Fundamental results from microgravity cell experiments with possible commericial applications

Some of the major milestones are presented for studies in cell biology that were conducted by the Soviet Union and the United States in the upper layers of the atmosphere and in outer space for more than thirty-five years. The goals have changed as new knowledge is acquired and the priorities for the use of microgravity have shifted toward basic research and commercial applications. Certain details concerning the impact of microgravity on cell systems is presented. However, it needs to be emphasized that in planning and conducting microgravity experiments, there are some important prerequisites not normally taken into account. Apart from the required background knowledge of previous microgravity and ground-based experiments, the investigator should have the understanding of the hardware as a physical unit, the complete knowledge of its operation, the range of its capabilities and the anticipation of problems that may occur. Moreover, if the production of commercial products in space is to be manifested, data obtained from previous microgravity experiments must be used to optimize the design of flight hardware

Rats, Mice, and People: Rodent Biology and Management

Farm Management,

Microparticle alpha-2-macroglobulin enhances pro-resolving responses and promotes survival in sepsis

Incorporation of locally produced signaling molecules into cell-derived vesicles may serve as an endogenous mediator delivery system. We recently reported that levels alpha-2-macroglobulin (A2MG)-containing microparticles are elevated in plasma from patients with sepsis. Herein, we investigated the immunomodulatory actions of A2MG containing microparticles during sepsis. Administration of A2MG-enriched (A2MG-E)-microparticles to mice with microbial sepsis protected against hypothermia, reduced bacterial titers, elevated immunoresolvent lipid mediator levels in inflammatory exudates and reduced systemic inflammation. A2MG-E microparticles also enhanced survival in murine sepsis, an action lost in mice transfected with siRNA for LRP1, a putative A2MG receptor. In vitro, A2MG was functionally transferred onto endothelial cell plasma membranes from microparticles, augmenting neutrophil–endothelial adhesion. A2MG also modulated human leukocyte responses: enhanced bacterial phagocytosis, reactive oxygen species production, cathelicidin release, prevented endotoxin induced CXCR2 downregulation and preserved neutrophil chemotaxis in the presence of LPS. A significant association was also found between elevated plasma levels of A2MG-containing microparticles and survival in human sepsis patients. Taken together, these results identify A2MG enrichment in microparticles as an important host protective mechanism in sepsis

Microparticle alpha-2-macroglobulin enhances pro-resolving responses and promotes survival in sepsis

These studies were supported by The Wellcome Trust (program 086867/Z/08) and the William Harvey Research Foundation to MP, the United Kingdom Intensive Care Society to CJH and the National Institutes of Health GM Grant P01GM095967 (awarded to Charles N. Serhan). LVN is supported by an Arthritis Research UK Career Development Fellowship (19909). EPSRC Seed Funding Cross disciplinary Grant (QMUL) awarded to GBS and MP. This work forms part of the research themes contributing to the translational research portfolio of Barts and The London NIHR Cardiovascular BRU

Features of postoperative immune suppression are reversible with interferon gamma and independent of interleukin-6 pathways

OBJECTIVE The aim of this study was to evaluate the role of interleukin (IL)-6 pathways in postoperative immune suppression and to assess the reversibility of this phenomenon. BACKGROUND The postoperative period is characterized by increased IL-6 production and features of immune suppression. In vitro, IL-6 mediates anti-inflammatory effects through inhibition of interferon gamma (IFN-γ) pathways. The significance of the immunomodulatory effects of IL-6 in the clinical setting of postoperative immune suppression remains unclear. METHODS Patients over 45 years old undergoing elective surgery, involving the gastrointestinal tract, were recruited. IL-6 levels were assayed using an enzyme linked immunosorbent assay preoperatively, and at 24 and 48 hours. Peripheral blood mononuclear cells from healthy volunteers were cultured in perioperative serum and CD14Human Leukocyte Antigen-DR (HLA-DR) [monocyte HLA-DR (mHLA-DR)] geometric mean florescent intensity was measured in the presence and absence of IL-6 neutralizing antibody and recombinant IFN-γ. RESULTS Of the 108 patients, 41 developed a postoperative infection. The IL-6 levels increased 19-fold from the preoperative sample to 24 hours postoperatively (P < 0.0001). Higher IL-6 levels at 24 (P = 0.0002) and 48 hours (P = 0.003) were associated with subsequent postoperative infectious complications. mHLA-DR mean florescent intensity fell when healthy peripheral blood mononuclear cells were cultured with postoperative serum compared with preoperative serum (P = 0.008). This decrease was prevented by the presence of IFN-γ in the culture media, but not by the presence of IL-6-neutralizing antibody. CONCLUSIONS IL-6 levels increase after a major surgery and are associated with an increased susceptibility to postoperative infections. Serum obtained from postoperative patients induces an immunosuppressive response, reflected in reduced mHLA-DR levels, mediated through IL-6 independent pathways and is reversible with IFN-γ. These data may have therapeutic implications for the prevention of infection in patients undergoing major surgery

