1,169 research outputs found
The clinical trial of FK 506 as primary and rescue immunosuppression in pediatric cardiac transplantation
Editorial: Partial left ventriculectomy for dilated cardiomyopathy in children
AbstractJ Thorac Cardiovasc Surg 1999;117:918–91
Book review: Algorithms and the end of politics: how technology shapes 21st-century American life by Scott Timcke
In Algorithms and the End of Politics: How Technology Shapes 21st-Century American Life, Scott Timcke explores how digital technologies are impacting US politics and society today. With a timely and original main argument, this book will be particularly suited to those well versed in political and philosophical discourse and interested in Marxist critique, the logics of capitalism, technocracy, post-politics, data and new technologies, finds Juan M. del Nido
Male Neighbors’ Behavior: Bystander Effect in Domestic Violence Cases
This research was twofold and aimed to explore male neighbors’ behavior as bystanders of domestic violence (DV) cases. Study 1 used survey on 94 male respondents to obtain description about bystander behavior and examine the relationship between situational barriers, neighborhood cohesion, and bystander’s intention to help victims. Study 2 used qualitative approach with instrumental case study, involving three male participants to understand the dynamic of bystander effect on male neighbors who had witnessed DV. Bystander effect (BS) is a phenomenon in which individual is less likely to intervene in an emergency if bystander present. BS was analyzed based on three root psychological processes, namely: diffusion of responsibility, audience inhibition, and pluralistic ignorance; the three appeared in the bystander intervention stages. An important finding was the role of neighborhood cohesion which interacted with DV-supporting norm; such that bystanders from highly cohesive neighborhood were resistant to help victims of real DV cases although social cohesion was a notable predictor of intention to help. The evidences in this research expanded Latané’s (1981) theory of social impact as well as supporting Levine (1999) and Banyard and colleagues’ (2004) notion of distorted thinking as a root of bystander inaction. Implication of the findings for community-based interventions is discussed
Frataxin knockdown in human astrocytes triggers cell death and the release of factors that cause neuronal toxicity
© 2014 Elsevier Inc. Friedreich's ataxia (FA) is a recessive, predominantly neurodegenerative disorder caused in most cases by mutations in the first intron of the frataxin (FXN) gene. This mutation drives the expansion of a homozygous GAA repeat that results in decreased levels of FXN transcription and frataxin protein. Frataxin (Fxn) is a ubiquitous mitochondrial protein involved in iron-sulfur cluster biogenesis, and a decrease in the levels of this protein is responsible for the symptoms observed in the disease. Although the pathological manifestations of FA are mainly observed in neurons of both the central and peripheral nervous system, it is not clear if changes in non-neuronal cells may also contribute to the pathogenesis of FA, as recently suggested for other neurodegenerative disorders. Therefore, the aims of this study were to generate and characterize a cell model of Fxn deficiency in human astrocytes (HAs) and to evaluate the possible involvement of non-cell autonomous processes in FA. To knockdown frataxin in vitro, we transduced HAs with a specific shRNA lentivirus (shRNA37), which produced a decrease in both frataxin mRNA and protein expression, along with mitochondrial superoxide production, and signs of p53-mediated cell cycle arrest and apoptotic cell death. To test for non-cell autonomous interactions we cultured wild-type mouse neurons in the presence of frataxin-deficient astrocyte conditioned medium, which provoked a delay in the maturation of these neurons, a decrease in neurite length and enhanced cell death. Our findings confirm a detrimental effect of frataxin silencing, not only for astrocytes, but also for neuron-glia interactions, underlining the need to take into account the role of non-cell autonomous processes in FA.“l'Association Française de l'Ataxie de Friedreich” (AFAF), as well as the Spanish National Research Plan (SAF 2012-38042) and the Autonomous Government of Madrid (S20/BMD-2331). The Center for Biomedical Research on Rare Diseases (“Centro de Investigación Biomédica en Red sobre Enfermedades Raras”, CIBERER) is an initiative supported by the “Instituto de Salud Carlos III”.Peer Reviewe
