An Anti-Human ICAM-1 Antibody Inhibits Rhinovirus-Induced Exacerbations of Lung Inflammation

Human rhinoviruses (HRV) cause the majority of common colds and acute exacerbations of asthma and chronic obstructive pulmonary disease (COPD). Effective therapies are urgently needed, but no licensed treatments or vaccines currently exist. Of the 100 identified serotypes, ∼90% bind domain 1 of human intercellular adhesion molecule-1 (ICAM-1) as their cellular receptor, making this an attractive target for development of therapies; however, ICAM-1 domain 1 is also required for host defence and regulation of cell trafficking, principally via its major ligand LFA-1. Using a mouse anti-human ICAM-1 antibody (14C11) that specifically binds domain 1 of human ICAM-1, we show that 14C11 administered topically or systemically prevented entry of two major groups of rhinoviruses, HRV16 and HRV14, and reduced cellular inflammation, pro-inflammatory cytokine induction and virus load in vivo. 14C11 also reduced cellular inflammation and Th2 cytokine/chemokine production in a model of major group HRV-induced asthma exacerbation. Interestingly, 14C11 did not prevent cell adhesion via human ICAM-1/LFA-1 interactions in vitro, suggesting the epitope targeted by 14C11 was specific for viral entry. Thus a human ICAM-1 domain-1-specific antibody can prevent major group HRV entry and induction of airway inflammation in vivo

Numerical Simulation of a Passive Control of the Flow Around an Aerofoil Using a Flexible, Self Adaptive Flaplet

© 2018 The Author(s) Self-activated feathers are used by almost all birds to adapt their wing characteristics to delay stall or to moderate its adverse effects (e.g., during landing or sudden increase in angle of attack due to gusts). Some of the feathers are believed to pop up as a consequence of flow separation and to interact with the flow and produce beneficial modifications of the unsteady vorticity field. The use of self adaptive flaplets in aircrafts, inspired by birds feathers, requires the understanding of the physical mechanisms leading to the mentioned aerodynamic benefits and the determination of the characteristics of optimal flaps including their size, positioning and ideal fabrication material. In this framework, this numerical study is divided in two parts. Firstly, in a simplified scenario, we determine the main characteristics that render a flap mounted on an aerofoil at high angle of attack able to deliver increased lift and improved aerodynamic efficiency, by varying its length, position and its natural frequency. Later on, a detailed direct numerical simulation analysis is used to understand the origin of the aerodynamic benefits introduced by the flaplet movement induced by the interaction with the flow field. The parametric study that has been carried out, reveals that an optimal flap can deliver a mean lift increase of about 20% on a NACA0020 aerofoil at an incidence of 20 o degrees. The results obtained from the direct numerical simulation of the flow field around the aerofoil equipped with the optimal flap at a chord Reynolds number of 2 × 10 4 shows that the flaplet movement is mainly induced by a cyclic passage of a large recirculation bubble on the aerofoil suction side. In turns, when the flap is pushed downward, the induced plane jet displaces the trailing edge vortices further downstream, away from the wing, moderating the downforce generated by those vortices and regularising the shedding cycle that appears to be much more organised when the optimal flaplet configuration is selected

Body size estimation in women with anorexia nervosa and healthy controls using 3D avatars

A core feature of anorexia nervosa is an over-estimation of body size. However, quantifying this over-estimation has been problematic as existing methodologies introduce a series of artefacts and inaccuracies in the stimuli used for judgements of body size. To overcome these problems, we have: (i) taken 3D scans of 15 women who have symptoms of anorexia (referred to henceforth as anorexia spectrum disorders, ANSD) and 15 healthy control women, (ii) used a 3D modelling package to build avatars from the scans, (iii) manipulated the body shapes of these avatars to reflect biometrically accurate, continuous changes in body mass index (BMI), (iv) used these personalized avatars as stimuli to allow the women to estimate their body size. The results show that women who are currently receiving treatment for ANSD show an over-estimation of body size which rapidly increases as their own BMI increases. By contrast, the women acting as healthy controls can accurately estimate their body size irrespective of their own BMI. This study demonstrates the viability of combining 3D scanning and CGI techniques to create personalised realistic avatars of individual patients to directly assess their body image perception

History of clinical transplantation

The emergence of transplantation has seen the development of increasingly potent immunosuppressive agents, progressively better methods of tissue and organ preservation, refinements in histocompatibility matching, and numerous innovations is surgical techniques. Such efforts in combination ultimately made it possible to successfully engraft all of the organs and bone marrow cells in humans. At a more fundamental level, however, the transplantation enterprise hinged on two seminal turning points. The first was the recognition by Billingham, Brent, and Medawar in 1953 that it was possible to induce chimerism-associated neonatal tolerance deliberately. This discovery escalated over the next 15 years to the first successful bone marrow transplantations in humans in 1968. The second turning point was the demonstration during the early 1960s that canine and human organ allografts could self-induce tolerance with the aid of immunosuppression. By the end of 1962, however, it had been incorrectly concluded that turning points one and two involved different immune mechanisms. The error was not corrected until well into the 1990s. In this historical account, the vast literature that sprang up during the intervening 30 years has been summarized. Although admirably documenting empiric progress in clinical transplantation, its failure to explain organ allograft acceptance predestined organ recipients to lifetime immunosuppression and precluded fundamental changes in the treatment policies. After it was discovered in 1992 that long-surviving organ transplant recipient had persistent microchimerism, it was possible to see the mechanistic commonality of organ and bone marrow transplantation. A clarifying central principle of immunology could then be synthesized with which to guide efforts to induce tolerance systematically to human tissues and perhaps ultimately to xenografts

