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1.
ACS Nano ; 18(22): 14403-14413, 2024 Jun 04.
Artículo en Inglés | MEDLINE | ID: mdl-38775684

RESUMEN

The highly reversible plating/stripping of Zn is plagued by dendrite growth and side reactions on metallic Zn anodes, retarding the commercial application of aqueous Zn-ion batteries. Herein, a distinctive nano dual-phase diamond (NDPD) comprised of an amorphous-crystalline heterostructure is developed to regulate Zn deposition and mechanically block dendrite growth. The rich amorphous-crystalline heterointerfaces in the NDPD endow modified Zn anodes with enhanced Zn affinity and result in homogeneous nucleation. In addition, the unparalleled hardness of the NDPD effectively overcomes the high growth stress of dendrites and mechanically impedes their proliferation. Moreover, the hydrophobic surfaces of the NDPD facilitate the desolvation of hydrate Zn2+ and prevent water-mediated side reactions. Consequently, the Zn@NDPD presents an ultrastable lifespan exceeding 3200 h at 5 mA cm-2 and 1 mAh cm-2. The practical application potential of Zn@NDPD is further demonstrated in full cells. This work exhibits the great significance of a chemical-mechanical synergistic anode modification strategy in constructing high-performance aqueous Zn-ion batteries.

2.
J Mol Diagn ; 25(9): 682-691, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37599029

RESUMEN

Twin pregnancy constitutes significant risks for maternal and fetal health, which is usually detected by ultrasound examination at early gestation. However, the imaging-based approach may not accurately identify all twins confounded by practical or clinical variables. The analysis of fetal cell-free DNA in noninvasive prenatal screening assays can completement the ultrasound method for twin detection, which differentiates fraternal or identical twins based on their distinct genotypes. Here, a new noninvasive prenatal screening employing high-coverage next-generation sequencing for targeted nucleotide polymorphisms was developed for detection of zygosity and determination of fetal fraction in twin pregnancies. This method utilizes a binary analysis of both the number and allelic fraction of fetus-specific single-nucleotide polymorphisms to infer the zygosity. In 323 samples collected from 215 singleton, 90 dizygotic, and 18 monozygotic twin pregnancies, all 90 dizygotic twins were correctly detected, with a 100% sensitivity and a 100% specificity. In addition, this method can detect complex pregnancies, such as egg donors, contamination, and twins with complete hydatidiform mole. The fetus-specific fetal fraction change was monitored in nine dizygotic twin pregnancies, which demonstrated highly variable dynamics of fetal cell-free DNA turnover up to 7 weeks after twin reduction. Overall, this study provides a new noninvasive prenatal screening strategy for the accurate identification of twin zygosity and quantification of fetal fraction, which has important clinical implications for the management of twin pregnancies.


Asunto(s)
Ácidos Nucleicos Libres de Células , Embarazo Gemelar , Femenino , Embarazo , Humanos , Embarazo Gemelar/genética , Polimorfismo de Nucleótido Simple , Feto , Alelos
3.
Cell Discov ; 8(1): 109, 2022 Oct 13.
Artículo en Inglés | MEDLINE | ID: mdl-36229437

RESUMEN

Current non-invasive prenatal screening (NIPS) analyzes circulating fetal cell-free DNA (cfDNA) in maternal peripheral blood for selected aneuploidies or microdeletion/duplication syndromes. Many genetic disorders are refractory to NIPS largely because the maternal genetic material constitutes most of the total cfDNA present in the maternal plasma, which hinders the detection of fetus-specific genetic variants. Here, we developed an innovative sequencing method, termed coordinative allele-aware target enrichment sequencing (COATE-seq), followed by multidimensional genomic analyses of sequencing read depth, allelic fraction, and linked single nucleotide polymorphisms, to accurately separate the fetal genome from the maternal background. Analytical confounders including multiple gestations, maternal copy number variations, and absence of heterozygosity were successfully recognized and precluded for fetal variant analyses. In addition, fetus-specific genomic characteristics, including the cfDNA fragment length, meiotic error origins, meiotic recombination, and recombination breakpoints were identified which reinforced the fetal variant assessment. In 1129 qualified pregnancies tested, 54 fetal aneuploidies, 8 microdeletions/microduplications, and 8 monogenic variants were detected with 100% sensitivity and 99.3% specificity. Using the comprehensive cfDNA genomic analysis tools developed, we found that 60.3% of aneuploidy samples had aberrant meiotic recombination providing important insights into the mechanism underlying meiotic nondisjunctions. Altogether, we show that the genetic deconvolution of the fetal and maternal cfDNA enables thorough and accurate delineation of fetal genome which paves the way for the next-generation prenatal screening of essentially all types of human genetic disorders.

