Prostaglandin E Positively Modulates Endothelial Progenitor Cell Homeostasis: An Advanced Treatment Modality for Autologous Cell Therapy

Aims: The mobilization of endothelial progenitor cells (EPC) and their functioning in postnatal neovascularization are tightly regulated. To identify new modulators of EPC homeostasis, we screened biologically active prostaglandin E compounds for their effects on EPC production, trafficking and function. Methods and Results: We found that EPC are a rich source for prostaglandin E 2 (PGE 2), stimulating their number and function in an auto- and paracrine manner. In vivo blockade of PGE 2 production by selective cyclooxygenase-2 inhibition virtually abrogated ischemia-induced EPC mobilization demonstrating its crucial role in EPC homeostasis following tissue ischemia. Conversely, ex vivo treatment of isolated EPC with the clinically approved PGE 1 analogue alprostadil enhanced EPC number and function. These effects were mediated by increased expression of the chemokine receptor CXCR4 and were dependent on nitric oxide synthase activity. Most importantly, ex vivo PGE 1 pretreatment of isolated EPC significantly enhanced their neovascularization capacity in a murine model of hind limb ischemia as assessed by laser Doppler analysis, exercise stress test and immunohistochemistry. Conclusions: The conserved role for PGE in the regulation of EPC homeostasis suggests that ex vivo modulation of the prostaglandin pathway in isolated progenitor cells may represent a novel and safe strategy to facilitate cell-based therapies. Copyright (C) 2009 S. Karger AG, Base

Late Holocene sea- and land-level change on the U.S. southeastern Atlantic coast

Late Holocene relative sea-level (RSL) reconstructions can be used to estimate rates of land-level (subsidence or uplift) change and therefore to modify global sea-level projections for regional conditions. These reconstructions also provide the long-term benchmark against which modern trends are compared and an opportunity to understand the response of sea level to past climate variability. To address a spatial absence of late Holocene data in Florida and Georgia, we reconstructed ~ 1.3 m of RSL rise in northeastern Florida (USA) during the past ~ 2600 years using plant remains and foraminifera in a dated core of high salt-marsh sediment. The reconstruction was fused with tide-gauge data from nearby Fernandina Beach, which measured 1.91 ± 0.26 mm/year of RSL rise since 1900 CE. The average rate of RSL rise prior to 1800 CE was 0.41 ± 0.08 mm/year. Assuming negligible change in global mean sea level from meltwater input/removal and thermal expansion/contraction, this sea-level history approximates net land-level (subsidence and geoid) change, principally from glacio-isostatic adjustment. Historic rates of rise commenced at 1850–1890 CE and it is virtually certain (P = 0.99) that the average rate of 20th century RSL rise in northeastern Florida was faster than during any of the preceding 26 centuries. The linearity of RSL rise in Florida is in contrast to the variability reconstructed at sites further north on the U.S. Atlantic coast and may suggest a role for ocean dynamic effects in explaining these more variable RSL reconstructions. Comparison of the difference between reconstructed rates of late Holocene RSL rise and historic trends measured by tide gauges indicates that 20th century sea-level trends along the U.S. Atlantic coast were not dominated by the characteristic spatial fingerprint of melting of the Greenland Ice Sheet

Structure and Molecular Mechanism of ER Stress Signaling by the Unfolded Protein Response Signal Activator IRE1

The endoplasmic reticulum (ER) is an important site for protein folding and maturation in eukaryotes. The cellular requirement to synthesize proteins within the ER is matched by its folding capacity. However, the physiological demands or aberrations in folding may result in an imbalance which can lead to the accumulation of misfolded protein, also known as “ER stress.” The unfolded protein response (UPR) is a cell-signaling system that readjusts ER folding capacity to restore protein homeostasis. The key UPR signal activator, IRE1, responds to stress by propagating the UPR signal from the ER to the cytosol. Here, we discuss the structural and molecular basis of IRE1 stress signaling, with particular focus on novel mechanistic advances. We draw a comparison between the recently proposed allosteric model for UPR induction and the role of Hsp70 during polypeptide import to the mitochondrial matrix

Strategy and rationale for urine collection protocols employed in the NEPTUNE study

Abstract Background Glomerular diseases are potentially fatal, requiring aggressive interventions and close monitoring. Urine is a readily-accessible body fluid enriched in molecular signatures from the kidney and therefore particularly suited for routine clinical analysis as well as development of non-invasive biomarkers for glomerular diseases. Methods The Nephrotic Syndrome Study Network (NEPTUNE; ClinicalTrials.gov Identifier NCT01209000) is a North American multicenter collaborative consortium established to develop a translational research infrastructure for nephrotic syndrome. This includes standardized urine collections across all participating centers for the purpose of discovering non-invasive biomarkers for patients with nephrotic syndrome due to minimal change disease, focal segmental glomerulosclerosis, and membranous nephropathy. Here we describe the organization and methods of urine procurement and banking procedures in NEPTUNE. Results We discuss the rationale for urine collection and storage conditions, and demonstrate the performance of three experimental analytes (neutrophil gelatinase-associated lipocalin [NGAL], retinol binding globulin, and alpha-1 microglobulin) under these conditions with and without urine preservatives (thymol, toluene, and boric acid). We also demonstrate the quality of RNA and protein collected from the urine cellular pellet and exosomes. Conclusions The urine collection protocol in NEPTUNE allows robust detection of a wide range of proteins and RNAs from urine supernatant and pellets collected longitudinally from each patient over 5 years. Combined with the detailed clinical and histopathologic data, this provides a unique resource for exploration and validation of new or accepted markers of glomerular diseases. Trial registration ClinicalTrials.gov Identifier NCT01209000http://deepblue.lib.umich.edu/bitstream/2027.42/116023/1/12882_2015_Article_185.pd

