Novel IL10 gene family associations with systemic juvenile idiopathic arthritis

Juvenile idiopathic arthritis (JIA) is the most common cause of chronic childhood disability and encompasses a number of disease subgroups. In this study we have focused on systemic JIA (sJIA), which accounts for approximately 11% of UK JIA cases. This study reports the investigation of three members of the IL10 gene family as candidate susceptibility loci in children with sJIA. DNA from 473 unaffected controls and 172 patients with sJIA was genotyped for a single nucleotide polymorphism (SNP) in IL19 and IL20 and two SNPs in IL10. We examined evidence for association of the four SNPs by single marker and haplotype analysis. Significant differences in allele frequency were observed between cases and controls, for both IL10-1082 (p = 0.031) and IL20-468 (p = 0.028). Furthermore, examination of the haplotypes of IL10-1082 and IL20-468 revealed greater evidence for association (global p = 0.0006). This study demonstrates a significant increased prevalence of the low expressing IL10-1082 genotype in patients with sJIA. In addition, we show a separate association with an IL20 polymorphism, and the IL10-1082A/IL20-468T haplotype. The two marker 'A-T' haplotype confers an odds ratio of 2.24 for sJIA. This positive association suggests an important role for these cytokines in sJIA pathogenesis.     

Phylogenetic relationships among the species of the genus Testudo (Testudines: Testudinidae) inferred from mitochondrial 12S rRNA gene sequences

To test phylogenetic relationships within the genus Testudo (Testudines: Testudinidae), we have sequenced a fragment of the mitochondrial (mt) 12S rRNA gene of 98 tortoise specimens belonging to the genera Testudo, Indotestudo, and Geochelone. Maximum likelihood and neighbor-joining methods identify two main clades of Mediterranean tortoises, one composed of the species Testudo graeca, Testudo marginata, and Testudo kleinmanni and a second of Testudo hermanni, Testudo horsfieldii, and Indotestudo elongata. The first clade, but not the second, was also supported by maximum parsimony analysis. Together with the genus Geochelone, a star-like radiation of these clades was suggested, as a sister-group relationship between the two Testudo clades could not be confirmed. The intraspecies genetic variation was examined by sequencing the mt 12S rRNA fragment from 28 specimens of T. graeca and 49 specimens of T. hermanni from various geographic locations. Haplotype diversity was found to be significantly larger in T. graeca compared with T. hermanni, suggestive of reduced genetic diversity in the latter species, perhaps due to Pleistocene glaciations affecting northern and middle Europe or other sources of lineage reduction. No ancient mt 12S rRNA gene haplotypes were identified in T. graeca and/or T. hermanni originating from islands in the Mediterranean Sea, suggesting that these islands harbor tortoise populations introduced from the European and African mainland.     

Effects of elevated ammonia concentrations on survival, metabolic rates, and glutamine synthetase activity in the Antarctic pteropod mollusk Clione limacina antarctica

Information on the effects of elevated ammonia on invertebrates in general, and polar Mollusks in particular, is scant. Questions of ammonia sensitivity are interesting for several reasons, particularly since predicted global change scenarios include increasing anthropogenic nitrogen and toxic ammonia. Furthermore, polar zooplankton species are often lipid-rich, and authors have speculated that there is a linkage between elevated levels of lipids/trimethylamine oxide and enhanced ammonia tolerance. In the present study, we sought to examine ammonia tolerance and effects of elevated exogenous ammonia on several key aspects of the physiology and biochemistry of the pteropod mollusk, Clione limacina antarctica. We determined that the 96-h LC₅₀ value for this species is 7.465?mM total ammonia (Upper 95% CL?=?8.498?mM and Lower 95% CL?=?6.557?mM) or 0.51?mg/L as unionized ammonia (NH₃) (at a pH of 7.756). While comparative data for mollusks are limited, this value is at the lower end of reported values for other species. When the effects of lower ammonia concentrations (0.07?mM total ammonia) on oxygen consumption and ammonia excretion rates were examined, no effects were noted. However, total ammonia levels as low as 0.1?mM (or 0.007?mg/l NH₃) elevated the activity of the ammonia detoxification enzyme glutamine synthetase by approximately 1.5-fold. The values for LC₅₀ and observable effects on biochemistry for this one species are very close to permissible marine ammonia concentrations, indicating a need to more broadly determine the sensitivity of zooplankton to potential elevated ammonia levels in polar regions.     

Diverse spore rains and limited local exchange shape fern genetic diversity in a recently created habitat colonized by long-distance dispersal

Background and Aims

Populations established by long-distance colonization are expected to show low levels of genetic variation per population, but strong genetic differentiation among populations. Whether isolated populations indeed show this genetic signature of isolation depends on the amount and diversity of diaspores arriving by long-distance dispersal, and time since colonization. For ferns, however, reliable estimates of long-distance dispersal rates remain largely unknown, and previous studies on fern population genetics often sampled older or non-isolated populations. Young populations in recent, disjunct habitats form a useful study system to improve our understanding of the genetic impact of long-distance dispersal.

