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Hereditary dyserythropoietic anemias, or congenital dyserythropoietic anemias (CDAs), are rare disorders disrupting normal erythroid lineage development, resulting in ineffective erythropoiesis and monolinear cytopenia. CDAs include three main types (I, II, III), transcription‐factor‐related forms, and syndromic forms. The widespread use of next‐generation sequencing in the last decade has unveiled novel causative genes and unexpected genotype–phenotype correlations. The discovery of the genetic defects underlying the CDAs not only facilitates accurate diagnosis but also enhances understanding of CDA pathophysiology. Notable advancements include identifying a hepatic‐specific role of the SEC23B loss‐of‐function in iron metabolism dysregulation in CDA II, deepening CDIN1 dysfunction during erythroid differentiation, and uncovering a recessive CDA III form associated with RACGAP1 variants. Current treatments primarily rely on supportive measures tailored to disease severity and clinical features. Comparative studies with pyruvate kinase deficiency have illuminated new therapeutic avenues by elucidating iron dyshomeostasis and dyserythropoiesis mechanisms. We herein discuss recent progress in diagnostic methodologies, novel gene discoveries, and enhanced comprehension of CDA pathogenesis and molecular genetics. [ABSTRACT FROM AUTHOR]

The use of biostimulants and biofilms in agriculture is constantly increasing, as they may support plant growth and productivity by improving nutrient absorption, increasing stress resilience and providing sustainable alternatives to chemical management practices. In this work, two commercial products based on Trichoderma afroharzianum strain T22 (Trianum P®) and a seaweed extract from Ascophyllum nodosum (Phylgreen®) were tested on industrial tomato plants (Solanum lycopersicum var. Heinz 5108F1) in a field experiment. The effects of single and combined applications of microbial and plant biostimulants on plants grown on two different biodegradable mulch films were evaluated in terms of changes in the metabolic profiles of leaves and berries. Untargeted metabolomics analysis by LC-MS Q-TOF revealed the presence of several significantly accumulated compounds, depending on the biostimulant treatment, the mulch biofilm and the tissue examined. Among the differential compounds identified, some metabolites, belonging to alkaloids, flavonoids and their derivatives, were more abundant in tomato berries and leaves upon application of Trichoderma-based product. Interestingly, the biostimulants, when applied alone, similarly affected the plant metabolome compared to control or combined treatments, while significant differences were observed according to the mulch biofilm applied. [ABSTRACT FROM AUTHOR]

Nine isolates of Trichoderma were obtained from the diverse phases of compost preparation and the production of different commercial varieties of oyster mushrooms Pleurotus spp. with the apparent presence of green mould disease. The isolates were morphologically and genetically characterized. Molecular fingerprinting indicated that the isolates belonged to the species T. pleuroticola and T. harzianum. In order to identify control measures, changes in temperature, pH, and application of fungicides were tested on the present isolates, using known Trichoderma biocontrol strains as a reference. Fungicide effects on the growth of Pleurotus isolates were also assessed. The optimal growth temperatures were 25 °C for Trichoderma isolates and 28 °C for Pleurotus isolates, and Trichoderma always grew faster than Pleurotus. In particular, a reduction of about 30% was recorded for some of the Trichoderma isolates when comparing the colony growth at 25 and 28 °C. Trichoderma isolates developed well within a wide pH range, with the best growth occurring between pH 5 and 7, whereas Pleurotus preferred more alkaline conditions (pH 8 to 9). Prochloraz and metrafenone were found to inhibit Trichoderma growth with different dose responses that did not affect the growth of Pleurotus spp. In particular, metrafenone was the most effective active ingredient that inhibited the majority of the Trichoderma isolates (1–25% growth reduction). [ABSTRACT FROM AUTHOR]

