Subgroups of Paediatric Acute Lymphoblastic Leukaemia Might Differ Significantly in Genetic Predisposition to Asparaginase Hypersensitivity

L-asparaginase (ASP) is a key element in the treatment of paediatric acute lymphoblastic leukaemia (ALL). However, hypersensitivity reactions (HSRs) to ASP are major challenges in paediatric patients. Our aim was to investigate genetic variants that may influence the risk to Escherichia coli-derived ASP hypersensitivity. Sample and clinical data collection was carried out from 576 paediatric ALL patients who were treated according to protocols from the Berlin—Frankfurt—Münster Study Group. A total of 20 single nucleotide polymorphisms (SNPs) in GRIA1 and GALNT10 genes were genotyped. Patients with GRIA1 rs4958351 AA/AG genotype showed significantly reduced risk to ASP hypersensitivity compared to patients with GG genotype in the T-cell ALL subgroup (OR = 0.05 (0.01–0.26); p = 4.70E-04), while no such association was found in pre-B-cell ALL. In the medium risk group two SNPs of GRIA1 (rs2055083 and rs707176) were associated significantly with the occurrence of ASP hypersensitivity (OR = 0.21 (0.09–0.53); p = 8.48E-04 and OR = 3.02 (1.36–6.73); p = 6.76E-03, respectively). Evaluating the genders separately, however, the association of rs707176 with ASP HSRs was confined only to females. Our results suggest that genetic variants of GRIA1 might influence the risk to ASP hypersensitivity, but subgroups of patients can differ significantly in this respect.     

Towards a Supertree of Arthropoda: A Species-Level Supertree of the Spiny,Slipper and Coral Lobsters (Decapoda: Achelata)

While supertrees have been built for many vertebrate groups (notably birds, mammals and dinosaurs), invertebrates have attracted relatively little attention. The paucity of supertrees of arthropods is particularly surprising given their economic and ecological importance, as well as their overwhelming contribution to biodiversity. The absence of comprehensive archives of machine-readable source trees, coupled with the need for software implementing repeatable protocols for managing them, has undoubtedly impeded progress. Here we present a supertree of Achelata (spiny, slipper and coral lobsters) as a proof of concept, constructed using new supertree specific software (the Supertree Toolkit; STK) and following a published protocol. We also introduce a new resource for archiving and managing published source trees. Our supertree of Achelata is synthesised from morphological and molecular source trees, and represents the most complete species-level tree of the group to date. Our findings are consistent with recent taxonomic treatments, confirming the validity of just two families: Palinuridae and Scyllaridae; Synaxidae were resolved within Palinuridae. Monophyletic Silentes and Stridentes lineages are recovered within Palinuridae, and all sub-families within Scyllaridae are found to be monophyletic with the exception of Ibacinae. We demonstrate the feasibility of building larger supertrees of arthropods, with the ultimate objective of building a complete species-level phylogeny for the entire phylum using a divide and conquer strategy.     

The Customer Isn't Always Right—Conservation and Animal Welfare Implications of the Increasing Demand for Wildlife Tourism

Tourism accounts for 9% of global GDP and comprises 1.1 billion tourist arrivals per annum. Visits to wildlife tourist attractions (WTAs) may account for 20–40% of global tourism, but no studies have audited the diversity of WTAs and their impacts on the conservation status and welfare of subject animals. We scored these impacts for 24 types of WTA, visited by 3.6–6 million tourists per year, and compared our scores to tourists’ feedback on TripAdvisor. Six WTA types (impacting 1,500–13,000 individual animals) had net positive conservation/welfare impacts, but 14 (120,000–340,000 individuals) had negative conservation impacts and 18 (230,000–550,000 individuals) had negative welfare impacts. Despite these figures only 7.8% of all tourist feedback on these WTAs was negative due to conservation/welfare concerns. We demonstrate that WTAs have substantial negative effects that are unrecognised by the majority of tourists, suggesting an urgent need for tourist education and regulation of WTAs worldwide.     

Synthetic prions with novel strain-specified properties

Prions are infectious proteins that possess multiple self-propagating structures. The information for strains and structural specific barriers appears to be contained exclusively in the folding of the pathological isoform, PrP^Sc. Many recent studies determined that de novo prion strains could be generated in vitro from the structural conversion of recombinant (rec) prion protein (PrP) into amyloidal structures. Our aim was to elucidate the conformational diversity of pathological recPrP amyloids and their biological activities, as well as to gain novel insights in characterizing molecular events involved in mammalian prion conversion and propagation. To this end we generated infectious materials that possess different conformational structures. Our methodology for the prion conversion of recPrP required only purified rec full-length mouse (Mo) PrP and common chemicals. Neither infected brain extracts nor amplified PrP^Sc were used. Following two different in vitro protocols recMoPrP converted to amyloid fibrils without any seeding factor. Mouse hypothalamic GT1 and neuroblastoma N2a cell lines were infected with these amyloid preparations as fast screening methodology to characterize the infectious materials. Remarkably, a large number of amyloid preparations were able to induce the conformational change of endogenous PrP^C to harbor several distinctive proteinase-resistant PrP forms. One such preparation was characterized in vivo habouring a synthetic prion with novel strain specified neuropathological and biochemical properties.     

A real-time computational model for estimating kinematics of ankle ligaments

Background: An accurate assessment of ankle ligament kinematics is crucial in understanding the injury mechanisms and can help to improve the treatment of an injured ankle, especially when used in conjunction with robot-assisted therapy. A number of computational models have been developed and validated for assessing the kinematics of ankle ligaments. However, few of them can do real-time assessment to allow for an input into robotic rehabilitation programs. Method: An ankle computational model was proposed and validated to quantify the kinematics of ankle ligaments as the foot moves in real-time. This model consists of three bone segments with three rotational degrees of freedom (DOFs) and 12 ankle ligaments. This model uses inputs for three position variables that can be measured from sensors in many ankle robotic devices that detect postures within the foot–ankle environment and outputs the kinematics of ankle ligaments. Validation of this model in terms of ligament length and strain was conducted by comparing it with published data on cadaver anatomy and magnetic resonance imaging. Results: The model based on ligament lengths and strains is in concurrence with those from the published studies but is sensitive to ligament attachment positions. Conclusions: This ankle computational model has the potential to be used in robot-assisted therapy for real-time assessment of ligament kinematics. The results provide information regarding the quantification of kinematics associated with ankle ligaments related to the disability level and can be used for optimizing the robotic training trajectory.     

Search for lectins in seeds of tropical trees of Kerala, India

Tissue specific plant lectins were searched in the seeds of 44 tropical trees of Kerala, India. Seeds of only 12 plant species showed lectin activity. N-acetyl-D-galactosamine was the best inhibitor of lectin activity for the majority of the seeds. Lectin activity in the seeds of 4 species were not inhibited by any of the mono- or polysaccharides used. This revised version was published online in July 2006 with corrections to the Cover Date.