Sensitivity to Gravitational Waves from Compact Binary Coalescences Achieved during LIGO's Fifth and Virgo's First Science Run

We summarize the sensitivity achieved by the LIGO and Virgo gravitational wave detectors for compact binary coalescence (CBC) searches during LIGO's fifth science run and Virgo's first science run. We present noise spectral density curves for each of the four detectors that operated during these science runs which are representative of the typical performance achieved by the detectors for CBC searches. These spectra are intended for release to the public as a summary of detector performance for CBC searches during these science runs.Comment: 12 pages, 5 figure

Directional limits on persistent gravitational waves using LIGO S5 science data

The gravitational-wave (GW) sky may include nearby pointlike sources as well as astrophysical and cosmological stochastic backgrounds. Since the relative strength and angular distribution of the many possible sources of GWs are not well constrained, searches for GW signals must be performed in a model-independent way. To that end we perform two directional searches for persistent GWs using data from the LIGO S5 science run: one optimized for pointlike sources and one for arbitrary extended sources. The latter result is the first of its kind. Finding no evidence to support the detection of GWs, we present 90% confidence level (CL) upper-limit maps of GW strain power with typical values between 2-20x10^-50 strain^2 Hz^-1 and 5-35x10^-49 strain^2 Hz^-1 sr^-1 for pointlike and extended sources respectively. The limits on pointlike sources constitute a factor of 30 improvement over the previous best limits. We also set 90% CL limits on the narrow-band root-mean-square GW strain from interesting targets including Sco X-1, SN1987A and the Galactic Center as low as ~7x10^-25 in the most sensitive frequency range near 160 Hz. These limits are the most constraining to date and constitute a factor of 5 improvement over the previous best limits.Comment: 10 pages, 4 figure

Expression of Ovine Herpesvirus -2 Encoded MicroRNAs in an Immortalised Bovine - Cell Line

Ovine herpesvirus-2 (OvHV-2) infects most sheep, where it establishes an asymptomatic, latent infection. Infection of susceptible hosts e.g. cattle and deer results in malignant catarrhal fever, a fatal lymphoproliferative disease characterised by uncontrolled lymphocyte proliferation and non MHC restricted cytotoxicity. The same cell populations are infected in both cattle and sheep but only in cattle does virus infection cause dysregulation of cell function leading to disease. The mechanism by which OvHV-2 induces this uncontrolled proliferation is unknown. A number of herpesviruses have been shown to encode microRNAs (miRNAs) that have roles in control of both viral and cellular gene expression. We hypothesised that OvHV-2 encodes miRNAs and that these play a role in pathogenesis. Analysis of massively parallel sequencing data from an OvHV-2 persistently-infected bovine lymphoid cell line (BJ1035) identified forty-five possible virus-encoded miRNAs. We previously confirmed the expression of eight OvHV-2 miRNAs by northern hybridization. In this study we used RT-PCR to confirm the expression of an additional twenty-seven OvHV-2-encoded miRNAs. All thirty-five OvHV-2 miRNAs are expressed from the same virus genome strand and the majority (30) are encoded in an approximately 9 kb region that contains no predicted virus open reading frames. Future identification of the cellular and virus targets of these miRNAs will inform our understanding of MCF pathogenesis

Demographic, clinical and antibody characteristics of patients with digital ulcers in systemic sclerosis: data from the DUO Registry

OBJECTIVES: The Digital Ulcers Outcome (DUO) Registry was designed to describe the clinical and antibody characteristics, disease course and outcomes of patients with digital ulcers associated with systemic sclerosis (SSc). METHODS: The DUO Registry is a European, prospective, multicentre, observational, registry of SSc patients with ongoing digital ulcer disease, irrespective of treatment regimen. Data collected included demographics, SSc duration, SSc subset, internal organ manifestations, autoantibodies, previous and ongoing interventions and complications related to digital ulcers. RESULTS: Up to 19 November 2010 a total of 2439 patients had enrolled into the registry. Most were classified as either limited cutaneous SSc (lcSSc; 52.2%) or diffuse cutaneous SSc (dcSSc; 36.9%). Digital ulcers developed earlier in patients with dcSSc compared with lcSSc. Almost all patients (95.7%) tested positive for antinuclear antibodies, 45.2% for anti-scleroderma-70 and 43.6% for anticentromere antibodies (ACA). The first digital ulcer in the anti-scleroderma-70-positive patient cohort occurred approximately 5 years earlier than the ACA-positive patient group. CONCLUSIONS: This study provides data from a large cohort of SSc patients with a history of digital ulcers. The early occurrence and high frequency of digital ulcer complications are especially seen in patients with dcSSc and/or anti-scleroderma-70 antibodies