4.
Am J Transl Res ; 14(5): 3448-3455, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35702122

RESUMEN

Percutaneous vertebroplasty (PVP) via the unilateral posterosuperior approach has achieved good clinical results for the treatment of osteoporotic vertebral compression fractures. This study compared the biomechanical performance of a single vertebral body after PVP by the unilateral posterosuperior, unipedicular, and bipedicular approaches. Twenty-one vertebral bodies from the osteoporotic spine segments (T11-L1) of seven older female cadavers were randomly assigned to the unipedicular (group A), bipedicular (group B), or unilateral posterosuperior approach group (group C). After constructing the fracture compression model, PVP was performed by the different approaches. CT scans showed symmetrical, evenly distributed bone cement in groups B and C and unilaterally distributed cement in group A. The recovery rates of the anterior vertebral body height in groups B and C were significantly higher than those in group A after PVP (P<0.05). The left curvature elastic moduli after PVP were significantly higher in group A than in groups B and C; however, the right curvature moduli in group A were lower than in the other groups (P<0.05). The flexion, extension, and vertical compression elastic moduli were lowest in group B (P<0.05). After PVP, failure strength and stiffness in groups B and C were comparable (P>0.05) and higher than those in group A (P<0.05). PVP through the unilateral posterosuperior approach was superior to the unipedicular approach and comparable to the bipedicular approach based on the biomechanical performance of a single vertebral body. Due to its safety, simplicity, and efficacy, the unilateral posterosuperior approach is recommended for clinical application.

5.
BMJ Open ; 11(8): e053617, 2021 08 27.
Artículo en Inglés | MEDLINE | ID: mdl-34452972

RESUMEN

INTRODUCTION: Chromosomal abnormalities and monogenic disorders account for ~15%-25% of recognisable birth defects. With limited treatment options, preconception and prenatal screening were developed to reduce the incidence of such disorders. Currently, non-invasive prenatal screening (NIPS) for common aneuploidies is implemented worldwide with superiority over conventional serum or sonographic screening approaches. However, the clinical validity for the screening of frequent chromosome segmental copy number variations and monogenic disorders still awaits to be proved. METHODS AND ANALYSIS: This study is a multicentre, prospective study. The participants were recruited from three tertiary hospitals in China starting from 10 April 2021. The study is expected to conclude before 10 October 2022. Pregnant women with abnormal prenatal screening results indicated for invasive prenatal diagnosis or those who decide to terminate their pregnancies due to abnormal ultrasound findings will be evaluated for enrolment. Cell-free DNA extracted from the maternal plasma will be used for an analytically validated comprehensive NIPS test developed by Beijing BioBiggen Technology Co. (Beijing, China). The diagnostic results from prenatal or postnatal specimens as well as the pregnancy outcome data will be collected to examine the clinical sensitivity, specificity, positive and negative predictive values of the test. ETHICS AND DISSEMINATION: This study was approved by the Obstetrics and Gynecology Hospital of Fudan University (2020-178). Results of this study will be disseminated to public through scientific conferences and a peer-reviewed journal. Written informed consents will be obtained from participants. TRIAL REGISTRATION NUMBER: ChiCTR2100045739.


Asunto(s)
Trastornos de los Cromosomas , Variaciones en el Número de Copia de ADN , Aneuploidia , Femenino , Humanos , Estudios Multicéntricos como Asunto , Embarazo , Resultado del Embarazo , Diagnóstico Prenatal , Estudios Prospectivos
6.
Mol Genet Genomic Med ; 9(9): e1763, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-34296532

RESUMEN

BACKGROUND: Nicolaides-Baraitser syndrome (NCBRS) is a severe neurodevelopmental disorder with multiple abnormalities. To date, all pathogenic variants in SMARCA2 causing NCBRS are de novo and most are missense variants located in the ATPase domain of SMARCA2 protein. METHODS: In this study, a familial trio whole-exome sequencing was performed on the proband presenting with intellectual disability, early-onset epilepsy, and autistic features. A novel missense variant c.553C>G (p.Gln185Glu) in SMARCA2 was identified, which is located in the QLQ domain. The same variant was subsequently also found in the mother's ongoing pregnancy. Samples from accessible tissues such as saliva and sperm other than blood were collected from the parents, and the detection of the target variant was performed by amplicon-based deep sequencing. RESULTS: Low-level mosaicism of the target variant c.553C>G (p.Gln185Glu) was detected in the father's sperm with allele fraction of 2.8% by amplicon-based deep sequencing, which was not detected in either parents' blood or saliva specimens. Heterozygosity of this variant was confirmed in the proband. CONCLUSION: This is the first report of paternal germline mosaicism for a SMARCA2 disease-causing variant. In addition, the missense variant c.553C>G (p.Gln185Glu) in the QLQ domain causes mainly neurological and developmental phenotypes with unremarkable characteristic facial features and limb abnormalities. Our findings expand the phenotypic spectrum and mode of genetic transmission associated with the SMARCA2 variants.


