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1.
Mol Cell ; 69(1): 48-61.e6, 2018 01 04.
Artículo en Inglés | MEDLINE | ID: mdl-29304333

RESUMEN

The carboxy-terminal domain (CTD) of RNA polymerase (Pol) II is composed of a repetition of YSPTSPS heptads and functions as a loading platform for protein complexes that regulate transcription, splicing, and maturation of RNAs. Here, we studied mammalian CTD mutants to analyze the function of tyrosine1 residues in the transcription cycle. Mutation of 3/4 of the tyrosine residues (YFFF mutant) resulted in a massive read-through transcription phenotype in the antisense direction of promoters as well as in the 3' direction several hundred kilobases downstream of genes. The YFFF mutant shows reduced Pol II at promoter-proximal pause sites, a loss of interaction with the Mediator and Integrator complexes, and impaired recruitment of these complexes to chromatin. Consistent with these observations, Pol II loading at enhancers and maturation of snRNAs are altered in the YFFF context genome-wide. We conclude that tyrosine1 residues of the CTD control termination of transcription by Pol II.


Asunto(s)
ARN Polimerasa II/genética , ARN Mensajero/biosíntesis , Terminación de la Transcripción Genética/fisiología , Transcripción Genética/fisiología , Tirosina/genética , Línea Celular Tumoral , Cromatina/metabolismo , Humanos , Mutación/genética , Regiones Promotoras Genéticas/genética , ARN Polimerasa II/metabolismo , ARN Nuclear Pequeño/genética
2.
Genome Res ; 32(7): 1328-1342, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-34162697

RESUMEN

Broad domains of H3K4 methylation have been associated with consistent expression of tissue-specific, cell identity, and tumor suppressor genes. Here, we identified broad domain-associated genes in healthy human thymic T cell populations and a collection of T cell acute lymphoblastic leukemia (T-ALL) primary samples and cell lines. We found that broad domains are highly dynamic throughout T cell differentiation, and their varying breadth allows the distinction between normal and neoplastic cells. Although broad domains preferentially associate with cell identity and tumor suppressor genes in normal thymocytes, they flag key oncogenes in T-ALL samples. Moreover, the expression of broad domain-associated genes, both coding and noncoding, is frequently deregulated in T-ALL. Using two distinct leukemic models, we showed that the ectopic expression of T-ALL oncogenic transcription factor preferentially impacts the expression of broad domain-associated genes in preleukemic cells. Finally, an H3K4me3 demethylase inhibitor differentially targets T-ALL cell lines depending on the extent and number of broad domains. Our results show that the regulation of broad H3K4me3 domains is associated with leukemogenesis, and suggest that the presence of these structures might be used for epigenetic prioritization of cancer-relevant genes, including long noncoding RNAs.


Asunto(s)
Leucemia-Linfoma Linfoblástico de Células T Precursoras , Epigénesis Genética , Histonas/metabolismo , Humanos , Oncogenes , Leucemia-Linfoma Linfoblástico de Células T Precursoras/genética
3.
BMC Plant Biol ; 24(1): 1011, 2024 Oct 28.
Artículo en Inglés | MEDLINE | ID: mdl-39465379

RESUMEN

An efficacious strategy to adapt to climate change involves optimizing the planting season, a technique that has been extensively utilized to enhance the use of solar radiation and temperature resources in rice cultivation. Field experiments were executed in the middle and lower reaches of the Yangtze River, China, employing three distinct rice cultivars and seven disparate sowing periods spanning 2019 to 2021. The objective of assessing the impact of sowing date on apparent radiation use efficiency (RUEA), accumulated temperature use efficiencies (TUE), and overall rice yield. Subsequent to the delay of sowing dates, the duration of the comprehensive growth period initially exhibited a declining trajectory before subsequently escalating, with the reduction predominantly ascribed to a decrease in the number of days preceding heading. Furthermore, there was a tendency for both the mean daily and effective cumulative solar radiation to decline over the course of the growing period. The yield of the three rice varieties demonstrated an initial surge, which was then followed by a subsequent decline in reaction to the delay of sowing dates. A correlation analysis disclosed that solar radiation and effective cumulative temperature (EAT) were the predominant elements impacting grain yield. The outcomes of the path analysis indicate that EAT exerts the most substantial influence on yield, succeeded by cumulative total solar radiation (TSR), while photothermal quotient (PTQ) demonstrates the least impact on yield. There was a significant positive correlation between EAT and cumulative TSR with spikelets per panicle (0.237** and 0.218**), grain filling (0.753** and 0.576**), and grain weight (0.339** and 0.359**), respectively. The findings of this study indicate that an increase in yield is facilitated when the EAT after heading exceeds 594.9 ℃, the EAT surpasses 2016.7 ℃, the cumulative TSR before heading is above 1548.7 MJ m- 2, the cumulative TSR after heading is over 603.0 MJ m- 2, and the cumulative total radiation throughout the entire growth period is more than 2151.8 MJ m- 2. Furthermore, the most optimal sowing date, as identified by this study, is June 6. This study provides key insights into boosting rice productivity in the middle and lower reaches of the Yangtze River, China by analyzing the impact of temperature and solar radiation on yield and identifying optimal growth conditions. Clinical trial number Not applicable.


