EchoBASE: an integrated post-genomic database for Escherichia coli

EchoBASE (http://www.ecoli-york.org) is a relational database designed to contain and manipulate information from post-genomic experiments using the model bacterium Escherichia coli K-12. Its aim is to collate information from a wide range of sources to provide clues to the functions of the approximately 1500 gene products that have no confirmed cellular function. The database is built on an enhanced annotation of the updated genome sequence of strain MG1655 and the association of experimental data with the E.coli genes and their products. Experiments that can be held within EchoBASE include proteomics studies, microarray data, protein–protein interaction data, structural data and bioinformatics studies. EchoBASE also contains annotated information on ‘orphan’ enzyme activities from this microbe to aid characterization of the proteins that catalyse these elusive biochemical reactions

A Single Dose of Neuron-Binding Human Monoclonal Antibody Improves Spontaneous Activity in a Murine Model of Demyelination

Our laboratory demonstrated that a natural human serum antibody, sHIgM12, binds to neurons in vitro and promotes neurite outgrowth. We generated a recombinant form, rHIgM12, with identical properties. Intracerebral infection with Theiler's Murine Encephalomyelitis Virus (TMEV) of susceptible mouse strains results in chronic demyelinating disease with progressive axonal loss and neurologic dysfunction similar to progressive forms of multiple sclerosis. To study the effects of rHIgM12 on the motor function of TMEV-infected mice, we monitored spontaneous nocturnal activity over many weeks. Nocturnal behavior is a sensitive measure of rodent neurologic function because maximal activity changes are expected to occur during the normally active night time monitoring period. Mice were placed in activity boxes eight days prior to treatment to collect baseline spontaneous activity. After treatment, activity in each group was continuously recorded over 8 weeks. We chose a long 8-week monitoring period for two reasons: (1) we previously demonstrated that IgM induced remyelination is present by 5 weeks post treatment, and (2) TMEV-induced demyelinating disease in this strain progresses very slowly. Due to the long observation periods and large data sets, differences among treatment groups may be difficult to appreciate studying the original unfiltered recordings. To clearly delineate changes in the highly fluctuating original data we applied three different methods: (1) binning, (2) application of Gaussian low-pass filters (GF) and (3) polynomial fitting. Using each of the three methods we showed that compared to control IgM and saline, early treatment with rHIgM12 induced improvement in both horizontal and vertical motor function, whereas later treatment improved only horizontal activity. rHIgM12 did not alter activity of normal, uninfected mice. This study supports the hypothesis that treatment with a neuron-binding IgM not only protects neurons in vitro, but also influences functional motor improvement

Results from 730 kg days of the CRESST-II Dark Matter Search

The CRESST-II cryogenic Dark Matter search, aiming at detection of WIMPs via elastic scattering off nuclei in CaWO$_4$ crystals, completed 730 kg days of data taking in 2011. We present the data collected with eight detector modules, each with a two-channel readout; one for a phonon signal and the other for coincidently produced scintillation light. The former provides a precise measure of the energy deposited by an interaction, and the ratio of scintillation light to deposited energy can be used to discriminate different types of interacting particles and thus to distinguish possible signal events from the dominant backgrounds. Sixty-seven events are found in the acceptance region where a WIMP signal in the form of low energy nuclear recoils would be expected. We estimate background contributions to this observation from four sources: 1) "leakage" from the e/\gamma-band 2) "leakage" from the \alpha-particle band 3) neutrons and 4) Pb-206 recoils from Po-210 decay. Using a maximum likelihood analysis, we find, at a high statistical significance, that these sources alone are not sufficient to explain the data. The addition of a signal due to scattering of relatively light WIMPs could account for this discrepancy, and we determine the associated WIMP parameters.Comment: 17 pages, 13 figure

Antibody signatures in patients with histopathologically defined multiple sclerosis patterns

