Improving corporate governance in state-owned corporations in China: which way forward?

This article discusses corporate governance in China. It outlines the basic agency problem in Chinese listed companies and questions the effectiveness of the current mechanisms employed to improve their standards of governance. Importantly, it considers alternative means through which corporate practice in China can be brought into line with international expectations and stresses the urgency with which this task must be tackled. It concludes that regulators in China must construct a corporate governance model which is compatible with its domestic setting and not rush to adopt governance initiatives modelled on those in cultures which are fundamentally different in the hope of also reproducing their success

β2-adrenergic signalling promotes cell migration by upregulating expression of the metastasis-associated molecule LYPD3

Metastasis is associated with poor prognosis in breast cancer. Although some studies suggest beta-blockers increase survival by delaying metastasis, others have been discordant. This study provides both insights into the anomalous findings and identifies potential biomarkers that may be treatment targets. Cell line models of basal-type and oestrogen receptor-positive breast cancer were profiled for basal levels of adrenoceptor gene/protein expression, and β2-adrenoceptor mediated cell behaviour including migration, invasion, adhesion, and survival in response to adrenoceptor agonist/antagonist treatment. Protein profiling and histology identified biomarkers and drug targets. Baseline levels of adrenoceptor gene expression are higher in basal-type rather than oestrogen receptor-positive cancer cells. Norepinephrine (NE) treatment increased invasive capacity in all cell lines but did not increase proliferation/survival. Protein profiling revealed the upregulation of the pro-metastatic gene Ly6/PLAUR Domain-Containing Protein 3 (LYPD3) in norepinephrine-treated MDA-MB-468 cells. Histology confirmed selective LYPD3 expression in primary and metastatic breast tumour samples. These findings demonstrate that basal-type cancer cells show a more aggressive adrenoceptor-β2-activated phenotype in the resting and stimulated state, which is attenuated by adrenoceptor-β2 inhibition. This study also highlights the first association between ADRβ2 signalling and LYPD3; its knockdown significantly reduced the basal and norepinephrine-induced activity of MCF-7 cells in vitro. The regulation of ADRβ2 signalling by LYPD3 and its metastasis promoting activities, reveal LYPD3 as a promising therapeutic target in the treatment of breast and other cancers

Nucleoside diphosphate kinase A as a controller of AMP-kinase in airway epithelia

This review integrates recent understanding of a novel role for NDPK-A in two related directions: Firstly, its role in an airway epithelial cell when bound to the luminal (apical) membrane and secondly in the cytosol of many different cells (epithelial and non-epithelial) where an isoform-specific interaction occurs with a regulatory partner, AMPKα1. Thus NDPK-A is present in both a membrane and cytosolic environment but in the apical membrane, its roles are not understood in detail; preliminary data suggest that it co-localises with the cystic fibrosis protein (CFTR). In cytosol, we find that NDPK-A is coupled to the catalytic alpha1 isoform of the AMP-activated protein kinase (AMPKα subunit), which is part of a heterotrimeric protein complex that responds to cellular energy status by switching off ATP-consuming pathways and switching on ATP-generating pathways when ATP is limiting. We find that ATP is located within this complex and ‘fed’ from NDPK to AMPK without ever ‘seeing’ bulk solution. Importantly, the reverse can also happen such that AMPK activity can be made to decline when NDPK-A ‘steals’ ATP from AMPK. Thus we propose a novel paradigm in NDPK-A function by suggesting that AMP-kinase can be regulated by NDPK-A, independently of AMP

Which older people decline participation in a primary care trial of physical activity and why: insights from a mixed methods approach

