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1.
BMC Plant Biol ; 24(1): 307, 2024 Apr 22.
Artículo en Inglés | MEDLINE | ID: mdl-38644483

RESUMEN

BACKGROUND: Luffa (Luffa spp.) is an economically important crop of the Cucurbitaceae family, commonly known as sponge gourd or vegetable gourd. It is an annual cross-pollinated crop primarily found in the subtropical and tropical regions of Asia, Australia, Africa, and the Americas. Luffa serves not only as a vegetable but also exhibits medicinal properties, including anti-inflammatory, antidiabetic, and anticancer effects. Moreover, the fiber derived from luffa finds extensive applications in various fields such as biotechnology and construction. However, luffa Fusarium wilt poses a severe threat to its production, and existing control methods have proven ineffective in terms of cost-effectiveness and environmental considerations. Therefore, there is an urgent need to develop luffa varieties resistant to Fusarium wilt. Single-plant GWAS (sp-GWAS) has been demonstrated as a promising tool for the rapid and efficient identification of quantitative trait loci (QTLs) associated with target traits, as well as closely linked molecular markers. RESULTS: In this study, a collection of 97 individuals from 73 luffa accessions including two major luffa species underwent single-plant GWAS to investigate luffa Fusarium wilt resistance. Utilizing the double digest restriction site associated DNA (ddRAD) method, a total of 8,919 high-quality single nucleotide polymorphisms (SNPs) were identified. The analysis revealed the potential for Fusarium wilt resistance in accessions from both luffa species. There are 6 QTLs identified from 3 traits, including the area under the disease progress curve (AUDPC), a putative disease-resistant QTL, was identified on the second chromosome of luffa. Within the region of linkage disequilibrium, a candidate gene homologous to LOC111009722, which encodes peroxidase 40 and is associated with disease resistance in Cucumis melo, was identified. Furthermore, to validate the applicability of the marker associated with resistance from sp-GWAS, an additional set of 21 individual luffa plants were tested, exhibiting 93.75% accuracy in detecting susceptible of luffa species L. aegyptiaca Mill. CONCLUSION: In summary, these findings give a hint of genome position that may contribute to luffa wild resistance to Fusarium and can be utilized in the future luffa wilt resistant breeding programs aimed at developing wilt-resistant varieties by using the susceptible-linked SNP marker.


Asunto(s)
Resistencia a la Enfermedad , Fusarium , Estudio de Asociación del Genoma Completo , Luffa , Enfermedades de las Plantas , Polimorfismo de Nucleótido Simple , Sitios de Carácter Cuantitativo , Fusarium/fisiología , Polimorfismo de Nucleótido Simple/genética , Enfermedades de las Plantas/microbiología , Enfermedades de las Plantas/genética , Resistencia a la Enfermedad/genética , Luffa/genética , Luffa/microbiología , Genoma de Planta , Marcadores Genéticos , Variación Genética
2.
Plant J ; 110(4): 1198-1212, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-35306708

RESUMEN

In seed plants, phospho-base N-methyltransferase (PMT) catalyzes a key step in the biosynthesis pathway of phosphatidylcholine (PC), the most abundant phospholipid class. Arabidopsis thaliana possesses three copies of PMT, with PMT1 and PMT3 play a primary role because the pmt1 pmt3 double mutant shows considerably reduced PC content with a pale seedling phenotype. Although the function of PMT1 and PMT3 may be redundant because neither of the parental single mutants showed a similar mutant phenotype, major developmental defects and possible functional divergence of these PMTs underlying the pale pmt1 pmt3 seedling phenotype are unknown. Here, we show the major developmental defect of the pale seedlings in xylem of the hypocotyl with partial impairments in chloroplast development and photosynthetic activity in leaves. Although PMT1 and PMT3 are localized at the endoplasmic reticulum, their tissue-specific expression pattern was distinct in hypocotyls and roots. Intriguingly, the function of PMT3 but not PMT1 requires its characteristic N-terminal sequence in addition to the promoter because truncation of the N-terminal sequence of PMT3 or substitution with PMT1 driven by the PMT3 promoter failed to rescue the pale pmt1 pmt3 seedling phenotype. Thus, PMT3 function requires the N-terminal sequence in addition to its promoter, whereas the PMT1 function is defined by the promoter.


