Colocalization and Interaction Study of Neuronal JNK3, JIP1, and β-Arrestin2 Together with PSD95

c-Jun N-terminal kinases (JNKs) are stress-activated serine/threonine protein kinases belonging to the mitogen-activated protein kinase (MAPK) family. Among them, JNK3 is selectively expressed in the central nervous system, cardiac smooth muscle, and testis. In addition, it is the most responsive JNK isoform to stress stimuli in the brain, and it is involved in synaptic dysfunction, an essential step in neurodegenerative processes. JNK3 pathway is organized in a cascade of amplification in which signal transduction occurs by stepwise, highly controlled phosphorylation. Since different MAPKs share common upstream activators, pathway specificity is guaranteed by scaffold proteins such as JIP1 and β-arrestin2. To better elucidate the physiological mechanisms regulating JNK3 in neurons, and how these interactions may be involved in synaptic (dys)function, we used (i) super-resolution microscopy to demonstrate the colocalization among JNK3–PSD95–JIP1 and JNK3–PSD95–β-arrestin2 in cultured hippocampal neurons, and (ii) co-immunoprecipitation techniques to show that the two scaffold proteins and JNK3 can be found interacting together with PSD95. The protein-protein interactions that govern the formation of these two complexes, JNK3–PSD95–JIP1 and JNK3–PSD95–β-arrestin2, may be used as targets to interfere with their downstream synaptic events.     

Scoping Review on Platelets and Tumor Angiogenesis: Do We Need More Evidence or Better Analysis?

Platelets are an active component of the tumor microenvironment (TME), involved in the regulation of multiple tumor processes, including angiogenesis. They are generated rich in angiogenic factors in their granules to actively participate in the hemostatic process by megakaryocytes and further enriched in angiogenic factors by all components of the tumor microenvironment to control the angiogenic process because of their preferential relationship with the endothelial component of vessels. In recent decades, the literature has reported a great deal of evidence on the role of platelets in tumor angiogenesis; however, it is unclear whether the number or mean volume of platelets and/or their content and localization in TME may have clinical relevance in the choice and management of therapy for the cancer patient. In this scoping review, we collected and critically reviewed the scientific evidence supporting a close relationship between platelets, cancer, and angiogenesis. The aim of this work was to define the landscape of platelet-activated angiogenesis in cancer progression and analyze what and how much evidence is present in the last 20 years in the literature at both the preclinical and clinical levels, to answer whether platelets could be a useful determinant for analyzing tumor angiogenesis. In conclusion, this scoping review indicates that there is much evidence, both preclinical and clinical, but in the preclinical context, studies demonstrate the direct involvement of platelets in tumor angiogenesis; in the clinical context the evidence is indirect, though strong, and the indication of how and to what extent platelet content contributes to tumor angiogenesis is lacking. So, do we need more evidence or better analysis? More molecular and quali-quantitative data is needed to translate the results obtained in preclinical studies into the clinical setting. This information about platelets, if correlated with tumor type and its biology, including tumor vasculature, type of angiogenesis, and patient characteristics (age, sex, comorbidities, drug treatments for chronic diseases) could be an important pa- rameter for correlating platelet biology to angiogenesis, for personalizing cancer therapy, and for clinical prognosis.     

Erythro–Magneto–HA–Virosome: A Bio-Inspired Drug Delivery System for Active Targeting of Drugs in the Lungs

Over the past few decades, finding more efficient and selective administration routes has gained significant attention due to its crucial role in the bioavailability, absorption rate and pharmacokinetics of therapeutic substances. The pulmonary delivery of drugs has become an attractive target of scientific and biomedical interest in the health care research area, as the lung, thanks to its high permeability and large absorptive surface area and good blood supply, is capable of absorbing pharmaceuticals either for local deposition or for systemic delivery. Nevertheless, the pulmonary drug delivery is relatively complex, and strategies to mitigate the effects of mechanical, chemical and immunological barriers are required. Herein, engineered erythrocytes, the Erythro–Magneto–Hemagglutinin (HA)–virosomes (EMHVs), are used as a novel strategy for efficiently delivering drugs to the lungs. EMHV bio-based carriers exploit the physical properties of magnetic nanoparticles to achieve effective targeting after their intravenous injection thanks to an external magnetic field. In addition, the presence of hemagglutinin fusion proteins on EMHVs’ membrane allows the DDS to anchor and fuse with the target tissue and locally release the therapeutic compound. Our results on the biomechanical and biophysical properties of EMHVs, such as the membrane robustness and deformability and the high magnetic susceptibility, as well as their in vivo biodistribution, highlight that this bio-inspired DDS is a promising platform for the controlled and lung-targeting delivery of drugs, and represents a valuable alternative to inhalation therapy to fulfill unmet clinical needs.     

