Experimental study of intrinsic multiple Andreev reflections effect in GdO(F)FeAs superconductor array junctions

We report the first observation of the intrinsic multiple Andreev reflections effect (IMARE) in S-n-S-...-S-arrays (S = superconductor, n = normal metal) formed by "break-junction" technique in GdO(F)FeAs superconductor (Tc = 48 - 53 K). We show that superconducting gap peculiarities at dI/dV-spectra sharpen dramatically in the arrays as compared with that in the single-contact spectra; this enables to improve significantly accuracy of the bulk superconducting parameters determination. Using IMARE, we determined the large and the small gap values \Delta_L = 11 +- 1.1 meV and \Delta_S = 2.6 +- 0.4 meV. The BCS-ratio 2\Delta_L/kTc^{local} = 5.0 - 5.9 > 3.52 (Tc^{local} is the contact area critical temperature) evidences for a strong electron-boson coupling. The results obtained agree well with our previous data by Andreev spectroscopy for single SnS-contacts.Comment: 6 pages, 6 figure

8H-Chromeno[2′,3′:4,5]imidazo[2,1-a]isoquinoline

The title compound, C18H12N2O, comprises two aromatic fragments, viz., imidazo[2,1-a]isoquinoline and benzene, linked by oxygen and methyl­ene bridges. Despite the absence of a common conjugative system within the mol­ecule, it adopts an essentially planar conformation with an r.m.s. deviation of 0. 036 Å. In the crystal, due to this structure, mol­ecules form stacks along the b axis by π⋯π stacking inter­actions, with shortest C⋯C distances in the range 3.340 (4)–3.510 (4) Å. The mol­ecules are bound by inter­molecular C—H⋯O inter­actions within the stacks and C—H⋯π inter­actions between the stacks

Features of effector lymphocyte subsets in patients with uveal melanoma in recurrent and chronic herpesvirus infection

The aim of the study is to conduct a comparative analysis of percentages for peripheral blood effector lymphocyte subsets in patients with uveal melanoma manifested by recurrent and chronic herpesvirus infection. There were 141 subjects enrolled: 70 patients with uveal melanoma, 38 patients with corneal ulcers and involvement of the uveal tract as well as 33 healthy donors. Immunophenotyping was performed by using laser flow cytometry with panel of monoclonal antibodies to differentiate lymphocyte subpopulations. IgM and IgG antibodies to herpesvirus infections were determined by using enzyme-linked immunosorbent assay on an automatic ELISA analyzer Lazurit (USA) with diagnostic kits of CJSC “Vector-Best” (Koltsovo). The data obtained showed that the absolute number of blood lymphocytes (CD45+) in patients with uveal melanoma did not differ from those in healthy donors. In contrast, patients with corneal ulcers and involvement of the uveal tract had this parameter increased. A decreased relative and absolute count of T cells (CD3+) in uveal melanoma, but increased absolute CD3+ number in inflammation was observed. No difference in relative and absolute content of the CD3+CD4+ helper/inducer subpopulation in patients with recurrent herpesvirus infections was found. Corneal ulcers in cancer patients revealed significantly increased absolute level of CD3+CD4+ helpers/inductor cells. Chronic herpesvirus infection in uveal melanoma patients showed increased relative and absolute number of cytotoxic T lymphocytes (CD3+CD8+). Recurrent herpesvirus infection was featured with decreased relative number of T lymphocytes (CD3+CD8+), upon inflammation, there was noted increased absolute and decreased relative number compared with healthy subjects. Double positive T cells increased in tumor and inflammation. B lymphocytes (CD19+) increased in melanoma and inflammation. The relative number of blood natural killer cells (CD16+CD56+) in uveal melanoma increased upon recurrent infection. Inflammation was coupled to decreased relative level of natural killer cells (CD16+CD56+). Melanoma showed no changes in CD4+/ CD8+ ratio; upon inflammation, its increase was noted in acute and chronic herpesvirus infections (p < 0.05). The suppression of the immune system in uveal melanoma, restricting antiviral defense, was revealed. The data obtained seem to be important for development of personalized approaches to prognosis and treatment of patients with uveal melanoma

