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Background Comparative genomics can inform us about the processes of mutation and selection across diverse taxa. Among seed plants, gymnosperms have been lacking in genomic comparisons. Recent EST and full-length cDNA collections for two conifers, Sitka spruce (Picea sitchensis) and loblolly pine (Pinus taeda), together with full genome sequences for two angiosperms, Arabidopsis thaliana and poplar (Populus trichocarpa), offer an opportunity to infer the evolutionary processes underlying thousands of orthologous protein-coding genes in gymnosperms compared with an angiosperm orthologue set. Results Based upon pairwise comparisons of 3,723 spruce and pine orthologues, we found an average synonymous genetic distance (dS) of 0.191, and an average dN/dS ratio of 0.314. Using a fossil-established divergence time of 140 million years between spruce and pine, we extrapolated a nucleotide substitution rate of 0.68 × 10-9 synonymous substitutions per site per year. When compared to angiosperms, this indicates a dramatically slower rate of nucleotide substitution rates in conifers: on average 15-fold. Coincidentally, we found a three-fold higher dN/dS for the spruce-pine lineage compared to the poplar-Arabidopsis lineage. This joint occurrence of a slower evolutionary rate in conifers with higher dN/dS, and possibly positive selection, showcases the uniqueness of conifer genome evolution. Conclusions Our results are in line with documented reduced nucleotide diversity, conservative genome evolution and low rates of diversification in conifers on the one hand and numerous examples of local adaptation in conifers on the other hand. We propose that reduced levels of nucleotide mutation in large and long-lived conifer trees, coupled with large effective population size, were the main factors leading to slow substitution rates but retention of beneficial mutations.

Objective: Previous isolated reports have hypothesized that chewing coca leaves, a pre-Columbian tradition found in certain regions of South America, may be associated with the development of oral squamous cell carcinoma (OSCC). Coca chewing (CC) is a habit that shares many characteristics with the well-known practice of betel chewing observed in Asia. The aim of this study is to analyze the association between CC and OSCC among patients who attended the Señor del Milagro Hospital in Salta, Argentina., Study Design: A case-control study was conducted from 2013 to 2018. For each case of OSCC, three healthy control patients were included. Odds ratios were calculated to compare demographics, concurrent oral conditions, and other classical risk factors for OSCC., Results: A total of 62 cases and 180 controls were included, adjusted for sex and age. OSCC was significantly associated with tobacco use (27.4% vs 9.4%, P = .001), CC (62.9% vs 32.2%, P < .001), and poor oral condition (81.1% vs 67.7%, P = .02). In the multivariate analysis, smoking (OR = 2.77, 95% CI 1.23-6.25, P = .0139), CC (OR = 2.98, 95% CI 1.58-5.63, P = .0007), and poor oral condition (OR = 3.1, 95% CI 1.62-5.85, P = .0006) remained independently associated with OSCC development., Conclusions: Chewing coca leaves could be considered a risk factor for oral cancer in a subset of Argentinean patients. Further studies are necessary to validate our findings and to elucidate the underlying pathways linking this habit to oral carcinogenesis., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Combined therapy constitutes the standard of care in RA. Jak inhibitors (Jaki) have shown efficacy in monotherapy, a modality used in cases where it is not possible to use Disease-Modifying Anti Rheumatic Drugs (csDMARDs)., Objectives: To estimate the prevalence (total and by drug), reason for using and the increase over the time of bDMARDs or tsDMARDs as monotherapy after the availability of the Jaki. To analyze the differential characteristics between patients with monotherapy vs combined therapy., Methods: Cross-sectional multicenter study. Consecutive patients with a diagnosis of RA (ACR/EULAR 2010) under treatment with bDMARDs or tsDMARDs started from 2013 were included. Socio-demographic, clinic, and therapeutic data were collected., Results: A total of 505 RA patients were included. Since 2013, the prevalence of monotherapy usage was (any) 49%. The drugs used as monotherapy were Jaki in 41% and TNF-blockers in 30%. The leading causes of monotherapy use were intolerance/adverse events (62%), medical decision or lack of adherence (37.7%). The highest socioeconomic level and a better functional status at diagnosis were predictors of monotherapy use. The use of the second line of treatments and less polypharmacy were independent factors associated with this therapeutic modality., Conclusions: The current prevalence of monotherapy in RA was 49%, the Jaki were the most used drug in this modality. Monotherapy increases from year to year. There are differential characteristics in patients using monotherapy.

