CCAAT/enhancer binding protein α predicts poorer prognosis and prevents energy starvation-induced cell death in hepatocellular carcinoma

CCAAT enhancer binding protein α (C/EBPα) plays an essential role in cellular differentiation, growth, and energy metabolism. Here, we investigate the correlation between C/EBPα and hepatocellular carcinoma (HCC) patient outcomes and how C/EBPα protects cells against energy starvation. Expression of C/EBPα protein was increased in the majority of HCCs examined (191 pairs) compared with adjacent nontumor liver tissues in HCC tissue microarrays. Its upregulation was correlated significantly with poorer overall patient survival in both Kaplan-Meier survival (P = 0.017) and multivariate Cox regression (P = 0.028) analyses. Stable C/EBPα-silenced cells failed to establish xenograft tumors in nude mice due to extensive necrosis, consistent with increased necrosis in human C/EBPα-deficient HCC nodules. Expression of C/EBPα protected HCC cells in vitro from glucose and glutamine starvation-induced cell death through autophagy-involved lipid catabolism. Firstly, C/EBPα promoted lipid catabolism during starvation, while inhibition of fatty acid beta-oxidation significantly sensitized cell death. Secondly, autophagy was activated in C/EBPα-expressing cells, and the inhibition of autophagy by ATG7 knockdown or chloroquine treatment attenuated lipid catabolism and subsequently sensitized cell death. Finally, we identified TMEM166 as a key player in C/EBPα-mediated autophagy induction and protection against starvation.

CONCLUSION: The C/EBPα gene is important in that it links HCC carcinogenesis to autophagy-mediated lipid metabolism and resistance to energy starvation; its expression in HCC predicts poorer patient prognosis.

Promoting Community Renewable Energy in a Corporate Energy World

Small-scale, decentralized and community-owned renewable energy is widely acknowledged to be a desirable feature of low carbon futures, but faces a range of challenges in the context of conventional, centralized energy systems. This paper draws on transition frameworks to investigate why the UK has been an inhospitable context for community-owned renewables and assesses whether anything fundamental is changing in this regard. We give particular attention to whether political devolution, the creation of elected governments for Scotland, Wales and Northern Ireland, has affected the trajectory of community renewables. Our analysis notes that devolution has increased political attention to community renewables, including new policy targets and support schemes. However, these initiatives are arguably less important than the persistence of key features of socio-technical regimes: market support systems for renewable energy and land-use planning arrangements that systemically favour major projects and large corporations, and keep community renewables to the margins. There is scope for rolling out hybrid pathways to community renewables, via joint ownership or through community benefit funds, but this still positions community energy as an adjunct to energy pathways dominated by large, corporate generation facilities

Managerial failure in mid-Victorian Britain?: Corporate expansion during a promotion boom

This article examines the mid-1840s expansion of the British railway network, which was associated with a large deterioration in shareholder value. Using a counterfactual approach and new data on railway competition, we argue that the expansion of the railway companies, and their subsequent decline in financial performance, was not due to managerial failure. Rather, the promotion of new routes by established railways and mergers with other companies was part of a managerial strategy to maintain incumbent positions, and may have been preferable to not expanding whilst their competitors did.

"Republic of Instability":Artifice, Death and the Afterlife in Mark Doty's "Murano"

An article on a single poem by Mark Doty, published as part of the "Hospitable Forms: Post-Secular Thought in New-Century Poetics" feature.

“Local politics and global corporate crime in Irish crime fiction : Alan Glynn's Winterland trilogy",

Why Are Some Subsidiaries of Multinationals the Source of Novel Practices while Others Are Not? National, Corporate and Functional Influences

It has frequently been argued that multinational companies are moving towards network forms whereby subsidiaries share different practices with the rest of the company. This paper presents large-scale empirical evidence concerning the extent to which subsidiaries input novel practices into the rest of the multinational. We investigate this in the field of human resources through analysis of a unique international data set in four host countries - Canada, Ireland, Spain and the UK - and address the question of how we can explain variation between subsidiaries in terms of whether they initiate the diffusion of practices to other subsidiaries. The data support the argument that multiple, rather than single, factor explanations are required to more effectively understand the factors promoting or retarding the diffusion of human resource practices within multinational companies. It emerges that national, corporate and functional contexts all matter. More specifically, actors at subsidiary level who seek to initiate diffusion appear to be differentially placed according to their national context, their place within corporate structures and the extent to which the human resource function is internationally networked.

Predictors of place of death for those in receipt of home-based palliative care services in Ontario, Canada

Many cancer patients die in institutional settings despite their preference to die at home. A longitudinal, prospective cohort study was conducted to comprehensively assess the determinants of home death for patients receiving home-based palliative care. Data collected from biweekly telephone interviews with caregivers (n=302) and program databases were entered into a multivariate logistic model. Patients with high nursing costs (odds ratio [OR]: 4.3; confidence interval [CI]: 1.8-10.2) and patients with high personal support worker costs (OR: 2.3; CI: 1.1-4.5) were more likely to die at home than those with low costs. Patients who lived alone were less likely to die at home than those who cohabitated (OR: 0.4; CI: 0.2-0.8), and those with a high propensity for a home-death preference were more likely to die at home than those with a low propensity (OR: 5.8; CI: 1.1-31.3). An understanding of the predictors of place of death may contribute to the development of effective interventions that support home death.

