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1.
Genome Res ; 32(5): 864-877, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-35361625

RESUMEN

The ecology and genetic diversity of the model yeast Saccharomyces cerevisiae before human domestication remain poorly understood. Taiwan is regarded as part of this yeast's geographic birthplace, where the most divergent natural lineage was discovered. Here, we extensively sampled the broadleaf forests across this continental island to probe the ancestral species' diversity. We found that S. cerevisiae is distributed ubiquitously at low abundance in the forests. Whole-genome sequencing of 121 isolates revealed nine distinct lineages that diverged from Asian lineages during the Pleistocene, when a transient continental shelf land bridge connected Taiwan to other major landmasses. Three lineages are endemic to Taiwan and six are widespread in Asia, making this region a focal biodiversity hotspot. Both ancient and recent admixture events were detected between the natural lineages, and a genetic ancestry component associated with isolates from fruits was detected in most admixed isolates. Collectively, Taiwanese isolates harbor genetic diversity comparable to that of the whole Asia continent, and different lineages have coexisted at a fine spatial scale even on the same tree. Patterns of variations within each lineage revealed that S. cerevisiae is highly clonal and predominantly reproduces asexually in nature. We identified different selection patterns shaping the coding sequences of natural lineages and found fewer gene family expansion and contractions that contrast with domesticated lineages. This study establishes that S. cerevisiae has rich natural diversity sheltered from human influences, making it a powerful model system in microbial ecology.


Asunto(s)
Biodiversidad , Saccharomyces cerevisiae , Asia , Humanos , Filogenia , Saccharomyces cerevisiae/genética , Taiwán , Secuenciación Completa del Genoma
2.
Environ Res ; 216(Pt 3): 114566, 2023 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-36273597

RESUMEN

Antibiotic resistance has become a comprehensive and complicated environmental problem. It is of great importance to effectively determine the abundance of various antibiotic resistance genes (ARGs) in the environment. Here, we attempted to find a practical method for monitoring environmental antibiotic resistance. The results of culture-based analysis of antibiotic resistance and metagenomic sequencing indicate that egrets inhabiting along the urban river (Jinjiang River) can be used as the sentinel of environmental antibiotic resistance. The antibiotic resistance in the environment fluctuated with time, while that in the wild bird was relatively stable. The network analysis based on metagenomic sequencing data gave the co-occurrence pattern of ARGs. The overall situation of the antibiotic resistance in the river was determined by quantifying several module hub genes of the co-occurrence network in river sediments. The temporal and spatial distribution of ARGs in Jinjiang River is highly correlated with that of human gut-specific bacteriophage (crAssphage), which indicates that one main source of the antibiotic resistance in the river is likely to be municipal sewage. The mobility potential of ARGs varying among different niches suggests the transmission direction of antibiotic resistance in the environment.


Asunto(s)
Aves , Farmacorresistencia Microbiana , Metagenómica , Ríos , Animales , Antibacterianos/farmacología , Aves/microbiología , China , Farmacorresistencia Microbiana/genética , Genes Bacterianos , Monitoreo del Ambiente
3.
BMC Bioinformatics ; 22(1): 259, 2021 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-34016036

RESUMEN

BACKGROUND: Whole exome sequencing (WES) is widely adopted in clinical and research settings; however, one of the practical concerns is the potential false negatives due to incomplete breadth and depth of coverage for several exons in clinically implicated genes. In some cases, a targeted gene panel testing may be a dependable option to ascertain true negatives for genomic variants in known disease-associated genes. We developed a web-based tool to quickly gauge whether all genes of interest would be reliably covered by WES or whether targeted gene panel testing should be considered instead to minimize false negatives in candidate genes. RESULTS: WEScover is a novel web application that provides an intuitive user interface for discovering breadth and depth of coverage across population-scale WES datasets, searching either by phenotype, by targeted gene panel(s) or by gene(s). Moreover, the application shows metrics from the Genome Aggregation Database to provide gene-centric view on breadth of coverage. CONCLUSIONS: WEScover allows users to efficiently query genes and phenotypes for the coverage of associated exons by WES and recommends use of panel tests for the genes with potential incomplete coverage by WES.


