A novel isoform of the Ly108 gene ameliorates murine lupus

Studies of human systemic lupus erythematosus patients and of murine congenic mouse strains associate genes in a DNA segment on chromosome 1 with a genetic predisposition for this disease. The systematic analysis of lupus-prone congenic mouse strains suggests a role for two isoforms of the Ly108 receptor in the pathogenesis of the disease. In this study, we demonstrate that Ly108 is involved in the pathogenesis of lupus-related autoimmunity in mice. More importantly, we identified a third protein isoform, Ly108-H1, which is absent in two lupus-prone congenic animals. Introduction of an Ly108-H1–expressing transgene markedly diminishes T cell–dependent autoimmunity in congenic B6.Sle1b mice. Thus, an immune response–suppressing isoform of Ly108 can regulate the pathogenesis of lupus.Peer Reviewe

A novel isoform of the Ly108 gene ameliorates murine lupus

The expression of the new Ly108 isoform H1 weakens lupus-like disease of C57BL/6.Sle1b mice

Origin and evolution of Cenozoic magmatism of Sardinia (Italy). A combined isotopic (Sr-Nd-Pb-O-Hf-Os) and petrological view

The Cenozoic igneous activity of Sardinia is essentially concentrated in the 38-0.1 Myr time range. On the basis of volcanological, petrographic, mineralogical, geochemical and isotopic considerations, two main rock types can be defined. The first group, here defined SR (Subduction-Related) comprises Late Eocene-Middle Miocene (~ 38-15 Ma) igneous rocks, essentially developed along the Sardinian Trough, a N-S oriented graben developed during the Late Oligocene-Middle Miocene. The climax of magmatism is recorded during the Early Miocene (~ 23-18 Ma) with minor activity before and after this time range. Major and trace element indicators, as well as Sr-Nd-Pb-Hf-Os-O isotope systematic indicate complex petrogenetic processes including subduction-related metasomatism, variable degrees of crustal contamination at shallow depths, fractional crystallization and basic rock partial melting. Hybridization processes between mantle and crustal melts and between pure mantle and crustally contaminated mantle melts increased the isotopic and elemental variability of the composition of the evolved (intermediate to acid) melts. The earliest igneous activity, pre-dating the Early Miocene magmatic climax, is related to the pushing effects exerted by the Alpine Tethys over the Hercynian or older lower crust, rather than to dehydration processes of the oceanic plate itself. The second group comprises volcanic rocks emplaced from ~ 12 to ~ 0.1 Ma. The major and, partially, trace element content of these rocks roughly resemble magmas emplaced in within-plate tectonic settings. From a Sr-Nd-Pb-Hf-Os isotopic point of view, it is possible to subdivide these rocks in two subgroups. The first, defined RPV (Radiogenic Pb Volcanic) group comprises the oldest and very rare products (~ 12-4.4 Ma) occurring only in the southern sectors of Sardinia. The second group, defined UPV (Unradiogenic Pb Volcanic), comprises rocks emplaced in the remaining central and northern sectors during the ~ 4.8-0.1 Ma time range. The origin of the RPV rocks remains quite enigmatic, since they formed just a few Myr after the end of a subduction-related igneous activity but do not show any evidence of slab-derived metasomatic effects. In contrast, the complex origin of the mafic UPV rocks, characterized by low 206Pb/204Pb (17.4-18.1), low 143Nd/144Nd (0.51232-0.51264), low 176Hf/177Hf (0.28258-0.28280), mildly radiogenic 87Sr/86Sr (~ 0.7044) and radiogenic 187Os/188Os ratios (0.125-0.160) can be explained with a mantle source modified after interaction with ancient delaminated lower crustal lithologies. The strong isotopic difference between the RPV and UPV magmas and the absence of lower crustal-related features in the SR and RPV remain aspects to be solved

Aquatic ecotoxicity of lanthanum : a review and an attempt to derive water and sediment quality criteria

