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1.
J Magn Reson Imaging ; 59(2): 587-598, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37220191

RESUMEN

BACKGROUND: The delineation of brain arteriovenous malformations (bAVMs) is crucial for subsequent treatment planning. Manual segmentation is time-consuming and labor-intensive. Applying deep learning to automatically detect and segment bAVM might help to improve clinical practice efficiency. PURPOSE: To develop an approach for detecting bAVM and segmenting its nidus on Time-of-flight magnetic resonance angiography using deep learning methods. STUDY TYPE: Retrospective. SUBJECTS: 221 bAVM patients aged 7-79 underwent radiosurgery from 2003 to 2020. They were split into 177 training, 22 validation, and 22 test data. FIELD STRENGTH/SEQUENCE: 1.5 T, Time-of-flight magnetic resonance angiography based on 3D gradient echo. ASSESSMENT: The YOLOv5 and YOLOv8 algorithms were utilized to detect bAVM lesions and the U-Net and U-Net++ models to segment the nidus from the bounding boxes. The mean average precision, F1, precision, and recall were used to assess the model performance on the bAVM detection. To evaluate the model's performance on nidus segmentation, the Dice coefficient and balanced average Hausdorff distance (rbAHD) were employed. STATISTICAL TESTS: The Student's t-test was used to test the cross-validation results (P < 0.05). The Wilcoxon rank test was applied to compare the median for the reference values and the model inference results (P < 0.05). RESULTS: The detection results demonstrated that the model with pretraining and augmentation performed optimally. The U-Net++ with random dilation mechanism resulted in higher Dice and lower rbAHD, compared to that without that mechanism, across varying dilated bounding box conditions (P < 0.05). When combining detection and segmentation, the Dice and rbAHD were statistically different from the references calculated using the detected bounding boxes (P < 0.05). For the detected lesions in the test dataset, it showed the highest Dice of 0.82 and the lowest rbAHD of 5.3%. DATA CONCLUSION: This study showed that pretraining and data augmentation improved YOLO detection performance. Properly limiting lesion ranges allows for adequate bAVM segmentation. LEVEL OF EVIDENCE: 4 TECHNICAL EFFICACY STAGE: 1.


Asunto(s)
Aprendizaje Profundo , Malformaciones Arteriovenosas Intracraneales , Humanos , Encéfalo/diagnóstico por imagen , Procesamiento de Imagen Asistido por Computador/métodos , Malformaciones Arteriovenosas Intracraneales/diagnóstico por imagen , Malformaciones Arteriovenosas Intracraneales/cirugía , Angiografía por Resonancia Magnética , Imagen por Resonancia Magnética , Estudios Retrospectivos , Niño , Adolescente , Adulto Joven , Adulto , Persona de Mediana Edad , Anciano
2.
Sensors (Basel) ; 23(22)2023 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-38005585

RESUMEN

The transform domain provides a useful tool in the field of confidential data hiding and protection. In order to protect and transmit patients' information and competence, this study develops an amplitude quantization system in a transform domain by hiding patients' information in an electrocardiogram (ECG). In this system, we first consider a non-linear model with a hiding state switch to enhance the quality of the hidden ECG signals. Next, we utilize particle swarm optimization (PSO) to solve the non-linear model so as to have a good signal-to-noise ratio (SNR), root mean square error (RMSE), and relative root mean square error (rRMSE). Accordingly, the distortion of the shape in each ECG signal is tiny, while the hidden information can fulfill the needs of physiological diagnostics. The extraction of hidden information is reversely similar to a hiding procedure without primary ECG signals. Preliminary outcomes confirm the effectiveness of our proposed method, especially an Amplitude Similarity of almost 1, an Interval RMSE of almost 0, and SNRs all above 30.


Asunto(s)
Electrocardiografía , Procesamiento de Señales Asistido por Computador , Humanos , Electrocardiografía/métodos , Relación Señal-Ruido , Algoritmos
3.
PLoS One ; 18(3): e0283473, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36961826

RESUMEN

SARS-CoV-2 pandemic has profound impacts on human life and global economy since the outbreak in 2019. With the new variants continue to emerge with greater immune escaping capability, the protectivity of the available vaccines is compromised. Therefore, development a vaccine that is capable of inducing immunity against variants including omicron strains is in urgent need. In this study, we developed a protein-based vaccine BCVax that is consisted of antigen delta strain spike protein and QS21-based adjuvant AB801 in nanoparticle immune stimulation complex format (AB801-ISCOM). Results from animal studies showed that high level of anti-S protein IgG was induced after two doses of BCVax and the IgG was capable of neutralizing multiple variants of pseudovirus including omicron BA.1 or BA.2 strains. In addition, strong Th1 response was stimulated after BCVax immunization. Furthermore, BCvax with AB801-ISCOM as the adjuvant showed significant stronger immunity compared with the vaccine using aluminum hydroxide plus CpG 1018 as the adjuvant. BCVax was also evaluated as a booster after two prior vaccinations, the IgG titers and pseudovirus neutralization activities against BA.2 or BA.4/BA.5 were further enhanced suggesting BCVax is a promising candidate as booster. Taken together, the pre-clinical data warrant BCVax for further development in clinic.