Asunto(s)
Exoma , Genómica , Exoma/genética , Secuenciación de Nucleótidos de Alto Rendimiento , Fenotipo , Secuenciación del Exoma
4.
Am J Respir Cell Mol Biol ; 62(4): 479-492, 2020 04.
Artículo en Inglés | MEDLINE | ID: mdl-31944822

RESUMEN

Idiopathic pulmonary fibrosis is a lung disease with limited therapeutic options that is characterized by pathological fibroblast activation and aberrant lung remodeling with scar formation. YAP (Yes-associated protein) is a transcriptional coactivator that mediates mechanical and biochemical signals controlling fibroblast activation. In this study, we developed a high-throughput small-molecule screen for YAP inhibitors in primary human lung fibroblasts. Multiple HMG-CoA (hydroxymethylglutaryl-coenzyme A) reductase inhibitors (statins) were found to inhibit YAP nuclear localization via induction of YAP phosphorylation, cytoplasmic retention, and degradation. We further show that the mevalonate pathway regulates YAP activation, and that simvastatin treatment reduces fibrosis markers in activated human lung fibroblasts and in the bleomycin mouse model of pulmonary fibrosis. Finally, we show that simvastatin modulates YAP in vivo in mouse lung fibroblasts. Our results highlight the potential of small-molecule screens for YAP inhibitors and provide a mechanism for the antifibrotic activity of statins in idiopathic pulmonary fibrosis.


Asunto(s)
Proteínas Adaptadoras Transductoras de Señales/antagonistas & inhibidores , Proteínas de Ciclo Celular/antagonistas & inhibidores , Inhibidores de Hidroximetilglutaril-CoA Reductasas/farmacología , Fibrosis Pulmonar/tratamiento farmacológico , Acilcoenzima A/metabolismo , Animales , Biomarcadores/metabolismo , Bleomicina/farmacología , Núcleo Celular/efectos de los fármacos , Núcleo Celular/metabolismo , Citoplasma/efectos de los fármacos , Citoplasma/metabolismo , Fibroblastos/efectos de los fármacos , Fibroblastos/metabolismo , Humanos , Ácido Mevalónico/metabolismo , Ratones , Fosfoproteínas/metabolismo , Fibrosis Pulmonar/metabolismo , Transducción de Señal/efectos de los fármacos , Simvastatina/farmacología , Bibliotecas de Moléculas Pequeñas/farmacología , Proteínas Señalizadoras YAP
5.
Pharmacogenomics J ; 20(5): 672-680, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32029903

RESUMEN

This study explored the effect of OPRM1 promoter region DNA methylation on the outcome of treatment with the opioid antagonist naltrexone (NTX) for alcohol dependence (AD). Ninety-three patients with DSM-IV AD [41 African Americans (AAs) and 52 European Americans (EAs)] received double-blind treatment with NTX or placebo for at least three months. Relapse to heavy drinking was assessed during the first 13 weeks of the trial. Peripheral blood methylation levels of 33 CpG units in the OPRM1 promoter region were quantified using Sequenom EpiTYPER technology. Bayesian logistic regression was used to analyze the effects of NTX treatment, CpG methylation, CpG methylation × NTX treatment, and age on AD relapse. The Random Forest machine learning algorithm was applied to select AD relapse predictors. No significant effect of individual OPRM1 promoter CpG units on AD relapse was observed in either AAs or EAs. Age was significantly associated with AD relapse in EAs, among whom older subjects had a lower relapse rate. Random forest analyses revealed that the prediction rate for AD relapse reached 66.0% with five top variables (age and four CpG units; ranked by their importance to AD relapse) in the prediction model. These findings suggest that methylation levels of individual OPRM1 promoter CpG units do not contribute significantly to inter-individual variation in NTX response. However, the age of subjects in combination with a cluster of specific OPRM1 promoter CpG units may affect NTX treatment outcome. Additional studies of OPRM1 DNA methylation changes during and after NTX treatment of AD are needed.