Rare earth elements (REE) used to be taken as tracers of geological origin for fluvial transport. Nowadays their increased applications in innovative environmental-friendly technology (e.g. in catalysts, superconductors, lasers, batteries) and medical applications (e.g. MRI contrast agent) lead to man-made, elevated levels in the environment. So far, no regulatory thresholds for REE concentrations and emissions to the environment have been set because information on risks from REE is scarce. However, evidence gathers that REE have to be acknowledged as new, emerging contaminants with manifold ways of entry into the environment, e.g. through waste water from hospitals or through industrial effluents. This paper reviews existing information on bioaccumulation and ecotoxicity of lanthanum in the aquatic environment. Lanthanum is of specific interest as one of the major lanthanides in industrial effluents. This review focuses on the freshwater and the marine environment, and tackles the water column and sediments. From these data, methods to derive quality criteria for sediment and water are discussed and preliminary suggestions are made

27Al NMR Study of the pH Dependent Hydrolysis Products of Al2(SO4)3 in Different Physiological Media

Soluble inorganic aluminium compounds like aluminium sulfate or aluminium chloride have been challenged by the European Chemical Agency to induce germ cell mutagenicity. Before conducting mutagenicity tests, the hydrolysis products in water and in physiological solutions should be determined as a function of the concentration and pH. We used different 27Al NMR spectroscopic techniques (heteronuclear Overhauser effect spectroscopy (HOESY), exchange spectroscopy (EXSY), diffusion ordered (DOSY)) in this work to gain the information to study the aluminium species in solutions with Al2(SO4)3 concentrations of 50.0, 5.0, and 0.5 g/L and their pH and time dependent transformation. At low pH, three different species were present in all physiological solutions and water: [Al(OH)n(H2O)6 − n](3 − n)+ (n = 0–2), [Al(H2O)5SO4]+, and [Al2(OH)2(H2O)8]4+. Increasing pH reduced the amounts of the two monomer species, with a complete loss at pH 5 for solutions with a concentration of 50.0 g/L and at pH 4 for solutions with a concentration of 5.0 g/L. The dimer species [Al2(OH)2(H2O)8]4+ is present in a pH range between 3 and 6. Less symmetric oligomeric and probably asymmetric aluminium species are formed at pH of 5 and 6. The pH value is the driving force for the formation of aluminium species in all media, whereas the specific medium had only minor effect. No conclusive information could be obtained at pH 7 due to signal loss related to fast quadrupole relaxation of asymmetric aluminium species. A slight reduction of the content of the symmetric aluminium species due to the formation of oligomeric species was observed over a period of 6 weeks. Reference 27Al NMR experiments conducted on saturated water solutions of AlCl3 and those with a concentration of 50 g/L show that the type of salt/counter ion at the same concentration and pH influences the hydrolysis products formed

Interlimb communication to the knee flexors during walking in humans

A strong coordination between the two legs is important for maintaining a symmetric gait pattern and adapting to changes in the external environment. In humans as well as animals, receptors arising from the quadriceps muscle group influence the activation of ipsilateral muscles. Moreover, strong contralateral spinal connections arising from quadriceps and hamstring afferents have been shown in animal models. Therefore, the aims of the present study were to assess if such connections also exist in humans and to elucidate on the possible pathways. Contralateral reflex responses were investigated in the right leg following unexpected unilateral knee joint rotations during locomotion in either the flexion or extension direction. Strong reflex responses in the contralateral biceps femoris (cBF) muscle with a mean onset latency of 76 ± 6 ms were evoked only from ipsilateral knee extension joint rotations in the late stance phase. To investigate the contribution of a transcortical pathway to this response, transcranial magnetic and electrical stimulation were applied. Motor evoked potentials elicited by transcranial magnetic stimulation, but not transcranial electrical stimulation, were facilitated when elicited at the time of the cBF response to a greater extent than the algebraic sum of the cBF reflex and motor evoked potentials elicited separately, indicating that a transcortical pathway probably contributes to this interlimb reflex. The cBF reflex response may therefore be integrated with other sensory input, allowing for responses that are more flexible. We hypothesize that the cBF reflex response may be a preparation of the contralateral leg for early load bearing, slowing the forward progression of the body to maintain dynamic equilibrium during walking