Recognition of the class Ib molecule Qa-1(b) by putative activating receptors CD94/NKG2C and CD94/NKG2E on mouse natural killer cells.

The heterodimeric CD94/NKG2A receptor, expressed by mouse natural killer (NK) cells, transduces inhibitory signals upon recognition of its ligand, Qa-1(b), a nonclassical major histocompatibility complex class Ib molecule. Here we clone and express two additional receptors, CD94/NKG2C and CD94/NKG2E, which we show also bind to Qa-1(b). Within their extracellular carbohydrate recognition domains, NKG2C and NKG2E share extensive homology with NKG2A (93-95% amino acid similarity); however, NKG2C/E receptors differ from NKG2A in their cytoplasmic domains (only 33% similarity) and contain features that suggest that CD94/NKG2C and CD94/NKG2E may be activating receptors. We employ a novel blocking anti-NKG2 monoclonal antibody to provide the first direct evidence that CD94/NKG2 molecules are the only Qa-1(b) receptors on NK cells. Molecular analysis reveals that NKG2C and NKG2E messages are extensively alternatively spliced and approximately 20-fold less abundant than NKG2A message in NK cells. The organization of the mouse Cd94/Nkg2 gene cluster, presented here, shows striking similarity with that of the human, arguing that the entire CD94/NKG2 receptor system is relatively primitive in origin. Analysis of synonymous substitution frequencies suggests that within a species, NKG2 genes may maintain similarities with each other by concerted evolution, possibly involving gene conversion-like events. These findings have implications for understanding NK cells and also raise new possibilities for the role of Qa-1 in immune responses

Prior and Present Evidence: How Prior Experience Interacts with Present Information in a Perceptual Decision Making Task

Vibrotactile discrimination tasks have been used to examine decision making processes in the presence of perceptual uncertainty, induced by barely discernible frequency differences between paired stimuli or by the presence of embedded noise. One lesser known property of such tasks is that decisions made on a single trial may be biased by information from prior trials. An example is the time-order effect whereby the presentation order of paired stimuli may introduce differences in accuracy. Subjects perform better when the first stimulus lies between the second stimulus and the global mean of all stimuli on the judged dimension ("preferred" time-orders) compared to the alternative presentation order ("nonpreferred" time-orders). This has been conceptualised as a "drift" of the first stimulus representation towards the global mean of the stimulus-set (an internal standard). We describe the influence of prior information in relation to the more traditionally studied factors of interest in a classic discrimination task.Sixty subjects performed a vibrotactile discrimination task with different levels of uncertainty parametrically induced by increasing task difficulty, aperiodic stimulus noise, and changing the task instructions whilst maintaining identical stimulus properties (the "context").The time-order effect had a greater influence on task performance than two of the explicit factors-task difficulty and noise-but not context. The influence of prior information increased with the distance of the first stimulus from the global mean, suggesting that the "drift" velocity of the first stimulus towards the global mean representation was greater for these trials.Awareness of the time-order effect and prior information in general is essential when studying perceptual decision making tasks. Implicit mechanisms may have a greater influence than the explicit factors under study. It also affords valuable insights into basic mechanisms of information accumulation, storage, sensory weighting, and processing in neural circuits

Investigating off-Hugoniot states using multi-layer ring-up targets

Laser compression has long been used as a method to study solids at high pressure. This is commonly achieved by sandwiching a sample between two diamond anvils and using a ramped laser pulse to slowly compress the sample, while keeping it cool enough to stay below the melt curve. We demonstrate a different approach, using a multilayer ‘ring up’ target whereby laser-ablation pressure compresses Pb up to 150 GPa while keeping it solid, over two times as high in pressure than where it would shock melt on the Hugoniot. We find that the efficiency of this approach compares favourably with the commonly used diamond sandwich technique and could be important for new facilities located at XFELs and synchrotrons which often have higher repetition rate, lower energy lasers which limits the achievable pressures that can be reached

Frequency and Nature of Incidental Extra-Enteric Lesions Found on Magnetic Resonance Enterography (MR-E) in Patients with Inflammatory Bowel Diseases (IBD)

