A Spontaneous, Recurrent Mutation in Divalent Metal Transporter-1 Exposes a Calcium Entry Pathway

Divalent metal transporter-1 (DMT1/DCT1/Nramp2) is the major Fe(2+) transporter mediating cellular iron uptake in mammals. Phenotypic analyses of animals with spontaneous mutations in DMT1 indicate that it functions at two distinct sites, transporting dietary iron across the apical membrane of intestinal absorptive cells, and transporting endosomal iron released from transferrin into the cytoplasm of erythroid precursors. DMT1 also acts as a proton-dependent transporter for other heavy metal ions including Mn(2+), Co(2+), and Cu(2), but not for Mg(2+) or Ca(2+). A unique mutation in DMT1, G185R, has occurred spontaneously on two occasions in microcytic (mk) mice and once in Belgrade (b) rats. This mutation severely impairs the iron transport capability of DMT1, leading to systemic iron deficiency and anemia. The repeated occurrence of the G185R mutation cannot readily be explained by hypermutability of the gene. Here we show that G185R mutant DMT1 exhibits a new, constitutive Ca(2+) permeability, suggesting a gain of function that contributes to remutation and the mk and b phenotypes

Responsible participation and housing: restoring democratic theory to the scene

Tensions between individual liberty and collective social justice characterise many advanced liberal societies. These tensions are reflected in the challenges posed for representative democracy both by participatory democratic practices and by the current emphasis on (so-called) responsible participation. Based on the example of ‘community’ housing associations in Scotland, this paper explores these tensions. It is argued that the critique of responsibility may have been over-stated – that, in particular, ‘community’ housing associations offer the basis for relatively more inclusive and effective processes of decision-making than council housing, which relies on the traditional processes and institutions of representative local government for its legitimacy

Psychosocial factors associated with the mental health of Indigenous children living in high income countries: a systematic review

Indigenous children living in high income countries such as Australia, New Zealand, Canada and the United States of America (USA) are disproportionately affected by mental health problems when compared to their non-Indigenous counterparts. Childhood mental health disorders such as anxiety, depression and externalising behaviours are associated with a range of negative outcomes that are overrepresented in Indigenous communities, including high rates of suicidal ideation and completed suicide. The long-term sequelae of poor childhood mental health is believed to significantly contribute to the many health and social 'gaps' between Indigenous and non-Indigenous populations that occur throughout the lifespan. This systematic review of published evidence aimed to identify modifiable psychosocial risk and protective factors common to Indigenous children living in developed countries. These factors are associated with mental health outcomes typically reflected in school-aged children. The results may inform policy and aid the design of initiatives to improve the mental health of Indigenous children, as well as identifying areas for further research.The research reported in this paper is a project of the Australian Primary Health Care Research Institute which is supported by a grant from the Australian Government Department of Health and Ageing under the Primary Health Care Research Evaluation and Development Strategy

Banking from Leeds, not London: regional strategy and structure at the Yorkshire Bank, 1859–1952

Industrial philanthropist Edward Akroyd created the Yorkshire Penny Savings Bank in 1859. Despite competition from the Post Office Savings Bank after 1861 and a serious reserve problem in 1911, it sustained his overall strategy to become a successful regional bank. Using archival and contemporary sources to build on recent scholarship illustrating how savings banks were integrated into local economies and the complementary roles of philanthropy and paternalism, we analyse an English regional bank's strategy, including an assessment of strategic innovation, ownership changes and management structure. This will demonstrate that the founder's vision continued, even though the 1911 crisis radically altered both strategy and structure

Proposed Tool to Compare and Assess the Applicability of Taste Assessment Techniques for Pharmaceuticals

Palatability is amongst the most important determinants of whether or not a child will take a medicine. In order to increase concordance with treatment regimens it is often necessary to utilise a range of formulation techniques to improve the palatability of medicines. These can include selecting a different molecule or version of a molecule (such as a different polymorph or salt form), various taste masking techniques and/or the inclusion of flavours and sweeteners. In order to be able to understand the taste of the Active Pharmaceutical Ingredient (API) and to validate the formulation approach used, it is necessary to be able to use the most reliable taste evaluation method possible. Multiple in vivo and in vitro methods exist nowadays or are proposed in the literature but are often little understood by the pharmaceutical product development community. In particular, different methods may be more relevant at different stages of product development. The aim of this article is to propose a tool to guide the selection of the most appropriate method for the desired evaluation. A spreadsheet-based tool is proposed that is designed to allow the systematic assessment of the applicability of any taste assessment technique existing or new to the users proposed application. A series of criteria are defined that will allow the user to assess the analytical, usability and availability factors for the technique that is being considered. Such a systematic review will help the user to understand the benefits and risks of using each methodology for that application. The use of the tool is illustrated based on currently available data and literature. As new/existing methods are developed/improved, the outcomes of the tool may change

The need to address fragmentation and silos in mortality information systems: the case of Ghana and Peru

Objectives: We aimed to understand the information architecture and degree of integration of mortality surveillance systems in Ghana and Peru. Methods: We conducted a cross-sectional study using a combination of document review and unstructured interviews to describe and analyse the sub-systems collecting mortality data. Results: We identified 18 and 16 information subsystems with independent databases capturing death events in Peru and Ghana respectively. The mortality information architecture was highly fragmented with a multiplicity of unconnected data silos and with formal and informal data collection systems. Conclusion: Reliable and timely information about who dies where and from what underlying cause is essential to reporting progress on Sustainable Development Goals, ensuring policies are responding to population health dynamics, and understanding the impact of threats and events like the COVID-19 pandemic. Integrating systems hosted in different parts of government remains a challenge for countries and limits the ability of statistics systems to produce accurate and timely information. Our study exposes multiple opportunities to improve the design of mortality surveillance systems by integrating existing subsystems currently operating in silos

Housing theory, housing research and housing policy

Jim Kemeny in 1992 criticised existing housing research for neglecting social theory and being overly positivist and policy focused. The result has been a strengthening of the conceptual basis of housing research in general, but also a growing schism between researchers who focus on policy relevancy and those that pursue more theoretical work. This paper challenges this schism and argues for theoretically based and policy relevant research. First the paper argues that the policy-making process is complex and can vary between different countries, situations and over time. Therefore, it is argued that many styles of research can influence policy in the right circumstances. Second, the paper challenges the idea that there can be theoretically-free housing research arguing that all research has a theoretical foundation even though in many studies it is not explicit. Finally, the paper engages with the debate about where theory for housing research should come from and what it would look like