Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 43
Filtrar
Más filtros

Banco de datos
Tipo del documento
Intervalo de año de publicación
1.
EMBO J ; 38(21): e102361, 2019 10 04.
Artículo en Inglés | MEDLINE | ID: mdl-31613024

RESUMEN

The E3 ubiquitin ligase RNF8 (RING finger protein 8) is a pivotal enzyme for DNA repair. However, RNF8 hyper-accumulation is tumour-promoting and positively correlates with genome instability, cancer cell invasion, metastasis and poor patient prognosis. Very little is known about the mechanisms regulating RNF8 homeostasis to preserve genome stability. Here, we identify the cellular machinery, composed of the p97/VCP ubiquitin-dependent unfoldase/segregase and the Ataxin 3 (ATX3) deubiquitinase, which together form a physical and functional complex with RNF8 to regulate its proteasome-dependent homeostasis under physiological conditions. Under genotoxic stress, when RNF8 is rapidly recruited to sites of DNA lesions, the p97-ATX3 machinery stimulates the extraction of RNF8 from chromatin to balance DNA repair pathway choice and promote cell survival after ionising radiation (IR). Inactivation of the p97-ATX3 complex affects the non-homologous end joining DNA repair pathway and hypersensitises human cancer cells to IR. We propose that the p97-ATX3 complex is the essential machinery for regulation of RNF8 homeostasis under both physiological and genotoxic conditions and that targeting ATX3 may be a promising strategy to radio-sensitise BRCA-deficient cancers.


Asunto(s)
Adenosina Trifosfatasas/metabolismo , Ataxina-3/metabolismo , Roturas del ADN de Doble Cadena , Reparación del ADN , Proteínas de Unión al ADN/metabolismo , Homeostasis , Proteínas Nucleares/metabolismo , Ubiquitina-Proteína Ligasas/metabolismo , Ubiquitina/metabolismo , Adenosina Trifosfatasas/genética , Ataxina-3/genética , Supervivencia Celular , Cromatina/genética , Proteínas de Unión al ADN/genética , Inestabilidad Genómica , Células HEK293 , Células HeLa , Humanos , Proteínas Nucleares/genética , Complejo de la Endopetidasa Proteasomal/metabolismo , Proteolisis , Transducción de Señal , Ubiquitina-Proteína Ligasas/genética , Ubiquitinación
2.
Gen Physiol Biophys ; 42(6): 521-529, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37994428

RESUMEN

Skeletal muscle atrophy severely impacts one's quality of life. The effects and mechanism of polydatin on skeletal muscle atrophy are unclear. This study investigated the effects and mechanism of polydatin on TNF-α-induced skeletal muscle cells. The skeletal muscle cell atrophy model was established by inducing C2C12 cells with TNF-α. Cell viability, IL-1ß levels and cell apoptosis were assessed. The mRNA and protein expression levels of apoptosis-related proteins were measured. Meanwhile, the binding of polydatin to AKT was analyzed by molecular docking. TNF-α reduced cell fusion and viability while up-regulated IL-1ß level and promoted cell apoptosis. TNF-α activated AKT, NF-κB, and p38 MAPK signaling pathways. Polydatin reversed these effects induced by TNF-α, with a low concentration being more effective. Polydatin was predicted to bind to GLY162, PHE161, GLU198, THR195 and GLU191 sites of AKT protein through van der Waals force and conventional hydrogen bonds. Overexpression of AKT led to increased phosphorylation levels of AKT, p38, and p65 proteins, as well as IL-1ß levels and cell apoptosis. Polydatin inhibited TNF-α-induced apoptosis of C2C12 cells by regulating NF-κB and p38 MAPK signaling pathways through AKT. This suggests that polydatin shows promise as a new drug for the treatment of skeletal muscle atrophy.


