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.     

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.     

Transmission of parasites in the coastal waters of the Arctic seas and possible effect of climate change

The review deals with the biodiversity, life cycles, distribution and temperature adaptations of parasites circulating in the coastal waters of northern polar seas. Special attention is given to helminths of marine birds, which are the most common parasites in the coastal waters. Among them, the focus is on trematodes. Factors responsible for the impoverished species composition of parasites in the Arctic are analyzed. It is shown that species without free-living larvae in the life cycle have an advantage in this environment. The abundance of cestodes and acanthocephalans in Arctic seabirds is linked with the high proportion of crustaceans in their diet. The phenomenon of nonspecific parasitism (occurrence of parasites in atypical host species) is analyzed from an evolutionary viewpoint. Characteristic features in the spatial distribution of infection of marine coastal invertebrates with parasite larvae are considered, and factors that determine it are specified. The prevalence of infection in intermediate hosts is closely connected with the abundance of final hosts, which makes it possible to estimate the abundance of final hosts in a given region and reveal trends in its changes. Trematodes have a high potential for temperature acclimation. This facilitates their transmission in the northern seas but, on the other hand, makes it unlikely that the transmission process would be intensified upon an increase in summer temperatures resulting from climate warming. However, intensification of transmission may well occur due to the prolongation of the warm season (“transmission window”), which has been predicted and is already observed. It is suggested that warming in the Arctic promotes both the entry of certain “southern” species into the Arctic and the trans-Arctic interpenetration of the North Atlantic and North Pacific parasitic faunas. A case is made for the necessity to broaden the scope of parasitological research in the Arctic and Subarctic, including parasitological monitoring at the reference sites of the sea coast.     

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.     

The Cultural-Historical Development of Mental Processes and the Theory of Stepwise Formation of Mental Actions and Concepts

The article examines the problem of the relationship between universal and specific forms of cultural–historical development of mental processes. From different methodological approaches, the author prefers an activity approach which emphasizes genetic primacy of external practical activity. This approach allows, according to the author, universality of internalization and at the same time ethnic uniqueness of mental processes. The article clarifies the problem of internalization through two practical examples: 1) the development of mental counting actions and 2) the process of human goal setting.