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1.
BMC Plant Biol ; 24(1): 946, 2024 Oct 11.
Artículo en Inglés | MEDLINE | ID: mdl-39390400

RESUMEN

BACKGROUND: Heterosis is a common phenomenon in plants and has been extensively applied in crop breeding. However, the superior traits in the hybrids can only be maintained in the first generation but segregate in the following generations. Maintaining heterosis in generations has been challenging but highly desirable in crop breeding. Recent study showed that maternally produced diploid seeds could be achieved in rice by knocking out three meiosis related genes, namely REC8, PAIR1, OSD1 to create MiMe in combination with egg cell specific expression of BBM transcription factor, a technology called clonal seeds. Interestingly, there has been very limited reports indicating the feasibility of this approach in other crops. RESULTS: In this study, we aimed to test whether clonal seeds could be created in cotton. We identified the homologs of the three meiosis related genes in cotton and used the multiplex CRISPR/Cas9 gene editing system to simultaneously knock out these three genes in both A and D sub-genomes. More than 50 transgenic cotton plants were generated, and fragment analysis indicated that multiple gene knockouts occurred in the transgenic plants. However, all the transgenic plants were sterile apparently due to the lack of pollen. Pollination of the flowers of the transgenic plants using the wild type pollens could not generate seeds, an indication of defects in the formation of female sexual cells in the transgenic plants. In addition, we generated transgenic cotton plants expressing the cotton BBM gene driven by the Arabidopsis egg cell specific promoter pDD45. Two transgenic plants were obtained, and both showed severely reduced fertility. CONCLUSIONS: Overall, our results indicate that knockout of the clonal seeds related genes in cotton causes sterility and how to manipulate genes to create clonal seeds in cotton requires further research.


Asunto(s)
Gossypium , Infertilidad Vegetal , Plantas Modificadas Genéticamente , Semillas , Gossypium/genética , Gossypium/fisiología , Semillas/genética , Plantas Modificadas Genéticamente/genética , Infertilidad Vegetal/genética , Genes de Plantas , Sistemas CRISPR-Cas , Edición Génica/métodos , Fitomejoramiento , Meiosis/genética
2.
Cancer Control ; 30: 10732748221148913, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36599103

RESUMEN

BACKGROUND: The neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), systemic immune-inflammatory index (SII), systemic inflammation response index (SIRI), and Onodera's prognostic nutritional index (OPNI) have been reported as prognostic markers for various cancers. We evaluated the prognostic value of the NLR, PLR, MLR, SII, SIRI, and OPNI for poorly-to moderately-differentiated cervical squamous cell carcinoma (CSCC). PATIENTS AND METHODS: We retrospectively analyzed the cases of 109 patients with early-stage poorly-to moderately-differentiated CSCC who underwent radical surgery at our institution in 2014-2017. The optimal cutoff points for the NLR, PLR, MLR, SII, SIRI, and OPNI were determined by receiver operating characteristic curves. Overall survival was analyzed by the Kaplan-Meier method. We performed a multivariate analysis using the Cox proportional hazard regression model to determine the independent prognostic indicators for early-stage poorly-to moderately-differentiated CSCC. RESULTS: The appropriate cutoff points were: NLR, 1.72; PLR, 111.96; MLR, .24; SII, 566.23; SIRI, 1.38; and OPNI, 52.68. The OS of the patients with a high OPNI (P = .04), low SII (P = .03), or low SIRI (P = .01) was significantly better. The uni- and multivariate analyses identified only the OPNI as an independent prognostic marker for early-stage poorly-to moderately-differentiated CSCC (P = .04 and P = .02). CONCLUSION: The OPNI is an independent prognostic marker for early-stage poorly-to moderately-differentiated CSCC; the NLR, PLR, MLR, SII, and SIRI are not.


Asunto(s)
Carcinoma de Células Escamosas , Inflamación , Humanos , Pronóstico , Estudios Retrospectivos , Carcinoma de Células Escamosas/cirugía , Carcinoma de Células Escamosas/patología , Linfocitos/patología
3.
BMC Plant Biol ; 22(1): 610, 2022 Dec 24.
Artículo en Inglés | MEDLINE | ID: mdl-36564751

