scholarly journals Path to Diversity and to Resistant Uniformity: Intracellular Adaptation to Nutrient Environment

2021 ◽  
Author(s):  
Victoria Korogodina
Keyword(s):  
Culture Medium ◽  
Statistical Approach ◽  
Energy Landscape ◽  
Gene Mutations ◽  
Yeast Cells ◽  
Published Data ◽  
Folding Energy ◽  
Protein Conformations ◽  
Nutrient Environment ◽  
Appearance Frequency

Abstract Two adaptation strategies are known, which provide variability and resistance of population. We study the laws of adaptation by the example of proteins and changes in their conformations. The data were obtained in the experiments of V.I. Korogodin on yeast cells with mutations, which have demonstrated the effect of the culture medium on the appearance frequency of pseudo-wild type cells. Here, these archived and published data are analyzed by the statistical approach. Statistical analysis shows the emergence of a sequence of independent foci of the pseudo-wild cells induced by intracellular factor and their association with the cytosolic and nuclear-mitochondrial oxidative pathways; the foci dispersions conform the regularities of the folding energy landscape; intracellular imbalances and gene mutations affect their frequency and diversity. We conclude that the paths from diversity to uniformity of protein conformations obeys the laws of the energy landscape. The nuclear-mitochondrial machinery generates new proteins and their homogeneous foci. Variable foci consist mainly of the former conformations remodeled under ROS from several cytosolic sources. Strong gene expression induces oxidative stress, which increases the frequency of homogeneous conformations and reduces variability. Further, stress activates a new focus of new homogeneous conformations.

scholarly journals The Role of RNA in DNA Breaks, Repair and Chromosomal Rearrangements

Biomolecules ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 550
Author(s):  
Matvey Mikhailovich Murashko ◽  
Ekaterina Mikhailovna Stasevich ◽  
Anton Markovich Schwartz ◽  
Dmitriy Vladimirovich Kuprash ◽  
Aksinya Nicolaevna Uvarova ◽  
...  
Keyword(s):  
Chromosomal Rearrangements ◽  
Gene Mutations ◽  
Nonhomologous End Joining ◽  
Published Data ◽  
Dna Double Strand Breaks ◽  
Dna Breaks ◽  
End Joining ◽  
Homology Directed Repair ◽  
Chromosome Aberration Frequency

Incorrect reparation of DNA double-strand breaks (DSB) leading to chromosomal rearrangements is one of oncogenesis’s primary causes. Recently published data elucidate the key role of various types of RNA in DSB formation, recognition and repair. With growing interest in RNA biology, increasing RNAs are classified as crucial at the different stages of the main pathways of DSB repair in eukaryotic cells: nonhomologous end joining (NHEJ) and homology-directed repair (HDR). Gene mutations or variation in expression levels of such RNAs can lead to local DNA repair defects, increasing the chromosome aberration frequency. Moreover, it was demonstrated that some RNAs could stimulate long-range chromosomal rearrangements. In this review, we discuss recent evidence demonstrating the role of various RNAs in DSB formation and repair. We also consider how RNA may mediate certain chromosomal rearrangements in a sequence-specific manner.

scholarly journals Children with 5′-end NF1 gene mutations are more likely to have glioma

2017 ◽  
Vol 3 (5) ◽  
pp. e192 ◽  
Author(s):  
Corina Anastasaki ◽  
Stephanie M. Morris ◽  
Feng Gao ◽  
David H. Gutmann
Keyword(s):  
Gene Mutation ◽  
Statistical Significance ◽  
Gene Mutations ◽  
Neurofibromatosis Type ◽  
Published Data ◽  
Data Sets ◽  
Nonsense Mutations ◽  
Data Set ◽  
Nf1 Gene ◽  
The Relationship

