Biology subjects

Toffoli, M.

Publications and source records attributed to Toffoli, M..

5 recordsLinked to original sources

bioRxiv2024

Characterization of immunity-inducing rhizobacteria highlights diversity in plant-microbe interactions

The narrow region of soil surrounding roots (rhizosphere) contains an astonishing diversity of microorganisms. Some rhizosphere bacteria can improve plant health and immunity, via direct competition with pathogens or by establishing heightened immunity in aboveground tissues, a phenomenon known as Induced Systemic Resistance (ISR). We screened a bacterial library from agricultural soils to identify strains that, after root treatment, induce immunity in Solanum lycopersicum (tomato) against the fungal pathogen Botrytis cinerea. Here, we report the establishment of a screening method and characterization of a subset of five strains, belonging to the species Bacillus velezensis, Paenibacillus peoriae and Pseudomonas parafulva, that induced systemic resistance in tomato. However interestingly, only two of them triggered canonical ISR in Arabidopsis, indicating plant host specificity and/or alternative modes of actions. Furthermore, some of the strains displayed direct anti-microbial activity. We also found the requirement of the lipid-binding protein DIR1 in ISR establishment, indicating a possible convergence of SAR and ISR signaling. Finally, we found that P. parafulva TP18m, also displayed strong effects on root development. Taken together, we have identified taxonomically diverse immunity-inducing bacteria. Our characterization revealed diverse features, highlighting the complexity of bacteria- host interaction in the rhizosphere. HighlightWe identified taxonomically diverse rhizobacteria that induce systemic resistance in tomato plants to Botrytis after application to the root. These bacteria display diverse modes of action to improve plant health.

plant biology↗

bioRxiv2022

Sex-specific microglial responses to glucocerebrosidase inhibition: relevance to GBA1-linked Parkinson disease

Microglia are heterogenous cells characterized by distinct populations each contributing to specific biological processes in the nervous system, including neuroprotection. To elucidate the impact of sex-specific microglia heterogenicity to the susceptibility of neuronal stress, we analysed the dynamic changes in shape and motility occurring in primary mouse microglia following pro-inflammatory or neurotoxic insults, thus finding sex-specific responses of microglial subpopulations. Male microglia exhibited a pro-inflammatory phenotype, whereas female microglia showed enhanced neuroprotective capabilities associated with the activation of Nrf2 detoxification pathway in neurons. The sex difference in neuroprotective functions is lost by inhibition of glucocerebrosidase, the product of the GBA1 gene, mutations of which are the major risk factor for Parkinsons disease (PD). This finding is consistent with the increased risk of PD observed in female carriers of GBA1 mutation, when compared with wild type population, suggesting a role for microglial functionality in the etiopathogenesis of PD-GBA1.

neuroscience↗

bioRxiv2020

Complement Component 3 expressed by the endometrial ectopic tissue is involved in the endometriotic lesion formation through mast cell activation

The pathophysiology of endometriosis (EM) is an excellent example of immune dysfunction, reminiscent of tumor microenvironment as well. Here, we report that an interplay between C3 and mast cells (MCs) is involved in the pathogenesis of ectopic EM. C3 is at the epicenter of the regulatory feed forward loop, amplifying the inflammatory microenvironment, in which the MCs are protagonists. Thus, C3 can be considered a marker of EM and its local synthesis can promote the engraftment of the endometriotic cysts. We generated a murine model of EM via injection of minced uterine tissue from a donor mouse, into the peritoneum of the recipient mice. The wild type mice showed greater amount of cyst formation in the peritoneum compared to C3 knock-out mice. This study offers an opportunity for novel therapeutic intervention in EM, a difficult to treat gynecological condition. SummaryC3 produced by the endometriotic tissue is involved in the lesion development through mast cell activation

immunology↗

bioRxiv2019

Fine-mapping of SNCA in REM sleep behavior disorder and overt synucleinopathies

ObjectiveREM-sleep behavior disorder (RBD) is a prodromal synucleinopathy, as >80% will eventually convert to overt synucleinopathy. We performed an in-depth analysis of the SNCA locus to identify RBD-specific risk variants.\n\nMethodsFull sequencing and genotyping of SNCA was performed in isolated/idiopathic RBD (iRBD, n=1,076), Parkinsons disease (PD, n=1,013), and dementia with Lewy bodies (DLB, n=415), and in control subjects (n=6,155). A replication cohort from 23andMe of PD patients with probable RBD (pRBD) was also analyzed (cases n=1,782, controls n=131,250). Adjusted logistic regression models and meta-analyses were performed. Effects on conversion rate were analyzed in 432 RBD patients with available data using Kaplan-Meier survival analysis.\n\nResultsA 5-region SNCA variant (rs10005233) was associated with iRBD (OR=1.43, p=1.1E-08), which was replicated in pRBD. This variant is in linkage disequilibrium (LD) with other 5 risk variants across the different synucleinopathies. An independent iRBD-specific suggestive association (rs11732740) was detected at the 3 of SNCA (OR=1.32, p=4.7E-04, not statistically significant after Bonferroni correction). Homozygous carriers of both iRBD-specific SNPs were at highly increased risk for iRBD (OR=5.74, p=2E-06). The known top PD-associated variant (3 variant rs356182) had an opposite direction of effect in iRBD compared to PD.\n\nInterpretationThere is a distinct pattern of association at the SNCA locus in RBD as compared to PD, with an opposite direction of effect at the 3 of SNCA. Several 5 SNCA variants are associated with iRBD and with pRBD in overt synucleinopathies, and may suggest a cognitive component to this region.

genetics↗

bioRxiv2018

Detection of GBA missense mutations and other variants using the Oxford Nanopore MinION

PurposeMutations in GBA cause Gaucher disease when biallelic, and are strong risk factors for Parkinsons disease when heterozygous. GBA analysis is complicated by the nearby pseudogene. We aimed to design and validate a method for sequencing GBA on the Oxford Nanopore MinION.\n\nMethodsWe sequenced an 8.9 kb amplicon from DNA samples of 17 individuals, including patients with Parkinsons and Gaucher disease, on older and current (R9.4) flow cells. These included samples with known mutations, assessed in a blinded fashion on the R9.4 data. We used NanoOK for quality metrics, two different aligners (Graphmap and NGMLR), Nanopolish and Sniffles to call variants, and Whatshap for phasing.\n\nResultsWe detected all known mutations, including the common p.N409S (N370S) and p.L483P (L444P), and three rarer ones, at the correct zygosity, as well as intronic SNPs. In a sample with the complex RecNciI allele, we detected an additional coding mutation, and a 55-base pair deletion. We confirmed compound heterozygosity where relevant. False positives were easily identified.\n\nConclusionThe Oxford Nanopore MinION can detect missense mutations and an exonic deletion in this difficult gene, with the added advantage of phasing and intronic analysis. It can be used as an efficient diagnostic tool.

genetics↗