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Results for “episodic positive selection”

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PubMed2026

Evolutionary dynamics of the chloroplast genome in Abutilon (Malvoideae, Malvaceae).

The genus Abutilon Mill. (Malvaceae) comprises approximately 178 species distributed across tropical and subtropical regions, many of which hold significant ornamental, economic, and medicinal value; yet its taxonomic classification remains challenging. In this study, six species were sequenced from herbarium specimens, and the chloroplast (cp.) genomes of ten additional species were assembled de novo from publicly available raw data. Three previously reported cp. genomes were also incorporated to characterise cp. genome structure, identify polymorphic loci, and perform phylogenetic analyses. The cp. genomes ranged from 159,458 to 160,454 bp and exhibited the typical quadripartite structure, with each genome containing 112 unique genes (78 protein-coding, 30 tRNA, and 4 rRNA) that showed conserved content and organisation. These genomes exhibited high similarity in GC content, inverted repeat boundaries, relative synonymous codon usage, amino acid frequencies, and substitution patterns. However, notable variation was observed in the total number of simple sequence repeats, ranging from 70 to 97 per genome. Selection analyses indicated predominant purifying selection, with evidence of episodic positive selection detected in rpoC2, rbcL, and ycf1. Two codons in rbcL were clade-specific and provided phylogenetic signal distinguishing Australian and Old World pantropical species. Nucleotide diversity analysis identified six highly polymorphic intergenic spacers (trnH-psbA, rps19-rpl2, psbT-pbf1, psaC-ndhD, trnR-atpA, and ndhJ-ndhK) that may be suitable for taxonomic studies. The phylogeny from maximum likelihood (ML) and Bayesian inference (BI) resolved two major clades: one comprising an exclusively Australian lineage occurring predominantly in arid and semi-arid environments, and the other a pantropical lineage spanning multiple continents. Abutilon grandifolium was recovered as sister to the remaining sampled Abutilon taxa in both ML and BI analyses, although no biogeographic origin inference can be drawn from this placement pending broader taxon sampling and integration of nuclear genomic data. These findings provide insights into the evolutionary dynamics of the cp. genome in Abutilon and offer a foundational genomic framework for refining Abutilon taxonomy.

Genome, Chloroplast↗

PubMed2026

Introgression among maternal lineages inferred from complete mitogenomes and molecular dating helps resolve phylogeography of European roe deer.

BACKGROUND: The European roe deer (Capreolus capreolus) is one of the most widespread ungulates in Europe, with a phylogeographic structure mainly shaped by Pleistocene glacial cycles and secondary contacts with the Siberian roe deer (C. pygargus). METHODS: We sequenced 52 complete mitogenomes of C. capreolus from Slovenia, Poland and France, and combined them with 24 publicly available sequences of C. capreolus and C. pygargus, yielding an alignment of 76 genomes representing 59 haplotypes (42 from C. capreolus and 17 from C. pygargus). Phylogeographic structure was assessed using a median-joining network, and divergence times were estimated using a time-calibrated Bayesian phylogeny based on mitochondrial coding regions, incorporating published ancient C. pygargus mitogenomes. We additionally screened mitochondrial protein-coding genes for selection. RESULTS: The haplotype network recovered the three major European roe deer clades (Eastern, Central, and Western) and detected Central-clade haplotypes in France. Two Polish haplotypes (Cp9 and Cp10), detected in C. capreolus, clustered within the C. pygargus mitochondrial lineage, supporting mitochondrial introgression. Time-calibrated phylogenies placed introgressed haplotypes within established C. pygargus lineages. Selection analyses provided limited evidence for episodic positive selection restricted to a small number of codons. CONCLUSIONS: Whole mitogenomes improve resolution of roe deer phylogeography and reveal introgressed maternal lineages, while time-calibrated phylogenies and selection tests add evolutionary context for interpreting mtDNA diversity in genus Capreolus.

Animals↗

PubMed2025

Molecular evolution of the members of the Snq2/Pdr18 subfamily of Pdr transporters in the Hemiascomycete yeasts.

