Crystal structure of the MurG:UDP-GlcNAc complex reveals common structural principles of a superfamily of glycosyltransferases

MurG is an essential glycosyltransferase that forms the glycosidic linkage between N-acetyl muramyl pentapeptide and N-acetyl glucosamine in the biosynthesis of the bacterial cell wall. This enzyme is a member of a major superfamily of NDP-glycosyltransferases for which no x-ray structures containing intact substrates have been reported. Here we present the 2.5-A crystal structure of Escherichia coli MurG in complex with its donor substrate, UDP-GlcNAc. Combined with genomic analysis of other superfamily members and site-specific mutagenesis of E. coli MurG, this structure sheds light on the molecular basis for both donor and acceptor selectivity for the superfamily. This structural analysis suggests that it will be possible to evolve new glycosyltransferases from prototypical superfamily members by varying two key loops while maintaining the overall architecture of the family and preserving key residues.     

Understanding and enhancing adherence in adults with diabetes

This article reviews selected recent literature on adult diabetes patient-centered adherence to diabetes care recommendations. We describe more fully a limited number of articles that have particular lessons for diabetes clinicians and researchers. Each article was reviewed for methodology, adherence measures, and types of outcome data collected. This process produced a few studies evaluating an intervention to promote adherence, subsequent targeted behavior changes, as well as health outcomes. Using a standard measure of diabetes self-care adherence over multiple studies may be an important way to compare results across diverse interventions. Advances in research designs and measures show promising results for understanding and enhancing adherence in adults coping with diabetes. Much more behavioral research in diabetes is needed in order to significantly improve the health and quality of life in this population.     

The regulation and consequences of immune-mediated cell death in atheromatous diseases

Atheromatous diseases are lipid and cell-rich vascular disorders that include coronary artery disease (CAD), transplant vascular disease (TVD), and restenosis. Considering the inflammatory nature of these diseases, cytotoxic immune mechanisms such as the FasL and granzyme/perforin pathways most likely play important roles in the development and remodeling of many lesions. Furthermore, although the contributions of immune responses to each disease vary, the correspondent localization of certain mediators and effectors suggests that they may contribute to a spectrum of atheromatous diseases. In this review, the contribution of immune cell-mediated cell death in the onset and pathogenesis of CAD and TVD is examined.     

Efficient induction of CD8 T-associated immune protection by vaccination with mRNA transfected dendritic cells

Dendritic cells are excellent targets for antigen-specific immune intervention. Here we attempted to introduce a CD8 T cell-dependent epitope into dendritic cells for presentation on major histocompatibility complex class I and induction of immunity. Murine bone-marrow-derived dendritic cells were subjected to electroporation with mRNA transcribed in vitro from a plasmid encoding lymphocytic choriomeningitis virus glycoprotein or enhanced green fluorescent protein under the control of a T7 promotor. The transfection efficiency of dendritic cells was 22 to 40%. Maturation was not inhibited by the electroporation. Dendritic cells electroporated with the appropriate antigen induced cell number-dependent in vitro proliferation in CD8 T cells expressing a transgenic receptor recognizing the 33 to 41 sequence of lymphocytic choriomeningitis virus glycoprotein in association with H-2Kb/Db, indicating correct synthesis, processing, and presentation of the epitope. Naive C57BL/6 mice vaccinated with electroporated dendritic cells and challenged with lymphocytic choriomeningitis virus were protected. Vaccination induced epitope-specific T cells as assessed by tetramer staining in blood and spleen. These results indicate that targeting dendritic cells with antigen-encoding mRNA can induce antigen-specific CD8 T cell responses as well as protective anti-viral immunity in vivo. Targeting dendritic cells with antigen-encoding mRNA may find wider application for immune intervention in disorders such as autoimmunity and cancer.     

Human masticatory muscle forces during static biting

Muscle forces determine joint loads, but the objectives governing the mix of muscle forces involved are unknown. This study tested the hypothesis that masticatory muscle forces exerted during static biting are consistent with objectives of minimization of joint loads (MJL) or muscle effort (MME). To do this, we compared numerical model predictions with data measured from six subjects. Biting tasks which produced moments on molar and incisor teeth were modeled based on MJL or MME. The slope of predicted vs. electromyographic (EMG) data for an individual was compared with a perfect match slope of 1.00. Predictions based on MME matched best with EMG activity for molar biting (slopes, 0.89-1.16). Predictions from either or both models matched EMG results for incisor biting (best-match slopes, 0.95-1.07). Muscle forces during isometric biting appear to be consistent with objectives of MJL or MME, depending on the individual, biting location, and moment.     

The silent dragon--hepatitis C

The hepatitis C virus is the most common bloodborne pathogen in the world. A disease with no cure or vaccine, it kills between 8,000 and 10,000 people annually in the United States. Only recently have experts begun to understand the virus, its natural progression, and how it differs from other hepatitis viruses. Most transmission is a result of direct percutaneous exposure, and the disease is more common among minority groups. Alpha interferon and ribavirin are the currently approved first-line treatment medications. Evolving medication therapies, full liver transplantation from nonliving donors, and split liver transplantation from living donors hold promise for the 170 million people who are thought to carry the virus. AORN J17 (June 2003) 1191-1204.     

Pulmonary strongyloidiasis presenting as chronic bronchitis leading to interlobular septal fibrosis and cured by treatment

Two patients presented with long-standing chronic bronchitis and exertional dyspnoea of 5 and 3 months' duration, respectively, and had interlobular septal fibrosis on chest high resolution CT. In the past both had lived in areas in which Strongyloides stercoralis was known to be endemic. Serological tests confirmed the diagnosis of pulmonary strongyloidiasis, and both patients were treated with anti-helminthic medications, including albendazole and ivermectin. Following this there was complete resolution of both symptomatic and radiological manifestations of their disease. An awareness of the possibility of Strongyloides infection presenting with respiratory symptoms in patients exposed to this parasite is important in the management of such patients.     

Assessing depression in the cardiac patient. When is the appropriate time to assess depression in the patient undergoing coronary revascularization?

Depression is a well-established risk factor for cardiovascular disease-related morbidity and mortality. It is common to screen for depression in patients undergoing coronary revascularization prior to revascularization; however, the validity of this assessment is unclear as some patients may experience transient, reactive depression rather than persistent depression. The authors evaluated whether an initial or 1-month postprocedure screen was optimal for identifying consistently depressed patients. Depression at 1-month postprocedure was a stronger predictor of depression at months 2 to 6 than baseline depression. After adjusting potential confounding variables, there was a much stronger relationship between 1-month and 6-month depression status (OR = 28.7 if depressed at 1 month, p < .001) than between baseline and 6-month depression status (OR = 6.5 if depressed at baseline, p < .001). Screening for depression at the time of revascularization is not as predictive of depression at 6 months as it is 1 month postprocedure.