Asunto(s)
Oryza , Ríos , Oryza/crecimiento & desarrollo , Oryza/efectos de la radiación , Oryza/genética , China , Cambio Climático , Temperatura , Estaciones del Año , Producción de Cultivos/métodos , Luz Solar , Productos Agrícolas/crecimiento & desarrollo
4.
Curr Atheroscler Rep ; 26(11): 639-648, 2024 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-39240492

RESUMEN

PURPOSE OF REVIEW: Health data sciences can help mitigate high burden of cardiovascular disease (CVD) management in South Asia by increasing availability and affordability of healthcare services. This review explores the current landscape, challenges, and strategies for leveraging digital health technologies to improve CVD outcomes in the region. RECENT FINDINGS: Several South Asian countries are implementing national digital health strategies that aim to provide unique health account numbers for patients, creating longitudinal digital health records while others aim to digitize healthcare services and improve health outcomes. Significant challenges impede progress, including lack of interoperability, inadequate training of healthcare workers, cultural barriers, and data privacy concerns. Leveraging digital health for CVD management involves using big data for early detection, employing artificial intelligence for diagnostics, and integrating multiomics data for health insights. Addressing these challenges through policy frameworks, capacity building, and international cooperation is crucial for improving CVD outcomes in region.


Asunto(s)
Enfermedades Cardiovasculares , Humanos , Enfermedades Cardiovasculares/terapia , Enfermedades Cardiovasculares/epidemiología , Asia/epidemiología , Ciencia de los Datos/métodos , Telemedicina , Macrodatos , Salud Digital , Sur de Asia
5.
Alzheimers Dement ; 20(7): 4602-4612, 2024 07.
Artículo en Inglés | MEDLINE | ID: mdl-38842100

RESUMEN

INTRODUCTION: We investigated the effect vigorous physical activity (VPA) on the risk of incident mild cognitive impairment (MCI) and probable dementia among individuals with high-risk hypertension. METHODS: Baseline self-reported frequency of VPA was categorized into low VPA (<1 session/week), and high VPA (≥1 session/week). We used multivariate Cox regression analysis to examine the association of VPA categories with incident MCI and probable dementia events. RESULTS: Participants in the high VPA category, compared with low VPA, experienced lower events rates (per 1000 person-years) of MCI (13.9 vs 19.7), probable dementia (6.3 vs 9.0), and MCI/probable dementia (18.5 vs 25.8). In the multivariate Cox regression model, high VPA, compared with low VPA, was associated with lower risk of MCI, probable dementia, and MCI/probable dementia (HR [95% CI]: 0.81 [0.68-0.97], 0.80 [0.63-1.03], and 0.82 [0.70-0.96]), respectively. DISCUSSION: This study provides evidence that VPA may preserve cognitive function in high-risk patients with hypertension. HIGHLIGHTS: Hypertension is associated with an increased risk of cognitive impairment Physical activity (PA) is associated with a lower risk of decline in cognition The effect of ≥1 sessions of vigorous-intensity PA (VPA) per week was assessed This analysis included SPRINT MIND trial participants with high-risk hypertension ≥1 VPA sessions/week was associated with lower risk of future cognitive impairment.


