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Focused Ultrasound Blood-Brain Barrier Opening (FUS-BBBO) can deliver adeno-associated viral vectors (AAVs) to treat genetic disorders of the brain. However, such disorders often affect large brain regions. Moreover, the applicability of FUS-BBBO in the treatment of brain-wide genetic disorders has not yet been evaluated. Herein, we evaluated the transduction efficiency and safety of opening up to 105 sites simultaneously. Increasing the number of targeted sites increased gene delivery efficiency at each site. We achieved transduction of up to 60% of brain cells with comparable efficiency in the majority of the brain regions. Furthermore, gene delivery with FUS-BBBO was safe even when all 105 sites were targeted simultaneously without negative effects on animal weight or neuronal loss. To evaluate the application of multi-site FUS-BBBO for gene therapy, we used it for gene editing using the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated 9 (Cas9) system and found effective gene editing, but also a loss of neurons at the targeted sites. Overall, this study provides a brain-wide map of transduction efficiency, shows the synergistic effect of multi-site targeting on transduction efficiency, and is the first example of large brain volume gene editing after noninvasive gene delivery with FUS-BBBO.
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Edición Génica , Terapia Genética , Animales , Técnicas de Transferencia de Gen , Barrera Hematoencefálica , Encéfalo , Sistemas CRISPR-CasRESUMEN
In this paper, we describe the potential of the LHCb experiment to detect stealth physics. This refers to dynamics beyond the standard model that would elude searches that focus on energetic objects or precision measurements of known processes. Stealth signatures include long-lived particles and light resonances that are produced very rarely or together with overwhelming backgrounds. We will discuss why LHCb is equipped to discover this kind of physics at the Large Hadron Collider and provide examples of well-motivated theoretical models that can be probed with great detail at the experiment.
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Obesity is associated with poorer responses to chemo- and radiation therapy for breast cancer, which leads to higher mortality rates for obese women who develop breast cancer. Adipose stem cells (ASCs) are an integral stromal component of the tumor microenvironment (TME). In this study, the effects of obesity-altered ASCs (obASCs) on estrogen receptor positive breast cancer cell's (ER+BCCs) response to radiotherapy (RT) were evaluated. We determined that BCCs had a decreased apoptotic index and increased surviving fraction following RT when co-cultured with obASCs compared to lnASCs or non-co-cultured cells. Further, obASCs reduced oxidative stress and induced IL-6 expression in co-cultured BCCs after radiation. obASCs produce increased levels of leptin relative to ASCs from normal-weight individuals (lnASCs). obASCs upregulate the expression of IL-6 compared to non-co-cultured BCCs, but BCCs co-cultured with leptin knockdown obASCs did not upregulate IL-6. The impact of shLeptin obASCs on radiation resistance of ER+BCCs demonstrate a decreased radioprotective ability compared to shControl obASCs. Key NOTCH signaling players were enhanced in ER+BBCs following co-culture with shCtrl obASCs but not shLep obASCs. This work demonstrates that obesity-altered ASCs, via enhanced secretion of leptin, promote IL-6 and NOTCH signaling pathways in ER+BCCs leading to radiation resistance.
