Results from both residue- and community-based network analyses reveal that this precise action of protease is accomplished by the presence of robust communication paths between the mutational sites and the functionally relevant regions: active site and flaps. While the communication is more direct in the wild type, it traverses across multiple intermediate residues in mutants, leading to weak signaling and unregulated motions of flaps. The global integrity of the protease network is, however, maintained through the neighboring residues, which exhibit high degrees of conservation, consistent with clinical data and mutagenesis studies. PMID:26892689

  5. Overcoming ABC transporter-mediated multidrug resistance: Molecular mechanisms and novel therapeutic drug strategies.

    PubMed

    Li, Wen; Zhang, Han; Assaraf, Yehuda G; Zhao, Kun; Xu, Xiaojun; Xie, Jinbing; Yang, Dong-Hua; Chen, Zhe-Sheng

    2016-07-01

    Multidrug resistance is a key determinant of cancer chemotherapy failure. One of the major causes of multidrug resistance is the enhanced efflux of drugs by membrane ABC transporters. Targeting ABC transporters projects a promising approach to eliminating or suppressing drug resistance in cancer treatment. To reveal the functional mechanisms of ABC transporters in drug resistance, extensive studies have been conducted from identifying drug binding sites to elucidating structural dynamics. In this review article, we examined the recent crystal structures of ABC proteins to depict the functionally important structural elements, such as domains, conserved motifs, and critical amino acids that are involved in ATP-binding and drug efflux. We inspected the drug-binding sites on ABC proteins and the molecular mechanisms of various substrate interactions with the drug binding pocket. While our continuous battle against drug resistance is far from over, new approaches and technologies have emerged to push forward our frontier. Most recent developments in anti-MDR strategies include P-gp inhibitors, RNA-interference, nano-medicines, and delivering combination strategies. With the advent of the 'Omics' era - genomics, epigenomics, transcriptomics, proteomics, and metabolomics - these disciplines play an important role in fighting the battle against chemoresistance by further unraveling the molecular mechanisms of drug resistance and shed light on medical therapies that specifically target MDR.

  6. Bulgecin A as a β-lactam enhancer for carbapenem-resistant Pseudomonas aeruginosa and carbapenem-resistant Acinetobacter baumannii clinical isolates containing various resistance mechanisms

    PubMed Central

    Skalweit, Marion J; Li, Mei

    2016-01-01

    Genetic screening of Pseudomonas aeruginosa (PSDA) and Acinetobacter baumannii (ACB) reveals genes that confer increased susceptibility to β-lactams when disrupted, suggesting novel drug targets. One such target is lytic transglycosylase. Bulgecin A (BlgA) is a natural product of Pseudomonas mesoacidophila and a lytic transglycosolase inhibitor that works synergistically with β-lactams targeting PBP3 for Enterobacteriaceae. BlgA also weakly inhibits di-Zn2+ metallo-β-lactamases like L1 of Stenotrophomonas maltophilia. We hypothesized that because of its unique mechanism of action, BlgA could restore susceptibility to carbapenems in carbapenem-resistant PSDA (CR-PSDA) and carbapenem-resistant ACB, as well as ACB resistant to sulbactam. A BlgA-containing extract was prepared using a previously published protocol. CR-PSDA clinical isolates demonstrating a variety of carbapenem resistance mechanisms (VIM-2 carbapenemases, efflux mechanisms, and AmpC producer expression) were characterized with agar dilution minimum inhibitory concentration (MIC) testing and polymerase chain reaction. Growth curves using these strains were prepared using meropenem, BlgA extract, and meropenem plus BlgA extract. A concentrated Blg A extract combined with low concentrations of meropenem, was able to inhibit the growth of clinical strains of CR-PSDA for strains that had meropenem MICs ≥8 mg/L by agar dilution, and a clinical strain of an OXA-24 producing ACB that had a meropenem MIC >32 mg/L and intermediate ampicillin/sulbactam susceptibility. Similar experiments were conducted on a TEM-1 producing ACB strain resistant to sulbactam. BlgA with ampicillin/sulbactam inhibited the growth of this organism. As in Enterobacteriaceae, BlgA appears to restore the efficacy of meropenem in suppressing the growth of CR-PSDA and carbapenem-resistant ACB strains with a variety of common carbapenem resistance mechanisms. BlgA extract also inhibits VIM-2 β-lactamase in vitro. BlgA may prove to be

  7. Mechanics based model for predicting structure-induced rolling resistance (SRR) of the tire-pavement system

    NASA Astrophysics Data System (ADS)

    Shakiba, Maryam; Ozer, Hasan; Ziyadi, Mojtaba; Al-Qadi, Imad L.