Objective:To ascertain the relationship between the germline NF1 gene mutation and glioma development in patients with neurofibromatosis type 1 (NF1).Methods:The relationship between the type and location of the germline NF1 mutation and the presence of a glioma was analyzed in 37 participants with NF1 from one institution (Washington University School of Medicine [WUSM]) with a clinical diagnosis of NF1. Odds ratios (ORs) were calculated using both unadjusted and weighted analyses of this data set in combination with 4 previously published data sets.Results:While no statistical significance was observed between the location and type of the NF1 mutation and glioma in the WUSM cohort, power calculations revealed that a sample size of 307 participants would be required to determine the predictive value of the position or type of the NF1 gene mutation. Combining our data set with 4 previously published data sets (n = 310), children with glioma were found to be more likely to harbor 5′-end gene mutations (OR = 2; p = 0.006). Moreover, while not clinically predictive due to insufficient sensitivity and specificity, this association with glioma was stronger for participants with 5′-end truncating (OR = 2.32; p = 0.005) or 5′-end nonsense (OR = 3.93; p = 0.005) mutations relative to those without glioma.Conclusions:Individuals with NF1 and glioma are more likely to harbor nonsense mutations in the 5′ end of the NF1 gene, suggesting that the NF1 mutation may be one predictive factor for glioma in this at-risk population.

scholarly journals Computational Protein Stabilization Can Affect Folding Energy Landscapes and Lead to Domain-Swapped Dimers

2021 ◽  
Author(s):  
Klara Markova ◽  
Antonin Kunka ◽  
Klaudia Chmelova ◽  
Martin Havlasek ◽  
Petra Babkova ◽  
...  
Keyword(s):  
Protein Folding ◽  
Protein Design ◽  
Energy Landscape ◽  
Single Point ◽  
Three Dimensional ◽  
Protein Stabilization ◽  
Dimensional Structure ◽  
Evolutionary Analysis ◽  
Folding Energy

<p>The functionality of a protein depends on its unique three-dimensional structure, which is a result of the folding process when the nascent polypeptide follows a funnel-like energy landscape to reach a global energy minimum. Computer-encoded algorithms are increasingly employed to stabilize native proteins for use in research and biotechnology applications. Here, we reveal a unique example where the computational stabilization of a monomeric α/β-hydrolase enzyme (<i>T</i><sub>m</sub> = 73.5°C; Δ<i>T</i><sub>m</sub> > 23°C) affected the protein folding energy landscape. Introduction of eleven single-point stabilizing mutations based on force field calculations and evolutionary analysis yielded catalytically active domain-swapped intermediates trapped in local energy minima. Crystallographic structures revealed that these stabilizing mutations target cryptic hinge regions and newly introduced secondary interfaces, where they make extensive non-covalent interactions between the intertwined misfolded protomers. The existence of domain-swapped dimers in a solution is further confirmed experimentally by data obtained from SAXS and crosslinking mass spectrometry. Unfolding experiments showed that the domain-swapped dimers can be irreversibly converted into native-like monomers, suggesting that the domain-swapping occurs exclusively <i>in vivo</i>. Our findings uncovered hidden protein-folding consequences of computational protein design, which need to be taken into account when applying a rational stabilization to proteins of biological and pharmaceutical interest.</p>

scholarly journals Computational Protein Stabilization Can Affect Folding Energy Landscapes and Lead to Domain-Swapped Dimers

2021 ◽  
Author(s):  
Klara Markova ◽  
Antonin Kunka ◽  
Klaudia Chmelova ◽  
Martin Havlasek ◽  
Petra Babkova ◽  
...  
Keyword(s):  
Protein Folding ◽  
Protein Design ◽  
Energy Landscape ◽  
Single Point ◽  
Three Dimensional ◽  
Protein Stabilization ◽  
Dimensional Structure ◽  
Evolutionary Analysis ◽  
Folding Energy

<p>The functionality of a protein depends on its unique three-dimensional structure, which is a result of the folding process when the nascent polypeptide follows a funnel-like energy landscape to reach a global energy minimum. Computer-encoded algorithms are increasingly employed to stabilize native proteins for use in research and biotechnology applications. Here, we reveal a unique example where the computational stabilization of a monomeric α/β-hydrolase enzyme (<i>T</i><sub>m</sub> = 73.5°C; Δ<i>T</i><sub>m</sub> > 23°C) affected the protein folding energy landscape. Introduction of eleven single-point stabilizing mutations based on force field calculations and evolutionary analysis yielded catalytically active domain-swapped intermediates trapped in local energy minima. Crystallographic structures revealed that these stabilizing mutations target cryptic hinge regions and newly introduced secondary interfaces, where they make extensive non-covalent interactions between the intertwined misfolded protomers. The existence of domain-swapped dimers in a solution is further confirmed experimentally by data obtained from SAXS and crosslinking mass spectrometry. Unfolding experiments showed that the domain-swapped dimers can be irreversibly converted into native-like monomers, suggesting that the domain-swapping occurs exclusively <i>in vivo</i>. Our findings uncovered hidden protein-folding consequences of computational protein design, which need to be taken into account when applying a rational stabilization to proteins of biological and pharmaceutical interest.</p>

