Structure and functional motifs of GCR1, the only plant protein with a GPCR fold?

Whether GPCRs exist in plants is a fundamental biological question. Interest in deorphanizing new G protein coupled receptors (GPCRs), arises because of their importance in signaling. Within plants, this is controversial as genome analysis has identified 56 putative GPCRs, including GCR1 which is reportedly a remote homologue to class A, B and E GPCRs. Of these, GCR2, is not a GPCR; more recently it has been proposed that none are, not even GCR1. We have addressed this disparity between genome analysis and biological evidence through a structural bioinformatics study, involving fold recognition methods, from which only GCR1 emerges as a strong candidate. To further probe GCR1, we have developed a novel helix alignment method, which has been benchmarked against the the class A – class B - class F GPCR alignments. In addition, we have presented a mutually consistent set of alignments of GCR1 homologues to class A, class B and class F GPCRs, and shown that GCR1 is closer to class A and /or class B GPCRs than class A, class B or class F GPCRs are to each other. To further probe GCR1, we have aligned transmembrane helix 3 of GCR1 to each of the 6 GPCR classes. Variability comparisons provide additional evidence that GCR1 homologues have the GPCR fold. From the alignments and a GCR1 comparative model we have identified motifs that are common to GCR1, class A, B and E GPCRs. We discuss the possibilities that emerge from this controversial evidence that GCR1 has a GPCR fol

Natural and anthropogenic drivers of Bornean elephant movement strategies

Endangered Bornean elephants are severely threatened by ongoing habitat transformation and increasing levels of human-elephant conflict. Understanding how elephants move across intact and transformed landscapes, as well as within them, is therefore of vital importance for the successful implementation of conservation management initiatives. We combined remote sensing and GPS telemetry data to identify broad habitat utilization and key movement areas to aid elephant management and conflict mitigation in three spatially-isolated populations in central and eastern Sabah, Malaysian Borneo. Home ranges were estimated using Brownian Bridge Movement Models and specific behavioral movement traits were identified by pathway analyses. These behavioral traits enabled a fine-scale evaluation of movements between and adjacent to forest patches and the role of large-scale agriculture in shaping elephant movements. Both natural (topological) and anthropogenic (agricultural) landscape features were found to have a broad influence on elephant movements. All elephant populations exhibited human-mediated behavioral responses, regardless of disturbance level. Throughout their range, elephants appeared to actively select relatively degraded forests, as measured by aboveground carbon density. However, elephants actively avoided urbanized areas, including roads and villages. Throughout the elephant range, high-speed, low-trajectory movements were found at low aboveground carbon locations, with 27% of all such movements located in large-scale agriculture. Our results suggest that agriculture impacts movement strategies of elephants, with evidence of repeat agricultural use pointing towards an active rationale for this behavior. Elephants were also found to use ridgelines as movement pathways, providing further context for the protection of such forested areas. The Lower Kinabatangan population, located in small remnant forests, travelled further to meet their ecological needs, suggesting the population is under added strain. Our work represents the broadest landscape assessment of Bornean elephant movements to-date and has important implications for both future work and habitat-level protected area management strategies

NASA Flight Planning Branch Space Shuttle Lessons Learned

Planning products and procedures that allowed the mission Flight Control Teams and the Astronaut crews to plan, train and fly every Space Shuttle mission were developed by the Flight Planning Branch at the NASA Johnson Space Center in Houston, Texas. As the Space Shuttle Program came to a close, lessons learned were collected from each phase of the successful execution of these Space Shuttle missions. Specific examples of how roles and responsibilities of console positions that develop the crew and vehicle attitude timelines have been analyzed and will be discussed. Additionally, the relationships and procedural hurdles experienced through international collaboration have molded operations. These facets will be explored and related to current and future operations with the International Space Station and future vehicles. Along with these important aspects, the evolution of technology and continual improvement of data transfer tools between the Space Shuttle and ground team has also defined specific lessons used in improving the control team s effectiveness. Methodologies to communicate and transmit messages, images, and files from the Mission Control Center to the Orbiter evolved over several years. These lessons were vital in shaping the effectiveness of safe and successful mission planning and have been applied to current mission planning work in addition to being incorporated into future space flight planning. The critical lessons from all aspects of previous plan, train, and fly phases of Space Shuttle flight missions are not only documented in this paper, but are also discussed regarding how they pertain to changes in process and consideration for future space flight planning

On the Origins of the High-Latitude H-alpha Background

The diffuse high-latitude H-alpha background is widely believed to be predominantly the result of in-situ recombination of ionized hydrogen in the warm interstellar medium of the Galaxy. Instead, we show that both a substantial fraction of the diffuse high-latitude H-alpha intensity in regions dominated by Galactic cirrus dust and much of the variance in the high-latitude H-alpha background are the result of scattering by interstellar dust of H-alpha photons originating elsewhere in the Galaxy. We provide an empirical relation, which relates the expected scattered H-alpha intensity to the IRAS 100um diffuse background intensity, applicable to about 81% of the entire sky. The assumption commonly made in reductions of CMB observations, namely that the observed all-sky map of diffuse H-alpha light is a suitable template for Galactic free-free foreground emission, is found to be in need of reexamination.Comment: 26 pages, 5 figures, Accepted for publication in Ap

Southern Ocean control of silicon stable isotope distribution in the deep Atlantic Ocean

