Molecular determinants of ER-Golgi contacts identified through a new FRET-FLIM system.
Publication Date: 18/01/2019, on The Journal of cell biology
by Venditti R, Rega LR, Masone MC, Santoro M, Polishchuk E, Sarnataro D, Paladino S, D'Auria S, Varriale A, Olkkonen VM, Di Tullio G, Polishchuk R, De Matteis MA
ER-TGN contact sites (ERTGoCS) have been visualized by electron microscopy, but their location in the crowded perinuclear area has hampered their analysis via optical microscopy as well as their mechanistic study. To overcome these limits we developed a FRET-based approach and screened several candidates to search for molecular determinants of the ERTGoCS. These included the ER membrane proteins VAPA and VAPB and lipid transfer proteins possessing dual (ER and TGN) targeting motifs that have been hypothesized to contribute to the maintenance of ERTGoCS, such as the ceramide transfer protein CERT and several members of the oxysterol binding proteins. We found that VAP proteins, OSBP1, ORP9, and ORP10 are required, with OSBP1 playing a redundant role with ORP9, which does not involve its lipid transfer activity, and ORP10 being required due to its ability to transfer phosphatidylserine to the TGN. Our results indicate that both structural tethers and a proper lipid composition are needed for ERTGoCS integrity.
Ultra-short term HRV features as surrogates of short term HRV: a case study on mental stress detection in real life.
Publication Date: 17/01/2019, on BMC medical informatics and decision making
by Castaldo R, Montesinos L, Melillo P, James C, Pecchia L
This paper suggests a method to assess the extent to which ultra-short Heart Rate Variability (HRV) features (less than 5 min) can be considered as valid surrogates of short HRV features (nominally 5 min). Short term HRV analysis has been widely investigated for mental stress assessment, whereas the validity of ultra-short HRV features remains unclear. Therefore, this study proposes a method to explore the extent to which HRV excerpts can be shortened without losing their ability to automatically detect mental stress.
Milk From Cow Fed With High Forage/Concentrate Ratio Diet: Beneficial Effect on Rat Skeletal Muscle Inflammatory State and Oxidative Stress Through Modulation of Mitochondrial Functions and AMPK Activity.
Publication Date: 17/01/2019, on Frontiers in physiology
by Trinchese G, Cavaliere G, Penna E, De Filippo C, Cimmino F, Catapano A, Musco N, Tudisco R, Lombardi P, Infascelli F, Messina G, Muredda L, Banni S, Monda M, Crispino M, Mollica MP
Milk and dairy products are relevant components of daily diet and are part of dietary recommendation in many countries due to their content of key nutrients. However, the relatively high content of saturated fat of the milk and its extensive usage for every age group raises concerns about its potential negative health effects. Therefore, in the last years, several researchers dedicated their attention to milk production and quality. Milk fatty acids profile depend on cow feeding and in particular on the type of forage and concentrate and forage/concentrate ratio. It was demonstrated that feeding dairy cows with a 70/30 forage/concentrate ratio yields milk with a low ω6:ω3 ratio and high CLA levels. In this work, we demonstrated that the supplementation of rats diet with this high forage milk (HFM) results, in the skeletal muscle of these animals, in a reduced lipid content and inflammation levels, and an improved mitochondrial lipid oxidation, and redox status through modulation of AMPK activity.
Crowding and conformation interplay on human DNA G-quadruplex by ultraviolet resonant Raman scattering.
Publication Date: 14/01/2019, on Physical chemistry chemical physics : PCCP
by Di Fonzo S, Bottari C, Brady JW, Tavagnacco L, Caterino M, Petraccone L, Amato J, Giancola C, Cesàro A
The G-quadruplex-forming telomeric sequence (TTAGGG)4TT was investigated by polarized Ultraviolet Resonance Raman Scattering (UVRR) at 266 nm. The presence of 40% poly(ethylene glycol) and the so-called "self-crowding" condition were used to induce the hybrid-to-parallel topology transition. Analysis of frequency shifts with temperature showed the role of several functional groups in the topological transitions and provides structural dynamical information. Circular dichroism under similar conditions was used as a reference. UVRR shed light on the effect of intramolecular interactions and of local and environmental dynamics in promoting different G-quadruplex topologies, induced by solution conditions or by temperature changes. Overall, these findings showed the enormous potential of this spectroscopy for G-quadruplex conformational studies.
Comparison of alternate and original forms of the Montreal Cognitive Assessment (MoCA): an Italian normative study.
