Skeletal muscle as a regulator of the longevity protein, Klotho

Klotho is a powerful longevity protein that has been linked to the prevention of muscle atrophy, osteopenia, and cardiovascular disease. Similar anti-aging effects have also been ascribed to exercise and physical activity. While an association between muscle function and Klotho expression has been previously suggested from longitudinal cohort studies, a direct relationship between circulating Klotho and skeletal muscle has not been investigated. In this paper, we present a review of the literature and preliminary evidence that, together, suggests Klotho expression may be modulated by skeletal muscle activity. Our pilot clinical findings performed in young and aged individuals suggest that circulating Klotho levels are upregulated in response to an acute exercise bout, but that the response may be dependent on fitness level. A similar upregulation of circulating Klotho is also observed in response to an acute exercise in young and old mice, suggesting that this may be a good model for mechanistically probing the role of physical activity on Klotho expression. Finally, we highlight overlapping signaling pathways that are modulated by both Klotho and skeletal muscle and propose potential mechanisms for cross-talk between the two. It is hoped that this review will stimulate further consideration of the relationship between skeletal muscle activity and Klotho expression, potentially leading to important insights into the well-documented systemic anti-aging effects of exercise. © 2014 Avin, Coen, Huang, Stolz, Sowa, Dubé, Goodpaster, O'Doherty and Ambrosio

Indexing multi-dimensional uncertain data with arbitrary probability density functions

Research Session 26: Spatial and Temporal DatabasesIn an "uncertain database", an object o is associated with a multi-dimensional probability density function (pdf), which describes the likelihood that o appears at each position in the data space. A fundamental operation is the "probabilistic range search" which, given a value p q and a rectangular area r q, retrieves the objects that appear in r q with probabilities at least p q. In this paper, we propose the U-tree, an access method designed to optimize both the I/O and CPU time of range retrieval on multi-dimensional imprecise data. The new structure is fully dynamic (i.e., objects can be incrementally inserted/deleted in any order), and does not place any constraints on the data pdfs. We verify the query and update efficiency of U-trees with extensive experiments.postprintThe 31st International Conference on Very Large Data Bases (VLDB 2005), Trondheim, Norway, 30 August-2 September 2005. In Proceedings of 31st VLDB, 2005, v. 3, p. 922-93

Evaluation of Five Methods for Total DNA Extraction from Western Corn Rootworm Beetles

Background: DNA extraction is a routine step in many insect molecular studies. A variety of methods have been used to isolate DNA molecules from insects, and many commercial kits are available. Extraction methods need to be evaluated for their efficiency, cost, and side effects such as DNA degradation during extraction. Methodology/Principal Findings: From individual western corn rootworm beetles, Diabrotica virgifera virgifera, DNA extractions by the SDS method, CTAB method, DNAzol reagent, Puregene solutions and DNeasy column were compared in terms of DNA quantity and quality, cost of materials, and time consumed. Although all five methods resulted in acceptable DNA concentrations and absorbance ratios, the SDS and CTAB methods resulted in higher DNA yield (ng DNA vs. mg tissue) at much lower cost and less degradation as revealed on agarose gels. The DNeasy kit was most time-efficient but was the costliest among the methods tested. The effects of ethanol volume, temperature and incubation time on precipitation of DNA were also investigated. The DNA samples obtained by the five methods were tested in PCR for six microsatellites located in various positions of the beetle’s genome, and all samples showed successful amplifications. Conclusion/Significance: These evaluations provide a guide for choosing methods of DNA extraction from western corn rootworm beetles based on expected DNA yield and quality, extraction time, cost, and waste control. The extraction conditions for this mid-size insect were optimized. The DNA extracted by the five methods was suitable for further molecular applications such as PCR and sequencing by synthesis

A cost-effectiveness analysis of a preventive exercise program for patients with advanced head and neck cancer treated with concomitant chemo-radiotherapy

In recent years, concomitant chemo-radiotherapy (CCRT) has become an indispensable organ preserving treatment modality for advanced head and neck cancer, improving local control and overall survival in several anatomical sites [1]. Unfortunately, CCRT can have a detrimental effect on many functions of the upper respiratory and digestive system. Sequellae such as pain, oedema, xerostomia and fibrosis negatively affect mouth opening (trismus), chewing, swallowing and speech [1]. Several studies investigating long-term effects of CCRT have concluded that swallowing and nutritional dysfunction tend to be persistent and can be severe [2-4]. Not surprisingly, therefore, CCRT can have a negative effect on patients‟ quality of life (QoL) [2]. Moreover, even before onset of treatment patients may already present with pain, impaired swallowing, trismus, aspiration, dietary restrictions and tube dependency, and loss of body weight, because the tumour may disrupt the normal anatomy and thus interfere with normal function [1]. Many studies refer to the importance of rehabilitation after, and even during treatment, in order to support and improve those functions [2]. However, as yet, few studies have investigated the effects of (preventive) rehabilitation exercises on the predictable and inevitable swallowing and mouth opening problems for this patient group. In addition, little is known about the costs and benefits of such exercise programs for head and neck cancer. As the clinical effectiveness is established [4], it is now relevant to embark on cost-effectiveness as a contribution to decision making on coverage. The aim of this study was to analyze the incremental cost-effectiveness for a preventive exercise program (PREP) versus usual care (UC) for patients with advanced head and neck cancer treated at the Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital (NKI-AVL)

Decreased 3D observer variation with matched CT-MRI, for target delineation in Nasopharynx cancer

