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We present a multiomic cell atlas of human lung development that combines single-cell RNA and ATAC sequencing, high-throughput spatial transcriptomics, and single-cell imaging. Coupling single-cell methods with spatial analysis has allowed a comprehensive cellular survey of the epithelial, mesenchymal, endothelial, and erythrocyte/leukocyte compartments from 5-22 post-conception weeks. We identify previously uncharacterized cell states in all compartments. These include developmental-specific secretory progenitors and a subtype of neuroendocrine cell related to human small cell lung cancer. Our datasets are available through our web interface (https://lungcellatlas.org). To illustrate its general utility, we use our cell atlas to generate predictions about cell-cell signaling and transcription factor hierarchies which we rigorously test using organoid models.
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Feto , Pulmón , Humanos , Diferenciación Celular , Perfilación de la Expresión Génica , Pulmón/citología , Organogénesis , Organoides , Atlas como Asunto , Feto/citologíaRESUMEN
The human brain develops through a tightly organized cascade of patterning events, induced by transcription factor expression and changes in chromatin accessibility. Although gene expression across the developing brain has been described at single-cell resolution1, similar atlases of chromatin accessibility have been primarily focused on the forebrain2-4. Here we describe chromatin accessibility and paired gene expression across the entire developing human brain during the first trimester (6-13 weeks after conception). We defined 135 clusters and used multiomic measurements to link candidate cis-regulatory elements to gene expression. The number of accessible regions increased both with age and along neuronal differentiation. Using a convolutional neural network, we identified putative functional transcription factor-binding sites in enhancers characterizing neuronal subtypes. We applied this model to cis-regulatory elements linked to ESRRB to elucidate its activation mechanism in the Purkinje cell lineage. Finally, by linking disease-associated single nucleotide polymorphisms to cis-regulatory elements, we validated putative pathogenic mechanisms in several diseases and identified midbrain-derived GABAergic neurons as being the most vulnerable to major depressive disorder-related mutations. Our findings provide a more detailed view of key gene regulatory mechanisms underlying the emergence of brain cell types during the first trimester and a comprehensive reference for future studies related to human neurodevelopment.
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Human limbs emerge during the fourth post-conception week as mesenchymal buds, which develop into fully formed limbs over the subsequent months1. This process is orchestrated by numerous temporally and spatially restricted gene expression programmes, making congenital alterations in phenotype common2. Decades of work with model organisms have defined the fundamental mechanisms underlying vertebrate limb development, but an in-depth characterization of this process in humans has yet to be performed. Here we detail human embryonic limb development across space and time using single-cell and spatial transcriptomics. We demonstrate extensive diversification of cells from a few multipotent progenitors to myriad differentiated cell states, including several novel cell populations. We uncover two waves of human muscle development, each characterized by different cell states regulated by separate gene expression programmes, and identify musculin (MSC) as a key transcriptional repressor maintaining muscle stem cell identity. Through assembly of multiple anatomically continuous spatial transcriptomic samples using VisiumStitcher, we map cells across a sagittal section of a whole fetal hindlimb. We reveal a clear anatomical segregation between genes linked to brachydactyly and polysyndactyly, and uncover transcriptionally and spatially distinct populations of the mesenchyme in the autopod. Finally, we perform single-cell RNA sequencing on mouse embryonic limbs to facilitate cross-species developmental comparison, finding substantial homology between the two species.
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The cellular landscape of the human intestinal tract is dynamic throughout life, developing in utero and changing in response to functional requirements and environmental exposures. Here, to comprehensively map cell lineages, we use single-cell RNA sequencing and antigen receptor analysis of almost half a million cells from up to 5 anatomical regions in the developing and up to 11 distinct anatomical regions in the healthy paediatric and adult human gut. This reveals the existence of transcriptionally distinct BEST4 epithelial cells throughout the human intestinal tract. Furthermore, we implicate IgG sensing as a function of intestinal tuft cells. We describe neural cell populations in the developing enteric nervous system, and predict cell-type-specific expression of genes associated with Hirschsprung's disease. Finally, using a systems approach, we identify key cell players that drive the formation of secondary lymphoid tissue in early human development. We show that these programs are adopted in inflammatory bowel disease to recruit and retain immune cells at the site of inflammation. This catalogue of intestinal cells will provide new insights into cellular programs in development, homeostasis and disease.
