Management of Post-Harvest Anthracnose: Current Approaches and Future Perspectives

Anthracnose is a severe disease caused by Colletotrichum spp. on several crop species. Fungal infections can occur both in the field and at the post-harvest stage causing severe lesions on fruits and economic losses. Physical treatments and synthetic fungicides have traditionally been the preferred means to control anthracnose adverse effects; however, the urgent need to decrease the use of toxic chemicals led to the investigation of innovative and sustainable protection techniques. Evidence for the efficacy of biological agents and vegetal derivates has been reported; however, their introduction into actual crop protection strategies requires the solutions of several critical issues. Biotechnology-based approaches have also been explored, revealing the opportunity to develop innovative and safe methods for anthracnose management through genome editing and RNA interference technologies. Nevertheless, besides the number of advantages related to their use, e.g., the putative absence of adverse effects due to their high specificity, a number of aspects remain to be clarified to enable their introduction into Integrated Pest Management (IPM) protocols against Colletotrichum spp. disease

Tumor-Associated Macrophages in Multiple Myeloma: Key Role in Disease Biology and Potential Therapeutic Implications

Multiple myeloma (MM) is characterized by multiple relapse and, despite the introduction of novel therapies, the disease becomes ultimately drug-resistant. The tumor microenvironment (TME) within the bone marrow niche includes dendritic cells, T-cytotoxic, T-helper, reactive B-lymphoid cells and macrophages, with a complex cross-talk between these cells and the MM tumor cells. Tumor-associated macrophages (TAM) have an important role in the MM pathogenesis, since they could promote plasma cells proliferation and angiogenesis, further supporting MM immune evasion and progression. TAM are polarized towards M1 (classically activated, antitumor activity) and M2 (alternatively activated, pro-tumor activity) subtypes. Many studies demonstrated a correlation between TAM, disease progression, drug-resistance and reduced survival in lymphoproliferative neoplasms, including MM. MM plasma cells in vitro could favor an M2 TAM polarization. Moreover, a possible correlation between the pro-tumor effect of M2 TAM and a reduced sensitivity to proteasome inhibitors and immunomodulatory drugs was hypothesized. Several clinical studies confirmed CD68/CD163 double-positive M2 TAM were associated with increased microvessel density, chemoresistance and reduced survival, independently of the MM stage. This review provided an overview of the biology and clinical relevance of TAM in MM, as well as a comprehensive evaluation of a potential TAM-targeted immunotherapy

Exploring the Potential of Portable Spectroscopic Techniques for the Biochemical Characterization of Roots in Shallow Landslides

In the present work, Raman, Fourier Transform Infrared (FTIR) and elemental Laser-Induced Breakdown Spectroscopy (LIBS) spectroscopic techniques were used for the assessment of the influence of plant root composition towards shallow landslide occurrence. For this purpose, analyses were directly carried out on root samples collected from chestnut forests of the Garfagnana basin (northern Apennines, Italy) in different areas devoid and affected by shallow landslides due to frequent heavy rain events. Results have highlighted a correlation between the biochemical constituents of wooden roots and the sampling areas. In particular, different content of lignin/cellulose, as well as minerals nutrients, have been detected in roots collected where shallow landslides occurred, with respect to more stable areas. The results achieved are in line with the scientific literature which has demonstrated the link between the chemical composition of roots with their mechanical properties and, in particular, tensile strength and cohesion. Finally, portable spectroscopic instrumentations were employed without the need for either any sample preparation for Raman and LIBS spectroscopy or minimal preparation for FTIR spectroscopy. This novel and fast approach has allowed achieving information on the content of the major constituents of the root cell, such as cellulose and lignin, as well as their mineral nutrients. This approach could be reasonably included among the vegetation protection actions towards instability, as well as for the evaluation of shallow landslide susceptibility, combining geological, vegetational and biochemical parameters with sustainability

Drug resistance and minimal residual disease in multiple myeloma

Great progress has been made in improving survival in multiple myeloma (MM) patients over the last 30 years. New drugs have been introduced and complete responses are frequently seen. However, the majority of MM patients do experience a relapse at a variable time after treatment, and ultimately the disease becomes drug-resistant following therapies. Recently, minimal residual disease (MRD) detection has been introduced in clinical trials utilizing novel therapeutic agents to measure the depth of response. MRD can be considered as a surrogate for both progression-free and overall survival. In this perspective, the persistence of a residual therapy-resistant myeloma plasma cell clone can be associated with inferior survivals. The present review gives an overview of drug resistance in MM, i.e., mutation of β5 subunit of the proteasome; upregulation of pumps of efflux; heat shock protein induction for proteasome inhibitors; downregulation of CRBN expression; deregulation of IRF4 expression; mutation of CRBN, IKZF1, and IKZF3 for immunomodulatory drugs and decreased target expression; complement protein increase; sBCMA increase; and BCMA down expression for monoclonal antibodies. Multicolor flow cytometry, or next-generation flow, and next-generation sequencing are currently the techniques available to measure MRD with sensitivity at 10-5. Sustained MRD negativity is related to prolonged survival, and it is evaluated in all recent clinical trials as a surrogate of drug efficacy