Asunto(s)
Consumo de Bebidas Alcohólicas/prevención & control , Alcoholismo/tratamiento farmacológico , Alcoholismo/genética , Metilación de ADN , Naltrexona/uso terapéutico , Antagonistas de Narcóticos/uso terapéutico , Variantes Farmacogenómicas , Regiones Promotoras Genéticas , Receptores Opioides mu/antagonistas & inhibidores , Receptores Opioides mu/genética , Adulto , Factores de Edad , Abstinencia de Alcohol , Consumo de Bebidas Alcohólicas/genética , Consumo de Bebidas Alcohólicas/metabolismo , Alcoholismo/diagnóstico , Alcoholismo/metabolismo , Método Doble Ciego , Humanos , Persona de Mediana Edad , Naltrexona/efectos adversos , Antagonistas de Narcóticos/efectos adversos , Farmacogenética , Receptores Opioides mu/metabolismo , Recurrencia , Factores de Tiempo , Resultado del Tratamiento , Estados Unidos
6.
Ecotoxicol Environ Saf ; 198: 110687, 2020 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-32361489

RESUMEN

A marine diatom, Thalassiosira sp. OUC2, was isolated from natural seawater collected from Daya Bay, China. This diatom degraded 1.25-40 mg L-1p-xylene within five days, at a removal efficiency exceeding 98%. Gas chromatography-mass spectrometer (GC-MS) analysis indicated that p-xylene was converted into 4-methylbenzyl alcohol, p-toluic acid, and p-cresol in the presence of strain OUC2. Meanwhile, proteomic analysis showed that, after exposure to p-xylene, several algal enzymes were significantly upregulated: including monooxygenase, alcohol dehydrogenase, benzaldehyde dehydrogenase, benzoate 1,2-dioxygenase, and catechol 2,3-dioxygenase. Moreover, ecotoxicological tests suggested that the intermediate metabolites were less toxic than the parent compound (p-xylene). Thalassiosira sp. OUC2 may thus be suitable for the remediation of p-xylene-contaminated marine environments.


Asunto(s)
Biodegradación Ambiental , Diatomeas/metabolismo , Contaminantes Químicos del Agua/metabolismo , Xilenos/metabolismo , Benzoatos , China , Cromatografía de Gases y Espectrometría de Masas , Proteómica , Agua de Mar
7.
Ecotoxicol Environ Saf ; 189: 109995, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31785947

RESUMEN

The use of p-chloroaniline (PCA) in various aspects leads to its existence and accumulation in the environment. Relevant researches showed that PCA was a prime toxic pollutant that had imposed a serious risk to public health and the environment. This paper investigated the toxicity effects of PCA on Platymonas subcordiformis (P. subcordiformis) and the biodegradation of PCA by the marine microalga. In the toxicity experiments, the EC50 of PCA on P. subcordiformis at 24 h, 48 h, 72 h and 96 h was 41.42, 24.04, 17.15 and 13.05 mg L-1, respectively. The pigment parameters including chlorophyll a, chlorophyll b, carotenoids, photosynthetic O2 release rate, respiration O2 consumption rate and the chlorophyll fluorescence parameters including Fv/Fm, ETR and qP decreased greatly while antioxidant enzyme activities (SOD, CAT) and the chlorophyll fluorescence parameter NPQ increased when P. subcordiformis exposed to PCA compared with the control group. Fv/Fm would be a suitable indicator for assessing the toxicity of PCA in marine environment based on the analysis of Pearson's correlation coefficient and Integrated Biomarker Response (IBR). The degradation assay in P. subcordiformis indicated that the green marine microalga had the ability to remove and degrade PCA, and the order of removal and degradation proportion of PCA was 2 mg L-1 > 5 mg L-1>10 mg L-1. The maximum removal and biodegradation percentage was 54% and 34%, respectively.


Asunto(s)
Compuestos de Anilina/toxicidad , Chlorophyta/efectos de los fármacos , Contaminantes Químicos del Agua/toxicidad , Compuestos de Anilina/metabolismo , Biodegradación Ambiental , Carotenoides/metabolismo , Clorofila/metabolismo , Clorofila A/metabolismo , Chlorophyta/metabolismo , Oxígeno/metabolismo , Fotosíntesis/efectos de los fármacos , Contaminantes Químicos del Agua/metabolismo
8.
Ecotoxicol Environ Saf ; 184: 109658, 2019 Nov 30.
Artículo en Inglés | MEDLINE | ID: mdl-31520955

