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Neurosteroids are pleiotropic molecules involved in various neurodegenerative diseases with neuroinflammation. We assessed neurosteroids’ serum levels in a cohort of Parkinson’s Disease (PD) patients with heterozygous glucocerebrosidase (GBA) mutations (GBA-PD) compared with matched cohorts of consecutive non-mutated PD (NM-PD) patients and healthy subjects with (GBA-HC) and without (NM-HC) GBA mutations. A consecutive cohort of GBA-PD was paired for age, sex, disease duration, Hoehn and Yahr stage, and comorbidities with a cohort of consecutive NM-PD. Two cohorts of GBA-HC and HC were also considered. Clinical assessment included the Movement Disorder Society revision of the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) and the Montreal Cognitive Assessment (MoCA). Serum samples were processed and analyzed by liquid chromatography coupled with the triple quadrupole mass spectrometry. Twenty-two GBA-PD (males: 11, age: 63.68), 22 NM-PD (males: 11, age: 63.05), 14 GBA-HC (males: 8; age: 49.36), and 15 HC (males: 4; age: 60.60) were studied. Compared to NM-PD, GBA-PD showed more hallucinations and psychosis (p < 0.05, Fisher’s exact test) and higher MDS-UPDRS part-II (p < 0.05). Most of the serum neurosteroids were reduced in both GBA-PD and NM-PD compared to the respective control cohorts, except for 5α-dihydroprogesterone. Allopregnanolone was the only neurosteroid significantly lower (p < 0.01, Dunn’s test) in NM-PD compared to GBA-PD patients. Only in GBA-PD, allopregnanolone, and pregnanolone levels correlated (Spearman) with a more severe MDS-UPDRS part-III. Allopregnanolone levels also negatively correlated with MoCA scores, and pregnanolone levels correlated with more pronounced bradykinesia. This pilot study provides the first observation of changes in neurosteroid peripheral levels in GBA-PD. The involvement of the observed changes in the development of neuropsychological and motor symptoms of GBA-PD deserves further attention.

Chronic lymphocytic leukemia (CLL) is a widespread type of leukemia that predominantly targets B lymphocytes, undermining the balance between cell proliferation and apoptosis. In healthy B cells, miR-15/16, a tandem of microRNAs, functions as a tumor suppressor, curbing the expression of the antiapoptotic B cell lymphoma 2 protein (Bcl-2). Conversely, in CLL patients, a recurring deletion on chromosome 13q14, home to the miR15-a and miR16-1 genes, results in Bcl-2 overexpression, thereby fostering the onset of the pathology. In the present research, a novel approach utilizing humanized ferritin-based nanoparticles was employed to successfully deliver miR15-a and miR-16-1 into MEG01 cells, a model characterized by the classic CLL deletion and overexpression of the human ferritin receptor (TfR1). The loaded miR15-a and miR16-1, housed within modified HumAfFt, were efficiently internalized via the MEG01 cells and properly directed into the cytoplasm. Impressively, the concurrent application of miR15-a and miR16-1 demonstrated a robust capacity to induce apoptosis through the reduction in Bcl-2 expression levels. This technology, employing RNA-loaded ferritin nanoparticles, hints at promising directions in the battle against CLL, bridging the substantial gap left by traditional transfection agents and indicating a pathway that may offer hope for more effective treatments.