    2016-05-01

    The structure-induced rolling resistance of pavements, and its impact on vehicle fuel consumption, is investigated in this study. The structural response of pavement causes additional rolling resistance and fuel consumption of vehicles through deformation of pavement and various dissipation mechanisms associated with inelastic material properties and damping. Accurate and computationally efficient models are required to capture these mechanisms and obtain realistic estimates of changes in vehicle fuel consumption. Two mechanistic-based approaches are currently used to calculate vehicle fuel consumption as related to structural rolling resistance: dissipation-induced and deflection-induced methods. The deflection-induced approach is adopted in this study, and realistic representation of pavement-vehicle interactions (PVIs) is incorporated. In addition to considering viscoelastic behavior of asphalt concrete layers, the realistic representation of PVIs in this study includes non-uniform three-dimensional tire contact stresses and dynamic analysis in pavement simulations. The effects of analysis type, tire contact stresses, pavement viscoelastic properties, pavement damping coefficients, vehicle speed, and pavement temperature are then investigated.

  8. Mechanisms of group A Streptococcus resistance to reactive oxygen species.

    PubMed

    Henningham, Anna; Döhrmann, Simon; Nizet, Victor; Cole, Jason N

    2015-07-01

    Streptococcus pyogenes, also known as group A Streptococcus (GAS), is an exclusively human Gram-positive bacterial pathogen ranked among the 'top 10' causes of infection-related deaths worldwide. GAS commonly causes benign and self-limiting epithelial infections (pharyngitis and impetigo), and less frequent severe invasive diseases (bacteremia, toxic shock syndrome and necrotizing fasciitis). Annually, GAS causes 700 million infections, including 1.8 million invasive infections with a mortality rate of 25%. In order to establish an infection, GAS must counteract the oxidative stress conditions generated by the release of reactive oxygen species (ROS) at the infection site by host immune cells such as neutrophils and monocytes. ROS are the highly reactive and toxic byproducts of oxygen metabolism, including hydrogen peroxide (H2O2), superoxide anion (O2•(-)), hydroxyl radicals (OH•) and singlet oxygen (O2*), which can damage bacterial nucleic acids, proteins and cell membranes. This review summarizes the enzymatic and regulatory mechanisms utilized by GAS to thwart ROS and survive under conditions of oxidative stress. PMID:25670736

  9. Mechanisms of group A Streptococcus resistance to reactive oxygen species.

    PubMed

    Henningham, Anna; Döhrmann, Simon; Nizet, Victor; Cole, Jason N

    2015-07-01

    Streptococcus pyogenes, also known as group A Streptococcus (GAS), is an exclusively human Gram-positive bacterial pathogen ranked among the 'top 10' causes of infection-related deaths worldwide. GAS commonly causes benign and self-limiting epithelial infections (pharyngitis and impetigo), and less frequent severe invasive diseases (bacteremia, toxic shock syndrome and necrotizing fasciitis). Annually, GAS causes 700 million infections, including 1.8 million invasive infections with a mortality rate of 25%. In order to establish an infection, GAS must counteract the oxidative stress conditions generated by the release of reactive oxygen species (ROS) at the infection site by host immune cells such as neutrophils and monocytes. ROS are the highly reactive and toxic byproducts of oxygen metabolism, including hydrogen peroxide (H2O2), superoxide anion (O2•(-)), hydroxyl radicals (OH•) and singlet oxygen (O2*), which can damage bacterial nucleic acids, proteins and cell membranes. This review summarizes the enzymatic and regulatory mechanisms utilized by GAS to thwart ROS and survive under conditions of oxidative stress.

