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SUMMARY: Single-neuron morphology, the study of the structure, form, and shape of a group of specialized cells in the nervous system, is of vital importance to define the type of neurons, assess changes in neuronal development and aging and determine the effects of brain disorders and treatments. Despite the recent surge in the amount of available neuron morphology reconstructions due to advancements in microscopy imaging, existing computational and deep learning methods for modeling neuron morphology have been limited in both scale and accuracy. In this paper, we propose MorphRep, a model for learning meaningful representation of neuron morphology pre-trained with over 250 000 existing neuron morphology data. By encoding the neuron morphology into graph-structured data, using graph transformers for feature encoding and enforcing the consistency between multiple augmented views of neuron morphology, MorphRep achieves the state of the art performance on widely used benchmarking datasets. Meanwhile, MorphRep can accurately characterize the neuron morphology space across neuron morphometrics, fine-grained cell types, brain regions and ages. Furthermore, MorphRep can be applied to distinguish neurons under a wide range of conditions, including genetic perturbation, drug injection, environment change and disease. In summary, MorphRep provides an effective strategy to embed and represent neuron morphology and can be a valuable tool in integrating cell morphology into single-cell multiomics analysis. AVAILABILITY AND IMPLEMENTATION: The codebase has been deposited in https://github.com/YaxuanLi-cn/MorphRep.
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Neuronas , Neuronas/citología , Animales , Humanos , Aprendizaje Profundo , Procesamiento de Imagen Asistido por Computador/métodos , Encéfalo/citologíaRESUMEN
Elimination of autoreactive developing B cells is an important mechanism to prevent autoantibody production. However, how B cell receptor (BCR) signaling triggers apoptosis of immature B cells remains poorly understood. We show that BCR stimulation up-regulates the expression of the lysosomal-associated transmembrane protein 5 (LAPTM5), which in turn triggers apoptosis of immature B cells through two pathways. LAPTM5 causes BCR internalization, resulting in decreased phosphorylation of SYK and ERK. In addition, LAPTM5 targets the E3 ubiquitin ligase WWP2 for lysosomal degradation, resulting in the accumulation of its substrate PTEN. Elevated PTEN levels suppress AKT phosphorylation, leading to increased FOXO1 expression and up-regulation of the cell cycle inhibitor p27Kip1 and the proapoptotic molecule BIM. In vivo, LAPTM5 is involved in the elimination of autoreactive B cells and its deficiency exacerbates autoantibody production. Our results reveal a previously unidentified mechanism that contributes to immature B cell apoptosis and B cell tolerance.
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Apoptosis , Tolerancia Inmunológica , Proteínas de la Membrana , Células Precursoras de Linfocitos B , Inhibidor p27 de las Quinasas Dependientes de la Ciclina/metabolismo , Proteína Forkhead Box O1/metabolismo , Humanos , Lisosomas/metabolismo , Proteínas de la Membrana/genética , Fosfohidrolasa PTEN/metabolismo , Células Precursoras de Linfocitos B/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ubiquitina-Proteína Ligasas/metabolismoRESUMEN
BACKGROUND: The formation and domestication of ornamental traits are influenced by various aspects, such as the recognition of esthetic values and cultural traditions. Camellia japonica is widely appreciated and domesticated around the world mainly due to its rich variations in ornamental traits. Ornamental camellias have a diverse range of resources, including different bud variations from Camellia spp. as well as inter- and intra- specific hybridization. Despite research on the formation of ornamental traits, a basic understanding of their genetics and genomics is still lacking. RESULTS: Here, we report the chromosomal-level reference genome of C. japonica through combining multiple DNA-sequencing technologies and obtain a high-density genetic linkage map of 4255 markers by sequencing 98 interspecific F1 hybrids between C. japonica and C. chekiangoleosa. We identify two whole-genome duplication events in C. japonica: one is a shared ancient γ event, and the other is revealed to be specific to genus Camellia. Based on the micro-collinearity analysis, we find large-scale segmental duplication of chromosome 8, resulting to two copies of the AGAMOUS loci, which may play a key role in the domestication of floral shapes. To explore the regulatory mechanisms of seasonal flowering, we have analyzed year-round gene expression patterns of C. japonica and C. azalea-a sister plant of continuous flowering that has been widely used for cross breeding. Through comparative analyses of gene co-expression networks and annual gene expression patterns, we show that annual expression rhythms of some important regulators of seasonal growth and development, including GIGANTEA and CONSTANS of the photoperiod pathway, have been disrupted in C. azalea. Furthermore, we reveal that the distinctive expression patterns of FLOWERING LOCUS T can be correlated with the seasonal activities of flowering and flushing. We demonstrate that the regulatory module involved in GIGANTEA, CONSTANS, and FLOWERING LOCUS T is central to achieve seasonality. CONCLUSIONS: Through the genomic and comparative genomics characterizations of ornamental Camellia spp., we propose that duplication of chromosomal segments as well as the establishment of gene expression patterns has played a key role in the formation of ornamental traits (e.g., flower shape, flowering time). This work provides a valuable genomic platform for understanding the molecular basis of ornamental traits.
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Camellia , Estaciones del Año , Camellia/genética , Fitomejoramiento , Genómica , Flores/genética , Expresión Génica , Regulación de la Expresión Génica de las PlantasRESUMEN
Iron sulfides with high theoretical capacity confront the challenges of low rate capability and severe capacity fading for sodium storage, which are mainly caused by poor electron/ion transport kinetics and drastic volume fluctuations during cycling. Herein, to mitigate these obstacles, a multi-step synthetic tactic involving solvothermal, carbonization, and subsequent sulfurization is put forward for the construction of wire-like structure by confining Fe7S8 particles in porous N-doped carbon framework (denoted as Fe7S8/PNC) using zinc iron nitrilotriacetate as template. By partially substituting Fe3+ with Zn2+ in the metal coordination complex, the porous structure of coordination complex derived carbon framework can be regulated through pore structure engineering of Zn nanodroplets. The desired porous and robust core/shell structure can not only afford favorable electron/Na+ transport paths and additional active sites for Na+ storage, but also provide reinforced structural integrity of interior Fe7S8 particles by retarding the pulverization and buffering the mechanical stress against volume fluctuations. As anode for sodium-ion batteries, the optimal Fe7S8/PNC delivers a high reversible capacity (743 mAh g-1 at 0.1 A g-1), superior rate capability (553 mAh g-1 at 10 A g-1), and long-term cycling stability (602 mAh g-1 at 5 A g-1 with 98.5% retention after 1000 cycles).
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INTRODUCTION: Quisqualis indica L. (QIL) has a long history as a traditional Chinese herb in China, but the study of volatile components in QIL from different geographical sources has been relatively rare. OBJECTIVES: To establish an optimal headspace gas chromatography-mass spectrometry (HS-GC-MS) method to comprehensively analyse the volatile component profile and screen quality markers of QIL from different origins. METHODS: Response surface methodology (RSM) was used to optimise the conditions for headspace analysis. The volatile components of QIL from four main origins of southwest China were analysed and identified by HS-GC-MS. The similarity of all samples of QIL was evaluated by fingerprint. The differences of the volatile components in QIL from different origins were distinguished by chemometrics. RESULTS: According to the optimal conditions of RSM, a total of 31 volatile components were identified, including fatty acids, aldehydes, alcohols, alkyl pyrazines, and other volatile components. Similarity evaluation presented that there were 26 common volatile components with different contents in all samples. Principal component analysis (PCA) showed that QIL from four different origins could be roughly divided into four categories. Hierarchical cluster analysis (HCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) indicated that QIL from different origins had obvious regional characteristics. CONCLUSION: The optimised HS-GC-MS method provided a strategy to rapidly, effectively, and accurately elucidate the volatile component profile of QIL from different origins, and seven important differential components were screened for quality evaluation and origin traceability.
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Quimiometría , Compuestos Orgánicos Volátiles , Cromatografía de Gases y Espectrometría de Masas/métodos , Análisis por Conglomerados , Aldehídos/análisis , Alcoholes/análisis , Compuestos Orgánicos Volátiles/análisisRESUMEN
In the present study, five experiments (N = 233) were designed to explore whether sourness as a sensory experience could implicitly impact social emotions of envy and jealousy in Chinese culture. Experiment 1 (n = 63) explored the implicit conceptual association between sourness words (vs. bitterness words) and envy/jealousy words. Experiment 2 (n = 70) and 3 (n = 20) examined the priming effects of imagined and tasted sourness (vs. bitterness and sweetness) on self-rated emotional intensity in envy- and jealousy-arousing situations, respectively. Experiment 4 (n = 40) and 5 (n = 40) further testified the priming effects of imagined and tasted sourness (vs. bitterness and sweetness) on self-rated emotional intensity in four types of social situations (i.e., envy, jealousy, sad and happy events), respectively. In the results, sourness was found as the only taste that not only conceptually associated with envy/jealousy, but also significantly primed envy/jealousy feelings. The possible mechanism underlying the association of sourness-envy/jealousy was discussed.
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Pueblos del Este de Asia , Celos , Humanos , Emociones , Gusto , FelicidadRESUMEN
Yogurt and its related products are popular worldwide. During transportation and storage, Lactobacillus delbrueckii ssp. bulgaricus in yogurt continues to metabolize to form lactic acid, the postacidification phenomenon of yogurt. Postacidification of yogurt is a widespread phenomenon in the dairy industry. Many scholars have done research on controlling the postacidification process, but few report on the molecular mechanisms involved. In this study, we used a molecular-assisted approach to screen food additives that can inhibit postacidification and analyzed its effects on yogurt quality as well as its regulatory mechanism from multi-omics perspectives in combination. The copper ion was found to upregulate the expression of the LDB_RS05285 gene, and the copper transporter-related genes were regulated by copper. Based on the metabolic-level analysis, copper was found to promote lactose hydrolysis, accumulate a large amount of glucose and galactose, inhibit the conversion of glucose to lactic acid, and reduce the production of lactic acid. The significantly greater abundance of l-isoleucine and l-phenylalanine increased the abundance of 3-methylbutyraldehyde (â¼1.2 times) and benzaldehyde (â¼7.9 times) to different degrees, which contributed to the formation of the overall flavor of yogurt. Copper not only stabilizes the acidity of yogurt, but also it improves the flavor of yogurt. Through this established method involving quantitative and correlation analyses at the transcriptional and metabolic levels, this study provides guidance for the research and development of food additives that inhibit postacidification of yogurt and provide a reference for studying the changes of metabolites during storage of yogurt.
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Cobre , Lactobacillus delbrueckii , Animales , Fermentación , Cobre/metabolismo , Yogur/análisis , Lactobacillus delbrueckii/metabolismo , Glucosa/metabolismo , Operón , Ácido Láctico/metabolismo , Streptococcus thermophilus/metabolismoRESUMEN
Mobile and wearable devices have enabled numerous applications, including activity tracking, wellness monitoring, and human-computer interaction, that measure and improve our daily lives. Many of these applications are made possible by leveraging the rich collection of low-power sensors found in many mobile and wearable devices to perform human activity recognition (HAR). Recently, deep learning has greatly pushed the boundaries of HAR on mobile and wearable devices. This paper systematically categorizes and summarizes existing work that introduces deep learning methods for wearables-based HAR and provides a comprehensive analysis of the current advancements, developing trends, and major challenges. We also present cutting-edge frontiers and future directions for deep learning-based HAR.
