The Activated Type 1–Polarized Cd8+ T Cell Population Isolated from an Effector Site Contains Cells with Flexible Cytokine Profiles

The capacity of activated T cells to alter their cytokine expression profiles after migration into an effector site has not previously been defined. We addressed this issue by paired daughter analysis of a type 1–polarized CD8+ effector T cell population freshly isolated from lung parenchyma of influenza virus–infected mice. Single T cells were activated to divide in vitro; individual daughter cells were then micromanipulated into secondary cultures with and without added IL-4 to assess their potential to express type 2 cytokine genes. The resultant subclones were analyzed for type 1 and 2 cytokine mRNAs at day 6–7. When the most activated (CD44highCD11ahigh) CD8+ subpopulation from infected lung was compared with naive or resting (CD44lowCD11alow) CD8+ cells from infected lung and from normal lymph nodes (LNs), both clonogenicity and plasticity of the cytokine response were highest in the LN population and lowest in the activated lung population, correlating inversely with effector function. Multipotential cells were nevertheless detected among clonogenic CD44highCD11ahigh lung cells at 30–50% of the frequency in normal LNs. The data indicate that activated CD8+ T cells can retain the ability to proliferate and express new cytokine genes in response to local stimuli after recruitment to an effector site

Analysis of the MOST light curve of the heavily spotted K2IV component of the single-line spectroscopic binary II Pegasi

Continuous photometric observations of the visible component of the single-line, K2IV spectroscopic binary II Peg carried out by the MOST satellite during 31 consecutive days in 2008 have been analyzed. On top of spot-induced brightness modulation, eleven flares were detected of three distinct types characterized by different values of rise, decay and duration times. The flares showed a preference for occurrence at rotation phases when the most spotted hemisphere is directed to the observer, confirming previous similar reports. An attempt to detect a grazing primary minimum caused by the secondary component transiting in front of the visible star gave a negative result. The brightness variability caused by spots has been interpreted within a cold spot model. An assumption of differential rotation of the primary component gave a better fit to the light curve than a solid-body rotation model.Comment: Accepteed to MNRA

Novel Picornavirus Detected in Wild Deer: Identification, Genomic Characterisation, and Prevalence in Australia

The use of high-throughput sequencing has facilitated virus discovery in wild animals and helped determine their potential threat to humans and other animals. We report the complete genome sequence of a novel picornavirus identified by next-generation sequencing in faeces from Australian fallow deer. Genomic analysis revealed that this virus possesses a typical picornavirus-like genomic organisation of 7554 nt with a single open reading frame (ORF) encoding a polyprotein of 2225 amino acids. Based on the amino acid identity comparison and phylogenetic analysis of the P1, 2C, 3CD, and VP1 regions, this novel picornavirus was closely related to but distinct from known bopiviruses detected to date. This finding suggests that deer/bopivirus could belong to a novel species within the genus Bopivirus, tentatively designated as “Bopivirus C”. Epidemiological investigation of 91 deer (71 fallow, 14 sambar and 6 red deer) and 23 cattle faecal samples showed that six fallow deer and one red deer (overall prevalence 7.7%, 95% confidence interval [CI] 3.8–15.0%) tested positive, but deer/bopivirus was undetectable in sambar deer and cattle. In addition, phylogenetic and sequence analyses indicate that the same genotype is circulating in south-eastern Australia. To our knowledge, this study reports for the first time a deer-origin bopivirus and the presence of a member of genus Bopivirus in Australia. Further epidemiological and molecular studies are needed to investigate the geographic distribution and pathogenic potential of this novel Bopivirus species in other domestic and wild animal species

Molecular Epidemiology and Characterization of Picobirnavirus in Wild Deer and Cattle from Australia: Evidence of Genogroup I and II in the Upper Respiratory Tract

