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Exploring the Proteomic Landscape of Traumatic Brain Injury Models
(Stellenbosch University, 2025-03) Vorster, Melissa Sona; Patterton, Hugh George; Tabb, David Lee; Loos, Ben; Eckert, Stephan; Stellenbosch University. Faculty of Science. Centre for Bioinformatics and Computational Biology.
Background: Traumatic brain injury (TBI) is a multifaceted condition characterized by primary and secondary injury mechanisms, leading to significant molecular and cellular disruptions. Understanding these processes at the proteomic level is critical for developing targeted therapeutic strategies. Systematic reviews and meta-analyses can provide insights into the broader landscape of TBI research, while experimental comparisons of TBI models can refine our understanding of their relevance to human pathology. Research Gap: Current models fail to capture the full complexity of human TBI, particularly the interplay between biochemical and biomechanical mechanisms. Comparative analyses of TBI models and integrative proteomic studies remain limited. Objective: This study aimed to integrate findings from a systematic review, conduct a meta-analysis of publicly available proteomic datasets, and evaluate two chemical TBI models, sodium dithionite (SDT) and 2-deoxy-D-glucose (2DG), to better understand TBI-associated proteomic changes. Method: A systematic review and meta-analysis identified key proteins and pathways altered in TBI. Proteomic analyses of SDT and 2DG models were conducted to assess their ability to replicate TBI pathologies, including oxidative stress, apoptosis, autophagy, and metabolic dysfunction. Comparative analyses explored shared and distinct molecular responses. Key Findings: The systematic review and meta-analysis identified critical proteins and pathways linked to oxidative stress, mitochondrial dysfunction, and cell death. SDT induced oxidative stress and excitotoxicity, while 2DG disrupted metabolic pathways and caused energy depletion. Both models showed overlapping responses, such as inflammation and mitochondrial dysfunction, and distinct pathway activations. Limitations included the inability of chemical models to replicate biomechanical injury, the static nature of proteomic analyses, and incomplete metadata affecting reproducibility. Implications: By combining systematic review, meta-analysis, and experimental model comparison, this study offers a comprehensive framework for understanding TBI at the proteomic level. These findings highlight the strengths and limitations of current models and inform future research directions, including integrating mechanical and chemical models, employing longitudinal and multi-omics approaches, and improving metadata reporting and experimental validation. This approach will enhance the translational relevance of findings and support the development of targeted therapies and biomarkers to improve TBI management and outcomes.
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The incidence of retinoblastoma in South Africa : findings from the South African National Cancer Registry (2004–2018)
(Taylor & Francis, 2022-12) Stuart, Kelsey V.; Shepherd, Daniel J.; Kruger, Mariana; Singh, Elvira
ABSTRACT: Purpose: To determine the frequency and incidence rate of retinoblastoma in children in South Africa from 2004 to 2018.
Methods: Incident cases of histologically diagnosed retinoblastoma were identified from the South African National Cancer Registry. Crude incidence rates were calculated using national population data on children <15 years and live births. Incidence rates were stratified and compared by age, sex and population group. Direct age-standardised incidence rates and comparative incidence ratios were calculated.
Results: The overall age-standardised incidence rate for children <15 years was 3.3 per million or 1 per 21 641 live births. Age-specific rates for children aged 0–4, 5–9 and 10–14 years were 7.7, 0.8 and 0.2 per million, respectively. There was no difference in incidence rates by sex. White children had a significantly higher incidence rate compared to other population groups, but this finding may be due to systemic biases introduced by access to healthcare in South Africa or study methodology.
Conclusion: This is the largest study to provide population-based, histologically confirmed national estimates of retinoblastoma incidence from an African nation to date and affirms the need for high-quality cancer registries across the African continent.
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Brain ageing in schizophrenia : evidence from 26 international cohorts via the ENIGMA Schizophrenia consortium
(Nature, 2022-12-09) Constantinides, Constantinos; Han, Laura K. M.; Alloza, Clara; Antonucci, Linda Antonella; Arango, Celso; Ayesa-Arriola, Rosa; Banaj, Nerisaq; Bertolino, Alessandro; Borgwardt, Stefan; Bruggemann, Jason; Bustillo, Juan; Bykhovski, Oleg; Calhoun, Vince; Catts, Stanley; Chung, Young-Chul; Crespo-Facorro, Benedicto; Diaz-Caneja, Covadonga M.; Donohoe, Gary; Du Plessis, Stefan; Edmond, Jesse; Ehrlich, Stefan; Emsley, Robin; Eyler, Lisa T.; Fuentes-Claramonte, Paola; Georgiadis, Foivos; Green, Melissa; Guerrero-Pedraza, Amalia; Ha, Minji; Hahn, Tim; Henskens, Frans A.; Holleran, Laurena; Homan, Stephanie; Jahanshad, Neda; Janssen, Joost; Ji, Ellen; Kaiser, Stefan; Kaleda, Vasily; Kim, Minah; Kim, Woo-Sung; Kirschner, Matthias; Kochunov, Peter; Kwak, Yoo Bin; Kwon, Jun Soo; Lebedeva, Irina; Liu, Jingyu; Mitchie, Patricia; Michielse, Stijn; Mothersill, David; Mowry, Bryan; Ortiz-Garcia de la Foz, Victor; Pantelis, Christos; Pergola, Giulio; Piras, Fabrizio; Pomarol-Clotet, Edith; Preda, Adrian; Quide, Yann; Rasser, Paul E.; Rootes-Murdy, Kelly; Salvador, Raymond; Sangiuliano, Marina; Sarro, Salvador; Schall, Ulrich; Schmidt, Andre; Scott, Rodney J.; Selvaggi, Pierluigi; Sim, Kang; Skoch, Antonin; Spalletta, Gianfranco; Spaniel, Filip; Thomopoulos, Sophia I.; Tomecek, David; Tomyshev, Alexander S.; Tordesillas-Gutierrez, Diana; Van Amelsvoort, Therese; Vazquez-Bourgon, Javier; Vecchio, Daniela; Voineskos, Aristotle; Weickert, Cynthia S.; Weickert, Thomas; Thompson, Paul M.; Schmaal, Lianne; Van Erp, Theo G. M.; Turner, Jessica; Cole, James H.; ENIGMA Schizophrenia Consortium; Dima, Danai; Walton, Esther
Schizophrenia (SZ) is associated with an increased risk of life-long cognitive impairments, age-related chronic disease, and premature mortality. We investigated evidence for advanced brain ageing in adult SZ patients, and whether this was associated with clinical characteristics in a prospective meta-analytic study conducted by the ENIGMA Schizophrenia Working Group. The study included data from 26 cohorts worldwide, with a total of 2803 SZ patients (mean age 34.2 years; range 18–72 years; 67% male) and 2598 healthy controls (mean age 33.8 years, range 18–73 years, 55% male). Brain-predicted age was individually estimated using a model trained on independent data based on 68 measures of cortical thickness and surface area, 7 subcortical volumes, lateral ventricular volumes and total intracranial volume, all derived from T1-weighted brain magnetic resonance imaging (MRI) scans. Deviations from a healthy brain ageing trajectory were assessed by the difference between brain-predicted age and chronological age (brain-predicted age difference [brain-PAD]). On average, SZ patients showed a higher brain-PAD of +3.55 years (95% CI: 2.91, 4.19; I2 = 57.53%) compared to controls, after adjusting for age, sex and site (Cohen’s d = 0.48). Among SZ patients, brain-PAD was not associated with specific clinical characteristics (age of onset, duration of illness, symptom severity, or antipsychotic use and dose). This large-scale collaborative study suggests advanced structural brain ageing in SZ. Longitudinal studies of SZ and a range of mental and somatic health outcomes will help to further evaluate the clinical implications of increased brain-PAD and its ability to be influenced by interventions.
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CRISPR/Cas-based tools for the targeted control of plant viruses
(Wiley, 2022-08-03) Robertson, Gaelle; Burger, Johan; Campa, Manuela
Plant viruses are known to infect most economically important crops and pose a major threat to global food security. Currently, few resistant host phenotypes have been delineated, and while chemicals are used for crop protection against insect pests and bacterial or fungal diseases, these are inefficient against viral diseases. Genetic engineering emerged as a way of modifying the plant genome by introducing functional genes in plants to improve crop productivity under adverse environmental conditions. Recently, new breeding technologies, and in particular the exciting CRISPR/Cas (clustered regularly interspaced short palindromic repeats/CRISPR-associated proteins) technology, was shown to be a powerful alternative to engineer resistance against plant viruses, thus has great potential for reducing crop losses and improving plant productivity to directly contribute to food security. Indeed, it could circumvent the “Genetic modification” issues because it allows for genome editing without the integration of foreign DNA or RNA into the genome of the host plant, and it is simpler and more versatile than other new breeding technologies. In this review, we describe the predominant features of the major CRISPR/Cas systems and outline strategies for the delivery of CRISPR/Cas reagents to plant cells. We also provide an overview of recent advances that have engineered CRISPR/Cas-based resistance against DNA and RNA viruses in plants through the targeted manipulation of either the viral genome or susceptibility factors of the host plant genome. Finally, we provide insight into the limitations and challenges that CRISPR/Cas technology currently faces and discuss a few alternative applications of the technology in virus research.
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Socially Inclusive Heritage Conservation Land-Use Management in Small Towns: A Case Study in the Greater Oudtshoorn Municipality
(Stellenbosch : Stellenbosch University, 2025-03) Adendorff, Rudi; Geyer Jr, H. S.; Donaldson, S. E.; Stellenbosch University. Faculty of Arts and Social Sciences. Dept. of Geography and Environmental Studies.
This study addresses the critical issue of heritage loss due to inadequate conservation measures and limited municipal resources in small rural towns. As local governments are struggling to provide social development and even basic services, heritage conservation is a low-priority objective and is often disregarded by inadequately resourced municipalities. The study therefore also addresses the challenge of socially inclusive approaches to heritage conservation that aim to preserve the cultural heritage of various social groups in previously disadvantaged communities. This dilemma requires that heritage conservation overcomes heritage dissonance by incorporating the varying perspectives and narratives of heritage.
For this study a mixed-methods approach has been employed, by combining GIS data and aerial photographs to create an inventory of historical structures. This was accomplished in order to categorise the heritage grading, conservation worthiness and condition rating of structures in the study areas of De Rust, Dysselsdorp, De Hoop, and Armoed/Volmoed. These study areas are all situated within the Greater Oudtshoorn Municipality, Western Cape. Thereafter, key stakeholders within the local community were interviewed to acquire detailed information on the significance as well as on potential threats to these structures. Finally, the application of land-use policies was evaluated in order to determine their effectiveness in terms of internationally recognised heritage conservation guidelines.
Key findings have revealed a variety of heritage conservation outcomes in the study areas. While the heritage conservation measures in De Rust and Volmoed were well developed and included a high percentage of buildings with impressive grading values under the National Heritage Resources Act (NHRA), a large number of dwellings were graded as “Not Conservation Worthy” (NCW) as a result of considerable alterations and modifications. Issues such as drug-related crime, historical disassociation due to objections against colonial and apartheid-era heritage, conflicting socio-economic uses of structures, and the need for security-related alterations to the structures collide with heritage conservation efforts, resulting in the further deterioration of historical structures. Excessive heritage structure restoration costs also impose significant financial burdens upon impoverished homeowners, particularly in previously disadvantaged communities. Heritage conservation is often neglected by local municipalities, thus resulting in the deterioration of both tangible and intangible heritage assets.
Nevertheless, many deteriorated heritage sites without conservation-worthy buildings such as Die Ou Lokasie and Dysselsdorp, hold particular sentimental value for the local Coloured community because of their historic relations to the sites. Subconscious biases in heritage conservation exists when intangible aspects of living heritage that are evident in practices, traditions, and community identity are neglected, leading to even further negligence of tangible heritage. In order to address heritage dissonance, contrasting perspectives of local history should be engaged to reassess the different meanings and significance of heritage. Finally, socially inclusive heritage conservation requires the implementation of targeted land-use management policies, such as Heritage Protection Overlay Zones (HPOZ) or heritage-sensitive zones, by proactively involving diverse communities and local heritage organisations in heritage conservation efforts.