The receptor-binding domain of pseudorabies virus glycoprotein gC is composed of multiple discrete units that are functionally redundant

Many herpesviruses attach to cells in a two-step process, using the glycoprotein gC family of homologs to bind the primary receptor, heparan sulfate (HS) proteoglycan, and glycoprotein gD homologs to bind an unknown secondary receptor. We have previously shown by deletion analysis that the amino-terminal one-third of gC from pseudorabies virus (PRV), a swine herpesvirus, includes at least the principal HS receptor-binding domain. This portion of PRV gC contains three discrete clusters of basic residues that exactly or nearly match proposed consensus sequences for heparin-binding domains (HBDs); four additional potential HBDs lie in the distal two-thirds of the glycoprotein. We now specifically implicate each of the three amino-terminal HBDs in virus attachment. Mutational analysis demonstrated that any one of the three HBDs could mediate efficient virus infectivity; HS-dependent PRV attachment to cells was eliminated only after all three amino-terminal HBDs were altered. Furthermore, the binding dysfunction was due to a disruption of the specific HBDs and not to total charge loss. Thus, unlike previously described viral receptor-binding domains, the PRV gC receptor-binding domain is composed of multiple, discrete units that can function independently of one another. These units may function redundantly either to increase binding affinity or perhaps to effectively increase the virus's host range.     

Evaluation of a collective kitchens program: using the Population Health Promotion Model.

To evaluate the impact of the Calgary Health Region Collective Kitchen Program on various Population Health Promotion Model health determinants, data were collected through mail-in questionnaires that examined the members' (n=331) and coordinators' (n=58) perspectives of the program. Seventy-nine members (24%) and 26 coordinators (45%) were included in the study. Three incomplete questionnaires (from prenatal program members) were discarded. Sixty-one percent of members who reported income level and family size (n=61) had incomes below the low-income cut-off. Fifty-eight members (73%) reported improvements in their lives because of the program. Sixty-four members (81%) perceived they learned to feed their families healthier foods. The members reported their fruit and vegetable consumption before and since joining a collective kitchen, and the proportion of those consuming at least five fruit and vegetable servings a day rose from 29% to 47%. The most common reasons for joining this program concerned social interactions and support. Over 90% of the coordinators perceived that they were competent to coordinate a kitchen. The results indicate that the collective kitchens program addresses several health determinants, and may increase members' capacity to attain food security and to achieve improved nutritional health.     

Evaluating non-speech sound visualizations for the deaf

Sounds such as co-workers chatting nearby or a dripping faucet help us maintain awareness of and respond to our surroundings. Without a tool that communicates ambient sounds in a non-auditory manner, maintaining this awareness is difficult for people who are deaf. We present an iterative investigation of peripheral, visual displays of ambient sounds. Our major contributions are: (1) a rich understanding of what ambient sounds are useful to people who are deaf, (2) a set of visual and functional requirements for a peripheral sound display, based on feedback from people who are deaf, (3) lab-based evaluations investigating the characteristics of four prototypes, and (4) a set of design guidelines for successful ambient audio displays, based on a comparison of four implemented prototypes and user feedback. Our work provides valuable information about the sound awareness needs of the deaf and can help to inform further design of such applications.     

The phosphorylation of eukaryotic initiation factor eIF4E in response to phorbol esters, cell stresses, and cytokines is mediated by distinct MAP kinase pathways

Initiation factor eIF4E binds to the 5'-cap of eukaryotic mRNAs and plays a key role in the mechanism and regulation of translation. It may be regulated through its own phosphorylation and through inhibitory binding proteins (4E-BPs), which modulate its availability for initiation complex assembly. eIF4E phosphorylation is enhanced by phorbol esters. We show, using specific inhibitors, that this involves both the p38 mitogen-activated protein (MAP) kinase and Erk signaling pathways. Cell stresses such as arsenite and anisomycin and the cytokines tumor necrosis factor-alpha and interleukin-1beta also cause increased phosphorylation of eIF4E, which is abolished by the specific p38 MAP kinase inhibitor, SB203580. These changes in eIF4E phosphorylation parallel the activity of the eIF4E kinase, Mnk1. However other stresses such as heat shock, sorbitol, and H2O2, which also stimulate p38 MAP kinase and increase Mnk1 activity, do not increase phosphorylation of eIF4E. The latter stresses increase the binding of eIF4E to 4E-BP1, and we show that this blocks the phosphorylation of eIF4E by Mnk1 in vitro, which may explain the absence of an increase in eIF4E phosphorylation under these conditions.     