The transporters of the ATP-Binding Cassette (ABC) Superfamily involved in the Multidrug Resistance (MDR) phenomena are also known as ABC-Pleiotropic Drug Resistance (PDR) proteins. The homologs of the Saccharomyces cerevisiae SNQ2 and PDR18 genes were identified in 171 yeast genomes, representing 68 different hemiascomycetous species. All early-divergent yeast species analyzed in this work lack Snq2/Pdr18 homologs, suggesting that the origin of these ABC-PDR genes in hemiascomycete yeasts resulted from a horizontal transfer event. The evolutionary pathway of the Snq2/Pdr18 protein subfamily in pathogenic Candida species was also reconstructed, revealing a main gene lineage leading to the Candida albicans SNQ2 gene. The results indicate that, after the gene duplication event at the origin of the SNQ2/PDR18 paralogs, the PDR18 ortholog has been under strong diversifying selection and suggest that a small portion of the sequence of the SNQ2 ancestral ortholog might have been under mild positive selection. The results also showed that strong positive selection was exerted over one of the two paralogs generated by the Whole Genome Duplication (WGD) event, corresponding to the duplicate at the origin of a "short-lived" WGD sublineage.

Evolution, Molecular↗

PubMed2026

Genomic characterization of avian metapneumovirus subtypes A and B in United States poultry by targeted amplicon sequencing.

Avian metapneumovirus (aMPV) subtypes A and B emerged in United States poultry in late 2023 and early 2024, prompting genome-scale surveillance from clinical samples. Here, we developed and optimized targeted amplicon sequencing (TAS) assays for both subtypes and applied them to 104 subtype-positive clinical samples collected from chicken and turkey farms across nine US states between early 2024 and early 2026. TAS recovered 91 genomes suitable for comparative analysis, including 44 aMPV-A and 47 aMPV-B sequences, with successful recovery extending to Ct values of 34.6 for aMPV-A and 31.2 for aMPV-B. Recovered genomes showed near-complete breadth and high mapping efficiency. Phylogenetic analyses of both G-gene and whole-genome datasets showed that US aMPV-A field strains formed a distinct monophyletic lineage within group IV and resolved into three closely related clusters. Cluster 2, first recognized in North Carolina and later detected in Ohio, spread across 30 turkey and chicken farms. Cluster 2 genomes were defined by a concentrated G-protein hotspot within residues 209-275, and most North Carolina Cluster 2 genomes carried 10-11 nonsynonymous substitutions in this region, including multiple proline substitutions suggestive of local structural change. Missouri Cluster 3 remained cohesive but distinct from both Cluster 1 and Cluster 2 in the G-gene and whole-genome trees. In contrast, US aMPV-B field strains remained highly homogeneous across hosts and states, with more than 99% nucleotide identity by both G-gene and WGS analyses. We also identified 12 vaccine-derived genomes on both vaccinated and nonvaccinated farms. These included six genomes related to aMPV-A vaccine and six related to aMPV-B vaccines (VCO3/50 and 1062), all of which retained vaccine-defining markers together with additional substitutions consistent with continued circulation after vaccine use in the field. Selection analyses showed that the G gene had the highest gene-wise dN/dS ratio in both subtypes. Additional elevated signal was observed in SH and M2, and candidate positively or episodically selected codons were concentrated in the subtype A Cluster 2 G-gene hotspot. These findings show that TAS supports direct-from-sample aMPV genomic surveillance and provides genomic context for field clusters, vaccine-derived lineages, and continued adaptive change in aMPV in US poultry.

Animals↗

PubMed1992

Does the VP1 gene of foot-and-mouth disease virus behave as a molecular clock?

We have carried out a phylogenetic study of the evolution of the VP1 gene sequence from different serological types and subtypes of foot-and-mouth disease virus (FMDV). The maximum-likelihood method developed by Hasegawa and co-workers (Hasegawa et al. 1985) for the estimation of evolutionary parameters and branching dates has been used to decide between alternative models of evolution: constant versus variable rates. The results obtained indicate that a constant rate model, i.e., a molecular clock, seems to be the most plausible one. However, additional information suggests the possibility that the appearance of serotype CS has been accompanied by an episode of rapid evolution (Villaverde et al. 1991). We discuss the possibility that this evolution of RNA viruses was due to episodic positive Darwinian selection, which would have helped the new variant to escape the immunogenic pressure from the hosts.

