scholarly journals Increasing production of the antibiotic-abyssomicin C in Micromonospora maris

2020 ◽  
Vol 2 (7A) ◽  
Author(s):  
Yanhua Zhong ◽  
Jem Stach ◽  
Michael Hall

Abyssomicin C is a polyketide antibiotic produced by Micromonospora maris AB-18-032. Previous work on abyssomicin C indicated that it inhibits growth of infectious pathogens such as Methicillin-resistant S. aureus (MRSA) and vancomycin-resistant S. aureus (VRSA). It does this by suppressing para-aminobenzoic acid (pABA) synthesis, which is required for folic acid biosynthesis in bacteria. This makes abyssomicin C an appealing antibiotic drug, as it is specific only to bacteria. However, its yield in chemical synthesis (4 %) and biosynthesis (60.0 mg/L) are low. Ribosome engineering, through the selection of streptomycin-resistant and rifampin-resistant mutants, of M. maris may result in strains with a higher titer of production. After screening by bioassay and sequencing, the mutant genes in six Ochi mutants were identified. Of these mutants, four of them are able to produce a higher titer of abyssomicin C. The other two strains were detected to produce the other secondary metabolite.

2003 ◽  
Vol 10 (6) ◽  
pp. 1085-1089 ◽  
Author(s):  
Masato Nakamura ◽  
Kazuya Nakamura ◽  
Takayuki Miyazawa ◽  
Yukinobu Tohya ◽  
Masami Mochizuki ◽  
...  

ABSTRACT Canine parvovirus (CPV) is classified as a member of the feline parvovirus (FPV) subgroup. CPV isolates are divided into three antigenic types: CPV type 2 (CPV-2), CPV-2a, and CPV-2b. Recently, new antigenic types of CPV were isolated from Vietnamese leopard cats and designated CPV-2c(a) or CPV-2c(b). CPV-2c viruses were distinguished from the other antigenic types of the FPV subgroup by the absence of reactivity with several monoclonal antibodies (MAbs). To characterize the antigenicity of CPV-2c, a panel of MAbs against CPV-2c was generated and epitopes recognized by these MAbs were examined by selection of escape mutants. Four MAbs were established and classified into three groups on the basis of their reactivities: MAbs which recognize CPV-2a, CPV-2b, and CPV-2c (MAbs 2G5 and 20G4); an MAb which reacts with only CPV-2b and CPV-2c(b) (MAb 21C3); and an MAb which recognizes all types of the FPV subgroup viruses (MAb 19D7). The reactivity of MAb 20G4 with CPV-2c was higher than its reactivities with CPV-2a and CPV-2b. These types of specificities of MAbs have not been reported previously. A mapping study by analysis of neutralization-resistant mutants showed that epitopes recognized by MAbs 21C3 and 19D7 belonged to antigenic site A. Substitution of the residues in site B and the other antigenic site influenced the epitope recognized by MAb 2G5. It was suggested that the epitope recognized by MAb 20G4 was related to antigenic site B. These MAbs are expected to be useful for the detection and classification of FPV subgroup isolates.


2003 ◽  
Vol 47 (8) ◽  
pp. 2606-2614 ◽  
Author(s):  
George P. Allen ◽  
Glenn W. Kaatz ◽  
Michael J. Rybak