Asunto(s)
Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/genética , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Metiltransferasas/genética , Metiltransferasas/metabolismo , Mutación , Fosfatidilcolinas , Plantones/metabolismo
3.
Magn Reson Med ; 89(2): 536-549, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36198001

RESUMEN

PURPOSE: Through-time spiral GRAPPA is a real-time imaging technique that enables ungated, free-breathing evaluation of the left ventricle. However, it requires a separate fully-sampled calibration scan to calculate GRAPPA weights. A self-calibrated through-time spiral GRAPPA method is proposed that uses a specially designed spiral trajectory with interleaved arm ordering such that consecutive undersampled frames can be merged to form calibration data, eliminating the separate fully-sampled acquisition. THEORY AND METHODS: The proposed method considers the time needed to acquire data at all points in a GRAPPA calibration kernel when using interleaved arm ordering. Using this metric, simulations were performed to design a spiral trajectory for self-calibrated GRAPPA. Data were acquired in healthy volunteers using the proposed method and a comparison electrocardiogram-gated and breath-held cine scan. Left ventricular functional values and image quality are compared. RESULTS: A 12-arm spiral trajectory was designed with a temporal resolution of 32.72 ms/cardiac phase with an acceleration factor of 3. Functional values calculated using the proposed method and the gold-standard method were not statistically significantly different (paired t-test, p < 0.05). Image quality ratings were lower for the proposed method, with statistically significantly different ratings (Wilcoxon signed rank test, p < 0.05) for two of five image quality aspects rated (level of artifact, blood-myocardium contrast). CONCLUSIONS: A self-calibrated through-time spiral GRAPPA reconstruction can enable ungated, free-breathing evaluation of the left ventricle in 71 s. Functional values are equivalent to a gold-standard cine technique, although some aspects of image quality may be inferior due to the real-time nature of the data collection.


Asunto(s)
Respiración , Función Ventricular Izquierda , Humanos , Artefactos , Contencion de la Respiración , Corazón , Algoritmos , Procesamiento de Imagen Asistido por Computador/métodos , Imagen por Resonancia Cinemagnética/métodos , Reproducibilidad de los Resultados
4.
MAGMA ; 36(3): 513-523, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-36574163

RESUMEN

OBJECTIVE: The goal of this work was to assess the feasibility of performing MRF in the liver on a 0.55 T scanner and to examine the feasibility of water-fat separation using rosette MRF at 0.55 T. MATERIALS AND METHODS: Spiral and rosette MRF sequences were implemented on a commercial 0.55 T scanner. The accuracy of both sequences in T1 and T2 quantification was validated in the ISMRM/NIST system phantom. The efficacy of rosette MRF in water-fat separation was evaluated in simulations and water/oil phantoms. Both spiral and rosette MRF were performed in the liver of healthy subjects. RESULTS: In the ISMRM/NIST phantom, both spiral and rosette MRF achieved good agreement with reference values in T1 and T2 measurements. In addition, rosette MRF enables water-fat separation and can generate water- and fat- specific T1 maps, T2 maps, and proton density images from the same dataset for a spatial resolution of 1.56 × 1.56 × 5mm3 within the acquisition time of 15 s. CONCLUSION: It is feasible to measure T1 and T2 simultaneously in the liver using MRF on a 0.55 T system with lower performance gradients compared to state-of-the-art 1.5 T and 3 T systems within an acquisition time of 15 s. In addition, rosette MRF enables water-fat separation along with T1 and T2 quantification with no time penalty.


Asunto(s)
Imagen por Resonancia Magnética , Agua , Humanos , Imagen por Resonancia Magnética/métodos , Abdomen , Hígado/diagnóstico por imagen , Fantasmas de Imagen , Procesamiento de Imagen Asistido por Computador/métodos
5.
Gene Ther ; 29(9): 555-565, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-35999303

RESUMEN

Gene therapy constitutes one of the most promising mode of disease treatments. Two key properties for therapeutic delivery vectors are its transduction efficiency (how well the vector delivers therapeutic cargo to desired target cells) and specificity (how well it avoids off-target delivery into unintended cells within the body). Here we developed an integrated bioinformatics and experimental pipeline that enables multiplex measurement of transduction efficiency and specificity, particularly by measuring how libraries of delivery vectors transduce libraries of diverse cell types. We demonstrated that pairing high-throughput measurement of AAV identity with high-resolution single-cell RNA transcriptomic sequencing maps how natural and engineered AAV variants transduce individual cells within human cerebral and ocular organoids. We further demonstrate that efficient AAV transduction observed in organoids is recapitulated in vivo in non-human primates. This library-on-library technology will be important for determining the safety and efficacy of therapeutic delivery vectors.