Asunto(s)
COVID-19 , ISCOMs , Animales , Humanos , Vacunas contra la COVID-19 , SARS-CoV-2 , Subunidades de Proteína , COVID-19/prevención & control , Glicoproteína de la Espiga del Coronavirus/genética , Adyuvantes Inmunológicos , Adyuvantes Farmacéuticos , Animales de Laboratorio , Inmunoglobulina G , Anticuerpos Antivirales , Anticuerpos Neutralizantes
4.
Opt Express ; 30(12): 22233-22246, 2022 Jun 06.
Artículo en Inglés | MEDLINE | ID: mdl-36224926

RESUMEN

We propose a measurement method for sensitive and label-free detections of virus-like particles (VLPs) using color images of nanoplasmonic sensing chips. The nanoplasmonic chip consists of 5×5 gold nanoslit arrays and the gold surface is modified with specific antibodies for spike protein. The resonant wavelength of the 430-nm-period gold nanoslit arrays underwater environment is about 570 nm which falls between the green and red bands of the color CCD. The captured VLPs by the specific antibodies shift the plasmonic resonance of the gold nanoslits. It results in an increased brightness of green pixels and decreased brightness of red pixels. The image contrast signals of (green - red) / (red + green) show good linearity with the surface particle density. The experimental tests show the image contrast method can detect 100-nm polystyrene particles with a surface density smaller than 2 particles/µm2. We demonstrate the application for direct detection of SARS-CoV-2 VLPs using a simple scanner platform. A detection limit smaller than 1 pg/mL with a detection time less than 30 minutes can be achieved.


Asunto(s)
Técnicas Biosensibles , COVID-19 , Nanoestructuras , Anticuerpos , Técnicas Biosensibles/métodos , Oro/química , Humanos , Nanoestructuras/química , Poliestirenos , SARS-CoV-2 , Glicoproteína de la Espiga del Coronavirus , Resonancia por Plasmón de Superficie/métodos
5.
Diagnostics (Basel) ; 12(4)2022 Apr 10.
Artículo en Inglés | MEDLINE | ID: mdl-35453994

RESUMEN

Differentiating tumor tissue from dense breast tissue can be difficult. Dual-energy CT (DECT) could be suitable for making diagnoses at breast cancer follow-ups. This study investigated the contrast in DECT images and iodine maps for patients with breast cancer being followed-up. Chest CT images captured in 2019 were collected. Five cases of metastatic breast cancer in the lungs were analyzed; the contrast-to-noise ratio (for breast tissue and muscle: CNRb and CNRm, respectively), tumor-to-breast mammary gland ratio (T/B), and tumor-to-muscle ratio (T/M) were calculated. For 84 cases of no metastasis, monochromatic spectral and iodine maps were obtained to compare differences under various breast densities using the K-means algorithm. The optimal T/B, T/M, and CNRb (related to mammary glands) were achieved for the 40-keV image. Conversely, CNRm (related to lungs) was better for higher energy. The optimal balance was achieved at 80 keV. T/B, T/M, and CNR were excellent for iodine maps, particularly for density > 25%. In conclusion, energy of 80 keV is the parameter most suitable for observing the breast and lungs simultaneously by using monochromatic spectral images. Adding iodine mapping can be appropriate when a patient's breast density is greater than 25%.

6.
Front Endocrinol (Lausanne) ; 12: 647184, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34335463

RESUMEN

The aim of this study was to analyze the differences in the distribution of abdominal adipose tissue between the two subtypes of primary aldosteronism (PA) using abdominal computed tomography. We retrospectively analyzed patients diagnosed as having essential hypertension (EH) or PA from the prospectively collected Taiwan Primary Aldosteronism Investigation (TAIPAI) database. Patients with PA were divided into the subgroups of idiopathic hyperaldosteronism (IHA) and unilateral aldosterone-producing adenoma (APA). Patients' basic clinicodemographic data were collected, and a self-developed CT-based software program was used to quantify the abdominal adiposity indexes, including visceral adipose tissue (VAT) area, VAT ratio, waist circumference (WC), subcutaneous adipose tissue (SAT) area, and SAT ratio. We included 190 patients with EH and 436 patients with PA (238 with IHA and 198 with APA). The APA group had significantly lower abdominal adiposity indexes than the other groups. We also found negative correlations of aldosterone-to-renin ratio (ARR) with VAT area, VAT ratio, WC, and body mass index (BMI) in the APA group. After propensity score matching (which left 184 patients each in the IHA and APA groups), patients in the APA group still had significantly lower WC, SAT area, SAT ratio, and VAT ratio than those in the IHA group. Furthermore, logistic regression analysis indicated that lower probability of abdominal obesity was significantly related to patients with APA. Our data revealed that the distribution of abdominal adipose tissue was similar in patients with IHA and those with EH, but the abdominal adiposity indexes were significantly lower in patients with APA than in those with IHA and EH.


Asunto(s)
Grasa Abdominal/diagnóstico por imagen , Hiperaldosteronismo/diagnóstico por imagen , Radiografía Abdominal/métodos , Tomografía Computarizada por Rayos X/métodos , Adulto , Anciano , Aldosterona , Bases de Datos Factuales , Hipertensión Esencial/diagnóstico por imagen , Femenino , Humanos , Masculino , Persona de Mediana Edad , Obesidad Abdominal , Puntaje de Propensión , Estudios Prospectivos , Renina , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Programas Informáticos , Taiwán/epidemiología , Circunferencia de la Cintura
7.
J Hypertens ; 39(12): 2353-2360, 2021 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-34313632

RESUMEN

OBJECTIVE: Aldosterone overproduction and lipid metabolic disturbances between idiopathic hyperaldosteronism (IHA) and unilateral aldosterone-producing adenoma (APA) have been inconsistently linked in patients with primary aldosteronism. Moreover, KCNJ5 mutations are prevalent among APAs and enhance aldosterone synthesis in adrenal cortex. We aimed to investigate the prevalence of metabolic syndrome (MetS) in each primary aldosteronism subtype and observe the role of KCNJ5 mutations among APAs on the distribution of abdominal adipose tissues quantified using computed tomography (CT), including their changes postadrenalectomy. DESIGN AND METHODS: We retrospectively collected 244 and 177 patients with IHA and APA at baseline. Patients with APA had undergone adrenalectomy, and gene sequencing revealed the absence (n = 75) and presence (n = 102) of KCNJ5 mutations. We also recruited 31 patients with APA who had undergone CT-scan 1-year postadrenalectomy. RESULTS: The patients with APA harbouring KCNJ5 mutations had significantly lower prevalence of MetS and smaller distribution in waist circumference, subcutaneous adipose tissue (SAT), and visceral adipose tissue (VAT) than the other groups. Logistic regression analysis indicated that the VAT area correlated significantly with KCNJ5 mutations among the APAs. Only participants with KCNJ5 mutations had significant increases in triglycerides, cholesterol, SAT, and VAT after 1-year postadrenalectomy. CONCLUSION: This study is the first to demonstrate that MetS and abdominal obesity were less prevalent in the patients with APA harbouring KCNJ5 mutations compared with the IHA group and the non-KCNJ5-mutated APA group. Increasing prevalence of dyslipidaemia and abdominal obesity was observed in patients with KCNJ5 mutations 1-year postadrenalectomy.


Asunto(s)
Neoplasias de la Corteza Suprarrenal , Adenoma Corticosuprarrenal , Canales de Potasio Rectificados Internamente Asociados a la Proteína G , Hiperaldosteronismo , Enfermedades Metabólicas , Obesidad Abdominal , Neoplasias de la Corteza Suprarrenal/epidemiología , Neoplasias de la Corteza Suprarrenal/genética , Adenoma Corticosuprarrenal/epidemiología , Adenoma Corticosuprarrenal/genética , Aldosterona , Canales de Potasio Rectificados Internamente Asociados a la Proteína G/genética , Humanos , Hiperaldosteronismo/epidemiología , Hiperaldosteronismo/genética , Enfermedades Metabólicas/epidemiología , Enfermedades Metabólicas/genética , Mutación , Obesidad Abdominal/epidemiología , Obesidad Abdominal/genética , Prevalencia , Estudios Retrospectivos
8.
Cell ; 184(12): 3125-3142.e25, 2021 06 10.
Artículo en Inglés | MEDLINE | ID: mdl-33930289

RESUMEN

The N6-methyladenosine (m6A) RNA modification is used widely to alter the fate of mRNAs. Here we demonstrate that the C. elegans writer METT-10 (the ortholog of mouse METTL16) deposits an m6A mark on the 3' splice site (AG) of the S-adenosylmethionine (SAM) synthetase pre-mRNA, which inhibits its proper splicing and protein production. The mechanism is triggered by a rich diet and acts as an m6A-mediated switch to stop SAM production and regulate its homeostasis. Although the mammalian SAM synthetase pre-mRNA is not regulated via this mechanism, we show that splicing inhibition by 3' splice site m6A is conserved in mammals. The modification functions by physically preventing the essential splicing factor U2AF35 from recognizing the 3' splice site. We propose that use of splice-site m6A is an ancient mechanism for splicing regulation.


Asunto(s)
Adenosina/análogos & derivados , Sitios de Empalme de ARN/genética , Empalme del ARN/genética , Factor de Empalme U2AF/metabolismo , Adenosina/metabolismo , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Caenorhabditis elegans/genética , Secuencia Conservada/genética , Dieta , Células HeLa , Humanos , Intrones/genética , Metionina Adenosiltransferasa , Metilación , Metiltransferasas/química , Ratones , Mutación/genética , Conformación de Ácido Nucleico , Unión Proteica , Precursores del ARN/química , Precursores del ARN/genética , Precursores del ARN/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , ARN Nuclear Pequeño , S-Adenosilmetionina , Transcriptoma/genética
9.
Antioxidants (Basel) ; 10(2)2021 Feb 13.
Artículo en Inglés | MEDLINE | ID: mdl-33668606

RESUMEN

The antioxidant capacity of erythrocytes protects individuals against the harmful effects of oxidative stress. Despite improved hemodynamic efficiency, the effect of eccentric cycling training (ECT) on erythrocyte antioxidative capacity remains unclear. This study investigates how ECT affects erythrocyte antioxidative capacity and metabolism in sedentary males. Thirty-six sedentary healthy males were randomly assigned to either concentric cycling training (CCT, n = 12) or ECT (n = 12) at 60% of the maximal workload for 30 min/day, 5 days/week for 6 weeks or to a control group (n = 12) that did not receive an exercise intervention. A graded exercise test (GXT) was performed before and after the intervention. Erythrocyte metabolic characteristics and O2 release capacity were determined by UPLC-MS and high-resolution respirometry, respectively. An acute GXT depleted Glutathione (GSH), accumulated Glutathione disulfide (GSSG), and elevated the GSSG/GSH ratio, whereas both CCT and ECT attenuated the extent of the elevated GSSG/GSH ratio caused by a GXT. Moreover, the two exercise regimens upregulated glycolysis and increased glucose consumption and lactate production, leading to intracellular acidosis and facilitation of O2 release from erythrocytes. Both CCT and ECT enhance antioxidative capacity against severe exercise-evoked circulatory oxidative stress. Moreover, the two exercise regimens activate erythrocyte glycolysis, resulting in lowered intracellular pH and enhanced O2 released from erythrocytes.

10.
Cell Rep ; 32(7): 108038, 2020 08 18.
Artículo en Inglés | MEDLINE | ID: mdl-32814042

RESUMEN

The 5' end of eukaryotic mRNAs is protected by the m7G-cap structure. The transcription start site nucleotide is ribose methylated (Nm) in many eukaryotes, whereas an adenosine at this position is further methylated at the N6 position (m6A) by the mammalian Phosphorylated C-terminal domain (CTD)-interacting Factor 1 (PCIF1) to generate m6Am. Here, we show that although the loss of cap-specific m6Am in mice does not affect viability or fertility, the Pcif1 mutants display reduced body weight. Transcriptome analyses of mutant mouse tissues support a role for the cap-specific m6Am modification in stabilizing transcripts. In contrast, the Drosophila Pcif1 is catalytically dead, but like its mammalian counterpart, it retains the ability to associate with the Ser5-phosphorylated CTD of RNA polymerase II (RNA Pol II). Finally, we show that the Trypanosoma Pcif1 is an m6Am methylase that contributes to the N6,N6,2'-O-trimethyladenosine (m62Am) in the hypermethylated cap4 structure of trypanosomatids. Thus, PCIF1 has evolved to function in catalytic and non-catalytic roles.


Asunto(s)
ARN Mensajero/genética , ARN Mensajero/metabolismo , Proteínas Represoras/genética , Proteínas Represoras/metabolismo , Complejos de Ubiquitina-Proteína Ligasa/genética , Complejos de Ubiquitina-Proteína Ligasa/metabolismo , Proteínas Adaptadoras Transductoras de Señales/genética , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Animales , Drosophila melanogaster , Células HeLa , Humanos , Ratones , Ratones Endogámicos C57BL , Ratones Mutantes , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Transcripción Genética
11.
Cell Rep ; 29(13): 4422-4434.e13, 2019 12 24.
Artículo en Inglés | MEDLINE | ID: mdl-31875550

RESUMEN

RNA polymerase II transcripts receive a protective 5',5'-triphosphate-linked 7-methylguanosine (m7G) cap, and its removal by decapping enzymes like DCP2 is critical for initiation of RNA decay. Alternative RNA caps can be acquired when transcription initiation uses metabolites like nicotinamide adenine dinucleotide (NAD), generating NAD-RNAs. Here, we identify human NUDT12 as a cytosolic NAD-RNA decapping enzyme. NUDT12 is active only as homodimers, with each monomer contributing to creation of the two functional catalytic pockets. We identify an ∼600-kDa dodecamer complex between bleomycin hydrolase (BLMH) and NUDT12, with BLMH being required for localization of NUDT12 to a few discrete cytoplasmic granules that are distinct from P-bodies. Both proteins downregulate gene expression when artificially tethered to a reporter RNA in vivo. Furthermore, loss of Nudt12 results in a significant upregulation of circadian clock transcripts in mouse liver. Overall, our study points to a physiological role for NUDT12 in the cytosolic surveillance of NAD-RNAs.


Asunto(s)
Cisteína Endopeptidasas/metabolismo , Citoplasma/metabolismo , Endorribonucleasas/metabolismo , NAD/metabolismo , Pirofosfatasas/metabolismo , Caperuzas de ARN/metabolismo , Animales , Repetición de Anquirina , Biocatálisis , Relojes Circadianos/genética , Gránulos Citoplasmáticos/metabolismo , Estabilidad de Enzimas , Guanosina/análogos & derivados , Guanosina/metabolismo , Células HeLa , Humanos , Hígado/metabolismo , Ratones , Ratones Noqueados , Peso Molecular , Multimerización de Proteína , Pirofosfatasas/química , ARN Mensajero/genética , ARN Mensajero/metabolismo
12.
Mol Cell ; 71(6): 986-1000.e11, 2018 09 20.
Artículo en Inglés | MEDLINE | ID: mdl-30197299

RESUMEN

Internal modification of RNAs with N6-methyladenosine (m6A) is a highly conserved means of gene expression control. While the METTL3/METTL14 heterodimer adds this mark on thousands of transcripts in a single-stranded context, the substrate requirements and physiological roles of the second m6A writer METTL16 remain unknown. Here we describe the crystal structure of human METTL16 to reveal a methyltransferase domain furnished with an extra N-terminal module, which together form a deep-cut groove that is essential for RNA binding. When presented with a random pool of RNAs, METTL16 selects for methylation-structured RNAs where the critical adenosine is present in a bulge. Mouse 16-cell embryos lacking Mettl16 display reduced mRNA levels of its methylation target, the SAM synthetase Mat2a. The consequence is massive transcriptome dysregulation in ∼64-cell blastocysts that are unfit for further development. This highlights the role of an m6A RNA methyltransferase in facilitating early development via regulation of SAM availability.


Asunto(s)
Adenosina/análogos & derivados , Metiltransferasas/metabolismo , Metiltransferasas/ultraestructura , Adenosina/metabolismo , Animales , Desmetilación , Desarrollo Embrionario/genética , Desarrollo Embrionario/fisiología , Expresión Génica/genética , Células HEK293 , Humanos , Metionina Adenosiltransferasa , Metilación , Metiltransferasas/fisiología , Ratones/embriología , Ratones Noqueados , ARN , Procesamiento Postranscripcional del ARN/fisiología , ARN Mensajero/metabolismo , ARN Nuclear Pequeño/metabolismo
13.
PLoS Genet ; 13(8): e1006956, 2017 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-28827804

RESUMEN

Small RNAs called PIWI -interacting RNAs (piRNAs) are essential for transposon control and fertility in animals. Primary processing is the small RNA biogenesis pathway that uses long single-stranded RNA precursors to generate millions of individual piRNAs, but the molecular mechanisms that identify a transcript as a precursor are poorly understood. Here we demonstrate that artificial tethering of the piRNA biogenesis factor, Armi, to a transcript is sufficient to direct it into primary processing in Drosophila ovaries and in an ovarian cell culture model. In the fly ovarian somatic follicle cells, the transcript becomes cleaved in a stepwise manner, with a 5'→3' directionality, liberating U1-containing ~24 nt piRNAs that are loaded into Piwi. Although uridines are preferred for generation of piRNA 5' ends, processing takes place even in their absence, albeit at a lower efficiency. We show that recombinant Armi has 5'→3' helicase activity, and mutations that abolish this activity also reduce piRNA processing in vivo. Another somatic piRNA pathway factor Yb, an interactor of Armi, is also able to trigger piRNA biogenesis when tethered to a transcript. Tethering-mediated primary piRNA biogenesis is also functional in the fly ovarian germline and loads all the three PIWI proteins present in this environment. Our study finds a broad correlation between piRNA processing and localization of the tethered factors to the cytoplasmic perinuclear ribonucleoprotein granules called germline nuage or somatic Yb bodies. We conclude that transcripts bound by Armi and Yb are identified as piRNA precursors, resulting in localization to cytoplasmic processing granules and their subsequent engagement by the resident piRNA biogenesis machinery.


Asunto(s)
Proteínas de Drosophila/genética , Ovario/crecimiento & desarrollo , ARN Helicasas/genética , ARN Interferente Pequeño/genética , Animales , Elementos Transponibles de ADN/genética , Drosophila melanogaster/genética , Drosophila melanogaster/crecimiento & desarrollo , Femenino , Fertilidad/genética , Células Germinativas/crecimiento & desarrollo , Ovario/metabolismo , ARN Interferente Pequeño/biosíntesis
14.
J Card Fail ; 23(6): 455-463, 2017 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-28435004

RESUMEN

BACKGROUND: Percutaneous ventricular restoration therapy with the use of a left ventricle (LV)-partitioning Parachute device has emerged as a clinical treatment option for LV apical aneurysm after extensive anterior myocardial infarction (AMI). We assessed changes of diastolic mechanics and functional improvements following LV Parachute device implantation by means of cardiac computerized tomography (CCT). METHODS AND RESULTS: CCT data were obtained from 28 patients before and after LV Parachute device implantation. Diastolic functional indices were determined by means of quantitative CCT assessment: 1) transmitral velocities in early (E) and late (A) diastole and ratio (E/A); 2) early diastolic mitral septal tissue velocity (Ea) and E/Ea; and 3) vortex formation time (VFT). Functional improvements were assessed with the use of New York Heart Association (NYHA) functional classification. Among the study patients, there were no significant differences in all transmitral velocities and E/A, though there was significantly increased Ea, reduced E/Ea, and greater VFT 6 months after LV Parachute device implantation. Finally, the improvement of diastolic functional indices after Parachute treatment correlated with observed clinical functional alterations (Δ E/Ea and Δ NYHA functional class:, r = 0.563; P = .002; Δ VFT and Δ NYHA functional class: r = -0.507; P = .006). CONCLUSIONS: LV Parachute device implantation therapy in heart failure caused by AMI and LV apical aneurysm formation showed improvements in several diastolic functional mechanics according to CCT-based measures.


Asunto(s)
Insuficiencia Cardíaca/diagnóstico por imagen , Corazón Auxiliar/tendencias , Isquemia Miocárdica/diagnóstico por imagen , Tomografía Computarizada por Rayos X/tendencias , Disfunción Ventricular Izquierda/diagnóstico por imagen , Función Ventricular Izquierda/fisiología , Anciano , Femenino , Insuficiencia Cardíaca/fisiopatología , Insuficiencia Cardíaca/cirugía , Humanos , Masculino , Persona de Mediana Edad , Isquemia Miocárdica/fisiopatología , Isquemia Miocárdica/cirugía , Estudios Retrospectivos , Resultado del Tratamiento , Disfunción Ventricular Izquierda/fisiopatología , Disfunción Ventricular Izquierda/cirugía
15.
Phytomedicine ; 23(14): 1706-1715, 2016 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-27912872

RESUMEN

BACKGROUND: Typhonium blumei Nicolson & Sivadasan (Araceae) is a traditional Chinese medicinal herb possessing detumescent, detoxifying, and anti-inflammatory activities. It is used in Taiwan as a folk medicine to treat cancer and inflammatory diseases. Typhonium blumei is usually not distinguished from Typhonium roxburghii Schott and they are commonly used interchangeably. PURPOSE: To evaluate and compare the anti-allergic and anti-inflammatory properties of T. blumei and T. roxburghii, their composition profiles and molecular basis of the anti-allergic effect. METHODS: The methanolic plant extracts were partitioned with different solvents to obtain the nonpolar fractions. The anti-allergic activity of the nonpolar fractions was assessed by A23187- and antigen-induced degranulation assays using RBL-2H3 mast cells. Several molecular targets were investigated: FcεRI receptor expression by flow cytometry, calcium influx by live cells imaging fluorescent microscopy, cytokines mRNA expression by RT-PCR, and protein expression by Western blotting. The anti-inflammatory activity was evaluated using superoxide anion and elastase release assays in human neutrophils. TLC, NMR and GC-MS analyses were conducted to evaluate the chemical composition of the fractions. RESULTS: The nonpolar fractions of both Typhonium species showed potent inhibitory activity in A23187-induced degranulation assay in RBL-2H3 cells. They also inhibited superoxide production and elastase release in human neutrophils. T. blumei nonpolar fractions inhibited antigen-induced ß-hexosaminidase and histamine release. The nonpolar fractions of T. blumei significantly inhibited calcium influx upon activation with either A23187 or an antigen. The fractions did not affect FcεRI receptor expression, mRNA level of IL-4 and MCP-1 cytokine production or MAPK proteins expression, but did suppress the calcium signaling pathway via PI3K/PLCγ2. The active fractions were rich in fatty acids with palmitic, linoleic and α-linolenic acids identified as the major fatty acids in both plants. The content of omega-3 unsaturated fatty acids was higher in T. roxburghii nonpolar fractions compared to T. blumei. CONCLUSION: Both species possess potent anti-allergic and anti-inflammatory activities. The inhibition of degranulation in mast cells was attributed to calcium influx modulation. The obtained results support the traditional use of T. blumei in the treatment of inflammatory diseases as well as its substitution with T. roxburghii.


Asunto(s)
Antialérgicos/farmacología , Antiinflamatorios/farmacología , Araceae/química , Calcio/metabolismo , Degranulación de la Célula/efectos de los fármacos , Medicamentos Herbarios Chinos/farmacología , Ácidos Grasos/farmacología , Animales , Antialérgicos/uso terapéutico , Antiinflamatorios/uso terapéutico , Línea Celular , Citocinas/metabolismo , Medicamentos Herbarios Chinos/uso terapéutico , Ácidos Grasos/análisis , Ácidos Grasos/uso terapéutico , Liberación de Histamina/efectos de los fármacos , Humanos , Interleucina-4/metabolismo , Mastocitos/efectos de los fármacos , Mastocitos/metabolismo , Neutrófilos/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Fosfolipasa C gamma/metabolismo , Fosforilación/efectos de los fármacos , Fitoterapia , Ratas , Receptores de IgE/metabolismo , Transducción de Señal , beta-N-Acetilhexosaminidasas/metabolismo
16.
Mol Cell ; 61(1): 138-52, 2016 Jan 07.
Artículo en Inglés | MEDLINE | ID: mdl-26669262

RESUMEN

PIWI-interacting RNAs (piRNAs) guide PIWI proteins to suppress transposons in the cytoplasm and nucleus of animal germ cells, but how silencing in the two compartments is coordinated is not known. Here we demonstrate that endonucleolytic slicing of a transcript by the cytosolic mouse PIWI protein MILI acts as a trigger to initiate its further 5'→3' processing into non-overlapping fragments. These fragments accumulate as new piRNAs within both cytosolic MILI and the nuclear MIWI2. We also identify Exonuclease domain-containing 1 (EXD1) as a partner of the MIWI2 piRNA biogenesis factor TDRD12. EXD1 homodimers are inactive as a nuclease but function as an RNA adaptor within a PET (PIWI-EXD1-Tdrd12) complex. Loss of Exd1 reduces sequences generated by MILI slicing, impacts biogenesis of MIWI2 piRNAs, and de-represses LINE1 retrotransposons. Thus, piRNA biogenesis triggered by PIWI slicing, and promoted by EXD1, ensures that the same guides instruct PIWI proteins in the nucleus and cytoplasm.


Asunto(s)
Proteínas Argonautas/metabolismo , Núcleo Celular/enzimología , Citosol/enzimología , Exonucleasas/metabolismo , Procesamiento Postranscripcional del ARN , ARN Interferente Pequeño/metabolismo , Proteínas de Unión al ARN/metabolismo , Secuencia de Aminoácidos , Animales , Proteínas Argonautas/química , Proteínas Argonautas/genética , Proteínas Portadoras/metabolismo , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/genética , Drosophila melanogaster/metabolismo , Exonucleasas/química , Exonucleasas/genética , Femenino , Regulación de la Expresión Génica , Masculino , Ratones Transgénicos , Modelos Moleculares , Datos de Secuencia Molecular , Complejos Multiproteicos , Dominios y Motivos de Interacción de Proteínas , Interferencia de ARN , ARN Interferente Pequeño/genética , Proteínas de Unión al ARN/química , Proteínas de Unión al ARN/genética
17.
Sci Rep ; 5: 15087, 2015 Oct 12.
Artículo en Inglés | MEDLINE | ID: mdl-26455819

RESUMEN

A fully transparent resistive memory (TRRAM) based on Hafnium oxide (HfO2) with excellent transparency, resistive switching capability, and environmental stability is demonstrated. The retention time measured at 85 °C is over 3 × 10(4) sec, and no significant degradation is observed in 130 cycling test. Compared with ZnO TRRAM, HfO2 TRRAM shows reliable performance under harsh conditions, such as high oxygen partial pressure, high moisture (relative humidity = 90% at 85 °C), corrosive agent exposure, and proton irradiation. Moreover, HfO2 TRRAM fabricated in cross-bar array structures manifests the feasibility of future high density memory applications. These findings not only pave the way for future TRRAM design, but also demonstrate the promising applicability of HfO2 TRRAM for harsh environments.

18.
Neurosci Biobehav Rev ; 55: 444-52, 2015 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-25956248

RESUMEN

The etymology of schizophrenia implies poor functional integration of sensory, cognitive and affective processes. Multisensory integration (MSI) is a spontaneous perceptual-cognitive process by which relevant information from multiple sensory modalities is extracted to generate a holistic experience. Deficits in MSI may hinder prompt and appropriate behavioural responses in a complex and transient environment. Despite extensive investigation of sensory, cognitive and affective processing in patients with schizophrenia, little is known about how MSI is affected in the illness. We systemically searched the PubMed electronic database and reviewed twenty-nine behavioural and neuroimaging studies examining MSI in patients with schizophrenia. The available evidence indicates impaired MSI for non-emotional stimuli in schizophrenia, especially for linguistic information. There is also evidence for altered MSI for emotional stimuli, although findings are inconsistent and may be modality-specific. Brain functional alterations in the superior temporal cortex and inferior frontal cortex appear to underlie the deficits in both non-emotional and emotional MSI. The limitations of the experimental paradigms used and directions for future research are also discussed.


Asunto(s)
Encéfalo/fisiopatología , Percepción/fisiología , Esquizofrenia/fisiopatología , Psicología del Esquizofrénico , Afecto/fisiología , Percepción Auditiva/fisiología , Mapeo Encefálico , Cognición/fisiología , Humanos , Imagen por Resonancia Magnética , Percepción Visual/fisiología
19.
RNA ; 21(5): 833-9, 2015 May.
Artículo en Inglés | MEDLINE | ID: mdl-25778731

RESUMEN

Piwi-interacting RNAs (piRNAs) guide Piwi argonautes to their transposon targets for silencing. The highly conserved protein Maelstrom is linked to both piRNA biogenesis and effector roles in this pathway. One defining feature of Maelstrom is the predicted MAEL domain of unknown molecular function. Here, we present the first crystal structure of the MAEL domain from Bombyx Maelstrom, which reveals a nuclease fold. The overall architecture resembles that found in Mg(2+)- or Mn(2+)-dependent DEDD nucleases, but a clear distinguishing feature is the presence of a structural Zn(2+) ion coordinated by the conserved ECHC residues. Strikingly, metazoan Maelstrom orthologs across the animal kingdom lack the catalytic DEDD residues, and as we show for Bombyx Maelstrom are inactive as nucleases. However, a MAEL domain-containing protein from amoeba having both sequence motifs (DEDD and ECHC) is robustly active as an exoribonuclease. Finally, we show that the MAEL domain of Bombyx Maelstrom displays a strong affinity for single-stranded RNAs. Our studies suggest that the ancient MAEL nuclease domain evolved to function as an RNA-binding module in metazoan Maelstrom.


Asunto(s)
Bombyx/metabolismo , Evolución Molecular , Proteínas de Insectos/química , ARN Interferente Pequeño/metabolismo , Proteínas de Unión al ARN/química , Ribonucleasas/química , Secuencia de Aminoácidos , Animales , Bombyx/genética , Cristalografía por Rayos X , Proteínas de Drosophila/química , Proteínas de Drosophila/genética , Proteínas de Insectos/genética , Modelos Moleculares , Datos de Secuencia Molecular , Estructura Terciaria de Proteína , Proteínas de Unión al ARN/genética , Ribonucleasas/genética , Homología de Secuencia
20.
Materials (Basel) ; 8(8): 4805-4816, 2015 Jul 29.
Artículo en Inglés | MEDLINE | ID: mdl-28793473

RESUMEN

Acoustically modulated methane jet diffusion flames were used to enhance carbon nanostructure synthesis. A catalytic nickel substrate was employed to collect the deposit materials at sampling position z = 10 mm above the burner exit. The fabrication of carbon nano-onions (CNOs) and carbon nanotubes (CNTs) was significantly enhanced by acoustic excitation at frequencies near the natural flickering frequency (ƒ = 20 Hz) and near the acoustically resonant frequency (ƒ = 90 Hz), respectively. At these characteristic frequencies, flow mixing was markedly enhanced by acoustic excitation, and a flame structure with a bright slender core flame was generated, which provided a favorable flame environment for the growth of carbon nanomaterials. The production rate of CNOs was high at 20 Hz (near the natural flickering frequency), at which the gas temperature was about 680 °C. Additionally, a quantity of CNTs was obtained at 70-95 Hz, near the acoustically resonant frequency, at which the gas temperature was between 665 and 830 °C. However, no carbon nanomaterials were synthesized at other frequencies. The enhanced synthesis of CNOs and CNTs is attributed to the strong mixing of the fuel and oxidizer due to the acoustic excitation at resonant frequencies.

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