ABSTRACT The differential effects of moxifloxacin and levofloxacin on the development of resistance in four Streptococcus pneumoniae isolates were examined by using an in vitro pharmacodynamic model. Therapeutic regimens (moxifloxacin: peak, 4.5 μg/ml; half-life [t 1/2], 12 h; and levofloxacin: peak, 6 μg/ml; t 1/2, 6 h) were tested against two fluoroquinolone-susceptible isolates (strains 79 and ATCC 49619) and KD2138 and KD2139 (parC and gyrA mutants, respectively, of ATCC 49619). Mutant prevention concentration (MPC)-targeted regimens with modified pharmacokinetics of each drug were simulated to match the area under the concentration-time curve (AUC) above the MPC for the two fluoroquinolones. Moxifloxacin MICs and MPCs (MIC/MPC) for isolates 79, ATCC 49619, KD2138, and KD2139, respectively, were 0.125 and 0.5, 0.125 and 0.5, 0.25 and 8, and 0.25 and 4 μg/ml. Levofloxacin MICs and MPCs for the same isolates were 1 and 4, 0.5 and 2, 1 and 64, and 0.5 and 32 μg/ml, respectively. Therapeutic levofloxacin concentrations led to isolation of mutants of ATCC 49619 (S79Y in ParC), KD2138 (S81Y in GyrA), and KD2139 (S79Y in ParC). Therapeutic moxifloxacin concentrations against the gyrA mutant KD2139 resulted in outgrowth of a mutant with a ParC substitution (S79Y) but caused no emergence of mutants of the other three isolates. MPC-targeted moxifloxacin (lower-than-normal peak = 0.75 to 1.5 μg/ml, administered at levofloxacin's t 1/2) caused growth of a GyrA variant (S81Y) of KD2138 and a ParC variant (S79Y) of KD2139, while no mutants of ATCC 49619 were recovered. MPC-targeted levofloxacin (higher-than-normal peak = 14.5 to 29.5 μg/ml, administered at moxifloxacin's t 1/2) against KD2138 and KD2139 did not prevent the development of the mutations observed in therapeutic regimens, but resistance in the fluoroquinolone-susceptible ATCC 49619 was no longer noted. Normalization of the respective AUC/MPC ratios of moxifloxacin and levofloxacin did not eliminate differences in resistance selectivity of the two agents in all cases. We conclude that the reduced recovery of resistant mutants of S. pneumoniae following moxifloxacin exposure compared to levofloxacin may be due to intrinsic differences between the drugs. Increasing the concentration and exposure (t 1/2) to exceed the MPC may prevent mutations from occurring in fluoroquinolone-susceptible strains. However, this strategy did not prevent the selection of secondary mutants in strains with preexisting mutations. Further study of the MPC concept to evaluate these relationships is warranted.


p -Aminobenzoic acid-dependent M 48-34 strains of Escherichia coli grown with and without sulphathiazole (ST) were investigated with respect to the enhanced capacities they acquire simultaneously for the synthesis of folic acid and resistance. The washed cells of the sensitive strain grown in drug-free media contain a small amount of intracellularly accumulated folic acid precursor(s). The precursors are converted by the washed cells into folic acid in the presence of p -aminobenzoic acid (PABA) alone. The washed cells harvested from cultures containing a sub-inhibitory concentration of sulphathiazole contain a three-four times greater amount of intracellular folic acid precursor(s) which are converted into folic acid in the above manner. Following the utilization of the intracellular presursor(s) these cells on retesting manifest the capability of synthesizing folic acid from PABA and synthetic 2-amino- 4-hydroxy-6-carboxypteridine. This is a newly acquired character which is lacking in the cells grown in the absence of sulphathiazole. Higher intracellular folic acid-precursor accumula­tion and ability to synthesize folic acid from PABA and synthetic pteridine is possessed by the strains made resistant by successive transfers in the increasing concentrations of sulpha­thiazole. During these transfers, the amounts of sulphathiazole are so graded that the cells in the inocula are capable of surviving from 65 to 87·7% and therefore, the chances of selecting pre-existant resistant mutants, believed to occur at the rate of 10 ‒8 to 10 ‒9 , are reduced to a minimum or improbable level. The strain which is made resistant to 1·0 μ g ST by four successive transfers in graded amounts of sulphathiazole loses the acquired synthetic and resistance characters following three successive transfers in drug-free media, the strain made resistant to 15·0 μ g ST still possessed a fraction of the acquired abilities after twenty successive drug-free transfers, and the strain which was made resistant to 40 μ g ST did not show any decrease in the acquired characters after thirty successive drug-free transfers. It is to be noted that when the strain reversibly resistant to 1·0 μ g ST is grown in sulphathiazole and an antagonist concentration of PABA they fail to manifest the two characters. Similar concen­trations of PABA present during the growth of the resistant strains do not alter to any degree the acquired characters. Colonies of the parent sensitive cells appearing on agar plates con­taining various concentrations of sulphathiazole inoculated into drug-free media yield descendant cells which manifest the two characters, but lost them after two or three successive drug-free transfers, in a manner similar to 1·0 μ g ST-resistant cells discussed above.


