The low affinity IgE receptor, Fc⑀RII (CD23), is both a positive and negative regulator of IgE synthesis. The proteinase activity that converts the membrane-bound form of CD23 into a soluble species (sCD23) is an important regulator of the function of CD23 and may be an important therapeutic target for the control of allergy and inflammation. We have characterized the catalytic activity of ADAM (a disintegrin and metalloproteinase) 10 toward human CD23. We found that ADAM10 efficiently catalyzes the cleavage of peptides derived from two distinct cleavage sites in the CD23 backbone. Tissue inhibitors of metalloproteinases and a specific prodomain-based inhibitor of ADAM10 perturb the release of endogenously produced CD23 from human leukemia cell lines as well as primary cultures of human B-cells. Expression of a mutant metalloproteinase-deficient construct of ADAM10 partially inhibited the production of sCD23. Similarly, small inhibitory RNA knockdown of ADAM10 partially inhibited CD23 release and resulted in the accumulation of the membrane-bound form of CD23 on the cells. ADAM10 contributes to CD23 shedding and thus could be considered a potential therapeutic target for the treatment of allergic disease.The low affinity IgE receptor Fc⑀RII (CD23) is a 46-kDa type II membrane protein that is expressed on B-cells and cells of the myeloid lineage (1). CD23 has multiple functions. It is both a positive and negative regulator of IgE synthesis (2). It facilitates IgE-dependent antigen presentation through its binding of IgEantigen complexes (3,4). Moreover, the release of proinflammmatory cytokines from macrophages is stimulated by CD23 binding to CD18/11b and /11c (complement receptors 3 and 4) (5-7).In humans, two isoforms of CD23 that differ by only seven amino acids in the short N-terminal cytoplasmic domain are observed (8). CD23a is expressed only on B-cells. Stimulation of B-cells and cells of the myeloid lineage with interleukin-4 (IL-4) 3 induces the expression of CD23b. The C-terminal extracellular domain consists of a globular fold that has homology to the C-type lectin family (9). This globular domain has been shown to contain two distinct binding sites, one for IgE and a second that recognizes CD21 (complement receptor 2) (10, 11). At the cell surface CD23 self-assembles to form homotrimers that have a higher affinity for IgE than the CD23 monomer (12, 13). The self-association is driven by a leucine zipper-like domain (14) that connects the N-terminal cytoplasmic and transmembrane domains to the C-terminal globular domain.Homotrimeric CD23 molecules exhibit a 15-nm ␣-helical coiled coil stalk that extends the globular C-terminal domains from the plasma membrane (15). Cleavage in the stalk region by a membrane-associated endoproteolytic activity generates soluble fragments of CD23 (sCD23) that possess apparent molecular masses of 37, 33, and 29 kDa (16). All three of these sCD23 fragments exist as homotrimers (15). Smaller fragments of CD23 (25 and 16 kDa) are known. However, these are thought to be form...

Approximately 1.2 million people in the United States live with HIV infection. Medical advancements have increased the life expectancy and this cohort is aging. HIV-positive individuals have a high incidence of frailty (~20%) characterized by depression and sedentary behavior. Exercise would be healthy, but due to the frail status of many HIV-positive individuals, conventional exercise is too taxing. The aim of this study was to evaluate the effectiveness and acceptability of a novel game-based training program (exergame) in ameliorating some aspects of frailty in HIVinfected individuals. Ten older people living with HIV were enrolled in an exergame intervention. Patients performed balance exercises such as weight shifting, ankle reaching, and obstacle crossing. Real-time visual/audio lower-extremity joint motion feedback was provided using wearable sensors to assist feedback and encourage subjects to accurately execute each exercise task. Patients trained twice a week for 45 min for 6 weeks. Changes in balance, gait, psychosocial parameters and quality of life parameters were assessed at the beginning, midterm and at conclusion of the training program. Ten patients completed the study and their results analyzed. The mean age was 57.2 ± 9.2 years. The participants showed a significant reduction in center of mass sway (78.2%, p = .045) during the semi-tandem balance stance with eyes closed and showed a significant increase in gait speed during a dual task motor-cognitive assessment (9.3%, p = .048) with an increase in stride velocity of over 0.1 m/sec. A significant reduction in reported pain occurred (43.5%, p = .041). Preliminary results of this exergame intervention show promise in improving balance and mobility while requiring older people living with HIV to be more active. The exergame can be continued at home and may have long term as well as short-term benefits for ameliorating frailty associated with HIV infection.

Injurious falls are a prevalent and serious problem faced by a growing elderly population. Accurate assessment and long-term monitoring of falls-risk could prove useful in the prevention of falls, by identifying those at risk of falling early so targeted intervention may be prescribed. Previous studies have demonstrated the feasibility of using triaxial accelerometry to estimate the risk of a person falling in the near future, by characterizing their movement as they execute a restricted sequence of predefined movements in an unsupervised environment, termed a directed routine. This study presents an improvement on this previously published system, which relied explicitly on time-domain features extracted from the accelerometry signals. The proposed improvement incorporates features derived from spectral analysis of the same accelerometry signals; in particular the harmonic ratios between signal harmonics and the fundamental frequency component are used. Employing these additional frequency-domain features, in combination with the previously reported time-domain features, an increase in the observed correlation with the clinical gold-standard risk of falling, from = 0:81 to = 0:96, was achieved when using manually annotated event segmentation markers; using an automated algorithm to segment the signals gave corresponding results of = 0:73 and = 0:99, before and after the inclusion of spectral features. The strong correlation with falls-risk observed in this preliminary study further supports the feasibility of using an unsupervised assessment of falls-risk in the home environment.

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