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1.
J Therm Biol ; 119: 103802, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38340466

RESUMEN

Residual feed intake (RFI) is a nutritional variable used in genetic improvement programs, the relationship between the environment and the availability of energy and protein in the diet has not yet been explored. Thus, the aim was to evaluate interactions between RFI and thermal environment on performance, nitrogen balance, ingestive behavior and carcass yield of Dorper lambs receiving diets containing different concentrate levels. Dorper lambs (male, n = 64, 17.83 ± 2.43 kg and 110 ± 10 days of age) were confined individually for 40 days for RFI classification. Lambs were separated into positive RFI (n = 30) and negative RFI (n = 30) and remained confined for another 60 days. The animals were distributed in a randomized block design, with a 2 × 2 × 3 factorial scheme, with 2 confinement environments (full sun or shade), 2 groups of feed efficiency (RFI positive or RFI negative) and three diets containing different concentrate levels (30, 45 and 60%), with 5 replications in each treatment. Isolated effects of concentrate level were observed for dry matter intake and digestibility, feeding, rumination, idle and chewing times, feeding efficiency, ingested, excreted and absorbed nitrogen, and on cooling losses, hot and cold carcass yield (P < 0.05). There was an effect of environment × concentrate interaction on performance, retained nitrogen and nitrogen balance (P < 0.05). There was an effect of RFI × environment interaction on the dry matter rumination efficiency, hot and cold carcass weight (P < 0.05). Under experimental conditions, RFI did not influence the productive performance of Dorper lambs. Interactions between environment and diet indicate better performance for Dorper lamb confined in the shade and receiving a higher proportion of concentrate. Animals with negative RFI show better performance and carcass weight when confined in shade, while animals with positive RFI showed better responses to these variables when confined in full sun.


Asunto(s)
Alimentación Animal , Ingestión de Alimentos , Animales , Masculino , Alimentación Animal/análisis , Dieta/veterinaria , Ingestión de Alimentos/fisiología , Conducta Alimentaria , Nitrógeno/metabolismo , Ovinos , Oveja Doméstica
2.
J Therm Biol ; 117: 103709, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37717402

RESUMEN

The thermal environment is important in unit production because the perception of thermal stress can reduce fertility, and productive performance, therefore its management is necessary. The use of non-invasive methods, such as infrared thermography and real-time ultrasonography, are widely used to evaluate indicators in animal production, without the need to slaughter the animals. Thus, we aimed to assess the effect of the thermal environment on the physiological parameters and carcass characteristics of Dorper sheep with positive and negative residual feed intake (RFI) using infrared thermography and real-time ultrasonography techniques. Twenty uncastrated male Dorper sheep (17.8 ± 2.4 kg) were confined for 40 days for RFI classification. Sheep were separated into positive RFI (n = 10) and negative RFI (n = 10). The experimental design was in randomized blocks, in a 2 × 2 factorial arrangement, with 2 thermal environments (full sun or shade) and two feed efficiency groups (positive RFI or negative RFI), with 5 replications. The sheep remained in confinement for 60 days. The animals were slaughtered at the end of the experiment and the carcasses dissected for tissue separation. Rectal temperature (RT) and respiratory rate (RR) were measured at two times (14:00 h and 18:00 h) for periods of 5 days. The RR was determined by indirect auscultation of heart sounds at the level of the laryngotracheal region. The RT was measured introduced a digital clinical thermometer into the animal's rectum. Surface temperature (ST) was obtained using a thermographic infrared camera, collecting the temperatures of the eyeball and skin surface in the regions of the head, ribs, rump, flank and shin. Sheep confined in full sun showed higher RR (P = 0.0001), ST ribs (P = 0.0020), ST rumb (P = 0.0055), ST flank (P = 0.0001) and heat tolerance coefficient (HTC) (P = 0.0010). For sheep confined in full sun, a strong correlation was observed between the RR and the mean ST (MST; r = 0.6826; P = 0.0236) and between the final loin eye area (LEAf) with the real LEA (LEAr) (r = 0.9263; P = 0.0001) and slaughter body weight (SBW) (r = 0.7532; P = 0.0325). For negative RFI sheep, a positive correlation was observed between the RR and the ST rump (r = 0.7343; P = 0.0025) and ST ribs (r = 0.6560; P = 0.0178) and the MST (r = 0.7435; P = 0.0001), between the MST and the LEAr (r = 0.6837; P = 0.0025) and the final LEA (r = 0.6771; P = 0.0144), and between the final LEA and LEAr (r = 0.9942; P = 0.0001), BW (r = 0.8415; P = 0.0277) and MST (r = 0.6771; P = 0.0045). Positive RFI sheep confined to shade showed a high correlation between final LEA and LEAr (r = 0.9372; P = 0.0001). The use of shading in confined Dorper sheep, regardless of the RFI classification, reduces the effects of heat stress on physiological parameters.

