scholarly journals Novel Antibiotics Targeting Bacterial Replicative DNA Polymerases

Antibiotics ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 776
Author(s):  
Joana A. Santos ◽  
Meindert H. Lamers
Keyword(s):  
Dna Replication ◽  
Dna Polymerase ◽  
Steady Increase ◽  
Rna Translation ◽  
Antiviral Therapies ◽  
Polymerase Inhibitors ◽  
New Antibiotics ◽  
Replicative Polymerases ◽  
New Generation ◽  
First Time

Multidrug resistance is a worldwide problem that is an increasing threat to global health. Therefore, the development of new antibiotics that inhibit novel targets is of great urgency. Some of the most successful antibiotics inhibit RNA transcription, RNA translation, and DNA replication. Transcription and translation are inhibited by directly targeting the RNA polymerase or ribosome, respectively. DNA replication, in contrast, is inhibited indirectly through targeting of DNA gyrases, and there are currently no antibiotics that inhibit DNA replication by directly targeting the replisome. This contrasts with antiviral therapies where the viral replicases are extensively targeted. In the last two decades there has been a steady increase in the number of compounds that target the bacterial replisome. In particular a variety of inhibitors of the bacterial replicative polymerases PolC and DnaE have been described, with one of the DNA polymerase inhibitors entering clinical trials for the first time. In this review we will discuss past and current work on inhibition of DNA replication, and the potential of bacterial DNA polymerase inhibitors in particular as attractive targets for a new generation of antibiotics.

Recent developments in low-voltage SEM of polymers

1993 ◽  
Vol 51 ◽  
pp. 866-867
Author(s):  
S.J. Krause ◽  
W.W. Adams
Keyword(s):  
Low Voltage ◽  
Chromatic Aberration ◽  
Thermal Electron ◽  
Analytical Technique ◽  
Recent Developments ◽  
Beam Currents ◽  
New Generation ◽  
First Time ◽  
Voltage Scanning ◽  
Beam Damage

Over the past decade low voltage scanning electron microscopy (LVSEM) of polymers has evolved from an interesting curiosity to a powerful analytical technique. This development has been driven by improved instrumentation and in particular, reliable field emission gun (FEG) SEMs. The usefulness of LVSEM has also grown because of an improved theoretical and experimental understanding of sample-beam interactions and by advances in sample preparation and operating techniques. This paper will review progress in polymer LVSEM and present recent results and developments in the field.In the early 1980s a new generation of SEMs produced beam currents that were sufficient to allow imaging at low voltages from 5keV to 0.5 keV. Thus, for the first time, it became possible to routinely image uncoated polymers at voltages below their negative charging threshold, the "second crossover", E2 (Fig. 1). LVSEM also improved contrast and reduced beam damage in sputter metal coated polymers. Unfortunately, resolution was limited to a few tenths of a micron due to the low brightness and chromatic aberration of thermal electron emission sources.

PrimPol (Primase/Polymerase), replicating enzyme – A mini review

2020 ◽  
Vol 2 (4) ◽  
pp. 89-92
Author(s):  
Muhammad Amir ◽  
Sabeera Afzal ◽  
Alia Ishaq
Keyword(s):  
Dna Replication ◽  
Dna Polymerase ◽  
Genetic Information ◽  
Nuclear Dna ◽  
De Novo ◽  
Dna Polymerases ◽  
Test Site ◽  
Mitochondrial Dna Replication ◽  
Dna Template ◽  
Preliminary Phase

Polymerases were revealed first in 1970s. Most important to the modest perception the enzyme responsible for nuclear DNA replication that was pol , for DNA repair pol and for mitochondrial DNA replication pol  DNA construction and renovation done by DNA polymerases, so directing both the constancy and discrepancy of genetic information. Replication of genome initiate with DNA template-dependent fusion of small primers of RNA. This preliminary phase in replication of DNA demarcated as de novo primer synthesis which is catalyzed by specified polymerases known as primases. Sixteen diverse DNA-synthesizing enzymes about human perspective are devoted to replication, reparation, mutilation lenience, and inconsistency of nuclear DNA. But in dissimilarity, merely one DNA polymerase has been called in mitochondria. It has been suggest that PrimPol is extremely acting the roles by re-priming DNA replication in mitochondria to permit an effective and appropriate way replication to be accomplished. Investigations from a numeral of test site have significantly amplified our appreciative of the role, recruitment and regulation of the enzyme during DNA replication. Though, we are simply just start to increase in value the versatile roles that play PrimPol in eukaryote.

