Biology subjects

Mele, S.

Publications and source records attributed to Mele, S..

8 recordsLinked to original sources

bioRxiv2026

Residual cortical responses and network reorganization in inherited retinal degeneration: electrophysiological evidence

Retinitis pigmentosa (RP) progressively deprives the retina of input, but whether the responsiveness of the visual cortex declines in parallel, remains preserved, or increases through compensatory gain remains unclear. Indeed, a weaker visually evoked response cannot, on its own, distinguish these possibilities, since it is equally compatible with a passively degraded input and with an actively recalibrated cortex. We combined spatially resolved steady-state visual evoked potentials (SSVEPs), which index stimulus-driven activity, with transcranial magnetic stimulation combined with electroencephalography (TMS-EEG), which probes cortical reactivity independently of vision, in patients with RP and in healthy controls. Nine patients (PTs) with RP (five women, age range 28 to 69 years) and nineteen sex-, age-, and handedness-matched healthy controls (thirteen women, mean age 42.6 years) were tested. They underwent SSVEP recordings to stimuli presented at three eccentricities (central, intermediate, peripheral) and single-pulse TMS-EEG over the left and right occipital cortex and, as a non-visual control site, the dominant motor cortex. We quantified SSVEP amplitude and phase at 12 Hz, early TMS-evoked potentials, oscillatory power, inter-trial phase synchrony, and functional connectivity and graph-theoretical network measures derived from the weighted phase lag index. SSVEP amplitude followed the expected central-to-peripheral gradient: PTs were comparable to healthy controls at the center, reduced but still above their own resting baseline at intermediate eccentricity, and no longer distinguishable from baseline in the periphery; phase differed from controls in a quarter of the central and half of the intermediate sectors. Occipital stimulation elicited a larger early negative deflection after left-hemisphere stimulation in PTs compared to controls, a stronger beta-band event-related spectral perturbation after stimulation of either hemisphere, and stronger, more efficiently distributed post-stimulus connectivity, despite comparable pre-stimulus connectivity, resting motor threshold, and most early evoked components. The pattern was site- and hemisphere-specific: left occipital stimulation produced widespread, mainly contralateral effects; right occipital stimulation a more circumscribed ipsilateral one, and motor cortex stimulation showed altered alpha-band activity without the bilateral occipital beta effect. Together, these results show that progressive retinal deafferentation in RP does not produce a parallel decline in cortical responsiveness. Visually driven activity weakens with eccentricity, while direct cortical perturbation reveals preserved and, at selected sites, enhanced reactivity. This dissociation is consistent with a homeostatic increase in cortical gain rather than a uniform loss of cortical function, and indicates that the deafferented cortex retains, and in places strengthens, its capacity to respond as retinal input deteriorates.

neuroscience↗

bioRxiv2026

Drosophila beanbag (beba) encodes a novel insect receptor tyrosine kinase associated with reproductive niche organisation

Receptor tyrosine kinases (RTKs) are cell surface proteins that govern many critical cell fate decisions and their dysregulation is a major cause of diseases such as cancer. Much of what we know about how these proteins work in cells and tissues comes from model organisms such as the fruit fly Drosophila. Here, we identify and characterise a previously unstudied Drosophila receptor tyrosine kinase encoded by CG3277, which we name beanbag (beba). Ectopic beba expression activated Akt and ERK phosphorylation and produced gain-of-function phenotypes resembling those caused by other Drosophila RTKs. Using a MiMIC-derived T2A-GAL4 allele, we show that Drosophila beba is expressed in digestive, nervous and reproductive systems, in locations suggestive of potential roles in endoreplication and/or stem cell niche support. Animals transheterozygous for beba loss-of-function alleles were viable, developed at a normal rate, and showed no detectable change in enterocyte DNA content under standard conditions. However, beba loss-of-function females had fewer ovarioles, consistent with a role in the ovarian terminal filament, and males had increased testis hub cell number and hub volume, suggesting beba may regulate somatic niche architecture in the Drosophila gonad. Phylogenetic analysis places Beba within a Ret/Tor-related RTK radiation and supports the existence of a distinct Beba family in insects. Together, our data define Beba as a lineage-restricted Drosophila RTK with specialised roles in reproductive niche organisation.