Background: Clinically evident interstitial lung disease (ILD) affects 10%-42% of RA patients with prognostic implications. The aim of this study was to discern which factors are associated with the presence of ILD in RA patients and to develop a score that could help to stratify the risk of having ILD in RA patients., Methods: Case-control study. We included RA patients recruited from ILD and rheumatology clinics. We retrieved the following data: gender, age, presence of extra articular manifestations, disease activity scores, antibodies status, ESR, and medication use. Multivariate logistic regression was performed. A risk indicator score was developed., Results: Of 118 patients included in this study, 52 (44%) had RA-ILD (cases) and 66 (56%) had RA without ILD (controls). Twenty-six patients were male (22%), the mean age was 56.6±15.6 years. Five variables were significantly associated with the presence of ILD: male gender, smoking, extraarticular manifestations, a CDAI score>28, and ESR>80mm/h. The AUC of the final model curve was 0.86 (95%CI 0.79-0.92). Two potential cut-off points of the risk indicator score were chosen: a value of 2 points showed a sensitivity of 90.38% and a specificity of 63.64%, while a value of 4 points showed a sensitivity of 51.9% and a specificity of 90.9%., Conclusion: This study identified risk factors that could help identify which RA patients are at risk of having ILD through the development of a risk indicator score. This score needs to be validated in an independent cohort., (Copyright © 2019 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.)

Objective: To estimate the prevalence of musculoskeletal disorders (MSK) and rheumatic diseases in an indigenous Wichi population in Argentina., Methods: This is a cross-sectional, community-based study using the Community-Oriented Program for the Control of Rheumatic Diseases (COPCORD) methodology in ≥ 18-year-old subjects. Validated surveys were conducted by trained interviewers. Subjects with MSK pain (positive cases) were evaluated by internists and rheumatologists for diagnosis and treatment., Results: A total of 648 interviews were performed (90.4% of the census population). Mean age was 37.5 years (SD 14.8), and 379 (58.5%) were female. The mean years of education was 7.0 (SD 3.7); 552 subjects (85.2%) were covered by the public health care system. A total of 216 (33.3%) subjects had MSK pain in the last 7 days. Rheumatic disease prevalence was as follows: mechanical back pain (19.0%), rheumatic regional pain syndrome (5.2%), osteoarthritis (3.2%), rheumatoid arthritis (RA) (3.2%), inflammatory back pain (1.2%), undifferentiated arthritis (0.3%), Sjögren syndrome (0.15%), and fibromyalgia (0.15%). RA patients included 19 (90.5%) women and 9 (42.9%) with RA family history. One hundred percent were seropositive and 66.7% showed radiologic erosions. The mean of Disease Activity Score [DAS-28 (ESR)] at the time of diagnosis was 5.1 (SD 1.5) and the Health Assessment Questionnaire Disability Index (HAQ-DI) was 0.8 (SD 0.4)., Conclusion: RA prevalence was 3.2%, one of the highest reported using the COPCORD methodology in indigenous and non-indigenous peoples in Latin America, with a high percentage of family cases. Pain and functional capacity were the variables allowing patients' early referral to a specialist. Key Points • The RA prevalence was 3.2%, one of the highest reported using COPCORD methodology in indigenous and non-indigenous peoples in Latin America. • The patients with RA had high percentage of familiar history of RA. • The pain and functional capacity were the variables associated with a diagnosis of any rheumatic disease and should be considered for early referral. • The mean of the delay in the diagnosis was 5.8 years. In this community, the lack of the "migration health" phenomenon may be a social determinant that negatively impacts their health.

