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Biology subjects

Masi, S.

Publications and source records attributed to Masi, S..

5 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↗

AI-driven Classification of Heart Failure Preserved and Reduced Ejection Fraction Patients Using the Total Protein Approach

Heart failure (HF) presents two major subtypes: HF with preserved ejection fraction (HFpEF) and HF with reduced ejection fraction (HFrEF), each one with distinct metabolic characteristics. This study utilized artificial intelligence, high-resolution mass spectrometry and the Total Protein Approach (TPA) to identify key features differentiating these subtypes. Aldolase A (ALDOA), a glycolytic enzyme, was found upregulated in HFrEF patients, reflecting an increased glycolysis pathway, while Arginase 1 (ARG1), a key enzyme in the urea cycle, was also elevated, indicating an increased urea pathway. In contrast, HFpEF patients showed TPA ALDOA and ARG1 levels similar to healthy controls. The combined use of ALDOA and ARG1 TPA values successfully classified 82% of patients (14 out of 17). Additionally, most HFpEF patients were over 80 years old, suggesting an age-related metabolic shift. The combination of ALDOA and ARG1 are promising biomarkers for distinguishing HFpEF and HFrEF using the TPA approach, with potential implications for targeted therapies.

biochemistry↗

N-acylethanolamine acid amidase inhibition reduces SARS-CoV-2 infection in Human Precision cut-lung slices and downregulates NF-kappaB signalling.

Like other positive-sense RNA viruses, SARS-CoV-2 manipulates host lipid metabolism to facilitate its replication by enhancing lipogenesis and lipid droplet formation. In doing so, SARS-CoV-2 infection perturbs bioactive lipid levels associated with the inflammatory response. One of these, Palmitoylethanolamide (PEA) is suppressed during SARS-CoV-2 infection since it activates the Peroxisome Proliferator-Activated Receptor- (PPAR-), a transcription factor that suppresses the nuclear factor-B (NF-{kappa}B), which is mandatory to sustain SARS-CoV-2 replication. PEA levels are regulated by N-acylethanolamine acid amidase (NAAA), a lysosomal enzyme responsible for catalysing the breakdown of PEA. We hypothesized that NAAA inhibition might interfere with SARS-CoV-2 replication since it will lead PEA to accumulate, activating PPAR- and, consequently, suppressing NF-{kappa}B. Our results reveal that genetic or chemical ablation of NAAA significantly suppresses SARS-CoV-2 replication by three log10 in human-derived precision-cut lung slices. Therefore, we investigated whether inhibiting NAAA could influence NF-{kappa}B activation through the activation of PPAR-. We observed PPAR- increased expression in NAAA-/-cells, while PPAR- expression remained low in infected parental cells. As expected, the elevated PPAR- expression correlated with a parallel reduction in NF-{kappa}B activation when NAAA is ablated. These findings underscore NAAA as an essential host factor for SARS-CoV-2 replication and propose a potential mechanism of action rooted in the attenuation of NF-{kappa}B activation during viral replication. Author summaryOver the past three years, COVID-19 has claimed nearly 7 million lives worldwide, prompting extensive efforts to find effective treatments. While RNA-based vaccines have been developed rapidly, they alone have not completely halted the spread of the virus, making the search for antiviral therapies crucial. One promising approach targets the anti-inflammatory lipid PEA, which has shown some success in COVID-19 clinical trials. PEA is quickly degraded by the enzyme NAAA. Researchers have found that inhibiting NAAA can enhance and prolong PEA anti-inflammatory effects. NAAA inhibitors have already shown effectiveness in reducing chronic pain and lung inflammation in animal models and have also been effective against Zika virus replication. Our research focused on testing the NAAA inhibitor ARN726 against SARS-CoV-2. In human lung cells and lung tissue samples, ARN726 significantly reduced SARS-CoV-2 replication and inflammation. We discovered that this inhibition suppresses the NF-{kappa}B pathway, which the virus uses to fuel its replication and sustain Cytokine storm. Overall, our findings suggest that NAAA inhibitors like ARN726 could be repurposed to combat COVID-19 and potentially other coronaviruses, offering a novel and effective antiviral strategy.

microbiology↗

N-acylethanolamine acid amide hydrolase is a novel target for drugs against SARS-CoV-2 and Zika virus

Several compounds have been tested against SARS-CoV-2; at present, COVID-19 treatments decrease the deleterious inflammatory response and acute lung injury. However, the best therapeutic response would be expected by combining anti-inflammatory properties, while concomitantly blocking viral replication. These combined effects should drastically reduce both infection rate and severe complications induced by novel SARS-CoV-2 variants. Therefore, we explored the antiviral potency of a class of anti-inflammatory compounds that inhibit the N-Acylethanolamine acid amidase (NAAA). This enzyme catalyzes the hydrolysis of palmitoylethanolamide (PEA), a bioactive lipid that mediates anti-inflammatory and analgesic activity through the activation of peroxisome proliferator receptor- (PPAR-). Similarly, this pathway is likely to be a significant target to impede viral replication since PPAR- activation leads to dismantling of lipid droplets, where viral replication of Flaviviruses and Coronaviruses occurs. Here, we show that either genetic or pharmacological inhibition of the NAAA enzyme leads to five-fold reduction in the replication of both SARS-CoV-2 and ZIKV in various cell lines. Once NAAA enzyme is blocked, both ZIKV and SARS CoV-2 replication decrease, which parallels a sudden five-fold decrease in virion release. These effects induced by NAAA inhibition occurs concomitantly with stimulation of autophagy during infection. Remarkably, parallel antiviral and anti-inflammatory effects of NAAA antagonism were confirmed in ex-vivo experiments, within SARS-CoV-2 infected human PBMC cells, in which both viral genomes and TNF- production drop by ~60%. It is known that macrophages contribute to viral spread, excessive inflammation and macrophage activation syndrome that NAAA inhibitors might prevent, reducing the macrophage-induced acute respiratory distress syndrome and subsequent death of COVID-19 patients.

microbiology↗

Mammal extinctions and the increasing isolation of humans on the tree of life

A sixth great mass extinction is ongoing due to the direct and indirect effects of human pressures. However, not all lineages are impacted equally. As humans, we frequently believe that we hold a unique place on Earth. Here, we show that our current impacts on the natural world risk to heighten that expectation. Evolutionary proximity to Homo sapiens emerges as a powerful predictor of extinction risk among mammals. Our analysis shows that the species most closely related to H. sapiens are exposed to a large variety of threat types and that they may also have greater intrinsic sensitivity to threats. Pruning back the tree of life around us will lead to our species being among those with the fewest close relatives. We will erase our evolutionary history, forcing its uniqueness. If no action is taken, we will lose crucial biodiversity for the preservation of Earth ecosystems, and a key reference to what makes us human.

ecology↗