Speaking on the record: A theory of composition

This article explores ways in which some of what has been achieved through the use of writing can be achieved in the domain of the oral and ways in which the use of oral forms might be revalued as literate composition. Toward these ends, I introduce a new word and practice to provide a counterpart to writing in a spoken modality: Spriting in its general form is the activity of speaking “on the record” that yields a technologically supported representation of oral speech with essential properties of writing, such as permanence, and offers possibilities of editing, indexing, and scanning but without the difficult transition to a deeply different form of representation such as writing itself. Literacy is defined here as the sophisticated structures and elements that characterize linguistic stories and ideas, largely but not completely independent of the material ways in which these structures are realized. That is, this article distinguishes literacy from letteracy, which refers to textual decoding and encoding abilities, and I introduce another new term, prosodacy, which refers to oral decoding and encoding abilities. Based on outcomes from two years of exploratory empirical work with adult learners and young children using novel spriting software I designed and developed for them, I discuss four areas in which spriting-like activities and technology can have a positive impact on literacy development and education.     

Opinions of consultant obstetricians in the Northern Region regarding the provision of intrapartum care by GPs

Consultants with experience of GP intrapartum care believe it is safe for the low-risk woman. However, GPs are perceived as lacking enthusiasm and as having varying degrees of obstetric expertise. Consultants feel that women themselves are not requesting more intrapartum care from GPs.     

Atherogenesis and the homocysteine-folate-cobalamin triad: do we need standardized analyses?

BACKGROUND: Bioscientists, physicians and nutritionists are newly interested in the homocysteine-folate-cobalamin triad, in part because homocysteine may be important both in atherogenesis and thrombogenesis. Homocysteine imbalance may be an early marker for cobalamin disorders because cobalamin is a cofactor in remethylation of homocysteine to methionine. METHODS: In 139 men and 32 women of similar mean age of 65 years, we measured markers which have been cited as risk for atherosclerosis: serum homocysteine, folate, total cobalamin, holotranscobalamin I and II, (TCI and TCII), total serum cholesterol (SCHOL), high density lipoprotein cholesterol (HDLC), triglycerides (STG) as well as red blood cell (RBC) folate, food records and body composition by whole body counting of potassium-forty (40K). RESULTS: Statistical relationships among the data showed healthy women had lower mean serum homocysteine and their mean RBC folate and TCI and TCII were higher than men. Eighty-three subjects had TCII much lower than 60 pg/ml (subnormal), yet only 11 of these men and two women had total cobalamin < 200 pg/ml (abnormal). Fifty-two subjects with serum homocysteine greater than 17.5 nmol/ml had TCII less than 60 pg/ml, suggesting serum homocysteine may be a marker for early cobalamin negative balance. None of the subjects in the study had serum folate below abnormal values, i.e., less than 1.6 mg/ml. All subjects had RBC folate within normal range. Serum homocysteine showed inverse relationship with RBC folate and serum total cobalamin, TCI and TCII. CONCLUSIONS: 1) importance of using serum holotranscobalamin TCI and TCII as markers of cobalamin deficiency, 2) necessity to use documented quantitative components of dietary intake if strong comparisons are to be made among quantitative values of serum or plasma homocysteine, folate, cobalamin, and nutrients in food intake.     

Transport coefficients of AlGaN/GaN heterostructures

We have experimentally determined the effective mass (m*) of GaN, the classical (τ _c), and quantum (τ _q) scattering times for a two-dimensional electron gas residing at the interface of an AlGaN/GaN heterostructure, using the Shubnikovde Haas effect. The ratio of the two scattering times, τ _c/τ _q, suggests that, at low temperatures, the scattering mechanism limiting the mobility is due to remote ionized impurities located in AlGaN. This study should provide sample growers with information useful for improving the quality of the nitride heterostuctures.     

Activation of human dendritic cells following infection with Mycobacterium tuberculosis

Dendritic cells (DC) play an essential role in the initiation of primary T cell responses to foreign Ag. It is likely that these potent APC are critical in the initiation of immune responses to pathogens, such as bacteria or parasites. However, little is known about the interaction of these important APC with pathogens. To address this issue, the interaction of the bacterium Mycobacterium tuberculosis with human DC was studied. DC generated from human peripheral blood by short term culture in medium containing recombinant human cytokines granulocyte-macrophage-CSF and IL-4 were capable of phagocytosing M. tuberculosis. Infection of DC with live M. tuberculosis bacilli resulted in increased APC surface expression of the costimulatory molecules CD54, CD40, and B7.1, as well as MHC class I molecules. In addition, infected DC secreted elevated levels of inflammatory cytokines, including TNF-alpha, IL-1, and IL-12. M. tuberculosis-infected human monocytes also secreted inflammatory cytokines, but exhibited no enhancement of costimulatory or MHC class I molecule expression. These data indicate that infection with M. tuberculosis results in the direct activation and maturation of these DC. In vivo, such activation may facilitate migration to the lymph nodes, and enhance presentation of Ag to T cells, thereby facilitating the induction of the immune response against this pathogen.