scholarly journals Developmentally-orchestrated mitochondrial processes prime the selection against harmful mtDNA mutations

2019 ◽  
Author(s):  
Zhe Chen ◽  
Zong-Heng Wang ◽  
Guofeng Zhang ◽  
Christopher K. E. Bleck ◽  
Dillon J. Chung ◽  
...  
Keyword(s):  
Stress Test ◽  
Mitochondrial Fission ◽  
Purifying Selection ◽  
Minor Role ◽  
Individual Genome ◽  
Mtdna Mutations ◽  
Mtdna Replication ◽  
A Minor ◽  
Selection Mechanisms ◽  
Pole Plasm

AbstractAlthough mitochondrial DNA (mtDNA) is prone to mutation and not all conventional DNA repair systems operate in mitochondria, deleterious mutations are exceedingly rare. How the transmission of detrimental mtDNA mutations is restricted through the maternal lineage is debated. Here, we use Drosophila to dissect the mechanisms of mtDNA selective inheritance and understand their molecular underpinnings. Our observations support a purifying selection at the organelle level based on a series of developmentally-orchestrated mitochondrial processes. We demonstrate that mitochondrial fission, together with the lack of mtDNA replication in early germarium, effectively segregates mtDNA into individual organelles. After mtDNA segregation, mtDNA transcription begins, which leads to the activation of respiration in each organelle. The expression of mtDNA-encoded genes allows the functional manifestation of different mitochondrial genotypes in heteroplasmic cells, and hence functions as a stress test for each individual genome and sets the stage for the replication competition. We also show that the Balbiani body has a minor role in mtDNA selective inheritance by supplying healthy mitochondria to the pole plasm. The two selection mechanisms may act synergistically to secure the transmission of functional mtDNA through Drosophila oogenesis.

scholarly journals Mitochondrial DNA segregation and replication restrict the transmission of detrimental mutation

2020 ◽  
Vol 219 (7) ◽  
Author(s):  
Zhe Chen ◽  
Zong-Heng Wang ◽  
Guofeng Zhang ◽  
Christopher K.E. Bleck ◽  
Dillon J. Chung ◽  
...  
Keyword(s):  
Mitochondrial Dna ◽  
Stress Test ◽  
Mitochondrial Fission ◽  
Minor Role ◽  
Deleterious Mutations ◽  
Mtdna Mutations ◽  
Electron Transport Chains ◽  
Repair Mechanisms ◽  
A Minor ◽  
Pole Plasm

Although mitochondrial DNA (mtDNA) is prone to accumulate mutations and lacks conventional DNA repair mechanisms, deleterious mutations are exceedingly rare. How the transmission of detrimental mtDNA mutations is restricted through the maternal lineage is debated. Here, we demonstrate that mitochondrial fission, together with the lack of mtDNA replication, segregate mtDNA into individual organelles in the Drosophila early germarium. After mtDNA segregation, mtDNA transcription begins, which activates respiration. Mitochondria harboring wild-type genomes have functional electron transport chains and propagate more vigorously than mitochondria containing deleterious mutations in hetreoplasmic cells. Therefore, mtDNA expression acts as a stress test for the integrity of mitochondrial genomes and sets the stage for replication competition. Our observations support selective inheritance at the organelle level through a series of developmentally orchestrated mitochondrial processes. We also show that the Balbiani body has a minor role in mtDNA selective inheritance by supplying healthy mitochondria to the pole plasm. These two mechanisms may act synergistically to secure the transmission of functional mtDNA through Drosophila oogenesis.

scholarly journals Identification of the Genome Segments of Bluetongue Virus Type 26/Type 1 Reassortants Influencing Horizontal Transmission in a Mouse Model

Viruses ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2208
Author(s):  
Houssam Attoui ◽  
Baptiste Monsion ◽  
Bernard Klonjkowski ◽  
Stéphan Zientara ◽  
Peter P. C. Mertens ◽  
...  
Keyword(s):  
Mouse Model ◽  
Bluetongue Virus ◽  
Reverse Genetics ◽  
Horizontal Transmission ◽  
Clinical Signs ◽  
Small Ruminants ◽  
Minor Role ◽  
Individual Genome ◽  
A Minor ◽  
Reassortant Viruses

