Secondary biochemical and morphological consequences in lysosomal storage diseases

More than 50 hereditary lysosomal storage disorders (LSDs) are currently described. Most of these disorders are due to a deficiency of certain hydrolases/glycosidases and subsequent accumulation of nonhydrolyzable carbohydrate-containing compounds in lysosomes. Such accumulation causing hypertrophy of the lysosomal compartment is a characteristic feature of affected cells in LSDs. The investigation of biochemical and cellular parameters is of particular interest for understanding “life” of lysosomes in the normal state and in LSDs. This review highlights the wide spectrum of biochemical and morphological changes during developing LSDs that are extremely critical for many metabolic processes inside the various cells and tissues of affected persons. The data presented will help establish new complex strategies for metabolic correction of LSDs.     

Biosorption of Cr(VI) by Ceratocystis paradoxa MSR2 Using Isotherm Modelling,Kinetic Study and Optimization of Batch Parameters Using Response Surface Methodology

This study is focused on the possible use of Ceratocystis paradoxa MSR2 native biomass for Cr(VI) biosorption. The influence of experimental parameters such as initial pH, temperature, biomass dosage, initial Cr(VI) concentration and contact time were optimized using batch systems as well as response surface methodology (RSM). Maximum Cr(VI) removal of 68.72% was achieved, at an optimal condition of biomass dosage 2g L⁻¹, initial Cr(VI) concentration of 62.5 mg L⁻¹ and contact time of 60 min. The closeness of the experimental and the predicted values exhibit the success of RSM. The biosorption mechanism of MSR2 biosorbent was well described by Langmuir isotherm and a pseudo second order kinetic model, with a high regression coefficient. The thermodynamic study also revealed the spontaneity and exothermic nature of the process. The surface characterization using FT-IR analysis revealed the involvement of amine, carbonyl and carboxyl groups in the biosorption process. Additionally, desorption efficiency of 92% was found with 0.1 M HNO₃. The Cr(VI) removal efficiency, increased with increase in metal ion concentration, biomass concentration, temperature but with a decrease in pH. The size of the MSR2 biosorbent material was found to be 80 μm using particle size analyzer. Atomic force microscopy (AFM) visualizes the distribution of Cr(VI) on the biosorbent binding sites with alterations in the MSR2 surface structure. The SEM-EDAX analysis was also used to evaluate the binding characteristics of MSR2 strain with Cr(VI) metals. The mechanism of Cr(VI) removal of MSR2 biomass has also been proposed.     

Simplified Aeroelastic Model for Fluid Structure Interaction between Microcantilever Sensors and Fluid Surroundings

Fluid-structural coupling occurs when microcantilever sensors vibrate in a fluid. Due to the complexity of the mechanical characteristics of microcantilevers and lack of high-precision microscopic mechanical testing instruments, effective methods for studying the fluid-structural coupling of microcantilevers are lacking, especially for non-rectangular microcantilevers. Here, we report fluid-structure interactions (FSI) of the cable-membrane structure via a macroscopic study. The simplified aeroelastic model was introduced into the microscopic field to establish a fluid-structure coupling vibration model for microcantilever sensors. We used the finite element method to solve the coupled FSI system. Based on the simplified aeroelastic model, simulation analysis of the effects of the air environment on the vibration of the commonly used rectangular microcantilever was also performed. The obtained results are consistent with the literature. The proposed model can also be applied to the auxiliary design of rectangular and non-rectangular sensors used in fluid environments.     

Broad Anatomical Variation within a Narrow Wood Density Range—A Study of Twig Wood across 69 Australian Angiosperms