Asunto(s)
Dependovirus , Vectores Genéticos , Animales , Bioensayo , Dependovirus/metabolismo , Vectores Genéticos/genética , ARN/metabolismo , Transducción Genética , Tropismo Viral
6.
J Exp Bot ; 73(9): 2952-2970, 2022 05 13.
Artículo en Inglés | MEDLINE | ID: mdl-35560187

RESUMEN

Phosphatidylglycerol (PG) is the only major phospholipid in the thylakoid membrane of chloroplasts. PG is essential for photosynthesis, and loss of PG in Arabidopsis thaliana results in severe defects of growth and chloroplast development, with decreased chlorophyll accumulation, impaired thylakoid formation, and down-regulation of photosynthesis-associated genes encoded in nuclear and plastid genomes. However, how the absence of PG affects gene expression and plant growth remains unclear. To elucidate this mechanism, we investigated transcriptional profiles of a PG-deficient Arabidopsis mutant pgp1-2 under various light conditions. Microarray analysis demonstrated that reactive oxygen species (ROS)-responsive genes were up-regulated in pgp1-2. However, ROS production was not enhanced in the mutant even under strong light, indicating limited impacts of photooxidative stress on the defects of pgp1-2. Illumination to dark-adapted pgp1-2 triggered down-regulation of photosynthesis-associated nuclear-encoded genes (PhANGs), while plastid-encoded genes were constantly suppressed. Overexpression of GOLDEN2-LIKE1 (GLK1), a transcription factor gene regulating chloroplast development, in pgp1-2 up-regulated PhANGs but not plastid-encoded genes along with chlorophyll accumulation. Our data suggest a broad impact of PG biosynthesis on nuclear-encoded genes partially via GLK1 and a specific involvement of this lipid in plastid gene expression and plant development.


Asunto(s)
Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/genética , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Clorofila/metabolismo , Cloroplastos/metabolismo , Expresión Génica , Regulación de la Expresión Génica de las Plantas , Fosfatidilgliceroles/metabolismo , Fotosíntesis/genética , Plastidios/genética , Plastidios/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Factores de Transcripción/metabolismo
7.
J Exp Bot ; 73(9): 2985-2994, 2022 05 13.
Artículo en Inglés | MEDLINE | ID: mdl-35560207

RESUMEN

Phosphorus (P) is an essential nutrient for plants. Membrane lipid remodeling is an adaptive mechanism for P-starved plants that replaces membrane phospholipids with non-P galactolipids, presumably to retrieve scarce P sources and maintain membrane integrity. Whereas metabolic pathways to convert phospholipids to galactolipids are well-established, the mechanism by which phospholipid biosynthesis is involved in this process remains elusive. Here, we report that phospho-base N-methyltransferases 1 and 2 (PMT1 and PMT2), which convert phosphoethanolamine to phosphocholine (PCho), are transcriptionally induced by P starvation. Shoots of seedlings of pmt1 pmt2 double mutant showed defective growth upon P starvation; however, membrane lipid profiles were unaffected. We found that P-starved pmt1 pmt2 with defective leaf growth had reduced PCho content, and the growth defect was rescued by exogenous supplementation of PCho. We propose that PMT1 and PMT2 are induced by P starvation to produce PCho mainly for leaf growth maintenance, rather than for phosphatidylcholine biosynthesis, in membrane lipid remodeling.


Asunto(s)
Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Galactolípidos/metabolismo , Regulación de la Expresión Génica de las Plantas , Lípidos de la Membrana/metabolismo , Metiltransferasas/genética , Fosfolípidos/metabolismo , Fósforo/metabolismo , Fosforilcolina/metabolismo , Hojas de la Planta/metabolismo
8.
Phys Chem Chem Phys ; 25(1): 124-130, 2022 Dec 21.
Artículo en Inglés | MEDLINE | ID: mdl-36475566

RESUMEN

Constructing an artificial solid electrolyte interphase (SEI) layer is an effective strategy for solving uncontrolled Li dendrite growth resulting from an unstable and heterogeneous Li/electrolyte interface. Herein, we develop a hybrid layer of a LiZn alloy and a polyethylene oxide (PEO) polymer to protect the Li metal anode for achieving a Li dendrite-free Li metal anode surface. The LiZn alloy is advantageous for fast Li+ transport, and is uniformly dispersed in the PEO matrix to regulate electronic and Li+ ion flux distributions homogeneously. Furthermore, the flexible PEO network can alleviate the volume change during cycling. The synergistic effect enables Li deposition underneath the hybrid film. Hence, the hybrid protection film results in significantly improved cycling stability with respect to the pristine Li metal anode. A symmetric Li/Li cell with a composite protective layer can be cycled for over 1000 h at a current density of 1 mA cm-2 with a fixed capacity of 1 mA h cm-2, and a full cell with a high areal capacity of the LiFePO4 (2.45 mA h cm-2) cathode exhibits an outstanding cycling performance.

