Biology subjects

Mazzoni, F.

Publications and source records attributed to Mazzoni, F..

3 recordsLinked to original sources

bioRxiv2026

Microscale Characterization of Undecalcified Bone Tissue Using Correlative Atomic Force Microscopy and Histology

Characterizing bone tissue in its mineralized state remains technically challenging. Conventional approaches typically compromise mechanical integrity through decalcification or lack the structural resolution necessary to capture microscale heterogeneity. Here we present an integrated workflow combining atomic force microscopy (AFM) with histological and immunofluorescence assays on adjacent undecalcified bone tissue cryosections. Using a tape-transfer mounting approach, we resolve mechanically and structurally distinct tissue types within a minimally processed single mouse femur section. Furthermore, we show that decalcification substantially alters nanoscale surface topography and local mechanical properties. Applied to an aging cohort of C57BL/6J female mice spanning 7 to 115 weeks, the proposed method detects age-associated changes in bone matrix structure and stiffness. The approach provides a practical methodology for spatially correlating nanomechanical properties with molecular markers in bone and other mineralized tissues, with broad applicability to disease models including cancer metastasis, osteoporosis, and osteoarthritis.

biophysics↗

bioRxiv2026

Phosphatidylserine exposure by developing astrocytes initiates microglia-mediated developmental cell death

Developmental cell death is classically attributed to apoptosis, yet in mammalian retina, large numbers of developing astrocytes die non-apoptotically during a defined developmental window. Astrocyte death is important for patterning a cellular template that guides angiogenesis, but the underlying mechanism remains unknown. Here we show that healthy developing astrocytes initiate their own elimination by recruiting microglia via regulated exposure of the membrane lipid phosphatidylserine. Experimentally increasing phosphatidylserine exposure in astrocytes, but not neurons, accelerates their removal by microglia without changing how many astrocytes ultimately survive. This acceleration causes profound vascular defects resembling pathological features of retinopathy of prematurity. Genetic disruption of MFGE8, a phosphatidylserine-binding protein, suppresses microglia-mediated astrocyte killing and prevents vascular pathology despite continued phosphatidylserine exposure. This mechanism extends beyond the retina, because phosphatidylserine also initiates astrocyte death in developing cerebral cortex. Together, these findings identify phosphatidylserine exposure as a developmental signal that times microglia-mediated astrocyte elimination, with essential consequences for neurovascular development.

neuroscience↗

bioRxiv2022

Inflammation Of The Retinal Pigment Epithelium Drives Early-Onset Photoreceptor Degeneration In Mertk-Associated Retinitis Pigmentosa

Severe, early-onset photoreceptor (PR) degeneration associated with MERTK mutations is thought to result from failed phagocytosis by retinal pigment epithelium (RPE). Notwithstanding, the severity and onset of PR degeneration in mouse models of Mertk ablation is determined by the hypomorphic expression or the loss of the Mertk paralog Tyro3. Here we find that loss of Mertk and reduced expression/loss of Tyro3 led to RPE inflammation even before eye-opening. Incipient RPE inflammation cascaded to involve microglia activation and PR degeneration with monocyte infiltration. Inhibition of RPE inflammation with the JAK1/2 inhibitor ruxolitinib mitigated PR degeneration in Mertk-/- mice. Neither inflammation nor severe, early-onset PR degeneration were observed in mice with defective phagocytosis alone. Thus, inflammation drives severe, early-onset PR degeneration-associated with Mertk loss of function.

immunology↗