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Abstract The lack of effective therapies for visual restoration in Retinitis pigmentosa and macular degeneration has led to the development of new strategies, such as optogenetics and retinal prostheses. However, visual restoration is poor due to the massive light-evoked activation of retinal neurons, regardless of the segregation of visual information in ON and OFF channels, which is essential for contrast sensitivity and spatial resolution. Here, we show that Ziapin2, a membrane photoswitch that modulates neuronal capacitance and excitability in a light-dependent manner, is capable of reinstating, in mouse and rat genetic models of photoreceptor degeneration, brisk and sluggish ON, OFF, and ON-OFF responses in retinal ganglion cells evoked by full-field stimuli, with reactivation of their excitatory and inhibitory conductances. Intravitreally injected Ziapin2 in fully blind rd10 mice restores light-driven behavior and optomotor reflexes. The results indicate that Ziapin2 is a promising molecule for reinstating physiological visual responses in the late stages of retinal degeneration.

The management of grapevine from diseases is now particularly focused on the development of environmentally friendly strategies. Although sulphur is not in itself a toxic substance, its extensive use in powdery mildew, in organic vineyards especially, may cause environmental problems and plant phytotoxicity and affect the health and safety of viticultural workers. The activity of sulphur applied at doses reduced up to 50% in tank mixtures with silicates or Equisetum arvense-based products was assessed on powdery mildew in grapevine. Two-year trials were carried out applying the products every 7–10 days in the period of greatest risk for disease infections, in two organic vineyards in the Abruzzo region, Italy. In both vineyards throughout all trial years, at harvest, disease incidence and severity on leaves and bunches in the silicon + sulphur treatments were generally significantly lower compared to both the sulphur at full dose and to the control. In all trials, in both vineyards, a strong activity of silicon + sulphur mixtures towards disease on leaves was observed. This effect could be decisive in lowering the potential inoculum in the following season. In the Ari vineyard, vines treated with the mixtures always increased yield quantity and quality, given the higher contents of soluble solids and lower levels of total acidity. In the Cellino vineyard, probably due to the young age of the vines, increases in yield quantity were observed, with lesser effects on quality. The promising activity of the mixtures needs further studies to confirm these positive results. Furthermore, in both vineyards, the source of primary inoculum of the pathogen was observed as chasmothecia on the leaves.

Abstract Visual information processing in the retina requires the rhythmic expression of clock genes. The intrinsic retinal circadian clock is independent of the master clock located in the hypothalamic suprachiasmatic nucleus and emerges from retinal cells, including glia. Less clear is how glial oscillators influence the daily regulation of visual information processing in the mouse retina. Here, we demonstrate that the adult conditional deletion of the gene Bmal1 in GLAST-positive glial cells alters retinal physiology. Specifically, such deletion was sufficient to lower the amplitude of the electroretinogram b-wave recorded under light-adapted conditions. Furthermore, recordings from > 20,000 retinal ganglion cells (RGCs), the retina output, showed a non-uniform effect on RGCs activity in response to light across different cell types and over a 24-h period. Overall, our results suggest a new role of a glial circadian gene in adjusting mammalian retinal output throughout the night-day cycle.

Grapevine grafting is an essential practice in viticulture and over the years, various bench grafting techniques have been developed to mechanize the nursery process and to increase the yield in number of viable cuttings. Bench grafting is a fundamental nursery practice that can potentially affect the quality of propagation material also in young decline associated to grapevine trunk diseases and has been recently reported to influence leaf symptoms development associated with diseases of Esca complex. The study aimed to investigate how three bench grafting methods [i.e., (i) Omega graft as mechanical technique, (ii) Whip and Tongue graft as manual technique and (iii) Full Cleft graft as semi-mechanical technique] can influence these phenomena. Specifically, the different methods were compared for their effect on the anatomical development of the grafting point and the functionality of the xylem, also considering two factors: the grapevine cultivar (Cabernet Sauvignon, Glera and Teroldego) and the scion/rootstock diameter (thin and large). Observations by light microscopy on the anatomical evolution and measurements on the xylem morphology and hydraulic traits were correlated with the grafting methods and the investigated varieties. The anatomical observations revealed that the mechanical (Omega) and semi-mechanical (Full Cleft) grafting methods have a faster callusing response while the manual technique (Whip and Tongue) has a slower but greater vascularization of the differentiated callus. Significant differences between cultivars and/or grafting types were also detected in necrotic area on the grafted tissues. Statistical analysis of the grapevine vessels suggested differences in xylem parameters between cultivars, while grafting type had no significant effects. On the other hand, the grafting type significantly affected the intrinsic growth rate. The study confirms the potential incidence of lesions and dysfunctionalities correlated with the grafting method applied, which can potentially induce grafted vine declines in vineyards due to the necrotic area detected on the grafted tissues.

Esca disease, the most common grapevine wood disease in Europe, causes yield losses correlated with the foliar symptoms’ expression. In two vineyards located in the Abruzzo Region of Italy, each of which were investigated for esca symptoms after 1994, different applications of macro- and microelements were performed in two consecutive growing seasons. The main aim of the work consisted of verifying the effects of the fertilizer applications on the foliar symptoms’ expression, in order to deepen knowledge of the nature of the symptom, which is still unclear. For each treatment, in each year, the leaf content of macro- and microelements and the composition of berries and musts were assessed. The effects of these applications on vegetative growth and yield quantity were also verified. The trials were carried out on symptomatic, asymptomatic and apparently healthy vines. All applications, in particular those with microelements, increased the foliar symptoms’ expression, and a greater vegetative growth was detected only in vines treated with NPK fertilizers. The symptoms’ increase was always associated in the leaf with a decrease of calcium, and to a lesser extent, magnesium, reinforcing the hypothesis of the plant’s hypersensitive reaction in the development of foliar symptoms, given the role of calcium in the defense response. The vineyards were in nutritional balance regardless of the fertilizer applications. The general increase in foliar symptoms and the decrease in sugars in the musts of asymptomatic treated vines underlined the importance of the vegetative-productive balance, in Esca infected vineyards especially, in order to limit the symptoms’ expression and the decrease in yield.