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Envejecimiento , Sistema Nervioso Entérico/citología , Feto/citología , Salud , Intestinos/citología , Intestinos/crecimiento & desarrollo , Ganglios Linfáticos/citología , Ganglios Linfáticos/crecimiento & desarrollo , Adulto , Animales , Niño , Enfermedad de Crohn/patología , Conjuntos de Datos como Asunto , Sistema Nervioso Entérico/anatomía & histología , Sistema Nervioso Entérico/embriología , Sistema Nervioso Entérico/crecimiento & desarrollo , Células Epiteliales/citología , Femenino , Feto/anatomía & histología , Feto/embriología , Humanos , Intestinos/embriología , Intestinos/inervación , Ganglios Linfáticos/embriología , Ganglios Linfáticos/patología , Ratones , Ratones Endogámicos C57BL , Organogénesis , Receptores de IgG/metabolismo , Transducción de Señal , Análisis Espacio-Temporal , Factores de TiempoRESUMEN
Significant efforts are ongoing to develop refined differentiation protocols to generate midbrain dopamine (DA) neurons from pluripotent stem cells for application in disease modeling, diagnostics, drug screening and cell-based therapies for Parkinson's disease. An increased understanding of the timing and molecular mechanisms that promote the generation of distinct subtypes of human midbrain DA during development will be essential for guiding future efforts to generate molecularly defined and subtype-specific DA neurons from pluripotent stem cells. Here, we use droplet-based single-cell RNA sequencing to transcriptionally profile the developing human ventral midbrain (VM) when the DA neurons are generated (6-11â weeks post-conception) and their subsequent differentiation into functional mature DA neurons in primary fetal 3D organoid-like cultures. This approach reveals that 3D cultures are superior to monolayer conditions for their ability to generate and maintain mature DA neurons; hence, they have the potential to be used for studying human VM development. These results provide a unique transcriptional profile of the developing human fetal VM and functionally mature human DA neurons that can be used to guide stem cell-based therapies and disease modeling approaches in Parkinson's disease.
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Enfermedad de Parkinson , Células Madre Pluripotentes , Humanos , Enfermedad de Parkinson/genética , Enfermedad de Parkinson/terapia , Neuronas Dopaminérgicas , Mesencéfalo , Diferenciación Celular/genéticaRESUMEN
Polyionic liquid hydrogels attract increasing attention due to their unique properties and potential applications. However, research on amino acid-based polyionic liquid hydrogels is still in its infancy stage. Moreover, the effect of amino acid types on the properties of hydrogels is rarely studied to date. In this work, amino acid-based polyionic liquid hydrogels (D/L-PCAA hydrogels) are synthesized by copolymerizing vinyl choline-amino acid ionic liquids and acrylic acids using Al3+ as a crosslinking agent and bacterial cellulose (BC) as a reinforcing agent. The effects of amino acid types on mechanical and antimicrobial properties are systematically investigated. D-arginine-based hydrogel (D-PCArg) shows the highest tensile strength (220.7 KPa), D-phenylalanine-based hydrogel (D-PCPhe) exhibits the highest elongation at break (1346%), and L-aspartic acid-based hydrogel (L-PCAsp) has the highest elastic modulus (206.9 KPa) and toughness (1.74 MJ m-3). D/L-PCAsp hydrogels demonstrate stronger antibacterial capacity against Escherichia coli and Staphylococcus aureus, and D/L-PCPhe hydrogels possess higher antifungal activity against Cryptococcus neoformans. Moreover, the resultant hydrogels exhibit prominent hemocompatibility and low toxicity, as well as excellent self-healing capabilities (86%) and conductivity (2.8 S m-1). These results indicate that D/L-PCAA hydrogel provides a promise for applications in wound dressings.
