Explore the vast range of titles available.

Parkinson’s disease (PD) is a movement disorder associated with severe loss of mainly dopaminergic neurons in the substantia nigra. Pathological hallmarks include Lewy bodies, and loss of neuromelanin, due to degeneration of neuromelanin-containing dopaminergic neurons. Despite being described over 200 years ago, the etiology of PD remains unknown. Here, we highlight the roles of reactive oxygen species (ROS), iron, alpha synuclein (α-syn) and neuromelanin in a toxic feedback loop culminating in neuronal death and spread of the disease. Dopaminergic neurons are particularly vulnerable due to decreased antioxidant concentration with aging, constant exposure to ROS and presence of neurotoxic compounds (e.g. ortho-quinones). ROS and iron increase each other’s levels, creating a state of oxidative stress. α-Syn aggregation is influenced by ROS and iron but also increases ROS and iron via its induced mitochondrial dysfunction and ferric-reductase activity. Neuromelanin’s binding affinity is affected by increased ROS and iron. Furthermore, during neuronal death, neuromelanin is degraded in the extracellular space, releasing its bound toxins. This cycle of events continues to neighboring neurons in the form of a toxic loop, causing PD pathology. The increase in ROS and iron may be an important target for therapies to disrupt this toxic loop, and therefore diets rich in certain ‘nutraceuticals’ may be beneficial. Turmeric is an attractive candidate, as it is known to have anti-oxidant and iron chelating properties. More studies are needed to test this theory and if validated, this would be a step towards development of lifestyle-based therapeutic modalities to complement existing PD treatments.

Background The prevalence of Parkinson’s disease (PD) is increasing in sub-Saharan Africa, but little is known about the genetics of PD in these populations. Due to their unique ancestry and diversity, sub-Saharan African populations have the potential to reveal novel insights into the pathobiology of PD. In this study, we aimed to characterise the genetic variation in known and novel PD genes in a group of Black South African and Nigerian patients. Methods We recruited 33 Black South African and 14 Nigerian PD patients, and screened them for sequence variants in 751 genes using an Ion AmpliSeq™ Neurological Research panel. We used bcftools to filter variants and annovar software for the annotation. Rare variants were prioritised using MetaLR and MetaSVM prediction scores. The effect of a variant on ATP13A2’s protein structure was investigated by molecular modelling. Results We identified 14,655 rare variants with a minor allele frequency ≤ 0.01, which included 2448 missense variants. Notably, no common pathogenic mutations were identified in these patients. Also, none of the known PD-associated mutations were found highlighting the need for more studies in African populations. Altogether, 54 rare variants in 42 genes were considered deleterious and were prioritized, based on MetaLR and MetaSVM scores, for follow-up studies. Protein modelling showed that the S1004R variant in ATP13A2 possibly alters the conformation of the protein. Conclusions We identified several rare variants predicted to be deleterious in sub-Saharan Africa PD patients; however, further studies are required to determine the biological effects of these variants and their possible role in PD. Studies such as these are important to elucidate the genetic aetiology of this disorder in patients of African ancestry.

BackgroundConcussion occurs when biomechanical forces transmitted to the head result in neurological deficits. Personality may affect the balance between safe and dangerous play potentially influencing concussion risk. Dopamine receptor D2 (DRD2) and dopamine receptor D4 (DRD4) genetic polymorphisms were previously associated with personality traits.ObjectivesThis case–control genetic association study investigated the associations of (1) DRD2 and DRD4 genotypes with concussion susceptibility and personality, (2) personality with concussion susceptibility and (3) the statistical model of genotype, personality and concussion susceptibility.MethodsIn total, 138 non-concussed controls and 163 previously concussed cases were recruited from high school (n=135, junior), club and professional rugby teams (n=166, senior). Participants were genotyped for DRD2 rs12364283 (A>G), DRD2 rs1076560 (C>A) and DRD4 rs1800955 (T>C) genetic variants. Statistical analyses including structural equation modelling were performed using the R environment and STATA.ResultsThe rs1800955 CC genotype (p=0.014) and inferred DRD2 (rs12364283–rs1076560)–DRD4 (rs1800955) A–C–C allele combination (p=0.019) were associated with decreased concussion susceptibility in juniors. The rs1800955 TT and CT genotypes were associated with low reward dependence in juniors (p<0.001) and seniors (p=0.010), respectively. High harm avoidance was associated with decreased concussion susceptibility in juniors (p=0.009) and increased susceptibility in seniors (p=0.001). The model showed that a genetic variant was associated with personality while personality was associated with concussion susceptibility.ConclusionThese findings highlight the linear relationship between genetics, personality and concussion susceptibility. Identifying a genetic profile of ‘high risk’ behaviour, together with the development of personalised behavioural training, can potentially reduce concussion risk.

