Biology subjects

Nita, A.

Publications and source records attributed to Nita, A..

5 recordsLinked to original sources

bioRxiv2024

Integrated hepatic ferroptosis gene signature dictates pathogenic features of ferroptosis

Background & AimsFerroptosis, a distinctive form of cell death induced by iron-dependent lipid peroxidation, is implicated in various biological processes, including liver diseases. Establishing an iron overload-induced ferroptosis model and identifying hepatic gene signatures associated with ferroptosis are crucial for understanding its role in liver pathogenesis. MethodsF-box and leucine-rich repeat protein 5 (FBXL5) is a substrate-recognition component of the SCF E3 ligase complex that restricts intracellular iron levels. In this study, we used liver-specific Fbxl5-null mice to establish an iron overload-induced ferroptosis model. Transcriptome analysis identified genes involved in hepatic ferroptosis. Integrating these gene signatures with another ferroptosis model enabled the assessment of ferroptosis-related pathology in murine liver injury models and in 174 patients undergoing liver resection surgery. ResultsIron overload induced severe liver damage in liver-specific Fbxl5-null mice, characterized by elevated liver enzymes, histopathological changes, and lipid peroxidation. Transcriptome analysis revealed a distinct set of genes associated with hepatic ferroptosis response. Generating a gene signature for evaluating ferroptosis enhanced the understanding of ferroptosis-related pathologies in liver diseases. Iron overload exacerbated liver damage in murine ischemia-reperfusion injury models via ferroptosis induction. In human patients, elevated serum iron levels correlated with sustained post-operative liver damage, indicating heightened susceptibility to ferroptosis. ConclusionHere, a murine model of iron overload-induced hepatic ferroptosis was established, and a gene signature indicative of hepatic ferroptosis response in both mice and humans was identified. These findings underscore the role of ferroptosis in liver injury progression and suggest potential therapeutic targets for liver disease intervention. HIGHLIGHTSO_LILiver-specific Fbxl5 knockout mice provide an iron-induced ferroptotic injury model C_LIO_LIIntegrated gene signature of iron- and acetaminophen-induced liver injury dictates ferroptosis C_LIO_LIIron overload aggravates hepatic ischemia-reperfusion injury in mice C_LIO_LIPatients with high iron levels show delayed post-operative liver damage recovery C_LI IMPACT AND IMPLICATIONSOur study elucidated the critical role of iron in liver disease pathogenesis and ischemia-reperfusion injury (IRI). By establishing a murine model of iron overload-induced ferroptosis, we confirmed that iron overload exacerbated hepatic IRI, underscoring the importance of ferroptosis in liver damage. Additionally, the development of an integrated gene signature for hepatic ferroptosis response provides a valuable tool for evaluating ferroptosis in liver diseases. Via analysis of patient data, we also highlighted the clinical relevance of ferroptosis in post-operative liver damage, offering insights into potential therapeutic strategies targeting iron and ferroptosis to improve outcomes in patients with liver diseases.

molecular biology↗

bioRxiv2020

Governance networks around grasslands with contrasting management history

Romanian grasslands have high nature value, being among the most important biodiversity hotspots at the European level. The European Union Common Agricultural Policy (CAP) contradicts the Biodiversity Strategy to 2020 objective by hindering coordinated grassland governance and collaboration among the involved actors. At the European level, few attempts have been made in creating conceptual strategies for implementing conservation measures in a multi-actor and multi-scale governance setting. Our paper focuses on a comparative network analysis of grassland landscape governance of three Romanian regions (Iron Gates Natural Park - SW; Sighisoara - Tarnava Mare - center; and Dobrogea - SE), representatives for grassland management in mountain and lowland settings. We investigated the structural characteristics of one-mode directed grassland governance networks in the three protected areas (standard cohesion and reciprocity metrics and exponential random graph models), the position of institutions participating in networks (node-level centrality metrics), and the perception of CAP influence on grassland governance by farmers benefiting of CAP agri-environmental payments. In Sighisoara, grasslands governance has been centralized but biodiversity-friendly, while in Iron Gates, grasslands were traditionally managed through a decentralized, community-level system, and this type of governance continues to date. Whereas for Dobrogeas grasslands, the governance was performed in an intensive, centralized state-run management regime during the communist time and by large landowners after the transition period ended. Our findings illustrate the structure of the three governance networks and dissimilar patterns of collaboration, indicating distinct particularities to be considered when exploring barriers to and options for successful governance in traditionally managed grasslands in the context of CAP measures-driven management.

ecology↗

bioRxiv2019

Elucidation of protein-protein interactions necessary for maintenance of the BCR-ABL signaling complex

