A top-down proteomic approach reveals a salivary protein profile able to classify Parkinson's disease with respect to Alzheimer's disease patients and to healthy controls

Parkinson's disease (PD) is a complex neurodegenerative disease with motor and non-motor symptoms. Diagnosis is complicated by lack of reliable biomarkers. To individuate peptides and/or proteins with diagnostic potential for early diagnosis, severity and discrimination from similar pathologies, the salivary proteome in 36 PD patients was investigated in comparison with 36 healthy controls (HC) and 35 Alzheimer's disease (AD) patients. A top-down platform based on HPLC-ESI-IT-MS allowed characterizing and quantifying intact peptides, small proteins and their PTMs (overall 51). The three groups showed significantly different protein profiles, PD showed the highest levels of cystatin SA and antileukoproteinase and the lowest of cystatin SN and some statherin proteoforms. HC exhibited the lowest abundance of thymosin & beta;4, short S100A9, cystatin A, and dimeric cystatin B. AD patients showed the highest abundance of & alpha;-defensins and short oxidized S100A9. Moreover, different proteoforms of the same protein, as S-cysteinylated and S-glutathionylated cystatin B, showed opposite trends in the two pathological groups. Statherin, cystatins SA and SN classified accurately PD from HC and AD subjects. & alpha;-defensins, histatin 1, oxidized S100A9, and P-B fragments were the best classifying factors between PD and AD patients. Interestingly statherin and thymosin & beta;4 correlated with defective olfactory functions in PD patients. All these outcomes highlighted implications of specific proteoforms involved in the innate-immune response and inflammation regulation at oral and systemic level, suggesting a possible panel of molecular and clinical markers suitable to recognize subjects affected by PD

Prospezioni sismiche, geoelettriche ed elettromagnetiche ad alta risoluzione in prossimità della foce del Fiume Volturno

Nell’ambito dell’Obiettivo Realizzativo 2.3 “Sviluppo e allestimento di sensoristica e sistemi innovativi per osservazioni dell’iterazione terra-aria per la qualità dell’aria e degli ecosistemi agro-forestali” del progetto PON I-AMICA (Infrastruttura di Alta tecnologia per il Monitoraggio Integrato Climatico-Ambientale), l’Istituto per l’Ambiente Marino Costiero del Consiglio Nazionale delle Ricerche (CNR-I.A.M.C.) di Napoli, coordinato dal dott. Vincenzo Di Fiore, ha eseguito delle prospezioni sismiche, geoelettriche ed elettromagnetiche in un’area prospiciente la foce del Fiume Volturno. Tali indagini hanno avuto come obiettivo: La valutazione dell’intrusione nelle falde acquifere di componenti idrosaline provenienti dalla vicina area costiera; Lo studio, con risoluzione metrica, della porzione superficiale (0 - 80 metri di profondità) del sottosuolo al fine di caratterizzare, in termini di spessori e di velocità di propagazione, le serie riflettive che caratterizzano l’area in esame

Phosphorylation of FAM134C by CK2 controls starvation-induced ER-phagy.