The aim of this study was to determine the occurrence of extra-enteric findings in a large cohort of patients undergoing magnetic resonance enterography (MR-E) and to classify the clinical significance of these findings.We retrospectively analyzed 1154 MR-E performed in 1006 patients referred to our radiological department between 1999-2005. The reasons for referral were suspected or proven inflammatory bowel diseases (IBD) (n = 710), further diagnostic work-up for small bowel disease because of non-specific abdominal symptoms (SBD; n = 182) or suspected small bowel malignancies (SBM; n = 114). All extra-enteric findings were reviewed by a radiologist and a gastroenterologist and were classified as having high, moderate, or low significance for further diagnostic or therapeutic procedures.The average age of all patients was 40+/-16 (Mean+/-SD) years (y) (IBD 35+/-13 y; SBD 49+/-16 y; SBM 57+/-15 y). A total of 1113 extra-enteric findings were detected in 600 of 1006 patients (59.6%). Of these findings 180 (16.2%) were judged as having a high, 212 (19.0%) a moderate and 721 (64.8%) a low significance. On a per group basis in patients with IBD 12.0% of the findings were of major clinical significance compared to 13.7% and 33.3% in patients with SBD and SBM, respectively. The most common major findings were abscesses (69.9%) in the IBD group and extraintestinal tumors, metastases or masses in the SBD and SBM groups (41.9% and 74.2%, respectively).MR-E reveals a substantial number of extra-enteric findings, supporting the role of a cross-sectional imaging method for the evaluation of the small bowel

Wild Type and Mutant 2009 Pandemic Influenza A (H1N1) Viruses Cause More Severe Disease and Higher Mortality in Pregnant BALB/c Mice

BACKGROUND: Pregnant women infected by the pandemic influenza A (H1N1) 2009 virus had more severe disease and higher mortality but its pathogenesis is still unclear. PRINCIPAL FINDINGS: We showed that higher mortality, more severe pneumonitis, higher pulmonary viral load, lower peripheral blood T lymphocytes and antibody responses, higher levels of proinflammatory cytokines and chemokines, and worse fetal development occurred in pregnant mice than non-pregnant controls infected by either wild type (clinical isolate) or mouse-adapted mutant virus with D222G substitution in hemagglutinin. These disease-associated changes and the lower respiratory tract involvement were worse in pregnant mice challenged by mutant virus. Though human placental origin JEG-3 cell line could be infected and proinflammatory cytokines or chemokines were elevated in amniotic fluid of some mice, no placental or fetal involvement by virus were detected by culture, real-time reverse transcription polymerase chain reaction or histopathological changes. Dual immunofluorescent staining of viral nucleoprotein and type II alveolar cell marker SP-C protein suggested that the majority of infected alveolar epithelial cells were type II pneumocytes. CONCLUSION: The adverse effect of this pandemic virus on maternal and fetal outcome is largely related to the severe pulmonary disease and the indirect effect of inflammatory cytokine spillover into the systemic circulation

Characteristics of mentally ill offenders from 100 psychiatric court reports

<p>Abstract</p> <p>Background</p> <p>There is an increasing probability that the psychiatrist will, willingly or not, come into contact with mentally ill offenders in the course of their practice. There are increasing rates of violence, substance abuse and other psychiatric disorders that are of legal importance. Therefore, the aim of this work was to investigate the rates of different mental disorders in 100 court reports and to investigate the characteristics of mentally ill offenders.</p> <p>Methods</p> <p>All cases referred from different departments of the legal system to the forensic committee for assessment of legal accountability over 13-months duration were included. A specially designed form was prepared for data collection. Cases were classified into five groups: murder, robbery, financial offences, violent and simple offences and a group for other offences. Data were subjected to statistical analysis and comparisons between different groups of subjects were performed by analysis of variance (ANOVA).</p> <p>Results</p> <p>Men constituted 93% of cases. In all, 73% of offenders were younger than 40 years old. Schizophrenia cases made up 13% of the total, substance related cases constituted 56% and amphetamine cases alone made up 21%; 10% of cases were antisocial personality disorders, and 51% of cases were classified as having a low education level. Unemployment was found in 34% of cases. The final decision of the forensic committee was full responsibility in 46% of cases and partial responsibility in 11% of cases, with 33% considered non-responsible. A total of 58% of cases had had contact with psychiatric healthcare prior to the offence and in 9% of cases contact had been in the previous 12 weeks. A history of similar offences was found in 32% of cases. In all, 14% of the offences were murders, 8% were sexual crimes, and 31% were violent/simple crimes.</p> <p>Conclusions</p> <p>The ability of the legal system to detect cases was good, while the ability of the healthcare system to predict crimes and offences was weak, as 58% of cases had had previous contact with the healthcare system previously. Substance abuse, especially amphetamine abuse, played an important role.</p

