Faculty of Science (Research Outputs)

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    Knock-down of LRP/LR promotes apoptosis in early and late stage colorectal carcinoma cells via caspase activation
    (BioMed Central, 2018-05) Vania, Leila; Rebelo, Thalia M.; Ferreira, Eloise; Weiss, Stefan F. T.
    Background: Cancer remains one of the leading causes of death around the world, where incidence and mortality rates are at a constant increase. Tumourigenic cells are characteristically seen to over-express the 37 kDa/67 kDa laminin receptor (LRP/LR) compared to their normal cell counterparts. This receptor has numerous roles in tumourigenesis including metastasis, angiogenic enhancement, telomerase activation, cell viability and apoptotic evasion. This study aimed to expose the role of LRP/LR on the cellular viability of early (SW-480) and late (DLD-1) stage colorectal cancer cells. Methods: siRNA were used to down-regulate the expression of LRP/LR in SW-480 and DLD-1 cells which was assessed using western blotting. Subsequently, cell survival was evaluated using the MTT cell survival assay and confocal microscopy. Thereafter, Annexin V-FITC/PI staining and caspase activity assays were used to investigate the mechanism underlying the cell death observed upon LRP/LR knockdown. The data was analysed using Student’s ttest with a confidence interval of 95%, with p-values of less than 0.05 seen as significant. Results: Here we reveal that siRNA-mediated knock-down of LRP led to notable decreases in cell viability through increased levels of apoptosis, apparent by compromised membrane integrity and significantly high caspase-3 activity. Down-regulated LRP resulted in a significant increase in caspase-8 and -9 activity in both cell lines. Conclusions: These findings show that the receptor is critically implicated in apoptosis and that LRP/LR downregulation induces apoptosis in early and late stage colorectal cancer cells through both apoptotic pathways. Thus, this study suggests that siRNA-mediated knock-down of LRP could be a possible therapeutic strategy for the treatment of early and late stage colorectal carcinoma.
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    The IGCP 714 Project “3GEO– Geoclimbing & Geotrekking in Geoparks”– Selection of Geodiversity Sites Equipped for Climbing for Combining Outdoor and Multimedia Activities
    (Springer, 2025-07) Knight, Jasper; Bollati, Irene Maria; Masseroli, Anna; Mohammed, Al Kindi,; Cezar, Lucas; Chrobak-Žuffová, Anna; Dongre, Ashish; Fassoulas, Charalampos; Fazio, Eugenio; Garcia-Rodríguez, Manuel; Matthews, Jack J.; Fraga de Araújo Pereira, Ricardo Galeno; Viani, Cristina; Williams, Mark; Amato, Giuseppe M.; Apuani, Tiziana; de Castro, Emanuel; Fernández-Escalante, Enrique; Fernandes, Magda; Forzese, Martina; Gianotti, Franco; Goyanes, Gabriel; Loureiro, Fabio; Kandekar, Avinash; Kolendrianou, Maria; Maniscalco, Rosanna; Nikolakakis, Emmanouel; Palomba, Mauro; Pelfini, Manuela; Tronti, Gianluca; Zanoletti, Enrico; Zerboni, Andrea; Zucali, Michele
    The IGCP 714 project “3GEO – Geoclimbing & Geotrekking in Geoparks” is financed by the International Geoscience Programme (IGCP) and supported by the International Union of Geological Sciences (IUGS). In this paper, we report on the results of the first phase of the project focused on the criteria to be adopted to select geodiversity sites equipped for climbing or trekking. The selection of geoclimbing sites and geotrekking routes is aimed at combining multimedia tools and outdoor activities for Geosciences promotion and conservation in UNESCO Global Geoparks, aspiring geoparks or geoparks project, and also in protected areas featuring geoheritage sites. Indeed, both outdoor activities and multimedia tools favour the pursuing of many of the United Nations Sustainable Development Goals (e.g., 3, 4, 8, 11). An international consortium of geoscientists from 12 different countries selected, through the proposed procedure, 22 geoclimbing sites, and then they also detected 30 geotrekking routes mirroring Earth geodiversity. At some test sites (geoclimbing and geotrekking) multimedia tools and digital outcrop models have been developed through different methodological approaches (e.g., Structure from Motion and Multi-View Stereo photogrammetry), to open the way to the second part of the project still in progress. These sites and the relative virtual models are herein also shown. The fnal aim of the IGCP 714 project is indeed to create an open data repository (digital outcrop models, videos, virtual tours, photos, scientific information, and interpretations) to upload data of the selected sites to mirror Earth geodiversity for different users including tourists and school groups.
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    Insights into the genetics of blood pressure in black South African individuals: the Birth to Twenty cohort
    (BMC, 2018) Hendry, Liesl M.; Sahibdeen, Venesa; Choudhury, Ananyo; Norris, Shane A.; Ramsay, Michèle; Lombard, Zané
    Background: Cardiovascular diseases (CVDs) are the leading cause of non-communicable disease deaths globally, with hypertension being a major risk factor contributing to CVDs. Blood pressure is a heritable trait, with relatively few genetic studies having been performed in Africans. This study aimed to identify genetic variants associated with variance in systolic (SBP) and diastolic (DBP) blood pressure in black South Africans. Methods: Genotyping was performed using the Metabochip in a subset of participants (mixed sex; median age 17.9) and their adult female caregivers (median age 41.0) from the Birth to Twenty cohort (n = 1947). Data were analysed as a merged dataset (all participants and caregivers together) in GEMMA (v0.94.1) using univariate linear mixed models, incorporating a centered relatedness matrix to account for the relatedness between individuals and with adjustments for age, sex, BMI and principal components of the genotype information. Results: Association analysis identified regions of interest in the NOS1AP (DBP: rs112468105 - p = 7.18 × 10−5 and SBP: rs4657181 - p = 4.04 × 10−5), MYRF (SBP: rs11230796 - p = 2.16 × 10−7, rs400075 - p = 2.88 × 10−7) and POC1B (SBP: rs770373 - p = 7.05 × 10−5, rs770374 - p = 9.05 × 10−5) genes and some intergenic regions (DACH1|LOC440145 (DBP: rs17240498 - p = 4.91 × 10−6 and SBP: rs17240498 - p = 2.10 × 10−5) and INTS10|LPL (SBP: rs55830938 - p = 1.30 × 10−5, rs73599609 - p = 5.78 × 10−5, rs73667448 - p = 6.86×10−5)). Conclusions: The study provided further insight into the contribution of genetic variants to blood pressure in black South Africans. Future functional and replication studies in larger samples are required to confirm the role of the identified loci in blood pressure regulation and whether or not these variants are African-specific.