Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “permissive genetic background”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

5 recordsLinked to original sources
PubMed1978

Fv-1 regulation of lymphoma development and of thymic ecotropic and xenotropic MuLV expression in mice of the AKR/J x RF/J cross.

The incidence of spontaneous thymic lymphoma has been studied in crosses between AKR/J and RF/J mice. AKR mice develop a high incidence of this disease. RF mice transmit a marked resistance to development of the disease to F1 hybrid mice of the AKR x RF cross. This resistance is associated with a reduction of endogenous ecotropic and xenotropic MuLV expression in the prelymphomatous thymus. The RF gene governing the coordinate suppression of these three phenotypes has been mapped to the Fv-1 locus. These results indicate that the particular Fv-1 allele of AKR mice provides a permissive genetic background for endogenous ecotropic and xenotropic MuLV expression and that these viral activities may be etiologically involved in the development of spontaneous thymic lymphoma in the mouse.

Aging↗
PubMed1979

Pathology of dementia.

A group of diseases of the brain characterized by dementia have been discussed. The pathologic features of each were described and illustrated. It seems that, in summary, several points merit emphasis. First of all, as more people survive to the seventh, eighth, and ninth decades, the most common dementia, senile Alzheimer's disease, will become a more significant public health problem. Second, while at the present time there is no successful therapy available, there are some glimmerings of hope on the horizon. The discovery of the agent of Creutzfeldt-Jakob disease seems to have placed us on the fringe of a whole new series of advances. A novel type of disease agent awaits characterization and definition, and there are hints that similar agents could be responsible for the development of the degenerative diseases, perhaps in conjunction with environmental toxins and in the medium of a permissive genetic background. In the case of Huntington's chorea, it seems reasonable that a pharmacologic agent could be found to control the symptoms such as L-dopa therapy has done for patients with Parkinson's disease. It may develop, however, that such an agent will control the choreiform movements but will not influence the dementing condition.

Adult↗
PubMed2026

Historical metabolic adaptation potentiates the rapid evolution of flonicamid resistance in Myzus persicae.

Rapid adaptation to novel environments is often shaped not only by newly acquired mutations but also by historical genetic backgrounds established through prior evolutionary events. However, the extent to which such historical contingency contributes to the rapid evolution of insecticide resistance remains poorly understood. Here, we investigated the emergence of resistance to flonicamid, a recently deployed insecticide, in the green peach aphid, Myzus persicae. We show that constitutive overexpression of the P450 enzymes CYP6CY3 and CYP6CY4, already widespread in populations of M. persicae before flonicamid deployment, confers a previously cryptic tolerance phenotype to flonicamid. However, biochemical and transgenic analyses demonstrated that these metabolic adaptations provide only weak protection against flonicamid. Following flonicamid deployment, however, a novel target-site mutation, NaamV251I, in the recently identified molecular target of 4-trifluoromethylnicotinamide (TFNA-AM), emerged in M. persicae on a genetic background of CYP6CY3 or CYP6CY4 overexpression. Structural modeling, enzymatic assays, and CRISPR-Cas9 genome editing demonstrated that this mutation reduces target sensitivity and independently confers moderate resistance. Strikingly, combining the nicotinamidase (Naam) mutation with pre-existing CYP6CY3 or CYP6CY4 overexpression produced substantially elevated resistance phenotypes that far exceeded the effects of either mechanism alone. Our results demonstrate that the pre-existing metabolic background did not itself evolve further following flonicamid deployment but fundamentally altered the phenotypic consequences of a subsequently acquired target-site mutation. These findings provide direct evidence that historical adaptive variation can potentiate rapid resistance evolution to newly introduced insecticides and reveal how interactions between past and contemporary adaptations shape evolutionary responses to novel environmental challenges.

Animals↗
PubMed2026

Structural complexity and mechanistic diversity of MECOM rearrangements in myeloid neoplasms.

Rearrangements involving MECOM at chromosome 3q26.2 are recurrent in myeloid neoplasms, classically represented by inv(3)(q21q26.2) and t(3;3)(q21;q26.2), which reposition the GATA2-distal haematopoietic enhancer and drive aberrant EVI1 overexpression. However, the full structural and mechanistic diversity of MECOM rearrangements (MECOM-r) is yet to be explored. We retrospectively analysed 97 cases with cytogenetically defined MECOM-r and identified 12 with complex rearrangements using GTG-banded karyotyping and tri-colour interphase/metaphase fluorescence in situ hybridisation analyses. These 12 cases demonstrated remarkable structural heterogeneity. The abnormalities encompassed translocations, inversions, insertions, duplications, and deletions, which often coexisted within the same specimen as multiple rearranged subclones. Insertional events emerged as a distinct mechanism of MECOM activation. These encompassed insertions of MYNN and/or MECOM into chromosomes 1 and 6, insertion of chromosome 8 segment into MECOM, and inverted insertions between homologous chromosome 3 segments. Recurrent breakpoints at 3q21 across multiple cases, together with localised copy number imbalances frequently involving the MYNN and GOLIM4 loci at 3q26.2, underscore the architectural fragility of these two regions. Co-occurring abnormalities such as -5/del(5q), -7/del(7q), and TP53 loss were common, reflecting a permissive genomic background for chromosomal reassembly. Our findings expand the mechanistic landscape of MECOM-r beyond canonical inv(3)/t(3;3), establishing 3q21 and 3q26.2 as structural 'hotspots' and genomic instability hubs. Distinct from fusion-driven oncogenes such as KMT2A, MECOM activation results from enhancer hijacking and regional structural remodelling, leading to EVI1 overexpression and clonal evolution in myeloid malignancies.

Humans↗
PubMed1977

Multiple interactions of a DNA-binding protein in vivo. III. Phage T4 gene-32 mutations differentially affect insertion-type recombination and membrane properties.

We have investigated in in vivo roles of T4 gene-32 protein in recombination. We have studied the effects of gene-32 mutations under conditions that allow normal DNA replication and are permissive for progeny production. Under these conditions, certain gene-32 mutations specifically reduce insertion-type (short-interval) recombination but none affect crossover-type (long-interval) recombination (see Figure 5). Heterozygote frequencies in all gene-32 mutants are similar to or higher than in a gene-32+ background and are not correlated with recombination deficiencies. "Recombination-deficient" alleles are dominant or codominant over the "recombination-proficient" gene 32 mutation tsL171. This explains apparent discrepancies between a gene-32 map deduced from two-factor crosses and the map derived from three-factor crosses. We have also found that the "recombination proficient" mutation tsL171 and it homdoalleles suppress the characteristic plaque morphology of rII mutants. Under restrictive conditions, tsL171 is partially suppressed by rII mutations, which allow the use of host ligase in recombination. Our present and previous results are discussed in terms of current recombination models. We conclude that gene-32 protein functions in recombination by forming a complex with DNA, with recombination enzymes and with membrane components. Since gene-32 protein interacts with many components of this recombination complex, gene-32 mutations may differentially affect various recombination steps.

Alleles↗