Abstract The retina is a complex circuit of the central nervous system whose aim is to encode visual stimuli prior the higher order processing performed in the visual cortex. Due to the importance of its role, modeling the retina to advance in interpreting its spiking activity output is a well studied problem. In particular, it has been shown that latent variable models can be used to model the joint distribution of Retinal Ganglion Cells (RGCs). In this work, we validate the applicability of Restricted Boltzmann Machines to model the spiking activity responses of a large a population of RGCs recorded with high-resolution electrode arrays. In particular, we show that latent variables can encode modes in the RGC activity distribution that are closely related to the visual stimuli. In contrast to previous work, we further validate our findings by comparing results associated with recordings from retinas under normal and altered encoding conditions obtained by pharmacological manipulation. In these conditions, we observe that the model reflects well-known physiological behaviors of the retina. Finally, we show that we can also discover temporal patterns, associated with distinct dynamics of the stimuli.

Fomitiporia mediterranea (Fmed) is the primary Basidiomycota species causing white rot in European vineyards affected by the Esca complex of diseases (ECD). In the last few years, an increasing number of studies have highlighted the importance of reconsidering the role of Fmed in ECD etiology, justifying an increase in research interest related to Fmed’s biomolecular pathogenetic mechanisms. In the context of the current re-evaluation of the binary distinction (brown vs. white rot) between biomolecular decay pathways induced by Basidiomycota species, our research aims to investigate the potential for non-enzymatic mechanisms adopted by Fmed, which is typically described as a white rot fungus. Our results demonstrate how, in liquid culture reproducing nutrient restriction conditions often found in wood, Fmed can produce low molecular weight compounds, the hallmark of the non-enzymatic “chelator-mediated Fenton” (CMF) reaction, originally described for brown rot fungi. CMF reactions can redox cycle with ferric iron, generating hydrogen peroxide and ferrous iron, necessary reactants leading to hydroxyl radical (•OH) production. These observations led to the conclusion that a non-enzymatic radical-generating CMF-like mechanism may be utilized by Fmed, potentially together with an enzymatic pool, to contribute to degrading wood constituents; moreover, indicating significant variability between strains.

Grapevine trunk diseases are widespread in all grape-growing countries. The diseases included in the Esca complex of diseases are particularly common in European vineyards. Their distinctive foliar symptoms are well known to be associated not only with losses in quantity, as with all grapevine wood diseases, but also with losses in the quality of the crop. Protection of pruning wounds is known to reduce infections in artificial inoculations and, to some extent, reduce the external leaf symptoms. The application of biological control agents in the field is typically started at the first appearance of symptoms. In this article, the two strains belonging to two different species, Trichoderma asperellum ICC 012 and T. gamsii ICC 080, which are present in a commercial formulation, were tested in vitro, in vivo in artificial inoculation, and in the field in long-term experiments where the wounds on four young asymptomatic vineyards were protected since 1 or 2 years after planting. The in vitro trials highlighted the different temperature requirements of the two strains, the direct mycoparasitizing activity of T. asperellum, and the indirect activity shown by both Trichoderma strains. The in vivo trials confirmed the ability of the two strains to reduce the colonization following artificial inoculations with the high, unnatural concentration of spores used in artificial infections, even if with variable efficacy, and with long persistence as they could be reisolated 7 months post-application. The preventive applications carried out over 9 years showed a very high reduction in symptom development in the treated vines, on annual and cumulated incidence and on the death of vines, with disease reduction varying from 66 to almost 90%. Early and annual application of protection to the pruning wounds appears to be the best method for reducing damages caused by grapevine leaf stripe disease (a disease of the Esca complex of diseases). Trichoderma appears to offer an efficient, environmentally friendly, and long-lasting protection in the presence of a natural inoculum concentration.

Fomitiporia mediterranea M. Fisch. (Fmed) is a basidiomycete first described in 2002, and was considered up to then as part of Fomitiporia punctata (P. Karst) Murrill. This fungus can degrade lignocellulosic biomass, causing white rot and leaving bleached fibrous host residues. In Europe Fmed is considered the main grapevine wood rot (Esca) agent within the Esca disease complex, which includes some of the most economically important Grapevine Trunk Diseases (GTDs). This review summarises and evaluates published research on Fmed, on white rot elimination by curettage or management by treatments with specific products applied to diseased grapevines, and on the relationship between wood symptoms and Grapevine Leaf Stripe Disease (GLSD) in the Esca disease complex. Information is also reviewed on the fungus biology, mechanisms of pathogenicity, and their possible relationships with external foliar symptoms of the Esca disease complex. Information on Fmed control strategies is also reviewed.

Grapevine trunk diseases (GTDs) are a serious and growing threat to vineyards worldwide. The need for innovative control tools persists since pesticides used against some GTDs have been banned and only methods to prevent infections or to reduce foliar symptoms have been developed so far. In this context, the application of imaging methods, already applied to study plant–microbe interactions, represents an interesting approach to understand the effect of experimental treatments applied to reduce fungal colonization, on GTD-related pathogens activity. To this aim, trials were carried out to evaluate the efficacy of copper-based treatments, formulated with hydroxyapatite (HA) as co-adjuvant with innovative delivery properties, loaded with two different copper(II) compounds (tribasic sulfate and sulfate pentahydrate), and applied to grapevine propagation material to inhibit fungal wood colonization. The treated rootstock (Vitis berlandieri × Vitis riparia cv. K5BB) and scion cuttings (Vitis vinifera L., cv. Chardonnay) had been inoculated with a strain of Phaeoacremonium minimum (Pmi) compared to uninoculated rootstocks. Experimental treatments were applied during the water-soaking process, comparing the copper(II) compounds pure or formulated with HA, to hydrate the cuttings. After callusing, grafted vines were grown under greenhouse conditions in a nursery and inoculated with Pmi::gfp7 or with Pmi wild-type. Fifteen weeks post-inoculation, woody tissues close to the inoculation site were sampled to evaluate the efficiency of the treatments by studying the plant–microbe interaction by confocal laser scanning microscopy (CLSM). Copper and further elements were also quantified in the same tissues immediately after the treatments and on the CLSM samples. Finally, the grapevine defense responses were studied in the leaves of cuttings treated with the same formulations. The present investigation confirmed the relevant interaction of Pmi and the related transformed strain on the vascular tissues of grafted vines. Furthermore, in vitro assay revealed (i) the fungistatic effect of HA and the reduced effect of Cu fungicide when combined with HA. In planta assays showed (ii) the reduction of Pmi infection in propagation material treated with HA-Cu formulations, (iii) the movement of HA-Cu formulations inside the plant tissues and their persistence over time, and (iv) the plant defense reaction following the treatment with pure HA or Cu, or combined.

