Genetic linkage and transmission disequilibrium of marker haplotypes at chromosome 1q41 in human systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by the production of autoantibodies to a wide range of self-antigens. Recent genome screens have implicated numerous chromosomal regions as potential SLE susceptibility loci. Among these, the 1q41 locus is of particular interest, because evidence for linkage has been found in several independent SLE family collections. Additionally, the 1q41 locus appears to be syntenic with a susceptibility interval identified in the NZM2410 mouse model for SLE. Here, we report the results of genotyping of 11 microsatellite markers within the 1q41 region in 210 SLE sibpair and 122 SLE trio families. These data confirm the modest evidence for linkage at 1q41 in our family collection (LOD = 1.21 at marker D1S2616). Evidence for significant linkage disequilibrium in this interval was also found. Multiple markers in the region exhibit transmission disequilibrium, with the peak single marker multiallelic linkage disequilibrium noted at D1S490 (pedigree disequilibrium test [PDT] global P value = 0.0091). Two- and three-marker haplotypes from the 1q41 region similarly showed strong transmission distortion in the collection of 332 SLE families. The finding of linkage together with significant transmission disequilibrium provides strong evidence for a susceptibility locus at 1q41 in human SLE.     

Effects of Nasal Corticosteroids on Boosts of Systemic Allergen-Specific IgE Production Induced by Nasal Allergen Exposure

BackgroundAllergen exposure via the respiratory tract and in particular via the nasal mucosa boosts systemic allergen-specific IgE production. Intranasal corticosteroids (INCS) represent a first line treatment of allergic rhinitis but their effects on this boost of allergen-specific IgE production are unclear.AimHere we aimed to determine in a double-blind, placebo-controlled study whether therapeutic doses of an INCS preparation, i.e., nasal fluticasone propionate, have effects on boosts of allergen-specific IgE following nasal allergen exposure.MethodsSubjects (n = 48) suffering from grass and birch pollen allergy were treated with daily fluticasone propionate or placebo nasal spray for four weeks. After two weeks of treatment, subjects underwent nasal provocation with either birch pollen allergen Bet v 1 or grass pollen allergen Phl p 5. Bet v 1 and Phl p 5-specific IgE, IgG_1–4, IgM and IgA levels were measured in serum samples obtained at the time of provocation and one, two, four, six and eight weeks thereafter.ResultsNasal allergen provocation induced a median increase to 141.1% of serum IgE levels to allergens used for provocation but not to control allergens 4 weeks after provocation. There were no significant differences regarding the boosts of allergen-specific IgE between INCS- and placebo-treated subjects.ConclusionIn conclusion, the application of fluticasone propionate had no significant effects on the boosts of systemic allergen-specific IgE production following nasal allergen exposure.

Trial Registration

http://clinicaltrials.gov/ {"type":"clinical-trial","attrs":{"text":"NCT00755066","term_id":"NCT00755066"}}NCT00755066     

Method to Measure Tone of Axial and Proximal Muscle

The control of tonic muscular activity remains poorly understood. While abnormal tone is commonly assessed clinically by measuring the passive resistance of relaxed limbs¹, no systems are available to study tonic muscle control in a natural, active state of antigravity support. We have developed a device (Twister) to study tonic regulation of axial and proximal muscles during active postural maintenance (i.e. postural tone). Twister rotates axial body regions relative to each other about the vertical axis during stance, so as to twist the neck, trunk or hip regions. This twisting imposes length changes on axial muscles without changing the body''s relationship to gravity. Because Twister does not provide postural support, tone must be regulated to counteract gravitational torques. We quantify this tonic regulation by the restive torque to twisting, which reflects the state of all muscles undergoing length changes, as well as by electromyography of relevant muscles. Because tone is characterized by long-lasting low-level muscle activity, tonic control is studied with slow movements that produce "tonic" changes in muscle length, without evoking fast "phasic" responses. Twister can be reconfigured to study various aspects of muscle tone, such as co-contraction, tonic modulation to postural changes, tonic interactions across body segments, as well as perceptual thresholds to slow axial rotation. Twister can also be used to provide a quantitative measurement of the effects of disease on axial and proximal postural tone and assess the efficacy of intervention.     

First record of the pantropical blue tick Rhipicephalus microplus in Namibia

The invasive pantropical blue tick, Rhipicephalus microplus, has recently been collected from cattle in Namibia. A cross-sectional study aimed at recording the geographic distribution of Rhipicephalus decoloratus and establishing whether R. microplus is present in Namibia was conducted towards the end of summer (March–April) 2013. Ticks were collected from cattle on 18 privately owned farms across a large geographical scale. Ticks were collected from three to five cattle per farm and species belonging to the genera Hyalomma and Rhipicephalus were recovered. Rhipicephalus decoloratus was present on all farms and R. microplus was recorded on four of the farms. The small numbers of R. microplus compared to R. decoloratus collected in the mixed infestations, suggests that the introduction events were recent.     

