The hr1 and Fusion Peptide Regions of the Subgroup B Avian Sarcoma and Leukosis Virus Envelope Glycoprotein Influence Low pH-Dependent Membrane Fusion

The avian sarcoma and leukosis virus (ASLV) envelope glycoprotein (Env) is activated to trigger fusion by a two-step mechanism involving receptor-priming and low pH fusion activation. In order to identify regions of ASLV Env that can regulate this process, a genetic selection method was used to identify subgroup B (ASLV-B) virus-infected cells resistant to low pH-triggered fusion when incubated with cells expressing the cognate TVB receptor. The subgroup B viral Env (envB) genes were then isolated from these cells and characterized by DNA sequencing. This led to identification of two frequent EnvB alterations which allowed TVB receptor-binding but altered the pH-threshold of membrane fusion activation: a 13 amino acid deletion in the host range 1 (hr1) region of the surface (SU) EnvB subunit, and the A32V amino acid change within the fusion peptide of the transmembrane (TM) EnvB subunit. These data indicate that these two regions of EnvB can influence the pH threshold of fusion activation

Effects of Protein Deficiency on Perinatal and Postnatal Health Outcomes

There are a variety of environmental insults that can occur during pregnancy which cause low birth weight and poor fetal health outcomes. One such insult is maternal malnutrition, which can be further narrowed down to a low protein diet during gestation. Studies show that perinatal protein deficiencies can impair proper organ growth and development, leading to long-term metabolic dysfunction. Understanding the molecular mechanisms that underlie how this deficiency leads to adverse developmental outcomes is essential for establishing better therapeuticstrategies that may alleviate or prevent diseases in later life. This chapter reviews how perinatal protein restriction in humans and animals leads to metabolic disease, and it identifies the mechanisms that have been elucidated, to date. These include alterations in transcriptional and epigenetic mechanisms, as well as indirect means such as endoplasmic reticulum (ER) stress and oxidative stress. Furthermore, nutritional and pharmaceutical interventions are highlighted to illustrate that the plasticity of the underdeveloped organs during perinatal life can be exploited to prevent onset of long-term metabolic disease

Existence of a lens-shaped cluster of surfaces self-shrinking by mean curvature

We rigorously show the existence of a rotationally and centrally symmetric "lens-shaped" cluster of three surfaces, meeting at a smooth common circle, forming equal angles of 120 degrees, self-shrinking under the motion by mean curvature.Comment: 22 pages, 2 figure

Modeling and Analysis of the Molecular Basis of Pain in Sensory Neurons

Intracellular calcium dynamics are critical to cellular functions like pain transmission. Extracellular ATP plays an important role in modulating intracellular calcium levels by interacting with the P2 family of surface receptors. In this study, we developed a mechanistic mathematical model of ATP-induced P2 mediated calcium signaling in archetype sensory neurons. The model architecture, which described 90 species connected by 162 interactions, was formulated by aggregating disparate molecular modules from literature. Unlike previous models, only mass action kinetics were used to describe the rate of molecular interactions. Thus, the majority of the 252 unknown model parameters were either association, dissociation or catalytic rate constants. Model parameters were estimated from nine independent data sets taken from multiple laboratories. The training data consisted of both dynamic and steady-state measurements. However, because of the complexity of the calcium network, we were unable to estimate unique model parameters. Instead, we estimated a family or ensemble of probable parameter sets using a multi-objective thermal ensemble method. Each member of the ensemble met an error criterion and was located along or near the optimal trade-off surface between the individual training data sets. The model quantitatively reproduced experimental measurements from dorsal root ganglion neurons as a function of extracellular ATP forcing. Hypothesized architecture linking phosphoinositide regulation with P2X receptor activity explained the inhibition of P2X-mediated current flow by activated metabotropic P2Y receptors. Sensitivity analysis using individual and the whole system outputs suggested which molecular subsystems were most important following P2 activation. Taken together, modeling and analysis of ATP-induced P2 mediated calcium signaling generated qualitative insight into the critical interactions controlling ATP induced calcium dynamics. Understanding these critical interactions may prove useful for the design of the next generation of molecular pain management strategies

Mapping new work practices in the smart city

The proliferation of digital connectivity and mobility is having a profound impact on collaboration practices and coworking spaces in urban environments. This chapter focuses on nomadic patterns of designers, freelancers, hackers, and creative professionals, and seeks to map the urban spaces that they occupy and navigate in order to go about their work practices. After a brief introduction on the use of office space and recently emerged city bound working practices, we first review previous studies and current literature about the impact of digital connectivity and mobility on collaboration and coworking spaces. Two cases (the Centre for Social Innovation in Toronto, Canada, and The Edge, a digital culture centre at the State Library of Queensland in Brisbane, Australia) will be introduced as examples of social practices in, and uses / employments of coworking and collaboration spaces. The subsequent discussion of best practices and future designs of collaboration and coworking spaces will focus on three distinct themes: First, the tension between universal vs specialised demands on space; second, the need for perpetual messiness, and; third, the unfolding urban ecology of work spaces. Finally, we will conclude with some considerations on the configuration and promotion of collaborative working practices especially with regards to urban planning

The Role of Dendritic Cells in Immune Regulation and Allergic Airway Inflammation

Dendritic cells (DC) are potent antigen presenting cells that display an extraordinary capacity to present antigen to naïve T-cells and initiate primary immune responses. In the context of the lung and upper airway it is clear that DC play a key role in the regulation of adaptive immune responses to inhaled antigen. DC are particularly sensitive to signals derived from microbes, allergens and the airway tissue microenvironment. By the nature of the signals they provide at the time of antigen presentation, DC can polarize naïve T-cells into either T-helper type 1 (Th1) or Th2 effector cells, and are increasingly recognized as having a central role in the establishment of T-cell memory and peripheral immune tolerance. DC form a network within the upper airway and lung, and are rapidly recruited from the circulation in response to a variety of proinflammatory stimuli. Studies using animal models have highlighted the role of DC in both the initiation and maintenance of allergic airway inflammation. In early childhood, human DC are functionally immature, and this is thought to contribute to the development of allergic sensitization in those children who are genetically at risk for the development of atopy. Increased numbers of airway mucosal DC are found in both allergic rhinitis and asthma, while studies of blood-derived DC have emphasized important differences between the function of DC from atopic and normal individuals. This article reviews recent information on the involvement of DC in allergic airway disease, and the mechanisms by which DC could be exploited as targets for therapy in asthma and allergic rhinitis