Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 5.698
Filtrar
1.
Mil Med Res ; 8(1): 13, 2021 02 16.
Artículo en Inglés | MEDLINE | ID: mdl-33593415

RESUMEN

BACKGROUND: Until January 18, 2021, coronavirus disease-2019 (COVID-19) has infected more than 93 million individuals and has caused a certain degree of panic. Viral pneumonia caused by common viruses such as respiratory syncytial virus, rhinovirus, human metapneumovirus, human bocavirus, and parainfluenza viruses have been more common in children. However, the incidence of COVID-19 in children was significantly lower than that in adults. The purpose of this study was to describe the clinical manifestations, treatment and outcomes of COVID-19 in children compared with those of other sources of viral pneumonia diagnosed during the COVID-19 outbreak. METHODS: Children with COVID-19 and viral pneumonia admitted to 20 hospitals were enrolled in this retrospective multi-center cohort study. A total of 64 children with COVID-19 were defined as the COVID-19 cohort, of which 40 children who developed pneumonia were defined as the COVID-19 pneumonia cohort. Another 284 children with pneumonia caused by other viruses were defined as the viral pneumonia cohort. The epidemiologic, clinical, and laboratory findings were compared by Kolmogorov-Smirnov test, t-test, Mann-Whitney U test and Contingency table method. Drug usage, immunotherapy, blood transfusion, and need for oxygen support were collected as the treatment indexes. Mortality, intensive care needs and symptomatic duration were collected as the outcome indicators. RESULTS: Compared with the viral pneumonia cohort, children in the COVID-19 cohort were mostly exposed to family members confirmed to have COVID-19 (53/64 vs. 23/284), were of older median age (6.3 vs. 3.2 years), and had a higher proportion of ground-glass opacity (GGO) on computed tomography (18/40 vs. 0/38, P < 0.001). Children in the COVID-19 pneumonia cohort had a lower proportion of severe cases (1/40 vs. 38/284, P = 0.048), and lower cases with high fever (3/40 vs. 167/284, P < 0.001), requiring intensive care (1/40 vs. 32/284, P < 0.047) and with shorter symptomatic duration (median 5 vs. 8 d, P < 0.001). The proportion of cases with evaluated inflammatory indicators, biochemical indicators related to organ or tissue damage, D-dimer and secondary bacterial infection were lower in the COVID-19 pneumonia cohort than those in the viral pneumonia cohort (P < 0.05). No statistical differences were found in the duration of positive PCR results from pharyngeal swabs in 25 children with COVID-19 who received antiviral drugs (lopinavir-ritonavir, ribavirin, and arbidol) as compared with duration in 39 children without antiviral therapy [median 10 vs. 9 d, P = 0.885]. CONCLUSION: The symptoms and severity of COVID-19 pneumonia in children were no more severe than those in children with other viral pneumonia. Lopinavir-ritonavir, ribavirin and arbidol do not shorten the duration of positive PCR results from pharyngeal swabs in children with COVID-19. During the COVID-19 outbreak, attention also must be given to children with infection by other pathogens infection.


Asunto(s)
/epidemiología , Síndrome Respiratorio Agudo Grave/epidemiología , Adolescente , /terapia , Niño , Preescolar , China/epidemiología , Femenino , Humanos , Lactante , Masculino , Pandemias , Estudios Retrospectivos , Síndrome Respiratorio Agudo Grave/fisiopatología , Síndrome Respiratorio Agudo Grave/terapia , Índice de Severidad de la Enfermedad
2.
Nanotechnology ; 2021 Feb 24.
Artículo en Inglés | MEDLINE | ID: mdl-33626514

RESUMEN

Narrow bandgap semiconductors like InSb are very suitable for high-performance room temperature infrared photodetectors, but the fragile nature of the wafer materials hinders their application as inflexible/wearable devices. Here, we present a method to fabricate a photodetector device of assembled crystalline InSb nanowires (NWs) arrays on a flexible substrate that balances the high performance and flexibility therefore facilitate its application in wearable devices. The InSb NWs were synthesized by means of vapor-liquid-solid (VLS) technique, with gold nanoclusters as seeding particles. The morphological and crystal properties were investigated by using scanning electron microscopy (SEM), X-ray diffraction (XRD) and high-resolution transmission electron microscopy (HRTEM), which revealed the unique spike shape and high crystallinity with (111) and (220) planes of InSb NWs. The flexible infrared photodetector devices were fabricated by transferring the nanowires onto transparent and stretchable polydimethylsiloxane (PDMS) substrate with pre-deposited gold electrodes. Current versus time measurement of photodetector devices under light shown photo-responsivity and sensitivity to mid-IR at the bias as low as 0.1V while attached to curved surfaces (suitable for skin implants). High-performance NW device yields efficient rise and decay times down to 1 second and short time lag for infrared detection. Based on dark current, calculated specific detectivity of the flexible photodetector was 1.4 x 1012 Jones. The performance and durably render such devices to be promising application as wearable infrared photodetectors.

