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1.
Nature ; 619(7969): 311-316, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37438592

RESUMEN

Coral reefs are losing the capacity to sustain their biological functions1. In addition to other well-known stressors, such as climatic change and overfishing1, plastic pollution is an emerging threat to coral reefs, spreading throughout reef food webs2, and increasing disease transmission and structural damage to reef organisms3. Although recognized as a global concern4, the distribution and quantity of plastics trapped in the world's coral reefs remains uncertain3. Here we survey 84 shallow and deep coral ecosystems at 25 locations across the Pacific, Atlantic and Indian ocean basins for anthropogenic macrodebris (pollution by human-generated objects larger than 5 centimetres, including plastics), performing 1,231 transects. Our results show anthropogenic debris in 77 out of the 84 reefs surveyed, including in some of Earth's most remote and near-pristine reefs, such as in uninhabited central Pacific atolls. Macroplastics represent 88% of the anthropogenic debris, and, like other debris types, peak in deeper reefs (mesophotic zones at 30-150 metres depth), with fishing activities as the main source of plastics in most areas. These findings contrast with the global pattern observed in other nearshore marine ecosystems, where macroplastic densities decrease with depth and are dominated by consumer items5. As the world moves towards a global treaty to tackle plastic pollution6, understanding its distribution and drivers provides key information to help to design the strategies needed to address this ubiquitous threat.


Asunto(s)
Arrecifes de Coral , Plásticos , Plásticos/efectos adversos , Plásticos/análisis , Cadena Alimentaria , Océano Pacífico , Océano Atlántico , Océano Índico , Tamaño de la Partícula , Actividades Humanas , Caza
2.
Nucleic Acids Res ; 51(W1): W198-W206, 2023 07 05.
Artículo en Inglés | MEDLINE | ID: mdl-36987846

RESUMEN

Proteins form complex interactions in the cellular environment to carry out their functions. They exhibit a wide range of binding modes depending on the cellular conditions, which result in a variety of ordered or disordered assemblies. To help rationalise the binding behavior of proteins, the FuzPred server predicts their sequence-based binding modes without specifying their binding partners. The binding mode defines whether the bound state is formed through a disorder-to-order transition resulting in a well-defined conformation, or through a disorder-to-disorder transition where the binding partners remain conformationally heterogeneous. To account for the context-dependent nature of the binding modes, the FuzPred method also estimates the multiplicity of binding modes, the likelihood of sampling multiple binding modes. Protein regions with a high multiplicity of binding modes may serve as regulatory sites or hot-spots for structural transitions in the assembly. To facilitate the interpretation of the predictions, protein regions with different interaction behaviors can be visualised on protein structures generated by AlphaFold. The FuzPred web server (https://fuzpred.bio.unipd.it) thus offers insights into the structural and dynamical changes of proteins upon interactions and contributes to development of structure-function relationships under a variety of cellular conditions.


Asunto(s)
Computadores , Proteínas , Conformación Proteica , Proteínas/química , Dominios Proteicos , Programas Informáticos
3.
Bioinformatics ; 39(12)2023 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-38060268

RESUMEN

SUMMARY: The Local Disordered Region Sampling (LDRS, pronounced loaders) tool is a new module developed for IDPConformerGenerator, a previously validated approach to model intrinsically disordered proteins (IDPs). The IDPConformerGenerator LDRS module provides a method for generating all-atom conformations of intrinsically disordered protein regions at N- and C-termini of and in loops or linkers between folded regions of an existing protein structure. These disordered elements often lead to missing coordinates in experimental structures or low confidence in predicted structures. Requiring only a pre-existing PDB or mmCIF formatted structural template of the protein with missing coordinates or with predicted confidence scores and its full-length primary sequence, LDRS will automatically generate physically meaningful conformational ensembles of the missing flexible regions to complete the full-length protein. The capabilities of the LDRS tool of IDPConformerGenerator include modeling phosphorylation sites using enhanced Monte Carlo-Side Chain Entropy, transmembrane proteins within an all-atom bilayer, and multi-chain complexes. The modeling capacity of LDRS capitalizes on the modularity, the ability to be used as a library and via command-line, and the computational speed of the IDPConformerGenerator platform. AVAILABILITY AND IMPLEMENTATION: The LDRS module is part of the IDPConformerGenerator modeling suite, which can be downloaded from GitHub at https://github.com/julie-forman-kay-lab/IDPConformerGenerator. IDPConformerGenerator is written in Python3 and works on Linux, Microsoft Windows, and Mac OS versions that support DSSP. Users can utilize LDRS's Python API for scripting the same way they can use any part of IDPConformerGenerator's API, by importing functions from the "idpconfgen.ldrs_helper" library. Otherwise, LDRS can be used as a command line interface application within IDPConformerGenerator. Full documentation is available within the command-line interface as well as on IDPConformerGenerator's official documentation pages (https://idpconformergenerator.readthedocs.io/en/latest/).


