X-ray harmonic comb from relativistic electron spikes

X-ray devices are far superior to optical ones for providing nanometre spatial and attosecond temporal resolutions. Such resolution is indispensable in biology, medicine, physics, material sciences, and their applications. A bright ultrafast coherent X-ray source is highly desirable, for example, for the diffractive imaging of individual large molecules, viruses, or cells. Here we demonstrate experimentally a new compact X-ray source involving high-order harmonics produced by a relativistic-irradiance femtosecond laser in a gas target. In our first implementation using a 9 Terawatt laser, coherent soft X-rays are emitted with a comb-like spectrum reaching the 'water window' range. The generation mechanism is robust being based on phenomena inherent in relativistic laser plasmas: self-focusing, nonlinear wave generation accompanied by electron density singularities, and collective radiation by a compact electric charge. The formation of singularities (electron density spikes) is described by the elegant mathematical catastrophe theory, which explains sudden changes in various complex systems, from physics to social sciences. The new X-ray source has advantageous scalings, as the maximum harmonic order is proportional to the cube of the laser amplitude enhanced by relativistic self-focusing in plasma. This allows straightforward extension of the coherent X-ray generation to the keV and tens of keV spectral regions. The implemented X-ray source is remarkably easily accessible: the requirements for the laser can be met in a university-scale laboratory, the gas jet is a replenishable debris-free target, and the harmonics emanate directly from the gas jet without additional devices. Our results open the way to a compact coherent ultrashort brilliant X-ray source with single shot and high-repetition rate capabilities, suitable for numerous applications and diagnostics in many research fields

Clinical Features of Autoimmune Autonomic Ganglionopathy and the Detection of Subunit-Specific Autoantibodies to the Ganglionic Acetylcholine Receptor in Japanese Patients

Autoimmune autonomic ganglionopathy (AAG) is a rare acquired channelopathy that is characterized by pandysautonomia, in which autoantibodies to ganglionic nicotinic acetylcholine receptors (gAChR) may play a central role. Radioimmunoprecipitation (RIP) assays have been used for the sensitive detection of autoantibodies to gAChR in the serum of patients with AAG. Here, we developed luciferase immunoprecipitation systems (LIPS) to diagnose AAG based on IgGs to both the α3 and β4 gAChR subunits in patient serum. We reviewed the serological and clinical data of 50 Japanese patients who were diagnosed with AAG. With the LIPS testing, we detected anti-α3 and -β4 gAChR antibodies in 48% (24/50) of the patients. A gradual mode of onset was more common in the seropositive group than in the seronegative group. Patients with AAG frequently have orthostatic hypotension and upper and lower gastrointestinal tract symptoms, with or without anti-gAChR. The occurrence of autonomic symptoms was not significantly different between the seropositive and seronegative group, with the exception of achalasia in three patients from the seropositive group. In addition, we found a significant overrepresentation of autoimmune diseases in the seropositive group and endocrinological abnormalities as an occasional complication of AAG. Our results demonstrated that the LIPS assay was a useful novel tool for detecting autoantibodies against gAChR in patients with AAG

Epidemiology of Campylobacter jejuni Isolated from Patients with Guillain-Barré and Fisher Syndromes in Japan

Campylobacter jejuni isolation is the standard for the diagnosis of this type of bacterial infection, but there have been no epidemiological studies of a large number of C. jejuni isolates from patients with Guillain-Barré syndrome (GBS) and Fisher syndrome (FS). For 13 years, stool specimens from GBS/FS patients have been sent from 378 hospitals throughout Japan to the Tokyo Metropolitan Institute of Public Health. A total of 113 strains (11%) were isolated from the stool specimens from 1,049 patients. The isolation rate did not differ by region. The rates were 22% for 449 patients with a history of diarrhea and 2% for the others. An additional 18 isolates were provided by various hospitals. There was no noticeable seasonal distribution in the onset of C. jejuni isolated from patients with GBS/FS. The male/female ratios were 1.7:1 for GBS and 2.2:1 for FS. The patient age range showed a peak in 10- to 30-year-old subjects who had GBS and in 10- to 20-year-old subjects who had FS. The predominance of young adults and male patients who had C. jejuni-associated GBS/FS may be related to the preponderance of young adults and male patients who had C. jejuni enteritis. The median interval from diarrhea onset to neurologic symptom onset was 10 days for GBS/FS. Penner's C. jejuni serotype HS:19 was more frequently present in GBS (67%) than in enteritis (6%) patients. HS:2 was more frequent in FS (41%) than in enteritis (14%) patients. These findings suggest that certain C. jejuni strains specifically trigger GBS and that others specifically trigger FS

Complex of GM1-and GD1a-Likelipo-Oligosaccharide mimics GM1b,inducing anti-GM1b antibodies

