Biology subjects

Bergadano, A.

Publications and source records attributed to Bergadano, A..

5 recordsLinked to original sources

bioRxiv2026

Comparable phosphene size and contrast properties, but differing detection reliability for optogenetic versus electrical stimulation of macaque V1

Cortical visual prostheses aim to restore vision by stimulating primary visual cortex (V1) to evoke artificial percepts (phosphenes). Electrical stimulation has long served this purpose, and optogenetic approaches promise higher spatial resolution via cell-type specificity. Recent investigations have demonstrated localized behavioral responses to optogenetic V1 stimulation (1--3), but the applied perimetry paradigms cannot dissociate a genuine percept from a reflexive oculomotor response, leaving the perceptual character of optogenetic phosphenes unresolved. To address this gap, two macaques received optogenetic V1 injections guided by laminar electrophysiology and performed detection and discrimination tasks under interleaved electrical, optogenetic, and visual stimulation, enabling direct within-subject comparison. Electrical stimulation reliably evoked detectable percepts (positive d' in 100% of sessions), with thresholds scaling with current, resembling visual contrast-response functions. Optogenetic stimulation was far less reliable, with positive d' in only ~50% of sessions, despite confirmed V1 activation. Despite this reliability difference, optogenetically evoked percepts closely resembled electrically and visually evoked percepts in perceptual character: perceived size (~1{degrees} of visual angle) was comparable across conditions and scaled similarly with eccentricity. Similarly, perceived contrast equivalents (5%-11% visual-contrast equivalent) were broadly comparable across stimulation approaches. These findings indicate that successful optogenetic activation engages the same perceptual encoding mechanisms as electrical and natural vision, but that reliable detection may additionally depend on circuit-level mechanisms not consistently engaged by current optogenetic parameters. The comparable percept size further suggests optogenetic stimulation may not confer the enhanced spatial resolution often proposed as its key advantage.

neuroscience↗

bioRxiv2026

Shifting Perspectives on Biotherapeutic Treatment in Ulcerative Colitis using Lipid Mesophases: Formulation Design and Preclinical Validation

Biotherapeutics are required to achieve high remission rates in patients with severe ulcerative colitis (UC); however, adverse effects, complex dosing regimens, administration routes, and low patient compliance may limit their widespread clinical use. Given the localized nature of UC, this study aimed to develop and evaluate a localized delivery strategy for infliximab (IFX), an anti-tumor necrosis factor- (TNF-) monoclonal antibody (mAb) recommended by the European Crohns and Colitis Organization (ECCO) and the American Crohns & Colitis Foundation for moderately-to-severely active UC. Exploiting the intrinsic biocompatibility, mucoadhesivity, and protein-entrapment capacity of lipid mesophases (LMPs), IFX was encapsulated within the gel matrix, providing protection against enzymatic and environmental degradation. IFX-loaded LMPs were designed for targeted delivery to inflamed colonic tissues via rectal or oral administration, with patient-centric oral dosage forms manufactured using a 3D printing approach. A comprehensive physicochemical characterization was performed to elucidate mesophase self-assembly and its relationship with IFX release profiles in biorelevant fluids. Therapeutic efficacy was evaluated in vivo using a dextran sulfate sodium (DSS)-induced colitis rat model, which demonstrated rectal gel retention for at least 8 h and colonic targeting of the oral formulation within 6 h. Under severe inflammatory conditions, LMP-based formulations reduced disease activity, inflammatory biomarkers (TNF- and fecal lactoferrin), and colon shortening to values comparable to those of healthy controls, outperforming the therapeutic efficacy of subcutaneous IFX. Overall, this study establishes a biocompatible delivery platform that enables targeted colonic IFX release and suppresses systemic absorption, representing a promising advancement in the biotherapeutic treatment of UC.

pathology↗

bioRxiv2025

Hot cue: Physiologically controlled release from an in situ forming liposomal depot

Poor treatment adherence, often referred to as the "silent epidemic", is a growing global issue that significantly contributes to preventable illness, premature death, and rising healthcare costs. Among compliance-enhancing strategies, controlled-release depots designed for intermediate treatment cycles represent a suitable approach, particularly in contexts where frequent dosing is impractical. Current long-acting injectable formulations, though, are often hindered by challenges in injectability, delayed onset, and complex manufacturing. Here, we present a thermoresponsive, in situ forming liposomal depot (TILD) designed to modulate the release of membrane-associated drugs following subcutaneous administration. Using buprenorphine as a model analgesic, we demonstrate that TILD responds to subcutaneous divalent cations with immediate surface-drug release and to body temperature with sustained diffusion through a fluidized bilayer. Molecular simulations guided the system design, and structural and colloidal characterizations validated its responsiveness to physiological cues. In vivo, TILD formed stable depots and maintained therapeutic drug levels for up to four days in both rats and Beagle dogs. Pharmacodynamics studies in rats confirmed the delivery of prolonged analgesia.

pharmacology and toxicology↗

bioRxiv2023

An adaptable, user-friendly score sheet to monitor welfare in experimental fish

Fish are increasingly used as experimental animals across research fields. Currently, a quarter of all experimental animals used in Europe are fish. Less than 20% of these are standard model species. Welfare assessments for experimental fish are in their infancy compared to rodents. This can be attributed to the diversity of species used, the relative recency of fish as go-to model for research, and challenges to assess welfare and pain in non-vocal underwater species. The lack of guidelines and tools presents a challenge for researchers (particularly, for newcomers), for ethics committees, and for implementing refinement measures. Here, we present an adaptable, user-friendly score sheet for fish. The parameters contained in the excel tool are based on a literature review, have been validated by expert interviews, and evaluated by a fish pathologist. The tool allows to score individuals as well as groups, calculates summary scores and visualizes trends. We provide the underlying literature, give use examples and provide instructions on the adaptation and use of the score sheet. We hope that this tool will empower researchers to include welfare assessment in their routines, foster discussions on fish welfare parameters among scientists, facilitate interactions with ethics committees, and most importantly, enable the refinement of fish experiments.

animal behavior and cognition↗

bioRxiv2022

Wet Adhesive Hydrogels to Correct Malacic Trachea (Tracheomalacia): A Proof of Concept

Tracheomalacia (TM) is a condition in which the anterior part of the trachea consisting of cartilage and/or the posterior part consisting muscle are too soft to ensure its mechanical support. This situation may result in an excessive and potentially lethal collapse of the airway in the newborns. Current treatment techniques include tracheal reconstruction, tracheoplasty, endo- and extraluminal stents, but are all facing important limitations. To reduce the shortcomings of actual TM treatments, this work proposes a new strategy by wrapping an adhesive hydrogel patch extraluminally around a malacic trachea. To validate this approach, first a numerical model revealed that a hydrogel patch with sufficient mechanical and adhesion strength can potentially preserve the tracheas physiological shape. Accordingly, a new hydrogel formulation was synthesized employing the hydroxyethyl acrylamide (HEAam) and polyethylene glycol methacrylate (PEGDMA) as main polymer network and crosslinker, respectively. These hydrogels provide excellent adhesion on wet tracheal surfaces, thanks to a two-step photo-polymerization approach. Ex vivo experiments revealed that the developed adhesive hydrogel patches can restrain the collapsing of malacic trachea under applied negative pressure. This study, to be confirmed by in vivo studies, is open to the possibility of a new treatment in the difficult clinical situation of tracheomalacia in newborns.

bioengineering↗