This article is available through the Brunel Open Access Publishing Fund. Copyright 2014 Rogers et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Background: Physical activity is of vital importance to older peoples’ health. Physical activity intervention studies with older people often have low recruitment, yet little is known about non-participants. Methods: Patients aged 60–74 years from three UK general practices were invited to participate in a nurse-supported pedometer-based walking intervention. Demographic characteristics of 298 participants and 690 non-participants were compared. Health status and physical activity of 298 participants and 183 non-participants who completed a survey were compared using age, sex adjusted odds ratios (OR) (95% confidence intervals). 15 non-participants were interviewed to explore perceived barriers to participation. Results: Recruitment was 30% (298/988). Participants were more likely than non-participants to be female (54% v 47%; p = 0.04) and to live in affluent postcodes (73% v 62% in top quintile; p < 0.001). Participants were more likely than non-participants who completed the survey to have an occupational pension OR 2.06 (1.35-3.13), a limiting longstanding illness OR 1.72 (1.05-2.79) and less likely to report being active OR 0.55 (0.33-0.93) or walking fast OR 0.56 (0.37-0.84). Interviewees supported general practice-based physical activity studies, particularly walking, but barriers to participation included: already sufficiently active, reluctance to walk alone or at night, physical symptoms, depression, time constraints, trial equipment and duration. Conclusion: Gender and deprivation differences suggest some selection bias. However, trial participants reported more health problems and lower activity than non-participants who completed the survey, suggesting appropriate trial selection in a general practice population. Non-participant interviewees indicated that shorter interventions, addressing physical symptoms and promoting confidence in pursuing physical activity, might increase trial recruitment and uptake of practice-based physical activity endeavours.The National Institute for Health Research (NIHR) under its Research for Patient Benefit Programme (Grant Reference Number PB-PG-0909-20055)

Cytoplasmic PML promotes TGF-β-associated epithelial–mesenchymal transition and invasion in prostate cancer

Epithelial–mesenchymal transition (EMT) is a key event that is involved in the invasion and dissemination of cancer cells. Although typically considered as having tumour-suppressive properties, transforming growth factor (TGF)-β signalling is altered during cancer and has been associated with the invasion of cancer cells and metastasis. In this study, we report a previously unknown role for the cytoplasmic promyelocytic leukaemia (cPML) tumour suppressor in TGF-β signalling-induced regulation of prostate cancer-associated EMT and invasion. We demonstrate that cPML promotes a mesenchymal phenotype and increases the invasiveness of prostate cancer cells. This event is associated with activation of TGF-β canonical signalling pathway through the induction of Sma and Mad related family 2 and 3 (SMAD2 and SMAD3) phosphorylation. Furthermore, the cytoplasmic localization of promyelocytic leukaemia (PML) is mediated by its nuclear export in a chromosomal maintenance 1 (CRM1)-dependent manner. This was clinically tested in prostate cancer tissue and shown that cytoplasmic PML and CRM1 co-expression correlates with reduced disease-specific survival. In summary, we provide evidence of dysfunctional TGF-β signalling occurring at an early stage in prostate cancer. We show that this disease pathway is mediated by cPML and CRM1 and results in a more aggressive cancer cell phenotype. We propose that the targeting of this pathway could be therapeutically exploited for clinical benefit

Latent HIV in primary T lymphocytes is unresponsive to histone deacetylase inhibitors

Recently, there is considerable interest in the field of anti-HIV therapy to identify and develop chromatin-modifying histone deacetylase (HDAC) inhibitors that can effectively reactivate latent HIV in patients. The hope is that this would help eliminate cells harboring latent HIV and achieve an eventual cure of the virus. However, how effectively these drugs can stimulate latent HIVs in quiescent primary CD4 T cells, despite their relevant potencies demonstrated in cell line models of HIV latency, is not clear. Here, we show that the HDAC inhibitors valproic acid (VPA) and trichostatin A (TSA) are unable to reactivate HIV in latently infected primary CD4 T cells generated in the H80 co-culture system. This raises a concern that the drugs inhibiting HDAC function alone might not be sufficient for stimulating latent HIV in resting CD4 T cells in patients and not achieve any anticipated reduction in the pool of latent reservoirs

Critical research gaps and translational priorities for the successful prevention and treatment of breast cancer