ObjectivesJust as people with the same weight can have different body builds, woods with the same wood density can have different anatomies. Here, our aim was to assess the magnitude of anatomical variation within a restricted range of wood density and explore its potential ecological implications.MethodsTwig wood of 69 angiosperm tree and shrub species was analyzed. Species were selected so that wood density varied within a relatively narrow range (0.38–0.62 g cm^-3). Anatomical traits quantified included wood tissue fractions (fibres, axial parenchyma, ray parenchyma, vessels, and conduits with maximum lumen diameter below 15 μm), vessel properties, and pith area. To search for potential ecological correlates of anatomical variation the species were sampled across rainfall and temperature contrasts, and several other ecologically-relevant traits were measured (plant height, leaf area to sapwood area ratio, and modulus of elasticity).ResultsDespite the limited range in wood density, substantial anatomical variation was observed. Total parenchyma fraction varied from 0.12 to 0.66 and fibre fraction from 0.20 to 0.74, and these two traits were strongly inversely correlated (r = -0.86, P < 0.001). Parenchyma was weakly (0.24 ≤|r|≤ 0.35, P < 0.05) or not associated with vessel properties nor with height, leaf area to sapwood area ratio, and modulus of elasticity (0.24 ≤|r|≤ 0.41, P < 0.05). However, vessel traits were fairly well correlated with height and leaf area to sapwood area ratio (0.47 ≤|r|≤ 0.65, all P < 0.001). Modulus of elasticity was mainly driven by fibre wall plus vessel wall fraction rather than by the parenchyma component.ConclusionsOverall, there seem to be at least three axes of variation in xylem, substantially independent of each other: a wood density spectrum, a fibre-parenchyma spectrum, and a vessel area spectrum. The fibre-parenchyma spectrum does not yet have any clear or convincing ecological interpretation.     

Small Heat-Shock Proteins,IbpAB, Protect Non-Pathogenic Escherichia coli from Killing by Macrophage-Derived Reactive Oxygen Species

Many intracellular bacterial pathogens possess virulence factors that prevent detection and killing by macrophages. However, similar virulence factors in non-pathogenic bacteria are less well-characterized and may contribute to the pathogenesis of chronic inflammatory conditions such as Crohn’s disease. We hypothesize that the small heat shock proteins IbpAB, which have previously been shown to reduce oxidative damage to proteins in vitro and be upregulated in luminal non-pathogenic Escherichia strain NC101 during experimental colitis in vivo, protect commensal E. coli from killing by macrophage-derived reactive oxygen species (ROS). Using real-time PCR, we measured ibpAB expression in commensal E. coli NC101 within wild-type (wt) and ROS-deficient (gp91phox^-/-) macrophages and in NC101 treated with the ROS generator paraquat. We also quantified survival of NC101 and isogenic mutants in wt and gp91phox^-/- macrophages using gentamicin protection assays. Similar assays were performed using a pathogenic E. coli strain O157:H7. We show that non-pathogenic E. coli NC101inside macrophages upregulate ibpAB within 2 hrs of phagocytosis in a ROS-dependent manner and that ibpAB protect E. coli from killing by macrophage-derived ROS. Moreover, we demonstrate that ROS-induced ibpAB expression is mediated by the small E. coli regulatory RNA, oxyS. IbpAB are not upregulated in pathogenic E. coli O157:H7 and do not affect its survival within macrophages. Together, these findings indicate that ibpAB may be novel virulence factors for certain non-pathogenic E. coli strains.     

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.     

Effect of Bone Mineral Density on Rotator Cuff Tear: An Osteoporotic Rabbit Model

IntroductionAn increased bone mineral density (BMD) in the proximity to tendon insertion can improve rotator cuff repair and healing. However, how a decrease of BMD in the humeral head affects the biomechanical properties of the rotator cuff tendon is still unclear. Previous studies have demonstrated ovariectomy in animals to lead to osteoporosis and decreased BMD, and Teriparatide (PTH) administration to improve BMD and strength of bone. This study aimed to explore the correlation between humeral head BMD and infraspinatus (ISP) tendon insertion strength, and if an increase in bone quantity of the humeral head can improve the strength of the rotator cuff.ResultsSignificant differences were observed in the measured humeral head BMD of the Control and OVX-PTH groups compared to the OVX-Saline group (P = 0.0004 and P = 0.0024, respectively). No significant difference was found in failure stress among the three groups, but an expected trend with the control group and OVX-PTH group presenting higher failure strength compared to the OVX-Saline group. BMD at the humeral head showed a positive linear correlation with stress (r² = 0.54). Histology results showed the superiority in OVX-PTH group ISP enthesis compared to the OVX-Saline group.ConclusionBone loss of the humeral head leads to decreased tendon/bone insertion strength of the infraspinatus tendon enthesis. Teriparatide administration can increase bone density of the humeral head and may improve the mechanical properties of the infraspinatus tendon enthesis.