Selective degradation of the endoplasmic reticulum (ER) via autophagy (ER-phagy) is initiated by ER-phagy receptors, which facilitate the incorporation of ER fragments into autophagosomes. FAM134 reticulon family proteins (FAM134A, FAM134B, and FAM134C) are ER-phagy receptors with structural similarities and nonredundant functions. Whether they respond differentially to the stimulation of ER-phagy is unknown. Here, we describe an activation mechanism unique to FAM134C during starvation. In fed conditions, FAM134C is phosphorylated by casein kinase 2 (CK2) at critical residues flanking the LIR domain. Phosphorylation of these residues negatively affects binding affinity to the autophagy proteins LC3. During starvation, mTORC1 inhibition limits FAM134C phosphorylation by CK2, hence promoting receptor activation and ER-phagy. Using a novel tool to study ER-phagy in vivo and FAM134C knockout mice, we demonstrated the physiological relevance of FAM134C phosphorylation during starvation-induced ER-phagy in liver lipid metabolism. These data provide a mechanistic insight into ER-phagy regulation and an example of autophagy selectivity during starvation.We thank G. Diez Roux and P. Ashley-Norman for critical reading of the manuscript. We thank the microscopy, MS, advanced histopathology, and FACS facilities at TIGEM Institute. We thank E. Nusco for helping us with AAV injections. Funding: This work was supported by European Research Council (ERC) (714551), Telethon intramural grants, and Associazione Italiana per la Ricerca sul Cancro (AIRC) (IG 2015 Id 17717) (to C.S.) and Telethon Foundation (TMPGCBX16TT), AFM Telethon (Trampoline Grant), and AIRC (MFAG-2020-24856) (to P.G.). G.D.L. is a recipient of AIRC fellowship “Francesco Alicino” (25407). V.L. acknowledges funding from the ERC (101001784), the Italian MIUR-PRIN 2017 (2017FJZZRC), and the Swiss National Supercomputing Center (CSCS) (project ID u8). The work of A.S. was supported by the German Research Foundation DFG (SFB1177/2 and WO210/20-2) and the Dr. Rolf M. Schwiete Stiftung (13/2017). A.E. is supported by the RETOS projects Programme of Spanish Ministry of Science, Innovation and Universities, Spanish State Research Agency (grants SAF2015-67538-R and PID2019-104012RB-I00), and the ERC (638891). A.B.P.-G. is a recipient of Ph.D. fellowship from MICIU/AEI (BES-2017-081381). A.R. is a recipient of Umberto Veronesi Foundation postdoctoral fellowship. Author contributions: G.D.L. and F.I. performed most of the experiments. F.I. and A.B.P.-G. performed in vivo experiments. M.M. performed mutagenesis experiments. S.A. and V.L. performed LC3-FAM134C binding analysis. C.P.Q.M. performed in vitro phosphorylation assays. L.C. analyzed CK2 substrate phosphorylation. F.S., A.P., C.C., and A.S. analyzed proteomic data. G.N. provided critical suggestions. A.R. performed proteomic experiments. A.E. supervised in vivo experiments. M.R., L.A.P., and O.M. supervised CK2 experiments. C.S. designed the study. P.G. and C.S. conceived and supervised the experiments. C.S., P.G., V.L., and M.R. wrote the paper. G.D.L. and F.I. prepared the figures. All the authors read the manuscript. Competing interests: The authors declare that they have no competing interests. Data and materials availability: All data needed to evaluate the conclusions in the paper are present in the paper and/or the Supplementary Materials.S

Application of X-Band Wave Radar for Coastal Dynamic Analysis: Case Test of Bagnara Calabra (South Tyrrhenian Sea, Italy)

Sea state knowledge has a key role in evaluation of coastal erosion, the assessment of vulnerability and potential in coastal zone utilization, and development of numerical models to predict its evolution. X-band radar measurements were conducted to observe the spatial and temporal variation of the sea-state parameters along a 3 km long sandy-gravelly pocket beaches forming a littoral cell on Bagnara Calabra. We produced a sequence of 1000 images of the sea state extending offshore up to 1 mile. The survey has allowed monitoring the coastline, the directional wave spectra, the sea surface current fields, and the significant wave heights and detecting strong rip currents which cause scours around the open inlets and affect the stability of the submerged reef-type breakwaters. The possibility to validate the data acquired with other datasets (e.g., LaMMA Consortium) demonstrates the potential of the X-band radar technology as a monitoring tool to advance the understanding of the linkages between sea conditions, nearshore sediment dynamics, and coastal change. This work proves the possibility to obtain relevant information (e.g., wave number, period, and direction) for evaluation of local erosion phenomena and of morphological changes in the nearshore and surf zone

Monitoraggio integrato di un'area marino-costiera: la foce del fiume Volturno (Mar Tirreno centrale)

Vengono presentati i risultati dell’attività di monitoraggio svolta nel corso del progetto PONa3_00363 I-AMICA (Infrastruttura di Alta tecnologia per il Monitoraggio Integrato Climatico-Ambientale; www.i-amica.it/i-amica/), nell’ambito delle attività relative all’Obiettivo Realizzativo 4.4 (Processi di interfaccia biosfera-idrosfera e funzionalità degli ecosistemi costieri). L’attività, che ha avuto come scopo l’acquisizione di conoscenze avanzate sulle dinamiche e/o variazioni nel tempo degli ecosistemi marino-costieri in relazione ai processi fisici, chimici e biologici che caratterizzano il loro habitat, si è sviluppata attraverso la sperimentazione di nuove metodologie di monitoraggio in relazione alle specifiche caratteristiche dell’area marino-costiera prospiciente la foce del fiume Volturno (Golfo di Gaeta). In particolare, oltre che sulle tecniche di monitoraggio classiche, lo studio si è principalmente focalizzato sulla acquisizione ed interpretazione di dati ambientali sia in colonna d’acqua che nei sedimenti a fondo mare e sulla identificazione di specie e/o associazioni di specie significative (bio-indicatori) da un punto di vista ambientale ed indicative dello stato di salute del sistema costiero. Poiché il sistema costiero rappresenta una struttura naturale complessa e delicata, la cui evoluzione è il risultato di delicati equilibri fisici, chimici e biologici, fortemente condizionabili dagli interventi antropici, l’attività di monitoraggio è stata integrata da studi sulla variazione della linea di costa, da studi sismostratigrafici della piana deltizia, sedimentologici e morfo-batimetrici dei fondali.Published1-714A. Oceanografia e climaJCR Journa