Asunto(s)
Apoptosis , Músculo Esquelético , FN-kappa B , Factor de Necrosis Tumoral alfa , Atrofia , Simulación del Acoplamiento Molecular , Músculo Esquelético/patología , FN-kappa B/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Factor de Necrosis Tumoral alfa/farmacología , Animales , Ratones
3.
Bull Math Biol ; 84(3): 32, 2022 01 24.
Artículo en Inglés | MEDLINE | ID: mdl-35067773

RESUMEN

The COVID-19 pandemic has had a considerable impact on global health and economics. The impact in African countries has not been investigated thoroughly via fitting epidemic models to the reported COVID-19 deaths. We downloaded the data for the 12 most-affected countries with the highest cumulative COVID-19 deaths to estimate the time-varying basic reproductive number ([Formula: see text]) and infection attack rate. We develop a simple epidemic model and fitted it to reported COVID-19 deaths in 12 African countries using iterated filtering and allowing a flexible transmission rate. We observe high heterogeneity in the case-fatality rate across the countries, which may be due to different reporting or testing efforts. South Africa, Tunisia, and Libya were most affected, exhibiting a relatively higher [Formula: see text] and infection attack rate. Thus, to effectively control the spread of COVID-19 epidemics in Africa, there is a need to consider other mitigation strategies (such as improvements in socioeconomic well-being, healthcare systems, the water supply, and awareness campaigns).


Asunto(s)
COVID-19 , Pandemias , Humanos , Conceptos Matemáticos , Modelos Biológicos , SARS-CoV-2 , Sudáfrica
4.
Sensors (Basel) ; 19(12)2019 Jun 22.
Artículo en Inglés | MEDLINE | ID: mdl-31234500

RESUMEN

. In recent years, the industrial use of the internet of things (IoT) has been constantly growing and is now widespread. Wireless sensor networks (WSNs) are a fundamental technology that has enabled such prevalent adoption of IoT in industry. WSNs can connect IoT sensors and monitor the working conditions of such sensors and of the overall environment, as well as detect unexpected system events in a timely and accurate manner. Monitoring large amounts of unstructured data generated by IoT devices and collected by the big-data analytics systems is a challenging task. Furthermore, detecting anomalies within the vast amount of data collected in real time by a centralized monitoring system is an even bigger challenge. In the context of the industrial use of the IoT, solutions for monitoring anomalies in distributed data flow need to be explored. In this paper, a low-power distributed data flow anomaly-monitoring model (LP-DDAM) is proposed to mitigate the communication overhead problem. As the data flow monitoring system is only interested in anomalies, which are rare, and the relationship among objects in terms of the size of their attribute values remains stable within any specific period of time, LP-DDAM integrates multiple objects as a complete set for processing, makes full use of the relationship among the objects, selects only one "representative" object for continuous monitoring, establishes certain constraints to ensure correctness, and reduces communication overheads by maintaining the overheads of constraints in exchange for a reduction in the number of monitored objects. Experiments on real data sets show that LP-DDAM can reduce communication overheads by approximately 70% when compared to an equivalent method that continuously monitors all objects under the same conditions.

5.
J Med Syst ; 43(2): 39, 2019 Jan 10.
Artículo en Inglés | MEDLINE | ID: mdl-30631957

RESUMEN

Aiming at the problem of low accuracy of classification learning algorithm caused by serious imbalance of sample set in medical diagnostic application, this paper proposes a distribution-sensitive oversampling algorithm for imbalanced data. The algorithm accurately divides the minority samples into noise samples, unstable samples, boundary samples and stable samples according to the location of the minority samples. Different samples are processed differently to select the most suitable sample for the synthesis of new samples. In the case of sample synthesis, a distribution-sensitive sample synthesis method is adopted. Different sample synthesis methods are selected according to their different distance from the surrounding minority samples, so as to ensure that the newly synthesized samples have the same characteristics with the original minority samples. The real medical diagnostic data test shows that this algorithm improves the accuracy rate of classification learning algorithm compared with the existing sampling algorithms, especially for the accuracy rate and recall rate of minority classes.