Bluetongue virus serotypes 1 to 24 are transmitted primarily by infected Culicoides midges, in which they also replicate. However, “atypical” BTV serotypes (BTV-25, -26, -27 and -28) have recently been identified that do not infect and replicate in adult Culicoides, or a Culicoides derived cell line (KC cells). These atypical viruses are transmitted horizontally by direct contact between infected and susceptible hosts (primarily small ruminants) causing only mild clinical signs, although the exact transmission mechanisms involved have yet to be determined. We used reverse genetics to generate a strain of BTV-1 (BTV-1 RGC7) which is less virulent, infecting IFNAR(−/−) mice without killing them. Reassortant viruses were also engineered, using the BTV-1 RGC7 genetic backbone, containing individual genome segments derived from BTV-26. These reassortant viruses were used to explore the genetic control of horizontal transmission (HT) in the IFNAR(−/−) mouse model. Previous studies showed that genome segments 1, 2 and 3 restrict infection of Culicoides cells, along with a minor role for segment 7. The current study demonstrates that genome segments 2, 5 and 10 of BTV-26 (coding for proteins VP2, NS1 and NS3/NS3a/NS5, respectively) are individually sufficient to promote HT.

scholarly journals Computational Analysis Suggests That Lyssavirus Glycoprotein Gene Plays a Minor Role in Viral Adaptation

2011 ◽  
Vol 2011 ◽  
pp. 1-11 ◽  
Author(s):  
Kevin Tang ◽  
Xianfu Wu
Keyword(s):  
Positive Selection ◽  
Purifying Selection ◽  
Host Shift ◽  
Likelihood Method ◽  
Minor Role ◽  
Glycoprotein Gene ◽  
Glycoprotein G ◽  
Viral Adaptation ◽  
A Minor ◽  
Computational Analyses

The Lyssavirus glycoprotein (G) is a membrane protein responsible for virus entry and protective immune responses. To explore possible roles of the glycoprotein in host shift or adaptation of Lyssavirus, we retrieved 53 full-length glycoprotein gene sequences from NCBI GenBank. The sequences were from different host isolates over a period of 70 years in 21 countries. Computational analyses detected 1 recombinant (AY987478, a dog isolate of CHAND03, genotype 1 in India) with incongruent phylogenetic support. No recombination was detected when AY98748 was excluded in the analyses. We applied different selection models to identify selection pressure on the glycoprotein gene. One codon at amino acid residual 483 was found to be under weak positive selection with marginal probability of 95% by using the maximum likelihood method. We found no significant evidence of positive selection on any site of the glycoprotein gene when the putative recombinant AY987478 was excluded. The computational analyses suggest that the G gene has been under purifying selection and that the evolution of the G gene may not play a significant role in Lyssavirus adaptation.

The Effect of Path Length and Display Size on Memory for Spatial Information

2012 ◽  
Vol 59 (3) ◽  
pp. 147-152 ◽  
Author(s):  
Katherine Guérard ◽  
Sébastien Tremblay
Keyword(s):  
Path Length ◽  
Potential Role ◽  
Spatial Information ◽  
Recall Performance ◽  
Minor Role ◽  
Length Effect ◽  
Serial Memory ◽  
Fixed Reference ◽  
A Minor

In serial memory for spatial information, some studies showed that recall performance suffers when the distance between successive locations increases relatively to the size of the display in which they are presented (the path length effect; e.g., Parmentier et al., 2005) but not when distance is increased by enlarging the size of the display (e.g., Smyth & Scholey, 1994). In the present study, we examined the effect of varying the absolute and relative distance between to-be-remembered items on memory for spatial information. We manipulated path length using small (15″) and large (64″) screens within the same design. In two experiments, we showed that distance was disruptive mainly when it is varied relatively to a fixed reference frame, though increasing the size of the display also had a small deleterious effect on recall. The insertion of a retention interval did not influence these effects, suggesting that rehearsal plays a minor role in mediating the effects of distance on serial spatial memory. We discuss the potential role of perceptual organization in light of the pattern of results.

Use of Different Tissue Thromboplastins in the Control of Anticoagulant-Therapy

1958 ◽  
Vol 02 (05/06) ◽  
pp. 462-480 ◽  
Author(s):  
Marc Verstraete ◽  
Patricia A. Clark ◽  
Irving S. Wright
Keyword(s):  
Prothrombin Time ◽  
Anticoagulant Therapy ◽  
Factor Vii ◽  
Rabbit Brain ◽  
Minor Role ◽  
Rabbit Lung ◽  
Coagulation Mechanism ◽  
Time Test ◽  
The One ◽  
A Minor

SummaryAn analysis of the results of prothrombin time tests with different types of thromboplastins sheds some light on the problem why the administration of coumarin is difficult to standardize in different centers. Our present ideas on the subject, based on experimental data may be summarized as follows.Several factors of the clotting mechanism are influenced by coumarin derivatives. The action of some of these factors is by-passed in the 1-stage prothrombin time test. The decrease of the prothrombin and factor VII levels may be evaluated in the 1-stage prothrombin time determination (Quick-test). The prolongation of the prothrombin times are, however, predominantly due to the decrease of factor VII activity, the prothrombin content remaining around 50 per cent of normal during an adequate anticoagulant therapy. It is unlikely that this degree of depression of prothrombin is of major significance in interfering with the coagulation mechanism in the protection against thromboembolism. It may, however, play a minor role, which has yet to be evaluated quantitatively. An exact evaluation of factor VII is, therefore, important for the guidance of anticoagulant therapy and the method of choice is the one which is most sensitive to changes in factor VII concentration. The 1-stage prothrombin time test with a rabbit lung thromboplastin seems the most suitable method because rabbit brain preparations exhibit a factor VII-like activity that is not present in rabbit lung preparations.

