EPO-receptor is present in mouse C2C12 and human primary skeletal muscle cells but EPO does not influence myogenesis.

Abstract The role and regulation of the pleiotropic cytokine erythropoietin (EPO) in skeletal muscle are controversial. EPO exerts its effects by binding its specific receptor (EPO-R), which activates intracellular signaling and gene transcription in response to internal and external stress signals. EPO is suggested to play a direct role in myogenesis via the EPO-R, but several studies have questioned the effect of EPO treatment in muscle in vitro and in vivo. The lack of certainty surrounding the use of nonspecific EPO-R antibodies contributes to the ambiguity of the field. Our study demonstrates that the EPO-R gene and protein are expressed at each stage of mouse C2C12 and human skeletal muscle cell proliferation and differentiation and validates a specific antibody for the detection of the EPO-R protein. However, in our experimental conditions, EPO treatment had no effect on mouse C2C12 and human muscle cell proliferation, differentiation, protein synthesis or EPO-R expression. While an increase in Akt and MAPK phosphorylation was observed, we demonstrate that this effect resulted from the stress caused by changing medium and not from EPO treatment. We therefore suggest that skeletal muscle EPO-R might be present in a nonfunctional form, or too lowly expressed to play a role in muscle cell function

Repeatless: transforming surface pattern with generative design

Much of the initial use of digital technology within the printed textile industry has focused on the particular advantages that it has over previous fabric printing methods. Examples include simplifying workflow, producing relatively cheap short runs, or allowing designers to work with photographic imagery and unlimited colour palettes. This paper firstly identifies that digital fabric printing has a fundamentally different possibility in relation to its forerunners. Formerly, printing was essentially the ability to reproduce the same image (or text) over and over again. Digital printing, however, does not have to work from static information; it can print a design that changes as it is being printed. Secondly, the research demonstrates that digital technology can provide the content with which to do this, creating a design that not only changes as it is being printed, but that never repeats. This is achieved by a generative software application. The resulting code is based on cellular automata, a method of mathematical modelling that allows the elements within a system to evolve in relation to each other. In this case, the elements are the individual motifs or other visual components and the system is the overall design. The rules that govern how the motifs arrange themselves are based on methods used by printed textile designers to ensure the eye can roam freely over a design, balancing the arrangement and scale of the motifs, for example, or the negative space between them. The degree of complexity possible with cellular automata allows the qualitative design process to be modelled with a richness that maps the skills of creating pattern into code. The output is a non-repeating design of infinite length that can be saved section by section to be streamed to a digital printer, exploiting the technology in an entirely novel fashion. Seen individually, digital design and digital printing technology present a large number of new possibilities for the printed textile industry. This paper shows a way that interdisciplinary, practice-led research can integrate them and offer a method to shift the paradigms of what pattern is and the way in which it can be reproduced

Repeatless: combining science, technology and design to re-think print and pattern for the future

Digital technology offers a method to fundamentally change the way printed textile designs and surface patterns are created and applied. Within industry, pre-digital textile printing processes mechanically transfer the same design again and again down the entire substrate's length. The patterns they reproduce have to repeat identically and cannot be altered without stopping and reconfiguring the printer. The practice-led research in this paper firstly proposes that digital technology could allow a design to change as it is being printed. The application of dyestuff or other colour by a digital printer is controlled by data corresponding to the design. This need not be static; the printer could be receiving constantly evolving information, producing pattern that need never do the same thing twice. The second proposal is that generative systems be used to create evolving pattern. The possibility that digital fabric printing could remove the need for repeating pattern has been identified (Briggs and Bunce, 1995) and others have considered its implications on pattern design (Ujiie, 2006; Tallon, 2011; Bowles and Isaac, 2012). Within a textiles context, interactive design (Paramanik, 2013), the use of randomness to create non-repeating design (Carlisle, 2002), animated pattern (Richardson, 2007 and 2009) and tapestry-based applications (Sutton, 1981; Moallemi and Wainer, 2008) have been considered. However, in comparison with other creative industries such as architecture (Fraser, 1995) and graphics (Maeda, 2000) that have established areas of practice where generative systems produce design outcomes, the field has been relatively unexplored in textiles. In this research, a software application uses cellular automata, a method of mathematical modelling that allows the elements within a system to evolve in relation to each other (Wolfram, 1994). Here, the elements are the motifs or other individual images and the system is the overall design. The final proposal concerns the rules by which the elements interact; it is here that the traditions of printed textiles can be exploited. When designing a repeat pattern, practitioners use a number of methods to ensure that the eye can roam freely over a design, balancing the arrangement and scale of the motifs, for example, or the negative space between them (Day, 1903; Bowles and Isaac, 2012). Whilst these are generally used to disguise the repetitive structure that underlies such designs, the methods have two distinctive points of interest in this context. Firstly, they determine the compositional quality of the design. Secondly, they can be quantified to a workable degree as design rules. These rules can be used to create algorithms, which can in turn be translated into the code (in this case Processing (Reas and Fry, 2007)) that forms the generative software application. The output is a repeatless design of any length that can be saved section by section to be streamed to a digital printer for application to fabric or other substrates, exploiting the technology in an entirely novel fashion. The outcomes demonstrate a method of re-thinking print and pattern for the future, providing a new way of exploiting digital technology that is workable on an industrial scale