The detection of burnt areas from satellite imagery is one of the most straightforward and useful applications of satellite remote sensing. In general, the approach relies on a change detection analysis applied on pre- and post-event images. This change detection analysis usually is carried out by comparing the values of specific spectral indices such as: NBR (normalised burn ratio), BAI (burn area index), MIRBI (mid-infrared burn index). However, some potential sources of error arise, particularly when near-real-time automated approaches are adopted. An automated approach is mandatory when the burnt area monitoring should operate systematically on a given area of large size (country). Potential sources of errors include but are not limited to clouds on the pre- or post-event images, clouds or topographic shadows, agricultural practices, image pixel size, level of damage, etc. Some authors have already noted differences between global databases of burnt areas based on satellite images. Sources of errors could be related to the spatial resolution of the images used, the land-cover mask adopted to avoid false alarms, and the quality of the cloud and shadow masks. This paper aims to compare different burnt areas datasets (EFFIS, ESACCI, Copernicus, FIRMS, etc.) with the objective to analyse their differences. The comparison is restricted to the Italian territory. Furthermore, the paper aims to identify the degree of approximation of these satellite-based datasets by relying on ground survey data as ground truth. To do so, ground survey data provided by CUFA (Comando Unità Forestali, Ambientali e Agroalimentari Carabinieri) and CFVA (Corpo Forestale e Vigilanza Ambientale Sardegna) were used. The results confirm the existence of significant differences between the datasets. The subsequent comparison with the ground surveys, which was conducted while also taking into account their own approximations, allowed us to identify the accuracy of the satellite-based datasets.

(1) Background: Cerebellar ataxia with neuropathy and vestibular areflexia syndrome (CANVAS) is characterized by late-onset cerebellar ataxia, bilateral vestibulopathy, and sensory neuronopathy mostly due to biallelic RFC1 expansion. (2) Objectives: The aim of this case series is to describe vestibular, gait, and speech alterations in CANVAS via a systematic approach. (3) Methods: All patients (n = 5) underwent a standardized clinical–instrumental examination, including the perceptual and acoustic analysis of speech, instrumental gait, and balance analysis (posturographic data were acquired using a force plate [Kistler, Winterthur, Switzerland] while 3D gait analysis, inclusive of surface electromyography, was acquired using a motion capture system [SMART DX, BTS Bioengineering, Milan, Italy], a wireless electromyograph [FreeEMG, BTS Bioengineering, Milan, Italy]), and vestibular assessment with video-oculography. (4) Results: Five patients were included in the analysis: three females (patients A, B, C) and two males (patients D and E) with a mean age at evaluation of 62 years (SD ± 15.16, range 36–74). The mean age of symptoms’ onset was 55.6 years (SD ± 15.04, range 30–68), and patients were clinically and instrumentally evaluated with a mean disease duration of 6.4 years (SD ± 0.54, range 6–7). Video-Frenzel examination documented spontaneous downbeat nystagmus enhanced on bilateral gaze in all patients, except for one presenting with slight downbeat nystagmus in the supine position. All patients exhibited different degrees of symmetrically reduced VOR gain for allsix semicircular canals on the video-head impulse test and an unexpectedly normal (“false negative”) VOR suppression, consistent with combined cerebellar dysfunction and bilateral vestibular loss. Posturographic indices were outside their age-matched normative ranges in all patients, while 3D gait analysis highlighted a reduction in ankle dorsiflexion (limited forward rotation of the tibia over the stance foot during the stance phase of gait and fatigue of the dorsiflexor muscles) and variable out-of-phase activity of plantar flexors during the swing phase. Finally, perceptual-acoustic evaluation of speech showed ataxic dysarthria in three patients. Dysdiadochokinesis, rhythm instability, and irregularity were observed in the oral diadochokinesis task. (5) Conclusions: CANVAS is a recently discovered syndrome that is gaining more and more relevance within late-onset ataxias. In this paper, we aimed to contribute to a detailed description of its phenotype.

Objective: Stakeholders—farmers from four different European areas (Campania (IT), Kujawsko-Pomorskie (PL), Limburg (NL), Andalusia (ES))—are asked to share, from the OPERA project, their opinions on five criteria that all aim at improving the use of irrigation advisory services (IASs). Each criterion has different characteristics that affect the way farmers rank it. The present study has two objectives. The first is to individuate the priorities of the preferences expressed by the stakeholders. The second objective is to carry out a ranking of the weights of the criteria by case study, ranking the groups and their associated properties among farmers’ profiles. Methods: The answers to 120 questionnaires dispensed to the future users of IASs in the four agricultural sites were analyzed in detail, and then the given priorities were evaluated through the analytic hierarchy process (AHP). The AHP methodology was used to determine the relative weights of the five assessment criteria, and finally, to select the one with major value. Results and conclusions: The results show that A5 (assuring economic sustainability) was the most important criterion. The contributions provided by this study are twofold: Firstly, it presents an application of a methodology that involves the conversion of a linguistic judgement of farmers in a correspondence weight. Secondly, it tackles decision making regarding improving the use of IASs, evaluating the preferences expressed by the stakeholders. Irrigation advisory services can play a key role in assisting users to adopt new techniques and technologies for more efficient water use and increased production.