Aphthovirus↗

PubMed1989

Nitrate tolerance. A review of the evidence.

Organic nitrates are well established in the treatment of a wide variety of cardiovascular disorders, most notably angina pectoris and congestive heart failure. However, attenuation of, or tolerance to, haemodynamic and anti-ischaemic effects may occur with all long-acting nitrate formulations. In the majority of patients continuous administration of long acting nitrates tends to promote the development of attenuation, while intermittent administration avoids it. Likewise, higher-doses appear to induce attenuation to a greater degree than lower doses. Attenuation of haemodynamic effects and exercise tolerance in heart failure patients, and of clinical end-points in angina patients, appears to be less than attenuation of exercise testing end-points in angina patients. While the use of intermittent therapy avoids the development of attenuation, it may expose the patient to an as yet undefined risk of silent and/or symptomatic anginal episodes occurring during the nitrate-free interval. Likewise, the role of concomitant therapy in avoiding this potential risk remains to be defined. Means of avoiding attenuation may include the coadministration of sulfhydryl donors such as N-acetylcysteine. Alternatively, angiotension-converting enzyme (ACE) inhibitors such as captopril may block renin-angiotensin system-induced reflex sympathetic stimulation. Attenuation may occur to a greater or lesser degree in individual patients. The proportion of attenuators vs non-attenuators remains to be defined, as does a means of identifying such patients prospectively by clinical and/or laboratory parameters. Conflicting results among smaller studies may reflect variable proportions of attenuators vs non-attenuators. However, conflicting results among larger studies may reflect differences in patient selection criteria, such as selecting patients with positive and reproducible stress tests and little in the way of spontaneously occurring angina versus selecting patients with positive but variable stress tests and frequent episodes of spontaneously induced angina. The former group may reflect pure fixed coronary artery disease with little in the way of vasospasm, or change in vasomotor tone, while the latter group may reflect greater variability in vasomotor tone and/or more in the way of plaque instability. The clinical efficacy of long acting nitrates might therefore be expected to be greatest in those patients with larger numbers of spontaneously occurring angina episodes. Recent data suggest that nitrates may have important direct effects on coronary vessels including dilating eccentric coronary stenoses, dilating intercoronary collateral channels and having greater dilating effects on more diseased segments as opposed to less diseased coronary segments.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1992

AMPA and NMDA receptor antagonists do not decrease hippocampal glutamate concentrations during transient global ischemia.

Increased extracellular concentrations of glutamate during episodes of cerebral ischemia may be due in part to a positive glutaminergic feedback loop. We evaluated the effect of selective AMPA or NMDA receptor antagonists on hippocampal extracellular concentrations of excitatory amino acids during ischemia and reperfusion. Thirteen New Zealand white rabbits were subjected to 10 min of global cerebral ischemia produced by neck tourniquet inflation (20 psi) combined with systemic hypotension during halothane (1-1.5%) anesthesia. Hippocampal extracellular concentrations of glutamate, aspartate, and glycine were monitored using in vivo microdialysis. NBQX (a selective AMPA receptor antagonist), MK801 (a noncompetitive NMDA receptor antagonist), or 5% dextrose was administered starting 1 h before ischemia. The NBQX group (n = 4) received 5 mg.kg-1 of NBQX intravenously (dissolved in 5% dextrose) over 5 min followed by an infusion of 5 mg.kg-1.h-1. The 5% dextrose group (n = 4) received an equivalent volume of 5% dextrose. The peak concentrations of glutamate, aspartate, and glycine in the early reperfusion period were 5-8-fold, 9-10-fold, and 4-5-fold higher than preischemic values, respectively. There were no significant differences, however, among the three groups in the concentrations of glutamate, aspartate, or glycine at any time during the study. These results do not support the existence of a positive feedback loop for glutamate mediated via AMPA or NMDA autoreceptors in the hippocampus during transient global ischemia or reperfusion.

