Cooperative Stimulation of Dendritic Cells by Cryptococcus neoformans Mannoproteins and CpG Oligodeoxynucleotides

While mannosylation targets antigens to mannose receptors on dendritic cells (DC), the resultant immune response is suboptimal. We hypothesized that the addition of toll-like receptor (TLR) ligands would enhance the DC response to mannosylated antigens. Cryptococcus neoformans mannoproteins (MP) synergized with CpG-containing oligodeoxynucleotides to stimulate enhanced production of proinflammatory cytokines and chemokines from murine conventional and plasmacytoid DC. Synergistic stimulation required the interaction of mannose residues on MP with the macrophage mannose receptor (MR), CD206. Moreover, synergy with MP was observed with other TLR ligands, including tripalmitoylated lipopeptide (Pam3CSK4), polyinosine-polycytidylic acid (pI:C), and imiquimod. Finally, CpG enhanced MP-specific MHC II-restricted CD4+ T-cell responses by a mechanism dependent upon DC expression of CD206 and TLR9. These data suggest a rationale for vaccination strategies that combine mannosylated antigens with TLR ligands and imply that immune responses to naturally mannosylated antigens on pathogens may be greatly augmented if TLR and MR are cooperatively stimulated.National Institutes of Health (RO1 AI25780, RO1 AI37532, K08 AI 53542

Treadmill exercise within lower body negative pressure protects leg lean tissue mass and extensor strength and endurance during bed rest.

Leg muscle mass and strength are decreased during reduced activity and non-weight-bearing conditions such as bed rest (BR) and spaceflight. Supine treadmill exercise within lower body negative pressure (LBNPEX) provides full-body weight loading during BR and may prevent muscle deconditioning. We hypothesized that a 40-min interval exercise protocol performed against LBNPEX 6 days week(-1) would attenuate losses in leg lean mass (LLM), strength, and endurance during 6° head-down tilt BR, with similar benefits for men and women. Fifteen pairs of healthy monozygous twins (8 male and 7 female pairs) completed 30 days of BR with one sibling of each twin pair assigned randomly as the non-exercise control (CON) and the other twin as the exercise subject (EX). Before and after BR, LLM and isokinetic leg strength and endurance were measured. Mean knee and ankle extensor and flexor strength and endurance and LLM decreased from pre- to post-BR in the male CON subjects (P < 0.01), but knee extensor strength and endurance, ankle extensor strength, and LLM were maintained in the male EX subjects. In contrast, no pre- to post-BR changes were significant in the female subjects, either CON or EX, likely due to their lower pre-BR values. Importantly, the LBNPEX countermeasure prevents or attenuates declines in LLM as well as extensor leg strength and endurance. Individuals who are stronger, have higher levels of muscular endurance, and/or have greater LLM are likely to experience greater losses during BR than those who are less fit

Introduction to the Special Issue: Terrorist Online Propaganda and Radicalization

This is the introduction to issue 1 of volume 40 of Studies in Conflict & Terrorism, which was a special issue focused on terrorist online propaganda and radicalisation

Carbon dioxide and water vapor production at rest and during exercise. A report on data collection for the Crew and Thermal Systems Division

The current environmental control device in the shuttle uses lithium hydroxide (LiOH) filter canisters to remove carbon dioxide (CO2) from the cabin air, requiring several bulky filter canisters that can only be used once and must be changed frequently. To alleviate a stowage problem and decrease launch weight, the Crew and Thermal Systems Division (CTSD) at the NASA Johnson Space Center has been researching a system to be used on future shuttle missions. This system uses two beds of solid amine material to absorb CO2 and water, later desorbing them to space vacuum. In this way the air scrubbing medium is regenerable and reusable. To identify the efficacy of this regenerable CO2 removal system (RCRS), CTSD began investigations in the shuttle mockup. The purpose of this investigation was to support the CTSD program by determining mean levels of carbon dioxide and water vapor production in normal, healthy males and females age-matched with the astronaut corps. Subjects' responses were measured at rest and during exercise at intensity levels equivalent to normal shuttle operation activities. The results were used to assess the adjustments made to RCRS and are reported as a reference for future investigations in shuttle environmental control

