Identification And Characterization Of A Second Encephalitogenic Determinant Of Myelin Proteolipid Protein (Residues 178-191) For SJL Mice

We previously described a synthetic peptide of myelin proteolipid protein (PLP), peptide 139-151, which induces experimental allergic encephalomyelitis in SJL/J (H-2s) mice. We have now identified an additional determinant, PLP residues 178-191, that is also a potent encephalitogen in this strain. When PLP peptide 178-191 was compared with peptide 139-151 on an equimolar basis, the day of onset of disease induced by PLP 178-191 was earlier, but the incidence, severity, and histologic features were indistinguishable. Lymph node cells from animals immunized with the whole PLP molecule responded to both PLP 178-191 and 139-151, suggesting immunologic codominance of the two epitopes. PLP 178-191 elicited stronger proliferative responses and this may relate to the earlier onset of disease induced with this peptide. Two CD4+, peptide-specific, I-A(s)-restricted T cell lines, selected by stimulation of lymph node cells with either PLP 178-191 or 139-151, were each encephalitogenic in naive syngeneic mice. The presence of multiple encephalitogenic codominant PLP epitopes within a single mouse strain emphasizes the complexity of the immune response to PLP and its potential as a target Ag in autoimmune demyelinating diseases

The mitochondrial tRNA-derived fragment, mt-tRF-Leu^TAA, couples mitochondrial metabolism to insulin secretion.

The contribution of the mitochondrial electron transfer system to insulin secretion involves more than just energy provision. We identified a small RNA fragment (mt-tRF-Leu <sup>TAA</sup> ) derived from the cleavage of a mitochondrially-encoded tRNA that is conserved between mice and humans. The role of mitochondrially-encoded tRNA-derived fragments remains unknown. This study aimed to characterize the impact of mt-tRF-Leu <sup>TAA</sup> , on mitochondrial metabolism and pancreatic islet functions. We used antisense oligonucleotides to reduce mt-tRF-Leu <sup>TAA</sup> levels in primary rat and human islet cells, as well as in insulin-secreting cell lines. We performed a joint transcriptome and proteome analysis upon mt-tRF-Leu <sup>TAA</sup> inhibition. Additionally, we employed pull-down assays followed by mass spectrometry to identify direct interactors of the fragment. Finally, we characterized the impact of mt-tRF-Leu <sup>TAA</sup> silencing on the coupling between mitochondrial metabolism and insulin secretion using high-resolution respirometry and insulin secretion assays. Our study unveils a modulation of mt-tRF-Leu <sup>TAA</sup> levels in pancreatic islets in different Type 2 diabetes models and in response to changes in nutritional status. The level of the fragment is finely tuned by the mechanistic target of rapamycin complex 1. Located within mitochondria, mt-tRF-Leu <sup>TAA</sup> interacts with core subunits and assembly factors of respiratory complexes of the electron transfer system. Silencing of mt-tRF-Leu <sup>TAA</sup> in islet cells limits the inner mitochondrial membrane potential and impairs mitochondrial oxidative phosphorylation, predominantly by affecting the Succinate (via Complex II)-linked electron transfer pathway. Lowering mt-tRF-Leu <sup>TAA</sup> impairs insulin secretion of rat and human pancreatic β-cells. Our findings indicate that mt-tRF-Leu <sup>TAA</sup> interacts with electron transfer system complexes and is a pivotal regulator of mitochondrial oxidative phosphorylation and its coupling to insulin secretion

Neutrino oscillation parameters from MINOS, ICARUS and OPERA combined

We perform a detailed analysis of the capabilities of the MINOS, ICARUS and OPERA experiments to measure neutrino oscillation parameters at the atmospheric scale with their data taken separately and in combination. MINOS will determine $\Delta m^2_{32}$ and $\sin^2 2\theta_{23}$ to within 10% at the 99% C.L. with 10 kton-years of data. While no one experiment will determine $\sin^2 2\theta_{13}$ with much precision, if its value lies in the combined sensitivity region of the three experiments, it will be possible to place a lower bound of O(0.01) at the 95% C.L. on this parameter by combining the data from the three experiments. The same bound can be placed with a combination of MINOS and ICARUS data alone.Comment: Version to appear in PR

The asymmetry and temporal dynamics of incidental letter-location bindings in working memory.