9.
Res Nurs Health ; 45(3): 327-336, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35184319

RESUMEN

This randomized controlled trial was conducted to evaluate the effects of a 3-month-long Chan-Chuang qigong program on patients' physical performance and quality of life while excluding the influence caused by the progression of their cognitive impairment. Patients with mild to moderate cognitive impairment were recruited from two dementia daycare centers in Taiwan. The control group (n = 41) received the standardized plan of treatment, and the qigong group (n = 39) received the standardized plan of treatment plus the Chan-Chuang qigong program. The outcomes were muscle strength, muscle endurance, exercise capacity, and quality of life. After controlling for the progression of cognitive impairment, the qigong group showed significant improvements over the control group and baseline in muscle strength and exercise capacity at Months 2 and 3 (p < 0.05) and in muscle endurance at Months 1, 2, and 3 (p < 0.05). The Cognitron test scores were significantly associated with muscle strength (p = 0.03), whereas the Corsi block-tapping test scores were significantly associated with exercise capacity (p = 0.001). Furthermore, a significant between-group difference was detected in the physical (p = 0.01), not mental (p = 0.83), component of quality of life. The 3-month Chan-Chuang qigong program can be applied for patients with mild to moderate cognitive impairment as complementary therapy to improve their muscle strength, muscle endurance, exercise capacity, and physical quality of life. This program should be practiced for at least 2 months to achieve satisfactory results.


Asunto(s)
Disfunción Cognitiva , Qigong , Disfunción Cognitiva/terapia , Humanos , Rendimiento Físico Funcional , Calidad de Vida , Taiwán
10.
Int J Mol Sci ; 23(14)2022 Jul 19.
Artículo en Inglés | MEDLINE | ID: mdl-35887309

RESUMEN

A transparent cornea is paramount for vision. Corneal opacity is one of the leading causes of blindness. Although conventional corneal transplantation has been successful in recovering patients' vision, the outcomes are challenged by a global lack of donor tissue availability. Bioengineered corneal tissues are gaining momentum as a new source for corneal wound healing and scar management. Extracellular matrix (ECM)-scaffold-based engineering offers a new perspective on corneal regenerative medicine. Ultrathin stromal laminar tissues obtained from lenticule-based refractive correction procedures, such as SMall Incision Lenticule Extraction (SMILE), are an accessible and novel source of collagen-rich ECM scaffolds with high mechanical strength, biocompatibility, and transparency. After customization (including decellularization), these lenticules can serve as an acellular scaffold niche to repopulate cells, including stromal keratocytes and stem cells, with functional phenotypes. The intrastromal transplantation of these cell/tissue composites can regenerate native-like corneal stromal tissue and restore corneal transparency. This review highlights the current status of ECM-scaffold-based engineering with cells, along with the development of drug and growth factor delivery systems, and elucidates the potential uses of stromal lenticule scaffolds in regenerative therapeutics.


Asunto(s)
Sustancia Propia , Trasplante de Córnea , Colágeno , Córnea , Trasplante de Córnea/métodos , Humanos , Cicatrización de Heridas
11.
Magn Reson Med ; 85(1): 103-119, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-32720408