Asunto(s)
Disfunción Cognitiva , Ejercicio Físico , Hipertensión , Humanos , Disfunción Cognitiva/epidemiología , Masculino , Femenino , Hipertensión/epidemiología , Anciano , Demencia/epidemiología , Incidencia , Factores de Riesgo , Persona de Mediana Edad
6.
Eur J Orthop Surg Traumatol ; 34(5): 2407-2412, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38619601

RESUMEN

PURPOSE: This study aims to compare the functional and radiological outcomes following both guided growth surgery (GGS) and acute corrective osteotomy (ACO) correction of angular deformities in children with rickets. METHODS: A total of 8 and 7 children who had gradual GGS and ACO correction, respectively, for angular deformities due to rickets from 2002 to 2022 were recalled for follow-up. Demographic data, types of rickets, data on pharmacological treatment, biochemical parameters, recurrence of angular deformity and postoperative complications were obtained from the medical records. A radiographic evaluation of the leg was performed to determine the tibiofemoral angle. For functional evaluation, the Active Scale for Kids (ASK) and Lower Extremity Functional Scale (LEFS) instruments were used for children below and above 15 years old, respectively. RESULTS: In terms of the tibiofemoral angle, the GGS group documented greater angle changes compared to the ACO group, but the difference was not significant. In terms of functional outcomes, the overall score percentage of both groups was comparable with the GGS group showing a trend of higher score percentage compared to the ACO group. The GGS group presented no complication while 2 neurovascular injuries and 1 implant failure were recorded in the ACO group. CONCLUSION: Both GGS and ACO procedures resulted in similar radiographic and functional outcomes for the treatment of rickets in children. GGS may be advantageous in terms of reducing complications of surgery. Nevertheless, the choice of surgical intervention should be made based on the patient's circumstances and the surgeon's preference.


Asunto(s)
Osteotomía , Raquitismo , Humanos , Femenino , Masculino , Niño , Estudios Transversales , Raquitismo/cirugía , Osteotomía/métodos , Resultado del Tratamiento , Adolescente , Preescolar , Radiografía , Tibia/cirugía , Tibia/diagnóstico por imagen , Tibia/anomalías , Complicaciones Posoperatorias/etiología , Fémur/cirugía , Fémur/anomalías , Fémur/diagnóstico por imagen , Deformidades Congénitas de las Extremidades Inferiores/cirugía
7.
Environ Res ; 217: 114621, 2023 01 15.
Artículo en Inglés | MEDLINE | ID: mdl-36347396

RESUMEN

The rapid industrialization of the world is disparagingly manipulating our environment and natural ecosystem. The researchers are taking keen interest to invent novel material as photocatalyst for non-degradable organic pollutants. Solar energy-driven practices employing semiconductors are a novel approach towards wastewater remediation. Here in, we successfully synthesized a vigorous photocatalysts comprising of g-C3N4 and doped ZnO-W/M (M = Co, Ce, Yb, Sm) by co-precipitation followed by metals doping via calcination approach. The structural, morphological, and photocatalytic applications for organic pollutants of synthesized heterostructure nanocomposites were examined by XRD, FTIR, SEM, EDX and UV visible spectrophotometer. Diffraction peaks attributed to both g-C3N4 and ZnO-W were detected in the XRD spectra. The FTIR spectra also inveterate the formation of g-C3N4/ZnO-W/M composites. The SEM images reveal an agglomerated morphology and EDS analysis also confirmed close contact between g-C3N4, ZnO-W and doped metals. The abridged energy band gap of g-C3N4/ZnO-W/M (M = Ce, Yb, Sm, Co) nanocomposites calculated via Tauc plot are 2.68, 2.88, 3.24 and 3.29 eV respectively. Narrowing of bandgap is considered an imperative triumph for the degradation of industrial effluents. The photocatalytic activity was performed against four different dyes and follows the trend Ce > Yb > Sm > Co. The recyclability tests were carried out for different dyes and no substantial catalytic activity loss was observed even after the fourth experimental run, which proves that reported ternary heterojunctions exhibit high mechanical stability and reusability.The species trapping experiment exposed that generated h+ are the principal active specie for dye photodegradation reactions. This work disseminates a novel photocatalyst for the removal of synthetic dyes.


Asunto(s)
Nanocompuestos , Óxido de Zinc , Óxido de Zinc/química , Ecosistema , Catálisis , Nanocompuestos/química , Colorantes
8.
Nucleic Acids Res ; 49(5): 2488-2508, 2021 03 18.
Artículo en Inglés | MEDLINE | ID: mdl-33533919

