DOPAL derived alpha-synuclein oligomers impair synaptic vesicles physiological function

Parkinson's disease is a neurodegenerative disorder characterized by the death of dopaminergic neurons and by accumulation of alpha-synuclein (aS) aggregates in the surviving neurons. The dopamine catabolite 3,4-dihydroxyphenylacetaldehyde (DOPAL) is a highly reactive and toxic molecule that leads to aS oligomerization by covalent modifications to lysine residues. Here we show that DOPAL-induced aS oligomer formation in neurons is associated with damage of synaptic vesicles, and with alterations in the synaptic vesicles pools. To investigate the molecular mechanism that leads to synaptic impairment, we first aimed to characterize the biochemical and biophysical properties of the aS-DOPAL oligomers; heterogeneous ensembles of macromolecules able to permeabilise cholesterol-containing lipid membranes. aS-DOPAL oligomers can induce dopamine leak in an in vitro model of synaptic vesicles and in cellular models. The dopamine released, after conversion to DOPAL in the cytoplasm, could trigger a noxious cycle that further fuels the formation of aS-DOPAL oligomers, inducing neurodegeneration

La vivencia de un grupo de jubilados-anciano: investigación - acción

The present study aims at comprehending the retired people through a group experience as well as allowing them to reflect about their condition. The authors utilized the research-action methodology, with 25 retired subjects who worked in the University, aging from 51 to 79 years old. The narratives related to their experiences were obtained through verbal interaction, group discussions and interviews. From the analysis of the experiences emerged questions associated to the retired-elderly interests, their physical and mental health, relationship, learning process, social environment and leisure.Este estudio se propone comprender la situación del jubilado, a través de la vivencia en grupo, y permitir que los jubilados refleccionen con respecto a su condición. Se ha utilizado la metodologia de la investigación - acción, con 25 sujetos jubilados de la Universidad, con edad entre 51 y 79 años. Las narraciones respecto de las vivencias fueron obtenidas por medio de interacción verbal, discusión en grupo y entrevista. En el análisis de las vivencias han emergido cuestiones relacionadas a los intereses de los jubilados ancianos, cuanto a la salud física y mental, relacionamiento, aprendizaje, ambiente social y ocio

Methyl-binding domain protein-based DNA isolation from human blood serum combines DNA analyses and serum-autoantibody testing

<p>Abstract</p> <p>Background</p> <p>Circulating cell free DNA in serum as well as serum-autoantibodies and the serum proteome have great potential to contribute to early cancer diagnostics via non invasive blood tests. However, most DNA preparation protocols destroy the protein fraction and therefore do not allow subsequent protein analyses. In this study a novel approach based on methyl binding domain protein (MBD) is described to overcome the technical difficulties of combining DNA and protein analysis out of one single serum sample.</p> <p>Methods</p> <p>Serum or plasma samples from 98 control individuals and 54 breast cancer patients were evaluated upon silica membrane- or MBD affinity-based DNA isolation via qPCR targeting potential DNA methylation markers as well as by protein-microarrays for tumor-autoantibody testing.</p> <p>Results</p> <p>In control individuals, an average DNA level of 22.8 ± 25.7 ng/ml was detected applying the silica membrane based protocol and 8.5 ± 7.5 ng/ml using the MBD-approach, both values strongly dependent on the serum sample preparation methods used. In contrast to malignant and benign tumor serum samples, cell free DNA concentrations were significantly elevated in sera of metastasizing breast cancer patients. Technical evaluation revealed that serum upon MBD-based DNA isolation is suitable for protein-array analyses when data are consistent to untreated serum samples.</p> <p>Conclusion</p> <p>MBD affinity purification allows DNA isolations under native conditions retaining the protein function, thus for example enabling combined analyses of DNA methylation and autoantigene-profiles from the same serum sample and thereby improving minimal invasive diagnostics.</p

Metabolizable Protein: 1. Predicting Equations to Estimate Microbial Crude Protein Synthesis in Small Ruminants