Tomato is a great source of bioactive compounds, is important for human health, and is cultivated worldwide. However, the high inputs required for its cultivation must be sustainably managed in order to limit yield losses, thus obtaining high-quality and environmentally friendly production. In this perspective, we compared four biostimulant treatments, i.e., Ascophyllum nodosum extract—Bio; microbial biostimulant containing the micro-organism Trichoderma afroharzianum—Mic; a combination of both—M-B; not treated—Control) and three mulch treatments (biodegradable film Ecovio—ECO; biodegradable film MaterBi®—NOV; bare soil—BS) and evaluated their effects on yield and quality traits in processing tomato. Both biodegradable films elicited a 27.0% yield increase compared to plants grown on bare soil, and biostimulants determined a 23.7% increase over the Control, with the best performance recorded for M-B (+24.8%). Biodegradable MaterBi® film (NOV) was associated with higher total soluble solids (TSS) and firmness values (average of 4.9 °Brix and 1.30 kg cm−2, respectively), even if a significant effect of biostimulants was observed only for the second element. Carotenoid content was higher in non-treated plants grown on bare soil as well as hydrophilic antioxidant activity (AA), but in this case, no differences between biostimulant treatments were recorded. The lipophilic AA in NOV-treated plants was about six and four times higher than observed in BS and ECO treatments, respectively; NOV also caused a 38.7% increase in ascorbic acid content over the Control but was not different from ECO. All biostimulant treatments elicited a 30% increase in phenol content compared to Control plants. Our findings highlight that microbial biostimulants based on A. nodosum extract and T. afroharzianum (both applied singularly and combined) can be considered a sustainable tool for increasing yield and improve some quality traits of processing tomato; in addition, we also confirmed the capability of biodegradable mulches, in particular, MaterBi®, to enhance the agronomic performance of tomato. [ABSTRACT FROM AUTHOR]

Background: Next-generation sequencing-based genetic testing represents a great opportunity to identify hereditary predispositions to specific pathological conditions and to promptly implement health surveillance or therapeutic protocols in case of disease. The term secondary finding refers to the active search for causative variants in genes associated with medically actionable conditions. Methods: We evaluated 59 medically actionable ACMG genes using a targeted in silico analysis of clinical exome sequencing performed in 383 consecutive individuals referred to our Medical Genetics Unit. A three-tier classification system of SFs for assessing their clinical impact and supporting a decisionmaking process for reporting was established. Results: We identified SFs with high/moderate evidence of pathogenicity in 7.0% (27/383) of analyzed subjects. Among these, 12/27 (44.4%) were carriers of a high-risk recessive disease allele. The most represented disease domains were cancer predisposition (33.3%), cardiac disorders (16.7%), and familial hypercholesterolemia (12.5%). Conclusion: Although still debated, ensuring during NGS-based genetic testing an opportunistic screening might be valuable for personal and familial early management and surveillance of medically actionable disorders, the individual's reproductive choices, and the prevalence assessment of underestimated hereditary genetic diseases. [ABSTRACT FROM AUTHOR]

Environmental concerns raised by synthetic nematicides are encouraging integrated management strategies based on their combination with non-chemical control tools, such as biocontrol agents and/or organic amendments. In this study, the combination of the fumigant 1,3-dichloropropene (1,3-D) with a commercial formulation of the biocontrol agent Trichoderma harzianum (TH) and an organic fertilizer (OF) was investigated in two consecutive tomato crops for its effect on the root-knot nematode Meloidogyne incognita and plant growth and yield. The application of 1,3-D was only performed on the first crop, while TH and OF were provided to both crops. Almost all treatments significantly reduced nematode infestation in both crops, though the greatest nematicidal effect was caused by a combination of the three products. The treatment with 1,3-D limited its nematicidal efficacy to the first crop only. Fumigant integration with TH and OF also resulted in the greatest increases of plant growth and yield. Therefore, the integrated management of root-knot nematodes with a soil fumigant, a bionematicide as T. harzianum and a source of organic matter demonstrated effective nematode suppression though limiting the number of chemical applications. [ABSTRACT FROM AUTHOR]

The contamination of agricultural products with mycotoxins causes risks to animal and human health and severe economic losses. Mycotoxicoses can be reduced by preventing fungal infection using chemical and biological approaches. The chemical strategies can release toxic molecules; therefore, strategies for biological control are being evaluated, such as using nontoxic fungi and their metabolites. This work evaluated the effect of exoenzymes produced by the beneficial fungus Trichoderma afroharzianum strain T22 in degrading Aflatoxin B1 (AFB1) and Ochratoxin A (OTA). The ability of Trichoderma to produce hydrolases was stimulated by using different inducing substrates. The highest AFB1 and OTA degradation activity was obtained using a medium containing lyophilized mushrooms and crude fiber. The T. afroharzianum T22's ability to reduce mycotoxins may be attributed to peroxidase enzymes. This study showed that T.afroharzianum strain T22 or its peroxidase supplementation could represent a sustainable strategy for the degradation of AFB1 and OTA in feed and food products. [ABSTRACT FROM AUTHOR]

