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Carboni, A.

Publications and source records attributed to Carboni, A..

7 recordsLinked to original sources

Reproducibility of Scientific Claims in Drosophila Immunity: A Retrospective Analysis of 400 Publications

Drosophila immunity has been the focus of intense study and has impacted other research fields including innate immunity and agriculturally or epidemiologically relevant investigations of insect pests and vectors. Unsurprisingly for such a large body of work, some published results were later found to be irreplicable. Although some results have been contradicted in the literature, many have no published follow-up, either due to a lack of research or low motivation to publish negative or contradictory results. We have addressed this by performing a reproducibility project that analyses the conceptual replicability of claims from articles published on Drosophila immunity before 2011. To assess replicability, we extracted claims from 400 articles on the Drosophila immune response to bacteria and fungi and performed preliminary verification by comparing these claims to other published literature in the field. Using alternative approaches, we also experimentally tested some unchallenged claims, with no published follow-up. The intent of this analysis was to centralize evidence on insights and findings to improve clarity for scientists that may base research programs on these data. Although the aim of the ReproSci project is to assess the replicability of claims made in articles published in the field of Drosophila immunity, it is in no way an assessment of the scientific value of the research. All our data are published on a publicly available website associated with this article (https://ReproSci.epfl.ch/) that encourages community participation. This article provides a short summary of claims that were found to have contradictory evidence, which may help the community to assess past findings on Drosophila immunity and improve clarity going forward. Statistical analysis of this reproducibility study and metascience insights obtained from this approach are discussed in a companion article.

genetics↗

Never mind the repeat: How speech expectations reduce tracking at the cocktail party

When the brain focuses on a conversation in a noisy environment, it exploits past experience to prioritize relevant elements from the auditory scene. This prompts the question of what changes occur in the selective neural processing of speech mixtures as listeners garner prior experience about single speech objects. In three different priming experiments, we quantified cortical selection of temporal landmarks from continuous speech, applying the temporal response function (TRF) method to single-trial electroencephalography (EEG) recordings. The designs specifically addressed how attention interacts with exact (Experiment 1), voice (Experiment 2a), or message (Experiment 2b) content priming of the target or background speakers in cortical responses to speech. Our results demonstrate that, during multispeaker listening, attentional gains typical of cortical responses under speech selection are met with attenuations as a consequence of prior experience. The changes were observed at the P2 processing stage (220-320 ms) of speech envelope onset processing and were specific to responses to primed speech targets (Experiment 1). Suppressions at stages earlier than the P2, or under partial priming conditions (Experiments 2a and 2b), were not observed. An exploratory analysis suggests the observed P2 reduction predicts listeners ability to report target words, consistent with this component encoding in part temporal prediction error about onset edge cues exclusive to target speech. Our results show that at this late and definitive stage of selective attention, the auditory system may test the evidence for its own predictive model of the noise-invariant speech stream. Precise inference of its temporal structure is bound to tag all checkpoints where auditory evidence can be most reliably connected into higher-order representations of continuous speech.

neuroscience↗

Loss of precise auditory sampling as a sign of value-driven visual attentional capture

Conditioning sensory signals endows persistent salience that influences attention, even after they no longer connect with rewards. As distractors shape multisensory target processing, conditioning phenomena remain poorly understood in relation to continuous sensory encoding. We investigate the effects of value-driven attentional capture by visual cues on the ability to reliably phase-lock cortical activity to temporal modulations of sound in audiovisual (AV) displays. Listening to periodically-modulated sound, observers discriminated between two visual object streams flickering at different rates, searching for an AV match. Also in view were peripheral color cues, used to evaluate how they modulate participant tracking fidelity as a result of color-reward associative training. Behavioral and electroencephalography (EEG) recordings (N=31) show that performance impoverished in presence of colors previously associated with reward, and so did tracking reliability measured by phase locking of AV responses. Decreased temporal precision predicted participants reward-driven distraction, evidencing the attentional shift away from the multimodal target timing structure. Loss of consistency was furthermore present in auditory response estimates, suggesting value-driven attentional capture withdraws cortical tracking fidelity across the senses. The findings are consistent with inter-modal competition at times when incentive salience cues overtake top-down tracking of multisensory streams connected in time.

neuroscience↗

A humoral stress response protects Drosophila tissues from antimicrobial peptides

