scholarly journals Search for a doubly charged DDK bound state in ϒ(1S, 2S) inclusive decays and via direct production in e+e− collisions at s=10.520 , 10.580, and 10.867 GeV

2020 ◽  
Vol 102 (11) ◽  
Author(s):  
Y. Li ◽  
S. Jia ◽  
C. P. Shen ◽  
I. Adachi ◽  
H. Aihara ◽  
...  
Keyword(s):  
Bound State ◽  
Direct Production ◽  
Inclusive Decays ◽  
Doubly Charged

CRYO-Electron Microscopy of the Acto-Myosin-ATP Complex

1990 ◽  
Vol 48 (1) ◽  
pp. 248-249
Author(s):  
John Trinickt ◽  
Howard White
Keyword(s):  
Electron Microscopy ◽  
Atp Hydrolysis ◽  
Myosin Head ◽  
Bound State ◽  
Cross Linking ◽  
Weakly Bound ◽  
Cryo Electron Microscopy ◽  
Myosin Subfragment 1 ◽  
Attached State ◽  
High Fraction

The primary force of muscle contraction is thought to involve a change in the myosin head whilst attached to actin, the energy coming from ATP hydrolysis. This change in attached state could either be a conformational change in the head or an alteration in the binding angle made with actin. A considerable amount is known about one bound state, the so-called strongly attached state, which occurs in the presence of ADP or in the absence of nucleotide. In this state, which probably corresponds to the last attached state of the force-producing cycle, the angle between the long axis myosin head and the actin filament is roughly 45°. Details of other attached states before and during power production have been difficult to obtain because, even at very high protein concentration, the complex is almost completely dissociated by ATP. Electron micrographs of the complex in the presence of ATP have therefore been obtained only after chemically cross-linking myosin subfragment-1 (S1) to actin filaments to prevent dissociation. But it is unclear then whether the variability in attachment angle observed is due merely to the cross-link acting as a hinge.We have recently found low ionic-strength conditions under which, without resorting to cross-linking, a high fraction of S1 is bound to actin during steady state ATP hydrolysis. The structure of this complex is being studied by cryo-electron microscopy of hydrated specimens. Most advantages of frozen specimens over ambient temperature methods such as negative staining have already been documented. These include improved preservation and fixation rates and the ability to observe protein directly rather than a surrounding stain envelope. In the present experiments, hydrated specimens have the additional benefit that it is feasible to use protein concentrations roughly two orders of magnitude higher than in conventional specimens, thereby reducing dissociation of weakly bound complexes.

REACTIONS OF DOUBLY CHARGED IONS WITH VARIOUS NEUTRALS

1979 ◽  
Vol 40 (C7) ◽  
pp. C7-21-C7-22
Author(s):  
K. Peska ◽  
E. Alge ◽  
H. Villinger ◽  
H. Störi ◽  
W. Lindinger
Keyword(s):  
Doubly Charged Ions ◽  
Doubly Charged ◽  
Charged Ions

Binding Mechanism and Structural Insights into the Identified Protein Target of Covid-19 with In-Vitro Effective Drug Ivermectin

2020 ◽  
Author(s):  
Parth Sarthi Sen Gupta ◽  
Satyaranjan Biswal ◽  
Saroj Kumar Panda ◽  
Abhik Kumar Ray ◽  
Malay Kumar Rana
Keyword(s):  
Ternary Complex ◽  
Bound State ◽  
Molecular Target ◽  
Cooperative Interaction ◽  
Effective Drug ◽  
Rna Dependent Rna Polymerase ◽  
Protein Target ◽  
Ternary Complex Formation ◽  
Structural Insights

<p>While an FDA approved drug Ivermectin was reported to dramatically reduce the cell line of SARS-CoV-2 by ~5000 folds within 48 hours, the precise mechanism of action and the COVID-19 molecular target involved in interaction with this in-vitro effective drug are unknown yet. Among 12 different COVID-19 targets studied here, the RNA dependent RNA polymerase (RdRp) with RNA and Helicase NCB site show the strongest affinity to Ivermectin amounting -10.4 kcal/mol and -9.6 kcal/mol, respectively. Molecular dynamics of corresponding protein-drug complexes reveals that the drug bound state of RdRp with RNA has better structural stability than the Helicase NCB site, with MM/PBSA free energy of -135.2 kJ/mol, almost twice that of Helicase (-76.6 kJ/mol). The selectivity of Ivermectin to RdRp is triggered by a cooperative interaction of RNA-RdRp by ternary complex formation. Identification of the target and its interaction profile with Ivermectin can lead to more powerful drug designs for COVID-19 and experimental exploration. </p>

Directed Evolution of P450 Fatty Acid Decarboxylases via High-Throughput Screening Towards Improved Catalytic Activity

2019 ◽  
Author(s):  
Huifang Xu ◽  
Weinan Liang ◽  
Linlin Ning ◽  
Yuanyuan Jiang ◽  
Wenxia Yang ◽  
...  
Keyword(s):  
Catalytic Activity ◽  
Fatty Acid ◽  
Directed Evolution ◽  
High Throughput ◽  
High Throughput Screening ◽  
Colorimetric Detection ◽  
Screening Method ◽  
Random Mutagenesis ◽  
Direct Production ◽  
Consumption Activity

P450 fatty acid decarboxylases (FADCs) have recently been attracting considerable attention owing to their one-step direct production of industrially important 1-alkenes from biologically abundant feedstock free fatty acids under mild conditions. However, attempts to improve the catalytic activity of FADCs have met with little success. Protein engineering has been limited to selected residues and small mutant libraries due to lack of an effective high-throughput screening (HTS) method. Here, we devise a catalase-deficient <i>Escherichia coli</i> host strain and report an HTS approach based on colorimetric detection of H<sub>2</sub>O<sub>2</sub>-consumption activity of FADCs. Directed evolution enabled by this method has led to effective identification for the first time of improved FADC variants for medium-chain 1-alkene production from both DNA shuffling and random mutagenesis libraries. Advantageously, this screening method can be extended to other enzymes that stoichiometrically utilize H<sub>2</sub>O<sub>2</sub> as co-substrate.

Determination of non-metallic inclusions in metal alloys by spark atomic emission spectrometry (review)

2018 ◽  
Vol 84 (12) ◽  
pp. 5-19
Author(s):  
D. N. Bock ◽  
V. A. Labusov
Keyword(s):  
Spectral Line ◽  
Internal Standard ◽  
Detection Limits ◽  
Radiation Detectors ◽  
Metal Alloys ◽  
Emission Spectrometry ◽  
Direct Production ◽  
Metallic Inclusions ◽  
Dissolved Form

A review of publications regarding detection of non-metallic inclusions in metal alloys using optical emission spectrometry with single-spark spectrum registration is presented. The main advantage of the method - an extremely short time of measurement (~1 min) – makes it useful for the purposes of direct production control. A spark-induced impact on a non-metallic inclusion results in a sharp increase (flashes) in the intensities of spectral lines of the elements that comprise the inclusion because their content in the metal matrix is usually rather small. The intensity distribution of the spectral line of the element obtained from several thousand of single-spark spectra consists of two parts: i) the Gaussian function corresponding to the content of the element in a dissolved form, and ii) an asymmetric additive in the region of high intensity values ??attributed to inclusions. Their quantitative determination is based on the assumption that the intensity of the spectral line in the single-spark spectrum is proportional to the content of the element in the matter ablated by the spark. Thus, according to the calibration dependence constructed using samples with a certified total element content, it is possible not only to determine the proportions of the dissolved and undissolved element, but also the dimensions of the individual inclusions. However, determination of the sizes is limited to a range of 1 – 20 µm. Moreover, only Al-containing inclusions can be determined quantitatively nowadays. Difficulties occur both with elements hardly dissolved in steels (O, Ca, Mg, S), and with the elements which exhibit rather high content in the dissolved form (Si, Mn). It is also still impossible to determine carbides and nitrides in steels using C and N lines. The use of time-resolved spectrometry can reduce the detection limits for inclusions containing Si and, possibly, Mn. The use of the internal standard in determination of the inclusions can also lower the detection limits, but may distort the results. Substitution of photomultipliers by solid-state linear radiation detectors provided development of more reliable internal standard, based on the background value in the vicinity of the spectral line. Verification of the results is difficult in the lack of standard samples of composition of the inclusions. Future studies can expand the range of inclusions to be determined by this method.

Bioactive Secondary Metabolites from Endophytic Fungi

2020 ◽  
Vol 27 (11) ◽  
pp. 1836-1854 ◽  
Author(s):  
Elena Ancheeva ◽  
Georgios Daletos ◽  
Peter Proksch
Keyword(s):  
Secondary Metabolites ◽  
Endophytic Fungi ◽  
Host Plants ◽  
Biological Activities ◽  
Cytotoxic Agents ◽  
Special Focus ◽  
Plant Metabolites ◽  
Direct Production ◽  
Bioactive Secondary Metabolites ◽  
Fungal Genes

Background: Endophytes represent a complex community of microorganisms colonizing asymptomatically internal tissues of higher plants. Several reports have shown that endophytes enhance the fitness of their host plants by direct production of bioactive secondary metabolites, which are involved in protecting the host against herbivores and pathogenic microbes. In addition, it is increasingly apparent that endophytes are able to biosynthesize medicinally important “phytochemicals”, originally believed to be produced only by their host plants. Objective: The present review provides an overview of secondary metabolites from endophytic fungi with pronounced biological activities covering the literature between 2010 and 2017. Special focus is given on studies aiming at exploration of the mode of action of these metabolites towards the discovery of leads from endophytic fungi. Moreover, this review critically evaluates the potential of endophytic fungi as alternative sources of bioactive “plant metabolites”. Results: Over the past few years, several promising lead structures from endophytic fungi have been described in the literature. In this review, 65 metabolites are outlined with pronounced biological activities, primarily as antimicrobial and cytotoxic agents. Some of these metabolites have shown to be highly selective or to possess novel mechanisms of action, which hold great promises as potential drug candidates. Conclusion: Endophytes represent an inexhaustible reservoir of pharmacologically important compounds. Moreover, endophytic fungi could be exploited for the sustainable production of bioactive “plant metabolites” in the future. Towards this aim, further insights into the dynamic endophyte - host plant interactions and origin of endophytic fungal genes would be of utmost importance.

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