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Aminoácidos , Antibacterianos , Escherichia coli , Hidrogeles , Líquidos Iónicos , Staphylococcus aureus , Hidrogeles/química , Hidrogeles/farmacología , Hidrogeles/síntesis química , Escherichia coli/efectos de los fármacos , Aminoácidos/química , Aminoácidos/farmacología , Staphylococcus aureus/efectos de los fármacos , Antibacterianos/química , Antibacterianos/farmacología , Antibacterianos/síntesis química , Líquidos Iónicos/química , Líquidos Iónicos/farmacología , Pruebas de Sensibilidad Microbiana , Antifúngicos/farmacología , Antifúngicos/química , Antifúngicos/síntesis química , Antiinfecciosos/química , Antiinfecciosos/farmacología , Antiinfecciosos/síntesis químicaRESUMEN
RNA abundance is a powerful indicator of the state of individual cells. Single-cell RNA sequencing can reveal RNA abundance with high quantitative accuracy, sensitivity and throughput1. However, this approach captures only a static snapshot at a point in time, posing a challenge for the analysis of time-resolved phenomena such as embryogenesis or tissue regeneration. Here we show that RNA velocity-the time derivative of the gene expression state-can be directly estimated by distinguishing between unspliced and spliced mRNAs in common single-cell RNA sequencing protocols. RNA velocity is a high-dimensional vector that predicts the future state of individual cells on a timescale of hours. We validate its accuracy in the neural crest lineage, demonstrate its use on multiple published datasets and technical platforms, reveal the branching lineage tree of the developing mouse hippocampus, and examine the kinetics of transcription in human embryonic brain. We expect RNA velocity to greatly aid the analysis of developmental lineages and cellular dynamics, particularly in humans.
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Encéfalo/citología , Cresta Neural/metabolismo , Neuronas/citología , Empalme del ARN/genética , ARN/análisis , ARN/genética , Análisis de Secuencia de ARN , Análisis de la Célula Individual , Animales , Encéfalo/embriología , Encéfalo/metabolismo , Linaje de la Célula/genética , Células Cromafines/citología , Células Cromafines/metabolismo , Conjuntos de Datos como Asunto , Femenino , Ácido Glutámico/metabolismo , Hipocampo/citología , Hipocampo/embriología , Hipocampo/metabolismo , Cinética , Masculino , Ratones , Cresta Neural/citología , Neuronas/metabolismo , Reproducibilidad de los Resultados , Factores de Tiempo , Transcripción Genética/genéticaRESUMEN
Afforestation is beneficial to improving soil carbon pools. However, due to the lack of deep databases, the variations in soil carbon and the combined effects of multiple factors after afforestation have yet to be adequately explored in >1 m deep soils, especially in areas with deep-rooted plants and thick vadose zones. This study examined the multivariate controls of soil organic carbon (SOC) and inorganic carbon (SIC) in 0-18 m deep under farmland, grassland, willow, and poplar in loess deposits. The novelty of this study is that the factors concurrently affecting deep soil carbon were investigated by multiwavelet coherence and structural equation models. On average, the SOC density (53.1 ± 5.0 kg m-2) was only 12% of SIC density (425.4 ± 13.8 kg m-2), with depth-dependent variations under different land use types. In the soil profiles, the variations in SOC were more obvious in the 0-6 m layer, while SIC variations were mainly observed in the 6-12 m layer. Compared with farmland (SOC: 17.0 kg m-2; SIC: 122.9 kg m-2), the plantation of deciduous poplar (SOC: 28.5 kg m-2; SIC: 144.2 kg m-2) increased the SOC and SIC density within the 0-6 m layer (p < 0.05), but grassland and evergreen willow impacted SOC and SIC density insignificantly. The wavelet coherence analysis showed that, at the large scale (>4 m), SOC and SIC intensities were affected by total nitrogen-magnetic susceptibility and magnetic susceptibility-water content, respectively. The structural equation model further identified that SOC density was directly controlled by total nitrogen (path coefficient = 0.64) and indirectly affected by magnetic susceptibility (path coefficient = 0.36). Further, SOC stimulated the SIC deposition by improving water conservation and electrical conductivity. This study provides new insights into afforestation-induced deep carbon cycles, which have crucial implications for forest management and enhancing ecosystem sustainability in arid regions.