The progressive reduction in the quantities of copper regulated by the European Union is focusing the research on new formulations with a reduced copper content but equally effective. In this regard, the activity of an Italian copper chabasite-rich zeolitite, which proved to be effective against grapevine grey mold and sour rot, was assessed against downy mildew. A two-year study was carried out in the Abruzzo region, Italy, in a cv. Montepulciano vineyard. The applications of the copper zeolitite showed the same good results obtained by a standard integrated/conventional strategy based on contact and systemic fungicides. At harvest, in both trial years, the plants with infected bunches in the untreated control ranged from 86.25% to 100%, compared to 15–30% of the treated plants. Furthermore, infected bunches and berries of the untreated control vines were 70–100% while treated ones never exceeded 2.32%. Furthermore, an increase in the polyphenol content and color intensity in wines made from vines treated with copper zeolitite was confirmed and appeared to be particularly evident in hot and dry seasons. The activity of copper zeolitite towards downy mildew, the potential use against grey mold and sour rot and the protection of grapes from high temperatures indicate that this product is a promising tool for a viticulture environmentally friendly control strategy.

The progressive degeneration of retinal photoreceptors is one of the most significant causes of blindness in humans. Conjugated polymers represent an attractive solution to the field of retinal prostheses, and a multi-layer fully organic prosthesis implanted subretinally in dystrophic Royal College of Surgeons (RCS) rats was able to rescue visual functions. As a step toward human translation, we report here the fabrication and in vivo testing of a similar device engineered to adapt to the human-like size of the eye of the domestic pig, an excellent animal paradigm to test therapeutic strategies for photoreceptors degeneration. The active conjugated polymers were layered onto two distinct passive substrates, namely electro-spun silk fibroin (ESF) and polyethylene terephthalate (PET). Naive pigs were implanted subretinally with the active device in one eye, while the contralateral eye was sham implanted with substrate only. Retinal morphology and functionality were assessed before and after surgery by means of in vivo optical coherence tomography and full-field electroretinogram (ff-ERG) analysis. After the sacrifice, the retina morphology and inflammatory markers were analyzed by immunohistochemistry of the excised retinas. Surprisingly, ESF-based prostheses caused a proliferative vitreoretinopathy with disappearance of the ff-ERG b-wave in the implanted eyes. In contrast, PET-based active devices did not evoke significant inflammatory responses. As expected, the subretinal implantation of both PET only and the PET-based prosthesis locally decreased the thickness of the outer nuclear layer due to local photoreceptor loss. However, while the implantation of the PET only substrate decreased the ff-ERG b-wave amplitude with respect to the pre-implant ERG, the eyes implanted with the active device fully preserved the ERG responses, indicating an active compensation of the surgery-induced photoreceptor loss. Our findings highlight the possibility of developing a new generation of conjugated polymer/PET-based prosthetic devices that are highly biocompatible and potentially suitable for subretinal implantation in patients suffering from degenerative blindness.

Abstract Neuronal responses to external stimuli vary from trial to trial partly because they depend on continuous spontaneous variations of the state of neural circuits, reflected in variations of ongoing activity prior to stimulus presentation. Understanding how post-stimulus responses relate to the pre-stimulus spontaneous activity is thus important to understand how state dependence affects information processing and neural coding, and how state variations can be discounted to better decode single-trial neural responses. Here we exploited high-resolution CMOS electrode arrays to record simultaneously from thousands of electrodes in in-vitro cultures stimulated at specific sites. We used information-theoretic analyses to study how ongoing activity affects the information that neuronal responses carry about the location of the stimuli. We found that responses exhibited state dependence on the time between the last spontaneous burst and the stimulus presentation and that the dependence could be described with a linear model. Importantly, we found that a small number of selected neurons carry most of the stimulus information and contribute to the state-dependent information gain. This suggests that a major value of large-scale recording is that it individuates the small subset of neurons that carry most information and that benefit the most from knowledge of its state dependence.

Promoter-proximal transcripts have been proposed to act ascis-acting elements regulating transcription. Here, the authors provide evidence that a promoter-proximal RNA, in combination with other epigenetic regulators, controls transcription of E-cadherin in epithelial cancers.

Oxidative stress and inflammation determine retinal ganglion cell degeneration, leading to retinal impairment and vision loss. Müller glial cells regulate retinal repair under injury, through gliosis. Meanwhile, reactive gliosis can turn in pathological effects, contributing to neurodegeneration. In the present study, we tested whether Cord Blood Serum (CBS), rich of growth factors, might improve the viability of Müller cells under in vitro damage. BDNF, NGF, TGF-α, GDNF and EGF levels were measured in CBS samples by Human Magnetic Luminex Assay. CBS effects were evaluated on rat (rMC-1) and human (MIO-M1) Müller cells, under H2O2 and IL-1β damage. Cells grown with FBS or CBS both at 5% were exposed to stress and analyzed in terms of cell viability, GFAP, IL-6 and TNF-α expression. CBS was also administrated after treatment with K252a, inhibitor of the neurotrophin receptor Trk. Cell viability of rMC-1 and MIO-M1 resulted significantly improved when pretreated with CBS and exposed to H2O2 and IL-1β, in comparison to the standard culture with FBS. Accordingly, the gliosis marker GFAP resulted down-regulated following CBS priming. In parallel, we observed a lower expression of the inflammatory mediators in rMC-1 (TNF-α) and MIO-M1 (IL-6, TNF- α), especially in presence of inflammatory damage. Trk inhibition through K252a administration impaired the effects of CBS under stress conditions on MIO-M1 and rMC-1 viability, not significantly different from FBS condition. CBS is enriched with neurotrophins and its administration to rMC-1 and MIO-M1 attenuates the cytotoxic effects of H2O2 and IL-1β. Moreover, the decrease of the main markers of gliosis and inflammation suggests a promising use of CBS for neuroprotection aims. This study is a preliminary basis that prompts future investigations to deeply explore and confirm the CBS potential.

The activity of Italian chabasite-rich zeolitites for control of grey mould, sour rot and grapevine moth was compared to that from synthetic fungicides and insecticides in three vineyards in the Abruzzo region of Italy. Persistence of zeolitites on grapevine canopies has enabled applications to be carried out before rainfall events, which are likely to predispose for infections by grey mould and sour rot pathogens. Applications for control of Lobesia botrana (grapevine moth) were carried out after the peak of the male flight, and the presence of eggs on grape berries was also assessed. Disease and pest control were very satisfactory and comparable to those obtained from synthetic fungicides and insecticides. In addition, there were no differences among treatments for yield, berry composition, or wine ethyl alcohol, pH and total acidity. Phenolic compounds increased in wine from zeolitite-treated plants where the treatment was carried out within 15 days from grape harvest. These promising results have strategic value, because zeolitites provided simultaneous control of grey mould, sour rot and L. botrana. However, since these compounds have been tested for the first time for the control of diseases and L. botrana, the results obtained in this study require further validation.

