Biology subjects

Ragusa, M.

Publications and source records attributed to Ragusa, M..

7 recordsLinked to original sources

bioRxiv2025

The effects of adolescent stress on adult social behavior and basolateral amygdala GABAergic neurons with perineuronal nets depend on prenatal stress history

Developmental stress is a well-established risk factor for mental health disorders, yet the neural mechanisms underlying these outcomes remain incompletely understood. Inhibitory brain networks, particularly within the amygdala, are disrupted by stress and implicated in stress-related psychopathologies. Using a rodent model, the current study investigated the isolated and combined effects of prenatal and adolescent stress on adult social interactions and GABAergic neurons surrounded by perineuronal nets (PNNs) in the basolateral amygdala (BLA). Male and female rats were exposed to chronic variable stressors (CVS) prenatally (PS), during adolescence (AS), or during both prenatal and adolescent periods (PS+AS). In adulthood, all animals were tested for social behavior with same-sex weight-matched partners, and brains were collected for identification of BLA inhibitory neurons (GAD67 staining) and PNNs (Wisteria Floribunda Agglutinin staining). For social behavior, AS alone robustly increased social investigation in adulthood relative to non-stressed (NS) controls and animals exposed to combined PS+AS. PS+AS subjects did not significantly differ from NS controls, suggesting that prenatal stress exposure prevented adolescent stress-induced increases in adult social investigation. An analogous data pattern was observed in the BLA. AS alone decreased the number GAD67+ neurons surrounded by PNNs (co-labeled) relative to NS controls and subjects exposed to combined PS+AS. When the percentage of total GAD67+ neurons co-labeled with PNNs was assessed, both PS alone and AS alone reduced the proportion of GAD67+ neurons surrounded by PNNs, whereas combined PS+AS had no effect. Overall, these data suggest that prenatal stress exposure prevents adolescent stress-induced disruptions to perineuronal nets surrounding inhibitory neurons in the BLA, potentially conferring resilience to adolescent stress-induced changes in inhibitory function and social behavior. HighlightsO_LIAdolescent stress exposure increased social investigation in adulthood. C_LIO_LIAdolescent stress decreased the number of BLA cells co-labeled with GAD67 and WFA. C_LIO_LIPrenatal or adolescent stress decreased the proportion of inhibitory neurons with PNNs. C_LIO_LIWhen preceded by prenatal stress, effects of adolescent stress were not observed. C_LI

neuroscience↗

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

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

The third coiled coil domain of Atg11 is required for shaping mitophagy initiation sites

Selective autophagy is the capture of specific cytosolic contents in double membrane vesicles that subsequently fuse with the vacuole or lysosome, thereby delivering cargo for degradation. Selective autophagy receptors (SARs) mark the cargo for degradation and, in yeast, recruit Atg11, the scaffolding protein for selective autophagy initiation. The mitochondrial protein Atg32 is the yeast SAR that mediates mitophagy, the selective autophagic capture of mitochondria. Atg11- Atg32 interactions concentrate Atg32 into puncta that are thought to represent sites of mitophagy initiation. However, it is unclear how Atg11 concentrates Atg32 to generate mitophagy initiation sites. We show here that the coiled coil 3 (CC3) domain of Atg11 is required for concentrating Atg32 into puncta. We determined the structure of the majority of the CC3, demonstrating that the CC3 forms a parallel homodimer whose dimer interface is formed by a small number of hydrophobic residues. We further show that the CC3 dimerization interface is required for shaping Atg32 into functional mitophagy initiation sites and for delivery of mitochondria to the vacuole. Our findings suggest that Atg11 self-interactions help concentrate SARs as a necessary precondition for cargo capture.

cell biology↗

bioRxiv2020

Effects of C-peptide replacement therapy on bone microarchitecture parameters in streptozotocin-diabetic rats.

Pathological pathways involved in the development of diabetic complications are still unclear. Several studies suggested a pathogenic role of C-peptide deficiency in vascular and neuropathic complications. However, to date, the role of C-peptide on diabetes-related bone loss has not been investigated. The objective of this study was to test the effects of a 6-week regimen of rat C-peptide infusion on bone by combining micro-CT imaging with histological testing. Twenty-three, four-month-old male Wistar rats were randomly divided into three groups: Normal control group; Sham diabetic control group; Diabetic plus C-peptide group. Diabetes was induced by injection of streptozotocin. Rat C-peptide was delivered via subcutaneously osmopumps. We assessed several trabecular microarchitectural parameters and cellular and matrix proteins in bone tissue sections. At the end of the study, both the normal control and diabetic plus C-peptide groups had a higher tibia weight than the diabetic control group (p = 0.05 and p = 0.02, respectively). C-peptide levels significantly and positively correlated with the trabecular thickness (r= 0.45, p=0.08) and negatively with structure model index (r= -0.40, p=0.09). Furthermore, it positively correlated with one of the histological assessments (i.e. PLIN1 score; p=0.02). Micro-CT evaluation showed significant inter-group differences in trabecular thickness (p=0.02), trabecular space (p = 0.05) and cross-sectional thickness (p=0.05). Diabetic plus C-peptide group showed a higher trabecular thickness (p<0.001), cross-sectional thickness (p=0.03) and a lower trabecular space (p=0.05) than the normal control group. Both the normal control and diabetic plus C-peptide groups had more Runx-2 and PLIN1 positive cells in comparison to the diabetic control group (p = 0.045 and p = 0.034). For the first time we demonstrated that the diabetic rats receiving rat C-peptide had higher quality of trabecular bone, than diabetic rats not receiving it. C-peptide could have a role in the prevention of diabetes-related bone loss.

systems biology↗

bioRxiv2019

Conserved abilities of individual recognition and genetically modulated social responses in young chicks (Gallus gallus)

The ability to recognise familiar individuals and the motivation to stay in contact with conspecifics are important to establish social relationships from the beginning of life. To understand the genetic basis of early social behaviour, we studied the different responses to familiar/unfamiliar individuals and social reinstatement in 4-day-old domestic chicks (Gallus gallus) in three genetically isolated breeds: Padovana, Polverara and Robusta. All breeds showed a similar ability to discriminate between familiar and unfamiliar individuals, staying closer to familiar individuals. Social reinstatement motivation measured as the average distance between subjects, latency to the first step and exploration of the arena (a proxy for the lack of fear), differed between breeds. More socially motivated chicks that stayed in closer proximity, were also less fearful and explored the environment more extensively. These results suggest that modulation of social behaviour shows larger genetic variability than the ability to recognise social partners, which appears to be an adaptive ability widespread at the species level even for very young animals.

neuroscience↗

bioRxiv2019

A transient time window for early predispositions in newborn chicks

Neonates of different species are born with a set of predispositions that influence their early orienting responses toward the first stimuli encountered in their life. Human neonates and domestic chicks exhibit several similarities in the predisposition for attending to objects that move with speed changes, face-like stimuli and biological motion. Although early predispositions are connected to physiological development, little is known on the temporal course of early predispositions (whether they are stable or change in time) and on their genetic basis. To address these issues, we tested the preference for objects that change in speed vs. linear motion in three chicken breeds (Padovana, Polverara and Robusta maculata) within one day after hatching and three days after hatching. We found that the predisposition to preferentially attend to changes in speed is fixed at the species level on the first day of life and that it disappears by day three. These results indicate the existence of a short and transient time window of early predispositions that does not depend on visual experience.

animal behavior and cognition↗