RESUMEN

With the continuous demand from industry for chemical raw materials, a large amount of high-salinity wastewater containing phenol is discharged into the aquatic environment, and the leakage of dangerous chemicals into the sea may lead to phenol pollution of the ocean. Phenol is a common chemical posing serious environmental hazard. Biodegradation is an effective, low-cost, environment-friendly method of removing phenol from water, but in hypersaline environments, traditional freshwater organisms are less efficacious. Here, at least 17 genera of bacteria from three phyla are found that can degrade phenol in different saline environments. The sources and taxonomy of halotolerant and halophilic bacteria are reviewed. Moreover, the pathway of phenol removal, kinetics of biodegradation, influencing factors, and recent treatment processes of wastewater are discussed.


Asunto(s)
Bacterias/metabolismo , Fenol/análisis , Aguas Residuales/química , Contaminantes Químicos del Agua/análisis , Organismos Acuáticos/metabolismo , Archaea/metabolismo , Biodegradación Ambiental , Fenol/metabolismo , Solución Salina , Salinidad , Aguas Residuales/microbiología , Contaminantes Químicos del Agua/metabolismo
9.
Ecotoxicol Environ Saf ; 169: 654-661, 2019 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-30496998

RESUMEN

The environmental risk issues of p-choroaniline have been concerned by the widespread application and transportation of this important chemical intermediate. The information about the toxicity of p-chloroaniline was mainly concentrated on freshwater organisms while the current knowledge on marine organisms was scarce yet. In this study, acute toxicity and toxic physiology characteristic of p-chloroaniline to Phaeodactylum tricornutum (P. tricornutum) were first determined. In the acute experiments, the effect of the p-choroaniline to P. tricornutum showed time- and dose-dependent response, which the half maximum effective concentration (EC50) at 24 h, 48 h and 96 h was 35.35, 20.10 and 10.00 mgL-1, respectively. Toxic physiology assays in P. tricornutum indicated that the p-choroaniline induced significant changes of photosynthetic pigments (Chl-a, Chl-b, Caro, Chl-a/b and Chl-(a+b)/Caro), Chlorophyll fluorescence parameters (Fv/Fm, ETR, qP and NPQ), rates of photosynthetic O2 release and respiration O2 consumption, and antioxidant enzyme activities (SOD, CAT). The obvious decrease of Fv/Fm, ETR and chl-a in low p-choroaniline treatments (≤ 5.00 mgL-1) compared with the control could be observed, which implied that these parameters could be taken as sensitive indicators for the environmental assessment. Meanwhile, the activities of SOD and CAT significant increase in p-choroaniline stress after 24 h and the extent of the increase has fallen after 96 h. These toxicity data obtained here might provide available basic data for the ecological risk assessment of p-choroaniline pollution.


Asunto(s)
Compuestos de Anilina/toxicidad , Antioxidantes/metabolismo , Diatomeas , Consumo de Oxígeno/efectos de los fármacos , Fotosíntesis/efectos de los fármacos , Contaminantes Químicos del Agua/toxicidad , Clorofila/metabolismo , Diatomeas/efectos de los fármacos , Diatomeas/enzimología , Diatomeas/crecimiento & desarrollo , Pruebas de Toxicidad Aguda , Pruebas de Toxicidad Subcrónica
10.
Ecotoxicol Environ Saf ; 168: 443-449, 2019 Jan 30.
Artículo en Inglés | MEDLINE | ID: mdl-30408745

RESUMEN

Microcosm experiments were conducted to examine the attenuation of selected chemicals, i.e. m-xylene (MX), o-xylene (OX) and p-xylene (PX), under simulated marine conditions. Natural attenuation and the contribution of oxidation, photodegradation, biodegradation and volatilization to total attenuation were evaluated. The development of attenuation was in agreement with pseudo-first-order kinetics for all xylenes. The half-lives of MX, OX, and PX under optimal conditions were 0.76, 0.74 and 0.88 days, respectively. Attenuation kinetics were proposed to analyze the natural attenuation of xylenes. The leading attenuation type of MX, OX, and PX was volatilization, and the attenuation rate constants (KV) were 0.5587, 0.6733, and 0.4821 d-1, respectively. Biodegradation of OX (Kb: 0.0003 d-1) was extremely inhibited. The attenuation kinetics presented the attenuation of xylenes in microcosm. The reaction kinetics could be applied to analyze the natural attenuation of chemicals. MX and OX can be converted to one another under certain conditions. Toluene and ethylbenzene were detected for OX in the OP (oxidation and photodegradation) experiment under simulated marine conditions. 4-Methylbenzyl alcohol, p-methyl benzaldehyde and p-toluic acid, as the major intermediates, were identified during the natural attenuation of PX using GC/MS.