RESUMEN

Lysine-ε-acetylation (Kac) is a reversible post-translational modification that plays important roles during plant-pathogen interactions. Some pathogens can deliver secreted effectors encoding acetyltransferases or deacetylases into host cell to directly modify acetylation of host proteins. However, the function of these acetylated host proteins in plant-pathogen defense remains to be determined. Employing high-resolution tandem mass spectrometry, we analyzed protein abundance and lysine acetylation changes in maize infected with Puccinia polysora (P. polysora) at 0 h, 12 h, 24 h, 48 h and 72 h. A total of 7412 Kac sites from 4697 proteins were identified, and 1732 Kac sites from 1006 proteins were quantified. Analyzed the features of lysine acetylation, we found that Kac is ubiquitous in cellular compartments and preferentially targets lysine residues in the -F/W/Y-X-X-K (ac)-N/S/T/P/Y/G- motif of the protein, this Kac motif contained proteins enriched in basic metabolism and defense-associated pathways during fungal infection. Further analysis of acetylproteomics data indicated that maize regulates cellular processes in response to P. polysora infection by altering Kac levels of histones and non-histones. In addition, acetylation of pathogen defense-related proteins presented converse patterns in signaling transduction, defense response, cell wall fortification, ROS scavenging, redox reaction and proteostasis. Our results provide informative resources for studying protein acetylation in plant-pathogen interactions, not only greatly extending the understanding on the roles of acetylation in vivo, but also providing a comprehensive dynamic pattern of Kac modifications in the process of plant immune response.


Asunto(s)
Lisina , Zea mays , Lisina/metabolismo , Zea mays/metabolismo , Procesamiento Proteico-Postraduccional , Puccinia , Acetilación , Proteoma/metabolismo
4.
PLoS Genet ; 15(8): e1008377, 2019 08.
Artículo en Inglés | MEDLINE | ID: mdl-31465456

RESUMEN

Intercellular communication in adjacent cell layers determines cell fate and polarity, thus orchestrating tissue specification and differentiation. Here we use the maize stomatal apparatus as a model to investigate cell fate determination. Mutations in ZmBZU2 (bizui2, bzu2) confer a complete absence of subsidiary cells (SCs) and normal guard cells (GCs), leading to failure of formation of mature stomatal complexes. Nuclear polarization and actin accumulation at the interface between subsidiary mother cells (SMCs) and guard mother cells (GMCs), an essential pre-requisite for asymmetric cell division, did not occur in Zmbzu2 mutants. ZmBZU2 encodes a basic helix-loop-helix (bHLH) transcription factor, which is an ortholog of AtMUTE in Arabidopsis (BZU2/ZmMUTE). We found that a number of genes implicated in stomatal development are transcriptionally regulated by BZU2/ZmMUTE. In particular, BZU2/ZmMUTE directly binds to the promoters of PAN1 and PAN2, two early regulators of protodermal cell fate and SMC polarization, consistent with the low levels of transcription of these genes observed in bzu2-1 mutants. BZU2/ZmMUTE has the cell-to-cell mobility characteristic similar to that of BdMUTE in Brachypodium distachyon. Unexpectedly, BZU2/ZmMUTE is expressed in GMC from the asymmetric division stage to the GMC division stage, and especially in the SMC establishment stage. Taken together, these data imply that BZU2/ZmMUTE is required for early events in SMC polarization and differentiation as well as for the last symmetrical division of GMCs to produce the two GCs, and is a master determinant of the cell fate of its neighbors through cell-to-cell communication.


Asunto(s)
Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Regulación de la Expresión Génica de las Plantas , Proteínas de Plantas/metabolismo , Células Madre/fisiología , Zea mays/fisiología , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Comunicación Celular/genética , Diferenciación Celular/genética , División Celular/genética , Polaridad Celular/genética , Mutación , Proteínas de Plantas/genética , Estomas de Plantas/citología , Estomas de Plantas/fisiología , Plantas Modificadas Genéticamente , Regiones Promotoras Genéticas/genética
5.
J Integr Plant Biol ; 64(12): 2314-2326, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-35972795

RESUMEN

Plasticity in root system architecture (RSA) allows plants to adapt to changing nutritional status in the soil. Phosphorus availability is a major determinant of crop yield, and RSA remodeling is critical to increasing the efficiency of phosphorus acquisition. Although substantial progress has been made in understanding the signaling mechanism driving phosphate starvation responses in plants, whether and how epigenetic regulatory mechanisms contribute is poorly understood. Here, we report that the Switch defective/sucrose non-fermentable (SWI/SNF) ATPase BRAHMA (BRM) is involved in the local response to phosphate (Pi) starvation. The loss of BRM function induces iron (Fe) accumulation through increased LOW PHOSPHATE ROOT1 (LPR1) and LPR2 expression, reducing primary root length under Pi deficiency. We also demonstrate that BRM recruits the histone deacetylase (HDA) complex HDA6-HDC1 to facilitate histone H3 deacetylation at LPR loci, thereby negatively regulating local Pi deficiency responses. BRM is degraded under Pi deficiency conditions through the 26 S proteasome pathway, leading to increased histone H3 acetylation at the LPR loci. Collectively, our data suggest that the chromatin remodeler BRM, in concert with HDA6, negatively regulates Fe-dependent local Pi starvation responses by transcriptionally repressing the RSA-related genes LPR1 and LPR2 in Arabidopsis thaliana.