(1) Influenza causes a significant health and socio-economic burden every year, and health personnel (HP) are at higher risk of exposure to respiratory pathogens than the general population. (2) The study’s purpose was to describe and compare influenza vaccine uptake and its prognostic factors among Medical Doctors (MDs) and Non-Medical Health Personnel (NMHP) vs. Non-HP (NHP). We analyzed 2014–2018 data (n = 105,608) from the Italian Behavioral Risk Factor Surveillance System PASSI that, since 2008, has been collecting health-related information continuously in sampled adults. (3) MDs and NMHP represented, respectively, 1.1% and 4.6% of the sample. Among HP, 22.8% (CI 19.8–26.1%) of MDs and 8.5% (CI 7.5–9.5%) of NMHP reported to have been vaccinated vs. 6.3% (CI 6.1–6.5%) in NHP. This difference is confirmed in the three categories (MDs, NMHP, NHP), even more across age groups: in 18–34 yy, respectively, 9.9%, 4.4%, 3.4% vs. 28.4%, 13.9%, 10.6% in 50–64 yy. PASSI surveillance shows an increasing influenza vaccination uptake over time, especially among MDs (22.2% in 2014 vs. 30.5% in 2018). (4) Despite such an increase, especially among younger HP, influenza vaccination uptake is low. Even more under pandemic scenarios, these figures represent key information to address effective strategies for disease prevention and health promotion.

Natural flavor and fragrance market size is expected to grow steadily due to the rising consumer demand of natural ingredients. This market request is guided by the general opinion that the production of natural compounds leads to a reduction of pollution, with inherent advantages for the environment and people’s health. The biotransformation reactions have gained high relevance in the production of natural products. In this context, few pieces of research have described the role of microalgae in the oxidation of terpenoids. In this present study, we questioned the role of microalgal based oxidation in the synthesis of high-value flavors and fragrances. This study investigated the role of three different microalgae strains, Chlorella sp. (211.8b and 211.8p) and Chlorococcum sp. (JB3), in the oxidation of different terpenoid substrates: α-ionone, β-ionone, theaspirane and valencene. Unfortunately, the experimental data showed that the microalgal strains used are not responsible for the substrate oxidation. In fact, our experiments demonstrate that the transformation of the four starting compounds is a photochemical reaction that involves the oxygen as oxidant. Even though these findings cast a shadow on the use of these microorganisms for an industrial purpose, they open a new possible strategy to easily obtain nootkatone in a natural way by just using an aqueous medium, oxygen and light.

Some major future global challenges are linked to more efficient use of water for irrigation to respond to the growing water scarcity coupled with the increasing food demand. Although irrigation advisory services (IASs) are considered effective instruments to increase water use efficiency in agriculture, their diffusion remains limited. This is due to several constraints mainly linked to their low accessibility and high costs. To overcome the bottlenecks associated with IASs’ adoption, this paper proposes a business model (BM) as a tool for scaling up IASs within a business perspective, with the aim of encouraging the diffusion of this technology while enhancing the associated environmental and social benefits. Drawn from the experience of the OPERA project, we structured the business model taking advantage of the opinion of relevant stakeholders and IASs’ potential users to identify specific limitations and understand their needs. It turned out that farmers are willing to adopt IASs but require that the service is easily accessible, with high-quality information that are delivered at an affordable cost. Indeed, here a BM with an innovative way to produce and deliver value is proposed. The value proposition is built upon key features namely, integration, customization, accessibility, and sustainability that reflect users’ needs and preferences. Our BM also provides a detailed revenues strategy that guarantees the financial sustainability of IASs. To design and represent our BM, the “Business Model Canvas ©” has been adopted. We concluded that an innovative and well-structured BM has the potential to leave the IASs profitable and capable to ensure environmental and social sustainability.

