Factors affecting the production of Trichoderma harzianum secondary metabolites during the interaction with different plant pathogens

Strains of Trichoderma spp. produce numerous bioactive secondary metabolites. The in vitro production and antibiotic activities of the major compounds synthesized by Trichoderma harzianum strains T22 and T39 against Leptosphaeria maculans, Phytophthora cinnamomi and Botrytis cinerea were evaluated. Moreover, the eliciting effect of viable or nonviable biomasses of Rhizoctonia solani, Pythium ultimum or B. cinerea on the in vitro production of these metabolites was also investigated. T22azaphilone, 1-hydroxy-3-methyl-anthraquinone, 1,8-dihydroxy-3-methyl-anthraquinone, T39butenolide, harzianolide, harzianopyridone were purified, characterized and used as standards. In antifungal assays, T22azaphilone and harzianopyridone inhibited the growth of the pathogens tested even at low doses (1-10 mu g per plug), while high concentrations of T39butenolide and harzianolide were needed (> 100 mu g per plug) for inhibition. The in vitro accumulation of these metabolites was quantified by LC/MS. T22azaphilone production was not enhanced by the presence of the tested pathogens, despite its antibiotic activity. On the other hand, the anthraquinones, which showed no pathogen inhibition, were stimulated by the presence of P. ultimum. The production of T39butenolide was significantly enhanced by co-cultivation with R. solani or B. cinerea. Similarly, viable and nonviable biomasses of R. solani or B. cinerea increased the accumulation of harzianopyridone. Finally, harzianolide was not detected in any of the interactions examined. The secondary metabolites analysed in this study showed different levels of antibiotic activity. Their production in vitro varied in relation to: (i) the specific compound; (ii) the phytopathogen used for the elicitation; (iii) the viability of the elicitor; and (iv) the balance between elicited biosynthesis and biotransformation rates. The use of cultures of phytopathogens to enhance yields of Trichoderma metabolites could improve the production and application of novel biopesticides and biofertilizers based on the active compounds instead of the living microbe. This could have a significant beneficial impact on the management of diseases in crop plants

Tissue-Resident Innate Immune Cell-Based Therapy: A Cornerstone of Immunotherapy Strategies for Cancer Treatment

Cancer immunotherapy has led to impressive advances in cancer treatment. Unfortunately, in a high percentage of patients is difficult to consistently restore immune responses to eradicate established tumors. It is well accepted that adaptive immune cells, such as B lymphocytes, CD4+ helper T lymphocytes, and CD8+ cytotoxic T-lymphocytes (CTLs), are the most effective cells able to eliminate tumors. However, it has been recently reported that innate immune cells, including natural killer cells (NK), dendritic cells (DC), macrophages, myeloid-derived suppressor cells (MDSCs), and innate lymphoid cells (ILCs), represent important contributors to modulating the tumor microenvironment and shaping the adaptive tumor response. In fact, their role as a bridge to adaptive immunity, make them an attractive therapeutic target for cancer treatment. Here, we provide a comprehensive overview of the pleiotropic role of tissue-resident innate immune cells in different tumor contexts. In addition, we discuss how current and future therapeutic approaches targeting innate immune cells sustain the adaptive immune system in order to improve the efficacy of current tumor immunotherapies

Genome-Wide Patterns of Homozygosity Reveal the Conservation Status in Five Italian Goat Populations

The application of genomic technologies has facilitated the assessment of genomic inbreeding based on single nucleotide polymorphisms (SNPs). In this study,we computed several runs of homozygosity (ROH) parameters to investigate the patterns of homozygosity using Illumina Goat SNP50 in five Italian local populations: Argentata dell’Etna (N = 48), Derivata di Siria (N = 32), Girgentana (N = 59), Maltese (N = 16) andMessinese (N = 22). The ROH results showed well-defined differences among the populations. A total of 3687 ROH segments >2 Mb were detected in the whole sample. The Argentata dell’Etna and Messinese were the populations with the lowest mean number of ROH and inbreeding coefficient values, which reflect admixture and gene flow. In the Girgentana, we identified an ROH pattern related with recent inbreeding that can endanger the viability of the breed due to reduced population size. The genomes of Derivata di Siria and Maltese breeds showed the presence of long ROH (>16 Mb) that could seriously impact the overall biological fitness of these breeds. Moreover, the results confirmed that ROH parameters are in agreement with the known demography of these populations and highlighted the different selection histories and breeding schemes of these goat populations. In the analysis of ROH islands, we detected harbored genes involved with important traits, such as formilk yield, reproduction, and immune response, and are consistentwith the phenotypic traits of the studied goat populations. Finally, the results of this study can be used for implementing conservation programs for these local populations in order to avoid further loss of genetic diversity and to preserve the production and fitness traits. In view of this, the availability of genomic data is a fundamental resource

Is chlorophyll-athe best surrogate for organic matter enrichment in submicron primary marine aerosol?

