Cytokine expression and secretion by skeletal muscle cells : regulatory mechanisms and exercise effects

Cytokines are important mediators of various aspects of health and disease, including appetite, glucose and lipid metabolism, insulin sensitivity, skeletal muscle hypertrophy and atrophy. Over the past decade or so, considerable attention has focused on the potential for regular exercise to counteract a range of disease states by modulating cytokine production. Exercise stimulates moderate to large increases in the circulating concentrations of interleukin (IL)-6, IL-8, IL-10, IL-1 receptor antagonist, granulocyte-colony stimulating factor, and smaller increases in tumor necrosis factor-α, monocyte chemotactic protein-1, IL-1β, brain-derived neurotrophic factor, IL-12p35/p40 and IL-15. Although many of these cytokines are also expressed in skeletal muscle, not all are released from skeletal muscle into the circulation during exercise. Conversely, some cytokines that are present in the circulation are not expressed in skeletal muscle after exercise. The reasons for these discrepant cytokine responses to exercise are unclear. In this review, we address these uncertainties by summarizing the capacity of skeletal muscle cells to produce cytokines, analyzing other potential cellular sources of circulating cytokines during exercise, and discussing the soluble factors and intracellular signaling pathways that regulate cytokine synthesis (e.g., RNA-binding proteins, microRNAs, suppressor of cytokine signaling proteins, soluble receptors).

Low probability differentials and the cryptanalysis of full-round CLEFIA-128

So far, low probability differentials for the key schedule of block ciphers have been used as a straightforward proof of security against related-key differential analysis. To achieve resistance, it is believed that for cipher with k-bit key it suffices the upper bound on the probability to be 2− k . Surprisingly, we show that this reasonable assumption is incorrect, and the probability should be (much) lower than 2− k . Our counter example is a related-key differential analysis of the well established block cipher CLEFIA-128. We show that although the key schedule of CLEFIA-128 prevents differentials with a probability higher than 2− 128, the linear part of the key schedule that produces the round keys, and the Feistel structure of the cipher, allow to exploit particularly chosen differentials with a probability as low as 2− 128. CLEFIA-128 has 214 such differentials, which translate to 214 pairs of weak keys. The probability of each differential is too low, but the weak keys have a special structure which allows with a divide-and-conquer approach to gain an advantage of 27 over generic analysis. We exploit the advantage and give a membership test for the weak-key class and provide analysis of the hashing modes. The proposed analysis has been tested with computer experiments on small-scale variants of CLEFIA-128. Our results do not threaten the practical use of CLEFIA.

Using viewer’s facial expression and heart rate for sports video highlights detection

Viewer interests, evoked by video content, can potentially identify the highlights of the video. This paper explores the use of facial expressions (FE) and heart rate (HR) of viewers captured using camera and non-strapped sensor for identifying interesting video segments. The data from ten subjects with three videos showed that these signals are viewer dependent and not synchronized with the video contents. To address this issue, new algorithms are proposed to effectively combine FE and HR signals for identifying the time when viewer interest is potentially high. The results show that, compared with subjective annotation and match report highlights, ‘non-neutral’ FE and ‘relatively higher and faster’ HR is able to capture 60%-80% of goal, foul, and shot-on-goal soccer video events. FE is found to be more indicative than HR of viewer’s interests, but the fusion of these two modalities outperforms each of them.

Multi-layered model of individual HIV infection progression and mechanisms of phenotypical expression

Cite as: Perrin, Dimitri (2008) Multi-layered model of individual HIV infection progression and mechanisms of phenotypical expression. PhD thesis, Dublin City University.

Edge-weighting of gene expression graphs

In recent years, considerable research efforts have been directed to micro-array technologies and their role in providing simultaneous information on expression profiles for thousands of genes. These data, when subjected to clustering and classification procedures, can assist in identifying patterns and providing insight on biological processes. To understand the properties of complex gene expression datasets, graphical representations can be used. Intuitively, the data can be represented in terms of a bipartite graph, with weighted edges corresponding to gene-sample node couples in the dataset. Biologically meaningful subgraphs can be sought, but performance can be influenced both by the search algorithm, and, by the graph-weighting scheme and both merit rigorous investigation. In this paper, we focus on edge-weighting schemes for bipartite graphical representation of gene expression. Two novel methods are presented: the first is based on empirical evidence; the second on a geometric distribution. The schemes are compared for several real datasets, assessing efficiency of performance based on four essential properties: robustness to noise and missing values, discrimination, parameter influence on scheme efficiency and reusability. Recommendations and limitations are briefly discussed. Keywords: Edge-weighting; weighted graphs; gene expression; bi-clustering

A Mammalian Circadian Clock Model Incorporating Daytime Expression Elements

Models of the mammalian clock have traditionally been based around two feedback loops-the self-repression of Per/Cry by interfering with activation by BMAL/CLOCK, and the repression of Bmal/Clock by the REV-ERB proteins. Recent experimental evidence suggests that the D-box, a transcription factor binding site associated with daytime expression, plays a larger role in clock function than has previously been understood. We present a simplified clock model that highlights the role of the D-box and illustrate an approach for finding maximum-entropy ensembles of model parameters, given experimentally imposed constraints. Parameter variability can be mitigated using prior probability distributions derived from genome-wide studies of cellular kinetics. Our model reproduces predictions concerning the dual regulation of Cry1 by the D-box and Rev-ErbA/ROR response element (RRE) promoter elements and allows for ensemble-based predictions of phase response curves (PRCs). Nonphotic signals such as Neuropeptide Y (NPY) may act by promoting Cry1 expression, whereas photic signals likely act by stimulating expression from the E/E' box. Ensemble generation with parameter probability restraints reveals more about a model's behavior than a single optimal parameter set.

