Basic Science and Pathogenesis.

Background: Emerging evidence support the notion that loss of splicing repression by TDP-43, an RNA binding protein that was first implicated in ALS-FTD, underlies their pathogenesis. Previously, we showed that delivery of an AAV9 vector at early postnatal day expressing a fusion protein, termed CTR comprised of the N-terminal region of TDP-43 and an unrelated splicing repressor termed RAVER1 complemented the loss of TDP-43 in mice lacking TDP-43 in spinal motor neurons (ChAT-IRES-Cre;tardbp mice). To translate this potential therapeutic strategy to the clinic, it will be important to demonstrate benefit of such AAV delivery of CTR to motor neurons in adult mice.

Basic Science and Pathogenesis.

Background: TDP-43 proteinopathy, initially discovered in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), coexists with tauopathy in a variety of neurodegenerative disorders, including Alzheimer's Disease (AD). While such co-pathology is strongly associated with worsened neurodegeneration and steeper cognitive decline, how these two pathologies influence each other to exacerbate neuron loss remains elusive. That loss of TDP-43 splicing repression occurring in presymptomatic ALS-FTD suggests that loss of TDP-43 function could facilitate the pathological conversion of tau to accelerate tauopathy and neuron loss.

Deciphering network dysregulations and temporo-spatial dynamics in disorders of consciousness: insights from minimum spanning tree analysis.

Objectives: The neural mechanism associated with impaired consciousness is not fully clear. We aim to explore the association between static and dynamic minimum spanning tree (MST) characteristics and neural mechanism underlying impaired consciousness.

Methods: MSTs were constructed based on full-length functional magnetic resonance imaging (fMRI) signals and fMRI signal segments within each time window.

Healthcare burden of public hospital gout admissions in New South Wales, Australia.

Background And Aims: In New Zealand, the Māori and Pacific Islander population has a higher rate of hospital admissions for gout; however, we lack data for these population groups who reside in Australia. This study examined the pattern of hospital gout admissions in New South Wales (NSW), the most populous state of Australia, with a particular focus on the Māori and Pacific Islander population.

Methods: This was a retrospective cohort study exploring the pattern of gout admissions in NSW public hospitals in the financial years 2017/2018 to 2019/2020.

Targeting Ubiquitin-Proteasome System (UPS) in Treating Osteoarthritis.

Despite osteoarthritis (OA) being recognised for over a century as a debilitating disease that affects millions, there are huge gaps in our understanding of the underlying pathophysiology that drives this disease. Present day studies that focussed on ubiquitination (Ub) and ubiquitylation-like (Ubl) modification related mechanisms have brought light into the possibility of attenuating OA development by targeting these specific proteins in chondrocytes. In the present review, we discuss recent advances in studies involving Ub ligases and deubiquitinating enzymes (DUBs) which are of importance in the development of OA, and may offer potential therapeutic strategies for OA.