  10. Flexible and mechanical strain resistant large area SERS active substrates

    NASA Astrophysics Data System (ADS)

    Singh, J. P.; Chu, Hsiaoyun; Abell, Justin; Tripp, Ralph A.; Zhao, Yiping

    2012-05-01

    We report a cost effective and facile way to synthesize flexible, uniform, and large area surface enhanced Raman scattering (SERS) substrates using an oblique angle deposition (OAD) technique. The flexible SERS substrates consist of 1 μm long, tilted silver nanocolumnar films deposited on flexible polydimethylsiloxane (PDMS) and polyethylene terephthalate (PET) sheets using OAD. The SERS enhancement activity of these flexible substrates was determined using 10-5 M trans-1,2-bis(4-pyridyl) ethylene (BPE) Raman probe molecules. The in situ SERS measurements on these flexible substrates under mechanical (tensile/bending) strain conditions were performed. Our results show that flexible SERS substrates can withstand a tensile strain (ε) value as high as 30% without losing SERS performance, whereas the similar bending strain decreases the SERS performance by about 13%. A cyclic tensile loading test on flexible PDMS SERS substrates at a pre-specified tensile strain (ε) value of 10% shows that the SERS intensity remains almost constant for more than 100 cycles. These disposable and flexible SERS substrates can be integrated with biological substances and offer a novel and practical method to facilitate biosensing applications.

  11. Mechanisms of group A Streptococcus resistance to reactive oxygen species

    PubMed Central

    Henningham, Anna; Döhrmann, Simon; Nizet, Victor; Cole, Jason N.

    2015-01-01

    Streptococcus pyogenes, also known as group A Streptococcus (GAS), is an exclusively human Gram-positive bacterial pathogen ranked among the ‘top 10’ causes of infection-related deaths worldwide. GAS commonly causes benign and self-limiting epithelial infections (pharyngitis and impetigo), and less frequent severe invasive diseases (bacteremia, toxic shock syndrome and necrotizing fasciitis). Annually, GAS causes 700 million infections, including 1.8 million invasive infections with a mortality rate of 25%. In order to establish an infection, GAS must counteract the oxidative stress conditions generated by the release of reactive oxygen species (ROS) at the infection site by host immune cells such as neutrophils and monocytes. ROS are the highly reactive and toxic byproducts of oxygen metabolism, including hydrogen peroxide (H2O2), superoxide anion (O2•−), hydroxyl radicals (OH•) and singlet oxygen (O2*), which can damage bacterial nucleic acids, proteins and cell membranes. This review summarizes the enzymatic and regulatory mechanisms utilized by GAS to thwart ROS and survive under conditions of oxidative stress. PMID:25670736

  12. Bonding Mechanisms in Resistance Microwelding of 316 Low-Carbon Vacuum Melted Stainless Steel Wires

    NASA Astrophysics Data System (ADS)

    Khan, M. I.; Kim, J. M.; Kuntz, M. L.; Zhou, Y.

    2009-04-01

    Resistance microwelding (RMW) is an important joining process used in the fabrication of miniature instruments, such as electrical and medical devices. The excellent corrosion resistance of 316 low-carbon vacuum melted (LVM) stainless steel (SS) wire makes it ideal for biomedical applications. The current study examines the microstructure and mechanical properties of crossed resistance microwelded 316LVM wire. Microtensile and microhardness testing was used to analyze the mechanical performance of welds, and fracture surfaces were examined using scanning electron microscopy. Finally, a bonding mechanism is proposed based on optimum joint breaking force (JBF) using metallurgical observations of weld cross sections. Moreover, comparisons with RMWs of Ni, Au-plated Ni, and SUS304 SS wire are discussed.

  13. Genetics and mechanism of resistance to deltamethrin in the house fly, Musca domestica L., from Pakistan.

    PubMed

    Khan, Hafiz Azhar Ali; Akram, Waseem; Haider, Muhammad Saleem

    2015-08-01

    Deltamethrin (a pyrethroid insecticide) has widely been used against the house fly, Musca domestica, a pest found in livestock facilities worldwide. Although, cases of both metabolic and physiological resistance to deltamethrin have been reported in different parts of the world, no studies have been reported to characterize this resistance in house flies from Pakistan. In the present study, we investigated a field strain of house flies for potential to develop resistance to deltamethrin. Also, its stability, possible mechanisms and cross-resistance potential to other insecticides. Before the selection experiments, the field strain showed 8.41-, 3.65-, 8.39-, 2.68-, 19.17- and 5.96-fold resistance to deltamethrin, bifenthrin, lambda-cyhalothrin, chlorpyrifos, profenofos and spinosad, respectively, compared with the reference strain (Lab-susceptible). Continuous selection of the field strain (Delta-SEL) with deltamethrin for six generations (G1-G6) in the laboratory increased the resistance ratio to 176.34 after bioassay at G7. The Delta-SEL strain was reared for the next four generations without exposure to deltamethrin and bioassayed at G11 which revealed that the resistance was stable. The Delta-SEL strain at G7 showed cross-resistance to all other insecticides except spinosad, when compared to the bioassays before the selection experiment (G1). Crosses between Delta-SEL and Lab-susceptible strains revealed an autosomal and incomplete dominant mode of resistance to deltamethrin. A direct test using a monogenic inheritance model revealed that the resistance was governed by more than one factor. Moreover, synergism studies with the enzyme inhibitors PBO and DEF reduced the resistance to deltamethrin in the selected strain up to 2.51- and 2.19-fold, respectively, which revealed that the resistance was possibly due to microsomal oxidase and esterase activity. It is concluded that the resistance to deltamethrin was autosomal and incompletely dominant. The high cross-resistance