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Investigation on MMACHC-R161Q pathological mutant from cblC disease

The cblC disease is a rare inborn disorder of the vitamin B12 (cobalamin, Cbl) metabolism characterized by combined methylmalonic aciduria and homocystinuria. The clinical consequences are devastating and, even when early treated with current therapies, the affected children manifest symptoms involving vision, growth, and learning. The molecular genetic cause of the disease was found in the mutations of the gene coding for MMACHC, a 282 amino acid protein that transports and processes the various forms of Cbl. Here we present the biophysical characterization of wild type MMACHC and a variant, p.R161Q, resulting from the most common missense pathological mutation found in cblC patients. By using a biophysical approach we investigated the stability of the two proteins and their ability to bind and transform the vitamin B12, and to assemble in a dimeric structure. Moreover, interesting indications about the behaviour of the proteins resulted from the Molecular Dynamics (MD) simulations. Overall, our results reveal how a biophysical approach based on the complementarity of computational and experimental methods can offer new insights in the study of the specific effects of the pathological cblC mutation and help prospecting new routes for the cblC treatment

Klebsiella pneumoniae Lipopolysaccharides Serotype O2afg Induce Poor Inflammatory Immune Responses Ex Vivo

Currently, Klebsiella pneumoniae is a pathogen of clinical relevance due to its plastic ability of acquiring resistance genes to multiple antibiotics. During K. pneumoniae infections, lipopolysaccharides (LPS) play an ambiguous role as they both activate immune responses but can also play a role in immune evasion. The LPS O2a and LPS O2afg serotypes are prevalent in most multidrug resistant K. pneumoniae strains. Thus, we sought to understand if those two particular LPS serotypes were involved in a mechanism of immune evasion. We have extracted LPS (serotypes O1, O2a and O2afg) from K. pneumoniae strains and, using human monocytes ex vivo, we assessed the ability of those LPS antigens to induce the production of pro-inflammatory cytokines and chemokines. We observed that, when human monocytes are incubated with LPS serotypes O1, O2a or O2afg strains, O2afg and, to a lesser extent, O2a but not O1 failed to elicit the production of pro-inflammatory cytokines and chemokines, which suggests a role in immune evasion. Our preliminary data also shows that nuclear translocation of NF-κB, a process which regulates an immune response against infections, occurs in monocytes incubated with LPS O1 and, to a smaller extent, with LPS O2a, but not with the LPS serotype O2afg. Our results indicate that multidrug resistant K. pneumoniae expressing LPS O2afg serotypes avoid an initial inflammatory immune response and, consequently, are able to systematically spread inside the host unharmed, which results in the several pathologies associated with this bacterium

Web Health Application for ADHD Monitoring (WHAAM): Context-Driven Framework

The Framework (FW) summarizes the experiences and vision of the WHAAM project partners, providing the basis for the development of the WHAAM app and online services. There are many approaches to the treatment of ADHD, with excellent resources available. This FW is a working tool based on partners' experiences, inspiring subsequent project activities. It is divided into three parts: part A explores general issues related to ADHD, focusing on key life contexts such as school, family, and social relationships. Each context is explored in terms of assessment, intervention and support. Part B delves into the relationship between ICT use and ADHD treatment. Finally, Part C briefly explains the main features of the WHAAM app, including functionality and interfaces. The WHAAM project considers the app and online service accessible via PC and mobile devices as a significant advancement in monitoring process management

The Tempered Polymerization of Human Neuroserpin

Neuroserpin, a member of the serpin protein superfamily, is an inhibitor of proteolytic activity that is involved in pathologies such as ischemia, Alzheimer's disease, and Familial Encephalopathy with Neuroserpin Inclusion Bodies (FENIB). The latter belongs to a class of conformational diseases, known as serpinopathies, which are related to the aberrant polymerization of serpin mutants. Neuroserpin is known to polymerize, even in its wild type form, under thermal stress. Here, we study the mechanism of neuroserpin polymerization over a wide range of temperatures by different techniques. Our experiments show how the onset of polymerization is dependent on the formation of an intermediate monomeric conformer, which then associates with a native monomer to yield a dimeric species. After the formation of small polymers, the aggregation proceeds via monomer addition as well as polymer-polymer association. No further secondary mechanism takes place up to very high temperatures, thus resulting in the formation of neuroserpin linear polymeric chains. Most interesting, the overall aggregation is tuned by the co-occurrence of monomer inactivation (i.e. the formation of latent neuroserpin) and by a mechanism of fragmentation. The polymerization kinetics exhibit a unique modulation of the average mass and size of polymers, which might suggest synchronization among the different processes involved. Thus, fragmentation would control and temper the aggregation process, instead of enhancing it, as typically observed (e.g.) for amyloid fibrillation

X-ray polarimetry of the accreting pulsar GX 301-2

The phase- and energy-resolved polarization measurements of accreting X-ray pulsars (XRPs) allow us to test different theoretical models of their emission, as well as to provide an avenue to determine the emission region geometry. We present the results of the observations of the XRP GX 301-2 performed with the Imaging X-ray Polarimetry Explorer (IXPE). GX 301-2 is a persistent XRP with one of the longest known spin periods of ~680 s. A massive hyper-giant companion star Wray 977 supplies mass to the neutron star via powerful stellar winds. We do not detect significant polarization in the phase-averaged data using spectro-polarimetric analysis, with the upper limit on the polarization degree (PD) of 2.3% (99% confidence level). Using the phase-resolved spectro-polarimetric analysis we get a significant detection of polarization (above 99% c.l.) in two out of nine phase bins and marginal detection in three bins, with a PD ranging between ~3% and ~10%, and a polarization angle varying in a very wide range from ~0 deg to ~160 deg. Using the rotating vector model we obtain constraints on the pulsar geometry using both phase-binned and unbinned analysis getting excellent agreement. Finally, we discuss possible reasons for a low observed polarization in GX 301-2.Comment: 10 pages, 10 figures, submitted to A&