Agronomic strategies for Sustainable Management of Durum Wheat Cultivation in Mediterranean Area

L’azoto è un elemento nutritivo fondamentale per la produzione di cereali, tuttavia ha un significativo impatto ambientale. Nel presente elaborato vengono valutate diverse pratiche agronomiche al fine di incrementare la sostenibilità della coltivazione del frumento duro, e migliorare la sua produttività e qualità. Gli studi sono stati tutti condotti nell’area del Mediterraneo, definita come una delle regioni maggiormente colpita dai cambiamenti climatici in corso. In quest’area, quindi, la gestione sostenibile dell’azoto diventa ancora più importante. L'obiettivo generale è stato perseguito valutando le risposte di diversi genotipi di frumento duro alla gestione sostenibile della fertilizzazione azotata sia in sistemi produttivi biologici che a basso input. Definire il sistema produttivo agricolo che da solo sia in grado di garantire alla popolazione mondale un'alimentazione sicura e sostenibile è impossibile. Tuttavia, per garantire contemporaneamente l’accesso al cibo e la sostenibilità ambientale, sarà necessario ricorrere a sistemi agricoli innovativi, compresi quelli a basso input e biologici. In conclusione, i risultati descritti in questo elaborato hanno contribuito a far progredire il grado di conoscenza sulla sostenibilità, sulla produttività e su diversi aspetti qualitativi del frumento duro in ambiente mediterraneo. Tuttavia, molte questioni significative restano da indagare e saranno oggetto di futuri studi.Nitrogen is the most requested element in cereal systems and has the most significant impact on the environment. This Ph.D. dissertation deals with different agronomic strategies to improve the sustainability of durum wheat cultivation, together with its productivity and quality. Studies were conducted in the Mediterranean area, de!ned as one of the regions most vulnerable to climatic changes. Since, in this area the efficiently use of nitrogen is more critical. The main objective was pursued evaluating the responses of different durum wheat genotypes to the sustainable management of nitrogen fertilizers in organic and low-input systems. Define the best farming system that alone can satisfy the world safe and sustainable feeding is impossible. However, innovative farming systems, including low-input and organic ones, will be necessary for both food access and ecosystem security. In conclusion, the results described in this Ph.D. advance the current state of the knowledge about improving the sustainability, productivity and different quality aspects of durum wheat under Mediterranean conditions. However, several significant issues remain to be investigated in future research

Towards structure determination of protein-ligand complexes of TrkA and TrkB receptors: from protein production to crystal optimization