Repeatless: innovating print and pattern design with generative systems

Pre-digital textile printing technologies used in mass production mechanically transfer the same design repeatedly down the entire length of a substrate. The patterns they reproduce have to loop identically and cannot be altered without stopping and reconfiguring the printer. Whilst acknowledging that digital technology might eliminate the need for repeat, existing research and practice (Carlisle, 2002; Richardson, 2009; Häberle, 2011 and 2013; Schofield, 2012; McDonald, 2013; Paramanik, 2013) require a design to be completed prior to printing. It is proposed that if a dynamic pattern could be created that changed in real time, it could be streamed section by section to a digital fabric printer to produce a repeatless design of potentially infinite length. It is suggested that a generative system be used to do this, specifically a cellular automaton, coded in the Processing environment (Reas and Fry, 2007). Within it, motifs or other visual elements interact via a series of algorithms, using a grammar developed from traditional, non-digital methods of designing repeat pattern for printed textiles. The outcome is a design of any length that never repeats; furthermore the algorithms offer criteria by which the quality of the outcomes might be tested via peer review. This project is an interdisciplinary, practice-led MPhil/PhD, covering design, generative systems, computer programming and complexity. It is the particular synthesis of elements from the different areas that make this work innovative, shifting the paradigms of what pattern is and the way it can be reproduced

Repeatless: the use of digital technology to extend the possibilities of printed textile design

This paper describes an original, interdisciplinary model by which repeatless patterns can be generated dynamically in real time and streamed to a digital printer. The model produces designs that have a negligible probability of repeating. Their underlying structure is based on cellular automata, modeling traditional pattern design methods of arranging motifs or other design elements. The motifs within the pattern respond in real-time to each other, creating a composition of indefinite length. This is sent to a digital fabric printer as it is being generated, exploiting the technology in an entirely novel fashion

Cellular localization and associations of the major lipolytic proteins in human skeletal muscle at rest and during exercise

Lipolysis involves the sequential breakdown of fatty acids from triacylglycerol and is increased during energy stress such as exercise. Adipose triglyceride lipase (ATGL) is a key regulator of skeletal muscle lipolysis and perilipin (PLIN) 5 is postulated to be an important regulator of ATGL action of muscle lipolysis. Hence, we hypothesized that non-genomic regulation such as cellular localization and the interaction of these key proteins modulate muscle lipolysis during exercise. PLIN5, ATGL and CGI-58 were highly (>60%) colocated with Oil Red O (ORO) stained lipid droplets. PLIN5 was significantly colocated with ATGL, mitochondria and CGI-58, indicating a close association between the key lipolytic effectors in resting skeletal muscle. The colocation of the lipolytic proteins, their independent association with ORO and the PLIN5/ORO colocation were not altered after 60 min of moderate intensity exercise. Further experiments in cultured human myocytes showed that PLIN5 colocation with ORO or mitochondria is unaffected by pharmacological activation of lipolytic pathways. Together, these data suggest that the major lipolytic proteins are highly expressed at the lipid droplet and colocate in resting skeletal muscle, that their localization and interactions appear to remain unchanged during prolonged exercise, and, accordingly, that other post-translational mechanisms are likely regulators of skeletal muscle lipolysis

Statin-induced increases in atrophy gene expression occur independently of changes in PGC1α protein and mitochondrial content

One serious side effect of statin drugs is skeletal muscle myopathy. Although the mechanism(s) responsible for statin myopathy remains to be fully determined, an increase in muscle atrophy gene expression and changes in mitochondrial content and/or function have been proposed to play a role. In this study, we examined the relationship between statin-induced expression of muscle atrophy genes, regulators of mitochondrial biogenesis, and markers of mitochondrial content in slow- (ST) and fast-twitch (FT) rat skeletal muscles. Male Sprague Dawley rats were treated with simvastatin (60 or 80 mg·kg(-1)·day(-1)) or vehicle control via oral gavage for 14 days. In the absence of overt muscle damage, simvastatin treatment induced an increase in atrogin-1, MuRF1 and myostatin mRNA expression; however, these were not associated with changes in peroxisome proliferator gamma co-activator 1 alpha (PGC-1α) protein or markers of mitochondrial content. Simvastatin did, however, increase neuronal nitric oxide synthase (nNOS), endothelial NOS (eNOS) and AMPK α-subunit protein expression, and tended to increase total NOS activity, in FT but not ST muscles. Furthermore, simvastatin induced a decrease in β-hydroxyacyl CoA dehydrogenase (β-HAD) activity only in FT muscles. These findings suggest that the statin-induced activation of muscle atrophy genes occurs independent of changes in PGC-1α protein and mitochondrial content. Moreover, muscle-specific increases in NOS expression and possibly NO production, and decreases in fatty acid oxidation, could contribute to the previously reported development of overt statin-induced muscle damage in FT muscles

Creatine transporter (SLC6A8) knockout mice display an increased capacity for in vitro creatine biosynthesis in skeletal muscle.

