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

Weakly acidic pH reduces inflammatory cytokine expression in airway epithelial cells

Background Aspiration lung disease (ALD) is a common cause of respiratory morbidity in children and adults with severe neurodisability (sND). Recent studies suggest that chronic microaspiration of gastric contents is associated with mild rather than low, airway acidification. We investigated inflammatory responses to infection by airway epithelial cells (AECs) exposed to weakly acidic media. Methods Using pH measurements from children with sND at high risk of ALD as a guide, we incubated AECs in weakly acidic (pH5.5–7.4) media alone; in combination with lipopolysaccharide (LPS); or prior to LPS stimulation at normal pH. Interleukin (IL) -6 and IL-8 expression were measured. Results IL-6/8 expression in AECs simultaneously exposed to weakly acidic media and LPS for 4 h was reduced with no effect on cell viability. Pre-incubation of AECs at weakly acidic pH also reduced subsequent LPS-induced cytokine expression. Suppression of inflammation was greatest at lower pHs (pH 5.5–6.0) for prolonged periods (16/24 h), but this also adversely affected cell viability. Conclusion AEC inflammatory responses to bacterial stimuli is markedly reduced in a mildly acidic environment

Eurasian beaver activity increases water storage, attenuates flow and mitigates diffuse pollution from intensively-managed grasslands

This is the final version of the article. Available from Elsevier via the DOI in this record.Beavers are the archetypal keystone species, which can profoundly alter ecosystem structure and function through their ecosystem engineering activity, most notably the building of dams. This can have a major impact upon water resource management, flow regimes and water quality. Previous research has predominantly focused on the activities of North American beaver (Castor canadensis) located in very different environments, to the intensive lowland agricultural landscapes of the United Kingdom and elsewhere in Europe. Two Eurasian beavers (Castor fiber) were introduced to a wooded site, situated on a first order tributary, draining from intensively managed grassland. The site was monitored to understand impacts upon water storage, flow regimes and water quality. Results indicated that beaver activity, primarily via the creation of 13 dams, has increased water storage within the site (holding ca. 1000m(3) in beaver ponds) and beavers were likely to have had a significant flow attenuation impact, as determined from peak discharges (mean 30±19% reduction), total discharges (mean 34±9% reduction) and peak rainfall to peak discharge lag times (mean 29±21% increase) during storm events. Event monitoring of water entering and leaving the site showed lower concentrations of suspended sediment, nitrogen and phosphate leaving the site (e.g. for suspended sediment; average entering site: 112±72mgl(-1), average leaving site: 39±37mgl(-1)). Combined with attenuated flows, this resulted in lower diffuse pollutant loads in water downstream. Conversely, dissolved organic carbon concentrations and loads downstream were higher. These observed changes are argued to be directly attributable to beaver activity at the site which has created a diverse wetland environment, reducing downstream hydrological connectivity. Results have important implications for beaver reintroduction programs which may provide nature based solutions to the catchment-scale water resource management issues that are faced in agricultural landscapes.The Devon Beaver Project is led by Devon Wildlife Trust, monitored by the University of Exeter, and funded by Devon Wildlife Trust and Westland Countryside Stewards

Plasma electrons above Saturn's main rings: CAPS observations

We present observations of thermal ( similar to 0.6 - 100eV) electrons observed near Saturn's main rings during Cassini's Saturn Orbit Insertion (SOI) on 1 July 2004. We find that the intensity of electrons is broadly anticorrelated with the ring optical depth at the magnetic footprint of the field line joining the spacecraft to the rings. We see enhancements corresponding to the Cassini division and Encke gap. We suggest that some of the electrons are generated by photoemission from ring particle surfaces on the illuminated side of the rings, the far side from the spacecraft. Structure in the energy spectrum over the Cassini division and A-ring may be related to photoelectron emission followed by acceleration, or, more likely, due to photoelectron production in the ring atmosphere or ionosphere

Correlated fragile site expression allows the identification of candidate fragile genes involved in immunity and associated with carcinogenesis