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Tejido Adiposo/citología , Neoplasias de la Mama/radioterapia , Leptina/metabolismo , Células Madre Mesenquimatosas/metabolismo , Obesidad/metabolismo , Comunicación Paracrina/efectos de la radiación , Receptores de Estrógenos/metabolismo , Tejido Adiposo/metabolismo , Animales , Apoptosis/efectos de la radiación , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Proliferación Celular/efectos de la radiación , Supervivencia Celular/efectos de la radiación , Técnicas de Cocultivo , Daño del ADN/efectos de la radiación , Femenino , Técnicas de Silenciamiento del Gen , Humanos , Interleucina-6/metabolismo , Leptina/genética , Células MCF-7 , Ratones , Estrés Oxidativo/efectos de la radiación , ARN Interferente Pequeño , Radiación , Receptores Notch/metabolismo , Puntos de Control de la Fase S del Ciclo Celular/efectos de la radiación , Transducción de Señal/efectos de la radiación , Microambiente Tumoral , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
The adapted DIRAC experiment at the CERN PS accelerator observed for the first time long-lived hydrogenlike π^{+}π^{-} atoms, produced by protons hitting a beryllium target. A part of these atoms crossed the gap of 96 mm between the target and a 2.1 µm thick platinum foil, in which most of them dissociated. Analyzing the observed number of atomic pairs, n_{A}^{L}=436_{-61}^{+157}|_{tot}, the lifetime of the 2p state is found to be τ_{2p}=(0.45_{-0.30}^{+1.08}|_{tot})×10^{-11} s, not contradicting the corresponding QED 2p state lifetime τ_{2p}^{QED}=1.17×10^{-11} s. This lifetime value is three orders of magnitude larger than our previously measured value of the π^{+}π^{-} atom ground state lifetime τ=(3.15_{-0.26}^{+0.28}|_{tot})×10^{-15} s. Further studies of long-lived π^{+}π^{-} atoms will allow us to measure energy differences between p and s atomic states and so to discriminate between the isoscalar and isotensor ππ scattering lengths with the aim to check QCD predictions.
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The protease kallikrein 4 (KLK4) plays a pivotal role during dental enamel formation by degrading the major enamel protein, amelogenin, prior to the final steps of enamel hardening. KLK4 dysfunction is known to cause some types of developmental defect in enamel but the mechanisms responsible for transient retention of KLK4 in semi-hardened enamel matrix remain unclear. To address contradictory reports about the affinity of KLK4 for enamel hydroxyapatite-like mineral, we used pure components in quasi-physiological conditions and found that KLK4 binds hydroxyapatite directly. Hypothesising KLK4 self-destructs once amelogenin is degraded, biochemical analyses revealed that KLK4 progressively lost activity, became aggregated, and autofragmented when incubated without substrate in both the presence and absence of reducer. However, with non-ionic detergent present as proxy substrate, KLK4 remained active and intact throughout. These findings prompt a new mechanistic model and line of enquiry into the role of KLK4 in enamel hardening and malformation.
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Esmalte Dental/química , Esmalte Dental/ultraestructura , Durapatita/química , Calicreínas/química , Calicreínas/ultraestructura , Sitios de Unión , Activación Enzimática , Estabilidad de Enzimas , Unión Proteica , Especificidad por SustratoRESUMEN
BACKGROUND/OBJECTIVE: Vitamin D deficiency during pregnancy is associated with poor birth outcomes in some studies, but few have examined weight beyond birth. In addition, little is known about how vitamin D influences DNA methylation of regulatory regions known to be involved in growth, as possible mediators to weight status in offspring. SUBJECTS/METHODS: We conducted linear regressions to assess maternal plasma 25-hydroxyvitamin D (25(OH)D) by quartile and birth weight for gestational age z-score, 1-year weight-for-length z-score and 3-year body mass index (BMI) z-score among 476 mother/infant dyads from a prospective cohort. We assessed maternal 25(OH)D and infant DNA methylation at nine differentially methylated regions (DMRs) of genomically imprinted genes with known functions in fetal growth, including H19, IGF2, MEG3, MEG3-IG, MEST, NNAT, PEG3, PLAGL1 and SGCE/PEG10. RESULTS: Mean (standard deviation, s.d.) maternal 25(OH)D was 41.1 (14.2) nmol l-m at a mean (s.d.) of 13.2 (5.5) weeks gestation. After adjustment for potential confounders, the first (Q1) and second (Q2) quartiles of 25(OH)D, compared to the fourth (Q4), were associated with lower birth weight for gestational age z-scores (-0.43 units; CI: -0.79, -0.07; P=0.02 for Q1 and -0.56 units; CI: -0.89, -0.23; P=0.001 for Q2). Q1 compared to Q4 was associated with higher 1-year weight-for-length z-scores (0.78 units; 0.08, 1.54; P=0.04) and higher 3-year BMI z-scores (0.83 units; 0.11, 0.93; P=0.02). We did not observe associations between maternal 25(OH)D and methylation for any of the nine DMRs after correcting for multiple testing. CONCLUSIONS: Reduced maternal 25(OH)D was associated with lower birth weight for gestational age z-scores but higher 1-year weight-for-length and 3-year BMI z-scores in offspring. However, 25(OH)D does not appear to be operating through the regulatory sequences of the genomically imprinted genes we examined.
