Post-translational processing of the glycoproteins of lymphocytic choriomeningitis virus.

Intracellular events in the synthesis, glycosylation, and transport of the lymphocytic choriomeningitis virus (LCMV) glycoproteins have been examined. We have shown by N-glycanase digestion that LCMV strain Arm-4 bears five oligosaccharides on GP-1 and two on GP-2. By pulse-chase labeling experiments in the presence of drugs which inhibit N-linked oligosaccharide addition and processing we demonstrate that addition of high mannose precursor oligosaccharides is necessary for transport and cleavage of the viral GP-C glycoprotein. Moreover, in the presence of tunicamycin which inhibits en bloc addition of these mannose-rich side chains, virus budding was substantially decreased and infectious virions were reduced by more than 1000-fold in the supernatant medium. Incubation in the presence of castantospermine, which permits addition of oligomannosyl-rich chains but blocks further processing, restored transport and cleavage of GP-C and maturation of virions. Finally, by temperature block experiments we have determined that maturation of GP-C oligosaccharides to an endoglycosidase H resistant form precedes cleavage to GP-1 and GP-2. The latter process is most likely to occur in the Golgi or post-Golgi compartment

Interactions between downslope flows and a developing cold-air pool

A numerical model has been used to characterize the development of a region of enhanced cooling in an alpine valley with a width of order (Formula presented.) km, under decoupled stable conditions. The region of enhanced cooling develops largely as a region of relatively dry air which partitions the valley atmosphere dynamics into two volumes, with airflow partially trapped within the valley by a developing elevated inversion. Complex interactions between the region of enhanced cooling and the downslope flows are quantified. The cooling within the region of enhanced cooling and the elevated inversion is almost equally partitioned between radiative and dynamic effects. By the end of the simulation, the different valley atmospheric regions approach a state of thermal equilibrium with one another, though this cannot be said of the valley atmosphere and its external environment.Peer reviewe

Pollutant dispersion in a developing valley cold-air pool

Pollutants are trapped and accumulate within cold-air pools, thereby affecting air quality. A numerical model is used to quantify the role of cold-air-pooling processes in the dispersion of air pollution in a developing cold-air pool within an alpine valley under decoupled stable conditions. Results indicate that the negatively buoyant downslope flows transport and mix pollutants into the valley to depths that depend on the temperature deficit of the flow and the ambient temperature structure inside the valley. Along the slopes, pollutants are generally entrained above the cold-air pool and detrained within the cold-air pool, largely above the ground-based inversion layer. The ability of the cold-air pool to dilute pollutants is quantified. The analysis shows that the downslope flows fill the valley with air from above, which is then largely trapped within the cold-air pool, and that dilution depends on where the pollutants are emitted with respect to the positions of the top of the ground-based inversion layer and cold-air pool, and on the slope wind speeds. Over the lower part of the slopes, the cold-air-pool-averaged concentrations are proportional to the slope wind speeds where the pollutants are emitted, and diminish as the cold-air pool deepens. Pollutants emitted within the ground-based inversion layer are largely trapped there. Pollutants emitted farther up the slopes detrain within the cold-air pool above the ground-based inversion layer, although some fraction, increasing with distance from the top of the slopes, penetrates into the ground-based inversion layer.Peer reviewe

Infliximab for the treatment of intravenous immunoglobulin resistant Kawasaki disease complicated by coronary artery aneurysms: a case report

This case report describes an 8 year old boy with IVIG resistant Kawasaki disease complicated by severe bilateral coronary artery aneurysms successfully treated with infliximab, a monoclonal antibody against tumour necrosis factor alpha

Connecting research and practice in TESOL: a community of practice perspective

In line with a growing interest in teacher research engagement in second language education, this article is an attempt to shed light on teachers’ views on the relationship between teaching and practice. The data comprise semi-structured interviews with 20 teachers in England, examining their views about the divide between research and practice in their field, the reasons for the persistence of the divide between the two and their suggestions on how to bridge it. Wenger’s (1998) Community of Practice (CoP) is used as a conceptual framework to analyse and interpret the data. The analysis indicates that teacher experience, learning and ownership of knowledge emerging from participation in their CoP are key players in teachers’ professional practice and in the development of teacher identity. The participants construe the divide in the light of the differences they perceive between teaching and research as two different CoPs, and attribute the divide to the limited mutual engagement, absence of a joint enterprise and lack of a shared repertoire between them. Boundary encounters, institutionalised brokering and a more research-oriented teacher education provision are some of the suggestions for bringing the two communities together

