Dephasing in (Ga,Mn)As nanowires and rings

To understand quantum mechanical transport in ferromagnetic semiconductor the knowledge of basic material properties like phase coherence length and corresponding dephasing mechanism are indispensable ingredients. The lack of observable quantum phenomena prevented experimental access to these quantities so far. Here we report about the observations of universal conductance fluctuations in ferromagnetic (Ga,Mn)As. The analysis of the length and temperature dependence of the fluctuations reveals a T^{-1} dependence of the dephasing time.Comment: 5 pages, 4 figure

Pluripotent stem cells and their dynamic niche

Cell-seeded implants are a regenerative medicine strategy that aims to replace injured tissue and restore tissue function. Pluripotent stem cells are promising cell candidates for the development of regenerative medicine therapies as they have the ability to self-renew and commit towards numerous cell types. In vivo, stem cells reside in a dynamic niche, a stem cell-specific microenvironment that possesses chemical, biological and mechanical cues, which drive the stem cell fate and renewal. The connection between stem cells and their niche is a two-way relationship consisting of both cell–cell interac‐tion and cell–extracellular matrix (ECM) interactions. An alternative regenerative medicine approach is the manipulation of the stem cell microenvironment. Hence, novel strategies have been developed including 3D biomaterials and bioreactor technologies providing topographical, chemical and mechanical cues to recreate the stem cell niche. Understanding the mechanisms controlling stem cell fate and the dynamic nature of thestem cell niche will enable researchers to replicate this stem cell-specific microenvironment, and therefore, harness and control the valuable attributes which stem cells possess. This chapter elucidates the importance of pluripotent stem cells and their dynamic niche in regenerative medicine. It further presents novel strategies to replicate chemical, topographical and mechanical stimuli which are essential for the regulation of stem cell fate and hence tissue regeneration

Current advances on the regeneration of musculoskeletal interfaces

The regeneration of the musculoskeletal system has been widely investigated. There is now detailed knowledge about the organs composing this system. Research has also investigated the zones between individual tissues where physical, mechanical, and biochemical properties transition. However, the understanding of the regeneration of musculoskeletal interfaces is still lacking behind. Numerous disorders and injuries can degrade or damage tissue interfaces. Their inability to regenerate can delay the tissue repair and regeneration process, leading to graft instability, high morbidity, and pain. Moreover, the knowledge of the mechanism of tissue interface development is not complete. This review presents an overview of the most recent approaches of the regeneration of musculoskeletal interfaces, including the latest in vitro, preclinical, and clinical studies

Unilateral cranial defect bone reconstruction utilising 3D design and manufacturing

A cranial contour defect can occur when bone is removed following direct trauma, removal of a tumor or for surgical access to the brain. These defects impair function (protection) and aesthetic contour and require a design strategy for reconstructing the defect. In principle, if the defect is unilateral (one side) then designing a form to restore the contour could be assisted by attaining a mirror image of the undamaged side of the skull. As an alternative to mirroring the undamaged skull an interpolated surface could also be generated for repairing this cranial defect. A case with a unilateral left temporal bone defect was considered for this study. A cranioplasty reconstruction was to be performed to restore the bone contour. The patient's Computed Tomography (CT) scan (1 mm slice thickness) was saved in the raw file format Digital Imaging and Communication in Medicine (DICOM). The DICOM data was converted to a standard tessellation file (stl.) using MIMICS software (Materialise V24. Belgium). The stl. file of the skull was used to generate a 3D design of the implant using Computer-aided Design/ Computer-aided Manufacturing (CAD/CAM) software. The design was used to 3D print a base template, which could finally be used to fabricate the physical implant to restore the defect. This case explored the two techniques of mirroring and interpolation for repairing a cranial defect. A comparison of the two techniques was performed. Feedback from the surgeon suggested that interpolation provided a digitally accurate implant surface comparable to a mirrored implant

Optimizing cranial implant and fixture design using different materials in cranioplasty

Cranial implants are used to secure intracranial structures, reconstruct the skull contour, normalise cerebral hemodynamic, and repair cranial defects. Larger bone defects require intervention for repair from an implant made from autologous bone or other material. To repair such defects using implants, materials necessitate biocompatibility with the natural bone. Patient Specific Implants (PSI) are designed to repair specific cranial defects following standard procedures for implant design, fabrication and cranioplasty. Autologous bone, bone cement comprising HydroxyApatite (HA), Poly methyl methacrylate (PMMA), Medical Grade Titanium Alloy (Ti-6Al-4V) and Polyether-ether-ketone (PEEK), are widely used to fabricate PSI for repairing different types of bone defects. To optimize a PSI for shape, size and weight, it is essential to design the implant using 3D modelling and fabrication techniques. Effective attachment of an implant material with a defective skull is also influenced by the joints and fixture arrangements at the interface, these fixtures can be of various types, materials and have different joining procedures. In this study, a comparative analysis of different cranial implant materials (Autologous Bone, PMMA, PEEK and Ti-6Al-4V) attached to a defective skull with Ti-6Al-4V and PEEK fixture plates has been performed, using Finite Element Analysis (FEA). Two types of fixture designs were used as Square 'X' and Linear shapes, which were fixed along the interface between implant and the skull. Four fixture plates were fixed symmetrically along the boundary for maximising stability. The findings suggested that all the implant materials were able to sustain extreme boundary conditions such as external loads of 1780N and IntraCranial Pressure (ICP) of 15mmHg without failures. PEEK implants exhibited 13.5 % to 35% lower von Mises stresses in comparison to autologous bone implants and Square 'X' fixture design provided higher stress relieving results in comparison to Linear fixtures by nearly 18.4% for Ti-6Al-4V fixture material and 10.9% for PEEK fixture material, thereby, encouraging PEEK as an alternative to conventional cranial implant and fixture materials