Exercise Thermoregulation Following 13 Days of Bed Rest

This investigation examined two potential mechanisms, altered skin blood flow (SBF) and sweating rate (SR) responses, that may be responsible for an elevated core temperature during exercise after bed rest (BR) and space flight. Seven healthy men (29 +/- 5 yr, 179.6 +/- 7.1 cm, 77.2 +/- 17.0kg; mean +/- SD) underwent 13 days of 6 deg head-down BR. Pre- and post-BR, subjects completed supine submaximal cycle ergometry (20 min at 40% and 20 min at 65% of pre-BR supine VO2pk) in a thermoneutral room (23.4 +/- 0.5 C, 56 +/- 8 %RH) during, heat production (VO2 ; indirect calorimetry), intestinal temperature (T(sub in) ; ingestible pill), SBF (laser Doppler velocimetry), local SR (dew point hygrometry), and total sweat loss (TSL; Delta body weight) were measured. Pre- and post- BR plasma volume (PV) was measured using I-125 dilution. After BR, T(sub in) was elevated at rest (36.99 +/- 0.14 vs. 37.30 +/- 0.06 C; p<_0.05) and at the end of exercise (37.57 +/- 0.13 vs. 37.90 +/- 0.09 C; P less than or equal to 0.05). However, the increase in T(sub in) from rest to the end of exercise was not different after BR (0.59 +/- 0.07 vs. 0.60 +/- 0.07 C). There was no difference in VO2 pre- to post-BR during rest (0.28 +/- 0.04 vs. 0.24 +/- 0.03 1 multiplied by min(exp -1) ) or 40% VO2pk (0.95 +/- 0.08 vs. 0.96 +/- 0.05 1 multiplied by min(exp -1)), but VO2 was significantly less at the end of the 65% VO2pk stage (1.53 +/- 0.09 vs. 1.42 +/- 0.11 1 multiplies by min(exp - 1); p less than or equal to 0.05). The percent change in SBF from rest to end of exercise was less after BR (211 +/- 53 vs. 96 +/- 31%; p less than or equal to 0.05), the threshold for the onset of SBF was greater (37.17 +/- 0.18vs. 37.51 +/- 0.17 C; p less than or equal to 0.05), and the slope of the response tended to be reduced (536 +/- 184 vs. 201 +/- 46 %A PC; p=0.08). TSL was not different after BR (0.42+0.06 vs. 0.44 +/- 0.08 kg), but the T in threshold at the onset of sweating was delayed significantly (37.06 +/- 0.1 1 vs. 37.34 +/- 0.06 C; p less than or equal to 0.05). However, the slope of SR was not changed after BR (3.45 +/- 1.22 vs. 2.58 +/- 0.71 mg multiplied by min(exp -1) multiplied by cm sq). PV was decreased by 11% after BR (3,259 +/- 177 vs. 2,894 +/- 138 ml; p less than or equal to 0.05). These results suggest that exercise SBF and SR responses after BR are altered, and heat production is unchanged or reduced, consistent with observations following space flight. The higher resting T(sub in) with a proportional increase in T(sub in) during exercise and delayed onset of SBF and SR suggest a centrally-mediated elevation in the thermoregulatory set point during microgravity exposure

Growing older with health and vitality: a nexus of physical activity, exercise and nutrition

The preservation of skeletal muscle mass and strength with advancing age are, we propose, critical aspects of ageing with health and vitality. Physical inactivity and poor nutrition are known to accelerate the gradual age-related decline in muscle mass and strength&mdash;sarcopenia&mdash;however, both are subject to modification. The main purpose of this review is to present the latest, evidence-based recommendations for physical activity and exercise, as well as diet for older adults that would help in preserving muscle mass and strength. We take the position that future physical activity/exercise guidelines need to make specific reference to resistance exercise and highlight the benefits of higher-intensity aerobic exercise training, alongside advocating older adults perform aerobic-based physical activity and household tasks (e.g.,carrying groceries). In terms of dietary recommendations, greater emphasis should be placed onoptimalrather thanminimumprotein intakes for older adults. Indeed, guidelines that endorse a daily protein intake of 1.2&ndash;1.5g/kg BM/day, which are levels 50&ndash;90% greater than the current protein Recommendation Dietary Allowance (0.8g/kg BM/day), are likely to help preserve muscle mass and strength and are safe for healthy older adults. Being cognisant of factors (e.g., reduced appetite) that may preclude older adults from increasing their total daily protein intake, we echo the viewpoint of other active researchers in advocating that protein recommendations for older adults be based on a per meal approach in order to maximize muscle protein synthesis (MPS). On this basis, assuming three meals are consumed daily, a protein dose of 0.4&ndash;0.5g/kg BM should be contained in each meal. We are beginning to understand ways in which to increase the utilization of ingested protein for the stimulation of MPS, namely by increasing the proportion of leucine contained in a given dose of protein, co-ingesting other nutrients (e.g., carbohydrate and fat or supplementation with n-3 polyunsaturated fatty acids) or being physically active prior to protein intake. Clearly, developing simple lifestyle interventions targeted at preserving muscle mass and strength with advancing age is crucial for facilitating longer, healthier lives into older age

Lower Limb Venous Compliance is Different Between Men and Women Following 60 Days of Head-Down Bedrest but Is Not Associated with Venoconstriction Dysfunction

Space flight-induced orthostatic intolerance (OI) is more prevalent in female (F) than male (M) astronauts. The mechanisms explaining the higher incidence of OI in F are unclear. We tested the hypothesis that venous compliance would be higher in F more than M following 6 deg head-down bed rest (BR) and would be associated with constrictor dysfunction. Using 2-D ultrasound, dorsal hand (DHV) and dorsal foot (DFV) vein compliances were determined in 24 subjects (10 F, 14 M; 35 +/- 1 yr) by measuring mean diameter response to increasing congestion pressure (0, 20, 30, and 40 mmHg) before and after 60 d of BR. Constrictor function was assessed by intravenous infusions of Ketorolac (KE; 1.5 ig/min) Phenylephrine (PE; 3160 ng/min), and L-NMMA (50 ig/min). The effects of BR between F vs. M and hand vs. foot were determined using mixed-effects linear regression. DFV but not DHV compliance changed in response to BR (p=0.012). Mean DFV increased significantly (0.903 mm to 1.191mm) in F but decreased in M (1.353 mm to 1.154 mm). DFV constrictor response was not different between sexes in response to BR (KE; p=0.647, PE; p=0.717, and L-NMMA; p=0.825). These BR data suggest that the higher incidence of OI in F astronauts may be related to increased lower limb venous compliance, contributing to blood pooling upon standing. Notably, changes to DFV compliance was not accompanied by impaired constrictor function