Biology subjects

Coelho, F.

Publications and source records attributed to Coelho, F..

3 recordsLinked to original sources

bioRxiv2022

Understanding Hybrid Lipid-Polymer Gene Delivery Nanoparticle Assembly with Fluorescence Cross Correlation Spectroscopy

Hybrid lipid-polymer-nucleic acid nanoparticles (LPNPs) provide unique delivery strategies for nonviral gene therapy. Since LPNPs consist of multiple components that can undergo different pairwise interactions between them, LPNPs are difficult to prepare and characterize. Here we demonstrate that the interaction between the polycation (polylysine) and DNA is robust through an innovative implementation of fluorescence cross-correlation spectroscopy, implying that the polycation is not displaced by cationic liposomes in the formation process. Hence, the polycation-DNA cores (polyplexes) and liposome shells must be oppositely charged to associate. Furthermore, we prove that the liposome:polyplex number ratio ({rho}N) is the primary critical parameter to predict stable LPNP formation. We establish that{rho} N [≥] 1 is required to ensure that every polyplex is enveloped by a liposome, avoiding the coexistence of oppositely charged species and thereby inhibiting aggregation. We expect our observations to be valid for the formation of many other LPNPs and composite nanomaterials.

biophysics↗

bioRxiv2021

Transmission dynamics and control of Sporotrichosis in domestic felines

Sporotrichosis is a subcutaneous mycosis with a global distribution, also known as "rose gardeners disease". Brazil is experiencing a rapid spread of the zoonotic transmission of of Sporothrix brasiliensis, the main etiological agent of this disease in this country, affecting domestic felines. Cost-effective interventions need to be developed to control this emergent public health problem. To allow for the comparison of alternative control strategies, we propose in this paper, a mathematical model representing the transmission of S. brasiliensis among cats, stratified by age and sex. Analytical properties of the model are derived and simulations show possible strategies for reducing the endemic levels of the disease in the cat population, with a positive impact on human health. The scenarios included mass treatment of infected cats and mass implementation of contact reduction practices, such as neutering. The results indicate that mass treatment can reduce substantially the disease prevalence, and this effect is potentialized when combined with neutering or other contact-reduction interventions. On the other hand, contact-reduction methods alone are not sufficient to reduce prevalence. Author summarySporotrichosis, as a neglected tropical mycosis, has in domestic cats a very important reservoir for Sporothrix sp., its pathogen. Infected cats can easily transmit the fungus to other cats and also to humans by means of scratching and biting. Here we propose a mathematical model incorporating all forms of transmission of Sporothrix within a cat population, taking into account age and sex-related behavioral differences which can affect the transmission dynamics. The model also includes a treated compartment, which facilitates the exploration of pharmacological interventions to reduce the prevalence of the disease. We derive the next-generation matrix for the model, which allows the calculation of the diseases basic reproduction number under different scenarios. Using the model, we explore different control scenarios involving treatment of the disease, but also the contribution of neutering of cats to the reduction of transmission through changes induced by neutering, of the cats social interactions.

bioinformatics↗

bioRxiv2018

Fbxw7 is a critical regulator of Schwann cell myelinating potential

Myelin insulates and protects axons in vertebrate nervous systems. In the central nervous system (CNS), oligodendrocytes (OLs) make numerous myelin sheaths on multiple axons, whereas in the peripheral nervous system (PNS) myelinating Schwann cells (SCs) make just one myelin sheath on a single axon. Why the myelinating potentials of OLs and SCs are so fundamentally different is unclear. Here, we find that loss of Fbxw7, an E3 ubiquitin ligase component, enhances the myelinating potential of SCs. Fbxw7 mutant SCs are seen myelinating multiple axons in a fashion reminiscent of OLs as well as aberrantly myelinating large axons while simultaneously ensheathing small unmyelinated axons - typically distinct roles of myelinating SCs and non-myelinating Remak SCs, respectively. We found that several of the Fbxw7 mutant phenotypes, including the ability to generate thicker myelin sheaths, were due to dysregulation of mTOR. However, the remarkable ability of mutant SCs to either myelinate multiple axons or myelinate some axons while simultaneously encompassing other unmyelinated axons is independent of mTOR signaling. This indicates distinct roles for Fbxw7 in regulating multiple aspects of SC behavior and that novel Fbxw7-regulated mechanisms control modes of myelination previously thought to fundamentally distinguish myelinating SCs from non-myelinating SCs and OLs. Our data reveal unexpected plasticity in the myelinating potential of SCs, which may have important implications for our understanding of both PNS and CNS myelination and myelin repair.

neuroscience↗