INTRODUCTION Breast cancer remains a significant scientific, clinical and societal challenge. This gap analysis has reviewed and critically assessed enduring issues and new challenges emerging from recent research, and proposes strategies for translating solutions into practice. METHODS More than 100 internationally recognised specialist breast cancer scientists, clinicians and healthcare professionals collaborated to address nine thematic areas: genetics, epigenetics and epidemiology; molecular pathology and cell biology; hormonal influences and endocrine therapy; imaging, detection and screening; current/novel therapies and biomarkers; drug resistance; metastasis, angiogenesis, circulating tumour cells, cancer 'stem' cells; risk and prevention; living with and managing breast cancer and its treatment. The groups developed summary papers through an iterative process which, following further appraisal from experts and patients, were melded into this summary account. RESULTS The 10 major gaps identified were: (1) understanding the functions and contextual interactions of genetic and epigenetic changes in normal breast development and during malignant transformation; (2) how to implement sustainable lifestyle changes (diet, exercise and weight) and chemopreventive strategies; (3) the need for tailored screening approaches including clinically actionable tests; (4) enhancing knowledge of molecular drivers behind breast cancer subtypes, progression and metastasis; (5) understanding the molecular mechanisms of tumour heterogeneity, dormancy, de novo or acquired resistance and how to target key nodes in these dynamic processes; (6) developing validated markers for chemosensitivity and radiosensitivity; (7) understanding the optimal duration, sequencing and rational combinations of treatment for improved personalised therapy; (8) validating multimodality imaging biomarkers for minimally invasive diagnosis and monitoring of responses in primary and metastatic disease; (9) developing interventions and support to improve the survivorship experience; (10) a continuing need for clinical material for translational research derived from normal breast, blood, primary, relapsed, metastatic and drug-resistant cancers with expert bioinformatics support to maximise its utility. The proposed infrastructural enablers include enhanced resources to support clinically relevant in vitro and in vivo tumour models; improved access to appropriate, fully annotated clinical samples; extended biomarker discovery, validation and standardisation; and facilitated cross-discipline working. CONCLUSIONS With resources to conduct further high-quality targeted research focusing on the gaps identified, increased knowledge translating into improved clinical care should be achievable within five years

Proteomic Insights into the Hidden World of Phloem Sap Feeding

The physical interface between a phloem-feeding insect and its host plant is a single cell buried deep within the plant tissue. As such, the molecular interactions between these notorious agricultural pests and the crop plants upon which they feed are diffi cult to study. ‘Omic’ technologies have proved crucial in revealing some of the fascinating detail of the molecular interplay between these partners. Here we review the role of proteomics in identifying putative components of the secreted saliva of phloem-feeding insects, particularly aphids, and discuss the limited knowledge concerning the function of these proteins

A telehealth integrated asthma-COPD service for primary care: a proposal for a pilot feasibility study in Crete, Greece

<p>Abstract</p> <p>Background</p> <p>Chronic obstructive pulmonary disease (COPD) and asthma are considered underdiagnosed and misdiagnosed chronic diseases. In The Netherlands, a COPD-asthma telemedicine service has been developed to increase GPs' ability to diagnose and manage COPD and asthma. A telemedicine COPD-asthma service may benefit Greece as it is a country, partly due to its geography, that does not have easy access to pulmonologists.</p> <p>Findings</p> <p>Therefore, a pilot feasibility study has been designed in Greece in order to establish this telemedicine service. Ten rural practices, in the island of Crete, with an average population of 2000 patients per practice will pilot the project supported by three pulmonologists. This paper presents the translated interfaces, the flowcharts and the steps that are considered as necessary for this feasibility study in Crete, Greece.</p

A Systems Approach to Improving Rural Care in Ethiopia

Background: Multiple interventions have been launched to improve the quality, access, and utilization of primary health care in rural, low-income settings; however, the success of these interventions varies substantially, even within single studies where the measured impact of interventions differs across sites, centers, and regions. Accordingly, we sought to examine the variation in impact of a health systems strengthening intervention and understand factors that might explain the variation in impact across primary health care units. Methodology/Principal Findings: We conducted a mixed methods positive deviance study of 20 Primary Health Care Units (PHCUs) in rural Ethiopia. Using longitudinal data from the Ethiopia Millennium Rural Initiative (EMRI), we identified PHCUs with consistently higher performance (n = 2), most improved performance (n = 3), or consistently lower performance (n = 2) in the provision of antenatal care, HIV testing in antenatal care, and skilled birth attendance rates. Using data from site visits and in-depth interviews (n = 51), we applied the constant comparative method of qualitative data analysis to identify key themes that distinguished PHCUs with different performance trajectories. Key themes that distinguished PHCUs were 1) managerial problem solving capacity, 2) relationship with the woreda (district) health office, and 3) community engagement. In higher performing PHCUs and those with the greatest improvement after the EMRI intervention, health center and health post staff were more able to solve day-to-day problems, staff had better relationships with the woreda health official, an