Asunto(s)
Proteínas Intrínsecamente Desordenadas , Programas Informáticos , Biblioteca de Genes , Proteínas de la Membrana , Documentación
5.
Proc Natl Acad Sci U S A ; 118(10)2021 03 09.
Artículo en Inglés | MEDLINE | ID: mdl-33608481

RESUMEN

The current rate of species extinction is rapidly approaching unprecedented highs, and life on Earth presently faces a sixth mass extinction event driven by anthropogenic activity, climate change, and ecological collapse. The field of conservation genetics aims at preserving species by using their levels of genetic diversity, usually measured as neutral genome-wide diversity, as a barometer for evaluating population health and extinction risk. A fundamental assumption is that higher levels of genetic diversity lead to an increase in fitness and long-term survival of a species. Here, we argue against the perceived importance of neutral genetic diversity for the conservation of wild populations and species. We demonstrate that no simple general relationship exists between neutral genetic diversity and the risk of species extinction. Instead, a better understanding of the properties of functional genetic diversity, demographic history, and ecological relationships is necessary for developing and implementing effective conservation genetic strategies.


Asunto(s)
Variación Genética , Genoma , Endogamia , Modelos Genéticos , Animales , Genética de Población
6.
Pediatr Dermatol ; 41(3): 556-557, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38556801

RESUMEN

Lymphoplasmocytic plaque in children (LPC) is a rare and distinctive skin disorder primarily affecting the pediatric population. Characterized by its unique histopathological features, the condition manifests as well-defined plaques with a predominance of lymphocytes and plasma cells infiltrating the dermis. Despite its limited prevalence, recognizing this entity is crucial for accurate diagnosis and appropriate management of affected patients. We report the case of a 10-year-old male presenting with LPC in the extensor surface of the upper arm, a rarely reported location, treated with both topical and intralesional corticosteroids resulting in partial improvement.


Asunto(s)
Enfermedades de la Piel , Humanos , Masculino , Niño , Enfermedades de la Piel/patología , Enfermedades de la Piel/diagnóstico , Enfermedades de la Piel/tratamiento farmacológico , Linfocitos/patología , Brazo/patología , Células Plasmáticas/patología
7.
Proteins ; 91(12): 1658-1683, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37905971

RESUMEN

We present the results for CAPRI Round 54, the 5th joint CASP-CAPRI protein assembly prediction challenge. The Round offered 37 targets, including 14 homodimers, 3 homo-trimers, 13 heterodimers including 3 antibody-antigen complexes, and 7 large assemblies. On average ~70 CASP and CAPRI predictor groups, including more than 20 automatics servers, submitted models for each target. A total of 21 941 models submitted by these groups and by 15 CAPRI scorer groups were evaluated using the CAPRI model quality measures and the DockQ score consolidating these measures. The prediction performance was quantified by a weighted score based on the number of models of acceptable quality or higher submitted by each group among their five best models. Results show substantial progress achieved across a significant fraction of the 60+ participating groups. High-quality models were produced for about 40% of the targets compared to 8% two years earlier. This remarkable improvement is due to the wide use of the AlphaFold2 and AlphaFold2-Multimer software and the confidence metrics they provide. Notably, expanded sampling of candidate solutions by manipulating these deep learning inference engines, enriching multiple sequence alignments, or integration of advanced modeling tools, enabled top performing groups to exceed the performance of a standard AlphaFold2-Multimer version used as a yard stick. This notwithstanding, performance remained poor for complexes with antibodies and nanobodies, where evolutionary relationships between the binding partners are lacking, and for complexes featuring conformational flexibility, clearly indicating that the prediction of protein complexes remains a challenging problem.