Asunto(s)
Deformidades Congénitas del Pie/genética , Mutación de Línea Germinal , Hipotricosis/genética , Discapacidad Intelectual/genética , Mosaicismo , Fenotipo , Factores de Transcripción/genética , Células Cultivadas , Niño , Facies , Deformidades Congénitas del Pie/patología , Humanos , Hipotricosis/patología , Discapacidad Intelectual/patología , Masculino , Mutación Missense , Factores de Transcripción/química
7.
Mol Genet Genomic Med ; 8(2): e1053, 2020 02.
Artículo en Inglés | MEDLINE | ID: mdl-31880409

RESUMEN

BACKGROUND: Next-generation sequencing (NGS)-based panels have gained traction as a strategy for reproductive carrier screening. Their value for screening Ashkenazi Jewish (AJ) individuals, who have benefited greatly from population-wide targeted testing, as well as Sephardi/Mizrahi Jewish (SMJ) individuals (an underserved population), has not been fully explored. METHODS: The clinical utilization by 6,805 self-reported Jewish individuals of an expanded NGS panel, along with several ancillary assays, was assessed retrospectively. Data were extracted for a subset of 96 diseases that, during the panel design phase, were classified as being AJ-, SMJ-, or pan-Jewish/pan-ethnic-relevant. RESULTS: 64.6% of individuals were identified as carriers of one or more of these 96 diseases. Over 80% of the reported variants would have been missed by following recommended AJ screening guidelines. 10.7% of variants reported for AJs were in "SMJ-relevant genes," and 31.2% reported for SMJs were in "AJ-relevant genes." Roughly 2.5% of individuals carried a novel, likely pathogenic variant. One in 16 linked cohort couples was identified as a carrier couple for at least one of these 96 diseases. CONCLUSION: For maximal carrier identification, this study supports using expanded NGS panels for individuals of all Jewish backgrounds. This approach can better empower at-risk couples for reproductive decision making.


Asunto(s)
Tamización de Portadores Genéticos/estadística & datos numéricos , Enfermedades Genéticas Congénitas/etnología , Judíos/genética , Tamización de Portadores Genéticos/normas , Enfermedades Genéticas Congénitas/genética , Secuenciación de Nucleótidos de Alto Rendimiento/normas , Secuenciación de Nucleótidos de Alto Rendimiento/estadística & datos numéricos , Humanos , Guías de Práctica Clínica como Asunto , Atención Preconceptiva/normas , Atención Preconceptiva/estadística & datos numéricos
8.
Cell Rep ; 28(1): 190-201.e3, 2019 07 02.
Artículo en Inglés | MEDLINE | ID: mdl-31269439

RESUMEN

The regeneration capacity of neonatal mouse heart is controversial. In addition, whether epicardial cells provide a progenitor pool for de novo heart regeneration is incompletely defined. Following apical resection of the neonatal mouse heart, we observed limited regeneration potential. Fate-mapping of Tbx18MerCreMer mice revealed that newly formed coronary vessels and a limited number of cardiomyocytes were derived from the T-box transcription factor 18 (Tbx18) lineage. However, further lineage tracing with SM-MHCCreERT2 and Nfactc1Cre mice revealed that the new smooth muscle and endothelial cells are in fact derivatives of pre-existing coronary vessels. Our data show that neonatal mouse heart can regenerate but that its potential is limited. Moreover, although epicardial cells are multipotent during embryogenesis, their contribution to heart repair through "stem" or "progenitor" cell conversion is minimal after birth. These observations suggest that early embryonic heart development and postnatal heart regeneration are distinct biological processes. Multipotency of epicardial cells is significantly decreased after birth.