Sensitivity to Gravitational Waves from Compact Binary Coalescences Achieved during LIGO's Fifth and Virgo's First Science Run

We summarize the sensitivity achieved by the LIGO and Virgo gravitational wave detectors for compact binary coalescence (CBC) searches during LIGO's fifth science run and Virgo's first science run. We present noise spectral density curves for each of the four detectors that operated during these science runs which are representative of the typical performance achieved by the detectors for CBC searches. These spectra are intended for release to the public as a summary of detector performance for CBC searches during these science runs

On the rules of co-existence between sheep, cattle, and OvHV-2

Malignant catarrhal fever (MCF) is a lethal disease of ruminants and swine, characterized by vasculitis, necrosis, and accumulation of activated, dysregulated cytotoxic lymphocytes in various tissues. It is transmitted from so-called “reservoir” animal species to “indicator” animal species. Ovine gammaherpesvirus 2 (OvHV-2) is one of several causative agents of MCF, circulating among all sheep breeds worldwide, which represent the “reservoir” of this virus. Natural infection of sheep proceeds without clinical symptoms. The disease is characterized by proliferation of cytotoxic T-cells, which form perivascular infiltrates of lymphoid as well as non-lymphoid organs, leading to necrosis and tissue destruction. However, little is known about the immunopathogenic pathways leading to disease. Moreover, at the time when this work was initiated, only limited data were available for the situation in sheep. Therefore, we first analyzed the cell populations targeted by the virus during natural infection of lambs, since the range of targeted cells may be important for the pathogenesis, especially if it is different in sheep and indicator animals, respectively. In most sheep we found a first peak of viral DNA in CD4+ T-helpercells, followed by a second peak in CD8+ cytotoxic T-cells. Both, CD4+ as well as CD8+ cells are also found to harbor viral DNA in lymphocytes of cattle with MCF. From this finding we suggest that rather a species-specific fine-tuning of viral gene expression than the types of targeted cells may be accountable for the disease. The second question addressed in this work was whether production of viral particles leading to cell lysis is among the pathological factors of MCF. Diseases due to gammaherpesvirus infections are mostly associated to latent infection, during which only a limited number of viral proteins are expressed. These are important to tie the viral DNA to host chromosomes, ensuring synchronous replication of viral DNA with cellular DNA, to provide viral DNA to each daughter cell and likely render the host cell increased resistance against apoptosis. However, persistent infection with Human herpesvirus 8 (HHV-8) as an exception is depending on a mixture of latently and lytically infected cells. To address whether this may be the case during MCF as well, we produced antisera against structural viral proteins and tested several tissue samples of experimentally infected rabbits therewith. We detected viral proteins in epithelial and M-cells of the appendix of infected animals. Interestingly, in situ hybridization revealed viral RNA in the infected epithelial cells but not in M-cells. These data suggest that active OvHV-2 replication may play a role in the pathogenesis of the disease. Thirdly, we tested the gene expression patterns of OvHV-2 and the relative abundances of host cell transcripts in lymphocytes of diseased cattle to identify pathways possibly involved in the pathogenesis of MCF. To this, host and virus gene expression patterns were analyzed by microarrray. Only two regions of the viral genome were found to be transcriptionally active, one encoding a latency-associated nuclear antigen, which can be found during latency of other gammaherpesviruses as well. The other with no predicted open reading frame, which may represent micro RNA (miRNA). So far miRNA was not discussed as a pathological factor of MCF and opens completely new attempts. As could be expected, a large number of host genes related to inflammation, lymphocyte activation, cell proliferation and apoptosis were found to be at different abundances compared to healthy animals. One of these transcripts with decreased expression was IL-2. Since the phenotype of mice with IL-2 deficiency perfectly matches the clinical signs of MCF, we assume that IL-2 deficiency may play an important role in the development of disease

