Intra-tumor heterogeneity: lessons from microbial evolution and clinical implications

Multiple subclonal populations of tumor cells can coexist within the same tumor. This intra-tumor heterogeneity will have clinical implications and it is therefore important to identify factors that drive or suppress such heterogeneous tumor progression. Evolutionary biology can provide important insights into this process. In particular, experimental evolution studies of microbial populations, which exist as clonal populations that can diversify into multiple subclones, have revealed important evolutionary processes driving heterogeneity within a population. There are transferrable lessons that can be learnt from these studies that will help us to understand the process of intra-tumor heterogeneity in the clinical setting. In this review, we summarize drivers of microbial diversity that have been identified, such as mutation rate and environmental influences, and discuss how knowledge gained from microbial experimental evolution studies may guide us to identify and understand important selective factors that promote intra-tumor heterogeneity. Furthermore, we discuss how these factors could be used to direct and optimize research efforts to improve patient care, focusing on therapeutic resistance. Finally, we emphasize the need for longitudinal studies to address the impact of these potential tumor heterogeneity-promoting factors on drug resistance, metastatic potential and clinical outcome.

Handbook of institutional investment and fiduciary duty

Foreword by Al Gore, former Vice President of the United States Endorsements by Keith Ambachsheer, James Gifford, John Kay, Bob Monks, Knut Rostad and Anne Stausboll

A critical account of the relationship between institutional trust, risk perception, and technology acceptance with an application to genetically modified foods

This article critically reflects on the widely held view of a causal chain with trust in public authorities impacting technology acceptance via perceived risk. It first puts forward conceptual reason against this view, as the presence of risk is a precondition for trust playing a role in decision making. Second, results from consumer surveys in Italy and Germany are presented that support the associationist model as counter hypothesis. In that view, trust and risk judgments are driven by and thus simply indicators of higher order attitudes toward a certain technology which determine acceptance instead. The implications of these findings are discussed.

Bioethics through the telescope: institutional ethics in the NHS

The article argues for a broader conception of bioethics. The principles that dominate current thinking are generally individualistic and do not represent the real world inhabited by patients, doctors, hospitals and the NHS as a whole. Rather than focus almost exclusively on the micro-end of the analytical spectrum, bioethics, and medical lawyers in particular, should take the institutional dimensions of health and health care more seriously, ie use a telescope to understand the dynamics that drive the subject, not just a microscope.

Comparison of bioactivities, binding properties and intra-follicular levels of bovine follistatins

Five isoforms of follistatin (FST) (Mr 31, 33, 35, 37, 41kDa) were purified from bovine follicular fluid (bFF). Comparison of their activin- and heparan sulphate proteoglycan (HSP)-binding properties and bio-potencies in neutralization of activin-A action in vitro revealed that all five isoforms bound activin-A, but with different affinities. Only the 31kDa isoform (FST-288) bound to HSP. FST-288 also showed the greatest biopotency with 35 and 41kDa isoforms being least potent. To determine whether bovine follicle development is associated with changing intrafollicular FST and activin profiles, we analyzed bFF from dominant (DF) and subordinate (SF) follicles collected at strategic times during a synchronized estrous cycle. Total FST, activin-A and activin-AB were measured by immunoassay while individual FST isoforms were quantified by immunoblotting. Follicle diameter was positively correlated with estrogen:progesterone ratio (r=0.56) in bFF but negatively correlated with activin-A (r=-0.34), activin-AB (r=-0.80) and ‘total’ FST (r=-0.70) levels. Follicle diameter was positively correlated with abundance of the 41 kDa isoform (r=0.59) but negatively correlated with abundance of 33 and 31 kDa isoforms (r=-0.56, -0.41). Both follicle status (DF vs SF) and cycle stage affected total FST, activin-A, activin-B levels while follicle status, but not cycle stage, affected abundance of 41, 37, 33 and 31kDa FST isoforms. Collectively, these findings indicate that intrafollicular FST isoforms that differ in their ability to bind and neutralise activins and associate with cell-surface proteoglycans, show divergent changes during follicle development. Enhanced FST production may have an important negative role, either directly or via inhibition of the positive effects of activins, on follicle growth and function during follicular waves.

EU housing markets: the role of institutional factors

Using cluster analysis this study reveals significant heterogeneity in the institutional characteristics of European mortgage markets. Distinct clusters are formed which can be related to differences in the mortgage credit system, the relative importance of the owner-occupation and the property specific fiscal system. The paper then tests for multiple structural breaks. We find evidence that structural breaks in European housing markets often coincide with a changes in housing market policy.