Asunto(s)
Vasos Coronarios/citología , Lesiones Cardíacas/metabolismo , Corazón/fisiología , Miocitos Cardíacos/citología , Pericardio/citología , Regeneración/fisiología , Células Madre/citología , Proteínas de Dominio T Box/metabolismo , Animales , Animales Recién Nacidos , Diferenciación Celular/genética , Diferenciación Celular/fisiología , Linaje de la Célula , Vasos Coronarios/metabolismo , Células Endoteliales/citología , Células Endoteliales/metabolismo , Técnicas de Sustitución del Gen , Lesiones Cardíacas/genética , Ratones , Miocitos Cardíacos/metabolismo , Neovascularización Fisiológica , Pericardio/metabolismo , Regeneración/genética , Células Madre/metabolismo , Proteínas de Dominio T Box/genética
9.
Methods Mol Biol ; 1942: 11-27, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-30900172

RESUMEN

Fragile X syndrome (FXS) is characterized by mental retardation and in the vast majority of cases it is caused by expansion of CGG trinucleotide repeats in the 5' untranslated region (or UTR) in the FMR1 gene on the X chromosome. The size and methylation status of CGG repeats are correlated with the clinical phenotype of FMR1-related disorders. The methods used for clinical genetic testing of FXS include polymerase chain reaction (PCR) amplification and Southern blot analyses, which effectively detect alleles with repeats in the normal, intermediate, premutation, and full mutation size ranges, as well as the methylation status of FMR1 promoter region.


Asunto(s)
Southern Blotting/métodos , Proteína de la Discapacidad Intelectual del Síndrome del Cromosoma X Frágil/genética , Síndrome del Cromosoma X Frágil/diagnóstico , Pruebas Genéticas , Mutación , Reacción en Cadena de la Polimerasa/métodos , Metilación de ADN , Femenino , Síndrome del Cromosoma X Frágil/genética , Humanos , Masculino , Repeticiones de Trinucleótidos
10.
J Biol Chem ; 293(24): 9162-9175, 2018 06 15.
Artículo en Inglés | MEDLINE | ID: mdl-29735531

RESUMEN

Chondrocyte hypertrophy is the terminal step in chondrocyte differentiation and is crucial for endochondral bone formation. How signaling pathways regulate chondrocyte hypertrophic differentiation remains incompletely understood. In this study, using a Tbx18:Cre (Tbx18Cre/+) gene-deletion approach, we selectively deleted the gene for the signaling protein SMAD family member 4 (Smad4f/f ) in the limbs of mice. We found that the Smad4-deficient mice develop a prominent shortened limb, with decreased expression of chondrocyte differentiation markers, including Col2a1 and Acan, in the humerus at mid-to-late gestation. The most striking defects in these mice were the absence of stylopod elements and failure of chondrocyte hypertrophy in the humerus. Moreover, expression levels of the chondrocyte hypertrophy-related markers Col10a1 and Panx3 were significantly decreased. Of note, we also observed that the expression of runt-related transcription factor 2 (Runx2), a critical mediator of chondrocyte hypertrophy, was also down-regulated in Smad4-deficient limbs. To determine how the skeletal defects arose in the mouse mutants, we performed RNA-Seq with ChIP-Seq analyses and found that Smad4 directly binds to regulatory elements in the Runx2 promoter. Our results suggest a new mechanism whereby Smad4 controls chondrocyte hypertrophy by up-regulating Runx2 expression during skeletal development. The regulatory mechanism involving Smad4-mediated Runx2 activation uncovered here provides critical insights into bone development and pathogenesis of chondrodysplasia.


Asunto(s)
Desarrollo Óseo , Condrocitos/patología , Subunidad alfa 1 del Factor de Unión al Sitio Principal/genética , Eliminación de Gen , Regulación del Desarrollo de la Expresión Génica , Proteína Smad4/genética , Animales , Diferenciación Celular , Proliferación Celular , Condrocitos/citología , Condrocitos/metabolismo , Condrogénesis , Subunidad alfa 1 del Factor de Unión al Sitio Principal/metabolismo , Hipertrofia/genética , Hipertrofia/metabolismo , Hipertrofia/patología , Ratones , Osteocondrodisplasias/genética , Osteocondrodisplasias/metabolismo , Osteocondrodisplasias/patología , Proteína Smad4/metabolismo
11.
Elife ; 62017 09 12.
Artículo en Inglés | MEDLINE | ID: mdl-28895531

RESUMEN

Achieving confidence in the causality of a disease locus is a complex task that often requires supporting data from both statistical genetics and clinical genomics. Here we describe a combined approach to identify and characterize a genetic disorder that leverages distantly related patients in a health system and population-scale mapping. We utilize genomic data to uncover components of distant pedigrees, in the absence of recorded pedigree information, in the multi-ethnic BioMe biobank in New York City. By linking to medical records, we discover a locus associated with both elevated genetic relatedness and extreme short stature. We link the gene, COL27A1, with a little-known genetic disease, previously thought to be rare and recessive. We demonstrate that disease manifests in both heterozygotes and homozygotes, indicating a common collagen disorder impacting up to 2% of individuals of Puerto Rican ancestry, leading to a better understanding of the continuum of complex and Mendelian disease.