1975 ◽  
Vol 26 ◽  
pp. 395-407
Author(s):  
S. Henriksen

The first question to be answered, in seeking coordinate systems for geodynamics, is: what is geodynamics? The answer is, of course, that geodynamics is that part of geophysics which is concerned with movements of the Earth, as opposed to geostatics which is the physics of the stationary Earth. But as far as we know, there is no stationary Earth – epur sic monere. So geodynamics is actually coextensive with geophysics, and coordinate systems suitable for the one should be suitable for the other. At the present time, there are not many coordinate systems, if any, that can be identified with a static Earth. Certainly the only coordinate of aeronomic (atmospheric) interest is the height, and this is usually either as geodynamic height or as pressure. In oceanology, the most important coordinate is depth, and this, like heights in the atmosphere, is expressed as metric depth from mean sea level, as geodynamic depth, or as pressure. Only for the earth do we find “static” systems in use, ana even here there is real question as to whether the systems are dynamic or static. So it would seem that our answer to the question, of what kind, of coordinate systems are we seeking, must be that we are looking for the same systems as are used in geophysics, and these systems are dynamic in nature already – that is, their definition involvestime.


Author(s):  
Zimmatul Liviana

The research grammatical interference in a collection ofshort stories Biarkan Aku Memula iwork Nurul F. Hudaisa collection ofshort storiesset in the back that Is start work Let Nurul F. Huda contains many grammatical interference.The problem of this   study were(1)how   the various morphologi calinterference containedin   a   collection of short stories Biarkan Aku Memulai work Nurul F. Huda. (2)how the various syntactic interference contained in a collection of short stories Biarkan Aku Memulai work Nurul F. Huda. The purposeof this studyis to describe the morphological and         Syntactic interference contained in a collection of short stories Biarkan Aku Memulai work Nurul F. Huda. Sociolinguistics is the study of language variation and use in society. Interference is the event of the use of language elements of one into the other language elements that occur in the speakers themselves. This research uses descriptive qualitative method because to describe the actual realityin order to obtainan accurateand objective. Qualitative descriptive methods were used to analyzethe elements ofa word orphrase that incorporated elements of other languages with the analysis and description of the formulation of the problem is the answer. Data collection techniques using observation techniques, the determination ofthe object of research, the selection of short stories.Based on the analysis of the data in this study can be found that there are six forms of interference morphology, namely (1) the prefix nasal N-sound, (2) the addition of the suffix, (3) the exchange prefix, (4) exchange suffixes, (5) exchange konfiks, (6) removal affixes. While the syntactic interference only on the words and phrases in a sentence. The results of the study it can be concluded that the interference morphology more common than syntactic interference.


Author(s):  
Yochai Benkler ◽  
Robert Faris ◽  
Hal Roberts

This chapter presents a model of the interaction of media outlets, politicians, and the public with an emphasis on the tension between truth-seeking and narratives that confirm partisan identities. This model is used to describe the emergence and mechanics of an insular media ecosystem and how two fundamentally different media ecosystems can coexist. In one, false narratives that reinforce partisan identity not only flourish, but crowd-out true narratives even when these are presented by leading insiders. In the other, false narratives are tested, confronted, and contained by diverse outlets and actors operating in a truth-oriented norms dynamic. Two case studies are analyzed: the first focuses on false reporting on a selection of television networks; the second looks at parallel but politically divergent false rumors—an allegation that Donald Trump raped a 13-yearold and allegations tying Hillary Clinton to pedophilia—and tracks the amplification and resistance these stories faced.