Asunto(s)
Algoritmos , Macrodatos , Interpretación Estadística de Datos , Diagnóstico , Toma de Decisiones Clínicas , Humanos , Aprendizaje Automático
6.
Appl Math Comput ; 359: 512-524, 2019 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-32287502

RESUMEN

Numerous efforts have been devoted to investigating the network activities and dynamics of isolated networks. Nevertheless, in practice, most complex networks might be interconnected with each other (due to the existence of common components) and exhibit layered properties while the connections on different layers represent various relationships. These types of networks are characterized as multiplex networks. A two-layered multiplex network model (usually composed of a virtual layer sustaining unaware-aware-unaware (UAU) dynamics and a physical one supporting susceptible-infected-recovered-dead (SIRD) process) is presented to investigate the spreading property of fatal epidemics in this manuscript. Due to the incorporation of the virtual layer, the recovered and dead individuals seem to play different roles in affecting the epidemic spreading process. In details, the corresponding nodes on the virtual layer for the recovered individuals are capable of transmitting information to other individuals, while the corresponding nodes for the dead individuals (which are to be eliminated) on the virtual layer should be removed as well. With the coupled UAU-SIRD model, the relationships between the focused variables and parameters of the epidemic are studied thoroughly. As indicated by the results, the range of affected individuals will be reduced by a large amount with the incorporation of virtual layers. Furthermore, the effects of recovery time on the epidemic spreading process are also investigated aiming to consider various physical conditions. Theoretical analyses are also derived for scenarios with and without required time periods for recovery which validates the reducing effects of incorporating virtual layers on the epidemic spreading process.

7.
Med Care ; 54(10): 907-12, 2016 10.
Artículo en Inglés | MEDLINE | ID: mdl-27367867

RESUMEN

BACKGROUND: Oral anticoagulation reduces the risk of stroke in atrial fibrillation but is often underused. OBJECTIVES: To identify factors associated with oral anticoagulant prescribing and adherence after stroke or transient ischemic attack (TIA). RESEARCH DESIGN: Retrospective cohort study using linked Ontario Stroke Registry and prescription claims data. SUBJECTS: Consecutive patients with atrial fibrillation and ischemic stroke/TIA admitted to 11 stroke centers in Ontario, Canada between 2003 and 2011. MEASURES: We used modified Poisson regression models to determine predictors of anticoagulant prescribing and multiple logistic regression to determine predictors of 1-year adherence. RESULTS: Of the 5781 patients in the study cohort, 4235 (73%) were prescribed oral anticoagulants at discharge. Older patients were less likely to receive anticoagulation [adjusted relative risk (aRR) for each additional year=0.997; 95% confidence interval (CI), 0.995-0.998], as were those with TIA compared with ischemic stroke (aRR=0.904; 95% CI, 0.865-0.945), prior gastrointestinal bleed (aRR=0.778; 95% CI, 0.693-0.873), dementia (aRR=0.912; 95% CI, 0.856-0.973), and those from a long-term care facility (aRR=0.810; 95% CI, 0.737-0.891). After limiting the sample to those without obvious contraindications to anticoagulation, age, dementia, and long-term care residence continued to be associated with lower prescription of oral anticoagulants. One-year adherence to therapy was similar across most patient groups. CONCLUSIONS: Age, dementia, and long-term care residence are predictors of lower oral anticoagulant use for secondary stroke prevention and represent key target areas for quality improvement initiatives.


Asunto(s)
Anticoagulantes/uso terapéutico , Accidente Cerebrovascular/prevención & control , Factores de Edad , Anciano , Anciano de 80 o más Años , Demencia/complicaciones , Femenino , Humanos , Modelos Logísticos , Masculino , Cumplimiento de la Medicación/estadística & datos numéricos , Casas de Salud/estadística & datos numéricos , Ontario/epidemiología , Distribución de Poisson , Pautas de la Práctica en Medicina/estadística & datos numéricos , Sistema de Registros , Estudios Retrospectivos , Accidente Cerebrovascular/complicaciones
8.
J Stroke Cerebrovasc Dis ; 24(2): 500-6, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-25542761

