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Biology subjects

Borghi, F.

Publications and source records attributed to Borghi, F..

5 recordsLinked to original sources

Nanostructured Zirconia thin films as neurogliomorphic interface for neural cells of central and peripheral nervous system

Recent advances in neuroscience have highlighted the central role of glial cells, particularly astrocytes, in regulating neural network activity through calcium-dependent neuron-glia communication. In parallel, nanostructured cluster-assembled materials have emerged as promising candidates for developing brain-machine interfaces, because of their biomimetic morphology, mechanotransductive properties and neuromorphic behavior. Among these, nanostructured zirconium oxide (ns-ZrOx) thin films have recently demonstrated memristive and signal-processing capabilities compatible with biohybrid neural systems, yet their interaction with heterogeneous neuroglial networks remains poorly understood. Here, we investigate the biocompatibility and functional effects of ns-ZrOx interfaces on primary astrocytes and dorsal root ganglion (DRG) neuron-glia co-cultures, comparing nanostructured and flat zirconia substrates. Both substrates supported cellular adhesion, survival, and differentiation. However, ns-ZrOx selectively enhanced glial calcium signaling, increasing transient amplitude and accelerating response kinetics in both central and peripheral glial populations. Our findings identify ns-ZrOx as an active neurogliomorphic interface capable of modulating neuron-glia communication through nanoscale material properties. By bridging glial physiology with neuromorphic nanomaterials, this work supports the development of hybrid bioelectronic platforms integrating living neural networks with adaptive functional materials for brain-inspired computing and advanced neural interfaces.

bioengineering↗

Nuclear Speckle Dynamics are Controlled by Polyphosphate Inhibition of CLK Proteins

Nuclear speckles (NS) are membrane-less nuclear organelles that act as critical hubs for pre-mRNA splicing. Defects in splicing are linked to several human diseases, including cancer, Alzheimers disease, and dystrophies. While CLK kinases regulate the mobilization of splicing factors from NS, the molecular mechanisms underlying NS assembly and dissolution remain unclear. Using an adaptation of the Biotinylation by Antibody Recognition (BAR) technique, we identify polyphosphate (polyP) as a novel and essential regulator of NS dynamics. Polyphosphate, a highly conserved polyanion composed of a chain of phosphate molecules, is involved in several functions in mammalian cells. Here, we show that polyP interacts with the NS core component SRRM2, and polyP depletion disrupts NS organization releasing splicing factors into the nucleoplasm. RNA-seq analysis reveals that polyP depletion increases exon inclusion, particularly in long genes with multiple exons, highlighting its role in splicing regulation. Mechanistically, we demonstrate that polyP acts as a physiological inhibitor of CLK3 kinase, preventing the phosphorylation of SR proteins and thereby maintaining NS stability. Our findings not only expand our understanding of NS biology but also provide new insights into the polyP involvement in splicing-related diseases. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=90 SRC="FIGDIR/small/633116v1_ufig1.gif" ALT="Figure 1"> View larger version (22K): org.highwire.dtl.DTLVardef@1dc44b6org.highwire.dtl.DTLVardef@2339e4org.highwire.dtl.DTLVardef@ade454org.highwire.dtl.DTLVardef@69482b_HPS_FORMAT_FIGEXP M_FIG C_FIG

cell biology↗

The glycocalyx affects force loading-dependent mechanotransductive topography sensing at the nanoscale

The cell/microenvironment interface is the starting point of integrin-mediated mechanotransduction, but many details of mechanotransductive signal integration remain elusive due to the complexity of the involved (extra)cellular structures, such as the glycocalyx. We used nano-bio-interfaces reproducing the complex nanotopographical features of the extracellular matrix to analyse the glycocalyx impact on PC12 cell mechanosensing at the nanoscale (e.g., by force spectroscopy with functionalised probes). Our data demonstrates that the glycocalyx configuration affects spatio-temporal nanotopography-sensitive mechanotransductive events at the cell/microenvironment interface. Opposing effects of glycocalyx removal were observed, when comparing flat and specific nanotopographical conditions. The excessive retrograde actin flow speed and force loading are strongly reduced on certain nanotopographies upon removal of the native glycocalyx, while on the flat substrate we observe the opposite trend. Our results highlight the importance of the glycocalyx configuration in a molecular clutch force loading-dependent cellular mechanism for mechanosensing of microenvironmental nanotopographical features.

biophysics↗

Acute and chronic effects of exams week on cortisol production in undergraduate students

University students often experience heightened stress during exam periods, which can trigger psychosocial stress and increase cortisol production. This study aims to investigate both the short- and long-term effects of exam-related stress on the hypothalamic-pituitary-adrenal (HPA) axis, focusing on cortisol production and rhythmicity. Twenty-seven undergraduate students (18-24 years) from a biological sciences program participated in this study. Hair cortisol was measured for two months (October and November), while salivary cortisol was collected during final exams in November to assess cortisol rhythmicity. Saliva samples were taken five times per day across three consecutive days. Hair cortisol levels were significantly higher in November, reflecting increased chronic stress during exam periods. However, salivary cortisol maintained a normal circadian rhythm and preserved cortisol awakening response (CAR), despite elevated stress levels. The rhythmicity of cortisol production remained stable across the exam period, though an increase in cortisol before bedtime on the second and third days suggests heightened stress or anticipatory anxiety. Although university exams induce psychosocial stress, students demonstrated resilience in maintaining cortisol rhythmicity and CAR. These findings suggest adaptive stress responses in students, mitigating the risk of stress-related mental health issues. Further research using hair cortisol analysis could provide insights into cumulative stress exposure and aid in developing preventive mental health strategies for university students.

physiology↗

Neuronal Cells Confinement by Micropatterned Cluster-Assembled Dots with Mechanotransductive Nanotopography

The in vitro fabrication of neural networks able to simulate brain circuits and to maintain their native connectivity is of strategic importance to gain a deep understanding of neural circuit physiology and brain natural computational algorithm(s). This would also enable a wide-range of applications including the development of efficient brain-on-chip devices or brain-computer interfaces. Chemical and mechanotransductive cues cooperate to promote proper development and functioning of neural networks. Since the 80s, controlled growth of mammalian neuronal cells on micrometric patterned chemical cues with the development of synaptic connections and electrical activity has been reported, however the role of mechanotransductive signaling on the growth/organization of neural networks has not been investigated so far. Here we report the fabrication and characterization of patterned substrates for neuronal culture with a controlled structure both at the nano- and microscale suitable for the selective adhesion of neuronal cells. Nanostructured micrometric dots were patterned on passivated cell-repellent glass substrates by supersonic cluster beam deposition of zirconia nanoparticles through stencil masks. Cluster-assembled nanostructured zirconia surfaces are characterized by nanotopographical features that can direct the maturation of neural networks by mechanotransductive signaling. Our approach produces a controlled microscale pattern of adhesive areas with predetermined nanoscale morphology. We have validated these micropatterned substrates using a neuronal cell line (PC12 cells) and cultured hippocampal neurons. While cells have been uniformly plated on the substrates, they adhered only on the nanostructured zirconia regions, remaining effectively confined inside the nanostructured dots on which they were found to grow, move and differentiate.

bioengineering↗