PMI 5011 regulates the ubiquitin proteasome system in skeletal muscle

Insulin resistance in type 2 diabetes is associated with impaired glucose and protein metabolism in skeletal muscle. The impaired insulin signaling in skeletal muscle affects muscle mass by tilting the balance between skeletal muscle protein synthesis and degradation toward degradation, a process that is primarily regulated by the ubiquitin-proteasome system. Studies have shown that an extensively characterized ethanol extract of Artemisia dracunculus L (Russian Tarragon), termed PMI 5011, enhances insulin signaling in human primary skeletal muscle cells and in a rodent model of insulin resistance. The aim of this project is to determine if the effect of PMI 5011 on insulin signaling extends to regulation of ubiquitin-proteasome activity in skeletal muscle. To evaluate the effect of PMI 5011 on the ubiquitin-proteasome system, we used two in vitro models of insulin resistance in C2C12 myotubes and the KKAy mouse model of insulin resistance in vivo. Our studies show that PMI 5011 enhances the inhibitory effect of insulin on proteasome activity and ubiquitylation in skeletal muscle in vitro and in vivo. In addition, PMI 5011 inhibits non-proteasomal protein degradation in vivo, indicating that PMI 5011 is a potent inhibitor of skeletal muscle protein degradation. PMI 5011 also regulates the expression of Atrogin-1 and MuRF-1, muscle-specific ubiquitin ligases that are required for ubiquitin-dependent protein degradation in skeletal muscle. Both Atrogin-1 and MuRF-1 gene and protein expression is elevated with impaired insulin signaling and our studies show that PMI 5011 reduces the expression of these ligases while enhancing Akt phosphorylation. In summary, these studies demonstrate that PMI 5011 regulates the ubiquitin-proteasome in insulin resistant states in vitro and in vivo. PMI 5011 may therefore be a therapeutic target for enhancing insulin sensitivity leading to conservation of muscle mass in type 2 diabetes

C4: An Interdisciplinary Approach to Improving Retention with Developmental Students

In this session, we describe an interdisciplinary learning community program designed to improve retention among freshman students with three developmental placements. We will discuss how a similar program could be developed at other institutions and emphasize issues of transferability and scalability in the context of declining resources and retention

Online kk-Median with Consistent Clusters

We consider the online $k$-median clustering problem in which $n$ points arrive online and must be irrevocably assigned to a cluster on arrival. As there are lower bound instances that show that an online algorithm cannot achieve a competitive ratio that is a function of $n$ and $k$, we consider a beyond worst-case analysis model in which the algorithm is provided a priori with a predicted budget $B$ that upper bounds the optimal objective value. We give an algorithm that achieves a competitive ratio that is exponential in the the number $k$ of clusters, and show that the competitive ratio of every algorithm must be linear in $k$. To the best of our knowledge this is the first investigation in the literature that considers cluster consistency using competitive analysis.Comment: 28 pages, 7 figure

Can plant resistance to specialist herbivores be explained by plant chemistry or resource use strategy?

At both a macro- and micro-evolutionary level, selection of and performance on host plants by specialist herbivores are thought to be governed partially by host plant chemistry. Thus far, there is little evidence to suggest that specialists can detect small structural differences in secondary metabolites of their hosts, or that such differences affect host choice or performance of specialists. We tested whether phytochemical differences between closely related plant species are correlated with specialist host choice. We conducted no-choice feeding trials using 17 plant species of three genera of tribe Senecioneae (Jacobaea, Packera, and Senecio; Asteraceae) and a more distantly related species (Cynoglossum officinale; Boraginaceae) containing pyrrolizidine alkaloids (PAs), and four PA-sequestering specialist herbivores of the genus Longitarsus (Chrysomelidae). We also assessed whether variation in feeding by specialist herbivores is attributable to different resource use strategies of the tested plant species. Plant resource use strategy was quantified by measuring leaf dry matter content, which is related to both plant nutritive value and to plant investment in quantitative defences. We found no evidence that intra-generic differences in PA profiles affect feeding by specialist herbivores. Instead, our results indicate that decisions to begin feeding are related to plant resource use strategy, while decisions to continue feeding are not based on any plant characteristics measured in this study. These findings imply that PA composition does not significantly affect host choice by these specialist herbivores. Leaf dry matter content is somewhat phylogenetically conserved, indicating that plants may have difficulty altering resource use strategy in response to selection pressure by herbivores and other environmental factors on an evolutionary time scal

