Structure and hydration of phytoglycogen nanoparticles: Nature\u27s dendrimer

Nature offers amazing examples of nanostructured molecules and materials. I will focus on phytoglycogen, a highly-branched polymer of glucose produced in the form of dense, monodisperse nanoparticles by some varieties of plants such as sweet corn. The particles are chemically simple, but have a special dendrimeric or tree-like structure that produces interesting and unusual properties such as extraordinary water retention, and low viscosity and exceptional stability in water. These properties point to a wide variety of potential applications from cosmetics to drug delivery, yet these applications need to be enabled by a deeper understanding of the unique structure of the particles and their interaction with water. To achieve this, we have used a wide range of techniques. Neutron scattering has revealed that the nanoparticles have uniform size and density and are highly hydrated, with each nanoparticle containing about 250% of its mass in water [1]. Surface-sensitive infrared absorption measurements on phytoglycogen films show that the high degree of branching in phytoglycogen leads to a well ordered “network” structure of the hydration water within the particles [2]. Rheology measurements have revealed weak interactions between the particles, allowing loading of the particles into water up to 20% w/w before significant increases in viscosity are observed, showing that this is an interesting model system for studying soft colloid physics [3]. Taken together, these studies provide new insights that are key to fully understanding and exploiting these materials in new technologies and therapies. [1] J.D. Nickels, J. Atkinson, E. Papp-Szabo, C. Stanley, S.O. Diallo, S. Perticaroli, B. Baylis, P. Mahon, G. Ehlers, J. Katsaras and J.R. Dutcher. Structure and Hydration of Highly-Branched, Monodisperse Phytoglycogen Nanoparticles, Biomacromolecules 17, 735-743 (2016). [2] M. Grossutti and J.R. Dutcher. Correlation Between Chain Architecture and Hydration Water Structure in Polysaccharides, Biomacromolecules 17, 1198-1204 (2016). [3] H. Shamana, E. Papp-Szabo, J. Atkinson, C. Miki and J.R. Dutcher. Phytoglycogen Nanoparticles in Water: A Model Soft Colloid System, in preparation

Down-regulation of CD46 by Piliated Neisseria gonorrhoeae

Human membrane cofactor protein (CD46) protects host cells against complement attack and may function as a receptor for pathogenic Neisseriae. We assessed CD46 expression in the human cervical cell line ME-180 after exposure to Neisseria gonorrhoeae. Piliated but not nonpiliated gonococci adhered to cells and produced up to an 80% reduction in CD46 surface expression by 6 h that persisted for at least 24 h. This response required a minimum multiplicity of infection of 10 and was not prevented by antibodies to CD46. CD46 down-regulation was not attributable to intracellular retention or a global or specific shutdown of mRNA or protein synthesis. Substantial quantities of CD46 were found in the supernatants, indicating a specific shedding of this protein. Adherent gonococci lacking the pilus retraction protein PilT did not down-regulate CD46 but de-repression of pilT expression restored CD46 down-regulation. After experimental infection of human volunteers with a gonococcal variant incapable of inducing CD46 down-regulation, variants of this strain were reisolated that exhibited CD46 down-regulation. Pilus-mediated interactions of gonococci with human epithelial cells results in a pathogen-induced manipulation of the host cell environment in which a membrane protein is removed from epithelial cells by liberation into the surrounding milieu

Timing and mechanism of conceptus demise in a complement regulatory membrane protein deficient mouse

PROBLEM: Crry is a widely expressed type 1 transmembrane complement regulatory protein in rodents which protects self-tissue by downregulating C3 activation. Crry METHOD OF STUDY: We investigated the basis of Crry RESULTS: We narrowed the critical period of the complement effect from 6.5 to 8.5 days post-coitus (dpc), which is immediately after the conceptus is exposed to maternal blood. Deposition by 5.5 dpc of maternal C3b on the placental vasculature lacking Crry CONCLUSION: Our data are most consistent with the deposition of C3b being responsible for the failure of the allantois to fuse to the chorion leading to subsequent conceptus demise

Experiences of Loneliness Associated with Being an Informal Caregiver: A Qualitative Investigation

Although providing care to a family member or friend may provide psychological benefits, informal (i.e., unpaid) caregivers also encounter difficulties which may negatively affect their quality of life as well as their mental and physical health. Loneliness is one important challenge that caregivers face, with this psychological state being associated with morbidity and premature mortality. Although previous research has identified loneliness as an issue associated with being an informal caregiver, there is a paucity of evidence that attempts to understand this phenomenon in depth. This study aimed to examine informal caregivers' reflections on, and accounts of, experiences of loneliness linked to their caregiving situation. As part of a cross-sectional, qualitative study, sixteen semi-structured interviews were conducted with 8 spousal caregivers, 4 daughters caring for a parent, 3 mothers caring for a child (or children), and 1 woman looking after her partner. The cared-for persons were suffering from a range of mental and physical health conditions (e.g., dementia, frailty due to old age, multiple sclerosis, depression, autism). Data were analyzed using an inductive thematic analysis. Experiences of loneliness were described by reference to a context of shrunken personal space and diminished social interaction caused by the restrictions imposed by the caregiving role. Loneliness was also articulated against a background of relational deprivations and losses as well as sentiments of powerlessness, helplessness, and a sense of sole responsibility. Social encounters were also seen to generate loneliness when they were characterized by some form of distancing. Though not all sources or circumstances of loneliness in caregivers are amenable to change, more opportunities for respite care services, as well as a heightened sensibility and social appreciation of caregivers' valued contributions could help caregivers manage some forms of loneliness

