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[Evolution of H3 antigen of influenza viruses isolated during 1968-1976].

Influenza viruses type A isolated in 1968--1976 were found to have changes in the content of the antigenic determinant H3. The experiments showed that while in the viruses isolated in 1968--1972 the H3 antigen was dominating, in the A/Port Chalmers/1/73 virus and some viruses isolated in 1975--1976 this antigen became more and more minor. A correlation was observed between the content of H3 antigen in viruses and the capacity of anti-H3 antiserum to inhibit the infectious activity of viruses. The prepared monospecific serum to H3 antigen contained no antibody to the other two antigenic determinants of virus or to neuraminidase and host cell antigen and was completely free from inhibitors. The serum could be used in HI, CFT, and immunodiffusion tests for the analysis of the antigenic composition of newly isolated influenza viruses.

Antigens, Viral

Thyroid radiation dose during panoramic and cephalometric dental x-ray examinations.

Radiation exposure from panoramic equipment can be reduced significantly by use of smaller film, adjustment of the beam height to the height of the smaller film, and careful positioning of patients. These techniques have no adverse effect on the quality of the diagnostic information needed in dentistry. In addition to describing methods of reducing exposures from panoramic machines, this study demonstrates that the use of a barrier collar during static, cephalometric examinations can appreciably reduce thyroid exposure. Since the objective is to obtain diagnostic information from the film without irradiating the thyroid, the application of a lead-impregnated collar is a minor inconvenience, easily borne by the patient and operator. It should be noted that the use of the collar during panoramic examinations affords little or no protection since the relative motion of the panoramic machine places the axis of movement inside the head and neck of the patient. While the evolution of diagnostic radiology may have reached a high level of technical refinement of equipment and film the clinician still must avoid unnecessary exposure for X-ray examinations and must carefully select the best type of examination to be used for each patient. For example, a complete panoramic examination to determine the position of a known unerupted third molar tooth is probably not an exercise of good judgment since other examinations, such as periapical, could yield the same information with less exposure. Decisions must be made with good judgment, value being placed on relative risks versus the benefits of diagnostic yield.

Adolescent

Detecting Introgression in Shallow Phylogenies: How Minor Molecular Clock Deviations Lead to Major Inference Errors.

Recent theoretical and algorithmic advances in introgression detection, coupled with the growing availability of genome-scale data, have highlighted the widespread occurrence of interspecific gene flow across the tree of life. However, current methods largely depend on the molecular clock assumption-a questionable premise given empirical evidence of substitution rate variation across lineages. While such rate heterogeneity is known to compromise gene flow detection among divergent lineages, its impact on closely related taxa at shallow evolutionary timescales remains poorly understood, likely because these taxa are often assumed to adhere to a molecular clock. To address this gap, we combine theoretical analyses and simulations to evaluate the robustness of widely used site pattern methods (D-statistic and HyDe) to rate variation across phylogenetic timescales. Our results demonstrate that both methods exhibit high sensitivity to even minor deviations from the molecular clock at shallow timescales, complementing previous findings at deeper scales. Specifically, in young phylogenies (with an age of 3 × 105 generations) with small population sizes, weak (17% difference) and moderate (33% difference) rate variation can inflate false-positive rates up to 35% and 100%, respectively, using site pattern counts from a 500 Mb genome. Employing a more distant outgroup intensifies these spurious signals. Our study demonstrates that summary tests for introgression are pervasively vulnerable to minor rate variations and underscores the critical need for advanced methodologies to disentangle genuine introgression from false signals generated by rate heterogeneity.

Phylogeny

Structural similarities between C6 and C7 of human complement.

A new method for the isolation of C6 and C7 by affinity chromatography of human serum with anti-C6 and anti-C7 coupled to Sepharose is described. C6 and C7 prepared by this method are hemolytically fully active, homogeneous proteins obtained in 25% yield. A comparison of the properties of isolated C6 and C7 gave the following results: The amino acid composition of the two proteins is very similar. The m.w. calculated from the amino acid content is 124,800 for C6 and 120,800 for C7. Both components are single chain glycoproteins migrating upon electrophoresis at pH 8.6 as beta 2-globulins, Both proteins are polymorphic as detected by isoelectrofocusing in polyacrylamide gels and range in their isoelectric points from pH 6.15 to 6.7. The UV spectra reveal only minor differences; the extinction coefficients are: EC6 = 1.71 cm2 X mg-1 and EC7 = 1.92 cm2 X mg-1. CD-spectra show 8% alpha-helix and 10% beta-structure for C6 and 10% alpha-helix and 14% beta-structure for C7. The structural similarities of C6 and C7 suggest their evolution from a common ancestral gene.