Animals↗

PubMed1990

Prevention of infection and graft-versus-host disease by suppression of intestinal microflora in children treated with allogeneic bone marrow transplantation.

The effect of suppression with antimicrobial agents of the intestinal microflora of paediatric bone marrow graft recipients on severe bacterial and fungal infections and on moderate to severe acute graft-versus-host disease was studied retrospectively. Data on 65 cases of bone marrow transplantation for either severe bone marrow failure or leukaemia, performed in a strict protective environment with either complete or selective gastrointestinal decontamination, were evaluated. All bone marrow grafts were from HLA-identical siblings and were not depleted of T-lymphocytes. Twenty percent of the recipients had one or more episodes of septicaemia during the granulocytopenic period after transplantation, mostly due to gram-positive bacteria. Only five children died due to infection, in each case caused by a microorganism originating from the endogenous flora. Complete gastrointestinal decontamination was superior to selective gastrointestinal decontamination in preventing infectious complications (p less than 0.001). The same was the case for the prevention of acute graft-versus-host disease of grade II or higher, which was observed in 7 of 40 (17.5%) completely decontaminated children versus 9 of 18 (50%) selectively decontaminated children evaluable for graft-versus-host disease (p less than 0.01). It is concluded that complete gastrointestinal decontamination in a strict protective environment is a feasible and very effective method for preventing severe infections and acute graft-versus-host disease after allogeneic bone marrow transplantation in children and adolescents; it resulted in a low transplantation-related mortality of 26% and a good quality of survival in 69% of the graft recipients.

Adolescent↗

PubMed1987

On the overdispersed molecular clock.

Rates of molecular evolution at some loci are more irregular than described by simple Poisson processes. Three situations under which molecular evolution would not follow simple Poisson processes are reevaluated from the viewpoint of the neutrality hypothesis: concomitant or multiple substitutions in a gene, fluctuating substitution rates in time caused by coupled effects of deleterious mutations and bottlenecks, and changes in the degree of selective constraints against a gene (neutral space) caused by successive substitutions. The common underlying assumption that these causes are lineage nonspecific excludes the case where mutation rates themselves change systematically among lineages or taxonomic groups, and severely limits the extent of variation in the number of substitutions among lineages. Even under this stringent condition, however, the third hypothesis, the fluctuating neutral space model, can generate fairly large variation. This is described by a time-dependent renewal process, which does not exhibit any episodic nature of molecular evolution. It is argued that the observed elevated variances in the number of nucleotide or amino acid substitutions do not immediately call for positive Darwinian selection in molecular evolution.

Animals↗

PubMed1990

Selective deficits in cognition and memory in high-functioning parkinsonian patients.

To evaluate the profile and extent of cognitive deficits in Parkinson's disease, afflicted patients of exceptional professional distinction, who continue to function successfully in leadership positions, were compared neuropsychologically to neurologically normal individuals, matched for sex, age, education and professional standing. While patients showed relative preservation of verbal skills and higher executive function, they exhibited a significant reduction in episodic memory and visuospatial function. The observation of circumscribed impairment in this select group of Parkinsonian patients further implicates cognitive and memory deficits as consistent features of Parkinson's disease.

Adult↗

PubMed1989

Closed-chest ablation of retrograde conduction in patients with atrioventricular nodal reentrant tachycardia.

We applied a new technique of catheter ablation to treat atrioventricular nodal reentrant tachycardia and preserve anterograde conduction, performing this procedure in 21 patients with repetitive episodes of tachycardia refractory to antiarrhythmic drugs. Using atrial activation in the His-bundle lead as a reference, we selected the optimal site of ablation by positioning an electrode catheter so that atrial activation occurred simultaneously with or earlier than the reference activation during tachycardia. At this site, the His-bundle deflection was completely absent or was present only at a low amplitude (less than 0.1 mV). In the majority of patients, these criteria could be met by withdrawing the catheter 5 to 10 mm from the site of the His-bundle recording (adjacent to the reference catheter). Shocks of 160 or 240 J were delivered at this site (cumulative energy [mean +/- SD], 689 +/- 442 J). Treatment resulted in preferential abolition or impairment of retrograde nodal conduction. Anterograde conduction, although modified, was preserved in 19 patients; complete heart block persisted in 2 patients. Sixteen patients remained free of arrhythmia, without medication or implantation of a pacemaker, for a mean follow-up period of 14 +/- 8 months (range, 7 to 42). Tachycardia was not inducible in 14 patients in a follow-up electrophysiologic study performed 3.6 +/- 6 months after the procedure. We conclude that catheter ablation is an effective alternative for the treatment of atrioventricular nodal tachycardia in patients with drug-resistant tachycardia.

