Granzyme B in inflammatory diseases: apoptosis, inflammation, extracellular matrix remodeling, epithelial-to-mesenchymal transition and fibrosis

Inflammation is strictly interconnected to anti-inflammatory mechanisms to maintain tissue homeostasis. The disruption of immune homeostasis can lead to acute and chronic inflammatory diseases, as cardiovascular, pulmonary, metabolic diseases and cancer. The knowledge of the mechanisms involved in the development and progression of these pathological conditions is important to find effective therapies. Granzyme B (GrB) is a serine protease produced by a variety of immune, non-immune and tumor cells. Apoptotic intracellular and multiple extracellular functions of GrB have been recently identified. Its capability of cleaving extracellular matrix (ECM) components, cytokines, cell receptors and clotting proteins, revealed GrB as a potential multifunctional pro-inflammatory molecule with the capability of contributing to the pathogenesis of different inflammatory conditions, including inflammaging, acute and chronic inflammatory diseases and cancer. Here we give an overview of recent data concerning GrB activity on multiple targets, potentially allowing this enzyme to regulate a wide range of crucial biological processes that play a role in the development, progression and/or severity of inflammatory diseases. We focus our attention on the promotion by GrB of perforin-dependent and perforin-independent (anoikis) apoptosis, inflammation derived by the activation of some cytokines belonging to the IL-1 cytokine family, ECM remodeling, epithelial-to-mesenchymal transition (EMT) and fibrosis. A greater comprehension of the pathophysiological consequences of GrB-mediated multiple activities may favor the design of new therapies aim to inhibit different inflammatory pathological conditions such as inflammaging and age-related diseases, EMT and organ fibrosis

An Exploration of Home Attachment Representations using an Adaptation of Adult Attachment Interview: Preliminary Data on the Home Attachment Interview

Background: In analysing the literature on household as a physical structure strongly linked to cultural and affective aspects, as well as to universal central psychological needs, a universe of meanings was found. The household, conceptualised as home and safe shelter that contains and protects, but also as a favourite place where the most important relationships of each human being unfold, suggests to use attachment theory perspective as a potentially useful framework to conceptualize the construct of home attachment. However, this perspective needs to be further investigated in order to understand its complex nature. Therefore, this pilot study aims to investigate how individuals represent their own homes according to their feelings and emotions related to their household.Methods: A qualitative-quantitative survey has been carried out with 50 adults (50% females) divided into five different age groups (from late adolescence to old age). An adapted version of the Adult Attachment Interview, the Home Attachment Interview, was administered.Results: Analysis identified the relevant aspects that distinguish the "house" as a physical structure, and the "home", that symbolically encloses emotional and affective experiences suggesting a perception of the "house" as "home", being a special place characterised by a strong attachment relationship connoted symbolically and affectively.Conclusions: Attachment theoretical and methodological tools used in the study appear especially useful to investigate and understand the construct of home attachment

Experimental results of crystal-assisted slow extraction at the SPS

The possibility of extracting highly energetic particles from the Super Proton Synchrotron (SPS) by means of silicon bent crystals has been explored since the 1990's. The channelling effect of a bent crystal can be used to strongly deflect primary protons and eject them from the synchrotron. Many studies and experiments have been carried out to investigate crystal channelling effects. The extraction of 120 and 270 GeV proton beams has already been demonstrated in the SPS with dedicated experiments located in the ring. Presently in the SPS, the UA9 experiment is performing studies to evaluate the possibility to use bent silicon crystals to steer particle beams in high energy accelerators. Recent studies on the feasibility of extraction from the SPS have been made using the UA9 infrastructure with a longer-term view of using crystals to help mitigate slow extraction induced activation of the SPS. In this paper, the possibility to eject particles into the extraction channel in LSS2 using the bent crystals already installed in the SPS is presented. Details of the concept, simulations and measurements carried out with beam are presented, before the outlook for the future is discussed.Comment: 4 pages, 7 figures, submitted to to International Particle Accelerator Conference (IPAC) 2017 in Copenhagen, Denmar

Laser Marking of Titanium Coating for Aerospace Applications

Abstract In the aerospace industry, in order to ensure the identification and the traceability of the products, high repeatability, non-invasive and durable marking processes are required. Laser marking is one of the most advanced marking technologies. Compared to traditional marking processes, like punches, microdot, scribing or electric discharge pencil etcher, laser marking offers several advantages, such us: non-contact working, high repeatability, high scanning speed, mark width comparable to the laser spot dimension, high flexibility and high automation of the process itself. In order to assure the mark visibility for the component lifetime, an appropriate depth of the mark is required. In this way, a stable behaviour is ensured also when the component operates in aggressive environments (i.e. in presence of oxidation, corrosion and wear phenomena). The mark depth is strongly affected by the laser source kind and by the process parameters, such us average power, pulse frequency and scanning speed. Moreover, an excessive mark penetration could cause stress concentrations and reduce the fatigue life of the component. Consequently, an appropriate selection of the process parameters is required in order to assure visibility and to avoid excessive damage. Cold Spray Deposition (CSD) is a relative new technology that allows to produce surface coatings without significant substrate temperature increasing. In aeronautics fields this technology is useful to coat materials sensible to temperature, such as solution tempered aluminum alloy, with a titanium layer. Aim of the work is to characterize the laser marking process on CSD Ti coating, in order to study the influence of the laser marking process parameters (pulse power and scanning speed), on the groove geometry of the marking. The experimental marking tests were carried out through a 30 W MOPA Q-Switched Yb:YAG fibre laser; under different process conditions. The groove geometry was measured through a HIROX HK9700 optical microscope. The results showed the effectiveness of the laser process to produce high quality marks on the titanium layer. Moreover, a correlation between the process parameters and the mark's geometry was clearly observed

