Exercise Prior to Pregnancy Enhances the Suppressive Function of Tregs in Offspring in a Mouse Model of Asthma

Regulatory T cells (Tregs) are a specialized subset of T cells responsible for peripheral tolerance and the mediation of inappropriate immune responses, such as those seen in asthma and allergy. Our lab is interested in the role that exercise plays in Treg responses. Using a mouse model of asthma, we have shown that exercise increases both the number and suppressive function of Tregs. It has been shown that exposing nursing dams to allergens confers protection against airway hyperresponsiveness and inflammation (trademarks of asthma) in pups exposed to the same allergen. In the present study, we wanted to determine if the exercise-induced increase in number and suppressive function of Tregs would be similarly passed from dams to their pups. Male pups from dams that were exercised prior to pregnancy (E) and pups from sedentary dams (S) were OVA-sensitized and challenged beginning at 4wks of age. Mice were sacrificed and tissues were taken for cell analysis. When co-cultured with CD4+CD25- responder cells, Tregs from E pups enhanced suppression of responder cells between 8.4-10% when compared to Tregs from S pups. While the number of Tregs from the mediastinal lymph node was not significantly different between E and S pups, there was a significant decrease in the number of CD4+ and CD8+ T cells in E pups from S pups (51.24% + 10.2 vs. 33.51% + 3.3 and 21.42% + 7.3 vs. 12.94% + 1.2, respectively), indicating a reduction in cellular infiltration and a muted immune response to allergen. Although not significant, there was a doubling of the number of Tregs in the thymus and bone marrow of E pups compared to S pups. This study indicates that exercise prior to pregnancy may confer some Treg-mediated protection against asthma

The Impact of Long Duration Spaceflight on Plasma Antimicrobial Proteins

Introduction: Robust immunity is essential for further human exploration of the solar system beyond Earth’s orbit. Spaceflight has been associated with immune perturbations and latent viral reactivation. However, logistical constraints have restricted many of these studies to simple pre- and post-flight measures, which are greatly confounded by the stressors associated with launch, landing and re-adaptation to the 1G environment. More in-flight immune data are required particularly during long-duration (3-6 months) spaceflight missions. This study examined the effects of spaceflight on plasma antimicrobial proteins (AMPs) and reactivation of latent herpesviruses. Methods: Plasma, saliva and urine samples were obtained from 20 crewmembers who spent ~6-months on the International Space Station (ISS). Samples were collected 180 and 45-days before launch, in-flight (at ‘early, ‘mid’ and ‘late’ stages of the mission), immediately upon return to Earth (R+0) and 30 days following return (R+30). Plasma LL-37, HNP 1-3 and lysozyme concentrations were determined by ELISA. Saliva Epstein-Barr virus (EBV), varicella zoster virus (VZV) and urine cytomegalovirus (CMV) DNA levels were quantified by Real-Time PCR. Maximum likelihood linear mixed models (LMM) were used to determine main effects of time (pre-flight, in-flight, R+0 and R+30), and EBV, VZV and CMV viral shedding status (shedding or non-shedding) on the concentration of each AMPs. Results: Lower plasma levels of LL-37 were found at R+0, compared to pre-flight, in-flight and R+30 (-80.6%, -80.2% and -73.49% respectively; p \u3c 0.01). Plasma HNP 1-3 levels were elevated above pre-flight level during flight, at R+0 and R+30 (+24%, +40% and +17% respectively; p \u3c 0.01). Only those crewmembers found to shed CMV had a significant reduction in plasma LL-37 at R+0 (p \u3c 0.05). Similarly, crewmembers found to shed VZV at R+0 had lower HNP 1-3 concentrations than crewmembers who did not shed VZV (-68.9%; p \u3c 0.01). Finally, only those crewmembers who shed EBV had increased plasma levels of HNP 1-3 at R+0 (p \u3c 0.01). Plasma lysozyme levels were unaffected by spaceflight or latent viral shedding. Conclusion: Long-duration spaceflight alters plasma LL-37 and HNP 1-3 levels and are linked to the reactivation of latent herpesviruses. The in-flight changes observed for HNP 1-3 indicate that certain immune perturbations may be independent of launch/landing stress. Future studies are required to determine if spaceflight induced immune dysregulation increases the risk of an adverse health event before exploration-class planetary missions (i.e. to Mars) can be considered

Evaluation of techniques for performing cellular isolation and preservation during microgravity conditions

