Biosystems & Integrative Sciences Institute

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Temporal and geographical research trends of antimicrobial resistance in wildlife - A bibliometric analysis

Publication . Torres, Rita Tinoco; Carvalho, João; Cunha, Mónica V.; Serrano, Emmanuel; Palmeira, Josman Dantas; Fonseca, Carlos

Antimicrobial resistance (AMR) is a complex and global problem. Despite the growing literature on AMR in the medical and veterinary settings, there is still a lack of knowledge on the wildlife compartment. The main aim of this study was to report the global trends in AMR research in wildlife, through a bibliometric study of articles found in the Web of Science database. Search terms were "ANTIMICROBIAL" OR "ANTIBIOTIC" AND "RESISTANT" OR "RESISTANCE" and "WILDLIFE" "MAMMAL" "BIRD" "REPTILE" "FERAL" "FREE RANGE". A total of 219 articles were obtained, published between 1979 and 2019. A rising interest in the last decades towards this topic becomes evident. During this period, the scientific literature was distributed among several scientific areas, however it became more multidisciplinary in the last years, focusing on the "One Health" paradigm. There was a geographical bias in the research outputs: most published documents were from the United States, followed by Spain, Portugal and the United Kingdom. The most productive institutions in terms of publication number were located in Portugal and Spain. An important level of international collaboration was identified. An analysis of the main keywords showed an overall dominance of "AMR", "E. coli", "genes", "prevalence", "bacteria", "Salmonella spp." and "wild birds". This is the first study providing a global overview of the spatial and temporal trends of research related to AMR in wildlife. Given the growth tendency over the last years, it is envisaged that scientific production will expand in the future. In addition to offering a broad view of the existing research trends, this study identifies research gaps both in terms of geographical incidence and in relation to unexplored subtopics. Unearthing scientific areas that should be explored in the future is key to designing new strategic research agendas in AMR research in wildlife and to inform funding programs.

2020-12Journal article

Open access

MAPK inhibition requires active RAC1 signaling to effectively improve iodide uptake by thyroid follicular cells

Publication . Faria, Márcia; Domingues, Rita; Bugalho, Maria João; Matos, Paulo; Silva, Ana Luísa

The Sodium/Iodide Symporter (NIS) is responsible for the active transport of iodide into thyroid follicular cells. Differentiated thyroid carcinomas (DTCs) usually preserve the functional expression of NIS, allowing the use of radioactive iodine (RAI) as the treatment of choice for metastatic disease. However, a significant proportion of patients with advanced forms of TC become refractory to RAI therapy and no effective therapeutic alternatives are available. Impaired iodide uptake is mainly caused by the defective functional expression of NIS, and this has been associated with several pathways linked to malignant transformation. MAPK signaling has emerged as one of the main pathways implicated in thyroid tumorigenesis, and its overactivation has been associated with the downregulation of NIS expression. Thus, several strategies have been developed to target the MAPK pathway attempting to increase iodide uptake in refractory DTC. However, MAPK inhibitors have had only partial success in restoring NIS expression and, in most cases, it remained insufficient to allow effective treatment with RAI. In a previous work, we have shown that the activity of the small GTPase RAC1 has a positive impact on TSH-induced NIS expression and iodide uptake in thyroid cells. RAC1 is a downstream effector of NRAS, but not of BRAF. Therefore, we hypothesized that the positive regulation induced by RAC1 on NIS could be a relevant signaling cue in the mechanism underlying the differential response to MEK inhibitors, observed between NRAS- and BRAF-mutant tumors. In the present study, we found that the recovery of NIS expression induced through MAPK pathway inhibition can be enhanced by potentiating RAC1 activity in thyroid cell systems. The negative impact on NIS expression induced by the MAPK-activating alterations, NRAS Q61R and BRAF V600E, was partially reversed by the presence of the MEK 1/2 inhibitors AZD6244 and CH5126766. Notably, the inhibition of RAC1 signaling partially blocked the positive impact of MEK inhibition on NIS expression in NRAS Q61R cells. Conversely, the presence of active RAC1 considerably improved the rescue of NIS expression in BRAF V600E thyroid cells treated with MEK inhibitors. Overall, our data support an important role for RAC1 signaling in enhancing MAPK inhibition in the context of RAI therapy in DTC, opening new opportunities for therapeutic intervention.

2021Journal article

Open access

Dynamic regulation of Grapevine’s microRNAs in response to Mycorrhizal Symbiosis and high temperature

Publication . Campos, Catarina; Coito, João Lucas; Cardoso, Hélia; Silva, Jorge Marques da; Pereira, Helena Sofia; Viegas, Wanda; Nogales, Amaia

MicroRNAs (miRNAs) are non-coding small RNAs that play crucial roles in plant development and stress responses and can regulate plant interactions with beneficial soil microorganisms such as arbuscular mycorrhizal fungi (AMF). To determine if root inoculation with distinct AMF species affected miRNA expression in grapevines subjected to high temperatures, RNA-seq was conducted in leaves of grapevines inoculated with either Rhizoglomus irregulare or Funneliformis mosseae and exposed to a high-temperature treatment (HTT) of 40 C for 4 h per day for one week. Our results showed that mycorrhizal inoculation resulted in a better plant physiological response to HTT. Amongst the 195 identified miRNAs, 83 were considered isomiRs, suggesting that isomiRs can be biologically functional in plants. The number of differentially expressed miRNAs between temperatures was higher in mycorrhizal (28) than in non-inoculated plants (17). Several miR396 family members, which target homeobox-leucine zipper proteins, were only upregulated by HTT in mycorrhizal plants. Predicted targets of HTT-induced miRNAs in mycorrhizal plants queried to STRING DB formed networks for Cox complex, and growth and stress-related transcription factors such as SQUAMOSA promoter-binding-like-proteins, homeobox-leucine zipper proteins and auxin receptors. A further cluster related to DNA polymerase was found in R. irregulare inoculated plants. The results presented herein provide new insights into miRNA regulation in mycorrhizal grapevines under heat stress and can be the basis for functional studies of plant-AMF-stress interactions.

2023-03Journal article

Open access

SensAI+Expanse : Prediction of Emotional Valence Changes on Humans in Context by an Artificial Agent Towards Empathy

Publication . Henriques, Nuno Andrade da Cruz; Coelho, Helder Manuel Ferreira; Garcia-Marques, Leonel

The field of Cognitive Science is broader enough on the interdisciplinary study of the brain, mind, and intelligence with a scientific research community gaining momentum over the last few decades. Specifically, joining the two fields of psychology and artificial intelligence (AI) one may envision agents, embodied or not, human-like or wearable, with the ability to significantly change the way humans live. This research conceive the artificial agent as a non-anthropomorphic with adaptive empathy for human-agent interaction (HAI) synergy towards better companionship. Therefore, the main objectives of this research are (a) to build a predictive model for each human user on context-based emotional valence changes; and (b) to study the age, gender, and human behaviour neutrality and robustness of the artificial agent regarding the prediction ability. The context include geographically located data from sensors, text sentiment analysis, and human emotional valence self-report, all timestamped events, using a common mobile device such as a smartphone. Also, to analyse and discuss the results on how to leverage such a model to adapt interaction strategies in order to foster higher levels of empathy between a non-anthropomorphic agent and its interacting human. For these goals SensAI+Expanse is developed where SensAI acts as an embodied nearby agent and Expanse encompass the machine learning resources in efficient manner, i.e., a distributed, fault-tolerant, mobile and Cloud-based platform from scratch as a research tool to continuously, online, gather and process data towards automated machine learning (AutoML) and prediction. The study is designed with a methodology in place to avoid the Western, Educated, Industrialized, Rich, and Democratic (WEIRD) societies bias. This goal is accomplished by collecting data in the wild and worldwide by making use of the publicly accessible Google Play repository for the Android™ SensAI smartphone application. Eligible participants are diverse in age, gender, and behaviour on self-reporting emotional valence. In order to balance the gender distribution by age a dichotomy approach using age median (M = 34) is used. Regarding participation duration, two thirds (33/49) of the eligible individuals for analysis remain interacting for the required minimum of four weeks. The analysis of the results show evidence of significant behaviour differences between some age and gender combinations regarding self-reported emotional valence. Furthermore, the results from a comparison study between state-of-the-art algorithms revealed Extreme Gradient Boosting on average the best model for prediction (F1 = 0:91) with efficient energy use, and explainable using feature importance inspection. Moreover, the artificial agent remained neutral regarding human demographics and, simultaneously, able to reveal individual idiosyncrasies. Therefore, this research contributions include results with evidence, restricted to population and data samples available, of differences in behaviour amongst some combinations of age ranges versus gender. The main contribution is a novel platform for studies regarding human emotional valence changes in context. This system may complement and supersede (eventually) traditional long-list self-appraisal questionnaires. The SensAI+Expanse platform contributes with several parts such as a mobile device application (SensAI) able to adapt and learn in order to predict emotional valence states with high performance, a cloud computing (Cloud) service (SensAI Expanse) with ready-to-action analysis and processing modules towards AutoML. Additionally, smartphone sensing add a contribution for continuous, non-invasive and personalised health check. In the future, developments about human-agent relationships regarding affective interactions are foreseen. Further, the measurement of empathetic reactions and evaluating outcomes may be used to verify and validate health status thus improving care and significantly change the way humans live.

2020-09-16Doctoral thesis

Open access

Ecological drivers of Mycobacterium avium subsp. paratuberculosis detection in mongoose (Herpestes ichneumon) using IS900 as proxy

Publication . Cunha, Mónica V.; Rosalino, L. M.; Leão, Célia; Bandeira, Victor; Fonseca, Carlos; Botelho, Ana; Reis, Ana C.

Mycobacterium avium subsp. paratuberculosis (MAP) is the etiological agent of Johne's disease or paratuberculosis, a chronic infection affecting domestic ruminants worldwide. Despite sporadic reports of MAP occurrence in non-ruminants, information on the risk factors predisposing for infection is still scarce and evidence of transmission paths linking the livestock-wildlife-environment interfaces also remains lacking. In this study, we predicted that environmental, host-related, land use and human driven disturbance factors would modulate carnivore exposure to MAP. To test these hypotheses, we performed a retrospective survey, based on microbiological and molecular methods, in mainland Portugal including five sympatric species from the Herpestidae, Canidae, Viverridae, and Mustelidae families (n = 202) and examined 16 variables as putative predictors of MAP occurrence. Molecular evidence of MAP using IS900 as proxy was demonstrated in 7.43% (95%CI: 4.55-11.9) of surveyed carnivores, the highest proportions being registered for red fox (Vulpes vulpes) (10%; 95%CI: 4.0-23) and Egyptian mongoose (Herpestes ichneumon) (6.0%; 95%CI: 3.2-11). We demonstrate that important species of the Mediterranean carnivore guild, such as stone marten (Martes foina) and common genet (Genetta genetta), may also be exposed to MAP, being this the first time that occurrence in genet is reported. The high proportion of DNA-positive specimens, concurrent with the apparent lack of gastro-enteric lesions and molecular confirmation of IS900 in feces, argue for the presence of subclinical carriers that occasionally shed bacteria, potentially aiding as source of infection to susceptible species and possibly contributing for environmental contamination. Achievement of MAP isolation would prove beyond any doubt that MAP is present in this wildlife population. Ecological modelling results suggested that the probability of MAP infection using IS900 as proxy in mongoose is positively associated with higher altitude and temperature stability, as well as with lower annual rainfall. Density of livestock farms was found not to be a significant predictor, which may indicate that the livestock-wildlife interface is probably not important as an infection route for mongoose.

2020-01Journal article

Open access