The potential etiopathogenetic role and diagnostic utility of CD3+ CD56+ regulatory T lymphocytes in Myelodysplastic Syndromes

Serio et al. show a significant reduction of CD3+CD56+ regulatory T cells (TR3-56) in bone marrow (BM) of low-risk myelodysplastic subjects, as compared with the high-risk and the AML group; in addition, the BM frequency of mature granulocytes, a recognised marker of residual effective haematopoiesis, was observed to inversely correlate with TR3-56 in the MDS cohort. Such data are of great interest and confirm and extend, in an independent MDS cohort, the trend-increase of BM TR3-56 from very low/low risk to high/very high risk MDS and the inverse correlation with the cytotoxic T-cell (CTL) activity, likely fostering the escape of leukaemic blasts to immune-surveillance, by us recently described

Metabolic patterns of bacterial communities in aerobic compost teas associated with potential biocontrol of soilborne plant diseases

Aerated compost teas (ACTs) are organic products obtained by forced aeration of composts suspended in liquid phase. These products may be biological control tools alternative to synthetic fungicides, because ACTs contain antagonistic microorganisms. In this study, soilborne disease suppressive ability of seven water ACTs, extracted from five horticultural residue-based composts, from an animal waste anaerobic solid digestate and from a commercial municipal waste compost, was assessed using in vitro and in vivo systems. All the ACTs inhibited in vitro growth of Verticillium dahliae, Fusarium oxysporum f. sp. lycopersici, Rhizoctonia solani, Sclerotinia minor, Sclerotium rolfsii and Botrytis cinerea. Filter or thermal sterilization eliminated in vitro suppression, suggesting that microorganisms play key roles in pathogen inhibition. Drenching applications of raw ACTs have potential to reduced disease symptoms caused by R. solani on savoy cabbage, S. minor on lettuce and S. rolfsii on pepper, improved the biomass production and did not show any sign of phytotoxicity. Both in vitro and in vivo suppressiveness of ACTs may be explained by antagonistic  bacterial communities that provide general suppression activities. The metabolic BIOLOG GN and GP profiles reflected the functional potential of the numerically dominant members of the microbial communities used as inoculum. This study has demonstrated that useful resident microorganisms, including mainly Gram-positive and Gram-negative antagonistic bacteria, are likely to be responsible for biological control activity of ACTs

Bone marrow CD3+ CD56+ regulatory T lymphocytes (TR3 -56 cells) are inversely associated with activation and expansion of bone marrow cytotoxic T cells in IPSS-R very-low/low risk MDS patients

Background Emergence of dysplastic haematopoietic precursor/s, cytopenia and variable leukaemia risk characterise myelodysplastic syndromes (MDS). Impaired immune-regulation, preferentially affecting cytotoxic T cells (CTL), has been largely observed in MDS. Recently, we described the TR3-56 T cell subset, characterised by the co-expression of CD3 and CD56, as a novel immune-regulatory population, able to modulate cytotoxic functions. Here, we address the involvement of TR3-56 cells in MDS pathogenesis/progression. Objectives To analyse the relationship between TR3-56 and CTL activation/expansion in bone marrow (BM) of very-low/low-risk MDS subjects. Methods Peripheral blood and BM specimens, obtained at disease onset in a cohort of 58 subjects, were analysed by immune-fluorescence and flow cytometry, to preserve the complexity of the biological sample. Results We observed that a trend-increase of BM TR3-56 in high/very-high MDS stage, as compared with very-low/low group, associates with a decreased activation of BM resident CTL; significant correlation of TR3-56 with BM blasts has been also revealed. In addition, in very-low/low-risk subjects the TR3-56 amount in BM inversely correlates with the presence of activated BM CTL showing a skewed V beta T-cell repertoire. Conclusions These data add TR3-56 to the immune-regulatory network involved in MDS pathogenesis/progression. Better knowledge of the immune-mediated processes associated with the disease might improve MDS clinical management

Managing Rhizoctonia Damping-Off of Rocket (Eruca sativa) Seedlings by Drench Application of Bioactive Potato Leaf Phytochemical Extracts

