336 research outputs found
Critical early events in hematopoietic cell seeding and engraftment.
Durable hematopoietic stem cell engraftment requires efficient homing to and seeding in the recipient bone marrow. Dissection of cellular and molecular mechanisms by retrospective analysis of functional engraftment studies imposes severe limitations on the understanding of the early stages of this process. We have established an experimental approach for in vivo functional imaging of labeled cells at the level of recipient bone marrow in real time. The adhesive interaction of hematopoietic cells with the bone marrow stroma evolves as the most important early event. Adhesion to the marrow, rather than the vascular endothelium, determines the efficiency of both homing and seeding, and is absolutely essential to maintain cell viability in the marrow. Seeding and engraftment may be improved either by bypassing homing or by localized transplant of a large number of cells in a relatively small marrow space. There is functional redundancy in the molecular pathways that mediate the cell-stroma interaction, such that blockage of a single pathway has only minor effect on homing and seeding. We hypothesize that successfully seeding-engrafting cells undergo extensive phenotypic changes as a consequence of interaction with the stroma, without engaging in rapid proliferation. Surprisingly, Fas-ligand appears to promote hematopoietic cell engraftment by immunomodulatory and trophic effects
\u27Texas Maroon’ Bluebonnet
The Texas state flower, the bluebonnet, encompasses all six of the Lupinus species native to Texas. The most widespread and popular bluebonnet, Lupinus texensis Hook., is a winter annual that produces violet-blue [violet-blue group 96A, Royal Horticultural
Society (RHS), 1982] racemes in early to midspring and is predominately self-pollinating.
The Texas Dept. of Transportation uses this species widely for floral displays along roadsides throughout much of the state (Andrews, 1986). Rare white and even rarer pink variants exist in native populations, and a breeding project was initiated in 1985 to develop bluebonnets with novel flower colors for use as bedding plants. ‘Abbott Pink’ was the first seed-propagated cultivar to be developed from this program (Parsons and Davis, 1993). The second cultivar, ‘Barbara Bush’ with novel lavender shade flowers, was developed more recently (Parsons et al., 1994). As with the cultivars previously developed, we used recurrent phenotypic selection to develop ‘Texas Maroon’. This cultivar is intended for use as a bedding plant for maroon flower color
Gender and Vascular Complications in the JAK2 V617F-Positive Myeloproliferative Neoplasms
We previously found that gender influenced the JAK2 V617F allele burden, but it is unknown whether this gender difference in molecular epidemiology influences complications in the myeloproliferative neoplasms (MPNs). Historically, vascular complications represented the most common cause of mortality in polycythemia vera and essential thrombocytosis and contributed to morbidity in primary myelofibrosis. To determine the influence of gender on vascular complications, we retrospectively analyzed associations between gender and vascular complications. Despite their younger age, less prevalent dyslipidemia or smoking history, lower white blood counts, and lower JAK2 V617F allele burden, women had higher rates of abdominal venous thrombosis and comparable rates of all vascular complications. Vascular risk is currently not easily stratified by MPN-disease burden or traditional risk factors. Our analysis contributes to growing literature emphasizing gender differences in the MPN and further supports the important impact of individual and host variation on MPN clinical manifestations, and especially vascular risk
Randomized phase 3 evaluation of trifarotene 50 μg/g cream treatment of moderate facial and truncal acne.
BACKGROUND: Acne vulgaris often affects the face, shoulders, chest, and back, but treatment of nonfacial acne has not been rigorously studied.
OBJECTIVES: Assess the safety and efficacy of trifarotene 50 μg/g cream, a novel topical retinoid, in moderate facial and truncal acne.
METHODS: Two phase III double-blind, randomized, vehicle-controlled, 12-week studies of once-daily trifarotene cream versus vehicle in subjects aged 9 years or older. The primary end points were rate of success on the face, as determined by the Investigator\u27s Global Assessment (clear or almost clear and ≥2-grade improvement), and absolute change from baseline in inflammatory and noninflammatory counts from baseline to week 12. The secondary end points were rate of success on the trunk (clear or almost clear and ≥2-grade improvement) and absolute change in truncal inflammatory and noninflammatory counts from baseline to week 12. Safety was assessed through adverse events, local tolerability, vital signs, and routine laboratory testing results.
RESULTS: In both studies, at week 12 the facial success rates according to the Investigator\u27s Global Assessment and truncal Physician\u27s Global Assessment and change in inflammatory and noninflammatory lesion counts (both absolute and percentage) were all highly significant (P \u3c .001) in favor of trifarotene when compared with the vehicle.
LIMITATIONS: Adjunctive topical or systemic treatments were not studied.
CONCLUSION: These studies demonstrate that trifarotene appears to be safe, effective, and well tolerated in treatment of both facial and truncal acne
Variations in mid-latitude North Atlantic surface water properties during the mid-Brunhes (MIS 9–14) and their implications for the thermohaline circulation
© The Authors, 2010. This article is distributed under the terms of the Creative Commons Attribution 3.0 License. The definitive version was published in Climate of the Past 6 (2010): 531-552, doi:10.5194/cp-6-531-2010.Stable isotope and ice-rafted debris records from three core sites in the mid-latitude North Atlantic (IODP Site U1313, MD01-2446, MD03-2699) are combined with records of ODP Sites 1056/1058 and 980 to reconstruct hydrographic conditions during the middle Pleistocene spanning Marine Isotope Stages (MIS) 9–14 (300–540 ka). Core MD03-2699 is the first high-resolution mid-Brunhes record from the North Atlantic's eastern boundary upwelling system covering the complete MIS 11c interval and MIS 13. The array of sites reflect western and eastern basin boundary current as well as north to south transect sampling of subpolar and transitional water masses and allow the reconstruction of transport pathways in the upper limb of the North Atlantic's circulation. Hydrographic conditions in the surface and deep ocean during peak interglacial MIS 9 and 11 were similar among all the sites with relative stable conditions and confirm prolonged warmth during MIS 11c also for the mid-latitudes. Sea surface temperature (SST) reconstructions further reveal that in the mid-latitude North Atlantic MIS 11c is associated with two plateaus, the younger one of which is slightly warmer. Enhanced subsurface northward heat transport in the eastern boundary current system, especially during early MIS 11c, is denoted by the presence of tropical planktic foraminifer species and raises the question how strongly it impacted the Portuguese upwelling system. Deep water ventilation at the onset of MIS 11c significantly preceded surface water ventilation. Although MIS 13 was generally colder and more variable than the younger interglacials the surface water circulation scheme was the same. The greatest differences between the sites existed during the glacial inceptions and glacials. Then a north – south trending hydrographic front separated the nearshore and offshore waters off Portugal. While offshore waters originated from the North Atlantic Current as indicated by the similarities between the records of IODP Site U1313, ODP Site 980 and MD01-2446, nearshore waters as recorded in core MD03-2699 derived from the Azores Current and thus the subtropical gyre. Except for MIS 12, Azores Current influence seems to be related to eastern boundary system dynamics and not to changes in the Atlantic overturning circulation.The
Fundacao para a Ciencia e a Tecnologia (FCT) through the
PORTO (PDCT/MAR/58282/2004) and SEDPORT projects (PDCTM/
40017/2003), and postdoctoral (SFRH/BPD/21691/2005)
and PhD (SFRH/BP/13749/2003) fellowships funded A. V. and
T. R. Additional funding to T. R. and J. G. was provided by the
Consolider-Ingenio 2100 Project CE-CSD2007-0067
Interacting Factors Driving a Major Loss of Large Trees with Cavities in a Forest Ecosystem
Large trees with cavities provide critical ecological functions in forests worldwide, including vital nesting and denning resources for many species. However, many ecosystems are experiencing increasingly rapid loss of large trees or a failure to recruit new large trees or both. We quantify this problem in a globally iconic ecosystem in southeastern Australia--forests dominated by the world's tallest angiosperms, Mountain Ash (Eucalyptus regnans). Tree, stand and landscape-level factors influencing the death and collapse of large living cavity trees and the decay and collapse of dead trees with cavities are documented using a suite of long-term datasets gathered between 1983 and 2011. The historical rate of tree mortality on unburned sites between 1997 and 2011 was >14% with a mortality spike in the driest period (2006-2009). Following a major wildfire in 2009, 79% of large living trees with cavities died and 57-100% of large dead trees were destroyed on burned sites. Repeated measurements between 1997 and 2011 revealed no recruitment of any new large trees with cavities on any of our unburned or burned sites. Transition probability matrices of large trees with cavities through increasingly decayed condition states projects a severe shortage of large trees with cavities by 2039 that will continue until at least 2067. This large cavity tree crisis in Mountain Ash forests is a product of: (1) the prolonged time required (>120 years) for initiation of cavities; and (2) repeated past wildfires and widespread logging operations. These latter factors have resulted in all landscapes being dominated by stands ≤72 years and just 1.16% of forest being unburned and unlogged. We discuss how the features that make Mountain Ash forests vulnerable to a decline in large tree abundance are shared with many forest types worldwide.This work was supported by Australian Research Council DP1097170; Parks Victoria; and Victorian Department of Sustainability and Environment. The
funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
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