genetics↗

bioRxiv2026

From encoding to conscious report: Electrophysiological signatures of iconic memory revealed by a partial report task

Despite numerous investigations, a comprehensive electrophysiological characterization of iconic memory remains lacking. Through a partial report paradigm, we aimed to shed light on this topic by disentangling electrophysiological activity related to stimulus perception from that linked with the specific task. We collected EEG data from 26 participants while they performed a partial report task. They were shown circular arrays of six letters lasting 100 ms. After the stimulus, an acoustic cue instructed the participant to report on which side of the array. Differences between reporting conditions were primarily evident in the time window 850-1100 ms, characterized by a positive component predominantly over parieto-occipital electrodes ipsilateral to the reporting side. Through linear regression, we also found a positive relationship between P1 and participants accuracy, as well as negative relationships between P3, VCR, TIF, and accuracy. Our results provide an overview of the different processes involved in iconic memory, corroborating the distinction between a series of neural mechanisms responsible for encoding and maintaining the entire stimulus and higher-order processes in charge of selecting an information subset for conscious report. The TIF component, in particular, could act as a key filtering mechanism to prevent irrelevant information from being selected for further processing. Our results provide, for the first time, a thorough characterization of the electrophysiological dynamics behind iconic memory. Moreover, implications for the consciousness debate are discussed, particularly regarding the overflow argument and how our results could be read through its lens.

neuroscience↗

bioRxiv2026

A flexible diet platform for the nutrigenomic screening of Drosophila disease models

Nutrient-gene interactions shape metabolic disease phenotypes, but systematic testing is limited by the effort required to produce defined diets. We developed a flexible protocol that assembles precisely defined synthetic diets for Drosophila melanogaster from individual stock solutions. Using this approach, we generated a rational array of 51 single-nutrient-varied diets and demonstrated that flexible and standard preparation methods produce comparable developmental timing, survival, adult body weight, and starvation resistance in wildtype flies. Applying the dietary array to a Drosophila model of isolated sulfite oxidase deficiency, a severe condition caused by impaired sulfur amino acid catabolism, revealed nutrient-specific effects on pupal survival and pupariation timing, including rescue by cysteine depletion and other amino acid modified diets. This platform provides a scalable in vivo framework for mapping genotype-specific nutritional responses across Drosophila disease models. Key pointsO_LIDeveloped a flexible platform for assembling precisely defined synthetic diets in Drosophila. C_LIO_LIGenerated a rational 51-diet array, enabling scalable nutrigenomic screening. C_LIO_LIFlexible and standard diet preparations yielded matching developmental and adult fitness outcomes. C_LIO_LIDietary array screening in a sulfite oxidase deficiency model recapitulated cysteine sensitivity and identified novel nutrient modifiers. C_LI

genetics↗

bioRxiv2025

SAMBA: A Segment Anything Model-based tool for semi-automated Behavioural Analysis of Drosophila and other model organisms

Quantitative behavioural analysis is a powerful approach for linking genotype to phenotype, but many existing tools require specialised hardware, extensive preprocessing, or coding expertise. We present SAMBA (Segment Anything Model for Behavioural Analysis), an open-access, Google Colab-based pipeline that harnesses the Segment Anything Model 2 (SAM2) for accurate, semi-automated tracking without thresholding or background subtraction. With minimal user input, SAMBA extracts movement parameters, detects behavioural states, and supports batch processing. Validating SAMBA in a Drosophila melanogaster model of 3-hydroxyisobutyryl-CoA hydrolase (HIBCH) deficiency revealed impaired locomotion, reduced speed, and altered decision-making, highlighting its ability to capture nuanced phenotypes in neurometabolic disease. We further demonstrate adaptability to adult Drosophila and larval zebrafish, underscoring its cross-species utility. By combining foundation-model segmentation with an accessible interface, SAMBA lowers technical barriers to high-throughput behavioural phenotyping and is readily extendable to diverse model organisms, life stages, and experimental paradigms. This flexibility positions SAMBA as a valuable platform for accelerating disease mechanism studies, genetic screens, and preclinical testing. SUMMARY STATEMENTWe present an easy-to-use, open-access tool designed for Drosophila larval movement analysis, and readily customised for other applications, enabling rapid, scalable assessment of organism behaviour without specialised equipment or coding expertise.