Retinal neurodegeneration can impair visual perception at different levels, involving not only photoreceptors, which are the most metabolically active cells, but also the inner retina. Compensatory mechanisms may hide the first signs of these impairments and reduce the likelihood of receiving timely treatments. Therefore, it is essential to characterize the early critical steps in the neurodegenerative progression to design adequate therapies. This paper describes and correlates early morphological and biochemical changes in the degenerating retina with in vivo functional analysis of retinal activity and investigates the progression of neurodegenerative stages for up to 7 months. For these purposes, Sprague–Dawley rats were exposed to 1000 lux light either for different durations (12 h to 24 h) and examined seven days afterward (7d) or for a fixed duration (24 h) and monitored at various time points following the exposure (up to 210d). Flash electroretinogram (fERG) recordings were correlated with morphological and histological analyses to evaluate outer and inner retinal disruptions, gliosis, trophic factor release, and microglial activation. Twelve hours or fifteen hours of exposure to constant light led to a severe retinal dysfunction with only minor morphological changes. Therefore, early pathological signs might be hidden by compensatory mechanisms that silence retinal dysfunction, accounting for the discrepancy between photoreceptor loss and retinal functional output. The long-term analysis showed a transient functional recovery, maximum at 45 days, despite a progressive loss of photoreceptors and coincident increases in glial fibrillary acidic protein (GFAP) and basic fibroblast growth factor-2 (bFGF-2) expression. Interestingly, the progression of the disease presented different patterns in the dorsal and ventral retina. The information acquired gives us the potential to develop a specific diagnostic tool to monitor the disease’s progression and treatment efficacy.

Esca of grapevine causes yield losses correlated with incidence and severity symptom expression. Factors associated with leaf symptom mechanisms are yet to be fully clarified. Therefore, in 2019 and 2020, macro and microelement analyses and leaf reflectance measurements were carried out on leaves at different growth stages in a vineyard located in Abruzzo, central Italy. Surveys were carried out on leaves of both never leaf-symptomatic vines and different categories of diseased vine shoots. Never leaf-symptomatic and diseased vines were also treated with a fertilizer mixture that proved to be able to limit the symptom expression. Results showed that untreated asymptomatic diseased vines had high calcium contents for most of the vegetative season. On the contrary, treated asymptomatic diseased vines showed higher contents of calcium, magnesium, and sodium, at berries pea-sized, before the onset of symptoms. These vines had better physiological efficiency showing higher water index (WI), normalized difference vegetation index (NDVI), and green normalized difference vegetation index (GNDVI) values, compared to untreated asymptomatic vines, at fruit set. Results confirmed the strong response of the plant to symptom expression development and the possibility of limiting this response with calcium and magnesium applications carried out before the symptom onset.

The worldwide increase in the number and use of agrochemicals impacts nearby soil and freshwater ecosystems. Beyond the excess in applications and dosages, the inadequate management of remnants and the rinsing water of containers and application equipment worsen this problem, creating point sources of pollution. Advanced oxidation processes (AOPs) such as photocatalytic and photo-oxidation processes have been successfully applied in degrading organic pollutants. We developed a simple prototype to be used at farms for quickly degrading pesticides in water solutions by exploiting a UV–H2O2-mediated AOP. As representative compounds, we selected the insecticide imidacloprid, the herbicide terbuthylazine, and the fungicide azoxystrobin, all in their commercial formulation. The device efficiency was investigated through the disappearance of the parent molecule and the degree of mineralization. The toxicity of the pesticide solutions, before and during the treatment, was assessed by Vibrio fischeri and Pseudokirchneriella subcapitata inhibition assays. The results obtained have demonstrated a cost-effective, viable alternative for detoxifying the pesticide solutions before their disposal into the environment, even though the compounds, or their photoproducts, showed different sensitivities to physicochemical degradation. The bioassays revealed changes in the inhibitory effects on the organisms in agreement with the analytical data.

The activity of two zeolitites, differing in the presence of copper and their particle size, was assessed in a Trebbiano d’Abruzzo white berry cultivar, towards grapevine grey mould and sour rot, a serious problem in almost all grapevine-growing areas. In 2018 and 2019, zeolitites were applied before forecast of rainfalls, which likely induce infection. In 2019, further applications were carried out 10 or 2 days before harvest, regardless of the rainfall, in order to verify the effect of the zeolitite residue on leaf reflectance and composition of grapes and wines. Both zeolitites significantly reduced the infections. Only the vines treated 2 days before harvest, especially with copper zeolitite, showed a decrease in leaf reflectance. However, no differences in the yield composition related to the time of zeolitite application, as well as a decrease of yield quality, were ever recorded. Furthermore, analysis of samples collected from vines treated with zeolitites showed increases in grape soluble solids and in wine alcohol content. Our results suggest the use of zeolitites against grapevine rots as a possible effective alternative to the application of synthetic fungicides in the development of environmentally friendly control strategies.

The high mortality rate of colorectal cancer (CRC) patients is directly associated with metastatic dissemination. However, therapeutic options specifically for metastasis are still limited. We previously identified Metastasis-Associated in Colon Cancer 1 (MACC1) as a major causal metastasis-inducing gene. Numerous studies confirmed its value as a biomarker for metastasis risk. We investigated the inhibitory impact of saffron on MACC1-induced cancer cell growth and motility. Saffron crudes restricted the proliferation and migration of MACC1-expressing CRC cells in a concentration- and MACC1-dependent manner. Saffron delays cell cycle progression at G2/M-phase and does not induce apoptosis. Rescue experiments showed that these effects are reversible. Analysis of active saffron compounds elucidated that crocin was the main compound that reproduced total saffron crudes effects. We showed the interaction of MACC1 with the cancer stem cell (CSC) marker DCLK1, which contributes to metastasis formation in different tumor entities. Saffron extracts reduced DCLK1 with crocin being responsible for this reduction. Saffron’s anti-proliferative and anti-migratory effects in MACC1-expressing cells are mediated by crocin through DCLK1 down-regulation. This research is the first identification of saffron-based compounds restricting cancer cell proliferation and motility progression via the novel target MACC1.