Evaluación ambiental de terminales de usuario multiantena en redes LTE-A
Este trabajo tiene como objetivos el análisis medioambiental de los terminales de usuario (UE) en redes LTE-A que incorporen estructuras MIMO y su posible influencia sobre el abonado. Inicialmente se describen los principios de funcionamiento así como las características y ventajas de los sistemas MIMO. A continuación se estudian los escenarios más probables para la explotación comercial de estos equipos, entre las que cabe destacar el control y la gestión de cultivos en invernaderos, y se analizan desde un punto de vista ambiental. Por último, se obtienen conclusiones sobre su posible repercusión en la salud del usuario
Estudio de reflectarray multihaz para aplicaciones de satélite en banda Ka utilizando discriminación en frecuencia
This contribution describes a design concept based on beam squint effect in printed reflectarrays that allows to produce multiple contiguous beams at 19.5 and 20 GHz, by discriminating in frequency. A 1.6-m reflectarray has been proposed to produce 10 beams separated 0.5 degree using five feeds with frequency reuse. The simulated radiation patterns show a peak gain better than 47.6 dBi, with side-lobe levels close to -24 dB. The proposed concept can be suitable for multiple spot beam satellites in Ka-band
Enhanced production of herpes simplex virus 1 amplicon vectors by gene modification and optimization of packaging cell growth medium
Herpes simplex virus 1 (HSV-1)-derived amplicon vectors are
unique in their ability to accommodate large DNA molecules
allowing whole genomic loci to be included with all of their regulatory
elements. Additional advantages of these amplicons
include their minimal toxicity and ability to persist as episomes,
with negligible risk of insertional mutagenesis, being
particularly well-suited for gene therapy of neurological disorders
due to their outstanding ability to deliver genes into neurons
and other neural cells. However, extensive gene therapy
application has been hindered by difficulties in vector production.
This work improved HSV-1 amplicons production by genetic
modification of the packaging cell line and optimization
of the culture medium. A stably-transfected Vero 2-2 cell line
overexpressing the anti-apoptotic Bcl-2 protein was generated,
exhibiting an increased resistance to apoptosis, prolonged culture
duration, and a significant improvement in viral vector
production. Additionally, supplementation of the growth medium
with antioxidants, polyamines, amino acids, and reduced
glutathione further increased the yield of packaged amplicon
vectors. With these modifications, HSV-1 amplicons could be
isolated from culture supernatants instead of cell lysates, leading
to vector preparations with higher titer and purity and
paving the way for generation of stable cell lines that are
capable of continuous herpesviral vector productionThis work was supported by grants of the
Spanish National Research Plan (SAF 2015–69361-R), Friedreich
Ataxia Research Alliance (FARA), FARA Ireland, Spanish FEDAES,
GENEFA, and Babel Famil
Future prospects of gene therapy for Friedreich's ataxia
Friedreich’s ataxia is an autosomal recessive neurogenetic disease that is mainly associated with atrophy of the spinal cord and progressive neurodegeneration in the cerebellum. The disease is caused by a GAA-expansion in the first intron of the frataxin gene leading to a decreased level of frataxin protein, which results in mitochondrial dysfunction. Currently, there is no effective treatment to delay neurodegeneration in Friedreich’s ataxia. A plausible therapeutic approach is gene therapy. Indeed, Friedreich’s ataxia mouse models have been treated with viral vectors en-coding for either FXN or neurotrophins, such as brain-derived neurotrophic factor showing promising results. Thus, gene therapy is increasingly consolidating as one of the most promising therapies. However, several
hurdles have to be overcome, including immunotoxicity and pheno-toxicity. We review the state of the art of gene therapy in Friedreich’s ataxia, addressing the main challenges and the most feasible solutions for themComunidad Autónoma de Madrid (NEUROMETAB-CM, B2017/BMD-3700) and Spanish Ministerio de Ciencia e Innovación (MICINN, grant PID2019-111338RB-I00), co-financed by Agencia Estatal de Investigación and Fondo Europeo de Desarrollo Regional (AEI/FEDER, EU). We also acknowledge institutional support to the CBMSO from Fundación Ramón Areces. Gabriel Ocaña-Santero receive
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