Asunto(s)
Algoritmos , Mapeo de Interacción de Proteínas , Mapeo de Interacción de Proteínas/métodos , Conformación Proteica , Unión Proteica , Simulación del Acoplamiento Molecular , Biología Computacional/métodos , Programas Informáticos
8.
Cogn Affect Behav Neurosci ; 23(3): 522-542, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37173606

RESUMEN

Risk and uncertainty are central concepts of decision neuroscience. However, a comprehensive review of the literature shows that most studies define risk and uncertainty in an unclear fashion or use both terms interchangeably, which hinders the integration of the existing findings. We suggest uncertainty as an umbrella term that comprises scenarios characterized by outcome variance where relevant information about the type and likelihood of outcomes may be somewhat unavailable (ambiguity) and scenarios where the likelihood of outcomes is known (risk).These conceptual issues are problematic for studies on the temporal neurodynamics of decision-making under risk and ambiguity, because they lead to heterogeneity in task design and the interpretation of the results. To assess this problem, we conducted a state-of-the-art review of ERP studies on risk and ambiguity in decision-making. By employing the above definitions to 16 reviewed studies, our results suggest that: (a) research has focused more on risk than ambiguity processing; (b) studies assessing decision-making under risk often implemented descriptive-based paradigms, whereas studies assessing ambiguity processing equally implemented descriptive- and experience-based tasks; (c) descriptive-based studies link risk processing to increased frontal negativities (e.g., N2, N400) and both risk and ambiguity to reduced parietal positivities (e.g., P2, P3); (d) experience-based studies link risk to increased P3 amplitudes and ambiguity to increased frontal negativities and the LPC component; (e) both risk and ambiguity processing seem to be related with cognitive control, conflict monitoring, and increased cognitive demand; (f) further research and improved tasks are needed to dissociate risk and ambiguity processing.

9.
Mutagenesis ; 38(5): 273-282, 2023 10 14.
Artículo en Inglés | MEDLINE | ID: mdl-37357800

RESUMEN

The comet assay is widely used in biomonitoring studies for the analysis of DNA damage in leukocytes and peripheral blood mononuclear cells. Rather than processing blood samples directly, it can be desirable to cryopreserve whole blood or isolated cells for later analysis by the comet assay. However, this creates concern about artificial accumulation of DNA damage during cryopreservation. In this study, 10 laboratories used standardized cryopreservation and thawing procedures of monocytic (THP-1) or lymphocytic (TK6) cells. Samples were cryopreserved in small aliquots in 50% foetal bovine serum, 40% cell culture medium, and 10% dimethyl sulphoxide. Subsequently, cryopreserved samples were analysed by the standard comet assay on three occasions over a 3-year period. Levels of DNA strand breaks in THP-1 cells were increased (four laboratories), unaltered (four laboratories), or decreased (two laboratories) by long-term storage. Pooled analysis indicates only a modest positive association between storage time and levels of DNA strand breaks in THP-1 cells (0.37% Tail DNA per year, 95% confidence interval: -0.05, 0.78). In contrast, DNA strand break levels were not increased by cryopreservation in TK6 cells. There was inter-laboratory variation in levels of DNA strand breaks in THP-1 cells (SD = 3.7% Tail DNA) and TK6 reference sample cells (SD = 9.4% Tail DNA), whereas the intra-laboratory residual variation was substantially smaller (i.e. SD = 0.4%-2.2% Tail DNA in laboratories with the smallest and largest variation). In conclusion, the study shows that accumulation of DNA strand breaks in cryopreserved mononuclear blood cell lines is not a matter of concern.


Asunto(s)
Daño del ADN , Leucocitos Mononucleares , Ensayo Cometa/métodos , Leucocitos Mononucleares/metabolismo , Criopreservación/métodos , ADN/metabolismo
10.
Mutagenesis ; 38(5): 264-272, 2023 Oct 14.
Artículo en Inglés | MEDLINE | ID: mdl-37357815