Publication Date: 14/01/2019, on Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology
by Siciliano M, Chiorri C, Passaniti C, Sant'Elia V, Trojano L, Santangelo G
The Montreal Cognitive Assessment (MoCA) is a screening test widely used in clinical practice and suited for detection of Mild Cognitive Impairment. Alternate forms of the MoCA were developed to avoid "learning effect" in serial assessments, and the present study aimed at investigating inter-form parallelism and at providing normative values for the Italian versions of MoCAs 2 and 3.
Is Shouldice the best NON-MESH inguinal hernia repair technique? A systematic review and network metanalysis of randomized controlled trials comparing Shouldice and Desarda.
Publication Date: 09/01/2019, on International journal of surgery (London, England)
by Bracale U, Melillo P, Piaggio D, Pecchia L, Cuccurullo D, Milone M, De Palma GD, Cavallaro G, Campanelli G, Merola G, Stabilini C
Current guidelines state that the Shouldice technique has lower recurrence rates than other suture repairs and therefore is strongly recommended in non-mesh inguinal hernia repair. Recently a new tissue repair technique has been proposed by Desarda and studied in trials against Lichtenstein technique.
On the pH-Modulated Ru-Based Prodrug Activation Mechanism.
Publication Date: 07/01/2019, on Inorganic chemistry
by Caterino M, Herrmann M, Merlino A, Riccardi C, Montesarchio D, Mroginski MA, Musumeci D, Ruffo F, Paduano L, Hildebrandt P, Kozuch J, Vergara A
The Ru-based prodrug AziRu efficiently binds to proteins, but the mechanism of its release is still disputed. Herein, in order to test the hypothesis of a reduction-mediated Ru release from proteins, a Raman-assisted crystallographic study on AziRu binding to a model protein (hen egg white lysozyme), in two different oxidation states, Ru and Ru, was carried out. Our results indicate Ru reduction, but the Ru release upon reduction is dependent on the reducing agent. To better understand this process, a pH-dependent, spectroelectrochemical surface-enhanced Raman scattering (SERS) study was performed also on AziRu-functionalized Au electrodes as a surrogate and simplest model system of Ru- and Ru-based drugs. This SERS study provided a p K of 6.0 ± 0.4 for aquated AziRu in the Ru state, which falls in the watershed range of pH values separating most cancer environments from their physiological counterparts. These experiments also indicate a dramatic shift of the redox potential E by >600 mV of aquated AziRu toward more positive potentials upon acidification, suggesting a selective AziRu reduction in cancer lumen but not in healthy ones. It is expected that the nature of the ligands (e.g., pyridine vs imidazole, present in well-known Ru complex NAMI-A) will modulate the p K and E, without affecting the underlying reaction mechanism.
A novel SLC20A2 gene mutation causing primary familial brain calcification in an Ukrainian patient.
Publication Date: 03/01/2019, on Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology
by Oliva M, Capaldo G, D'Amico A, Colavito D, Elefante A, Straccia G, Ugga L, Puoti G
Methods for Monitoring Macroautophagy in Pancreatic Cancer Cells.
Publication Date: 01/01/2019, on Methods in molecular biology (Clifton, N.J.)
by Vidoni C, Ferraresi A, Seca C, Secomandi E, Isidoro C
Macroautophagy is a catabolic process through which redundant, aged, or damaged cellular structures are first enclosed within double-membrane vesicles (called autophagosomes), and thereafter degraded within lysosomes. Macroautophagy provides a primary route for the turnover of macromolecules, membranes and organelles, and as such plays a major role in cell homeostasis. As part of the stress response, autophagy is crucial to determine the cell fate in response to extracellular or intracellular injuries. Autophagy is involved in cancerogenesis and in cancer progression. Here we illustrate the essential methods for monitoring autophagy in pancreatic cancer cells.
Early posterior vitreous detachment is associated with LAMA5 dominant mutation.
Publication Date: 27/12/2018, on Ophthalmic genetics
by Napolitano F, Di Iorio V, Di Iorio G, Melone MAB, Gianfrancesco F, Simonelli F, Esposito T, Testa F, Sampaolo S
Extracellular matrix molecular components, previously linked to multisystem syndromes include collagens, fibrillins and laminins. Recently, we described a novel multisystem syndrome caused by the c.9418G>A p.(V3140M) mutation in the laminin alpha-5 (LAMA5) gene, which affects connective tissues of all organs and apparatus in a three generation family. In the same family, we have also reported a myopic trait, which, however, was linked to the Prolyl 4-hydroxylase subunit alpha-2 (P4HA2) gene. Results of investigation on vitreous changes and their pathogenesis are reported in the present study.
Correction to: Thrombus aspiration in hyperglycemic ST-elevation myocardial infarction (STEMI) patients: clinical outcomes at 1-year follow-up.
