Association between monocyte Fcgamma subclass expression and acute coronary syndrome

BACKGROUND: Atherosclerosis lesions contain abundant immunoglobulins complexed with oxidized LDL (OxLDL) that are endocytosed by macrophages to form foam cells. While recent evidence supports a role for the macrophage scavenger receptor pathway in 75-90% of OxLDL uptake, in vitro evidence suggests another potential uptake pathway could involve autoantibody binding to IgG subclass-specific Fc receptors. OBJECTIVE AND METHODS: To address this mechanism from an in vivo standpoint, the objective of this study was to utilize flow cytometry to prospectively determine monocyte Fcgamma (FcR) I, II, and III receptor expression levels in patients with acute coronary syndrome (ACS, n = 48), diabetes mellitus (DM, n = 59), or neither (C, n = 88). RESULTS: Increased FcR I expression was found in the ACS versus DM groups [geometric mean, (95% CI) = 2.26 (2.07, 2.47) versus 1.83 (1.69, 1.98) (p < 0.001)] and versus C [1.90 (1.78, 2.03) (p = 0.005)]. Similar relationships were found with both the FcR II receptor [ACS mean = 4.57 (4.02, 5.19) versus DM 3.61 (3.22, 4.05) (p = 0.021) and versus C 3.86 (3.51, 4.24) (p = 0.09)] and FcR III receptor [ACS mean = 1.55 (1.44, 1.68) versus DM 1.36 (1.27, 1.46) (p = 0.038) and versus C 1.37 (1.30, 1.45) (p = 0.032)]. There was no difference between DM and C groups in FcR I, II or III expression. CONCLUSIONS: This in vivo data supports a possible second OxLDL-autoantibody macrophage uptake mechanism through an Fc receptor-mediated pathway and a potential relationship between atherosclerotic plaque macrophage FcR levels and ACS.     

Structure-activity relationship studies on 2-heteroaryl-4-arylimidazoles NPY5 receptor antagonists

A series of 2-heteroaryl-4-arylimidazoles with potent in vitro activity at the NPY5 receptor was developed. Introduction of electron-withdrawing groups on the 4-aryl ring led to a significant improvement of in vitro potency. Several analogues from this series had anorectic activity in rodent feeding models, but were also found to have undesired behavioral effects in spontaneous locomotor activity.     

The Arabidopsis transposable element Tag1 is widely distributed among Arabidopsis ecotypes

Tag1 is an autonomous transposable element (3.3 kb in length) first identified as an insertion in the CHL1 (NRT1) gene of Arabidopsis thaliana. Tag1 has been found in the Landsberg erecta ecotype of A. thaliana but not in Columbia or WS. In this paper, 41 additional ecotypes were examined for the presence of Tag1. Using an internal Tag1 fragment as probe, we found that DNA from 19 of the 41 ecotypes strongly hybridized to Tag1. Almost all of the Tag1-containing ecotypes had only one or two copies of Tag1 per haploid genome, as determined by Southern blot analysis. The only exception, Bf-1 from Bretagny-sur-Orge, France, had four copies. Two ecotypes, Di-G and S96, gave identical Southern blot patterns to that of Landsberg erecta and were subsequently shown to contain Tag1 at the same two positions found in Landsberg erecta (loci designated as Tag1-2 and Tag1-3). Two other ecotypes, Ag-0 and Lo-1, had a Tag1 element located at Tag1-2 but not at Tag1-3. The distance between these two loci was determined to be 0.37 cM. Analysis of DNA from two related species, A. griffithiana and A. pumila, showed that both species contain sequences that hybridize to Tag1 and that could be amplified with an oligonucleotide specific to the terminal inverted repeats of Tag1. These results show that Tag1 and related elements are present, and may be useful for insertional mutagenesis, in many A. thaliana ecotypes and several Arabidopsis species.     

