SELECTED METABOLIC AND HEMODYNAMIC RESPONSES TO REPEATED STEADY-STATE BOUTS OF INDOOR CYCLING, UTILISING MARGINAL INCREASES IN MECHANICAL POWER OUTPUT: CONSIDERATIONS FOR THE EVALUATION OF INDIVIDUAL COMPETITIVE ROAD CYCLISTS USING A PORTABLE ON-BICYCLE C

Introduction It has been demonstrated by Sanderson, Cavanaugh et a1. (1985), and the authors, (1987 , that impul e and average net power distributions (W) generated about the pedal spindle and crank arms, vary with individual cyclists, either creating a mechanically desirable circular cycling pattern where the impulse is 'smoothed', or a 'butterfly' distribution indicating unequal force distribution(s throughout each pedaling cycle. Based on research performed indoors by Cavanaugh (1985), and Anderson (1986), and this group outdoors at the United States Cycling Federation Camp in Colorado in 1987 and 1988, it appears that techniques employed to reduce the counter-propulsive tangential crank arm forces could possible improve average net power magnitudes produced by individual elite cyclists outdoors during competition, and thus improve their overall time(s) recorded for selected events

Therapeutic inflammatory monocyte modulation using immune-modifying microparticles

Inflammatory monocyte-derived effector cells play an important role in the pathogenesis of numerous inflammatory diseases. However, no treatment option exists that is capable of modulating these cells specifically. We show that infused negatively charged, immune-modifying microparticles (IMPs), derived from polystyrene, microdiamonds, or biodegradable poly(lactic-co-glycolic) acid, were taken up by inflammatory monocytes, in an opsonin-independent fashion, via the macrophage receptor with collagenous structure (MARCO). Subsequently, these monocytes no longer trafficked to sites of inflammation; rather, IMP infusion caused their sequestration in the spleen through apoptotic cell clearance mechanisms and, ultimately, caspase-3-mediated apoptosis. Administration of IMPs in mouse models of myocardial infarction, experimental autoimmune encephalomyelitis, dextran sodium sulfate-induced colitis, thioglycollate- induced peritonitis, and lethal flavivirus encephalitis markedly reduced monocyte accumulation at inflammatory foci, reduced disease symptoms, and promoted tissue repair. Together, these data highlight the intricate interplay between scavenger receptors, the spleen, and inflammatory monocyte function and support the translation of IMPs for therapeutic use in diseases caused or potentiated by inflammatory monocytes.15 page(s

Protection of mice deficient in mature B cells from West Nile virus infection by passive and active immunization.

B cell activating factor receptor (BAFFR)-/- mice have a profound reduction in mature B cells, but unlike μMT mice, they have normal numbers of newly formed, immature B cells. Using a West Nile virus (WNV) challenge model that requires antibodies (Abs) for protection, we found that unlike wild-type (WT) mice, BAFFR-/- mice were highly susceptible to WNV and succumbed to infection within 8 to 12 days after subcutaneous virus challenge. Although mature B cells were required to protect against lethal infection, infected BAFFR-/- mice had reduced WNV E-specific IgG responses and neutralizing Abs. Passive transfer of immune sera from previously infected WT mice rescued BAFFR-/- and fully B cell-deficient μMT mice, but unlike μMT mice that died around 30 days post-infection, BAFFR-/- mice survived, developed WNV-specific IgG Abs and overcame a second WNV challenge. Remarkably, protective immunity could be induced in mature B cell-deficient mice. Administration of a WNV E-anti-CD180 conjugate vaccine 30 days prior to WNV infection induced Ab responses that protected against lethal infection in BAFFR-/- mice but not in μMT mice. Thus, the immature B cells present in BAFFR-/- and not μMT mice contribute to protective antiviral immunity. A CD180-based vaccine may promote immunity in immunocompromised individuals

Nitric oxide controls an inflammatory-like Ly6ChiPDCA1+ DC subset that regulates Th1 immune responses

NO produced by DCs suppresses a Ly6ChiPDCA1+ DC subpopulation resembling inflammatory DCs, highly responsive to TLR stimulation and capable of initiating strong Th1 immune responses