Failure of3H-serine to induce radioactivity in presumed glycinergic retinal neurons

Summary ³H-serine does not label retinal neurons selectively when injected intraocularly in rabbits, as would have been expected if it had been converted to neutrotransmitter glycine. The reason is unknown, but one possibility is that the conversion was blocked during the conditions of the experiment.This work was supported by the Swedish Medical Research Council (project No. 04X-2321) and the Faculty of Medicine, University of Lund.     

Unconventional superconductivity in PuCoGa5

In the Bardeen-Cooper-Schrieffer theory of superconductivity, electrons form (Cooper) pairs through an interaction mediated by vibrations in the underlying crystal structure. Like lattice vibrations, antiferromagnetic fluctuations can also produce an attractive interaction creating Cooper pairs, though with spin and angular momentum properties different from those of conventional superconductors. Such interactions have been implicated for two disparate classes of materials--the copper oxides and a set of Ce- and U-based compounds. But because their transition temperatures differ by nearly two orders of magnitude, this raises the question of whether a common pairing mechanism applies. PuCoGa5 has a transition temperature intermediate between those classes and therefore may bridge these extremes. Here we report measurements of the nuclear spin-lattice relaxation rate and Knight shift in PuCoGa5, which demonstrate that it is an unconventional superconductor with properties as expected for antiferromagnetically mediated superconductivity. Scaling of the relaxation rates among all of these materials (a feature not exhibited by their Knight shifts) establishes antiferromagnetic fluctuations as a likely mechanism for their unconventional superconductivity and suggests that related classes of exotic superconductors may yet be discovered.     

Complex organic matter in Titan's atmospheric aerosols from in situ pyrolysis and analysis

Aerosols in Titan's atmosphere play an important role in determining its thermal structure. They also serve as sinks for organic vapours and can act as condensation nuclei for the formation of clouds, where the condensation efficiency will depend on the chemical composition of the aerosols. So far, however, no direct information has been available on the chemical composition of these particles. Here we report an in situ chemical analysis of Titan's aerosols by pyrolysis at 600 degrees C. Ammonia (NH3) and hydrogen cyanide (HCN) have been identified as the main pyrolysis products. This clearly shows that the aerosol particles include a solid organic refractory core. NH3 and HCN are gaseous chemical fingerprints of the complex organics that constitute this core, and their presence demonstrates that carbon and nitrogen are in the aerosols.     

A common haplotype of interferon regulatory factor 5 (IRF5) regulates splicing and expression and is associated with increased risk of systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by activation of the type I interferon (IFN) pathway. Here we convincingly replicate association of the IFN regulatory factor 5 (IRF5) rs2004640 T allele with SLE in four independent case-control cohorts (P = 4.4 x 10(-16)) and by family-based transmission disequilibrium test analysis (P = 0.0006). The rs2004640 T allele creates a 5' donor splice site in an alternate exon 1 of IRF5, allowing expression of several unique IRF5 isoforms. We also identify an independent cis-acting variant associated with elevated expression of IRF5 and linked to the exon 1B splice site. Haplotypes carrying the variant associated with elevated expression and lacking the exon 1B donor site do not confer risk of SLE. Thus, a common IRF5 haplotype driving elevated expression of multiple unique isoforms of IRF5 is an important genetic risk factor for SLE, establishing a causal role for type I IFN pathway genes in human autoimmunity.     

CCN1: a novel inflammation-regulated biphasic immune cell migration modulator

In this study, we performed a comprehensive analysis of the effect of CCN1 on the migration of human immune cells. The molecule CCN1, produced by fibroblasts and endothelial cells, is considered as an important matrix protein promoting tissue repair and immune cell adhesion by binding various integrins. We recently reported that CCN1 therapy is able to suppress acute inflammation in vivo. Here, we show that CCN1 binds to various immune cells including T cells, B cells, NK cells, and monocytes. The addition of CCN1 in vitro enhances both actin polymerization and transwell migration. Prolonged incubation with CCN1, however, results in the inhibition of migration of immune cells by a mechanism that involves downregulation of PI3Kγ, p38, and Akt activation. Furthermore, we observed that immune cells themselves produce constitutively CCN1 and secretion is induced by pro-inflammatory stimuli. In line with this finding, patients suffering from acute inflammation had enhanced serum levels of CCN1. These findings extend the classical concept of CCN1 as a locally produced cell matrix adhesion molecule and suggest that CCN1 plays an important role in regulating immune cell trafficking by attracting and locally immobilizing immune cells.     