Screening of cytokines in blood serum and lacrimal liquid in wet and atrophic forms of age-related macular degeneration

Cytokines play an integral role in pathogenesis of age-related macular degeneration (AMD). Of particular interest are the late stages of this disease, which causes progressive visual impairment. Therapy-induced effects of post-treatment cytokine concentrations also need to be studied, both at long and short observation terms. These studies are of vital importance if the atrophy occurs during antiangiogenic therapy. Our purpose was to study an array of 45 cytokines, in blood serum (BS) and lacrimal liquid (LL) of the patients with wet and atrophic AMD.The study included 70 people (85 eyes) with stage 3-4 AMD according to AREDS. Depending on the form of AMD, 3 groups were discerned: I group (n = 24) included the patients with “geographic atrophy”; II group (n = 22), consisted of the patients with macular atrophy treated with antiangiogenic therapy of wet AMD; III group (n = 24), comprised the patients with a wet AMD who did not previously receive the treatment. Control group consisted of healthy volunteers (n = 25). All the groups were comparable for age and gender. The patients underwent a comprehensive ophthalmological examination to make a diagnosis. A multiplex study of the local (in the BS) and systemic (in the LL) cytokine status was carried out on a MAGPIX device (platform хMAP, Luminex Corporation, USA) in the Luminexx PONENT 3.1 software, using Procarta Plex kits (eBioscience, Austria). We determined 45 cytokines causing various biological effects, i.e., IL-1á, IL-1â, IL-1ra, IL-2, IL-4, IL-5, IL-6, IL-7, IL-9, IL-10, IL-12p70, IL-13, IL-15, IL-17A, IL-18, IL-21, IL-22, IL-23, IL-27, IL-31, IFNá, IFNã, IL-8/CXCL8, IP-10/CXCL10, SDF-1á/CXCL12, MCP-1/CCL2, MIP-1á/CCL3, MIP-1â/ CCL4, RANTES/CCL5, Eotaxin/CCL11, TNFá, TNFâ, GM-CSF, VEGF-A, VEGF-D, FGF-2, EGF, PDGF-BB, HGF, SCF, GRO-á, NGF-â, BDNF, LIF, PIGF-1.Screening of a wide range of cytokines showing various biological effects was carried out in BS and LL of patients with atrophic and wet forms of AMD. It has been shown that the late stages of the disease are associated with local and systemic changes of pro / anti-inflammatory mediators (IL-1â, IL-1ra, IL-18, LIF), chemoattractant cytokines (IL-8/CXCL8, IP-10/CXCL10, MCP-1/CCL2, MIP-1á/CCL3, MIP-1â/ CCL4, RANTES/CCL5, Eotaxin/CCL11), hematopoietic regulators (IL-7), and growth factors with known angiogenic activity (EGF, HGF, PDGF-BB, VEGF-A). Altered concentrations of numerous chemokines, e.g., IP-10/CXCL10, SDF-1á/CXCL12, MIP-1á/CCL3, MIP-1â/CCL4, RANTES/CCL5 and Eotaxin/CCL11 (p < 0.05) in BS of the patients with atrophic and wet AMD may be of interest for the search of biomarkers associated with various clinical phenotypes of the disease and may be also helpful for development of new therapeutic strategies

Holarctic phylogeographic structure of Eurasian wigeon (Mareca penelope)

The Eurasian wigeon (Mareca penelope) is one of the most numerous migrant species of waterfowl in the Palearctic. Annually, significant part of the world’s wigeon population makes seasonal flights over distances from tens to thousands or more kilometers. According to different estimates based on banding data, five geographic populations of the species were described in the Palearctic. However, distinct borders between the populations have not been identified. At the same time, no phylogeographic studies have been carried out for the complete native range of wigeon so far. In addition to the fundamental importance of such a study, knowledge of the genetic structure of populations is necessary for the development of measures to increase the number of and preserve this valuable game species. The aim of our work was a phylogeographic analysis of the wigeon across its vast native range in the Palearctic including ducks wintering in North America. We examined genetic diversity and differentiation of wigeon populations identified with banding data, phylogenetic relationships of mtDNA haplotypes and demographic history of populations and species as a whole by sequencing a 661 base-pair 5’-fragment of the mitochondrial control region from 195 individual ducks collected throughout the Palearctic and Nearctic. Genetic diversity was high in all studied populations. A reconstruction of haplotypes phylogeny revealed the absence of geographic structure in the data. Nonetheless, analysis of molecular variance (AMOVA) identified two groups of populations: EuropeanSiberian and East Asian. The former included wigeons from Europe, Siberia and the Atlantic coast of North America, and the latter comprised ducks from Russian Far East, Kamchatka Peninsula, Chukotka Autonomous District, the Aleutian Islands, Alaska, and the Pacific coast of North America

