IDENTIFICATION AND CHARACTERIZATION OF THE 'GUT VASCULAR BARRIER'

In order to protect the body from a wide range of harmful environmental agents, the intestine has developed a number of barrier mechanisms to limit the entry of potential hazards. These include the physical barrier formed by the epithelial layer and the intestinal immune system that is important to induce either tolerance against food antigens and intestinal flora or inflammatory responses against dangerous microorganisms. It has been demonstrated that tolerance against commensal bacteria is strictly compartmentalized, in the sense that the systemic immune system is completely unprimed by these bacteria. It was demonstrated that the mLNs function as a \u201cfirewall\u201d confining induction of tolerance to the mucosa while the systemic immune system remains ignorant to these bacteria. However, in these studies how the bacterial flora is excluded from the entrance in the bloodstream via the intestinal blood vessels has not been analyzed. Here, we describe a new barrier that we called the GVB (gut vascular barrier) that plays a fundamental role in controlling the spreading of molecules and bacteria to systemic sites. We found that intestinal endothelial cells (ECs) express the main components of TJs (occludin, JAM-A, CLDN-12, ZO-1 and cingulin) and AJs (VE-cadherin and junctional \u3b2-catenin), indicating the presence of a barrier that excludes bacteria from passing through the paracellular route. In addition, we observed the existence of a \u201cgut vascular unit\u201d (GVU) whereby ECs were associated with enteric glial cells and pericytes, whose role in the establishment of the endothelial barrier phenotype remains to be analyzed. Moreover, we show that GVB integrity could be modified by Salmonella typhimurium infection. Indeed, upon infection ECs up-regulated the expression of PLVAP, that has been previously used as a marker of immature/damaged vascular barrier in the brain, and up-regulated caveolin-1, the major component of caveolae. These changes correlated with a higher permeability of the endothelium to small molecules and to bacteria. One way by which S. typhimurium could modify the barrier properties of the intestinal blood vessels could be through the negative regulation of the Wnt/\u3b2-catenin signaling pathway. Indeed, we found that the activation of \u3b2-catenin was reduced upon Salmonella infection in vitro. Consistently, we found that Salmonella was incapable to modify ECs permeability and to spread systemically in mice where \u3b2-catenin was constitutively activated by genetic means only in vascular ECs. Furthermore, it appeared that the TTSS encoded by Salmonella pathogenicity island-2 was involved in the regulation of Wnt/\u3b2-catenin signaling pathway in ECs. Finally, preliminary results show that the microbiota could induce GVB maturation and maintenance. However, the mechanisms involved in these processes as well as the bacterial species responsible for this process have not been investigated yet

Augmented Reality to Engage Visitors of Science Museums through Interactive Experiences

In the last years, interactive exhibitions based on digital technologies have become widely common, thanks to their flexibility and effectiveness in engaging visitors and creating memorable experiences. One of the topics in which digital technologies can be particularly effective is the communication of abstract concepts that are difficult for the human mind to imagine. An emblematic example is the astronomy discipline, which requires us to imagine and understand phenomena far away from our everyday life. In this paper, the authors present a research project, MARSS, in which digital technologies are used effectively to enhance the Users' Experience of the Museo Astronomico di Brera located in Milan. Specifically, the MARSS project aims at designing and developing a new digital journey inside the museum to allow different categories of visitors to enjoy the exhibition in an engaging and interactive way. The paper presents the design and development phases of the experience and its evaluation with users. The results of the evaluation indicate that the digital interactive experience is appreciated by users and is successful in translating the content of high scientific value into more engaging and easily understandable elements

Elastic Chiral Waveguides with Gyro-Hinges

This article presents a novel chiral structure, consisting of Euler–Bernoulli beams connected to gyroscopic spinners.Anew type of boundary condition is introduced, which is referred to as a gyrohinge. In this system, flexural waves are coupled with rotational motion.Time-harmonic conditions are derived by assuming small nutation angles of the spinners. It is shown that the eigenfrequencies of a finite beam with gyro-hinges at one or both ends change dramatically with the moments of inertia and the spin and precession rates of the spinners. The formulation is then extended to elastic beams with periodically-spaced gyro-hinges, whose dispersion properties are investigated in detail. In particular, it is shown how stop-bands and standing modes are affected by the introduction of gyroscopic spinners at the junctions. It is also demonstrated that a periodic system composed of beams connected by gyro-hinges represents a good approximation of a gyrobeam, a theoretical structural element consisting of an elastic beam possessing a continuous distribution of stored angular momentum. The gyricity coefficient of a gyrobeam is then interpreted in terms of the physical parameters of the system of beams with gyroscopic spinners. This article opens a new perspective on the design and practical implementation of chiral mechanical systems

