Interplay between Humoral and CLA+ T Cell Response against Candida albicans in Psoriasis

Candida albicans (CA) infections have been associated with psoriasis onset or disease flares. However, the integrated immune response against this fungus is still poorly characterized in psoriasis. We studied specific immunoglobulins in plasma and the CA response in cocultures of circulating memory CD45RA⁻ cutaneous lymphocyte antigen (CLA)^+/− T cell with autologous epidermal cells from plaque and guttate psoriasis patients (cohort 1, n = 52), and also healthy individuals (n = 17). A complete proteomic profile was also evaluated in plaque psoriasis patients (cohort 2, n = 114) regarding their anti-CA IgA levels. Increased anti-CA IgA and IgG levels are present in the plasma from plaque but not guttate psoriasis compared to healthy controls. CA cellular response is confined to CLA⁺ T cells and is primarily Th17. The levels of anti-CA IgA are directly associated with CLA⁺ Th17 response in plaque psoriasis. Proteomic analysis revealed distinct profiles in psoriasis patients with high anti-CA IgA. C-C motif chemokine ligand 18, chitinase-3-like protein 1 and azurocidin were significantly elevated in the plasma from plaque psoriasis patients with high anti-CA levels and severe disease. Our results indicate a mechanism by which Candida albicans exposure can trigger a clinically relevant IL-17 response in psoriasis. Assessing anti-CA IgA levels may be useful in order to evaluate chronic psoriasis patients.     

Methamphetamine Blocks Adenosine A2A Receptor Activation via Sigma 1 and Cannabinoid CB1 Receptors

Methamphetamine is, worldwide, one of the most consumed drugs of abuse. One important side effect is neurodegeneration leading to a decrease in life expectancy. The aim of this paper was to check whether the drug affects one of the receptors involved in neurodegeneration/neuroprotection events, namely the adenosine A_2A receptor (A_2AR). First, we noticed that methamphetamine does not affect A_2A functionality if the receptor is expressed in a heterologous system. However, A_2AR becomes sensitive to the drug upon complexes formation with the cannabinoid CB₁ receptor (CB₁R) and the sigma 1 receptor (σ₁R). Signaling via both adenosine A_2AR and cannabinoid CB₁R was affected by methamphetamine in cells co-expressing the two receptors. In striatal primary cultures, the A_2AR–CB₁R heteromer complex was detected and methamphetamine not only altered its expression but completely blocked the A_2AR- and the CB₁R-mediated activation of the mitogen activated protein kinase (MAPK) pathway. In conclusion, methamphetamine, with the participation of σ₁R, alters the expression and function of two interacting receptors, A_2AR, which is a therapeutic target for neuroprotection, and CB₁R, which is the most abundant G protein-coupled receptor (GPCR) in the brain.     

Melanin Distribution in Human Skin: Influence of Cytoskeletal,Polarity, and Centrosome-Related Machinery of Stratum basale Keratinocytes

Melanin granules cluster within supra-nuclear caps in basal keratinocytes (KCs) of the human epidermis, where they protect KC genomic DNA against ultraviolet radiation (UVR) damage. While much is known about melanogenesis in melanocytes (MCs) and a moderate amount about melanin transfer from MC to KC, we know little about the fate of melanin once inside KCs. We recently reported that melanin fate in progenitor KCs is regulated by rare asymmetric organelle movement during mitosis. Here, we explore the role of actin, microtubules, and centrosome-associated machinery in distributing melanin within KCs. Short-term cultures of human skin explants were treated with cytochalasin-B and nocodazole to target actin filaments and microtubules, respectively. Treatment effects on melanin distribution were assessed by the Warthin–Starry stain, on centrosome-associated proteins by immunofluorescence microscopy, and on co-localisation with melanin granules by brightfield microscopy. Cytochalasin-B treatment disassembled supra-nuclear melanin caps, while nocodazole treatment moved melanin from the apical to basal KC domain. Centrosome and centriolar satellite-associated proteins showed a high degree of co-localisation with melanin. Thus, once melanin granules are transferred to KCs, their preferred apical distribution appears to be facilitated by coordinated movement of centrosomes and centriolar satellites. This mechanism may control melanin’s strategic position within UVR-exposed KCs.     

Cardioinotropic Effects in Subchronic Intoxication of Rats with Lead and/or Cadmium Oxide Nanoparticles

Subchronic intoxication was induced in outbred male rats by repeated intraperitoneal injections with lead oxide (PbO) and/or cadmium oxide (CdO) nanoparticles (NPs) 3 times a week during 6 weeks for the purpose of examining its effects on the contractile characteristics of isolated right ventricle trabeculae and papillary muscles in isometric and afterload contractions. Isolated and combined intoxication with these NPs was observed to reduce the mechanical work produced by both types of myocardial preparation. Using the in vitro motility assay, we showed that the sliding velocity of regulated thin filaments drops under both isolated and combined intoxication with CdO–NP and PbO–NP. These results correlate with a shift in the expression of myosin heavy chain (MHC) isoforms towards slowly cycling β–MHC. The type of CdO–NP + PbO–NP combined cardiotoxicity depends on the effect of the toxic impact, the extent of this effect, the ratio of toxicant doses, and the degree of stretching of cardiomyocytes and muscle type studied. Some indices of combined Pb–NP and CdO–NP cardiotoxicity and general toxicity (genotoxicity included) became fully or partly normalized if intoxication developed against background administration of a bioprotective complex.     