3.
Sensors (Basel) ; 20(12)2020 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-32575775

RESUMEN

Data acquisition is a crucial stage in the execution of condition monitoring (CM) of rotating machinery, by means of vibration analysis. However, the major challenge in the execution of this technique lies in the features of the recording equipment (accuracy, resolution, sampling frequency and number of channels) and the cost they represent. The present work proposes a low-cost data acquisition system, based on Raspberry-Pi, with a high sampling frequency capacity in the recording of up to three channels. To demonstrate the effectiveness of the proposed data acquisition system, a case study is presented in which the vibrations registered in a bearing are analyzed for four degrees of failure.

4.
PLoS Genet ; 12(9): e1006318, 2016 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-27662573

RESUMEN

Several studies propose an influence of chromatin on pre-mRNA splicing, but it is still unclear how widespread and how direct this phenomenon is. We find here that when assembled in vivo, the U2 snRNP co-purifies with a subset of chromatin-proteins, including histones and remodeling complexes like SWI/SNF. Yet, an unbiased RNAi screen revealed that the outcome of splicing is influenced by a much larger variety of chromatin factors not all associating with the spliceosome. The availability of this broad range of chromatin factors impacting splicing further unveiled their very context specific effect, resulting in either inclusion or skipping, depending on the exon under scrutiny. Finally, a direct assessment of the impact of chromatin on splicing using an in vitro co-transcriptional splicing assay with pre-mRNAs transcribed from a nucleosomal template, demonstrated that chromatin impacts nascent pre-mRNP in their competence for splicing. Altogether, our data show that numerous chromatin factors associated or not with the spliceosome can affect the outcome of splicing, possibly as a function of the local chromatin environment that by default interferes with the efficiency of splicing.

6.
Chemistry ; 19(3): 892-904, 2013 Jan 14.
Artículo en Inglés | MEDLINE | ID: mdl-23197418

RESUMEN

An exhaustive experimental study based on X-ray diffraction analysis, NMR, FTIR-ATR (attenuated total reflection), and Raman spectroscopy as well as theoretical calculations is reported in order to understand how the non-covalent intermolecular contacts are fundamental to explain structure-property relationships and allowing us to correlate a basic macroscopic property (i.e., the melting point, T(m)) with the structural variables of a family of enantiopure 1,4-dialkyl-1,2,4-triazolium salts. The effect of different structural vectors such as the ring size, the spatial disposition of the substituent, the substitution on the oxygen atom, the nature of the anion, or the N4 alkylation of the triazole on the intermolecular interactions of these chiral salts of a well-defined 3D structure is reported. The non-covalent intermolecular contacts mainly implicating the triazolium H3 proton are fundamental to explain structure-property relationships and, therefore, the physical properties of these new chiral salts, rather than simple anion-cation interactions. Overall, our findings highlight the importance of the specific supramolecular interactions for the understanding of the physical properties of triazolium salts and ionic liquids.