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Peso al Nacer/fisiología , Metilación de ADN/genética , Impresión Genómica/genética , Vitamina D/sangre , Adulto , Preescolar , Femenino , Humanos , Lactante , Recién Nacido , Madres , Embarazo , Estudios Prospectivos , Factores Socioeconómicos , Adulto JovenRESUMEN
BACKGROUND: Preoperative chemoradiotherapy followed by surgical mesorectal resection is the standard of care for locally advanced rectal carcinomas. Yet, predicting that patients will respond to treatment remains an unmet clinical challenge. EXPERIMENTAL DESIGN: Using laser-capture microdissection we isolated RNA from stroma and tumour glands from prospective pre-treatment samples (n = 15). Transcriptomic profiles were obtained hybridising PrimeView Affymetrix arrays. We modelled a carcinoma-associated fibroblast-specific genes filtering data using GSE39396. RESULTS: The analysis of differentially expressed genes of stroma/tumour glands from responder and non-responder patients shows that most changes were associated with the stromal compartment; codifying mainly for extracellular matrix and ribosomal components. We built a carcinoma-associated fibroblast (CAF) specific classifier with genes showing changes in expression according to the tumour regression grade (FN1, COL3A1, COL1A1, MMP2 and IGFBP5). We assessed these five genes at the protein level by means of immunohistochemical staining in a patient's cohort (n = 38). For predictive purposes we used a leave-one-out cross-validated model with a positive predictive value (PPV) of 83.3%. Random Forest identified FN1 and COL3A1 as the best predictors. Rebuilding the leave-one-out cross-validated regression model improved the classification performance with a PPV of 93.3%. An independent cohort was used for classifier validation (n = 36), achieving a PPV of 88.2%. In a multivariate analysis, the two-protein classifier proved to be the only independent predictor of response. CONCLUSION: We developed a two-protein immunohistochemical classifier that performs well at predicting the non-response to neoadjuvant treatment in rectal cancer.
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Perfilación de la Expresión Génica , Inmunohistoquímica/métodos , Terapia Neoadyuvante , Neoplasias del Recto/terapia , Colágeno Tipo I/genética , Cadena alfa 1 del Colágeno Tipo I , Colágeno Tipo III/genética , Terapia Combinada , Citocinas/genética , Femenino , Fibronectinas , Humanos , Proteína 5 de Unión a Factor de Crecimiento Similar a la Insulina/genética , Masculino , Metaloproteinasa 2 de la Matriz/genética , Persona de Mediana Edad , Pronóstico , Neoplasias del Recto/clasificación , Neoplasias del Recto/genética , Neoplasias del Recto/patología , TranscriptomaRESUMEN
Carbon dioxide (CO2) molecules show a rich orientation landscape when they are enclathrated in type I hydrates. Previous studies have described experimentally their preferential orientations, and some theoretical works have explained, but only partially, these experimental results. In the present paper, we use classical molecular dynamics and electronic density functional theory to advance in the theoretical description of CO2 orientations within type I hydrates. Our results are fully compatible with those previously reported, both theoretical and experimental, the geometric shape of the cavities in hydrate being, and therefore, the steric constraints, responsible for some (but not all) preferential angles. In addition, our calculations also show that guest-guest interactions in neighbouring cages are a key factor to explain the remaining experimental angles. Besides the implication concerning equation of state hydrate modeling approximations, the conclusion is that these guest-guest interactions should not be neglected, contrary to the usual practice.