Age-related macular degeneration (AMD) is one of the leading causes of visual loss in western countries, it has no cure, and its incidence will grow in the future, for the overall population aging. Albino rats with retinal degeneration induced by exposure to high-intensity light (light-damage, LD) have been extensively used as a model of AMD to test neuroprotective agents. Among them, trophic factors (NGF and BDNF) have been shown to play a significant role in photoreceptors’ survival. Interestingly, cord blood serum (CBS) is an extract full of chemokines and trophic factors; we, therefore, hypothesized that CBS could be an excellent candidate for neuroprotection. Here, we investigate whether CBS-based eye drops might mitigate the effects of light-induced retinal degeneration in albino rats. CBS treatment significantly preserved flash-electroretinogram (f-ERG) response after LD and reduced the “hot-spot” extension. Besides, CBS-treated animals better preserved the morphology of the outer nuclear layer, together with a reduction in microglia migration and activation. Interestingly, the treatment did not modulate reactive gliosis and activation of the self-protective mechanism (FGF2). In conclusion, our results suggest that CBS-based eye drops might be successfully used to mitigate retinal neurodegenerative processes such as AMD.

Grapevine leaf stripe disease (GLSD) is the most important syndrome of the esca disease complex. GLSD foliar symptoms are associated with grapevine yield losses and decline in vigour of host plants. Relationship between incidence and severity of GLSD symptoms and reductions grape quantity and quality has been demonstrated. In 2010–2012, foliar applications of mixtures of fertilizers based on calcium, magnesium and seaweed reduced symptom expression and increased yield quantity and quality. In the present study, mixture applications were carried out in 2013-2015 in different vineyards located in Abruzzo and Emilia-Romagna Regions (north-central Italy). These treatments reduced GLSD symptom incidence and severity, and applications of seaweed without calcium and magnesium was not effective. This confirmed involvement of the nutrients in the reduction of leaf symptom expression. Mechanical properties and absorbance difference measurements demonstrated increased berry quality from vines treated with the mixture. In trials carried out in 2015, the efficacy of the mixture applied in tank mix with other pest and disease control products was not reduced. We conclude that applications of calcium, magnesium and seaweed mixtures are effective for reducing the impacts of GLSD in vineyards.

A protocol is offered as a guideline for managers of rootstock mother grapevines, and as a potential research framework for to reduce infections by Grapevine Trunk Disease (GTD) pathogens in rootstock mother vines and cuttings. Latent infections by GTD pathogens in rootstock cuttings are a major source of the pathogens in grafted nursery vines and subsequently in new vineyards. The many pruning cuts made at the crowns of mother vines predispose them to infection which is transmitted to the new shoots via the xylem. Direct penetration by epiphytic inoculum on the bark of the shoots/canes can also occur. Mother vines with unprotected pruning wounds are typically heavily infected, particularly if they are not trellised. Availability of pruning wound treatments is limited in many countries. The spread of GTD pathogen inoculum can be reduced by avoiding sprinkler and flood irrigation, by trellising mother vines so that canopies are off the soil, and by spraying fungicides or painting wounds immediately after canes are harvested. Frequent trunk renewal aids in reducing inoculum. Cuts should be made to retain long internodes on the mother vines, cuttings should not contact the soil and pruning debris should be promptly destroyed. Cutting implements should be disinfested regularly and cuttings should be dipped in a registered fungicide or sterilant. Soaking cuttings increases fungal populations in the basal wounds and softens the bark, favouring penetration by pathogen inoculum. Dormant bench grafting in nurseries produces more GTD-symptomatic vines than field chip budding, so improved management for rootstock mother vines is more important where dormant cuttings are bench grafted. GTD epidemiology in source blocks is summarised, and best practice protocols for mother vine management and pre-grafting stages of propagation are suggested. Similar principles could be applied to scion mother vine management.

Two vineyards in the Abruzzo Region, central Italy, affected by grapevine leaf stripe disease (GLSD), were monitored for incidence and severity of foliar symptoms of the disease for 21 consecutive years (1994 to 2014). Each year, rainfall and temperature were recorded. Correlations between symptom incidence or severity and rainfall or temperature of different periods of the year or single months were assessed. July rainfall and temperature were highly correlated with incidence and severity of leaf symptoms. The vineyards were characterized by high longevity, vigour and yields, and a particular dynamic of GLSD. In the period following 2005, the year of peak vine mortality, there was a decrease of the expression of foliar symptoms, which was not correlated with both of the climate parameters. Greater mortality occurred for vines showing severe symptoms at the first appearance of GLSD than for vines with low severity.

Purpose. To report data which happened to be observed in two glaucoma patients treated with Cord Blood Serum (CBS) eye drops. Design. A case report and retrospective data analysis. Methods. CBS topical eye drops, characterized in advance for growth factors (GFs) content, were administered for two months with the aim to relieve their subjective symptoms, in two patients who had referred ocular surface discomfort, although in absence of any sign of keratopathy. As patients were also affected by advanced glaucoma at risk of vision loss and under treatment with hypotensive drugs, they had been also monitored over the same period with IOP controls and visual field tests in our unit. Results. During subsequent visits, data from Mean Deviation and Pattern Standard Deviation in the visual fields were retrospectively collected and compared with before and after treatment with CBS, and an amelioration was observed. Conclusions. CBS contains a combination of GFs, which potentially exert a neuroprotective action and elect CBS as an interesting natural source to be delivered in neurodegenerative ocular disorders. The incidentally observed amelioration in these two patients deserves further investigation in this respect.

Grapevine leaf stripe disease (GLSD) is a tracheomycosis caused by Phaeomoniella chlamydospora and Phaeoacremonium minimum. Impacts on yields of grapes were correlated with the incidence and severity of GLSD symptoms on vine canopies. In 2012 and 2013, vines in two vineyards were treated with nine applications of a mixture of leaf fertilizers containing calcium, magnesium and seaweed extracts. At different growth stages, leaves were sampled from treated and control plots of healthy, GLSD-asymptomatic, or GLSD-symptomatic vines and contents were measured of the phytoalexins trans-resveratrol, trans-ε-viniferin, trans-δ-viniferin and trans-pterostilbene. Grape ripening was also monitored from veraison to harvest during both vintages. The treatments caused significant reductions in canopy symptom expression. Increased phytoalexin contents were measured from ‘fruit set’ to ‘berries developing colour’ stages. Trans-resveratrol peak was recorded in asymptomatic diseased vines at the ‘berries pea-sized’ stage, and trans-ε-viniferin and trans-δ-viniferin increased at the ‘berries beginning to touch’ stage, compared to the contents recorded in untreated asymptomatic vines. From ‘berries developing colour’ to harvest, all treated vines had lower amounts of phytoalexins than the control ones. At harvest, treated healthy and symptomatic vines produced berries with similar amounts of total sugars compared to untreated vines. Treated asymptomatic vines produced berries with greater amounts of total sugars compared to the untreated vines. These results indicate that increased phytoalexin content recorded from ‘fruit set’ to ‘berries beginning to touch’ in asymptomatic vines treated with the mineral/seaweed mixture may reduce symptoms of GLSD.