Predictive model of small choroidal melanoma progression after eye-saving treatment based on clinical, morphometric and immunological parameters

Choroidal melanoma is a malignant tumor characterized by early metastasis and poor vital prognosis. Prognostic indexes for the tumor development are of importance, depending on various factors and making it possible to optimize therapeutic measures. Usage of present models for prediction of the uveal melanoma course enables optimal management of the patients with a malignant tumor upon primary admission, and to perform maximally efficient counseling. So far, however, a complex of clinical, morphometric and immunological indexes predictive for unfavorable course of initial choroidal melanoma following the eye-saving treatment remains not fully determined. Our purpose was to create a prognostic model for initial choroidal melanoma after eye-saving treatment, basing on clinical, morphometric and immunological parameters.We have performed examination and treatment of 31 patients with small choroidal melanoma (53.7 to 12.2 years old). To perform the analysis, we used clinical data (age, decreased vision, tumor localization, degree of pigmentation, presence of hemorrhages, orange pigmentation), morphometric indexes (intra- and subretinal exudate and disorganization of pigment of the retinal epithelium) and immunological parameters (serum levels of pro-inflammatory, pro-angiogenic, proliferative, metastasis-causing cytokines). Selection of variables for this model was based on assessment of significant differences between the groups with chorio-retinal scar (n = 14) and residual tumor and/or continued tumor growth (n = 17).Multivariate analysis with conditional exclusion of variables revealed prognostic significance with four markers: morphometric, i.e., disorganization of the pigment in retinal pigment epithelium – Z1 (rs = 0.455); immunological, increased blood serum concentration of hepatocyte growth factor (HGF) – Z2 (rs = 0.377); level of pro-inflammatory chemokine RANTES – Z3 (rs = 0.362), content of transforming growth factor (TGF-2â) – Z4 (rs = 0.431). A formula was calculated where P (z) is the value of the logistic function; Z, linear combination of symptoms; bo , intercept (free term), bi – regression coefficients for parameters Zi.P (z) = 1 : 1 + e – b0– b1z1– b2z2– b3z3– b4z4The logistic function increases monotonically and takes the values from 0 to 1 for any b and Z values [P∈ (0;1)]. If P (Z) is under the cutoff value, chorioretinal scar prognosis is predicted, at the higher values, a residual tumor or continued growth is expected. In ROC analysis, the area under the curve with this model was 0.891±0.11, thus providing good predictive quality.Usage of the predictive model is a possible solution for planning and correcting treatment strategy in the patients with small choroidal melanoma, in order to minimize complications and errors, and to ensure control of treatment

Features of systemic cytokine production in Behcet's disease associated with uveitis without ocular lesions