Treating ruminant feeds with exogenous fibrolytic enzymes may potentially increase forage cell wall degradability and thus feed efficiency. In nature, fungi biosynthesize lignocellulolytic enzymes that can break down lignocellulosic material into its sugar components, thereby providing ready fermentable substrates. This work showed the in vitro fibrolytic activity of three Trichoderma strains (T. atroviride strain P1, T. afroharzianum strain T22, T. reesei strain T67). Total protein concentration and enzymatic (e.g., glucanase, cellulase, and xylanase) activities were determined in fungal culture filtrates after 7 and 14 days of growth on different fiber-based media. The enzymatic mixtures produced by Trichoderma spp. showed the highest concentration of fibrolytic enzymes and were added to industrial feed to test their ability to hydrolyze insoluble fibers. The supplementation of industrial feeds containing medium-fiber or low-fiber concentrates with T22 enzymes produced in the presence of lyophilized mushrooms and durum wheat fiber reduced hemicellulose concentration up to 33% and 24%, respectively. These results may offer novel opportunities to develop livestock feeds with improved fiber digestibility. [ABSTRACT FROM AUTHOR]

Effects of Microbial Metabolites on Plant-Microbe Interactions Greater understanding about the effects induced by microbial metabolites on the host plant or by the host plant on the metabolism of the associated microbes could ultimately lead to the development of new crop protection bio-formulations for improving crop quality and yields. Forty-eight hours after inoculation, I Trichoderma i induced a greater expression of defense-related genes than the calcium nitrate application, that also down-regulated expression of genes involved in plant growth and development processes. Keywords: microbial community; microbiomes; plant protection products; plant-microbe interactions; volatilome; proteome; metabolome; transcriptome EN microbial community microbiomes plant protection products plant-microbe interactions volatilome proteome metabolome transcriptome 1 5 5 01/24/22 20220118 NES 220118 The future scenario in the agricultural sector, challenged by regulatory pressure, public concern and environmental issues, continues to motivate the development of alternative methods to chemicals for applications as fertilizers and pesticides (Martin, [11]). Microbial community, microbiomes, plant protection products, plant-microbe interactions, volatilome, proteome, metabolome, transcriptome. [Extracted from the article]

Endophytic fungi have several well-established beneficial effects on plant health and growth, and are a huge source of bioactive compounds. The endophyte Drechslera sp. strain 678, isolated from the roots of an Australian native grass Neurachne alopecuroidea, demonstrated efficacy against four plant pathogens (Pythium ultimum, Rhizoctonia solani, Botrytis cinerea, Alternaria alternata). In addition, strain 678 was capable of degrading a common additive used in gasoline, known as methyl tertiary-butyl ether (MtBE). Thus, the organic extracts obtained from the culture filtrate of strain 678 were studied. Metabolomic analysis revealed the presence of two major bioactive metabolites, monocerin and an alkynyl substituted epoxycyclohexenone derivative, which showed good antifungal activity. The Drechslera sp. strain 678 and its compounds show promise for applications in biocontrol and bioremediation activities in agriculture or as a remediation option for MtBE contamination in soil. [ABSTRACT FROM AUTHOR]