Asunto(s)
Líquidos Iónicos/química , Triazoles/química , Sustancias Macromoleculares/química , Modelos Moleculares , Estructura Molecular , Sales (Química)/química
7.
Parkinsonism Relat Disord ; 106: 105245, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36542985

RESUMEN

INTRODUCTION: Nonspecific areas of brain white matter hyperintensity (WMH) are commonly found in the elderly. Some studies have shown that the presence, quantity, and location of WMHs may be associated with the development of cognitive and motor decline in patients with Parkinson's disease (PD), but the results remain controversial. This study aimed to evaluate the relationship of WMH to motor and non-motor symptoms, including dysautonomia and rapid eye movement sleep behavior disorder (RBD), in patients with PD. METHODS: Brain magnetic resonance images were acquired from 120 patients diagnosed with PD and analyzed for WMH classification and quantification. Motor symptoms were quantified using sub-scores of the Movement Disorder Society-Unified Parkinson Disease Rating Scale (MDS-UPDRS)-III. Dysautonomia was evaluated by autonomic reactivity tests, and polysomnography was used for the diagnosis of RBD. RESULTS: Age, total value of the MDS-UPDRS-III tremor sub-score, and the presence of dysautonomia were found to be linearly positively associated. Specifically, the duration of PD was positively associated with rigidity, bradykinesia, axial symptoms, prevalence of dysautonomia, and RBD sub-scores. However, in the multivariate analysis adjusted for variables of interest, no statistical significance was found for any of the models. CONCLUSION: The presence, quantity, and location of WMH were not associated with the analyzed motor and non-motor manifestations of PD.


Asunto(s)
Leucoaraiosis , Enfermedad de Parkinson , Trastorno de la Conducta del Sueño REM , Sustancia Blanca , Humanos , Anciano , Enfermedad de Parkinson/complicaciones , Enfermedad de Parkinson/diagnóstico por imagen , Enfermedad de Parkinson/patología , Sustancia Blanca/diagnóstico por imagen , Sustancia Blanca/patología , Temblor/complicaciones , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Trastorno de la Conducta del Sueño REM/etiología , Trastorno de la Conducta del Sueño REM/complicaciones , Leucoaraiosis/patología
8.
Arq Neuropsiquiatr ; 81(5): 417-425, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-37156532

RESUMEN

BACKGROUND: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a genetic cause of ischemic stroke and the most common form of non-atherosclerotic stroke. Despite being the most prevalent vascular hereditary disease, clinical data regarding the Brazilian population are scarce. Considering that the Brazilian population has one of the most heterogeneous genetic constitutions in the world, knowledge about genetic and epidemiological profiles is mandatory. The present study aimed to elucidate the epidemiological and clinical features of CADASIL in Brazil. METHODS: We performed a case series study comprising 6 rehabilitation hospitals in Brazil and reported the clinical and epidemiological data from the medical records of patients admitted from 2002 to 2019 with genetic confirmation. RESULTS: We enrolled 26 (16 female) patients in whom mutations in exons 4 and 19 were the most common. The mean age at the onset of the disease was of 45 years. Ischemic stroke was the first cardinal symptom in 19 patients. Cognitive impairment, dementia, and psychiatric manifestations were detected in 17, 6, and 16 patients respectively. In total, 8 patients had recurrent migraines, with aura in 6 (75%) of them. White matter hyperintensities in the temporal lobe and the external capsule were found in 20 (91%) and 15 patients (68%) respectively. The median Fazekas score was of 2. Lacunar infarcts, microbleeds, and larger hemorrhages were observed in 18 (82%), 9, and 2 patients respectively. CONCLUSION: The present is the most extensive series of Brazilian CADASIL patients published to date, and we have reported the first case of microbleeds in the spinal cord of a CADASIL patient. Most of our clinical and epidemiological data are in accordance with European cohorts, except for microbleeds and hemorrhagic strokes, for which rates fall in between those of European and Asian cohorts.