Verbal-spatial bindings are integral to routine cognitive operations (e.g., reading), yet the processes supporting them in working memory are little understood. Campo and colleagues [Campo, P., Poch, C., Parmentier, F. B. R., Moratti, S., Elsley, J. V., Castellanos, N., … Maestú, F. (2010). Oscillatory activity in prefrontal and posterior regions during implicit letter-location binding. Neuroimage, 49, 2807-2815] recently reported data suggesting obligatory letter-location binding when participants were directed to remember the letters in a display (of letters in locations), but no evidence for binding when instructed to remember the filled locations. The present study contrasted two explanations for this binding asymmetry. First, it may result from an obligatory dependence on "where" during the representation of "what" information, while "where" information may be held independently of its contents (the strong asymmetry hypothesis). Second, it may constitute a snapshot of a dynamic feature inhibition process that had partially completed by test: the asymmetrical inhibition hypothesis. Using Campo and colleagues' task with a variable retention interval between display and test, we presented four consonants in distinct locations and contrasted performance between "remember letters" and "remember locations" instructions. Our data supported the strong asymmetry hypothesis through demonstrating binding in the verbal task, but not in the spatial task. Critically, when present, verbal-spatial bindings were remarkably stable, enduring for at least 15 seconds

Measurement of single charged pion production in the charged-current interactions of neutrinos in a 1.3 GeV wide band beam

Single charged pion production in charged-current muon neutrino interactions with carbon is studied using data collected in the K2K long-baseline neutrino experiment. The mean energy of the incident muon neutrinos is 1.3 GeV. The data used in this analysis are mainly from a fully active scintillator detector, SciBar. The cross section for single $\pi^{+}$ production in the resonance region ($W<2$ GeV/$c^2$) relative to the charged-current quasi-elastic cross section is found to be 0.734 $^{+0.140}_{-0.153}$. The energy-dependent cross section ratio is also measured. The results are consistent with a previous experiment and the prediction of our model.Comment: 15 pages, 12 figures, 7 tables. Uses revtex4. Minor revisions to match version accepted for publication in Physical Review

Genome-Wide Linkage Scan for Genes Influencing Plasma Triglyceride Levels in the Veterans Administration Genetic Epidemiology Study

OBJECTIVE—Elevated plasma triglyceride concentration is a component of the insulin resistance syndrome and is commonly associated with type 2 diabetes, obesity, and coronary heart disease. The goal of our study was to perform a genome-wide linkage scan to identify genetic regions that influence variation in plasma triglyceride levels in families that are enriched with individuals with type 2 diabetes

Development of intuitive rules: Evaluating the application of the dual-system framework to understanding children's intuitive reasoning

This is an author-created version of this article. The original source of publication is Psychon Bull Rev. 2006 Dec;13(6):935-53 The final publication is available at www.springerlink.com Published version: http://dx.doi.org/10.3758/BF0321390

Inhibition of Vaginal Lactobacilli by a Bacteriocin-Like Inhibitor Produced by Enterococcus faecium 62-6: Potential Significance for Bacterial Vaginosis

Objective: Bacterial vaginosis (BV) is characterized by a shift in vaginal tract ecology, which includes a decrease in the concentration and/or prevalence of facultative lactobacilli. Currently, mechanisms which could account for the disappearance of lactobacilli are not well understood. The objective of this study was to determine whether vaginal streptococci/enterococci can produce bacteriocin-like inhibitors antagonistic to vaginal lactobacilli. Methods: Seventy strains of vaginal streptococci or enterococci were tested for antagonistic activities against vaginal lactobacilli using the deferred antagonism technique. Results: One strain, Enterococcus faecium 62-6, which strongly inhibited growth of lactobacilli was selected for further characterization. The spectrum of inhibitory activity of strain 62-6 included Gram-positive organisms from the vaginal environment, although native lactobacilli from the same host were resistant to inhibitor action. Following growth inMRSbroth the strain 62-6 inhibitor was shown to be heat- (100℃, 30 minutes), cold- (4℃, less than 114 days) and pH- (4–7) stable. The sensitivity of inhibitor-containing supernatants to pepsin and α-chymotrypsin suggested an essential proteinaceous component. The inhibitor was sensitive to lipase but resistant to lysozyme. Dialysis of inhibitor-containing culture supernatants suggested a molecular mass greater than 12 000 Da. All physicochemical properties were consistent with its classification as a bacteriocin-like inhibitor. Kinetic assays demonstrated a sharp onset of inhibitor production coinciding with a concentration of 62-6 of 10(7) cfu/ml, suggesting that production may be regulated by quorum sensing. Conclusions: These results may have clinical significance as a novel mechanism to account for the decline of vaginal Lactobacillus populations and contribute to both the establishment and recurrence of BV

Evidence for oscillation of atmospheric neutrinos

We present an analysis of atmospheric neutrino data from a 33.0 kiloton-year (535-day) exposure of the Super-Kamiokande detector. The data exhibit a zenith angle dependent deficit of muon neutrinos which is inconsistent with expectations based on calculations of the atmospheric neutrino flux. Experimental biases and uncertainties in the prediction of neutrino fluxes and cross sections are unable to explain our observation. The data are consistent, however, with two-flavor nu_mu nu_tau oscillations with sin^2(2theta)>0.82 and 5x10^-4 < delta m^2 < 6x10^-3 eV^2 at 90% confidence level.Comment: 9 pages (two-column) with 4 figures. Small corrections to Eqn.4 and Fig.3. Final version to appear in PR