Genomic and epigenomic studies require the precise transfer of microliter volumes among different types of tubes in order to purify DNA, RNA, or protein from biological samples and subsequently perform analyses of DNA methylation, RNA expression, and chromatin modifications on a genome-wide scale. Epigenomic and transcriptional analyses of human blood cells, for example, require separation of purified cell types to avoid confounding contributions of altered cellular proportions, and long-term preservation of these cells requires their isolation and transfer into appropriate freezing media. There are currently no protocols for these cellular isolation procedures on the International Space Station (ISS). Currently human blood samples are either frozen as mixed cell populations (within the CPT collection tubes) with poor yield of viable cells required for cell-type isolations, or returned under ambient conditions, which requires timing with Soyuz missions. Here we evaluate the feasibility of translating terrestrial cell purification techniques to the ISS. Our evaluations were performed in microgravity conditions during parabolic atmospheric flight. The pipetting of open liquids in microgravity was evaluated using analog-blood fluids and several types of pipette hardware. The best-performing pipettors were used to evaluate the pipetting steps required for peripheral blood mononuclear cell (PBMC) isolation following terrestrial density-gradient centrifugation. Evaluation of actual blood products was performed for both the overlay of diluted blood, and the transfer of isolated PBMCs. We also validated magnetic purification of cells. We found that positive-displacement pipettors avoided air bubbles, and the tips allowed the strong surface tension of water, glycerol, and blood to maintain a patent meniscus and withstand robust pipetting in microgravity. These procedures will greatly increase the breadth of research that can be performed on board the ISS, and allow improvised experimentation by astronauts on extraterrestrial missions

Inside-Out Evacuation of Transitional Protoplanetary Disks by the Magneto-Rotational Instability

How do T Tauri disks accrete? The magneto-rotational instability (MRI) supplies one means, but protoplanetary disk gas is typically too poorly ionized to be magnetically active. Here we show that the MRI can, in fact, explain observed accretion rates for the sub-class of T Tauri disks known as transitional systems. Transitional disks are swept clean of dust inside rim radii of ~10 AU. Stellar coronal X-rays ionize material in the disk rim, activating the MRI there. Gas flows from the rim to the star, at a rate limited by the depth to which X-rays ionize the rim wall. The wider the rim, the larger the surface area that the rim wall exposes to X-rays, and the greater the accretion rate. Interior to the rim, the MRI continues to transport gas; the MRI is sustained even at the disk midplane by super-keV X-rays that Compton scatter down from the disk surface. Accretion is therefore steady inside the rim. Blown out by radiation pressure, dust largely fails to accrete with gas. Contrary to what is usually assumed, ambipolar diffusion, not Ohmic dissipation, limits how much gas is MRI-active. We infer values for the transport parameter alpha on the order of 0.01 for GM Aur, TW Hyd, and DM Tau. Because the MRI can only afflict a finite radial column of gas at the rim, disk properties inside the rim are insensitive to those outside. Thus our picture provides one robust setting for planet-disk interaction: a protoplanet interior to the rim will interact with gas whose density, temperature, and transport properties are definite and decoupled from uncertain initial conditions. Our study also supplies half the answer to how disks dissipate: the inner disk drains from the inside out by the MRI, while the outer disk photoevaporates by stellar ultraviolet radiation.Comment: Accepted to Nature Physics June 7, 2007. The manuscript for publication is embargoed per Nature policy. This arxiv.org version contains more technical details and discussion, and is distributed with permission from the editors. 10 pages, 4 figure

Dynamical Boson Stars

The idea of stable, localized bundles of energy has strong appeal as a model for particles. In the 1950s John Wheeler envisioned such bundles as smooth configurations of electromagnetic energy that he called {\em geons}, but none were found. Instead, particle-like solutions were found in the late 1960s with the addition of a scalar field, and these were given the name {\em boson stars}. Since then, boson stars find use in a wide variety of models as sources of dark matter, as black hole mimickers, in simple models of binary systems, and as a tool in finding black holes in higher dimensions with only a single killing vector. We discuss important varieties of boson stars, their dynamic properties, and some of their uses, concentrating on recent efforts.Comment: 79 pages, 25 figures, invited review for Living Reviews in Relativity; major revision in 201

Modern optical astronomy: technology and impact of interferometry

The present `state of the art' and the path to future progress in high spatial resolution imaging interferometry is reviewed. The review begins with a treatment of the fundamentals of stellar optical interferometry, the origin, properties, optical effects of turbulence in the Earth's atmosphere, the passive methods that are applied on a single telescope to overcome atmospheric image degradation such as speckle interferometry, and various other techniques. These topics include differential speckle interferometry, speckle spectroscopy and polarimetry, phase diversity, wavefront shearing interferometry, phase-closure methods, dark speckle imaging, as well as the limitations imposed by the detectors on the performance of speckle imaging. A brief account is given of the technological innovation of adaptive-optics (AO) to compensate such atmospheric effects on the image in real time. A major advancement involves the transition from single-aperture to the dilute-aperture interferometry using multiple telescopes. Therefore, the review deals with recent developments involving ground-based, and space-based optical arrays. Emphasis is placed on the problems specific to delay-lines, beam recombination, polarization, dispersion, fringe-tracking, bootstrapping, coherencing and cophasing, and recovery of the visibility functions. The role of AO in enhancing visibilities is also discussed. The applications of interferometry, such as imaging, astrometry, and nulling are described. The mathematical intricacies of the various `post-detection' image-processing techniques are examined critically. The review concludes with a discussion of the astrophysical importance and the perspectives of interferometry.Comment: 65 pages LaTeX file including 23 figures. Reviews of Modern Physics, 2002, to appear in April issu