Absorption of sulphur dioxide by electrosprayed droplets

This paper describes and discusses experimental results on the absorption of sulphur dioxide in electrified water sprays, either when the polluted gas is treated as is or when the gas is exposed to a corona source to ionize the sulphur dioxide. The experiments revealed that an electrified spray with a charge-to-mass ratio of 50 μC · kg⁻¹ enabled the absorption rate of droplets to double, regardless of their polarities. Corona charging gave rise to an increase in the SO₂ depletion rate over the scrubber wall, while negligible effects appeared on the actual droplets absorption rate. These findings suggested that faster absorption rates mostly, though not uniquely, depend on the modifications on the morphological and interfacial properties of the sprayed droplets induced by the free electric charge imposed on their surface. Conversely, the absorption rates were negligibly affected by the electrical interactions between droplets (either charged or uncharged) and the sulphur dioxide ions/radicals originating from the corona source.     

CFD modeling of LPG vessels under fire exposure conditions

Fire exposure of tanks used for the storage and transportation of liquefied gases under pressure may cause complex heat‐ and mass‐transfer phenomena that may contribute to compromise the integrity of the vessels in accident scenarios. Heat transfer through vessel lading results in the heat‐up of the internal fluid and the increase of vessel internal pressure. However, local temperature gradients in the liquid phase cause liquid stratification phenomena that result in a more rapid vaporization and pressure build‐up in the liquid phase. These fundamental phenomena were analyzed by a computational fluid dynamic model. The model was specifically focused on the early steps of vessel heat‐up, when liquid stratification plays a relevant role in determining the vessel internal pressure. A two‐dimensional transient simulation was set up using ANSYS FLUENT in order to predict the evolution of the liquid and vapor phases during the tank heat up. The model was validated against large scale experimental data available for liquefied petroleum gas vessels exposed to hydrocarbon fires, and was applied to case studies derived from recent accidental events in order to assess the expected time of pressure build‐up in different fire scenarios. © 2014 American Institute of Chemical Engineers AIChE J 60: 4292–4305, 2014     

