Accurate volume alignment of arbitrarily oriented tibiae based on a mutual attention network for osteoarthritis analysis

Damage to cartilage is an important indicator of osteoarthritis progression, but manual extraction of cartilage morphology is time-consuming and prone to error. To address this, we hypothesize that automatic labeling of cartilage can be achieved through the comparison of contrasted and non-contrasted Computer Tomography (CT). However, this is non-trivial as the pre-clinical volumes are at arbitrary starting poses due to the lack of standardized acquisition protocols. Thus, we propose an annotation-free deep learning method, D-net, for accurate and automatic alignment of pre- and post-contrasted cartilage CT volumes. D-Net is based on a novel mutual attention network structure to capture large-range translation and full-range rotation without the need for a prior pose template. CT volumes of mice tibiae are used for validation, with synthetic transformation for training and tested with real pre- and post-contrasted CT volumes. Analysis of Variance (ANOVA) was used to compare the different network structures. Our proposed method, D-net, achieves a Dice coefficient of 0.87, and significantly outperforms other state-of-the-art deep learning models, in the real-world alignment of 50 pairs of pre- and post-contrasted CT volumes when cascaded as a multi-stage network

A New Role for TIMP-1 in Modulating Neurite Outgrowth and Morphology of Cortical Neurons

BACKGROUND:Tissue inhibitor of metalloproteinases-1 (TIMP-1) displays pleiotropic activities, both dependent and independent of its inhibitory activity on matrix metalloproteinases (MMPs). In the central nervous system (CNS), TIMP-1 is strongly upregulated in reactive astrocytes and cortical neurons following excitotoxic/inflammatory stimuli, but no information exists on its effects on growth and morphology of cortical neurons. PRINCIPAL FINDINGS:We found that 24 h incubation with recombinant TIMP-1 induced a 35% reduction in neurite length and significantly increased growth cones size and the number of F-actin rich microprocesses. TIMP-1 mediated reduction in neurite length affected both dendrites and axons after 48 h treatment. The effects on neurite length and morphology were not elicited by a mutated form of TIMP-1 inactive against MMP-1, -2 and -3, and still inhibitory for MMP-9, but were mimicked by a broad spectrum MMP inhibitor. MMP-9 was poorly expressed in developing cortical neurons, unlike MMP-2 which was present in growth cones and whose selective inhibition caused neurite length reductions similar to those induced by TIMP-1. Moreover, TIMP-1 mediated changes in cytoskeleton reorganisation were not accompanied by modifications in the expression levels of actin, betaIII-tubulin, or microtubule assembly regulatory protein MAP2c. Transfection-mediated overexpression of TIMP-1 dramatically reduced neuritic arbour extension in the absence of detectable levels of released extracellular TIMP-1. CONCLUSIONS:Altogether, TIMP-1 emerges as a modulator of neuronal outgrowth and morphology in a paracrine and autrocrine manner through the inhibition, at least in part, of MMP-2 and not MMP-9. These findings may help us understand the role of the MMP/TIMP system in post-lesion pre-scarring conditions

TIMP-3 interaction with aggrecanase 1 (ADAMTS-4) and aggrecanse 2 (ADAMTS-5)investigated by site-directed mutagenesis

Degradation of the proteoglycan aggrecan, one ofthe major components ofthe cartilage matrix, is thought to be a critical step in the development of osteoarthritis (OA). Both matrix metalloproteinases (MMPs) and aggrecanases [members of the ADAMTS (a disintegrin and metalloprotease with thrombospondin motifs) family have been shown to degrade aggrecan in vitro. However, there is debate as to their relative roles in vivo. The tissue inhibitor of metalloproteinases 3 (TIMP-3), which inhibits the MMPs, is the most potent tissue inhibitor of the aggrecanases, ADAMTS-4 and ADAMTS-S. The purpose of this thesis is to investigate the key elements of TIMP-3 interaction with the ADAMTS enzymes with the aim of engineering an inhibitor that would discriminate between the MMPs and the ADAMTSs, which would provide insight into the relative contributions of MMPs and ADAMTSs in aggrecan degradation in the OA disease process. Initially I describe the characterisation of a new recombinant substrate based on the interglobular domain of aggrecan, designed to enable rapid quantification of aggrecanase activity. This assay was used to determine which region of the N-terminal inhibitory domain of TIMP-3 (N-TIMP-3) is responsible for the inhibition of ADAMTS-4 and ADAMTS-S. I determined this by expressing chimeras of N-TIMP-I which does not inhibit the aggrecanases and N-TIMP-3. I shall then describe the kinetic analysis of aggrecanase inhibition by several N-TIMP-3 mutants that have previously been shown to be poor inhibitors of MMPs, but are potent inhibitors of a related proteinase, ADAM-I7 (tumor necrosis factor a converting enzyme). These mutants were found to be good inhibitors of both ADAMTS-4 and ADAMTS-S, and effectively protected aggrecan.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

D-net: Siamese based network with mutual attention for volume alignment

Alignment of contrast and non contrast-enhanced imaging is essential for quantification of changes in several biomedical applications. In particular, the extraction of cartilage shape from contrast-enhanced Computed Tomography (CT) of tibiae requires accurate alignment of the bone, currently performed manually. Existing deep learning-based methods for alignment require a common template or are limited in rotation range. Therefore, we present a novel network, D-net, to estimate arbitrary rotation and translation between 3D CT scans that additionally does not require a prior template. D-net is an extension to the branched Siamese encoder-decoder structure connected by new mutual, non-local links, which efficiently capture long-range connections of similar features between two branches. The 3D supervised network is trained and validated using preclinical CT scans of mouse tibiae with and without contrast enhancement in cartilage. The presented results show a significant improvement in the estimation of CT alignment, outperforming the current comparable methods

Synthesis of zinc selenide/graphene oxide composite via direct and indirect hydrothermal method

Zinc selenide/graphene oxide (ZnSe/GO) composite is synthesized using hydrothermal method. Two different methods such as direct and indirect route have been investigated to form the ZnSe/GO composite. In this research, the graphene oxide used was in sheet and liquid form. The synthesized composite was then characterized using X-ray diffraction (XRD) for phase identification, field emission scanning electron microscopy (FESEM) for morphology analysis and ultraviolet-visible spectroscopy (UV-Vis) for optical properties. ZnSe/GO composite showed absorption peak ranging from 460 to 480 nm with the optical band gap obtained through Tauc equation. The optical band gap of the ZnSe/GO composite has been tuned down to a smaller value as compared to the bulk ZnSe compound. The optical band gap has been reduced to around 2.53 eV when liquid graphene oxide was used while around 2.23 to 2.32 eV when graphene oxide sheet was used. The purity of ZnSe/GO composite synthesis via indirect hydrothermal method is higher than those synthesized via direct hydrothermal method. The type of graphene oxide will affect the morphology of the composite where the ZnSe compound was either wrapped by tiny thorn-like substance or graphene oxide layer

Strain-induced cesium bismuth bromide perovskite/bismuth oxide bromide composite with enhanced optical properties

Perovskite halides are well suited for optoelectronic applications because of their excellent optical properties. Among them, cesium bismuth bromide (Cs3Bi2Br9) has emerged as a promising lead-free optical material to replace lead-based perovskite halides. This can be achieved by introducing a hydrated perovskite passivation layer, BiOBr. However, previous work was solely limited to bismuth oxide bromide (BiOBr) passivation on the Cs3Bi2Br9 surface layer and did not address composite synthesis from two different phases. Herein, we report the discovery and characterization of Cs3Bi2Br9/BiOBr composite via a pre-precipitation method using isopropanol (IPA) and hydrous ethanol (EtOH). Williamson-Hall plot analysis of the X-ray diffraction (XRD) results showed the successful formation of a Cs3Bi2Br9/BiOBr composite with an induced-strain effect when EtOH was introduced. The ultraviolet–visible (UV–Vis) and photoluminescence (PL) spectra showed that the absorption and emission peaks of Cs3Bi2Br9 were located at 340 nm and 410 nm, respectively. A redshift in the absorption onset and energy bandgap generates a 190% increase in PL emission for the EtOH-synthesized perovskite sample. The enhancement is correlated to the induced effect in the Cs3Bi2Br9 phase, where BiOBr could act as an agent to improve the optical properties of Cs3Bi2Br9 by inducing strains other than the surface passivation layer

In vivo imaging of matrix metalloprotease 12 and matrix metalloprotease 13 activities in the mouse model of collagen-induced arthritis

Objective: To develop enzyme-activatable Förster resonance energy transfer (FRET) substrate probes to detect matrix metalloproteinase 12 (MMP-12) and MMP-13 activities in vivo in mouse models of inflammatory arthritis. Methods: Peptidic FRET probes activated by MMP-12 and MMP-13 were reverse designed from inhibitors selected from a phosphinic peptide inhibitor library. Selectivity of the probes was demonstrated in vitro using MMP-1, MMP-2, MMP-3, MMP-12, and MMP-13. In vivo activation of the probes was tested in the zymosan-induced mouse model of inflammation, and probe specificity was evaluated by the MMP inhibitor GM6001 and specific synthetic inhibitors of MMP-12 and MMP-13. The probes were used to monitor these enzyme activities in the collagen-induced arthritis (CIA) model in vivo. Results: The MMP-12 and MMP-13 activity probes (MMP12ap and MMP13ap, respectively) discriminated between the activities of the 2 enzymes. The in vivo activation of these probes was inhibited by GM6001 and by their respective specific inhibitors. In the CIA model, MMP12ap activation peaked 5 days after disease onset and showed strong correlation with disease severity during this time (r = 0.85, P < 0.0001). MMP13ap activation increased gradually after disease onset and correlated with disease severity over a longer period of 15 days (r = 0.58, P < 0.0001). Conclusion: We generated two selective FRET probes that can be used to monitor MMP-12 and MMP-13 activities in live animals. MMP12ap follows the initial stage of inflammation in CIA, while MMP13ap follows the progression of the disease. The specificity of these probes is useful in monitoring the efficacy of MMP inhibitors. © 2014, American College of Rheumatology