Quantum Charge Transport and Conformational Dynamics of Macromolecules

We study the dynamics of quantum excitations inside macromolecules which can undergo conformational transitions. In the first part of the paper, we use the path integral formalism to rigorously derive a set of coupled equations of motion which simultaneously describe the molecular and quantum transport dynamics, and obey the fluctuation/dissipation relationship. We also introduce an algorithm which yields the most probable molecular and quantum transport pathways in rare, thermally-activated reactions. In the second part of the paper, we apply this formalism to simulate the propagation of a charge during the collapse of a polymer from an initial stretched conformation to a final globular state. We find that the charge dynamics is quenched when the chain reaches a molten globule state. Using random matrix theory we show that this transition is due to an increase of quantum localization driven by dynamical disorder.Comment: 11 pages, 2 figure

Gestione ecosostenibile delle infestanti in ambiente urbano e vivaistico

In ottemperanza al nuovo quadro normativo relativo all’uso sostenibile dei prodotti fitosanitari (Direttiva 2009/128/CE - D.L. 150/2012, DM 22 gennaio 2014) il lavoro ha avuto lo scopo di verificare l’efficienza di strategie alternative alla gestione convenzionale della flora infestante in ambienti urbani e in vivai, comparando diserbo chimico tradizionale e meccanico con tecniche innovative. In particolare sono state valutate la tecnica del pirodiserbo, l’utilizzo di acqua a temperatura prossima al punto di ebollizione (sistema Eco Weed) e di acido pelargonico, un erbicida disseccante estratto la prima volta dalle foglie di Pelargonium roseum. La sperimentazione delle diverse tecniche di controllo è stata preceduta da uno studio della flora e della vegetazione al fine di pianificare nel modo più efficace gli interventi di contenimento delle infestanti, in funzione delle peculiarità delle specie e dell’habitat. I risultati hanno evidenziato concrete e valide alternative all’impiego del glifosate e del decespugliatore, sia in ambiente urbano che nei vivai

Constraints on (2060) Chiron's size, shape, and surrounding material from the November 2018 and September 2019 stellar occultations

After the discovery of rings around the largest known Centaur object, (10199) Chariklo, we carried out observation campaigns of stellar occultations produced by the second-largest known Centaur object, (2060) Chiron, to better characterize its physical properties and presence of material on its surroundings. We predicted and successfully observed two stellar occultations by Chiron. These observations were used to constrain its size and shape by fitting elliptical limbs with equivalent surface radii in agreement with radiometric measurements. Constraints on the (2060) Chiron shape are reported for the first time. Assuming an equivalent radius of R$_{equiv}$ = 105$^{+6}_{-7}$ km, we obtained a semi-major axis of a = 126 $\pm$ 22 km. Considering Chiron's true rotational light curve amplitude and assuming it has a Jacobi equilibrium shape, we were able to derive a 3D shape with a semi-axis of a = 126 $\pm$ 22 km, b = 109 $\pm$ 19 km, and c = 68 $\pm$ 13 km, implying in a volume-equivalent radius of R$_{vol}$ = 98 $\pm$ 17 km, implying a density of 1119 $\pm$ 4 kg m$^{-3}$. We determined the physical properties of the 2011 secondary events around Chiron, which may then be directly compared with those of Chariklo rings, as the same method was used. Data obtained from SAAO in 2018 do not show unambiguous evidence of the proposed rings, mainly due to the large sampling time. Meanwhile, we discarded the possible presence of a permanent ring similar to (10199) Chariklo's C1R in optical depth and extension. Using the first multi-chord stellar occultation by (2060) Chiron and considering it to have a Jacobi equilibrium shape, we derived its 3D shape. New observations of a stellar occultation by (2060) Chiron are needed to further investigate the material's properties around Chiron, such as the occultation predicted for September 10, 2023

IFN-\u3b3 and other serum cytokines in head and neck squamous cell carcinomas

Altered immune responses have been reported in head and neck cancer, and some of these responses have been associated with poor clinical outcomes. A multiple-array technology platform was used to simultaneously evaluate the levels of 25 cytokines. Pre-treatment serum levels were evaluated in 31 HNSCC patients and 6 healthy controls. The levels of 8 cytokines, specifically IL-1ra, IL-2, IL-5, IL-6, IL-8, IL-17, IFN-\u3b3 and IP-10, were significantly higher in patients than in controls. Among cancer patients we observed lower levels of IFN-\u3b3 and IL-7 in cases with nodal metastases compared to those with cN0 disease. We observed increases in the levels of some serum cytokines in HNSCC patients, as well as reductions in selected cytokines associated with regional progression. These findings provide an intriguing perspective on the development and validation of novel markers for follow-up evaluations and predictions of regional spreading in HNSCC patients

Metabolite and lipoprotein profiles reveal sex-related oxidative stress imbalance in de novo drug-naive Parkinson's disease patients