Bone Marrow-Mesenchymal Stromal Cell Secretome as Conditioned Medium Relieves Experimental Skeletal Muscle Damage Induced by Ex Vivo Eccentric Contraction

Bone marrow-mesenchymal stem/stromal cells (MSCs) may offer promise for skeletal muscle repair/regeneration. Growing evidence suggests that the mechanisms underpinning the beneficial effects of such cells in muscle tissue reside in their ability to secrete bioactive molecules (secretome) with multiple actions. Hence, we examined the effects of MSC secretome as conditioned medium (MSC-CM) on ex vivo murine extensor digitorum longus muscle injured by forced eccentric contraction (EC). By combining morphological (light and confocal laser scanning microscopies) and electrophysiological analyses we demonstrated the capability of MSC-CM to attenuate EC-induced tissue structural damages and sarcolemnic functional properties’ modifications. MSC-CM was effective in protecting myofibers from apoptosis, as suggested by a reduced expression of pro-apoptotic markers, cytochrome c and activated caspase-3, along with an increase in the expression of pro-survival AKT factor. Notably, MSC-CM also reduced the EC-induced tissue redistribution and extension of telocytes/CD34⁺ stromal cells, distinctive cells proposed to play a “nursing” role for the muscle resident myogenic satellite cells (SCs), regarded as the main players of regeneration. Moreover, it affected SC functionality likely contributing to replenishment of the SC reservoir. This study provides the necessary groundwork for further investigation of the effects of MSC secretome in the setting of skeletal muscle injury and regenerative medicine.     

Effect of HCl pre-treatment on corrosion resistance of cerium-based conversion coatings on magnesium and magnesium alloys

The corrosion protection afforded by a cerium conversion coating, formed by immersion in a solution containing rare earth salt and hydrogen peroxide, on pure magnesium and two magnesium alloys, AZ91 and AM50, has been studied. The effect of HCl pre-treatments on the morphology and on the corrosion resistance of the cerium conversion layer was investigated. A thicker and more homogeneous distribution of the conversion coating was obtained when the sample surface was pre-treated with acid. Higher amounts of cerium on the surface of the pre-treated samples were detected. The cerium conversion coating increased the corrosion resistance of the alloys because it ennobled the corrosion potential and decreased both the anodic and cathodic current. The acid pre-treatment further increased the corrosion resistance of the coated alloys. After five days of immersion in chloride environment the untreated samples showed localized corrosion while the chemical conversion coated samples appeared unaffected.     

Autocalibration with the Minimum Number of Cameras with Known Pixel Shape

In 3D reconstruction, the recovery of the calibration parameters of the cameras is paramount since it provides metric information about the observed scene, e.g., measures of angles and ratios of distances. Autocalibration enables the estimation of the camera parameters without using a calibration device, but by enforcing simple constraints on the camera parameters. In the absence of information about the internal camera parameters such as the focal length and the principal point, the knowledge of the camera pixel shape is usually the only available constraint. Given a projective reconstruction of a rigid scene, we address the problem of the autocalibration of a minimal set of cameras with known pixel shape and otherwise arbitrarily varying intrinsic and extrinsic parameters. We propose an algorithm that only requires 5 cameras (the theoretical minimum), thus halving the number of cameras required by previous algorithms based on the same constraint. To this purpose, we introduce as our basic geometric tool the six-line conic variety (SLCV), consisting in the set of planes intersecting six given lines of 3D space in points of a conic. We show that the set of solutions of the Euclidean upgrading problem for three cameras with known pixel shape can be parameterized in a computationally efficient way. This parameterization is then used to solve autocalibration from five or more cameras, reducing the three-dimensional search space to a two-dimensional one. We provide experiments with real images showing the good performance of the technique.     

Synthesis and properties of aminopropyl nucleic acids

Oligonucleotides that contain up to three aminopropyl nucleoside analogues have been synthesized. Dimers of aminopropyl adenine and thymidine were prepared and used as building blocks by applying phosphoramidite chemistry. Both R and S isomers of the aminopropyl nucleosides were used. This incorporation led to a reduction of thermal stability of double-stranded DNA. Furthermore, the (R)-adenine analogue, which yielded (S)-APNA, can be considered as a candidate for universal base pairing.     

Porous poly(2-hydroxyethyl acrylate) hydrogels prepared by radical polymerisation with methanol as diluent

Dynamic-mechanical and water sorption properties of porous and non-porous hydrogels have been studied as a function of their porosity and crosslinking density. Porous hydrogels with different crosslinking densities were prepared by co-polymerisation of 2-hydroxyethyl acrylate and ethyleneglycol dimethacrylate in solution in methanol. Pores were formed due to the segregation of the solvent from the polymer network during the polymerisation process. The porosity of the samples was observed by scanning electron microscopy. The pores collapse during the drying process after polymerisation but they reopen when the xerogel is immersed in liquid water. Bulk polymer networks with varying crosslinking densities were also synthesised and used as a reference in the analysis of the porous hydrogels. Water sorption from the gas phase and from the liquid phase was studied by means of equilibrium sorption isotherms and immersion experiments, respectively. Dynamic-mechanical spectroscopy conducted on the xerogels shows that the elastic modulus in the rubber-like state highly depends on the amount of solvent used in the polymerisation what is attributed to the presence of discontinuity surfaces in the xerogel although the pores are closed.