Beneficial fungal strains of the genus Trichoderma are used as biofungicides and plant growth promoters. Trichoderma strains promote the activation of plant defense mechanisms of action, including the production of phenolic metabolites. In this work, we analyzed the effects of selected Trichoderma strains (T. asperellum KV906, T. virens GV41, and T. harzianum strains TH1, M10, and T22) and their metabolites (harzianic acid and 6-pentyl-α-pyrone) on drupes of young olive trees (4-year-old) cv. Carolea. This study used the untargeted analysis of drupe metabolome, carried out by LC–MS Q-TOF, to evaluate the phenolics profiles and target metabolomics approach to detect oleuropein and luteolin. The untargeted approach showed significant differences in the number and type of phenolic compounds in olive drupes after Trichoderma applications (by root dipping and drench soil irrigation method) compared to control. The levels of oleuropein (secoiridoid) and luteolin (flavonoid) varied according to the strain or metabolite applied, and in some cases, were less abundant in treated plants than in the control. In general, flavonoids' levels were influenced more than secoiridoid production. The dissimilar aptitudes of the biological treatments could depend on the selective competence to cooperate with the enzymes involved in producing the secondary metabolites to defend plants by environmental stresses. Our results suggest that using selected fungi of the genus Trichoderma and their metabolites could contribute to selecting the nutraceutical properties of the olive drupe. The use of the metabolites would bring further advantages linked to the dosage in culture and storage. [ABSTRACT FROM AUTHOR]

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The hereditary anemias are a relatively heterogeneous set of disorders that can show wide clinical and genetic heterogeneity, which often hampers correct clinical diagnosis. The classical diagnostic workflow for these conditions generally used to start with analysis of the family and personal histories, followed by biochemical and morphological evaluations, and ending with genetic testing. However, the diagnostic framework has changed more recently, and genetic testing is now a suitable approach for differential diagnosis of these patients. There are several approaches to this genetic testing, the choice of which depends on phenotyping, genetic heterogeneity, and gene size. For patients who show complete phenotyping, single-gene testing remains recommended. However, genetic analysis now includes next-generation sequencing, which is generally based on custom-designed targeting panels and whole-exome sequencing. The use of next-generation sequencing also allows the identification of new causative genes, and of polygenic conditions and genetic factors that modify disease severity of hereditary anemias. In the research field, whole-genome sequencing is useful for the identification of non-coding causative mutations, which might account for the disruption of transcriptional factor occupancy sites and cis- regulatory elements. Moreover, advances in high-throughput sequencing techniques have now resulted in the identification of genome-wide profiling of the chromatin structures known as the topologically associating domains. These represent a recurrent disease mechanism that exposes genes to inappropriate regulatory elements, causing errors in gene expression. This review focuses on the challenges of diagnosis and research into hereditary anemias, with indications of both the advantages and disadvantages. Finally, we consider the future perspectives for the use of next-generation sequencing technologies in this era of precision medicine. [ABSTRACT FROM AUTHOR]

Biocontrol fungal strains of the genus Trichoderma can antagonize numerous plant pathogens and promote plant growth using different mechanisms of action, including the production of secondary metabolites (SMs). In this work we analyzed the effects of repeated applications of selected Trichoderma strains or SMs on young olive trees on the stimulation of plant growth and on the development of olive leaf spot disease caused by Fusicladium oleagineum. In addition, metabolomic analyses and gene expression profiles of olive leaves were carried out by LC--MS Q-TOF and real-time RT-PCR, respectively. A total of 104 phenolic compounds were detected from olive leave extracts and 20 were putatively identified. Targeted and untargeted approaches revealed significant differences in both the number and type of phenolic compounds accumulated in olive leaves after Trichoderma applications, as compared to water-treated plants. Different secoiridoids were less abundant in treated plants than in controls, while the accumulation of flavonoids (including luteolin and apigenin derivatives) increased following the application of specific Trichoderma strain. The induction of defense-related genes, and of genes involved in the synthesis of the secoiridoid oleuropein, was also analyzed and revealed a significant variation of gene expression according to the strain or metabolite applied. [ABSTRACT FROM AUTHOR]

Many Trichoderma spp. are successful plant beneficial microbial inoculants due to their ability to act as biocontrol agents with direct antagonistic activities to phytopathogens, and as biostimulants capable of promoting plant growth. This work investigated the effects of treatments with three selected Trichoderma strains (T22, TH1, and GV41) to strawberry plants on the productivity, metabolites and proteome of the formed fruits. Trichoderma applications stimulated plant growth, increased strawberry fruit yield, and favored selective accumulation of anthocyanins and other antioxidants in red ripened fruits. Proteomic analysis of fruits harvested from the plants previously treated with Trichoderma demonstrated that the microbial inoculants highly affected the representation of proteins associated with responses to stress/external stimuli, nutrient uptake, protein metabolism, carbon/energy metabolism and secondary metabolism, also providing a possible explanation to the presence of specific metabolites in fruits. Bioinformatic analysis of these differential proteins revealed a central network of interacting molecular species, providing a rationale to the concomitant modulation of different plant physiological processes following the microbial inoculation. These findings indicated that the application of Trichoderma -based products exerts a positive impact on strawberry, integrating well with previous observations on the molecular mechanisms activated in roots and leaves of other tested plant species, demonstrating that the efficacy of using a biological approach with beneficial microbes on the maturing plant is also able to transfer advantages to the developing fruits. [ABSTRACT FROM AUTHOR]