RESUMEN

BACKGROUND: Lower quality of care and poorer outcomes are suspected when new trainees (eg, residents) start in July in teaching hospitals, the so-called "the July effect." We evaluated outcomes and processes of care among patients with an acute ischemic stroke (AIS) admitted in July versus other 11 months of the year. METHODS: We evaluated AIS patients admitted to 11 tertiary stroke centers in Ontario, Canada between July 1, 2003, and March 31, 2008, identified from the Registry of the Canadian Stroke Network. The main outcomes were death at 30 days and poor functional outcome defined as death at 30 days or a modified Rankin Scale 3-5 at discharge. RESULTS: Of 10,319 eligible AIS patients, 882 (8.5%) were admitted in July and 9437 during the remaining months. There was no difference in baseline characteristics or stroke severity between the 2 groups. Patients admitted in July were less likely to receive thrombolysis (12% vs. 16%; odds ratio (OR), .72; 95% confidence interval (CI), .59-.89), dysphagia screening (64% vs. 68%; OR, .86; 95% CI, .74-.99), and stroke unit care (62% vs. 68%; OR, .78; 95% CI, .68-.90). July admission was not associated with either of higher death at 30 days (adjusted OR, .88; 95% CI, .74-1.03) or poor functional outcome (adjusted OR, .92; 95% CI, .74-1.14). Results remained consistent in the sensitivity analysis by including both July and August as part of the "July effect." CONCLUSIONS: AIS patients admitted to tertiary stroke centers during July had similar outcomes despite slightly less frequent thrombolysis and stroke unit care.


Asunto(s)
Isquemia Encefálica/tratamiento farmacológico , Hospitales de Enseñanza , Calidad de la Atención de Salud , Accidente Cerebrovascular/tratamiento farmacológico , Terapia Trombolítica , Anciano , Anciano de 80 o más Años , Isquemia Encefálica/mortalidad , Femenino , Hospitalización , Humanos , Internado y Residencia , Masculino , Sistema de Registros , Estudios Retrospectivos , Accidente Cerebrovascular/mortalidad , Resultado del Tratamiento
9.
ArXiv ; 2024 Jun 11.
Artículo en Inglés | MEDLINE | ID: mdl-38947914

RESUMEN

Diffusion models have been demonstrated as powerful deep learning tools for image generation in CT reconstruction and restoration. Recently, diffusion posterior sampling, where a score-based diffusion prior is combined with a likelihood model, has been used to produce high quality CT images given low-quality measurements. This technique is attractive since it permits a one-time, unsupervised training of a CT prior; which can then be incorporated with an arbitrary data model. However, current methods rely on a linear model of x-ray CT physics to reconstruct or restore images. While it is common to linearize the transmission tomography reconstruction problem, this is an approximation to the true and inherently nonlinear forward model. We propose a new method that solves the inverse problem of nonlinear CT image reconstruction via diffusion posterior sampling. We implement a traditional unconditional diffusion model by training a prior score function estimator, and apply Bayes rule to combine this prior with a measurement likelihood score function derived from the nonlinear physical model to arrive at a posterior score function that can be used to sample the reverse-time diffusion process. This plug-and-play method allows incorporation of a diffusion-based prior with generalized nonlinear CT image reconstruction into multiple CT system designs with different forward models, without the need for any additional training. We develop the algorithm that performs this reconstruction, including an ordered-subsets variant for accelerated processing and demonstrate the technique in both fully sampled low dose data and sparse-view geometries using a single unsupervised training of the prior.

10.
Medicine (Baltimore) ; 103(5): e35859, 2024 Feb 02.
Artículo en Inglés | MEDLINE | ID: mdl-38306545

RESUMEN

This study aimed to determine the potential mechanisms through which long noncoding (Lnc) RNA cancer susceptibility candidate 15 (CASC15) affects hepatocellular carcinoma (HCC). We retrieved HCC RNA-seq and clinical information from the UCSC Xena database. The differential expression (DE) of CASC15 was detected. Overall survival was analyzed using Kaplan-Meier (K-M) curves. Molecular function and signaling pathways affected by CASC15 were determined using Gene Set Enrichment Analysis. Associations between CASC15 and the HCC microenvironment were investigated using immuno-infiltration assays. A differential CASC15-miRNA-mRNA network and HCC-specific CASC15-miRNA-mRNA ceRNA network were constructed. The overexpression of CASC15 in HCC tissues was associated with histological grade, clinical stage, pathological T stage, poor survival, more complex immune cell components, and 12 immune checkpoints. We identified 27 DE miRNAs and 270 DE mRNAs in the differential CASC15-miRNA-mRNA network, and 10 key genes that were enriched in 12 cancer-related signaling pathways. Extraction of the HCC-specific CASC15-miRNA-mRNA network revealed that IGF1R, MET, and KRAS were associated with HCC progression and occurrence. Our bioinformatic findings confirmed that CASC15 is a promising prognostic biomarker for HCC, and elevated levels in HCC are associated with the tumor microenvironment. We also constructed a disease-specific CASC15-miRNA-mRNA regulatory ceRNA network that provides a new perspective for the precise indexing of patients with elevated levels of CASC15.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , MicroARNs , ARN Largo no Codificante , Humanos , Carcinoma Hepatocelular/patología , MicroARNs/genética , MicroARNs/metabolismo , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Neoplasias Hepáticas/patología , ARN Mensajero/metabolismo , Regulación Neoplásica de la Expresión Génica , Redes Reguladoras de Genes , Microambiente Tumoral/genética
11.
Gait Posture ; 107: 293-305, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-37926657