Sub-genomic RNA of defective interfering (D.I.) dengue viral particles is replicated in the same manner as full length genomes

The predicted secondary structure of sub-genomic RNA in dengue virus defective interfering (D.I.) particles from patients, or generated in vitro, resembled that of the 3′ and 5′ regions of wild type dengue virus (DENV) genomes. While these structures in the sub-genomic RNA were found to be essential for its replication, their nucleotide sequences were not, so long as any new sequences maintained wild type RNA secondary structure. These observations suggested that these sub-genomic fragments of RNA from dengue viruses were replicated in the same manner as the full length genomes of their wild type, “helper”, viruses and that they probably represent the smallest fragments of DENV RNA that can be replicated during a natural infection. While D.I. particles containing sub-genomic RNA are completely parasitic, the relationship between wild type and D.I. DENV may be symbiotic, with the D.I. particles enhancing the transmission of infectious DENV.

Matter and movement: Expression as topological continuity or a return to Butades' wall

This paper aims to address the ways in which drawing can be understood as the becoming-expressive of materials, site, and body, over time. The discussion pivots around a series of studies that replace linear or causal relationships – in history, drawing and expression – with topological movement. My approach is largely through a speculative case study. In a rereading of the familiar Butades myth, I examine how a shadow tracing can variously be taken as the first mimetic art with its origins in the urge to “capture”, and, antithetically, as the originary expressive folding of matter, site and body. The paper is divided into five sections. The first presents the Butades myth, identifying the representational problem that lies at the roots of its traditional telling. The next three sections outline a series of topologies that facilitate a discussion of the Butades myth from historical, disciplinary, and expressive perspectives. The final section aims to show the relevance of this discussion to a contemporary drawing practice, using my own drawing research as a case study. The field of inquiry is that of representational critique. The fold, an image associated with a topological geometry, replaces the relational or signifying disjuncture of representational structures, and suggests a becoming- expressive of subject and object, form and matter.

Knowledge unlatched: A global library consortium model for funding open access scholarly books: Full report on the Proof of Concept Pilot 2014

This special issue of Cultural Science Journal is devoted to the report of a groundbreaking experiment in re-coordinating global markets for specialist scholarly books and enabling the knowledge commons: the Knowledge Unlatched proof-of-concept pilot. The pilot took place between January 2012 and September 2014. It involved libraries, publishers, authors, readers and research funders in the process of developing and testing a global library consortium model for supporting Open Access books. The experiment established that authors, librarians, publishers and research funding agencies can work together in powerful new ways to enable open access; that doing so is cost effective; and that a global library consortium model has the potential dramatically to widen access to the knowledge and ideas contained in book-length scholarly works.

Evaluation of cooperative exploration strategies using full system simulation

This paper compares different state-of-the-art exploration strategies for teams of mobile robots exploring an unknown environment. The goal is to help in determining a best strategy for a given multi-robot scenario and optimization target. Experiments are done in a 2D-simulation environment with 5 robots that are equipped with a horizontal laser range finder. Required components like SLAM, path planning and obstacle avoidance of every robot are included in a full-system simulation. To evaluate different strategies the time to finish exploration, the number of measurements that have been integrated into the map and the development in size of the explored area over time are used. The results of extensive test runs on three environments with different characteristics show that simple strategies can perform fairly well in many situations but specialized strategies can improve performance with regards to their targeted evaluation measure.

Modulating exercise-induced hormesis: Does less equal more?

Hormesis enco 16 mpasses the notion that low levels of stress stimulate or upregulate 17 existing cellular and molecular pathways that improve the capacity of cells and organisms to 18 withstand greater stress. This notion underlies much of what we know about how exercise 19 conditions the body and induces long-term adaptations. During exercise, the body is 20 exposed to various forms of stress, including thermal, metabolic, hypoxic, oxidative, and 21 mechanical stress. These stressors activate biochemical messengers, which in turn activate 22 various signaling pathways that regulate gene expression and adaptive responses. 23 Historically, antioxidant supplements, nonsteroidal anti-inflammatory drugs, and 24 cryotherapy have been favored to attenuate or counteract exercise-induced oxidative stress 25 and inflammation. However, reactive oxygen species and inflammatory mediators are key 26 signaling molecules in muscle, and such strategies may mitigate adaptations to exercise. 27 Conversely, withholding dietary carbohydrate and restricting muscle blood flow during 28 exercise may augment adaptations to exercise. In this review article, we combine, integrate, 29 and apply knowledge about the fundamental mechanisms of exercise adaptation. We also 30 critically evaluate the rationale for using interventions that target these mechanisms under 31 the overarching concept of hormesis. There is currently insufficient evidence to establish 32 whether these treatments exert dose-dependent effects on muscle adaptation. However, 33 there appears to be some dissociation between the biochemical/molecular effects and 34 functional/performance outcomes of some of these treatments. Although several of these 35 treatments influence common kinases, transcription factors and proteins, it remains to be 36 determined if these interventions complement or negate each other, and whether such 37 effects are strong enough to influence adaptations to exercise.