RESUMEN

The formamidopyrimidine DNA glycosylase (Fpg)-modified comet assay is widely used for the measurement of oxidatively generated damage to DNA. However, there has not been a recommended long-term positive control for this version of the comet assay. We have investigated potassium bromate as a positive control for the Fpg-modified comet assay because it generates many Fpg-sensitive sites with a little concurrent generation of DNA strand breaks. Eight laboratories used the same procedure for the treatment of monocytic THP-1 cells with potassium bromate (0, 0.5, 1.5, and 4.5 mM) and subsequent cryopreservation in a freezing medium consisting of 50% foetal bovine serum, 40% RPMI-1640 medium, and 10% dimethyl sulphoxide. The samples were analysed by the Fpg-modified comet assay three times over a 3-year period. All laboratories obtained a positive concentration-response relationship in cryopreserved samples (linear regression coefficients ranging from 0.79 to 0.99). However, there was a wide difference in the levels of Fpg-sensitive sites between the laboratory with the lowest (4.2% Tail DNA) and highest (74% Tail DNA) values in THP-1 cells after exposure to 4.5 mM KBrO3. In an attempt to assess sources of inter-laboratory variation in Fpg-sensitive sites, comet images from one experiment in each laboratory were forwarded to a central laboratory for visual scoring. There was high consistency between measurements of %Tail DNA values in each laboratory and the visual score of the same comets done in the central laboratory (r = 0.98, P < 0.001, linear regression). In conclusion, the results show that potassium bromate is a suitable positive comet assay control.

11.
Mutagenesis ; 38(5): 253-263, 2023 Oct 14.
Artículo en Inglés | MEDLINE | ID: mdl-37233347

RESUMEN

Measurement of DNA migration in the comet assay can be done by image analysis or visual scoring. The latter accounts for 20%-25% of the published comet assay results. Here we assess the intra- and inter-investigator variability in visual scoring of comets. We include three training sets of comet images, which can be used as reference for researchers who wish to use visual scoring of comets. Investigators in 11 different laboratories scored the comet images using a five-class scoring system. There is inter-investigator variation in the three training sets of comets (i.e. coefficient of variation (CV) = 9.7%, 19.8%, and 15.2% in training sets I-III, respectively). However, there is also a positive correlation of inter-investigator scoring in the three training sets (r = 0.60). Overall, 36% of the variation is attributed to inter-investigator variation and 64% stems from intra-investigator variation in scoring between comets (i.e. the comets in training sets I-III look slightly different and this gives rise to heterogeneity in scoring). Intra-investigator variation in scoring was also assessed by repeated analysis of the training sets by the same investigator. There was larger variation when the training sets were scored over a period of six months (CV = 5.9%-9.6%) as compared to 1 week (CV = 1.3%-6.1%). A subsequent study revealed a high inter-investigator variation when premade slides, prepared in a central laboratory, were stained and scored by investigators in different laboratories (CV = 105% and 18%-20% in premade slides with comets from unexposed and hydrogen peroxide-exposed cells, respectively). The results indicate that further standardization of visual scoring is desirable. Nevertheless, the analysis demonstrates that visual scoring is a reliable way of analysing DNA migration in comets.

12.
Mutagenesis ; 38(5): 283-294, 2023 Oct 14.
Artículo en Inglés | MEDLINE | ID: mdl-37228081

RESUMEN

The comet assay is a simple and versatile method for measurement of DNA damage in eukaryotic cells. More specifically, the assay detects DNA migration from agarose gel-embedded nucleoids, which depends on assay conditions and the level of DNA damage. Certain steps in the comet assay procedure have substantial impact on the magnitude of DNA migration (e.g. electric potential and time of electrophoresis). Inter-laboratory variation in DNA migration levels occurs because there is no agreement on optimal assay conditions or suitable assay controls. The purpose of the hCOMET ring trial was to test potassium bromate (KBrO3) as a positive control for the formamidopyrimidine DNA glycosylase (Fpg)-modified comet assay. To this end, participating laboratories used semi-standardized protocols for cell culture (i.e. cell culture, KBrO3 exposure, and cryopreservation of cells) and comet assay procedures, whereas the data acquisition was not standardized (i.e. staining of comets and image analysis). Segregation of the total variation into partial standard deviation (SD) in % Tail DNA units indicates the importance of cell culture procedures (SD = 10.9), comet assay procedures (SD = 12.3), staining (SD = 7.9) and image analysis (SD = 0.5) on the overall inter-laboratory variation of DNA migration (SD = 18.2). Future studies should assess sources of variation in each of these steps. On the positive side, the hCOMET ring trial demonstrates that KBrO3 is a robust positive control for the Fpg-modified comet assay. In conclusion, the hCOMET ring trial has demonstrated a high reproducibility of detecting genotoxic effects by the comet assay, but inter-laboratory variation of DNA migration levels is a concern.