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Aprendizaje Profundo , Dispositivos Electrónicos Vestibles , Actividades Humanas , HumanosRESUMEN
Drought and salinity have become major environmental problems that affect the production of agriculture, forestry and horticulture. The identification of stress-tolerant genes from plants adaptive to harsh environments might be a feasible strategy for plant genetic improvement to address the challenges brought by global climate changes. In this study, a dehydration-upregulated gene MfWRKY7 of resurrection Plant Myrothamnusflabellifolia, encoding a group IId WRKY transcription factor, was cloned and characterized. The overexpression of MfWRKY7 in Arabidopsis increased root length and tolerance to drought and NaCl at both seedling and adult stages. Further investigation indicated that MfWRKY7 transgenic plants had higher contents of chlorophyll, proline, soluble protein, and soluble sugar but a lower water loss rate and malondialdehyde content compared with wild-type plants under both drought and salinity stresses. Moreover, the higher activities of antioxidant enzymes and lower accumulation of O2- and H2O2 in MfWRKY7 transgenic plants were also found, indicating enhanced antioxidation capacity by MfWRKY7. These findings showed that MfWRKY7 may function in positive regulation of responses to drought and salinity stresses, and therefore, it has potential application value in genetic improvement of plant tolerance to abiotic stress.
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Arabidopsis , Craterostigma , Arabidopsis/metabolismo , Craterostigma/genética , Sequías , Regulación de la Expresión Génica de las Plantas , Peróxido de Hidrógeno/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Modificadas Genéticamente/genética , Plantas Modificadas Genéticamente/metabolismo , Cloruro de Sodio/metabolismo , Estrés Fisiológico/genéticaRESUMEN
Unsubstituted pyridin-2-amine has a high quantum yield and is a potential scaffold for a fluorescent probe. However, the facile access to conjugated highly substituted aminopyridines and the study of their fluorescent properties is scarce. In this paper, synthesis and fluorescent properties of multisubstituted aminopyridines were studied based on a recently developed Rh-catalyzed coupling of vinyl azide with isonitrile to form a vinyl carbodiimide intermediate, following tandem cyclization with an alkyne. An aminopyridine substituted with an azide group as a potential probe was further designed, synthesized, and evaluated. The "clicking-and-probing" experiment of it on BSA protein showed the potential of aminopyridine as a scaffold of a biological probe.
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BACKGROUND: Auxins play key roles in the phytohormone network. Early auxin response genes in the AUX/IAA, SAUR, and GH3 families show functional redundancy, which makes it very difficult to study the functions of individual genes based on gene knockout analysis or transgenic technology. As an alternative, chemical genetics provides a powerful approach that can be used to address questions relating to plant hormones. RESULTS: By screening a small-molecule chemical library of compounds that can induce abnormal seedling and vein development, we identified and characterized a piperazine compound 1-[(4-bromophenoxy) acetyl]-4-[(4-fluorophenyl) sulfonyl] piperazine (ASP). The Arabidopsis DR5::GFP line was used to assess if the effects mentioned were correlated with the auxin response, and we accordingly verified that ASP altered the auxin-related pathway. Subsequently, we examined the regulatory roles of ASP in hypocotyl and root development, auxin distribution, and changes in gene expression. Following ASP treatment, we detected hypocotyl elongation concomitant with enhanced cell elongation. Furthermore, seedlings showed retarded primary root growth, reduced gravitropism and increased root hair development. These phenotypes were associated with an increased induction of DR5::GUS expression in the root/stem transition zone and root tips. Auxin-related mutants including tir1-1, aux1-7 and axr2-1 showed phenotypes with different root-development pattern from that of the wild type (Col-0), and were insensitive to ASP. Confocal images of propidium iodide (PI)-stained root tip cells showed no detectable damage by ASP. Furthermore, RT-qPCR analyses of two other genes, namely, Ethylene Response Factor (ERF115) and Mediator 18 (MED18), which are related to cell regeneration and damage, indicated that the ASP inhibitory effect on root growth was not attributable to toxicity. RT-qPCR analysis provided further evidence that ASP induced the expression of early auxin-response-related genes. CONCLUSIONS: ASP altered the auxin response pathway and regulated Arabidopsis growth and development. These results provide a basis for dissecting specific molecular components involved in auxin-regulated developmental processes and offer new opportunities to discover novel molecular players involved in the auxin response.
