Biology subjects

Russo, T.

Publications and source records attributed to Russo, T..

8 recordsLinked to original sources

bioRxiv2026

Characterizing the SASP-Dependent Paracrine Spreading of Senescence Between Human Brain Cell Types

One of the defining phenotypes of a senescent cell is the senescence-associated secretory phenotype (SASP), which can propagate senescence in neighboring cells both in vitro and in vivo. Importantly, this paracrine spreading of senescence can act in a cell non-autonomous manner, influencing neighboring cell populations and contributing to immune cell recruitment. As cellular senescence has recently been linked to both age-related neurodegenerative phenotypes and local inflammation and is more clearly defined across brain cell types in a cell-type-dependent manner, an urgent question remains regarding how a cell-type-specific paracrine spreading of senescence occurs in the brain. Here, we set out to profile the cell-type-specific features of the SASP and characterize the directionality of paracrine senescence-spreading between major brain cell types. Through this analysis, we identified key SASP ligand-receptor pairs involved in this paracrine dissemination. Targeting these factors with specific inhibitors, we prevented the paracrine spreading of senescence in a brain cell-type-dependent manner. Taken together, we identified specific SASP targets for therapeutic intervention in the context of human brain cells and thereby informed the SASP-dependent reaction of immune cells and age-related tissue dysfunction across both normal aging and models of neurodegenerative disease.

neuroscience↗

bioRxiv2026

Application of eDNA metabarcoding for high-resolution reconstruction of the trophic web of an Arctic fjord

In the face of a rapidly changing Arctic, the ecosystem of Kongsfjorden was put under the spotlight to explore its community composition and structural dynamics. An eDNA metabarcoding approach was implemented to carry out a Food Web Analysis. eDNA samples were collected using metaprobes, innovative passive samplers, deployed under two different sampling configurations: in association with set fish traps in the coastal area and a towed sampling along a central transect, an offshore domain of the fjord. Amplification of the mithocondrial COI and ribosomal 18S genes was conducted in order to obtain a comprehensive view of metazoans and protists communities, respectively. The output taxa from the metabarcoding process constituted trophic webs nodes while producers-consumers and prey-predators relationships were identified through a literature review. Qualitative food networks were successfully obtained for each sampled site and for the two domains identified in the ecosystem, the coastal and offshore areas. Moreover, these networks were characterized by using four food web indicators: Species Richness (N), Number of links (L), Direct Connectance (C) and Generality (G). Differences in the apical part of the webs instantly emerged, as well as a clear separation between the coastal and offshore domain. Analyzing the values of the trophic indicators allowed for a deeper consideration regarding the nets structure and relative stability. Overall, eDNA proved sensitive and precise in capturing differences between the two domains and in providing insights into ecosystem structure. Moreover, eDNA-based Food Web Analysis could set the basis for long term monitoring studies in the same area, being cost-effective, rapid and easy to implement when compared to traditional methods.

ecology↗

bioRxiv2025

Targeted and efficient AAV therapy for neuroblastoma via direct capsid-antibody coupling

Adeno-associated viral (AAV) vectors are widely used in gene therapy for their versatility and safety, but their broad tropism limits cell-specific applications such as targeting primary or metastatic tumor cells. To address this, we developed AAV-STITCH, a strategy using SpyTag technology to covalently attach polypeptides to the AAV capsid. This allows precise, dose-dependent coupling of an anti-GD2 ScFv to a galactose-binding-deficient AAV9-W503A capsid, redirecting tropism specifically to GD2-expressing neuroblastoma (NB) cells. In pseudometastatic xenograft mouse models, AAV-STITCHGD2 selectively transduced NB tumor cells without transduction of healthy tissues. Furthermore, delivery of a suicide gene via AAV-STITCHGD2 suppressed tumor growth and extended survival in mice with subcutaneous and pseudometastatic NB xenografts. These findings establish the feasibility of engineering AAVs with cell-type-specific transduction properties, providing a powerful and adaptable platform for the selective elimination of NB tumor cells. This technology marks a meaningful advance toward next-generation, targeted cancer therapies with strong clinical potential.

