Ca2+signalling: A common language for organelles crosstalk in Parkinson's disease

Parkinson's disease (PD) is a neurodegenerative disease caused by multifactorial pathogenic mechanisms. Familial PD is linked with genetic mutations in genes whose products are either associated with mitochondrial function or endo-lysosomal pathways. Of note, mitochondria are essential to sustain high energy demanding synaptic activity of neurons and alterations in mitochondrial Ca2+ signaling have been proposed as causal events for neurodegenerative process, although the mechanisms responsible for the selective loss of specific neuronal populations in the different neurodegenerative diseases is still not clear. Here, we specifically discuss the importance of a correct mitochondrial communication with the other organelles occurring at regions where their membranes become in close contact. We discuss the nature and the role of contact sites that mitochondria establish with ER, lysosomes, and peroxisomes, and how PD related proteins participate in the regulation/dysregulation of the tethering complexes. Unravelling molecular details of mitochondria tethering could contribute to identify specific therapeutic targets and develop new strategies to counteract the progression of the disease

Development of active and biodegradables containers for agricultural crops

En este trabajo, se propone el desarrollo de recipientes biodegradables para cultivos que puedan ser trasplantados directamente y actuar como fertilizantes. Se eligió gelatina bovina como material base, que se procesó en una mini mezcladora-inyectora junto con una solución concentrada de urea que actuó como plastificante. Se realizaron estudios reológicos y de tracción para evaluar la inyección de las mezclas y las prestaciones mecánicas relacionadas con la aplicación propuesta. Considerando que estos materiales biodegradables tienen baja resistencia al agua, se propuso incrementar la estabilidad de los recipientes mediante recubrimiento superficial. Asimismo, se estudió y analizó su influencia en el contenido de humedad, materia soluble e hinchamiento en agua destilada. Se observó que las muestras recubiertas fueron significativamente más estables en agua que las muestras control, lo que evidencia la buena calidad y homogeneidad del recubrimiento, que avala la factibilidad del sistema seleccionado y su potencial desarrollo de contenedores biodegradablesIn this paper, the development of biodegradable containers for crops that could be transplanted directly and act as fertilizers is proposed. Bovine gelatin was chosen as the base material, which was processed in a mini-injector mixer with a concentrated urea solution acted as a plasticizer. Rheological and tensile tests were performed in order to evaluate the injection of gelatin based formulations and mechanical properties related to the proposed application. Taking into account that biodegradable materials have a low water resistance, the increment of container stability was proposed using a surface coating. In addition, the influence of moisture content, the soluble matter and swelling were studied and analyzed. It was observed that coated samples were significantly more stable than the control ones, which guarantees the feasibility of the selected system and its potential development of biodegradable containers.Fil: Poggio, Franco. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Planta Piloto de Ingeniería Química. Universidad Nacional del Sur. Planta Piloto de Ingeniería Química; ArgentinaFil: Ciannamea, Emiliano Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Planta Piloto de Ingeniería Química. Universidad Nacional del Sur. Planta Piloto de Ingeniería Química; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones en Ciencia y Tecnología de Materiales. Universidad Nacional de Mar del Plata. Facultad de Ingeniería. Instituto de Investigaciones en Ciencia y Tecnología de Materiales; ArgentinaFil: Castillo, Luciana Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Planta Piloto de Ingeniería Química. Universidad Nacional del Sur. Planta Piloto de Ingeniería Química; ArgentinaFil: Barbosa, Silvia Elena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Planta Piloto de Ingeniería Química. Universidad Nacional del Sur. Planta Piloto de Ingeniería Química; Argentin

A Holistic Review of a Galactic Interaction

Our situation as occupants of the Milky Way (MW) Galaxy, bombarded by the Sagittarius dwarf galaxy, provides an intimate view of physical processes that can lead to the dynamical heating of a galactic disc. While this evolution is instigated by Sagittarius, it is also driven by the intertwined influences of the dark matter halo and the disc itself. We analyse an N-body simulation following a Sagittarius-like galaxy interacting with a MW-like host to disentangle these different influences during the stages of a minor merger. The accelerations in the disc plane from each component are calculated for each snapshot in the simulation, and then decomposed into Fourier series on annuli. The analysis maps quantify and compare the scales of the individual contributions over space and through time: (i) accelerations due to the satellite are only important around disc passages; (ii) the influence around these passages is enhanced and extended by the distortion of the dark matter halo; (iii) the interaction drives disc asymmetries within and perpendicular to the plane and the self-gravity of these distortions increase in importance with time eventually leading to the formation of a bar. These results have interesting implications for identifying different influences within our own Galaxy. Currently, Sagittarius is close enough to a plane crossing to search for localized signatures of its effect at intermediate radii, the distortion of the MW's dark matter halo should leave its imprint in the outer disc and the disc's own self-consistent response is sculpting the intermediate and inner disc.Comment: 19 pages, 18 figures, published in the Monthly Notices of the Royal Astronomical Societ

Development of behavioral parameters and ERPs in a novel-target visual detection paradigm in children, adolescents and young adults

Background: The present study analyzes the development of ERPs related to the process of selecting targets based on their novelty. Methods: One hundred and sixty-seven subjects from 6 to 26 years old were recorded with 30 electrodes during a visual target novelty paradigm. Results: Behavioral results showed good performance in children that improved with age: a decrease in RTs and errors and an increase in the d′ sensitivity parameter with age were obtained. In addition, the C response bias parameter evolved from a conservative to a neutral bias with age. Fronto-polar Selection Positivity (FSP) was statistically significant in all the age groups when standards and targets were compared. There was a statistically significant difference in the posterior Selection Negativity (SN) between the target and standard conditions in all age groups. The P3a component obtained was statistically significant in the emergent adult (18–21 years) and young adult (22–26 years) groups. The modulation of the P3b component by novel targets was statistically significant in all the age groups, but it decreased in amplitude with age. Peak latencies of the FSP and P3b components decreased with age. Conclusions: The results reveal differences in the ERP indexes for the cognitive evaluation of the stimuli presented, depending on the age of the subjects. The ability of the target condition to induce the modulation of the studied components would depend on the posterior-anterior gradient of cortex maturation and on the gradient of maturation of the low to higher order association areas.Ministerio de Economía y Competitividad PSI2013-47506-

Biomarkers in Coronary Artery Bypass Surgery: Ready for Prime Time and Outcome Prediction?

Coronary artery bypass surgery (CABG) is still one of the most frequently performed surgical procedures all over the world. The results of this procedure have been constantly improved over the years with low perioperative mortality rates, with relatively low complication rates. To further improve these outstanding results, the clinicians focused their attention at biomarkers as outcome predictors. Although biological testing for disease prediction has already been discussed many times, the role of biomarkers in outcome prediction after CABG is still controversial. In this article, we reviewed the current knowledge regarding the role of genetic and dynamic biomarkers and their possible association with the occurrence of adverse clinical outcomes after CABG. We also took into consideration that the molecular pathway activation and the possible imbalance may affect hard outcomes and graft patency. We analyzed biomarkers classified in two different categories depending on their possibility to change over time: genetic markers and dynamic markers. Moreover, we evaluated these markers by dividing them, into sub-categories, such as inflammation, hemostasis, renin-angiotensin, endothelial function, and other pathways. We showed that biomarkers might be associated with unfavorable outcomes after surgery, and in some cases improved outcome prediction. However, the identification of a specific panel of biomarkers or of some algorithms including biomarkers is still in an early developmental phase. Finally, larger studies are needed to analyze broad panel of biomarkers with the specific aim to evaluate the prediction of hard outcomes and graft patency

Evidence of a vertical kinematic oscillation beyond the Radcliffe Wave

The Radcliffe Wave (RW) is a recently discovered sinusoidal vertical feature of dense gas in the proximity of the Sun. In the disk plane, it is aligned with the Local Arm. However, the origin of its vertical undulation is still unknown. This study constrains the kinematics of the RW, using young stars and open clusters as tracers, and explores the possibility of this oscillation being part of a more extended vertical mode. We study the median vertical velocity trends of the young stars and clusters along with the RW and extend it further to the region beyond it. We discover a kinematic wave in the Galaxy, distinct from the warp, with the amplitude of oscillation depending on the age of the stellar population. We perform a similar analysis in the N-body simulation of a satellite as massive as the Sagittarius dwarf galaxy impacting the galactic disk. When projected in the plane, the spiral density wave induced by the satellite impact is aligned with the RW, suggesting that both may be the response of the disk to an external perturbation. However, the observed kinematic wave is misaligned. It appears as a kinematic wave travelling radially, winding up faster than the density wave matched by the RW, questioning its origin. If a satellite galaxy is responsible for this kinematic wave, we predict the existence of a vertical velocity dipole that should form across the disk and this may be measurable with the upcoming Gaia DR3 and DR4.Comment: Accepted for publication in Astronomy & Astrophysics Letter

