The extrinsic apoptotic pathway in aged skeletal muscle: Roles of tumor necrosis factor-alpha and interleukin-15

Apoptosis is implicated in the loss of skeletal muscle mass following periods of reduced activity (i.e.-disuse) as well as during the normal aging process (i.e.-sarcopenia). Aging is also characterized by elevations in circulating cytokines, specifically TNF-alpha, which has been associated with the sarcopenic process. The specific signaling components that participate in the pro-apoptotic pathway downstream of the type I TNF receptor (i.e.-extrinsic apoptotic pathway) within skeletal muscle have not been clarified. Additionally, few studies have been performed with the aim of disrupting this apoptotic pathway, and thereby sparing muscle mass in the aged. Therefore, the purposes of this dissertation were to characterize the extrinsic apoptotic pathway within aged skeletal muscles and to test the effectiveness of another cytokine, IL-15, at disrupting this apoptotic pathway. Apoptotic signaling markers involved in the extrinsic pathway, including tumor necrosis factor-alpha (TNF-alpha), TNF receptor (TNFR), fas-associated death domain protein (FADD), TNFR-associated death domain protein (TRADD), caspase-8, caspase-3, BCL-3 interacting domain protein (Bid), and FLICE-inhibiting protein (FLIP), as well as the cytokine interleukin-15 (IL-15), were accessed in skeletal muscles from aged rodents and compared to muscles from young adult rodents. Muscles from aged animals were smaller and the incidence of apoptosis was greater when compared to muscles from young adult rodents. Additionally, aged muscles expressed greater mRNA and protein contents for the apoptotic markers involved in the extrinsic pathway, thereby suggesting the extrinsic pathway is active in skeletal muscles. Furthermore, IL-15 mRNA concentrations were, in general, greater in aged muscles and following periods of muscle unloading. However, over-expression of IL-15 was unable to disrupt this apoptotic pathway in either aged rodents or in myoblast cultures stimulated with TNF-alpha. These data suggest that while the extrinsic apoptotic pathway is active within aged skeletal muscles, and that TNF-alpha is able to promote these apoptotic changes in myoblast cultures, IL-15 is not an effective agent at disrupting this pathway and preserving muscle mass

Relationship Between Lung Function and Skeletal Muscle Morphology in Predicting Risk of Cachexia

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Signal Compression via Neural Implicit Representations

Existing end-to-end signal compression schemes using neural networks are largely based on an autoencoder-like structure, where a universal encoding function creates a compact latent space and the signal representation in this space is quantized and stored. Recently, advances from the field of 3D graphics have shown the possibility of building implicit representation networks, i.e., neural networks returning the value of a signal at a given query coordinate. In this paper, we propose using neural implicit representations as a novel paradigm for signal compression with neural networks, where the compact representation of the signal is defined by the very weights of the network. We discuss how this compression framework works, how to include priors in the design, and highlight interesting connections with transform coding. While the framework is general, and still lacks maturity, we already show very competitive performance on the task of compressing point cloud attributes, which is notoriously challenging due to the irregularity of the domain, but becomes trivial in the proposed framework

Learning Robust Graph-Convolutional Representations for Point Cloud Denoising

Point clouds are an increasingly relevant geometric data type but they are often corrupted by noise and affected by the presence of outliers. We propose a deep learning method that can simultaneously denoise a point cloud and remove outliers in a single model. The core of the proposed method is a graph-convolutional neural network able to efficiently deal with the irregular domain and the permutation invariance problem typical of point clouds. The network is fully-convolutional and can build complex hierarchies of features by dynamically constructing neighborhood graphs from similarity among the high-dimensional feature representations of the points. The proposed approach outperforms state-of-the-art denoising methods showing robust performance in the challenging setup of high noise levels and in presence of structured noise

Analytics readiness: Is your institution primed for success?

What is necessary for an institution to begin using analytics to inform teaching and learning? This session will review and discuss current findings and components of learning analytics frameworks as identified by experts in the field. The audience will engage in discussion and hands-on activities that synthesize these ideas to begin to identify the readiness of learning analytics success at their own institutions. Furthermore, participants will collaboratively develop the core elements of a crowdsourced survey instrument that will focus on the elements necessary for institutional-level readiness and the likelihood of achieving success in learning analytics

Is your institution ready to innovate with learning analytics?