Asunto(s)
Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/metabolismo , Histonas/metabolismo , Cromatina/metabolismo , Fosfatos/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Fósforo/metabolismo , Regulación de la Expresión Génica de las Plantas , Histona Desacetilasas/metabolismo , Adenosina Trifosfatasas/genética , Adenosina Trifosfatasas/metabolismo
6.
New Phytol ; 226(3): 785-797, 2020 05.
Artículo en Inglés | MEDLINE | ID: mdl-31901205

RESUMEN

In Arabidopsis, the plasma membrane transporter PUT3 is important to maintain the cellular homeostasis of polyamines and plays a role in stabilizing mRNAs of some heat-inducible genes. The plasma membrane Na+ /H+ transporter SOS1 and the protein kinase SOS2 are two salt-tolerance determinants crucial for maintaining intracellular Na+ and K+ homeostasis. Here, we report that PUT3 genetically and physically interacts with SOS1 and SOS2, and these interactions modulate PUT3 transport activity. Overexpression of PUT3 (PUT3OE) results in hypersensitivity of the transgenic plants to polyamine and paraquat. The hypersensitivity of PUT3OE is inhibited by the sos1 and sos2 mutations, which indicates that SOS1 and SOS2 are required for PUT3 transport activity. A protein interaction assay revealed that PUT3 physically interacts with SOS1 and SOS2 in yeast and plant cells. SOS2 phosphorylates PUT3 both in vitro and in vivo. SOS1 and SOS2 synergistically activate the polyamine transport activity of PUT3, and PUT3 also modulates SOS1 activity by activating SOS2 in yeast cells. Overall, our findings suggest that both plasma-membrane proteins PUT3 and SOS1 could form a complex with the protein kinase SOS2 in response to stress conditions and modulate the transport activity of each other through protein interactions and phosphorylation.


Asunto(s)
Proteínas de Arabidopsis , Proteínas Serina-Treonina Quinasas , Intercambiadores de Sodio-Hidrógeno , Antiportadores , Arabidopsis , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Membrana Celular/metabolismo , Proteínas de Transporte de Membrana , Poliaminas , Proteínas Quinasas
7.
Psychol Sci ; 30(10): 1434-1448, 2019 10.
Artículo en Inglés | MEDLINE | ID: mdl-31503519

RESUMEN

Perception and action interact in nearly every moment of daily life. Previous studies have demonstrated not only that perceptual input shapes action but also that various factors associated with action-including individual abilities and biomechanical costs-influence perceptual decisions. However, it is unknown how action fluency affects the sensitivity of early-stage visual perception, such as orientation. To address this question, we used a dual-task paradigm: Participants prepared an action (e.g., grasping), while concurrently performing an orientation-change-detection task. We demonstrated that as actions became more fluent (e.g., as grasping errors decreased), perceptual-discrimination performance also improved. Importantly, we found that grasping training prior to discrimination enhanced subsequent perceptual sensitivity, supporting the notion of a reciprocal relation between perception and action.


Asunto(s)
Fuerza de la Mano , Orientación , Percepción Visual , Conducta , Fenómenos Biomecánicos , Femenino , Humanos , Masculino , Movimiento , Adulto Joven
8.
Biochem Biophys Res Commun ; 465(3): 414-420, 2015 Sep 25.
Artículo en Inglés | MEDLINE | ID: mdl-26260319

RESUMEN

Calbindin-D28k, a key regulator of calcium homeostasis plays a cytoprotective role in various tissues. We used serum free (SFM) and charcoal stripped serum (csFBS) culture media as models of cellular stress to modulate calbindin D28k expression and identify regulatory cis-elements and trans-acting factors in kidney and beta cells. The murine calbindin-D28k promoter activity was significantly upregulated under SFM or csFBS condition. Promoter analysis revealed evolutionary conserved regulatory cis-elements and deletion of 23 nt from +117/+139 as critical for basal transcription. Bioinformatics analysis of the promoter revealed conserved NFAT and TFII regulators elements. Forced expression of NFAT stimulated promoter activity. Inhibition of NFAT transcriptional activity by FK506 attenuated calbindin-D28k expression. TFII-I was shown to be necessary for basal promoter activity and to act cooperatively with NFAT. Using chromatin immunoprecipitation (ChIP) assays, NFAT was shown to bind to both proximal and distal promoter regions. ChIP assays also revealed recruitment of TFII to the -36/+139 region. Knockdown of TFII-I decreased promoter activity. In summary, calbindin-D28k expression during serum deprivation is partly regulated by NFAT and TF-II. This regulation may be important in vivo during ischemia and growth factor withdrawal to regulate cellular function and maintenance.