Albumin synthesis after intense intermittent exercise in human subjects

Yang, Roger C., Gary W. Mack, Robert R. Wolfe, and Ethan R. Nadel. Albumin synthesis after intense intermittent exercise inhuman subjects. J. Appl. Physiol.84(2): 584-592, 1998.We measured hepatic albumin synthesis infive volunteers (4 men and 1 woman) at 3 and 6 h after recovery fromintense exercise. A primed-constant infusion of a stable isotopictracer of phenylalanine was used to determine hepatic fractionalsynthetic rate (FSR) and absolute synthetic rate (ASR) of albumin fromthe enrichment of phenylalanine in albumin. The infusion of the stableisotope tracer began 2 h after upright exercise or upright rest.Albumin FSR and ASR were 6.39 ± 0.48%/day and 120 ± 9 mg · kg bodywt¹ · day¹,respectively, 3-6 h after recovery from exercise; the FSR and ASRon the time control study day were 5.94 ± 0.47%/day and 104 ± 9 mg · kg bodywt¹ · day¹,respectively. The 6 and 16% increases(P < 0.05) in FSR and ASR afterexercise were associated with an elevated plasma albumin content at 5 and 6 h of recovery (P < 0.05), anincreased total protein content throughout recovery(P < 0.05), and a negative freewater clearance (P < 0.05) at 2, 3, and 6.5 h of recovery compared with baseline values; these variableswere unchanged from their baselines on the time control study day.Increased albumin content and reduced free water clearance contributeto a retention of fluid within the circulation after intense exercise. The measured increase in albumin synthesis could not account for theentire increase in albumin content at 6 h of recovery from exercise.However, we estimate that if the increased activity was maintained forthe next 18 h, it could account for the expected increase in albumincontent at 24 h of recovery.

     

Representations of Nature on the Mongolian Steppe: An Investigation of Scientific Knowledge Construction

Extensive land degradation across the Mongolian steppe has prompted a variety of multinational and multidisciplinary research projects over recent years. The situation provides an important opportunity to investigate and illuminate some of the international, national, and local dimensions of scientific practice that critically condition the production of environmental knowledge. In this article I juxtapose the competing knowledge bases and assumptions of various relevant groups (including natural vs. social scientists, nationalist Chinese vs. ethnic Mongolians, and urban intellectuals vs. indigenous herders) to develop the argument that multiple ideological and institutional boundaries work together to circumscribe scientific inquiry and data collection. The situated construction of knowledge undermines prospects for improving incremental objectivity and impedes more comprehensive understanding of serious environmental problems. [Chinese grasslands, land degradation, indigenous knowledge, sociology of science, interdisciplinary research]     

Autoantibodies to components of the mitotic apparatus

Autoantibodies directed to a variety of cellular antigens and organelles are a feature of autoimmune diseases. They have proven useful in a clinical setting to establish diagnosis, estimate prognosis, follow disease progression, alter therapy, and initiate new investigations. Cellular and molecular biologists have used autoantibodies as probes to identify molecules involved in key cellular processes. One of the most interesting sets of autoantibodies are those that target antigens within the mitotic apparatus (MA). The MA includes chromosomes, spindle microtubules and centrosomes. The identification, localization, function, and clinical relevance of MA autoantigens is the focus of this review. Abbreviations: ATP – adenosine triphosphate; CENP – centromere protein; CREST – calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, telangiectasia; HMG – high mobility group; IB – intercellular bridge; IIF – indirect immunofluorescence; MAPs – microtubule associated proteins; NuMA – nuclear mitotic apparatus; NOR – nucleolar organizer; PBC – primary biliary cirrhosis; PM – polymyositis; Pol I, II, III – RNA polymerases; RA-rheumatoid arthritis; SLE – systemic lupus erythematosus; SS – Sjögren's syndrome; SSc – systemic sclerosis; topo – topoisomerase.     

