MHC class I A region diversity and polymorphism in macaque species

The HLA-A locus represents a single copy gene that displays abundant allelic polymorphism in the human population, whereas, in contrast, a nonhuman primate species such as the rhesus macaque (Macaca mulatta) possesses multiple HLA-A-like (Mamu-A) genes, which parade varying degrees of polymorphism. The number and combination of transcribed Mamu-A genes present per chromosome display diversity in a population of Indian animals. At present, it is not clearly understood whether these different A region configurations are evolutionarily stable entities. To shed light on this issue, rhesus macaques from a Chinese population and a panel of cynomolgus monkeys (Macaca fascicularis) were screened for various A region-linked variations. Comparisons demonstrated that most A region configurations are old entities predating macaque speciation, whereas most allelic variation (>95%) is of more recent origin. The latter situation contrasts the observations of the major histocompatibility complex class II genes in rhesus and cynomolgus macaques, which share a high number of identical alleles (>30%) as defined by exon 2 sequencing.     

Tetraspanins in the humoral immune response

The tetraspanins represent a large superfamily of four-transmembrane proteins that are expressed on all nucleated cells. Tetraspanins play a prominent role in the organization of the plasma membrane by co-ordinating the spatial localization of transmembrane proteins and signalling molecules into 'tetraspanin microdomains'. In immune cells, tetraspanins interact with key leucocyte receptors [including MHC molecules, integrins, CD4/CD8 and the BCR (B-cell receptor) complex] and as such can modulate leucocyte receptor activation and downstream signalling pathways. There is now ample evidence that tetraspanins on B-lymphocytes are important in controlling antibody production. The tetraspanin CD81 interacts with the BCR complex and is critical for CD19 expression and IgG production, whereas the tetraspanin CD37 inhibits IgA production and is important for IgG production. By contrast, the tetraspanins CD9, Tssc6 and CD151 appear dispensable for humoral immune responses. Thus individual tetraspanin family members have specific functions in B-cell biology, which is evidenced by recent studies in tetraspanin-deficient mice and humans. The present review focuses on tetraspanins expressed by B-lymphocytes and discusses novel insights into the function of tetraspanins in the humoral immune response.     

Butler-Volmer-Monod model for describing bio-anode polarization curves

A kinetic model of the bio-anode was developed based on a simple representation of the underlying biochemical conversions as described by enzyme kinetics, and electron transfer reactions as described by the Butler-Volmer electron transfer kinetics. This Butler-Volmer-Monod model was well able to describe the measured bio-anode polarization curves. The Butler-Volmer-Monod model was compared to the Nernst-Monod model described the experimental data significantly better. The Butler-Volmer-Monod model has the Nernst-Monod model as its full electrochemically reversible limit. Contrary to the Nernst-Monod model, the Butler-Volmer-Monod model predicts zero current at equilibrium potential. Besides, the Butler-Volmer-Monod model predicts that the apparent Monod constant is dependent on anode potential, which was supported by experimental results.     

Managing genetic testing: the relative powerlessness of actors in stable practices

Abstract

Genetics is a field in which ethical and social problems have been most pressing. Despite this, new tests often are introduced almost immediately after the isolation of a new gene. Considerations of whether a particular test should be introduced at all seem to have little effect on the development and introduction of new tests. This paper explores how this lack of social and ethical assessment can be understood. In order to do so, the sociohistorical context of clinical genetics and the way in which this practice came about will be analysed in this paper with respect to the Dutch service for clinical genetics. It will be argued that the fragmented way in which tasks and responsibility have become distributed within clinical genetics services has led to a situation in which actors seem to have no control over the introduction of genetic tests.     

Sensitivity and Validity of Psychometric Tests for Assessing Driving Impairment: Effects of Sleep Deprivation

ObjectiveTo assess drug induced driving impairment, initial screening is needed. However, no consensus has been reached about which initial screening tools have to be used. The present study aims to determine the ability of a battery of psychometric tests to detect performance impairing effects of clinically relevant levels of drowsiness as induced by one night of sleep deprivation.MethodsTwenty four healthy volunteers participated in a 2-period crossover study in which the highway driving test was conducted twice: once after normal sleep and once after one night of sleep deprivation. The psychometric tests were conducted on 4 occasions: once after normal sleep (at 11 am) and three times during a single night of sleep deprivation (at 1 am, 5 am, and 11 am).ResultsOn-the-road driving performance was significantly impaired after sleep deprivation, as measured by an increase in Standard Deviation of Lateral Position (SDLP) of 3.1 cm compared to performance after a normal night of sleep. At 5 am, performance in most psychometric tests showed significant impairment. As expected, largest effect sizes were found on performance in the Psychomotor Vigilance Test (PVT). Large effects sizes were also found in the Divided Attention Test (DAT), the Attention Network Test (ANT), and the test for Useful Field of View (UFOV) at 5 and 11 am during sleep deprivation. Effects of sleep deprivation on SDLP correlated significantly with performance changes in the PVT and the DAT, but not with performance changes in the UFOV.ConclusionFrom the psychometric tests used in this study, the PVT and DAT seem most promising for initial evaluation of drug impairment based on sensitivity and correlations with driving impairment. Further studies are needed to assess the sensitivity and validity of these psychometric tests after benchmark sedative drug use.     