Shell we cook it? An experimental approach to the microarchaeological record of shellfish roasting

In this paper, we investigate the microarchaeological traces and archaeological visibility of shellfish cooking activities through a series of experimental procedures with direct roasting using wood-fueled fires and controlled heating in a muffle furnace. An interdisciplinary geoarchacological approach, combining micromorphology, FTIR (in transmission and ATR collection modes), TGA and XRD, was used to establish a baseline on the mineralogical transformation of heated shells from aragonite to calcite and diagnostic sedimentary traces produced by roasting fire features. Our experimental design focused on three main types of roasting procedures: the construction of shallow depressions with heated rocks (pebble cuvette experiments), placing shellfish on top of hot embers and ashes (fire below experiment), and by kindling short-lived fires on top of shellfish (fire above experiments). Our results suggest that similar shellfish roasting procedures will largely create microstratigraphic signatures of anthropogenically reworked combusted material spatially "disconnected" from the actual combustion locus. The construction of shallow earth ovens might entail an increased archaeological visibility, and some diagnostic signatures of in situ hearths can be obtained by fire below roasting activities. We also show that macroscopic visual modifications and mineralogical characterization of discarded shellfish might be indicative of specific cooking activities versus secondary burning.Max Planck Societyinfo:eu-repo/semantics/publishedVersio

Holocene history of the 79°N ice shelf reconstructed from epishelf lake and uplifted glaciomarine sediments

Nioghalvfjerdsbrae, or 79°N Glacier, is the largest marine-terminating glacier draining the Northeast Greenland Ice Stream (NEGIS). In recent years, its ∼70 km long fringing ice shelf (hereafter referred to as the 79°N ice shelf) has thinned, and a number of small calving events highlight its sensitivity to climate warming. With the continued retreat of the 79°N ice shelf and the potential for accelerated discharge from NEGIS, which drains 16 % of the Greenland Ice Sheet (GrIS), it has become increasingly important to understand the long-term history of the ice shelf in order to put the recent changes into perspective and to judge their long-term significance. Here, we reconstruct the Holocene dynamics of the 79°N ice shelf by combining radiocarbon dating of marine molluscs from isostatically uplifted glaciomarine sediments with a multi-proxy investigation of two sediment cores recovered from Blåsø, a large epishelf lake 2-13 km from the current grounding line of 79°N Glacier. Our reconstructions suggest that the ice shelf retreated between 8.5 and 4.4 kacalBP, which is consistent with previous work charting grounding line and ice shelf retreat to the coast as well as open marine conditions in Nioghalvfjerdsbrae. Ice shelf retreat followed a period of enhanced atmospheric and ocean warming in the Early Holocene. Based on our detailed sedimentological, microfaunal, and biomarker evidence, the ice shelf reformed at Blåsø after 4.4 kacalBP, reaching a thickness similar to present by 4.0 kacalBP. Reformation of the ice shelf coincides with decreasing atmospheric temperatures, the increased dominance of Polar Water, a reduction in Atlantic Water, and (near-)perennial sea-ice cover on the adjacent continental shelf. Along with available climate archives, our data indicate that the 79°N ice shelf is susceptible to collapse at mean atmospheric and ocean temperatures ∼2 °C warmer than present, which could be achieved by the middle of this century under some emission scenarios. Finally, the presence of "marine"markers in the uppermost part of the Blåsø sediment cores could record modern ice shelf thinning, although the significance and precise timing of these changes requires further work