Kunitz-type (PKPI) and Potato type I (Pin1) protease inhibitors (PIs) are two families of serine proteinase inhibitors often associated to plant storage organs and with well known insecticidal and nematicidal activities. Noteworthy, their ability to limit fungal and bacterial pathogenesis in vivo or to influence plant physiology has not been investigated in detail. To this aim, we generated a set of PVX-based viral constructs to transiently and heterologously express two potato PKPI (PKI1 , PKI2) and three potato Pin1 (PPI3A2 , PPI3B2 , PPI2C4) genes in Nicotiana benthamiana plants, a widely used model for plant-pathogen interaction studies. Interestingly, transgenic plants expressing most of the tested PIs showed to be highly resistant against two economically important necrotrophic fungal pathogens, Botrytis cinerea and Alternaria alternata. Unexpectedly, overexpression of the PKI2 Kunitz-type or of the PPI2C4 and PPI3A2 Potato type I inhibitor genes also lead to a dramatic reduction in the propagation and symptom development produced by the bacterial pathogen Pseudomonas syringae. We further found that localized expression of PPI2C4 and PKI2 in N. benthamiana leaves caused an increase in cell expansion and proliferation which lead to tissue hypertrophy and trichome accumulation. In line with this, the systemic expression of these proteins resulted in plants with enhanced shoot and root biomass. Collectively, our results indicate that PKPI and Pin1 PIs might represent valuable tools to simultaneously increase plant fitness and broad-spectrum resistance toward phytopathogens. [ABSTRACT FROM AUTHOR]

Periodic epidemics of black rot disease occur worldwide causing substantial yield losses. Xanthomonas campestris pv. campestris (Xcc) represents one of the most common bacteria able to cause the above disease in cruciferous plants such as broccoli, cabbage, cauliflower, and Arabidopsis thaliana. In agriculture, several strategies are being developed to contain the Xanthomona s infection. The use of bacteriophages could represent a valid and efficient approach to overcome this widespread phenomenon. Several studies have highlighted the potential usefulness of implementing phage therapy to control plant diseases as well as Xcc infection. In the present study, we characterized the effect of a lytic phage on the plant Brassica oleracea var. gongylodes infected with Xcc and, for the first time, the correlated plant metabolic response. The results highlighted the potential benefits of bacteriophages: reduction of bacterium proliferation, alteration of the biofilm structure and/or modulation of the plant metabolism and defense response. [ABSTRACT FROM AUTHOR]

A total of fifteen potential methyl t-butyl ether (MtBE)-degrading bacterial strains were isolated from contaminated soil. They have been identified as belonging to the genera Bacillus, Pseudomonas, Kocuria, Janibacter, Starkeya, Bosea, Mycolicibacterium, and Rhodovarius. Bacillus aryabhattai R1B, S. novella R8b, and M. mucogenicum R8i were able to grow using MtBE as carbon source, exhibiting different growth behavior and contaminant degradation ability. Their biocontrol ability was tested against various fungal pathogens. Both S. novella R8b and B. aryabhattai were effective in reducing the development of necrotic areas on leaves within 48 hours from Botritys cinerea and Alternaria alternata inoculation. Whereas, M. mucogenicum effectively controlled B. cinerea after 72 hours. Similar results were achieved using Pythium ultimum, in which the application of isolated bacteria increased seed germination. Only M. mucogenicum elicited tomato plants resistance against B. cinerea. This is the first report describing the occurrence of bioremediation and biocontrol activities in M. mucogenicum, B. aryabhattai and S. novella species. The production of maculosin and its antibiotic activity against Rhizoctonia solani has been reported for first time from S. novella. Our results highlight the importance of multidisciplinary approaches to achieve a consistent selection of bacterial strains useful for plant protection and bioremediation purposes. [ABSTRACT FROM AUTHOR]