The purpose of this paper is to provide an assessment of the economic convenience of adopting adaptation measures to climate change at farm level. Concerns raised about climate risks on agriculture indicate that adaptation of the agricultural sector to climate change is necessary to mitigate the negative consequences of climate change. Despite many opportunities to implement climate adaptation measures at farm level, there are several obstacles to their adoption. Farmers’ decision to implement adaptation measures lies in the difficulty of accessing knowledge about adaptation practices and in the lack of resources for upfront investments required by adaptation. The need to investigate economic convenience in terms of costs and benefits of adopting adaptation measures to prevent or reduce damage from adverse climatic events by farmers arises from this consideration. More importantly, climate protection and management of climate change are European environmental policy objectives. However, adaptation to climate change remains complex, and literature on the costs and benefit of agricultural adaptation is limited. Based on these considerations, this paper provides an analysis of the economic convenience of adopting adaptation measures in Italian farms. The economic convenience to implement adaptation measures is calculated on the reduction of the impact of climate damage. Our results show the economic convenience of adaptation measures. These findings help to improve the still too limited access to information on adaptation policies at farm level as well as the benefits that adaptation produces in economic and environmental terms, on human and ecosystem health. This study supports farmers’ decisions in adopting climate adaptation measures and provides information for policy makers to identify specific financial instruments for adaptation measures.

Sirtuins are NAD+-dependent protein lysine deacylases implicated in metabolic regulation and aging-related dysfunctions. The nuclear isoform Sirt1 deacetylates histones and transcription factors and contributes, e.g., to brain and immune cell functions. Upon infection by human immunodeficiency virus 1 (HIV1), Sirt1 deacetylates the viral transactivator of transcription (Tat) protein to promote the expression of the viral genome. Tat, in turn, inhibits Sirt1, leading to the T cell hyperactivation associated with HIV infection. Here, we describe the molecular mechanism of Tat-dependent sirtuin inhibition. Using Tat-derived peptides and recombinant Tat protein, we mapped the inhibitory activity to Tat residues 34–59, comprising Tat core and basic regions and including the Sirt1 deacetylation site Lys50. Tat binds to the sirtuin catalytic core and inhibits Sirt1, Sirt2, and Sirt3 with comparable potencies. Biochemical data and crystal structures of sirtuin complexes with Tat peptides reveal that Tat exploits its intrinsically extended basic region for binding to the sirtuin substrate binding cleft through substrate-like β-strand interactions, supported by charge complementarity. Tat Lys50 is positioned in the sirtuin substrate lysine pocket, although binding and inhibition do not require prior acetylation and rely on subtle differences to the binding of regular substrates. Our results provide mechanistic insights into sirtuin regulation by Tat, improving our understanding of physiological sirtuin regulation and the role of this interaction during HIV1 infection.

Parkinson’s disease (PD) is a multifarious neurodegenerative disease. Its pathology is characterized by a prominent early death of dopaminergic neurons in the pars compacta of the substantia nigra and the presence of Lewy bodies with aggregated α-synuclein. Although the α-synuclein pathological aggregation and propagation, induced by several factors, is considered one of the most relevant hypotheses, PD pathogenesis is still a matter of debate. Indeed, environmental factors and genetic predisposition play an important role in PD. Mutations associated with a high risk for PD, usually called monogenic PD, underlie 5% to 10% of all PD cases. However, this percentage tends to increase over time because of the continuous identification of new genes associated with PD. The identification of genetic variants that can cause or increase the risk of PD has also given researchers the possibility to explore new personalized therapies. In this narrative review, we discuss the recent advances in the treatment of genetic forms of PD, focusing on different pathophysiologic aspects and ongoing clinical trials.