Identification of Genes and Proteins Necessary for Catabolism of Acyclic Terpenes and Leucine/Isovalerate in Pseudomonas aeruginosa

Geranyl-coenzyme A (CoA)-carboxylase (GCase; AtuC/AtuF) and methylcrotonyl-CoA-carboxylase (MCase; LiuB/LiuD) are characteristic enzymes of the catabolic pathway of acyclic terpenes (citronellol and geraniol) and of saturated methyl-branched compounds, such as leucine or isovalerate, respectively. Proteins encoded by two gene clusters (atuABCDEFGH and liuRABCDE) of Pseudomonas aeruginosa PAO1 were essential for acyclic terpene utilization (Atu) and for leucine and isovalerate utilization (Liu), respectively, as revealed by phenotype analysis of 10 insertion mutants, two-dimensional gel electrophoresis, determination of GCase and MCase activities, and Western blot analysis of wild-type and mutant strains. Analysis of the genome sequences of other pseudomonads (P. putida KT2440 and P. fluorescens Pf-5) revealed candidate genes for Liu proteins for both species and candidate genes for Atu proteins in P. fluorescens. This result concurred with the finding that P. fluorescens, but not P. putida, could grow on acyclic terpenes (citronellol and citronellate), while both species were able to utilize leucine and isovalerate. A regulatory gene, atuR, was identified upstream of atuABCDEFGH and negatively regulated expression of the atu gene cluster.     

The relationship between cell division and elongation during development of the nectar-yielding petal spur in Centranthus ruber (Valerianaceae)

Background and Aims Floral spurs are hollow, tubular outgrowths that typically conceal nectar. By their involvement in specialized pollinator interactions, spurs have ecological and evolutionary significance, often leading to speciation. Despite their importance and diversity in shape and size among angiosperm taxa, detailed investigations of the mechanism of spur development have been conducted only recently.Methods Initiation and growth of the nectar-yielding petal spur of Centranthus ruber ‘Snowcloud’ was investigated throughout seven stages, based on bud size and developmental events. The determination of the frequency of cell division, quantified for the first time in spurs, was conducted by confocal microscopy following 4'',6-diamidino-2-phenylindole (DAPI) staining of mitotic figures. Moreover, using scanning electron microscospy of the outer petal spur surface unobstructed by trichomes, morphometry of epidermal cells was determined throughout development in order to understand the ontogeny of this elongate, hollow tube.Key Results Spur growth from the corolla base initially included diffuse cell divisions identified among epidermal cells as the spur progressed through its early stages. However, cell divisions clearly diminished before a petal spur attained 30 % of its final length of 4·5 mm. Thereafter until anthesis, elongation of individual cells was primarily responsible for the spur’s own extension. Consequently, a prolonged period of anisotropy, wherein epidermal cells elongated almost uniformly in all regions along the petal spur’s longitudinal axis, contributed principally to the spur’s mature length.Conclusions This research demonstrates that anisotropic growth of epidermal cells – in the same orientation as spur elongation – chiefly explains petal spur extension in C. ruber. Representing the inaugural investigation of the cellular basis for spur ontogeny within the Euasterids II clade, this study complements the patterns in Aquilegia species (order Ranunculales, Eudicots) and Linaria vulgaris (order Lamiales, Euasterids I), thereby suggesting the existence of a common underlying mechanism for petal spur ontogeny in disparate dicot lineages.     

Analysis of Biochemical Equilibria Relevant to the Immune Response: Finding the Dissociation Constants

This paper analyzes the biochemical equilibria between bivalent receptors, homo-bifunctional ligands, monovalent inhibitors, and their complexes. Such reaction schemes arise in the immune response, where immunoglobulins (bivalent receptors) bind to pathogens or allergens. The equilibria may be described by an infinite system of algebraic equations, which accounts for complexes of arbitrary size n (n being the number of receptors present in the complex). The system can be reduced to just 3 algebraic equations for the concentrations of free (unbound) receptor, free ligand and free inhibitor. Concentrations of all other complexes can be written explicitly in terms of these variables. We analyze how concentrations of key (experimentally-measurable) quantities vary with system parameters. Such measured quantities can furnish important information about dissociation constants in the system, which are difficult to obtain by other means. We provide analytical expressions and suggest specific experiments that could be used to determine the dissociation constants.