The first step in utilizing immune-modulating therapies: immune status determination

Recently, a single center study conducted by Oiva and coworkers and published in Critical Care demonstrated that phospho-specific whole blood flow cytometry could be used to assess activated signaling pathways in leukocytes isolated from pancreatitis patients. The authors demonstrated that this methodology had the potential to determine the current status of a patient's immune state. Although the experimental cohort was clinically homogeneous, the observed data were heterogeneous. Altogether, these results suggest that prior to administering immune-modulatory therapies in inflammatory diseases, it will be beneficial to first determine immune status. Rapid results from whole blood phospho-specific flow cytometry may allow for determination of immune status, improve early diagnosis, and provide a rational basis for immunomodulatory therapies

A study of some chemical and physical properties of the clay minerals nontronite, attapulgite and saponite

Publication authorized October 12, 1942."The bulletin comprises the major part of the thesis presented by O.G. Caldwell for the degree of doctor of philosophy in the University of Missouri"--P. [3].Digitized 2007 AES.Includes bibliographical references (pages 49-51)

The Effect of Ghrelin upon the Early Immune Response in Lean and Obese Mice during Sepsis

Introduction It is well established that obesity-related hormones can have modulatory effects associated with the immune response. Ghrelin, a hormone mainly derived from endocrine cells of the gastric mucosa, regulates appetite, energy expenditure and body weight counteracting leptin, a hormone mainly derived from adipocytes. Additionally, receptors of both have been detected on immune cells and demonstrated an immune regulatory function during sepsis. Methods In the present study, the effect of peripheral ghrelin administration on early immune response and survival was investigated with lean mice and mice with diet-induced obesity using cecal ligation and puncture to induce sepsis. Results In the obese group, we found that ghrelin treatment improved survival, ameliorated hypothermia, and increased hyperleptinemia as compared to the lean controls. We also observed that ghrelin treatment divergently regulated serum IL-1 beta and TNF-alpha concentrations in both lean and obese septic mice. Ghrelin treatment initially decreased but later resulted in increased bacteriaemia in lean mice while having no impact upon obese mice. Similarly, ghrelin treatment increased early neutrophil oxidative burst while causing a decrease 48 hours after sepsis inducement. Conclusion In conclusion, as the immune response to sepsis temporally changes, ghrelin treatment differentially mediates this response. Specifically, we observed that ghrelin conferred protective effects during the early phase of sepsis, but during the later phase deteriorated immune response and outcome. These adverse effects were more pronounced upon lean mice as compared to obese mice

Peripheral, but not central, CB1 antagonism provides food intake-independent metabolic benefits in diet-induced obese rats.

OBJECTIVE Blockade of the CB1 receptor is one of the promising strategies for the treatment of obesity. Although antagonists suppress food intake and reduce body weight, the role of central versus peripheral CB1 activation on weight loss and related metabolic parameters remains to be elucidated. We therefore specifically assessed and compared the respective potential relevance of central nervous system (CNS) versus peripheral CB1 receptors in the regulation of energy homeostasis and lipid and glucose metabolism in diet-induced obese (DIO) rats. RESEARCH DESIGN AND METHODS Both lean and DIO rats were used for our experiments. The expression of key enzymes involved in lipid metabolism was measured by real-time PCR, and euglycemic-hyperinsulinemic clamps were used for insulin sensitivity and glucose metabolism studies. RESULTS Specific CNS-CB1 blockade decreased body weight and food intake but, independent of those effects, had no beneficial influence on peripheral lipid and glucose metabolism. Peripheral treatment with CB1 antagonist (Rimonabant) also reduced food intake and body weight but, in addition, independently triggered lipid mobilization pathways in white adipose tissue and cellular glucose uptake. Insulin sensitivity and skeletal muscle glucose uptake were enhanced, while hepatic glucose production was decreased during peripheral infusion of the CB1 antagonist. However, these effects depended on the antagonist-elicited reduction of food intake. CONCLUSIONS Several relevant metabolic processes appear to independently benefit from peripheral blockade of CB1, while CNS-CB1 blockade alone predominantly affects food intake and body weight

Water and Soil Conservation Experiments at Spur, Texas.

67 p

Scald Injury-Induced T Cell Dysfunction Can Be Mitigated by Gr1+ Cell Depletion and Blockage of CD47/CD172a Signaling

Infection is a common and severe complication of burn injury: Sepsis accounts for 47% of postburn mortality. Burn-induced T cell suppression likely contributes to the increased infection susceptibility in burn patients. However, little is known about the kinetics of T cell dysfunction after burn and its underlying mechanisms. In this study, we show in a murine scald injury model that T cell activation of both CD4+ and CD8+ T cells as well as T cell cytokine production is suppressed acutely and persistently for at least 11 days after burn injury. Purified T cells from scald-injured mice exhibit normal T cell functions, indicating an extrinsically mediated defect. We further show that T cell dysfunction after burn appears to be cell-to-cell contact dependent and can be ameliorated by depletion of myeloid-derived suppressor cells. These cells expand after burn injury, particularly a subset expressing the checkpoint inhibitor CD172a, and infiltrate germinal centers. Expression of CD172a appears to be driven by ingestion of immature reticulocytes. Immature reticulocytes are drastically increased in the spleen of scald mice and may contribute to immunosuppression through more direct mechanisms as well. Overall, our study newly identifies two cell populations, myeloid-derived suppressor cells and immature reticulocytes, as well as the CD47/CD172a-signaling pathways as mediators of T cell suppressors after burn and thus opens up new research opportunities in the search for new therapies to combat increased infection susceptibility and the associated morbidity and mortality in burn victims

