Biology subjects

Sebastian, A.

Publications and source records attributed to Sebastian, A..

24 records · Page 2Linked to original sources

bioRxiv2021

Adolescent social stress decrease of adult morphine-induced behavioral sensitization is dependent upon genetic background

1Deaths related to opioid use have skyrocketed in the United States, leading to a public health epidemic. Research has shown that both biological (genes) and environmental (stress) precursors are linked to opioid use. In particular, stress during adolescence - a critical period of frontal lobe development - influences the likelihood of abusing drugs. However, little is known about the biological mechanisms through which adolescent stress leads to long-term risk of opioid use, or whether genetic background moderates this response. Male and female C57BL/6J and BALB/cJ mice were exposed to chronic variable social stress (CVSS) or control conditions throughout adolescence and then tested for morphine locomotor sensitization or morphine consumption in adulthood. To examine possible mechanisms that underlie stress-induced changes in morphine behaviors, we assessed physiological changes in response to acute stress exposure and prefrontal cortex miRNA gene expression. Adolescent stress did not influence morphine sensitization or consumption in BALB/cJ animals, and there was limited evidence of stress effects in female C57BL/6J mice. In contrast, male C57BL/6J mice exposed to adolescent CVSS had blunted morphine sensitization compared to control animals; no differences were observed in the acute locomotor response to morphine administration or morphine consumption. Physiologically, C57BL/6J mice exposed to CVSS had an attenuated corticosterone recovery following an acute stressor and downregulation of twelve miRNA in the prefrontal cortex compared to control mice. The specificity of the effects for C57BL/6J versus BALB/cJ mice provides evidence of a gene by environmental interaction influencing opioid behaviors. Long-term differences in stress reactivity or miRNA expression suggests two possible biological mechanisms to evaluate in future research.

animal behavior and cognition↗

bioRxiv2020

Cortical network mechanisms of response inhibition

Both the right inferior frontal gyrus (rIFG) and the pre-supplementary motor area (pre-SMA) are crucial for successful response inhibition. However, the particular functional roles of those two regions have been controversially debated for more than a decade now. It is unclear whether the rIFG directly initiates stopping or serves an attentional function, whereas the stopping is triggered by the pre-SMA. The current multimodal MEG/fMRI study sought to clarify the role and temporal activation order of both regions in response inhibition using a selective stopping task. This task dissociates inhibitory from attentional processes. Our results reliably reveal a temporal precedence of rIFG over pre-SMA. Moreover, connectivity during response inhibition is directed from rIFG to pre-SMA and predicts stopping performance. Response inhibition is implemented via beta-band oscillations. Our findings support the hypothesis that response inhibition is initiated by the rIFG as a form of attention-independent top-down control.

neuroscience↗

bioRxiv2019

Artificial selection finds new hypotheses for the mechanism of Wolbachia-mediated dengue blocking in mosquitoes

Wolbachia is an intracellular bacterium that blocks virus replication in insects and has been introduced into the mosquito, Aedes aegypti for the biocontrol of arboviruses including dengue, Zika and chikungunya. Despite ongoing research, the mechanism of Wolbachia-mediated virus blocking remains unclear. We recently used experimental evolution to reveal that Wolbachia-mediated dengue blocking could be selected upon in the A. aegypti host and showed evidence that strong levels of blocking could be maintained by natural selection. In this study, we investigate the genetic variation associated with blocking and use these analyses to generate testable hypotheses surrounding the mechanism of Wolbachia-mediated dengue blocking. From our results, we hypothesise that Wolbachia may block virus replication by increasing the regeneration rate of mosquito cells via the Notch signalling pathway. We also propose that Wolbachia modulates the hosts transcriptional pausing pathway either to prime the hosts anti-viral response or to directly inhibit viral replication.

evolutionary biology↗

bioRxiv2018

A Combined Behavioral and Neuroimaging Battery to Test Positive Appraisal Style Theory of Resilience in Longitudinal Studies

Resilience is the maintenance or rapid recovery of mental health during and after stressor exposure. It is becoming increasingly clear that resilience results from a complex and dynamic process of adaptation to stressors involving the biological, psychological and social levels. Positive appraisal style theory of resilience (PASTOR) claims that the common final pathway to maintained mental health lies in the non-negative (non-catastrophizing, non-pessimistic) appraisal of potential stressors, permitting the organism to fine-tune stress responses to optimal levels, thus avoiding unnecessary stress, inefficient deployment of resources and concomitant deleterious allostatic load effects. Successful adaptation consists in developing or strengthening a positive appraisal style. Another key element of PASTOR is that a positive appraisal style is strongly determined by the efficacy and efficiency of the neural and cognitive processes that underlie positive stressor appraisal. We here present a combined behavioral and functional magnetic resonance imaging (fMRI) battery designed to assess such processes repeatedly in longitudinal settings. The battery includes tests of stress reactivity and recovery, reward sensitivity, safety learning and memory in the context of fear conditioning and extinction, volitional situation-focused reappraisal, volitional self-focused reappraisal, and emotional interference inhibition, along with structural MRI and resting-state MRI scans. A detailed description of the battery methods is provided. The feasibility of the battery was successfully tested in N=55 healthy subjects; group results of the individual tasks largely replicate existing literature.

neuroscience↗

bioRxiv2018

Real-time in vivo Global Transcriptional Dynamics During Plasmodium falciparum Blood-stage Development

Genome-wide analysis of transcription in the human malaria parasite Plasmodium falciparum has revealed robust variation in steady-state mRNA abundance throughout the 48-hour intraerythrocytic developmental cycle (IDC) suggesting that this process is highly dynamic and tightly regulated. However, the precise timing of mRNA transcription and decay remains poorly understood due to the utilization of methods that only measure total RNA and cannot differentiate between newly transcribed, decaying and stable cellular RNAs. Here we utilize rapid 4-thiouracil (4-TU) incorporation via pyrimidine salvage to specifically label, capture and quantify newly-synthesized P. falciparum RNA transcripts at every hour throughout the IDC following erythrocyte invasion. This high resolution global analysis of the transcriptome captures the timing and rate of transcription for each newly synthesized mRNA in vivo, revealing active transcription throughout all stages of the IDC. To determine the fraction of active transcription and/or transcript stabilization contributing to the total mRNA abundance at each timepoint we have generated a statistical model to fit the data for each gene which reveals varying degrees of transcription and stabilization for each mRNA corresponding to developmental transitions and independent of abundance profile. Finally, our results provide new insight into co-regulation of mRNAs throughout the IDC through regulatory DNA sequence motifs associated with these processes, thereby expanding our understanding of P. falciparum mRNA dynamics.

microbiology↗

bioRxiv2017

Comprehensive profiling of TCRβ repertoire in a non-model species (the bank vole) using high-throughput sequencing

In recent years, immune repertoire profiling with high-throughput sequencing (HTS) has advanced our understanding of adaptive immunity. However, fast progress in the field applied mostly to human and mouse research, with only few studies devoted to other model vertebrates. We present the first in-depth characterization of the TCR{beta} repertoire in a non-model mammal with limited genomic resources available - the bank vole (Myodes glareolus). We used 5'RACE and Illumina HTS to describe V and J segments and to qualitatively characterize preferential V-J segment usage and CDR3 length distribution. Finally, a molecular protocol integrating unique molecular identifiers was used for quantitative analysis of CDR3 repertoire with stringent error correction. We found 37 V and 11 J genes that were orthologous to mice genes. A conservative, lower bound estimation of the TCR{beta} repertoire was 1.7-2.3x105 clonotypes, and the degree of sharing of the observed repertoire between any two individuals was 3.6% of nucleotide sequences and 14.3% of amino acid sequences. Our work adds a crucial element to the immunogenetic resources available for the bank vole, an important species in ecological and evolutionary research. The workflow that we developed can be applied for immune repertoire sequencing of non-model species, including endangered vertebrates.

immunology↗