Asunto(s)
Calbindina 1/genética , Factores de Transcripción NFATC/genética , Elementos Reguladores de la Transcripción/genética , Factores de Transcripción TFII/genética , Animales , Secuencia de Bases , Sitios de Unión , Medio de Cultivo Libre de Suero , Perros , Células HEK293 , Células HeLa , Humanos , Células de Riñón Canino Madin Darby , Datos de Secuencia Molecular , Regiones Promotoras Genéticas , Unión Proteica
9.
Ethn Dis ; 25(2): 220-5, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26118152

RESUMEN

OBJECTIVE: To estimate behavior risk factors and diabetes preventive health care among Asian/Pacific Islanders (API) diagnosed with type 2 diabetes. DESIGN: Population-based telephone survey. PARTICIPANTS: APIs and non-Hispanic Whites (NHW) surveyed in the 2009 Behavioral Risk Factor Surveillance System (BRFSS) data. MAIN OUTCOME MEASURES: Diabetes preventive health care (taking insulin, taking educational classes, receiving flu shot and pneumococcal vaccine, blood sugar check, cholesterol check, HbA1C check, and eye and foot examination), behavior risk factors (fruit and vegetable consumption, physical exercise, smoking and binge drinking). RESULTS: By constructing the logistic regression model, odds ratios (OR) were calculated to compare the risk factors and preventive care between NHW and API groups. Compared with NHW, the APIs were significantly less likely to check their blood sugar at least once a day (OR = .59, 95% CI = .393-.886), got flu shots (OR = .597, 95% CI = .394-.903) and have had pneumococcal vaccines (OR = .455, 95% CI = .296-.7). The results also showed that APIs eat more fruits, are more likely to be physically active, and are less likely to participate in binge drinking and smoking. There are no differences between these two groups for diabetes education, having seen professionals for diabetes within past year, having cholesterol or HbA1C checked in past year, and having an eye or foot exam in past year. CONCLUSIONS: Our results can inform the best intervention strategies to deliver diabetes preventive health care services for the APIs with type 2 diabetes and to help NHWs reduce risk factors for diabetes.


Asunto(s)
Asiático/psicología , Diabetes Mellitus Tipo 2/prevención & control , Conductas Relacionadas con la Salud/etnología , Disparidades en Atención de Salud/etnología , Nativos de Hawái y Otras Islas del Pacífico/psicología , Población Blanca/psicología , Sistema de Vigilancia de Factor de Riesgo Conductual , Diabetes Mellitus Tipo 2/etnología , Diabetes Mellitus Tipo 2/psicología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Islas del Pacífico/etnología , Servicios Preventivos de Salud , Factores de Riesgo , Autocuidado
10.
Biotechnol J ; 19(6): e2400140, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38896410

RESUMEN

Artificial Intelligence (AI) technology is spearheading a new industrial revolution, which provides ample opportunities for the transformational development of traditional fermentation processes. During plasmid fermentation, traditional subjective process control leads to highly unstable plasmid yields. In this study, a multi-parameter correlation analysis was first performed to discover a dynamic metabolic balance among the oxygen uptake rate, temperature, and plasmid yield, whilst revealing the heating rate and timing as the most important optimization factor for balanced cell growth and plasmid production. Then, based on the acquired on-line parameters as well as outputs of kinetic models constructed for describing process dynamics of biomass concentration, plasmid yield, and substrate concentration, a machine learning (ML) model with Random Forest (RF) as the best machine learning algorithm was established to predict the optimal heating strategy. Finally, the highest plasmid yield and specific productivity of 1167.74 mg L-1 and 8.87 mg L-1/OD600 were achieved with the optimal heating strategy predicted by the RF model in the 50 L bioreactor, respectively, which was 71% and 21% higher than those obtained in the control cultures where a traditional one-step temperature upshift strategy was applied. In addition, this study transformed empirical fermentation process optimization into a more efficient and rational self-optimization method. The methodology employed in this study is equally applicable to predict the regulation of process dynamics for other products, thereby facilitating the potential for furthering the intelligent automation of fermentation processes.