Publication Date: 27/12/2018, on Cardiovascular diabetology
by Sardu C, Barbieri M, Balestrieri ML, Siniscalchi M, Paolisso P, Calabrò P, Minicucci F, Signoriello G, Portoghese M, Mone P, D'Andrea D, Gragnano F, Bellis A, Mauro C, Paolisso G, Rizzo MR, Marfella R
Following publication of the original article , the authors reported an error in Acknowledgment section. The last sentence should read as "All authors have read and approval the submission to Cardiovascular Diabetology.
Neuro-Behçet's disease presenting as an isolated progressive cognitive and behavioral syndrome.
Publication Date: 25/12/2018, on Neurocase
by Saracino D, Allegorico L, Barbarulo AM, Pollo B, Giaccone G, D'Amico A, D'Incerti L, Bugiani O, Di Iorio G, Sampaolo S, Melone MAB
Behçet's disease is a chronic inflammatory disorder manifesting as a vasculitis that affects arteries and veins of any size. Up to 44% of cases may also present with neurological symptoms, thus defining Neuro-Behçet's disease. We describe a case of Neuro-Behçet's disease characterized by progressive behavioral and cognitive deterioration prevailing over other neurological symptoms, without evident systemic involvement.
S29434, a quinone reductase 2 inhibitor: main biochemical and cellular characterization.
Publication Date: 19/12/2018, on Molecular pharmacology
by Boutin JA, Bouillaud F, Janda E, Gacsalyi I, Guillaumet G, Hirsch EC, Kane DA, Nepveu F, Reybier K, Dupuis P, Bertrand M, Chhour M, Le Diguarher T, Antoine M, Brebner K, Da Costa H, Ducrot P, Giganti A, Goswami V, Guedouari H, Michel PP, Patel A, Paysant J, Stojko J, Viaud-Massuard MC, Ferry G
Quinone reductase 2 (QR2, E.C. 188.8.131.52) is an enzyme with a feature that has attracted attention for several decades: in standard conditions, instead of recognizing NAD(P)H as an electron donor, it recognizes putative metabolites of NADH such as N-methyl- and N-ribosyl-dihydronicotinamide. QR2 has been particularly associated with reactive oxygen species and memory, strongly suggesting a link among QR2 (as a possible key element in pro-oxidation), autophagy, and neurodegeneration. In molecular and cellular pharmacology, understanding physiopathological associations can be difficult because of a lack of specific and powerful tools. Here we present a thorough description of the potent, nanomolar inhibitor S29434 (IC50 = 5 to 16 nM) of QR2 at different organizational levels. We provide full detailed syntheses; describe its co-crystallization with and behavior at QR2 on a millisecond timeline; show that it penetrates cell membranes and inhibits QR2-mediated ROS production within the 100 nM range; and describe its actions in several in vivo models, and lack of actions in various ROS-producing systems. The inhibitor is fairly stable in vivo, penetrates cells, specifically inhibits QR2, and shows activities that suggest a key role for this enzyme in different pathological conditions including neurodegenerative diseases.
Modulating interoception by insula stimulation: A double-blinded tDCS study.
Publication Date: 17/12/2018, on Neuroscience letters
by Sagliano L, Magliacano A, Parazzini M, Fiocchi S, Trojano L, Grossi D
Interoception consists in the perception and processing of internal body signals, such as heartbeat. Previous neuroimaging studies revealed that attention to heartbeat activated bilateral insula and premotor regions. In the present double-blind study, we aimed at testing the role of insula in interoception by means of transcranial direct current stimulation (tDCS) interfering with its activity. Sixteen healthy participants responded to a questionnaire to evaluate the tendency to be internally focused and performed a heartbeat counting task before and after tDCS in three sessions (left insula stimulation, right insula stimulation, sham stimulation). Real and reported heartbeat were recorded and used to calculate the accuracy scores. A significant interaction between stimulation condition and time (pre- and post-stimulation) was found due to a significant improvement of the interoceptive accuracy in the sham condition only. Our results demonstrated that stimulation over the insula reduced the possibility to improve the precision with which individuals detect internal signals.
Circulating levels of IL-1 family cytokines and receptors in Alzheimer's disease: new markers of disease progression?
Publication Date: 12/12/2018, on Journal of neuroinflammation
by Italiani P, Puxeddu I, Napoletano S, Scala E, Melillo D, Manocchio S, Angiolillo A, Migliorini P, Boraschi D, Vitale E, Di Costanzo A
Although the mechanisms underlying AD neurodegeneration are not fully understood, it is now recognised that inflammation could play a crucial role in the initiation and progression of AD neurodegeneration. A neuro-inflammatory network, based on the anomalous activation of microglial cells, includes the production of a number of inflammatory cytokines both locally and systemically. These may serve as diagnostic markers or therapeutic targets for AD neurodegeneration.