Chemical Phenomena

The histogenesis of mixed cervical carcinomas. The concept of endocervical columnar-cell dysplasia.

In a case of cervical adenocarcinoma in situ, accompanied by relatively minor squamous-cell dysplasia, the neoplastic glandular cells were associated with "abnormal" but not clearly cancerous surface cells of the endocervix. Measurements of the nuclear DNA of these cells revealed an aneuploid pattern similar to that of epidermoid dysplasias. It is suggested that endocervical dysplasia is a valid entity and represents a step in the evolution of cervical adenocarcinoma from reserve cells comparable to the position of epidermoid dysplasia in the genesis of epidermoid carcinoma.

Adenocarcinoma

Patterns of molecular variation. I. Interspecific comparisons of electromorphs in the Drosophila mulleri complex.

The average mobility of electromorphs at an enzyme locus in a single population was defined as the weighted average mobility of the electromorphs in that population, where the electromorph frequencies are the weights. A derivative distance measure was defined whose taxonomic utility was determined in the Drosophila mulleri species complex. Most of the variation in this metric was at the interspecific level, primarily among clusters of sibling species. The electromorphs of some loci were equally and regularly spaced, while those of other loci were less regular in their spacing. Overall, these minor perturbations from regular spacing did not noticeably detract from the taxonomic utility of average mobility, and cluster analysis yielded the same taxonomic relationships as more conventional nonmolecular treatments. On the other hand, electromorph spacing may be related to functional constraints on the enzyme molecules. Some possible implications of the results for the modes of selection during evolution of the different enzymes are discussed.

Alcohol Oxidoreductases

Morphological studies on the periostracum of the fresh-water mussel Amblema (Uniondae): light microscopy, transmission electron microscopy, and scanning electron microscopy.

The structure of the periostracum in the fresh-water mussel Amblema has been described using light microscopy, transmission elec;ron microscopy, and scanning electron microscopy. The structure and evolutive course of the periostracum was studied along its entire length, from the periostracal groove until it forms the tough outer covering of the shell. At least five structurally and functionally distinct regions were identified. In addition, the periostracum itself was seen to be a multilayered structure consisting of three major layers which are themselves subdivided into minor layers. From these morphological observations, a regulatory role for the various periostracal layers in mineral trapping, nucleation, and the subsequent formation of the prismatic and nacreous layers of the shell can be postulated.

Animals

Saccharin- or quinine-induced changes in the rat pups following prolonged ingestion by the dam.

Effects presumably induced by a chronic free ingestion of saccharin (0.40 mg/ml) or of quinine (0.25 mg/ml) by female rats during the pregestative, gestative and lactating periods were investigated in the ensuing progeny. Preweaned pups were studied from birth up to weaning (21 days of age) by means of selected gross behavioral tests. The saccharin litters were mainly characterized by a slowering in the body growth evolution. The quinine pups demonstrate several physical anomalies: (1) congenital malformations in 5% of the animals; (2) a significantly reduced birth weight followed by a persistent growth retardation, and (3) a significant delay in the teeth eruption (1.6 and 2.6 days) and in the eye openings (1.6 days). In comparison to the untreated offspring, the saccharin pups showed minor effects whereas quinine-exposed rats were clearly impaired in several features of the postnatal physical development. Therefore, the addition of the sweetener to morphine solution may be convenient for the voluntary oral consumption of the narcotic. Conversely, quinine, used to habituate animals to drinking bitter solutions, has to be rejected in this narcotization procedure as being a harmful agent to the growing rat.

Abnormalities, Drug-Induced

Tuberous xanthoma in homozygous type II hyperlipoproteinemia. A histologic, histochemical, and electron microscopical study.