Stabilization of the i-motif structure by the intra-strand cross-link formation

The i-motif structures are formed by oligonucleotides containing cytosine tracts under acidic conditions. The folding of the i-motif under physiological conditions is of great interest because of its biological role. In this study, we investigated the effect of the intra-strand cross-link on the stability of the i-motif structure. The 4-vinyl-substituted analog of thymidine (T-vinyl) was incorporated into the 5′-end of the human telomere complementary strand, which formed the intra-strand cross-link with the internal adenine. The intra-strand cross-linked i-motif displayed CD spectra similar to that of the natural i-motif at acidic pH, which was transformed into a random coil with the increasing pH. The pH midpoint for the transition from the i-motif to random coil increased from pH 6.1 for the natural one to pH 6.8 for the cross-linked one. The thermodynamic parameters were obtained by measuring the thermal melting behaviors by CD and UV, and it was determined that the intra-strand cross-linked i-motif is stabilized due to a favorable entropy effect. Thus, this study has clearly indicated the validity of the intra-strand cross-linking for stabilization of the i-motif structure.

Research data management and openness: the role of data sharing in developing institutional policies and practices

Purpose: To investigate the relationship between research data management (RDM) and data sharing in the formulation of RDM policies and development of practices in higher education institutions (HEIs). Design/methodology/approach: Two strands of work were undertaken sequentially: firstly, content analysis of 37 RDM policies from UK HEIs; secondly, two detailed case studies of institutions with different approaches to RDM based on semi-structured interviews with staff involved in the development of RDM policy and services. The data are interpreted using insights from Actor Network Theory. Findings: RDM policy formation and service development has created a complex set of networks within and beyond institutions involving different professional groups with widely varying priorities shaping activities. Data sharing is considered an important activity in the policies and services of HEIs studied, but its prominence can in most cases be attributed to the positions adopted by large research funders. Research limitations/implications: The case studies, as research based on qualitative data, cannot be assumed to be universally applicable but do illustrate a variety of issues and challenges experienced more generally, particularly in the UK. Practical implications: The research may help to inform development of policy and practice in RDM in HEIs and funder organisations. Originality/value: This paper makes an early contribution to the RDM literature on the specific topic of the relationship between RDM policy and services, and openness – a topic which to date has received limited attention.

Institutional multilingualism in NGOs: Amnesty International’s strategic understanding of multilingualism

Institutional multilingualism is most often associated with large intergovernmental institutions such as the European Union and the United Nations. Multilingualism in non-governmental organisations (NGOs), however, has remained invisible to a large extent. Yet these organisations have been identified as very powerful in world politics in the globalised 21st century. Like international governmental organisations (IGOs), they operate across linguistic and language borders. This raises the questions if NGOs actually use language and translation in the same way as IGOs. This article examines Amnesty International as a case study and explores what official multilingualism means for this organisation, how it is reflected in its language policy, and how it is put into practice. By gaining insight into the particular case of Amnesty International, this article aims to make a contribution to institutional translation studies.

Investigation of institutional investors’ responsible investment practices in UK

The focus of Corporate Governance is shifting from the role of directors to active ownership. Based on their fiduciary duty to other shareholders, it is believed that institutional investors have an important role to play in this regard. However, the Pension Funds and the Sovereign Wealth Organisations are not driven by the same set of objectives. In addition, Environmental Social and Governance (ESG) issues in investment decision-making are now becoming more important and they are capable of becoming the mainstream in the future. However, there are widespread variations in perception of fiduciary responsibilities, ESG issues appraisal, as well as the strategies adopted by institutional investors on shareholder engagement as responsible investors. Responsible Investment market is largely driven by institutional investors and they are expected to continue to lead the way. This research work investigates the role of the main asset owners and their advisors in responsible investment practices in the UK. It adopts a qualitative approach using semi-structured interviews, questionnaire and meetings observations. Gathered data is analysed using grounded theory and the findings highlight the perception of the various investor groups to corporate governance. The research work contributes to the body of knowledge by assessing the corporate governance perspectives of the various classes of institutional investors which may have practical implications for other countries.

A structuration theory perspective on the institutional change in Higher Education sector

Budgeting system has been traditionally viewed as a control mechanism rather than a communication tool to facilitate the institutionalisation of organisational change. A good budgeting system not only reflects the organisational reality but also socially constructs the reality. This paper uses the structuration perspective to understand budget-related behaviour in a UK research-intensive university and especially, study the role of budgeting system in achieving organisational sustainability. Giddens’ structuration theory offers a valuable framework for the study of the duality of structure and emphasises on the structural properties of social systems. Based on the semi-structured interviews with top management and budget holders, it is concluded that in this specific context, budgeting system may place a significant role in establishing and legitimising institutional change.