DARC shuttles inflammatory chemokines across the blood-brain barrier during autoimmune central nervous system inflammation

The Duffy antigen/receptor for chemokines, DARC, belongs to the family of atypical heptahelical chemokine receptors that do not couple to G proteins and therefore fail to transmit conventional intracellular signals. Here we show that during experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis, the expression of DARC is upregulated at the blood-brain barrier. These findings are corroborated by the presence of a significantly increased number of subcortical white matter microvessels staining positive for DARC in human multiple sclerosis brains as compared to control tissue. Using an in vitro blood-brain barrier model we demonstrated that endothelial DARC mediates the abluminal to luminal transport of inflammatory chemokines across the blood-brain barrier. An involvement of DARC in experimental autoimmune encephalomyelitis pathogenesis was confirmed by the observed ameliorated experimental autoimmune encephalomyelitis in Darc(-/-) C57BL/6 and SJL mice, as compared to wild-type control littermates. Experimental autoimmune encephalomyelitis studies in bone marrow chimeric Darc(-/-) and wild-type mice revealed that increased plasma levels of inflammatory chemokines in experimental autoimmune encephalomyelitis depended on the presence of erythrocyte DARC. However, fully developed experimental autoimmune encephalomyelitis required the expression of endothelial DARC. Taken together, our data show a role for erythrocyte DARC as a chemokine reservoir and that endothelial DARC contributes to the pathogenesis of experimental autoimmune encephalomyelitis by shuttling chemokines across the blood-brain barrier.

Proteome-wide screening of the European porcine reproductive and respiratory syndrome virus reveals a broad range of T cell antigen reactivity.

The porcine reproductive and respiratory syndrome virus (PRRSV) is a rapidly evolving and diversifying pathogen necessitating the development of improved vaccines. Immunity to PRRSV is not well understood although there are data suggesting that virus-specific T cell IFN-γ responses play an important role. We therefore aimed to better characterise the T cell response to genotype 1 (European) PRRSV by utilising a synthetic peptide library spanning the entire proteome and a small cohort of pigs rendered immune to PRRSV-1 Olot/91 by repeated experimental infection. Using an IFN-γ ELISpot assay as a read-out, we were able to identify 9 antigenic regions on 5 of the viral proteins and determine the corresponding responder T cell phenotype. The diversity of the IFN-γ response to PRRSV proteins suggests that antigenic regions are scattered throughout the proteome and no one single antigen dominates the T cell response. To address the identification of well-conserved T cell antigens, we subsequently screened groups of pigs infected with a closely related avirulent PRRSV-1 strain (Lelystad) and a divergent virulent subtype 3 strain (SU1-Bel). Whilst T cell responses from both groups were observed against many of the antigens identified in the first study, animals infected with the SU1-Bel strain showed the greatest response against peptides representing the non-structural protein 5. The proteome-wide peptide library screening method used here, as well as the antigens identified, warrant further evaluation in the context of next generation vaccine development.

Cartografías de la ciudad. Representación y estilización lingüística en mapas mentales de Buenos Aires

Desde un enfoque constructivista del espacio urbano como producto social, en el presente artículo presentamos algunos aspectos teóricos y metodológicos para el análisis de las representaciones geosociales y la identidad urbana para luego investigar a partir de una selección de mapas mentales la imagen espacial que los hablantes expresan a través de las variedades lingüísticas que distinguen, estilizan y ubican en su cartografía mental de la ciudad. Se trata de un primer acercamiento a un corpus recopilado en 2013, que permite observar, por un lado, que la percepción del espacio urbano está basada en la fuerte identificación de los porteños con los barrios de la ciudad y, por otro lado, que existe en el imaginario colectivo una dicotomía norte-sur estilizada que se refleja tanto en lo social, lo espacial y lo lingüístico.

Organosulfur donor with hydroxy groups and its conducting salt: crystal structures and physical properties

Crystal structures of organosulfur donor 2-(5′,6′-dihydro[1,3]dithiolo[4,5-b][1,4]-dithiin-2′-ylidene)-6,7-di-hydro-5H-[1,3]dithiolo[4,5-b][1,4]dithiepine-6,6-dimethanol (D) and its conducting salt D2I3 are described. Conductivity properties of D2I3 are also discussed.