Bioconcentration kinetics of five metals (Ag, Cd, Co, Mn, and Zn) were determined in the scleractinian coral Stylophora pistillata (entire symbiotic association vs. cultured symbionts), using radiotracer techniques. Among contrasting element behaviors observed in S. pistillata, the highest efficiency of concentration and retention was observed for Ag in the symbiotic association (CFss reaching 5000 and T b½>1 year). Predominant proportion of this metal was found associated with the skeleton whereas the other metals were mainly present in the coral tissues (including host tissues and symbionts). A 96-h exposure of cultured symbionts (isolated zooxantellae from S. pistillata) indicated that they displayed a very high potential for metal bioconcentration (higher by 1 to 3 orders of magnitude compared to the skeleton). In addition, among the five elements investigated, Ag had the highest concentration factor in the cultured symbionts. Contrasting kinetic characteristics of skeleton vs. tissues offer interesting implications for biomonitoring purposes. Indeed, the skeleton was shown to display stable metal concentrations after an exposure (long retention time) and thereby allows recording contamination event on the long term, whereas the concentrations within coral tissues rapidly increased during the exposure and dropped when non-contaminating conditions were restored, allowing information on the current (short term) contamination status. The present study confirms that the coral can be seen as a two-compartment box model for metal bioconcentration: the tissues sensus latto as a first box governing metal entrance (with a crucial role played by the symbionts) and the skeleton as a second box where metal detoxification (storage) is taking place; the first box also depurates toward the environment when non-contaminating conditions are restored.

This study aims to determine the level of adherence to treatment in ankylosing spondylitis (AS) patients and to identify possible factors associated to lack of adherence. We included consecutive AS patients (NY modified criteria). Sociodemographic and clinical data were collected. Patients answered auto-reported questionnaires: Bath Ankylosing Spondylitis Disease Activity Index, Bath Ankylosing Spondylitis Functional Index, Ankylosing Spondylitis Quality of Life, and Center for Epidemiological Studies Depression scale. Patients with rheumatoid arthritis (RA) (ACR'87 criteria) were assessed as the control group. The adherence of the studied groups to medical treatment and exercises was measured by means of two questionnaires: Compliance Questionnaire on Rheumatology (CQR) and Exercise Attitude Questionnaire-18 (EAQ-18). The study included 59 patients with AS and 53 patients with RA. Of the AS patients, 43 (72.9%) were male, median age 47 years (interquartile range (IQR) 33-57) and median disease duration of 120 months (IQR 33-57). Of the RA patients, 37 (69.8%) were female, had a median age of 56 years (IQR 43.5-60) and a median disease duration of 156 months (IQR 96-288). There were no significant differences in the results of the adherence questionnaires between both groups, with a total median of 68.42 for the CQR in both groups and of 40.7 in AS vs. 42.6 in RA for the EAQ. When dichotomizing patients as adherent and non-adherent, taking as good adherence a cut value in the CQR and EAQ higher than 60, adherence to pharmacological treatment was significantly higher in RA vs. AS (92.5 vs. 74.6%, p = 0.01) and there were no differences in the EAQ. On the uni- and multivariate analysis, lack of adherence to treatment was not associated to sex, age, disease duration, education, health insurance, depressive status, and disease activity parameters in neither group of patients. AS have an acceptable adherence to pharmacological treatment, although it is lower than RA patients; nonetheless, both groups show a lack of adherence to exercise.