RESUMEN

The ubiquitous family of dimeric transcription factors AP-1 is made up of Fos and Jun family proteins. It has long been thought to operate principally at gene promoters and how it controls transcription is still ill-understood. The Fos family protein Fra-1 is overexpressed in triple negative breast cancers (TNBCs) where it contributes to tumor aggressiveness. To address its transcriptional actions in TNBCs, we combined transcriptomics, ChIP-seqs, machine learning and NG Capture-C. Additionally, we studied its Fos family kin Fra-2 also expressed in TNBCs, albeit much less. Consistently with their pleiotropic effects, Fra-1 and Fra-2 up- and downregulate individually, together or redundantly many genes associated with a wide range of biological processes. Target gene regulation is principally due to binding of Fra-1 and Fra-2 at regulatory elements located distantly from cognate promoters where Fra-1 modulates the recruitment of the transcriptional co-regulator p300/CBP and where differences in AP-1 variant motif recognition can underlie preferential Fra-1- or Fra-2 bindings. Our work also shows no major role for Fra-1 in chromatin architecture control at target gene loci, but suggests collaboration between Fra-1-bound and -unbound enhancers within chromatin hubs sometimes including promoters for other Fra-1-regulated genes. Our work impacts our view of AP-1.


Asunto(s)
Elementos de Facilitación Genéticos , Regulación Neoplásica de la Expresión Génica , Proteínas Proto-Oncogénicas c-fos/metabolismo , Neoplasias de la Mama Triple Negativas/genética , Sitios de Unión , Línea Celular Tumoral , Cromatina/química , Cromatina/metabolismo , Epigénesis Genética , Antígeno 2 Relacionado con Fos/metabolismo , Humanos , Motivos de Nucleótidos , Regiones Promotoras Genéticas , Proteínas Proto-Oncogénicas c-fos/fisiología , Factor de Transcripción AP-1/metabolismo , Neoplasias de la Mama Triple Negativas/metabolismo , Factores de Transcripción p300-CBP/metabolismo
9.
J Biosoc Sci ; 55(1): 169-173, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-34866563

RESUMEN

The aim of this study was to determine the trend of consanguineous marriage among the Arab population in Israel. Socio-demographic data for the Arab population were extracted from national health surveys conducted in Israel in 2007 and 2017. The prevalence of consanguineous marriage among the Arab population in Israel increased significantly from 36.3% to 41.6% in the decade from 2007 to 2017. First-cousin and closer marriages constituted about 50% of total consanguineous marriages in the two periods surveyed. Consanguinity was found to be significantly related to religion and place of residence. Thus, the prevalence of consanguineous marriage remains high among the Arab population in Israel, similar to other Arab societies. These findings affect the health of future generations and impose a challenge for health care professionals.


Asunto(s)
Árabes , Familia , Humanos , Consanguinidad , Israel/epidemiología , Religión
10.
Phytother Res ; 37(2): 627-644, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36420866

RESUMEN

Until now, no specific and effective treatment exists for coronavirus disease 2019 (COVID-19). Since honey and Nigella sativa (HNS) have established antiviral, antibacterial, antiinflammatory, antioxidant, and immunomodulatory properties, we tested their efficacy for this disease in a multicenter, placebo-controlled, and randomized clinical trial at four medical care facilities in Pakistan. RT-PCR confirmed COVID-19 adults showing moderate or severe disease were enrolled in the trial. Patients were randomly assigned in a 1:1 ratio to receive either honey (1 g kg-1 day-1 ) and Nigella sativa seeds (80 mg kg-1 day-1 ) or a placebo for up to 13 days along with standard care. The outcomes included symptoms' alleviation, viral clearance, and 30-day mortality in the intention-to-treat population. Three hundred and thirteen patients, 210 with moderate and 103 with severe disease, underwent randomization from April 30 to July 29, 2020. Among the moderate cases, 107 were assigned to HNS, whereas 103 were assigned to the placebo group. Among the severe cases, 50 were given HNS, and 53 were given the placebo. HNS resulted in ~50% reduction in time taken to alleviate symptoms as compared to placebo (moderate cases: 4 vs. 7 days, Hazard Ratio [HR]: 6.11; 95% Confidence Interval [CI]: 4.23-8.84, p < 0.0001 and for severe cases: 6 vs. 13 days, HR: 4.04; 95% CI: 2.46-6.64; p < 0.0001). HNS also cleared the virus earlier than placebo in both moderate cases (6 vs. 10 days, HR: 5.53; 95% CI: 3.76-8.14, p < 0.0001) and severe cases (8.5 vs. 12 days, HR: 4.32; 95% CI: 2.62-7.13, p < 0.0001). HNS further led to a better clinical score on day 6 with normal activity resumption in 63.6% vs. 10.9% among moderate cases (OR: 0.07; 95% CI: 0.03-0.13, p < 0.0001) and hospital discharge in 50% versus 2.8% in severe cases (OR: 0.03; 95% CI: 0.01-0.09, p < 0.0001). In severe cases, the mortality rate was less than 1/4th in the HNS group than in placebo (4% vs. 18.87%, OR: 0.18; 95% CI: 0.02-0.92, p = 0.029). No HNS-related adverse effects were observed. HNS, compared with placebo, significantly improved symptoms, expedited viral load clearance, and reduced mortality in COVID-19 patients. This trial was registered on April 15, 2020 with ClinicalTrials.gov Identifier: NCT04347382.