Grapevine leaf stripe disease (GLSD) is one of the most common diseases in the esca complex. Losses in grape yields and quality caused by GLSD are correlated with the severity of the leaf symptoms. The time course of phytoalexin levels was examined in vine leaves of two vineyards, in leaves of healthy, asymptomatic/diseased and symptomatic vines. Symptomatic leaves were further divided into four categories according to symptom severity: 1, 5% chlorosis; 2, 20% chlorosis; 3, 40% leaf surface covered with tiger stripes; or 4, 65% leaf surface covered with tiger stripes. Leaves were sampled at three growth stages: ‘berries beginning to touch’; ‘berries developing colour’; and ‘berries ripe for harvesting’. The phytoalexins trans-resveratrol, trans-ε-viniferin; trans-δ-viniferin; and trans-pterostilbene were detected and assayed. Patterns of each of the phytoalexins were similar at each growth stage to those found earlier for trans-resveratrol, with an increased phytoalexin levels with increasing leaf symptom severity on the leaf blade, especially at the stages ‘berries beginning to touch’ and ‘berries ripe for harvest’. A laboratory test was also carried out. Petioles of healthy grapevine leaves were immersed in culture filtrates of Phaeomoniella chlamydospora and then dipped in solutions of trans-resveratrol or trans-pterostilbene to assess the effects of these substances on the leaf blades. Adding these phytoalexins did not influence the effects of P. chlamydospora. These results indicated that phytoalexins increased in the leaves after GLSD symptoms appeared, and not before host response (phytoalexin synthesis) to control symptom development.

Developing neuronal systems intrinsically generate coordinated spontaneous activity that propagates by involving a large number of synchronously firing neurons. In vivo, waves of spikes transiently characterize the activity of developing brain circuits and are fundamental for activity-dependent circuit formation. In vitro, coordinated spontaneous spiking activity, or network bursts (NBs), interleaved within periods of asynchronous spikes emerge during the development of 2D and 3D neuronal cultures. Several studies have investigated this type of activity and its dynamics, but how a neuronal system generates these coordinated events remains unclear. Here, we investigate at a cellular level the generation of network bursts in spontaneously active neuronal cultures by exploiting high-resolution multielectrode array recordings and computational network modelling. Our analysis reveals that NBs are generated in specialized regions of the network (functional neuronal communities) that feature neuronal links with high cross-correlation peak values, sub-millisecond lags and that share very similar structural connectivity motifs providing recurrent interactions. We show that the particular properties of these local structures enable locally amplifying spontaneous asynchronous spikes and that this mechanism can lead to the initiation of NBs. Through the analysis of simulated and experimental data, we also show that AMPA currents drive the coordinated activity, while NMDA and GABA currents are only involved in shaping the dynamics of NBs. Overall, our results suggest that the presence of functional neuronal communities with recurrent local connections allows a neuronal system to generate spontaneous coordinated spiking activity events. As suggested by the rules used for implementing our computational model, such functional communities might naturally emerge during network development by following simple constraints on distance-based connectivity.

Both age related macular degeneration (AMD) and light induced retinal damage share the common major role played by oxidative stress in the induction/progression of degenerative events. Light damaged (LD) rats have been widely used as a convenient model to gain insight into the mechanisms of degenerative disease, to enucleate relevant steps and to test neuroprotectants. Among them, saffron has been shown to ameliorate degenerative processes and to regulate many genes and protective pathways. Saffron has been also tested in AMD patients. We extended our analysis to a possible additional effect regulated by saffron and compared in AMD patients a pure antioxidant treatment (Lutein/zeaxanthin) with saffron treatment. Methods: Animal model. Sprague-Dawley (SD) adult rats, raised at 5 lux, were exposed to 1000 lux for 24 h and then either immediately sacrificed or placed back at 5 lux for 7 days recovery period. A group of animals was treated with saffron. We performed in the animal model: (1) SDS-PAGE analysis; (2) Western Blotting (3) Enzyme activity assay (4) Immunolabelling; in AMD patients: a longitudinal open-label study 29 (±5) months in two groups of patients: lutein/zeaxanthin (19) and saffron (23) treated. Visual function was tested every 8 months by ERG recordings in addition to clinical examination. Results: Enzymatic activity of MMP-3 is reduced in LD saffron treated retinas and is comparable to control as it is MMP-3 expression. LD treated retinas do not present “rosettes” and microglia activation and migration is highly reduced. Visual function remains stable in saffron treated AMD patients while deteriorates in the lutein/zeaxanthin group. Conclusion: Our results provide evidence of an additional way of action of saffron treatment confirming the complex nature of neuroprotective activities of its chemical components. Accordingly, long term follow-up in AMD patients reveals an added value of saffron supplementation treatment compared to classical antioxidant protocol.

Vineyards containing vines affected with grapevine leaf stripe disease (GLSD), one of the diseases of the esca complex, suffer losses in grape yield and quality every growing season. To examine the relation between GLSD foliar symptoms and levels of phytoalexins in grapevine, phytoalexin levels were monitored in the leaves of symptomatic, asymptomatic/diseased, and healthy grapevine leaves, at various growth stages, in two vineyards in Italy, over four growing seasons. At the same time, the leaf symptoms of the vines at some of those growth stages were recorded in each vineyard and in each growing season. The compounds extracted and identified were: trans-resveratrol, trans-pterostilbene, trans-ε-viniferin and trans-δ-viniferin. The most common phytoalexin found was resveratrol. Amounts of all the phytoalexins were generally greater in symptomatic leaves than in asymptomatic/diseased or healthy leaves. In symptomatic leaves, resveratrol levels were greatest at pre-bunch closure, and peaks in pterostilbene occurred at the same time. Leaves of each category (symptomatic, asymptomatic/diseased, healthy) had lower amounts of these compounds at veraison and generally higher amounts at the stages of harvesting and/or the softening of berries. It seems therefore that the formation and pattern over time of the phytoalexins was linked to the growth stage of the vines. Leaf symptoms never occurred before pre-bunch closure, but became much more common from veraison to harvest. This study provides evidence of a relationship between the levels of phytoalexins, grapevine growth stage, and the seasonal pattern of development of GLSD symptoms.

