Biology subjects

Rigoni, D.

Publications and source records attributed to Rigoni, D..

3 recordsLinked to original sources

bioRxiv2024

TumFlow: An AI Model for Predicting New Anticancer Molecules

MotivationMelanoma is a severe form of skin cancer increasing globally with about 324.000 cases in 2020, making it the fifth most common cancer in the United States. Conventional drug discovery methods face limitations due to the inherently time consuming and costly. However, the emergence of artificial intelligence (AI) has opened up new possibilities. AI models can effectively simulate and evaluate the properties of a vast number of potential drug candidates, substantially reducing the time and resources required by traditional drug discovery processes. In this context, the development of AI normalizing flow models, employing machine learning techniques to create new molecular structures, holds great promise for accelerating the discovery of effective anticancer therapies. ResultsThis manuscript introduces a novel AI model, named TumFlow, aimed at generating new molecular entities with potential therapeutic value in cancer treatment. It has been trained on the comprehensive NCI-60 dataset, encompassing thousands of molecules tested across 60 tumour cell lines, with a specific emphasis on the melanoma SK-MEL-28 cell line. The model successfully generated new molecules with predicted improved efficacy in inhibiting tumour growth while being synthetically feasible. This represents a significant advancement over conventional generative models, which often produce molecules that are challenging or impossible to synthesize. Furthermore, TumFlow has also been utilized to optimize molecules known for their efficacy in clinical melanoma treatments. This led to the creation of novel molecules with a predicted enhanced likelihood of effectiveness against melanoma, currently undocumented on PubChem. Availability and Implementationhttps://github.com/drigoni/TumFlow. Supplementary informationUploaded.

bioinformatics↗

bioRxiv2023

Nicotine in adolescence freezes dopamine circuits in an immature state

Nicotine use during adolescence is largely associated with negative long-term outcomes, including addiction to nicotine in adulthood. How nicotine acts on developing neurocircuitry in adolescence remains largely unknown, but may hold the key for informing more effective intervention efforts. We found transient nicotine exposure in early adolescence was sufficient for adult mice to show a marked vulnerability to nicotine. Brain-wide activity mapping showed that these mice had an enhanced response to an acute nicotine injection and widespread disruption of functional connectivity in comparison to controls, particularly within dopaminergic networks. Neurophysiological analysis further revealed that their ventral tegmental area (VTA) dopamine neurons show an immature basal plasticity signature and an adolescent-like imbalance in nicotine-induced activity between nucleus accumbens (NAc) and amygdala (AMG)-projecting pathways, known to respectively produce the reinforcing and anxiogenic effects of nicotine. The anxiogenic effect of nicotine is abolished in adult mice treated with nicotine in adolescence, strongly resembling the normal phenotype of young mice. Together these results suggest that nicotine exposure in adolescence somehow "froze" both their neural circuit and behavioral reaction to nicotine, carrying an adolescent-like vulnerability to the drug into adulthood. Finally, we are able to "thaw" the behavioral response to acute nicotine in adolescent-exposed mice by chemogenetically resetting the balance between the underlying NAc- and AMG-projecting dopamine circuits, restoring a mature anxiety-like response to acute nicotine. Together, our results highlight how diverse dopamine pathways can be impacted by experience in adolescence, and further suggest that the perseverance of a developmental imbalance between dopamine pathways may alter vulnerability profiles for later dopamine-dependent psychopathologies.

neuroscience↗

bioRxiv2019

I believe, therefore I am: Effects of self-control beliefs on behavioral and electrophysiological markers of inhibitory and emotional attention control

In this study, a placebo/nocebo neuro-stimulation procedure was employed to investigate if expectations about self-control can influence self-control exertion. More specifically, we recorded behavioral and electrophysiological responses in an emotional antisaccade task in a between-subjects design, in which one group was led to believe that self-control was enhanced (MSC group) and the other that self-control was weakened (LSC group). This set-up allowed to investigate both response and emotional inhibition, as well as different stages at which control can be exerted during task performance, using Event-Related Potential (ERP) methods. Results showed that the bogus neuro-stimulation indeed installed the expectation of respectively better or worse self-control capacity, as well as the retrospective evaluation at the end of the experiment that the neuro-stimulation changed their self-control in that direction. Participants in the MSC compared to the LSC group showed higher accuracy in trials in which inhibitory control was necessary (antisaccade trials). ERP results showed no effect of the placebo/nocebo manipulation at the level of attention and inhibitory control. In sum, this study showed that high-order cognitive processes are not immune to the influence of expectations induced by a placebo/nocebo procedure, and shows that instructions alone can induce a placebo/nocebo effect in cognitive functioning.

neuroscience↗