A single amino acid in the HA of pH1N1 2009 influenza virus affects cell tropism in human airway epithelium, but not transmission in ferrets

The first pandemic of the 21(st) century, pandemic H1N1 2009 (pH1N1 2009), emerged from a swine-origin source. Although human infections with swine-origin influenza have been reported previously, none went on to cause a pandemic or indeed any sustained human transmission. In previous pandemics, specific residues in the receptor binding site of the haemagglutinin (HA) protein of influenza have been associated with the ability of the virus to transmit between humans. In the present study we investigated the effect of residue 227 in HA on cell tropism and transmission of pH1N1 2009. In pH1N1 2009 and recent seasonal H1N1 viruses this residue is glutamic acid, whereas in swine influenza it is alanine. Using human airway epithelium, we show a differential cell tropism of pH1N1 2009 compared to pH1N1 2009 E227A and swine influenza suggesting this residue may alter the sialic acid conformer binding preference of the HA. Furthermore, both pH1N1 2009 E227A and swine influenza multi-cycle viral growth was found to be attenuated in comparison to pH1N1 2009 in human airway epithelium. However this altered tropism and viral growth in human airway epithelium did not abrogate respiratory droplet transmission of pH1N1 2009 E227A in ferrets. Thus, acquisition of E at residue 227 was not solely responsible for the ability of pH1N1 2009 to transmit between humans.

Monitoring the penetration enhancer dimethyl sulfoxide in human stratum corneum in vivo by confocal raman spectroscopy

The stratum corneum (SC) barrier typically consists of layers of corneocytes embedded in a lipid continuum that regulates barrier function. The lipid domain containing ceramides, cholesterol, and free fatty acids provides the major pathway for most drugs permeating across SC. Penetration enhancers diminish the SC barrier function. The classic enhancer is dimethyl sulfoxide (DMSO). Its mechanisms of action remain unclear, although DMSO disrupts lipid organisation and may displace protein-bound water. Here we use confocal Raman spectroscopy to probe molecular interactions between a finite (depleting) dose of DMSO and SC, as functions of depth and time, providing novel information about residence time and location of DMSO in human SC in vivo

Role of lipids in human nutrition

Fat is a major contributor to energy intake in most Western diets, supplying 35–40% of food energy. It is described as being ‘energy-dense’, because a gram of fat (9 kcal/g) yields more than twice as much metabolisable energy as a gram of either carbohydrate or protein (4 kcal/g). Most of the fat we consume in our diet is in the form of triacylglycerol (90-95%), with cholesterol and phospholipids making up the bulk of the remainder. Dietary advice invariably stresses the importance of fat reduction, yet fats have diverse roles in human nutrition. They are important as a source of energy, both for immediate utilisation by the body and in laying down a storage depot (adipose tissue) for later utilisation when food intake is reduced, they act as a vehicle for the ingestion and absorption of fat-soluble vitamins, and they have diverse structural and functional roles in the body. Cholesterol is also an essential component of cell membranes and is the precursor for synthesis of hormones. This chapter describes the structure, digestion, transport and functional properties of dietary fat in the body and explains the basis of associations between fat consumption and chronic disease.

Attaching-effacing bacteria in animals

Enteric bacteria with a demonstrable or potential ability to form attaching-effacing lesions, so-called attaching-effacing (AE) bacteria, have been found in the intestinal tracts of a wide variety of warm-blooded animal species, including man. In some host species, for example cattle, pigs, rabbits and human beings, attaching-effacing Escherichia coli (AEEC) have an established role as enteropathogens. In other host species, AE bacteria are of less certain significance. With continuing advances in the detection and typing of AE strains, the importance of these bacteria for many hosts is likely to become clearer. The pathogenic effects of AE bacteria result from adhesion to the intestinal mucosa by a variety of mechanisms, culminating in the formation of the characteristic intimate adhesion of the AE lesion. The ability to induce AE lesions is mediated by the co-ordinated expression of some 40 bacterial genes organized within a so-called pathogenicity island, known as the "Locus for Enterocyte Effacement". It is also believed that the production of bacterial toxins, principally Vero toxins, is a significant virulence factor for some A-EEC strains. Recent areas of research into AE bacteria include: the use of Citrobacter rodentium to model human AEEC disease; quorum-sensing mechanisms used by AEEC to modulate virulence gene expression; and the potential role of adhesion in the persistent colonization of the intestine by AE bacteria. This review of AE bacteria covers their molecular biology, their occurrence in various animal species, and the diagnosis, pathology and clinical aspects of animal diseases with which they are associated. Reference is made to human pathogens where appropriate. The focus is mainly on natural colonization and disease, but complementary experimental data are also included. (C) 2004 Elsevier Ltd. All rights reserved.

Dynamical complexity in a mean-field model of human EEG

A recently proposed mean-field theory of mammalian cortex rhythmogenesis describes the salient features of electrical activity in the cerebral macrocolumn, with the use of inhibitory and excitatory neuronal populations (Liley et al 2002). This model is capable of producing a range of important human EEG (electroencephalogram) features such as the alpha rhythm, the 40 Hz activity thought to be associated with conscious awareness (Bojak & Liley 2007) and the changes in EEG spectral power associated with general anesthetic effect (Bojak & Liley 2005). From the point of view of nonlinear dynamics, the model entails a vast parameter space within which multistability, pseudoperiodic regimes, various routes to chaos, fat fractals and rich bifurcation scenarios occur for physiologically relevant parameter values (van Veen & Liley 2006). The origin and the character of this complex behaviour, and its relevance for EEG activity will be illustrated. The existence of short-lived unstable brain states will also be discussed in terms of the available theoretical and experimental results. A perspective on future analysis will conclude the presentation.

Simultaneous mobile sink allocation in home environments with applications in mobile consumer robotics

This paper presents a novel mobile sink area allocation scheme for consumer based mobile robotic devices with a proven application to robotic vacuum cleaners. In the home or office environment, rooms are physically separated by walls and an automated robotic cleaner cannot make a decision about which room to move to and perform the cleaning task. Likewise, state of the art cleaning robots do not move to other rooms without direct human interference. In a smart home monitoring system, sensor nodes may be deployed to monitor each separate room. In this work, a quad tree based data gathering scheme is proposed whereby the mobile sink physically moves through every room and logically links all separated sub-networks together. The proposed scheme sequentially collects data from the monitoring environment and transmits the information back to a base station. According to the sensor nodes information, the base station can command a cleaning robot to move to a specific location in the home environment. The quad tree based data gathering scheme minimizes the data gathering tour length and time through the efficient allocation of data gathering areas. A calculated shortest path data gathering tour can efficiently be allocated to the robotic cleaner to complete the cleaning task within a minimum time period. Simulation results show that the proposed scheme can effectively allocate and control the cleaning area to the robot vacuum cleaner without any direct interference from the consumer. The performance of the proposed scheme is then validated with a set of practical sequential data gathering tours in a typical office/home environment.

Human versus animal: contrasting decomposition dynamics of mammalian analogues in experimental taphonomy

Taphonomic studies regularly employ animal analogues for human decomposition due to ethical restrictions relating to the use of human tissue. However, the validity of using animal analogues in soil decomposition studies is still questioned. This study compared the decomposition of skeletal muscle tissues (SMTs) from human (Homo sapiens), pork (Sus scrofa), beef (Bos taurus), and lamb (Ovis aries) interred in soil microcosms. Fixed interval samples were collected from the SMT for microbial activity and mass tissue loss determination; samples were also taken from the underlying soil for pH, electrical conductivity, and nutrient (potassium, phosphate, ammonium, and nitrate) analysis. The overall patterns of nutrient fluxes and chemical changes in nonhuman SMT and the underlying soil followed that of human SMT. Ovine tissue was the most similar to human tissue in many of the measured parameters. Although no single analogue was a precise predictor of human decomposition in soil, all models offered close approximations in decomposition dynamics.

Mediated action and sexual risk: Searching for 'culture' in discourses of homosexuality and AIDS prevention in China

This paper examines the concept of ‘culture’ and its relationship to HIV prevention. Culture is here seen as the interaction between human beings and the various ‘cultural tools’ they appropriate when taking action. Among these tools are ways of speaking which encode certain meanings, ideologies and social practices. When individuals take action with regard to AIDS, what they do is mediated through voices which they borrow strategically from their environ- ment. The textual tools that are available and the ways individuals adapt and combine them work to either limit or amplify their participation in HIV prevention. What are traditionally seen as ‘cultures’ or ‘sub-cultures’, or worse, ‘risk groups’, are, in this perspective, viewed as ‘communities of practice’, groups of individuals who share particular cultural tools and ways of using them. This conceptual framework is applied to recent discourses of homosexuality and AIDS prevention in China. An instance of ‘of� cial’ discourse in the form of an AIDS education pamphlet for ‘gays’ is analysed for the voices it contains and how these voices are strategically marshalled by the authors and mixed with other voices in ways which amplify participation in AIDS prevention for some and limit it for others. This ‘offical’ discourse is then compared to the discourse of homosexually active Chinese men recently interviewed in Beijing and Fuzhou to examine which of these of� cial voices and other voices they appropriate, and how they adapt these voices in responding to HIV.