Evidence supporting a role for N-epsilon-(3-formyl-3,4-dehydropiperidino)lysine accumulation in Muller glia dysfunction and death in diabetic retinopathy

Purpose: Recent evidence suggests that neuroglial dysfunction and degeneration contributes to the etiology and progression of diabetic retinopathy. Advanced lipoxidation end products (ALEs) have been implicated in the pathology of various diseases, including diabetes and several neurodegenerative disorders. The purpose of the present study was to investigate the possible link between the accumulation of ALEs and neuroretinal changes in diabetic retinopathy.

Methods: Retinal sections obtained from diabetic rats and age-matched controls were processed for immunohistochemistry using antibodies against several well defined ALEs. In vitro experiments were also performed using a human Muller (Moorfields/Institute of Ophthalmology-Muller 1 [ MIO-M1]) glia cell line. Western blot analysis was used to measure the accumulation of the acrolein-derived ALE adduct N epsilon-(3-formyl-3,4-dehydropiperidino)lysine (FDP-lysine) in Muller cells preincubated with FDP-lysine-modified human serum albumin (FDP-lysine-HSA). Responses of Muller cells to FDP-lysine accumulation were investigated by analyzing changes in the protein expression of heme oxygenase-1 (HO-1), glial fibrillary acidic protein (GFAP), and the inwardly rectifying potassium channel Kir4.1. In addition, mRNA expression levels of vascular endothelial growth factor (VEGF), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF alpha) were determined by reverse transcriptase PCR (RT-PCR). Apoptotic cell death was evaluated by fluorescence-activated cell sorting (FACS) analysis after staining with fluorescein isothiocyanate (FITC)-labeled annexin V and propidium iodide.

Results: No significant differences in the levels of malondialdehyde-, 4-hydroxy-2-nonenal-, and 4-hydroxyhexenal-derived ALEs were evident between control and diabetic retinas after 4 months of diabetes. By contrast, FDP-lysine immunoreactivity was markedly increased in the Muller glia of diabetic rats. Time-course studies revealed that FDP-lysine initially accumulated within Muller glial end feet after only a few months of diabetes and thereafter spread distally throughout their inner radial processes. Exposure of human Muller glia to FDP-lysine-HSA led to a concentration-dependent accumulation of FDP-lysine-modified proteins across a broad molecular mass range. FDP-lysine accumulation was associated with the induction of HO-1, no change in GFAP, a decrease in protein levels of the potassium channel subunit Kir4.1, and upregulation of transcripts for VEGF, IL-6, and TNF-alpha. Incubation of Muller glia with FDP-lysine-HSA also caused apoptosis at high concentrations.

Conclusions: Collectively, these data strongly suggest that FDP-lysine accumulation could be a major factor contributing to the Muller glial abnormalities occurring in the early stages of diabetic retinopathy.

The death of massive stars - II. Observational constraints on the progenitors of Type Ibc supernovae

The progenitors of many Type II core-collapse supernovae (SNe) have now been identified directly on pre-discovery imaging. Here, we present an extensive search for the progenitors of Type Ibc SNe in all available pre-discovery imaging since 1998. There are 12 Type Ibc SNe with no detections of progenitors in either deep ground-based or Hubble Space Telescope archival imaging. The deepest absolute BVR magnitude limits are between -4 and - 5 mag. We compare these limits with the observed Wolf-Rayet population in the Large Magellanic Cloud and estimate a 16 per cent probability that we have failed to detect such a progenitor by chance. Alternatively, the progenitors evolve significantly before core-collapse or we have underestimated the extinction towards the progenitors. Reviewing the relative rates and ejecta mass estimates from light-curve modelling of Ibc SNe, we find both incompatible with Wolf-Rayet stars with initial masses >25 M⊙ being the only progenitors. We present binary evolution models that fit these observational constraints. Stars in binaries with initial masses ≲ 20 M⊙ lose their hydrogen envelopes in binary interactions to become low-mass helium stars. They retain a low-mass hydrogen envelope until ≈104 yr before core-collapse; hence, it is not surprising that Galactic analogues have been difficult to identify.

The life and death of Irish social partnership: lessons for social pacts

From 1987 to 2009, Irish social partnership operated as a national framework for industrial relations. The contribution of the article is twofold. We seek to link the institutional dynamics of social partnership with the Régulation School's notions of modes of accumulation and regimes of régulation. This framework is used to explain the rise and fall of social partnership in Ireland. We argue that the regime of social partnership in Ireland can be divided into two distinct periods. In the first, social partnership contributed positively to a benign productivity-led mode of accumulation. In the second, it lost its economic functionality due mostly to financialisation taking a grip in the Irish economy. The conclusion is that social partnership had both positive and negative features, but it is unlikely to be repeated in the foreseeable future, at least not in Ireland.