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Carbono , Suelo , Suelo/química , Carbono/análisisRESUMEN
Parkinson's disease (PD) is an α-synucleinopathy characterized by the progressive loss of specific neuronal populations. Here, we develop a novel approach to transvascularly deliver proteins of complex quaternary structures, including α-synuclein preformed fibrils (pff). We show that a single systemic administration of α-synuclein pff triggers pathological transformation of endogenous α-synuclein in non-transgenic rats, which leads to neurodegeneration in discrete brain regions. Specifically, pff-exposed animals displayed a progressive deterioration in gastrointestinal and olfactory functions, which corresponded with the presence of cellular pathology in the central and enteric nervous systems. The α-synuclein pathology generated was both time dependent and region specific. Interestingly, the most significant neuropathological changes were observed in those brain regions affected in the early stages of PD. Our data therefore demonstrate for the first time that a single, transvascular administration of α-synuclein pff can lead to selective regional neuropathology resembling the premotor stage of idiopathic PD. Furthermore, this novel delivery approach could also be used to deliver a range of other pathogenic, as well as therapeutic, protein cargos transvascularly to the brain.
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Sistema Nervioso Entérico , Enfermedad de Parkinson , Animales , Encéfalo/metabolismo , Sistema Nervioso Entérico/metabolismo , Humanos , Neuronas/metabolismo , alfa-Sinucleína/metabolismoRESUMEN
Two strains designated as c1T and c7T, were isolated from the landfill leachate of a domestic waste treatment plant in Huizhou City, Guangdong Province, PR China. The cells of both strains were aerobic, rod-shaped, non-motile and formed yellow colonies on Reasoner's 2A agar plates. Strain c1T grew at 10-42 °C (optimum, 30 °C), pH 4.5-10.5 (optimum, pH 7.0) and 0-2.0â% (w/v) NaCl (optimum, 0-0.5â%). Strain c7T grew at 10-42 °C (optimum, 30 °C), pH 4.5-10.5 (optimum, pH 6.0) and 0-2.0â% (w/v) NaCl (optimum, 0-0.5â%). Phylogenetic analyses revealed that strains c1T and c7T belong to the genus Novosphingobium. The 16S rRNA gene sequence similarities of strains c1T and c7T to the type strains of Novosphingobium species were 94.5-98.2â% and 94.3-99.1â%, respectively. The calculated pairwise average nucleotide identity values among strains c1T, c7T and the reference strains were in the range of 75.2-85.9â% and the calculated pairwise average amino acid identity values among strains c1T, c7T and reference strains were in the range of 72.0-88.3â%. Their major respiratory quinone was Q-10, and the major cellular fatty acids were C18â:â1 ω7c, C18â:â0, C16â:â1 ω7c, C16â:â0 and C14â:â0 2OH. The major polar lipids of strains c1T and c7T were phosphatidylethanolamine, diphosphatidylglycerol, phosphatidylglycerol, sphingoglycolipid, unidentified lipids and unidentified phospholipid. Based on phenotypic, chemotaxonomic, phylogenetic and genomic results from this study, strains c1T and c7T should represent two independent novel species of Novosphingobium, for which the names Novosphingobium percolationis sp. nov. (type strain c1T=GDMCC 1.2555T=KCTC 82826T) and Novosphingobium huizhouense sp. nov. (type strain c7T=GDMCC 1.2556T=KCTC 82827T) are proposed. The gene function annotation results of strains c1T and c7T suggest that they could play an important role in the degradation of organic pollutants.
