Biology subjects

De Giorgi, F.

Publications and source records attributed to De Giorgi, F..

6 recordsLinked to original sources

bioRxiv2024

Selection strengthens the relationship between plant diversity and the metabolic profile of Plantago lanceolata

O_LIPlants growing in biodiverse communities often increase productivity, but how plant diversity impacts the metabolome and the underlying ecological and evolutionary processes remains unclear. This study investigated how plant species diversity and selection for growing in different diversity environments affects the leaf metabolome of Plantago lanceolata. C_LIO_LIWe compared the metabolites of plants derived from those that had been selected in the "Jena Experiment" for 17 years in plant communities with differing plant diversity with the metabolites of naive plants not subjected to this selection. The metabolic profiles of selected P. lanceolata phytometers were also compared after growing in experimental environments varying in plant species richness, soil history, and community plant history. C_LIO_LIResults showed volatile compound diversity in P. lanceolata decreased with plant species richness, primarily due to phenotypic plasticity rather than selection. Soil history further strengthened this relationship. Conversely, non-volatile compound diversity increased with plant species richness, but only in phytometers subjected diversity-driven selection. These effects were more pronounced when plants shared soil-plant history with their community. C_LIO_LIIn summary, our study revealed that both plastic and adaptative responses shape the metabolome of P. lanceolata in relation to plant diversity with these effects becoming stronger as plant and soil communities mature. C_LI

ecology↗

bioRxiv2024

Selection shapes plant performance in a grassland biodiversity experiment

O_LIThe increasing strength of positive biodiversity effects on plant community productivity in long-term biodiversity experiments has been shown to be related to mixed responses at species level. However, it is still not well understood if the varying environments in plant communities with different diversity also exert different selection pressures to which plant species respond adaptively or whether their responses are mainly due to phenotypic plasticity. C_LIO_LIWe conducted a transplant experiment for nine plant species in a 17-year-old grassland biodiversity experiment (Jena Experiment). We used offspring of plants selected in communities with different diversity or from plants which did not experience selection in the experiment (naive). In a Community History Experiment, offspring of selected plants were planted in three test environments: their original plant communities with original soil, newly assembled plant communities with original soil, and newly assembled plant communities with new soil. Additionally, in a Selection Experiment we compared the performance of selected plants grown in their original environment to the performance of naive plants grown in the same environment. C_LIO_LIIn all test environments, increasing species richness was on average associated with a decrease in plant individual biomass, reproductive output, relative growth rate, plant height, leaf greenness, and leaf nitrogen (N) concentration and an increase in SLA. C_LIO_LIIn the Community History Experiment survival was lower, while plant height, SLA, leaf N and C concentrations were highest in the test environment without plant and soil history. In high-diversity communities, individuals produced more biomass, grew taller and had higher leaf greenness in the original environment than in the other test environments. C_LIO_LIIn the Selection Experiment selected plants had weaker decline in their biomass, taller stature, and higher leaf C and N concentrations than C_LIO_LInaive plants with increasing species richness. C_LIO_LIIn both experiments, we found evidences of adaptive phenotypic responses. Specifically, in high-diversity communities, selected plants showed higher performance in their original environment, largely explained by plant community history and positive plant-soil feedbacks established over time. C_LIO_LISynthesis: Our study highlights the important role of eco-evolutionary feedbacks of species diversity, which affect plant performance over time. C_LI

ecology↗

bioRxiv2024

1.94 Angstrom structure of synthetic alpha-synuclein fibrils seeding MSA neuropathology

Summary ParagraphMultiple system atrophy (MSA) is a rapidly progressive neurodegenerative disease of unknown cause, typically affecting individuals aged 50-60 and leading to death within a decade1-3. It is characterized by glial cytoplasmic inclusions (GCIs) composed of fibrillar alpha-synuclein (aSyn)4-8, whose formation shows parallels with prion propagation9,10. While fibrils extracted from MSA brains have been structurally characterized11, their ability to replicate in a "protein-only" manner has been questioned12, and their capacity to induce GCIs in vivo remains unexplored. By contrast, the synthetic fibril strain 1B13,14, assembled from recombinant human aSyn, self-replicates in vitro and induces GCIs in mice15 - suggesting direct relevance to MSA - but awaited scrutiny at an atomic scale. Here, we report high-resolution structural analyses of 1B fibrils and of fibrils extracted from diseased mice injected with 1B that developed GCIs (1BP). We show in vivo that conformational templating enables fibril strain replication, resulting in MSA-like inclusion pathology. Remarkably, the structures of 1B and 1BP are highly similar and mimic the fold of aSyn observed in one protofilament of fibrils isolated from MSA patients11. Moreover, reinjection of crude mouse brain homogenates containing 1BP into new mice reproduces the same MSA-like pathology induced by the parent synthetic seed 1B. Our findings identify 1B as a synthetic pathogen capable of self-replication in vivo and reveal structural features of 1B/1BP that may underlie MSA pathology, offering insights for therapeutic strategies.