3.
Artículo en Inglés | MEDLINE | ID: mdl-33629455

RESUMEN

For the first time silver nanoclusters containing Ag(0) atoms protected by amino acids have been synthesized and structurally characterized. Chiral superatomic silver nanoclusters [Ag 47 L 12 (C≡C t Bu) 16 ]BF 4 (L = l -/ d - valine or l -/ d - isoleucine) have been prepared by reducing AgC≡C t Bu and amino acids (AAs) with NaBH 4 . Single crystal X-ray diffraction revealed that these clusters have T symmetry, and the Ag 47 metal kernel can be viewed as a tetracapped truncated tetrahedron (Ag 17 ) surrounded with six W-shaped Ag 5 units. The clusters are homochiral as evidenced by CD measurements. As for the strong CD signals, large contributions are found from the occupied Ag s,p states (superatomic D states) near the Fermi level. Electron counting revealed that these clusters are 18-electron systems, which suggests they are superatomic clusters. Their superatomic nature with a 1S 2 1P 6 1D 10 configuration was supported by DFT calculations. This work paves the way of taking AAs as facile chiral induction agents for the synthesis of metal nanoclusters.

4.
J Adv Nurs ; 2021 Feb 25.
Artículo en Inglés | MEDLINE | ID: mdl-33629754

RESUMEN

AIMS: To develop the Nurse's Communication Ability with Angry Patients Scale (NCAAPS) and evaluate its psychometric properties. DESIGN: An instrument development and validation study. METHODS: The survey was administered to 501 nurses from different emergency departments in China between 2 August 2019 and 3 October 2019. Data from 456 completed questionnaires were analysed to identify the factor structure of the NCAAPS. RESULTS: The content validity index was satisfactory. Four factors were included and 71.25% of the total variance was explained by 19 items in NCAAPS. Confirmatory factor analysis supported the four-factor structure. Cronbach's α coefficient was 0.96 for the overall scale and 0.81-0.92 for its subscales. Test-retest reliability was 0.740. CONCLUSION: We consider the NCAAPS to be a useful tool for measuring the ability of nurses to communicate with angry patients. IMPACT: It is anticipated that this new scale will help educators to identify specific areas of deficiency that could be targeted with training to improve the ability of nursing staff to communicate with angry patients.

5.
6.
Chemosphere ; 274: 129779, 2021 Jan 24.
Artículo en Inglés | MEDLINE | ID: mdl-33540317

RESUMEN

The degradation potential of microplastics remains a critical issue for researching marine litter, and it is one of the most important factors that can be used for calculating the persistence time of microplastics in certain conditions. However, there are lack of standard or approved methods for estimating the ageing stage of environmental microplastics. In this study, the potential of spectral-image fusion strategy was investigated to analyze the degradation degree of polyethylene microplastics in natural exposure of coastline. The proposed spectral-image fusion linear model showed a significant ability to classify the degradation degree of environmental microplastics samples with the best accuracy of 97.1% as compared to two single-sensing information-based linear models (with one spectral wavelength of the carbonyl index at 1720 cm-1 or three-channel components from LAB color-space). This is the first attempt to qualitatively measure the degradation degree of the naturally exposed microplastics based on spectral-image fusion model. The proposed fusion model based strategy is an effective tool for predicting the degradation degree of the field exposed microplastics.

