Bitter taste stimuli induce differential neural codes in mouse brain.

A growing literature suggests taste stimuli commonly classified as "bitter" induce heterogeneous neural and perceptual responses. Here, the central processing of bitter stimuli was studied in mice with genetically controlled bitter taste profiles. Using these mice removed genetic heterogeneity as a factor influencing gustatory neural codes for bitter stimuli. Electrophysiological activity (spikes) was recorded from single neurons in the nucleus tractus solitarius during oral delivery of taste solutions (26 total), including concentration series of the bitter tastants quinine, denatonium benzoate, cycloheximide, and sucrose octaacetate (SOA), presented to the whole mouth for 5 s. Seventy-nine neurons were sampled; in many cases multiple cells (2 to 5) were recorded from a mouse. Results showed bitter stimuli induced variable gustatory activity. For example, although some neurons responded robustly to quinine and cycloheximide, others displayed concentration-dependent activity (p<0.05) to quinine but not cycloheximide. Differential activity to bitter stimuli was observed across multiple neurons recorded from one animal in several mice. Across all cells, quinine and denatonium induced correlated spatial responses that differed (p<0.05) from those to cycloheximide and SOA. Modeling spatiotemporal neural ensemble activity revealed responses to quinine/denatonium and cycloheximide/SOA diverged during only an early, at least 1 s wide period of the taste response. Our findings highlight how temporal features of sensory processing contribute differences among bitter taste codes and build on data suggesting heterogeneity among "bitter" stimuli, data that challenge a strict monoguesia model for the bitter quality

Identification of hepatitis a virus mimotopes by phage display, antigenicity and immunogenicity

A phage-displayed peptide approach was used to identify ligands mimicking antigenic determinants of hepatitis A virus (HAV) for the first time. Bacteriophages displaying HAV mimotopes were isolated from a phage-display peptide library by affinity selection on serum antibodies from hepatitis A patients. Selected phage-peptides were screened for reactivity with sera from HAV infected patients and healthy controls. Four cloned peptides with different sequences were identified as mimotopes of HAV; three of them showed similarity in their amino acid sequences with at least one of the VP3 and VP1 antigenic proteins of HAV. One clone was recognised by 92% of the positive sera. The phagotopes competed effectively with HAV for absorption of anti-HAV-specific antibodies in human sera, as determined by ELISA. The four phage clones induced neutralising anti-HAV antibodies in immunised mice. These results demonstrate the potential of this method to elucidate the disease related epitopes of HAV and to use these mimotopes in diagnostic applications or in the development of a mimotope-based hepatitis A vaccine without the necessity of manipulation of the virus

Trade-offs, condition dependence and stopover site selection by migrating sandpipers

Western sandpipers Calidris mauri on southward migration fly over the Gulf of Alaska to the Strait of Georgia, British Columbia, where they stop for a few days to replenish reserves before continuing. In the Strait, individuals captured on the extensive tidal mudflats of the Fraser estuary (∼25000 ha) are significantly heavier (2.71 g, or >10% of lean body mass) than those captured on the small (<100 ha) mudflat of nearby Sidney Island. Previous work has shown that the difference cannot be attributed to seasonal timing, size, age or gender effects, and here we compare predictions made by six hypotheses about a diverse set of data to explain why, partway through a migratory journey of ∼10000 km, birds have such different body masses at two stopover sites within 40 km of each other. The ‘trade-off’ hypothesis – that the large Fraser estuary offers safety from predators, but a lower fattening rate, while the small Sidney Island site is more dangerous, but offers a higher fattening rate – made six successful predictions, all of which were upheld by the data. All other hypotheses failed at least one prediction. We infer that calidrid sandpipers arriving in the Strait of Georgia with little fat remaining (and therefore low body mass) choose to take advantage of the high feeding rate at small sites like Sidney Island because they are less vulnerable to avian predators than are individuals with higher fat reserves, who instead elect to feed at large open sites like the Fraser estuary mudflats

Moving on from CODES - The keystones for a whole systems approach to low carbon schools

Moves towards reducing the carbon footprint of new buildings require a new way of thinking. Design research suggests that the development of more innovative and sustainable solutions increasingly highlight the benefits arising from the integration and participation of multiple actors with a wide range of technical and contextual knowledge and expertise. The need to address complex problems more systematically has escalated the importance of cross-disciplinary collaborations and partnerships between stakeholders (Coley and Lemon, 2009). It is also becoming more widely accepted that the inter-connected dynamics of a system’s component parts is what determines its complexity suggesting that a holistic approach to problem solving cannot always rely on conventional methods. A mechanical problem is typically broken down into its parts before being able to systematically solve the problem piece by piece. Whilst this is powerful for some problems, and often requires extensive knowledge that aligns with the complicatedness of the task, complex issues, invariably involving people and their relationship with other actors (not necessarily human), do not lend themselves to such a reductionist approach. The design and subsequent operation of a school is one such complex phenomenon that requires a holistic approach which acknowledges the process of continual change that emerges from these interrelationships and patterns (Anarow, Greener et.al., 2003); it also requires collaboration, partnership and trust. This chapter will return to the Keystones on School Community Collaboration that emerged from the ENSI-CoDeS project (Collaboration of schools and communities for Sustainable Development, 2011-2014) and are summarised and reflected upon, with examples, in Espinet and Zachariou (2014). It will focus on the continuation of city based collaborations in the UK (Leicester)that were designed to ensure that the legacy of the Building Schools for the Future (BSF) Programme was one of enhanced sustainability facilitated through collaboration and partnership. The next section will summarise the BSF programme and will introduce the projects that will be considered alongside the CoDeS Keystones. The Keystones will then be introduced alongside examples derived from the projects and a final concluding section will explore what these projects and the Keystone concepts might tell us about the generic capabilities that have been introduced above and might underpin such collaboration in very different contexts