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Filogenia , Sphingomonadaceae , Contaminantes Químicos del Agua , Técnicas de Tipificación Bacteriana , Composición de Base , China , ADN Bacteriano/genética , Ácidos Grasos/química , Fosfolípidos/química , ARN Ribosómico 16S/genética , Análisis de Secuencia de ADN , Sphingomonadaceae/clasificación , Sphingomonadaceae/aislamiento & purificación , Ubiquinona/análogos & derivados , Ubiquinona/químicaRESUMEN
BACKGROUND: Gestational diabetes mellitus (GDM) is defined as impaired glucose tolerance in pregnancy and without a history of diabetes mellitus. While there are limited metabolomic studies involving advanced maternal age in China, we aim to investigate the metabolomic profiling of plasma and urine in pregnancies complicated with GDM aged at 35-40 years at early and late gestation. METHODS: Twenty normal and 20 GDM pregnant participants (≥ 35 years old) were enlisted from the Complex Lipids in Mothers and Babies (CLIMB) study. Maternal plasma and urine collected at the first and third trimester were detected using gas chromatography-mass spectrometry (GC-MS). RESULTS: One hundred sixty-five metabolites and 192 metabolites were found in plasma and urine respectively. Urine metabolomic profiles were incapable to distinguish GDM from controls, in comparison, there were 14 and 39 significantly different plasma metabolites between the two groups in first and third trimester respectively. Especially, by integrating seven metabolites including cysteine, malonic acid, alanine, 11,14-eicosadienoic acid, stearic acid, arachidic acid, and 2-methyloctadecanoic acid using multivariant receiver operating characteristic models, we were capable of discriminating GDM from normal pregnancies with an area under curve of 0.928 at first trimester. CONCLUSION: This study explores metabolomic profiles between GDM and normal pregnancies at the age of 35-40 years longitudinally. Several compounds have the potential to be biomarkers to predict GDM with advanced maternal age. Moreover, the discordant metabolome profiles between the two groups could be useful to understand the etiology of GDM with advanced maternal age.
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Diabetes Gestacional/sangre , Diabetes Gestacional/metabolismo , Diabetes Gestacional/orina , Edad Materna , Metaboloma , Adulto , Estudios de Casos y Controles , China/epidemiología , Femenino , Humanos , Metabolómica/métodos , Plasma/metabolismo , Embarazo , Primer Trimestre del Embarazo/metabolismo , Tercer Trimestre del Embarazo/metabolismo , Estudios Prospectivos , Curva ROCRESUMEN
In vitro models of corticogenesis from pluripotent stem cells (PSCs) have greatly improved our understanding of human brain development and disease. Among these, 3D cortical organoid systems are able to recapitulate some aspects of in vivo cytoarchitecture of the developing cortex. Here, we tested three cortical organoid protocols for brain regional identity, cell type specificity and neuronal maturation. Overall, all protocols gave rise to organoids that displayed a time-dependent expression of neuronal maturation genes such as those involved in the establishment of synapses and neuronal function. Comparatively, guided differentiation methods without WNT activation generated the highest degree of cortical regional identity, whereas default conditions produced the broadest range of cell types such as neurons, astrocytes and hematopoietic-lineage-derived microglia cells. These results suggest that cortical organoid models produce diverse outcomes of brain regional identity and cell type specificity and emphasize the importance of selecting the correct model for the right application.