Approximately 50% of chronic myeloid leukemia (CML) patients in deep remission experience a return of clinical CML after withdrawal of tyrosine kinase inhibitors (TKIs). This suggests signaling of inactive BCR-ABL, which allows for survival of cancer cells, leading to relapse. Understanding the dynamics of BCR-ABL signaling complex holds a key to the mechanism of BCR-ABL signaling. Here, we demonstrate that TKIs inhibit catalytic activity of BCR-ABL, but do not dissolve the BCR-ABL core signaling complex consisting of CrkL, SHC1, Grb2, SOS1, cCbl, and SHIP2. We show that CrkL binds to proline-rich regions located in C-terminal, intrinsically disordered region of BCR-ABL, that deletion of pleckstrin homology domain of BCR-ABL diminishes interaction with SHC1, and that BCR-ABL sequence motif located in disordered region around phosphorylated tyrosine 177 mediates binding of at least three core complex members, the Grb2, SOS1 and cCbl. Introduction of Y177F substitution blocks association with Grb2, SOS1 and cCbl. Further, we identified SHIP2 binding sites within the src-homology and tyrosine kinase domains of BCR-ABL. We found that BCR-ABL is unable to phosphorylate SHC1 in cells lacking SHIP2. Reintroducing SHIP2 into Ship2 knock-out cells restored SHC1 phosphorylation, which depended on inositol phosphatase activity of SHIP2. Our findings provide characterization of protein-protein interactions in the BCR-ABL signaling complex, and support the concept of targeting BCR-ABL signaling in CML by inhibition of its interactions with the members of the core complex.

molecular biology↗

bioRxiv2018

Who is researching biodiversity hotspots in Eastern Europe? A case study on grasslands from Romania

Farming landscapes of Europe are vital arenas for social-ecological sustainability because of their significant coverage and potential to integrate food production with biodiversity conservation. Knowledge gathered by scientific research is a critical ingredient for developing and implementing socio-economically and ecologically sustainable grassland management strategies for grasslands. The quality of scientific knowledge and its potential to address grasslands as complex social-ecological systems is strongly dependent on the creativity and scientific ambition of the researcher, but also on the network (from academic and non-academic sectors) around the researcher. The goal of this paper is to map the research network around Romanias grasslands. These systems have exceptional socio-cultural and economic values and are between the most biodiverse ecosystems of the world. Considering the multiple threats to these grasslands, it is an urgent need to understand the existing scientific knowledge profile around these systems. This paper aims at using bibliometrics analysis, a well-developed scientific domain that envisages network theory to analyze relationships between affiliations network, co-authorship network, and co-word analysis. The number of studies targeting grassland management in Romania is increasing mainly thanks to international involvement. However, the management of the grasslands is still deficient and the contribution of science to the process is virtually absent. The subject of research is mainly related to the biological and ecological characteristics of grasslands, a notable absence from internationally visible research being the management of grasslands, especially in the context of EU Common Agricultural Policies. To increase scientific performance, and better inform EU and local policies on grassland management, Romanian researchers should better capitalize on international collaborations and local academic leaders. Our findings can be used to identify research gaps and to improve collaboration and knowledge exchange between practitioners, scientists, policy makers, and stakeholders.

scientific communication and education↗

bioRxiv2018

Empirical analysis and modelling of Argos Doppler location errors in Romania

BackgroundAdvances in wildlife tracking technology have allowed researchers to understand the spatial ecology of many terrestrial and aquatic animal species. Argos Doppler is a technology that is widely used for wildlife tracking owing to the small size and low weight of the Argos transmitters. This allows them to be fitted to small-bodied species. The longer lifespan of the Argos units in comparison to units outfitted with miniaturized global positioning system (GPS) technology has also recommended their use. In practice, large Argos location errors often occur due to communication conditions such as transmitter settings, local environment, and the behavior of the tracked individual.\n\nMethodsConsidering the geographic specificity of errors and the lack of benchmark studies in Eastern Europe, the research objectives were: (1) to evaluate the accuracy of Argos Doppler technology under various environmental conditions in Romania, (2) to investigate the effectiveness of straightforward destructive filters for improving Argos Doppler data quality, and (3) to provide guidelines for processing Argos Doppler wildlife monitoring data. The errors associated with Argos locations in four geographic locations in Romania were assessed during static, low-speed and high-speed tests. The effectiveness of the Douglas Argos distance angle filter algorithm was then evaluated to ascertain its effect on the minimization of localization errors.\n\nResultsArgos locations received in the tests had larger associated horizontal errors than those indicated by the operator of the Argos system, including under ideal reception conditions. Positional errors were similar to those obtained in other studies outside of Europe. The errors were anisotropic, with larger longitudinal errors for the vast majority of the data. Errors were mostly related to speed of the Argos transmitter at the time of reception, but other factors such as topographical conditions and orientation of antenna at the time of the transmission also contributed to receiving low-quality data. The Douglas-Argos filter successfully excluded the largest errors while retaining a large amount of data when the threshold was set to the local scale (2 km).\n\nDiscussionFilter selection requires knowledge about the movement patterns and behavior of the species of interest, and the parametrization of the selected filter typically requires a trial and error approach. Selecting the proper filter reduces the errors while retaining a large amount of data. However, the post-processed data typically includes large positional errors; thus, we recommend incorporating Argos error metrics such as error ellipse or use complex modeling approaches when working with filtered data.

ecology↗