Background: Common fragile sites (cfs) are specific regions in the human genome that are particularly prone to genomic instability under conditions of replicative stress. Several investigations support the view that common fragile sites play a role in carcinogenesis. We discuss a genome-wide approach based on graph theory and Gene Ontology vocabulary for the functional characterization of common fragile sites and for the identification of genes that contribute to tumour cell biology. Results: Common fragile sites were assembled in a network based on a simple measure of correlation among common fragile site patterns of expression. By applying robust measurements to capture in quantitative terms the non triviality of the network, we identified several topological features clearly indicating departure from the Erdos-Renyi random graph model. The most important outcome was the presence of an unexpected large connected component far below the percolation threshold. Most of the best characterized common fragile sites belonged to this connected component. By filtering this connected component with Gene Ontology, statistically significant shared functional features were detected. Common fragile sites were found to be enriched for genes associated to the immune response and to mechanisms involved in tumour progression such as extracellular space remodeling and angiogenesis. Moreover we showed how the internal organization of the graph in communities and even in very simple subgraphs can be a starting point for the identification of new factors of instability at common fragile sites. Conclusion: We developed a computational method addressing the fundamental issue of studying the functional content of common fragile sites. Our analysis integrated two different approaches. First, data on common fragile site expression were analyzed in a complex networks framework. Second, outcomes of the network statistical description served as sources for the functional annotation of genes at common fragile sites by means of the Gene Ontology vocabulary. Our results support the hypothesis that fragile sites serve a function; we propose that fragility is linked to a coordinated regulation of fragile genes expression

Targeting Tregs in Juvenile Idiopathic Arthritis and Juvenile Dermatomyositis-Insights From Other Diseases

Regulatory T cells (Tregs) are believed to be dysfunctional in autoimmunity. Juvenile idiopathic arthritis (JIA) and juvenile dermatomyositis (JDM) result from a loss of normal immune regulation in specific tissues such as joints or muscle and skin, respectively. Here, we discuss recent findings in regard to Treg biology in oligo-/polyarticular JIA and JDM, as well as what we can learn about Treg-related disease mechanism, treatment and biomarkers in JIA/JDM from studies of other diseases. We explore the potential use of Treg immunoregulatory markers and gene signatures as biomarkers for disease course and/or treatment success. Further, we discuss how Tregs are affected by several treatment strategies already employed in the therapy of JIA and JDM and by alternative immunotherapies such as anti-cytokine or co-receptor targeting. Finally, we review recent successes in using Tregs as a treatment target with low-dose IL-2 or cellular immunotherapy. Thus, this mini review will highlight our current understanding and identify open questions in regard to Treg biology, and how recent findings may advance biomarkers and new therapies for JIA and JDM

Neuropsychiatric status after liver transplantation

A neuropsychiatric study of individuals who underwent successful liver transplantation an average of 3 years previously was conducted to assess quality of life in terms of cognitive capacity and psychiatric status, as well as social and behavioral functioning. Compared with a control group of patients with Crohn's disease, liver transplant patients did not differ on measures of intelligence, language, attention, concentration, spatial organization, memory, or learning. Performance on these diverse aspects of cognitive functioning was in the normal ranges for both groups when compared with normative or standardized test values. The control and liver transplant patients were not different from each other on measures of psychiatric status or social functioning; however, both groups exhibited some disruption of functioning in these two areas when contrasted with normative values. We conclude that relatively young individuals (mean age in this study, 27.8 years) do not exhibit debilitating long-term neuropsychiatric disability after liver transplantation, although some disturbance in social and psychiatric adjustment was observed. © 1984

Nonalcoholic Cirrhosis Associated With Neuropsycholo'gical Dysfunction in the Absence of Overt Evidence of Hepatic Encephalopathy

Although much is known about the neuropsychological functioning of cirrhotic individuals with Laennec's (alcohol associated) cirrhosis, little is known about the neuropsychological functioning of^individuals with nonalcoholic cirrhosis. In the present investigation, we have determined that individuals suffering from chronic nonalcoholic cirrhosis, despite the absence of clinical signs of hepatic encephalopathy, are impaired on neuropsychological tests that measure visuopractic capacity, visual scanning, and perceptual-motor speed. In contrast, intellectual, language, memory, attentional, motor, and learning abilities are intact. In comparison with a chronically ill control group of patients suffering from Crohn's disease, individuals with advanced nonalcoholic cirrhosis exhibit less emotional disturbance, but are more impaired in their daily activities. These findings indicate that individuals with nonalcoholic cirrhosis, even in the absence of overt clinical signs of encephalopathy, manifest neuropsychological impairments and experience significant disruption in the routines of everyday living. © 1984, American Gastroenterological Association. All rights reserved