Asunto(s)
Biodegradación Ambiental , Agua de Mar/química , Xilenos/química , Derivados del Benceno/química , Benzoatos/química , Alcoholes Bencílicos/química , Medios de Cultivo/química , Cromatografía de Gases y Espectrometría de Masas , Semivida , Concentración de Iones de Hidrógeno , Tolueno/química
11.
Bull Environ Contam Toxicol ; 103(3): 441-446, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31201469

RESUMEN

The toxic effects of p-xylene, 4-methylbenzyl alcohol, p-methyl benzaldehyde, and p-toluic acid on two marine microalgae (Phaeodactylum tricornutum Bohlin, and Skeletonema costatum) were investigated. p-Xylene was the most toxic to Pha. tricornutum with a 96 h EC50 value of 6.76 mg L-1. Based on the 96 h EC50 values for two microalgae, the toxicity of the four chemicals, in descending order, was: p-xylene, p-methyl benzaldehyde, 4-methylbenzyl alcohol, then p-toluic acid. The results showed that the toxicity of the transformed products of p-xylene was lower than that of p-xylene.


Asunto(s)
Microalgas/efectos de los fármacos , Estramenopilos/efectos de los fármacos , Contaminantes Químicos del Agua/toxicidad , Xilenos/toxicidad , Benzaldehídos/toxicidad , Benzoatos/toxicidad , Alcoholes Bencílicos/toxicidad
12.
Ecotoxicol Environ Saf ; 157: 441-456, 2018 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-29655160

RESUMEN

With the development of industrial production and continuous demand for chemicals, a large volume of wastewater containing phenols was discharged into the aquatic environment. Moreover, chemical leakage further increased the emission of phenols into aquatic systems. Phenol and its methylated derivative (cresols) were selected due to their extensive use in industry and ecotoxicity to freshwater and marine organisms. This review focused on the ecotoxicity of phenol and m-, o-, and p-cresol on aquatic systems. The mechanism of action of phenols was also discussed. The aim of this literature review was to summarise the knowledge of the behaviour, and toxicity on marine and freshwater organisms, of phenols as well as to try to select a series of sensitive biomarkers suitable for ecotoxicological assessment and environmental monitoring in aquatic environments.


Asunto(s)
Organismos Acuáticos , Cresoles/toxicidad , Ecotoxicología , Fenol/toxicidad , Contaminantes Químicos del Agua/toxicidad , Biodegradación Ambiental , Fenómenos Químicos , Monitoreo del Ambiente , Agua Dulce/química , Sustancias Peligrosas/toxicidad , Pruebas de Toxicidad , Aguas Residuales/análisis
13.
Mol Microbiol ; 2014 Sep 30.
Artículo en Inglés | MEDLINE | ID: mdl-25266672

RESUMEN

Streptomyces coelicolor is a model for studying bacteria renowned as the foremost source of natural products used clinically. Post-genomic studies have revealed complex patterns of gene expression and links to growth, morphological development and individual genes. However, the underlying regulation remains largely obscure, but undoubtedly involves steps after transcription initiation. Here we identify sites involved in RNA processing and degradation as well as transcription within a nucleotide-resolution map of the transcriptional landscape. This was achieved by combining RNA-sequencing approaches suited to the analysis of GC-rich organisms. Escherichia coli was analysed in parallel to validate the methodology and allow comparison. Previously, sites of RNA processing and degradation had not been mapped on a transcriptome-wide scale for E. coli. Through examples, we show the value of our approach and data sets. This includes the identification of new layers of transcriptional complexity associated with several key regulators of secondary metabolism and morphological development in S. coelicolor and the identification of host-encoded leaderless mRNA and rRNA processing associated with the generation of specialized ribosomes in E. coli. New regulatory small RNAs were identified for both organisms. Overall the results illustrate the diversity in mechanisms used by different bacterial groups to facilitate and regulate gene expression.