Neurotrophins (NGF, BDNF, NT3 and NT4/5) are a family of closely related growth factors, that promote neuronal proliferation, differentiation, survival and apoptosis, as well as formation and modulation of synaptic networks in peripheral and central nervous system. Key mediators of these pleiotropic effects are at one side the tropomyosin kinase receptors (TrkA, TrkB and TrkC), that are selectively and specifically activated by neurotrophins via binding to the d5 sub-domain of the extracellular region, and on the other side p75 neurotrophin receptor, characterized by unspecific and lower affinity interactions that generally lead to death signals. Their pivotal role in development and maintenance of the nervous system has made NT-Trks axes pharmacological targets of great interest to achieve neuroprotective and neurogenic effects in pathological conditions. To address the current lack of therapeutic agents for treating and slowing down neurodegenerative diseases, the “EuroNeurotrophin” (ENT) network aimed to discover new small compounds with neurotrophin-like effects. Within the network, several mimetics with agonist effects on TrkA and TrkB receptors have been developed, but biophysical and structural information is missing. Therefore, key objective of the PhD project was to elucidate the structural features for ligand binding by X-ray crystallography and to integrate such structural information with biophysical characterization of binding affinity values and kinetic profiles, as well as to provide the first structure at high resolution of the complex between BDNF and TrkB extracellular domain. First, efforts focused on developing purification protocols for the production at high yields of the d5 domains of TrkA and TrkB in E. coli expression system. By varying intrinsic proprieties and extrinsic factors affecting the solubility of the recombinant proteins, different constructs of TrkA-d5 and TrkB-d5 were designed and several expression, purification and refolding strategies were tested. Among all, the co-expression approach resulted in increased solubility of the TrkB-d5 and crystallization screens were set up, while a low yield of natively fold TrkA-d5 monomer was obtained by protein recovery and refolding from inclusion bodies, no sufficient for structural studies. Second, the whole extracellular domains of TrkA and TrkB receptors were produced in Hek293 cells suspension, using a glycosidase inhibitor to decrease the complexity and heterogeneity of the N-glycosylation. The recombinant ectodomains were used for crystallization screening and preliminary studies by cryo-electron microscopy, as well as for biophysical characterization of the binding of mimetic compounds by Grating Coupled Interferometry. Showing binding affinity values in micromolar range, two ENT small compounds BNN27 and ENT-C117 were confirmed to be TrkA and TrkB selective ligands, respectively, and ENT-A010 compound to bind with similar affinity both receptors. As regards as the structural studies, both TrkA-NGF and TrkB-BDNF complexes consisted of small and heterogeneous particles, which could not allow a structure reconstruction by Cryo-EM. From the crystallization screening, no diffracting crystals of TrkA and TrkB were obtained. However, several precipitating conditions of TrkA-NGF complex gave rise to needle-like and plate crystals, which were used for microseeding matrix screening, opening up an iterative process that may lead to crystal formation

Strobilurin Effects on Nitrogen Use Efficiency for the Yield and Protein in Durum Wheat Grown under Rainfed Mediterranean Conditions

In wheat, the increase in nitrogen use efficiency (NUE) and optimization of the nitrogen doses to be used are both very important aspects for improving sustainable and productive agriculture. The aim of this study was to investigate, under rainfed Mediterranean conditions, the influence of strobilurin treatment and N fertilization on durum wheat N use efficiency for yield (NUEy) and protein (NUEp) and on the contribution of their components, nitrogen uptake efficiency (UPE) and nitrogen utilization efficiency (NUtE). Two durum wheat cultivars (Saragolla and Sfinge) were grown for two years in field conditions under five nitrogen treatments (60 kg ha−1 N60; 90 and 120 kg ha−1 given two and three times; N90, N90T3, N120 and N120T3) comparing a control without strobilurin treatment (ST0) and one application of strobilurin (STaz). In Sfinge, STaz caused a decrease in UPE and NUEp and an increase in NUtE and NUEy. In Saragolla, the opposite behavior was observed. Moreover, strobilurin positively affected the contribution of UPE and negatively that of NUtE to NUEy only in Saragolla. Furthermore, strobilurin determined higher NUEy and NUEp values under most of the N treatments adopted in the drier year. With this study, we supported the hypothesis that in Mediterranean conditions, the possibility of reducing N rate application from 120 to 90 kg ha−1 with a strobilurin-based treatment, even in the absence of fungal diseases, could represent a useful agronomic strategy for durum wheat grown under drought conditions as those predicted under the ongoing climate change

combined effects of deficit irrigation and strobilurin application on gas exchange yield and water use efficiency in tomato solanum lycopersicum l

Abstract Water is the major factor limiting plant productivity in many regions of the world. The aim of this study was to evaluate the combined effect of deficit irrigation (restitution of 100%, 50% and 0% of plant consumption: WR100, WR50 and WR0, respectively) and strobilurin treatment (no agrochemical added vs azoxystrobin treatment) in two tomato genotypes, IT-22/025, a wild-type plant, and Ikram, a commercial hybrid. Water use efficiency (WUE), physiological, yield and quality parameters and the expression of ERD15, a gene involved in abiotic stress response were evaluated. The two genotypes showed a different behaviour in response to water stress. Stomatal conductance decrease from WR100 to WR50 was in mean 27.5% for IT-22/025 and 44.5% for Ikram. Moreover, in Ikram, water stress decreased transpiration more than assimilation rate, while the opposite occurred in IT-22/025. The ERD15 expression decrease from WR100 to WR50 was higher for IT-22/025. These effects corresponded to higher total fresh fruit yield and WUE for IT-22/025. Strobilurin determined lower stomata conductance, maintaining higher assimilation rate, leading to an increase in WUE in WR0. Finally, strobilurin caused an increase in ERD15 expression only in IT-22/025. This study underlines the possibility to reduce the water used in tomato crop, maintaining acceptable yield and quality, by using agronomic and genetic strategy