RESUMEN

BACKGROUND: Finding the best subset of gait features among biomechanical variables is considered very important because of its ability to identify relevant sports and clinical gait pattern differences to be explored under specific study conditions. This study proposes a new method of metaheuristic optimization-based selection of optimal gait features, and then investigates how much contribution the selected gait features can achieve in gait pattern recognition. METHODS: Firstly, 800 group gait datasets performed feature extraction to initially eliminate redundant variables. Then, the metaheuristic optimization algorithm model was performed to select the optimal gait feature, and four classification algorithm models were used to recognize the selected gait feature. Meanwhile, the accuracy results were compared with two widely used feature selection methods and previous studies to verify the validity of the new method. Finally, the final selected features were used to reconstruct the data waveform to interpret the biomechanical meaning of the gait feature. RESULTS: The new method finalized 10 optimal gait features (6 ankle-related and 4-related knee features) based on the extracted 36 gait features (85 % variable explanation) by feature extraction. The accuracy in gait pattern recognition among the optimal gait features selected by the new method (99.81 % ± 0.53 %) was significantly higher than that of the feature-based sorting of effect size (94.69 % ± 2.68 %), the sequential forward selection (95.59 % ± 2.38 %), and the results of previous study. The interval between reconstructed waveform-high and reconstructed waveform-low curves based on the selected feature was larger during the whole stance phase. SIGNIFICANCE: The selected gait feature based on the proposed new method (metaheuristic optimization-based selection) has a great contribution to gait pattern recognition. Sports and clinical gait pattern recognition can benefit from population-based metaheuristic optimization techniques. The metaheuristic optimization algorithms are expected to provide a practical and elegant solution for sports and clinical biomechanical feature selection with better economy and accuracy.


Asunto(s)
Análisis de la Marcha , Deportes , Humanos , Algoritmos , Marcha , Extremidad Inferior
12.
Medicine (Baltimore) ; 102(10): e33228, 2023 Mar 10.
Artículo en Inglés | MEDLINE | ID: mdl-36897679

RESUMEN

Abnormal transient receptor potential (TRP) channel function interferes with intracellular calcium-based signaling and causes malignant phenotypes. However, the effects of TRP channel-related genes on hepatocellular carcinoma (HCC) remain unclear. This study aimed to identify HCC molecular subtypes and prognostic signatures based on TRP channel-related genes to predict prognostic risks. Unsupervised hierarchical clustering was applied to identify HCC molecular subtypes using the expression data of TRP channel-related genes. This was followed by a comparison of the clinical and immune microenvironment characteristics between the resulting subtypes. After screening for differentially expressed genes among subtypes, prognostic signatures were identified to construct risk score-based prognostic and nomogram models and predict HCC survival. Finally, tumor drug sensitivities were predicted and compared between the risk groups. Sixteen TRP channel-related genes that were differentially expressed between HCC and non-tumorous tissues were used to identify 2 subtypes. Cluster 1 had higher TRP scores, better survival status, and lower levels of clinical malignancy. Immune-related analyses also revealed higher infiltration of M1 macrophages and higher immune and stromal scores in Cluster 1 than in Cluster 2. After screening differentially expressed genes between subtypes, 6 prognostic signatures were identified to construct prognostic and nomogram models. The potential of these models to assess the prognostic risk of HCC was further validated. Furthermore, Cluster 1 was more distributed in the low-risk group, with higher drug sensitivities. Two HCC subtypes were identified, of which Cluster 1 was associated with a favorable prognosis. Prognostic signatures related to TRP channel genes and molecular subtypes can be used to predict HCC risk.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Pronóstico , Nomogramas , Señalización del Calcio , Microambiente Tumoral
13.
Medicine (Baltimore) ; 102(30): e34365, 2023 Jul 28.
Artículo en Inglés | MEDLINE | ID: mdl-37505155