7.
BMC Urol ; 21(1): 26, 2021 Feb 17.
Artículo en Inglés | MEDLINE | ID: mdl-33596896

RESUMEN

BACKGROUND: A history of prior cancer commonly results in exclusion from cancer clinical trials. However, whether a prior cancer history has an adversely impact on clinical outcomes for patients with advanced prostate cancer (APC) remains largely unknown. We therefore aimed to investigate the impact of prior cancer history on these patients. METHODS: We identified patients with advanced prostate cancer diagnosed from 2004 to 2010 in the Surveillance, Epidemiology, and End Results (SEER) database. Propensity score matching (PSM) was used to balance baseline characteristics. Kaplan-Meier method and the Cox proportional hazard model were utilized for survival analysis. RESULTS: A total of 19,772 eligible APC patients were included, of whom 887 (4.5 %) had a history of prior cancer. Urinary bladder (19 %), colon and cecum (16 %), melanoma of the skin (9 %) malignancies, and non-hodgkin lymphoma (9 %) were the most common types of prior cancer. Patients with a history of prior cancer had slightly inferior overall survival (OS) (AHR = 1.13; 95 % CI [1.02-1.26]; P = 0.017) as compared with that of patients without a prior cancer diagnosis. Subgroup analysis further indicated that a history of prior cancer didn't adversely impact patients' clinical outcomes, except in patients with a prior cancer diagnosed within 2 years, at advanced stage, or originating from specific sites, including bladder, colon and cecum, or lung and bronchus, or prior chronic lymphocytic leukemia. CONCLUSIONS: A large proportion of APC patients with a prior cancer history had non-inferior survival to that of patients without a prior cancer diagnosis. These patients may be candidates for relevant cancer trials.

8.
BMC Public Health ; 21(1): 354, 2021 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-33588816

RESUMEN

BACKGROUND: There is limited information about the types of recreational drugs used by men who have sex with men (MSM) in China or the consequent impact on sexual health and human immunodeficiency virus (HIV) acquisition. METHODS: We recruited MSM from seven cities in China between 2012 and 2013 using multiple approaches including advertisements on gay websites, collaborating with local MSM community-based organizations, peer referrals, and venues such as gay bars and bathrooms visited by MSM. We divided participants into four subgroups based on the number of recreational drugs (RDs) used in the previous 6 months. We defined use of multiple RDs as use of ≥2 types of RDs. Demographics and HIV-related high-risk behaviors were collected, and blood samples were tested for recent HIV infection by the HIV-1 subtypes B, E, and D immunoglobulin G capture enzyme immunoassay (BED-CEIA). We used multivariable logistic regression adjusted for sociodemographics to determine the adjusted odds ratios (aORs) and associated 95% confidence intervals (CIs) of the subgroups of RD use for recent or established HIV infection. RESULTS: A total of 4496 Chinese MSM participated; 28.4% used RDs, and 5% used multiple types of RDs. The prevalence of each RD use was as follows: poppers (25.9%), ecstasy (2.4%), ketamine (1.2%), amphetamine (0.6%), tramadol (0.4%), methamphetamine (3.8%), and codeine (1.9%). Users of multiple RDs commonly used poppers combined with one or more other types of RDs. Multiple RD users were likely to be aged 26-30 years (vs. 18-25 and > 30 years), live in non-local cities (vs. local cities), never married (vs. married), have a high monthly income (vs. no income and 1-599 USD), use versatile positions during anal intercourse (vs. top or bottom), and have inadequate HIV-related prevention knowledge (vs. adequate). As the number of RDs used in the previous 6 months increased, the prevalence of HIV-related high-risk behaviors increased (P < 0.05 for all). The odds of recent HIV infection were higher among those who used one type (aOR = 2.2, 95% CI: 1.5-3.0) or two types of RD (aOR=2.3, 95% CI: 1.0-5.2) in the previous 6 months compared to the odds among those who did not use RDs. CONCLUSION: The level and pattern of multiple RD use among Chinese MSM were different from high-income countries. MSM who used more RDs are more likely to engage in high-risk sexual behaviors, and these behaviors may be associated with increases in new HIV infections.

9.
Med Sci Educ ; : 1-9, 2021 Feb 18.
Artículo en Inglés | MEDLINE | ID: mdl-33619444

RESUMEN

This study conveys preclinical healthcare professions students' sentiments at 14 universities during the 2020 COVID-19 pandemic. Essays about students' thoughts and experiences were thematically sorted and revealed a variety of sentiments spanning from positive (e.g., pride, respect) to the more negative (e.g., anxiety, guilt, disappointment, anger). Themes revealed respect for the healthcare profession, but also the realization of its limitations, sacrifices, and risks. Healthcare profession educators need to be aware that the COVID-19 pandemic has affected students emotionally and may have long-term effects on the global healthcare profession. This study can serve as a historic documentation of how this generation of students felt and adds to the literature on how the pandemic affected the healthcare profession.

