Common Polymorphisms in Human Langerin Change Specificity for Glycan Ligands

Langerin, a C-type lectin on Langerhans cells, mediates carbohydrate-dependent uptake of pathogens in the first step of antigen presentation to the adaptive immune system. Langerin binds a diverse range of carbohydrates including high mannose structures, fucosylated blood group antigens, and glycans with terminal 6-sulfated galactose. Mutagenesis and quantitative binding assays indicate that salt bridges between the sulfate group and two lysine residues compensate for the nonoptimal binding of galactose at the primary Ca(2+) site. A commonly occurring single nucleotide polymorphism (SNP) in human langerin results in change of one of these lysine residues, Lys-313, to isoleucine. Glycan array screening reveals that this amino acid change abolishes binding to oligosaccharides with terminal 6SO(4)-Gal and enhances binding to oligosaccharides with terminal GlcNAc residues. Structural analysis shows that enhanced binding to GlcNAc may result from Ile-313 packing against the N-acetyl group. The K313I polymorphism is tightly linked to another SNP that results in the change N288D, which reduces affinity for glycan ligands by destabilizing the Ca(2+)-binding site. Langerin with Asp-288 and Ile-313 shows no binding to 6SO(4)-Gal-terminated glycans and increased binding to GlcNAc-terminated structures, but overall decreased binding to glycans. Altered langerin function in individuals with the linked N288D and K313I polymorphisms may affect susceptibility to infection by microorganisms

'White knuckle care work' : violence, gender and new public management in the voluntary sector

Drawing on comparative data from Canada and Scotland, this article explores reasons why violence is tolerated in non-profit care settings. This article will provide insights into how workers' orientations to work, the desire to care and the intrinsic rewards from working in a non-profit context interact with the organization of work and managerially constructed workplace norms and cultures (Burawoy, 1979) to offset the tensions in an environment characterized by scarce resources and poor working conditions. This article will also outline how the same environment of scarce resources causes strains in management's efforts to establish such cultures. Working with highly excluded service users with problems that do not respond to easy interventions, workers find themselves working at the edge of their endurance, hanging on by their fingernails, and beginning to participate in various forms of resistance; suggesting that even among the most highly committed, 'white knuckle care' may be unsustainable

What do students want most from written feedback information? Distinguishing necessities from luxuries using a budgeting methodology

Feedback is a key concern for higher education practitioners, yet there is little evidence concerning the aspects of assessment feedback information that higher education students prioritise when their lecturers’ time and resources are stretched. One recent study found that in such circumstances, students actually perceive feedback information itself as a luxury rather than a necessity. We first re-examined that finding by asking undergraduates to ‘purchase’ characteristics to create the ideal lecturer, using budgets of differing sizes to distinguish necessities from luxuries. Contrary to the earlier research, students in fact considered good feedback information the single biggest necessity for lecturers to demonstrate. In a second study we used the same method to examine the characteristics of feedback information that students value most. Here, the most important perceived necessity was guidance on improvement of skills. In both studies, students’ priorities were influenced by their individual approaches to learning. These findings permit a more pragmatic approach to building student satisfaction in spite of growing expectations and demands

Constrained by managerialism : caring as participation in the voluntary social services

The data in this study show that care is a connective process, underlying and motivating participation and as a force that compels involvement in the lives of others, care is at least a micro-participative process. Care or affinity not only persisted in the face of opposition, but it was also used by workers as a counter discourse and set of practices with which to resist the erosion of worker participation and open up less autonomized practices and ways of connecting with fellow staff, clients and the communities they served. The data suggest that while managerialism and taylorised practice models may remove or reduce opportunities for worker participation, care is a theme or storyline that gave workers other ways to understand their work and why they did it, as well as ways they were prepared to resist managerial priorities and directives, including the erosion of various kinds of direct and indirect participation. The degree of resistance possible, even in the highly technocratic worksite in Australia, shows that cracks and fissures exist within managerialism

Propranolol treatment of infantile hemangioma endothelial cells: A molecular analysis

Infantile hemangiomas (IHs) are non-malignant, largely cutaneous vascular tumors affecting approximately 5–10% of children to varying degrees. During the first year of life, these tumors are strongly proliferative, reaching an average size ranging from 2 to 20 cm. These lesions subsequently stabilize, undergo a spontaneous slow involution and are fully regressed by 5 to 10 years of age. Systemic treatment of infants with the non-selective β-adrenergic receptor blocker, propranolol, has demonstrated remarkable efficacy in reducing the size and appearance of IHs. However, the mechanism by which this occurs is largely unknown. In this study, we sought to understand the molecular mechanisms underlying the effectiveness of β blocker treatment in IHs. Our data reveal that propranolol treatment of IH endothelial cells, as well as a panel of normal primary endothelial cells, blocks endothelial cell proliferation, migration, and formation of the actin cytoskeleton coincident with alterations in vascular endothelial growth factor receptor-2 (VEGFR-2), p38 and cofilin signaling. Moreover, propranolol induces major alterations in the protein levels of key cyclins and cyclin-dependent kinase inhibitors, and modulates global gene expression patterns with a particular affect on genes involved in lipid/sterol metabolism, cell cycle regulation, angiogenesis and ubiquitination. Interestingly, the effects of propranolol were endothelial cell-type independent, affecting the properties of IH endothelial cells at similar levels to that observed in neonatal dermal microvascular and coronary artery endothelial cells. This data suggests that while propranolol markedly inhibits hemangioma and normal endothelial cell function, its lack of endothelial cell specificity hints that the efficacy of this drug in the treatment of IHs may be more complex than simply blockage of endothelial function as previously believed