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Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/genética , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Regulación de la Expresión Génica de las Plantas , Ácidos Indolacéticos/farmacología , Complejo Mediador , Mutación , Piperazina , Raíces de Plantas/genética , Raíces de Plantas/metabolismoRESUMEN
KEY MESSAGE: The specific and high-level expression of 1Ax1 is determined by different promoter regions. HMW-GS synthesis occurs in aleurone layer cells. Heterologous proteins can be stored in protein bodies. High-molecular-weight glutenin subunit (HMW-GS) is highly expressed in the endosperm of wheat and relative species, where their expression level and allelic variation affect the bread-making quality and nutrient quality of flour. However, the mechanism regulating HMW-GS expression remains elusive. In this study, we analyzed the distribution of cis-acting elements in the 2659-bp promoter region of the HMW-GS gene 1Ax1, which can be divided into five element-enriched regions. Fragments derived from progressive 5' deletions were used to drive GUS gene expression in transgenic wheat, which was confirmed in aleurone layer cells, inner starchy endosperm cells, starchy endosperm transfer cells, and aleurone transfer cells by histochemical staining. The promoter region ranging from - 297 to - 1 was responsible for tissue-specific expression, while fragments from - 1724 to - 618 and from - 618 to - 297 were responsible for high-level expression. Under the control of the 1Ax1 promoter, heterologous protein could be stored in the form of protein bodies in inner starchy endosperm cells, even without a special location signal. Our findings not only deepen our understanding of glutenin expression regulation, trafficking, and accumulation but also provide a strategy for the utilization of wheat endosperm as a bioreactor for the production of nutrients and metabolic products.
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Evolución Biológica , Regulación de la Expresión Génica de las Plantas , Glútenes/biosíntesis , Glútenes/genética , Regiones Promotoras Genéticas/genética , Triticum/genética , Pan , Endospermo/metabolismo , Harina , Genes de Plantas/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Modificadas Genéticamente/genética , Subunidades de Proteína/biosíntesis , Subunidades de Proteína/genética , Almidón/metabolismoRESUMEN
OBJECTIVE: To study the association of fatty acid composition in human milk with breast milk jaundice (BMJ) in neonates. METHODS: A total of 30 full-term neonates who were admitted to the neonatal intensive care unit from October 2016 to October 2017 and were diagnosed with late-onset BMJ were enrolled as the BMJ group. Thirty healthy neonates without jaundice or pathological jaundice who were admitted to the confinement center during the same period of time were enrolled as the control group. Related clinical data were collected, including sex, mode of birth, feeding pattern, gestational age, birth weight, gravida, parity, and peak level of total serum bilirubin. Breast milk was collected from the mothers, and the MIRIS human milk analyzer was used to measure macronutrients (fat, protein, and carbohydrate) and calorie. Gas chromatography was used to analyze the content of different fatty acids in breast milk. RESULTS: The control group had higher levels of macronutrients in human milk than the BMJ group, with significant differences in fat, dry matter, and calorie (P < 0.05). In addition, 25 fatty acids were detected in breast milk, including 9 saturated fatty acids, 6 monounsaturated fatty acids, and 10 polyunsaturated fatty acids. The comparison of the percentage composition of different fatty acids showed that compared with the control group, the BMJ group had significantly lower percentage compositions of C15:0, C16:0, C17:0, C18:0, C20:0, C18:1n9t, C20:1n9, C18:3n6, C22:2, and C22:6n3 (DHA) and higher percentage compositions of C10:0, C12:0, C14:0 in breast milk (P < 0.05). CONCLUSIONS: Some macronutrients and fatty acid composition in human milk may be associated with the pathogenesis of BMJ in neonates.