Microbial crude protein (MCP) produced in rumen could be estimated by a variety of protocols of experimental sampling and analysis. However, a model to estimate this value is necessary when protein requirements are calculated for small ruminants. This model could be useful to calculate rumen degradable protein (RDP) requirements from metabolizable protein (MP). Then, our objective was to investigate if there is a difference in MCP efficiency between sheep and goats, and to fit equations to predict ruminal MCP production from dietary energy intake. The database consisted of 19 studies with goats (n = 176) and sheep (n = 316), and the variables MCP synthesis (g/day), total digestible nutrients (TDN), and organic matter (OM) intakes (g/day), and OM digestibility (g/kg DM) were registered for both species. The database was used for two different purposes, where 70% of the values were sorted to fit equations, and 30% for validation. A meta-analytical procedure was carried out using the MIXED procedure of SAS, specie was considered as the fixed dummy effect, and the intercept and slope nested in the study were considered random effects. No effect of specie was observed for the estimation of MCP from TDN, digestible Organic Matter (dOM), or metabolizable energy (ME) intakes (P &gt; 0.05), considering an equation with or without an intercept. Therefore, single models including both species at the same fitting were validated. The following equations MCP (g/day) = 12.7311 + 59.2956 × TDN intake (AIC = 3,004.6); MCP (g/day) = 15.7764 + 62.2612 × dOM intake (AIC = 2,755.1); and MCP (g/day) = 12.7311 + 15.3000 × ME intake (AIC = 3,007.3) presented lower values for the mean square error of prediction (MSEP) and its decomposition, and similar values for the concordance correlation coefficient (CCC) and for the residual mean square error (RMSE) when compared with equations fitted without an intercept. The intercept and slope pooled test was significant for equations without an intercept (P &lt; 0.05), indicating that observed and predicted data differed. In contrast, predicted and observed data for complete equations were similar (P &gt; 0.05)

Prospettive e potenzialità della digitalizzazione del settore forestale in Italia

Information and Communication Technologies (ICT) play a key role for improving the implementation of sustainable forest management at local, regional, and global level. The ICT potential to easily exploit a wider and more up-to-date set of information on the economic, environmental, and so- cial value of forests is of relevant help for the daily work of technicians, land owners, and companies in boosting the efficiency and effectiveness of forest management. The concept of “Precision Forestry” (PF) was developed from the early 2000s, as a branch of precision farming or precision agriculture. PF includes the use of ICT, remote and proximal sensing technologies, and other devices to coordinate and control several processes on a spatial scale (“Precision”) for monitoring, planning, and managing forest resources (“Forestry”). The aim of this monography is to collect and describe some of the most important PF experiences applied or potential- ly useful for the Italian forestry sector. It may represent a reference guide for the stakeholders, such as forest owners, professional technicians, public administrators, and policy makers. The book includes eleven chapters reviewing the main tech- nological tools available in the Italian context and the most recent advances of ICT in forestry, also focusing on the strengths and weaknesses of their practical implementation. The opportunities and challenges of implementing PF meth- ods, practices and technologies are also discussed. In the first two chapters the precision forestry concept and its historical development are introduced. In the third chap- ter some basic elements of ICT, GIS, Global Navigation Satellite Systems (GNSS), remote/proximal sensing, and related technologies which are essential for a better compre- hension of PF applications are recalled. In chapter 4 recent advances in large scale forest inventories with a focus on mapping and on the spatial estimation of forest variables integrating field surveys and multisource re- motely sensed data are described. Current advancements in the acquisition of field information including Terrestrial La- ser Scanning (TLS), new digital dendrometers, tree-talkers, terrestrial cameras, and APP for portable devices such as smartphones or tablets for dendrometric tree measures and new citizen science applications to support quantitative and qualitative spatial estimation of forest variables over large areas (i.e., forest health, fuel types) are also presented. The chapter ends up with the description of some experiences in the implementation of Forest Information Systems in Italy to provide a simple open-access to such new generation of spatial forest information. In chapter 5 PF tools, instruments, and technologies to sup- port sustainable forest management are illustrated. APPs developed to acquire field plots data to simulate manage- ment operations, the application of photogrammetric tech- nologies from Unmanned Aerial Vehicles and TLS data for monitoring with high-spatial scale forest monitoring and for acquiring indicators at single tree level are presented. A de- tailed description of new user-friendly tools for forest roadplanning, design and construction, as well as forest opera- tion planning is also included. Precision forest tree farming (with particular reference to poplar cultivation), useful to promote and increase the prof- itability and sustainability of forest plantations within the Italian context is described in chapter 6. The innovation and enhancement within the supply chain of wood plantations (from planting to harvesting, including monitoring and identification of stress) by soil proximal sensing techniques, Early Warning Systems, and specific software are highlight- ed. Considering the even higher market demands, promoted by the large-scale planting programs for climate changes mit- igation and the demands for propagation material for en- vironmental recovery, innovative techniques and methods supported by ICT in the forest nursery sector are described in chapter 7. In chapter 8 available technologies related to precision har- vesting are analyzed and described taking into consideration the wood chain efficiency, by means of improved commu- nications between the owner/buyer and operators as well as among machineries used in forest operations, health and safety of forest operators, environmental impacts mitigation and recovery, and operators training. Advanced communi- cation systems and sensors for the exchange of data and information between machines, machine-equipments and/or machine-operators, teleoperations and automation are also described. Chapters 9 and 10 are related to wood products traceabil- ity, timber quality assessment as well as the technologies for the optimization of wood transformation processes. The concepts of wood product traceability and tracing, togeth- er with latest digital technologies for the identification and tracking of the logs (i.e., fingerprinting and RFID), are de- tailly reported. Chapter 11 is finally dedicated to the relationship between the EU policy framework and the digitalization process in both agricultural and forestry sectors. The book summarizes, under a proactive and homogeneous framework, PF methods, tools and technologies in relation with the digital transition of the Italian forestry sectors. The authors hope this book will be useful for improving the implementation of sustainable forest management practic- es at all levels in Italy, providing a comprehensive review useful for policy makers, technicians, forestry owners and students