The new Common Agricultural Policy (CAP) for the period 2023–2027 commits farmers towards achieving ambitious environmental objectives through farm organization and management. This European agricultural policy has adapted to the contemporary challenges faced by the new model of agricultural development. It aims to enhance the contribution of agriculture to the EU’s environmental and climate objectives while providing better targeted support to small-scale farmers to promote farms’ competitiveness. The main objective of this paper is to describe Italian farms and classify them into groups based on their main characteristics, as well as to analyze their performance and behavior in terms of sustainability and competitiveness. The novelty and innovativeness of this study are found in the data used; a 2020 dataset from the Italian Farm Accounting Data Network (FADN) was used. The quality of FADN data in farm sustainability assessment is widely acknowledge in the literature. To achieve the purpose of this study, a multivariate analysis, in particular, the Principal Components Analysis (PCA), and a Cluster Analysis (CA) were applied. These analyses helped us to obtain the factorial axes which then enabled us to identify economic information on farms, and a better interpretation of farmers’ aptitude to undertake environmentally friendly actions. As a result, eight groups of farms were identified, and their characteristics and performance were described at Italian district level. The results of the study reflect the influence of European interventions towards encouraging farmers to use more environmentally friendly agricultural practices. Under this perspective, the findings contribute to the current debate on green architecture pursued by the future European agricultural policy.

Multiple system atrophy of the parkinsonian type (MSA-P) is a rare, fatal neurodegenerative disease with sporadic onset. It is still unknown if MSA-P is a primary oligodendropathy or caused by neuronal pathophysiology leading to severe, α-synuclein-associated neurodegeneration, mainly in the striatum. In this study, we generated and differentiated induced pluripotent stem cells (iPSCs) from patients with the clinical diagnosis of probable MSA-P (n = 3) and from three matched healthy controls into GABAergic striatal medium spiny neurons (MSNs). We found a significantly elevated release and neuronal distribution for α-synuclein, as well as hypoexcitability in the MSNs derived from the MSA-P patients compared to the healthy controls. These data suggest that the striatal hypoexcitable neurons of MSA-P patients contribute to a pathological α-synuclein burden which is likely to spread to neighboring cells and projection targets, facilitating disease progression.

Anderson–Fabry disease (AFD) is an inherited lysosomal storage disorder characterized by a composite and multisystemic clinical phenotype and frequent involvement of the central nervous system (CNS). Research in this area has largely focused on the cerebrovascular manifestations of the disease, and very little has been described about further neurological manifestations, which are known in other lysosomal diseases, such as Gaucher disease. In particular, a clinical and neuroimaging phenotype suggesting neurodegeneration as a putative mechanism has never been fully described for AFD, but the increased survival of affected patients with early diagnosis and the possibility of treatment have given rise to some isolated reports in the literature on the association of AFD with a clinical phenotype of Parkinson disease (PD). The data are currently scarce, but it is possible to hypothesize the molecular mechanisms of cell damage that support this association; this topic is worthy of further study in particular in relation to the therapeutic possibilities, which have significantly modified the natural history of the disease but which are not specifically dedicated to the CNS. In this review, the molecular mechanisms underlying this association will be proposed, and the available data with implications for future research and treatment will be rewritten.

Parkinson’s disease (PD) is a neurodegenerative disorder often associated with pre-motor symptoms involving both gastrointestinal and olfactory tissues. PD patients frequently suffer from hyposmia, hyposalivation, dysphagia and gastrointestinal dysfunctions. During the last few years it has been speculated that microbial agents could play a crucial role in PD. In particular, alterations of the microbiota composition (dysbiosis) might contribute to the formation of misfolded α-synuclein, which is believed to be the leading cause of PD. However, while several findings confirmed that there might be an important link between intestinal microbiota alterations and PD onset, little is known about the potential contribution of the nasal microbiota. Here, we describe the latest findings on this topic by considering that more than 80% of patients with PD develop remarkable olfactory deficits in their prodromal disease stage. Therefore, the nasal microbiota might contribute to PD, eventually boosting the gut microbiota in promoting disease onset. Finally, we present the applications of the seed amplification assays to the study of the gut and olfactory mucosa of PD patients, and how they could be exploited to investigate whether pathogenic bacteria present in the gut and the nose might promote α-synuclein misfolding and aggregation.