Neurodevelopmental Disorders and Suicide: A Narrative Review

Specific risk factors for self-harm and suicide in children and adolescents with neurodevelopmental disorders (NDD) may differ from those in the general population within this age range. In the present review paper, we conducted a narrative analysis of the literature, aiming to establish a connection between suicide and affective disorders in children and adolescents with NDD. Emotion dysregulation (ED) as an individual factor and adverse childhood experiences (ACE) as environmental factors are discussed as risk factors for suicidality in all individuals with NDD. We propose a theoretical model in which ED and ACE can directly lead to self-harm or suicide, directly or indirectly by interacting with depressive spectrum disorders. Additionally, we suggest that specific risk factors are more frequently associated with each of the neurodevelopmental disorders listed in the DSM-V. This review underlines the key points useful to improve the knowledge of the trajectory leading to suicide risk in NDDs with the purpose to facilitate the early identification of the suicide risk

Pharmacological Treatment of Bipolar Depression: A Review of Observational Studies

The persistence of depressive morbidity is frequent in bipolar disorder, and the pharmacological management of this symptomatology often lacks effectiveness. This systematic review aimed to summarize the results of the naturalistic observational studies on the pharmacological treatment of bipolar depression published through April 2022. The certainty of evidence was evaluated according to the GRADE approach. In sum, 16 studies on anticonvulsants, 20 on atypical antipsychotics, 2 on lithium, 28 on antidepressants, and 9 on other compounds were found. Lamotrigine, quetiapine, aripiprazole, and ketamine were the most investigated compounds. Overall, the results support the recommendations regarding the effectiveness of lamotrigine and quetiapine. In contrast to the current recommendations, aripiprazole was shown to be effective and generally well tolerated. Additionally, SSRIs were shown to be effective, but, since they were associated with a possibly higher switch risk, they should be used as an adjunctive therapy to mood stabilizers. Lithium was only studied in two trials but was shown to be effective, although the serum concentrations levels were not associated with clinical response. Finally, ketamine showed divergent response rates with a low certainty of evidence and, so far, unclear long-term effects. Heterogeneity in diagnosis, sample sizes, study designs, reporting of bias, and side effects limited the possibility of a head-to-head comparison

Temporal and design approaches and yield-weather relationships

The climate changes and the weather events affect agricultural production and farmers’ income. Several strategies may help improving the resilience of farms to climate change, and particular mention should be done to the weather index-based crop insurance schemes, as they rely on the yield-weather relationship. A vast majority of studies investigate the limitation of the weather index insurance, due to the complex relationships linking weather events and yields and the difficulty to capture them with an index (i.e., the basis risk). The literature has not devoted sufficient attention to compare different specifications within the same statistical model in yield-weather estimation. Our study, conducted on durum wheat in Italy, shows how the identification (and design) of the phenological stages (i.e., temporal specifications) may help capturing or depicting the yield-weather relationships. The negative effects of the low temperatures, especially during the early stages of durum wheat, is remarkable. Our findings contribute to the debate on the design of triggers in weather indexes (e.g., for minimum temperatures), stimulating new research directions to assist stakeholders interested in planning agricultural risk management interventions

1H-NMR-Based Metabolomics in Autism Spectrum Disorder and Pediatric Acute-Onset Neuropsychiatric Syndrome