Novel Antibiotics from Marine Sources

2011 ◽  
Vol 4 (3) ◽  
pp. 1446-1461 ◽  
Author(s):  
E.A. Martis ◽  
G M Doshi ◽  
G V Aggarwal ◽  
P P Shanbhag
Keyword(s):  
Pharmaceutical Industry ◽  
Resistant Bacteria ◽  
Drug Resistant ◽  
Drug Resistant Bacteria ◽  
Terrestrial Life ◽  
New Antibiotics ◽  
Antibiotic Compounds ◽  
New Generation ◽  
Novel Antibiotics ◽  
Untapped Resource

With the emergence of newer diseases, resistant forms of infectious diseases and multi-drug resistant bacteria, it has become essential to develop novel and more effective antibiotics. Current antibiotics are obtained from terrestrial life or made synthetically from intermediates. The ocean represents virtually untapped resource from which novel antibiotic compounds can be discovered. It is the marine world that will provide the pharmaceutical industry with the next generation of antibiotics. Marine antibiotics are antibiotics obtained from marine organisms. Scientists have reported the discovery of various antibiotics from marine bacteria (aplasmomycin, himalomycins, and pelagiomycins), sponges (Ara C, variabillin, strobilin, ircinin-1, aeroplysin, 3,5-dibromo-4-hydroxyphenylacetamide), coelenterates (asperidol and eunicin), mollusks (laurinterol and pachydictyol), tunicates (geranylhydroquinone and cystadytins), algae (cycloeudesmol, aeroplysinin-1(+), prepacifenol and tetrabromoheptanone), worms (tholepin and 3,5-dibromo-4-hydroxybezaldehyde), and actinomycetes (marinomycins C and D). This indicates that the marine environment, representing approximately half of the global diversity, is an enormous resource for new antibiotics and this source needs to be explored for the discovery of new generation antibiotics. The present article provides an overview of various antibiotics obtained from marine sources.

scholarly journals E. coli primase and DNA polymerase III holoenzyme are able to bind concurrently to a primed template during DNA replication

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Andrea Bogutzki ◽  
Natalie Naue ◽  
Lidia Litz ◽  
Andreas Pich ◽  
Ute Curth
Keyword(s):  
Dna Replication ◽  
Dna Polymerase ◽  
Protein Interactions ◽  
Dna Polymerase Iii ◽  
Protein Protein Interactions ◽  
Single Stranded Dna ◽  
E Coli ◽  
Polymerase Iii ◽  
C Terminus ◽  
Pol Iii

Abstract During DNA replication in E. coli, a switch between DnaG primase and DNA polymerase III holoenzyme (pol III) activities has to occur every time when the synthesis of a new Okazaki fragment starts. As both primase and the χ subunit of pol III interact with the highly conserved C-terminus of single-stranded DNA-binding protein (SSB), it had been proposed that the binding of both proteins to SSB is mutually exclusive. Using a replication system containing the origin of replication of the single-stranded DNA phage G4 (G4ori) saturated with SSB, we tested whether DnaG and pol III can bind concurrently to the primed template. We found that the addition of pol III does not lead to a displacement of primase, but to the formation of higher complexes. Even pol III-mediated primer elongation by one or several DNA nucleotides does not result in the dissociation of DnaG. About 10 nucleotides have to be added in order to displace one of the two primase molecules bound to SSB-saturated G4ori. The concurrent binding of primase and pol III is highly plausible, since even the SSB tetramer situated directly next to the 3′-terminus of the primer provides four C-termini for protein-protein interactions.

scholarly journals Histone H3 Lysine 4 Methylation Marks Postreplicative Human Cytomegalovirus Chromatin

2012 ◽  
Vol 86 (18) ◽  
pp. 9817-9827 ◽  
Author(s):  
Alexandra Nitzsche ◽  
Charlotte Steinhäußer ◽  
Katrin Mücke ◽  
Christina Paulus ◽  
Michael Nevels
Keyword(s):  
Dna Replication ◽  
Dna Synthesis ◽  
Histone Modification ◽  
Dna Polymerase ◽  
Human Cytomegalovirus ◽  
Viral Genome ◽  
Histone H3 ◽  
Viral Dna ◽  
The Impact ◽  
Preferential Incorporation

In the nuclei of permissive cells, human cytomegalovirus genomes form nucleosomal structures initially resembling heterochromatin but gradually switching to a euchromatin-like state. This switch is characterized by a decrease in histone H3 K9 methylation and a marked increase in H3 tail acetylation and H3 K4 methylation across the viral genome. We used ganciclovir and a mutant virus encoding a reversibly destabilized DNA polymerase to examine the impact of DNA replication on histone modification dynamics at the viral chromatin. The changes in H3 tail acetylation and H3 K9 methylation proceeded in a DNA replication-independent fashion. In contrast, the increase in H3 K4 methylation proved to depend widely on viral DNA synthesis. Consistently, labeling of nascent DNA using “click chemistry” revealed preferential incorporation of methylated H3 K4 into viral (but not cellular) chromatin during or following DNA replication. This study demonstrates largely selective epigenetic tagging of postreplicative human cytomegalovirus chromatin.

scholarly journals Electrodeposition of Copper and Brass Coatings with Olive-Like Structure