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Brazil has great potential to produce bioenergy since it is located in a tropical region that receives high incidence of solar energy and presents favorable climatic conditions for such purpose. However, the use of bioenergy in the country is below its productivity potential. The aim of the current study was to select full-sib progenies and families of elephant grass (Pennisetum purpureum S.) to optimize phenotypes relevant to bioenergy production through mixed models (REML/BLUP). The circulating diallel-based crossing of ten elephant grass genotypes was performed. An experimental design using the randomized block methodology, with three repetitions, was set to assess both the hybrids and the parents. Each plot comprised 14-m rows, 1.40 m spacing between rows, and 1.40 m spacing between plants. The number of tillers, plant height, culm diameter, fresh biomass production, dry biomass rate, and the dry biomass production were assessed. Genetic-statistical analyses were performed through mixed models (REML/BLUP). The genetic variance in the assessed families was explained through additive genetic effects and dominance genetic effects; the dominance variance was prevalent. Families such as Capim Cana D'África x Guaçu/I.Z.2, Cameroon x Cuba-115, CPAC x Cuba-115, Cameroon x Guaçu/I.Z.2, and IAC-Campinas x CPAC showed the highest dry biomass production. The family derived from the crossing between Cana D'África and Guaçu/I.Z.2 showed the largest number of potential individuals for traits such as plant height, culm diameter, fresh biomass production, dry biomass production, and dry biomass rate. The individual 5 in the family Cana D'África x Guaçu/I.Z.2, planted in blocks 1 and 2, showed the highest dry biomass production.
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Biocombustibles , Biomasa , Fitomejoramiento/métodos , Poaceae/genética , Selección Genética , Hibridación Genética , Fenotipo , Poaceae/crecimiento & desarrolloAsunto(s)
Enfermedad de Paget Extramamaria , Neoplasias de las Glándulas Sudoríparas , Humanos , Trastuzumab/uso terapéutico , Enfermedad de Paget Extramamaria/tratamiento farmacológico , Ingle , Anticuerpos Monoclonales Humanizados/uso terapéutico , Neoplasias de las Glándulas Sudoríparas/tratamiento farmacológicoRESUMEN
The genetic diversity of Campylobacter jejuni and Campylobacter coliisolates from commercial broiler farms was examined by multilocus sequence typing (MLST), with an assessment of the impact of the sample type and laboratory method on the genotypes of Campylobacter isolated. A total of 645C. jejuniand 106C. coli isolates were obtained from 32 flocks and 17 farms, with 47 sequence types (STs) identified. The Campylobacter jejuniisolates obtained by different sampling approaches and laboratory methods were very similar, with the same STs identified at similar frequencies, and had no major effect on the genetic profile of Campylobacter population in broiler flocks at the farm level. ForC. coli, the results were more equivocal. While some STs were widely distributed within and among farms and flocks, analysis of molecular variance (AMOVA) revealed a high degree of genetic diversity among farms forC. jejuni, where farm effects accounted for 70.5% of variance, and among flocks from the same farm (9.9% of variance for C. jejuni and 64.1% forC. coli). These results show the complexity of the population structure of Campylobacterin broiler production and that commercial broiler farms provide an ecological niche for a wide diversity of genotypes. The genetic diversity of C. jejuni isolates among broiler farms should be taken into account when designing studies to understand Campylobacter populations in broiler production and the impact of interventions. We provide evidence that supports synthesis of studies on C. jejuni populations even when laboratory and sampling methods are not identical.