RESUMEN

PURPOSE: This work aims to develop an approach for simultaneous water-fat separation and myocardial T1 and T2 quantification based on the cardiac MR fingerprinting (cMRF) framework with rosette trajectories at 3T and 1.5T. METHODS: Two 15-heartbeat cMRF sequences with different rosette trajectories designed for water-fat separation at 3T and 1.5T were implemented. Water T1 and T2 maps, water image, and fat image were generated with B0 inhomogeneity correction using a B0 map derived from the cMRF data themselves. The proposed water-fat separation rosette cMRF approach was validated in the International Society for Magnetic Resonance in Medicine/National Institute of Standards and Technology MRI system phantom and water/oil phantoms. It was also applied for myocardial tissue mapping of healthy subjects at both 3T and 1.5T. RESULTS: Water T1 and T2 values measured using rosette cMRF in the International Society for Magnetic Resonance in Medicine/National Institute of Standards and Technology phantom agreed well with the reference values. In the water/oil phantom, oil was well suppressed in the water images and vice versa. Rosette cMRF yielded comparable T1 but 2~3 ms higher T2 values in the myocardium of healthy subjects than the original spiral cMRF method. Epicardial fat deposition was also clearly shown in the fat images. CONCLUSION: Rosette cMRF provides fat images along with myocardial T1 and T2 maps with significant fat suppression. This technique may improve visualization of the anatomical structure of the heart by separating water and fat and could provide value in diagnosing cardiac diseases associated with fibrofatty infiltration or epicardial fat accumulation. It also paves the way toward comprehensive myocardial tissue characterization in a single scan.


Asunto(s)
Corazón , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , Agua , Corazón/diagnóstico por imagen , Humanos , Miocardio , Fantasmas de Imagen , Reproducibilidad de los Resultados
12.
Magn Reson Med ; 85(6): 3112-3124, 2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-33368649

RESUMEN

PURPOSE: The aim of this study was to develop a high-resolution 3D oxygen-17 (17 O) MRI method to delineate the kinetics of 17 O-enriched water (H217 O) across the entire mouse brain after a bolus injection via the tail vein. METHODS: The dynamic 17 O signal was acquired with a golden-means-based 3D radial sampling scheme. To achieve adequate temporal resolution with preserved spatial resolution, a k-space-weighted view sharing strategy was used in image reconstruction with an adaptive window size tailored to the kinetics of the 17 O signal. Simulation studies were performed to determine the adequate image reconstruction parameters. The established method was applied to delineating the kinetics of intravenously injected H217 O in vivo in the post-stroke mouse brain. RESULTS: The proposed dynamic 17 O-MRI method achieved an isotropic resolution of 1.21 mm (0.77 mm nominal) in mouse brain at 9.4T, with the temporal resolution increased gradually from 3 s at the initial phase of rapid signal increase to 15 s at the steady-state. The high spatial resolution enabled the delineation of the heterogeneous H217 O uptake and washout kinetics in stroke-affected mouse brain. CONCLUSION: The current study demonstrated a 3D 17 O-MRI method for dynamic monitoring of 17 O signal changes with high spatial and temporal resolution. The method can be utilized to quantify physiological parameters such as cerebral blood flow and blood-brain barrier permeability by tracking injected H217 O. It can also be used to measure oxygen consumption rate in 17 O-oxygen inhalation studies.


Asunto(s)
Interpretación de Imagen Asistida por Computador , Imagenología Tridimensional , Animales , Aumento de la Imagen , Imagen por Resonancia Magnética , Ratones , Isótopos de Oxígeno
13.
Medicina (Kaunas) ; 57(4)2021 Apr 10.
Artículo en Inglés | MEDLINE | ID: mdl-33920151

RESUMEN

Background and objectives: the aim of this study was to analyze the efficacy of a modified "amnion-assisted conjunctival epithelial redirection (ACER)" technique for the treatment of partial limbal stem cell deficiency (LSCD). Materials and methods: the medical records of three patients with partial LSCD who underwent corneal surface reconstruction with modified ACER following superficial keratectomy were retrospectively studied. Briefly, in this technique, an inner amniotic membrane (AM) layer was applied on the corneal surface to promote corneal re-epithelialization. The outer AM layer was applied as a barrier to prevent the invasion of conjunctival epithelial cells into the cornea before the corneal surface was completely covered by corneal epithelial cells derived from the remaining intact limbal stem cells. Results: in all three cases, the outer AM layer successfully kept the conjunctival epithelium away from the corneal surface and prevented an admixture of conjunctival epithelial cells with corneal epithelial cells. In all three patients, the cornea was completely re-epithelized with epithelial cells derived from the remaining healthy limbal stem cells, and a clear visual axis was maintained without recurrence for a mean follow-up period of 37.3 ± 8.6 months. Conclusions: the preliminary results suggest that modified ACER appears to be a viable option for patients with partial LSCD.