Dismemberment and subsequent burning are common methods employed in an attempt to conceal or destroy evidence. While kerf characteristics can be utilised to identify tool(s) used for dismemberment, further research is necessary to assess the effect of burning on these characteristics. In this study, a back (tenon) saw (13 teeth per inch) was used to manually inflict trauma on Ovis aries de-fleshed femur bones (n = 18). Three different cut marks (shallow false start, incomplete cut and complete transection) were made on the mid-shaft of each bone. Subsequently, the bones were burned for 20 minutes in a muffle furnace. Three burn temperatures were assessed: 400 °C, 600 °C and 800 °C. Saw mark characteristics of each cut type were assessed and compared pre- and post-burning. All pre-existing trauma was recognisable post-burning; however, metric and morphological alterations were apparent. An increase in kerf width was observed at 600 °C in false start lesions and 800 °C in incomplete cuts. Breakaway spur thickness decreased post-burning (at 400 °C and 800 °C) but length was not significantly affected. Mean inter-striation distance decreased post burning at all temperature groups. Saw marks were distinguishable from heat-related fractures across all temperature groups. One false start lesion was obliterated at 800 °C. Exit chipping, pull-out striae as well as striation regularity appeared to be more enhanced after heat exposure. These alterations indicate a temperature-dependent impact on these characteristics. Further research is necessary to assess the role of burn duration. •Increased fracturing and fragility in burnt bones with increased burn temperature.•Saw mark characteristics more evident in burned compared to unburnt bones.•Significant increase in kerf width and decrease in kerf depth at 800°C.

Concussion is a brain injury that occurs when biomechanical forces are transmitted to the head region resulting in neurological deficits. The accumulation of tau protein in autopsies of athletes with multiple concussions implicates tau in concussion-associated neurodegeneration. The TAU rs2435211 (C>T) and rs2435200 (G>A) polymorphisms are involved in pathological tau expression and neurodegenerative disease risk. The aims of this study were to investigate the associations of TAU (rs2435211, rs2435200) polymorphisms with concussion history and sustaining multiple concussions in rugby. In total, 140 non-concussed controls and 163 previously concussed participants (all cases group, N=163; clinically diagnosed, N=140; multiple concussed, N=87) were recruited from high school (N=135, junior), club and professional rugby teams (N=166, senior). Participants were genotyped for TAU rs2435211 and rs2435200 polymorphisms. In seniors, the rs2435200 AA genotype was significantly over-represented in the control group compared to the multiple concussed subgroup (P=0.033, control: 25%, N=16, multiple concussed: 11%, N=6; OR: 0.34, 95% CI 0.12–0.96). While the AG genotype was significantly under-represented in the control compared to multiple concussed (P=0.024, control: 45%, N=29, multiple concussed: 63%, N=36; OR: 2.34, 95% CI 1.11–4.95). The inferred TAU (rs2435211 C>T–rs2435200 G>A) T-G haplotype was significantly under-represented in the control (19%, N=12) compared to the all cases group (30%, N=28, P=0.031). The TAU-associated neurodegenerative pathway was implicated as a potential pathophysiological mechanism underlying concussion in seniors. In future, the identification of TAU polymorphisms associated with concussion risk may assist clinical management and reduce risk of severe complications.

Concussion refers to changes in neurological function due to biomechanical forces transmitted to the head. The APOE ε4 allele is associated with brain injury severity. The objective was to determine if APOE gene variants are associated with concussion history and severity in rugby players. In total, 128 non-concussed controls and 160 previously concussed participants (all cases N=160; diagnosed N=139) were recruited from high school (junior, N=121), club (N=116) and professional rugby teams (N=51). Participants were genotyped for rs405509 (G>T), rs429358 (T>C) and rs7412 (C>T) APOE variants. Statistical analyses were performed using the R environment. The rs405509 TT genotype was over-represented in controls compared to all cases (P=0.043; control: 29%, all cases: 18%; odds ratio: 0.55, 95% confidence interval 0.31–0.98). The APOE-ε isoform frequencies were not significantly different between groups (P>0.05). Additionally, the inferred APOE (rs405509-ε2/ε3/ε4) T-ε3 haplotype was over-represented in controls (41%) compared to diagnosed (32%, P=0.042). The G-ε3 haplotype was under-represented in controls (36%) compared to all cases (44%, P=0.019) and diagnosed (44%, P=0.021). The TT genotype was significantly associated with rapid recovery (P=0.048, <1 week: 51%, N=70, ≥1 week: 36%, N=29; odds ratio: 0.55, 95% confidence interval 0.30–1.01). These findings support the further elucidation of the APOE gene or closely-related genes in concussion aetiology. Although similar preliminary results were found when juniors were separately analysed, the under-powered sample size for junior subgroup requires future investigation in larger cohorts of junior-level athletes.

Personality traits have been proposed to affect the risk of sports concussion, but evidence is limited. Cloninger’s Tridimensional Personality Questionnaire (TPQ) measures novelty seeking, harm avoidance (HA), and reward dependence traits. The aim of this study was to investigate the relationship between TPQ scores and concussion history in rugby union players. Cross-sectional study. Rugby players from high schools, senior amateur clubs, and professional teams provided a self-reported concussion history and completed the TPQ. Participants reporting no previous concussions formed the control group, while participants reporting concussion formed the case group. A one-way analysis of covariance, with age as a covariate, was used to examine the differences in TPQ scores between groups. Of the 309 participants, 54% reported a minimum of one concussion (junior: 47%; amateur: 52%; professional: 72%). HA scores were significantly higher in junior players without a history of concussion compared to cases (p=0.006). Specifically, the junior control group had higher “anticipatory worry” (p=0.009) and “fear of uncertainty” (p=0.008). In contrast, the professional control group had lower HA scores than cases (p=0.009), while the amateur cohort displayed no differences between control and case groups. This study identified a novel association between HA and concussion in rugby players, adding evidence to the role of personality in a multifactorial risk-model of concussion. The findings suggest that lower HA may lead to increased dangerous play in youth rugby, influencing concussion susceptibility. Contrasting associations in the professional cohort suggest further research is required to understand the role of personality in concussion.

Evidence suggests that shared pathophysiological mechanisms in neuropsychiatric disorders (NPDs) may contribute to risk and resilience. We used single-gene and network-level transcriptomic approaches to investigate shared and disorder-specific processes underlying posttraumatic stress disorder (PTSD), Parkinson’s disease (PD) and schizophrenia in a South African sample. RNA-seq was performed on blood obtained from cases and controls from each cohort. Gene expression and weighted gene correlation network analyses (WGCNA) were performed using DESeq2 and CEMiTool, respectively. Significant differences in gene expression were limited to the PTSD cohort. However, WGCNA implicated, amongst others, ribosomal expression, inflammation and ubiquitination as key players in the NPDs under investigation. Differential expression in ribosomal-related pathways was observed in the PTSD and PD cohorts, and focal adhesion and extracellular matrix pathways were implicated in PD and schizophrenia. We propose that, despite different phenotypic presentations, core transdiagnostic mechanisms may play important roles in the molecular aetiology of NPDs.

Open science and collaboration are necessary to facilitate the advancement of Parkinson’s disease (PD) research. Hackathons are collaborative events that bring together people with different skill sets and backgrounds to generate resources and creative solutions to problems. These events can be used as training and networking opportunities, thus we coordinated a virtual 3-day hackathon event, during which 49 early-career scientists from 12 countries built tools and pipelines with a focus on PD. Resources were created with the goal of helping scientists accelerate their own research by having access to the necessary code and tools. Each team was allocated one of nine different projects, each with a different goal. These included developing post-genome-wide association studies (GWAS) analysis pipelines, downstream analysis of genetic variation pipelines, and various visualization tools. Hackathons are a valuable approach to inspire creative thinking, supplement training in data science, and foster collaborative scientific relationships, which are foundational practices for early-career researchers. The resources generated can be used to accelerate research on the genetics of PD.