NAAA-regulated lipid signaling governs the transition from acute to chronic pain

Chronic pain affects 1.5 billion people worldwide but remains woefully undertreated. Understanding the molecular events leading to its emergence is necessary to discover disease-modifying therapies. Here we show that N-acylethanolamine acid amidase (NAAA) is a critical control point in the progression to pain chronicity, which can be effectively targeted by small-molecule therapeutics that inhibit this enzyme. NAAA catalyzes the deactivating hydrolysis of palmitoylethanolamide, a lipid-derived agonist of the transcriptional regulator of cellular metabolism, peroxisome proliferator-activated receptor-α (PPAR-α). Our results show that disabling NAAA in spinal cord during a 72-h time window following peripheral tissue injury halts chronic pain development in male and female mice by triggering a PPAR-α-dependent reprogramming of local core metabolism from aerobic glycolysis, which is transiently enhanced after end-organ damage, to mitochondrial respiration. The results identify NAAA as a crucial control node in the transition to chronic pain and a molecular target for disease-modifying medicines

Electrical tuning of elastic wave propagation in nanomechanical lattices at MHz frequencies

Nanoelectromechanical systems (NEMS) that operate in the megahertz (MHz) regime allow energy transducibility between different physical domains. For example, they convert optical or electrical signals into mechanical motions and vice versa. This coupling of different physical quantities leads to frequency-tunable NEMS resonators via electromechanical non-linearities. NEMS platforms with single- or low-degrees of freedom have been employed to demonstrate quantum-like effects, such as mode cooling, mechanically induced transparency, Rabi oscillation, two-mode squeezing and phonon lasing. Periodic arrays of NEMS resonators with architected unit cells enable fundamental studies of lattice-based solid-state phenomena, such as bandgaps, energy transport, non-linear dynamics and localization, and topological properties, directly transferrable to on-chip devices. Here we describe one-dimensional, non-linear, nanoelectromechanical lattices (NEML) with active control of the frequency band dispersion in the radio-frequency domain (10–30 MHz). The design of our systems is inspired by NEMS-based phonon waveguides and includes the voltage-induced frequency tuning of the individual resonators. Our NEMLs consist of a periodic arrangement of mechanically coupled, free-standing nanomembranes with circular clamped boundaries. This design forms a flexural phononic crystal with a well-defined bandgap, 1.8 MHz wide. The application of a d.c. gate voltage creates voltage-dependent on-site potentials, which can significantly shift the frequency bands of the device. Additionally, a dynamic modulation of the voltage triggers non-linear effects, which induce the formation of a phononic bandgap in the acoustic branch, analogous to Peierls transition in condensed matter. The gating approach employed here makes the devices more compact than recently proposed systems, whose tunability mostly relies on materials’ compliance and mechanical non-linearities

Super-heavy fermion material as metallic refrigerant for adiabatic demagnetization cooling

Low-temperature refrigeration is of crucial importance in fundamental research of condensed matter physics, as the investigations of fascinating quantum phenomena, such as superconductivity, superfluidity and quantum criticality, often require refrigeration down to very low temperatures. Currently, cryogenic refrigerators with $^3$He gas are widely used for cooling below 1 Kelvin. However, usage of the gas is being increasingly difficult due to the current world-wide shortage. Therefore, it is important to consider alternative methods of refrigeration. Here, we show that a new type of refrigerant, super-heavy electron metal, YbCo$_2$Zn$_{20}$, can be used for adiabatic demagnetization refrigeration, which does not require 3He gas. A number of advantages includes much better metallic thermal conductivity compared to the conventional insulating refrigerants. We also demonstrate that the cooling performance is optimized in Yb$_{1-x}$Sc$_x$Co$_2$Zn$_{20}$ by partial Sc substitution with $x\sim$0.19. The substitution induces chemical pressure which drives the materials close to a zero-field quantum critical point. This leads to an additional enhancement of the magnetocaloric effect in low fields and low temperatures enabling final temperatures well below 100 mK. Such performance has up to now been restricted to insulators. Since nearly a century the same principle of using local magnetic moments has been applied for adiabatic demagnetization cooling. This study opens new possibilities of using itinerant magnetic moments for the cryogen-free refrigeration

Differential predictors of acute post-surgical pain intensity after abdominal hysterectomy and major joint arthroplasty

Author's personal copyBACKGROUND Psychological factors have a significant role in post-surgical pain, and their study can inform pain management. PURPOSE The aims of this study are to identify psychological predictors of post-surgical pain following abdominal hysterectomy (AH) and major joint arthroplasty (MJA) and to investigate differential predictors by type of surgery. METHOD One hundred forty-two women undergoing AH and 110 patients undergoing MJA were assessed 24 h before (T1) and 48 h after (T2) surgery. RESULTS A predictive post-surgical pain model was found for AH and MJA yielding pre-surgical pain experience and pain catastrophizing as significant predictors and a significant interaction of pre-surgical optimism and surgery type. Separate regression models by surgery type showed that pre-surgical optimism was the best predictor of post-surgical pain after MJA, but not after AH. CONCLUSIONS Findings highlight the relevance of psychological predictors for both surgeries and the value of targeting specific psychological factors by surgery type in order to effectively manage acute post-surgical pain.Supported by a project grant (PTDC/SAU-NEU/108557/2008) and by a PhD grant (SFRH/BD/36368/2007) from the Portuguese Foundation of Science and Technology, COMPETE, and FEDE