The present Phase I study investigated, for the first time, fosfomycin pharmacokinetics in humans after two 3 g doses of fosfomycin trometamol administered 27 h apart, according to the dose regimen recommended for the prophylactic indication for transrectal prostate biopsy in adult men. Plasma, urine and seminal plasma concentrations were measured after one and two consecutive doses in 24 healthy men, representative of the target population of the prophylactic indication. Prostate and seminal vesicle concentrations were estimated based on seminal plasma concentrations using a one-step regression method. The exposure to fosfomycin was very similar in rate (Cmax, tmax) after one and two doses. The AUC showed a minimal increment. On average, the apparent volume of distribution was high (>100 L), and the mean clearance had an intermediate value. The total amount and dose fraction of fosfomycin excreted in urine showed a small increment after two doses. The renal clearance was about 5 L/h. The fosfomycin concentration in the prostate and seminal vesicles showed that the antibiotic increased on average after two consecutive doses. This result confirmed the ability of fosfomycin to distribute into the prostate and into seminal vesicles after one single dose and that a two consecutive dose regimen increases the antibiotic availability inside these peripheral tissues.

This study aims to assess the potential of Sentinel-2 NDVI time series and Google Earth Engine to detect small land-use/land-cover changes (at the pixel level) in fire-disturbed environs. To capture both slow and fast changes, the investigations focused on the analysis of trends in NDVI time series, selected because they are extensively used for the assessment of post-fire dynamics mainly linked to the monitoring of vegetation recovery and fire resilience. The area considered for this study is the central–southern part of the Italian peninsula, in particular the regions of (i) Campania, (ii) Basilicata, (iii) Calabria, (iv) Toscana, (v) Umbria, and (vi) Lazio. For each fire considered, the study covered the period from the year after the event to the present. The multi-temporal analysis was performed using two main data processing steps (i) linear regression to extract NDVI trends and enhance changes over time and (ii) random forest classification to capture and categorize the various changes. The analysis allowed us to identify changes occurred in the selected case study areas and to understand and evaluate the trend indicators that mark a change in land use/land cover. In particular, different types of changes were identified: (i) woodland felling, (ii) remaking of paths and roads, and (ii) transition from wooded area to cultivated field. The reliability of the changes identified was assessed and confirmed by the high multi-temporal resolution offered by Google Earth. Results of this comparison highlighted that the overall accuracy of the classification was higher than 0.86.

Gene delivery is the basis for developing gene therapies that, in the future, may be able to cure virtually any disease, including viral infections. The use of short interfering RNAs (siRNAs) targeting viral replication is a novel strategy for treating HIV-1 infection. In this study, we prepared chitosan particles containing siRNA tat/rev via ionotropic gelation. Chitosan-based particles were efficiently internalized by cells, as evidenced by fluorescence microscopy. The antiviral effect of chitosan-based particles was studied on the C8166 cell line infected with HIV-1 and compared with the use of commercial liposomes (ESCORT). A significant reduction in HIV replication was also observed in cells treated with empty chitosan particles, suggesting that chitosan may interfere with the early steps of the HIV life cycle and have a synergic effect with siRNA to reduce viral replication significantly.