Behcet's disease (BD) is a systemic disease underlyed by chronic vasculitis. Hyperactivity of innate and adaptive immunity plays important role in its pathogenesis. Uveitis occurs in 30-70% of the patients, often recurring and reducing visual function. The objective of our work was to study the features of systemic production of immune mediators in BD patients, depending on presence and activity of uveitis. 116 BD patients were divided into 3 groups: (1) 41 patients with active uveitis (UA), (2) 64 subjects with uveitis remission (UR), (3) 11 uveitis-free BD patients (WU). Control group (CG) comprised 34 conditionally healthy people. Detection rate (%) and contents (pg/ml) were measured for IL-1β IL-2, IL-4, IL-5, IL-6, IL-12p70, IL-13, IL-18, IFNγ, CCL2/MCP-1, CCL3/MIP-1α, CCL4/MIP-1β, CCL5/RANTES, CCL11/Eotaxin, СXCL1/GRO-α, CXCL8/IL-8, CXCL10/IP-10, CXCL12/SDF-1α, GM-CSF, TNFα in blood serum by means of multiplex analysis using MAGPIX analyzer (Luminex Corp., USA), Procarta Plex “Human Th1/Th2&Chemokine Panel 20 plex” kits (Bioscience, Austria). TGF-P1, TGF-P2 levels were assayed by ELISA-test (“Vfector-Best”). All the BD patients showed high detection rates of CXCL1/GRO-α (but not its level) in comparison with CG. Detection rate and levels of IL-6, IL-8 were increased in 1st and 2nd BD groups, compared to CG. In UR, unlike UA and WU groups, IL-4 was detected more often than in CG. WU patients showed increased detection rate of only CXCL1/GRO -α. When compared with UA, WU patients had lower serum concentrations of IFNγ, MCP-1, IP-10, MIP-1a, SDF-1α, TGF-β1; UR patients also showed decreased serum levels of IL-18, Eotaxin, GRO-α, RANTES, TGF-β2. Our results indicate the importance of angiogenic and proinflammatory chemokines and cytokines in pathogenesis of BD uveitis, as well as imbalanced production of various immunomediators. Higher detection rates and levels of IL-6 and IL-8 in UA and UR patients may result from weak persistent intraocular inflammation, even upon relief of clinical symptoms, thus, probably, requiring therapeutic correction

EFFECT OF HUMAN HERPES VIRUS REACTIVATION ON SYSTEMIC CYTOKINE PRODUCTION IN PATIENTS WITH BEHCET’S DISEASE AND UVEITIS

Behcet’s disease (BD) is a systemic autoinflammatory-autoimmune disease (chronic systemic vasculitis) of unknown etiology, almost 70% of patients develop uveitis. BD pathogenesis is complex, human herpesviruses (HHV) play an important role among infectious trigger factors. Ability of herpesviruses to modulate cytokine production and evade host’s immune response is known.Aim of the study was to assess the effect of Herpes simplex virus type 1, Herpes simplex virus type 2, Cytomegalovirus, Epstein-Barr virus on systemic levels of chemokines, pro- and anti-inflammatory cytokines in BD with and without uveitis. Serum samples were collected from 116 BD patients chronically infected with HHV and examined in ELISA-test for markers of HHV reactivation (IgG-antibodies to immediate early HSV antigens 1, 2 and CMV, early EBV antigen). Concentration of IL-1β, IFNγ, MCP-1, IL-2, IL-4, IL-5, IL-6, IL-8, IL-12p70, IL-13, IL-18, TNFα, GMCSF, Eotaxin, GRO-α, IP-10, MIP-1α, MIP-1β, SDF-1α, RANTES detected in multiplex analysis. TGF-β1, TGF-β2 were measured in ELISA-test. Depending on presence and activity of uveitis 3 groups of patients with BD were identified: group 1 – active uveitis, group 2 – remission of uveitis, group 3 – BD without ocular manifestations. After serological study 2 subgroups were highlighted in each group: a) patients with antibody markers of reactivation of at least one HHV, b) patients chronically infected with HHV, without serological signs of reactivation. Mean level and detection rate of cytokines and chemokines in patients with active uveitis (1a, 1b) and in remission (2a, 2b) were compared with patients without eye damage (3a, 3b). Chronic HHV infection (subgroup “b”) was compared with reactivation (subgroup “a”). A significant increase of MCP-1/ CCL2, MIP-1α/CCL3, MIP-1β/CCL4, RANTES/CCL5, IP-10, SDF-1α chemokines in serum, as well as IFNγ, TGF-β1, and TGF-β2 was observed in patients with uveitis (regardless of their activity) and HHV reactivation compared to patients without uveitis. Our data indicate that systemic production of cytokines and chemokines in BD patients and uveitis could be affected by the activity of chronic herpesvirus infections, and the greatest changes are related to chemokines