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Summary: The 19th ISCB Student Council Symposium (SCS2023) organized by ISCB-SC adopted a hybrid format for the first time, allowing participants to engage in-person in Lyon, France, and virtually via an interactive online platform. The symposium prioritized inclusivity, featuring on-site sessions, poster presentations, and social activities for in-person attendees, while virtual participants accessed live sessions, interactive Q&A, and a virtual exhibit hall. Attendee statistics revealed a global reach, with Europe as the major contributor. SCS2023's success in bridging in-person and virtual experiences sets a precedent for future events in Computational Biology and Bioinformatics. Availability and Implementation: The details of the symposium, speaker information, schedules, and accepted abstracts, are available in the program booklet (https://doi.org/10.5281/zenodo.8173977). For organizers interested in adopting a similar hybrid model, it would be beneficial to have access to details regarding the online platform used, the types of sessions offered, and the challenges faced. Future iterations of SCS can address these aspects to further enhance accessibility and inclusivity.
RESUMO
Sorafenib is a multikinase inhibitor indicated for first-line treatment of unresectable hepatocellular carcinoma. Despite its widespread use in the clinic, the existing knowledge of sorafenib mode-of-action remains incomplete. To build upon the current understanding, we used the Cellular Thermal Shift Assay (CETSA) coupled to Mass Spectrometry (CETSA-MS) to monitor compound binding to its target proteins in the cellular context on a proteome-wide scale. Among the potential sorafenib targets, we identified aldehyde dehydrogenase 2 (ALDH2), an enzyme that plays a major role in alcohol metabolism. We validated the interaction of sorafenib with ALDH2 by orthogonal methods using pure recombinant protein, proving that this interaction is not mediated by other cellular components. Moreover, we showed that sorafenib inhibits ALDH2 activity, supporting a functional role for this interaction. Finally, we were able to demonstrate that both ALDH2 protein expression and activity were reduced in sorafenib-resistant cells compared to the parental cell line. Overall, our study allowed the identification of ALDH2 as a novel sorafenib target and sheds light on its potential role in both hepatocellular carcinoma and sorafenib resistance condition.
Assuntos
Aldeído-Desidrogenase Mitocondrial , Carcinoma Hepatocelular , Neoplasias Hepáticas , Proteoma , Sorafenibe , Sorafenibe/farmacologia , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/metabolismo , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Aldeído-Desidrogenase Mitocondrial/genética , Aldeído-Desidrogenase Mitocondrial/metabolismo , Linhagem Celular Tumoral , Inibidores de Proteínas Quinases/farmacologia , Antineoplásicos/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/genética , Ligação Proteica/efeitos dos fármacosRESUMO
Obesity entails metabolic alterations across multiple organs, highlighting the role of inter-organ communication in its pathogenesis. Extracellular vesicles (EVs) are communication agents in physiological and pathological conditions, and although they have been associated with obesity comorbidities, their protein cargo in this context remains largely unknown. To decipher the messages encapsulated in EVs, we isolated plasma-derived EVs from a diet-induced obese murine model. Obese plasma EVs exhibited a decline in protein diversity while control EVs revealed significant enrichment in protein-folding functions, highlighting the importance of proper folding in maintaining metabolic homeostasis. Previously, we revealed that gut-derived EVs' proteome holds particular significance in obesity. Here, we compared plasma and gut EVs and identified four proteins exclusively present in the control state of both EVs, revealing the potential for a non-invasive assessment of gut health by analyzing blood-derived EVs. Given the relevance of post-translational modifications (PTMs), we observed a shift in chromatin-related proteins from glycation to acetylation in obese gut EVs, suggesting a regulatory mechanism targeting DNA transcription during obesity. This study provides valuable insights into novel roles of EVs and protein PTMs in the intricate mechanisms underlying obesity, shedding light on potential biomarkers and pathways for future research.
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Vesículas Extracelulares , Proteômica , Humanos , Camundongos , Animais , Obesidade/metabolismo , Processamento de Proteína Pós-Traducional , Proteoma/metabolismo , Vesículas Extracelulares/metabolismoRESUMO
Bartonella spp. comprises emergent and re-emergent fastidious Gram-negative bacteria with worldwide distribution. Cats are the main reservoir hosts for Bartonella henselae and dogs represent opportunistic hosts for the bacteria. Even though ticks may also play a role in transmission, their competence as vectors for Bartonella spp. has not been totally understood. Considering only a few studies had a focus on screening Bartonella in animals, humans and ectoparasites in Portugal, this study aimed to address the molecular occurrence of Bartonella sp. in 123 stray cats, 25 stray dogs, 30 humans from Lisbon and 236 questing ticks within the country. Using a qPCR targeting the nuoG gene, it was possible to detect Bartonella sp. DNA on 20.32% of cat samples (25/123). From these positive samples, 13 sequences were characterized as B. henselae, 11 as B. clarridgeiae and 1 presented co-infection with both species. The absolute quantification of nuoGBartonella DNA in sampled cats ranged from 2.78 × 10 to 1.03 × 105 copies/µL. The sampled dogs, humans and ticks were negative. These results showed that B. henselae and B. clarridgeiae are circulating in stray cats from Lisbon. Additional and more extended studies should be conducted to determine the impact of such infections on humans, particularly those in constant and direct contact with cats.