Beta-glucosidase 1 (GBA1) is a second bile acid ß-glucosidase in addition to ß-glucosidase 2 (GBA2). Study in ß-glucosidase deficient mice and humans.

Beta-glucosidase 1 (GBA1; lysosomal glucocerebrosidase) and ß-glucosidase 2 (GBA2, non-lysosomal glucocerebrosidase) both have glucosylceramide as a main natural substrate. The enzyme-deficient conditions with glucosylceramide accumulation are Gaucher disease (GBA-/- in humans), modelled by the Gba-/- mouse, and the syndrome with male infertility in the Gba2-/- mouse, respectively. Before the leading role of glucosylceramide was recognised for both deficient conditions, bile acid-3-O-ß-glucoside (BG), another natural substrate, was viewed as the main substrate of GBA2. Given that GBA2 hydrolyses both BG and glucosylceramide, it was asked whether vice versa GBA1 hydrolyses both glucosylceramide and BG. Here we show that GBA1 also hydrolyses BG. We compared the residual BG hydrolysing activities in the GBA1-/-, Gba1-/- conditions (where GBA2 is the almost only active ß-glucosidase) and those in the Gba2-/- condition (GBA1 active), with wild-type activities, but we used also the GBA1 inhibitor isofagomine. GBA1 and GBA2 activities had characteristic differences between the studied fibroblast, liver and brain samples. Independently, the hydrolysis of BG by pure recombinant GBA1 was shown. The fact that both GBA1 and GBA2 are glucocerebrosidases as well as bile acid ß-glucosidases raises the question, why lysosomal accumulation of glucosylceramide in GBA1 deficiency, and extra-lysosomal accumulation in GBA2 deficiency, are not associated with an accumulation of BG in either condition.

Imaging hemorrhagic stroke with magnetic induction tomography: realistic simulation and evaluation.

Magnetic induction tomography (MIT) is a noncontact method for detecting the internal conductivity distribution of an object. This technology has the potential to be used in the biomedical area to check bio-impedance change inside the human body, for example to detect hemorrhage in the human brain. In this study the hemorrhagic stroke detectability with a 16-channel MIT system operating at 10 MHz was evaluated. Since the conductivity distribution is changed by the hemorrhagic stroke as well as the squeezed brain tissue around the stroke, deformation of the brain tissue is also considered and simulated with the help of a FEM-based linear bio-mechanical model in this paper. To simulate the raw measurement data as realistically as possible, the noise estimated from the experimental MIT system with hypothesis testing methods at 95% confidence level is added to the simulated measurements. Stroke images of 600 noisy samples for each detection assignment are reconstructed by the one-step Tikhonov-regularized inverse eddy current solution. Under the statistical framework, the detection failure is in control of a high false negative rate which represents a large artifact visualized in the reconstruction domain. The qualitative detectability of 18 detecting assignments, with three hemorrhagic positions (shallow, medial and center of the cerebrum) and two volume values (10 ml and 20 ml), overlaid by noise with three levels (standard deviation of phase change at 5 x 10(-3) degrees , 2.5 x 10(-3) degrees , 10 x 10(-3) degrees ), are investigated. These detecting assignments are compared with each other to find out which volumes of deformed spherical hemorrhagic stroke can be detected by the modeled MIT system.