Objective Molecular mimicry between Campylobacter jejuni lipo-oligosaccharides (LOSs) and human gangliosides GM1 and GD1a induces the production of anti-GM1 and anti-GD1a antibodies, and the development of Guillain-Barr\ue9 syndrome. Complexes of two different gangliosides form new molecular shapes capable of enhancing recognition by anti-ganglioside antibodies. To test the hypothesis that the complex of GM1-like and GD1a-like LOSs of C. jejuni induces the development of anti-GM1b antibodies in Guillain-Barr\ue9 syndrome patients. Methods Mass spectrometry analysis determined the LOS outer core structures, with which mice were immunized. IgG antibodies to single gangliosides and complex of gangliosides were tested in sera from Guillain-Barr\ue9 syndrome patients from whom C. jejuni LOS had been isolated. Results Two isolates from GBS patients who had anti-GM1b antibodies, but neither anti-GM1 nor -GD1a antibodies, expressed both GM1-like and GD1a-like LOSs, but not GM1b-like LOS. Anti-GM1b antibodies were induced in one of the mice immunized with the C. jejuni bearing GM1-like and GD1a-like LOS. Sera from 20 patients had antibodies to the complex of GM1 and GD1a, all of which carried anti-GM1b reactivity. Five of these sera harbored neither anti-GM1 nor anti-GD1a antibodies. IgG antibodies to the complex were absorbed by GM1b, but by neither GM1 nor GD1a. Conclusions GM1-like and GD1a-like LOSs form a GM1b epitope, inducing the development of anti- GM1b antibodies in patients with Guillain-Barr\ue9 syndrome subsequent to C. jejuni enteritis. Here, we present a new paradigm that the complex of two different structures forms a new molecular mimicry, inducing the production of autoantibodies.Peer reviewed: YesNRC publication: Ye

Electrophoresis-assisted open-tubular liquid chromatography/mass spectrometry for the analysis of lipooligosaccharide expressed by Campylobacter jejuni.

Lipooligosaccharide (LOS) is the major component of the external membrane of Campylobacter jejuni. LOS contains a hydrophobic moiety, lipid A, and a hydrophilic moiety, oligosaccharide. Due to the unique mimicry of human ganglioside structures and potential involvement in the induction of the autoimmune polyneuropathies, Guillain\u2013Barr\ue9 and Miller Fisher syndromes, the structural characterization of C. jejuni LOS has received much attention. We have been using capillary zone electrophoresis\u2013mass spectrometry to analyze O-deacylated LOS from C. jejuni. In an attempt to optimize the separation conditions, the effect of methanol on the separation of LOS was investigated. It was found that methanol resulted in stronger adsorption of LOS onto the wall of fused-silica capillary. In this paper, we applied this adsorption to perform electrophoresis-assisted open-tubular liquid chromatography electrospray mass spectrometry for the analysis of O-deacylated LOS mixtures from C. jejuni. The analytical potential of the proposed strategy for the analysis of O-deacylated LOS glycoforms from five bacterial colonies is demonstrated. Online tandem mass spectrometry is shown to provide a powerful tool for characterization of variations in the hexosamine backbone, phosphorylation of the lipid A, and sialic acid sequence information.Peer reviewed: YesNRC publication: Ye

GM1-like and GD1a-like lipo-oligosccharides (LOSs).

<p>(A) Schematic structures of GM1, GD1a and GM1b gangliosides, as well as GM1-like and GD1a-like LOSs of <i>Campylobacter jejuni</i>. (B) Proposed LOS outer core structure of <i>C</i>. <i>jejuni</i> strains (GC016 and GC105) isolated from patients with GBS who had anti-GM1b antibodies, but neither anti-GM1 nor anti-GD1a antibodies. Gal = Galactose; NeuAc = <i>N</i>-Acetylneuraminic acid; GalNAc = <i>N</i>-Acetylgalactosamine; Hep = L-<i>glycero</i>-D-<i>manno</i>-Heptose; Glc = Glucose; Kdo = 3-deoxy-D-<i>manno</i>-2-Octulosonic acid; <i>P</i>Etn = Phosphoethanolamine. (C) <i>C</i>. <i>jejuni</i> (GC016) LOS with and without neuraminidase treatment. Anti-GD1a monoclonal antibody reactivity to the LOS was decreased after the treatment, whereas anti-GM1 monoclonal antibody reactivity was increased. This indicates that the neuraminidase-treatment transformed GD1a-like LOS into GM1-like LOS by removing the terminal neuraminic acid. (D) Absorption studies using antibodies against cM1/D1a with various antigens. Anti-cM1/D1a IgG antibodies from the serum of a patient with GBS (S382) were absorbed by the intact GC016 LOS (black bar; GM1/GD1a mimics) and a mixture of GM1 and GD1a gangliosides (gray bar), but not by neuraminidase-treated GC016 LOS (GM1 mimic as shown in A) and NCTC11168 LOS (GM1/GM2 mimics).</p