Real-time and non-invasive measurements of cell mechanical behaviour with optical coherence phase microscopy

There is an unmet need in tissue engineering for non-invasive, label-free monitoring of cell mechanical behaviour in their physiological environment. Here, we describe a novel optical coherence phase microscopy (OCPM) set-up which can map relative cell mechanical behaviour in monolayers and 3D systems non-invasively, and in real-time. 3T3 and MCF-7 cells were investigated, with MCF-7 demonstrating an increased response to hydrostatic stimulus indicating MCF-7 being softer than 3T3, demonstrating the ability to provide qualitative data on cell mechanical behaviour. Quantitative measurements of 6% agarose beads have been taken with commercial Cell Scale Microsquisher® system demonstrating that their mechanical properties are in the same order of magnitude of cells, indicating that this is an appropriate test sample for the novel method desctibed

An IL1RL1 genetic variant lowers soluble ST2 levels and the risk effects of APOE-ε4 in female patients with Alzheimer’s disease

Changes in the levels of circulating proteins are associated with Alzheimer’s disease (AD), whereas their pathogenic roles in AD are unclear. Here, we identified soluble ST2 (sST2), a decoy receptor of interleukin-33–ST2 signaling, as a new disease-causing factor in AD. Increased circulating sST2 level is associated with more severe pathological changes in female individuals with AD. Genome-wide association analysis and CRISPR–Cas9 genome editing identified rs1921622, a genetic variant in an enhancer element of IL1RL1, which downregulates gene and protein levels of sST2. Mendelian randomization analysis using genetic variants, including rs1921622, demonstrated that decreased sST2 levels lower AD risk and related endophenotypes in females carrying the Apolipoprotein E (APOE)-ε4 genotype; the association is stronger in Chinese than in European-descent populations. Human and mouse transcriptome and immunohistochemical studies showed that rs1921622/sST2 regulates amyloid-beta (Aβ) pathology through the modulation of microglial activation and Aβ clearance. These findings demonstrate how sST2 level is modulated by a genetic variation and plays a disease-causing role in females with AD

Plasma phosphorylated-tau181 as a predictive biomarker for Alzheimer’s amyloid, tau and FDG PET status

Plasma phosphorylated-tau181 (p-tau181) showed the potential for Alzheimer’s diagnosis and prognosis, but its role in detecting cerebral pathologies is unclear. We aimed to evaluate whether it could serve as a marker for Alzheimer’s pathology in the brain. A total of 1189 participants with plasma p-tau181 and PET data of amyloid, tau or FDG PET were included from ADNI. Cross-sectional relationships of plasma p-tau181 with PET biomarkers were tested. Longitudinally, we further investigated whether different p-tau181 levels at baseline predicted different progression of Alzheimer’s pathological changes in the brain. We found plasma p-tau181 significantly correlated with brain amyloid (Spearman ρ = 0.45, P 18.85 pg/ml) at baseline had a higher risk of pathological progression in brain amyloid (HR: 2.32, 95%CI 1.32–4.08) and FDG PET (3.21, 95%CI 2.06–5.01) status. Plasma p-tau181 may be a sensitive screening test for detecting brain pathologies, and serve as a predictive biomarker for Alzheimer’s pathophysiology

Comprehensive analysis of epigenetic clocks reveals associations between disproportionate biological ageing and hippocampal volume

The concept of age acceleration, the difference between biological age and chronological age, is of growing interest, particularly with respect to age-related disorders, such as Alzheimer’s Disease (AD). Whilst studies have reported associations with AD risk and related phenotypes, there remains a lack of consensus on these associations. Here we aimed to comprehensively investigate the relationship between five recognised measures of age acceleration, based on DNA methylation patterns (DNAm age), and cross-sectional and longitudinal cognition and AD-related neuroimaging phenotypes (volumetric MRI and Amyloid-β PET) in the Australian Imaging, Biomarkers and Lifestyle (AIBL) and the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Significant associations were observed between age acceleration using the Hannum epigenetic clock and cross-sectional hippocampal volume in AIBL and replicated in ADNI. In AIBL, several other findings were observed cross-sectionally, including a significant association between hippocampal volume and the Hannum and Phenoage epigenetic clocks. Further, significant associations were also observed between hippocampal volume and the Zhang and Phenoage epigenetic clocks within Amyloid-β positive individuals. However, these were not validated within the ADNI cohort. No associations between age acceleration and other Alzheimer’s disease-related phenotypes, including measures of cognition or brain Amyloid-β burden, were observed, and there was no association with longitudinal change in any phenotype. This study presents a link between age acceleration, as determined using DNA methylation, and hippocampal volume that was statistically significant across two highly characterised cohorts. The results presented in this study contribute to a growing literature that supports the role of epigenetic modifications in ageing and AD-related phenotypes

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder