Biology subjects

Lucero, B.

Publications and source records attributed to Lucero, B..

5 recordsLinked to original sources

bioRxiv2025

Neural information sharing across the orienting attentional network predicts intelligence in children

Efficient brain functioning is often defined as the ability to achieve high performance with minimal cognitive resources. This study investigated the relationship between intelligence and attentional network efficiency in school-aged children, using electroencephalography (EEG) during the Attention Network Test (ANT). Participants were 38 children aged 11-14 years, recruited from schools in the Maule Region of Chile. Attentional network efficiency was assessed through event-related potentials (ERPs), midfrontal theta power as an index of conflict processing, and weighted Symbolic Mutual Information (wSMI) to quantify large-scale, nonlinear information sharing. Higher full-scale IQ scores were specifically associated with reduced wSMI within the orienting network, suggesting greater neural efficiency through less widespread information exchange between dorsal frontoparietal nodes. No significant associations were found between IQ and theta-band power during conflict processing. These findings provide novel evidence linking intelligence in childhood to network-level neural efficiency in attentional orienting, supporting the view that individual differences in cognitive ability reflect not only localized neural activity but also the efficiency of information integration within task-relevant networks.

neuroscience↗

bioRxiv2025

Structure-Activity Relationship and Target Investigation of Thiophen-2-yl-Pyrimidines against Schistosoma species

Chemotherapeutic options for schistosomiasis, a prevalent infectious disease of poverty, are limited to just one drug, praziquantel (PZQ), and alternatives are needed. Our previous studies identified thiophen-2-yl pyrimidines (TPPs), which are structurally derived from microtubule (MT)-active phenylpyrimidines, as potent paralytics of Schistosoma mansoni. Although relatively non-toxic to mammalian cells, the progenitor compound, 3, had poor aqueous solubility and was lipophilic potentially hindering preclinical advancement. To address these issues and expand on the structure-activity and structure-property relationships, 43 new TPP analogs were designed and synthesized, their lipophilicity calculated (cLogP), and their anti-schistosomal activity evaluated in culture. This effort yielded compound 38, which possessed an oxetane-containing amine moiety at C5, and an ortho, ortho-difluoroaniline at C6 of the TPP scaffold. Compared to 3, compound 38 had better aqueous solubility (46 vs. < 0.5 {micro}M) and decreased lipophilicity (logP calc. 4.48 vs. 6.81), with toxicity CC50 values > 20 {micro}M against three mammalian cell lines. Further, paralytic potency, as measured by the EC50 value for adult S. mansoni motility, was increased 14.5-fold (538 vs. 37 nM), and plasma half-life (t1/2) was improved 3-fold, from 0.48 to 1.51 h for a 40% loss in maximum plasma concentration (Cmax). In washout experiments, 38 produced a sustained paralysis of both juvenile and adult S. mansoni, possibly suggesting a broader in vitro efficacy spectrum compared to PZQ, which is inactive against the juvenile parasite. Also, the two other medically important species, Schistosoma haematobium and Schistosoma japonicum, were susceptible to 38. Finally, to identify potential protein targets, we synthesized a TPP photoaffinity labeling (PAL) probe that labeled several S. mansoni proteins by SDS-PAGE fluorescence analysis, although, notably, not tubulin, suggesting that the antischistosomal activity of 38 is a function of engaging other targets. Future work with the TPP series will aim to decrease toxicity further while improving PK properties to better support in vivo efficacy testing.

microbiology↗

bioRxiv2025

Photoaffinity labeling of protein targets in a complex metazoan: proof-of-concept using a probe for Schistosoma mansoni tubulin

Treatment of schistosomiasis, a prevalent neglected tropical disease, relies precariously on a single drug. The discovery and development of alternative anti-schistosomal small molecules most often relies on phenotypic (whole-organism) screening, whereas target- or "protein-first"-based discovery options are hampered by a paucity of genetic interrogation strategies and a complex biology. Here, we demonstrate the application of photoaffinity labeling (PAL) as a chemical biology strategy to probe protein target-ligand interactions in the schistosome. Using a triazolopyrimidine (TPD) probe that binds tubulin, we established a PAL workflow with living Schistosoma mansoni worms. The probe elicited deleterious phenotypic responses consistent with the TPD series and, upon UV light activation, covalently labeled tubulin as identified by proteomics. Specific concentration-dependent engagement of tubulin was confirmed using a photostable competitor TPD. When applied directly to worm lysates, the PAL workflow produced non-specific labeling, suggesting that the conformation of the protein target is important for ligand binding. The successful application of PAL for a metazoan is, to our knowledge, novel, and the platform should prove generally applicable to identifying potential drug targets, and exploring protein-ligand interactions, in schistosomes and other organisms.

cell biology↗

bioRxiv2023

Slow-wave brain connectivity predicts executive functioning and group belonging in socially vulnerable individuals

Important efforts have been made to describe the neural and cognitive features of healthy and clinical populations. However, the neural and cognitive features of socially vulnerable individuals remain largely unexplored, despite their proneness to developing neurocognitive disorders. Socially vulnerable individuals can be characterised as socially deprived, having a low socioeconomic status, suffering from chronic social stress, and exhibiting poor social adaptation. While it is known that such individuals are likely to perform worse than their peers on executive function tasks, studies on healthy but socially vulnerable groups are lacking. In the current study, we explore whether neural power and connectivity signatures can characterise executive function performance in healthy but socially vulnerable individuals, shedding light on the impairing effects that chronic stress and social disadvantages have on cognition. We measured resting-state electroencephalography and executive functioning in 38 socially vulnerable participants and 38 matched control participants. Our findings indicate that while neural power was uninformative, lower delta and theta phase synchrony are associated with worse executive function performance in all participants, whereas delta phase synchrony is higher in the socially vulnerable group compared to the control group. Finally, we found that delta phase synchrony and years of schooling are the best predictors for belonging to the socially vulnerable group. Overall, these findings suggest that exposure to chronic stress due to socioeconomic factors and a lack of education are associated with changes in slow-wave neural connectivity and executive functioning.

neuroscience↗

bioRxiv2023

Structure-Activity Relationships, Tolerability and Efficacy of Microtubule-Active 1,2,4-Triazolopyrimidines as Potential Candidates to Treat Human African Trypanosomiasis

Tubulin and microtubules (MTs) are potential protein targets to treat parasitic infections and our previous studies have shown that the triazolopyrimidine (TPD) class of MT- active compounds hold promise as antitrypanosomal agents. MT-targeting TPDs include structurally related but functionally diverse congeners that interact with mammalian tubulin at either one or two distinct interfacial binding sites; namely, the seventh and vinca sites, which are found within or between ,{beta}-tubulin heterodimers, respectively. Evaluation of the activity of 123 TPD congeners against cultured Trypanosoma brucei enabled a robust quantitative structure-activity relationship (QSAR) model and the prioritization of two congeners for in vivo pharmacokinetics (PK), tolerability and efficacy studies. Treatment of T. brucei-infected mice with tolerable doses of TPDs 3 and 4 significantly decreased blood parasitemia within 24 h. Further, two once-weekly doses of 4 at 10 mg/kg significantly extended the survival of infected mice relative to infected animals treated with vehicle. Further optimization of dosing and/or the dosing schedule of these CNS-active TPDs may provide alternative treatments for human African trypanosomiasis.

microbiology↗