Materials ◽  
2021 ◽  
Vol 14 (7) ◽  
pp. 1762
Author(s):  
Artur Maciej ◽  
Natalia Łatanik ◽  
Maciej Sowa ◽  
Izabela Matuła ◽  
Wojciech Simka
Keyword(s):  
Corrosion Resistance ◽  
Cathodic Current Density ◽  
Bath Composition ◽  
Cathodic Current ◽  
Corrosion Properties ◽  
Fine Grained ◽  
Electrodeposited Coating ◽  
Copper Zinc ◽  
New Generation ◽  
First Time

One method of creating a brass coating is through electrodeposition, which is most often completed in cyanide galvanic baths. Due to their toxicity, many investigations focused on the development of more environmentally friendly alternatives. The purpose of the study was to explore a new generation of non-aqueous cyanide-free baths based on 1-ethyl-3-methylimidazolium acetate ionic liquids. The study involved the formation of copper, zinc, and brass coatings. The influence of the bath composition, cathodic current density, and temperature was determined. The obtained coatings were characterized in terms of their morphology, chemical composition, phase composition, roughness, and corrosion resistance. It was found that the structure of the obtained coatings is strongly dependent on the process parameters. The three main structure types observed were as follows: fine-grained, porous, and olive-like. To the best knowledge of the authors, it is the first time the olive-like structure was observed in the case of an electrodeposited coating. The Cu-Zn coatings consisted of 19–96 at. % copper and exhibited relatively good corrosion resistance. A significant improvement of corrosion properties was found in the case of copper and brass coatings with the olive-like structure.

scholarly journals Interactome Analysis of KIN (Kin17) Shows New Functions of This Protein

2021 ◽  
Vol 43 (2) ◽  
pp. 767-781
Author(s):  
Vanessa Pinatto Gaspar ◽  
Anelise Cardoso Ramos ◽  
Philippe Cloutier ◽  
José Renato Pattaro Junior ◽  
Francisco Ferreira Duarte Junior ◽  
...  
Keyword(s):  
Dna Replication ◽  
Protein Interactions ◽  
Ribosome Biogenesis ◽  
Cell Metabolism ◽  
Cell Types ◽  
Protein Protein Interactions ◽  
Cellular Mechanisms ◽  
Cancerous Cell ◽  
First Time

KIN (Kin17) protein is overexpressed in a number of cancerous cell lines, and is therefore considered a possible cancer biomarker. It is a well-conserved protein across eukaryotes and is ubiquitously expressed in all cell types studied, suggesting an important role in the maintenance of basic cellular function which is yet to be well determined. Early studies on KIN suggested that this nuclear protein plays a role in cellular mechanisms such as DNA replication and/or repair; however, its association with chromatin depends on its methylation state. In order to provide a better understanding of the cellular role of this protein, we investigated its interactome by proximity-dependent biotin identification coupled to mass spectrometry (BioID-MS), used for identification of protein–protein interactions. Our analyses detected interaction with a novel set of proteins and reinforced previous observations linking KIN to factors involved in RNA processing, notably pre-mRNA splicing and ribosome biogenesis. However, little evidence supports that this protein is directly coupled to DNA replication and/or repair processes, as previously suggested. Furthermore, a novel interaction was observed with PRMT7 (protein arginine methyltransferase 7) and we demonstrated that KIN is modified by this enzyme. This interactome analysis indicates that KIN is associated with several cell metabolism functions, and shows for the first time an association with ribosome biogenesis, suggesting that KIN is likely a moonlight protein.

El español de la isla de La Graciosa desde una perspectiva prosódica

2021 ◽  
Vol 137 (2) ◽  
pp. 451-476
Author(s):  
Imelda Chaxiraxi Díaz Cabrera ◽  
Carolina Jorge Trujillo
Keyword(s):  
Canary Islands ◽  
Grammatical Morphology ◽  
Paper Format ◽  
New Generation ◽  
First Time ◽  
The Town

Abstract Manuel Alvar published the only linguistic work known on Spanish from the island of La Graciosa (Canary Islands) in 1965, focused on the town of Caleta del Sebo, to document, in the field of Linguistic geography, the ALEICan (Linguistic and ethnographic atlas of the Canary Islands [1975–1978]). Alvar’s studies used to cover the lexical, grammatical (morphology and syntax) and phonetic levels of the segmental type, but he did not consider prosodic aspects of speech which would later be incorporated into a new generation of atlases, which would go from paper format to multimedia. As the main exponent, the AMPER project (Atlas Multimédia Prosodique de l’Espace Roman) was created in 2001 and, within its framework, we intend to describe the melodic characteristics of a group of sentences emitted by a man and a woman from Caleta del Sebo, completing thus the study started by Alvar fifty-five years ago. In this way, the results will show for the first time if there is a prosodic proximity between the eighth island and the seven main islands, which have been widely described in previous works both in formal and in informal speech.

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