Modulation of the Folding Energy Landscape of Cytochromecwith Salt

2004 ◽  
Vol 126 (43) ◽  
pp. 13934-13935 ◽  
Author(s):  
Shi Zhong ◽  
Denis L. Rousseau ◽  
Syun-Ru Yeh
Keyword(s):  
Energy Landscape ◽  
Folding Energy

scholarly journals Effect of fluconazole on viability of Candida albicans over extended periods of time.

1996 ◽  
Vol 40 (11) ◽  
pp. 2622-2625 ◽  
Author(s):  
P G Sohnle ◽  
B L Hahn ◽  
M D Erdmann
Keyword(s):  
Candida Albicans ◽  
Marked Reduction ◽  
Culture Medium ◽  
Antimicrobial Agents ◽  
Yeast Cells ◽  
In Vitro Susceptibility ◽  
Fungistatic Activity ◽  
Susceptibility Tests ◽  
Infecting Organisms

The treatment of chronic mycoses may expose the infecting organisms to antimicrobial agents for extended periods of time. It is possible that an azole antifungal drug such as fluconazole, with primarily fungistatic activity in standard in vitro susceptibility tests, might be able to damage the fungal cells and reduce their viability over prolonged incubations under nonproliferating conditions. To test this possibility, Candida albicans yeast cells were exposed to various concentrations of fluconazole in RPMI 1640 tissue culture medium for 4 h at 37 degrees C, washed free of the drug, and then incubated at 37 degrees C for a 28-day period; enumeration of the remaining CFU at various times during this period revealed no increased loss of viability for the fluconazole-exposed organisms. However, when fluconazole was added to the organisms maintained in distilled water (with or without pretreatment with the drug), a marked reduction of viability was found. At 14 days of incubation with two strains of C. albicans, negative cultures were found for 7 of 10 and 10 of 11 samples, respectively, containing 1.0 microgram of fluconazole per ml versus 0 of 10 and 1 of 11 control samples (P of < 0.01 and 0.001, respectively). The effect of fluconazole on fungal viability under these conditions became noticeable at approximately 7 days and was greater when the samples were incubated at 37 degrees C rather than 25 degrees C. These findings suggest that fluconazole may have fungicidal effects on fungal cells during prolonged exposures under conditions in which the organisms are prevented from proliferating by lack of nutrients.

scholarly journals Accumulation of Selenium in Candida utilis Growing in Media of Increasing Concentration of this Element

2020 ◽  
Vol 10 (4) ◽  
pp. 1439 ◽  
Author(s):  
Marek Kieliszek ◽  
Anna Maria Kot ◽  
Kamil Piwowarek ◽  
Stanisław Błażejak
Keyword(s):  
Candida Utilis ◽  
Culture Medium ◽  
Dry Weight ◽  
Yeast Cells ◽  
Reciprocating Motion ◽  
Experimental Medium ◽  
Yeast Cultures ◽  
Cell Biomass ◽  
Icp Ms ◽  
Living Organisms

Selenium is considered an essential component of all living organisms. Studies on the enrichment of yeast cells with selenium, using the ability of cell biomass to bind this element, are being reported more and more. Yeast cultures were cultivated in YPD medium enriched with Na2SeO3 salts for 72 h at 28 °C on a shaker utilizing reciprocating motion. Selenium in cell biomass was determined with the use of ICP–MS. It was observed that the addition of selenium to the experimental medium (in the range of 4–100 mg/L) increased the content of this element in the yeast cell biomass. During the extension of cultivation time, the number of yeast cells and biomass yield exhibited a decreasing trend. Based on the obtained results, it was concluded that yeast cells exhibited the ability to accumulate selenium in both logarithmic and stationary growth phases. The dose of 20 and 30 mg/L of selenium in the culture medium meets the expectations in terms of both the content of selenium bound to yeast cells (1944 ± 110.8 μg/g dry weight) under 48-h cultivation. The obtained results confirmed that the Candida utilis ATCC 9950 strain exhibits the ability to bind selenium, which means that the biomass of these yeasts may be used as a natural source of selenium in the diet of humans and animals.

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