Malignant catarrhal fever of cattle is associated with low abundance of IL-2 transcript and a predominantly latent profile of ovine herpesvirus 2 gene expression

Background: Malignant catarrhal fever (MCF) is a lethal disease of cattle, characterized by vasculitis, necrosis, and accumulation of activated, dysregulated cytotoxic lymphocytes in various tissues. Ovine gamma herpesvirus 2 (OvHV-2) is a causative agent of MCF, which may trigger the disease through immunopathogenic pathways. Lymphocytes are the main target of the virus. However, the pathogenic basis of the disease is still mysterious. Methods/Findings:We hypothesized that the gene expression patterns of OvHV-2 and the relative abundances of host cell transcripts in lymphnodes may be used to identify pathways that help to explain the pathogenesis of MCF. Therefore, viral and host cell gene expression patterns in lymph nodes of animals with MCF and healthy controls were analyzed by microarray. Two regions on the viral genome were transcriptionally active, one encoding an orthologue to the latencyassociated nuclear antigen (ORF73) of other gamma herpesviruses, the other with no predicted open reading frame. A vast number of transcripts related to inflammatory processes, lymphocyte activation, cell proliferation and apoptosis were detected at different abundances. However, the IL-2 transcript was eminent among the transcripts, which were, compared to healthy controls, less abundant in animals with MCF. The ratio between CD4- and CD8-positive T-lymphocytes was decreased in the lymphnodes of animals with MCF compared to healthy controls. In contrast, the same ratio was stable, when peripheral blood lymphocytes were analyzed. Conclusions/Significance:The phenotype of mice with a deficient IL-2-system almost perfectly matches the clinical signs observed in cattle with MCF, which feature a significantly decreased IL-2 transcript abundance, compared to healthy cattle. This supports the hypothesis that immunopathogenic events are linked to the pathogenesis of MCF. IL-2-deficiency may play an important role in the process. Therefore, this work opens new avenues for research on MCF

Identification of peripheral blood mononuclear cells targeted by Ovine herpesvirus-2 in sheep

Sheep-associated malignant catarrhal fever (MCF), caused by Ovine herpesvirus 2 (OvHV-2), is usually a fatal disease of various ruminants and swine. In contrast, natural OvHV-2 infection in sheep, which are the main OvHV-2 reservoir, proceeds without any clinical symptoms. Since the range of targeted cells may be important for pathogenesis, we wanted to analyze the natural range of peripheral mononuclear blood cells (PBMC)targeted by OvHV-2. To this end, OvHV-2-free sheep were exposed to natural infection and blood samples were taken at intervals. Four different PBMC subpopulations were purified by fluorescence activated cell sorting (FACS) before being subjected to analysis for OvHV- 2-DNA. After an incubation period of between 11 and 12 weeks, all exposed sheep became positive for OvHV-2. In most sheep, a first peak of OvHV-2-DNA was identified in the CD2 and CD4 double positive subpopulation. However, with time, the highest load of OvHV-2-DNA shifted to the CD2-positive and CD4-negative T-cells. Furthermore, low amounts of OvHV-2-DNA were occasionally detected also in the fractions that represented either CD14-positive monocytes or triple negative cells (CD2 /CD4 /CD14 ). We conclude from these experiments that OvHV-2 has a similar host cellular range in sheep and cattle,respectively. Our results may be relevant in the context of comparative analysis of OvHV-2 pathogenesis in animal species that are susceptible to MCF

Cell cycle and apoptosis related transcripts affected in MCF in cattle.

<p>Cell cycle and apoptosis related transcripts affected in MCF in cattle.</p