RESUMEN

This study aimed to elucidate the prognostic value of the leucine rich repeat containing 1 (LRRC1) gene in hepatocellular carcinoma (HCC) and to determine the effects of high and low LRRC1 expression on mutation and immune cell infiltration. We downloaded HCC mRNA-seq expression and clinical data from University of California Santa Cruz Xena. The expression of LRRC1 was compared between HCC tumor and normal samples. Tumor samples were divided according to high and low LRRC1 expression. Differentially expressed genes between the 2 groups were identified, and function, mutation, and immune cell infiltration were analyzed. Genes associated with immune cells were identified using weighted gene co-expression network analysis, and transcription factors of these genes were predicted. Moreover, a prognostic model was developed and its performance was evaluated. The expression of LRRC1 was upregulated in HCC tissues, and this indicated a poor prognosis for patients with HCC. Differentially expressed genes between high and low LRRC1 expression were significantly enriched in pathways associated with cancer, amino acid metabolism, carbohydrate metabolism, and the immune system. We identified 15 differentially infiltrated immune cells between tumors with high and low LRRC1 expression and 14 of them correlated with LRRC1 gene expression. Weighted gene co-expression network analysis identified 83 immune cell-related genes, 27 of which had prognostic value. Cyclic AMP-response element binding protein regulated annexin A5, matrix metallopeptidase 9, and LRRC1 in the transcription factor regulatory network. Finally, a prognostic model composed of 7 genes were generated, which could accurately predict the prognosis of HCC patients. The LRRC1 gene might serve as a potential immune-associated prognostic biomarker for HCC.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/genética , Pronóstico , Neoplasias Hepáticas/genética , Anexina A5 , Proteína de Unión a Elemento de Respuesta al AMP Cíclico , Proteínas Portadoras , Proteínas de la Membrana/genética
14.
Front Vet Sci ; 9: 836043, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35529841

RESUMEN

Felines have significant advantages in terms of sports energy efficiency and flexibility compared with other animals, especially in terms of jumping and landing. The biomechanical characteristics of a feline (cat) landing from different heights can provide new insights into bionic robot design based on research results and the needs of bionic engineering. The purpose of this work was to investigate the adaptive motion adjustment strategy of the cat landing using a machine learning algorithm and finite element analysis (FEA). In a bionic robot, there are considerations in the design of the mechanical legs. (1) The coordination mechanism of each joint should be adjusted intelligently according to the force at the bottom of each mechanical leg. Specifically, with the increase in force at the bottom of the mechanical leg, the main joint bearing the impact load gradually shifts from the distal joint to the proximal joint; (2) the hardness of the materials located around the center of each joint of the bionic mechanical leg should be strengthened to increase service life; (3) the center of gravity of the robot should be lowered and the robot posture should be kept forward as far as possible to reduce machine wear and improve robot operational accuracy.

15.
Interdiscip Sci ; 14(1): 141-150, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-34463928

RESUMEN

DNA storage has been a thriving interdisciplinary research area because of its high density, low maintenance cost, and long durability for information storage. However, the complexity of errors in DNA sequences including substitutions, insertions and deletions hinders its application for massive data storage. Motivated by the divide-and-conquer algorithm, we propose a hierarchical error correction strategy for text DNA storage. The basic idea is to design robust codes for common characters which have one-base error correction ability including insertion and/or deletion. The errors are gradually corrected by the codes in DNA reads, multiple alignment of character lines, and finally word spelling. On one hand, the proposed encoding method provides a systematic way to design storage friendly codes, such as 50% GC content, no more than 2-base homopolymers, and robustness against secondary structures. On the other hand, the proposed error correction method not only corrects single insertion or deletion, but also deals with multiple insertions or deletions. Simulation results demonstrate that the proposed method can correct more than 98% errors when error rate is less than or equal to 0.05. Thus, it is more powerful and adaptable to the complicated DNA storage applications.