10.
J Speech Lang Hear Res ; : 1-13, 2021 Feb 23.
Artículo en Inglés | MEDLINE | ID: mdl-33621117

RESUMEN

Purpose The value of shared reading as an opportunity for learning word meanings, or semantics, is well established; it is less clear whether children learn about the orthography, or word spellings, in this context. We tested whether children can learn the spellings and meanings of new words at the same time during a tightly controlled shared reading session. We also examined whether individual differences in either or both of orthographic and semantic learning during shared reading in English were related to word reading in English and French concurrently and 6 months longitudinally in emergent English-French bilinguals. Method Sixty-two Grade 1 children (35 girls; M age = 75.89 months) listened to 12 short stories, each containing four instances of a novel word, while the examiner pointed to the text. Choice measures of the spellings and meanings of the novel words were completed immediately after reading each set of three stories and again 1 week later. Standardized measures of word reading as well as controls for nonverbal reasoning, vocabulary, and phonological awareness were also administered. Results Children scored above chance on both immediate and delayed measures of orthographic and semantic learning. Orthographic learning was related to both English and French word reading at the same time point and 6 months later. In contrast, the relations between semantic learning and word reading were nonsignificant for both languages after including controls. Conclusion Shared reading is a valuable context for learning both word meanings and spellings, and the learning of orthographic representations in particular is related to word reading abilities. Supplemental Material https://doi.org/10.23641/asha.13877999.

11.
Stem Cells ; 2021 Feb 23.
Artículo en Inglés | MEDLINE | ID: mdl-33621403

RESUMEN

Type 2 diabetes mellitus (T2DM) is a major threat to global public health, with increasing prevalence as well as high morbidity and mortality, to which immune dysfunction has been recognized as a crucial contributor. Mesenchymal stromal cells (MSCs), obtained from various sources and possessing potent immunomodulatory abilities, have displayed great therapeutic potential for T2DM. Interestingly, the immunomodulatory capabilities of MSCs are endowed and plastic. Among the multiple mechanisms involved in MSC-mediated immune regulation, the paracrine effects of MSCs have attracted much attention. Of note, extracellular vesicles (EVs), an important component of MSC secretome, have emerged as pivotal mediators of their immunoregulatory effects. Particularly, the necrobiology of MSCs, especially apoptosis, has recently been revealed to affect their immunomodulatory functions in vivo. In specific, a variety of preclinical studies have demonstrated the beneficial effects of MSCs on improving islet function and ameliorating insulin resistance. More importantly, clinical trials have further uncovered the therapeutic potential of MSCs for T2DM. In this review, we outline current knowledge regarding the plasticity and underlying mechanisms of MSC-mediated immune modulation, focusing on the paracrine effects. We also summarize the applications of MSC-based therapies for T2DM in both preclinical studies and clinical trials, with particular emphasis on the modulation of immune system. © AlphaMed Press 2021 SIGNIFICANCE STATEMENT: Type 2 diabetes mellitus (T2DM) is a serious disease with high morbidity and mortality around the world. In the course of the disease, immune dysfunction has been identified as a key pathogenic factor and also deemed as a potential therapeutic target. Remarkably, mesenchymal stromal cells (MSCs) possess pivotal immunoregulatory function mainly via paracrine mechanism. In the present review, we demonstrate the plasticity and underlying mechanisms of MSC-mediated immune modulation, and further uncovered the therapeutic potential of MSCs for T2DM.

12.
Artículo en Inglés | MEDLINE | ID: mdl-33624914

RESUMEN

The tracking of cellular senescence usually depends on the detection of senescence-associated ß-galactosidase (SA-ß-gal). Previous probes for SA-ß-gal with this purpose only cover a single dimension: the accumulation of this enzyme in lysosomes. However, this is insufficient to determine the destiny of senescence because endogenous ß-gal enriched in lysosomes is not only related to senescence, but also to some other physiological processes. To address this issue, we introduce our fluorescent probes including a second dimension: lysosomal pH, since de-acidification is a unique feature of the lysosomes in senescent cells. With this novel design, our probes achieved excellent discrimination of SA-ß-gal from cancer-associated ß-gal, which enables them to track cellular senescence as well as tissue aging more precisely. Our crystal structures of a model enzyme E. coli ß-gal mutant (E537Q) complexed with each probe further revealed the structural basis for probe recognition.