Cyanide Compounds

Chapter 4, “Cyanide Compounds,” illustrates an explosively developing research theme in which the cyanide ligand is used as a linking agent for the designed assembly of polynuclear metal complexes. Syntheses of several basic building blocks, such as K3[Cr(CN)6],Cr(Me3tacn)(CN)3,K4[Mo(CN)8],Na[W(CO)5CN],K[CpFe(CO)(CN)2],[NEt4][Cp*Rh(CN)3],[Fe4(bpy)8(μ-CN)4][PF6]4,. are given here. These units may be used in several ways to construct polynuclear compounds. One approach involves a hexacyanometalate core decorated with peripheral metal centers, e.g., [{Cu(tpa)(CN)}6Fe][ClO4]8. or [Cr{CNNi(tetren)}6][ClO4]9. An octacyanometalate unit can lead to higher nuclearity condensed compounds, as in [Co{Co(MeOH)3}8(μ-CN)30{Mo(CN)3}6]. Alternatively, a cluster core may be substituted with cyano complexes as ligands, as in [PPh4]2[Fe4S4{NCW(CO)5}4]. If there are two cis cyano ligands on the building block, then quadrilateral or square structures often result, as in {CpFe(CO(μ-CN)2Cu(PCy3)}2 and [Fe2Cu2(bpy)6(μ-CN)4][PF6]4 However, if there are three adjacent cyano ligands, then cubic cages may be constructed as in [(CpCo)4(Cp*Rh)4(μ-CN)12][PF6]4.

Facile Synthesis of Novel Functionalized Bis(ethylenedithio)tetrathiafulvalene (BEDT-TTF) Derivatives

An improved and efficient synthetic route to four functionalized bis(ethylenedithio)-tetrathiafulvalene (BEDT-TTF) derivatives 2−5 is reported. Tetrathiolate 1 was readily prepared from 2,2‘-bis(1,3,4,6-tetrathiapentalen-5-one) under carefully controlled conditions. Subsequent reaction of 1 with selected primary alkyl halides affords new functionalized BEDT-TTF derivatives in good yields.

The Utilization of Classical Spin Monte Carlo Methods to Simulate the Magnetic Behavior of Extended Three-Dimensional Cubic Networks Incorporating M(II) Ions with an S = 5/2 Ground State Spin

The numerical simulations of the magnetic properties of extended three-dimensional networks containing M(II) ions with an S = 5/2 ground-state spin have been carried out within the framework of the isotropic Heisenberg model. Analytical expressions fitting the numerical simulations for the primitive cubic, diamond, together with (10−3) cubic networks have all been derived. With these empirical formulas in hands, we can now extract the interaction between the magnetic ions from the experimental data for these networks. In the case of the primitive cubic network, these expressions are directly compared with those from the high-temperature expansions of the partition function. A fit of the experimental data for three complexes, namely [(N(CH3)4][Mn(N3)] 1, [Mn(CN4)]n 2, and [FeII(bipy)3][MnII2(ox)3] 3, has been carried out. The best fits were those obtained using the following parameters, J = −3.5 cm-1, g = 2.01 (1); J = −8.3 cm-1, g = 1.95 (2); and J = −2.0 cm-1, g = 1.95 (3).

The Design and Synthesis of Versatile Molecular Building Blocks: Working Towards the Controlled Self-Assembly of Novel Functional Materials

Our research goals are focused on the preparation of novel molecule-based materials that possess specifically designed properties in solution or in the solid state e.g. self-assembly, magnetism, conductivity and spin crossover phenomena. Most of our systems incorporate paramagnetic transition metal ions and the search for new molecule-based magnetic materials is a prominent theme. Specific areas of research include the preparation and study of oxalate based 2D and 3D magnets, probing the versatility of octacyanometalate building blocks as precursors for new molecular magnets, and the preparation of new tetrathiafulvalene (TIF) derivatives for applications in molecular and supramolecular chemistry.