β-glucocerebrosidase is a lysosomal hydrolase involved in the catabolism of the sphingolipid glucosylceramide. Biallelic loss of function mutations in this enzyme are responsible for the onset of Gaucher disease, while monoallelic β-glucocerebrosidase mutations represent the first genetic risk factor for Parkinson’s disease. Despite this evidence, the molecular mechanism linking the impairment in β-glucocerebrosidase activity with the onset of neurodegeneration in still unknown. In this frame, we developed two in vitro neuronal models of β-glucocerebrosidase deficiency, represented by mouse cerebellar granule neurons and human-induced pluripotent stem cells-derived dopaminergic neurons treated with the specific β-glucocerebrosidase inhibitor conduritol B epoxide. Neurons deficient for β-glucocerebrosidase activity showed a lysosomal accumulation of glucosylceramide and the onset of neuronal damage. Moreover, we found that neurons react to the lysosomal impairment by the induction of their biogenesis and exocytosis. This latter event was responsible for glucosylceramide accumulation also at the plasma membrane level, with an alteration in lipid and protein composition of specific signaling microdomains. Collectively, our data suggest that β-glucocerebrosidase loss of function impairs the lysosomal compartment, establishing a lysosome–plasma membrane axis responsible for modifications in the plasma membrane architecture and possible alterations of intracellular signaling pathways, leading to neuronal damage.

The valorization of biomass residuals constitutes a key aspect of circular economy and thus a major challenge for the scientific community. Among industrial wastes, plant residuals could represent an attractive source of bioactive compounds. In this context, a residue from the industrial extraction of Cucurbita pepo L. seeds, whose oil is commercialized for the treatment of genito-urinary tract pathologies, has been selected. Supercritical CO2 technology has been employed as a highly selective “green” methodology allowing the recovery of compounds without chemical degradation and limited operational costs. Free fatty acids have been collected in mild conditions while an enrichment in sterols has been selectively obtained from sc-CO2 extracts by appropriate modulation of process parameters (supercritical fluid pressure and temperature), hence demonstrating the feasibility of the technique to target added-value compounds in a selective way. Obtained fatty acids were thus converted into the corresponding ethanol carboxamide derivatives by lipase-mediated biocatalyzed reactions, while the hydroxylated derivatives of unsaturated fatty acids were obtained by stereoselective hydration reaction under reductive conditions in the presence of a selected FADH2-dependent oleate hydratase.

Tritium permeation into the Primary Heat Transfer System (PHTS) of DEMO and ITER reactors is one of the challenging issues to be solved in order to demonstrate the feasibility of nuclear fusion power plants construction. Several technologies were investigated as antipermeation and corrosion barriers to reduce the tritium permeation flux from the breeder into the PHTS. Within this frame, alumina coating manufactured by Pulsed Laser Deposition (PLD) and Atomic Layer Deposition (ALD) are two of the main candidates for the Water Cooled Lithium Lead (WCLL) Breeder Blanket (BB). In order to validate the performance of the coatings on relevant WCLL BB geometries, a mock-up was designed and will be characterized in an experimental facility operating with flowing lithium-lead, called TRIEX-II. The present work aims to illustrate the preliminary engineering design of a WCLL BB mock-up in order to deeply investigate permeation of hydrogen isotopes through PHTS water pipes. The permeation tests are planned in the temperature range between 330 and 500 °C, with hydrogen and deuterium partial pressure in the range of 1–1000 Pa. The hydrogen isotopes transport analysis carried out for the design and integration of the mock-up in TRIEX-II facility is also shown.

Corticobasal syndrome (CBS) is an atypical parkinsonian presentation characterized by heterogeneous clinical features and different underlying neuropathology. Most CBS cases are sporadic; nevertheless, reports of families and isolated individuals with genetically determined CBS have been reported. In this systematic review, we analyze the demographical, clinical, radiological, and anatomopathological features of genetically confirmed cases of CBS. A systematic search was performed using the PubMed, EMBASE, and Cochrane Library databases, included all publications in English from 1 January 1999 through 1 August 2020. We found forty publications with fifty-eight eligible cases. A second search for publications dealing with genetic risk factors for CBS led to the review of eight additional articles. GRN was the most common gene involved in CBS, representing 28 out of 58 cases, followed by MAPT, C9ORF72, and PRNP. A set of symptoms was shown to be significantly more common in GRN-CBS patients, including visuospatial impairment, behavioral changes, aphasia, and language alterations. In addition, specific demographical, clinical, biochemical, and radiological features may suggest mutations in other genes. We suggest a diagnostic algorithm to help in identifying potential genetic cases of CBS in order to improve the diagnostic accuracy and to better understand the still poorly defined underlying pathogenetic process.