A Probably Minor Role for Land-Applied Goat Manure in the Transmission of Coxiella burnetii to Humans in the 2007–2010 Dutch Q Fever Outbreak

In 2007, Q fever started to become a major public health problem in the Netherlands, with small ruminants as most probable source. In order to reduce environmental contamination, control measures for manure were implemented because of the assumption that manure was highly contaminated with Coxiella burnetii. The aims of this study were 1) to clarify the role of C. burnetii contaminated manure from dairy goat farms in the transmission of C. burnetii to humans, 2) to assess the impact of manure storage on temperature profiles in dunghills, and 3) to calculate the decimal reduction time of the Nine Mile RSA 493 reference strain of C. burnetii under experimental conditions in different matrices. For these purposes, records on distribution of manure from case and control herds were mapped and a potential relation to incidences of human Q fever was investigated. Additionally, temperatures in two dunghills were measured and related to heat resistance of C. burnetii. Results of negative binomial regression showed no significant association between the incidence of human Q fever cases and the source of manure. Temperature measurements in the core and shell of dunghills on two farms were above 40°C for at least ten consecutive days which would result in a strong reduction of C. burnetii over time. Our findings indicate that there is no relationship between incidence of human Q fever and land applied manure from dairy goat farms with an abortion wave caused by C. burnetii. Temperature measurements in dunghills on two farms with C. burnetii shedding dairy goat herds further support the very limited role of goat manure as a transmission route during the Dutch human Q fever outbreak. It is very likely that the composting process within a dunghill will result in a clear reduction in the number of viable C. burnetii.     

Syndromic Approach to Arboviral Diagnostics for Global Travelers as a Basis for Infectious Disease Surveillance

BackgroundArboviruses have overlapping geographical distributions and can cause symptoms that coincide with more common infections. Therefore, arbovirus infections are often neglected by travel diagnostics. Here, we assessed the potential of syndrome-based approaches for diagnosis and surveillance of neglected arboviral diseases in returning travelers.MethodTo map the patients high at risk of missed clinical arboviral infections we compared the quantity of all arboviral diagnostic requests by physicians in the Netherlands, from 2009 through 2013, with a literature-based assessment of the travelers’ likely exposure to an arbovirus.Results2153 patients, with travel and clinical history were evaluated. The diagnostic assay for dengue virus (DENV) was the most commonly requested (86%). Of travelers returning from Southeast Asia with symptoms compatible with chikungunya virus (CHIKV), only 55% were tested. For travelers in Europe, arbovirus diagnostics were rarely requested. Over all, diagnostics for most arboviruses were requested only on severe clinical presentation.ConclusionTravel destination and syndrome were used inconsistently for triage of diagnostics, likely resulting in vast under-diagnosis of arboviral infections of public health significance. This study shows the need for more awareness among physicians and standardization of syndromic diagnostic algorithms.     

Downy Mildew Resistance in Arabidopsis by Mutation of HOMOSERINE KINASE

Plant disease resistance is commonly triggered by early pathogen recognition and activation of immunity. An alternative form of resistance is mediated by recessive downy mildew resistant 1 (dmr1) alleles in Arabidopsis thaliana. Map-based cloning revealed that DMR1 encodes homoserine kinase (HSK). Six independent dmr1 mutants each carry a different amino acid substitution in the HSK protein. Amino acid analysis revealed that dmr1 mutants contain high levels of homoserine that is undetectable in wild-type plants. Surprisingly, the level of amino acids downstream in the aspartate (Asp) pathway was not reduced in dmr1 mutants. Exogenous homoserine does not directly affect pathogen growth but induces resistance when infiltrated in Arabidopsis. We provide evidence that homoserine accumulation in the chloroplast triggers a novel form of downy mildew resistance that is independent of known immune responses.