animal behavior and cognition↗

bioRxiv2024

Valine restriction extends survival in a Drosophila model of short-chain enoyl-CoA hydratase 1 (ECHS1) deficiency

Short-chain enoyl-CoA hydratase 1 deficiency (ECHS1D) is a rare genetic disorder caused by biallelic pathogenic variants in the ECHS1 gene. ECHS1D is characterised by severe neurological and physical impairment that often leads to childhood mortality. Therapies such as protein and single nutrient-restricted diets show poor efficacy, whereas development of new treatments is hindered by the low prevalence of the disorder and a lack of model systems for treatment testing. Here we report on the establishment of a Drosophila model of ECHS1D. Flies carrying mutations in Echs1 (CG6543) were characterised for their physical and metabolic phenotypes, and dietary intervention to improve fly model health was explored. The Echs1 null larvae recapitulated human ECHS1D phenotypes including elevated biomarkers (S-(2-carboxypropyl)cysteamine and 2,3-dihydroxy-2-methylbutyric acid), poor motor behaviour and early mortality, and could be rescued by expression of a human ECHS1 transgene. We observed that both restriction of valine in isolation, or all branched-chain amino acids (BCAAs - leucine, isoleucine, and valine) together, extended larval survival, supporting the idea that reducing BCAA pathway catabolic flux is beneficial in this disorder. Further, metabolic profiling revealed substantial changes to carbohydrate metabolism, suggesting that Echs1 loss causes widespread metabolic dysregulation beyond valine metabolism. The similarities between Drosophila and human ECHS1D suggest that the fly model is a valuable animal system in which to explore mechanisms of pathogenesis and novel treatment options for this disorder.

genetics↗

bioRxiv2024

The role of extra-striate areas in conscious motor behavior: a registered report with Fast-Optical Imaging

Disclosing the brain areas responsible for the emergence of visual awareness and their timing of activation represents one of the major challenges in consciousness research. In particular, isolating the neural processes strictly related to consciousness from concurrent neural dynamics either related to prerequisites or post-perceptual processing has long engaged consciousness research. In this framework, the present study aims at unravelling the spatio-temporal dynamics underlying conscious vision by adopting a distinctive experimental design in which both awareness and motor response are manipulated, allowing the segregation of neural activity strictly related to awareness from response-related mechanisms. To this aim, we will employ a GO/NOGO detection task, in which participants will respond or withhold responding according to the experimental condition. Critically, during the performance of the task, participants brain activity will be recorded by means of Event-Related Optical Signal (EROS) technique, which provides accurate information about brain functions both from the temporal and spatial point of view, simultaneously. The combination of this experimental design with EROS recording will enable us to pinpoint the neural correlates underlying conscious vision and to disentangle them from processes related to the response. In addition, by coupling conventional EROS analysis with Granger Causality analysis, we will be able to clarify the potential interplay between consciousness-related extra-striate areas and response-related motor areas.

neuroscience↗

bioRxiv2023

A defined diet for pre-adult Drosophila melanogaster

Drosophila melanogaster is unique among animal models because it has a fully defined synthetic diet available to study nutrient-gene interactions. However, use of this diet is limited to adult studies due to impaired larval development and survival. Here, we provide an adjusted formula that improves larval growth, development rate, and rescues survival. We demonstrate its use for exploring pre-adult diet compositions of therapeutic potential in a model of an inherited metabolic disorder.

genetics↗