ANTECEDENTES: Arteriopatia cerebral autossômica dominante com enfartes subcorticais e leucoencefalopatia (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy, CADASIL, em inglês) é uma causa genética de acidente vascular cerebral (AVC) isquêmico e a forma mais comum de acidente vascular cerebral não aterosclerótico. Apesar de ser a doença vascular hereditária mais prevalente que há, os dados clínicos para a população brasileira são escassos. Considerando que o Brasil tem uma das constituições genéticas mais heterogêneas do mundo, o conhecimento sobre perfis genéticos e epidemiológicos é obrigatório. Este estudo teve como objetivo elucidar as características clínicas e epidemiológicas de pacientes com CADASIL no Brasil. MéTODOS: Apresentamos uma série de casos envolvendo 6 hospitais de reabilitação no Brasil, e relatamos dados clínicos e epidemiológicos de prontuários de pacientes admitidos entre 2002 e 2019 com confirmação genética. RESULTADOS: incluímos 26 pacientes (16 mulheres) em que as mutações nos éxons 4 e 19 eram as mais comuns. A idade média de início da doença foi de 45 anos. O AVC isquêmico foi o primeiro sintoma cardinal em 19 pacientes. Comprometimento cognitivo, demência e manifestações psiquiátricas foram detectados em 17, seis e 16 pacientes, respectivamente. Ao todo, 8 pacientes apresentavam enxaqueca, sendo com aura em 6 (75%) pacientes. Hiperintensidades de substância branca no polo temporal e na cápsula externa foram encontradas em 20 (91%) e 15 pacientes (68%), respectivamente. A pontuação mediana na escala de Fazekas foi de 2. Infartos lacunares, microssangramentos e macro-hemorragias foram observadas em 18 (82%), 9 (41%) e 2 (9%) pacientes, respectivamente. CONCLUSãO: O presente estudo representa a mais extensa série de pacientes brasileiros com CADASIL publicada até o momento, e relatamos o primeiro caso de micro-hemorragia na medula espinhal de um paciente com CADASIL. A maior parte dos nossos dados clínicos e epidemiológicos está de acordo com as coortes europeias, exceto para micro-hemorragias e macro-hemorragias, para as quais as taxas se enquadram entre as das coortes europeias e asiáticas.


Asunto(s)
CADASIL , Accidente Cerebrovascular Isquémico , Humanos , Femenino , Persona de Mediana Edad , CADASIL/epidemiología , CADASIL/genética , CADASIL/diagnóstico , Brasil/epidemiología , Imagen por Resonancia Magnética , Hemorragia Cerebral/epidemiología
9.
Infect Drug Resist ; 16: 5309-5317, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37601560

RESUMEN

Pyogenic spondylodiscitis (PS) is a highly morbid and potentially fatal bacterial infection with an increasing incidence in recent decades. Its diagnosis and treatment are challenging, especially with the expansion of multidrug- or extensively drug-resistant bacteria. We report a rare case of PS caused by carbapenem-resistant Pseudomonas aeruginosa (CRPA) that was treated with ceftazidime-avibactam (C/A). The choice of C/A therapy was based on the patient's bacterial sensitivity profile and intolerance to the initial therapeutic regimen (polymyxin B and meropenem). The total antimicrobial treatment time was seven weeks. The evolution of the clinical course met the cure criteria, which was characterized by remission of signs and symptoms, normalization of inflammatory markers, and radiological improvement over 18 months of clinical follow-up. This is a rare case of CRPA spondylodiscitis that responded to C/A treatment.

10.
Artículo en Inglés | MEDLINE | ID: mdl-35627392

RESUMEN

BACKGROUND: Adherence to a nutritional program and physical activity are the fundamental aspects of treatment for weight loss and associated problems. Previous research has shown that self-monitoring using a mobile device improves self-management. METHODS: A total of 35 subjects (40.6 ± 9.24 years) participated in the study. During the control period (3 months), they received physical exercise guidelines and a personalized nutritional program, with the aim of promoting health status. In the experimental period (3 months), there was also a connection between the physical world (health care processes) and the digital world (app). All participants had their body composition and cardiovascular variables measured. They also underwent calcaneal densitometry to determine bone quality. Descriptive statistics, correlations and analysis of variance were performed (by a researcher who was not involved in the data collection) to study the changes between before and after interventions, as well as to make a comparison between treatments. RESULTS: The use of an app, in which there exist a prediction of the evolution, messages of results and advice, among others, mediated by the assistance of dietitians/nutritionists and sports scientists, had a positive impact on the improvement of health parameters, showing significant differences in all variables except troponin. CONCLUSIONS: The combination of healthy habits with the use of the app provided benefits, improving health.


