Publications by authors named "Onofri F"

High-pressure and temperature extraction (HPTE) can effectively recover bioactive compounds from olive pomace (OP). HPTE extract obtained by extracting OP with ethanol and water (50:50 /) at 180 °C for 90 min demonstrated a pronounced ability to preserve intracellular calcium homeostasis, shielding neurons from the harmful effects induced by N-methyl-d-aspartate (NMDA) receptor (NMDAR) overactivation, such as aberrant calpain activation. In this study, the extraction temperature was changed from 37 to 180 °C, and the extracts were evaluated for their antioxidant potency and ability to preserve crucial intracellular Ca-homeostasis necessary for neuronal survival.

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The rainbow patterns of oblate spheroidal drops have been observed in experiments nearly forty years ago [Nature312, 529 (1984)10.1038/312529a0]. However, the prediction for those complex patterns has been a challenge for conventional light scattering models.

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Attention deficit and hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by alterations in the mesocorticolimbic and nigrostriatal dopaminergic pathways. Polymorphisms in the Synapsin III (Syn III) gene can associate with ADHD onset and even affect the therapeutic response to the gold standard ADHD medication, methylphenidate (MPH), a monoamine transporter inhibitor whose efficacy appears related with the stimulation of brain-derived neurotrophic factor (BDNF). Interestingly, we previously showed that MPH can bind Syn III, which can regulate neuronal development.

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The analysis of nano- and microparticle suspensions with micro systems affords improved space-time yields, selectivity, reaction residence times and conversions capabilities. These capabilities are of primary importance in various fields of research and industry. The few microfluidic lab-on-a-chip approaches that have been developed are essentially designed to analyse fluid phases or involve the use of benchtop particle sizing instruments.

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The repressor-element 1-silencing transcription/neuron-restrictive silencer factor (REST/NRSF) controls hundreds of neuron-specific genes. We showed that REST/NRSF downregulates glutamatergic transmission in response to hyperactivity, thus contributing to neuronal homeostasis. However, whether GABAergic transmission is also implicated in the homeostatic action of REST/NRSF is unknown.

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The scattering patterns near the primary rainbow of oblate drops are simulated by extending the vectorial complex ray model (VCRM) [Opt. Lett.36, 370 (2011)OPLEDP0146-959210.

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Loss-of-function mutations in proline-rich transmembrane protein-2 (PRRT2) cause paroxysmal disorders associated with defective Ca dependence of glutamatergic transmission. We find that either acute or constitutive PRRT2 deletion induces a significant decrease in the amplitude of evoked excitatory postsynaptic currents (eEPSCs) that is insensitive to extracellular Ca and associated with a reduced contribution of P/Q-type Ca channels to the EPSC amplitude. This synaptic phenotype parallels a decrease in somatic P/Q-type Ca currents due to a decreased membrane targeting of the channel with unchanged total expression levels.

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We have recently demonstrated that bioactive molecules, extracted by high pressure and temperature from olive pomace, counteract calcium-induced cell damage to different cell lines. Here, our aim was to study the effect of the same extract on murine cortical neurons, since the preservation of the intracellular Ca-homeostasis is essential for neuronal function and survival. Accordingly, we treated neurons with different stimuli in order to evoke cytotoxic glutamatergic activation.

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Neuroinflammation is involved in the pathogenesis of several neurologic disorders, including epilepsy. Both changes in the input/output functions of synaptic circuits and cell Ca dysregulation participate in neuroinflammation, but their impact on neuron function in epilepsy is still poorly understood. Lipopolysaccharide (LPS), a toxic byproduct of bacterial lysis, has been extensively used to stimulate inflammatory responses both and LPS stimulates Toll-like receptor 4, an important mediator of the brain innate immune response that contributes to neuroinflammation processes.

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Article Synopsis
  • The LRRK2 protein has important functional areas at both ends that help it interact with other proteins, and mutations in the LRRK2 gene are associated with Parkinson's disease.
  • A new variant, E193K, in the N-terminal region of LRRK2 was examined for its effects on vesicle trafficking using advanced microscopy techniques.
  • The study found that the E193K variant disrupts LRRK2's normal binding to synaptic vesicles and enhances vesicle fusion, indicating that mutations in LRRK2 can significantly affect its role in cellular processes related to Parkinson's disease.
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Leucine-rich repeat kinase 2 (LRRK2) is a large multidomain scaffolding protein with kinase and GTPase activities involved in synaptic vesicle (SV) dynamics. While its role in Parkinson's disease has been largely investigated, little is known about LRRK2 physiological role and until now few proteins have been described as substrates. We have previously demonstrated that LRRK2 through its WD40 domain interacts with synapsin I, an important SV-associated phosphoprotein involved in neuronal development and in the regulation of neurotransmitter release.

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The image of the photonic jet (also called caustic) formed by a large, transparent, and spherical particle, reconstructed by digital in-line holography, is shown to be similar to the Airy pattern observed at the focus of a diffraction-limited lens. The analysis of this image, real or virtual depending on whether the particle relative refractive index is above or below one, allows characterizing the particle composition via its refractive index. Experiments clearly demonstrate the value of this method for the simultaneous 3D characterization and differentiation of the dynamics, size, and composition of gas, liquid, and solid particles in multiphase flows.