Asunto(s)
COVID-19 , Miel , Nigella sativa , Adulto , Humanos , SARS-CoV-2 , Pakistán/epidemiología , Resultado del Tratamiento
11.
Sensors (Basel) ; 23(18)2023 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-37765970

RESUMEN

This paper presents a comprehensive study on the classification of brain tumor images using five pre-trained vision transformer (ViT) models, namely R50-ViT-l16, ViT-l16, ViT-l32, ViT-b16, and ViT-b32, employing a fine-tuning approach. The objective of this study is to advance the state-of-the-art in brain tumor classification by harnessing the power of these advanced models. The dataset utilized for experimentation consists of a total of 4855 images in the training set and 857 images in the testing set, encompassing four distinct tumor classes. The performance evaluation of each model is conducted through an extensive analysis encompassing precision, recall, F1-score, accuracy, and confusion matrix metrics. Among the models assessed, ViT-b32 demonstrates exceptional performance, achieving a high accuracy of 98.24% in accurately classifying brain tumor images. Notably, the obtained results outperform existing methodologies, showcasing the efficacy of the proposed approach. The contributions of this research extend beyond conventional methods, as it not only employs cutting-edge ViT models but also surpasses the performance of existing approaches for brain tumor image classification. This study not only demonstrates the potential of ViT models in medical image analysis but also provides a benchmark for future research in the field of brain tumor classification.

12.
Am J Law Med ; 49(2-3): 301-313, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-38344793

RESUMEN

This Article analyzes the 2021 judgment of the Supreme Court of Pakistan in the case of Mst. Safia Bano v. Home Department, Government of Punjab. The case has garnered significant local and international attention due to the Court's ruling that a death sentence may not be carried out on a defendant who has a mental illness. Setting the case against the backdrop of Pakistan's Islamic and colonial contexts, this article argues that the Supreme Court has reshaped the insanity defense in Pakistani law by placing the determination of a defendant's mental state mainly in the hands of medical professionals. However, the Court's reliance on medical professionals and the subsequent downplaying of the "moral capacity" element of the insanity defense-a determination of law made by courts-has created an obstacle for courts to punish offenders more stringently in future cases due to the popular belief that mental health professionals are ill-equipped to answer broader questions of justice for victims and society. The article recommends that this issue can be remedied by establishing an objective legal test for insanity that considers Islamic law, Pakistani precedent, and advances in medical science.


Asunto(s)
Defensa por Insania , Trastornos Mentales , Humanos , Estados Unidos , Pakistán , Derechos Civiles , Principios Morales
13.
Mediators Inflamm ; 2022: 7853482, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36065376

RESUMEN

The adipose tissue NLRP3 inflammasome has recently emerged as a contributor to obesity-related metabolic inflammation. Recent studies have demonstrated that the activation of the NLRP3 inflammasome cleaves gasdermin D (GSDMD) and induces pyroptosis, a proinflammatory programmed cell death. However, whether GSDMD is involved in the regulation of adipose tissue function and the development of obesity-induced metabolic disease remains unknown. The aim of the present study was to investigate the role of GSDMD in adipose tissue inflammation as well as whole-body metabolism using GSDMD-deficient mice fed a high-fat diet (HFD) for 30 weeks. The effects of GSDMD deficiency on adipose tissue, liver, and isolated macrophages from wild-type (WT) and GSDMD knockout (KO) mice were examined. In addition, 3T3-L1 cells were used to examine the expression of GSDMD during adipogenesis. The results demonstrate that although HFD-induced inflammation was partly ameliorated in isolated macrophages and liver, adipose tissue remained unaffected by GSDMD deficiency. Compared with the WT HFD mice, GSDMD KO HFD mice exhibited a mild increase in HFD-induced glucose intolerance with increased systemic and adipose tissue IL-1ß levels. Interestingly, GSDMD deficiency caused accumulation of fat mass when challenged with HFD, partly by suppressing the expression of peroxisome proliferator-activated receptor gamma (PPARγ). The expression of GSDMD mRNA and protein was dramatically suppressed during adipocyte differentiation and was inversely correlated with PPARγ expression. Together, these findings indicate that GSDMD is not a prerequisite for HFD-induced adipose tissue inflammation and suggest a noncanonical function of GSDMD in regulation of fat mass through PPARγ.