Picobirnaviruses (PBVs) have been detected in several species of animals worldwide; however, data pertaining to their presence in Australian wild and domestic animals are limited. Although PBVs are mostly found in faecal samples, their detection in blood and respiratory tract samples raises questions concerning their tropism and pathogenicity. We report here PBV detection in wild deer and cattle from southeastern Australia. Through metagenomics, the presence of PBV genogroups I (GI) and II (GII) were detected in deer serum and plasma. Molecular epidemiology studies targeting the partial RNA-dependent RNA polymerase gene were performed in a wide range of specimens (serum, faeces, spleen, lung, nasal swabs, and trachea) collected from wild deer and cattle, with PCR amplification obtained in all specimen types except lung and spleen. Our results reveal the predominance of GI and concomitant detection of both genogroups in wild deer and cattle. In concordance with other studies, the detected GI sequences displayed high genetic diversity, however in contrast, GII sequences clustered into three distinct clades. Detection of both genogroups in the upper respiratory tract (trachea and nasal swab) of deer in the present study gives more evidence about the respiratory tract tropism of PBV. Although much remains unknown about the epidemiology and tropism of PBVs, our study suggests a wide distribution of these viruses in southeastern Australia

Engineering novel complement activity into a pulmonary surfactant protein

Complement neutralizes invading pathogens, stimulates inflammatory and adaptive immune responses, and targets non- or altered-self structures for clearance. In the classical and lectin activation pathways, it is initiated when complexes composed of separate recognition and activation subcomponents bind to a pathogen surface. Despite its apparent complexity, recognition-mediated activation has evolved independently in three separate protein families, C1q, mannose-binding lectins (MBLs), and serum ficolins. Although unrelated, all have bouquet-like architectures and associate with complement-specific serine proteases: MBLs and ficolins with MBL-associated serine protease-2 (MASP-2) and C1q with C1r and C1s. To examine the structural requirements for complement activation, we have created a number of novel recombinant rat MBLs in which the position and orientation of the MASP-binding sites have been changed. We have also engineered MASP binding into a pulmonary surfactant protein (SP-A), which has the same domain structure and architecture as MBL but lacks any intrinsic complement activity. The data reveal that complement activity is remarkably tolerant to changes in the size and orientation of the collagenous stalks of MBL, implying considerable rotational and conformational flexibility in unbound MBL. Furthermore, novel complement activity is introduced concurrently with MASP binding in SP-A but is uncontrolled and occurs even in the absence of a carbohydrate target. Thus, the active rather than the zymogen state is default in lectin·MASP complexes and must be inhibited through additional regions in circulating MBLs until triggered by pathogen recognition

MRI bone oedema scores are higher in the arthritis mutilans form of psoriatic arthritis and correlate with high radiographic scores for joint damage

10.1186/ar2586Arthritis Research and Therapy111R

A novel protamine variant reversal of heparin anticoagulation in human blood in vitro

AbstractPurpose: Protamine reversal of heparin anticoagulation during cardiovascular surgery may cause severe hypotension and pulmonary hypertension. A novel protamine variant, [+18RGD], has been developed that effectively reverses heparin anticoagulation without toxicity in canine experiments. Heretofore, human studies have not been undertaken. This investigation hypothesized that [+18RGD] would effectively reverse heparin anticoagulation of human blood in vitro. Methods: Fifty patients who underwent anticoagulation therapy during vascular surgery had blood sampled at baseline and 30 minutes after receiving heparin (150 IU/kg). Activated clotting times were used to define specific quantities of [+18RGD] or protamine necessary to completely reverse heparin anticoagulation in the blood sample of each patient. These defined amounts of [+18RGD] or protamine were then administered to the heparinized blood samples, and percent reversals of activated partial thromboplastin time, thrombin clotting time, and antifactor Xa/IIa levels were determined. In addition, platelet aggregation assays, as well as platelet and white blood cell counts were performed. Results: [+18RGD] and protamine were equivalent in reversing heparin as assessed by thrombin clotting time, antifactor Xa, antifactor IIa levels, and white blood cell changes. [+18RGD], when compared with protamine, was superior in this regard, as assessed by activated partial thromboplastin time (94.5 ± 1.0 vs 86.5 ± 1.3%δ, respectively; p < 0.001) and platelet declines (–3.9 ± 2.9 vs –12.8 ± 3.4 per mm3, respectively; p = 0.048). Platelet aggregation was also decreased for [+18RGD] compared with protamine (23.6 ± 1.5 vs 28.5 ± 1.9%, respectively; p = 0.048). Conclusions: [+18RGD] was as effective as protamine for in vitro reversal of heparin anticoagulation by most coagulation assays, was statistically more effective at reversal than protamine by aPTT assay, and was associated with lesser platelet reductions than protamine. [+18RGD], if less toxic than protamine in human beings, would allow for effective clinical reversal of heparin anticoagulation. (J Vasc Surg 1997;26:1043-8.

