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Giorgi, A.

Publications and source records attributed to Giorgi, A..

5 recordsLinked to original sources

Biophysical characterization of novel biomarkers and bioaffinity reagents (NanoMIPs): on the road for a low-cost diagnostic test for intestinal schistosomiasis

Schistosoma mansoni is a vector-borne intestinal parasite, endemic in [~]70 tropical countries. Most of the World Health Organization interventions are based on mass drug administration (MDA) and sanitation. Since the parasite does not induce permanent immunity, reinfection rate is high, inducing scheduling of several MDA campaigns. To follow up after treatment and avoid blind MDA, providing a new rapid and cheap diagnostic test is needed, since the most used method is fifty years-old, lacks sensitivity and efficiency. Venom Allergen-Like proteins (SmVALs) have been previously identified as secreted/excreted proteins and potential biomarkers. Here we present the biophysical characterization of SmVAL11 and SmVAL13, their recognition by both specific antibodies and molecularly imprinted polymers (nanoMIPs), an easy-to-standardize alternative. The specific antibodies showed no cross-reactivity, while initial characterization of the nanoMIPs indicates a promising level of selectivity, establishing them as a reliable, cost-effective alternative. Therefore, our results are promising for the future development of a new cheap diagnostic test of intestinal schistosomiasis.

biophysics↗

Pathogen priming reveals host immune training and microbiome conditioning in corals

UNSTRUCTURED ABSTRACTIn several species, vaccine-like approaches, where hosts are primed through controlled pathogen exposure, have proven effective in enhancing responses to subsequent infections. This principle remains unexplored in corals. Here, we demonstrate that chronic exposure to non-lethal concentrations of live or inactivated Vibrio coralliilyticus primes the coral holobiont to counter subsequent infections under heat stress. Non-primed corals experienced greater heat stress pathogen-driven bleaching and a significant decline in their photosynthetic efficiency compared to primed samples. These results were linked to microbiome conditioning and host gene expression modulation, including a layered, fine-tuned immune and cellular response to microbial invasion. This proof-of-concept challenges strictly innate immune responses in corals and positions immune priming and microbiome conditioning as integrated mechanisms of coral holobiont resilience. Together, these findings can contribute to redefine coral immunity concepts and lay the groundwork for developing new microbiome-based strategies to enhance coral health for reef conservation under climate change. LAY SUMMARYCoral reefs are increasingly threatened by rising seawater temperatures and disease. Unlike vertebrates, corals do not possess a classical adaptive immune system, so they have been thought to rely only on innate defenses. However, our study shows that corals may be more capable than previously believed. We demonstrate that exposing corals to non-lethal doses of a widespread bacterial pathogen can train them to better withstand subsequent infections under heat stress. Corals that were not pre-exposed suffered more pathogen caused bleaching and showed a stronger decline in physiological performance, while those that were primed were more resilient. This improved resistance appears to come from two coordinated processes. First, the corals associated bacterial community shifted in a way that seems to help protect the host. Second, the coral itself adjusted its gene expression, mounting a more effective and controlled response to infection. These findings suggest that corals may be able to remember past exposures and respond more effectively to future infections, even without a traditional adaptive immune system, providing a foundation for developing new strategies to support coral resilience.

microbiology↗

Primitive RNA-catalysis with guanine-rich oligonucleotide sequences - the case of a (GGC)3 nonamer

A cornerstone of molecular evolution leading to the emergence of life on our planet is associated with appearance of the first catalytic RNA molecules. A question remains regarding the nature of the simplest catalytic centers that could mediate the chemistry needed for RNA-catalysis. In the current paper we provide a new example supporting our previously suggested model proposing that transiently formed open loop geometries could serve as temporary catalytic sites in the most ancient short oligonucleotides. In particular, using two independent detection techniques, PAGE and MALDI-ToF analysis, we show that prolonged thermal treatment of a 5-phosphorylated (GGC)3 sequence at weakly acidic or neutral pH in the presence of tris(hydroxymethyl)aminomethane, produces a species characterized by a (GGC)3G stoichiometry, which is compatible with the cleavage-terminal recombination chemistry suggested in our previous studies. Our new findings are complemented by microsecond-scale molecular dynamics simulations, showing that (GGC)3 dimers readily sample transient potentially catalytic geometries compatible with the experimentally observed terminal recombination chemistry.

biochemistry↗

Brainwide Mapping Of Endogenous Serotonergic Transmission Via Chemogenetic-fMRI

Serotonergic transmission affects behaviours and neuro-physiological functions via the orchestrated recruitment of distributed neural systems. It is however unclear whether serotonins modulatory effect entails a global regulation of brainwide neural activity, or is relayed and encoded by a set of primary functional substrates. Here we combine DREADD-based chemogenetics and mouse fMRI, an approach we term \"chemo-fMRI\", to causally probe the brainwide substrates modulated by phasic serotonergic activity. We describe the generation of a conditional knock-in mouse line that, crossed with serotonin-specific Cre-recombinase mice, allowed us to remotely stimulate serotonergic neurons during fMRI scans. We show that chemogenetic stimulation of the serotonin system does not affect global brain activity, but results in region-specific activation of a set of primary target regions encompassing parieto-cortical, hippocampal, and midbrain structures, as well as ventro-striatal components of the mesolimbic reward systems. Many of the activated regions also exhibit increased c-Fos immunostaining upon chemogenetic stimulation in freely-behaving mice, corroborating a neural origin for the observed functional signals. These results identify a set of regional substrates that act as primary functional targets of endogenous serotonergic stimulation, and establish causation between phasic activation of serotonergic neurons and regional fMRI signals. They further highlight a functional cross-talk between serotonin and mesolimbic dopamine systems hence providing a novel framework for understanding serotonin dependent functions and interpreting data obtained from human fMRI studies of serotonin modulating agents.

neuroscience↗

Serotonin Buffers Hippocampal Neuroplasticity And Emotional Behavior

Adaptation to environmental insults is an evolutionary mechanism essential for survival. The hippocampus participates in controlling adaptive responses to stress and emotional state through the modulation of neuroplasticity events, which are dysregulated in stress-related neuropsychiatric disorders. The neurotransmitter serotonin (5-HT) has been proposed as a pivotal player in hippocampal neuroplasticity in both normal and neuropsychiatric conditions though its role remains still poorly understood. Here, we investigated the impact of 5-HT deficiency on hippocampal activity combining RNA-seq, in vivo neuroimaging, neuroanatomical, biochemical and behavioral experiments on 5-HT depleted mice. We unveil that serotonin is required for appropriate activation of neuroplasticity adaptive mechanisms to environmental insults. Bidirectional deregulation of these programs in serotonin depleted mice is associated with opposite behavioral traits that model core symptoms of bipolar disorder. These findings delineate a previously unreported buffering role of 5-HT in instructing hippocampal activity and emotional responses to environmental demands.

neuroscience↗