The immune response against an invading pathogen is generally associated with collateral tissue damage caused by the immune system itself. Consequently, several resilience mechanisms have evolved to attenuate the negative impacts of immune effectors. Antimicrobial peptides (AMPs) are small, cationic peptides that contribute to innate defenses by targeting negatively charged membranes of microbes1, 2. While being protective against pathogens, AMPs can be cytotoxic to host cells1, 3. Little is known of mechanisms that protect host tissues from AMP-induced immunopathology. Here, we reveal that a family of stress-induced proteins, the Turandots4, 5, protect Drosophila host tissues from AMPs, increasing resilience to stress. Deletion of several Turandot genes increases fly susceptibility to environmental stresses due to trachea apoptosis and poor oxygen supply. Tracheal cell membranes expose high levels of phosphatidylserine, a negatively charged phospholipid, sensitizing them to the action of AMPs. Turandots are secreted from the fat body upon stress and bind to tracheal cells to protect them against AMPs. In vitro, Turandot A binds to phosphatidylserine on membranes and inhibits the pore-forming activity of Drosophila and human AMPs on eukaryotic cells without affecting their microbicidal activity. Collectively, these data demonstrate that Turandot stress proteins mitigate AMP cytotoxicity to host tissues and therefore improve their efficacy. This provides a first example of a humoral mechanism used by animals limiting host-encoded AMP collateral damages.

immunology↗

Cecropins contribute to Drosophila host defense against fungal and Gram-negative bacterial infection

Cecropins are small helical secreted peptides with antimicrobial activity that are widely distributed among insects. Genes encoding Cecropins are strongly induced upon infection, pointing to their role in host-defence. In Drosophila, four Cecropin genes clustered in the genome (CecA1, CecA2, CecB and CecC) are expressed upon infection downstream of the Toll and Imd pathways. In this study, we generated a short deletion{Delta} CecA-C removing the whole Cecropin locus. Using the{Delta} CecA-C deficiency alone or in combination with other antimicrobial peptide (AMP) mutations, we addressed the function of Cecropins in the systemic immune response.{Delta} CecA-C flies were viable and resisted challenge with various microbes as wild-type. However, removing{Delta} CecA-C in flies already lacking ten other AMP genes revealed a role for Cecropins in defence against Gram-negative bacteria and fungi. Measurements of pathogen loads confirm that Cecropins contribute to the control of certain Gram-negative bacteria, notably Enterobacter cloacae and Providencia heimbachae. Collectively, our work provides the first genetic demonstration of a role for Cecropins in insect host defence, and confirms their in vivo activity primarily against Gram-negative bacteria and fungi. Generation of a fly line ({Delta}AMP14) that lacks fourteen immune inducible AMPs provides a powerful tool to address the function of these immune effectors in host-pathogen interactions and beyond.

immunology↗

Differential neural encoding of sound under visual attention is shaped by audiovisual precision and unimodal uncertainty priors

Selective attentional biases arising from one sensory modality may manifest in another. The effects of visuospatial attention, often considered a foundation for visual object perception, are unclear in the auditory domain during audiovisual (AV) scene processing. This study investigates temporal and spatial factors that facilitate such cross-modal bias transfer at the neural level. Auditory encoding of random tone pips in AV scenes was investigated via a temporal response function model (TRF) of the participants electroencephalogram (N=30). The spatially uninformative pips were associated with spatially distributed visual contrast reversals ( flips) through asynchronous, probabilistic AV temporal onset distributions. Participants deployed visuospatial selection on these AV stimuli to perform a task. A late (~300 ms) cross-modal transfer of the unimodal attentional bias was found on the neural representation of pips. Transfer depended on the selected visual input being (i) presented during or shortly after a related sound in a relatively limited temporal window (<165 ms); and (ii) positioned across limited (1:4) visual foreground to background ratios. In addition, the magnitude of attentional enhancement was proportional to the proximity of flips to the foreground area. The results indicate that ongoing neural representations of sounds can incorporate relevant visuospatial attributes for auditory stream segregation.

neuroscience↗

Increasing heart vascularisation after myocardial infarction using brain natriuretic peptide stimulation of endothelial and WT1+ epicardium-derived cells.

Brain natriuretic peptide (BNP) treatment increases heart function and decreases heart dilation after myocardial infarction. Here, we investigated whether part of the cardioprotective effect of BNP in infarcted hearts related to improved neovascularisation. Infarcted mice were treated with saline or BNP for 10 days. BNP treatment increased vascularisation and the number of endothelial cells in the infarct border and remote zones of infarcted hearts. Endothelial cell lineage tracing showed that BNP directly stimulated the proliferation of resident mature endothelial cells in both areas of the infarcted hearts, via NPR-A binding and p38 MAP kinase activation. BNP also stimulated the proliferation of WT1+ epicardium-derived cells but only in the hypoxic area of infarcted hearts. Our results demonstrated that these immature cells have a natural capacity to differentiate into endothelial cells in infarcted hearts. BNP treatment increased their proliferation but not their differentiation capacity. We identified new roles for BNP and new therapeutic strategies to improve heart recovery in infarcted hearts.

cell biology↗