Histologic, histochemical, and ultrastructural studies of a tuberous xanthoma from a patient with homozygous type II hyperlipoproteinemia showed that all of the lipid was within histiocytic foam cells; no lipid was identified in interstitial regions or in blood vessels. Primitive mesenchymal cells, elongated perivascular and fibroblast-like cells, and lysosome-filled macrophages also were present within the xanthoma, indicating possible stages in the evolution of dermal mesenchymal cells into mature, cholesterol-rich foam cells. Morphologically, the lipid was in four different forms: large droplets, which were the dominant form, and membrane-bound crystals, concentric lamellar bodies, and ceroid. The paucity of membrane-bound lipid forms, relative to the abundant free lipid droplets, indicated that lysosomal digestion was a minor metabolic pathway for the intracellular metabolism of lipid in the xanthoma. Thus, nonlysosomal lipid storage in foam cells is a characteristic tissue response to the underlying metabolic defect in type II hyperlipoproteinemia.

Adolescent

DNA replication fidelity.

DNA replication fidelity is a key determinant of genome stability and is central to the evolution of species and to the origins of human diseases. Here we review our current understanding of replication fidelity, with emphasis on structural and biochemical studies of DNA polymerases that provide new insights into the importance of hydrogen bonding, base pair geometry, and substrate-induced conformational changes to fidelity. These studies also reveal polymerase interactions with the DNA minor groove at and upstream of the active site that influence nucleotide selectivity, the efficiency of exonucleolytic proofreading, and the rate of forming errors via strand misalignments. We highlight common features that are relevant to the fidelity of any DNA synthesis reaction, and consider why fidelity varies depending on the enzymes, the error, and the local sequence environment.

Base Pair Mismatch

Bile salts of the green turtle Chelonia mydas (L.)

1. Bile salts of the green turtle Chelonia mydas (L.) were analysed as completely as possible. 2. They consist of taurine conjugates of 3 alpha, 7 alpha, 12 alpha, 22 xi-tetrahydroxy-5 beta-cholestan-26-oic acid (tetrahydroxysterocholanic acid) and 3 alpha 12 alpha, 22 xi-trihydroxy-5 beta-cholestan-26-oic acid, with minor amounts of 3 alpha, 7 alpha, 12 alpha-trihydroxy-5beta-cholan-24-oic acid (cholic acid), 3alpha, 12 alpha-dihydroxy-5beta-cholan-24-oic acid (deoxycholic acid) and possibly other bile acids. 3. Cholic acid and deoxycholic acid represent the first known examples of bile acids common to chelonians and other animal forms: they may indicate independent evolution in chelonians to C24 bile acids. 4. The discovery of a 7-deoxy C27 bile acid is the first evidence that C27 bile acids or their conjugates have an enterohepatic circulation.

Animals

Perturbing H-NS function reveals roles in restricting virulence heterogeneity and pathogen adaptation.

Xenogeneic silencers, such as histone-like nucleoid structuring protein (H-NS), are critical for maintaining horizontally acquired genes in bacterial genomes and minimizing fitness costs associated with inappropriate expression. For bacterial pathogens, this has enabled the acquisition of costly virulence regulons, with H-NS balancing the need for tight silencing with rapid expression in host environments. For Salmonella enterica serovar Typhimurium (STm), survival in these environments relies on phenotypic heterogeneity in virulence gene expression and evolutionary adaptation. Although complete loss of hns is highly deleterious in STm, how subtle impairments to this global silencer disrupt heterogeneity in virulence gene expression and alter adaptation to host environments remains poorly understood. Here, we identify an STm hns hypomorph strain and find that its reduced H-NS DNA-binding affinity increases the proportion of virulence-expressing cells, resulting in enhanced epithelial cell infection in vitro. Furthermore, through experimental evolution in intracellular-like conditions in vitro, we demonstrate that both wild-type and mutant populations converge on disrupting the SPI-2 virulence regulon to improve fitness; however, the mutant population also acquires distinct adaptive mutations to resolve the underlying dysregulation in gene expression. These results suggest that H-NS sets single-cell virulence activation thresholds and that even minor disruptions to its silencing function impact pathogen adaptation, highlighting its role as a critical evolutionary buffer.

