Biology subjects

Vitale, A.

Publications and source records attributed to Vitale, A..

8 recordsLinked to original sources

bioRxiv2023

Detection of idiosyncratic gaze fingerprint signatures in humans

Do individuals possess a gaze fingerprint that reveals how they uniquely look at the world? We tested this question by examining intra- and inter-subject gaze similarity across 700 static pictures of complex natural scenes. Independent discovery (n=105) and replication (n=46) datasets revealed that gaze fingerprinting is possible at relatively high rates (e.g., 52- 63%) compared to chance (e.g., 1-2%). We also introduce the idea of a gaze fingerprint barcode, which can reveal how an individual can be gaze fingerprinted across a large array of stimuli. Pre-registered longitudinal follow-up experiments show that gaze fingerprint barcodes are stable within-individual over short (e.g., weeks to months) and long (e.g., years) time frames. Finally, we find that increased gaze fingerprintability is associated with decreased levels of autistic traits. Overall, this work showcases the potential of gaze fingerprinting and may help reveal precision biomarkers relevant for studying conditions with atypical gaze patterns, such as autism.

neuroscience↗

bioRxiv2022

Patterns of gene expression and allele-specific expression vary among macular tissues and clinical stages of Age-related Macular Degeneration

Age-related macular degeneration (AMD) is a complex neurodegenerative disease and is the leading cause of blindness in the aging population. Early AMD is characterized by drusen in the macula and causes minimal changes in visual function. The later stages are responsible for the majority of visual impairment and blindness and can be either manifest as geographic atrophy (dry) or neovascular disease (wet). Available medicines are directed against the wet form and do not cure vision loss. Therefore, it is imperative to identify preventive and therapeutic targets. As the mechanism for AMD is unclear, we aim to interrogate the disease-affected tissue - the macular neural retina and macular retina pigment epithelium (RPE)/choroid. We investigated differentially expressed genes expression (DEG) across the clinical stages of AMD in meticulously dissected and phenotyped eyes using a standardized published protocol (Owen et al., 2019). Donor eyes (n=27) were obtained from Caucasian individuals with an age range of 60-94 and 63% were male, and tissue from the macula RPE/choroid and macula neural retina were taken from the same eye. Donor eyes were recovered within 6 hours post mortem interval time to ensure maximal preservation of RNA quality and accuracy of diagnosis. Eyes were then phenotyped by retina experts using multi modal imaging (fundus photos and SD-OCT). Utilizing DESeq2, followed PCA, Benjamini Hochberg adjustment to control for the false discovery rate, and Bonferonni correction for the number of paired comparisons: a total of 26,650 genes were expressed in the macula RPE/choroid and/or macula retina among which significant differential expression was found for 1,204 genes between neovascular AMD and normal eyes, 40 genes between intermediate AMD and normal eyes, and 1,194 genes between intermediate AMD and neovascular AMD. A comparison of intermediate AMD versus normal eyes included TCN2, PON1, IFI6, GPR123, and TIMD4 as being some of the most significant DEGs in the macula RPE/choroid. A comparison of neovascular AMD versus normal eyes included SLC1A2, SLC24A1, SCAMP5, PTPRN, and SEMA7A as being some of the most significant DEGs in the macula RPE/choroid. Top pathways of DEGs in the macular RPE/choroid identified through Ingenuity Pathway Analysis (IPA) for the comparison of intermediate AMD with normal eyes were interferon signaling and Th1 and Th2 activation, while those for the comparison of neovascular AMD with normal eyes were the phototransduction and SNARE signaling pathways. Allele-specific expression (ASE) in coding regions of previously reported AMD risk loci identified by GWAS (Fritsche et al, 2016) revealed significant ASEs for C3 rs2230199 and CFH rs1061170 in the macula RPE/choroid for normal eyes and intermediate AMD, and for CFH rs1061147 in the macula RPE/choroid for normal eyes and intermediate and neovascular AMD. An investigation of the 34 established AMD risk loci revealed that 75% of them were significantly differentially expressed between normal macular RPE/choroid and macular neural retina, with 75% of these loci showing higher expression in the RPE. Similarly, disease state differences for the GWAS loci were only found to be statistically differentially expressed in the macular RPE/choroid. Moreover, the known coding variants in the previously identified GWAS loci including, CFH, C3, CFB, demonstrated ASE across AMD clinical stages in the macular RPE/choroid and not in the neural retina. These data at the bulk level underscore the importance of the RPE/choroid to AMD pathophysiology. While many bulk RNASeq data sets are publicly available, to the best of our knowledge this is one of the first publicly available datasets with both maculae RPE/choroid and macula neural retina from the same well phenotyped donor eye(s) where the macula is separated from the periphery. Our findings also underscore the importance of studying both macular tissue types to gain a full understanding of mechanisms leading to AMD. Our results provide insights into underlying biological mechanisms that may differentiate the disease subtypes and into the tissues affected by the disease.