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Técnicas Bacteriológicas/métodos , Infecciones por Campylobacter/veterinaria , Campylobacter coli/clasificación , Campylobacter jejuni/clasificación , Pollos/microbiología , Variación Genética , Manejo de Especímenes/métodos , Animales , Infecciones por Campylobacter/microbiología , Campylobacter coli/genética , Campylobacter coli/aislamiento & purificación , Campylobacter jejuni/genética , Campylobacter jejuni/aislamiento & purificación , Genotipo , Tipificación de Secuencias MultilocusRESUMEN
The observation of hydrogenlike πK atoms, consisting of π^{-}K^{+} or π^{+}K^{-} mesons, is presented. The atoms are produced by 24 GeV/c protons from the CERN PS accelerator, interacting with platinum or nickel foil targets. The breakup (ionization) of πK atoms in the same targets yields characteristic πK pairs, called "atomic pairs," with small relative momenta Q in the pair center-of-mass system. The upgraded DIRAC experiment observed 349±62 such atomic πK pairs, corresponding to a signal of 5.6 standard deviations. This is the first statistically significant observation of the strange dimesonic πK atom.
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Jatropha gossypiifolia L. (Euphorbiaceae) is widely used in popular medicine. However, further toxicological studies are necessary for its reliable use. The present study aimed to evaluate the cytotoxic, genotoxic, and mutagenic effects of ethanolic and aqueous leaf extracts of J. gossypiifolia, using the test system Allium cepa. In addition, the phytochemical profile of the extracts was also obtained. Seeds of A. cepa were subjected to different concentrations of the two extracts (0.001, 0.01, 0.1, 1, and 10 mg/mL). Distilled water was used for the negative control and methyl methanesulfonate (4 x 10(-4) M) and trifluralin (0.84 ppm) for the positive controls. The values of mitotic index at all concentrations of ethanolic extract and at 0.1, 1, and 10 mg/mL aqueous extract showed a significant decrease. Alterations, such as chromosome adherence, C-metaphases, chromosome bridges, nuclear buds, and micronuclei were verified in both extracts but chromosome loss indicating genotoxic activity was observed only in the ethanolic extract. Presence of micronuclei on administration of the extracts, also indicated mutagenic action at the chromosome level. In the ethanolic extract, aneugenicity seemed to be the main activity, probably as a result of the action of terpenes and/or flavonoids, whereas in the aqueous extract, clastogenic action appeared to be the principal activity, presumably as a consequence of the effect of flavonoids and/or saponins. Thus, we suggest that the extracts of this species should be used with great caution for medicinal purpose.
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Aberraciones Cromosómicas/inducido químicamente , Jatropha/efectos adversos , Cebollas/efectos de los fármacos , Extractos Vegetales/efectos adversos , Hojas de la Planta/química , Flavonoides , Jatropha/química , Jatropha/toxicidad , Índice Mitótico , Cebollas/genética , Extractos Vegetales/química , Extractos Vegetales/toxicidad , Saponinas , Semillas/efectos de los fármacos , Semillas/genéticaRESUMEN
INTRODUCTION: Supra-glottic airway devices (SADs) with an inbuilt drain channel, such as the LMA Proseal™ (LMA-P), LMA SupremeTM (LMA-S) and i-gel™ (i-gel), have been used for laparoscopic cholecystectomy. We compared safety, efficacy, and ease of use, as well as the incidence of adverse events between these devices. METHODS: One hundred and eighty adult, ASA 1-3 patients scheduled to undergo elective cholecystectomy under general anesthesia were randomly allocated to one of three groups: LMA-P, LMA-S or i-gel. The primary outcome was to evaluate oropharyngeal leak pressure (OLP). Secondary outcomes were to evaluated speed of insertion, ease of insertion of the device and the drain tube, as well as the incidence of intraoperative adverse events and postoperative oropharyngeal discomfort (POPD). RESULTS: Mean OLP was significantly higher for LMA-P (LMA-P 30.87; i-gel 29.28; LMA-S 29.02 cm H20, P = 0.007). OLP was correlated with a higher maximum tidal achieved volume (P = 0.025). Insertion times were shorter for the i-gel, which was 1.7 s faster to insert than LMA-P (P = 0.04). The success rate on first attempt was higher for the LMA-S (P = 0.004). The drain tube was easily inserted in the LMA-S group (p < 0.001). I-gel showed higher sore throat scoring 2 hours postoperatively (P = 0.008) and reported slower POPD decrease during that time (P < 0.001). CONCLUSIONS: Among SAD's, LMA-S is the easiest to insert (including the drain tube), LMA-P achieved the best leak pressure, and i-gel fastest to insert, although associated with the worst POPD scoring.