13.
Artículo en Inglés | MEDLINE | ID: mdl-33624917

RESUMEN

Amino acid dehydrogenases (AADHs) have shown considerable potential as biocatalysts in the asymmetric synthesis of chiral amino acids. However, compared to the widely studied α-AADHs, limited knowledge is available about ß-AADHs that enable the synthesis of ß-amino acids. Herein we report the crystal structures of a l - erythro -3,5-diaminohexanoate dehydrogenase and its variants, the only known member of ß-AADH family. Crystal structure analysis, site-directed mutagenesis studies and quantum chemical calculations revealed the differences in the substrate binding and catalytic mechanism from α-AADHs. A number of rationally engineered variants were then obtained with improved activity by 110-800 times toward various aliphatic ß-amino acids without enantioselectivity trade-off. Two ß-amino acids were prepared using the outstanding variants with excellent enantioselectivity (> 99% ee ) and high isolated yields (86%-87%). These results provide important insights into the molecular mechanism of 3,5-DAHDH, and establish a solid foundation for further design of ß-AADHs for the asymmetric synthesis of ß-amino acids.

14.
J Agric Food Chem ; 2021 Feb 19.
Artículo en Inglés | MEDLINE | ID: mdl-33605718

RESUMEN

Considering the severity of plant pathogen resistance toward commonly used agricultural microbicides, as well as the potential threats of agrichemicals to the eco-environment, there is a pressing need for antimicrobial approaches that are capable of inactivating pathogens efficiently without the risk of inducing resistances and harm. In this work, a porphyrin metal-organic framework (MOF) nanocomposite was constructed by incorporating 5,10,15,20-tetrakis(1-methyl-4-pyridinio)porphyrin tetra(p-toluenesulfonate) (TMPyP) as a photosensitizer (PS) in the cage of a variant MOF (HKUST-1) to efficiently produce singlet oxygen (1O2) to inactivate plant pathogens under light irradiation. The results showed that the prepared PS@MOF had a loading rate of PS about 12% (w/w) and excellent and broad-spectrum photodynamic antimicrobial activity in vitro against three plant pathogenic fungi and two pathogenic bacteria. Moreover, PS@MOF showed outstanding control efficacy against Sclerotinia sclerotiorum on cucumber in the pot experiment. Allium cepa chromosome aberration assays and safety evaluation on cucumber and Chinese cabbage indicated that PS@MOF had no genotoxicity and was safe to plants. Thus, porphyrin MOF demonstrated a great potential as an alternative and efficient new microbicide for sustainable plant disease management.

15.
Sci Adv ; 7(7)2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33568480

RESUMEN

Evidence that offspring traits can be shaped by parental life experiences in an epigenetically inherited manner paves a way for understanding the etiology of depression. Here, we show that F1 offspring born to F0 males of depression-like model are susceptible to depression-like symptoms at the molecular, neuronal, and behavioral levels. Sperm small RNAs, and microRNAs (miRNAs) in particular, exhibit distinct expression profiles in F0 males of depression-like model and recapitulate paternal depressive-like phenotypes in F1 offspring. Neutralization of the abnormal miRNAs in zygotes by antisense strands rescues the acquired depressive-like phenotypes in F1 offspring born to F0 males of depression-like model. Mechanistically, sperm miRNAs reshape early embryonic transcriptional profiles in the core neuronal circuits toward depression-like phenotypes. Overall, the findings reveal a causal role of sperm miRNAs in the inheritance of depression and provide insight into the mechanism underlying susceptibility to depression.

16.
Mol Ther ; 2021 Feb 10.
Artículo en Inglés | MEDLINE | ID: mdl-33578037

RESUMEN

Alzheimer's disease (AD)-one of the most common neurodegenerative diseases worldwide-impairs cognition, memory, and language ability and causes dementia. However, AD pathogenesis remains poorly elucidated. Recently, a potential link between AD and circular RNAs (circRNAs) has been uncovered, but only a few circRNAs that might be involved in AD have been identified. Here, we systematically investigated circRNAs in the APP/PS1 model mouse brain through deep RNA sequencing. We report that circRNAs are markedly enriched in the brain and that several circRNAs exhibit differential expression between wild-type and APP/PS1 mice. We characterized one abundant circRNA, circTulp4, derived from Intron1 of the gene Tulp4. Our results indicate that circTulp4 predominantly localizes in the nucleus and interacts with U1 small nuclear ribonucleoprotein particle (snRNP) and RNA polymerase II to modulate the transcription of its parental gene, Tulp4, and thereby regulate the function of the nervous system, and might participate in the development of AD.