genomics↗

bioRxiv2021

The structural role of bacterial eDNA in the formation of biofilm streamers

Across diverse habitats, bacteria are mainly found as biofilms, surface-attached communities embedded in a self-secreted matrix of extracellular polymeric substances (EPS), which enhances bacterial resistance to antimicrobial treatment and mechanical stresses. In the presence of flow and geometric constraints such as corners or constrictions, biofilms take the form of long, suspended threads known as streamers, which bear important consequences in industrial and clinical settings by causing clogging and fouling. The formation of streamers is thought to be driven by the viscoelastic nature of the biofilm matrix. Yet, little is known about the structural composition of streamers and how it affects their mechanical properties. Here, using a microfluidic platform that allows growing and precisely examining biofilm streamers, we show that extracellular DNA (eDNA) constitutes the backbone and is essential for the mechanical stability of Pseudomonas aeruginosa s streamers. This finding is supported by the observations that DNA-degrading enzymes prevent the formation of streamers and clear already formed ones, and that the antibiotic ciprofloxacin promotes their formation by increasing the release of eDNA. Furthermore, using mutants for production of the exopolysaccharide Pel, an important component of P. aeruginosa s EPS, we reveal a new, although indirect role of Pel, in tuning the mechanical properties of the streamers. Taken together, these results highlight the importance of eDNA and of its interplay with Pel in determining the mechanical properties of P. aeruginosa streamers, and suggest that targeting the composition of streamers can be an effective approach to control the formation of these biofilm structures.

biophysics↗

bioRxiv2020

Characterization of the antimicrobial activity of the cell-penetrating peptide TAT-RasGAP317-326

Antibiotic resistance is an increasing threat for public health, underscoring the need for new antibacterial agents. Antimicrobial peptides (AMPs) represent an alternative to classical antibiotics. TAT-RasGAP317-326 is a recently described AMP effective against a broad range of bacteria, but little is known about the conditions that may influence its activity. Using RNA-sequencing and screening of mutant libraries, we show that Escherichia coli and Pseudomonas aeruginosa respond to TAT-RasGAP317-326 by regulating metabolic and stress response pathways, possibly implicating two-component systems. Our results also indicate that bacterial surface properties, in particular integrity of the lipopolysaccharide layer, influence peptide binding and entry. Finally, we found differences between bacterial species with respect to their rate of resistance emergence against this peptide. Our findings provide the basis for future investigation on the mode of action of this peptide and its potential clinical use as an antibacterial agent.

microbiology↗

bioRxiv2020

Altered beta-band oscillations and connectivity underlie detail-oriented visual processing in autism

Sensory and perceptual anomalies have been increasingly recognized as core phenotypic markers for autism spectrum disorders (ASD). A neurophysiological characterization of these anomalies is of utmost importance to understand more complex behavioural manifestations within the spectrum. The present study employed electroencephalography (EEG) to test whether detail-oriented visual perception, a recognized hallmark of ASD, is associated with altered neural oscillations and functional connectivity in beta (and alpha) frequency bands, considering their role in feedback and top-down reentrant signalling in the typical population. A sample of children with diagnosis of ASD (N=18) and typically developing peers (TD; N=20) performed a visual crowding task, where they had to discriminate a peripheral target letter surrounded by flankers at different distances, together with a control condition with no flankers. In TD participants the amplitude of the target-locked N1 component and its cortical sources was significantly modulated as a function of visual crowding, whereas such modulation was absent in the ASD group, suggesting that their visual scene analysis takes place without a flexible neural computation. The comparison between groups showed a decreased activity in the ASD group in occipital, infero-temporal and inferior/middle frontal regions in conditions requiring detail-oriented perception as opposed to conditions requiring the discrimination of target in isolation. Moreover, in TD participants detail-oriented perception was associated with an event-related beta power reduction (15-30 Hz), which was not evident in the ASD group. A data-driven functional connectivity analysis highlighted in the ASD sample an increased connectivity in the beta frequency range between occipital and infero-temporal regions. Notably, individual hyperconnectivity indexes correlated to less severe ASD symptomatology and to a diminished detail-oriented perception, suggesting a potential compensatory mechanism. Overall, these results show that altered communication in the beta frequency band may explain atypical perception in ASD, reflecting aberrant feedback connectivity within the visual system with potential cascade effects in visual scene parsing and higher-order functions.