Codes of Fair Competition: The National Recovery Act, 1933-1935, and the Women’s Dress Manufacturing Industry

Controversial issues prevalent in today’s ready-to-wear apparel industry include the right of workers to join unions, the proliferation of sweatshops and sweatshop conditions, and design piracy. The idea of forming codes of conduct to establish criteria of ethical business practices is not new to the apparel industry. Indeed, the women’s dress manufacturing industry discussed and debated codes of fair competition under the New Deal Policies of the National Recovery Act (NRA) of 1933 to 1935. Primary sources for this study included governmental hearings in the establishment of the NRA Dress Code, The New York Times, Women’s Wear Daily, and the Journal of the Patent Office Society. The history of the NRA codes implemented in the U.S. women’s ready-to-wear apparel industry provides an important case study highlighting the difficulties and complexities of creating and achieving industry-wide standard practices through self-regulation. The failure of the NRA demonstrates that even with the joint cooperation of industry, labor, and consumer groups and the backing of the force of law, codes of fair competition proved impossible to enforce

Evaluation of techniques for performing cellular isolation and preservation during microgravity conditions

Genomic and epigenomic studies require the precise transfer of microliter volumes among different types of tubes in order to purify DNA, RNA, or protein from biological samples and subsequently perform analyses of DNA methylation, RNA expression, and chromatin modifications on a genome-wide scale. Epigenomic and transcriptional analyses of human blood cells, for example, require separation of purified cell types to avoid confounding contributions of altered cellular proportions, and long-term preservation of these cells requires their isolation and transfer into appropriate freezing media. There are currently no protocols for these cellular isolation procedures on the International Space Station (ISS). Currently human blood samples are either frozen as mixed cell populations (within the CPT collection tubes) with poor yield of viable cells required for cell-type isolations, or returned under ambient conditions, which requires timing with Soyuz missions. Here we evaluate the feasibility of translating terrestrial cell purification techniques to the ISS. Our evaluations were performed in microgravity conditions during parabolic atmospheric flight. The pipetting of open liquids in microgravity was evaluated using analog-blood fluids and several types of pipette hardware. The best-performing pipettors were used to evaluate the pipetting steps required for peripheral blood mononuclear cell (PBMC) isolation following terrestrial density-gradient centrifugation. Evaluation of actual blood products was performed for both the overlay of diluted blood, and the transfer of isolated PBMCs. We also validated magnetic purification of cells. We found that positive-displacement pipettors avoided air bubbles, and the tips allowed the strong surface tension of water, glycerol, and blood to maintain a patent meniscus and withstand robust pipetting in microgravity. These procedures will greatly increase the breadth of research that can be performed on board the ISS, and allow improvised experimentation by astronauts on extraterrestrial missions

A Randomized Trial of the Effects of Dietary n3-PUFAs on Skeletal Muscle Function and Acute Exercise Response in Healthy Older Adults

Skeletal muscle is critical for maintaining mobility, independence, and metabolic health in older adults. However, a common feature of aging is the progressive loss of skeletal muscle mass and function, which is often accompanied by mitochondrial impairments, oxidative stress, and insulin resistance. Exercise improves muscle strength, mitochondrial health, and cardiorespiratory fitness, but older adults often exhibit attenuated anabolic responses to acute exercise. Chronic inflammation associated with aging may contribute to this “anabolic resistance” and therapeutic interventions that target inflammation may improve exercise responsiveness. To this end, we conducted a randomized controlled trial to determine the effect of 6 months of dietary omega-3 polyunsaturated fatty acids (n3-PUFA) supplementation on skeletal muscle function (mass, strength), mitochondrial physiology (respiration, ATP production, ROS generation), and acute exercise responsiveness at the level of the muscle (fractional synthesis rate) and the whole-body (amino acid kinetics) in healthy older adults. When compared with a corn oil placebo (n = 33; 71.5 ± 4.8 years), older adults treated with 4 g/day n3-PUFA (n = 30; 71.4 ± 4.5 years) exhibited modest but significant increases in muscle strength (3.1 ± 14.7% increase in placebo vs. 7.5 ± 14.1% increase in n3-PUFA; p = 0.039). These improvements in muscle strength with n3-PUFA supplementation occurred in the absence of any effects on mitochondrial function and a minor attenuation of the acute response to exercise compared to placebo. Together, these data suggest modest benefits of dietary n3-PUFAs to muscle function in healthy older adults. Future studies may elucidate whether n3-PUFA supplementation improves the exercise response in elderly individuals with co-morbidities, such as chronic inflammatory disease or sarcopenia