Parkinson’s disease (PD) is the second most common degenerative disorder. Although the disease was described more than 200 years ago, its pathogenetic mechanisms have not yet been fully described. In recent years, the discovery of the association between mutations of the GBA gene (encoding for the lysosomal enzyme glucocerebrosidase) and PD facilitated a better understating of this disorder. GBA mutations are the most common genetic risk factor of the disease. However, mutations of this gene can be found in different phenotypes, such as Gaucher’s disease (GD), PD, dementia with Lewy bodies (DLB) and rapid eye movements (REM) sleep behavior disorders (RBDs). Understanding the pathogenic role of this mutation and its different manifestations is crucial for geneticists and scientists to guide their research and to select proper cohorts of patients. Moreover, knowing the implications of the GBA mutation in the context of PD and the other associated phenotypes is also important for clinicians to properly counsel their patients and to implement their care. With the present review we aim to describe the genetic, clinical, and therapeutic features related to the mutation of the GBA gene.

More than 25 years after the 1991 reform of the Union for the Protection of New Plant Varieties (UPOV) treaty, the regulation of Plant Variety Protection (PVP) is still controversial. While the incentives to private innovations are unquestionable, concerns have been raised about farmers’ access to resources, the weakening of their bargaining power, their entrepreneurial freedom, and ultimately their welfare. Our paper investigates the effect of PVP regulation on the governance of agri-food value chains (AFVC) with a small-scale survey of kiwi producers in Italy. We found that AFVC trading-protected (club) plant varieties are more likely to exhibit captive governance forms than those trading the free varieties. Nevertheless, the producers of club kiwis achieve higher returns from their investments and bear less risk than others. Because of the high demand for the club fruits, the breeders must give farmers highly profitable contract terms in order to elicit the production and to promote the adoption of the new cultivar. As a consequence, farmers are capturing a share of the value of innovation, even if the breeders have a strong protection. The long-run sustainability of this win-win agreement between breeders and farmers might be jeopardized should the demand for the new varieties fall.

We have cloned, purified, and characterized a β-carbonic anhydrase (CA, EC 4.2.1.1), BpsCAβ, from the pathogenic bacterium Burkholderia pseudomallei, responsible for the tropical disease melioidosis. The enzyme showed high catalytic activity for the physiologic CO2 hydration reaction to bicarbonate and protons, with the following kinetic parameters: kcat of 1.6 × 105 s−1 and kcat/KM of 3.4 × 107 M−1 s−1. An inhibition study with a panel of 38 sulfonamides and one sulfamate—including 15 compounds that are used clinically—revealed an interesting structure–activity relationship for the interaction of this enzyme with these inhibitors. Many simple sulfonamides and clinically used agents such as topiramate, sulpiride, celecoxib, valdecoxib, and sulthiame were ineffective BpsCAβ inhibitors (KI > 50 µM). Other drugs, such as ethoxzolamide, dorzolamide, brinzolamide, zonisamide, indisulam, and hydrochlorothiazide were moderately potent micromolar inhibitors. The best inhibition was observed with benzene-1,3-disulfonamides—benzolamide and its analogs acetazolamide and methazolamide—which showed KI in the range of 185–745 nM. The inhibition profile of BpsCAβ is very different from that of the γ-class enzyme from the same pathogen, BpsCAγ. Thus, identifying compounds that would effectively interact with both enzymes is relatively challenging. However, benzolamide was one of the best inhibitors of both of these CAs with KI of 653 and 185 nM, respectively, making it an interesting lead compound for the design of more effective agents, which may be useful tools for understanding the pathogenicity of this bacterium.