Asunto(s)
Tejido Adiposo , Dieta Alta en Grasa , Intolerancia a la Glucosa , Proteínas de Unión a Fosfato , Proteínas Citotóxicas Formadoras de Poros , Tejido Adiposo/metabolismo , Tejido Adiposo/patología , Animales , Dieta Alta en Grasa/efectos adversos , Intolerancia a la Glucosa/metabolismo , Inflamasomas/metabolismo , Inflamación/metabolismo , Ratones , Ratones Noqueados , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Obesidad/metabolismo , PPAR gamma/metabolismo , Proteínas de Unión a Fosfato/genética , Proteínas Citotóxicas Formadoras de Poros/genética
14.
Proc Natl Acad Sci U S A ; 116(51): 25839-25849, 2019 12 17.
Artículo en Inglés | MEDLINE | ID: mdl-31776254

RESUMEN

Naive CD4+ T lymphocytes differentiate into different effector types, including helper and regulatory cells (Th and Treg, respectively). Heritable gene expression programs that define these effector types are established during differentiation, but little is known about the epigenetic mechanisms that install and maintain these programs. Here, we use mice defective for different components of heterochromatin-dependent gene silencing to investigate the epigenetic control of CD4+ T cell plasticity. We show that, upon T cell receptor (TCR) engagement, naive and regulatory T cells defective for TRIM28 (an epigenetic adaptor for histone binding modules) or for heterochromatin protein 1 ß and γ isoforms (HP1ß/γ, 2 histone-binding factors involved in gene silencing) fail to effectively signal through the PI3K-AKT-mTOR axis and switch to glycolysis. While differentiation of naive TRIM28-/- T cells into cytokine-producing effector T cells is impaired, resulting in reduced induction of autoimmune colitis, TRIM28-/- regulatory T cells also fail to expand in vivo and to suppress autoimmunity effectively. Using a combination of transcriptome and chromatin immunoprecipitation-sequencing (ChIP-seq) analyses for H3K9me3, H3K9Ac, and RNA polymerase II, we show that reduced effector differentiation correlates with impaired transcriptional silencing at distal regulatory regions of a defined set of Treg-associated genes, including, for example, NRP1 or Snai3. We conclude that TRIM28 and HP1ß/γ control metabolic reprograming through epigenetic silencing of a defined set of Treg-characteristic genes, thus allowing effective T cell expansion and differentiation into helper and regulatory phenotypes.


Asunto(s)
Diferenciación Celular/fisiología , Reprogramación Celular/fisiología , Proteínas Cromosómicas no Histona/metabolismo , Epigénesis Genética/fisiología , Linfocitos T/metabolismo , Proteína 28 que Contiene Motivos Tripartito/metabolismo , Animales , Autoinmunidad/fisiología , Linfocitos T CD4-Positivos/metabolismo , Diferenciación Celular/genética , Plasticidad de la Célula/fisiología , Reprogramación Celular/genética , Homólogo de la Proteína Chromobox 5 , Colon/patología , Citocinas/metabolismo , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Regulación de la Expresión Génica , Silenciador del Gen , Histonas/metabolismo , Ratones , Ratones Noqueados , Fosfatidilinositol 3-Quinasas/metabolismo , Receptores de Antígenos de Linfocitos T/metabolismo , Linfocitos T Reguladores/inmunología , Linfocitos T Reguladores/metabolismo , Transcriptoma , Proteína 28 que Contiene Motivos Tripartito/genética
15.
Sensors (Basel) ; 22(24)2022 Dec 16.
Artículo en Inglés | MEDLINE | ID: mdl-36560301

RESUMEN

We develop a probabilistic model for determining the location of dc-link faults in MT-HVdc networks using discrete wavelet transforms (DWTs), Bayesian optimization, and multilayer artificial neural networks (ANNs) based on local information. Likewise, feedforward neural networks (FFNNs) are trained using the Levenberg-Marquardt backpropagation (LMBP) method, which multi-stage BO optimizes for efficiency. During training, the feature vectors at the sending terminal of the dc link are selected based on the norm values of the observed waveforms at various frequency bands. The multilayer ANN is trained using a comprehensive set of offline data that takes the denoising scheme into account. This choice not only helps to reduce the computational load but also provides better accuracy. An overall percentage error of 0.5144% is observed for the proposed algorithm when tested against fault resistances ranging from 10 to 485 Ω. The simulation results show that the proposed method can accurately estimate the fault site to a precision of 485 Ω and is more robust.