Asunto(s)
Enfermedades del Colágeno/epidemiología , Enfermedades del Colágeno/genética , Colágenos Fibrilares/genética , Epidemiología Molecular , Linaje , Adolescente , Adulto , Anciano , Niño , Femenino , Genotipo , Heterocigoto , Hispánicos o Latinos , Homocigoto , Humanos , Masculino , Persona de Mediana Edad , Familia de Multigenes , Enfermedades Musculoesqueléticas/epidemiología , Enfermedades Musculoesqueléticas/genética , Ciudad de Nueva York/epidemiología , Ciudad de Nueva York/etnología , Secuenciación Completa del Genoma , Adulto Joven
12.
Huan Jing Ke Xue ; 36(8): 2972-80, 2015 Aug.
Artículo en Chino | MEDLINE | ID: mdl-26592029

RESUMEN

Fifty-two dust samples were collected from four parks [Longting Park (P(L)), Tieta Park (P(T)), Qingmingshanghe Park (P(Q)), Xiangguosi Park (P(X))] located in Kaifeng City, China. Concentrations of Hg and As in dusts were measured by atomic fluorescence spectrometry (AFS), while Cr, Cu, Zn, Pb, Ni and Cd were analyzed by inductively coupled plasma mass-spectrometry (ICP-MS). The heavy metal pollution of dust was assessed using Geo-accumulation index (Igeo) and pollution load index (PLI). The health risk due to exposure to heavy metals in dust was assessed using the model recommended by USEPA. The non-carcinogen (HI) and carcinogen health risks (TCR) were also calculated to evaluate the potential risks to adults. The results showed that the average contents of Hg, Cu, Zn, Cd and Pb were much higher than those in control samples and the background values of fluvo-aquic soil in China. The samples were seriously polluted by Hg and Pb, besides, there was.moderate pollution, slight pollution of Cu and Zn, and no pollution of As, Cr and Ni. The PLI from the 4 Parks indicated that there was serious heavy metals pollution of dust in P(X), moderate pollution in P%, and slight pollution in P(T) and P(Q). The average HI of heavy metals in the four Parks was lower than one. The average HI decreased in the order of P(L) > P(X), > P(T) > P(Q), while the average TCR decreased in the order of P(L) > P(Q) > P(x) > P(T). The contribution rate of HQ(As) to HI was about 43.51% , and that of CR(As) to TCR was about 70.11%.


Asunto(s)
Polvo/análisis , Metales Pesados/análisis , Contaminantes del Suelo/análisis , China , Ciudades , Monitoreo del Ambiente , Parques Recreativos , Suelo
13.
PLoS One ; 9(8): e104503, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-25127126

RESUMEN

Proper formation of ureteral smooth muscle cells (SMCs) during embryogenesis is essential for ureter peristalsis that propels urine from the kidney to the bladder in mammals. Currently the molecular factors that regulate differentiation of ureteral mesenchymal cells into SMCs are incompletely understood. A recent study has reported that Smad4 deficiency reduces the number of ureteral SMCs. However, its precise role in the ureteral smooth muscle development remains largely unknown. Here, we used Tbx18:Cre knock-in mouse line to delete Smad4 to examine its requirement in the development of ureteral mesenchyme and SMC differentiation. We found that mice with specific deletion of Smad4 in Tbx18-expressing ureteral mesenchyme exhibited hydroureter and hydronephrosis at embryonic day (E) 16.5, and the mutant mesenchymal cells failed to differentiate into SMCs with increased apoptosis and decreased proliferation. Molecular markers for SMCs including alpha smooth muscle actin (α-SMA) and smooth muscle myosin heavy chain (SM-MHC) were absent in the mutant ureters. Moreover, disruption of Smad4 significantly reduced the expression of genes, including Sox9, Tbx18 and Myocardin associated with SMC differentiation. These findings suggest that Smad4 is essential for initiating the SMC differentiation program during ureter development.