Salmonella typhimurium

Cytogenetic aspects of phylogeny in the Bovidae. I. G-banding.

An extensive G-banding study of karyotypes of 12 species of Bovidae has been undertaken in an attempt to trace homologies and patterns of evolution of karyotype phenotypes throughout the family. G-banding profiles revealed a considerable degree of chromosome-arm homology throughout the group, which also extended into the related superfamilies, the Giraffoidea and Cervoidea. The conservation of banding patterns in chromosome arms strongly indicates that Robertsonian translocation type rearrangements have provided the major source of interspecies karyotype differences, with inversions and reciprocal and tandem translocations providing relatively minor contributions. Examples of individuals carrying newly arisen Robertsonian translocations are not infrequent, and in one instance there was evidence that two similar rearrangements had arisen independently in two species. Despite the extensive changes in karyotype organization, subfamilies within the Bovidae were characterized by the presence of common rearrangements, and those involving autosomal pairs 11 and 12 of the ox, as well as the X chromosome, separate the Bovinae from the Caprinae and Hippotraginae.

Animals

Multi-strain carriage and intrahost diversity of Staphylococcus aureus among Indigenous adults in the USA.

Staphylococcus aureus (SA) is an opportunistic pathogen and human commensal that is frequently present in the upper respiratory tract, gastrointestinal tract and skin. While SA can cause diseases ranging from minor skin infections to life-threatening bacteraemia, it can also be carried asymptomatically. Indigenous individuals in the Southwest USA experience high rates of invasive SA disease. As carriage is the most significant risk factor for disease, understanding the dynamics of SA carriage, and in particular co-carriage of multiple strains, is important to develop strategies to prevent transmission in vulnerable communities. Here, we investigated SA co-carriage and intrahost evolution by sampling several colonies from multiple anatomical sites and whole-genome sequencing (WGS) on 310 SA isolates collected from 60 Indigenous adults participating in a cross-sectional carriage study. We assessed the richness and diversity of SA isolates via differences in multilocus sequence type, core-genome SNPs and genome content. Using WGS data, we identified 95 distinct SA intra-subject lineages (ISLs) among 60 participants; co-carriage was detected in 42% (25/60). Notably, two participants each carried four distinct SA ISLs. Variation in antibiotic resistance determinants among carried strains was identified among 42% (25/60) of participants. Lastly, we found unequal distribution of clonal complex by body site, suggesting that certain lineages may be adapted to specific anatomical sites. Together, these findings suggest that co-carriage may occur more frequently than previously appreciated and further our understanding of SA intrahost diversity during carriage, which has implications for surveillance activities and epidemiological investigations.

Humans

Polyploidy-mediated variations in glutamate receptor proteins linked to Fusarium wilt resistance in upland cotton.

Cotton production in the US faces a serious threat from Fusarium oxysporum f. sp. vasinfectum race 4 (FOV4), a soil-borne fungus causing Fusarium wilt by infecting the roots and vascular system of susceptible cotton, leading to rapid wilting and death. Here, we investigate genetic mechanisms of resistance to FOV4 in the highly resistant upland cotton genotype "U1" using an early-generation segregating biparental population ("U1" × "CSX8308") with comprehensive genomic resources. Reference-grade genomic assemblies of the parents revealed minor structural variations between "U1" haplotypes, a high degree of collinearity at chromosome synteny and micro-synteny levels, and significant divergence from "CSX8308" with 8.9 million SNPs. QTL analysis identified significant markers on chromosomes D03 and A02 linked to reduced Fusarium wilt severity. Within these regions, two glutamate-receptor-like (GLR) genes showed structural variation and overlapped between translocated segments on A02 and D03, suggesting a rare but important reinforcing effect of parallel evolution between susceptible and resistant genotypes. Transcriptome profiles of "U1" under FOV4 infection reveal activation of calcium-binding proteins and transcription factors regulating plant hormones (ethylene, abscisic acid, jasmonic acid, and salicylic acid), along with enzymes involved in cell wall remodeling and phytoalexin production. Advancing cotton improvement depends on incorporating durable genetic disease resistance into high-yielding, high-quality cultivars.