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Organoides , Células Madre Pluripotentes , Humanos , Células Madre Pluripotentes/metabolismo , Diferenciación Celular , Neuronas/metabolismo , EncéfaloRESUMEN
How to fabricate bone tissue engineering scaffolds with excellent antibacterial and bone regeneration ability has attracted increasing attention. Herein, we produced a hierarchical porous ß-tricalcium phosphate (ß-TCP)/poly(lactic-co-glycolic acid)-polycaprolactone composite bone tissue engineering scaffold containing tetracycline hydrochloride (TCH) through a micro-extrusion-based cryogenic 3D printing of Pickering emulsion inks, in which the hydrophobic silica (h-SiO2) nanoparticles were used as emulsifiers to stabilize composite Pickering emulsion inks. Hierarchically porous scaffolds with desirable antibacterial properties and bone-forming ability were obtained. Grid scaffolds with a macroscopic pore size of 250.03 ± 75.88 µm and a large number of secondary micropores with a diameter of 24.70 ± 15.56 µm can be fabricated through cryogenic 3D printing, followed by freeze-drying treatment, whereas the grid structure of scaffolds printed or dried at room temperature was discontinuous, and fewer micropores could be observed on the strut surface. Moreover, the impartment of ß-TCP in scaffolds changed the shape and density of the micropores but endowed the scaffold with better osteoconductivity. Scaffolds loaded with TCH had excellent antibacterial properties and could effectively promote the adhesion, expansion, proliferation, and osteogenic differentiation of rat bone marrow-derived mesenchymal stem cells afterward. The scaffolds loaded with TCH could realize the strategy to "kill bacteria first, then induce osteogenesis". Such hierarchically porous scaffolds with abundant micropores, excellent antibacterial property, and improved bone-forming ability display great prospects in treating bone defects with infection.
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Osteogénesis , Ingeniería de Tejidos , Animales , Antibacterianos/farmacología , Regeneración Ósea , Emulsiones/farmacología , Porosidad , Impresión Tridimensional , Ratas , Dióxido de Silicio/farmacología , Andamios del Tejido/químicaRESUMEN
Estimating the recreational value of a coastal wetland park is useful in understanding wetland ecosystem and nurturing a balanced relationship between wetland tourism exploration and natural conservation. This study aims to apply appropriate methodologies to accurately estimate the recreational value of a coastal wetland park. The Nansha Wetland in China was used as the study site, and its recreational value was divided into non-use value (estimated using the choice experiment method (CEM)) and use value (estimated using travel cost interval analysis (TCIA)). The data were collected via questionnaires consisting of different choice experiment scenarios and travel cost investigations. The results showed that the per capita and total non-use values were 116.97 CNY/17.80 USD and 24.56 million CNY/3.74 million USD, respectively, and the per capita and total use values were 313.95 CNY/47.79 USD and 65.93 million CNY/10.04 million USD. Therefore, the per capita and total recreational values were 430.92 CNY/65.59 USD and 90.49 million CNY/13.77 million USD. CEM was used to identify tourists' trade-offs and preferences among the selected wetland attributes. As a result, tourists were found to have the largest marginal willingness to pay (MWTP) for "mangrove coverage," followed by "species of rare birds" and "water visibility." TCIA was used to solve the under-dispersion problem of the number of trips. Based on these findings, several managerial implications were identified, including adjusting ticket price based on the non-use value, regulating tourists' behaviors, enhancing the protection of mangroves, improving the water quality and the living habitats of migrant birds, and promoting science education and popularization.
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Ecosistema , Humedales , Conservación de los Recursos Naturales , Costos y Análisis de Costo , Parques Recreativos , ViajeRESUMEN
TGIF1 is a transcriptional repressor playing crucial roles in human development and function and is associated with holoprosencephaly and various cancers. TGIF1-directed transcriptional repression of specific genes depends on the recruitment of corepressor SIN3A. However, to date, the exact region of TGIF1 binding to SIN3A was not clear, and the structural basis for the binding was unknown. Here, we demonstrate that TGIF1 utilizes a C-terminal domain (termed as SIN3A-interacting domain, SID) to bind with SIN3A PAH2. The TGIF1 SID adopts a disordered structure at the apo state but forms an amphipathic helix binding into the hydrophobic cleft of SIN3A PAH2 through the nonpolar side at the holo state. Residues F379, L382 and V383 of TGIF1 buried in the hydrophobic core of the complex are critical for the binding. Moreover, homodimerization of TGIF1 through the SID and key residues of F379, L382 and V383 was evidenced, which suggests a dual role of TGIF1 SID and a correlation between dimerization and SIN3A-PAH2 binding. This study provides a structural insight into the binding of TGIF1 with SIN3A, improves the knowledge of the structure-function relationship of TGIF1 and its homologs and will help in recognizing an undiscovered SIN3A-PAH2 binder and developing a peptide inhibitor for cancer treatment.