neuroscience↗

bioRxiv2021

Similar neuronal imprint and absence of cross-seeded partner fibrils in α-synuclein aggregates from MSA and Parkinson's disease brains

Aggregated alpha-synuclein (-syn) is a principal constituent of Lewy bodies (LBs) and glial cytoplasmic inclusions (GCIs) observed respectively inside neurons in Parkinsons disease (PD) and oligodendrocytes in multiple system atrophy (MSA). Yet, the cellular origin, the pathophysiological role, and the mechanism of formation of these inclusions bodies (IBs) remain to be elucidated. It has recently been proposed that -syn IBs eventually cause the demise of the host cell by virtue of the cumulative sequestration of partner proteins and organelles. In particular, the hypothesis of a local cross-seeding of other fibrillization-prone proteins like tau or TDP-43 has also been put forward. We submitted sarkosyl-insoluble extracts of post-mortem brain tissue from PD, MSA and control subjects to a comparative proteomic analysis to address these points. Our studies indicate that: i) -syn is by far the most enriched protein in PD and MSA extracts compared to controls; ii) PD and MSA extracts share a striking overlap of their sarkosyl-insoluble proteomes, consisting of a vast majority of mitochondrial and neuronal synaptic proteins, and (iii) other fibrillization-prone protein candidates possibly cross-seeded by -syn are neither found in PD nor MSA extracts. Thus, our results (i) support the idea that pre-assembled building blocks originating in neurons serve to the formation of GCIs in MSA, (ii) show no sign of amyloid cross-seeding in either synucleinopathy, and (iii) point to the sequestration of mitochondria and of neuronal synaptic components in both LBs and GCIs.

neuroscience↗

bioRxiv2020

Emergence of stealth polymorphs that escape α-synuclein amyloid monitoring, take over and acutely spread in neurons

The conformational strain diversity characterizing -synuclein (-syn) amyloid fibrils is possibly at the origin of the different clinical presentations of synucleinopathies. Experimentally, various -syn fibril polymorphs have been obtained from distinct fibrillization conditions by altering the medium constituents and were selected by amyloid monitoring using the probe Thioflavin T (ThT). We report here that besides classical ThT positive products, fibrillization in saline simultaneously gives rise to competing fibril polymorphs that are invisible to ThT (stealth polymorphs), and that can take over. Due to competition, spontaneous generation of such stealth polymorphs bears on the apparent fibrillization kinetics and on the final plateau values. Their emergence has thus been ignored so far or mistaken for fibrillization inhibitions/failures. Compared to their ThT-positive counterparts, and as judged from their chemical shift resonances fingerprint, these new stealth polymorphs present a yet undescribed atomic organization and show an exacerbated propensity (approx. 20-fold) towards self-replication in cortical neurons. They also trigger a long distance synucleinopathic spread along nigro-striatal projections in vivo. In order to rapidly screen fibrillization products for the presence of such stealth polymorphs, we designed a simple multiplexed assay that can be easily and rapidly operated. This assay allows us to demonstrate the sustainability of the conformational replication of these novel and particularly invasive strains. It should also be of help to avoid erroneous upstream interpretations of fibrillization rates based on sole ThT, and to expedite further structural and functional characterization of stealth amyloid assemblies. One Sentence Summarystealth -synuclein fibrils take over

neuroscience↗

bioRxiv2019

A cooperative network of molecular "hot spots" highlights the complexity of LH3 collagen glycosyltransferase activities

Hydroxylysine glycosylations are collagen-specific post-translational modifications essential for maturation and homeostasis of fibrillar as well as non-fibrillar collagen molecules. Lysyl hydroxylase 3 (LH3) is the only human enzyme capable of performing two chemically-distinct collagen glycosyltransferase reactions using the same catalytic site: inverting beta-1,O-galactosylation of hydroxylysines and retaining alpha-1,2-glycosylation of galactosyl hydroxylysines. Here, we used structure-based mutagenesis to show that both glycosyltransferase activities are strongly dependent on a broad cooperative network of amino acid side chains which includes the first-shell environment of the glycosyltransferase catalytic site and shares features with both retaining and inverting enzymes. We identified critical "hot spots" leading to selective loss of inverting activity without affecting the retaining reaction. Finally, we present molecular structures of LH3 in complex with UDP-sugar analogs which provide the first structural templates for LH3 glycosyltransferase inhibitor development. Collectively, our data provide a comprehensive overview of the complex network of shapes, charges and interactions that enable LH3 glycosyltransferase activities, expanding the molecular framework for the manipulation of glycosyltransferase functions in biomedical and biotechnological applications.

biochemistry↗