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Colecistectomía Laparoscópica/instrumentación , Máscaras Laríngeas , Adulto , Anciano , Anestesia General , Colecistectomía Laparoscópica/efectos adversos , Trastornos de Deglución/epidemiología , Trastornos de Deglución/etiología , Disfonía/epidemiología , Disfonía/etiología , Diseño de Equipo , Femenino , Humanos , Máscaras Laríngeas/efectos adversos , Masculino , Persona de Mediana Edad , Comodidad del Paciente , Seguridad del Paciente , Faringitis/epidemiología , Faringitis/etiología , Complicaciones Posoperatorias/epidemiología , Estudios ProspectivosRESUMEN
BACKGROUND: To report the long-term results of adjuvant treatment with one cycle of modified bleomycin, etoposide, and cisplatin (BEP) in patients with clinical stage I (CS I) nonseminomatous germ-cell tumors (NSGCT) at high risk of relapse. PATIENTS AND METHODS: In a single-arm, phase II clinical trial, 40 patients with CS I NSGCT with vascular invasion and/or >50% embryonal cell carcinoma in the orchiectomy specimen received one cycle of adjuvant BEP (20 mg/m(2) bleomycin as a continuous infusion over 24 h, 120 mg/m(2) etoposide and 40 mg/m(2) cisplatin each on days 1-3). Primary end point was the relapse rate. RESULTS: Median follow-up was 186 months. One patient (2.5%) had a pulmonary relapse 13 months after one BEP and died after three additional cycles of BEP chemotherapy. Three patients (7.5%) presented with a contralateral metachronous testicular tumor, and three (7.5%) developed a secondary malignancy. Three patients (7.5%) reported intermittent tinnitus and one had grade 2 peripheral polyneuropathy (2.5%). CONCLUSIONS: Adjuvant chemotherapy with one cycle of modified-BEP is a feasible and safe treatment of patients with CS I NSGCT at high risk of relapse. In these patients, it appears to be an alternative to two cycles of BEP and to have a lower relapse rate than retroperitoneal lymph node dissection. If confirmed by other centers, 1 cycle of adjuvant BEP chemotherapy should become a first-line treatment option for this group of patients.
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Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Quimioterapia Adyuvante/métodos , Neoplasias de Células Germinales y Embrionarias/tratamiento farmacológico , Neoplasias Testiculares/tratamiento farmacológico , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Bleomicina/administración & dosificación , Bleomicina/efectos adversos , Cisplatino/administración & dosificación , Cisplatino/efectos adversos , Etopósido/administración & dosificación , Etopósido/efectos adversos , Estudios de Seguimiento , Humanos , Masculino , Recurrencia Local de Neoplasia/epidemiología , Neoplasias de Células Germinales y Embrionarias/mortalidad , Neoplasias de Células Germinales y Embrionarias/cirugía , Neoplasias Primarias Secundarias/epidemiología , Orquiectomía , Neoplasias Testiculares/mortalidad , Neoplasias Testiculares/cirugía , Tiempo , Adulto JovenRESUMEN
BACKGROUND: Several epidemiologic studies have demonstrated associations between periconceptional environmental exposures and health status of the offspring in later life. Although these environmentally related effects have been attributed to epigenetic changes, such as DNA methylation shifts at imprinted genes, little is known about the potential effects of maternal and paternal preconceptional overnutrition or obesity. OBJECTIVE: We examined parental preconceptional obesity in relation to DNA methylation profiles at multiple human imprinted genes important in normal growth and development, such as: maternally expressed gene 3 (MEG3), mesoderm-specific transcript (MEST), paternally expressed gene 3 (PEG3), pleiomorphic adenoma gene-like 1 (PLAGL1), epsilon sarcoglycan and paternally expressed gene 10 (SGCE/PEG10) and neuronatin (NNAT). METHODS: We measured methylation percentages at the differentially methylated regions (DMRs) by bisulfite pyrosequencing in DNA extracted from umbilical cord blood leukocytes of 92 newborns. Preconceptional obesity, defined as BMI ⩾30 kg m(-2), was ascertained through standardized questionnaires. RESULTS: After adjusting for potential confounders and cluster effects, paternal obesity was significantly associated with lower methylation levels at the MEST (ß=-2.57; s.e.