Formyl Peptide Receptor as a Novel Therapeutic Target for Anxiety-Related Disorders

Formyl peptide receptors (FPR) belong to a family of sensors of the immune system that detect microbe-associated molecules and inform various cellular and sensorial mechanisms to the presence of pathogens in the host. Here we demonstrate that Fpr2/3-deficient mice show a distinct profile of behaviour characterised by reduced anxiety in the marble burying and light-dark box paradigms, increased exploratory behaviour in an open-field, together with superior performance on a novel object recognition test. Pharmacological blockade with a formyl peptide receptor antagonist, Boc2, in wild type mice reproduced most of the behavioural changes observed in the Fpr2/3(-/-) mice, including a significant improvement in novel object discrimination and reduced anxiety in a light/dark shuttle test. These effects were associated with reduced FPR signalling in the gut as shown by the significant reduction in the levels of p-p38. Collectively, these findings suggest that homeostatic FPR signalling exerts a modulatory effect on anxiety-like behaviours. These findings thus suggest that therapies targeting FPRs may be a novel approach to ameliorate behavioural abnormalities present in neuropsychiatric disorders at the cognitive-emotional interface

CagI Is an Essential Component of the Helicobacter pylori Cag Type IV Secretion System and Forms a Complex with CagL

Helicobacter pylori, the causative agent of type B gastritis, peptic ulcers, gastric adenocarcinoma and MALT lymphoma, uses the Cag type IV secretion system to induce a strong proinflammatory response in the gastric mucosa and to inject its effector protein CagA into gastric cells. CagA translocation results in altered host cell gene expression profiles and cytoskeletal rearrangements, and it is considered as a major bacterial virulence trait. Recently, it has been shown that binding of the type IV secretion apparatus to integrin receptors on target cells is a crucial step in the translocation process. Several bacterial proteins, including the Cag-specific components CagL and CagI, have been involved in this interaction. Here, we have examined the localization and interactions of CagI in the bacterial cell. Since the cagI gene overlaps and is co-transcribed with the cagL gene, the role of CagI for type IV secretion system function has been difficult to assess, and conflicting results have been reported regarding its involvement in the proinflammatory response. Using a marker-free gene deletion approach and genetic complementation, we show now that CagI is an essential component of the Cag type IV secretion apparatus for both CagA translocation and interleukin-8 induction. CagI is distributed over soluble and membrane-associated pools and seems to be partly surface-exposed. Deletion of several genes encoding essential Cag components has an impact on protein levels of CagI and CagL, suggesting that both proteins require partial assembly of the secretion apparatus. Finally, we show by co-immunoprecipitation that CagI and CagL interact with each other. Taken together, our results indicate that CagI and CagL form a functional complex which is formed at a late stage of secretion apparatus assembly

