A Short ERAP2 That Binds IRAP Is Expressed in Macrophages Independently of Gene Variation

The M1 zinc metalloproteases ERAP1, ERAP2, and IRAP play a role in HLA-I antigen presentation by refining the peptidome either in the ER (ERAP1 and ERAP2) or in the endosomes (IRAP). They have also been entrusted with other, although less defined, functions such as the regulation of the angiotensin system and blood pressure. In humans, ERAP1 and IRAP are commonly expressed. ERAP2 instead has evolved under balancing selection that maintains two haplotypes, one of which undergoing RNA splicing leading to nonsense-mediated decay and loss of protein. Hence, likewise in rodents, wherein the ERAP2 gene is missing, about a quarter of the human population does not express ERAP2. We report here that macrophages, but not monocytes or other mononuclear blood cells, express and secrete an ERAP2 shorter form independent of the haplotype. The generation of this “short” ERAP2 is due to an autocatalytic cleavage within a distinctive structural motif and requires an acidic micro-environment. Remarkably, ERAP2 “short” binds IRAP and the two molecules are co-expressed in the endosomes as well as in the cell membrane. Of note, the same phenomenon could be observed in some cancer cells. These data prompt us to reconsider the role of ERAP2, which might have been maintained in humans due to fulfilling a relevant function in its “short” form.     

Challenges in Metabolomics-Based Tests,Biomarkers Revealed by Metabolomic Analysis,and the Promise of the Application of Metabolomics in Precision Medicine

Metabolomics helps identify metabolites to characterize/refine perturbations of biological pathways in living organisms. Pre-analytical, analytical, and post-analytical limitations that have hampered a wide implementation of metabolomics have been addressed. Several potential biomarkers originating from current targeted metabolomics-based approaches have been discovered. Precision medicine argues for algorithms to classify individuals based on susceptibility to disease, and/or by response to specific treatments. It also argues for a prevention-based health system. Because of its ability to explore gene–environment interactions, metabolomics is expected to be critical to personalize diagnosis and treatment. Stringent guidelines have been applied from the very beginning to design studies to acquire the information currently employed in precision medicine and precision prevention approaches. Large, prospective, expensive and time-consuming studies are now mandatory to validate old, and discover new, metabolomics-based biomarkers with high chances of translation into precision medicine. Metabolites from studies on saliva, sweat, breath, semen, feces, amniotic, cerebrospinal, and broncho-alveolar fluid are predicted to be needed to refine information from plasma and serum metabolome. In addition, a multi-omics data analysis system is predicted to be needed for omics-based precision medicine approaches. Omics-based approaches for the progress of precision medicine and prevention are expected to raise ethical issues.     

Focused Design of Novel Cyclic Peptides Endowed with GABARAP-Inhibiting Activity

(1) Background: Disfunctions in autophagy machinery have been identified in various conditions, including neurodegenerative diseases, cancer, and inflammation. Among mammalian autophagy proteins, the Atg8 family member GABARAP has been shown to be greatly involved in the autophagy process of prostate cancer cells, supporting the idea that GABARAP inhibitors could be valuable tools to fight the progression of tumors. (2) Methods: In this paper, starting from the X-ray crystal structure of GABARAP in a complex with an AnkirinB-LIR domain, we identify two new peptides by applying in silico drug design techniques. The two ligands are synthesized, biophysically assayed, and biologically evaluated to ascertain their potential anticancer profile. (3) Results: Two cyclic peptides (WC8 and WC10) displayed promising biological activity, high conformational stability (due to the presence of disulfide bridges), and K_d values in the low micromolar range. The anticancer assays, performed on PC-3 cells, proved that both peptides exhibit antiproliferative effects comparable to those of peptide K1, a known GABARAP inhibitor. (4) Conclusions: WC8 and WC10 can be considered new GABARAP inhibitors to be employed as pharmacological tools or even templates for the rational design of new small molecules.     

Mobility analysis of the typical gait of a radial symmetrical six-legged robot

Radial symmetrical hexapod robots have attracted the attention of the research community because of their flexibility. There is nonetheless still much to study on their kinematics, dynamics and locomotion. In this paper, initially, full body kinematics of a radial symmetrical six-legged robot with statically stable movements are reviewed. The kinematics analysis is made on cooperated swing legs over supporting legs. Using the robot screw theory and exponential product equations, the velocities and accelerations referring to the object reference frame of each robot part are presented in a compact form. This makes it easy to calculate kinetic energy and so to build the dynamics model using the Lagrangian method. Many ways of walking of six-legged robots have been introduced in specialized literature. However, mobility comparison is still open to research. Two main aspects of mobility are analyzed in detail in this paper. The first one concerns the mobility of three statically stable ways of walking (the insect-wave gait, mammal-kick gait and mixed gait) with the same duty factor on the same radial symmetrical hexapod robot. The stability, energy efficiency, turning flexibility, and terrain or environment adaptability among those gaits have been compared. The mixed gait presents important advantages over the other two, while those two are useful for some special terrain conditions where the mixed gait is limited. The second aspect that has been analyzed focuses on the mobility of the body. The body height, measured from the body bottom to the supporting surface, and the stride optimization factors are proposed according to the obstacles’ configuration and the energy optimization. The results of our study can be used for the intelligent locomotion control of some articulated multi-legged robots for walking statically-stably on a complicated surface.Most of our analyses have been successfully verified on the prototype which has been designed by Politecnico di Milano (POLIMI) and Beijing University of Astronautics and Aeronautics (BUAA) and developed by POLIMI in 2007.     