Early active multiple sclerosis (MS) lesions can be classified histologically into three main immunopathological patterns of demyelination (patterns I-III), which suggest pathogenic heterogeneity and may predict therapy response. Patterns I and II show signs of immune-mediated demyelination, but only pattern II is associated with antibody/complement deposition. In pattern III lesions, which include Baló's concentric sclerosis, primary oligodendrocyte damage was proposed. Serum antibody reactivities could reflect disease pathogenesis and thus distinguish histopathologically defined MS patterns. We established a customized microarray with more than 700 peptides that represent human and viral antigens potentially relevant for inflammatory demyelinating CNS diseases, and tested sera from 66 patients (pattern I n = 12; II n = 29; III n = 25, including 8 with Baló's), healthy controls, patients with Sjögren's syndrome and stroke patients. Cell-based assays were performed for aquaporin 1 (AQP1) and AQP4 antibody detection. No single peptide showed differential binding among study cohorts. Because antibodies can react with different peptides from one protein, we also analyzed groups of peptides. Patients with pattern II showed significantly higher reactivities to Nogo-A peptides as compared to patterns I (p = 0.02) and III (p = 0.02). Pattern III patients showed higher reactivities to AQP1 (compared to pattern I p = 0.002, pattern II p = 0.001) and varicella zoster virus (VZV, compared to pattern II p = 0.05). In patients with Baló's, AQP1 reactivity was also significantly higher compared to patients without Baló's (p = 0.04), and the former revealed distinct antibody signatures. Histologically, Baló's patients showed loss of AQP1 and AQP4 in demyelinating lesions, but no antibodies binding conformational AQP1 or AQP4 were detected. In summary, higher reactivities to Nogo-A peptides in pattern II patients could be relevant for enhanced axonal repair and remyelination. Higher reactivities to AQP1 peptides in pattern III patients and its subgroup of Baló's patients possibly reflect astrocytic damage. Finally, latent VZV infection may cause peripheral immune activation

The CRESST II Dark Matter Search

Direct Dark Matter detection with cryodetectors is briefly discussed, with particular mention of the possibility of the identification of the recoil nucleus. Preliminary results from the CREEST II Dark Matter search, with 730 kg-days of data, are presented. Major backgrounds and methods of identifying and dealing with them are indicated.Comment: Talk at DSU workshop, ITP Beijing, Oct. 2011. 9 figures, 2 table

MOG-IgG in primary and secondary chronic progressive multiple sclerosis: a multicenter study of 200 patients and review of the literature

Background: Antibodies to human full-length myelin oligodendrocyte glycoprotein (MOG-IgG) as detected by new-generation cell-based assays have recently been described in patients presenting with acute demyelinating disease of the central nervous system, including patients previously diagnosed with multiple sclerosis (MS). However, only limited data are available on the relevance of MOG-IgG testing in patients with chronic progressive demyelinating disease. It is unclear if patients with primary progressive MS (PPMS) or secondary progressive MS (SPMS) should routinely be tested for MOG-IgG. Objective: To evaluate the frequency of MOG-IgG among patients classified as having PPMS or SPMS based on current diagnostic criteria. Methods: For this purpose, we retrospectively tested serum samples of 200 patients with PPMS or SPMS for MOG-IgG using cell-based assays. In addition, we performed a review of the entire English language literature on MOG-IgG published between 2011 and 2017. Results: None of 139 PPMS and 61 SPMS patients tested was positive for MOG-IgG. Based on a review of the literature, we identified 35 further MOG-IgG tests in patients with PPMS and 55 in patients with SPMS; the only reportedly positive sample was positive just at threshold level and was tested in a non-IgG-specific assay. In total, a single borderline positive result was observed among 290 tests. Conclusion: Our data suggest that MOG-IgG is absent or extremely rare among patients with PPMS or SPMS. Routine screening of patients with typical PPMS/SPMS for MOG-IgG seems not to be justified

WD + MS systems as the progenitor of SNe Ia

We show the initial and final parameter space for SNe Ia in a ($\log P^{\rm i}, M_{\rm 2}^{\rm i}$) plane and find that the positions of some famous recurrent novae, as well as a supersoft X-ray source (SSS), RX J0513.9-6951, are well explained by our model. The model can also explain the space velocity and mass of Tycho G, which is now suggested to be the companion star of Tycho's supernova. Our study indicates that the SSS, V Sge, might be the potential progenitor of supernovae like SN 2002ic if the delayed dynamical-instability model due to Han & Podsiadlowski (2006) is appropriate. Following the work of Meng, Chen & Han (2009), we found that the SD model (WD + MS) with an optically thick wind can explain the birth rate of supernovae like SN 2006X and reproduce the distribution of the color excess of SNe Ia. The model also predicts that at least 75% of all SNe Ia may show a polarization signal in their spectra.Comment: 6 pages, 2 figures, accepted for publication in Astrophysics & Space Science (Proceeding of the 4th Meeting on Hot Subdwarf Stars and Related Objects, edited by Zhanwen Han, Simon Jeffery & Philipp Podsiadlowski