Parkinson’s disease (PD) is the neurological disorder showing the greatest rise in prevalence from 1990 to 2016. Despite clinical definition criteria and a tremendous effort to develop objective biomarkers, precise diagnosis of PD is still unavailable at early stage. In recent years, an increasing number of studies have used omic methods to unveil the molecular basis of PD, providing a detailed characterization of potentially pathological alterations in various biological specimens. Metabolomics could provide useful insights to deepen our knowledge of PD aetiopathogenesis, to identify signatures that distinguish groups of patients and uncover responsive biomarkers of PD that may be significant in early detection and in tracking the disease progression and drug treatment efficacy. The present work is the first large metabolomic study based on nuclear magnetic resonance (NMR) with an independent validation cohort aiming at the serum characterization of de novo drug-naive PD patients. Here, NMR is applied to sera from large training and independent validation cohorts of German subjects. Multivariate and univariate approaches are used to infer metabolic differences that characterize the metabolite and the lipoprotein profiles of newly diagnosed de novo drug-naive PD patients also in relation to the biological sex of the subjects in the study, evidencing a more pronounced fingerprint of the pathology in male patients. The presence of a validation cohort allowed us to confirm altered levels of acetone and cholesterol in male PD patients. By comparing the metabolites and lipoproteins levels among de novo drug-naive PD patients, age- and sex-matched healthy controls, and a group of advanced PD patients, we detected several descriptors of stronger oxidative stress

Heterogeneity of prodromal Parkinson symptoms in siblings of Parkinson disease patients

A prodromal phase of Parkinson’s disease (PD) may precede motor manifestations by decades. PD patients’ siblings are at higher risk for PD, but the prevalence and distribution of prodromal symptoms are unknown. The study objectives were (1) to assess motor and non-motor features estimating prodromal PD probability in PD siblings recruited within the European PROPAG-AGEING project; (2) to compare motor and non-motor symptoms to the well-established DeNoPa cohort. 340 PD siblings from three sites (Bologna, Seville, Kassel/Goettingen) underwent clinical and neurological evaluations of PD markers. The German part of the cohort was compared with German de novo PD patients (dnPDs) and healthy controls (CTRs) from DeNoPa. Fifteen (4.4%) siblings presented with subtle signs of motor impairment, with MDS-UPDRS-III scores not clinically different from CTRs. Symptoms of orthostatic hypotension were present in 47 siblings (13.8%), no different to CTRs (p = 0.072). No differences were found for olfaction and overall cognition; German-siblings performed worse than CTRs in visuospatial-executive and language tasks. 3/147 siblings had video-polysomnography-confirmed REM sleep behavior disorder (RBD), none was positive on the RBD Screening Questionnaire. 173/300 siblings had <1% probability of having prodromal PD; 100 between 1 and 10%, 26 siblings between 10 and 80%, one fulfilled the criteria for prodromal PD. According to the current analysis, we cannot confirm the increased risk of PD siblings for prodromal PD. Siblings showed a heterogeneous distribution of prodromal PD markers and probability. Additional parameters, including strong disease markers, should be investigated to verify if these results depend on validity and sensitivity of prodromal PD criteria, or if siblings’ risk is not elevated

Hybrid Shell Engineering of Animal Cells for Immune Protections and Regulation of Drug Delivery: Towards the Design of “Artificial Organs”

BACKGROUND: With the progress in medicine, the average human life expectancy is continuously increasing. At the same time, the number of patients who require full organ transplantations is augmenting. Consequently, new strategies for cell transplantation are the subject of great interest. METHODOLOGY/PRINCIPAL FINDINGS: This work reports the design, the synthesis and the characterisation of robust and biocompatible mineralised beads composed of two layers: an alginate-silica composite core and a Ca-alginate layer. The adequate choice of materials was achieved through cytotoxicity LDH release measurement and in vitro inflammatory assay (IL-8) to meet the biocompatibility requirements for medical purpose. The results obtained following this strategy provide a direct proof of the total innocuity of silica and alginate networks for human cells as underscored by the non-activation of immune defenders (THP-1 monocytes). The accessible pore size diameter of the mineralised beads synthesized was estimated between 22 and 30 nm, as required for efficient immuno-isolation without preventing the diffusion of nutrients and metabolites. The model human cells, HepG2, entrapped within these hybrid beads display a high survival rate over more than six weeks according to the measurements of intracellular enzymatic activity, respiration rate, as well as the "de novo" biosynthesis and secretion of albumin out of the beads. CONCLUSIONS/SIGNIFICANCE: The current study shows that active mammalian cells can be protected by a silica-alginate hybrid shell-like system. The functionality of the cell strain can be maintained. Consequently, cells coated with an artificial and a biocompatible mineral shell could respond physiologically within the human body in order to deliver therapeutic agents in a controlled fashion (i.e. insulin), substituting the declining organ functions of the patient

A geroscience approach for Parkinson's disease: Conceptual framework and design of PROPAG-AGEING project

Advanced age is the major risk factor for idiopathic Parkinson's disease (PD), but to date the biological relationship between PD and ageing remains elusive. Here we describe the rationale and the design of the H2020 funded project “PROPAG-AGEING”, whose aim is to characterize the contribution of the ageing process to PD development. We summarize current evidences that support the existence of a continuum between ageing and PD and justify the use of a Geroscience approach to study PD. We focus in particular on the role of inflammaging, the chronic, low-grade inflammation characteristic of elderly physiology, which can propagate and transmit both locally and systemically. We then describe PROPAG-AGEING design, which is based on the multi-omic characterization of peripheral samples from clinically characterized drug-naïve and advanced PD, PD discordant twins, healthy controls and "super-controls", i.e. centenarians, who never showed clinical signs of motor disability, and their offspring. Omic results are then validated in a large number of samples, including in vitro models of dopaminergic neurons and healthy siblings of PD patients, who are at higher risk of developing PD, with the final aim of identifying the molecular perturbations that can deviate the trajectories of healthy ageing towards PD development