Methods

Microsatellite markers were used to analyse the amount and distribution of genetic diversity in young populations of four widespread calcicole ferns (Asplenium scolopendrium, diploid; Asplenium trichomanes subsp. quadrivalens, tetraploid; Polystichum setiferum, diploid; and Polystichum aculeatum, tetraploid), which are rare in The Netherlands but established multiple populations in a forest (the Kuinderbos) on recently reclaimed Dutch polder land following long-distance dispersal. Reference samples from populations throughout Europe were used to assess how much of the existing variation was already present in the Kuinderbos.

Key Results

A large part of the Dutch and European genetic diversity in all four species was already found in the Kuinderbos. This diversity was strongly partitioned among populations. Most populations showed low genetic variation and high inbreeding coefficients, and were assigned to single, unique gene pools in cluster analyses. Evidence for interpopulational gene flow was low, except for the most abundant species.

Conclusions

The results show that all four species, diploids as well as polyploids, were capable of frequent long-distance colonization via single-spore establishment. This indicates that even isolated habitats receive dense and diverse spore rains, including genotypes capable of self-fertilization. Limited gene flow may conserve the genetic signature of multiple long-distance colonization events for several decades.     

Assessing the impact of feline immunodeficiency virus and bovine tuberculosis co-infection in African lions

Bovine tuberculosis (BTB), caused by Mycobacterium bovis, is a disease that was introduced relatively recently into the Kruger National Park (KNP) lion population. Feline immunodeficiency virus (FIV(ple)) is thought to have been endemic in lions for a much longer time. In humans, co-infection between Mycobacterium tuberculosis and human immunodeficiency virus increases disease burden. If BTB were to reach high levels of prevalence in lions, and if similar worsening effects would exist between FIV(ple) and BTB as for their human equivalents, this could pose a lion conservation problem. We collected data on lions in KNP from 1993 to 2008 for spatio-temporal analysis of both FIV(ple) and BTB, and to assess whether a similar relationship between the two diseases exists in lions. We found that BTB prevalence in the south was higher than in the north (72 versus 19% over the total study period) and increased over time in the northern part of the KNP (0-41%). No significant spatio-temporal differences were seen for FIV(ple) in the study period, in agreement with the presumed endemic state of the infection. Both infections affected haematology and blood chemistry values, FIV(ple) in a more pronounced way than BTB. The effect of co-infection on these values, however, was always less than additive. Though a large proportion (31%) of the lions was co-infected with FIV(ple) and M. bovis, there was no evidence for a synergistic relation as in their human counterparts. Whether this results from different immunopathogeneses remains to be determined.     

Sleep problems in individuals with 11q terminal deletion disorder (Jacobsen syndrome)

Characteristics of sleep and sleep problems were investigated in 43 individuals with 11q terminal deletion disorder (Jacobsen syndrome). Data were collected using a sleep questionnaire. Ten individuals (23%) had a sleep problem. Settling problems, frequent night waking and early waking occurred in 2 (4%), 7 (16%) and 2 (6%) individuals, respectively. Twenty-two individuals (54%) had a history of sleep problems. Twenty-five individuals (60%) showed restless sleep and 23 individuals (54%) slept in an unusual position. Apart from frequent coughs, no significant relationships were found between the presence of a sleep problem and other variables, such as age, level of ID, breathing problems, heart defects, constipation, daytime activity and behavioral diagnosis, restless sleep and sleeping in an unusual positions.     

In-vivo range of motion of the subtalar joint using computed tomography

Understanding in vivo subtalar joint kinematics is important for evaluation of subtalar joint instability, the design of a subtalar prosthesis and for analysing surgical procedures of the ankle and hindfoot. No accurate data are available on the normal range of subtalar joint motion. The purpose of this study was to introduce a method that enables the quantification of the extremes of the range of motion of the subtalar joint in a loaded state using multidetector computed tomography (CT) imaging. In 20 subjects, an external load was applied to a footplate and forced the otherwise unconstrained foot in eight extreme positions. These extreme positions were foot dorsiflexion, plantarflexion, eversion, inversion and four extreme positions in between the before mentioned positions. CT images were acquired in a neutral foot position and each extreme position separately. After bone segmentation and contour matching of the CT data sets, the helical axes were determined for the motion of the calcaneus relative to the talus between four pairs of opposite extreme foot positions. The helical axis was represented in a coordinate system based on the geometric principal axes of the subjects’ talus. The greatest relative motion between the calcaneus and the talus was calculated for foot motion from extreme eversion to extreme inversion (mean rotation about the helical axis of 37.3±5.9°, mean translation of 2.3±1.1 mm). A consistent pattern of range of subtalar joint motion was found for motion of the foot with a considerable eversion and inversion component.