bioengineering↗

bioRxiv2025

Regulatory Network Inference of Induced Senescent Midbrain Cell Types Reveals Cell Type-Specific Senescence-Associated Transcriptional Regulators

Cellular senescence of brain cell types has become an increasingly important perspective for both aging and neurodegeneration, specifically in the context of Parkinsons Disease (PD). The characterization of classical hallmarks of senescence is a widely debated topic, whereby the context in which a senescence phenotype is being investigated, such as the cell type, the inducing stressor, and/or the model system, is an extremely important aspect to consider when defining a senescent cell. Here, we describe a cell type-specific profile of senescence through the investigation of various canonical senescence markers in five human midbrain cell lines using chronic 5-Bromodeoxyuridine (BrdU) treatment as a model of DNA damage-induced senescence. We used principal component analysis (PCA) and subsequent regulatory network inference to define both unique and common senescence profiles in the cell types investigated, as well as revealed senescence-associated transcriptional regulators (SATRs). Functional characterization of one of the identified regulators, transcription factor AP4 (TFAP4), further highlights the cell type-specificity of the expression of the various senescence hallmarks. Our data indicates that SATRs modulate cell type-specific profiles of induced senescence in key midbrain cell types that play an important role in the context of aging and PD.

neuroscience↗

bioRxiv2025

Nuclear Import Defects Drive Cell Cycle Dysregulation in Neurodegeneration

Neurodegenerative diseases (NDDs) and other age-related disorders have been classically defined by a set of key pathological hallmarks. Two of these hallmarks, cell cycle dysregulation (CCD) and nucleocytoplasmic transport (NCT) defects, have long been debated as being either causal or consequential in the pathology of accelerated aging. Specifically, aberrant cell cycle activation in post-mitotic neurons has been shown to trigger neuronal cell death pathways and cellular senescence. Additionally, NCT has been observed to be progressively dysregulated during aging and in neurodegeneration, where the increased subcellular redistribution of nuclear proteins such as TAR DNA-Binding Protein-43 (TDP43) to the cytoplasm is a primary driver of many NDDs. However, the functional significance of NCT defects as either a primary driver or consequence of pathology, and how the redistribution of cell cycle machinery contributes to neurodegeneration, remains unclear. Here, we describe that pharmacological inhibition of importin-{beta} nuclear import is capable of perturbing cell cycle machinery both in mitotic neuronal cell lines and post-mitotic primary neurons in vitro. Our NemfR86S mouse model of motor neuron disease, characterized by nuclear import defects, further recapitulates the hallmarks of CCD in mitotic cell lines and in post-mitotic primary neurons in vitro, and in spinal motor neurons in vivo. The observed CCD is consistent with the transcriptional and phenotypical dysregulation observed in neuronal cell death and cellular senescence in NDDs. Together, this evidence suggests that impairment of nuclear import pathways resulting in CCD may be a common driver of pathology in neurodegeneration. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=106 SRC="FIGDIR/small/635269v1_figa1.gif" ALT="Figure 1"> View larger version (16K): org.highwire.dtl.DTLVardef@15a17d9org.highwire.dtl.DTLVardef@1d3af6eorg.highwire.dtl.DTLVardef@a291f5org.highwire.dtl.DTLVardef@11c9c5d_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOGraphical Abstract:C_FLOATNO Overview of Dysregulated Cell Cycle Mechanisms in Neuronal Cells. A nuclear import block drives cell cycle re-entry from G0, culminating in cell cycle arrest at G1/S. This cell cycle arrest is associated with activation of CKIs from the INK locus (p15, p16, p18, p19) and Cip/Kip (p21, p27) which act on specific CDK/Cyclin complexes. This activity is further associated with the G1/S downregulation E2F and stathmins, resulting in microtubule dysregulation and cell cycle arrest. C_FIG

neuroscience↗

bioRxiv2023

Assessing the overlap between fishing activities and chondrichthyans distribution exposes high-risk areas for bycatch of threatened species