Foliar symptoms of grapevine leaf stripe disease (GLSD, a disease within the esca complex) are linked to drastic alteration of photosynthetic function and activation of defense responses in affected grapevines several days before the appearance of the first visible symptoms on leaves. The present study suggests a methodology to investigate the relationships between high-resolution multispectral images (0.05 m/pixel) acquired using an Unmanned Aerial Vehicle (UAV), and GLSD foliar symptoms monitored by ground surveys. This approach showed high correlation between Normalized Differential Vegetation Index (NDVI) acquired by the UAV and GLSD symptoms, and discrimination between symptomatic from asymptomatic plants. High-resolution multispectral images were acquired during June and July of 2012 and 2013, in an experimental vineyard heavily affected by GLSD, located in Tuscany (Italy), where vines had been surveyed and mapped since 2003. Each vine was located with a global positioning system, and classified for appearance of foliar symptoms and disease severity at weekly intervals from the beginning of each season. Remote sensing and ground observation data were analyzed to promptly identify the early stages of disease, even before visual detection. This work suggests an innovative methodology for quantitative and qualitative analysis of spatial distribution of symptomatic plants. The system may also be used for exploring the physiological bases of GLSD, and predicting the onset of this disease.

Background: Physical training is believed the primary treatment of claudication symptoms. Although exercise therapy is self-effective, some drugs improving functional capacity have additive effects. TASC (Trans Atlantic Society Consensus) considers Propionil-L-Carnitine (PLC) and prostaglandin-E1 (PGE1) as poorly studied drugs with potential benefits in improving claudication. This retrospective, observational study was performed to compare the efficacy of PGE1 and PLC, and to evaluate both the immediate results of an intensive, short-course rehabilitation program and the outcome at one year follow-up. Methods: Twenty-five patients with severe-moderate claudication were selected. All patients were subjected to an intensive, supervised exercise program for 4 weeks in combination with either PGE1 (10 patients) or PLC (15 patients). Drugs were infused i.v. before every exercise session: 60 μg PGE1 within 2 hours and 600 mg PLC within 10 minutes. Patients were trained with the same supervised treadmill walking-exercise program. At the end of the rehabilitation period, patients were instructed to keep walking (advised home exercise). Initial claudication distance (ICD) and absolute claudication distance (ACD) were evaluated during a constant treadmill test (3 km/hour speed, 10% grade) at entry, after 4 weeks and at one year follow-up. A patient was considered as no-responder if his/her improvement in ACD was

In Mediterranean environments the adoption of Conservation Agriculture (CA) would allow growers to achieve environmental, agronomic and economic sustainability. We investigated the effect of different combination of crop establishment treatments and crop sequence (conventional tillage (CT) and durum wheat monocropping (WW); conventional tillage (CT) and durum wheat following faba beans (WF); zero tillage (ZT) and durum wheat monocropping (WW); zero tillage (ZF) and durum wheat following faba beans (WF) on yield, grain quality traits as well as on disease incidence and severity in durum wheat (var. Saragolla). The results of two years of data of a long-term experiment (seven-year experiment; split-plot design) are discussed. The CA approach (ZT + WF), which always induced the highest grain yields (6.1 t ha−1 and 3.3 t ha−1 in 2016 and 2017) thanks to an increased number of spikes m−2 (296 vs. 269 and 303 vs. 287 spikes m−2 in 2016 and 2017, respectively) as well as a more pronounced ear length, demonstrated significantly positive influences in terms of grain quality. It promoted grain protein accumulation (12.1% for ZT + WF vs. 11.4% for ZT + WW and 12.4% for ZT + WF vs. 10.6% for ZT + WW in 2016 and 2017) and improved the gluten quality (in terms of sodium dodecyl sulphate (SDS) sedimentation test) and colour of the grain. The abundance of crop residues determined a higher incidence and severity of Zymoseptoria tritici leaf symptoms under the CA system; nevertheless, the late appearance of infection was the main reason for not affecting yield and quality traits. The presence of faba beans (WF) in the rotation significantly reduced leaf symptoms in Z. tritici.

Experimental studies demonstrated that saffron (Crocus sativus) given as a dietary supplement counteracts the effects of bright continuous light (BCL) exposure in the albino rat retina, preserving both morphology and function and probably acting as a regulator of programmed cell death [1]. The purpose of this study was to ascertain whether the neuroprotective effect of saffron on rat retina exposed to BCL is associated with a modulation of the endocannabinoid system (ECS). To this aim, we used eight experimental groups of Sprague-Dawley rats, of which six were exposed to BCL for 24 hours. Following retinal function evaluation, retinas were quickly removed for biochemical and morphological analyses. Rats were either saffron-prefed or intravitreally injected with selective type-1 (CB1) or type-2 (CB2) cannabinoid receptor antagonists before BCL. Prefeeding and intravitreally injections were combined in two experimental groups before BCL. BCL exposure led to enhanced gene and protein expression of retinal CB1 and CB2 without affecting the other ECS elements. This effect of BCL on CB1 and CB2 was reversed by saffron treatment. Selective CB1 and CB2 antagonists reduced photoreceptor death, preserved morphology and visual function of retina, and mitigated the outer nuclear layer (ONL) damage due to BCL. Of interest, CB2-dependent neuroprotection was more pronounced than that conferred by CB1. These data suggest that BCL modulates only distinct ECS elements like CB1 and CB2, and that saffron and cannabinoid receptors could share the same mechanism in order to afford retinal protection.

A questionnaire covering all aspects of grapevine propagation including cultural and sanitation practices in mother blocks and harvest and transport of cuttings from mother blocks to nurseries, nursery operations and field nursery management, was mailed to all Management Committee members of the European COST Action FA1303 “Sustainable Control of Grapevine Trunk Diseases” for distribution to the identifiable nurseries in each European country. The main objective was to develop understanding of the current propagation practices and to identify those likely to have the greatest impacts on the quality of planting material, especially with regard to the control measures used against fungal trunk pathogen infections. The questionnaire was sent to 666 vine nurseries, and 146 replies were received (21.9% response rate) The study identified several risks factors which could increase infection by fungal trunk pathogens during the propagation processes, as well as a clear need for further research into the effects of treatments on grapevine viability, including hot water treatment, and the potential of biological agents and other strategies such as ozonation to control grapevine trunk diseases in nurseries.