L\u27auteur dramatique et la conscience professionnelle (1610-1640)

This dissertation falls within the scope of a number of socio-literary studies published since Alain Viala’s La Naissance de l’écrivain (1985). According to Viala, the “author” is the professional incarnation of the writer (in the mechanical sense of “scribe”). He is recognisable by his participation in the Republic of Letters and his validation by the various socio-political structures of his era (academies, salons, paying public, critics, printers). To be considered an author, or a professional man of letters, one must successfully emancipate oneself from purely intellectual milieus in order to build networks that allow for competition. Contrary to Viala’s assertion that the professional author is born in the French neo-classical era, in this dissertation, it is argued that pre-academic playwrights (c. 1610-1640) demonstrate their awareness of the extant and growing hierarchies of their field, the social purpose of their profession, and the aesthetic value of their works. Over the course of the pre-academic era, playwrights increasingly meet the criteria of the professional author

Measurement of studded shoe–surface interaction metrics during in situ performance analysis

Interaction between studded footwear and performance surfaces plays an important role in sport. Discretising this interaction into quantifiable measurements can help optimise design of outsoles and identify parameters for performance testing in situ. Here, we describe the development and validity of an image-based three-dimensional (3D) measurement system to investigate shoe–surface interactions during locomotion performance in situ by eight skilled footballers. By calculating individual stud positions, results revealed that the 3D kinematic data could be distilled to a number of shoe–surface interaction metrics such as orientation, velocity, translation distance and location of the centre of rotation. Findings show how the measurement system and simple analysis methods can be used to provide informative shoe–surface interaction metrics from in situ performance capture for the footwear communit

“It Takes a Village:” Innovative multi-sector collaboration to improve Public Health through Positive Youth Development program implementation, evaluation and data analysis

Breakout Session 2C: Worcester has a long history of effective collaboration for Positive Youth Development across our youth-serving agencies and programs. That collaborative spirit has recently taken hold as a primary strategy for improved Public Health of the overall community. The Community Health Improvement Plan supported by (CHNA 8) Coalition for Healthy Greater Worcester is a road map for improved Health Indicators. The breakout session will describe the current health and well-being of youth in Worcester and the innovative local collaborations that promote youth health and positive development across our community. Diverse funder support is integral to local youth development goals, objectives and outcomes, and the role of funders extends beyond financial support to include advisory and capacity-building roles. Multi-sector collaboration also provides access to data from multiple sources, which both measures impact and informs activities

Transgressive segregation of primary and secondary metabolites in F2 hybrids between Jacobaea aquatica and J. vulgaris

Hybridization between plant species can have a number of biological consequences; interspecific hybridization has been tied to speciation events, biological invasions, and diversification at the level of genes, metabolites, and phenotypes. This study aims to provide evidence of transgressive segregation in the expression of primary and secondary metabolites in hybrids between Jacobaeavulgaris and J. aquaticus using an NMR-based metabolomic profiling approach. A number of F2 hybrid genotypes exhibited metabolomic profiles that were outside the range encompassed by parental species. Expression of a number of primary and secondary metabolites, including jacaronone analogues, chlorogenic acid, sucrose, glucose, malic acid, and two amino acids was extreme in some F2 hybrid genotypes compared to parental genotypes, and citric acid was expressed in highest concentrations in J. vulgaris. Metabolomic profiling based on NMR is a useful tool for quantifying genetically controlled differences between major primary and secondary metabolites among plant genotypes. Interspecific plant hybrids in general, and specifically hybrids between J. vulgaris and J. aquatica, will be useful for disentangling the ecological role of suites of primary and secondary metabolites in plants, because interspecific hybridization generates extreme metabolomic diversity compared to that normally observed between parental genotypes