13.
J Toxicol Environ Health B Crit Rev ; 26(2): 67-96, 2023 02 17.
Artículo en Inglés | MEDLINE | ID: mdl-36692141

RESUMEN

Several studies have been conducted to address the potential adverse health risks attributed to exposure to nanoscale materials. While in vivo studies are fundamental for identifying the relationship between dose and occurrence of adverse effects, in vitro model systems provide important information regarding the mechanism(s) of action at the molecular level. With a special focus on exposure to inhaled (nano)particulate material toxicity assessment, this review provides an overview of the available human respiratory models and exposure systems for in vitro testing, advantages, limitations, and existing investigations using models of different complexity. A brief overview of the human respiratory system, pathway and fate of inhaled (nano)particles is also presented.


Asunto(s)
Nanopartículas , Sistema Respiratorio , Humanos , Polvo , Exposición por Inhalación/efectos adversos , Nanopartículas/toxicidad
14.
J Chem Phys ; 158(17)2023 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-37144719

RESUMEN

The structural characterization of proteins with a disorder requires a computational approach backed by experiments to model their diverse and dynamic structural ensembles. The selection of conformational ensembles consistent with solution experiments of disordered proteins highly depends on the initial pool of conformers, with currently available tools limited by conformational sampling. We have developed a Generative Recurrent Neural Network (GRNN) that uses supervised learning to bias the probability distributions of torsions to take advantage of experimental data types such as nuclear magnetic resonance J-couplings, nuclear Overhauser effects, and paramagnetic resonance enhancements. We show that updating the generative model parameters according to the reward feedback on the basis of the agreement between experimental data and probabilistic selection of torsions from learned distributions provides an alternative to existing approaches that simply reweight conformers of a static structural pool for disordered proteins. Instead, the biased GRNN, DynamICE, learns to physically change the conformations of the underlying pool of the disordered protein to those that better agree with experiments.


Asunto(s)
Proteínas Intrínsecamente Desordenadas , Proteínas , Resonancia Magnética Nuclear Biomolecular , Proteínas/química , Espectroscopía de Resonancia Magnética , Conformación Proteica , Proteínas Intrínsecamente Desordenadas/química
15.
Gerontology ; 69(6): 684-693, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36538907

RESUMEN

INTRODUCTION: Immunosenescence and inflammaging have been implicated in the pathophysiology of frailty. Torquetenovirus (TTV), a single-stranded DNA anellovirus, the major component of the human blood virome, shows an increased replication rate with advancing age. An elevated TTV viremia has been associated with an impaired immune function and an increased risk of mortality in the older population. The objective of this study was to analyze the relation between TTV viremia, physical frailty, and cognitive impairment. METHODS: TTV viremia was measured in 1,131 nonfrail, 45 physically frail, and 113 cognitively impaired older adults recruited in the MARK-AGE study (overall mean age 64.7 ± 5.9 years), and then the results were checked in two other independent cohorts from Spain and Portugal, including 126 frail, 252 prefrail, and 141 nonfrail individuals (overall mean age: 77.5 ± 8.3 years). RESULTS: TTV viremia ≥4log was associated with physical frailty (OR: 4.69; 95% CI: 2.06-10.67, p < 0.0001) and cognitive impairment (OR: 3.49, 95% CI: 2.14-5.69, p < 0.0001) in the MARK-AGE population. The association between TTV DNA load and frailty status was confirmed in the Spanish cohort, while a slight association with cognitive impairment was observed (OR: 1.33; 95% CI: 1.000-1.773), only in the unadjusted model. No association between TTV load and frailty or cognitive impairment was found in the Portuguese sample, although a negative association between TTV viremia and MMSE score was observed in Spanish and Portuguese females. CONCLUSIONS: These findings demonstrate an association between TTV viremia and physical frailty, while the association with cognitive impairment was observed only in the younger population from the MARK-AGE study. Further research is necessary to clarify TTV's clinical relevance in the onset and progression of frailty and cognitive decline in older individuals.


Asunto(s)
Disfunción Cognitiva , Fragilidad , Torque teno virus , Femenino , Anciano , Humanos , Anciano de 80 o más Años , Fragilidad/epidemiología , Torque teno virus/fisiología , Viremia/complicaciones , Anciano Frágil/psicología , Evaluación Geriátrica , Disfunción Cognitiva/complicaciones , Disfunción Cognitiva/epidemiología
16.
J Tissue Viability ; 32(2): 179-187, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-36792441