17.
Nanoscale ; 13(7): 4029-4037, 2021 Feb 25.
Artículo en Inglés | MEDLINE | ID: mdl-33533377

RESUMEN

The need for fast and accurate analysis of low-concentration species is ubiquitous nowadays. The separation and purification techniques restrict the highly sensitive detection of low-abundance nanoparticles. On the other hand, the commonly used separation techniques of labeling procedures limit their implementation in various applications. We report a microfluidic system with ultrahigh magnetic field for the label-free separation of nanoscale particles. Using high-permeability alloys and on-chip integrated magnetic micro-pole arrays, the external strong magnetic field can be conducted into the microfluidic device to form a magnetic field of high intensity and gradient, therefore separating particles of nanometer size with high efficiency. An ultrahigh gradient magnetic field greater than 105 T m-1 can be generated in the separation channel. Moreover, a negative magnetophoretic technique to separate nanoparticles is established in this device. Then, the label-free separation of nanoparticles is achieved in this microfluidic system perfused by a ferrofluid with an extremely low concentration (0.01%). A mixture of 0.2 µm and 1 µm particles is used to verify the performance of the device, where the recovery rate of 0.2 µm particles is 88.79%, and the purity reaches 94.72%. Experimental results show that the device can efficiently separate nanoscale particles with ultrahigh resolution, and in future, it may develop into a versatile and robust tool for the separation and purification of the biological samples of nanometer size.

18.
Food Chem ; 349: 128982, 2021 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-33561797

RESUMEN

This paper reports a selective, sensitive, and miniaturized analytical method based on a molecularly imprinted graphene oxide (MIP-GO) composite as adsorbent for miniaturized tip solid-phase extraction (MTSPE) to determine naphthalene-derived plant growth regulators (PGRs) in apples. The proposed method combines the advantages of MIP-GOs (high selectivity), MTSPE (low consumption), and high-performance liquid chromatography-fluorescence detection (high sensitivity). Under optimized conditions, the method exhibited appreciable linearity (2.00-200 ng/g), low detection limits (0.21-0.53 ng/g), high accuracy (absolute recoveries: 87.6-99.5%), and high precision (relative standard deviations ≤ 3.0%), along with low consumption (0.5 mL sample solution and 2.0 mg adsorbent). In addition, the adsorption performance of the MIP-GO adsorbent did not decrease over ten months, highlighting the long storage and operational lifetime of the adsorbent. The proposed method was employed for the analysis of naphthalene-derived PGR residues in apples and exhibited promising potential for application in food safety analysis.

19.
Endokrynol Pol ; 2021 Feb 23.
Artículo en Inglés | MEDLINE | ID: mdl-33619716

RESUMEN

Chronic hepatitis B is a severe, life-threatening health problem that can lead to cirrhosis and hepatocellular carcinoma. Nowadays, the management of hepatitis B is involved in nucleostide analogue. Adefovir dipivoxil is widely used in antivirus therapy, which can suppress hepatitis B virus replication in most patients, even in lamivudine-resistant patients. However, increasing reports about the adverse events were found in the last few years. We herein discuss one of its complications, hypophosphatemic osteomalacia, through a case report.

20.
Elife ; 102021 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-33587034

RESUMEN

The canonical Wnt pathway transcriptional co-activator ß-catenin regulates self-renewal and differentiation of mammalian nephron progenitor cells (NPCs). We modulated ß-catenin levels in NPC cultures using the GSK3 inhibitor CHIR9902 (CHIR) to examine opposing developmental actions of ß-catenin. Low CHIR-mediated maintenance and expansion of NPCs is independent of direct engagement of TCF/LEF/ß-catenin transcriptional complexes at low CHIR-dependent cell-cycle targets. In contrast, in high CHIR, TCF7/LEF1/ß-catenin complexes replaced TCF7L1/TCF7L2 binding on enhancers of differentiation-promoting target genes. Chromosome confirmation studies showed pre-established promoter-enhancer connections to these target genes in NPCs. High CHIR-associated de novo looping was observed in positive transcriptional feedback regulation to the canonical Wnt pathway. Thus, ß-catenin's direct transcriptional role is restricted to the induction of NPCs where rising ß-catenin levels switch inhibitory TCF7L1/TCF7L2 complexes to activating LEF1/TCF7 complexes at primed gene targets poised for rapid initiation of a nephrogenic program.

SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA