Autophagy and stress granules: the merging of two pathways in Parkinson's disease

Autophagy is compromised in Parkinson’s disease (PD) with a number of PD-associated genetic mutations leading to its dysregulation. Leucine-rich repeat kinase (LRRK2) mutations, causative of PD, aberrantly enhance autophagy. Our lab elucidated a LRRK2 gene regulatory network identifying transcripts showing coordinated expression level changes associated with PD. Histone deacetylase 6 (HDAC6) was found to be an important interactor with LRRK2, regulating many of the same transcripts. The majority of these transcripts associate with autophagy and the lysosomal complex. I hypothesized that LRRK2 interacts with HDAC6 to regulate autophagy. Silencing of HDAC6 in SH-SY5Y normalized the autophagosomal size altered by expression of PD-linked LRRK2 mutants. This work identified a key role for HDAC6 in mediating the autophagic dysfunction induced by the mutant LRRK2. In addition to autophagy, stress granule (SG) formation has emerged as a compelling mechanism in the pathogenesis of PD. RNA-binding proteins (RBPs), such as T-cell intracellular antigen-1 (TIA-1), are major component of SGs. I observed TIA-1 translocating from the nucleus to the cytoplasm in PD cortex without forming SGs. Hu antigen D (HuD) also showed changes, with the RBP more present in the cytoplasm than the nucleus in PD with no SGs observed. These preliminary studies lead to the hypothesis that low levels of SGs result from an inhibition by alpha-synuclein (syn), or hyperactive autophagy. For that purpose, brain tissues from a mouse model of PD (A53T-syn transgenic mouse) were examined by immunohistochemistry. There was no difference in TIA-1 expression in control and A53T-syn expressing mouse brains, or SG formation in primary neurons after treatment with recombinant A53T fibrils. To determine whether the lack of SGs in PD brain was due to activation of autophagy, BE-M17 cells were treated with rapamycin, an autophagy activator, which decreased SGs by 50%. Overexpression of TIA-1 in BE-M17 cells under arsenite treatment also increased autophagosomal size by 50%, indicating co-regulation of SGs and autophagy. My work indicates that the pathophysiology of PD is associated with a loss of SGs due to elevated activity of autophagy, presumably due to PD-linked LRRK2 mutations. This co-regulatory network may be a potential therapeutic target of PD

Lightning medicine in South Africa

South Africa has a rich history of lightning research; however, research on the clinical and pathological effects and features of lightning-related injury (keraunomedicine or lightning medicine) remains neglected locally. By providing an overview of keraunomedicine and focussing on South African perspectives, we hope to raise awareness and propose that a concerted and co-ordinated attempt be made to report and collate data regarding lightning strike victims in South Africa.S Afr Med J 2012;102(7):625-62

Lightning medicine in South Africa

South Africa has a rich history of lightning research; however, research on the clinical and pathological effects and features of lightning-related injury (keraunomedicine or lightning medicine) remains neglected locally. By providing an overview of keraunomedicine and focussing on South African perspectives, we hope to raise awareness and propose that a concerted and co-ordinated attempt be made to report and collate data regarding lightning strike victims in South Africa.http://www.samj.org.z

Lightning medicine in South Africa

South Africa has a rich history of lightning research; however, research on the clinical and pathological effects and features of lightning-related injury (keraunomedicine or lightning medicine) remains neglected locally. By providing an overview of keraunomedicine and focussing on South African perspectives, we hope to raise awareness and propose that a concerted and co-ordinated attempt be made to report and collate data regarding lightning strike victims in South Africa.http://www.samj.org.z

Lightning medicine in South Africa

South Africa has a rich history of lightning research; however, research on the clinical and pathological effects and features of lightning-related injury (keraunomedicine or lightning medicine) remains neglected locally. By providing an overview of keraunomedicine and focussing on South African perspectives, we hope to raise awareness and propose that a concerted and co-ordinated attempt be made to report and collate data regarding lightning strike victims in South Africa

May Measurement Month 2019: an analysis of blood pressure screening results from Australia.

May Measurement Month (MMM) is an annual global blood pressure (BP) screening campaign aimed at obtaining standardized BP measurements and other relevant health information from members of the community to increase awareness of elevated BP and the associated risks. Adults (≥18 years) were recruited through opportunistic sampling across the various Australian states during May 2019. Three BP readings were recorded in a standardized manner for each participant, and data on lifestyle factors and comorbidities were collected. Hypertension was defined as a systolic BP ≥140 mmHg, or a diastolic BP ≥90 mmHg (according to the MMM protocol) or taking antihypertensive medication. Multiple imputation was used to estimate participants' mean BP where three readings were not available. Of the 2877 participants, 901 (31.3%) had hypertension of whom 455 (50.5%) were aware of their condition, and 366 (40.6%) were on antihypertensive medication. Of those taking antihypertensive medication, 54.3% were controlled to <140/90 mmHg with the remaining 45.7% of participants inadequately treated. Approximately 74% of treated patients were on a single antihypertensive medication. The MMM campaign provides an important platform for standardized compilation of BP data and creation of BP awareness in Australia and other nations worldwide. Data from the 2019 MMM campaign highlight that BP control rates in Australia remain unacceptably low

Roll for Mixed Reality

Mixed-Reality (MR) is a growing area of interest in the tabletop board game market as a way of heightening the ways we can interact with our physical games. Traditional table-top roleplaying games (TTRPG) such as Dungeons & Dragons (D&D) and Warhammer are well known for their immersive phenomenological narrative experiences (White, 2014) and engaging analogue interaction with tangible game pieces (Liu et al, 2021). MR offers new ways of building on these elements to enhance the immersive and haptic interactive gameplay experience while retaining the popular elements of TTRPGs. This research explores the technical possibilities and limitations of holographic headsets such as the Microsoft Hololens with the purpose of enhancing immersion within encounters in the TTRPG experience.</p

Development of Northcote

Project 2, Investigation Programme (History) , 197