Asunto(s)
Algoritmos , Redes Neurales de la Computación , Teorema de Bayes , Simulación por Computador , Tiempo
16.
Isr Med Assoc J ; 24(4): 246-252, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-35415984

RESUMEN

BACKGROUND: Hookah smoking is a common activity around the world and has recently become a trend among youth. Studies have indicated a relationship between hookah smoking and a high prevalence of chronic diseases, cancer, cardiovascular, and infectious diseases. In Israel, there has been a sharp increase in hookah smoking among the Arabs. Most studies have focused mainly on hookah smoking among young people. OBJECTIVES: To examine the association between hookah smoking and socioeconomic characteristics, health status and behaviors, and knowledge in the adult Arab population and to build a prediction model using machine learning methods. METHODS: This quantitative study based is on data from the Health and Environment Survey conducted by the Galilee Society in 2015-2016. The data were collected through face-to-face interviews with 2046 adults aged 18 years and older. RESULTS: Using machine learning, a prediction model was built based on eight features. Of the total study population, 13.0% smoked hookah. In the 18-34 age group, 19.5% smoked. Men, people with lower level of health knowledge, heavy consumers of energy drinks and alcohol, and unemployed people were more likely to smoke hookah. Younger and more educated people were more likely to smoke hookah. CONCLUSIONS: Hookah smoking is a widespread behavior among adult Arabs in Israel. The model generated by our study is intended to help health organizations reach people at risk for smoking hookah and to suggest different approaches to eliminate this phenomenon.


Asunto(s)
Árabes , Fumar en Pipa de Agua , Adolescente , Adulto , Algoritmos , Humanos , Israel/epidemiología , Aprendizaje Automático , Masculino , Fumar en Pipa de Agua/epidemiología , Adulto Joven
17.
Int J Mol Sci ; 23(22)2022 Nov 21.
Artículo en Inglés | MEDLINE | ID: mdl-36430952

RESUMEN

Histological structure of thrombi is a strong determinant of the outcome of vascular recanalization therapy, the only treatment option for acute ischemic stroke (AIS) patients. A total of 21 AIS patients from this study after undergoing non-enhanced CT scan and multimodal MRI were treated with mechanical stent-based and manual aspiration thrombectomy, and thromboembolic retrieved from a cerebral artery. Complementary histopathological and imaging analyses were performed to understand their composition with a specific focus on fibrin, von Willebrand factor, and neutrophil extracellular traps (NETs). Though distinct RBC-rich and platelet-rich areas were found, AIS patient thrombi were overwhelmingly platelet-rich, with 90% of thrombi containing <40% total RBC-rich contents (1.5 to 37%). Structurally, RBC-rich areas were simple, consisting of tightly packed RBCs in thin fibrin meshwork with sparsely populated nucleated cells and lacked any substantial von Willebrand factor (VWF). Platelet-rich areas were structurally more complex with thick fibrin meshwork associated with VWF. Plenty of leukocytes populated the platelet-rich areas, particularly in the periphery and border areas between platelet-rich and RBC-rich areas. Platelet-rich areas showed abundant activated neutrophils (myeloperoxidase+ and neutrophil-elastase+) containing citrullinated histone-decorated DNA. Citrullinated histone-decorated DNA also accumulated extracellularly, pointing to NETosis by the activated neutrophils. Notably, NETs-containing areas showed strong reactivity to VWF, platelets, and high-mobility group box 1 (HMGB1), signifying a close interplay between these components.


