Could a dysfunction of ferritin be a determinant factor in the aetiology of some neurodegenerative diseases?

Background

The concentration of iron in the brain increases with aging. Furthermore, it has also been observed that patients suffering from neurological diseases (e.g. Parkinson, Alzheimer…) accumulate iron in the brain regions affected by the disease. Nevertheless, it is still not clear whether this accumulation is the initial cause or a secondary consequence of the disease. Free iron excess may be an oxidative stress source causing cell damage if it is not correctly stored in ferritin cores as a ferric iron oxide redox-inert form.

Scope

Both, the composition of ferritin cores and their location at subcellular level have been studied using analytical transmission electron microscopy in brain tissues from progressive supranuclear palsy (PSP) and Alzheimer disease (AD) patients.

Major conclusions

Ferritin has been mainly found in oligodendrocytes and in dystrophic myelinated axons from the neuropili in AD. In relation to the biomineralization of iron inside the ferritin shell, several different crystalline structures have been observed in the study of physiological and pathological ferritin. Two cubic mixed ferric–ferrous iron oxides are the major components of pathological ferritins whereas ferrihydrite, a hexagonal ferric iron oxide, is the major component of physiological ferritin. We hypothesize a dysfunction of ferritin in its ferroxidase activity.

General significance

The different mineralization of iron inside ferritin may be related to oxidative stress in olygodendrocites, which could affect myelination processes with the consequent perturbation of information transference.     

The effects of a loin muscling quantitative trait locus (LoinMAX™) on carcass and VIA-based traits in crossbred lambs

LoinMAX (LM) is a quantitative trait locus (QTL), which was found to be segregated in Australian Poll Dorset sheep, and maps to the distal end of sheep chromosome 18. LM-QTL was reported to increase Musculus longissimus dorsi area and weight by 11% and 8%, respectively. The aim of this study was to comprehensively evaluate the direct effects of LM-QTL in a genetic background typical of the stratified structure of the UK sheep industry, before it can be recommended for use in the United Kingdom. Crossbred lambs, either non-carriers or carrying a single copy of LM-QTL, were produced out of Scottish Mule ewes (Bluefaced Leicester × Scottish Blackface) artificially inseminated with semen from two Poll Dorset rams that were heterozygous for LM-QTL. Unexpectedly, one of these rams was also heterozygous for a QTL that affects the overall carcass muscling (MyoMAX™). This was accounted for by nesting MyoMAX™ status (carrier or non-carrier) within sire in the statistical analysis. Lambs were weighed and scanned by using X-ray computed tomography (CT) at an average age of 113 days. Ultrasound scan measurements, along with lamb weights, were taken at an average age of 140 days and lambs were then slaughtered. Carcasses were weighed and classified for fat cover and conformation scores, based on the Meat and Livestock Commission (MLC) carcass classification scheme, and then scanned by using a video image analysis (VIA) system. M. longissimus lumborum (MLL) width, as measured by CT scanning, was greater (P < 0.05) in lambs heterozygous for LM-QTL compared with non-carriers. MLL in LM-QTL carrier lambs was also significantly deeper, as measured by both ultrasound muscle depth at the third lumbar vertebrae (+3.7%; P < 0.05) and CT scanning at the fifth lumbar vertebrae (+3.4%; P < 0.01). Consequently, MLL area, was measured by using CT scanning, was significantly higher (+4.5%; P < 0.01) in lambs carrying a single copy of LM-QTL compared with non-carriers. Additional traits measured by CT, such as leg muscle dimensions, average muscle density and tissue proportions, were not significantly affected by LM-QTL. LM-QTL did not significantly affect total carcass lean or fat weights or MLC conformation and fat score classifications. Using previously derived algorithms, VIA could detect a significant effect of the LM-QTL on the predicted weight of saleable meat yield in the loin primal cut (+2.2%; P < 0.05), but not in the other primal cuts, or the total carcass.     

Predicting beef carcass composition using tissue weights of a primal cut assessed by computed tomography

The potential of the composition of the forerib measured by X-ray computed tomography (CT) as a predictor of carcass composition was evaluated using data recorded on 30 Aberdeen Angus and 43 Limousin crossbred heifers and steers. The left sides of the carcasses were split into 20 cuts, which were CT scanned and fully dissected into fat, muscle and bone. Carcass and forerib tissue weights were assessed by dissection and CT. Carcass composition was assessed very accurately by CT scanning of the primal cuts (adj-R2 = 0.97 for the three tissues). CT scanning predicted weights of fat, muscle and bone of the forerib with adj-R2 of 0.95, 0.91 and 0.75, respectively. Single regression models with the weights of fat, muscle or bone in the forerib measured by CT as the only predictors to estimate fat, muscle or bone of the left carcass obtained by CT showed adjusted coefficients of determination (adj-R2) of 0.79, 0.60 and 0.52, respectively. By additionally fitting breed and sex, accuracy increased to 0.85, 0.73 and 0.67. Using carcass and forerib weights in addition to the previous predictors improved significantly the prediction accuracy of carcass fat and muscle weights to adj-R2 values of 0.92 and 0.96, respectively, while the highest value for carcass bone weight was 0.77. In general, equations derived using CT data had lower adj-R2 values for bone, but better accuracies for fat and muscle compared to those obtained using dissection. CT scanning could be considered as an alternative very accurate and fast method to assess beef carcass composition that could be very useful for breeding programmes and research studies involving a large number of animals, including the calibration of other indirect methods (e.g. in vivo and carcass video image analysis).     

