IMPORTANCE:Ocular complications in infants with Congenital Zika Syndrome (CZS) have been reported. However, the molecular mechanisms underlying of eye dysfunctions are presently unknown. OBJECTIVE:A method (termed Cellular Imprinting Proteomics, CImP) for the identification and quantification of the ocular surface proteome using a minimally invasive membrane filter device is described. Moreover, The CImP method was applied to profile the molecular alterations in the eyes of infants exposed to Zika virus (ZIKV) infection during gestation. DESIGN, SETTINGS AND PARTICIMPANTS:The CImP method was applied to a cohort divided into three conditions: 1) Ctrl (infants with no infectious diseases, n=5). 2) Zikv (infants exposed to ZIKV gestation, with no microcephaly, n=5). 3) Zikv CZS (infants exposed to ZIKV, with microcephaly, n=3). All conditions were age and sex-matched. An improved impression cytology method was used to capture the outermost ocular surface cells. The number of impression cytology membrane collected was: Ctrl (12), Zikv (14) and Zikv CZS (8). Proteins were extracted and analysed using mass spectrometry-based proteomics technology followed by statistical analysis. Parallel reaction monitoring was performed to validate the expression of specific protein markers. RESULTS:Using the CImP method, 2209 proteins were identified on the membrane-captured conjunctiva epithelial cells. Modulation of neutrophil degranulation, cell death, ocular and neurodevelopment pathways are reported in infants with CZS compared to matched controls.Moreover, the molecular pattern of ocular surface cells retrieved from infants infected during the gestation but with no CZS was different from matched controls. CONCLUSIONS AND PERSPECTIVES: Molecular alterations in the ocular cell surface associatedto ZIKV infection with and without CZS complications are reported for the first time. We predict that this method will be introduced successfully in the study of several neurological diseases with the aim to identify novel diagnostic and therapeutic biomarkers. Introduction:Zika virus (ZIKV) is a positive-strand RNA virus belonging to the Flaviviridae family that is transmitted to humans predominantly by the female Aedes aegypti and Aedes albopictus mosquitos (1). Moreover, sexual contact, blood transfusions, laboratory and healthcare settings Subjects, materials and methods Patient cohortThis study comprises 13 infants with and without CZS referred to the Pediatric Service of the Antonio Pedro University Hospital, Fluminense Federal University, Niteroi, Brazil. This study was approved by Institutional review board and ethics committee of Fluminense Federal University, protocol CAAE number 79890517.6.0000.5243, and followed the guidelines of the Declaration of Helsinki. All samples were collected upon informed and written consent from the parents/legal guardians of each participant. Clinical examination was performed by a multidisciplinary team and all infants included in this study are part of a clinical follow up program currently in pr...

Unpublished letter in response to Hafri, A., & Firestone, C. (2021). The perception of relations. Trends in Cognitive Sciences. DOI: 10.1016/j.tics.2021.01.006

The etiological agent of Chagas disease, Trypanosoma cruzi, is subdivided into seven genetic subdivisions termed discrete typing units (DTUs), TcI-TcVI and Tcbat. The relevance of T. cruzi genetic diversity to the variable clinical course of the disease, virulence, pathogenicity, drug resistance, transmission cycles and ecological distribution justifies the concerted efforts towards understanding the population structure of T. cruzi strains. In this study, we introduce a novel approach termed 'phyloquant' to infer the evolutionary relationships and assignment of T. cruzi strains to their DTUs based on differential protein expression profiles evidenced by bottom up large scale mass spectrometry-based quantitative proteomic features. Mass spectrometry features analyzed using parsimony (MS1, iBAQ and LFQ) showed a close correlation between protein expression and T. cruzi DTUs and closely related trypanosome species. Although alternative topologies with minor differences between the three MS features analyzed were demonstrated, we show congruence to well accepted evolutionary relationships of T. cruzi DTUs; in all analyses TcI and Tcbat were sister groups, and the parental nature of genotype TcII and the hybrid genotypes TcV/TcVI were corroborated. Character mapping of genetic distance matrices based on phylogenetics and phyloquant clustering showed statistically significant correlations. We propose the first quantitative shotgun proteomics approach as a complement strategy to the genetic-based assignment of T. cruzi strains to DTUs and evolutionary inferences. Moreover, this approach allows for the identification of differentially regulated and strain/DTU/species-specific proteins, with potential application in the identification of strain/DTU specific biomarkers and candidate therapeutic targets. In