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Nunes, M.

Publications and source records attributed to Nunes, M..

8 recordsLinked to original sources

Prediction of fMRI activity using vector autoregressive models: a comparison of sparse and low-rank approaches

Vector autoregressive (VAR) models have a history of being used to examine functional connectivity in the brain, as captured by functional MRI studies. Such models allow for an estimation of Granger-causal relationships between regions of interest across the brain. Unfortunately, since the number of parameters in the VAR model scales as the square of the number of regions, and this is typically large compared to the number of temporal observations, these parameter estimates will exhibit high variance. To address this challenge, we introduce a low-rank pre-smoothing method that applies a low-rank approximation to the observations before fitting a VAR model. We estimate these models using individual subject data from both task-based and resting-state conditions, tuning hyperparameters at the population level. Our low-rank approach is directly compared against sparse and unconstrained estimation methods. Evaluations of predictive performance and model structure reveal that our pre-smoothing technique enables robust individual-level parameter estimation and significantly reduces prediction error, a finding further validated by synthetic experiments where the ground-truth parameters are known.

neuroscience↗

Cdc42 activation is necessary for heterosynaptic cooperation and competition

Synapses change their weights in response to neuronal activity and in turn, neuronal networks alter their response properties and ultimately allow the brain to store information as memories. As for memories, not all events are maintained over time. Maintenance of synaptic plasticity depends on the interplay between functional changes at synapses and the synthesis of plasticity-related proteins that are involved in stabilizing the initial functional changes. Different forms of synaptic plasticity coexist in time and across the neuronal dendritic area. Thus, homosynaptic plasticity refers to activity-dependent synaptic modifications that are input-specific, whereas heterosynaptic plasticity relates to changes in non-activated synapses. Heterosynaptic forms of plasticity, such as synaptic cooperation and competition allow neurons to integrate events that occur separated by relatively large time windows, up to one hour. Here, we show that activation of Cdc42, a Rho GTPase that regulates actin cytoskeleton dynamics, is necessary for the maintenance of long-term potentiation (LTP) in a time-dependent manner. Inhibiting Cdc42 activation does not alter the time-course of LTP induction and its initial expression but blocks its late maintenance. We show that Cdc42 activation is involved in the phosphorylation of cofilin, a protein involved in modulating actin filaments and that weak and strong synaptic activation leads to similar levels on cofilin phosphorylation, despite different levels of LTP expression. We show that Cdc42 activation is required for synapses to interact by cooperation or competition, supporting the hypothesis that modulation of the actin cytoskeleton provides an activity-dependent and time-restricted permissive state of synapses allowing synaptic plasticity to occur. We found that under competition, the sequence in which synapses are activated determines the degree of LTP destabilization, demonstrating that competition is an active destabilization process. Taken together, we show that a dynamic actin cytoskeleton is necessary for the expression of homosynaptic and heterosynaptic forms of plasticity. Determining the temporal and spatial rules that determine whether synapses cooperate or compete will allow us to understand how memories are associated. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=101 SRC="FIGDIR/small/559525v1_ufig1.gif" ALT="Figure 1"> View larger version (20K): org.highwire.dtl.DTLVardef@19541a3org.highwire.dtl.DTLVardef@86662org.highwire.dtl.DTLVardef@179b320org.highwire.dtl.DTLVardef@df1f8f_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LICdc42 is required for the maintenance of homosynaptic synaptic plasticity C_LIO_LIWeak and strong stimulation modulate actin by cofilin phosphorylation C_LIO_LICdc42 activation is necessary for heterosynaptic cooperation and competition C_LIO_LISynaptic competition is an active destabilization process C_LIO_LIThe time-window of synaptic cooperation and competition is activity dependent C_LI

neuroscience↗

Correlates of time to first citation in ecology and taxonomy

Several metrics exists to evaluate the impact of publications and researchers, but most are based on citation counts, which usually fail to capture the temporal aspect of citations. Time to first citation represents a useful metric for research evaluation, and informs the speed at which scientific knowledge is disseminated through the scientific community. Understanding which factors affect such metrics is important as they impact resource allocation and career progression, besides influencing knowledge promotion across disciplines. Many ecological works rely on species identity, which is the coin of taxonomy. Despite its importance, taxonomy is a discipline in crisis lacking staff, funds and prestige, which ultimately may affect the evaluation and dissemination of taxonomic works. We used a time-to-event analysis to investigate whether taxonomic, socioeconomic, and scientometric factors influence first citation speed across hundreds of ecological and taxonomic articles. Time to first citation differed greatly between these areas. Ecological studies were first cited much faster than taxonomic studies. Multitaxa articles received first citations earlier than studies focused on single major taxonomic groups. Article length and h-index among authors were negatively correlated with time to first citation, while the number of authors, number of countries, and Gross Domestic Product was unimportant. Knowledge dissemination is faster for lengthy, multitaxa, and ecological articles relative to their respective counterparts, as well as for articles with highly prolific authors. We stress that using several unrelated metrics is desirable when evaluating research from different-and even related-disciplines, particularly in the context of professional progression and grant allocation.

scientific communication and education↗

Carbamazepine Causes Changes in Maternal Reproductive Performance and Fetal Growth Retardation in Rats

PurposeCarbamazepine (CBZ) is widely used in the treatment of trigeminal neuralgia, affective disorders, and mainly as an anticonvulsant, specially by fertile women, due to their need to continuously use CBZ during pregnancy and the lactation period. CBZ crosses the placenta barrier and may impair pregnancy and the embryonic development. The aim of this study was to determine the effect of CBZ on maternal reproductive outcome, besides fetal growth and development in Wistar rats. MethodsRat dams received CBZ (20mg/Kg/day) or propylene glycol (vehicle) via intraperitoneal (i.p.) injection throughout the gestational period. On the 19th day of gestation, the ovary and uterine contents were examined, and the placenta and fetuses were analyzed. ResultsThe CBZ exposure during pregnancy caused a reduction in fetal weight, fetal weight classification, and crown-rump distance. CBZ also decreased the implantation index, average number of corpora lutea, fetal weights and crown-rump length and increased the pre and post-implantation loss rate. The CBZ-exposed fetus also presented external congenital malformations. ConclusionThe results suggest that maternal exposure to CBZ interfered on several maternal reproductive outcomes and can cause severe fetal intrauterine growth restriction (IUGR).

developmental biology↗

Non-apoptotic Role of Cleaved Caspase-3 in Rat Male Germ Cell Development

Germ cells emerge from the epiblast and migrate to the gonads, where they become gonocytes. The gonocytes are the precursors of the spermatogonial stem cells, but little is known about their differentiation. The rigid control of gonocyte proliferation, quiescence and pluripotency marker expression is crucial for spermatogonia development. We have previously suggested that cleaved caspase-3 (Casp3) might play a non-apoptotic role in gonocyte quiescence. Here we describe when rat fetal gonocyte enter mitotic arrest and show that Casp3 inhibition in these cells affects the expression of cell cycle genes. The expression of Ki67, p27Kip, Retinoblastoma 1 (pRb1), NANOG and CASP3 was investigated in 15, 17 and 19 days post coitum rat embryo gonads. The results show that Ki67 and pRB1 proteins are downregulated from 15 days post coitum to 19 days post coitum, whereas p27Kip, NANOG and CASP3 are upregulated. This suggests that rat germ cells start to enter quiescence around 15dpc and that CASP3 and NANOG seem to play a role in this process. CASP3 labelling formed a ring in gonocyte cytoplasm, which is clearly distinct from apoptotic cell labelling, and coincided with NANOG labelling. CASP3 inhibition lead to an increase of Pcna expression and to a decrease of p27kip and p21cip expression. These results suggest that cleaved CASP3 has a role in rat male germ cell development which can be related to the control of the cell cycle genes.

developmental biology↗

The evolutionary dynamics of Oropouche Virus (OROV) in South America

The Amazon basin is host to numerous arthropod-borne viral pathogens that cause febrile disease in humans. Among these, Oropouche orthobunyavirus (OROV) is a relatively understudied member of the Peribunyavirales that causes periodic outbreaks in human populations in Brazil and other South American countries. Although several studies have described the genetic diversity of the virus, the evolutionary processes that shape the viral genome remain poorly understood. Here we present a comprehensive study of the genomic dynamics of OROV that encompasses phylogenetic analysis, evolutionary rate estimates, inference of natural selective pressures, recombination and reassortment, and structural analysis of OROV variants. Our study includes all available published sequences, as well as a set of new OROV genomes sequences obtained from patients in Ecuador, representing the first set of viral genomes from this country. Our results show that differing evolutionary processes on the three segments that encompass the viral genome lead to variable evolutionary rates and TMRCAs that could be explained by cryptic reassortment. We also present the discovery of previously unobserved putative N-linked glycosylation sites, and codons which evolve under positive selection on the viral surface proteins, and discuss the potential role of these features in the evolution of the virus through a combined phylogenetic and structural approach.

evolutionary biology↗

Dynamics of Sox2 expression during rat germ cell development and its relationship with emergence of spermatogonia

1.The gonocytes represent a specific phase of male gem cell development that precedes spermatogonial stem cell differentiation. Here, we describe the expression of Sox2, an OCT4 partner, during rat germ cell development. Our hypothesis is that SOX2 has a cytoplasmic role during gonocyte-to-spermatogonia transition. Male rat embryos and testes were submitted to the analysis of Sox2 expression. Sox2 was detected in germ cells from 14 days post-conception (dpc) to 8dpp. SOX2 was present in 14dpc and 15dpc embryos and absent at 17 and 19dpc; however, it did not show direct correlation with mRNA. SOX2 labelling was detected after birth and its expression increased from 1dpp to 5dpp. SOX2 was localized in the cytoplasm and showed a granulated pattern similar to P-bodies. Indeed, GW182/SOX2 and LIN28/SOX2 double-labelling showed that SOX2 partially co-localized with the P-bodies components GW182 and LIN28. At 8dpp SOX2 was detected in the nucleus and/or in the cytoplasm of spermatogonia, whereas at 25dpp it was detected in the nucleus of rare spermatogonia. This suggests that SOX2 localization changes during gonocytes to spermatogonia transition.

developmental biology↗

Multiplex PCR method for MinION and Illumina sequencing of Zika and other virus genomes directly from clinical samples

Genome sequencing has become a powerful tool for studying emerging infectious diseases; however, genome sequencing directly from clinical samples without isolation remains challenging for viruses such as Zika, where metagenomic sequencing methods may generate insufficient numbers of viral reads. Here we present a protocol for generating coding-sequence complete genomes comprising an online primer design tool, a novel multiplex PCR enrichment protocol, optimised library preparation methods for the portable MinION sequencer (Oxford Nanopore Technologies) and the Illumina range of instruments, and a bioinformatics pipeline for generating consensus sequences. The MinION protocol does not require an internet connection for analysis, making it suitable for field applications with limited connectivity. Our method relies on multiplex PCR for targeted enrichment of viral genomes from samples containing as few as 50 genome copies per reaction. Viral consensus sequences can be achieved starting with clinical samples in 1-2 days following a simple laboratory workflow. This method has been successfully used by several groups studying Zika virus evolution and is facilitating an understanding of the spread of the virus in the Americas.

genomics↗