Sharks, rays, and chimaeras (chondrichthyans) play a crucial role in marine ecosystem functioning but are highly vulnerable to fishing. Hence, understanding the spatial overlap between chondrichthyans and fishing effort is essential for effective conservation and management. Here, we propose an integrated approach that combines Vessel Monitoring System data with geostatistical species distribution models to assess the potential impact of fishing on chondrichthyan populations in the western Adriatic Sea. By mapping the overlap between model-based chondrichthyan distribution, species richness, and the proportion of threathened species with bottom trawl fishing activities, we identify areas at high risk for chondrichthyan bycatch. Our findings show that many of these species are at risk across a large part of their distribution within the study area. Notably, there is a substantial spatial overlap between regions where threatened chondrichthyans are found and species-rich areas with locations of intensive bottom trawl fishing in the northern and central offshore regions of the western Adriatic, emphasizing the vulnerability of these species to fishing pressure. Furthermore, differences in overlap between distinct fishing gears highlight the importance of considering specific fishing practices when formulating management strategies. While our work provides novel insights to potential bycatch hotspots, limitations related to data sources, spatial resolution, and the inability to directly quantify fishing impacts should be considered. Nonetheless, our findings contribute to the development of targeted conservation and spatial management measures, offering a general approach to study model-based spatial hotspots aimed at protecting and sustaining chondrichthyan populations in the heavily exploited Adriatic Sea.

ecology↗

bioRxiv2023

The SATB1-MIR22-GBA axis mediates glucocerebroside accumulation inducing a cellular senescence-like phenotype in dopaminergic neurons

Idiopathic Parkinsons Disease (PD) is characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta, which is associated with neuroinflammation and reactive gliosis. The underlying cause of PD and the concurrent neuroinflammation are not well understood. In this study, we utilized human and murine neuronal lines, stem cell-derived dopaminergic neurons, and mice to demonstrate that three previously identified genetic risk factors for PD, namely SATB1, MIR22HG, and GBA, are components of a single gene regulatory pathway. Our findings indicate that dysregulation of this pathway leads to the upregulation of glucocerebrosides (GluCer), which triggers a cellular senescence-like phenotype in dopaminergic neurons. Specifically, we discovered that downregulation of the transcriptional repressor SATB1 results in the derepression of the microRNA miR-22-3p, leading to decreased GBA expression and subsequent accumulation of GluCer. Furthermore, our results demonstrate that an increase in GluCer alone is sufficient to impair lysosomal and mitochondrial function, thereby inducing cellular senescence dependent on S100A9 and stress factors. Dysregulation of the SATB1-MIR22-GBA pathway, observed in both PD patients and normal aging, leads to lysosomal and mitochondrial dysfunction due to the GluCer accumulation, ultimately resulting in a cellular senescence-like phenotype in dopaminergic neurons. Therefore, our study highlights a novel pathway involving three genetic risk factors for PD and provides a potential mechanism for the senescence-induced neuroinflammation and reactive gliosis observed in both PD and normal aging.

neuroscience↗

bioRxiv2020

All is fish that comes to the net: metabarcoding for rapid fisheries catch assessment

Monitoring marine resource exploitation is a key activity in fisheries science and biodiversity conservation. Since research surveys are time-consuming and costly, fishery-dependent data (i.e. derived directly from fishing vessels) are increasingly credited with a key role in expanding the reach of ocean monitoring. Fishing vessels may be seen as widely ranging data-collecting platforms, which could act as a fleet of sentinels for monitoring marine life, in particular exploited stocks. Here, we investigate the possibility of assessing catch composition of single hauls carried out by trawlers by applying DNA metabarcoding to the "slush" collected from fishing nets just after the end of hauling operations. We assess the performance of this approach in portraying {beta}-diversity and examining the quantitative relationship between species abundances in the catch and DNA amount in the slush (reads counts generated by amplicon sequencing). We demonstrate that the assemblages identified using DNA in the slush mirror those returned by visual inspection of net content and detect a strong relationship between read counts and species abundances in the catch. We therefore argue that this approach could be upscaled to serve as a powerful source of information on the structure of demersal assemblages and the impact of fisheries.

ecology↗