Fusarium

[Biological cycle of Tarsubulura perarmata (Ratzel, 1868) (author's transl)].

Tarsubulura perarmata (Ratzel, 1868) is described from a primate Tarsius bancanus and from Tupaidae: Tupaia glis and T. minor in Malaysia (Kuala Lumpur). Its biological cycle is done by the experimental infestation of crickets belonging to the genera Valanga and Oxya. The infective larvae are obtained after three weeks of development of 28 degrees C in the intermediate host. They differ from third stage larvae obtained from Subulurinae by the development of cuticular pharyngeal lobes. The early apparition of this ontogenetic character confirms the isolation of the genus Tarsubulura as compared to the general evolution of the Subuluridae.

Animals

Defining APOBEC-induced mutation signatures and modifying activities in yeast.

APOBEC cytidine deaminases guard cells in a variety of organisms from invading viruses and foreign nucleic acids. Recently, several human APOBECs have been implicated in mutating evolving cancer genomes. Expression of APOBEC3A and APOBEC3B in yeast allowed experimental derivation of the substitution patterns they cause in dividing cells, which provided critical links to these enzymes in the etiology of the COSMIC single base substitution (SBS) signatures 2 and 13 in human tumors. Additionally, the ability to scale yeast experiments to high-throughput screens allows use of this system to also investigate cellular pathways impacting the frequency of APOBEC-induced mutation. Here, we present validated methods utilizing yeast to determine APOBEC mutation signatures, genetic interactors, and chromosomal substrate preferences. These methods can be employed to assess the potential of other human APOBECs and APOBEC orthologs in different species to contribute to cancer genome evolution as well as define the pathways that protect the nuclear genome from inadvertent APOBEC activity during viral restriction.

Humans

Generation and validation of a Myh11Dre-Spp1Cre intersectional mouse model for lineage tracing of disease-associated smooth muscle cell states.

BACKGROUND: Phenotypic modulation of vascular smooth muscle cells (VSMCs) is a hallmark of vascular remodeling and cardiovascular disease. Recent lineage-tracing and single-cell transcriptomic studies have identified secreted phosphoprotein 1 (SPP1) as a prominent marker associated with disease-associated VSMC states, particularly those linked to fibrotic remodeling and vascular calcification. However, the cellular origins and fate of SPP1-associated VSMC populations remain incompletely understood. METHODS AND RESULTS: We generated a novel Spp1-rSTOPr-Cre (Spp1Cre) knock-in mouse line in which Cre recombinase is expressed from the endogenous Spp1 locus following Dre-mediated excision of a rox-flanked transcriptional STOP cassette. Correct targeting of the knock-in allele was validated by internal, 5' junction, 3' junction, and long-range PCR analyses, as well as Sanger sequencing. To establish an intersectional lineage-tracing strategy, Spp1Cre mice were crossed with Myh11DreERT2 and Rosa26-RSR-LSL-tdTomato-LSL-eGFP reporter mice, enabling permanent labeling of VSMC-derived populations following activation of the endogenous Spp1 locus. Under physiological conditions, eGFP-positive cells were detected at low frequency within the vascular wall and were predominantly negative for the contractile markers ACTA2 and MYH11. As a proof-of-principle application, eGFP-positive cells markedly expanded within atherosclerotic lesions induced by AAV-PCSK9D377Y and high-fat diet feeding. These lineage-traced cells remained largely ACTA2- and MYH11-negative, consistent with a modulated phenotype. Notably, only a minority of eGFP-positive cells expressed SPP1 or fibronectin at the time of analysis, demonstrating the utility of permanent lineage tracing for tracking cells with a history of endogenous Spp1 activation during vascular remodeling. CONCLUSION: We report the generation and validation of a novel Myh11Dre-Spp1Cre intersectional mouse model for lineage tracing of VSMC-derived populations that have activated the endogenous Spp1 locus. This genetic resource provides a valuable platform for investigating the origin, fate, and phenotypic evolution of Spp1-associated VSMC populations during vascular remodeling and cardiovascular disease.

Animals