Extensive MRO CRISM Observations of 1.27 micron O2 Airglow in Mars Polar Night and Their Comparison to MRO MCS Temperature Profiles and LMD GCM Simulations

The Martian polar night distribution of 1.27 micron (0-0) band emission from O2 singlet delta [O2(1Delta(sub g))] is determined from an extensive set of Mars Reconnaissance Orbiter (MRO) Compact Reconnaissance Imaging Spectral Mapping (CRISM) limb scans observed over a wide range of Mars seasons, high latitudes, local times, and longitudes between 2009 and 2011. This polar nightglow reflects meridional transport and winter polar descent of atomic oxygen produced from CO2 photodissociation. A distinct peak in 1.27 micron nightglow appears prominently over 70-90NS latitudes at 40-60 km altitudes, as retrieved for over 100 vertical profiles of O2(1Delta(sub g)) 1.27 micron volume emission rates (VER). We also present the first detection of much (x80+/-20) weaker 1.58 micron (0-1) band emission from Mars O2(1Delta(sub g)). Co-located polar night CRISM O2(1Delta(sub g)) and Mars Climate Sounder (MCS) (McCleese et al., 2008) temperature profiles are compared to the same profiles as simulated by the Laboratoire de Mtorologie Dynamique (LMD) general circulation/photochemical model (e.g., Lefvre et al., 2004). Both standard and interactive aerosol LMD simulations (Madeleine et al., 2011a) underproduce CRISM O2(1Delta(sub g)) total emission rates by 40%, due to inadequate transport of atomic oxygen to the winter polar emission regions. Incorporation of interactive cloud radiative forcing on the global circulation leads to distinct but insufficient improvements in modeled polar O2(1Delta(sub g)) and temperatures. The observed and modeled anti-correlations between temperatures and 1.27 mm band VER reflect the temperature dependence of the rate coefficient for O2(1Delta(sub g)) formation, as provided in Roble (1995)

Genomic characterisation of Eμ-Myc mouse lymphomas identifies Bcor as a Myc co-operative tumour-suppressor gene

The Eμ-Myc mouse is an extensively used model of MYC driven malignancy; however to date there has only been partial characterization of MYC co-operative mutations leading to spontaneous lymphomagenesis. Here we sequence spontaneously arising Eμ-Myc lymphomas to define transgene architecture, somatic mutations, and structural alterations. We identify frequent disruptive mutations in the PRC1-like component and BCL6-corepressor gene Bcor. Moreover, we find unexpected concomitant multigenic lesions involving Cdkn2a loss and other cancer genes including Nras, Kras and Bcor. These findings challenge the assumed two-hit model of Eμ-Myc lymphoma and demonstrate a functional in vivo role for Bcor in suppressing tumorigenesis.We acknowledge the following funding agencies: Leukaemia Foundation of Australia, Arrow Bone Marrow Transplant Foundation, National Health and Medical Research Council Australia, Cancer Council Victoria, Victorian Cancer Agency, Australian Cancer Research Foundation, Peter MacCallum Cancer Centre Foundation, National Institutes of Health