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Miglietta, S.

Publications and source records attributed to Miglietta, S..

3 recordsLinked to original sources

Spatial segregation and multi-scale space-use adjustments to socio-ecological variables in western gorillas

Background: Identifying the mechanisms that shape space-use dynamics and the scale at which they operate can provide insights into the socio-ecology of numerous animal species. This is crucial for addressing both applied (e.g., conservation) and theoretical questions (e.g., the coexistence or segregation of individuals). Yet, longitudinal views of the space-use dynamics are generally rare. Taking advantage of a long-term movement dataset (up to 8 years) on five habituated groups of wild western gorillas (Gorilla gorilla) in Central Africa, we investigated the dynamics of their space use in relation to the socio-ecological variables from everyday movement to home range shifts. Methods: We looked at which temporal scale their ranging movements are stationary to highlight the dynamics of home range settling and shifts. We also studied how daily space use is shaped by (i) foraging and intra-group constraints (i.e., diet, group size, presence of offspring), and by (ii) inter-group competition (direct or indirect), quantifying static and dynamic interactions in neighbouring group-dyads. Results: Gorilla groups shifted the centre of their home range 0.17 times per year by a distance larger than the mean home range radius. Movements within the home range were highly dependent on the group composition and the ecological features (with larger daily-travelled distances in the high-fruit season compared to the low-fruit season). The presence of dependent infants affected the daily-travel distance: the larger their number, the smaller the daily-travel distance. Furthermore, the frequently visited sites of the home range were also used the longest, but their locations differed seasonally, suggesting space use flexibility. Although there was little overlap between the home ranges of neighbouring groups, these groups did not seem to avoid each other more than expected at random. They could even venture into, and slept in, the central part of the home range of a neighbouring group. Conclusion: Our study suggests that spatial segregation should be the simple consequence of avoidance of depleted areas rather than of territorial behaviour. It shows how socio-ecological constraints may shape the space-use patterns at different scales in a non-territorial species, and questions the role of cognition in space-use dynamics.

ecology↗

Retinoic acid and proteotoxic stress induce AML cell death overcoming stromal cell protection

Acute myeloid leukemia (AML) patients bearing the ITD mutation in the tyrosine kinase receptor FLT3 (FLT3-ITD) present a poor prognosis and a high risk of relapse. FLT3-ITD is retained in the endoplasmic reticulum (ER) and generates intrinsic proteotoxic stress. We devised a strategy based on proteotoxic stress, generated by the combination of low doses of the differentiating agent retinoic acid (R), the proteasome inhibitor bortezomib (B), and the oxidative stress inducer arsenic trioxide (A). It exerts strong cytotoxic activity on FLT3-ITD+ AML cell lines and primary blasts isolated from patients, due to ER homeostasis imbalance and generation of oxidative stress. AML cells become completely resistant to the combination RBA when treated in co-culture with bone marrow stromal cells (BMSC). Nonetheless, we could overcome such protective effects by using high doses of ascorbic acid (Vitamin C) as an adjuvant. Importantly, the combination RBA plus ascorbic acid significantly prolongs the life span of a murine model of human FLT3-ITD+ AML without toxic effects. Furthermore, we show for the first time that the cross-talk between AML cells and BMSC upon treatment involves disruption of the actin cytoskeleton and the actin cap, increased thickness of the nuclei, and relocalization of the transcriptional co-regulator YAP in the cytosol of the BMSC. Our findings strengthen our previous work indicating induction of proteotoxic stress as a possible strategy in FLT3-ITD+ AML therapy and open to the possibility of identifying new therapeutic targets in the crosstalk between AML cells and BMSC, involving mechanotransduction and YAP signaling

cancer biology↗

Human platelet lysate derived extracellular vesicles enhance angiogenesis through miR-126

Objectivesextracellular vesicles (EVs) are key biological mediators of several physiological functions within the cell microenvironment. Platelets are the most abundant source of EVs in the blood. Similarly, platelet lysate (PL), the best platelet derivative and angiogenic performer for regenerative purposes, is enriched of EVs, but their role is still too poorly discovered to be suitably exploited. Here we explored the contribution of the EVs in PL, by investigating the angiogenic features extrapolated from that possessed by PL. Methodswe tested angiogenic ability and molecular cargo in 3D bioprinted models and by RNA sequencing analysis of PL-derived EVs. Resultsa subset of small vesicles is highly represented in PL. The EVs do not retain aggregation ability, preserving a low redox state in HUVEC and increasing the angiogenic tubularly-like structures in 3D endothelial bioprinted constructs. EVs resembled the miRNome profile of PL, mainly enriched of small RNAs and a high amount of miR-126, the most abundant angiogenic miRNA in platelets. The transfer of miR-126 by EVs in HUVEC after the in vitro inhibition of the endogenous form, restored angiogenesis, without involving VEGF as downstream target in this system. ConclusionsPL is a biological source of available EVs with angiogenic effects involving a miRNAs-based cargo. These properties can be exploited for targeted molecular/biological manipulation of PL, by potentially developing a product exclusively manufactured of EVs.

cell biology↗