Asunto(s)
Reactores Biológicos , Escherichia coli , Fermentación , Aprendizaje Automático , Plásmidos , Plásmidos/genética , Escherichia coli/genética , Escherichia coli/metabolismo , Escherichia coli/crecimiento & desarrollo , Reactores Biológicos/microbiología , Técnicas de Cultivo Celular por Lotes/métodos , Biomasa
11.
Sci Rep ; 13(1): 825, 2023 01 16.
Artículo en Inglés | MEDLINE | ID: mdl-36646722

RESUMEN

Humans exhibit remarkably complex cognitive abilities and adaptive behavior in daily life. Cognitive operation in the "mental workspace," such as mentally rotating a piece of luggage to fit into fixed trunk space, helps us maintain and manipulate information on a moment-to-moment basis. Skill acquisition in the "sensorimotor workspace," such as learning a new mapping between the magnitude of new vehicle movement and wheel turn, allows us to adjust our behavior to changing environmental or internal demands to maintain appropriate motor performance. While this cognitive and sensorimotor synergy is at the root of adaptive behavior in the real world, their interplay has been understudied due to a divide-and-conquer approach. We evaluated whether a separate domain-specific or common domain-general operation drives mental and sensorimotor rotational transformations. We observed that participants improved the efficiency of mental rotation speed after the visuomotor rotation training, and their learning rate for visuomotor adaptation also improved after their mental rotation training. Such bidirectional transfer between two widely different tasks highlights the remarkable reciprocal plasticity and demonstrates a common transformation mechanism between two intertwined workspaces. Our findings urge the necessity of an explicitly integrated approach to enhance our understanding of the dynamic interdependence between cognitive and sensorimotor mechanisms.


Asunto(s)
Aprendizaje , Desempeño Psicomotor , Humanos , Adaptación Psicológica , Movimiento , Adaptación Fisiológica
12.
Plants (Basel) ; 11(7)2022 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-35406939

RESUMEN

As a result of energy consumption and human activities, a large amount of carbon dioxide emissions has led to global warming, which seriously affects the growth and development of plants. Vegetables are an indispensable part of people's diet. In the plant kingdom, a variety of vegetables are highly sensitive to climate change. For them, an increase of just a few degrees above their optimum temperature threshold can result in a loss of yield and quality. Emerging strategies such as practice management and breeding varieties in response to above-optimal temperatures are critical for abiotic stress resistance of vegetable crops. In this study, the function and application of multiple strategies, including breeding improvement, epigenetic modification directed generation of alleles, gene editing techniques, and accumulation of mutations in multigenerational adaptation to abiotic stress, were discussed in vegetable crops. It is believed to be meaningful for plants to build plasticity under high temperature stress, thus generating more genetic structures for heat resistant traits in vegetable products.

13.
Stress Biol ; 2(1): 1, 2022 Jan 04.
Artículo en Inglés | MEDLINE | ID: mdl-37676343

RESUMEN

Lysine-ε-acetylation (Kac) is a post-translational modification (PTM) that is critical for metabolic regulation and cell signaling in mammals. However, its prevalence and importance in plants remain to be determined. Employing high-resolution tandem mass spectrometry, we analyzed protein lysine acetylation in five representative Arabidopsis organs with 2 ~ 3 biological replicates per organ. A total of 2887 Kac proteins and 5929 Kac sites were identified. This comprehensive catalog allows us to analyze proteome-wide features of lysine acetylation. We found that Kac proteins tend to be more uniformly expressed in different organs, and the acetylation status exhibits little correlation with the gene expression level, indicating that acetylation is unlikely caused by stochastic processes. Kac preferentially targets evolutionarily conserved proteins and lysine residues, but only a small percentage of Kac proteins are orthologous between rat and Arabidopsis. A large portion of Kac proteins overlap with proteins modified by other PTMs including ubiquitination, SUMOylation and phosphorylation. Although acetylation, ubiquitination and SUMOylation all modify lysine residues, our analyses show that they rarely target the same sites. In addition, we found that "reader" proteins for acetylation and phosphorylation, i.e., bromodomain-containing proteins and GRF (General Regulatory Factor)/14-3-3 proteins, are intensively modified by the two PTMs, suggesting that they are main crosstalk nodes between acetylation and phosphorylation signaling. Analyses of GRF6/14-3-3λ reveal that the Kac level of GRF6 is decreased under alkaline stress, suggesting that acetylation represses plant alkaline response. Indeed, K56ac of GRF6 inhibits its binding to and subsequent activation of the plasma membrane H+-ATPase AHA2, leading to hypersensitivity to alkaline stress. These results provide valuable resources for protein acetylation studies in plants and reveal that protein acetylation suppresses phosphorylation output by acetylating GRF/14-3-3 proteins.