Mating system variation in neotropical black mangrove, Avicennia germinans, at three spatial scales towards an expanding northern distributional limit

Climate-driven range expansion of ecosystem-defining foundation species can have wide-reaching ecological consequences. Expansion may also result in mating system changes in these foundation species because of the ecological characteristics of range margins, such as greater conspecific isolation and reduced pollinator availability. It is important to understand how mating systems may change during expansion due to their direct influence on intraspecific genetic and demographic dynamics. Here, we used 12 microsatellite loci to genotype progeny arrays of the neotropical black mangrove (Avicennia germinans) at six collection sites (n = 23 maternal trees; 1,612 genotyped propagules) along a latitudinal gradient towards a northern distributional limit on the Atlantic coast of Florida, USA (27.56–30.01oN), where mangroves have expanded into salt marsh over the past several decades. We assessed mating system variation at three spatial scales. First, at the species-distribution level, published outcrossing rates for tropical conspecifics were more than two times higher than those for subtropical Florida A. germinans, consistent with reductions in pollinator diversity and in mangrove abundance with latitude. Second, at the population level, Florida outcrossing rates did not systematically decline towards the northern range limit, but instead, a more open pollen-dispersal neighbourhood at the transition from mangrove to salt marsh dominance may elevate outcrossing until conspecific abundances become too low towards the range limit. Third, at the individual level, outcrossing increased as conspecific cover increased at the Florida range margin, consistent with density-dependent plastic shifts in mating system. These findings suggest that ecological structure influences the A. germinans mating system at varying spatial scales. Further research needs to evaluate the effect of A. germinans mating system variation on the survival and fitness of offspring and on the extent of population-level local adaptation at expanding distributional limits

Poverty index with time-varying consumption and income distributions

Starting from a stochastic agent-based model to represent market exchange in a developing economy, we study time variations of the probability density function of income with simultaneous variation of the consumption deprivation (CD), where CD represents the shortfall in consumption from the saturation level of an essential commodity, cereal. Together, these two models combine income-expenditure-based market dynamics with time variations in consumption due to income. In this new unified theoretical structure, exchange of trade in assets is only allowed when the income exceeds consumption-deprivation while CD itself is endogenously obtained from a separate kinetic model. Our results reveal that the nature of time variation of the CD function leads to a downward trend in the threshold level of consumption of basic necessities, suggesting a possible dietary transition in terms of lower saturation level of food-grain consumption, possibly through an improvement in the level of living. The new poverty index, defined as CD, is amenable to approximate probabilistic prediction within a short time horizon. A major achievement of this work is the intrinsic independence of the poverty index from an exogenous poverty line, making it more objective for policy formulation as opposed to existing poverty indices in the literature

Understanding the genetic diversity of the guayabillo (Psidium galapageium), an endemic plant of the Galapagos Islands

Oceanic archipelagos are known to host a variety of endemic plant species. The genetic diversity and structure of these species is an important indicator of their evolutionary history and can inform appropriate conservation strategies that mitigate the risks to which they’re exposed, including invasive species and environmental disturbances. A comprehensive consideration of the role of their natural history, as well as the landscape features and the geological history of the islands themselves is required to adequately understand any emerging patterns. Such is the case for the guayabillo (Psidium galapageium), an understudied endemic plant from the Galapagos Islands with important ecological and economic roles. In this study we designed and evaluated 13 informative SSR markers and used them to investigate the genetic diversity, population structure and connectivity of the guayabillo populations from San Cristobal, Isabela and Santa Cruz islands. A total of 208 guayabillo individuals were analyzed, revealing a strong population structure between islands and two distinct genetic lineages for the Santa Cruz population. Overall, the guayabillo genetic diversity is relatively high, an unusual pattern for an insular endemic species which is possibly explained by its polyploidy and the geographical features of the islands. These include their broad altitudinal ranges and habitat heterogeneity. For populations displaying a lower genetic diversity such as San Cristobal, the history of human disturbance could be an important factor explaining these observations. Some similarities between individuals in Santa Cruz and the San Cristobal population could be explained by population differentiation or distinct natural histories of separate lineages. Our findings highlight the complex population dynamics that shape the genetic diversity of species like the guayabillo and emphasize the need to explore the currently unresolved questions about this Galapagos endemic plant