The present study aimed to investigate whether skeletal muscle from whole body creatine transporter (CrT; SLC6A8) knockout mice (CrT(-/y)) actually contained creatine (Cr) and if so, whether this Cr could result from an up regulation of muscle Cr biosynthesis. Gastrocnemius muscle from CrT(-/y) and wild type (CrT(+/y)) mice were analyzed for ATP, Cr, Cr phosphate (CrP), and total Cr (TCr) content. Muscle protein and gene expression of the enzymes responsible for Cr biosynthesis L-arginine:glycine amidotransferase (AGAT) and guanidinoacetate methyltransferase (GAMT) were also determined as were the rates of in vitro Cr biosynthesis. CrT(-/y) mice muscle contained measurable (22.3 ± 4.3 mmol.kg(-1) dry mass), but markedly reduced (P < 0.05) TCr levels compared with CrT(+/y) mice (125.0 ± 3.3 mmol.kg(-1) dry mass). AGAT gene and protein expression were higher (~3 fold; P < 0.05) in CrT(-/y) mice muscle, however GAMT gene and protein expression remained unchanged. The in vitro rate of Cr biosynthesis was elevated 1.5 fold (P < 0.05) in CrT(-/y) mice muscle. These data clearly demonstrate that in the absence of CrT protein, skeletal muscle has reduced, but not absent, levels of Cr. This presence of Cr may be at least partly due to an up regulation of muscle Cr biosynthesis as evidenced by an increased AGAT protein expression and in vitro Cr biosynthesis rates in CrT(-/y) mice. Of note, the up regulation of Cr biosynthesis in CrT(-/y) mice muscle was unable to fully restore Cr levels to that found in wild type muscle

Lysine supply is a critical factor in achieving sustainable global protein economy

Production of animal-based protein is a significant global source of greenhouse gases, a major driver of agricultural land use and a source of nutrient loss to the environment. In this study, we provide a new assessment of the current sources of proteins in the human diet and analyze the options for increasing the use of plant-based sources, taking the protein quality, as indicated by the amino acid composition, into account. The results demonstrate the importance of sustainable global supply of lysine, one of the amino acids essential for human nutrition. It is demonstrated here that the current production of plant-based lysine that can be considered as replacement of lysine obtained from animal protein largely comes from soybean originating from a small number of countries. There are limited large scale options to broaden the supply of plant-based lysine, namely increase of soya production outsides its current main production areas, increase of production of legumes other than soya, obtaining plant-based lysine from sources not currently used for human consumption, or manufacturing lysine from non-standard plant-based sources (e.g. through fermentation from sugar). All of these options would require major changes in the structure of global agricultural production and associated agri-food systems and would have especially consequences on agricultural land use

Surgical Treatment of Iatrogenic Ventral Glottic Stenosis Using a Mucosal Flap Technique

OBJECTIVE: To describe a novel surgical technique for correcting postoperative ventral glottic stenosis (cicatrix or web formation) and the outcome in 2 Thoroughbred racehorses. STUDY DESIGN: Retrospective case report. ANIMALS: Thoroughbreds diagnosed with ventral glottic stenosis (n=2). METHODS: Horses presenting with iatrogenic ventral glottic stenosis and resultant exercise intolerance and abnormal exercise‐related noise were anesthetized and a midline sagittal skin incision was made over the ventral larynx and between the sternohyoideus muscles overlying the cricothyroid notch. The cricothyroid ligament, attached laryngeal cicatrix, and overlying mucosa were sagittally sectioned at the dorsal aspect of the cicatrix on the left side. The laryngeal mucosa, cicatrix, and underlying cricothyroid ligament immediately rostral and caudal to the cicatrix were sectioned in a medial (axial) direction as far as the right side of the cricothyroid notch. After resection of the majority of the attached cicatrix tissue, the residual mucosal flap (attached to the right side of the larynx) was reflected ventrally and sutured to the attachment of the cricothyroid ligament on the right side of the cricothyroid notch, creating an intact mucosal layer on the right side of the ventral larynx. RESULTS: Both horses had good intralaryngeal wound healing with minimal redevelopment of ventral glottic stenosis at 5 and 9 months postoperatively and were successfully returned to racing with complete absence of abnormal respiratory noise. CONCLUSION: The unique laryngeal anatomy of horses, with a cartilage‐free ventral laryngeal area (cricothyroid notch), allowed the use of this novel surgical technique to successfully treat ventral glottic stenosis