Produktivkraft als Versprechen

2016 ◽  
Vol 46 (185) ◽  
pp. 621-638 ◽  
Author(s):  
Christian Siefkes
Keyword(s):  
Private Consumption ◽  
Minor Role ◽  
Progressive Reduction ◽  
Internal Forces ◽  
A Minor

The ‘Fragment on Machines’ from Marx’s Grundrisse is often cited as an argument that the internal forces of capitalism will lead to its doom. But the argument that the progressive reduction of labor must doom capitalism lacks a proper foundation, as a comparison with the ‘Schemes of Reproduction’ given in Capital II shows. The latter, however, aren’t fully convincing either. In reality, more depends on the private consumption of capitalists than either model recognizes. Ultimately, most can be made of the ‘Fragment on Machines’ by reading it not as an exposure of capitalism’s internal contractions, but as a discussion of a possible communist future where labor (or work) will play but a minor role.

Effects of Myo-inositol Alone and in Combination with Seleno-Lmethionine on Cadmium-Induced Testicular Damage in Mice

2019 ◽  
Vol 12 (4) ◽  
pp. 311-323 ◽  
Author(s):  
Salvatore Benvenga ◽  
Antonio Micali ◽  
Giovanni Pallio ◽  
Roberto Vita ◽  
Consuelo Malta ◽  
...  
Keyword(s):  
Structural Changes ◽  
Natural Antioxidants ◽  
Minor Role ◽  
Positive Role ◽  
Testosterone Levels ◽  
Tnf Α ◽  
Testicular Lesions ◽  
A Minor ◽  
Immunohistochemical Analyses

Background: Cadmium (Cd) impairs gametogenesis and damages the blood-testis barrier. Objective: As the primary mechanism of Cd-induced damage is oxidative stress, the effects of two natural antioxidants, myo-inositol (MI) and seleno-L-methionine (Se), were evaluated in mice testes. Methods: Eighty-four male C57 BL/6J mice were divided into twelve groups: 0.9% NaCl (vehicle; 1 ml/kg/day i.p.); Se (0.2 mg/kg/day per os); Se (0.4 mg/kg/day per os); MI (360 mg/kg/day per os); MI plus Se (0.2 mg/kg/day); MI plus Se (0.4 mg/kg/day); CdCl2 (2 mg/kg/day i.p.) plus vehicle; CdCl2 plus MI; CdCl2 plus Se (0.2 mg/kg/day); CdCl2 plus Se (0.4 mg/kg/day); CdCl2 plus MI plus Se (0.2 mg/kg/day); and CdCl2 plus MI plus Se (0.4 mg/kg/day). After 14 days, testes were processed for biochemical, structural and immunohistochemical analyses. Results: CdCl2 increased iNOS and TNF-α expression and Malondialdehyde (MDA) levels, lowered glutathione (GSH) and testosterone, induced testicular lesions, and almost eliminated claudin-11 immunoreactivity. Se administration at 0.2 or 0.4 mg/kg significantly reduced iNOS and TNF-α expression, maintained GSH, MDA and testosterone levels, structural changes and low claudin-11 immunoreactivity. MI alone or associated with Se at 0.2 or 0.4 mg/kg significantly reduced iNOS and TNF-α expression and MDA levels, increased GSH and testosterone levels, ameliorated structural organization and increased claudin-11 patches number. Conclusion: We demonstrated a protective effect of MI, a minor role of Se and an evident positive role of the association between MI and Se on Cd-induced damages of the testis. MI alone or associated with Se might protect testes in subjects exposed to toxicants, at least to those with behavior similar to Cd.

Extraction of strontium and barium salts by the nitrobenzene solution of dicarbolide in the presence of glymes

1985 ◽  
Vol 50 (3) ◽  
pp. 581-599 ◽  
Author(s):  
Petr Vaňura ◽  
Emanuel Makrlík
Keyword(s):  
Stability Constants ◽  
Organic Phase ◽  
Equilibrium Constants ◽  
Minor Role ◽  
Nitrobenzene Solution ◽  
Ligand Structure ◽  
Stability Constants Of Complexes ◽  
Separation Factors ◽  
The Stability ◽  
A Minor

