Dendritic cell-dependent inhibition of B cell proliferation requires CD22

Recent studies have shown that dendritic cells (DCs) regulate B cell functions. In this study, we report that bone marrow (BM)-derived immature DCs, but not mature DCs, can inhibit BCR-induced proliferation of B cells in a contact-dependent manner. This inhibition is overcome by treatment with BAFF and is dependent on the BCR coreceptor CD22; however, it is not dependent on expression of the CD22 glycan ligand(s) produced by ST6Gal-I sialyltransferase. We found that a second CD22 ligand (CD22L) is expressed on CD11c(+) splenic and BM-derived DCs, which does not contain ST6Gal-I-generated sialic acids and which, unlike the B cell-associated CD22L, is resistant to neuraminidase treatment and sodium metaperiodate oxidation. Examination of splenic and BM B cell subsets in CD22 and ST6Gal-I knockout mice revealed that ST6Gal-I-generated B cell CD22L plays a role in splenic B cell development, whereas the maintenance of long-lived mature BM B cells depends only on CD22 and not on alpha2,6-sialic acids produced by ST6Gal-I. We propose that the two distinct CD22L have different functions. The alpha2,6-sialic acid-containing glycoprotein is important for splenic B cell subset development, whereas the DC-associated ST6Gal-I-independent CD22L may be required for the maintenance of long-lived mature B cells in the BM.     

Decorin regulates endothelial cell motility on collagen I through activation of insulin-like growth factor I receptor and modulation of alpha2beta1 integrin activity

The proteoglycan decorin is expressed by sprouting but not quiescent endothelial cells, and angiogenesis is dysregulated in its absence. Previously, we have shown that decorin core protein can bind to and activate insulin-like growth factor-I receptor (IGF-IR) in endothelial cells. In this study, we show that decorin promotes alpha2beta1 integrin-dependent endothelial cell adhesion and migration on fibrillar collagen type I. We provide evidence that decorin modulates cell-matrix interaction in this context by stimulating cytoskeletal and focal adhesion reorganization through activation of the IGF-IR and the small GTPase Rac. Further, the glycosaminoglycan moiety of decorin interacts with alpha2beta1, but not alpha1beta1 integrin, at a site distinct from the collagen I-binding A-domain, to allosterically modulate collagen I-binding activity of the integrin. We propose that induction of decorin expression in angiogenic, as opposed to quiescent, endothelial cells promotes a motile phenotype in an interstitial collagen I-rich environment by both signaling through IGF-IR and influencing alpha2beta1 integrin activity.     

Quantifying species composition in root mixtures using two methods: near-infrared reflectance spectroscopy and plant wax markers

Understanding of plant interactions is greatly limited by our ability to identify and quantify roots belonging to different species. We proposed and compared two methods for estimating the root biomass proportion of each species in artificial mixtures: near-infrared reflectance spectroscopy (NIRS) and plant wax markers. Two sets of artificial root mixtures composed of two or three herbaceous species were prepared. The proportion of root material of each species in mixtures was estimated from NIRS spectral data (i) and the concentration patterns of n-alkanes (ii), n-alcohols (iii), and n-alkanes +n-alcohols combined (iv). For each data set, calibration equations were developed using multivariate statistical models. The botanical composition of root mixtures was predicted well for all the species considered. The accuracy varied slightly among methods: alkanes < alcohols = alkanes + alcohols < NIRS. Correlation coefficients between predicted and actual root proportions ranged from 0.89 to 0.99 for alkanes + alcohols predictions and from 0.97 to 0.99 for NIRS predictions. These two methods provide promising potential for understanding allocation patterns and competitive interactions.     

Fate of carbon in upland grassland subjected to liming using in situ 13CO2 pulse-labelling

Knowledge of the fate of plant assimilate is fundamental to our understanding of the terrestrial carbon cycle, particularly if we are to predict the effects of changes in climate and land management practices on agroecosystems. Pulse-labelling experiments have revealed that some of the carbon fixed by plants is rapidly allocated below-ground and released back into the atmosphere in respiration. However, little is known about the fate of plant assimilate, not accounted for in soil respiration, in the longer term and how current management practices such as liming may affect this. In southern Scotland, UK, limed and unlimed acid grassland plots were pulse-labelled with ¹³CO₂ and the turnover of ¹³C was studied one and two years after labelling. In this study the amount of labelled carbon remaining in shoot, root, and bulk soil pools, and how this differed between limed and unlimed plots was investigated. The results indicated that plant-root turnover was faster, and plants invested less nitrogen in the roots in the limed plots than in the unlimed plots. More ¹³C remained in the soil in the unlimed treatment compared to the limed treatment, but the main difference was found in the particulate organic matter, which turned over relatively quickly. The label was still above natural abundance one and two years after labelling in many cases. In addition, the results demonstrate that a ¹³CO₂ pulse-label administered for only a few hours can be a useful approach for investigating turnover of carbon several years later.     

Multi-target-directed coumarin derivatives: hAChE and BACE1 inhibitors as potential anti-Alzheimer compounds

The complex etiology of Alzheimer's disease (AD) prompts scientists to develop multifunctional compounds to combat causes and symptoms of such neurodegeneration. To this aim we designed, synthesized, and tested a series of compounds by introducing halophenylalkylamidic functions on the scaffold of AP2238, which is a dual binding site acetylcholinesterase inhibitor. The inhibitory activity was successfully extended to the beta-site amyloid precursor protein cleavage enzyme, leading to the discovery of a potent inhibitor of this enzyme (3) and affording multifunctional compounds (2, 6, 8) for the treatment of AD.     

Improving the quality of care via maintenance of certification and the Web: an early status report

Few question the need for continuous professional development throughout a physician's career, but rapid changes in health care are creating demand for physicians to acquire new knowledge, skills, and attitudes to implement quality improvement in clinical practice. The Internet and World Wide Web are technologies that have the potential to facilitate deep change in physician practice and lifelong learning. This paper describes how the American Board of Internal Medicine (ABIM) has utilized the Web and the Internet to engage physicians in the competencies of practice-based learning and improvement and systems-based practice. Specifically, we describe how the ABIM developed and implemented Web-based practice improvement modules (PIMs) to help physicians measure and improve their clinical practice.     

Body Dissatisfaction and Binge Eating in Obese Women: The Role of Restraint and Depression

Objective: This study examined the association between body dissatisfaction and binge eating, and the mediating role of restraint and depression among obese women. Research Methods and Procedures: Participants were obese women taking part in a cognitive-behavioral treatment program who completed self-report measures at baseline (n = 89) and post-treatment follow-up (n = 69). Results: At baseline, body dissatisfaction was strongly correlated with binge eating score. This was partly a direct effect and partly mediated by depression. No mediating effect of restraint was observed. Over the treatment period, a reduction in body dissatisfaction was associated with a reduction in binge-eating score. As in the cross-sectional data, there was evidence for mediation by change in depression with the greatest improvement in binge eating among those who became more restrained and less depressed. Discussion: These results suggest that it would be valuable to address psychological well-being, and especially body image, as part of the management of binge-eating behavior in obesity.