Ultra-High Energy Cosmic Particles studies from space: , a possible next-generation experiment

After the Pierre Auger Observatory, it is likely that space-based experiments might be required for next-generation studies of Ultra-High Energy Cosmic Particles. An overview of this challenging task is presented, emphasizing the main design issues, the criticalities and the intermediate steps required to make this challenging task a reality.     

Nonsimple isotropic incompressible linear fluids surrounding one-dimensional structures

We introduce a model of fluid which has four main features: it readily emerges by a general continuum mechanical framework; it is a generalization maintaining most of the physical features of incompressible Newtonian fluids; it can model adherence interactions with one-dimensional structures surrounded by the fluid; the associated initial boundary-value problem is well-posed on three-dimensional domains.     

Simulation of retronasal aroma of white and red wine in a model mouth system. Investigating the influence of saliva on volatile compound concentrations

The influence of saliva on aroma release from white and red wines was studied in a model mouth system. Aroma compounds were analysed in the dynamic headspace of wines by solid phase micro extraction/gas chromatography with flame ionization detection. Volatile compounds were identified by solid phase micro extraction/gas chromatography-mass spectrometry, resulting in a total of 43 compounds in white wine and 41 in red wine. The results showed a greater influence of saliva on aroma release in white wine than red wine. In white wine treated with human saliva, esters and fusel alcohols, responsible for fruity and fusel oil odours, were reduced of 32–80%; by contrast, the concentration of 2-phenylethanol and furfural, responsible for rose and toasted almond notes, increased by 27% and by 155%, respectively. In red wine, treated with human saliva, only a few esters decrease, with a reduction of 22–51% due to protein-binding ability of polyphenols that are able to inhibit the activity of the saliva. C-13 norisoprenoids, vitispirane (eucalyptol) and TDN (kerosene), decreased both in white and red wine, showing a comparable variation while, for β-damascenone, the variation was insignificant.     

Effect of lithium intercalation on the photovoltaic performances of photovoltachromic cells

In the last few years, a new class of smart multifunctional photoelectrochemical devices has been attracting the interest of several academic institutions and industrial companies: photovoltachromic cells, combining the features of photoelectrochromic cells with those of dye‐sensitized solar cells. Here, we report the results of a detailed electrochemical analysis aiming at investigating the electrochemical behavior of these complex photoelectrochemical devices. In particular, we have been focused on the effect of Li⁺ ions displacement during the coloration of the electrochromic tungsten oxide on the performances of the photovoltaic unit. As we had previously observed striking differences between the performances of the barely photovoltaic mode (with the tungsten oxide in the bleached state) and the photovoltachromic mode (with the tungsten oxide in the colored state), we thus attempted to provide a reasonable physical interpretation to the observed phenomena. Copyright © 2013 John Wiley & Sons, Ltd.     

Comparative analysis of the outdoor performance of a dye solar cell mini‐panel for building integrated photovoltaics applications

New generation photovoltaic (PV) devices such as polymer and dye sensitized solar cells (DSC) have now reached a more mature stage of development, and among their various applications, building integrated PVs seems to have the most promising future, especially for DSC devices. This new generation technology has attracted an increasing interest because of its low cost due to the use of cheap printable materials and simple manufacturing techniques, easy production, and relatively high efficiency. As for the more consolidated PV technologies, DSCs need to be tested in real operating conditions and their performance compared with other PV technologies to put into evidence the real potential. This work presents the results of a 3 months outdoor monitoring activity performed on a DSC mini‐panel made by the Dyepower Consortium, positioned on a south oriented vertical plane together with a double junction amorphous silicon (a‐Si) device and a multi‐crystalline silicon (m‐Si) device at the ESTER station of the University of Rome Tor Vergata. Good performance of the DSC mini‐panel has been observed for this particular configuration, where the DSC energy production compares favorably with that of a‐Si and m‐Si especially at high solar angles of incidence confirming the suitability of this technology for the integration into building facades. This assumption is confirmed by the energy produced per nominal watt‐peak for the duration of the measurement campaign by the DSC that is 12% higher than that by a‐Si and only 3% lower than that by m‐Si for these operating conditions. Copyright © 2013 John Wiley & Sons, Ltd.     

Unraveling the Dynamic Nanoscale Reducibility (Ce4+ → Ce3+) of CeOx–Ru in Hydrogen Activation

The interaction of molecular hydrogen with ceria is of important relevance for heterogeneous catalysis related to green chemistry and renewable energy. Here, the complex structural transformations of a well‐defined cerium oxide model catalyst are followed in situ and in real time when exposed to a reactive H₂ environment. By using electron spectromicroscopy and diffraction with chemical and structural sensitivities, it is demonstrated that the transition from CeO₂ to crystalline Ce₂O₃ occurs through a mixture of transient, coexisting phases on the nanoscale. The findings establish a clear relationship between structure and functionality for hydrogen dissociation over ceria(111), bearing profound implications on the nature of the reduction (Ce⁴⁺ → Ce³⁺) and mechanism for H₂ scission.