Search for Gravitational Wave Bursts from Six Magnetars

Soft gamma repeaters (SGRs) and anomalous X-ray pulsars (AXPs) are thought to be magnetars: neutron stars powered by extreme magnetic fields. These rare objects are characterized by repeated and sometimes spectacular gamma-ray bursts. The burst mechanism might involve crustal fractures and excitation of non-radial modes which would emit gravitational waves (GWs). We present the results of a search for GW bursts from six galactic magnetars that is sensitive to neutron star f-modes, thought to be the most efficient GW emitting oscillatory modes in compact stars. One of them, SGR 0501+4516, is likely similar to 1 kpc from Earth, an order of magnitude closer than magnetars targeted in previous GW searches. A second, AXP 1E 1547.0-5408, gave a burst with an estimated isotropic energy >10(44) erg which is comparable to the giant flares. We find no evidence of GWs associated with a sample of 1279 electromagnetic triggers from six magnetars occurring between 2006 November and 2009 June, in GW data from the LIGO, Virgo, and GEO600 detectors. Our lowest model-dependent GW emission energy upper limits for band-and time-limited white noise bursts in the detector sensitive band, and for f-mode ringdowns (at 1090 Hz), are 3.0 x 10(44)d(1)(2) erg and 1.4 x 10(47)d(1)(2) erg, respectively, where d(1) = d(0501)/1 kpc and d(0501) is the distance to SGR 0501+4516. These limits on GW emission from f-modes are an order of magnitude lower than any previous, and approach the range of electromagnetic energies seen in SGR giant flares for the first time.United States National Science FoundationScience and Technology Facilities Council of the United KingdomMax-Planck-SocietyState of Niedersachsen/GermanyItalian Istituto Nazionale di Fisica NucleareFrench Centre National de la Recherche ScientifiqueAustralian Research CouncilCouncil of Scientific and Industrial Research of IndiaIstituto Nazionale di Fisica Nucleare of ItalySpanish Ministerio de Educacion y CienciaConselleria d'Economia Hisenda i Innovacio of the Govern de les Illes BalearsFoundation for Fundamental Research on Matter supported by the Netherlands Organisation for Scientific ResearchPolish Ministry of Science and Higher EducationFoundation for Polish ScienceRoyal SocietyScottish Funding CouncilScottish Universities Physics AllianceNational Aeronautics and Space Administration NNH07ZDA001-GLASTCarnegie TrustLeverhulme TrustDavid and Lucile Packard FoundationResearch CorporationAlfred P. Sloan FoundationRussian Space AgencyRFBR 09-02-00166aIPN JPL Y503559 (Odyssey), NASA NNG06GH00G, NASA NNX07AM42G, NASA NNX08AC89G (INTEGRAL), NASA NNG06GI896, NASA NNX07AJ65G, NASA NNX08AN23G (Swift), NASA NNX07AR71G (MESSENGER), NASA NNX06AI36G, NASA NNX08AB84G, NASA NNX08AZ85G (Suzaku), NASA NNX09AU03G (Fermi)Astronom

Search for Gravitational Waves from Low Mass Compact Binary Coalescence in LIGO's Sixth Science Run and Virgo's Science Runs 2 and 3

We report on a search for gravitational waves from coalescing compact binaries using LIGO and Virgo observations between July 7, 2009 and October 20, 2010. We searched for signals from binaries with total mass between 2 and 25 solar masses; this includes binary neutron stars, binary black holes, and binaries consisting of a black hole and neutron star. The detectors were sensitive to systems up to 40 Mpc distant for binary neutron stars, and further for higher mass systems. No gravitational-wave signals were detected. We report upper limits on the rate of compact binary coalescence as a function of total mass, including the results from previous LIGO and Virgo observations. The cumulative 90%-confidence rate upper limits of the binary coalescence of binary neutron star, neutron star- black hole and binary black hole systems are 1.3 x 10^{-4}, 3.1 x 10^{-5} and 6.4 x 10^{-6} Mpc^{-3}yr^{-1}, respectively. These upper limits are up to a factor 1.4 lower than previously derived limits. We also report on results from a blind injection challenge.Comment: 11 pages, 5 figures. For a repository of data used in the publication, go to: . Also see the announcement for this paper on ligo.org at: <http://www.ligo.org/science/Publication-S6CBCLowMass/index.php

Implications For The Origin Of GRB 051103 From LIGO Observations

We present the results of a LIGO search for gravitational waves (GWs) associated with GRB 051103, a short-duration hard-spectrum gamma-ray burst (GRB) whose electromagnetically determined sky position is coincident with the spiral galaxy M81, which is 3.6 Mpc from Earth. Possible progenitors for short-hard GRBs include compact object mergers and soft gamma repeater (SGR) giant flares. A merger progenitor would produce a characteristic GW signal that should be detectable at the distance of M81, while GW emission from an SGR is not expected to be detectable at that distance. We found no evidence of a GW signal associated with GRB 051103. Assuming weakly beamed gamma-ray emission with a jet semi-angle of 30 deg we exclude a binary neutron star merger in M81 as the progenitor with a confidence of 98%. Neutron star-black hole mergers are excluded with > 99% confidence. If the event occurred in M81 our findings support the the hypothesis that GRB 051103 was due to an SGR giant flare, making it the most distant extragalactic magnetar observed to date.Comment: 8 pages, 3 figures. For a repository of data used in the publication, go to: https://dcc.ligo.org/cgi-bin/DocDB/ShowDocument?docid=15166 . Also see the announcement for this paper on ligo.org at: http://www.ligo.org/science/Publication-GRB051103/index.ph