Asunto(s)
Epitelio Corneal , Limbo de la Córnea , Amnios/trasplante , Humanos , Limbo de la Córnea/cirugía , Estudios Retrospectivos , Células Madre
14.
Plant Physiol ; 179(2): 433-445, 2019 02.
Artículo en Inglés | MEDLINE | ID: mdl-30518673

RESUMEN

Phosphatidylcholine (PC) is a primary class of membrane lipids in most eukaryotes. In plants, the primary PC biosynthetic pathway and its role in plant growth and development remain elusive due to lack of a mutant model with substantially decreased PC content. Recently, a double mutant of Arabidopsis (Arabidopsis thaliana) PHOSPHO-BASE N-METHYLTRANSFERASE 1 (PMT1) and PMT3 was reported with reduced PC content and defective plant growth. However, residual PC content as well as the nonlethal phenotype of the mutant suggests an additional enzyme contributes to PC biosynthesis. In this article, we report on the role of three PMTs in PC biosynthesis and plant development, with a focus on PMT2. PMT2 had the highest expression level among the three PMTs, and it was highly expressed in roots. The pmt1 pmt2 double mutant enhanced the defects in root growth, cell viability, and PC content of pmt1, suggesting that PMT2 functions together with PMT1 in roots. Chemical inhibition of PMT activity in wild-type roots reproduced the short root phenotype observed in pmt1 pmt2, suggesting that PMT1 and PMT2 are the major PMT isoforms in roots. In shoots, pmt1 pmt2 pmt3 enhanced the phenotype of pmt1 pmt3, showing seedling lethality and further reduced PC content without detectable de novo PC biosynthesis. These results suggest that PMTs catalyze an essential reaction step in PC biosynthesis and that the three PMTs have differential tissue-specific functions in PC biosynthesis and plant growth.


Asunto(s)
Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Metiltransferasas/metabolismo , Fosfatidilcolinas/biosíntesis , Arabidopsis/genética , Proteínas de Arabidopsis/genética , Regulación de la Expresión Génica de las Plantas , Prueba de Complementación Genética , Metiltransferasas/genética , Mutación , Raíces de Plantas/enzimología , Raíces de Plantas/genética , Raíces de Plantas/crecimiento & desarrollo , Brotes de la Planta/genética , Brotes de la Planta/metabolismo , Plantas Modificadas Genéticamente , Plantones/genética , Plantones/metabolismo
15.
J Cardiovasc Magn Reson ; 22(1): 74, 2020 10 12.
Artículo en Inglés | MEDLINE | ID: mdl-33040733

RESUMEN

AIM: Human Immunodeficiency Virus (HIV) patients commonly experience dyspnea for which an immediate cause may not be always apparent. In this prospective cohort study of HIV patients with exercise limitation, we use cardiopulmonary exercise testing (CPET) coupled with exercise cardiovascular magnetic resonance (CMR) to elucidate etiologies of dyspnea. METHODS AND RESULTS: Thirty-four HIV patients on antiretroviral therapy with dyspnea and exercise limitation (49.7 years, 65% male, mean absolute CD4 count 700) underwent comprehensive evaluation with combined rest and maximal exercise treadmill CMR and CPET. The overall mean oxygen consumption (VO2) peak was reduced at 23.2 ± 6.9 ml/kg/min with 20 patients (58.8% of overall cohort) achieving a respiratory exchange ratio > 1. The ventilatory efficiency (VE)/VCO2 slope was elevated at 36 ± 7.92, while ventilatory reserve (VE: maximal voluntary ventilation (MVV)) was within normal limits. The mean absolute right ventricular (RV) and left ventricular (LV) contractile reserves were preserved at 9.0% ± 11.2 and 9.4% ± 9.4, respectively. The average resting and post-exercise mean average pulmonary artery velocities were 12.2 ± 3.9 cm/s and 18.9 ± 8.3 respectively, which suggested lack of exercise induced pulmonary artery hypertension (PAH). LV but not RV delayed enhancement were identified in five patients. Correlation analysis found no relationship between peak VO2 measures of contractile RV or LV reserve, but LV and RV stroke volume correlated with PET CO2 (p = 0.02, p = 0.03). CONCLUSION: Well treated patients with HIV appear to have conserved RV and LV function, contractile reserve and no evidence of exercise induced PAH. However, we found evidence of impaired ventilation suggesting a non-cardiopulmonary etiology for dyspnea.