Asunto(s)
Aplicaciones Móviles , Nutricionistas , Ejercicio Físico , Femenino , Estado de Salud , Humanos , Masculino , Persona de Mediana Edad , Pérdida de Peso
11.
PLoS One ; 17(8): e0272841, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36006964

RESUMEN

Escherichia coli as water-borne bacteria exists in the recirculation water of coal flotation and affects the recovery of coal flotation. In order to study the effect of Escherichia coli on coal flotation, we changed the concentration of Escherichia coli and pH in the coal flotation system and found that Escherichia coli had an adverse effect on coal flotation. The concentration of Escherichia coli was negatively correlated with the recovery of coal. When the concentration of Escherichia coli reached 5.0 × 109 cells/ml, the recovery of coal flotation was 50.25%, and the change of pH basically did not affect the adverse effect of Escherichia coli on coal flotation. The mechanism was studied through Zeta potential, Fourier transform infrared spectroscopy, Scanning electron microscopy and Contact angle measurements. The results revealed that Escherichia coli could be adsorbed to the coal surface by hydrogen bonding, which changed the hydrophobicity of the coal surface and then reduced the recovery of coal flotation.


Asunto(s)
Carbón Mineral , Escherichia coli , Carbón Mineral/análisis , Microscopía Electrónica de Rastreo , Espectroscopía Infrarroja por Transformada de Fourier , Agua
12.
Cells ; 11(22)2022 11 17.
Artículo en Inglés | MEDLINE | ID: mdl-36429078

RESUMEN

Over 80% of patients with pancreatic ductal adenocarcinoma (PDAC) are diagnosed at a late stage and are locally advanced or with concurrent metastases. The aggressive phenotype and relative chemo- and radiotherapeutic resistance of PDAC is thought to be mediated largely by its prominent stroma, which is supported by an extracellular matrix (ECM). Therefore, we investigated the impact of tissue-matched human ECM in driving PDAC and the role of the ECM in promoting chemotherapy resistance. Decellularized human pancreata and livers were recellularized with PANC-1 and MIA PaCa-2 (PDAC cell lines), as well as PK-1 cells (liver-derived metastatic PDAC cell line). PANC-1 cells migrated into the pancreatic scaffolds, MIA PaCa-2 cells were able to migrate into both scaffolds, whereas PK-1 cells were able to migrate into the liver scaffolds only. These differences were supported by significant deregulations in gene and protein expression between the pancreas scaffolds, liver scaffolds, and 2D culture. Moreover, these cell lines were significantly more resistant to gemcitabine and doxorubicin chemotherapy treatments in the 3D models compared to 2D cultures, even after confirmed uptake by confocal microscopy. These results suggest that tissue-specific ECM provides the preserved native cues for primary and metastatic PDAC cells necessary for a more reliable in vitro cell culture.


Asunto(s)
Adenocarcinoma , Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Línea Celular Tumoral , Neoplasias Pancreáticas/patología , Carcinoma Ductal Pancreático/metabolismo , Páncreas/patología , Matriz Extracelular/metabolismo , Adenocarcinoma/metabolismo , Neoplasias Pancreáticas
13.
Nat Cell Biol ; 24(10): 1487-1498, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-36109670

RESUMEN

The liver has been studied extensively due to the broad number of diseases affecting its vital functions. However, therapeutic advances have been hampered by the lack of knowledge concerning human hepatic development. Here, we addressed this limitation by describing the developmental trajectories of different cell types that make up the human liver at single-cell resolution. These transcriptomic analyses revealed that sequential cell-to-cell interactions direct functional maturation of hepatocytes, with non-parenchymal cells playing essential roles during organogenesis. We utilized this information to derive bipotential hepatoblast organoids and then exploited this model system to validate the importance of signalling pathways in hepatocyte and cholangiocyte specification. Further insights into hepatic maturation also enabled the identification of stage-specific transcription factors to improve the functionality of hepatocyte-like cells generated from human pluripotent stem cells. Thus, our study establishes a platform to investigate the basic mechanisms directing human liver development and to produce cell types for clinical applications.