Implementation and testing of the first prompt search for gravitational wave transients with electromagnetic counterparts

Aims. A transient astrophysical event observed in both gravitational wave (GW) and electromagnetic (EM) channels would yield rich scientific rewards. A first program initiating EM follow-ups to possible transient GW events has been developed and exercised by the LIGO and Virgo community in association with several partners. In this paper, we describe and evaluate the methods used to promptly identify and localize GW event candidates and to request images of targeted sky locations. Methods. During two observing periods (Dec 17 2009 to Jan 8 2010 and Sep 2 to Oct 20 2010), a low-latency analysis pipeline was used to identify GW event candidates and to reconstruct maps of possible sky locations. A catalog of nearby galaxies and Milky Way globular clusters was used to select the most promising sky positions to be imaged, and this directional information was delivered to EM observatories with time lags of about thirty minutes. A Monte Carlo simulation has been used to evaluate the low-latency GW pipeline's ability to reconstruct source positions correctly. Results. For signals near the detection threshold, our low-latency algorithms often localized simulated GW burst signals to tens of square degrees, while neutron star/neutron star inspirals and neutron star/black hole inspirals were localized to a few hundred square degrees. Localization precision improves for moderately stronger signals. The correct sky location of signals well above threshold and originating from nearby galaxies may be observed with ~50% or better probability with a few pointings of wide-field telescopes.Comment: 17 pages. This version (v2) includes two tables and 1 section not included in v1. Accepted for publication in Astronomy & Astrophysic

First Low-Latency LIGO+Virgo Search for Binary Inspirals and their Electromagnetic Counterparts

Aims. The detection and measurement of gravitational-waves from coalescing neutron-star binary systems is an important science goal for ground-based gravitational-wave detectors. In addition to emitting gravitational-waves at frequencies that span the most sensitive bands of the LIGO and Virgo detectors, these sources are also amongst the most likely to produce an electromagnetic counterpart to the gravitational-wave emission. A joint detection of the gravitational-wave and electromagnetic signals would provide a powerful new probe for astronomy. Methods. During the period between September 19 and October 20, 2010, the first low-latency search for gravitational-waves from binary inspirals in LIGO and Virgo data was conducted. The resulting triggers were sent to electromagnetic observatories for followup. We describe the generation and processing of the low-latency gravitational-wave triggers. The results of the electromagnetic image analysis will be described elsewhere. Results. Over the course of the science run, three gravitational-wave triggers passed all of the low-latency selection cuts. Of these, one was followed up by several of our observational partners. Analysis of the gravitational-wave data leads to an estimated false alarm rate of once every 6.4 days, falling far short of the requirement for a detection based solely on gravitational-wave data.Comment: 13 pages, 13 figures. For a repository of data used in the publication, go to: http://dcc.ligo.org/cgi-bin/DocDB/ShowDocument?docid=P1100065 Also see the announcement for this paper on ligo.org at: http://www.ligo.org/science/Publication-S6CBCLowLatency

Immunodominant Antigens of Leishmania chagasi Associated with Protection against Human Visceral Leishmaniasis

One of the most striking features of infection by Leishmania chagasi is that infection leads to a spectrum of clinical outcomes ranging from asymptomatic infection to active disease. The existence of asymptomatic infected people has served as an incentive to believe that an effective vaccine is possible, but unfortunately no successful immunological characterization of such cases was obtained. Patients recovered from visceral leishmaniasis show a similar immunological profile to asymptomatic infected individuals and both exhibit a strong cell-mediated immune response against Leishmania antigens and are resistant to disease. Since the past decade several approaches were undertaken to try to shed light on the immunological profile associated with such “resistance” to infections, notwithstanding antigenic recognition profile associated to resistance to infection was not successfully explored. In the present manuscript we describe a specific IgG recognizing pattern associated with resistant individuals (asymptomatic infected people and recovery patients to visceral leishmaniasis). These data highlight the possibility of using specific proteins in serological tests for the identification of asymptomatic infected individuals