A Computational Investigation on the Connection between Dynamics Properties of Ribosomal Proteins and Ribosome Assembly

Assembly of the ribosome from its protein and RNA constituents has been studied extensively over the past 50 years, and experimental evidence suggests that prokaryotic ribosomal proteins undergo conformational changes during assembly. However, to date, no studies have attempted to elucidate these conformational changes. The present work utilizes computational methods to analyze protein dynamics and to investigate the linkage between dynamics and binding of these proteins during the assembly of the ribosome. Ribosomal proteins are known to be positively charged and we find the percentage of positive residues in r-proteins to be about twice that of the average protein: Lys+Arg is 18.7% for E. coli and 21.2% for T. thermophilus. Also, positive residues constitute a large proportion of RNA contacting residues: 39% for E. coli and 46% for T. thermophilus. This affirms the known importance of charge-charge interactions in the assembly of the ribosome. We studied the dynamics of three primary proteins from E. coli and T. thermophilus 30S subunits that bind early in the assembly (S15, S17, and S20) with atomic molecular dynamic simulations, followed by a study of all r-proteins using elastic network models. Molecular dynamics simulations show that solvent-exposed proteins (S15 and S17) tend to adopt more stable solution conformations than an RNA-embedded protein (S20). We also find protein residues that contact the 16S rRNA are generally more mobile in comparison with the other residues. This is because there is a larger proportion of contacting residues located in flexible loop regions. By the use of elastic network models, which are computationally more efficient, we show that this trend holds for most of the 30S r-proteins

Identification of Zoonotic Genotypes of Giardia duodenalis

Giardia duodenalis, originally regarded as a commensal organism, is the etiologic agent of giardiasis, a gastrointestinal disease of humans and animals. Giardiasis causes major public and veterinary health concerns worldwide. Transmission is either direct, through the faecal-oral route, or indirect, through ingestion of contaminated water or food. Genetic characterization of G. duodenalis isolates has revealed the existence of seven groups (assemblages A to G) which differ in their host distribution. Assemblages A and B are found in humans and in many other mammals, but the role of animals in the epidemiology of human infection is still unclear, despite the fact that the zoonotic potential of Giardia was recognised by the WHO some 30 years ago. Here, we performed an extensive genetic characterization of 978 human and 1440 animal isolates, which together comprise 3886 sequences from 4 genetic loci. The data were assembled into a molecular epidemiological database developed by a European network of public and veterinary health Institutions. Genotyping was performed at different levels of resolution (single and multiple loci on the same dataset). The zoonotic potential of both assemblages A and B is evident when studied at the level of assemblages, sub-assemblages, and even at each single locus. However, when genotypes are defined using a multi-locus sequence typing scheme, only 2 multi-locus genotypes (MLG) of assemblage A and none of assemblage B appear to have a zoonotic potential. Surprisingly, mixtures of genotypes in individual isolates were repeatedly observed. Possible explanations are the uptake of genetically different Giardia cysts by a host, or subsequent infection of an already infected host, likely without overt symptoms, with a different Giardia species, which may cause disease. Other explanations for mixed genotypes, particularly for assemblage B, are substantial allelic sequence heterogeneity and/or genetic recombination. Although the zoonotic potential of G. duodenalis is evident, evidence on the contribution and frequency is (still) lacking. This newly developed molecular database has the potential to tackle intricate epidemiological questions concerning protozoan diseases

The Unknown Risk of Vertical Transmission in Sleeping Sickness—A Literature Review

Children with human African trypanosomiasis (HAT) present with a range of generally non-specific symptoms. Late diagnosis is frequent with often tragic outcomes. Trypanosomes can infect the foetus by crossing the placenta. Unequivocal cases of congenital infection that have been reported include newborn babies of infected mothers who were diagnosed with HAT in the first 5 days of life and children of infected mothers who had never entered an endemic country themselves

A longitudinal study on the occurrence of Cryptosporidium and Giardia in dogs during their first year of life

<p>Abstract</p> <p>Background</p> <p>The primary aim of this study was to obtain more knowledge about the occurrence of <it>Cryptosporidium </it>and <it>Giardia </it>in young dogs in Norway.</p> <p>The occurrence of these parasites was investigated in a longitudinal study by repeated faecal sampling of dogs between 1 and 12 months of age (litter samples and individual samples). The dogs were privately owned and from four large breeds. Individual faecal samples were collected from 290 dogs from 57 litters when the dogs were approximately 3, 4, 6, and 12 months old. In addition, pooled samples were collected from 43 of the litters, and from 42 of the mother bitches, when the puppies were approximately 1 and/or 2 months old.</p> <p>Methods</p> <p>The samples were purified by sucrose gradient flotation concentration and examined by immunofluorescent staining.</p> <p>Results</p> <p>128 (44.1%) of the young dogs had one or more <it>Cryptosporidium </it>positive samples, whilst 60 (20.7%) dogs had one or more <it>Giardia </it>positive samples. The prevalence of the parasites varied with age. For <it>Cryptosporidium</it>, the individual prevalence was between 5.1% and 22.5%, with the highest level in dogs < 6 months old, and declining with age. For <it>Giardia</it>, the individual prevalence was between 6.0% and 11.4%, with the highest level in dogs > 6 months old, but the differences between age groups were not statistically significant. Significant differences in prevalences were found in relation to geographic location of the dogs. Both parasites occurred at low prevalences in Northern Norway.</p> <p>Conclusion</p> <p>Both <it>Cryptosporidium </it>and <it>Giardia </it>are common in Norwegian dogs, with <it>Cryptosporidium </it>more prevalent than <it>Giardia</it>. Prevalences of the parasites were found to be influenced by age, geographical location, and infection status before weaning.</p