INNOVATION AND PLANT VARIETY PROTECTION IN THE EUROPEAN UNION: THE CASE OF CEREAL VARIETIES. AN EMPIRICAL LEGAL STUDY

Lo scopo della presente ricerca \ue8 quello di comprendere se e, nel caso, come la la privativa comunitaria per ritrovati vegetali sta promuovendo l\u2019innovazione tra le variet\ue0 cerealicole nell\u2019industria dell\u2019Unione Europea. La ricerca mira ad analizzare il quadro normativo del contesto scelto, in combinazione con l\u2019utilizzo di dati empirici. Il presente studio ha avuto origine da una ricerca sia accademica che applicata, quest\u2019ultima condotta all\u2019interno di una piccola-media impresa italiana che si occupa di ricerca e commercializzazione di sementi per l\u2019agricoltura, in particolar modo cereali. La sinergia dello studio accademico e applicato ha significativamente influenzato la scelta della metodologia empirico-legale per la presente ricerca. L\u2019innovazione rappresenta lo Zeitgeist della societ\ue0 contemporanea e ha il ruolo di rispondere alle sfide del terzo millennio. In questo contesto, la sicurezza alimentare sar\ue0 certamente una delle pi\uf9 grandi sfide globali da affrontare nei prossimi anni, a causa del previsto aumento della popolazione mondiale e del conseguente aumento della domanda di cibo. L\u2019agricoltura deve dunque essere in grado di incrementare e migliorare la sua produttivit\ue0, come pure di affrontare il cambiamento climatico e l\u2019efficiente gestione delle risorse. Alla luce di ci\uf2, il miglioramento genetico pu\uf2 certamente giocare un ruolo cruciale. Lo sviluppo di nuove variet\ue0 vegetali permette di migliorare la produttivit\ue0, di ottenere una migliore resistenza a patogeni e malattie, di diminuire la pressione delle attivit\ue0 agricole sull\u2019ambiente circostante, di migliorare l\u2019apporto nutritivo degli alimenti, e di facilitare l\u2019adattamento della pianta agli stress ambientali. Il miglioramento genetico non \ue8 rilevante solo per la sicurezza alimentare ma altres\uec per la sostenibilit\ue0 delle attivit\ue0 agricole poich\ue9 permette un minore impiego di prodotti chimici e un uso efficiente delle risorse naturali. Inoltre, la creazione di nuove variet\ue0 vegetali permette di ridurre la vulnerabilit\ue0 genetica delle piante poich\ue9 ne aumenta la diversit\ue0 genetica. In questo contesto, promuovere le attivit\ue0 di miglioramento genetico nel settore cerealicolo ha un ruolo fondamentale nell\u2019Unione Europea. Prima di tutto perch\ue9 la produzione agricola mondiale \ue8 costituita per larga parte da cereali, i quali rappresentano la base dell\u2019alimentazione umana. Inoltre, l\u2019Unione Europea \ue8 leader mondiale nella produzione cerealicola, in particolar modo di grano tenero. Oltretutto, la FAO afferma che i cereali sono oggetto di un\u2019allarmante erosione genetica: almeno trenta paesi hanno riportato episodi di erosione genetica avente ad oggetto variet\ue0 di cereali. Tuttavia, il miglioramento genetico richiede molto tempo e un grande dispendio di risorse economiche, naturali e umane per essere condotto in maniera efficiente. Questa \ue8 la ragione per cui sono stati promossi sistemi di protezione delle nuove variet\ue0 vegetali attraverso il conferimento di uno specifico diritto di propriet\ue0 intellettuale al costitutore della nuova variet\ue0 vegetale, al fine di ricompensare l\u2019inventore per l\u2019investimento fatto e, di conseguenza, stimolare ulteriore innovazione tra le variet\ue0 vegetali

Mechanical Complications of Myocardial Infarction

Complications of acute myocardial infarction are different and life threatening. Prompt diagnosis and therapy are essential. In this, chapter we will analyse mechanical complications, such as ventricular free wall rupture, ventricular septal defect, papillary muscle rupture, ischaemic mitral regurgitation, left ventricle aneurysm, and cardiogenic shock

Chapter Development of an innovative methodology to define patient-designed quality of life: a new version of a wellknown concept in healthcare

Patient quality of life (QoL) is a pivotal parameter, which is often used by clinicians to evaluate how treatments and therapies influence patients’ functionality and emotional state, aiming to ameliorate interventions and their outcomes. Currently, the majority of questionnaires assessing the QoL are designed with the main contribution of clinicians and, therefore, include items that are cantered on the disease rather than on its multifaceted impact on people’s life. The failure to truly grasp the patients’ perspective, their needs, aspirations, perceptions and emotional state, is a major drawback that sets medical care on clinical parameters alone. We aimed to bridge this gap by establishing an innovative patient-designed QoL index to provide a new, unbiased tool considering the patients’ perception of their own well-being. Based predominantly on patients’ contribution, we defined specific areas (physical, emotional, social, functional, economical) and the respective characterizing features, and applied a pseudo-Delphi methodology combined with customer-satisfaction techniques. For each feature, the degree of agreement and the importance were assessed on a Likert scale. A synthetic QoL index was created by weighting the importance of each item. The methodology tested led to the development of a valid patient-designed QoL index, providing a way forward that could potentially be applied to many different conditions. The areas and the features included are indeed common to all patients, irrespective of their disease. We found that the process of methodology development enhanced the patients’ awareness of their subjective experience with the disease, and enabled them to better present their situation to the clinicians. The patient-designed QoL index provides a descriptive model that can be helpful to patients, clinicians and third parties and that can be further integrated with clinical details to obtain an overall view of the course of treatment for each patient

The zebrafish/tumor xenograft angiogenesis assay as a tool for screening anti-angiogenic miRNAs

The zebrafish/tumor xenograft angiogenesis assay is used to approach tumor angiogenesis, a pivotal step in cancer progression and target for anti-tumor therapies. Here, we evaluated whether the assay could allow the identification of microRNAs having an anti-angiogenic potential. For that, we transfected DU-145 prostate cancer cells with four microRNAs (miR-125a, miR-320, miR-487b, miR-492) responsive to both anti- and pro-angiogenic stimuli applied to human umbilical vein endothelial cells. After transfection, DU-145 cells were injected close to the developing subintestinal vessels of transgenic Tg(Kdrl:eGFP)s843 zebrafish embryos that express green fluorescent protein under the control of Kdrl promoter. At 72 h post-fertilization, we observed that green fluorescent protein–positive neo-vessels infiltrated the graft of DU-145 transfected with miR-125a, miR-320, and miR-487b. Vice versa, neo-vessel formation and tumor cell infiltration were inhibited when DU-145 cells transfected with miR-492 were used. These results indicated that the zebrafish/tumor xenograft assay was adequate to identify microRNAs able to suppress the release of angiogenic growth factors by angiogenic tumor cells

A Novel Study and Meta-Analysis of the Genetic Variation of the Serotonin Transporter Promoter in the Italian Population Do Not Support a Large Effect on Alzheimer's Disease Risk

Alzheimer's disease (AD) is a neurodegenerative disorder whose clinical onset is mainly characterized by memory loss. During AD progression, behavioral and psychological symptoms of dementia (BPSD) frequently occur. In this paper we evaluated the association between AD and the short/long (S/L) functional polymorphism of the promoter region of the 5-hydroxytryptamine (5-HT) transporter gene (SLC6A4). The S-allele shows a 2-fold reduced transcriptional rate, causing an imbalance in 5-HT intracellular availability that might in turn trigger behavioral and cognitive alterations. We also genotyped the SLC6A4 promoter functional variant rs25531 (A → G). By comparing the genotypic and allelic frequencies in an Italian population of 235 AD and 207 controls, we found an association between 5-HTTLPR and AD (odds ratio for the L-allele versus the S-allele: 0.74, associated P value = .03), while no difference was found for the rs25531. A meta-analysis of studies in Italy assessing 5-HTTLPR and AD risk gave an estimation of odds ratio for the L-allele versus the S-allele of 0.85 (associated P value = .08). Overall, our findings are not supportive of a large genetic effect of the explored polymorphisms on AD risk

ATP7B Variants as Modulators of Copper Dyshomeostasis in Alzheimer's Disease

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Protein kinase B/AKT isoform 2 drives migration of human mesenchymal stem cells.