14.
BMC Genomics ; 14: 620, 2013 Sep 14.
Artículo en Inglés | MEDLINE | ID: mdl-24034785

RESUMEN

BACKGROUND: Sequencing of the genome of Propionibacterium acnes produced a catalogue of genes many of which enable this organism to colonise skin and survive exposure to the elements. Despite this platform, there was little understanding of the gene regulation that gives rise to an organism that has a major impact on human health and wellbeing and causes infections beyond the skin. To address this situation, we have undertaken a genome-wide study of gene regulation using a combination of improved differential and global RNA-sequencing and an analytical approach that takes into account the inherent noise within the data. RESULTS: We have produced nucleotide-resolution transcriptome maps that identify and differentiate sites of transcription initiation from sites of stable RNA processing and mRNA cleavage. Moreover, analysis of these maps provides strong evidence for 'pervasive' transcription and shows that contrary to initial indications it is not biased towards the production of antisense RNAs. In addition, the maps reveal an extensive array of riboswitches, leaderless mRNAs and small non-protein-coding RNAs alongside vegetative promoters and post-transcriptional events, which includes unusual tRNA processing. The identification of such features will inform models of complex gene regulation, as illustrated here for ribonucleotide reductases and a potential quorum-sensing, two-component system. CONCLUSIONS: The approach described here, which is transferable to any bacterial species, has produced a step increase in whole-cell knowledge of gene regulation in P. acnes. Continued expansion of our maps to include transcription associated with different growth conditions and genetic backgrounds will provide a new platform from which to computationally model the gene expression that determines the physiology of P. acnes and its role in human disease.


Asunto(s)
Propionibacterium acnes/genética , ARN Bacteriano/genética , Análisis de Secuencia de ARN/métodos , Iniciación de la Transcripción Genética , Secuencia Conservada , Regulación Bacteriana de la Expresión Génica , Regiones Promotoras Genéticas , Procesamiento Postranscripcional del ARN , ARN Mensajero/genética , Sitio de Iniciación de la Transcripción , Transcriptoma
15.
Artículo en Inglés | MEDLINE | ID: mdl-37027547

RESUMEN

Recently, learning-based algorithms have shown impressive performance in underwater image enhancement. Most of them resort to training on synthetic data and obtain outstanding performance. However, these deep methods ignore the significant domain gap between the synthetic and real data (i.e., inter-domain gap), and thus the models trained on synthetic data often fail to generalize well to real-world underwater scenarios. Moreover, the complex and changeable underwater environment also causes a great distribution gap among the real data itself (i.e., intra-domain gap). However, almost no research focuses on this problem and thus their techniques often produce visually unpleasing artifacts and color distortions on various real images. Motivated by these observations, we propose a novel Two-phase Underwater Domain Adaptation network (TUDA) to simultaneously minimize the inter-domain and intra-domain gap. Concretely, in the first phase, a new triple-alignment network is designed, including a translation part for enhancing realism of input images, followed by a task-oriented enhancement part. With performing image-level, feature-level and output-level adaptation in these two parts through jointly adversarial learning, the network can better build invariance across domains and thus bridging the inter-domain gap. In the second phase, an easy-hard classification of real data according to the assessed quality of enhanced images is performed, in which a new rank-based underwater quality assessment method is embedded. By leveraging implicit quality information learned from rankings, this method can more accurately assess the perceptual quality of enhanced images. Using pseudo labels from the easy part, an easy-hard adaptation technique is then conducted to effectively decrease the intra-domain gap between easy and hard samples. Extensive experimental results demonstrate that the proposed TUDA is significantly superior to existing works in terms of both visual quality and quantitative metrics.