COVID-19 in rheumatic diseases in Italy: first results from the Italian registry of the Italian Society for Rheumatology (CONTROL-19)

OBJECTIVES: Italy was one of the first countries significantly affected by the coronavirus disease 2019 (COVID-19) epidemic. The Italian Society for Rheumatology promptly launched a retrospective and anonymised data collection to monitor COVID-19 in patients with rheumatic and musculoskeletal diseases (RMDs), the CONTROL-19 surveillance database, which is part of the COVID-19 Global Rheumatology Alliance. METHODS: CONTROL-19 includes patients with RMDs and proven severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) updated until May 3rd 2020. In this analysis, only molecular diagnoses were included. The data collection covered demographic data, medical history (general and RMD-related), treatments and COVID-19 related features, treatments, and outcome. In this paper, we report the first descriptive data from the CONTROL-19 registry. RESULTS: The population of the first 232 patients (36% males) consisted mainly of elderly patients (mean age 62.2 years), who used corticosteroids (51.7%), and suffered from multi-morbidity (median comorbidities 2). Rheumatoid arthritis was the most frequent disease (34.1%), followed by spondyloarthritis (26.3%), connective tissue disease (21.1%) and vasculitis (11.2%). Most cases had an active disease (69.4%). Clinical presentation of COVID-19 was typical, with systemic symptoms (fever and asthenia) and respiratory symptoms. The overall outcome was severe, with high frequencies of hospitalisation (69.8%), respiratory support oxygen (55.7%), non-invasive ventilation (20.9%) or mechanical ventilation (7.5%), and 19% of deaths. Male patients typically manifested a worse prognosis. Immunomodulatory treatments were not significantly associated with an increased risk of intensive care unit admission/mechanical ventilation/death. CONCLUSIONS: Although the report mainly includes the most severe cases, its temporal and spatial trend supports the validity of the national surveillance system. More complete data are being acquired in order to both test the hypothesis that RMD patients may have a different outcome from that of the general population and determine the safety of immunomodulatory treatments

The Changing Landscape for Stroke\ua0Prevention in AF: Findings From the GLORIA-AF Registry Phase 2

Background GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non\u2013vitamin K antagonist oral anticoagulant (NOAC), became available. Objectives This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase&nbsp;1. Methods During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients\u2019 baseline characteristics. Atrial fibrillation&nbsp;disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics. Results Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA2DS2-VASc [Congestive heart failure, Hypertension, Age&nbsp; 6575 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score&nbsp; 652; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc&nbsp;= 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N&nbsp;= 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients received NOAC, VKA, and antiplatelet drugs, respectively; 7.5% received no antithrombotic treatment. NOAC use was less common in Asia (27.7%), where 27.5% of patients received VKA, 25.0% antiplatelet drugs, and 19.8% no antithrombotic treatment. Conclusions The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in&nbsp;Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in&nbsp;Asia&nbsp;and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701

caratterizzazione funzionale di un canale del potassio del cianobatterio Synechocystis sp. PCC 6803

