The Vanguard Method as Applied to the Design and Management of English and Welsh Children’s Services Departments

This paper follows several case studies where the children’s services departments of English and Welsh local authorities have fundamentally redesigned the way they worked following the application of the Vanguard Method (Seddon, Systems thinking in the public sector, 2008), a particular form of systems thinking. After first studying the way the children’s social care service worked as a system, the social workers in these authorities were able to demonstrate the way that government-prescribed IT and performance measures were restricting the way they could do what was shown to matter to the children in their care. The paper will document how, after being granted ministerial permission to suspend the use of their old performance measures and IT, a new set of operating principles was developed and employed. The redesigned system has shown encouraging early results. Evidence from these case studies (following Yin 2009) is presented in the form of recorded operational improvements and statements from participants. The paper will be of topical relevance to all involved in social care in the light of the government-commissioned Munro Review (Munro, The Munro Review of child protection: final report, 2011). The issues discussed will also be germane to the many other public sector partner agencies involved in the delivery of social care services (e.g. police, health, housing associations).     

Internalization of the human immunodeficiency virus does not require the cytoplasmic domain of CD4

Binding of the human immunodeficiency virus (HIV) to infectable host cells, such as B and T lymphocytes, monocytes and colorectal cells, is mediated by a high-affinity interaction between the gp120 component of the viral envelope glycoprotein and the CD4 receptor. Upon binding, it is thought that the second component of the envelope, gp41, mediates fusion between the viral envelope and host cell membranes. However, the early steps of HIV infection have not yet been thoroughly elucidated. Viral entry was first reported to be mediated by pH-dependent receptor-mediated endocytosis; subsequent studies have shown entry to be pH-independent. Although direct fusion of virus to plasma membranes of infected cells has been observed by electron microscopy, it is still formally possible that the infectious path of the virus involves receptor-mediated endocytosis. To gain a better understanding of receptor function in viral entry, we have analysed the ability of several altered or truncated forms of CD4 to serve as effective viral receptors. Our results indicate that domains beyond the HIV-binding region of CD4 are not required for viral infection. Some of the altered forms of CD4 that serve as effective HIV receptors are severely impaired in their ability to be endocytosed. These experiments therefore support the notion that viral fusion to the plasma membrane is sufficient for infection.     

Testing hypothesized evolutionary shifts toward stress tolerance in hybrid Helianthus species

We examined how plant traits related to growth and resource use have evolved during hybrid speciation and specialization into stressful habitats. Two desert sunflower species of homoploid hybrid origin are endemic to habitats with lower soil nutrient levels than those of their ancestral parent species. We hypothesized that the hybrid species would exhibit greater tolerance to low levels of soil nutrients than their parental species. The 2 hybrid species, Helianthus anomalus and H. deserticola , and their parental species, H. annuus and H. petiolaris , were compared for plant traits and growth through reproduction under 3 nutrient levels in a greenhouse study. An additional seedling study compared species for maximum seedling relative growth rate under optimum conditions. The hybrid species did have greater tolerance of nutrient limitation than the parental species, demonstrated by a resistance to change in stem height and diameter growth across treatments. A similar trend was observed in total biomass at final harvest. This ability to maintain growth may be partially explained by maintained investment in photosynthetic enzymes regardless of nutrient treatment. Though the hybrid species were more tolerant of nutrient stress, differences in the hybrid response to nutrient stress compared to the parental species' response were much smaller than expected from habitat comparisons. Helianthus anomalus has evolved a classic stress-tolerant phenotype, having long leaf lifespan, tough leaves, and slower early seedling relative growth rate. While both hybrid species have a conservative growth strategy, which confers greater stress tolerance than the parental species possess, functional trait differences among the hybrids suggest that the 2 species have experienced vastly different selective pressures.     

Positional cloning of zebrafish ferroportin1 identifies a conserved vertebrate iron exporter

Defects in iron absorption and utilization lead to iron deficiency and overload disorders. Adult mammals absorb iron through the duodenum, whereas embryos obtain iron through placental transport. Iron uptake from the intestinal lumen through the apical surface of polarized duodenal enterocytes is mediated by the divalent metal transporter, DMTi. A second transporter has been postulated to export iron across the basolateral surface to the circulation. Here we have used positional cloning to identify the gene responsible for the hypochromic anaemia of the zebrafish mutant weissherbst. The gene, ferroportin1, encodes a multiple-transmembrane domain protein, expressed in the yolk sac, that is a candidate for the elusive iron exporter. Zebrafish ferroportin1 is required for the transport of iron from maternally derived yolk stores to the circulation and functions as an iron exporter when expressed in Xenopus oocytes. Human Ferroportin1 is found at the basal surface of placental syncytiotrophoblasts, suggesting that it also transports iron from mother to embryo. Mammalian Ferroportin1 is expressed at the basolateral surface of duodenal enterocytes and could export cellular iron into the circulation. We propose that Ferroportin1 function may be perturbed in mammalian disorders of iron deficiency or overload.     

Cell-specific mitotic defect and dyserythropoiesis associated with erythroid band 3 deficiency

Most eukaryotic cell types use a common program to regulate the process of cell division. During mitosis, successful partitioning of the genetic material depends on spatially coordinated chromosome movement and cell cleavage. Here we characterize a zebrafish mutant, retsina (ret), that exhibits an erythroid-specific defect in cell division with marked dyserythropoiesis similar to human congenital dyserythropoietic anemia. Erythroblasts from ret fish show binuclearity and undergo apoptosis due to a failure in the completion of chromosome segregation and cytokinesis. Through positional cloning, we show that the ret mutation is in a gene (slc4a1) encoding the anion exchanger 1 (also called band 3 and AE1), an erythroid-specific cytoskeletal protein. We further show an association between deficiency in Slc4a1 and mitotic defects in the mouse. Rescue experiments in ret zebrafish embryos expressing transgenic slc4a1 with a variety of mutations show that the requirement for band 3 in normal erythroid mitosis is mediated through its protein 4.1R-binding domains. Our report establishes an evolutionarily conserved role for band 3 in erythroid-specific cell division and illustrates the concept of cell-specific adaptation for mitosis.