The Virtues of Balm in Late Medieval Literature

This article argues that balm, or balsam, was, by the late medieval period, believed to be a panacea, capable of healing wounds and illnesses, and also preventing putrefaction. Natural history and pharmacological texts on balm from the ancient and late antique periods emphasized specific qualities of balm, especially its heat; these were condensed and repeated in medieval encyclopedias. The rarity and cost of balsam, from antiquity through the medieval period, and the high rate of counterfeiting also demonstrate its high demand and significance in medicine and religious ritual. Travel writing and itineraria from the early and central medieval periods added a new layer to ideas about the capabilities of balsam: that it originated from a Christian miracle and was a particularly Christian plant

Granzyme B expression in visceral adipose tissue associates with local inflammation and glyco-metabolic alterations in obesity

Granzyme B (GrB) is a serine protease produced by immune and non-immune cells, able to promote multiple processes, like apoptosis, inflammation, extracellular matrix remodeling and fibrosis. GrB expression in visceral adipose tissue (VAT) was associated with tissue damage, local inflammation and insulin resistance in obesity murine model, but there is no data in humans. Aim of this study was to explore the expression of GrB in VAT from obese subjects in relation to adipose tissue injury, inflammation, metabolic alterations and GrB circulating levels. For this purpose, 85 obese individuals undergoing bariatric surgery and 35 healthy subjects (as control) were recruited at Sapienza University, Rome, Italy. Study participants underwent clinical work-up and routine biochemistry. mRNA expression of GrB in VAT and of a panel of VAT inflammatory markers was analyzed by real-time PCR. Serum GrB levels were measured by Elisa Affymetrix EBIO. We observed that 80% of obese patients expressed GrB mRNA in VAT, and GrB VAT expression was associated with the presence of local inflammation and glucose homeostasis alterations. Moreover, GrB serum levels, which were higher in obese subjects compared to non-obese healthy individuals, were associated with GrB expression in VAT and glyco-metabolic impairment. Our data show, for the first time in humans, that obese subjects with “sick” fat and altered glucose tolerance exhibit GrB expression in VAT, and suggest that GrB might contribute to obesity-related VAT inflammatory remodeling and glucose homeostasis dysregulation. Moreover, increased circulating GrB levels might represent a possible peripheral marker of VAT dysfunction in metabolic diseases

Shear wave elastography in varicocele patients. Prospective study to investigate correlation with semen parameters and histological findings

Aims: Shear wave elastosonography (SWE) is a non-invasive ultrasound imaging modality used to assess the mechanical properties of tissues such as rigidity and elasticity. In this prospective study, we investigated the effect of laparoscopic varicocelectomy on the elasticity, degree of fibrosis and function of the testes through SWE and we evaluated the correlation with semen parameters and histology findings. Methods: Male patients with monolateral left varicocele and a progressive alteration of the semen quality were enrolled prospectively. Patients were evaluated before varicocelectomy,3 and 6 months after surgery with semen analysis, ecocolordoppler US and SWE. In all patients a left testicular biopsy was performed at the time of varicocelectomy and it was repeated after 6 months in 55% of patients in order to investigate the histological findings and to correlate with SWE results. Results: The study was conducted on 82 patients. SWE showed a statistically significant difference between left and right testicles. Three months after surgery the mean left testicular volume increased, mean left SWE features decreased, and sperm count increased (p values < 0.0001). The SWE parameters, testicular volume and semen analysis values showed a statistically significant positive correlation between the pre and post-operative results (p value < 0.0001). The histological alterations were significantly changed 6 months postoperative with a complete morphology recovery in accordance with SWE results. Conclusions: SWE showed a statistically significant positive correlation with testicular volume, semen analysis, and histological findings. This study represents the first investigation that correlates the varicocele, the testis volume, the quality of the seminal fluid ant the histological findings with the ultrasound and SWE values

Upgrades Of the SPS, Transfer Line and LHC Injection Protection Devices For the HL-LHC Era

The challenging High Luminosity LHC (HL-LHC) beam requirements will lead in the future to unprecedented beam parameters along the LHC injector chain. In the SPS accelerator these requests translate into about a factor two higher intensity and brightness than the present design performance. In addition to the challenge of producing and accelerating such beams, these parameters affect the resistance of the existing equipment against beam impact. Most of the protection devices in the SPS ring, its transfer lines and the LHC injection areas will be put under operational constraints which are beyond their design specification. The equipment concerned has been reviewed and their resistance to the HL-LHC beams checked. Theoretical and simulation studies have been performed for the SPS beam scraping system, the protection devices and the dump absorbers of the SPS-to-LHC transfer lines, as well as for the LHC injection protection devices. The first results of these studies are reported, together with the future prospects.Comment: 3 p. Presented at 4th International Particle Accelerator Conference (IPAC 2013