This study was designed to investigate the migratory behavior of adult human mesenchymal stem cells (MSC) and the underlying mechanism. Cell migration was assessed by transwell, wound healing and time-lapse in vivo motility assays. Pharmacological inhibitors were used to determine the potential mechanism responsible for cell migration and invasion. The tests that were implemented revealed that MSC were fairly migratory. Protein kinase B (AKT) was strongly activated at the basal level. Through our analyses we demonstrated that pharmacological inactivation of AKT2 but not AKT1 significantly decreased cell migration and invasion. Although preliminary, collectively our results indicate that AKT2 activation plays a critical role in enabling MSC migration

Association between the c. 2495 A>G ATP7B Polymorphism and Sporadic Alzheimer's Disease

Nonceruloplasmin-bound copper (“free”) is reported to be elevated in Alzheimer's disease (AD). In Wilson's disease (WD) Cu-ATPase 7B protein tightly controls free copper body levels. To explore whether the ATP7B gene harbours susceptibility loci for AD, we screened 180 AD chromosomes for sequence changes in exons 2, 5, 8, 10, 14, and 16, where most of the Mediterranean WD-causing mutations lie. No WD mutation, but sequence changes corresponding to c.1216 T>G Single-Nucleotide Polymorphism (SNP) and c.2495 A>G SNP were found. Thereafter, we genotyped 190 AD patients and 164 controls for these SNPs frequencies estimation. Logistic regression analyses revealed either a trend for the c.1216 SNP (P = .074) or a higher frequency for c.2495 SNP of the GG genotype in patients, increasing the probability of AD by 74% (P = .028). Presence of the GG genotype in ATP7B c.2495 could account for copper dysfunction in AD which has been shown to raise the probability of the disease

A new case report of severe mucopolysaccharidosis type VII: diagnosis, treatment with haematopoietic cell transplantation and prenatal diagnosis in a second pregnancy

A new patient with severe mucopolysaccharidosis (MPS) type VII is reported. Non-immune hydrops fetalis (NIHF) was diagnosed during pregnancy. At birth, he showed generalized hydrops and dysmorphic features typical of MPS. Many diagnoses were excluded before reaching the diagnosis of MPS VII at 8 months of life. During the first year of life he had frequent respiratory infections associated with restrictive and obstructive bronchopneumopathy and underwent three surgical interventions: decompression of the spinal cord at the craniocervical junction, bilateral inguinal hernia, and bilateral clubfoot. At 14 months of life he underwent successful haematopoietic cell transplantation (HCT). During the following 10 months, his bronchopneumopathy progressively worsened, needing chronic pharmacological treatment and O2 administration. The patient died of respiratory insufficiency during a respiratory syncytial virus infection at 25 months of age. Molecular analysis showed the homozygous variant c.1617C > T, leading to the synonymous mutation p.Ser539=. This caused aberrant splicing with partial skipping of exon 10 (r.1616_1653del38) and complete skipping of exon 9 (r.1392_1476del85; r.1616_1653del38). No transcript of normal size was evident. The parents were both confirmed to be carriers. In a subsequent pregnancy, a prenatal diagnosis showed an affected fetus. Ultrasound examination before abortion showed NIHF. The skin and placenta examination by electron microscopy showed foamy intracytoplasmic vacuoles with a weakly electron-dense substrate. MPS VII is a very rare disease but it is possible that some cases go undiagnosed for several reasons, including that MPS VII, and other lysosomal storage diseases, are not included in the work-up for NIHF in many institutions, and the presence of anasarca at birth may be confounding for the recognition of the typical facial characteristics of the disease. This is the eighth patient affected by MPS VII who has undergone HCT. It is not possible to draw conclusions about the efficacy of HCT in MPS VII. Treatment with enzyme replacement is now available and will probably be beneficial for the patients who have a milder form with no or little cognitive involvement. Increased awareness among clinicians is needed for prompt diagnosis and to offer the correct treatment as early as possible

HIV-1 Vif binds to APOBEC3G mRNA and inhibits its translation

The HIV-1 viral infectivity factor (Vif) allows productive infection of non-permissive cells (including most natural HIV-1 targets) by counteracting the cellular cytosine deaminases APOBEC-3G (hA3G) and hA3F. The Vif-induced degradation of these restriction factors by the proteasome has been extensively studied, but little is known about the translational repression of hA3G and hA3F by Vif, which has also been proposed to participate in Vif function. Here, we studied Vif binding to hA3G mRNA and its role in translational repression. Filter binding assays and fluorescence titration curves revealed that Vif tightly binds to hA3G mRNA. Vif overall binding affinity was higher for the 3′UTR than for the 5′UTR, even though this region contained at least one high affinity Vif binding site (apparent Kd = 27 ± 6 nM). Several Vif binding sites were identified in 5′ and 3′UTRs using RNase footprinting. In vitro translation evidenced that Vif inhibited hA3G translation by two mechanisms: a main time-independent process requiring the 5′UTR and an additional time-dependent, UTR-independent process. Results using a Vif protein mutated in the multimerization domain suggested that the molecular mechanism of translational control is more complicated than a simple physical blockage of scanning ribosomes