Asunto(s)
Algoritmos , ADN , Secuencia de Bases , Simulación por Computador , ADN/química , Análisis de Secuencia de ADN/métodos
16.
Nat Cell Biol ; 24(1): 62-73, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-35013556

RESUMEN

Poly (ADP-ribose) polymerase (PARP) inhibitors elicit antitumour activity in homologous recombination-defective cancers by trapping PARP1 in a chromatin-bound state. How cells process trapped PARP1 remains unclear. Using wild-type and a trapping-deficient PARP1 mutant combined with rapid immunoprecipitation mass spectrometry of endogenous proteins and Apex2 proximity labelling, we delineated mass spectrometry-based interactomes of trapped and non-trapped PARP1. These analyses identified an interaction between trapped PARP1 and the ubiquitin-regulated p97 ATPase/segregase. We found that following trapping, PARP1 is SUMOylated by PIAS4 and subsequently ubiquitylated by the SUMO-targeted E3 ubiquitin ligase RNF4, events that promote recruitment of p97 and removal of trapped PARP1 from chromatin. Small-molecule p97-complex inhibitors, including a metabolite of the clinically used drug disulfiram (CuET), prolonged PARP1 trapping and enhanced PARP inhibitor-induced cytotoxicity in homologous recombination-defective tumour cells and patient-derived tumour organoids. Together, these results suggest that p97 ATPase plays a key role in the processing of trapped PARP1 and the response of tumour cells to PARP inhibitors.


Asunto(s)
Cromatina/metabolismo , Poli(ADP-Ribosa) Polimerasa-1/antagonistas & inhibidores , Poli(ADP-Ribosa) Polimerasa-1/metabolismo , Inhibidores de Poli(ADP-Ribosa) Polimerasas/farmacología , Proteína que Contiene Valosina/metabolismo , Línea Celular Tumoral , Disulfiram/análogos & derivados , Disulfiram/farmacología , Células HCT116 , Células HeLa , Humanos , Células MCF-7 , Neoplasias/tratamiento farmacológico , Proteínas Nucleares/metabolismo , Proteínas de Unión a Poli-ADP-Ribosa/metabolismo , Proteínas Inhibidoras de STAT Activados/metabolismo , Sumoilación , Factores de Transcripción/metabolismo , Ubiquitinación
17.
Chemosphere ; 263: 128175, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33297143

RESUMEN

Vacuum freeze-drying is a scientifically advanced method to prepare solid inoculants from oil degrading bacterium. The introduction of oil-degrading microbes or bioaugmentation can be an efficient way to bioremediate oil spills in marine areas, where oil-degrading bacteria are deficient. The purpose of this study is to evaluate the potential use of solid inoculants of LZ-2 bacteria to enhance the degradation rate of crude oil. In this study, response surface methodology (RSM) was incorporated into the experimental design to optimize a response, which is influenced by different protectants. Our results showed that five factors have interactive and synergistic protective effects on the growth of LZ-2. Optimal growth of freeze-dried LZ-2 (63.8%) was observed with a 10.5% solution of skim milk supplemented with 14.3% sucrose, 14.4% of trehalose, 4.9% of glycerin and 14.7% of ß-cyclodextrin. The culture grew in medium containing crude oil (3 g L-1) at 37 °C at 150 rpm for 30 d, GC and GC-MS analysis showed biodegradation of 44.2 and 21.6% for total saturate and aromatic hydrocarbons respectively. These results indicated that the solid inoculants of LZ-2 bacteria had the potential to be used for ex-situ bioremediation of hydrocarbon pollutants associated with crude oil.


