Biology subjects

Silva Pereira, S.

Publications and source records attributed to Silva Pereira, S..

5 recordsLinked to original sources

bioRxiv2024

m6A landscape is more pervasive when Trypanosoma brucei exits the cell cycle

N6-methyladenosine (m6A) is a mRNA modification with important roles in gene expression. In African trypanosomes, this post-transcriptional modification is detected in hundreds of transcripts and it affects the stability of the variant surface glycoprotein (VSG) transcript in the proliferating blood stream form. However, how m6A landscape varies across the life cycle remains poorly defined. Using full-length, non-fragmented RNA, we immunoprecipitated and sequenced m6A-modified transcripts across three life cycle stages of Trypanosoma brucei - slender (proliferative), stumpy (quiescent), and procyclic forms (proliferative). We found that 1037 transcripts are methylated in at least one of these three life cycle stages. While 21% of methylated transcripts are common in the three stages of the life cycle, globally each stage has a distinct methylome. Interestingly, 47% of methylated transcripts are detected in the quiescent stumpy form only, suggesting a critical role for m6A when parasites exit the cell cycle and prepare for transmission by the Tsetse fly. In this stage, we found that a significant proportion of methylated transcripts encodes for proteins involved in RNA metabolism, which is consistent with their reduced transcription and translation. Moreover, we found that not all major surface proteins are regulated by m6A, as procyclins are not methylated, and that, within the VSG repertoire, not all VSG transcripts are demethylated upon parasite differentiation to procyclic form. This study reveals that the m6A regulatory landscape is specific to each life cycle stage, becoming more pervasive as T. brucei exits the cell cycle. SummaryAfrican trypanosome parasites adapt to mammalian and insect hosts by adjusting gene expression, morphology, and metabolism. In this study, we focus on how N6-methyladenosine (m6A), a post-transcriptional modification, affects the parasites transcriptome throughout its differentiation from the mammalian host to the fly. We found that methylation is differentially regulated as the life cycle progresses, being particularly prevalent in the non-proliferative stumpy form, as more methylated transcripts are found at this insect-infective stage than in slender and procyclic forms. We further show that the not all parasite surface proteins are regulated by m6A and that the previously identified link between m6A methylation and the expression level of the major surface protein of bloodstream forms applies to the active variant surface glycoprotein, but not always to silent genes, suggesting two distinct regulatory mechanisms of (de)methylation.

molecular biology↗

bioRxiv2023

Neural entrainment to speech in theta range is affected by language properties but not by listeners' native language

A universal speech rhythm around 5 Hz, corresponding to syllable beats, is captured by neural oscillations in the human brain. However, there is significant variability in syllabic complexity across languages: some languages allow only simple syllables, while some allow more variation (a variation related to linguistic rhythm). Behavioral evidence suggests that humans show different patterns of speech segmentation depending on the linguistic rhythm of their native language. Here, we tested if the entrainment of neural oscillations in the theta range (3-8 Hz) to sentences of languages representative of different linguistic rhythms depends on participants native language rhythm or rather reflects language-specific rhythmic properties. We recorded EEG in two groups of participants: native speakers of English (stress-timed, Experiment 1) and native speakers of Spanish (syllable-timed, Experiment 2). Both groups listened to saltanaj resynthesized sentences from English (stress-timed), Spanish (syllable-timed) and Japanese (mora-timed), a procedure that removes comprehension but keeps language-specific phonological properties. Phase locking value between sentence envelopes and EEG showed the same pattern regardless of participants native language: lowest for English, intermediate for Spanish, and highest for Japanese. Our results suggest that entrainment to speech in the theta frequency range is sensitive to differences in variation in syllabic complexity across languages.

neuroscience↗

bioRxiv2019

Dynamical informational structures characterize the different human brain states of wakefulness and deep sleep

The dynamical activity of the human brain describes an extremely complex energy landscape changing over time and its characterisation is central unsolved problem in neuroscience. We propose a novel mathematical formalism for characterizing how the landscape of attractors sustained by a dynamical system evolves in time. This mathematical formalism is used to distinguish quantitatively and rigorously between the different human brain states of wakefulness and deep sleep. In particular, by using a whole-brain dynamical ansatz integrating the underlying anatomical structure with the local node dynamics based on a Lotka-Volterra description, we compute analytically the global attractors of this cooperative system and their associated directed graphs, here called the informational structures. The informational structure of the global attractor of a dynamical system describes precisely the past and future behaviour in terms of a directed graph composed of invariant sets (nodes) and their corresponding connections (links). We characterize a brain state by the time variability of these informational structures. This theoretical framework is potentially highly relevant for developing reliable biomarkers of patients with e.g. neuropsychiatric disorders or different levels of coma.

neuroscience↗

bioRxiv2019

Variant antigen diversity in Trypanosoma vivax is not driven by recombination

African trypanosomes are vector-borne haemoparasites that cause African trypanosomiasis in humans and animals. Parasite survival in the bloodstream depends on immune evasion, achieved by antigenic variation of the Variant Surface Glycoprotein (VSG) coating the trypanosome cell surface. Recombination, or rather directed gene conversion, is fundamental in Trypanosoma brucei, as both a mechanism of VSG gene switching and of generating antigenic diversity during infections. Trypanosoma vivax is a related, livestock pathogen also displaying antigenic variation, but whose VSG lack key structures necessary for gene conversion in T. brucei. Thus, this study tests a long-standing prediction that T. vivax has a more restricted antigenic repertoire. Here we show that global VSG repertoire is broadly conserved across diverse T. vivax clinical strains. We use sequence mapping, coalescent approaches and experimental infections to show that recombination plays little, if any, role in diversifying T. vivax VSG sequences. These results explain interspecific differences in disease, such as propensity for self-cure, and indicate that either T. vivax has an alternate mechanism for immune evasion or else a distinct transmission strategy that reduces its reliance on long-term persistence. The lack of recombination driving antigenic diversity in T. vivax has immediate consequences for both the current mechanistic model of antigenic variation in African trypanosomes and species differences in virulence and transmission strategy, requiring us to reconsider the wider epidemiology of animal African trypanosomiasis.

microbiology↗

bioRxiv2018

VAPPER: High-throughput Variant Antigen Profiling in African trypanosomes

BackgroundAnalysing variant antigen gene families on a population scale is a difficult challenge for conventional methods of read mapping and variant calling due to the great variability in sequence, copy number and genomic loci. In African trypanosomes, hemoparasites of humans and animals, this is complicated by variant antigen repertoires containing hundreds of genes subject to various degrees of sequence recombination.\n\nFindingsWe introduce Variant Antigen Profiler (VAPPER), a tool that allows automated analysis of variant antigen repertoires of African trypanosomes. VAPPER produces variant antigen profiles for any isolate of the veterinary pathogens Trypanosoma congolense and Trypanosoma vivax from genomic and transcriptomic sequencing data and delivers publication-ready figures that show how the queried isolate compares with a database of existing strains. VAPPER is implemented in Python. It can be installed to a local Galaxy instance from the ToolShed (https://toolshed.g2.bx.psu.edu/) or locally on a Linux platform via the command line (https://github.com/PGB-LIV/VAPPER). The documentation, requirements, examples, and test data are provided in the Github repository.\n\nConclusionOur approach is the first to allow large-scale analysis of trypanosome variant antigens and establishes two different methodologies that may be applicable to other multi-copy gene families that are otherwise refractory to high-throughput analysis.

bioinformatics↗