Adult↗

PubMed1987

Prediction of airway reactivity from responses to a standardized respiratory symptom questionnaire.

A standardized respiratory symptom questionnaire was administered to 200 male insulators who then underwent inhalational bronchial challenge to measure their airway reactivity. The results were analyzed to determine the value of questionnaire information in predicting airway reactivity measured objectively. Questionnaire information was grouped according to topic, scored according to severity, and then combined to create several airway reactivity indices by stepwise multivariate analysis. The final index selected for testing contained information on a history of "asthma," "wheeze," "episodes of cough with sputum," and "pneumonia." It had a sensitivity ranging from 5% to 67% and positive predictive value from 67% to 28% depending on the cutoff point chosen as indicative of increased airway reactivity. These results indicate that questionnaire information is not adequate for discriminating between those with and those without increased airway reactivity in population screening.

Adult↗

PubMed1977

Corneatransplantation and matching for HLA-A and B.

Analysis of 140 corneatransplantations performed without selection showed a significant correlation between the HLA-A and B match and the clinical outcome. Furthermore, a highly significant correlation was found between rejection episodes and a positive direct cell-mediated lympholysis.

Corneal Transplantation↗

PubMed1992

Prolonged cardiac arrest and complete AV block during upright tilt test in young patients with syncope of unknown origin--prognostic and therapeutic implications.

The purpose of this study was to define the history and prognosis of 12 patients (8 males, 4 females) with syncope of unknown origin (5 to 15 episodes), who developed prolonged asystole or complete AV block during the upright tilt test (UTT). The mean age (+/- SD) of the patients was 29 +/- 7.4 years, and all had normal neurological and cardiological findings on evaluation. These patients were selected from a larger group of 92 cases with positive UTT out of a total of 136 subjects who were referred for recurrence of syncope. Neither clinical nor autonomic nervous system evaluation distinguished these 12 patients from those with positive UTT. Following UTT, therapy was initiated and consisted of transdermal scopolamine in four, disopyramide in two, and beta-blockers in four patients. During follow-up (mean, 17 +/- 5.4 months), four patients had recurrences but none experienced episodes of life-threatening syncope. These patients do not show an enhanced risk of sudden death, and drug therapy seems to improve their clinical course. Only long-term follow-up would correctly identify a subgroup at higher risk.

Adult↗

PubMed1990

Fulguration for AV nodal tachycardia: results in 42 patients with a mean follow-up of 23 months.

This report describes a catheter ablation technique to treat atrioventricular nodal reentrant tachycardia while preserving anterograde conduction, and its application in 42 patients with drug-refractory repetitive episodes of tachycardia. One of these patients had common and reverse forms of tachycardia. Using atrial activation in the His-bundle lead as a reference, the optimal ablation site was selected by positioning an electrode catheter to obtain a synchronous or earlier atrial activation than the reference during tachycardia. At this site, His-bundle deflection was completely absent, or was present at a low amplitude (less than 0.1 mV). In the majority of patients, these criteria were found in the immediate vicinity of the site of proximal His-bundle recording (adjacent to the reference catheter). Shocks of 160 or 240 joules (J) were delivered at this site (mean +/- SD = 518 +/- 392 J/session) with a resulting preferential abolition of impairment of fast retrograde conduction. Anterograde conduction, though modified, was preserved in all patients, except for four (10%) patients who remained in complete heart block. Thirty patients (70%) remained free of arrhythmia without medication or pacemaker for a mean follow-up period of 23 +/- 13 (2-63) months. Six other patients (15%) were controlled with a previously ineffective medication.

Atrioventricular Node↗

PubMed1992

Defects in mitochondrial protein synthesis and respiratory chain activity segregate with the tRNA(Leu(UUR)) mutation associated with mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes.

Cytoplasts from two unrelated patients with MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes) harboring an A----G transition at nucleotide position 3243 in the tRNA(Leu(UUR)) gene of the mitochondrial genome were fused with human cells lacking endogenous mitochondrial DNA (mtDNA) (rho 0 cells). Selected cybrid lines, containing less than 15 or greater than or equal to 95% mutated genomes, were examined for differences in genetic, biochemical, and morphological characteristics. Cybrids containing greater than or equal to 95% mutant mtDNA, but not those containing normal mtDNA, exhibited decreases in the rates of synthesis and in the steady-state levels of the mitochondrial translation products. In addition, NADH dehydrogenase subunit 1 (ND 1) exhibited a slightly altered mobility on polyacrylamide gel electrophoresis. The mutation also correlated with a severe respiratory chain deficiency. A small but consistent increase in the steady-state levels of an RNA transcript corresponding to 16S rRNA + tRNA(Leu(UUR)) + ND 1 genes was detected. However, there was no evidence of major errors in processing of the heavy-strand-encoded transcripts or of altered steady-state levels or ratios of mitochondrial rRNAs or mRNAs. These results provide evidence for a direct relationship between the tRNALeu(UUR) mutation and the pathogenesis of this mitochondrial disease.

Acidosis, Lactic↗

PubMed1990

Incidence, risk, and prognosis factors of nosocomial pneumonia in mechanically ventilated patients.

Seventy-eight (24%) episodes of nosocomial pneumonia (NP) were detected in 322 consecutive mechanically ventilated patients admitted to a 1,000-bed teaching hospital from April 1987 through May 1988 to assess the incidence, risk, and prognosis factors of NP acquired during mechanical ventilation (MV). The risk and prognosis factors for developing NP during MV were studied using both univariate and multivariate statistical techniques. Multivariate analysis selected the following variables significantly associated with a higher risk for developing ventilator-associated pneumonia: more than one intubation during MV (p = 0.000012), a prior episode of aspiration of gastric content (p = 0.00018), a MV period longer than 3 days (p = 0.015), the presence of chronic obstructive pulmonary disease (COPD) (p = 0.048), and the use of positive end-expiratory pressure (PEEP) during MV (p = 0.092). The presence of an ultimately or rapidly fatal underlying disease (p = 0.0018), worsening of acute respiratory failure caused by pneumonia (p = 0.0096), the presence of septic shock (p = 0.016), an inappropriate antibiotic treatment (p = 0.02), and the type of intensive care unit (ICU) hospitalization (noncardiac surgery and nonsurgical ICU compared with post-cardiac surgery ICU) (p = 0.08) were those factors selected by a stepwise logistic regression analysis as independently worsening the prognosis. The overall fatality rate was 23% (73 of 322). The mortality of patients with NP was higher (33%; 26 of 78; p less than 0.01) when compared with fatality rates of patients without NP (19%; 47 of 244).(ABSTRACT TRUNCATED AT 250 WORDS)

Cross Infection↗

PubMed1975

Cell-mediated immunity to a serologically defined (SD) HL-A antigen panel in kidney-transplanted patients.

The graft-directed, cell-mediated immunity in kidney-allografted patients was examined with a seriologically defined (SD), donor-unrelated panel of antigenic material in clinical steady state, soon after transplantation, and during acute rejection episodes. The SD antigens were selected from the panel on the basis of predictions hypothesized from the SD match of donor and recipient. The cell-mediated immunity was measured by the direct leukocyte migration agarose test (LMAT). Positive reactions in kidney-transplanted patients were induced particularly by one preparation (antigen 52) and were unpredictable on the basis of SD classification. The investigation shows that other antigenic determinants, different from SD antigens, probably play an important role as inducers of cell-mediated, graft-associated immunity in kidney-transplanted patients.

Adult↗