Asunto(s)
Hepatocitos , Hígado , Humanos , Hígado/metabolismo , Hepatocitos/metabolismo , Diferenciación Celular , Organoides , Factores de Transcripción/genética , Factores de Transcripción/metabolismo
14.
J Hand Surg Am ; 36(8): 1343-6, 2011 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-21737211

RESUMEN

A chronic expanding hematoma can persist and increase in volume for more than 1 month after the first hemorrhage. It is rare, uncommon in the hand, little known among physicians, and an imitator of malignancy. Our purpose was to report a case of this condition in the soft tissues of an 8-year-old girl's hand that simulated an aggressive lesion, and to conduct a review on this subject.


Asunto(s)
Traumatismos de la Mano/diagnóstico , Traumatismos de la Mano/cirugía , Hematoma/diagnóstico , Hematoma/cirugía , Accidentes por Caídas , Ciclismo/lesiones , Niño , Enfermedad Crónica , Diagnóstico Diferencial , Femenino , Humanos , Imagen por Resonancia Magnética , Tomografía Computarizada por Rayos X
15.
Healthcare (Basel) ; 9(12)2021 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-34946391

RESUMEN

Several studies have demonstrated the positive effects of physical exercise programs on physical and mental health throughout life. It is necessary to know the factors that contribute to the well-being of older adults in order to achieve healthy aging. The aim of this study was to evaluate the relationship between well-being perception and the use of autonomy supportive coaching behaviours across a motivational aquatic resistance interval training program. Thirty-four women over 65 years of age from the province of Alicante, Spain, participated, and were randomly assigned to: motivational aquatic resistance interval training group (MART; age: 69.6 ± 5.01 years, height: 1.62 ± 7.88 m, weight: 75.3 ± 12.8 kg) and control group (CG; age: 67.7 ± 3.60 years, height: 1.54 ± 5.47 m, weight: 66.9 ± 10.2 kg). The MART program was conducted for 14 weeks, with three training sessions/week. The CG did not perform any physical activity during the study. Perception of autonomy support was assessed through the Autonomy-Supportive Coaching Questionnaire (ASCQ), Psychological needs by the Basic Psychological Needs in Exercise Scale (BPNES), Intrinsic motivation to exercise was assessed through Intrinsic Motivation Inventory (IMI) and Perception of Physical Activity by the International physical activity questionnaire (IPAQ). In MART, compared to CG, significant differences were observed in BPNS, IMI and IPAQ questionnaires used, except in the ASCQ. The differences were significant in all three cases in BPNS (p < 0.05 in autonomy and competence and p = 0.001 in relationship with others), obtaining better scores after intervention than previously. As for the IMI scale, significant differences were also obtained in both subscales. The level of physical activity also improved significantly, with higher scores on the IPAQ after the intervention than before (p < 0.001). In conclusion, when practitioners perceive greater well-being, satisfaction of their basic psychological needs, greater self-selection, volition, and autonomy instead of pressure, demand and control, the result is better behaviour with greater psychological well-being, adherence and consequent health benefits.

16.
J Neuropathol Exp Neurol ; 80(11): 1068­1077, 2021 11 19.
Artículo en Inglés | MEDLINE | ID: mdl-34718655

RESUMEN

Neuromuscular choristoma (NMC) are lesions of the peripheral nervous system characterized by an admixture of skeletal muscle fibers and nerves fascicles that are frequently associated with desmoid fibromatosis (DF). Mutations in CTNNB1, the gene for ß-catenin protein, are common in DF and related to its pathogenesis. They are restricted to exon 3, with 3 point mutations: T41A, S45F, and S45P. To understand the pathogenesis of NMC, we tested CTNNB1 status in 5 cases of NMC whether or not they were associated with DF. The screening of mutations in CTNNB1 gene was based on amplicon deep sequencing using the ION Proton platform. Three patients had the S45F mutation; in 2 the mutation was common to both lesions and in one the DF was wild type while the NMC had the S45F mutation. One patient had a T41A mutation in the NMC and no associated DF. In the last patient, the DF lesion had a T41A mutation; there was no lesion with the S45P mutation. The presence of similar CTNNB1 mutations in NMC/DF-associated lesions and sporadic DF reinforces the relationship between both lesions and points to a common pathogenic mechanism.