Asunto(s)
Miocitos del Músculo Liso/citología , Organogénesis/genética , Proteína Smad4/genética , Uréter/citología , Actinas/metabolismo , Animales , Apoptosis/genética , Diferenciación Celular/genética , Proliferación Celular/genética , Desarrollo Embrionario/genética , Técnicas de Sustitución del Gen , Hidronefrosis/genética , Hibridación in Situ , Mesodermo/citología , Ratones , Ratones Transgénicos , Cadenas Pesadas de Miosina/metabolismo , Proteínas Nucleares/biosíntesis , Factor de Transcripción SOX9/biosíntesis , Miosinas del Músculo Liso/metabolismo , Proteínas de Dominio T Box/biosíntesis , Proteínas de Dominio T Box/genética , Transactivadores/biosíntesis , Uréter/fisiología
14.
Cell Res ; 24(10): 1201-13, 2014 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-25145359

RESUMEN

The sinoatrial node (SAN) is essential for rhythmic beating of the heart; however, our understanding of what controls proper functioning of the SAN remains primitive. To explore molecular control of SAN function, we specifically deleted Baf250a, a key regulatory component of the ATP-dependent chromatin remodeling complex SWI/SNF, in the SAN. Deletion of Baf250a in the SAN led to sinus bradycardia. Time series analysis of dysregulated genes after deletion of Baf250a reveals a transcriptional hierarchy maintaining pacemaker cell identity, i.e., Baf250a activates the expression of Tbx3, and Baf250a, Tbx3 and histone deacetylase 3 coordinately repress the expression of Nkx2.5. Disruption of this repressive pathway switches on expression of Nkx2.5, which stimulates expression of Gata4 and Tbx5. These three cardiac transcription factors further turn on a contractile cardiomyocyte program in the SAN, which eventually leads to sick sinus disease (SSD). Our study suggests that disruption of key genetic pathways regulating cardiac lineage segregation may cause SSD and cardiac arrhythmias in general.


Asunto(s)
Proteínas de Unión al ADN/metabolismo , Epigénesis Genética , Proteínas de Homeodominio/metabolismo , Miocitos Cardíacos/metabolismo , Proteínas Nucleares/metabolismo , Nodo Sinoatrial/metabolismo , Factores de Transcripción/metabolismo , Animales , Antineoplásicos Hormonales/farmacología , Inmunoprecipitación de Cromatina , Análisis por Conglomerados , Proteínas de Unión al ADN/deficiencia , Proteínas de Unión al ADN/genética , Factor de Transcripción GATA4/metabolismo , Células HEK293 , Histona Desacetilasas/metabolismo , Proteína Homeótica Nkx-2.5 , Humanos , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Contracción Muscular/efectos de los fármacos , Miocitos Cardíacos/efectos de los fármacos , Proteínas Nucleares/deficiencia , Proteínas Nucleares/genética , Proteínas de Dominio T Box/deficiencia , Proteínas de Dominio T Box/genética , Proteínas de Dominio T Box/metabolismo , Tamoxifeno/farmacología
15.
Pak J Med Sci ; 30(2): 335-8, 2014 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-24772138

RESUMEN

OBJECTIVE: To compare the clinical application in the percutaneous vertebroplasty under the guidance of one or two C-arm fluoroscopes. METHODS: One hundred forty three elderly patients with Osteoporotic vertebral compression fractures (OVCFs) underwent percutaneous vertebroplasty under the guidance of one or two C-arm fluoroscopes. The number of pulsed imagings, the time of operation and the incidence of cement leakage were recorded. RESULTS: The average number of pulsed imagings was 16.00±1.58 vs 13.07±2.00 per patient under the guidance of one vs two C-arm fluoroscopes. The average time of operation was 48.42±5.00 minutes vs 39.70±7.42 minutes per patient under the guidance of one vs two C-arm fluoroscopes. The incidence of cement leakage was 20% vs 15.7% of the patients under the guidance of one vs two C-arm fluoroscopes. The differences in the number of pulsed imagings and the time of operation were statistically significant. The difference in incidence of cement leakage was not statistically significant. CONCLUSION: The two-fluoroscopic technique reduce the labor cost, the radiation, the time of operation and the operation risk.

16.
Dev Biol ; 391(1): 17-31, 2014 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-24727670

RESUMEN

Tbx18 has been shown to be essential for ureteral development. However, it remains unclear whether it plays a direct role in kidney development. Here we addressed this by focusing on examining the pattern and contribution of Tbx18+ cells in the kidney and its role in kidney vascular development. Expression studies and genetic lineage tracing revealed that Tbx18 is expressed in renal capsule, vascular smooth muscle cells and pericytes and glomerular mesangial cells in the kidney and that Tbx18-expressing progenitors contribute to these cell types. Examination of Tbx18(-/-) kidneys revealed large reduction in vasculature density and dilation of glomerular capillary loops. While SMA+ cells were reduced in the mutant, PDGFRß+ cells were seen in early capillary loop renal corpuscles in the mutant, but fewer than in the controls, and further development of the mesangium failed. Analysis of kidney explants cultured from E12.5 excluded the possibility that the defects observed in the mutant were caused by ureter obstruction. Reduced proliferation in glomerular tuft and increased apoptosis in perivascular mesenchyme were observed in Tbx18(-/-) kidneys. Thus, our analyses have identified a novel role of Tbx18 in kidney vasculature development.


Asunto(s)
Regulación del Desarrollo de la Expresión Génica , Mesangio Glomerular/embriología , Riñón/irrigación sanguínea , Riñón/embriología , Proteínas de Dominio T Box/genética , Proteínas de Dominio T Box/fisiología , Animales , Apoptosis , Diferenciación Celular , Linaje de la Célula , Proliferación Celular , Ratones , Ratones Transgénicos , Miocitos del Músculo Liso/citología , Miocitos del Músculo Liso/metabolismo , Pericitos/metabolismo , Receptor beta de Factor de Crecimiento Derivado de Plaquetas , Transducción de Señal , Factores de Tiempo
17.
Dev Biol ; 390(1): 68-79, 2014 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-24613616

RESUMEN

The vertebrate heart develops from mesoderm and requires inductive signals secreted from early endoderm. During embryogenesis, Nkx2.5 acts as a key transcription factor and plays essential roles for heart formation from Drosophila to human. In mice, Nkx2.5 is expressed in the early first heart field, second heart field pharyngeal mesoderm, as well as pharyngeal endodermal cells underlying the second heart field. Currently, the specific requirements for Nkx2.5 in the endoderm versus mesoderm with regard to early heart formation are incompletely understood. Here, we performed tissue-specific deletion in mice to dissect the roles of Nkx2.5 in the pharyngeal endoderm and mesoderm. We found that heart development appeared normal after endodermal deletion of Nkx2.5 whereas mesodermal deletion engendered cardiac defects almost identical to those observed on Nkx2.5 null embryos (Nkx2.5(-/-)). Furthermore, re-expression of Nkx2.5 in the mesoderm rescued Nkx2.5(-/-) heart defects. Our findings reveal that Nkx2.5 in the mesoderm is essential while endodermal expression is dispensable for early heart formation in mammals.


Asunto(s)
Corazón/embriología , Proteínas de Homeodominio/genética , Mesodermo/metabolismo , Miocardio/metabolismo , Factores de Transcripción/genética , Animales , Embrión de Mamíferos/embriología , Embrión de Mamíferos/metabolismo , Embrión de Mamíferos/ultraestructura , Endodermo/embriología , Endodermo/metabolismo , Femenino , Regulación del Desarrollo de la Expresión Génica , Proteína Homeótica Nkx-2.5 , Proteínas de Homeodominio/metabolismo , Inmunohistoquímica , Hibridación in Situ , Mesodermo/embriología , Ratones , Ratones Noqueados , Microscopía Electrónica de Rastreo , Faringe/embriología , Faringe/metabolismo , Embarazo , Factores de Tiempo , Factores de Transcripción/metabolismo
18.
Talanta ; 120: 297-303, 2014 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-24468373

RESUMEN

A chemodosimeter-based fluorescent detection method coupled with molecularly imprinted polymers (MIPs) extraction was developed for determination of L-cysteine (L-Cys) by combining molecular imprinting technique with fluorescent chemodosimeter. The MIPs prepared by precipitation polymerization with L-Cys as template, possessed high specific surface area of 145 m(2)/g and good thermal stability without decomposition lower than 300 °C, and were successfully applied as an adsorbent with excellent selectivity for L-Cys over other amino acids, and enantioselectivity was also demonstrated. A novel chemodosimeter, rhodamine B1, was synthesized for discriminating L-Cys from its structurally similar homocysteine and glutathione as well as various possibly co-existing biospecies in aqueous solutions with notable fluorescence enhancement when adding L-Cys. As L-Cys was added with increasing concentrations, an emission band peaked at 580 nm occurred and significantly increased in fluorescence intensity, by which the L-Cys could be sensed optically. High detectability up to 12.5 nM was obtained. An excellent linearity was found within the wide range of 0.05-50 µM (r=0.9996), and reasonable relative standard deviations ranging from 0.3% to 3.5% were attained. Such typical features as high selectivity, high sensitivity, easy operation and low cost enabled this MIPs-fluorometry to be potentially applicable for routine detection of trace L-Cys.


Asunto(s)
Cisteína/aislamiento & purificación , Impresión Molecular/métodos , Extracción en Fase Sólida/métodos , Adsorción , Cisteína/análisis , Colorantes Fluorescentes/análisis , Límite de Detección , Modelos Moleculares , Polímeros/química , Rodaminas/análisis , Espectrometría de Fluorescencia/métodos
19.
Electrophoresis ; 35(4): 474-81, 2014 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-24165973

RESUMEN

In this study, a method of pretreatment and speciation analysis of mercury by dispersive liquid-liquid microextraction along with CE was developed. The method was based on the fact that mercury species including methylmercury (MeHg), ethylmercury (EtHg), phenylmercury (PhHg), and Hg(II) were complexed with 1-(2-pyridylazo)-2-naphthol to form hydrophobic chelates and l-cysteine could displace 1-(2-pyridylazo)-2-naphthol to form hydrophilic chelates with the four mercury species. Factors affecting complex formation and extraction efficiency, such as pH value, type, and volume of extractive solvent and disperser solvent, concentration of the chelating agent, ultrasonic time, and buffer solution were investigated. Under the optimal conditions, the enrichment factors were 102, 118, 547, and 46, and the LODs were 1.79, 1.62, 0.23, and 1.50 µg/L for MeHg, EtHg, PhHg, and Hg(II), respectively. Method precisions (RSD, n = 5) were in the range of 0.29-0.54% for migration time, and 3.08-7.80% for peak area. Satisfactory recoveries ranging from 82.38 to 98.76% were obtained with seawater, lake, and tap water samples spiked at three concentration levels, respectively, with RSD (n = 5) of 1.98-7.18%. This method was demonstrated to be simple, convenient, rapid, cost-effective, and environmentally benign, and could be used as an ideal alternative to existing methods for analyzing trace residues of mercury species in water samples.


Asunto(s)
Electroforesis Capilar/métodos , Microextracción en Fase Líquida/métodos , Mercurio/análisis , Compuestos Organomercuriales/análisis , Contaminantes Químicos del Agua/análisis , Límite de Detección , Modelos Lineales , Mercurio/química , Mercurio/clasificación , Mercurio/aislamiento & purificación , Naftoles/química , Compuestos Organomercuriales/química , Compuestos Organomercuriales/clasificación , Compuestos Organomercuriales/aislamiento & purificación , Reproducibilidad de los Resultados , Contaminantes Químicos del Agua/química , Contaminantes Químicos del Agua/clasificación , Contaminantes Químicos del Agua/aislamiento & purificación
20.
ACS Appl Mater Interfaces ; 6(1): 305-13, 2014 Jan 08.
Artículo en Inglés | MEDLINE | ID: mdl-24344795

RESUMEN

A novel kind of Pb(2+) ion imprinted polymers (IIPs) was prepared based on ionic interactions via the synergy of dual functional monomers of methacrylic acid and vinyl pyridine for selective solid-phase extraction (SPE) of Pb(2+) in water samples. Suspension polymerization was employed for the formation of template Pb(2+)/monomer complex by self-assembly in the presence of ethylene glycol dimethacrylate cross-linker. The resulted Pb(2+) IIPs showed fast kinetics, high binding capacity, and the adsorption processes obeyed intraparticle diffusion kinetics and Langmuir isotherm models. The IIPs displayed excellent selectivity toward Pb(2+) over other metal ions such as Cu(2+), Cd(2+), Zn(2+), and Mn(2+) with selective coefficients above 30, as well as high anti-interference ability for Pb(2+) confronting with common coexisting various ions. Through 10 adsorption-desorption cycles, the reusable IIPs exhibited a good recoverability with the standard error within 5%. These features suggested the IIPs were ideal candidates for extraction and removal of Pb(2+) ions. Consequently, the IIPs were utilized as SPE sorbents and related parameters were optimized. An excellent linearity was presented in the range of 0.2-50 µg L(-1) (R(2) = 0.9998), as well as the limits of detection and quantification were achieved of 0.06 and 0.19 µg L(-1), respectively. A good repeatability was obtained with the relative standard deviation of 2.8%. Furthermore, real water samples were successfully analyzed and satisfactory recoveries varying from 95.5 to 104.6% were attained. The IIPs-SPE demonstrated potential application perspectives for rapid and high-effective cleanup and enrichment of trace Pb(2+) ions in complicated matrices.

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