Asunto(s)
Disnea/etiología , Prueba de Esfuerzo , Tolerancia al Ejercicio , Infecciones por VIH/complicaciones , Pulmón/fisiopatología , Imagen por Resonancia Magnética , Ventilación Pulmonar , Adulto , Fármacos Anti-VIH/uso terapéutico , Disnea/diagnóstico , Disnea/fisiopatología , Femenino , Infecciones por VIH/diagnóstico , Infecciones por VIH/tratamiento farmacológico , Humanos , Masculino , Persona de Mediana Edad , Consumo de Oxígeno , Valor Predictivo de las Pruebas , Estudios Prospectivos , Factores de Riesgo , Función Ventricular
16.
Hum Mutat ; 40(4): 374-379, 2019 04.
Artículo en Inglés | MEDLINE | ID: mdl-30556619

RESUMEN

Rapid advances in genomic technologies have facilitated the identification pathogenic variants causing human disease. We report siblings with developmental and epileptic encephalopathy due to a novel, shared heterozygous pathogenic 13 bp duplication in SYNGAP1 (c.435_447dup, p.(L150Vfs*6)) that was identified by whole genome sequencing (WGS). The pathogenic variant had escaped earlier detection via two methodologies: whole exome sequencing and high-depth targeted sequencing. Both technologies had produced reads carrying the variant, however, they were either not aligned due to the size of the insertion or aligned to multiple major histocompatibility complex (MHC) regions in the hg19 reference genome, making the critical reads unavailable for variant calling. The WGS pipeline followed different protocols, including alignment of reads to the GRCh37 reference genome, which lacks the additional MHC contigs. Our findings highlight the benefit of using orthogonal clinical bioinformatic pipelines and all relevant inheritance patterns to re-analyze genomic data in undiagnosed patients.


Asunto(s)
Biología Computacional/métodos , Análisis Mutacional de ADN/métodos , Mutación , Estudios de Asociación Genética/métodos , Genoma Humano , Genómica/métodos , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Fenotipo
17.
Plant J ; 96(5): 1064-1075, 2018 12.
Artículo en Inglés | MEDLINE | ID: mdl-30218542

RESUMEN

Phosphatidylcholine (PtdCho) is a predominant membrane lipid class in eukaryotes. Phospho-base N-methyltransferase (PMT) catalyzes a critical step in PtdCho biosynthesis. However, in Arabidopsis thaliana, the discovery of involvement of the specific PMT isoform in PtdCho biosynthesis remains elusive. Here, we show that PMT1 and PMT3 redundantly play an essential role in phosphocholine (PCho) biosynthesis, a prerequisite for PtdCho production. A pmt1 pmt3 double mutant was devoid of PCho, which affected PtdCho biosynthesis in vivo, showing severe growth defects in post-embryonic development. PMT1 and PMT3 were both highly expressed in the vasculature. The pmt1 pmt3 mutants had specifically affected leaf vein development and showed pale-green seedlings that were rescued by exogenous supplementation of PCho. We suggest that PMT1 and PMT3 are the primary enzymes for PCho biosynthesis and are involved in PtdCho biosynthesis and vascular development in Arabidopsis seedlings.


Asunto(s)
Proteínas de Arabidopsis/metabolismo , Arabidopsis/enzimología , Metiltransferasas/metabolismo , Fosfatidilcolinas/biosíntesis , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Membrana Celular/metabolismo , Lípidos de la Membrana/metabolismo , Redes y Vías Metabólicas , Metiltransferasas/genética , Hojas de la Planta/metabolismo , Raíces de Plantas/metabolismo , Plantas Modificadas Genéticamente , Plantones/metabolismo , Xilema/metabolismo
18.
Lancet ; 390(10094): 600-612, 2017 08 05.
Artículo en Inglés | MEDLINE | ID: mdl-28242111

RESUMEN

An estimated 95 million people worldwide are affected by cataract. Cataract still remains the leading cause of blindness in middle-income and low-income countries. With the advancement of surgical technology and techniques, cataract surgery has evolved to small-incisional surgery with rapid visual recovery, good visual outcomes, and minimal complications in most patients. With the development of advanced technology in intraocular lenses, the combined treatment of cataract and astigmatism or presbyopia, or both, is possible. Paediatric cataracts have a different pathogenesis, surgical concerns, and postoperative clinical course from those of age-related cataracts, and the visual outcome is multifactorial and dependent on postoperative visual rehabilitation. New developments in cataract surgery will continue to improve the visual, anatomical, and patient-reported outcomes. Future work should focus on promoting the accessibility and quality of cataract surgery in developing countries.


Asunto(s)
Extracción de Catarata/métodos , Catarata/etiología , Catarata/epidemiología , Extracción de Catarata/efectos adversos , Extracción de Catarata/tendencias , Humanos , Lentes Intraoculares , Cuidados Posoperatorios/métodos , Cuidados Preoperatorios/métodos , Factores de Riesgo
19.
Magn Reson Med ; 79(1): 256-263, 2018 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-28295552

RESUMEN

PURPOSE: The current study aimed to develop a three-dimensional (3D) dynamic oxygen-17 (17 O) MR imaging method with high temporal and spatial resolution to delineate the kinetics of 17 O water uptake and washout in the brains of mice with glioblastoma (GBM). METHODS: A 3D imaging method with a stack-of-stars golden-ratio-based radial sampling scheme was employed to acquire 17 O signal in vivo. A k-space-weighted image reconstruction method was used to improve the temporal resolution while preserving spatial resolution. Simulation studies were performed to validate the method. Using this method, the kinetics of 17 O water uptake and washout in the brains of mice with GBM were delineated after an intravenous bolus injection of 17 O water. RESULTS: The proposed 17 O imaging method achieved an effective temporal resolution of 7.56 s with a nominal voxel size of 5.625 µL in the mouse brain at 9.4 T. Reduced uptake and prolonged washout of 17 O water were observed in tumor tissue, suggesting compromised cerebral perfusion. CONCLUSION: This study demonstrated a promising dynamic 17 O imaging approach that can delineate 17 O water kinetics in vivo with high temporal and spatial resolution. It can also be used to image cerebral oxygen consumption rate in oxygen-17 inhalation studies. Magn Reson Med 79:256-263, 2018. © 2017 International Society for Magnetic Resonance in Medicine.


Asunto(s)
Neoplasias Encefálicas/diagnóstico por imagen , Encéfalo/diagnóstico por imagen , Glioblastoma/diagnóstico por imagen , Procesamiento de Imagen Asistido por Computador , Isótopos de Oxígeno/química , Agua/química , Algoritmos , Animales , Simulación por Computador , Medios de Contraste , Aumento de la Imagen , Interpretación de Imagen Asistida por Computador , Imagenología Tridimensional , Cinética , Imagen por Resonancia Magnética , Masculino , Ratones , Ratones Desnudos , Fantasmas de Imagen
20.
Magn Reson Med ; 80(6): 2681-2690, 2018 12.
Artículo en Inglés | MEDLINE | ID: mdl-29744935

RESUMEN

PURPOSE: The goal of this study was to develop a fast MR fingerprinting (MRF) method for simultaneous T1 and T2 mapping in DCE-MRI studies in mice. METHODS: The MRF sequences based on balanced SSFP and fast imaging with steady-state precession were implemented and evaluated on a 7T preclinical scanner. The readout used a zeroth-moment-compensated variable-density spiral trajectory that fully sampled the entire k-space and the inner 10 × 10 k-space with 48 and 4 interleaves, respectively. In vitro and in vivo studies of mouse brain were performed to evaluate the accuracy of MRF measurements with both fully sampled and undersampled data. The application of MRF to dynamic T1 and T2 mapping in DCE-MRI studies were demonstrated in a mouse model of heterotopic glioblastoma using gadolinium-based and dysprosium-based contrast agents. RESULTS: The T1 and T2 measurements in phantom showed strong agreement between the MRF and the conventional methods. The MRF with spiral encoding allowed up to 8-fold undersampling without loss of measurement accuracy. This enabled simultaneous T1 and T2 mapping with 2-minute temporal resolution in DCE-MRI studies. CONCLUSION: Magnetic resonance fingerprinting provides the opportunity for dynamic quantification of contrast agent distribution in preclinical tumor models on high-field MRI scanners.


Asunto(s)
Medios de Contraste/química , Imagen por Resonancia Magnética , Algoritmos , Animales , Encéfalo/diagnóstico por imagen , Mapeo Encefálico , Línea Celular Tumoral , Modelos Animales de Enfermedad , Disprosio/química , Gadolinio/química , Glioblastoma/diagnóstico por imagen , Humanos , Interpretación de Imagen Asistida por Computador/métodos , Procesamiento de Imagen Asistido por Computador/métodos , Imagenología Tridimensional/métodos , Modelos Lineales , Ratones , Ratones Desnudos , Trasplante de Neoplasias , Fantasmas de Imagen
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