2015 AMREP EMCR Best Paper Awards

Julian Smith


Biomedical Research
Dr Jay C Jha (Baker IDI)

Paper Title: “Genetic Targeting or Pharmacologic Inhibition of  NADPH Oxidase Nox4 Provides Renoprotection in Long-Term Diabetic Nephropathy”    
Journal: Journal of American Society of Nephrology [IF: 9.343]
Lay summary: Diabetic nephropathy may occur, in part, as a result of intra-renal oxidative stress. NADPH oxidases is the only known dedicated reactive oxygen species (ROS) forming enzyme family. This study identified Nox4 isoform of NADPH oxidases as the main source of renal ROS in a mouse model of diabetic nephropathy induced by streptozotocin administration in ApoEKO mice. Deletion of Nox4 resulted in renal protection from glomerular injury as evidenced by attenuated albuminuria, preserved structure, reduced glomerular accumulation of extracellular matrix proteins, attenuated glomerular macrophage infiltration, and reduced renal expression of monocyte chemoattractant protein-1 and NF-kB in streptozotocin-induced diabetic ApoE2/2 mice. Importantly, administration of the most specific Nox inhibitor, GKT137831, replicated these renoprotective effects of Nox4 deletion. Collectively, these results identify Nox4 as a key source of ROS responsible for kidney injury in diabetes and provide proof of principle for an innovative small molecule approach to treat and/or prevent chronic kidney failure.

Clinical Research
Dr Rebecca Segrave (Monash)

Paper Title: “Concurrent Cognitive Control Training Augments the Antidepressant Efficacy of tDCS: A Pilot Study”
Journal: Brain Stimulation [IF: 4.399]
Lay summary: Up to 50% of individuals with depression do not achieve remission with standard treatments, and new antidepressant therapies are greatly needed. This publication describes the results of a world-first pilot clinical trial that tested a new approach to depression treatment. Transcranial direct current stimulation (tDCS) is a gentle form of non-invasive brain stimulation. tDCS delivered to the resting brain has mild-to-moderate antidepressant effects. Dr Segrave tested the efficacy of delivering tDCS to an active brain region by combining it with specialised neurocognitive training, called Cognitive Control Training (CCT). She found that a course of tDCS + CCT resulted in substantially greater antidepressant outcomes than delivery of either tDCS or CCT alone. Neuropsychological testing additionally revealed that antidepressant response was associated with increased cognitive control after the first treatment, and enhanced cognitive control over negative information following cessation of treatment.

Public Health
Dr Jennifer Pilgrim (Monash)

Paper Title: “King hit fatalities in Australia 2000-2012: the role of alcohol and other drugs”
Journal: Drug and Alcohol Dependence [IF: 3.278]
Lay summary:  “King hits” are characterised by a single punch to the head that incapacitates a victim, causing them to fall to the ground unconscious. This secondary impact can cause fatal skull fractures and brain bleeds. My study examined the toxicology of fatal one-punch assaults in Australia. There were 90 fatal king hits reported to an Australian coroner between 2000 and 2012. Most were young men in their early 30s, who had been drinking alcohol at a pub at the weekend, when they were punched by a stranger following a brief altercation. With 73% involving alcohol at concentrations up to 4 times the legal driving limit, and only 11% of cases positive for illicit drugs, this study demonstrated that alcohol is the primary concern in these assaults. The results also showed that alcohol intoxication not only creates perpetrators, it also increases the risk of becoming a victim of a violent assault.

2015 Mid-Career Researcher Best Paper Award Winners

Biomedical Research
Dr Darren Henstridge (Baker IDI)

Paper Title: “Activating HSP72 in Rodent Skeletal Muscle Increases Mitochondrial Number and Oxidative Capacity and Decreases Insulin Resistance”
Journal: Diabetes [IF: 8.095]
Lay summary: Previously it has been demonstrated that induction of a protein called heat shock protein 72 (HSP72) protects against obesity and obesity-induced insulin resistance (pre-diabetes). The underlying mechanisms regarding this action were unknown. Here, we show in a pre-clinical mouse model, that HSP72 plays a pivotal role in increasing skeletal muscle mitochondrial number and oxidative metabolism (the ability to use and burn fats). Consequently this may be the mechanism via which increasing Hsp72 levels may offer protection against metabolic diseases such as obesity and type 2 diabetes