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Ácidos Grasos/análisis , Ictericia Neonatal/etiología , Leche Humana/química , Estudios de Casos y Controles , Femenino , Humanos , Recién Nacido , Nutrientes/análisis , EmbarazoRESUMEN
BACKGROUND: High-molecular-weight glutenin subunits (HMW-GSs) have important effects on bread-making quality. Allelic variations of HMW-GS in bread wheat varieties contribute in different ways to dough properties and bread volume. However, no systematic analysis has been done on the effects of allelic variation on bread-crumb structure, an important parameter when evaluating bread-making quality. In this study, seven Glu-1 deletion lines and one intact line harboring different encoding loci and derived from a cross between two spring wheat cultivars were used to investigate the contribution of a single Glu-1 locus, or combination of Glu-1 loci, to the crumb structure. RESULTS: Deletion of HMW-GS locus combinations resulted in a decline in slice size, brightness, and fineness of the bread crumb. A desirable crumb structure correlated well with preferred subunit combinations: high levels of GMPs, superior dough properties, and loaf volume. The effects of the HMW-GS combinations were ranked as Dx5 + Dy10 > Bx17 + By18 > Ax1 + Null. The Ax1 + Null allele affected the crumb structure by interacting with the Bx17 + By18 or Dx5 + Dy10. CONCLUSION: High-molecular-weight glutenin subunits had significant effects on the loaf volume and crumb structure; varying effects from different subunit combinations were observed. © 2018 Society of Chemical Industry.
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Pan/análisis , Glútenes/química , Triticum/química , Alelos , Peso Molecular , Control de Calidad , Triticum/genéticaRESUMEN
Organic matter (OM) is an important component of sediment. Bioturbation/bioirrigation can remobilize OM and heavy metals that were previously buried in the sediment. The remobilization of buried organic matter, thallium (Tl), cadmium (Cd), copper (Cu) and zinc (Zn) from sediment was studied in a laboratory experiment with three organisms: tubificid, chironomid larvae and loach. Results showed that bioturbation/bioirrigation promoted the release of dissolved organic matter (DOM) and dissolved Tl, Cd, Cu and Zn, but only dissolved Zn concentrations decreased with exposure time in overlying water. The presence of organisms altered the compositions of DOM released from sediment, considerably increasing the percentage of fulvic acid-like materials (FA) and humic acid-like materials (HA). In addition, bioturbation/bioirrigation accelerated the growth and reproduction of bacteria to enhance the proportion of soluble microbial byproduct-like materials (SMP). The DOM was divided into five regions in the three-dimensional excitation emission matrix (3D-EEM), and each part had different correlation with the dissolved heavy metal concentrations. Dissolved Cu had the best correlation with each of the DOM compositions, indicating that Cu in the sediment was in the organic-bound form. Furthermore, the organism type and heavy metal characteristics both played a role in influencing the remobilization of heavy metal.
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Monitoreo del Ambiente , Sedimentos Geológicos/química , Sustancias Húmicas/análisis , Metales Pesados/análisis , Contaminantes Químicos del Agua/análisisRESUMEN
BACKGROUND: Multidrug and toxic compound extrusion (MATE) transporter proteins are present in all organisms. Although the functions of some MATE gene family members have been studied in plants, few studies have investigated the gene expansion patterns, functional divergence, or the effects of positive selection. RESULTS: Forty-five MATE genes from rice and 56 from Arabidopsis were identified and grouped into four subfamilies. MATE family genes have similar exon-intron structures in rice and Arabidopsis; MATE gene structures are conserved in each subfamily but differ among subfamilies. In both species, the MATE gene family has expanded mainly through tandem and segmental duplications. A transcriptome atlas showed considerable differences in expression among the genes, in terms of transcript abundance and expression patterns under normal growth conditions, indicating wide functional divergence in this family. In both rice and Arabidopsis, the MATE genes showed consistent functional divergence trends, with highly significant Type-I divergence in each subfamily, while Type-II divergence mainly occurred in subfamily III. The Type-II coefficients between rice subfamilies I/III, II/III, and IV/III were all significantly greater than zero, while only the Type-II coefficient between Arabidopsis IV/III subfamilies was significantly greater than zero. A site-specific model analysis indicated that MATE genes have relatively conserved evolutionary trends. A branch-site model suggested that the extent of positive selection on each subfamily of rice and Arabidopsis was different: subfamily II of Arabidopsis showed higher positive selection than other subfamilies, whereas in rice, positive selection was highest in subfamily III. In addition, the analyses identified 18 rice sites and 7 Arabidopsis sites that were responsible for positive selection and for Type-I and Type-II functional divergence; there were no common sites between rice and Arabidopsis. Five coevolving amino acid sites were identified in rice and three in Arabidopsis; these sites might have important roles in maintaining local structural stability and protein functional domains. CONCLUSIONS: We demonstrate that the MATE gene family expanded through tandem and segmental duplication in both rice and Arabidopsis. Overall, the results of our analyses contribute to improved understanding of the molecular evolution and functions of the MATE gene family in plants.
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STUDY QUESTION: Does autologous transplantation of menstrual blood-derived stromal cells (menSCs) regenerate endometrium to support pregnancy in patients with severe Asherman's syndrome (AS)? SUMMARY ANSWER: Autologous menSCs transplantation significantly increases endometrial thickness (ET) for women with severe AS. WHAT IS KNOWN ALREADY: AS is a major cause of secondary infertility in women. Cell transplantation has been tried in a few clinical cases with encouraging results. STUDY DESIGN, SIZE, DURATION: In this experimental, non-controlled and prospective 3-year clinical study involving seven patients with AS, autologous menSCs were isolated and cultured from menstrual blood of each patient within ~2 weeks and then transplanted back into their uterus. Endometrial growth and pregnancy were assessed after cell therapy. PARTICIPANTS/MATERIALS, SETTING, METHOD: Infertile women, aged 20-40 years, diagnosed with severe AS (Grade III-V) by hysteroscopy and with menstrual fluid were recruited at the Shengjing Hospital affiliated to China Medical University. Autologous menSCs transplantation was conducted followed by HRT. Endometrial thickness was monitored with frozen embryo transfer (FET) as needed. MAIN RESULTS AND THE ROLE OF CHANCE: We successfully cultured menSCs from seven patients and transferred the autologous cells back to their uterus. Our results showed that the ET was significantly (P = 0.0002) increased to 7 mm in five women, which ensured embryo implantation. Four patients underwent FET and two of them conceived successfully. One patient had spontaneous pregnancy after second menSCs transplantation. LIMITATIONS, REASONS FOR CAUTION: Limited sample size, lack of rigorous controls or knowledge of underlying mechanism. WIDER IMPLICATIONS OF THE FINDINGS: Autologous menSCs transplantation is a potential option for treating women with severe AS. STUDY FUNDING/COMPETING INTERESTS: This study was supported by Liaoning Provincial Science and Technology Program. The sponsor and authors declare no conflicts of interest. TRIAL REGISTRATION NUMBER: Registered in the Chinese Clinical Trial Registry (ChiCTR-ONB-15007464).