Tandem repeats are genomic elements that are prone to changes in repeat number and are thus often polymorphic. These sequences are found at a high density at the start of human genes, in the gene's promoter. Increasing empirical evidence suggests that length variation in these tandem repeats can affect gene regulation. One class of tandem repeats, known as microsatellites, rapidly alter in repeat number. Some of the genetic variation induced by microsatellites is known to result in phenotypic variation. Recently, our group developed a novel method for measuring the evolutionary conservation of microsatellites, and with it we discovered that human microsatellites near transcription start sites are often highly conserved. In this study, we examined the properties of microsatellites found in promoters. We found a high density of microsatellites at the start of genes. We showed that microsatellites are statistically associated with promoters using a wavelet analysis, which allowed us to test for associations on multiple scales and to control for other promoter related elements. Because promoter microsatellites tend to be G/C rich, we hypothesized that G/C rich regulatory elements may drive the association between microsatellites and promoters. Our results indicate that CpG islands, G-quadruplexes (G4) and untranslated regulatory regions have highly significant associations with microsatellites, but controlling for these elements in the analysis does not remove the association between microsatellites and promoters. Due to their intrinsic lability and their overlap with predicted functional elements, these results suggest that many promoter microsatellites have the potential to affect human phenotypes by generating mutations in regulatory elements, which may ultimately result in disease. We discuss the potential functions of human promoter microsatellites in this context.

Microsatellites in and around genes have been shown to modulate levels of gene expression in multiple organisms, ranging from bacteria to humans. Here we will discuss promoter microsatellites known to modulate gene expression, with a few key examples related to the human brain. Many of the microsatellites we discuss are highly conserved in mammals, indicating that selection may favor their retention as "tuning knobs" of gene expression. We will also discuss the mechanisms by which microsatellites in promoters can alter gene expression as they expand and contract, with particular attention to secondary structures like Z-DNA and H-DNA. We suggest that promoter microsatellites, especially those that are highly conserved, may be an important source of human phenotypic variation.

Objective. To assess the relationship between work productivity with disease activity, functional capacity, life quality and radiological damage in patients with rheumatoid arthritis (RA). Methods. The study included consecutive employed patients with RA (ACR'87), aged over 18. Demographic, disease-related, and work-related variables were determined. The reduction of work productivity was assessed by WPAI-RA. Results. 90 patients were evaluated, 71% women. Age average is 50 years old, DAS28 4, and RAQoL 12. Median SENS is 18 and HAQ-A 0.87. Mean absenteeism was of 14%, presenting an average of 6.30 work hours wasted weekly. The reduction in performance at work or assistance was of 38.4% and the waste of productivity was of 45%. Assistance correlated with DAS28 (r = 0.446; P < 0.001), HAQ-A (r = 0.545; P < 0.001) and RAQoL (r = 0.475; P < 0.001). Lower total productivity was noticed in higher levels of activity and functional disability. Patients with SENS > 18 showed lower work productivity than those with SENS < 18 (50 versus 34; P = 0.04). In multiple regression analysis, variables associated with reduction of total work productivity were HAQ-A and RAQoL. Conclusion. RA patients with higher disease severity showed higher work productivity compromise.

Microsatellites make up ∼3% of the human genome, and there is increasing evidence that some microsatellites can have important functions and can be conserved by selection. To investigate this conservation, we performed a genome-wide analysis of human microsatellites and measured their conservation using a binary character birth--death model on a mammalian phylogeny. Using a maximum likelihood method to estimate birth and death rates for different types of microsatellites, we show that the rates at which microsatellites are gained and lost in mammals depend on their sequence composition, length, and position in the genome. Additionally, we use a mixture model to account for unequal death rates among microsatellites across the human genome. We use this model to assign a probability-based conservation score to each microsatellite. We found that microsatellites near the transcription start sites of genes are often highly conserved, and that distance from a microsatellite to the nearest transcription start site is a good predictor of the microsatellite conservation score. An analysis of gene ontology terms for genes that contain microsatellites near their transcription start site reveals that regulatory genes involved in growth and development are highly enriched with conserved microsatellites.