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Proteínas de Homeodominio/química , Proteínas de Homeodominio/metabolismo , Proteínas Represoras/química , Proteínas Represoras/metabolismo , Complejo Correpresor Histona Desacetilasa y Sin3/química , Complejo Correpresor Histona Desacetilasa y Sin3/metabolismo , Sitios de Unión , Dicroismo Circular , Células HeLa , Proteínas de Homeodominio/genética , Humanos , Modelos Moleculares , Mutación , Unión Proteica , Dominios Proteicos , Estructura Secundaria de Proteína , Proteínas Represoras/genética , Dispersión del Ángulo Pequeño , Complejo Correpresor Histona Desacetilasa y Sin3/genéticaRESUMEN
Clostridium perfringens autolysin (CpAcp) is a peptidoglycan hydrolase associated with cell separation, division, and growth. It consists of a signal peptide, ten SH3b domains, and a catalytic domain. The structure and function mechanisms of the ten SH3bs related to cell wall peptidoglycan binding remain unclear. Here, the structures of CpAcp SH3bs were studied through NMR spectroscopy and structural simulation. The NMR structure of SH3b6 was determined at first, which adopts a typical ß-barrel fold and has three potential ligand-binding pockets. The largest pocket containing eight conserved residues was suggested to bind with peptide ligand in a novel model. The structures of the other nine SH3bs were subsequently predicted to have a fold similar to SH3b6. Their ligand pockets are largely similar to those of SH3b6, although with varied size and morphology, except that SH3b1/2 display a third pocket markedly different from those in other SH3bs. Thus, it was supposed that SH3b3-10 possess similar ligand-binding ability, while SH3b1/2 have a different specificity and additional binding site for ligand. As an entirety, ten SH3bs confer a capacity for alternatively binding to various peptidoglycan sites in the cell wall. This study presents an initial insight into the structure and potential function of CpAcp SH3bs.
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Clostridium perfringens/enzimología , N-Acetil Muramoil-L-Alanina Amidasa/química , Secuencia de Aminoácidos , Dominio Catalítico , Escherichia coli , Ligandos , Espectroscopía de Resonancia Magnética , Simulación del Acoplamiento Molecular , Conformación Proteica , Relación Estructura-ActividadRESUMEN
Excess inorganic nitrogen in water poses a severe threat to enviroment. Removal of inorganic nitrogen by heterotrophic nitrifying-aerobic denitrifying microorganism is supposed to be a promising and applicable technology only if the removal rate can be maintained sufficiently high in real wastewater under various conditions, such as high concentration of salt and wide range of different nitrogen concentrations. Here, a new heterotrophic nitrifying-aerobic denitrifying bacterium was isolated and named as Pseudomonas mendocina TJPU04, which removes NH4+-N, NO3--N and NO2--N with average rate of 4.69, 5.60, 4.99 mg/L/h, respectively. It also maintains high nitrogen removal efficiency over a wide range of nitrogen concentrations. When concentration of NH4+-N, NO3--N and NO2--N was up to 150, 150 and 50 mg/L, 98%, 93%, and 100% removal efficiency could be obtained, respectively, after 30-h incubation under sterile condition. When it was applied under non-sterile condition, the ammonia removal efficiency was slightly lower than that under sterile condition. However, the nitrate and nitrite removal efficiencies under non-sterile condition were significantly higher than those under sterile condition. Strain TJPU04 also showed efficient nitrogen removal performance in the presence of high concentration of salt and nitrogen. In addition, the removal efficiencies of NH4+-N, NO3--N and TN in real wastewater were 91%, 52%, and 75%, respectively. These results suggest that strain TJPU04 is a promising candidate for efficient removal of inorganic nitrogen in wastewater treatment.