Galanin – 25 years with a multitalented neuropeptide

The skin, the largest organ of the body, functions as a barrier between the body proper and the external environment, as it is constantly exposed to noxious stressors. During the last few years, the concept of an interactive network involving cutaneous nerves, the neuroendocrine axis, and the immune system has emerged. The neuroendocrine system of the skin is composed of locally produced neuroendocrine mediators that interact with specific receptors. Among these mediators are neuropeptides, including members of the galanin peptide family--galanin, galanin-message-associated peptide, galanin-like peptide, and alarin--which are produced in neuronal as well as nonneuronal cells in the skin. Here we review the expression of the galanin peptides and their receptors in the skin, and the known functions of galanin peptides in different compartments of the skin. We discuss these data in light of the role of the galanin peptide family in inflammation and cell proliferation.     

ADAMTSL2 mutations in geleophysic dysplasia demonstrate a role for ADAMTS-like proteins in TGF-beta bioavailability regulation

Geleophysic dysplasia is an autosomal recessive disorder characterized by short stature, brachydactyly, thick skin and cardiac valvular anomalies often responsible for an early death. Studying six geleophysic dysplasia families, we first mapped the underlying gene to chromosome 9q34.2 and identified five distinct nonsense and missense mutations in ADAMTSL2 (a disintegrin and metalloproteinase with thrombospondin repeats-like 2), which encodes a secreted glycoprotein of unknown function. Functional studies in HEK293 cells showed that ADAMTSL2 mutations lead to reduced secretion of the mutated proteins, possibly owing to the misfolding of ADAMTSL2. A yeast two-hybrid screen showed that ADAMTSL2 interacts with latent TGF-beta-binding protein 1. In addition, we observed a significant increase in total and active TGF-beta in the culture medium as well as nuclear localization of phosphorylated SMAD2 in fibroblasts from individuals with geleophysic dysplasia. These data suggest that ADAMTSL2 mutations may lead to a dysregulation of TGF-beta signaling and may be the underlying mechanism of geleophysic dysplasia.     

Collapse of long-range charge order tracked by time-resolved photoemission at high momenta

Intense femtosecond (10(-15)?s) light pulses can be used to transform electronic, magnetic and structural order in condensed-matter systems on timescales of electronic and atomic motion. This technique is particularly useful in the study and in the control of materials whose physical properties are governed by the interactions between multiple degrees of freedom. Time- and angle-resolved photoemission spectroscopy is in this context a direct and comprehensive, energy- and momentum-selective probe of the ultrafast processes that couple to the electronic degrees of freedom. Previously, the capability of such studies to access electron momentum space away from zero momentum was, however, restricted owing to limitations of the available probing photon energy. Here, using femtosecond extreme-ultraviolet pulses delivered by a high-harmonic-generation source, we use time- and angle-resolved photoemission spectroscopy to measure the photoinduced vaporization of a charge-ordered state in the potential excitonic insulator 1T-TiSe(2 )(refs 12, 13). By way of stroboscopic imaging of electronic band dispersions at large momentum, in the vicinity of the edge of the first Brillouin zone, we reveal that the collapse of atomic-scale periodic long-range order happens on a timescale as short as 20?femtoseconds. The surprisingly fast response of the system is assigned to screening by the transient generation of free charge carriers. Similar screening scenarios are likely to be relevant in other photoinduced solid-state transitions and may generally determine the response times. Moreover, as electron states with large momenta govern fundamental electronic properties in condensed matter systems, we anticipate that the experimental advance represented by the present study will be useful to study the ultrafast dynamics and microscopic mechanisms of electronic phenomena in a wide range of materials.