Exercise and insulin resistance in PCOS: muscle insulin signalling and fibrosis

OBJECTIVE:Mechanisms of insulin resistance in polycystic ovary syndrome (PCOS) remain ill-defined, contributing to sub-optimal therapies. Recognising skeletal muscle plays a key role in glucose homeostasis we investigated early insulin signalling, its association with aberrant transforming growth factor β (TGFβ) regulated tissue fibrosis. We also explored the impact of aerobic exercise on these molecular pathways. METHODS:A secondary analysis from a cross-sectional study was undertaken in women with (n=30) or without (n=29) PCOS across lean and overweight BMIs. A subset of participants with (n=8) or without (n=8) PCOS who were overweight completed 12-weeks of aerobic exercise training. Muscle was sampled before and 30 min into a euglycaemic-hyperinsulinaemic clamp pre- and post-training. RESULTS:We found reduced signalling in PCOS of mechanistic target of rapamycin (mTOR). Exercise training augmented but did not completely rescue this signalling defect in women with PCOS. Genes in the TGFβ signalling network were upregulated in skeletal muscle in the overweight women with PCOS but were unresponsive to exercise training except for genes encoding LOX, collagen 1 and 3. CONCLUSIONS:We provide new insights into defects in early insulin signalling, tissue fibrosis, and hyperandrogenism in PCOS-specific insulin resistance in lean and overweight women. PCOS-specific insulin-signalling defects were isolated to mTOR, while gene expression implicated TGFβ ligand regulating a fibrosis in the PCOS-obesity synergy in insulin resistance and altered responses to exercise. Interestingly, there was little evidence for hyperandrogenism as a mechanism for insulin resistance

Labour supply and skills demands in fashion retailing

If, as Adam Smith once famously suggested, Britain was a nation of shopkeepers then it is now a nation of shopworkers. Retail is now a significant part of the UK economy, accounting for £256 billion in sales and one-third of all consumer spending (Skillsmart, 2007). It is the largest private sector employer in the UK, employing 3m workers, or 1 in 10 of the working population. For future job creation in the UK economy retail is also similarly prominent and the sector is expected to create a further 250,000 jobs to 2014 (Skillsmart, 2007). The centrality of retail to economic success and job creation is apparent in other advanced economies. For example, within the US, retail sales is the occupation with the largest projected job growth in the period 2004-2014 (Gatta et al., 2009) and in Australia retail accounts for 1 in 6 workers (Buchanan et al., 2003). Within the UK these workers are employed in approximately 290,000 businesses, encompassing large and small organizations and also a number of sub-sectors. This variance suggests that retail should not be regarded as homogenous in its labour demands. Hart et al. (2007) note how skill requirements and the types of workers employed may differ across the sector. This chapter further opens up this point, providing an analysis of the labour supply and skills demands for the sub-sectors of clothing, footwear and leather goods, which are described by Skillsmart (2007: 48) as being 'significant categories in UK retailing'

A Cordial Sync: Going Beyond Marginal Policies for Multi-Agent Embodied Tasks

Autonomous agents must learn to collaborate. It is not scalable to develop a new centralized agent every time a task's difficulty outpaces a single agent's abilities. While multi-agent collaboration research has flourished in gridworld-like environments, relatively little work has considered visually rich domains. Addressing this, we introduce the novel task FurnMove in which agents work together to move a piece of furniture through a living room to a goal. Unlike existing tasks, FurnMove requires agents to coordinate at every timestep. We identify two challenges when training agents to complete FurnMove: existing decentralized action sampling procedures do not permit expressive joint action policies and, in tasks requiring close coordination, the number of failed actions dominates successful actions. To confront these challenges we introduce SYNC-policies (synchronize your actions coherently) and CORDIAL (coordination loss). Using SYNC-policies and CORDIAL, our agents achieve a 58% completion rate on FurnMove, an impressive absolute gain of 25 percentage points over competitive decentralized baselines. Our dataset, code, and pretrained models are available at https://unnat.github.io/cordial-sync .Comment: Accepted to ECCV 2020 (spotlight); Project page: https://unnat.github.io/cordial-syn