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Desnitrificación/fisiología , Nitrificación/fisiología , Pseudomonas mendocina/metabolismo , Amoníaco/metabolismo , Biodegradación Ambiental , Nitratos/metabolismo , Nitrógeno/metabolismoRESUMEN
INTRODUCTION: Intrahepatic cholestasis of pregnancy (ICP) is a common maternal liver disease; development can result in devastating consequences, including sudden fetal death and stillbirth. Currently, recognition of ICP only occurs following onset of clinical symptoms. OBJECTIVE: Investigate the maternal hair metabolome for predictive biomarkers of ICP. METHODS: The maternal hair metabolome (gestational age of sampling between 17 and 41 weeks) of 38 Chinese women with ICP and 46 pregnant controls was analysed using gas chromatography-mass spectrometry. RESULTS: Of 105 metabolites detected in hair, none were significantly associated with ICP. CONCLUSION: Hair samples represent accumulative environmental exposure over time. Samples collected at the onset of ICP did not reveal any metabolic shifts, suggesting rapid development of the disease.
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Biomarcadores/análisis , Colestasis Intrahepática/diagnóstico , Cromatografía de Gases y Espectrometría de Masas/métodos , Cabello/química , Metaboloma , Complicaciones del Embarazo/diagnóstico , Adulto , Estudios de Casos y Controles , Colestasis Intrahepática/metabolismo , Femenino , Edad Gestacional , Humanos , Embarazo , Complicaciones del Embarazo/metabolismoRESUMEN
A fast-growing fungus with remarkable ability to degrade several azo dyes under non-sterile conditions was isolated and identified. This fungus was identified as Trichoderma tomentosum. Textile effluent of ten-fold dilution could be decolorized by 94.9% within 72h before optimization. Acid Red 3R model wastewater with a concentration of 85.5mgL-1 could be decolorized by 99.2% within the same time after optimization. High-level of manganese peroxidase and low-level of lignin peroxidase activities were detected during the process of decolorization from the culture supernatant, indicating the possible involvement of two enzymes in azo dye decolorization. No aromatic amine products were detected from the degradation products of Acid Red 3R by gas chromatography-mass spectrometry (GC/MS) analysis, indicating the possible involvement of a special symmetrical oxidative degradation pathway. Phytotoxicity assay confirmed the lower toxicity toward the test plant seeds of the degradation products when compared to the original dye.
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Compuestos Azo/análisis , Colorantes/análisis , Trichoderma/metabolismo , Aguas Residuales/química , Contaminantes Químicos del Agua/análisis , Biodegradación Ambiental , Cromatografía de Gases y Espectrometría de Masas , Peroxidasas/metabolismo , Industria Textil , Trichoderma/enzimologíaRESUMEN
Two experiments were conducted to examine bidirectional semantic associations between power and weight using a priming paradigm. Bidirectionality in the relationship between power and weight was demonstrated, utilising tasks that were identical except that the orders in which the stimuli were presented were reversed. In Experiment 1, an empty scale leaning either leftward or rightward was used as a priming stimulus, and a scale that appeared in equilibrium with a pair of power words was used as a target stimulus. In Experiment 2, a scale with a pair of words that appeared in equilibrium was used as a priming stimulus, and an empty scale leaning either leftward or rightward was used as a target stimulus. We identified interaction effects between power and weight in both experiments. Associations between power and weight provide evidence for both conceptual metaphor views and evolutionary theory. The bidirectionality of metaphorical effects is in line with the strong version of metaphoric structuring. Both language and experiential correlations play important roles in the development of the mapping between power and weight.