ORCID Profile
0000-0001-6268-5146
Current Organisation
Murdoch University
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Publisher: Springer Science and Business Media LLC
Date: 25-02-2020
Publisher: Informa UK Limited
Date: 10-2020
Publisher: Springer Science and Business Media LLC
Date: 27-11-2021
Publisher: ASTM International
Date: 05-2003
DOI: 10.1520/JFS2002084
Publisher: Elsevier BV
Date: 06-2018
Publisher: Informa UK Limited
Date: 23-01-2019
Publisher: Elsevier BV
Date: 02-2006
Publisher: Mary Ann Liebert Inc
Date: 09-2023
Publisher: Springer Science and Business Media LLC
Date: 07-01-2021
DOI: 10.1007/S12035-020-02238-0
Abstract: Amyotrophic lateral sclerosis (ALS) is a form of motor neuron disease (MND) that is characterized by the progressive loss of motor neurons within the spinal cord, brainstem, and motor cortex. Although ALS clinically manifests as a heterogeneous disease, with varying disease onset and survival, a unifying feature is the presence of ubiquitinated cytoplasmic protein inclusion aggregates containing TDP-43. However, the precise mechanisms linking protein inclusions and aggregation to neuronal loss are currently poorly understood. Bimolecular fluorescence complementation (BiFC) takes advantage of the association of fluorophore fragments (non-fluorescent on their own) that are attached to an aggregation-prone protein of interest. Interaction of the proteins of interest allows for the fluorescent reporter protein to fold into its native state and emit a fluorescent signal. Here, we combined the power of BiFC with the advantages of the zebrafish system to validate, optimize, and visualize the formation of ALS-linked aggregates in real time in a vertebrate model. We further provide in vivo validation of the selectivity of this technique and demonstrate reduced spontaneous self-assembly of the non-fluorescent fragments in vivo by introducing a fluorophore mutation. Additionally, we report preliminary findings on the dynamic aggregation of the ALS-linked hallmark proteins Fus and TDP-43 in their corresponding nuclear and cytoplasmic compartments using BiFC. Overall, our data demonstrates the suitability of this BiFC approach to study and characterize ALS-linked aggregate formation in vivo. Importantly, the same principle can be applied in the context of other neurodegenerative diseases and has therefore critical implications to advance our understanding of pathologies that underlie aberrant protein aggregation.
Publisher: Wiley
Date: 16-02-2008
Publisher: Emerald
Date: 24-12-2019
Abstract: Cold case review teams and the processes that they adopt in their endeavour to solve historic crimes are varied and largely underreported. Of the limited literature surrounding the topic of cold case reviews, the focus is on clearance rates and the selection of cases for review. While multiple reports and reviews have been undertaken and recommend that the interface between investigators and forensic scientists be improved, there is little evidence of cold case teams comprised of a mixture of investigators and scientists or experts. With the growing reliance on forensic science as an aide to solvability, the authors propose that the inclusion of forensic scientists to the central cold case investigation may be a critical factor in future success. The paper aims to discuss this issue. To support the proposed approach, the authors conducted a review of the current literature seeking insight into the reported make-up of cold case teams. In conjunction with this, the authors reviewed a number of commissioned reports intended to improve cold case reviews and forensic services. While many of the reviewed reports and recommendations suggested better integration with scientists and external expertise, little evidence of this in practice was reported within published literature. Open dialogue and cross pollination between police investigators and forensic scientists are likely to mitigate biases, inform case file triage and better equip investigations with contemporary and cutting-edge scientific solutions to the evidence analysis for cold cases. Furthermore, with respect to scientists within academia, large pools of resources by way of student interns or researchers may be available to assist resource-sparse policing jurisdictions. To the authors’ knowledge, this is the first peer-reviewed recommendation for the consideration of integrated forensic scientists within a cold case review team. Multiple reports suggest the need for closer ties, but it is the anecdotal experience of the authors that the benefits of a blended task force approach may yield greater success.
Publisher: Springer Science and Business Media LLC
Date: 29-08-2018
DOI: 10.1007/S00018-017-2632-8
Abstract: Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are fatal neurodegenerative disorders that have common molecular and pathogenic characteristics, such as aberrant accumulation and ubiquitylation of TDP-43 however, the mechanisms that drive this process remain poorly understood. We have recently identified CCNF mutations in familial and sporadic ALS and FTD patients. CCNF encodes cyclin F, a component of an E3 ubiquitin-protein ligase (SCF
Publisher: Elsevier
Date: 2013
Publisher: Wiley
Date: 27-04-2021
Publisher: Elsevier BV
Date: 2001
Publisher: Elsevier BV
Date: 15-08-2005
Publisher: ASTM International
Date: 11-1999
DOI: 10.1520/JFS14594J
Publisher: ASTM International
Date: 11-2001
DOI: 10.1520/JFS15156J
Publisher: Elsevier BV
Date: 06-2001
Publisher: Elsevier BV
Date: 08-2017
No related grants have been discovered for John Coumbaros.