Introduction: Spondyloarthritis (SpA) includes a group of diseases that share immunogenetic, clinical and radiologic findings, with a particular involvement of the axial skeleton and the entheses., Methods: SpA patients attending ambulatory care in 11 rheumatology services located in 6 Argentine provinces were included in a prospective, observational multicentre cohort of SpA in Argentina (Iberoamerican Spondyloarthritis Registry [RESPONDIA]). Data collected were transmitted online and stored in the Spanish spondyloarthritis registry (REGISPONSER) Web site. Sociodemographic, clinical features and diagnosis, disease activity, functional status, quality of life, work status, radiographic changes and treatment data were collected by means of validated tools., Results: A total of 402 patients were included; 59% were male, with median age of 48.3 years and median disease duration of 8 years; 68.7% of patients belonged to middle and lower-middle social classes. Eighty-six patients were diagnosed with ankylosing spondylitis (AS), 242 with psoriatic arthritis, 25 with reactive arthritis, 10 with SpA associated with inflammatory bowel disease, 33 with undifferentiated SpA and 6 with juvenile AS. The median score was 2.6 for the Bath AS Functional Index, 3.8 for the Bath AS Disease Activity Index and 5 for the Bath AS Radiology Index. The lower social class patients achieved a worse Bath AS Functional Index than other social classes and a worse Bath AS Disease Activity Index, compared with upper-middle class., Conclusions: The sociodemographic distribution pattern observed in these SpA patients was similar to that expected in the general population of Argentina, with worse functional capacity and higher disease activity observed in the lower social classes.

Microsatellites are popular genetic markers in molecular ecology, genetic mapping and forensics. Unfortunately, despite recent advances, the isolation of de novo polymorphic microsatellite loci often requires expensive and intensive groundwork. Primers developed for a focal species are commonly tested in a related, non-focal species of interest for the amplification of orthologous polymorphic loci; when successful, this approach significantly reduces cost and time of microsatellite development. However, transferability of polymorphic microsatellite loci decreases rapidly with increasing evolutionary distance, and this approach has shown its limits. Whole genome sequences represent an under-exploited resource to develop cross-species primers for microsatellites. Here we describe a three-step method that combines a novel in silico pipeline that we use to (1) identify conserved microsatellite loci from a multiple genome alignments, (2) design degenerate primer pairs, with (3) a simple PCR protocol used to implement these primers across species. Using this approach we developed a set of primers for the mammalian clade. We found 126,306 human microsatellites conserved in mammalian aligned sequences, and isolated 5,596 loci using criteria based on wide conservation. From a random subset of ~1000 dinucleotide repeats, we designed degenerate primer pairs for 19 loci, of which five produced polymorphic fragments in up to 18 mammalian species, including the distinctly related marsupials and monotremes, groups that diverged from other mammals 120-160 million years ago. Using our method, many more cross-clade microsatellite loci can be harvested from the currently available genomic data, and this ability is set to improve exponentially as further genomes are sequenced., (© 2011 Buschiazzo et al.)

Background: Corals worldwide are in decline due to climate change effects (e.g., rising seawater temperatures), pollution, and exploitation. The ability of corals to cope with these stressors in the long run depends on the evolvability of the underlying genetic networks and proteins, which remain largely unknown. A genome-wide scan for positively selected genes between related coral species can help to narrow down the search space considerably., Methodology/principal Findings: We screened a set of 2,604 putative orthologs from EST-based sequence datasets of the coral species Acropora millepora and Acropora palmata to determine the fraction and identity of proteins that may experience adaptive evolution. 7% of the orthologs show elevated rates of evolution. Taxonomically-restricted (i.e. lineage-specific) genes show a positive selection signature more frequently than genes that are found across many animal phyla. The class of proteins that displayed elevated evolutionary rates was significantly enriched for proteins involved in immunity and defense, reproduction, and sensory perception. We also found elevated rates of evolution in several other functional groups such as management of membrane vesicles, transmembrane transport of ions and organic molecules, cell adhesion, and oxidative stress response. Proteins in these processes might be related to the endosymbiotic relationship corals maintain with dinoflagellates in the genus Symbiodinium., Conclusion/relevance: This study provides a birds-eye view of the processes potentially underlying coral adaptation, which will serve as a foundation for future work to elucidate the rates, patterns, and mechanisms of corals' evolutionary response to global climate change.

The sequencing and comparison of vertebrate genomes have enabled the identification of widely conserved genomic elements. Chief among these are genes and cis-regulatory regions, which are often under selective constraints that promote their retention in related organisms. The conservation of elements that either lack function or whose functions are yet to be ascribed has been relatively little investigated. In particular, microsatellites, a class of highly polymorphic repetitive sequences considered by most to be neutrally evolving junk DNA that is too labile to be maintained in distant species, have not been comprehensively studied in a comparative genomic framework. Here, we used the UCSC alignment of the human genome against those of 11 mammalian and five nonmammalian vertebrates to identify and examine the extent of conservation of human microsatellites in vertebrate genomes. Out of 696,016 microsatellites found in human sequences, 85.39% were conserved in at least one other species, whereas 28.65% and 5.98% were found in at least one and three nonprimate species, respectively. An exponential decline of microsatellite conservation with increasing evolutionary time, a comparable distribution of conserved versus nonconserved microsatellites in the human genome, and a positive correlation between microsatellite conservation and overall sequence conservation, all suggest that most microsatellites are only maintained in genomes by chance, although exceptionally conserved human microsatellites were also found in distant mammals and other vertebrates. Our findings provide the first comprehensive survey of microsatellite conservation across deep evolutionary timescales, in this case 450 Myr of vertebrate evolution, and provide new tools for the identification of functional conserved microsatellites, the development of cross-species microsatellite markers and the study of microsatellite evolution above the species level.

The clam Gafrarium tumidum and the oyster Isognomon isognomon have been proposed as potential biomonitor species of metal contamination in the New Caledonia lagoon. The influence of dissolved concentrations of As, Cd, Co, Cr, Mn, and Zn on uptake and depuration kinetics, tissue and subcellular distribution of these elements was investigated in both species. Results indicate that both bivalves take up elements proportionally to the dissolved concentration for Cd, Cr and Mn in the surrounding water over the entire range of concentrations tested (three orders of magnitude), and up to the second and third highest added metal concentration tested for Co (23 ng l(-1)) and Zn (700 ng l(-1)), respectively. All elements were efficiently retained in bivalve tissues (estimated T(b1/2) ranging from 16d to infinity), suggesting that both species should be able to preserve a record of contamination events over a long period of time. Considering the specific range of concentrations examined here, G. tumidum and I. isognomon would therefore serve as adequate biomonitor species to monitor dissolved metal contamination in the New Caledonia lagoon waters., (Copyright (c) 2010 Elsevier Ltd. All rights reserved.)

Microsatellites are among the most versatile of genetic markers, being used in an impressive number of biological applications. However, the evolutionary dynamics of these markers remain a source of contention. Almost 20 years after the discovery of these ubiquitous simple sequences, new genomic data are clarifying our understanding of the structure, distribution and variability of microsatellites in genomes, especially for the eukaryotes. While these new data provide a great deal of descriptive information about the nature and abundance of microsatellite sequences within eukaryotic genomes, there have been few attempts to synthesise this information to develop a global concept of evolution. This review provides an up-to-date account of the mutational processes, biases and constraints believed to be involved in the evolution of microsatellites, particularly with respect to the creation and degeneration of microsatellites, which we assert may be broadly viewed as a life cycle. In addition, we identify areas of contention that require further research and propose some possible directions for future investigation., ((c) 2006 Wiley Periodicals, Inc.)