Modelling human choices: MADeM and decision‑making

Research supported by FAPESP 2015/50122-0 and DFG-GRTK 1740/2. RP and AR are also part of the Research, Innovation and Dissemination Center for Neuromathematics FAPESP grant (2013/07699-0). RP is supported by a FAPESP scholarship (2013/25667-8). ACR is partially supported by a CNPq fellowship (grant 306251/2014-0)

Expert consensus document:Cholangiocarcinoma: current knowledge and future perspectives consensus statement from the European Network for the Study of Cholangiocarcinoma (ENS-CCA)

Cholangiocarcinoma (CCA) is a heterogeneous group of malignancies with features of biliary tract differentiation. CCA is the second most common primary liver tumour and the incidence is increasing worldwide. CCA has high mortality owing to its aggressiveness, late diagnosis and refractory nature. In May 2015, the "European Network for the Study of Cholangiocarcinoma" (ENS-CCA: www.enscca.org or www.cholangiocarcinoma.eu) was created to promote and boost international research collaboration on the study of CCA at basic, translational and clinical level. In this Consensus Statement, we aim to provide valuable information on classifications, pathological features, risk factors, cells of origin, genetic and epigenetic modifications and current therapies available for this cancer. Moreover, future directions on basic and clinical investigations and plans for the ENS-CCA are highlighted

In Vitro and In Vivo Pharmacokinetics-Pharmacodynamics of GV143253A, a Novel Trinem

The aim of the present study was to characterize the pharmacokinetic-pharmacodynamic relationship of GV143253A, a novel trinem anti-methicillin-resistant Staphylococcus aureus (MRSA) agent active against gram-positive cocci, including multidrug-resistant clinical isolates. An in vitro pharmacodynamic study with methicillin-susceptible S. aureus (MSSA) and MRSA has shown that the duration of exposure to GV143253A rather than its concentration is the major determinant of the extent of bacterial killing. The in vitro findings were confirmed by use of a neutropenic murine model of thigh infection caused by MSSA ATCC 25923. From the dose-response curves, the static doses extrapolated for three different dosing intervals showed that more frequent dosing of GV143253A was more effective than less frequent dosing. A pharmacokinetic-pharmacodynamic analysis demonstrated that only the time during which the drug concentration exceeded the MIC (t>MIC) correlated with in vivo GV143253A activity. The value of t>MIC required to achieve a bacteriostatic effect in a thigh infection of neutropenic animals was 20% (95% confidence interval [CI], 18 to 22%) of the dosing interval. This result is similar to those reported in the literature for carbapenems and for GV104326A, another novel trinem compound. In addition, in order to compare the therapeutic efficacy of GV143253A to that of vancomycin in a thigh infection caused by MRSA in immunocompetent mice, suitable dosing regimens were designed on the basis of previous pharmacokinetic-pharmacodynamic findings for GV143253A and on the human pharmacokinetic profile of the glycopeptide. Although the pharmacokinetic profiles of the two agents were completely different, GV143253A showed good efficacy comparable to that of vancomycin, reducing by 4 log units the bacterial counts in the thighs of treated mice relative to untreated infected animals after 48 h of therapy. The results suggest that if the time of exposure to the pathogen above the MIC is at least 30% of the dosing interval, GV143253A could have a role in the clinical treatment of infections caused by MRSA, which is difficult to eradicate with current antibiotics

[A case of renal infarction: clinical and anatomic contribution].

A case o/ renal infarction presenting with acute abdomen is reported. Due to the extended renal damage nephrectomy wasperformed. Macroscopic appearance o/ the kidney (prevalent cortical vascular inforction) and o/ the surrounding tissues (retroperitoneal edema and abdominal ascites) suggested a comparison with epidemie haemorrhagic flver. Vascular supp/y to the kidney, in such cases, depends on the perforating arteries which may increase in number and size