16.
Front Aging ; 4: 1261121, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37881503

RESUMEN

Growth hormone (GH) signaling influences lifespan in a wide variety of mammalian species. We previously reported that a cluster of miRNAs located on the X-chromosome are de-repressed with age in male mouse liver, and a subset, the mir-465 family, can directly attenuate expression of the growth hormone receptor (GHR) in vitro leading to a reduction in GH signaling. Here we show that this cluster of miRNAs is also upregulated in the liver with age in females, and that calorie restriction and the Ames dwarf genotype, both known to delay aging, attenuate the upregulation of the miRNA cluster. Upregulation of mir-465 in vivo leads to a reduction in GHR mRNA in the liver and an attenuation of GH signaling, indicated by a reduction in GHR, IGF-1, IGFBP3, and ALS mRNA expression. There is a corresponding reduction in IGF-1 protein levels in the liver and plasma. These results suggest that the age-associated upregulation of the X-chromosomal cluster of miRNAs could influence lifespan.

17.
J Phys Chem B ; 127(38): 8116-8130, 2023 Sep 28.
Artículo en Inglés | MEDLINE | ID: mdl-37725055

RESUMEN

Recycling Kr and Xe from used nuclear fuel (UNF) is conducive to regenerating economy and protecting the environment, and it is urgent to screen or design high-performance cutting-edge metal-organic framework (MOF) materials for Kr/Xe adsorption separation. After grand canonical Monte Carlo (GCMC) simulations of Kr/Xe adsorption separation on 11,000 frameworks in CoRE MOFs (2019), the important structure-adsorption property relationship (SAPR) was induced; that is, the porosity (φ) at 0.30-0.40, LCD/PLD at 1.00-1.49, density (ρ) range between 1.20 and 2.30 g/cm3, and PLD at 2.40-3.38 Å can be utilized to screen for high-performance G-MOFs and hMOFs. In addition, the key "genes" (metal nodes and linkers) of MOFs determining the Kr/Xe adsorption separation were data-mined by a machine learning technique, which were assembled into novel MOFs. After comprehensive consideration of thermal stability and the adsorbent performance score (APS), eight promising MOFs on Kr/Xe separation with the APS more than 1290.89 were screened out and assembled, which are better than most of the reported frameworks. Note that the adsorption isotherms of these MOFs on Kr and Xe belong to type I curve with the thermodynamic equilibrium mechanism on Kr/Xe based on the confinement effect. Furthermore, according to the electronic structure calculations of the independent gradient model based on Hirshfeld partition (IGMH) and energy decomposition analysis, it is found that the interactions between guests and frameworks are vdW forces with dominant induction energy (Eind). In addition, the electrostatic potential gradients of frameworks are generally linearly negative correlated with Kr uptakes. Therefore, both the geometrical and electronic structures dominate the adsorption separation performance on Kr/Xe. Interestingly, these eight MOFs are also suitable for the separation of CH4/H2 with considerable selectivities and CH4 uptakes of up to 2566.67 and 3.04 mmol/g, respectively. Herein, the accurately constructed SAPR and material genomics strategy should be helpful for the experimental discovery of novel MOFs on Kr/Xe separation experimentally.

18.
EBioMedicine ; 95: 104746, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37544204

RESUMEN

BACKGROUND: Unravelling the relationships between candidate genes and autism spectrum disorder (ASD) phenotypes remains an outstanding challenge. Endophenotypes, defined as inheritable, measurable quantitative traits, might provide intermediary links between genetic risk factors and multifaceted ASD phenotypes. In this study, we sought to determine whether plasma metabolite levels could serve as endophenotypes in individuals with ASD and their family members. METHODS: We employed an untargeted, high-resolution metabolomics platform to analyse 14,342 features across 1099 plasma samples. These samples were collected from probands and their family members participating in the Autism Genetic Resource Exchange (AGRE) (N = 658), compared with neurotypical individuals enrolled in the PrecisionLink Health Discovery (PLHD) program at Boston Children's Hospital (N = 441). We conducted a metabolite quantitative trait loci (mQTL) analysis using whole-genome genotyping data from each cohort in AGRE and PLHD, aiming to prioritize significant mQTL and metabolite pairs that were exclusively observed in AGRE. FINDINGS: Within the AGRE group, we identified 54 significant associations between genotypes and metabolite levels (P < 5.27 × 10-11), 44 of which were not observed in the PLHD group. Plasma glutamine levels were found to be associated with variants in the NLGN1 gene, a gene that encodes post-synaptic cell-adhesion molecules in excitatory neurons. This association was not detected in the PLHD group. Notably, a significant negative correlation between plasma glutamine and glutamate levels was observed in the AGRE group, but not in the PLHD group. Furthermore, plasma glutamine levels showed a negative correlation with the severity of restrictive and repetitive behaviours (RRB) in ASD, although no direct association was observed between RRB severity and the NLGN1 genotype. INTERPRETATION: Our findings suggest that plasma glutamine levels could potentially serve as an endophenotype, thus establishing a link between the genetic risk associated with NLGN1 and the severity of RRB in ASD. This identified association could facilitate the development of novel therapeutic targets, assist in selecting specific cohorts for clinical trials, and provide insights into target symptoms for future ASD treatment strategies. FUNDING: This work was supported by the National Institute of Health (grant numbers: R01MH107205, U01TR002623, R24OD024622, OT2OD032720, and R01NS129188) and the PrecisionLink Biobank for Health Discovery at Boston Children's Hospital.