Fuzzy-logic based frequency controller for wind farms augmented with energy storage systems

Displacement of conventional synchronous generators by non-inertial units such as wind or solar generators will result in reduced-system inertia affecting under-frequency response. Frequency control is important to avoid equipment damage, load shedding, and possible blackouts. Wind generators along with energy storage systems can be used to improve the frequency response of low-inertia power system. This paper proposes a fuzzy-logic based frequency controller (FFC) for wind farms augmented with energy storage systems (wind-storage system) to improve the primary frequency response in future low-inertia hybrid power system. The proposed controller provides bidirectional real power injection using system frequency deviations and rate of change of frequency (RoCoF). Moreover, FFC ensures optimal use of energy from wind farms and storage units by eliminating the inflexible de-loading of wind energy and minimizing the required storage capacity. The efficacy of the proposed FFC is verified on the low-inertia hybrid power system.

Biliverdin modulates the expression of C5aR in response to endotoxin in part via mTOR signaling

Macrophages play a crucial role in the maintenance and resolution of inflammation and express a number of pro- and anti-inflammatory molecules in response to stressors. Among them, the complement receptor 5a (C5aR) plays an integral role in the development of inflammatory disorders. Biliverdin and bilirubin, products of heme catabolism, exert anti-inflammatory effects and inhibit complement activation. Here, we define the effects of biliverdin on C5aR expression in macrophages and the roles of Akt and mammalian target of rapamycin (mTOR) in these responses. Biliverdin administration inhibited lipopolysaccharide (LPS)-induced C5aR expression (without altering basal expression), an effect partially blocked by rapamycin, an inhibitor of mTOR signaling. Biliverdin also reduced LPS-dependent expression of the pro-inflammatory cytokines TNF-alpha and IL-6. Collectively, these data indicate that biliverdin regulates LPS-mediated expression of C5aR via the mTOR pathway, revealing an additional mechanism underlying biliverdin's anti-inflammatory effects.

The tumour-promoting receptor tyrosine kinase, EphB4, regulates expression of Integrin-β8 in prostate cancer cells

Background The EphB4 receptor tyrosine kinase is overexpressed in many cancers including prostate cancer. The molecular mechanisms by which this ephrin receptor influences cancer progression are complex as there are tumor-promoting ligand-independent mechanisms in place as well as ligand-dependent tumor suppressive pathways. Methods We employed transient knockdown of EPHB4 in prostate cancer cells, coupled with gene microarray analysis, to identify genes that were regulated by EPHB4 and may represent linked tumor-promoting factors. We validated target genes using qRT-PCR and employed functional assays to determine their role in prostate cancer migration and invasion. Results We discovered that over 500 genes were deregulated upon EPHB4 siRNA knockdown, with integrin β8 (ITGB8) being the top hit (29-fold down-regulated compared to negative non-silencing siRNA). Gene ontology analysis found that the process of cell adhesion was highly deregulated and two other integrin genes, ITGA3 and ITGA10, were also differentially expressed. In parallel, we also discovered that over-expression of EPHB4 led to a concomitant increase in ITGB8 expression. In silico analysis of a prostate cancer progression microarray publically available in the Oncomine database showed that both EPHB4 and ITGB8 are highly expressed in prostatic intraepithelial neoplasia, the precursor to prostate cancer. Knockdown of ITGB8 in PC-3 and 22Rv1 prostate cancer cells in vitro resulted in significant reduction of cell migration and invasion. Conclusions These results reveal that EphB4 regulates integrin β8 expression and that integrin β8 plays a hitherto unrecognized role in the motility of prostate cancer cells and thus targeting integrin β8 may be a new treatment strategy for prostate cancer.

Full scale experiments of a steel portal frame building

While numerous full scale experimental programs have been conducted around the world over the past 50 years to investigate the behaviour of steel portal frame buildings, none have comprehensively investigated the behaviour of such buildings under wind uplift. Wind uplift loads often govern designs in the Australian environment and this became the subject of a recent research project at Queensland University of Technology (OUT). This paper describes the full scale experiments on a steel portal frame building subject to wind uplift, racking and gravity loads. The portal rafter and column members utilised hollow flange beam (HFB) sections [5-8] though the paper's findings on the theoretical and experimental building responses relate to conventional types of steel portal frame buildings.