neuroscience↗

bioRxiv2019

The effect of flow on swimming bacteria controls the initial colonization of curved surfaces

The colonization of solid surfaces by bacteria is a widespread phenomenon with major consequences on environmental processes, biotechnology and human health. While much is known about the molecular mechanisms of surface colonization, the influence of the physical environment remains poorly understood. Here we show that the magnitude and location of colonization of non-planar surfaces by motile bacteria is largely controlled by the local flow conditions. Using microfluidic experiments with Pseudomonas aeruginosa and Escherichia coli, we demonstrate that the velocity gradients created by a curved surface drive preferential attachment to specific regions of the collecting surface, namely the leeward side of cylinders and immediately downstream of apexes on corrugated surfaces, locations that are in stark contrast to where non-motile cells attach. The preferential attachment location depends on the local hydrodynamic conditions and, as revealed by a mathematical model benchmarked on the observations, on cell morphology and swimming traits, while it is independent of the physicochemical properties of the surface. The interplay between imposed flow and bacterial motility further affects the overall attachment rate, increasing it by up to two orders of magnitude compared to the non-motile case at moderate flow velocities of up to twenty times the bacterial swimming speed. These results highlight the importance of fluid flow on the magnitude and location of bacterial colonization of surfaces and provide a mechanistic model to predict colonization in flow for a wide range of applications, from infection biology to bioremediation and biofouling.

biophysics↗

bioRxiv2019

Timing matters: primacy effects of experience on mood revealed using a novel Mood-Machine-Interface

Humans refer to their own mood state regularly in day-to-day as well as in clinical interactions. Theoretical accounts suggest that when reporting on our mood we integrate over the history of our experiences; yet, the temporal structure of this integration remains unexamined. Here we use a computational approach to quantitatively answer this question and show that early events exert a stronger influence on the reported mood compared to recent events. We show that a Primacy model accounts better for mood reports compared to a range of alternative temporal representations, and replicate this result across random, consistent or dynamic structures of reward environments, age groups and both healthy and depressed participants. Moreover, we find evidence for neural encoding of the Primacy, but not the Recency, model in frontal brain regions related to mood regulation. These findings hold implications for the timing of events in experimental or clinical settings and suggest new directions for individualized mood interventions. SignificanceHow we rate our own mood at any given moment is shaped by our experiences; but are the most recent experiences the most influential, as assumed by current theories? Using several sources of experimental data and mathematical modeling, we show that earlier experiences within a context are more influential than recent events, and replicate this finding across task environments, age groups, and in healthy and depressed participants. Additionally, we present neural evidence supporting this primacy model. Our findings show that delineating a temporal structure is crucial in modeling mood and this has key implications for its measurement and definition in both clinical and everyday settings.

neuroscience↗

bioRxiv2018

Single-nuclei RNA-seq on human retinal tissue provides improved transcriptome profiling.

Gene expression profiling is an effective way to provide insights into cell function. However, for heterogeneous tissues, bulk RNA-Seq can only provide the average gene expression profile for all cells from the tissue, making the interpretation of the sequencing result challenging. Single-cell RNA-seq, on the other hand, generates transcriptomic profiles of individual cell and cell types, making it a powerful method to decode the heterogeneity in complex tissues. The retina is a heterogeneous tissue composed of multiple cell types with distinct functions. Here we report the first single-nuclei RNA-seq transcriptomic study on human neural retinal tissue to identify transcriptome profile for individual cell types. Six retina samples from three healthy donors were profiled and RNA-seq data with high quality was obtained for 4730 single nuclei. All seven major cell types were observed from the dataset and signature genes for each cell type were identified by differential gene express analysis. The gene expression of the macular and peripheral retina was compared at the cell type level, showing significant improvement from previous bulk RNA-seq studies. Furthermore, our dataset showed improved power in prioritizing genes associated with human retinal diseases compared to both mouse single-cell RNA-seq and human bulk RNA-seq results. In conclusion, we demonstrated that feasibility of obtaining single cell transcriptome from human frozen tissues to provide additional insights that is missed by either the human bulk RNA-seq or the animal models.

genomics↗