=0.95; P=0.008), PEG3 (ß=-1.71; s.e.=0.61; P=0.005) and NNAT (ß=-3.59; s.e.=1.76; P=0.04) DMRs. Changes related to maternal obesity detected at other loci were as follows: ß-coefficient was +2.58 (s.e.=1.00; P=0.01) at the PLAGL1 DMR and -3.42 (s.e.=1.69; P=0.04) at the MEG3 DMR. CONCLUSION: We found altered methylation outcomes at multiple imprint regulatory regions in children born to obese parents, compared with children born to non-obese parents. In spite of the small sample size, our data suggest a preconceptional influence of parental life-style or overnutrition on the (re)programming of imprint marks during gametogenesis and early development. More specifically, the significant and independent association between paternal obesity and the offspring's methylation status suggests the susceptibility of the developing sperm for environmental insults. The acquired imprint instability may be carried onto the next generation and increase the risk for chronic diseases in adulthood.
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Metilación de ADN , Sangre Fetal/metabolismo , Impresión Genómica , Obesidad/genética , Padres , Cordón Umbilical/metabolismo , Adulto , Proteínas Reguladoras de la Apoptosis , Proteínas de Ciclo Celular/genética , Proteínas de Unión al ADN , Exposición a Riesgos Ambientales , Femenino , Humanos , Recién Nacido , Factor II del Crecimiento Similar a la Insulina/genética , Factor II del Crecimiento Similar a la Insulina/metabolismo , Factores de Transcripción de Tipo Kruppel/genética , Masculino , Proteínas de la Membrana/genética , Proteínas del Tejido Nervioso/genética , Obesidad/metabolismo , Embarazo , Proteínas/genética , Proteínas de Unión al ARN , Reproducibilidad de los Resultados , Sarcoglicanos/genética , Análisis de Secuencia de ADN , Factores de Transcripción/genética , Proteínas Supresoras de Tumor/genética , Cordón Umbilical/citologíaRESUMEN
Early vigour of rice, defined as seedling capacity to accumulate shoot dry weight (SDW) rapidly, is a complex trait. It depends on a genotype propensity to assimilate, store, and/or use non-structural carbohydrates (NSC) for producing large and/or numerous leaves, involving physiological trade-offs in the expression of component traits and, possibly, physiological and genetic linkages. This study explores a plant-model-assisted phenotyping approach to dissect the genetic architecture of rice early vigour, applying the Genome Wide Association Study (GWAS) to morphological and NSC measurements, as well as fitted parameters for the functional-structural plant model, Ecomeristem. Leaf size, number, SDW, and source-leaf NSC concentration were measured on a panel of 123 japonica accessions. The data were used to estimate Ecomeristem genotypic parameters driving organ appearance rate, size, and carbon dynamics. GWAS was performed based on 12 221 single-nucleotide polymorphisms (SNP). Twenty-three associations were detected at P <1×10(-4) and 64 at P <5×10(-4). Associations for NSC and model parameters revealed new regions related to early vigour that had greater significance than morphological traits, providing additional information on the genetic control of early vigour. Plant model parameters were used to characterize physiological and genetic trade-offs among component traits. Twelve associations were related to loci for cloned genes, with nine related to organogenesis, plant height, cell size or cell number. The potential use of these associations as markers for breeding is discussed.