Delayed Self-Synchronization in Homoclinic Chaos

The chaotic spike train of a homoclinic dynamical system is self-synchronized by re-inserting a small fraction of the delayed output. Due to the sensitive nature of the homoclinic chaos to external perturbations, stabilization of very long periodic orbits is possible. On these orbits, the dynamics appears chaotic over a finite time, but then it repeats with a recurrence time that is slightly longer than the delay time. The effect, called delayed self-synchronization (DSS), displays analogies with neurodynamic events which occur in the build-up of long term memories.Comment: Submitted to Phys. Rev. Lett., 13 pages, 7 figure

CYTOCHROME P450 3A13 AND ENDOTHELIN JOINTLY MEDIATE DUCTUS ARTERIOSUS CONSTRICTION TO OXYGEN IN MICE

The fetal ductus arteriosus (DA) contracts to oxygen, and this feature, maturing through gestation, is considered important for its closure at birth. We have previously obtained evidence of the involvement of cytochrome P-450, possibly of the 3A subfamily (CYP3A), in oxygen sensing and have also identified endothelin (ET)-1 as the attendant effector for the contraction. Here, we examined comparatively wild-type (WT) and CYP3Anull (Cyp3a(-/-)) mice for direct validation of this concept. We found that the CYP3A subfamily is represented only by CYP3A13 in the WT DA. CYP3A13 was also detected in the DA by immunofluorescence microscopy, being primarily colocalized with the endoplasmic reticulum in both endothelial and muscle cells. However, a distinct signal was also evident in the plasma membrane. Isolated DAs from term WT animals developed a sustained contraction to oxygen with transient contractions superimposed. Conversely, no tonic response occurred in Cyp3a(-/-) DAs, whereas the phasic response persisted unabated. Oxygen did not contract the preterm WT DA but caused a full-fledged contraction after retinoic acid (RA) treatment. RA also promoted an oxygen contraction in the Cyp3a(-/-) DA. However, responses of RA-treated WT and Cyp3a(-/-) mice differed in that only the former abated with ET-1 suppression. This implies the existence of an alternative target for RA responsible for the oxygen-induced contraction in the absence of CYP3A13. In vivo, the DA was constricted in WT and Cyp3a(-/-) newborns, although with a tendency to be less narrowed in the mutant. We conclude that oxygen acts primarily through the complex CYP3A13 (sensor)/ET-1 (effector) and, in an accessory way, directly onto ET-1. However, even in the absence of CYP3A13, the DA may close postnatally thanks to the contribution of ET-1 and the likely involvement of compensating mechanism(s) identifiable with an alternative oxygen-sensing system and/or the withdrawal of relaxing influence(s) operating prenatally

A Study on the Efficiency of Sustainable Wine Grape Vineyard Management Strategies

Crop protection strategies based on cupric products and mainly adopted in organic viticulture produce a consistent environmental impact due to the persistence of copper in soils and its negative effects on edaphic biodiversity. In this work, trials were carried out during the crop years 2018–2020 in a vineyard with an organic management by a low-copper strategy and in a conventional IPM management with an IPM strategy with reduced use of fungicides. Phytosanitary treatments have been strictly planned according to forecasting models, and fungicides have been partially substituted with substances improving the resistance mechanisms of plants. Different strategies of green manure management, in order to improve the health of vines, were also adopted. Results suggest the efficacy of the “GreenGrapes” plant protection strategy in conditions of low downy mildew pressure. Furthermore, no declines in the production quality have been recorded; conversely, the synergic effect of the green manure and the tested biostimulant substances (“GreenGrapes” protocols) and the green manure management improved yield and grape quality, compared with conventional conduction (IPM and Organic) with a grass covering

Quantitative analysis of the thermal distortions in a 100 W CW Nd:YAG ceramic slab laser.

Making use of an interferometric diagnostic system, we analyze the thermo-mechanical distortions taking place in the slab shaped ceramic Nd:YAG active medium of a 100 W class laser. These distortions are collected in different pumping regimes, both in static situations and during transient warm-up, and compared to the results of computer simulations. This procedure enables us to determine the relevance of different stress causes and thus to increase the specific power extraction of the active slab module

Fludarabine, high-dose cytarabine and idarubicin-based induction may overcome the negative prognostic impact of flt3-itd in npm1 mutated aml, irrespectively of flt3-itd allelic Burden

The mutations of NPM1 and FLT3-ITD represent the most frequent genetic aberration in acute myeloid leukemia. Indeed, the presence of an NPM1 mutation reduces the negative prognostic impact of FLT3-ITD in patients treated with conventional “3+7” induction. However, little information is available on their prognostic role with intensified regimens. Here, we investigated the efficacy of a fludarabine, high-dose cytarabine and idarubicin induction (FLAI) in 149 consecutive fit AML patients (median age 52) carrying the NPM1 and/or FLT3-ITD mutation, treated from 2008 to 2018. One-hundred-and-twenty-nine patients achieved CR (86.6%). After a median follow up of 68 months, 3-year overall survival was 58.6%. Multivariate analysis disclosed that both NPM1mut (p < 0.05) and ELN 2017 risk score (p < 0.05) were significant predictors of survival. NPM1-mutated patients had a favorable outcome, with no significant differences between patients with or without concomitant FLT3-ITD (p = 0.372), irrespective of FLT3-ITD allelic burden. Moreover, in landmark analysis, performing allogeneic transplantation (HSCT) in first CR proved to be beneficial only in ELN 2017 high-risk patients. Our data indicate that FLAI exerts a strong anti-leukemic effect in younger AML patients with NPM1mut and question the role of HSCT in 1st CR in NPM1mut patients with concomitant FLT3-ITD