My Ph.D. project was focused on the characterization of a prokaryotic potassium channel, called SynK, that was identified in the genome of the cyanobacterium Synechocystis sp. PCC6803, a photoheterotrophic organism. SynK was cloned, expressed, and assigned as a potassium selective channel. In order to study its physiological role, I produced a SynK-deficient Synechocystis strain, which is unable to grow under normal illumination conditions. Growth may be restored if an electron donor is added or if high-intensity illumination is applied. Western blotting experiments, performed with antibodies raised against SynK, revealed that expression of the channel protein is correlated with growth and seems to be regulated by redox-state. The location of SynK in thylakoid membranes was shown by immunogold electron microscopy. Fluorimetric experiments indicated that SynK-deficient cyanobacteria are unable to build up a proton gradient across the thylakoid membrane upon illumination. These data indicate the crucial role played by SynK in regulating photosynthesis in these organisms. I also worked on purification and molecular characterization of a higher plants thylakoid potassium channel that was identified by immunoblot using antibodies raised against the prokaryotic channel

Introduzione

Il volume discute le complesse dimensioni del Servizio Civile, di recente oggetto di una riforma strutturale che ha anche comportato la sua trasformazione in Servizio Civile universale, analizzandone sia gli aspetti organizzativi e politico-culturali, legati alla numerosit\ue0 e alla diversit\ue0 dei soggetti in esso coinvolti, alla diversit\ue0 dei contesti culturali e territoriali in cui viene attivato, alle differenti progettualit\ue0 che lo sostengono, sia la valenza educativa e culturale di una scelta che pu\uf2 avere una influenza determinante sulla vita di molti giovani, uomini e donne. Il dibattito che ha accompagnato l\u2019emanazione del Decreto legislativo 40/2017 \ue8 stato ampio e ha portato a una ridefinizione delle finalit\ue0 e dei settori di intervento del Servizio Civile, a una identificazione puntuale dei soggetti cui spetta la programmazione e l\u2019attuazione degli interventi, al ridisegno dei compiti e del ruolo degli operatori volontari del Servizio Civile universale, a una collocazione dell\u2019intervento nel contesto europeo. Restano sul tappeto alcuni temi irrisolti, o comunque affrontati in modo non del tutto convincente dalla nuova normativa: tra essi, i problemi centrali del riconoscimento delle competenze acquisite dagli operatori volontari secondo modalit\ue0 che vadano oltre gli aspetti quantitativi connessi a certificazioni burocratiche e della qualificazione degli enti coinvolti, verso una loro capacit\ue0 di progettare in modo pi\uf9 professionale garantendo una maggiore integrazione tra la salvaguardia dei quadri valoriali di riferimento e la valorizzazione del lavoro svolto individualmente dai singoli. Nel testo, la riflessione di natura teorica (anche in direzione di comparazione con la realt\ue0 europea) viene sostenuta e accompagnata dai risultati di una ricerca, svolta in riferimento al bando straordinario per le zone colpite dal sisma del 2012 in Emilia-Romagna, che ha avuto come finalit\ue0 principale quella di rilevare e analizzare alcune caratteristiche dell\u2019esperienza di Servizio Civile legate agli aspetti motivazionali, formativi e organizzativi percepiti dai giovani volontari e dalle strutture presso le quali hanno prestato servizio. Si presenta inoltre una approfondita ricerca valutativa sul Servizio Civile volontario svolta nel Comune di Ferrara, che analizza in chiave storica l\u2019evoluzione delle motivazioni e dei risultati del Servizio Civile stesso, valorizzando il punto di vista degli utenti e dei servizi coinvolti

Le nuove prospettive del Servizio Civile: idee da una ricerca

Nel presente contributo si riportano i materiali più significativi e le principali considerazioni emergenti dalla ricerca "Il Servizio Civile dei giovani - Bandi straordinari per le zone colpite dal sisma. Analisi della motivazione, della soddisfazione nei confronti dell'esperienza e del percorso di acquisizione di competenze nel contesto d'intervento", proponendo alcune osservazioni di commento riassuntivo relativamente ai seguenti nodi centrali dell'esperienza di Servizio Civile analizzati nell'ambito della ricerca: la motivazione al Servizio Civile, la formazione generale e specifica, l'organizzazione funzionale dei progetti, il clima relazionale, le competenze acquisite dai giovani volontari. Questi aspetti vengono considerati nella percezione da loro stessi fornita