Author(s):  
D. Josephine Selvarani Ruth

AbstractNickel Titanium Naval Ordinance Laboratory (NiTiNOL) is widely called as a shape memory alloy (SMA), a class of nonlinear smart material inherited with the functionally programmed property of varying electrical resistance during the transformation enabling to be positioned as a sensing element. The major challenge to instrument the SMA wires is to suppress the wires’ nonlinearity by proper selection of two important factors. The first factor is influenced by the mechanical biasing element and the other is to identify the sensing current for the sensing device (SMA wires + biasing). This paper focuses on developing SMA wires for sensing in different orientation types and configurations by removing the non-linearity in the system’s output by introducing inverse hysteresis to the wires through the passive mechanical element.


Sensors ◽  
2021 ◽  
Vol 21 (10) ◽  
pp. 3311
Author(s):  
Riccardo Ballarini ◽  
Marco Ghislieri ◽  
Marco Knaflitz ◽  
Valentina Agostini

In motor control studies, the 90% thresholding of variance accounted for (VAF) is the classical way of selecting the number of muscle synergies expressed during a motor task. However, the adoption of an arbitrary cut-off has evident drawbacks. The aim of this work is to describe and validate an algorithm for choosing the optimal number of muscle synergies (ChoOSyn), which can overcome the limitations of VAF-based methods. The proposed algorithm is built considering the following principles: (1) muscle synergies should be highly consistent during the various motor task epochs (i.e., remaining stable in time), (2) muscle synergies should constitute a base with low intra-level similarity (i.e., to obtain information-rich synergies, avoiding redundancy). The algorithm performances were evaluated against traditional approaches (threshold-VAF at 90% and 95%, elbow-VAF and plateau-VAF), using both a simulated dataset and a real dataset of 20 subjects. The performance evaluation was carried out by analyzing muscle synergies extracted from surface electromyographic (sEMG) signals collected during walking tasks lasting 5 min. On the simulated dataset, ChoOSyn showed comparable performances compared to VAF-based methods, while, in the real dataset, it clearly outperformed the other methods, in terms of the fraction of correct classifications, mean error (ME), and root mean square error (RMSE). The proposed approach may be beneficial to standardize the selection of the number of muscle synergies between different research laboratories, independent of arbitrary thresholds.


2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Elisabeth Gibert-Sotelo ◽  
Isabel Pujol Payet

Abstract The interest in morphology and its interaction with the other grammatical components has increased in the last twenty years, with new approaches coming into stage so as to get more accurate analyses of the processes involved in morphological construal. This special issue is a valuable contribution to this field of study. It gathers a selection of five papers from the Morphology and Syntax workshop (University of Girona, July 2017) which, on the basis of Romance and Latin phenomena, discuss word structure and its decomposition into hierarchies of features. Even though the papers share a compositional view of lexical items, they adopt different formal theoretical approaches to the lexicon-syntax interface, thus showing the benefit of bearing in mind the possibilities that each framework provides. This introductory paper serves as a guide for the readers of this special collection and offers an overview of the topics dealt in each contribution.


2003 ◽  
Vol 92 (3_suppl) ◽  
pp. 1091-1096 ◽  
Author(s):  
Nobuhiko Fujihara ◽  
Asako Miura

The influences of task type on search of the World Wide Web using search engines without limitation of search domain were investigated. 9 graduate and undergraduate students studying psychology (1 woman and 8 men, M age = 25.0 yr., SD = 2.1) participated. Their performance to manipulate the search engines on a closed task with only one answer were compared with their performance on an open task with several possible answers. Analysis showed that the number of actions was larger for the closed task ( M = 91) than for the open task ( M = 46.1). Behaviors such as selection of keywords (averages were 7.9% of all actions for the closed task and 16.7% for the open task) and pressing of the browser's back button (averages were 40.3% of all actions for the closed task and 29.6% for the open task) were also different. On the other hand, behaviors such as selection of hyperlinks, pressing of the home button, and number of browsed pages were similar for both tasks. Search behaviors were influenced by task type when the students searched for information without limitation placed on the information sources.


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