Plants produce a huge array of secondary metabolites that play a key role in defense mechanisms against detrimental microorganisms and herbivores, and represent a suitable alternative to synthetic fungicides in sustainable agriculture. In this work, twelve crude hydroethanolic extracts derived from leaves of different potato cultivars were chemically characterized by LC/MS and their antioxidant properties were investigated in vitro. Furthermore, the biological activity against the fungal pathogen Rhizoctonia solani was evaluated both in vitro and in vivo. Extracts showed the ability to inhibit R. solani growth in vitro and significantly reduced damping-off incidence in in vivo experiments. Furthermore, R. solani mycelia exposed to the extracts showed an altered morphology (low translucency, irregular silhouette, and cytoplasmatic content coagulation) compared to the untreated control in light microscopy examination. Principal component analysis conducted on identified chemical compounds highlighted significant metabolic variations across the different extracts. In particular, those that inhibited most of the growth of the pathogen were found to be enriched in α-chaconine or α-solanine content, indicating that their biological activity is affected by the abundance of these metabolites. These results clearly indicated that plant-derived compounds represent a suitable alternative to chemicals and could lead to the development of new formulates for sustainable control of plant diseases

phytophthora cinnamomi involved in the decline of holm oak quercus ilex stands in southern italy

n/

Polyketide synthases of Diaporthe helianthi and involvement of DhPKS1 in virulence on sunflower

Background The early phases of Diaporthe helianthi pathogenesis on sunflower are characterized by the production of phytotoxins that may play a role in host colonisation. In previous studies, phytotoxins of a polyketidic nature were isolated and purified from culture filtrates of virulent strains of D. helianthi isolated from sunflower. A highly aggressive isolate (7/96) from France contained a gene fragment of a putative nonaketide synthase (lovB) which was conserved in a virulent D. helianthi population. Results In order to investigate the role of polyketide synthases in D. helianthi 7/96, a draft genome of this isolate was examined. We were able to find and phylogenetically analyse 40 genes putatively coding for polyketide synthases (PKSs). Analysis of their domains revealed that most PKS genes of D. helianthi are reducing PKSs, whereas only eight lacked reducing domains. Most of the identified PKSs have orthologs shown to be virulence factors or genetic determinants for toxin production in other pathogenic fungi. One of the genes (DhPKS1) corresponded to the previously cloned D. helianthi lovB gene fragment and clustered with a nonribosomal peptide synthetase (NRPS) -PKS hybrid/lovastatin nonaketide like A. nidulans LovB. We used DhPKS1 as a case study and carried out its disruption through Agrobacterium-mediated transformation in the isolate 7/96. D. helianthi DhPKS1 deleted mutants were less virulent to sunflower compared to the wild type, indicating a role for this gene in the pathogenesis of the fungus. Conclusion The PKS sequences analysed and reported here constitute a new genomic resource that will be useful for further research on the biology, ecology and evolution of D. helianthi and generally of fungal plant pathogens

Adaptive and Innate Cytotoxic Effectors in Chronic Lymphocytic Leukaemia (CLL) Subjects with Stable Disease

Chronic lymphocytic leukaemia (CLL) is characterised by the expansion of a neoplastic mature B cell clone. CLL clinical outcome is very heterogeneous, with some subjects never requiring therapy and some showing an aggressive disease. Genetic and epigenetic alterations and pro-inflammatory microenvironment influence CLL progression and prognosis. The involvement of immune-mediated mechanisms in CLL control needs to be investigated. We analyse the activation profile of innate and adaptive cytotoxic immune effectors in a cohort of 26 CLL patients with stable disease, as key elements for immune-mediated control of cancer progression. We observed an increase in CD54 expression and interferon (IFN)-γ production by cytotoxic T cells (CTL). CTL ability to recognise tumour-targets depends on human leukocyte antigens (HLA)-class I expression. We observed a decreased expression of HLA-A and HLA-BC on B cells of CLL subjects, associated with a significant reduction in intracellular calnexin that is relevant for HLA surface expression. Natural killer (NK) cells and CTL from CLL subjects show an increased expression of the activating receptor KIR2DS2 and a reduction of 3DL1 and NKG2A inhibiting molecules. Therefore, an activation profile characterises CTL and NK cells of CLL subjects with stable disease. This profile is conceivable with the functional involvement of cytotoxic effectors in CLL control

A randomized clinical trial of lithium in multiple system atrophy.

The aim of our study was to test the safety and tolerability of lithium in multiple system atrophy (MSA). The study was randomized, placebo-controlled, and double-blind. The primary endpoint of the study was safety and tolerability. An interim analysis, performed 1 year after the first patient was randomized, showed a higher proportion of trial abandon (P < 0.01) and a higher number of adverse events (P < 0.02) in the lithium group. The trial was stopped by the Data Monitoring Committee. Overall, lithium was not well tolerated, and we do not encourage future studies with lithium in MSA patients