Local energy policy and managing low carbon transition: the case of Leicester, UK

National and local energy policies are implemented within a complex energy landscape that makes any evaluation of their impacts far from straightforward. Drawing upon a case study of Leicester this paper argues that the ability of local authorities to deliver significant energy savings within this landscape is questionable, albeit with other additional benefits being realised (e.g. job creation, community engagement). It examines existing domestic energy demand and multiple deprivation data for Leicester and neighbouring cities and combines this with a qualitative description of the transition process. The paper identifies the need for a more systematic analysis of how national energy policy translates to the local level and concludes that it is problematic even for a leading, pro-active and innovative local authority to have a statistically meaningful energy policy. Even where energy policies are favourable, carbon reduction is less easy to realise than other – more local - co-benefits and that in the light of significant financial and co-ordination constraints more attention needs to be given to how local communities can be more effectively supported in their desire to meet (or exceed) national targets.We acknowledge the financial assistance of the EPSRC Flexnet award (EP/E0411X/1) and all of the Leicester based contributors to the project, as well as the very helpful comments of two anonymous referees; the usual disclaimers apply

Class A scavenger receptor 1 (MSR1) restricts hepatitis C virus replication by mediating toll-like receptor 3 recognition of viral RNAs produced in neighboring cells

Persistent infections with hepatitis C virus (HCV) may result in life-threatening liver disease, including cirrhosis and cancer, and impose an important burden on human health. Understanding how the virus is capable of achieving persistence in the majority of those infected is thus an important goal. Although HCV has evolved multiple mechanisms to disrupt and block cellular signaling pathways involved in the induction of interferon (IFN) responses, IFN-stimulated gene (ISG) expression is typically prominent in the HCV-infected liver. Here, we show that Toll-like receptor 3 (TLR3) expressed within uninfected hepatocytes is capable of sensing infection in adjacent cells, initiating a local antiviral response that partially restricts HCV replication. We demonstrate that this is dependent upon the expression of class A scavenger receptor type 1 (MSR1). MSR1 binds extracellular dsRNA, mediating its endocytosis and transport toward the endosome where it is engaged by TLR3, thereby triggering IFN responses in both infected and uninfected cells. RNAi-mediated knockdown of MSR1 expression blocks TLR3 sensing of HCV in infected hepatocyte cultures, leading to increased cellular permissiveness to virus infection. Exogenous expression of Myc-MSR1 restores TLR3 signaling in MSR1-depleted cells with subsequent induction of an antiviral state. A series of conserved basic residues within the carboxy-terminus of the collagen superfamily domain of MSR1 are required for binding and transport of dsRNA, and likely facilitate acidification-dependent release of dsRNA at the site of TLR3 expression in the endosome. Our findings reveal MSR1 to be a critical component of a TLR3-mediated pattern recognition receptor response that exerts an antiviral state in both infected and uninfected hepatocytes, thereby limiting the impact of HCV proteins that disrupt IFN signaling in infected cells and restricting the spread of HCV within the liver

Local Energy Policy and Managing the Low Carbon Transition: The Case of Leicester

This paper seeks to provide insights into the links between the local and national energy policy. Leicester City Council has sought to take a leadership role on implementing innovative energy policies within their city. consequently, this paper investigates the impact of national and local energy policy in Leicester. It examines the consumption of energy within city, the network of players within energy policy and two flagship aspects of the policy the district heating scheme and the use of smart metering. The paper concludes that energy policy looks very different at local and national levels

METABOLISM STUDIES WITH ALGIN AND GELATIN

Algin, a salt of alginic acid extracted from kelp, and gelatin, produced from animal bones and skins, are used as stabilizing agents in the manufacture of ice cream and in certain other food products. Studies were conducted over a period of 10 weeks to determine the nutritive effects of the vegetable gum of algin and the protein of gelatin. The apparent digestibility of algin varied directly with the level fed. Algin was utilized efficiently after absorption. Gelatin was highly digested irrespective of the level fed, but more food was required per unit increase in live weight. No characteriztic symptoms were noted that couldbe attributed to acute or chroninic toxicity. Both algin and gelatin were found to be wholesome foods