Author Posting. © American Geophysical Union, 2012. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Global Geochemical Cycles 26 (2012): GB2035, doi:10.1029/2011GB004141.The fractionation of silicon (Si) stable isotopes by biological activity in the surface ocean makes the stable isotope composition of silicon (δ30Si) dissolved in seawater a sensitive tracer of the oceanic biogeochemical Si cycle. We present a high-precision dataset that characterizes the δ30Si distribution in the deep Atlantic Ocean from Denmark Strait to Drake Passage, documenting strong meridional and smaller, but resolvable, vertical δ30Si gradients. We show that these gradients are related to the two sources of deep and bottom waters in the Atlantic Ocean: waters of North Atlantic and Nordic origin carry a high δ30Si signature of ≥+1.7‰ into the deep Atlantic, while Antarctic Bottom Water transports Si with a low δ30Si value of around +1.2‰. The deep Atlantic δ30Si distribution is thus governed by the quasi-conservative mixing of Si from these two isotopically distinct sources. This disparity in Si isotope composition between the North Atlantic and Southern Ocean is in marked contrast to the homogeneity of the stable nitrogen isotope composition of deep ocean nitrate (δ15N-NO3). We infer that the meridional δ30Si gradient derives from the transport of the high δ30Si signature of Southern Ocean intermediate/mode waters into the North Atlantic by the upper return path of the meridional overturning circulation (MOC). The basin-scale deep Atlantic δ30Si gradient thus owes its existence to the interaction of the physical circulation with biological nutrient uptake at high southern latitudes, which fractionates Si isotopes between the abyssal and intermediate/mode waters formed in the Southern Ocean.This work was supported by Swiss National Science Foundation grants 200021-116473 and 200020-130361.2012-12-1

Time-sequenced Multi-Radio-Frequency Observations of Cygnus X-3 in Flare

Multifrequency observations from the VLA, VLBA and OVRO Millimeter Array of a major radio outburst of Cygnus X-3 in 2001 September are presented, measuring the evolution of the spectrum of the source over three decades in frequency, over a period of six days. Following the peak of the flare, as the intensity declines the high-frequency spectrum at frequency nu steepens from nu^{-0.4} to nu^{-0.6}, after which the spectral index remains at this latter terminal value; a trend previously observed but hitherto not satisfactorily explained. VLBA observations, for the first time, track over several days the expansion of a sequence of knots whose initial diameters are approximately 8 milliarcseconds. The light-crossing time within these plasmons is of the same order as the time-scale over which the spectrum is observed to evolve. We contend that properly accounting for light-travel time effects in and between plasmons which are initially optically thick, but which after expansion become optically thin, explains the key features of the spectral evolution, for example the observed timescale. Using the VLBA images, we have directly measured for the first time the proper motions of individual knots, analysis of which shows a two-sided jet whose axis is precessing. The best-fit jet speed is roughly beta = 0.63 and the precession period is about 5 days, significantly lower than fitted for a previous flare. Extrapolation of the positions of the knots measured by the VLBA back to zero-separation shows this to occur approximately 2.5 days after the detection of the rise in flux density of Cygnus X-3.Comment: 23 pages, 10 figures, accepted by Ap

Identifying alemtuzumab as an anti-myeloid cell antiangiogenic therapy for the treatment of ovarian cancer

<p>Abstract</p> <p>Background</p> <p>Murine studies suggest that myeloid cells such as vascular leukocytes (VLC) and Tie2⁺monocytes play a critical role in tumor angiogenesis and vasculogenesis. Myeloid cells are a primary cause of resistance to anti-VEGF therapy. The elimination of these cells from the tumor microenvironment significantly restricts tumor growth in both spontaneous and xenograft murine tumor models. Thus animal studies indicate that myeloid cells are potential therapeutic targets for solid tumor therapy. Abundant VLC and Tie2⁺monocytes have been reported in human cancer. Unfortunately, the importance of VLC in human cancer growth remains untested as there are no confirmed therapeutics to target human VLC.</p> <p>Methods</p> <p>We used FACS to analyze VLC in ovarian and non-ovarian tumors, and characterize the relationship of VLC and Tie2-monocytes. We performed qRT-PCR and FACS on human VLC to assess the expression of the CD52 antigen, the target of the immunotherapeutic Alemtuzumab. We assessed Alemtuzumab's ability to induce complement-mediated VLC killing in vitro and in human tumor ascites. Finally we assessed the impact of anti-CD52 immuno-toxin therapy on murine ovarian tumor growth.</p> <p>Results</p> <p>Human VLC are present in ovarian and non-ovarian tumors. The majority of VLC appear to be Tie2+ monocytes. VLC and Tie2+ monocytes express high levels of CD52, the target of the immunotherapeutic Alemtuzumab. Alemtuzumab potently induces complement-mediated lysis of VLC in vitro and ex-vivo in ovarian tumor ascites. Anti-CD52 immunotherapy targeting VLC restricts tumor angiogenesis and growth in murine ovarian cancer.</p> <p>Conclusion</p> <p>These studies confirm VLC/myeloid cells as therapeutic targets in ovarian cancer. Our data provide critical pre-clinical evidence supporting the use of Alemtuzumab in clinical trials to test its efficacy as an anti-myeloid cell antiangiogenic therapeutic in ovarian cancer. The identification of an FDA approved anti-VLC agent with a history of clinical use will allow immediate proof-of-principle clinical trials in patients with ovarian cancer.</p