Asunto(s)
Trampas Extracelulares , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Trombosis , Humanos , Trampas Extracelulares/metabolismo , Neutrófilos/metabolismo , Factor de von Willebrand/metabolismo , Histonas , Accidente Cerebrovascular/patología , Trombosis/patología , Fibrina/metabolismo , ADN
18.
Nucleic Acids Res ; 47(2): 700-715, 2019 01 25.
Artículo en Inglés | MEDLINE | ID: mdl-30476274

RESUMEN

Mammalian-wide interspersed repeats (MIRs) are retrotransposed elements of mammalian genomes. Here, we report the specific binding of zinc finger protein ZNF768 to the sequence motif GCTGTGTG (N20) CCTCTCTG in the core region of MIRs. ZNF768 binding is preferentially associated with euchromatin and promoter regions of genes. Binding was observed for genes expressed in a cell type-specific manner in human B cell line Raji and osteosarcoma U2OS cells. Mass spectrometric analysis revealed binding of ZNF768 to Elongator components Elp1, Elp2 and Elp3 and other nuclear factors. The N-terminus of ZNF768 contains a heptad repeat array structurally related to the C-terminal domain (CTD) of RNA polymerase II. This array evolved in placental animals but not marsupials and monotreme species, displays species-specific length variations, and possibly fulfills CTD related functions in gene regulation. We propose that the evolution of MIRs and ZNF768 has extended the repertoire of gene regulatory mechanisms in mammals and that ZNF768 binding is associated with cell type-specific gene expression.


Asunto(s)
Retroelementos , Factores de Transcripción/metabolismo , Transcripción Genética , Sitios de Unión , Línea Celular Tumoral , Supervivencia Celular , ADN/química , ADN/metabolismo , Eucromatina/metabolismo , Regulación de la Expresión Génica , Humanos , Motivos de Nucleótidos , Secuencias Repetitivas de Ácidos Nucleicos , Factores de Transcripción/química
19.
BMC Ophthalmol ; 20(1): 347, 2020 Aug 26.
Artículo en Inglés | MEDLINE | ID: mdl-32847574

RESUMEN

BACKGROUND: To calculate and evaluate the prevalence of reduced uncorrected distant visual acuity (UCDVA) in primary, middle and high schools in 6 districts of Changsha, Hunan, China. METHODS: A population-based retrospective study was conducted in 239 schools in 6 districts of Changsha. After routine eye examination to rule out diseases that can affect refraction, 250,980 eligible students from primary, middle and high schools were enrolled in the survey. Then the uncorrected distant and near visual acuity of each eye were measured. Categories of schools, districts, grades, eye exercises and sports time were also documented and analyzed. RESULTS: The overall prevalence of reduced UCDVA was 51.8% (95% confidence interval [CI]: 51.6-52.0%) in 6 districts of Changsha. Results of individual districts were as follows: Furong district 59.9%(95% CI: 57.9-61.8%), Tianxin district 62.3%(95% CI: 60.5-64.0%), Wangcheng district 47.8%(95% CI: 46.8-48.8%), Kaifu district 58.5%(95% CI: 58.0-58.9%), Yuhua district 47.0%(95% CI: 46.7-47.4%) and Yuelu district 52.6%(95% CI: 52.3-52.9%). The proportion of normal VA is seen to decrease from primary grade 3. The proportion of mildly reduced UCDVA is higher in primary grade 1 and 2. The proportion of moderately reduced UCDVA remains similar during 12 grades. The proportion of severely reduced UCDVA increases with grades. Multivariate analysis shows that the prevalence of reduced UCDVA is higher in key schools (risk ratio [RR] = 1.47, 95% CI 1.44-1.50) than non-key schools. CONCLUSIONS: According to the existing data analysis results, the prevalence of reduced UCDVA among primary, middle and high school students in Changsha is very high. Some effective measures need to be taken to prevent it.


Asunto(s)
Instituciones Académicas , Adolescente , Niño , China/epidemiología , Humanos , Prevalencia , Estudios Retrospectivos , Agudeza Visual
20.
Energy Convers Manag ; 222: 113188, 2020 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-32834298

RESUMEN

Thermoeconomic analysis, a combined application of thermodynamic and economic analyses, has emerged as an important tool to optimize the performance of desalination systems. Contrary to conventional economic analysis, it offers flexibility to investigate and improve the performance of each component in the system, individually. The current paper presents a comprehensive framework for conducting thermoeconomic analysis of desalination systems. In this regard, different energy calculation methods are discussed first. Then a detailed review of theoretical developments of thermoeconomic analyses is conducted to summarize the correlations/magnitude of important economic parameters. This is followed by a discussion on cost balance equations for important desalination components. Finally, a systematic thermoeconomic analysis model is developed for the mechanical vapor compression desalination system operating under different arrangements as an example. The monetary value of each stream calculated using appropriate fiscal parameters in the system is presented in the form of a cost flow diagram. The study can be used to conduct the thermoeconomic analysis of other commercial desalination systems.

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