From the green alga Cladophora sp. collected in Italy, the marine fungal strain A12 of Trichoderma citrinoviride was isolated, identified and characterized. LC-MS qTOF analysis was applied to perform a metabolic profile of the fungal culture. Chromatographic techniques and spectroscopic methods were used to isolate and characterize the major secondary metabolites produced by this strain in liquid culture. In particular, four known sorbicillinoids (trichodermanone C, spirosorbicillinol A, vertinolide and sorbicillin) were purified and identified, together with 2-phenylethanol and tyrosol. Moreover, metabolomic analysis allowed to detect small amounts of trichodimerol, rezishanone A, 2′,3′-dihydrosorbicillin and bisvertinol. For the first time a significant inhibitory effect on nitrite levels has been shown for trichodermanone C in lipopolysaccharide-stimulated J774A.1 macrophages. [ABSTRACT FROM AUTHOR]

CDA type I is a rare hereditary anemia, characterized by relative reticulocytopenia, and congenital anomalies. It is caused by biallelic mutations in one of the two genes: (i) CDAN1 , encoding Codanin-1, which is implicated in nucleosome assembly and disassembly; (ii) C15orf41 , which is predicted to encode a divalent metal ion-dependent restriction endonuclease with a yet unknown function. We described two cases of CDA type I, identifying the novel variant, Y94S, in the DNA binding domain of C15orf41, and the H230P mutation in the nuclease domain of the protein. We first analyzed the gene expression and the localization of C15orf41. We demonstrated that C15orf41 and CDAN1 gene expression is tightly correlated, suggesting a shared mechanism of regulation between the two genes. Moreover, we functionally characterized the two variants, establishing that the H230P leads to reduced gene expression and protein level, while Y94S induces a slight decrease of expression. We demonstrated that C15orf41 endogenous protein exhibits nuclear and cytosolic localization, being mostly in the nucleus. However, no altered nuclear-cytosolic compartmentalization of mutated C15orf41 was observed. Both mutants accounted for impaired erythroid differentiation in K562 cells, and H230P mutant also exhibits an increased S-phase of the cell cycle in these cells. Our functional characterization demonstrated that the two variants have different effects on the stability of the mutated mRNA, but both resulted in impaired erythroid maturation, suggesting the block of cell cycle dynamics as a putative pathogenic mechanism for C15orf41-related CDA I. [ABSTRACT FROM AUTHOR]

Olive mill waste (OMW), a byproduct from the extraction of olive oil, causes serious environmental problems for its disposal, and extensive efforts have been made to find cost-effective solutions for its management. Biochars produced from OMW were applied as soil amendment and found in many cases to successfully increase plant productivity and suppress diseases. This work aims to characterize biochars obtained by pyrolysis of OMW at 300 °C to 1000 °C using 13C NMR spectroscopy, LC-ESI-Q-TOF-MS and SEM (Scanning Electron Microscopy). Chemical characterization revealed that biochar composition varied according to the increase of pyrolysis temperature (PT). Thermal treated materials showed a progressive reduction of alkyl C fractions coupled to the enrichment in aromatic C products. In addition, numerous compounds present in the organic feedstock (fatty acids, phenolic compounds, triterpene acids) reduced (PT = 300 °C) or completely disappeared (PT ≥ 500 °C) in biochars as compared to untreated OMW. PT also affected surface morphology of biochars by increasing porosity and heterogeneity of pore size. The effects of biochars extracts on the growth of different organisms (two plants, one nematode and four fungal species) were also evaluated. When tested on different living organisms, biochars and OMW showed opposite effects. The root growth of Lepidium sativum and Brassica rapa, as well as the survival of the nematode Meloidogyne incognita, were inhibited by the untreated material or biochar produced at 300 °C, but toxicity decreased at higher PTs. Conversely, growth of Aspergillus, Fusarium, Rhizoctonia and Trichoderma fungi was stimulated by organic feedstock, while being inhibited by thermally treated biochars. Our findings showed a pattern of association between specific biochar chemical traits and its biological effects that, once mechanistically explained and tested in field conditions, may lead to effective applications in agriculture. [ABSTRACT FROM AUTHOR]