Asunto(s)
Coristoma/genética , Enfermedades Neuromusculares/genética , Neoplasias del Sistema Nervioso Periférico/genética , beta Catenina/genética , Adolescente , Adulto , Niño , Coristoma/diagnóstico por imagen , Coristoma/patología , Exones/genética , Femenino , Humanos , Inmunohistoquímica , Imagen por Resonancia Magnética , Masculino , Enfermedades Neuromusculares/diagnóstico por imagen , Enfermedades Neuromusculares/patología , Neoplasias del Sistema Nervioso Periférico/diagnóstico por imagen , Neoplasias del Sistema Nervioso Periférico/patología , Mutación Puntual , Análisis de Secuencia de ADN , Vía de Señalización Wnt/genética
17.
Science ; 371(6531): 839-846, 2021 02 19.
Artículo en Inglés | MEDLINE | ID: mdl-33602855

RESUMEN

Organoid technology holds great promise for regenerative medicine but has not yet been applied to humans. We address this challenge using cholangiocyte organoids in the context of cholangiopathies, which represent a key reason for liver transplantation. Using single-cell RNA sequencing, we show that primary human cholangiocytes display transcriptional diversity that is lost in organoid culture. However, cholangiocyte organoids remain plastic and resume their in vivo signatures when transplanted back in the biliary tree. We then utilize a model of cell engraftment in human livers undergoing ex vivo normothermic perfusion to demonstrate that this property allows extrahepatic organoids to repair human intrahepatic ducts after transplantation. Our results provide proof of principle that cholangiocyte organoids can be used to repair human biliary epithelium.


Asunto(s)
Enfermedades de los Conductos Biliares/terapia , Conductos Biliares Intrahepáticos/fisiología , Conductos Biliares/citología , Tratamiento Basado en Trasplante de Células y Tejidos , Células Epiteliales/citología , Organoides/trasplante , Animales , Bilis , Conductos Biliares/fisiología , Conductos Biliares Intrahepáticos/citología , Conducto Colédoco/citología , Células Epiteliales/fisiología , Vesícula Biliar/citología , Regulación de la Expresión Génica , Humanos , Hígado/fisiología , Trasplante de Hígado , Trasplante de Células Madre Mesenquimatosas , Ratones , Organoides/fisiología , RNA-Seq , Obtención de Tejidos y Órganos , Transcriptoma
18.
Genome Biol ; 21(1): 157, 2020 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-32611441

RESUMEN

BACKGROUND: Haematopoietic stem cells (HSCs) first arise during development in the aorta-gonad-mesonephros (AGM) region of the embryo from a population of haemogenic endothelial cells which undergo endothelial-to-haematopoietic transition (EHT). Despite the progress achieved in recent years, the molecular mechanisms driving EHT are still poorly understood, especially in human where the AGM region is not easily accessible. RESULTS: In this study, we take advantage of a human pluripotent stem cell (hPSC) differentiation system and single-cell transcriptomics to recapitulate EHT in vitro and uncover mechanisms by which the haemogenic endothelium generates early haematopoietic cells. We show that most of the endothelial cells reside in a quiescent state and progress to the haematopoietic fate within a defined time window, within which they need to re-enter into the cell cycle. If cell cycle is blocked, haemogenic endothelial cells lose their EHT potential and adopt a non-haemogenic identity. Furthermore, we demonstrate that CDK4/6 and CDK1 play a key role not only in the transition but also in allowing haematopoietic progenitors to establish their full differentiation potential. CONCLUSION: We propose a direct link between the molecular machineries that control cell cycle progression and EHT.