14.
BMJ Evid Based Med ; 27(2): 109-119, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-33298465

RESUMEN

INTRODUCTION: High-quality randomised controlled trials (RCTs) provide the most reliable evidence on the comparative efficacy of new medicines. However, non-randomised studies (NRS) are increasingly recognised as a source of insights into the real-world performance of novel therapeutic products, particularly when traditional RCTs are impractical or lack generalisability. This means there is a growing need for synthesising evidence from RCTs and NRS in healthcare decision making, particularly given recent developments such as innovative study designs, digital technologies and linked databases across countries. Crucially, however, no formal framework exists to guide the integration of these data types. OBJECTIVES AND METHODS: To address this gap, we used a mixed methods approach (review of existing guidance, methodological papers, Delphi survey) to develop guidance for researchers and healthcare decision-makers on when and how to best combine evidence from NRS and RCTs to improve transparency and build confidence in the resulting summary effect estimates. RESULTS: Our framework comprises seven steps on guiding the integration and interpretation of evidence from NRS and RCTs and we offer recommendations on the most appropriate statistical approaches based on three main analytical scenarios in healthcare decision making (specifically, 'high-bar evidence' when RCTs are the preferred source of evidence, 'medium,' and 'low' when NRS is the main source of inference). CONCLUSION: Our framework augments existing guidance on assessing the quality of NRS and their compatibility with RCTs for evidence synthesis, while also highlighting potential challenges in implementing it. This manuscript received endorsement from the International Society for Pharmacoepidemiology.


Asunto(s)
Atención a la Salud , Proyectos de Investigación , Toma de Decisiones , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto
15.
J Biol Chem ; 285(8): 5836-47, 2010 Feb 19.
Artículo en Inglés | MEDLINE | ID: mdl-19955175

RESUMEN

The transcription factor FoxN1 is essential for differentiation of thymic epithelial cell (TEC) progenitors during thymic organogenesis. However, limited information is available on the postnatal contribution of FoxN1 to thymic maintenance. To address this question, we generated a loxP-floxed FoxN1 (fx) mouse with three different promoter-driven inducible CreER(T) transgenes. Postnatal ubiquitous deletion of FoxN1 caused dramatic thymic atrophy in 5 days and more severe deterioration in medullary TECs (mTECs) than in cortical TECs (cTECs). Induction of FoxN1 deletion selectively in K5 promoter-driven somatic epithelial cells (mostly mTECs and possibly some adult epithelial stem cells) was sufficient to cause significant thymic atrophy, whereas FoxN1 deletion in K18 promoter-driven somatic epithelial cells (mostly cTECs) was not. Thymic atrophy resulted from increased apoptosis and was associated with activation of the p53 gene in mature mTECs. Although FoxN1 is required for the development of both mTECs and cTECs in thymic organogenesis, it is most important for the maintenance of mTECs in the postnatal thymus, which are in turn necessary to prevent thymic atrophy.


Asunto(s)
Células Epiteliales/metabolismo , Factores de Transcripción Forkhead/metabolismo , Regiones Promotoras Genéticas , Células Madre/metabolismo , Timo/crecimiento & desarrollo , Proteína p53 Supresora de Tumor/biosíntesis , Animales , Apoptosis , Atrofia , Células Epiteliales/patología , Factores de Transcripción Forkhead/genética , Técnicas de Silenciamiento del Gen , Ratones , Ratones Transgénicos , Células Madre/patología , Timo/patología , Factores de Tiempo , Transgenes , Proteína p53 Supresora de Tumor/genética
16.
Medicine (Baltimore) ; 100(32): e26868, 2021 Aug 13.
Artículo en Inglés | MEDLINE | ID: mdl-34397900

