Biology subjects

Ledda, M.

Publications and source records attributed to Ledda, M..

5 recordsLinked to original sources

bioRxiv2025

A fluid dynamics-model system for advancing Tissue Engineering and Cancer Research studies: Dynamic Culture with the innovative BioAxFlow Bioreactor

In this study, we test an innovative bioreactor, particularly suitable for tissue engineering applications, named BioAxFlow. Unlike traditional bioreactors, it does not rely on mechanical components to agitate the culture medium, but on the fluid-dynamics generated thanks to the unique geometry of the culture chamber. The flow generated within ensures continuous medium movement, promoting consistent cell exposure to nutrients and growth factors. Using the human osteosarcoma cell line SAOS-2, the bioreactors ability to enhance cell adhesion and proliferation on polylactic acid scaffolds, mimicking bone tissue matrix architecture, is tested. The findings show that the bioreactor significantly improved cell adhesion and growth compared to static cultures, promoting a homogeneous cell distribution across the scaffold surfaces, which is crucial for developing functional tissue constructs. The bioreactor preserves the osteogenic potential of SAOS-2 cells as assessed by the expression of key osteogenic markers. Additionally, it retains the tumorigenic characteristics of SAOS-2 cells, including the expression of pro-angiogenic factors and apoptosis-related genes. These results indicate that the BioAxFlow bioreactor is an effective platform for tissue engineering and cancer research, offering a promising tool for both regenerative medicine applications and drug testing.

bioengineering↗

bioRxiv2023

Unraveling Evolutionary Dynamics: Insights from In Silico Experiments on Selective Mechanisms in Controlled Environments

In this paper, we present a series of in silico experiments aimed at probing the evolutionary properties of our model. Our investigation encompasses multiple methodologies, beginning with the standard model used in population genetics for measuring natural selection. Next, we employ the Price equation, a well-established formalism known for its effectiveness in tracking how the relationship between parents and offspring evolves over time. In conclusion, we delve into the model results to explain, in the light of evolutionary theory, how the selective mechanism operates. Furthermore, the speculation about the mechanism will be hindered on the agents of the selective process. Even though natural selection can be considered as a statistical phenomenon, sprouting from the change in population frequencies, we argue that in models where there is a elevate control on the environment, it is possible to define the single element responsible for the selective pressure on the units of selection.

evolutionary biology↗

bioRxiv2023

An improved PDE6D inhibitor combines with Sildenafil to synergistically inhibit KRAS mutant cancer cell growth

The trafficking chaperone PDE6D (or PDE) was proposed as a surrogate target for K-Ras, leading to the development of a series of inhibitors that block its prenyl-binding pocket. These inhibitors suffered from low solubility and intracellular potency, preventing their clinical development. Here we developed a highly soluble PDE6D inhibitor (PDE6Di), Deltaflexin3, which has the currently lowest off-target activity, as we demonstrate in dedicated assays. We further increased the K-Ras focus, by exploiting that PKG2-mediated phosphorylation of Ser181 lowers K-Ras binding to PDE6D. Thus, the combination of Deltaflexin3 with the approved PKG2-activator Sildenafil synergistically inhibits cell- and microtumor growth. However, the overall cancer survival of the high PDE6D/ low PKG2 target population is higher than of the group with the opposite signature. Our results therefore suggest re-examining the interplay between PDE6D and K-Ras in cancer, while recommending the development of PDE6Di that plug, rather than stuff the hydrophobic pocket of PDE6D. SignificanceCombinations of a novel PDE6D inhibitor with Sildenafil synergistically focus the inhibition on K-Ras, however, survival data of the target population suggest an interplay of K-Ras and PDE6D that needs further exploration.

biochemistry↗

bioRxiv2023

Colorectal cancer as a Model for Biological Evolution

Complexity in cancer research has led to the creation of powerful analytical tools for helping experimental in vivo and in vitro methods. These tools range from systems of differential equations resolved in computer simulations, to lattice models and agent-based models (ABMs). These analytical methods are focused on studying cell behavior and dynamic cell populations. Among these, those that are increasingly used are ABMs because they can incorporate multi-scale features ranging from the individual up to the population level, mixing rules based on mathematical and conceptual parameters, and combining statistical/population assumptions with individual heterogeneity. In this work, we present an ABM that simulates tumor progression in a colonic crypt, with the aim of providing an experimental in silico environment for testing results achieved in traditional lab research, and developing alternative scenarios of tumor development. As the first part of an ongoing project, the long-term goal is to reproduce and study, the general evolutionary mechanisms of a biological system.

cancer biology↗

bioRxiv2020

Social Network Analysis of the Genealogy of Strawberry: Retracing the Wild Roots of Heirloom and Modern Cultivars

The widely recounted story of the origin of cultivated strawberry (Fragaria x ananassa) oversimplifies the complex interspecific hybrid ancestry of the highly admixed populations from which heirloom and modern cultivars have emerged. To develop deeper insights into the three century long domestication history of strawberry, we reconstructed the genealogy as deeply as possible--pedigree records were assembled for 8,851 individuals, including 2,656 cultivars developed since 1775. The parents of individuals with unverified or missing pedigree records were accurately identified by applying exclusion analysis to array-genotyped single nucleotide polymorphisms. We identified 187 wild octoploid and 1,171 F. x ananassa founders in the genealogy, from the earliest hybrids to modern cultivars. The pedigree networks for cultivated strawberry are exceedingly complex labyrinths of ancestral interconnections formed by diverse hybrid ancestry, directional selection, migration, admixture, bottlenecks, overlapping generations, and recurrent hybridization with common ancestors that have unequally contributed allelic diversity to heirloom and modern cultivars. Fifteen to 333 ancestors were predicted to have transmitted 90% of the alleles found in country-, region-, and continent-specific populations. Using parent-offspring edges in the global pedigree network, we found that selection cycle lengths over the last 200 years of breeding have been extraordinarily long (16.0-16.9 years/generation) but decreased to a present-day range of 6.0-10.0 years/generation. Our analyses uncovered conspicuous differences in the ancestry and structure of North American and European populations and shed light on forces that have shaped phenotypic diversity in F. x ananassa.

plant biology↗