Measles Virus Recognizes Its Receptor, CD46, via Two Distinct Binding Domains within SCR1-2

AbstractMeasles virus (MV) enters cells by attachment of the viral hemagglutinin to the major cell surface receptor CD46 (membrane cofactor protein). CD46 is a transmembrane glycoprotein whose ectodomain is largely composed of four conserved modules called short consensus repeats (SCRs). We have previously shown that MV interacts with SCR1 and SCR2 of CD46. (M. Manchesteret al.(1995)Proc. Natl. Acad. Sci. USA92, 2303–2307) Here we report mapping the MV interaction with SCR1 and SCR2 of CD46 using a combination of peptide inhibition and mutagenesis studies. By testing a series of overlapping peptides corresponding to the 126 amino acid SCR1-2 region for inhibition of MV infection, two domains were identified that interacted with MV. One domain was found within SCR1 (amino acids 37–56) and another within SCR2 (amino acids 85–104). These results were confirmed by constructing chimeras with complementary regions from structurally similar, but non-MV-binding, SCRs of decay accelerating factor (DAF; CD55). These results indicate that MV contacts at least two distinct sites within SCR1-2

Secreted NS1 of Dengue Virus Attaches to the Surface of Cells via Interactions with Heparan Sulfate and Chondroitin Sulfate E

Dengue virus (DENV) nonstructural protein-1 (NS1) is a secreted glycoprotein that is absent from viral particles but accumulates in the supernatant and on the plasma membrane of cells during infection. Immune recognition of cell surface NS1 on endothelial cells has been hypothesized as a mechanism for the vascular leakage that occurs during severe DENV infection. However, it has remained unclear how NS1 becomes associated with the plasma membrane, as it contains no membrane-spanning sequence motif. Using flow cytometric and ELISA-based binding assays and mutant cell lines lacking selective glycosaminoglycans, we show that soluble NS1 binds back to the surface of uninfected cells primarily via interactions with heparan sulfate and chondroitin sulfate E. DENV NS1 binds directly to the surface of many types of epithelial and mesenchymal cells yet attaches poorly to most peripheral blood cells. Moreover, DENV NS1 preferentially binds to cultured human microvascular compared to aortic or umbilical cord vein endothelial cells. This binding specificity was confirmed in situ as DENV NS1 bound to lung and liver but not intestine or brain endothelium of mouse tissues. Differential binding of soluble NS1 by tissue endothelium and subsequent recognition by anti-NS1 antibodies could contribute to the selective vascular leakage syndrome that occurs during severe secondary DENV infection

Coping with loneliness at University: a qualitative interview study with students in the UK

Leaving home to attend University constitutes a transition that is often characterized by an increased risk of loneliness, a psychological state that predicts poor mental health outcomes. Informed by a comprehensive conceptual framework of coping with stress, this study sought to examine the coping strategies young adults deploy to manage experiences of loneliness whilst studying at University. A qualitative, cross-sectional study was designed. Semi-structured interviews were conducted with 15 University students who had moved away from home to study, and who self-identified experiencing loneliness. We used directed qualitative content analysis to analyse the data both between and within participants. The results demonstrate that participants used a variety of coping strategies to manage the distressing experience of loneliness. Accommodation, mainly in the form of distraction, support-seeking, social isolation, self-reliance, and problem-solving behaviours were the most prevalent coping strategies mentioned. Coping reflecting helplessness, escape, submission, and more rarely, opposition, were also found, albeit less often. Students showed evidence of a wide-ranging coping repertoire, with the deployment of specific coping strategies presenting as highly selective and contextual. Strategies for coping with loneliness take into account constraints and opportunities in the environment, the availability and appropriateness of social resources, as well as individual resources and needs

Everything we do, everything we press: Data-driven remote performance management in a mobile workplace

© 2018 Copyright is held by the owner/author(s). This paper examines how data-driven performance monitoring technologies affect the work of telecommunications field engineers. As a mobile workforce, this occupational group rely on an array of smartphone applications to plan, manage and report on their jobs, and to liaise remotely with managers and colleagues. These technologies intend to help field engineers be more productive and have greater control over their work; however they also gather data related to the quantity and effectiveness of their labor. We conducted a qualitative study examining engineers' experiences of these systems. Our findings suggest they simultaneously enhance worker autonomy, support co-ordination with and monitoring of colleagues, but promote anxieties around productivity and the interpretation of data by management. We discuss the implications of datadriven performance management technologies on worker agency, and examine the consequences of such systems in an era of quantified workplaces