RESUMEN

AIM: To develop a systematic review on the prevalence and the incidence of pressure ulcers/injuries in adult patients in hospital emergency services. MATERIALS AND METHODS: Systematic review of prevalence and incidence studies developed according to the Preferred Reporting Items Form Systematic Review and Meta-Analysis Protocols and the Joanna Briggs Institute methodology. The inclusion criteria were based on the CoCoPop mnemonic. The main variables of interest were the "prevalence" and/or the "incidence" of "pressure ulcers/injuries" (Condition) reported in studies developed in hospital emergency services (Context) with adult participants (Population). The Systematic Review Protocol was registered in PROSPERO (CDR42021252906). RESULTS: The pressure ulcer/injury (point) prevalence ranged from 5.2% (at admission) to 12.3% (at discharge) and the pressure ulcer/injury incidence ranged from 4.5% to 78.4%. Most of the pressure ulcers/injuries documented were category/stage I. The most problematic anatomical locations were the sacrococcygeal region and the heels. The preventive measures should be implemented as soon as possible and are important in patients older than 75 years, with multiple comorbidities, high C-Reative Protein levels, cervical spine immobilization, presented to hospital emergency service by ambulance or with hypotension at the time of admission. CONCLUSIONS: The prevalence and incidence of pressure ulcers/injuries in hospital emergency services remains an understudied topic which could limit the generalization of our data. This systematic review highlighted that the management of pressure ulcers/injuries is a real and current challenge in hospital emergency services. It is important to identify the patients at (higher) risk to establish an (earlier) preventive care plan according to patients and emergency services' characteristics.


Asunto(s)
Lesiones por Aplastamiento , Úlcera por Presión , Adulto , Humanos , Estudios de Cohortes , Lesiones por Aplastamiento/complicaciones , Servicio de Urgencia en Hospital , Hospitalización , Úlcera por Presión/prevención & control
17.
Cities ; 132: 104058, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36312519

RESUMEN

Women are among the groups most affected by the pandemic as they are more likely to be dependent on public transport (PT), which was heavily restricted during COVID-19. Thus, there is a need to consider transport alternatives such as bike sharing that can ensure their mobility needs. By conducting a survey to the bike sharing system (BSS) of Lisbon, we explored differences in travel behaviour and attitudes between female and male users before and during COVID-19. We found men to have higher bike ownership rates, a higher modal share of personal bicycle regarding commuting, and more likely to use their own bikes if BSS was unavailable. Conversely, women more frequently combined BSS with PT and were more likely to use PT if BSS was unavailable. Moreover, while men were using BSS more frequently than women pre-pandemic, during COVID-19 women are using BSS as frequently as men. Our research provides evidence on the potential role of BSS as a transport alternative during pandemics, inducing women to take up cycling who otherwise would not cycle, therefore, potentially decreasing the current cycling gender gap. Findings suggest that introducing family/friend discounts and promoting BSS for exercising may increase the share of female cyclists.

18.
Hum Mol Genet ; 29(5): 736-744, 2020 03 27.
Artículo en Inglés | MEDLINE | ID: mdl-31841129

RESUMEN

Selective pressures imposed by pathogens have varied among human populations throughout their evolution, leading to marked inter-population differences at some genes mediating susceptibility to infectious and immune-related diseases. Here, we investigated the evolutionary history of a common polymorphism resulting in a Y529 versus C529 change in the cadherin related family member 3 (CDHR3) receptor which underlies variable susceptibility to rhinovirus-C infection and is associated with severe childhood asthma. The protective variant is the derived allele and is found at high frequency worldwide (69-95%). We detected genome-wide significant signatures of natural selection consistent with a rapid increase of the haplotypes carrying the allele, suggesting that non-neutral processes have acted on this locus across all human populations. However, the allele has not fixed in any population despite multiple lines of evidence suggesting that the mutation predates human migrations out of Africa. Using an approximate Bayesian computation method, we estimate the age of the mutation while explicitly accounting for past demography and positive or frequency-dependent balancing selection. Our analyses indicate a single emergence of the mutation in anatomically modern humans ~150 000 years ago and indicate that balancing selection has maintained the beneficial allele at high equilibrium frequencies worldwide. Apart from the well-known cases of the MHC and ABO genes, this study provides the first evidence that negative frequency-dependent selection plausibly acted on a human disease susceptibility locus, a form of balancing selection compatible with typical transmission dynamics of communicable respiratory viruses that might exploit CDHR3.