Asunto(s)
Contaminación por Petróleo , Petróleo , Biodegradación Ambiental , Hidrocarburos , Contaminación por Petróleo/análisis , Proyectos de Investigación
18.
Front Bioeng Biotechnol ; 9: 791238, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34988067

RESUMEN

The therapeutic benefit of high heel shoes (HHS) for plantar fasciitis treatment is controversial. It has been suggested that plantar fascia strain can be decreased by heel elevation of shoes which helps in body weight redistribution throughout the length of the foot. Yet it is a fact that the repetitive tension caused by HHS wearing resulting in plantar fasciitis is a high-risk disease in HHS individuals who suffer heel and plantar pain. To explore the biomechanical function on plantar fascia under HHS conditions, in this study, musculoskeletal modeling (MsM) and finite element method (FEM) were used to investigate the effect of heel height on strain distribution of plantar fascia. Three-dimensional (3D) and one-dimensional (1D) finite element models of plantar fascia were generated to analyze the computed strain variation in 3-, 5-, and 7-cm heel heights. For validation, the computed foot contact pressure was compared with experimental measurement, and the strain value on 1D fascia was compared with previous studies. Results showed that the peak strain of plantar fascia was progressively increased on both 3D and 1D plantar fascia as heel elevated from 3 to 7 cm, and the maximum strain of plantar fascia occurs near the heel pain site at second peak stance. The 3D fascia model predicted a higher strain magnitude than that of 1D and provided a more reliable strain distribution on the plantar fascia. It is concluded that HHS with narrow heel support could pose a high risk on plantar fasciitis development, rather than reducing symptoms. Therefore, the heel elevation as a treatment recommendation for plantar fasciitis is questionable. Further studies of different heel support structures of shoes to quantify the effectiveness of heel elevation on the load-bearing mechanism of plantar fascia are recommended.

19.
Healthcare (Basel) ; 9(10)2021 Oct 03.
Artículo en Inglés | MEDLINE | ID: mdl-34683001

RESUMEN

Kinematics data are primary biomechanical parameters. A principal component analysis (PCA) of waveforms is a statistical approach used to explore patterns of variability in biomechanical curve datasets. Differences in experienced and recreational runners' kinematic variables are still unclear. The purpose of the present study was to compare any differences in kinematics parameters for competitive runners and recreational runners using principal component analysis in the sagittal plane, frontal plane and transverse plane. Forty male runners were divided into two groups: twenty competitive runners and twenty recreational runners. A Vicon Motion System (Vicon Metrics Ltd., Oxford, UK) captured three-dimensional kinematics data during running at 3.3 m/s. The principal component analysis was used to determine the dominating variation in this model. Then, the principal component scores retained the first three principal components and were analyzed using independent t-tests. The recreational runners were found to have a smaller dorsiflexion angle, initial dorsiflexion contact angle, ankle inversion, knee adduction, range motion in the frontal knee plane and hip frontal plane. The running kinematics data were influenced by running experience. The findings from the study provide a better understanding of the kinematics variables for competitive and recreational runners. Thus, these findings might have implications for reducing running injury and improving running performance.

20.
Front Cardiovasc Med ; 8: 770975, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-35127851

RESUMEN

It is essential for patients with hypertension to effectively reduce and maintain appropriate blood pressure levels. As one of the non-pharmacological and invasive methods, physical exercise seems to improve blood pressure of the patients with hypertension. However, different volumes and intensities of physical exercise on the improvement of hypertension are different. To understand the effects of the type of exercise training on blood pressure and the other health status of patients with hypertension, a network meta-analysis was used to compare the mixed effects of different types of exercise training. This systematic review includes all eligible randomized controlled trials of PubMed, Medline, Cochrane Library, and CINAHL. Twelve studies met the inclusion criteria (n = 846 participants at the end of the study). The results show that a medium-intensity training (MIT) is best in improving the blood pressure of patients with hypertension, while a high-volume high-intensity interval training (HVHIIT) is better in reducing body mass and resting heart rate. In addition, the analysis of the exercise capacity shows that HVHIIT has a better effect on the improvement of patients with hypertension. Noticeably, long-term high-volume and appropriate intensity exercise can effectively improve the health status of patients with hypertension. In short, for patients with high blood pressure, MIT seems to be better at lowering blood pressure, while HVHIIT can better improve exercise ability and physical fitness. However, larger randomized controlled trials with a longer duration than those included in this meta-analysis are needed to confirm these results.

SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA