Biology subjects

Bravo, F.

Publications and source records attributed to Bravo, F..

5 recordsLinked to original sources

bioRxiv2025

Development of a Customizable Pacing Protocol to Induce Persistent Atrial Fibrillation in Swine

IntroductionPersistent atrial fibrillation (AFib) research is dependent on large animal models to understand pathogenesis and test new treatments and therapeutic techniques. While various methods have been established to induce persistent AFib in large animals, including electrical, surgical, pharmacological, and genetic approaches, each has distinct limitations. The most recent being the device industry no longer providing off-target rapid atrial pacing programs for use in animals. This challenge requires the development of a new accessible model of inducing atrial fibrillation in large animals. Methods UsedWe developed a wireless pacing system using a Raspberry Pi Pico W microcontroller (Pico) programmed for variable pacing frequencies. The device is powered by a subcutaneously implanted 9V battery. The Picos built-in Wi-Fi capabilities enable remote connection and real-time adjustment of pacing frequency output. This protocol describes a prospective study in which swine will undergo chronic right atrial pacing for 3-4 weeks to induce persistent AFib. We tested our device in a domestic swine. Vascular access was established through the left jugular vein and an active fixation pacing lead (Medtronic 5076) was implanted under fluoroscopic guidance in the right atrium. Proper lead positioning and pacing function were confirmed through electrocardiographic monitoring of both atrial and ventricular capture. Preliminary ResultsOscilloscope testing demonstrated frequency and voltage output concordant with the programmed frequencies while real-time adjustments were made through the Wi-Fi interface. A cardiac pacing wire was placed in the right ventricle then relocated to the right atrium and successful pacing with capture was verified using an electrocardiogram. ConclusionsThis protocol will provide a system capable of capturing atrial tissue with confirmed wireless power transfer capabilities that has minimal tissue heating and is physiologically safe. Combined with our literature review findings that electrical atrial pacing methods are most effective for inducing persistent AFib, our device provides researchers with the potential for an improved tool for creating large animal models of persistent AFib.

bioengineering↗

bioRxiv2023

Active Suppression of the Nigrostriatal Pathway during Optogenetic Stimulation Revealed by Simultaneous fPET/fMRI

The dopaminergic system is a central component of the brains neurobiological framework, governing motor control, reward responses, and playing an essential role in various brain disorders such as Parkinsons disease and schizophrenia. Within this complex network, the nigrostriatal pathway represents a critical circuit for dopamine transmission from the substantia nigra to the striatum, a connection that is vital to understanding many of the disease-related dysfunctions. However, stand-alone functional magnetic resonance imaging (fMRI) is unable to study the intricate interplay between brain activation and its molecular underpinnings. In our study, the simultaneous use of [18F]FDG functional positron emission tomography (fPET)/BOLD-fMRI provided a new insight that allowed us to demonstrate an active suppression of the nigrostriatal activity during optogenetic stimulation via presynaptic autoinhibition. Our in vivo observation emphasizes that the observed BOLD signal depression during neuronal stimulation does not correlate with neuronal inactivity, but results from an active suppression of neuronal firing as shown by the high [18F]FDG signal increase. This result not only illustrates the potential of simultaneous fPET/fMRI to understand the molecular mechanisms of brain function but also provides a new perspective on how neurotransmitters such as dopamine influence hemodynamic responses in the brain.

neuroscience↗

bioRxiv2023

We see what we hear: dissonant music engages early visual processing.

The neuroscientific examination of music processing in audiovisual contexts offers a valuable framework to assess how auditory information influences the emotional encoding of visual information. Using fMRI during naturalistic film viewing, we investigated the neural mechanisms underlying musics effect on valence inferences during mental state attribution. Thirty-eight participants watched the same short-film accompanied by systematically controlled consonant or dissonant music. Subjects were instructed to think about the main characters intentions. The results revealed that increasing levels of dissonance led to more negatively-valenced inferences, displaying the profound emotional impact of musical dissonance. Crucially, at the neuroscientific level and despite music being the sole manipulation, dissonance evoked the response of the primary visual cortex response (V1). Functional/effective connectivity analysis showed a stronger coupling between the auditory ventral stream (AVS) and V1 in response to tonal dissonance, and demonstrated the modulation of early visual processing via top-down feedback inputs from the AVS to V1. These V1 signal changes indicate the influence of high-level contextual representations associated with tonal dissonance on early visual cortices, serving to facilitate the emotional interpretation of visual information. The findings substantiate the critical role of audio-visual integration in shaping higher-order functions such as social cognition. Significance statementThe present study reveals responses in the primary visual cortex modulated by musical information: tonal dissonance recruits early visual processing via feedback interactions from the auditory ventral pathway to the primary visual cortex. We demonstrate that the auditory "what" ventral stream plays a role in assigning meaning to non-verbal sound cues, such as dissonant music conveying negative emotions, providing an interpretative framework that serves to process the audio-visual experience. Our results highlight the significance of employing systematically controlled music, which can isolate emotional valence from the arousal dimension, to elucidate the brains sound-to-meaning interface and its distributive crossmodal effects on early visual encoding during naturalistic film viewing. Data sharingAll relevant data are available from the figshare database DOI: 10.6084/m9.figshare.21345240

neuroscience↗

bioRxiv2023

Short-term thinning effect on inter- and intra-annual radial increment of Mediterranean Scots pine-oak mixed forest

Thinning treatment and mixed forest stands have been suggested as possible adaptation strategies to cope to climate change but there is still scarce knowledge about the combination of both subjects. In this study, we aim to better understand the thinning effect and the growth differences between two coexisting species on inter- and intra-annual cumulative radial increment patterns. We studied radial increment of a Scots pine-oak (Pinus sylvestris-Quercus pyrenaica) Mediterranean mixed forest during two climatically contrasted years (2016-2017) in north-western Spain. Data came from a thinning trial consisting in a randomized block experimental design with a control and two thinning treatments from below: a moderate and heavy thinning removing 25% and 50 % of initial basal area respectively focused on both species. Tree radial increment was analyzed based on bi-weekly readings from band dendrometers installed in 90 oak and pine trees. Non-linear mixed model based on double-Richards curve was fitted to show thinning and species differences in intra-annual cumulative radial increment patterns. Inter-annual basal area increment at species and stand levels were estimated using the model previously fitted at tree level and aggregating the results for exploring thinning effects at these levels. Scots pine leaded the tree and stand growth, and had also a better respond to early spring drought compared to oak. Heavy thinning increased tree radial increment for both species at the expense of decreased stand basal area. At species level, basal area increment decreased for Scots pine, however, heavy thinning generated the same oak basal area increment than control. Thus, heavy thinning may be good strategy towards a conversion from overaged coppice stands into high forests to conform a stable mixed forest stand. HighlightsO_LIScots pine leaded growth at tree and stand level C_LIO_LIScots pine trees may take advantage during early spring droughts C_LIO_LIHeavy thinning increased tree radial increment for both species C_LIO_LIHeavy thinning decreases stand basal area growth C_LI

ecology↗

bioRxiv2021

Humoral immune responses against seasonal coronaviruses predict efficiency of SARS-CoV-2 spike targeting, FcγR activation, and corresponding COVID-19 disease severity

Despite SARS-CoV-2 being a "novel" coronavirus, several studies suggest that detection of anti-spike IgG early in infection may be attributable to the amplification of humoral memory responses against seasonal hCoVs in severe COVID-19 patients. In this study, we examined this concept by characterizing anti-spike IgG from a cohort of non-hospitalized convalescent individuals with a spectrum of COVID-19 severity. We observed that anti-spike IgG levels positively correlated with disease severity, higher IgG cross-reactivity against betacoronaviruses (SARS-CoV-1 and OC43), and higher levels of proinflammatory Fc gamma receptor 2a and 3a (Fc{gamma}R2a & Fc{gamma}R3a) activation. In examining the levels of IgG targeting betacoronavirus conserved and immunodominant epitopes versus disease severity, we observed a positive correlation with the levels of IgG targeting the conserved S2FP region, and an inverse correlation with two conserved epitopes around the heptad repeat (HR) 2 region. In comparing the levels of IgG targeting non-conserved epitopes, we observed that only one of three non-conserved immunodominant epitopes correlated with disease severity. Notably, the levels of IgG targeting the receptor binding domain (RBD) were inversely correlated with severity. Importantly, targeting of the RBD and HR2 regions have both been shown to mediate SARS-CoV-2 neutralization. These findings show that, aside from antibody (Ab) targeting of the RBD region, humoral memory responses against seasonal betacoronaviruses are potentially an important factor in dictating COVID-19 severity, with anti-HR2-dominant Ab profiles representing protective memory responses, while an anti-S2FP dominant Ab profiles indicate deleterious recall responses. Though these profiles are masked in whole antigen profiling, these analyses suggest that distinct Ab memory responses are detectable with epitope targeting analysis. These findings have important implications for predicting severity of SARS-CoV-2 infections (primary and reinfections), and may predict vaccine efficacy in subpopulations with different dominant antibody epitope profiles.

microbiology↗