Extraction of microamounts of Sr2+ and Ba2+ (henceforth M2+) from the aqueous solutions of perchloric acid (0.0125-1.02 mol/l) by means of the nitrobenzene solutions of dicarbolide (0.004-0.05 mol/l of H+{Co(C2B9H11)2}-) was studied in the presence of monoglyme (only Ba2+), diglyme, triglyme, and tetraglyme (CH3O-(CH2-CH2O)nCH3, where n = 1, 2, 3, 4). The distribution of glyme betweeen the aqueous and organic phases, the extraction of the protonized glyme molecule HL+ together with the extraction of M2+ ion and of the glyme complex with the M2+ ion, i.e., ML2+ (where L is the molecule of glyme), were found to be the dominating reactions in the systems under study. In the systems with tri- and tetraglymes the extraction of H+ and M2+ ions solvated with two glyme molecules, i.e., the formation of HL2+ and ML22+ species, can probably play a minor role. The values of the respective equilibrium constants, of the stability constants of complexes formed in the organic phase, and the theoretical separation factors αBa/Sr were determined. The effect of the ligand structure on the values of extraction and stability constants in the organic phase is discussed.

scholarly journals The preendosomal compartment comprises distinct coated and noncoated endocytic vesicle populations.

1991 ◽  
Vol 113 (4) ◽  
pp. 731-741 ◽  
Author(s):  
S H Hansen ◽  
K Sandvig ◽  
B van Deurs
Keyword(s):  
Cell Surface ◽  
Coated Vesicles ◽  
Minor Role ◽  
Specific Marker ◽  
Con A ◽  
Early Endosomes ◽  
Gold Conjugate ◽  
Entire Cell ◽  
A Minor ◽  
Endocytic Vesicles

The transfer of molecules from the cell surface to the early endosomes is mediated by preendosomal vesicles. These vesicles, which have pinched off completely from the plasma membrane but not yet fused with endosomes, form the earliest compartment along the endocytic route. Using a new assay to distinguish between free and cell surface connected vesicle profiles, we have characterized the preedosomal compartment ultrastructurally. Our basic experimental setup was labeling of the entire cell surface at 4 degrees C with Con A-gold, warming of the cells to 37 degrees C to allow endocytosis, followed by replacing incubation medium with fixative, all within either 30 or 60 s. Then the fixed cells were incubated with anti-Con A-HRP to distinguish truly free (gold labeled) endocytic vesicles from surface-connected structures. Finally, analysis of thin (20-30 nm) serial sections and quantification of vesicle diameters were carried out. Based on this approach it is shown that the preendosomal compartment comprises both clathrin-coated and non-coated endocytic vesicles with approximately the same frequency but with distinct diameter distributions, the average noncoated vesicle being smaller (95 nm) than the average coated one (110 nm). In parallel experiments, using an anti-transferrin receptor gold-conjugate as a specific marker for clathrin-dependent endocytosis it is also shown that uncoating of coated vesicles plays only a minor role for the total frequency of noncoated vesicles. Furthermore, after perturbation of clathrin-dependent endocytosis by potassium depletion where uptake of transferrin is blocked, noncoated endocytic vesicles with Con A-gold, but not coated vesicles, exist already after 30 and 60 s. Finally, it is shown that the existence of small, free vesicles in the short-time experiments cannot be ascribed to recycling from the early endosomes.

scholarly journals Sun Protection and Sunburn in Children Aged 1–10 Years in Germany: Prevalence and Determinants

Children ◽  
2021 ◽  
Vol 8 (8) ◽  
pp. 668
Author(s):  
Tatiana Görig ◽  
Corinna Södel ◽  
Annette B. Pfahlberg ◽  
Olaf Gefeller ◽  
Eckhard W. Breitbart ◽  
...  
Keyword(s):  
Role Models ◽  
Skin Color ◽  
Role Model ◽  
Sun Protection ◽  
Minor Role ◽  
Positive Role ◽  
Protection Measures ◽  
Telephone Interviews ◽  
The Past ◽  
A Minor

Seeking shade, the use of textile sun protection and sunscreen, and protecting one’s eyes by wearing sunglasses are recommended sun protection measures in children. We aimed to quantify the use of these measures as well as the prevalence of sunburn in children aged 1 to 10 years in Germany and to identify their determinants. Data collected via telephone interviews in a nationwide sample of 554 parents or caregivers in family were analyzed. Use of sunscreen was the most common measure applied (77.8%), while sunglasses were least frequently used (12.5%). The prevalence of sunburn during the past year was 21.8%, and it was positively associated with children’s age. The use of sun protection measures was significantly associated with the age and skin color of the child, while characteristics and tanning behaviors of the caregivers only played a minor role. The use of sun protection measures was higher when caregivers perceived themselves as a role model (Odds Ratio (OR) = 4.33, p < 0.001). Our nationwide data show that there remains a need for the improved use of sun protection measures, especially in children aged 7 to 10 years. In educational material, parents should be encouraged to become positive role models for their children regarding sun protection.

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