Poloxomer 188 Has a Deleterious Effect on Dystrophic Skeletal Muscle Function

Duchenne muscular dystrophy (DMD) is an X-linked, fatal muscle wasting disease for which there is currently no cure and limited palliative treatments. Poloxomer 188 (P188) is a tri-block copolymer that has been proposed as a potential treatment for cardiomyopathy in DMD patients. Despite the reported beneficial effects of P188 on dystrophic cardiac muscle function, the effects of P188 on dystrophic skeletal muscle function are relatively unknown. Mdx mice were injected intraperitoneally with 460 mg/kg or 30 mg/kg P188 dissolved in saline, or saline alone (control). The effect of single-dose and 2-week daily treatment was assessed using a muscle function test on the Tibialis Anterior (TA) muscle in situ in anaesthetised mice. The test comprises a warm up, measurement of the force-frequency relationship and a series of eccentric contractions with a 10% stretch that have previously been shown to cause a drop in maximum force in mdx mice. After 2 weeks of P188 treatment at either 30 or 460 mg/kg/day the drop in maximum force produced following eccentric contractions was significantly greater than that seen in saline treated control mice (P = 0.0001). Two week P188 treatment at either dose did not significantly change the force-frequency relationship or maximum isometric specific force produced by the TA muscle. In conclusion P188 treatment increases susceptibility to contraction-induced injury following eccentric contractions in dystrophic skeletal muscle and hence its suitability as a potential therapeutic for DMD should be reconsidered

Kawasaki disease: a review with emphasis on cardiovascular complications

Kawasaki disease (KD) is an acute systemic vasculitis that is currently the leading cause of acquired heart disease in childhood in the United States. Cardiovascular complications are the major cause of morbidity, are responsible for virtually all deaths from KD and should be evaluated as soon as possible after the acute phase to establish the baseline status, in order to predict disease progression and determine adequate treatment. In selected patients, electrocardiography (ECG)-gated cardiac computed tomography (CT) and magnetic resonance (MR) imaging are valuable non-invasive techniques that can be used to help diagnose the cardiovascular complications associated with KD. In this article, we review the epidemiology, aetiology and pathogenesis, histopathology, clinical features, cardiovascular complications and imaging, focusing on the role of cardiac CT and MR on the initial assessment and follow-up of the cardiovascular complications of KD

Acute Kawasaki Disease: Not Just for Kids

Kawasaki Disease is a small-to-medium-vessel vasculitis that preferentially affects children. Kawasaki Disease can occur in adults, but the presentation may differ from that observed in children. Typical findings in both adults and children include fever, conjunctivitis, pharyngitis, and skin erythema progressing to a desquamating rash on the palms and soles. Adults more frequently present with cervical adenopathy (93% of adults vs. 15% of children), hepatitis (65% vs. 10%), and arthralgia (61% vs. 24–38%). In contrast, adults are less frequently affected by meningitis (10% vs. 34%), thrombocytosis (55% vs. 100%), and coronary artery aneurysms (5% vs. 18–25%). We report a case of acute Kawasaki Disease in a 24-year-old man who presented with rash, fever, and arthritis. He was successfully treated with high-dose aspirin and intravenous immunoglobulin (IVIG). Our case highlights the importance of considering Kawasaki Disease in adults presenting with symptoms commonly encountered in a general medical practice

Association of Kawasaki disease with tropospheric wind patterns

The causal agent of Kawasaki disease (KD) remains unknown after more than 40 years of intensive research. The number of cases continues to rise in many parts of the world and KD is the most common cause of acquired heart disease in childhood in developed countries. Analyses of the three major KD epidemics in Japan, major non-epidemic interannual fluctuations of KD cases in Japan and San Diego, and the seasonal variation of KD in Japan, Hawaii, and San Diego, reveals a consistent pattern wherein KD cases are often linked to large-scale wind currents originating in central Asia and traversing the north Pacific. Results suggest that the environmental trigger for KD could be wind-borne. Efforts to isolate the causative agent of KD should focus on the microbiology of aerosols