Building block libraries and structural considerations in the self-assembly of polyoxometalate and polyoxothiometalate systems

Inorganic metal-oxide clusters form a class of compounds that are unique in their topological and electronic versatility and are becoming increasingly more important in a variety of applications. Namely, Polyoxometalates (POMs) have shown an unmatched range of physical properties and the ability to form structures that can bridge several length scales. The formation of these molecular clusters is often ambiguous and is governed by self-assembly processes that limit our ability to rationally design such molecules. However, recent years have shown that by considering new building block principles the design and discovery of novel complex clusters is aiding our understanding of this process. Now with current progress in thiometalate chemistry, specifically polyoxothiometalates (POTM), the field of inorganic molecular clusters has further diversified allowing for the targeted development of molecules with specific functionality. This chapter discusses the main differences between POM and POTM systems and how this affects synthetic methodologies and reactivities. We will illustrate how careful structural considerations can lead to the generation of novel building blocks and further deepen our understanding of complex systems

Patterning Bacterial Communities on Epithelial Cells

Micropatterning of bacteria using aqueous two phase system (ATPS) enables the localized culture and formation of physically separated bacterial communities on human epithelial cell sheets. This method was used to compare the effects of Escherichia coli strain MG1655 and an isogenic invasive counterpart that expresses the invasin (inv) gene from Yersinia pseudotuberculosis on the underlying epithelial cell layer. Large portions of the cell layer beneath the invasive strain were killed or detached while the non-invasive E. coli had no apparent effect on the epithelial cell layer over a 24 h observation period. In addition, simultaneous testing of the localized effects of three different bacterial species; E. coli MG1655, Shigella boydii KACC 10792 and Pseudomonas sp DSM 50906 on an epithelial cell layer is also demonstrated. The paper further shows the ability to use a bacterial predator, Bdellovibrio bacteriovorus HD 100, to selectively remove the E. coli, S. boydii and P. sp communities from this bacteria-patterned epithelial cell layer. Importantly, predation and removal of the P. Sp was critical for maintaining viability of the underlying epithelial cells. Although this paper focuses on a few specific cell types, the technique should be broadly applicable to understand a variety of bacteria-epithelial cell interactionsopen3

Exercise and insulin resistance in PCOS: Muscle insulin signalling and fibrosis

Objective: Mechanisms of insulin resistance in polycystic ovary syndrome (PCOS) remain ill defined, contributing to sub-optimal therapies. Recognising skeletal muscle plays a key role in glucose homeostasis we investigated early insulin signalling, its association with aberrant transforming growth factor β (TGFβ)-regulated tissue fibrosis. We also explored the impact of aerobic exercise on these molecular pathways. Methods: A secondary analysis from a cross-sectional study was undertaken in women with (n = 30) or without (n = 29) PCOS across lean and overweight BMIs. A subset of participants with (n = 8) or without (n = 8) PCOS who were overweight completed 12 weeks of aerobic exercise training. Muscle was sampled before and 30 min into a euglycaemic-hyperinsulinaemic clamp pre and post training. Results: We found reduced signalling in PCOS of mechanistic target of rapamycin (mTOR). Exercise training augmented but did not completely rescue this signalling defect in women with PCOS. Genes in the TGFβ signalling network were upregulated in skeletal muscle in the overweight women with PCOS but were unresponsive to exercise training except for genes encoding LOX, collagen 1 and 3. Conclusions: We provide new insights into defects in early insulin signalling, tissue fibrosis, and hyperandrogenism in PCOS-specific insulin resistance in lean and overweight women. PCOS-specific insulin signalling defects were isolated to mTOR, while gene expression implicated TGFβ ligand regulating a fibrosis in the PCOS-obesity synergy in insulin resistance and altered responses to exercise. Interestingly, there was little evidence for hyperandrogenism as a mechanism for insulin resistance