The Influence of Interspecific Competition and Host Preference on the Phylogeography of Two African Ixodid Tick Species

A comparative phylogeographic study on two economically important African tick species, Amblyomma hebraeum and Hyalomma rufipes was performed to test the influence of host specificity and host movement on dispersion. Pairwise AMOVA analyses of 277 mtDNA COI sequences supported significant population differentiation among the majority of sampling sites. The geographic mitochondrial structure was not supported by nuclear ITS-2 sequencing, probably attributed to a recent divergence. The three-host generalist, A. hebraeum, showed less mtDNA geographic structure, and a lower level of genetic diversity, while the more host-specific H. rufipes displayed higher levels of population differentiation and two distinct mtDNA assemblages (one predominantly confined to South Africa/Namibia and the other to Mozambique and East Africa). A zone of overlap is present in southern Mozambique. A mechanistic climate model suggests that climate alone cannot be responsible for the disruption in female gene flow. Our findings furthermore suggest that female gene dispersal of ticks is more dependent on the presence of juvenile hosts in the environment than on the ability of adult hosts to disperse across the landscape. Documented interspecific competition between the juvenile stages of H. rufipes and H. truncatum is implicated as a contributing factor towards disrupting gene flow between the two southern African H. rufipes genetic assemblages.     

Evidence for the localization of the Arabidopsis cytokinin receptors AHK3 and AHK4 in the endoplasmic reticulum

Cytokinins are hormones that are involved in various processes of plant growth and development. The model of cytokinin signalling starts with hormone perception through membrane-localized histidine kinase receptors. Although the biochemical properties and functions of these receptors have been extensively studied, there is no solid proof of their subcellular localization. Here, cell biological and biochemical evidence for the localization of functional fluorophor-tagged fusions of Arabidopsis histidine kinase 3 (AHK3) and 4 (AHK4), members of the cytokinin receptor family, in the endoplasmic reticulum (ER) is provided. Furthermore, membrane-bound AHK3 interacts with AHK4 in vivo. The ER localization and putative function of cytokinin receptors from the ER have major impacts on the concept of cytokinin perception and signalling, and hormonal cross-talk in plants.     

Epifaunistic arthropod parasites of the four-striped mouse, Rhabdomys pumilio, in the Western Cape Province, South Africa

Flea, lice, mite, and tick species associated with 510 Rhabdomys pumilio were collected at 9 localities in the Western Cape Province, South Africa. The aims of the study were first to quantify the species richness, prevalence, and relative mean intensity of infestation of epifaunistic arthropod species associated with R. pumilio, and second to determine temporal variations in the mean abundance of the parasitic arthropods. Each mouse was examined under a stereoscopic microscope and its parasites were removed, identified, and quantified. The epifaunal population was made up of more than 25,000 individuals and included 8 flea, 1 sucking louse, 11 mite, and 13 ixodid tick species. Female-biased sex ratios were noted for 9 (30%) of the ectoparasite species. Three undescribed mite and 1 undescribed tick species were recovered, and new locality records for 2 flea, the louse, and 2 mite species were documented. A phoretic host association between a nonparasitic mite species, Psylloglyphus uilenbergi kivuensis, and 3 flea species, Chiastopsylla rossi, Hypsophthalmus temporis, and Listropsylla agrippinae, was recorded. The mean abundance of the parasitic mite and insect species were higher during the cold wet season, whereas ticks were more numerous during the warm dry months. The large number of ectoparasite species on R. pumilio, a locally abundant and regionally widespread species, is of medical and veterinary importance particularly in relation to the transmission of pathogens such as Anaplasma marginale, Babesia caballi, and Babesia canis to domestic animals; Rickettsia conori; Yersinia pestis; and the viral disease Crimean-Congo hemorrhagic fever to humans.     

Arthromyces and Blastosporella, two new genera of conidia-producing lyophylloid agarics (Agaricales, Basidiomycota) from the neotropics

Two new genera encompassing three new species of lyophylloid agarics that produce conidia on the basidiomata are described. Arthromyces is a genus comprised of two very different arthrospore-producing mushroom species found in the Greater Antilles and Central America. Blastosporella is a monotypic genus with spherical balls of blastospores covering the pileus surface with age and is known from Hispaniola and Colombia. A key to the species of Arthromyces is included.