Development of a biomimetic miniature robotic crawler

The paper presents the development of segmented artificial crawlers endowed with passive hook-shaped frictional microstructures. The goal is to find design rules for fabricating biomimetic, adaptable and mobile machines mimicking segmented animals with hydrostatic skeleton, and intended to move effectively along unstructured substrates. The paper describes the mechanical model, the design and the fabrication of a SMA-actuated segmented microrobot, whose locomotion is inspired by the peristaltic motion of Annelids, and in particular of earthworms (Lumbricus Terrestris). Experimental locomotion performance are compared with theoretical performance predicted by a purposely developed friction model -taking into account design parameters such as number of segments, body mass, special friction enhancement appendixes—and with locomotion performance of real earthworms as presented in literature. Experiments indicate that the maximum speed of the crawler prototype is 2.5 mm/s, and that 3-segment crawlers have almost the same velocity as earthworms having the same weight (and about 330% their length), whereas 4-segment crawlers have the same velocity, expressed as body lengths/s, as earthworms with the same mass (and about 270% their length). Arianna Menciassi (MS, 1995; PhD, 1999) joined the CRIM Lab of the Scuola Superiore Sant’Anna (Pisa, Italy) as a Ph.D. student in Bioengineering with a research program on the micromanipulation of mechanical and biological micro-objects. The main results of the activity on micromanipulation were presented at the IEEE International Conference on Robotics & Automation (May 2001, Seoul) in a paper titled “Force Feedback-based Microinstrument for Measuring Tissue Properties and Pulse in Microsurgery”, which won the “ICRA2001 Best Manipulation Paper Award”. In the year 2000, she was offered a position of Assistant Professor in Biomedical Robotics at the Scuola Superiore Sant’Anna and in June 2006 she obtained a promotion to Associate Professor. Her main research interests are in the field of biomedical microrobotics, biomimetics, microfabrication technologies, micromechatronics and microsystem technologies. She is working on several European projects and international projects for the development of minimally invasive instrumentation for medical applications and for the exploitation of micro- and nano-technologies in the medical field. Samuele Gorini received his Laurea Degree in Mechanical Engineering (with honors) from the University of Pisa, Italy, in 2001. In 2005 he obtained the Ph.D. in Microsystem Engineering with a thesis on locomotion methods and systems for miniaturised endoscopic devices. Since 2000, he has been working at the CRIM Lab of the Scuola Superiore Sant’Anna in Pisa, Italy. His research interests are in the field of biomedical robotics with a special focus on actuation technologies. Starting from the year 2004 he has been president of Era Endoscopy S.r.l., a start-up company of Scuola Superiore Sant’Anna developing novel devices for endoscopy. Dino Accoto (MS 1998, PhD 2002) is Assistant Professor of Biomedical Engineering at Scuola Sant’Anna (Pisa, Italy). He received the Laurea degree in Mechanical Engineering from the University of Pisa (cum laude) in 1998, the diploma in Engineering from the Scuola Sant’Anna (cum laude) in 1999 and the PhD degree from the Scuola Sant’Anna in 2002. From October 2001 to September 2002 he has been visiting scholar at the RPL-Lab, Stanford University (Ca, USA). Since 2004 he cooperates with the Biomedical Robotics & EMC Lab at Campus Bio-Medico University in Rome. His main research field is the modelling and development of small electromechanical systems, with a special attention to multi-physics and multi-domain approaches. The research, often inspired by the analysis of natural mechanisms, has been mainly applied to hybridizing microtechnologies, including microfluidics, and robotics. He has co-authored more than 30 papers, appeared in international journals and conference proceedings. Paolo Dario received his Dr. Eng. Degree in Mechanical Engineering from the University of Pisa, Italy, in 1977. He is currently a Professor of Biomedical Robotics at the Scuola Superiore Sant’Anna in Pisa.. He also teaches courses at the School of Engineering of the University of Pisa and at the Campus Biomedico University in Rome. He has been Visiting Professor at Brown University, Providence, RI, USA, at the Ecole Polytechnique Federale de Lausanne (EPFL), Lausanne, Switzerland, at Waseda University, Tokyo, Japan, at the College de France, Paris, and at the Ecole Normale Superieure de Cachan, France. He was the founder of the ARTS (Advanced Robotics Technologies and Systems) Laboratory and is currently the Co-ordinator of the CRIM (Center for the Research in Microengineering) Laboratory of the Scuola Superiore Sant’Anna, where he supervises a team of about 70 researchers and Ph.D. students. His main research interests are in the fields of medical robotics, bio-robotics, mechatronics and micro/nanoengineering, and specifically in sensors and actuators for the above applications, and in robotics for rehabilitation. He is the coordinator of many national and European projects, the editor of two books on the subject of robotics, and the author of more than 200 scientific papers (75 on ISI journals). He is Editor-in-Chief, Associate Editor and member of the Editorial Board of many international journals. Prof. Dario has served as President of the IEEE Robotics and Automation Society in the years 2002–2003. He has been the General Chair of the IEEE RAS-EMBS BioRob’06 Conference and he is the General Co-Chair of ICRA 2007 Conference. Prof. Dario is an IEEE Fellow, a Fellow of the European Society on Medical and Biological Engineering, and a recipient of many honors and awards, such as the Joseph Engelberger Award. He is also a member of the Board of the International Foundation of Robotics Research (IFRR).     

Functionalized lactic acid macromonomers via polycondensation as an alternative to ring opening polymerization

Engineered polylactic acid (PLA) nanoparticles synthesized from oligo(lactic acid) macromonomers have been studied over the last decades for controlled drug delivery. These macromonomers are typically produced via ring-opening polymerization (ROP) of the cyclic dimer lactide, initiated by 2-hydroxyethyl methacrylate (HEMA). This reaction route, despite leading to well-defined macromonomers, relies on the production of lactide from lactic acid, which burdens the ROP overall cost for more than 30%. In this work, we report the synthesis of PLA-based macromonomers by direct polycondensation of lactic acid in the presence of HEMA as a valuable alternative to ROP. In particular, we compare the two processes side by side, focusing on the production of three HEMA-LA_n macromonomers, with n = 2, 4, and 6. Detailed kinetic models are developed for both reaction systems, and the corresponding parameters are estimated by fitting the experimental data. Through these models, the reaction kinetics as well as the time evolution of the entire chain length distributions of the products from polycondensation and ROP could be reliably predicted. This way, we demonstrated that polycondensation is a valuable alternative to ROP only for macromonomers with an average chain length of up to 4 and that ROP remains the main route to longer chains, when a strict control over the chain length distribution is required.