Online learning has frequently been exemplified as a revolutionary instrument, particularly in higher education. Similarly, learning analytics has been lauded as a means to identify students who need help, empower students to be more independent, and personalize the learning experience. Online learning and learning analytics blend nicely in education\u27s quest for a transformational paradigm and, while conceptually appealing, institutions should be deliberate in their decision to adopt learning analytics. Institutional readiness for learning analytics is a complex endeavor involving a broad spectrum of resources and skills. Institutional reflection and self-study may allow stakeholders to set more realistic implementation goals. We\u27ll discuss the broad idea of institutional capacity and readiness for successful learning analytics innovations. Learning Objectives: Understand the broad concepts and themes associated with learning analytics readiness | Understand the complex nature of scalable and sustainable learning analytics initiative

Dysregulation of metabolic-associated pathways in muscle of breast cancer patients: preclinical evaluation of interleukin-15 targeting fatigue

Background Breast cancer patients report a perception of increased muscle fatigue, which can persist following surgery and standardized therapies. In a clinical experiment, we tested the hypothesis that pathways regulating skeletal muscle fatigue are down-regulated in skeletal muscle of breast cancer patients and that different muscle gene expression patterns exist between breast tumour subtypes. In a preclinical study, we tested the hypothesis that mammary tumour growth in mice induces skeletal muscle fatigue and that overexpression of the cytokine interleukin-15 (IL-15) can attenuate mammary tumourinduced muscle fatigue. Methods Early stage non-metastatic female breast cancer patients (n = 14) and female non-cancer patients (n = 6) provided a muscle biopsy of the pectoralis major muscle during mastectomy, lumpectomy, or breast reconstruction surgeries. The breast cancer patients were diagnosed with either luminal (ER+ /PR+ , n = 6), triple positive (ER+ /PR+ /Her2/neu+ , n = 5), or triple negative (ER/PR/Her2/neu, n = 3) breast tumours and were being treated with curative intent either with neoadjuvant chemotherapy followed by surgery or surgery followed by standard post-operative therapy. Biopsies were used for RNA-sequencing to compare the skeletal muscle gene expression patterns between breast cancer patients and non-cancer patients. The C57BL/6 mouse syngeneic mammary tumour cell line, E0771, was used to induce mammary tumours in immunocompetent mice, and isometric muscle contractile properties and fatigue properties were analysed following 4 weeks of tumour growth. Results RNA-sequencing and subsequent bioinformatics analyses revealed a dysregulation of canonical pathways involved in oxidative phosphorylation, mitochondrial dysfunction, peroxisome proliferator-activated receptor signalling and activation, and IL-15 signalling and production. In a preclinical mouse model of breast cancer, the rate of muscle fatigue was greater in mice exposed to mammary tumour growth for 4 weeks, and this greater muscle fatigue was attenuated in transgenic mice that overexpressed the cytokine IL-15. Conclusions Our data identify novel genes and pathways dysregulated in the muscles of breast cancer patients with early stage non-metastatic disease, with particularly aberrant expression among genes that would predispose these patients to greater muscle fatigue. Furthermore, we demonstrate that IL-15 overexpression can attenuate muscle fatigue associated with mammary tumour growth in a preclinical mouse model of breast cancer. Therefore, we propose that skeletal muscle fatigue is an inherent consequence of breast tumour growth, and this greater fatigue can be targeted therapeutically

Status of the Cylindical-GEM project for the KLOE-2 Inner Tracker

The status of the R&D on the Cylindrical-GEM (CGEM) detector foreseen as Inner Tracker for KLOE-2, the upgrade of the KLOE experiment at the DAFNE phi-factory, will be presented. The R&D includes several activities: i) the construction and complete characterization of the full-size CGEM prototype, equipped with 650 microns pitch 1-D longitudinal strips; ii) the study of the 2-D readout with XV patterned strips and operation in magnetic field (up to 1.5T), performed with small planar prototypes in a dedicated test at the H4-SPS beam facility; iii) the characterization of the single-mask GEM technology for the realization of large-area GEM foils.Comment: 4 pages, 10 figures, Presented at Vienna Conference on Instrumentation (Feb 15-20, 2010, Vienna, Austria). Submitted to the Proceeding

Niveles de hemoglobina en varones fumadores

Debido a la importancia de la hemoglobina como indicador nutricional, así como su papel en la oxigenación de los tejidos, fue realizado este estudio con el objetivo de observar la existencia o no de alteraciones en los niveles de hemoglobina de individuos fumadores donantes de sangre, de tal manera que dichas alteraciones causadas por el cigarrillo sean consideradas, al evaluar el estado de salud de un individuo fumador, así como en el diagnóstico de las patologías asociadas. Fueron seleccionados 121 varones, aparentemente sanos, fumadores y no fumadores,entre 20 y 60 años de edad, donantes de cinco bancos de sangre de Asunción, Paraguay. Los niveles promedios de hemoglobina en fumadores fueron 150 ± 8 g/L y en los no fumadores 148 ± 9 g/L, no siendo la diferencia significativa (p>0.05); sin embargo dentro del grupo de fumadores, la diferencia fue significativamente mayor en aquellos que fumaban de 11 a 20 cigarrillos /día (152 ± 9 g/L) que en aquellos que fumaban de 1 a 10 cigarrillos /día (148 ± 7 g/L) (p<0.05). Por lo tanto,el nivel medio de hemoglobina se incrementa con el número de cigarrillos consumidos por día. El coeficiente de correlación hallado fue de 0,38 con un nivel de confianza del 95%. Debemos seguir investigando, en nuestra población, la influencia del cigarrillo sobre los parámetros hematológicos,y el efecto que producen dichas alteraciones en el estado de salud de los fumadores