Abamectin has been proven to be effective in controlling root-knot nematodes (Meloidogyne spp.). In vitro and pot experiments were conducted to test the effects of Tervigo® and two new abamectin-based products (CHA 2061-02 EW and CHA 2080 SC), emulsion-water (EW) and liquid suspension-concentrate (SC) formulations, at different doses on M. incognita. The activity of the EW abamectin formulations were tested alone and in combination with indolebutyric acid (IBA), to assess the effect of the products applied as a soil drench to tomato planted in sterilized and naturally nematodeinfested soils. In vitro, both Tervigo® and CHA 2061-02 EW products mainly showed a nematostatic activity against second-stage juveniles (J2s) of M. incognita. For the most part, J2s that were immobilized following exposure to these products, after rinsing and transfer to water resumed mobility over time. Both formulations were also effective in vivo for the control of M. incognita-infested tomato plants. No visual symptoms of phytotoxicity were detected for either of the products. Root applications of CHA 2061-02 EW plus the addition of IBA improved overall plant growth, but not nematode control. Results demonstrated that both abamectin formulations have the potential for nematode control in tomato production. Additionally, the combination with IBA could be useful to enhance plant growth, in short-term production cycles or when nematode population densities are relatively low. Tested Abamectin-based products may be used for M. incognita management programs. [ABSTRACT FROM AUTHOR]

Trichodermabased products are considered an alternative to synthetic pesticides and fertilizers. TheseTrichodermaspp. are among the most studied and applied fungal BCAs in industry and agriculture and are known to secrete several secondary metabolites with different biological activities. The analysis of metabolic profiles (the ‘metabolome’) ofTrichodermaspecies is complex because of the wide range of compounds produced and the molecular activities identified, including the recently determined role in the activation of plant resistance to biotic and abiotic stresses and growth promotion. A new 10-member lactone, but-2-enoic acid 7-acetoxy-6-hydroxy-2-methyl-10-oxo-5,6,7,8,9,10-hexahydro-2H-oxecin-5-yl ester, named cremenolide (1), has been isolated from culture filtrates ofTrichoderma cremeum. The structure of cremenolide was determined by spectroscopic methods, including UV, MS, and 1D and 2D NMR analyses.In vitrotests showed that the purified compound inhibited the radial mycelium growth ofFusarium oxysporum,Botrytis cinereaandRhizoctonia solani, and exerted a significant promotion of growth of tomato seedlings. [ABSTRACT FROM PUBLISHER]

Trichoderma are ubiquitous soil fungi that include species widely used as biocontrol agents in agriculture. Many isolates are known to secrete several secondary metabolites with different biological activities towards plants and other microbes. Harzianic acid (HA) is a T. harzianum metabolite able to promote plant growth and strongly bind iron. In this work, we isolated from the culture filtrate of a T. harzianum strain a new metabolite, named isoharzianic acid (iso-HA), a stereoisomer of HA. The structure and absolute configuration of this compound has been determined by spectroscopic methods, including UV-Vis, MS, 1D and 2D NMR analyses. In vitro applications of iso-HA inhibited the mycelium radial growth of Sclerotinia sclerotiorum and Rhizoctonia solani. Moreover, iso HA improved the germination of tomato seeds and induced disease resistance. HPLC-DAD experiments showed that the production of HA and iso HA was affected by the presence of plant tissue in the liquid medium. In particular, tomato tissue elicited the production of HA but negatively modulated the biosynthesis of its analogue iso-HA, suggesting that different forms of the same Trichoderma secondary metabolite have specific roles in the molecular mechanism regulating the Trichoderma plant interaction. [ABSTRACT FROM AUTHOR]

Agriculture-relevant microorganisms are considered to produce secondary metabolites during processes of competition with other micro- and macro-organisms, symbiosis, parasitism or pathogenesis. Many different strains of the genus Trichoderma, in addition to a direct activity against phytopathogens, are well-known producers of secondary metabolites and compounds that substantially affect the metabolism of the host plant. Harzianic acid is a Trichoderma secondary metabolite, showing antifungal and plant growth promotion activities. This report demonstrates the ability of this tetramic acid to bind with a good affinity essential metals such as Fe3+, which may represent a mechanism of iron solubilisation that significantly alters nutrient availability in the soil environment for other microorganisms and the host plant. [ABSTRACT FROM AUTHOR]