Asunto(s)
Trastorno del Espectro Autista , Glutamina , Niño , Humanos , Trastorno del Espectro Autista/sangre , Trastorno del Espectro Autista/genética , Trastorno del Espectro Autista/metabolismo , Endofenotipos , Genotipo , Glutamina/sangre , Polimorfismo de Nucleótido Simple
19.
Food Sci Technol Int ; 18(5): 477-88, 2012 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-23144241

RESUMEN

Drying is the main process used to treat lotus seeds for storage. In this study, response surface methodology was used to optimize processing methods for microwave vacuum (MWV) drying of lotus seeds and to create a desirable product. A central composite design with three important factors: microwave output power (2.0-4.0 kW), vacuum degree (-0.070 to -0.090 MPa) and on/off ratio (68/52 s to 99/21 s) was used to study the response variables of drying time, shrinkage ratio, rehydration ratio and whiteness index. The optimum conditions for MWV drying of lotus seeds were determined to obtain a minimal drying time, minimal shrinkage ratio, maximum rehydration ratio and maximum whiteness index. The optimum drying conditions were found to be: microwave output power 3.2 kW, vacuum degree -0.083 MPa and on/off ratio 94/26 s. Under these optimal conditions, drying time, shrinkage ratio, rehydration ratio and whiteness index were found to be 10 min, 37.66%, 157.1% and 68.83, respectively.


Asunto(s)
Conservación de Alimentos/métodos , Nelumbo/química , Semillas/química , Fenómenos Químicos , China , Color , Conservación de Alimentos/instrumentación , Almacenamiento de Alimentos , Calor , Medicina Tradicional China , Microscopía Electrónica de Rastreo , Microondas , Nelumbo/ultraestructura , Semillas/ultraestructura , Estadística como Asunto , Propiedades de Superficie , Factores de Tiempo , Vacio , Agua/análisis
20.
Environ Pollut ; 293: 118541, 2022 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-34800588

RESUMEN

Antibiotics are widely applied to prevent and treat diseases occurred in mariculture. The often-open nature of mariculture production systems has led to antibiotic residue accumulation in the culturing and adjacent environments, which can adversely affect aquatic ecosystems, and even human. This review summarizes the occurrence, environmental behavior, and ecological effects of antibiotics in mariculture systems based on peer-reviewed papers. Forty-five different antibiotics (categorized into ten groups) have been detected in mariculture systems around the world, which is far greater than the number officially allowed. Indiscriminate use of antibiotics is relatively high among major producing countries in Asia, which highlights the need for stricter enforcement of regulations and policies and effective antibiotic removal methods. Compared with other environmental systems, some environmental characteristics of mariculture systems, such as high salinity and dissolved organic matter (DOM) content, can affect the migration and transformation processes of antibiotics. Residues of antibiotics favor the proliferation of antibiotic resistance genes (ARGs). Antibiotics and ARGs alter microbial communities and biogeochemical cycles, as well as posing threats to marine organisms and human health. This review may provide a valuable summary of the effects of antibiotics on mariculture systems.


Asunto(s)
Antibacterianos , Genes Bacterianos , Antibacterianos/farmacología , China , Materia Orgánica Disuelta , Farmacorresistencia Microbiana/genética , Ecosistema , Humanos
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