Normoxic polymer gel dosimetry using less toxic monomer of N-isopropyl acrylamide and X-ray computed tomography for radiation therapy applications

Background

Polymer gel dosimetry has been used extensively in radiation therapy for its capability in depicting a three dimensional view of absorbed dose distribution. However, more studies are required to find less toxic and more efficient polymers for application in radiotherapy dosimetry.

Aim

The purpose of this work was to evaluate the N-isopropyl acrylamide (NIPAM) gel dosimetric characteristics and optimize the protocol for X-ray computed tomography (CT) imaging of gel dosimeters for radiation therapy application.

Material and methods

A polymer gel dosimeter based on NIPAM monomer was prepared and irradiated with ⁶⁰Co photons. The CT number changes following irradiation were extracted from CT images obtained with different sets of imaging parameters.

Results

The results showed the dose sensitivity of ΔN_CT (H) = 0.282 ± 0.018 (H Gy⁻¹) for NIPAM gel dosimeter. The optimized set of imaging exposure parameters was 120 kV_p and 200 mA with the 10 mm slice thickness. Results of the depth dose measurement with gel dosimeter showed a great discrepancy with the actual depth dose data.

Conclusion

According to the current study, NIPAM-based gel dosimetry with X-ray CT imaging needs more technical development and formulation refinement to be used for radiation therapy application.     

Imaging growth dynamics of tumour spheroids using optical coherence tomography

Optical coherence tomography (OCT) was used to monitor the dynamics of tumour spheroid formation by the hanging drop method. In contrast to microscopy, the estimates obtained using OCT for the volume of the spheroid, were consistent with the measured changes in cell number as a function of time. The OCT images also revealed heterogeneous structures in the spheroids of ∼200 μm diameter. These corresponded to the necrotic regions identified by fluorescence of propidium iodide stained cells.     

Bone density spatial patterns in the distal radius reflect habitual hand postures adopted by quadrupedal primates

Primates adopt diverse hand postures during terrestrial and above-branch quadrupedal locomotion--knuckle-walking, digitigrady, and palmigrady--that incorporate varying degrees of wrist dorsiflexion (i.e., extension). Although relationships between hand postures, wrist joint range of motion, and the external properties of wrist bones (e.g., surface morphology) have been examined, the relationship between hand postures and the internal properties of wrist bones (e.g., bone density) remains largely unexplored. Because articular joint surfaces transmit mechanical loads between conjoining limb bones, measures of density (e.g., magnitudes and patterns) in the subchondral cortical plate of bone of the distal radius can be used to evaluate load regimes experienced by the wrist joint in different hand postures. We assessed apparent (i.e. optical) density patterns in several extant catarrhine primate taxa partitioned into different hand posture groups: knuckle-walking apes, digitigrade monkeys, and palmigrade monkeys. Computed tomography osteoabsorptiometry (CT-OAM) was used to construct maximum intensity projection (MIP) maps of apparent densities. High apparent density areas were characterized relative to a dorsal-volar reference plane and compared across hand posture groups. All groups had large percentage areas of high apparent density in the dorsal region of the distal radial articular surface. Only knuckle-walking apes, however, had a large percentage area of high apparent density in the volar region of the distal radial articular surface. These patterns are consistent with radiocarpal articulations in specific hand postures as evidenced by available radiographic data and suggest that the different habitual hand postures adopted by monkeys and African apes during quadrupedal locomotion have different stereotypic loading patterns. This has implications for understanding the functional morphology and evolution of knuckle-walking and digitigrade hand postures in primates.     

Reliable simulations of the human proximal femur by high-order finite element analysis validated by experimental observations

Background: The mechanical response of patient-specific bone to various load conditions is of major clinical importance in orthopedics. Herein we enhance the methods presented in Yosibash et al. [2007. A CT-based high-order finite element analysis of the human proximal femur compared to in-vitro experiments. ASME Journal of Biomechanical Engineering 129(3), 297–309.] for the reliable simulations of the human proximal femur by high-order finite elements (FEs) and validate the simulations by experimental observations.

Method of approach: A fresh-frozen human femur was scanned by quantitative computed tomography (QCT) and thereafter loaded (in vitro experiments) by a quasi-static force of up to 1250 N. QCT scans were manipulated to generate a high-order FE bone model with distinct cortical and trabecular regions having inhomogeneous isotropic elastic properties with Young's modulus represented by continuous spatial functions. Sensitivity analyses were performed to quantify parameters that mostly influence the mechanical response. FE results were compared to displacements and strains measured in the experiments.

Results: Young moduli correlated to QCT Hounsfield Units by relations in Keyak and Falkinstein [2003. Comparison of in situ and in vitro CT scan-based finite element model predictions of proximal femoral fracture load. Medical Engineering and Physics 25, 781–787.] were found to provide predictions that match the experimental results closely. Excellent agreement was found for both the displacements and strains. The presented study demonstrates that reliable and validated high-order patient-specific FE simulations of human femurs based on QCT data are achievable for clinical computer-aided decision making.     

采用OCT系统对组织光学通透的研究

组织通透方法采用高折射率化学试剂对生物组织进行渗透,改变组织的光学均匀性,可以有效地改善光学成像的穿透深度,受到生物医学光学研究领域的重视。利用光学相干层析成像技术,测量通透过程中不同测量深度下组织的散射特征的变化。通过采用系统信号对数的梯度值近似地表征光学散射系数,研究了通透过程中组织的散射特征随渗透时间和测量深度的动态关系。实验证明了组织通透可以有效地增加光子的穿透深度,并改善成像质量。研究发现:不同测量深度处组织的散射系数及其变化幅度、变化过程和变化趋势等均存在一定的差异性,并与组织的微观结构、其通透效果,化学试剂在组织中的渗透行为等有密切关系,有助于组织通透过程的理解,并为组织通透机制提供可能的实验依据。