The SPLASH Survey: Kinematics of Andromeda's Inner Spheroid

The combination of large size, high stellar density, high metallicity, and Sersic surface brightness profile of the spheroidal component of the Andromeda galaxy (M31) within R_proj ~ 20 kpc suggest that it is unlike any subcomponent of the Milky Way. In this work we capitalize on our proximity to and external view of M31 to probe the kinematical properties of this "inner spheroid." We employ a Markov chain Monte Carlo (MCMC) analysis of resolved stellar kinematics from Keck/DEIMOS spectra of 5651 red giant branch stars to disentangle M31's inner spheroid from its stellar disk. We measure the mean velocity and dispersion of the spheroid in each of five spatial bins after accounting for a locally cold stellar disk as well as the Giant Southern Stream and associated tidal debris. For the first time, we detect significant spheroid rotation (v_rot ~ 50 km/s) beyond R_proj ~ 5 kpc. The velocity dispersion decreases from about 140 km/s at R_proj = 7 kpc to 120 km/s at R_proj = 14 kpc, consistent to 2 sigma with existing measurements and models. We calculate the probability that a given star is a member of the spheroid and find that the spheroid has a significant presence throughout the spatial extent of our sample. Lastly, we show that the flattening of the spheroid is due to velocity anisotropy in addition to rotation. Though this suggests that the inner spheroid of M31 more closely resembles an elliptical galaxy than a typical spiral galaxy bulge, it should be cautioned that our measurements are much farther out (2 - 14 r_eff) than for the comparison samples.Comment: Accepted for publication in Ap

Thermoanaerosceptrum fracticalcis gen. nov. sp. nov., a novel fumarate-fermenting microorganism from a deep fractured carbonate aquifer of the US Great Basin

Deep fractured rock ecosystems across most of North America have not been studied extensively. However, the US Great Basin, in particular the Nevada National Security Site (NNSS, formerly the Nevada Test Site), has hosted a number of influential subsurface investigations over the years. This investigation focuses on resident microbiota recovered from a hydrogeologically confined aquifer in fractured Paleozoic carbonate rocks at 863 – 923 m meters below land surface. Analysis of the microorganisms living in this oligotrophic environment provides a perspective into microbial metabolic strategies required to endure prolonged hydrogeological isolation deep underground. Here we present a microbiological and physicochemical characterization of a deep continental carbonate ecosystem and describe a bacterial genus isolated from the ecosystem. Strain DRI-13T is a strictly anaerobic, moderately thermophilic, fumarate-respiring member of the phylum Firmicutes. This bacterium grows optimally at 55°C and pH 8.0, can tolerate a concentration of 100 mM NaCl, and appears to obligately metabolize fumarate to acetate and succinate. Culture-independent 16S rRNA gene sequencing indicates a global subsurface distribution, while the closest cultured relatives of DRI-13T are Pelotomaculum thermopropionicum (90.0% similarity) and Desulfotomaculum gibsoniae (88.0% similarity). The predominant fatty acid profile is iso-C15:0, C15:0, C16:0 and C14:0. The percentage of the straight-chain fatty acid C15:0 is a defining characteristic not present in the other closely related species. The genome is estimated to be 3,649,665 bp, composed of 87.3% coding regions with an overall average of 45.1% G+C content. Strain DRI-13T represents a novel genus of subsurface bacterium isolated from a previously uncharacterized rock-hosted geothermal habitat. The characterization of the bacterium combined with the sequenced genome provides insights into metabolism strategies of the deep subsurface biosphere. Based on our characterization analysis we propose the name Thermoanaerosceptrum fracticalcis (DRI-13T = DSM 100382T = ATCC TSD-12T)

Divergent adaptive and innate immunological responses are observed in humans following blunt trauma

<p>Abstract</p> <p>Background</p> <p>The immune response to trauma has traditionally been modeled to consist of the systemic inflammatory response syndrome (SIRS) followed by the compensatory anti-inflammatory response syndrome (CARS). We investigated these responses in a homogenous cohort of male, severe blunt trauma patients admitted to a University Hospital surgical intensive care unit (SICU). After obtaining consent, peripheral blood was drawn up to 96 hours following injury. The enumeration and functionality of both myeloid and lymphocyte cell populations were determined.</p> <p>Results</p> <p>Neutrophil numbers were observed to be elevated in trauma patients as compared to healthy controls. Further, neutrophils isolated from trauma patients had increased raft formation and phospho-Akt. Consistent with this, the neutrophils had increased oxidative burst compared to healthy controls. In direct contrast, blood from trauma patients contained decreased naïve T cell numbers. Upon activation with a T cell specific mitogen, trauma patient T cells produced less IFN-gamma as compared to those from healthy controls. Consistent with these results, upon activation, trauma patient T cells were observed to have decreased T cell receptor mediated signaling.</p> <p>Conclusions</p> <p>These results suggest that following trauma, there are concurrent and divergent immunological responses. These consist of a hyper-inflammatory response by the innate arm of the immune system concurrent with a hypo-inflammatory response by the adaptive arm.</p

Developing a strategy for the national coordinated soil moisture monitoring network

Soil moisture is a critical land surface variable, affecting a wide variety of climatological, agricultural, and hydrological processes. Determining the current soil moisture status is possible via a variety of methods, including in situ monitoring, remote sensing, and numerical modeling. Although all of these approaches are rapidly evolving, there is no cohesive strategy or framework to integrate these diverse information sources to develop and disseminate coordinated national soil moisture products that will improve our ability to understand climate variability. The National Coordinated Soil Moisture Monitoring Network initiative has developed a national strategy for network coordination with NOAA’s National Integrated Drought Information System. The strategy is currently in review within NOAA, and work is underway to implement the initial milestones of the strategy. This update reviews the goals and steps being taken to establish this national-scale coordination for soil moisture monitoring in the United States