RESUMEN

BACKGROUND: In recent years, related studies have revealed that tripartite motif-containing 59 (TRIM59) is related to the prognosis of lung cancer. However, these results have not been proved by any evidence. Therefore, this study evaluated the relationship between TRIM59 and the prognosis of lung cancer by carrying out meta-analysis. In addition, we explored the mechanism and related pathways of TRIM59 in lung cancer through bioinformatics analysis. METHODS: Comprehensive literature search was performed in China National Knowledge Infrastructure, Chinese Biomedical literature Database, Chinese Scientific and Journal Database, Wan Fang, Web of Science, PubMed, and EMBASE databases, and eligible studies were obtained based on the inclusion and exclusion criteria. The pooled hazard ratios and odds ratios were applied to assess the clinical value of TRIM59 expression for overall survival and clinicopathological features. Meanwhile, meta-analysis was conducted on the Stata 16.0. The mRNA expression level of TRIM59 in lung cancer was analyzed using Oncomine and Gene Expression Profiling Interactive Analysis (GEPIA) database. Gene Set Enrichment Analysis (GSEA) was used to predict the signaling pathways that TRIM59 might be involved in. The correlation between the expression level of TRIM59 in lung cancer and the abundance of immune cell invasion was analyzed by TIMER database. The survival analysis was verified by Kaplan-Meier Plotter database. RESULTS: The results of this meta-analysis would be submitted to peer-reviewed journals for publication. CONCLUSION: In this study, the application of meta-analysis and bioinformatics analysis will provide evidence support for the study on the prognosis and mechanism of TRIM59 in lung cancer.


Asunto(s)
Péptidos y Proteínas de Señalización Intracelular , Neoplasias Pulmonares , Proteínas de Motivos Tripartitos , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Biología Computacional , Perfilación de la Expresión Génica , Humanos , Péptidos y Proteínas de Señalización Intracelular/genética , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Metaanálisis como Asunto , Pronóstico , Proyectos de Investigación , Análisis de Supervivencia , Revisiones Sistemáticas como Asunto , Proteínas de Motivos Tripartitos/genética , Proteínas de Motivos Tripartitos/metabolismo
17.
Clin Transl Med ; 11(3): e313, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-33783990

RESUMEN

Lysine acetylation (Kac) as an important posttranslational modification of histones is essential for the regulation of gene expression in hepatocellular carcinoma (HCC). However, the atlas of whole acetylated proteins in HCC tissues and the difference in protein acetylation between normal human tissues and HCC tissues are unknown. In this report, we characterized the proteome and acetyl proteome (acetylome) profile of normal, paracancerous, and HCC liver tissues in human clinical samples by quantitative proteomics techniques. We identified 6781 acetylation sites of 2582 proteins and quantified 2492 acetylation sites of 1190 proteins in normal, paracancerous, and HCC liver tissues. Among them, 15 proteins were multiacetylated with more than 10 lysine residues. The histone acetyltransferases p300 and CBP were found to be hyperacetylated in hepatitis B virus pathway. Moreover, we found that 250 Kac sites of 214 proteins were upregulated and 662 Kac sites of 451 proteins were downregulated in HCC compared with normal liver tissues. Additionally, the acetylation levels of lysine 120 in histone H2B (H2BK120ac), lysine 18 in histone H3.3 (H3.3K18ac), and lysine 77 in histone H4 (H4K77ac) were increased in HCC. Interestingly, the higher levels of H2BK120ac, H3.3K18ac, and H4K77ac were significantly associated with worse prognosis, such as poorer survival and higher recurrence in an independent clinical cohort of HCC patients. Overall, this study lays a foundation for understanding the functions of acetylation in HCC and provides potential prognostic factors for the diagnosis and therapy of HCC.


Asunto(s)
Carcinoma Hepatocelular/etiología , Carcinoma Hepatocelular/metabolismo , Hepatitis B/complicaciones , Histonas/metabolismo , Neoplasias Hepáticas/etiología , Neoplasias Hepáticas/metabolismo , Proteómica/métodos , Acetilación , Humanos , Hígado/metabolismo , Pronóstico , Proteoma/metabolismo , Tasa de Supervivencia
18.
PLoS One ; 15(7): e0235980, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32678855

RESUMEN

This study establishes a model of prefabricated building project risk management system based on the Modified Teaching-Learning-Based-Optimization (MTLBO) algorithm and a prediction model of deep learning multilayer feedforward neural network (Backpropagation, BP neural network) to improve the requirements of risk management during the construction of large prefabricated building projects. First, we introduced the BP neural network algorithm based on deep learning. Second, the traditional Teaching-Learning-Based Optimization (TLBO) algorithm was modified by using information entropy, and the modified algorithm was simulated and tested in five test functions. Then, based on the BP neural network and MTLBO algorithm, we established the MTLBO-BP neural network prediction model and tested its performance. Finally, based on the MTLBO-BP neural network prediction model, MATLAB software was used to establish an intelligent model of the risk management system during the construction of prefabricated building projects, and the example verification was performed. In addition, the MTLBO algorithm was verified by test function simulation and established that global searchability is stronger than the TLBO algorithm. Of note, it is not easy to fall into a local optimum. The test results of the MTLBO-BP neural network prediction model revealed that the prediction model converges faster and exerts a better prediction effect. The example verification of the intelligent model of the risk management system during the construction of prefabricated building projects established in this study revealed that the algorithm proposed is more accurate in the reliability and cost prediction of the risk management of prefabricated building projects. Moreover, the algorithm proposed provides theoretical support for intelligent management and decision-making of prefabricated building projects. Overall, this study validates that this algorithm is essential for construction project management, decision-making, and quality assurance.