Asunto(s)
Ciclo Celular , Diferenciación Celular , Células Endoteliales/fisiología , Células Madre Hematopoyéticas/citología , Quinasas Ciclina-Dependientes/metabolismo , Hematopoyesis , Humanos , Células Madre Pluripotentes , Análisis de la Célula Individual
19.
Arq Bras Cardiol ; 115(6): 1144-1151, 2020 12.
Artículo en Inglés, Portugués | MEDLINE | ID: mdl-33470315

RESUMEN

BACKGROUND: Ischemic Stroke (IS) and Coronary Artery Disease (CAD) frequently coexist and share atherosclerotic disease risk factors. According to the American Heart Association, IS subtypes may be considered CAD risk equivalents, but the evidence for non-atherosclerotic IS is uncertain. Additionally, the Coronary Calcium Score (CCS) is an accurate marker to address CAD risk; however, CCS distribution between IS subtypes is not well characterized. OBJECTIVES: To compare the CCS between atherosclerotic and non-atherosclerotic IS groups; and to determine which covariates were associated with high CCS in IS. METHODS: This cross-sectional design included all patients with IS, 45 to 70 years of age at the time of the stroke, consecutively admitted to a rehabilitation hospital between August 2014 and December 2016, without prevalent CAD. All patients underwent CT scanning for CCS measurement. CCS≥100 was considered a high risk for CAD, with a significance level of p<0.05. RESULTS: From the 244 studied patients (mean age 58.4±6.8 years; 49% female), 164 (67%) had non-atherosclerotic etiology. The proportions of CCS≥100 were similar between the atherosclerotic and the non-atherosclerotic groups (33% [n=26] x 29% [n=47]; p= 0.54). Among all IS patients, only age ≥60 years was independently associated with CCS≥100 (OR 3.5; 95%CI 1.7-7.1), accounting for hypertension, dyslipidemia, diabetes, sedentarism, and family history of CAD. CONCLUSION: Atherosclerotic IS did not present a greater risk of CAD when compared to non-atherosclerotic IS according to CCS. Only age ≥60 years, but not etiology, was independently associated with CCS≥100.


FUNDAMENTO: O acidente vascular encefálico isquêmico (AVEi) e a doença arterial coronariana (DAC) coexistem frequentemente e compartilham fatores de risco para doença aterosclerótica. Segundo a American Heart Association , os subtipos de AVEi podem ser considerados equivalentes de risco para DAC, mas a evidência para o AVEi não-aterosclerótico não está bem definida. Além disso, o escore de cálcio coronário (CAC) é um marcador preciso para estimar o risco de DAC. Entretanto, a distribuição do CAC pelos subtipos de AVEi ainda não foi bem caracterizada. OBJETIVOS: Comparar o CAC entre os grupos de AVEi ateroscleróticos e não ateroscleróticos, e determinar quais covariáveis estão associadas a CAC alto no AVEi. MÉTODOS: Em um estudo transversal, incluímos todos os pacientes com AVEi, com idades entre 45 a 70 anos no momento do acidente vascular, consecutivamente admitidos em um hospital de reabilitação entre agosto de 2014 e dezembro de 2016, sem DAC prevalente. Todos os pacientes passaram por tomografia computadorizada (TC), para medir o CAC. CAC≥100 foi considerado alto risco de DAC. O nível de significância foi p<0,05. RESULTADOS: Dos 244 pacientes estudados (média de idade de 58,4±6,8 anos; 49% do sexo feminino), 164 (67%) apresentavam etiologia não-aterosclerótica. As proporções de CAC≥100 foram semelhantes entre os grupos ateroscleróticos e não-ateroscleróticos (33% [n=26] x 29% [n=47]; p= 0,54). Entre todos os pacientes com AVEi, apenas os de idade ≥60 anos foram associados independentemente a CAC≥100 (RC 3,5; 95% IC 1,7-7,1), ajustado para hipertensão, dislipidemia, diabetes, sedentarismo, e histórico familiar de DAC. CONCLUSÃO: O AVEi aterosclerótico não apresentou risco maior de DAC quando comparado ao AVEi não-aterosclerótico de acordo com o CAC. Apenas a faixa etária ≥60 anos ­ mas não a etiologia - foi associada independentemente a CAC≥100. (Arq Bras Cardiol. 2020; 115(6):1144-1151).


Asunto(s)
Isquemia Encefálica , Enfermedad de la Arteria Coronaria , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Anciano , Isquemia Encefálica/epidemiología , Isquemia Encefálica/etiología , Calcio , Angiografía Coronaria , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/epidemiología , Enfermedad de la Arteria Coronaria/etiología , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factores de Riesgo , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/etiología
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