The Radcliffe Wave as the gas spine of the Orion Arm

The Radcliffe Wave is a $\sim3$ kpc long coherent gas structure containing most of the star-forming complexes near the Sun. In this Letter we aim to find a Galactic context for the Radcliffe Wave by looking into a possible relationship between the gas structure and the Orion (Local) Arm. We use catalogs of massive stars and young open clusters based on \textit{Gaia} EDR3 astrometry, in conjunction with kiloparsec-scale 3D dust maps, to investigate the Galactic \textit{XY} spatial distributions of gas and young stars. We find a quasi-parallel offset between the luminous blue stars and the Radcliffe Wave, in that massive stars and clusters are found essentially inside and downstream from the Radcliffe Wave. We examine this offset in the context of color gradients observed in the spiral arms of external galaxies, where the interplay between density wave theory, spiral shocks, and triggered star formation has been used to interpret this particular arrangement of gas/dust and OB stars, and outline other potential explanations as well. We hypothesize that the Radcliffe Wave constitutes the gas reservoir of the Orion (Local) Arm, and presents itself as a prime laboratory to study the interface between Galactic structure, the formation of molecular clouds in the Milky Way, and star formation.Comment: Published in A&A Letter

Toll-like receptor 2 promotes breast cancer progression and resistance to chemotherapy

Cancer stem cells (CSCs) are the main drivers of disease progression and chemotherapy resistance in breast cancer. Tumor progression and chemoresistance might then be prevented by CSC-targeted therapies. We previously demonstrated that Toll-like Receptor (TLR)2 is overexpressed in CSCs and fuels their self-renewal. Here, we show that high TLR2 expression is linked to poor prognosis in breast cancer patients, therefore representing a candidate target for breast cancer treatment. By using a novel mammary cancer-prone TLR2(KO) mouse model, we demonstrate that TLR2 is required for CSC pool maintenance and for regulatory T cell induction. Accordingly, cancer-prone TLR2(KO) mice display delayed tumor onset and increased survival. Transplantation of TLR2(WT) and TLR2(KO) cancer cells in either TLR2(WT) or TLR2(KO) hosts shows that tumor initiation is mostly sustained by TLR2 expression in cancer cells. TLR2 host deficiency partially impairs cancer cell growth, implying a pro-tumorigenic effect of TLR2 expression in immune cells. Finally, we demonstrate that doxorubicin-induced release of HMGB1 activates TLR2 signaling in cancer cells, leading to a chemotherapy-resistant phenotype. Unprecedented use of TLR2 inhibitors in vivo reduces tumor growth and potentiates doxorubicin efficacy with no negative impact on the host immune system, opening new perspectives for the treatment of breast cancer patients

Untargeted metabolomics to go beyond the canonical effect of acetylsalicylic acid

15openInternationalItalian coauthor/editorGiven to its ability to irreversibly acetylate the platelet cyclooxygenase-1 enzyme, acetylsalicylic acid (ASA) is successfully employed for the prevention of cardiovascular disease. Recently, an antitumoral effect of ASA in colorectal cancer has been increasingly documented. However, the molecular and metabolic mechanisms by which ASA exerts such effect is largely unknown. Using a new, untargeted liquid chromatography–mass spectrometry approach, we have analyzed urine samples from seven healthy participants that each ingested 100 mg of ASA once daily for 1 week. Of the 2007 features detected, 25 metabolites differing after ASA ingestion (nominal p 1) were identified, and pathway analysis revealed low levels of glutamine and of metabolites involved in histidine and purine metabolisms. Likewise, consistent with an altered fatty acid β-oxidation process, a decrease in several short- and medium-chain acyl-carnitines was observed. An abnormal β-oxidation and a lower than normal glutamine availability suggests reduced synthesis of acetyl-Co-A, as they are events linked to one another and experimentally related to ASA antiproliferative effects. While giving an example of how untargeted metabolomics allows us to explore new clinical applications of drugs, the present data provide a direction to be pursued to test the therapeutic effects of ASA—e.g., the antitumoral effect—beyond cardiovascular protectionopenDi Minno, Alessandro; Porro, Benedetta; Turnu, Linda; Manega, Chiara Maria; Eligini, Sonia; Barbieri, Simone; Chiesa, Mattia; Poggio, Paolo; Squellerio, Isabella; Anesi, Andrea; Fiorelli, Susanna; Caruso, Donatella; Veglia, Fabrizio; Cavalca, Viviana; Tremoli, ElenaDi Minno, A.; Porro, B.; Turnu, L.; Manega, C.M.; Eligini, S.; Barbieri, S.; Chiesa, M.; Poggio, P.; Squellerio, I.; Anesi, A.; Fiorelli, S.; Caruso, D.; Veglia, F.; Cavalca, V.; Tremoli, E