Should we use central venous saturation to guide management in high-risk surgical patients?

Measurements of central venous oxygen saturation (ScvO(2)) have been successfully used to guide haemodynamic therapy in critical care. The efficacy of this approach in the treatment of severe sepsis and septic shock has stimulated interest in the use of ScvO(2 )to guide management in patients undergoing major surgery. The physiological basis of ScvO(2 )measurement is complex. A number of outstanding issues will need to be resolved before incorporating ScvO(2 )measurement into routine practice. First, it is not yet clear which value of ScvO(2 )should be targeted. Second, there is some uncertainty as to which interventions are the most effective for achieving the desired value of ScvO(2 )or how long this value should be maintained. The study by The Collaborative Study Group on Perioperative ScvO(2) Monitoring published in this edition of Critical Care may help provide answers to some of these questions. Our understanding of ScvO(2 )measurement remains limited, however, and the routine use of peri-operative ScvO(2)-guided goal-directed therapy cannot be recommended until a large randomised trial has confirmed the value of this approach

Manipulating ultracold atoms with a reconfigurable nanomagnetic system of domain walls

The divide between the realms of atomic-scale quantum particles and lithographically-defined nanostructures is rapidly being bridged. Hybrid quantum systems comprising ultracold gas-phase atoms and substrate-bound devices already offer exciting prospects for quantum sensors, quantum information and quantum control. Ideally, such devices should be scalable, versatile and support quantum interactions with long coherence times. Fulfilling these criteria is extremely challenging as it demands a stable and tractable interface between two disparate regimes. Here we demonstrate an architecture for atomic control based on domain walls (DWs) in planar magnetic nanowires that provides a tunable atomic interaction, manifested experimentally as the reflection of ultracold atoms from a nanowire array. We exploit the magnetic reconfigurability of the nanowires to quickly and remotely tune the interaction with high reliability. This proof-of-principle study shows the practicability of more elaborate atom chips based on magnetic nanowires being used to perform atom optics on the nanometre scale.Comment: 4 pages, 4 figure

Measurement of one-particle correlations and momentum distributions for trapped 1D gases

van Hove's theory of scattering of probe particles by a macroscopic target is generalized so as to relate the differential cross section for atomic ejection via stimulated Raman transitions to one-particle momentum-time correlations and momentum distributions of 1D trapped gases. This method is well suited to probing the longitudinal momentum distributions of 1D gases in situ, and examples are given for bosonic and fermionic atoms.Comment: 4 pages, 2 .eps figure

On the Importance of Intellectual Property Rights for E-science and the Integrated Health Record

An integrated health record (IHR) that enables clinical data to be shared at a national level has profound implications for medical research. Data that have been useful primarily within a single clinic will instead be free to move rapidly around a national network infrastructure. This raises challenges for technologists, clinical practice, and for the governance of these data. This article considers one specific issue that is currently poorly understood: how intellectual property (IP) relates to the sharing of medical data for research on large-scale electronic networks. Based on an understanding of current practices, this article presents recommendations for the governance of IP in an integrated health record