  14. Genetics and mechanism of resistance to deltamethrin in the house fly, Musca domestica L., from Pakistan.

    PubMed

    Khan, Hafiz Azhar Ali; Akram, Waseem; Haider, Muhammad Saleem

    2015-08-01

    Deltamethrin (a pyrethroid insecticide) has widely been used against the house fly, Musca domestica, a pest found in livestock facilities worldwide. Although, cases of both metabolic and physiological resistance to deltamethrin have been reported in different parts of the world, no studies have been reported to characterize this resistance in house flies from Pakistan. In the present study, we investigated a field strain of house flies for potential to develop resistance to deltamethrin. Also, its stability, possible mechanisms and cross-resistance potential to other insecticides. Before the selection experiments, the field strain showed 8.41-, 3.65-, 8.39-, 2.68-, 19.17- and 5.96-fold resistance to deltamethrin, bifenthrin, lambda-cyhalothrin, chlorpyrifos, profenofos and spinosad, respectively, compared with the reference strain (Lab-susceptible). Continuous selection of the field strain (Delta-SEL) with deltamethrin for six generations (G1-G6) in the laboratory increased the resistance ratio to 176.34 after bioassay at G7. The Delta-SEL strain was reared for the next four generations without exposure to deltamethrin and bioassayed at G11 which revealed that the resistance was stable. The Delta-SEL strain at G7 showed cross-resistance to all other insecticides except spinosad, when compared to the bioassays before the selection experiment (G1). Crosses between Delta-SEL and Lab-susceptible strains revealed an autosomal and incomplete dominant mode of resistance to deltamethrin. A direct test using a monogenic inheritance model revealed that the resistance was governed by more than one factor. Moreover, synergism studies with the enzyme inhibitors PBO and DEF reduced the resistance to deltamethrin in the selected strain up to 2.51- and 2.19-fold, respectively, which revealed that the resistance was possibly due to microsomal oxidase and esterase activity. It is concluded that the resistance to deltamethrin was autosomal and incompletely dominant. The high cross-resistance

  15. High level resistance against rhizomania disease by simultaneously integrating two distinct defense mechanisms.

    PubMed

    Pavli, Ourania I; Tampakaki, Anastasia P; Skaracis, George N

    2012-01-01

    With the aim of achieving durable resistance against rhizomania disease of sugar beet, the employment of different sources of resistance to Beet necrotic yellow vein virus was pursued. To this purpose, Nicotiana benthamiana transgenic plants that simultaneously produce dsRNA originating from a conserved region of the BNYVV replicase gene and the HrpZ(Psph) protein in a secreted form (SP/HrpZ(Psph)) were produced. The integration and expression of both transgenes as well as proper production of the harpin protein were verified in all primary transformants and selfed progeny (T1, T2). Transgenic resistance was assessed by BNYVV-challenge inoculation on T2 progeny by scoring disease symptoms and DAS-ELISA at 20 and 30 dpi. Transgenic lines possessing single transformation events for both transgenes as well as wild type plants were included in inoculation experiments. Transgenic plants were highly resistant to virus infection, whereas in some cases immunity was achieved. In all cases, the resistant phenotype of transgenic plants carrying both transgenes was superior in comparison with the ones carrying a single transgene. Collectively, our findings demonstrate, for a first time, that the combination of two entirely different resistance mechanisms provide high level resistance or even immunity against the virus. Such a novel approach is anticipated to prevent a rapid virus adaptation that could potentially lead to the emergence of isolates with resistance breaking properties.

  16. Mechanism of sulfonylurea herbicide resistance in the broadleaf weed, Kochia scoparia

    SciTech Connect

    Saari, L.L.; Cotterman, J.C.; Primiani, M.M. )

    1990-05-01

    Selection of kochia (Kochia scoparia) biotypes resistant to the sulfonylurea herbicide chlorsulfuron has oc