The first target of any therapy for retinal neurodegeneration is to slow down the progression of the disease and to maintain visual function. Cerium oxide or ceria nanoparticles reduce oxidative stress, which is known to play a pivotal role in neurodegeneration. Our aim was to investigate whether cerium oxide nanoparticles were able to mitigate neurodegeneration including microglial activation and related inflammatory processes induced by exposure to high intensity light. Cerium oxide nanoparticles were injected intravitreally or intraveinously in albino Sprague-Dawley rats three weeks before exposing them to light damage of 1000 lux for 24 h. Electroretinographic recordings were performed a week after light damage. The progression of retinal degeneration was evaluated by measuring outer nuclear layer thickness and TUNEL staining to quantify photoreceptors death. Immunohistochemical analysis was used to evaluate retinal stress, neuroinflammatory cytokines and microglial activation. Only intravitreally injected ceria nanoparticles were detected at the level of photoreceptor outer segments 3 weeks after the light damage and electoretinographic recordings showed that ceria nanoparticles maintained visual response. Moreover, this treatment reduced neuronal death and "hot spot" extension preserving the outer nuclear layer morphology. It is noteworthy that in this work we demonstrated, for the first time, the ability of ceria nanoparticles to reduce microglial activation and their migration toward outer nuclear layer. All these evidences support ceria nanoparticles as a powerful therapeutic agent in retinal neurodegenerative processes.

Grapevine leaf stripe disease (GLSD) seriously reduces the quality and quantity of grape production, and results in a shorter lifespan of vineyards. Recent research has shown that foliar applications of nutrients influence the development of GLSD foliar symptoms. Based on this knowledge the effect of foliar applications of a mixture of calcium chloride, magnesium nitrate and Fucales seaweed extract on the development of leaf symptoms was evaluated over a 3-year period from 2010 to 2012. Nine foliar applications of the full mixture and its individual mineral components, also in different combinations, were tested in three different vineyards, one of cv. Trebbiano d’Abruzzo and two of cv. Montepulciano d’Abruzzo in the Teramo province (Abruzzo, Italy). Treatments were applied every 10 days from the beginning of vegetative growth to pre-bunch closure. The final results were similar in all the three vineyards and in the three years leading to a significant reduction of symptom development in the vines treated with the full mixture, while lower effects were obtained by applying partial combinations or single components. Both quantity and quality of grapes from the treated vines increased, while no phytotoxic or other unwanted effects on grape growth were detected. Vines treated with the full mixture showed an increase in trans-resveratrol and flavonoids content, and a higher accumulation of calcium oxalate in crystal druses in the leaf mesophyll. These data can be a useful base to set up a control strategy against GLSD and give some input for better understanding the mechanisms involved in foliar symptom expression in GLSD.

Esca of grapevine is a fungal disease with a complex aetiology that is common in almost all regions of the world where grapes are cultivated. Despite much research, no effective control of the disease has been found. We investigated possible activity of fosetyl-aluminium (fosetyl-Al), an active ingredient in many fungicides against downy mildew, to inhibit development of esca in grapevine and the main pathogens linked to the disease, Phaeomoniella chlamydospora (Pch) and Phaeoacremonium aleophilum (Pal). In greenhouse experiments conducted on vines artificially inoculated with Pch or Pal, we found a reduction in necrosis in the woody tissue. In field experiments conducted over several years statistically significant reductions in the annual and cumulative incidence of the disease symptoms, and in cumulative vine mortality, were seen. The effect of fosetyl-Al treatments on leaf gas exchange, levels of resveratrol and å-viniferin in the wood, and enzymatic activities were also studied. Hypotheses regarding the mechanism of action of fosetyl-Al against esca are outlined, and the possible use of products containing the chemical, applied on foliage to control downy mildew, is discussed as a strategy for control of esca.

An experimental formulation based on copper oxychloride and gluconates, which is able to penetrate vine foliar tissue, was tested for wood treatment against some of the fungi involved in the diseases included in the esca disease complex. In vitro trials were carried out to: i) test the effect of the formulationon the mycelial growth rate of Phaeomoniella chlamydospora (Pch), Phaeoacremonium aleophilum (Pal) and Fomitiporia mediterranea (Fmed), and on the conidial germination of Pch and Pal; and ii) conduct a preliminaryinvestigation of the presence of the copper formulation on the ability of Pal to produce toxic metabolites. Trials were also conducted on potted vines to i) measure copper penetration into the trunk of potted vines using atomic absorption spectrophotometry; and ii) test the effect of the copper formulation on colonization ofthe fungus in trunks. Finally, the copper formulation was field-tested in vineyards showing leaf stripe. The implications of the tests in the control of the esca disease complex are discussed.

An examination was carried out under laboratory conditions to determine whether resveratrol, pterostilbene and mixtures of each stilbene with phosphorous acid had an inhibitory activity against some fungi involved in esca: Phaeoacremonium aleophilum, Phaeomoniella chlamydospora, Libertella blepharis (anamorph of Eutypa lata), Fomitiporia punctata and Stereum hirsutum. An inhibition of mycelial growth by resveratrol was not found but there was a clear correlation between pterostilbene concentration and reduction of radial growth confirming the antifungal activity of this phytoalexin. Although phosphorous acid proved to be generally ineffective, an increase of antifungal activity of stilbenes in the mixtures was observed with all fungi except F. punctata. The possible relation between fungal phenol oxidase activity and inhibition by mixtures of stilbenes and phosphorous acid was discussed.

The development of an effective control strategy for esca greatly depends on major progress in understanding the disease biology and epidemiology. Experimental trials were carried out in vineyards and single infected vines in order to evaluate the effectiveness of different fungicides, application methods and cultural practices in controlling esca: experiences with sodium arsenite, dinitro-orthocresol, fosetyl Al, triazoles and first attempts with Trichoderma are discussed. Ongoing trials show promising results with fosetyl Al activity against Phaeoacremonium spp. under laboratory and greenhouse conditions, with the prospect of a favourable effect on esca control. Research is now being focused on the potential of a control strategy to prevent or reduce the establishment and development of the disease. The management of esca should be based on the age of the plant, the stage of the infection as well as the degree of spread of the disease.