Asunto(s)
Asma/patología , Cadherinas/genética , Enterovirus/fisiología , Predisposición Genética a la Enfermedad , Haplotipos , Proteínas de la Membrana/genética , Polimorfismo de Nucleótido Simple , Selección Genética , Asma/etiología , Asma/historia , Teorema de Bayes , Proteínas Relacionadas con las Cadherinas , Niño , Genoma Humano , Historia Antigua , Humanos
19.
N Engl J Med ; 381(8): 705-715, 2019 08 22.
Artículo en Inglés | MEDLINE | ID: mdl-31433918

RESUMEN

BACKGROUND: The systematic evaluation of the results of time-series studies of air pollution is challenged by differences in model specification and publication bias. METHODS: We evaluated the associations of inhalable particulate matter (PM) with an aerodynamic diameter of 10 µm or less (PM10) and fine PM with an aerodynamic diameter of 2.5 µm or less (PM2.5) with daily all-cause, cardiovascular, and respiratory mortality across multiple countries or regions. Daily data on mortality and air pollution were collected from 652 cities in 24 countries or regions. We used overdispersed generalized additive models with random-effects meta-analysis to investigate the associations. Two-pollutant models were fitted to test the robustness of the associations. Concentration-response curves from each city were pooled to allow global estimates to be derived. RESULTS: On average, an increase of 10 µg per cubic meter in the 2-day moving average of PM10 concentration, which represents the average over the current and previous day, was associated with increases of 0.44% (95% confidence interval [CI], 0.39 to 0.50) in daily all-cause mortality, 0.36% (95% CI, 0.30 to 0.43) in daily cardiovascular mortality, and 0.47% (95% CI, 0.35 to 0.58) in daily respiratory mortality. The corresponding increases in daily mortality for the same change in PM2.5 concentration were 0.68% (95% CI, 0.59 to 0.77), 0.55% (95% CI, 0.45 to 0.66), and 0.74% (95% CI, 0.53 to 0.95). These associations remained significant after adjustment for gaseous pollutants. Associations were stronger in locations with lower annual mean PM concentrations and higher annual mean temperatures. The pooled concentration-response curves showed a consistent increase in daily mortality with increasing PM concentration, with steeper slopes at lower PM concentrations. CONCLUSIONS: Our data show independent associations between short-term exposure to PM10 and PM2.5 and daily all-cause, cardiovascular, and respiratory mortality in more than 600 cities across the globe. These data reinforce the evidence of a link between mortality and PM concentration established in regional and local studies. (Funded by the National Natural Science Foundation of China and others.).


Asunto(s)
Contaminación del Aire/efectos adversos , Exposición a Riesgos Ambientales/análisis , Mortalidad , Material Particulado/efectos adversos , Contaminación del Aire/análisis , Enfermedades Cardiovasculares/mortalidad , Causas de Muerte , Exposición a Riesgos Ambientales/efectos adversos , Exposición a Riesgos Ambientales/legislación & jurisprudencia , Salud Global , Humanos , Tamaño de la Partícula , Material Particulado/análisis , Enfermedades Respiratorias/mortalidad , Riesgo
20.
Cost Eff Resour Alloc ; 20(1): 71, 2022 Dec 16.
Artículo en Inglés | MEDLINE | ID: mdl-36527052

RESUMEN

BACKGROUND: Governments in Latin America are constantly facing the problem of managing scarce resources to satisfy alternative needs, such as housing, education, food, and healthcare security. Those needs, combined with increasing crime levels, require financial resources to be solved. OBJECTIVE: The objective of this review was to characterizar the health system and health expenditure of a large country (Brazil) and a small country (Chile) and identify some of the challenges these two countries face in improving the health services of their population. METHODS: A literature review was conducted by searching journals, databases, and other electronic resources to identify articles and research publications describing health systems in Brazil and Chile. RESULTS: The review showed that the economic restriction and the economic cycle have an impact on the funding of the public health system. This result was true for the Brazilian health system after 2016, despite the change to a unique health system one decade earlier. In the case of Chile, there are different positions about which one is the best health system: a dual public and private or just public one. As a result, a referendum on September 4, 2022, of a new constitution, which incorporated a unique health system, was rejected. At the same time, the Government ended the copayment in the public health system in September 2022, excluding illnesses referred to the private sector. Another issue detected was the fragility of the public and private sector coverage due to the lack of funding. CONCLUSIONS: The health care system in Chile and Brazil has improved in the last decades. However, the public healthcare systems still need additional funding and efficiency improvement to respond to the growing health requirements needed from the population.

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