We recently described a unique plasma metabolite profile in subjects with pediatric acute-onset neuropsychiatric syndrome (PANS), suggesting pathogenic models involving specific patterns of neurotransmission, neuroinflammation, and oxidative stress. Here, we extend the analysis to a group of patients with autism spectrum disorder (ASD), as a consensus has recently emerged around its immune-mediated pathophysiology with a widespread involvement of brain networks. This observational case-control study enrolled patients referred for PANS and ASD from June 2019 to May 2020, as well as neurotypical age and gender-matched control subjects. Thirty-four PANS outpatients, fifteen ASD outpatients, and twenty-five neurotypical subjects underwent physical and neuropsychiatric evaluations, alongside serum metabolomic analysis with 1H-NMR. In supervised models, the metabolomic profile of ASD was significantly different from controls (p = 0.0001), with skewed concentrations of asparagine, aspartate, betaine, glycine, lactate, glucose, and pyruvate. Metabolomic separation was also observed between PANS and ASD subjects (p = 0.02), with differences in the concentrations of arginine, aspartate, betaine, choline, creatine phosphate, glycine, pyruvate, and tryptophan. We confirmed a unique serum metabolomic profile of PANS compared with both ASD and neurotypical subjects, distinguishing PANS as a pathophysiological entity per se. Tryptophan and glycine appear as neuroinflammatory fingerprints of PANS and ASD, respectively. In particular, a reduction in glycine would primarily affect NMDA-R excitatory tone, overall impairing downstream glutamatergic, dopaminergic, and GABAergic transmissions. Nonetheless, we found metabolomic similarities between PANS and ASD that suggest a putative role of N-methyl-D-aspartate receptor (NMDA-R) dysfunction in both disorders. Metabolomics-based approaches could contribute to the identification of novel ASD and PANS biomarkers

The Impact of Methylphenidate on Pubertal Maturation and Bone Age in ADHD Children and Adolescents: Results from the ADHD Drugs Use Chronic Effects (ADDUCE) Project

Objective: The short-term safety of methylphenidate (MPH) has been widely demonstrated; however the long-term safety is less clear. The aim of this study was to investigate the safety of MPH in relation to pubertal maturation and to explore the monitoring of bone age.// Method: Participants from ADDUCE, a two-year observational longitudinal study with three parallel cohorts (MPH group, no-MPH group, and a non-ADHD control group), were compared with respect to Tanner staging. An Italian subsample of medicated-ADHD was further assessed by the monitoring of bone age.// Results: The medicated and unmedicated ADHD groups did not differ in Tanner stages indicating no higher risk of sexual maturational delay in the MPH-treated patients. The medicated subsample monitored for bone age showed a slight acceleration of the bone maturation after 24 months, however their predicted adult height remained stable.// Conclusion: Our results do not suggest safety concerns on long-term treatment with MPH in relation to pubertal maturation and growth

The Impact of Methylphenidate on Pubertal Maturation and Bone Age in ADHD Children and Adolescents:Results from the ADHD Drugs Use Chronic Effects (ADDUCE) Project

Objective: The short-term safety of methylphenidate (MPH) has been widely demonstrated; however the long-term safety is less clear. The aim of this study was to investigate the safety of MPH in relation to pubertal maturation and to explore the monitoring of bone age.Method: Participants from ADDUCE, a two-year observational longitudinal study with three parallel cohorts (MPH group, no-MPH group, and a non-ADHD control group), were compared with respect to Tanner staging. An Italian subsample of medicated-ADHD was further assessed by the monitoring of bone age.Results: The medicated and unmedicated ADHD groups did not differ in Tanner stages indicating no higher risk of sexual maturational delay in the MPH-treated patients. The medicated subsample monitored for bone age showed a slight acceleration of the bone maturation after 24 months, however their predicted adult height remained stable.Conclusion: Our results do not suggest safety concerns on long-term treatment with MPH in relation to pubertal maturation and growth.</p