Asunto(s)
Toma de Decisiones , Aprendizaje Profundo , Gestión de Riesgos/métodos , Arquitectura y Construcción de Instituciones de Salud , Seguridad
19.
BMC Complement Med Ther ; 20(1): 330, 2020 Nov 05.
Artículo en Inglés | MEDLINE | ID: mdl-33153455

RESUMEN

BACKGROUND: We evaluated the long-term cost-effectiveness of antihypertensive traditional Chinese medicines (TCMs) and to compare the cost-effectiveness of a combined treatment consisting of compound Apocynum tablets and Nifedipine sustained-release tablets with the cost-effectiveness of treatment with Nifedipine sustained-release tablets alone. METHODS: A Markov model was used to simulate the potential incremental cost-effectiveness per quality-adjusted life year (QALY) to be gained from compound Apocynum tablets and Nifedipine sustained-release tablets compared with Nifedipine sustained-release tablets alone. Model parameter estimates were informed by previously published studies. The direct medical costs of outpatients with hypertension were estimated from the health care provider's perspective. A 5% annual discount rate was applied to both costs and QALYs. RESULTS: TCMs combined with Nifedipine sustained-release tablets group generated a total 20-year cost of 11,517.94 RMB (US $1739.87), whereas Nifedipine sustained-release tablets alone group resulted in a 20-year cost of 7253.71 RMB (US $1095.73). TCMs combined with Nifedipine sustained-release tablets group resulted in a generation of 12.69 QALYs, whereas Nifedipine sustained-release tablets alone group resulted in 12.50. The incremental cost-utility ratio was 22,443.32 RMB (US $3390.23) per QALY. Considering the threshold of 1 GDP per capita in China in 2018 (US $9764.95), the combination of compound Apocynum tablets and Nifedipine sustained-release tablets was a cost-effective strategy. One-way and probabilistic sensitivity analysis showed unchanged results over an acceptable range. CONCLUSIONS: Combining Traditional Chinese Medicines with chemical medicines is more cost-effective strategy in the treatment of hypertension.


Asunto(s)
Antihipertensivos/economía , Apocynum , Hipertensión/tratamiento farmacológico , Medicina Tradicional China/economía , Nifedipino/economía , Antihipertensivos/uso terapéutico , Análisis Costo-Beneficio , Preparaciones de Acción Retardada , Quimioterapia Combinada , Humanos , Medicina Tradicional China/métodos , Nifedipino/uso terapéutico , Años de Vida Ajustados por Calidad de Vida , Comprimidos
20.
Artículo en Inglés | MEDLINE | ID: mdl-31993107

RESUMEN

PURPOSE: Asian Americans had high rate of type 2 diabetes and less risk for diabetes complications compared to white. The purpose of this study was to examine diabetic retinopathy and related healthcare management among Asian American adults with diabetes. MATERIALS AND METHOD: Asian and white type 2 diabetes participants from 2005-2017 Behavioral Risk Factor Surveillance System (BRFSS) data were used to perform the analysis. SAS 9.4 survey procedures were used to conduct the statistical test. Health care management variables (self-blood sugar check, eye check and HbA1C check with doctors, health care professional visit) were analyzed and compared between Asian and white. RESULTS: During 2005-2017, diabetic retinopathy (DR) rate among Asian Americans was 10% higher than white, and Asian Americans was more than 100% more likely to develop DR compared to white. Asian Americans was less likely to check their blood sugar once a day (P<0.05 for all years except 2005 and 2007) and more likely to see the health care professional and perform eye and HbA1C check even the relationship was not statistically significant. After adjusting all the demo-social factors and health care management factors, Asian still had higher rate of DR compared to white. CONCLUSION: Asian Americans had higher rate of DR rate compared to white. Asian and white all had low rate of selfcare of blood sugar. Interventions for DR need to apply among Asian population.

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