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Endometrio/citología , Ginatresia/terapia , Infertilidad Femenina/terapia , Menstruación/sangre , Células del Estroma/trasplante , Adulto , Endometrio/diagnóstico por imagen , Femenino , Humanos , Infertilidad Femenina/diagnóstico por imagen , Estudios Prospectivos , Trasplante Autólogo , Resultado del Tratamiento , UltrasonografíaRESUMEN
BACKGROUND: The caleosin genes encode proteins with a single conserved EF hand calcium-binding domain and comprise small gene families found in a wide range of plant species. These proteins may be involved in many cellular and biological processes coupled closely to the synthesis, degradation, or stability of oil bodies. Although previous studies of this protein family have been reported for Arabidopsis and other species, understanding of the evolution of the caleosin gene family in plants remains inadequate. RESULTS: In this study, comparative genomic analysis was performed to investigate the phylogenetic relationships, evolutionary history, functional divergence, positive selection, and coevolution of caleosins. First, 84 caleosin genes were identified from five main lineages that included 15 species. Phylogenetic analysis placed these caleosins into five distinct subfamilies (sub I-V), including two subfamilies that have not been previously identified. Among these subfamilies, sub II coincided with the distinct P-caleosin isoform recently identified in the pollen oil bodies of lily; caleosin genes from the same lineage tended to be clustered together in the phylogenetic tree. A special motif was determined to be related with the classification of caleosins, which may have resulted from a deletion in sub I and sub III occurring after the evolutionary divergence of monocot and dicot species. Additionally, several segmentally and tandem-duplicated gene pairs were identified from seven species, and further analysis revealed that caleosins of different species did not share a common expansion model. The ages of each pair of duplications were calculated, and most were consistent with the time of genome-wide duplication events in each species. Functional divergence analysis showed that changes in functional constraints have occurred between subfamilies I/IV, II/IV, and II/V, and some critical amino acid sites were identified during the functional divergence. Additional analyses revealed that caleosins were under positive selection during evolution, and seven candidate amino acid sites (70R, 74G, 88 L, 89G, 100 K, 106A, 107S) for positive selection were identified. Interestingly, the critical amino acid residues of functional divergence and positive selection were mainly located in C-terminal domain. Finally, three groups of coevolved amino acid sites were identified. Among these coevolved sites, seven from group 2 were located in the Ca2+-binding region of crucial importance. CONCLUSION: In this study, the evolutionary and expansion patterns of the caleosin gene family were predicted, and a series of amino acid sites relevant to their functional divergence, adaptive evolution, and coevolution were identified. These findings provide data to facilitate further functional analysis of caleosin gene families in the plant lineage.
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Proteínas de Unión al Calcio/genética , Evolución Molecular , Proteínas de Plantas/genética , Plantas/genética , Secuencia de Aminoácidos , Arabidopsis/química , Arabidopsis/genética , Proteínas de Unión al Calcio/química , Genes Duplicados , Filogenia , Células Vegetales/química , Proteínas de Plantas/química , Alineación de SecuenciaRESUMEN
BACKGROUND: GRAS proteins belong to a plant transcription factor family that is involved with multifarious roles in plants. Although previous studies of this protein family have been reported for Arabidopsis, rice, Chinese cabbage and other species, investigation of expansion patterns and evolutionary rate on the basis of comparative genomics in different species remains inadequate. RESULTS: A total of 289 GRAS genes were identified in Arabidopsis, B. distachyon, rice, soybean, S. moellendorffii, and P. patens and were grouped into seven subfamilies, supported by the similarity of their exon-intron patterns and structural motifs. All of tandem duplicated genes were found in group II except one cluster of rice, indicating that tandem duplication greatly promoted the expansion of group II. Furthermore, segment duplications were mainly found in the soybean genome, whereas no single expansion pattern dominated in other plant species indicating that GRAS genes from these five species might be subject to a more complex evolutionary mechanism. Interestingly, branch-site model analyses of positive selection showed that a number of sites were positively selected under foreground branches I and V. These results strongly indicated that these groups were experiencing higher positive selection pressure. Meanwhile, the site-specific model revealed that the GRAS genes were under strong positive selection in P. patens. DIVERGE v2.0 was used to detect critical amino acid sites, and the results showed that the shifted evolutionary rate was mainly attributed to the functional divergence between the GRAS genes in the two groups. In addition, the results also demonstrated the expression divergence of the GRAS duplicated genes in the evolution. In short, the results above provide a solid foundation for further functional dissection of the GRAS gene superfamily. CONCLUSIONS: In this work, differential expression, evolutionary rate, and expansion patterns of the GRAS gene family in the six species were predicted. Especially, tandem duplication events played an important role in expansion of group II. Together, these results contribute to further functional analysis and the molecular evolution of the GRAS gene superfamily.