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Adult neurogenesis is emerging as an important player in brain functions and homeostasis, while impaired or altered adult neurogenesis has been associated with a number of neuropsychiatric diseases, such as depression and epilepsy. Here we investigated the possibility that synapsins (Syns) I and II, beyond their known functions in developing and mature neurons, also play a role in adult neurogenesis. We performed a systematic evaluation of the distinct stages of neurogenesis in the hippocampal dentate gyrus of Syn I and Syn II knockout (KO) mice, before (2-months-old) and after (6-months-old) the appearance of the epileptic phenotype.

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Article Synopsis
  • Neurotransmission relies on synaptic vesicles (SVs) releasing neurotransmitters at the synapse, with a need for replenishment from a reserve pool during high activity.
  • Synapsins play a key role in maintaining this reserve pool and regulating the mobilization of SVs, but how this process works with other factors is not fully understood.
  • The study identifies intersectin, a scaffold protein, as crucial for SV replenishment, demonstrating that its interaction with synapsin I is essential for sustaining neurotransmission, highlighting its role in linking reserve pools to the endocytosis machinery at synapses.
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The capabilities and resolution of the rainbow technique were extended to estimate the size distribution and composition of droplets in liquid-liquid systems. For these droplets, essentially characterized by a low relative refractive index (m≈1.001-1.

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Article Synopsis
  • Mutations in the LRRK2 gene are linked to familial Parkinson's disease, with the protein having important interaction domains at both its ends.
  • This study used microscopy and assays to find that the N- and C-terminal domains of LRRK2 affect synaptic vesicle movement in opposing ways and bind to different proteins.
  • The G2385R variant in the C-terminal domain increases Parkinson's risk by altering protein interactions and synaptic vesicle fusion, potentially leading to impaired vesicular trafficking and disease progression.
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A new and computationally efficient approach is proposed for determining the refractive index of spherical and transparent particles, in addition to their size and 3D position, using digital in-line holography. The method is based on the localization of the maximum intensity position of the photonic jet with respect to the particle center retrieved from the back propagation of recorded holograms. Rigorous electromagnetic calculations and experimental results demonstrate that for liquid-liquid systems and droplets with a radius > 30µm, a refractive index measurement with a resolution inferior to 4 × 10 is achievable, revealing a significant potential for the use of this method to investigate multiphase flows.

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Abnormal Glu release occurs in the spinal cord of SOD1(G93A) mice, a transgenic animal model for human ALS. Here we studied the mechanisms underlying Glu release in spinal cord nerve terminals of SOD1(G93A) mice at a pre-symptomatic disease stage (30days) and found that the basal release of Glu was more elevated in SOD1(G93A) with respect to SOD1 mice, and that the surplus of release relies on synaptic vesicle exocytosis. Exposure to high KCl or ionomycin provoked Ca(2+)-dependent Glu release that was likewise augmented in SOD1(G93A) mice.

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Article Synopsis
  • Heterozygous mutations in PRRT2 are linked to disorders like epilepsy, kinesigenic dyskinesia, and migraines, primarily due to reduced PRRT2 expression.
  • PRRT2 is found at presynaptic terminals, and its silencing causes fewer synapses and more docked synaptic vesicles, disrupting normal neurotransmitter release.
  • PRRT2 is crucial for the final stages of neurotransmitter release by interacting with key synaptic proteins and influencing calcium sensitivity and release probability.
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Proline-rich transmembrane protein 2 (PRRT2) has been identified as the single causative gene for a group of paroxysmal syndromes of infancy, including epilepsy, paroxysmal movement disorders, and migraine. On the basis of topology predictions, PRRT2 has been assigned to the recently characterized family of Dispanins, whose members share the two-transmembrane domain topology with a large N terminus and short C terminus oriented toward the outside of the cell. Because PRRT2 plays a role at the synapse, it is important to confirm the exact orientation of its N and C termini with respect to the plasma membrane to get clues regarding its possible function.

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Background: Lrrk2, a gene linked to Parkinson's disease, encodes a large scaffolding protein with kinase and GTPase activities implicated in vesicle and cytoskeletal-related processes. At the presynaptic site, LRRK2 associates with synaptic vesicles through interaction with a panel of presynaptic proteins.

Results: Here, we show that LRRK2 kinase activity influences the dynamics of synaptic vesicle fusion.

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Synapsins (Syns) are synaptic vesicle-associated phosphoproteins involved in neuronal development and neurotransmitter release. While Syns are implicated in the regulation of brain-derived neurotrophic factor (BDNF)-induced neurotransmitter release, their role in the BDNF developmental effects has not been fully elucidated. By using primary cortical neurons from Syn I knockout (KO) and Syn I/II/III KO mice, we studied the effects of BDNF and nerve growth factor (NGF) on axonal growth.

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Organic Photo Sensor (OPS) technology allows printing on conformable plastic-like substrates complex-shaped, arbitrarily-sized and pre-aligned photosensitive elements. This article reports, to the best of our knowledge, the first investigation to implement this emerging technology for Multi-Angle Light Scattering (MALS) characterization of nano- and microparticle suspensions. Monte Carlo and Lorenz-Mie theory calculations as well as preliminary experimental results on latex suspensions clearly demonstrate the potential of the proposed approach.

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We report the first experimental validation of the Vectorial Complex Ray Model (VCRM) using the scattering patterns of large oblate droplets trapped in an acoustic field. The two principal radii and refractive index of the droplets are retrieved with a minimization method that involves VCRM predictions and experimental light scattering patterns. The latter are recorded in the droplet equatorial plane between the primary rainbow region and the associated hyperbolic-umbilic diffraction catastrophe.

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