Leishmaniasis is a neglected disease responsible for about 56,000 deaths every year. Despite its importance, there are no effective, safe and proper treatments for leishmaniasis due to strain resistance and/or drug side-effects. In this work we report the synthesis, molecular modeling, cytotoxicity and the antileishmanial profile of a series of 4-(1H-pyrazol-1-yl)benzenesulfonamides. Our experimental data showed an active profile for some compounds against Leishmania infantum and Leishmania amazonensis. The profile of two compounds against L. infantum was similar to that of pentamidine, but with lower cytotoxicity. Molecular modeling evaluation indicated that changes in electronic regions, orientation as well as lipophilicity of the derivatives were areas to improve the interaction with the parasitic target. Overall the compounds represent feasible prototypes for designing new molecules against L. infantum and L. amazonensis [ABSTRACT FROM AUTHOR]

Biallelic pathogenic variants in the SEC23B gene cause congenital dyserythropoietic anemia type II (CDA II), a rare hereditary disorder hallmarked by ineffective erythropoiesis, hemolysis, erythroblast morphological abnormalities, and hypo-glycosylation of some red blood cell membrane proteins. Abnormalities in SEC23B, which encodes the homonymous cytoplasmic COPII (coat protein complex II) component, disturb the endoplasmic reticulum to Golgi trafficking and affect different glycosylation pathways. The most harmful complication of CDA II is the severe iron overload. Within our case series (28 CDA II patients), approximately 36% of them exhibit severe iron overload despite mild degree of anemia and slightly increased levels of ERFE (the only erythroid regulator of hepcidin suppression). Thus, we hypothesized a direct role of SEC23B loss-of-function in the pathomechanism of hepatic iron overload. We established a hepatic cell line, HuH7, stably silenced for SEC23B. In silenced cells, we observed significant alterations of the iron status, due to both the alteration in BMP/SMADs pathway effectors and a reduced capability to sense BMP6 stimulus. We demonstrated that the loss-of-function of SEC23B is responsible of the impairment in glycosylation of the membrane proteins involved in the activation of the BMP/SMADs pathway with subsequent hepcidin suppression. Most of these data were confirmed in another hepatic cell line, HepG2, stably silenced for SEC23B. Our findings suggested that the pathogenic mechanism of iron overload in CDA II is associated to both ineffective erythropoiesis and to a specific involvement of SEC23B pathogenic variants at hepatic level. Finally, we demonstrated the ability of SEC23B paralog, i.e., SEC23A, to rescue the hepcidin suppression, highlighting the functional overlap between the two SEC23 paralogs in human hepatic cells. [ABSTRACT FROM AUTHOR]

Biofortification of crops via agricultural interventions represents an excellent way to supply micronutrients in poor rural populations, who highly suffer from these deficiencies. Soil microbes can directly influence plant growth and productivity, e.g., by contrasting plant pathogens or facilitating micronutrient assimilation in harvested crop-food products. Among these microbial communities, Trichoderma fungi are well-known examples of plant symbionts widely used in agriculture as biofertilizers or biocontrol agents. In this work, eleven Trichoderma strains and/or their bioactive metabolites (BAMs) were applied to lentil plants to evaluate their effects on plant growth and mineral content in greenhouse or field experiments. Our results indicated that, depending upon the different combinations of fungal strain and/or BAM, the mode of treatment (seed and/or watering), as well as the supplementary watering with solutions of iron (Fe) and zinc (Zn), the mineral absorption was differentially affected in treated plants compared with the water controls. In greenhouse conditions, the largest increase in Fe and Zn contents occurred when the compounds were applied to the seeds and the strains (in particular, T. afroharzianum T22, T. harzianum TH1, and T. virens GV41) to the soil. In field experiments, Fe and Zn contents increased in plants treated with T. asperellum strain KV906 or the hydrophobin HYTLO1 compared with controls. Both selected fungal strains and BAMs applications improved seed germination and crop yield. This biotechnology may represent an important challenge for natural biofortification of crops, thus reducing the risk of nutrient deficiencies. [ABSTRACT FROM AUTHOR]