Contains fulltext : 88137.pdf (publisher's version ) (Open Access)PURPOSE: To determine the variation in target delineation of nasopharyngeal carcinoma and the impact of measures to minimize this variation. MATERIALS AND METHODS: For ten nasopharyngeal cancer patients, ten observers each delineated the Clinical Target Volume (CTV) and the CTV elective. After 3D analysis of the delineated volumes, a second delineation was performed. This implied improved delineation instructions, a combined delineation on CT and co-registered MRI, forced use of sagittal reconstructions, and an on-line anatomical atlas. RESULTS: Both for the CTV and the CTV elective delineations, the 3D SD decreased from Phase 1 to Phase 2, from 4.4 to 3.3 mm for the CTV and from 5.9 to 4.9 mm for the elective. There was an increase agreement, where the observers intended to delineate the same structure, from 36 to 64 surface % (p = 0.003) for the CTV and from 17 to 59% (p = 0.004) for the elective. The largest variations were at the caudal border of the delineations but these were smaller when an observer utilized the sagittal window. Hence, the use of sagittal side windows was enforced in the second phase and resulted in a decreased standard deviation for this area from 7.7 to 3.3 mm (p = 0.001) for the CTV and 7.9 to 5.6 mm (p = 0.03) for the CTV elective. DISCUSSION: Attempts to decrease the variation need to be tailored to the specific causes of the variation. Use of delineation instructions multimodality imaging, the use of sagittal windows and an on-line atlas result in a higher agreement on the intended target

Developmental Robustness by Obligate Interaction of Class B Floral Homeotic Genes and Proteins

DEF-like and GLO-like class B floral homeotic genes encode closely related MADS-domain transcription factors that act as developmental switches involved in specifying the identity of petals and stamens during flower development. Class B gene function requires transcriptional upregulation by an autoregulatory loop that depends on obligate heterodimerization of DEF-like and GLO-like proteins. Because switch-like behavior of gene expression can be displayed by single genes already, the functional relevance of this complex circuitry has remained enigmatic. On the basis of a stochastic in silico model of class B gene and protein interactions, we suggest that obligate heterodimerization of class B floral homeotic proteins is not simply the result of neutral drift but enhanced the robustness of cell-fate organ identity decisions in the presence of stochastic noise. This finding strongly corroborates the view that the appearance of this regulatory mechanism during angiosperm phylogeny led to a canalization of flower development and evolution

A Computational Clonal Analysis of the Developing Mouse Limb Bud

A comprehensive spatio-temporal description of the tissue movements underlying organogenesis would be an extremely useful resource to developmental biology. Clonal analysis and fate mappings are popular experiments to study tissue movement during morphogenesis. Such experiments allow cell populations to be labeled at an early stage of development and to follow their spatial evolution over time. However, disentangling the cumulative effects of the multiple events responsible for the expansion of the labeled cell population is not always straightforward. To overcome this problem, we develop a novel computational method that combines accurate quantification of 2D limb bud morphologies and growth modeling to analyze mouse clonal data of early limb development. Firstly, we explore various tissue movements that match experimental limb bud shape changes. Secondly, by comparing computational clones with newly generated mouse clonal data we are able to choose and characterize the tissue movement map that better matches experimental data. Our computational analysis produces for the first time a two dimensional model of limb growth based on experimental data that can be used to better characterize limb tissue movement in space and time. The model shows that the distribution and shapes of clones can be described as a combination of anisotropic growth with isotropic cell mixing, without the need for lineage compartmentalization along the AP and PD axis. Lastly, we show that this comprehensive description can be used to reassess spatio-temporal gene regulations taking tissue movement into account and to investigate PD patterning hypothesis

Intra-Genomic Ribosomal RNA Polymorphism and Morphological Variation in Elphidium macellum Suggests Inter-Specific Hybridization in Foraminifera

Elphidium macellum is a benthic foraminifer commonly found in the Patagonian fjords. To test whether its highly variable morphotypes are ecophenotypes or different genotypes, we analysed 70 sequences of the SSU rRNA gene from 25 specimens. Unexpectedly, we identified 11 distinct ribotypes, with up to 5 ribotypes co-occurring within the same specimen. The ribotypes differ by varying blocks of sequence located at the end of stem-loop motifs in the three expansion segments specific to foraminifera. These changes, distinct from typical SNPs and indels, directly affect the structure of the expansion segments. Their mosaic distribution suggests that ribotypes originated by recombination of two or more clusters of ribosomal genes. We propose that this expansion segment polymorphism (ESP) could originate from hybridization of morphologically different populations of Patagonian Elphidium. We speculate that the complex geological history of Patagonia enhanced divergence of coastal foraminiferal species and contributed to increasing genetic and morphological variation

Cortical Surround Interactions and Perceptual Salience via Natural Scene Statistics

Spatial context in images induces perceptual phenomena associated with salience and modulates the responses of neurons in primary visual cortex (V1). However, the computational and ecological principles underlying contextual effects are incompletely understood. We introduce a model of natural images that includes grouping and segmentation of neighboring features based on their joint statistics, and we interpret the firing rates of V1 neurons as performing optimal recognition in this model. We show that this leads to a substantial generalization of divisive normalization, a computation that is ubiquitous in many neural areas and systems. A main novelty in our model is that the influence of the context on a target stimulus is determined by their degree of statistical dependence. We optimized the parameters of the model on natural image patches, and then simulated neural and perceptual responses on stimuli used in classical experiments. The model reproduces some rich and complex response patterns observed in V1, such as the contrast dependence, orientation tuning and spatial asymmetry of surround suppression, while also allowing for surround facilitation under conditions of weak stimulation. It also mimics the perceptual salience produced by simple displays, and leads to readily testable predictions. Our results provide a principled account of orientation-based contextual modulation in early vision and its sensitivity to the homogeneity and spatial arrangement of inputs, and lends statistical support to the theory that V1 computes visual salience