Vitamin D in the general population of young adults with autism in the Faroe Islands

Vitamin D deficiency has been proposed as a possible risk factor for developing autism spectrum disorder (ASD). 25-Hydroxyvitamin D3 (25(OH)D3) levels were examined in a cross-sectional population-based study in the Faroe Islands. The case group consisting of a total population cohort of 40 individuals with ASD (aged 15–24 years) had significantly lower 25(OH)D3 than their 62 typically-developing siblings and their 77 parents, and also significantly lower than 40 healthy age and gender matched comparisons. There was a trend for males having lower 25(OH)D3 than females. Effects of age, month/season of birth, IQ, various subcategories of ASD and Autism Diagnostic Observation Schedule score were also investigated, however, no association was found. The very low 25(OH)D3 in the ASD group suggests some underlying pathogenic mechanism

Updating Maryland\u27s Sea-level Rise Projections

With its 3,100 miles of tidal shoreline and low-lying rural and urban lands, The Free State is one of the most vulnerable to sea-level rise. Historically, Marylanders have long had to contend with rising water levels along its Chesapeake Bay and Atlantic Ocean and coastal bay shores. Shorelines eroded and low-relief lands and islands, some previously inhabited, were inundated. Prior to the 20th century, this was largely due to the slow sinking of the land since Earth’s crust is still adjusting to the melting of large masses of ice following the last glacial period. Over the 20th century, however, the rate of rise of the average level of tidal waters with respect to land, or relative sea-level rise, has increased, at least partially as a result of global warming. Moreover, the scientific evidence is compelling that Earth’s climate will continue to warm and its oceans will rise even more rapidly. Recognizing the scientific consensus around global climate change, the contribution of human activities to it, and the vulnerability of Maryland’s people, property, public investments, and natural resources, Governor Martin O’Malley established the Maryland Commission on Climate Change on April 20, 2007. The Commission produced a Plan of Action1 that included a comprehensive climate change impact assessment, a greenhouse gas reduction strategy, and strategies for reducing Maryland’s vulnerability to climate change. The Plan has led to landmark legislation to reduce the state’s greenhouse gas emissions and a variety of state policies designed to reduce energy consumption and promote adaptation to climate change

Ocean mass, sterodynamic effects, and vertical land motion largely explain US coast relative sea level rise

© The Author(s), 2021. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Harvey, T., Hamlington, B. D., Frederikse, T., Nerem, R. S., Piecuch, C. G., Hammond, W. C., Blewitt, G., Thompson, P. R., Bekaert, D. P. S., Landerer, F. W., Reager, J. T., Kopp, R. E., Chandanpurkar, H., Fenty, I., Trossman, D. S., Walker, J. S., & Boening, C. W. Ocean mass, sterodynamic effects, and vertical land motion largely explain US coast relative sea level rise. Communications Earth & Environment, 2(1), (2021): 233, https://doi.org/10.1038/s43247-021-00300-w.Regional sea-level changes are caused by several physical processes that vary both in space and time. As a result of these processes, large regional departures from the long-term rate of global mean sea-level rise can occur. Identifying and understanding these processes at particular locations is the first step toward generating reliable projections and assisting in improved decision making. Here we quantify to what degree contemporary ocean mass change, sterodynamic effects, and vertical land motion influence sea-level rise observed by tide-gauge locations around the contiguous U.S. from 1993 to 2018. We are able to explain tide gauge-observed relative sea-level trends at 47 of 55 sampled locations. Locations where we cannot explain observed trends are potentially indicative of shortcomings in our coastal sea-level observational network or estimates of uncertainty.The research was carried out in part at the Jet Propulsion Laboratory, California Institute of Technology, under a contract with the National Aeronautics and Space Administration. C.G.P. was supported by NASA grant 80NSSC20K1241. B.D.H., T.C.H., and T.F. were supported by NASA JPL Task 105393.281945.02.25.04.59. R.E.K. and J.S.W. were supported by U.S. National Aeronautics and Space Administration (grants 80NSSC17K0698, 80NSSC20K1724 and JPL task 105393.509496.02.08.13.31) and U.S. National Science Foundation (grant ICER-1663807). P.R.T. acknowledges financial support from the NOAA Global Ocean Monitoring and Observing program in support of the University of Hawaii Sea Level Center (NA11NMF4320128). The ECCO project is funded by the NASA Physical Oceanography; Modeling, Analysis, and Prediction; and Cryosphere Programs

Undergraduate research. Genomics Education Partnership

The Genomics Education Partnership offers an inclusive model for undergraduate research experiences incorporated into the academic year science curriculum, with students pooling their work to contribute to international data bases

Association between contraceptive implant knowledge and intent with implant uptake among postpartum Malawian women: a prospective cohort study

Abstract Background Long-acting reversible contraception (LARC) can assist women with birth spacing and reduce unintended pregnancies. Sub-Saharan Africa has low uptake of the two available methods of LARC, the subdermal implant and intrauterine contraception (IUC). Our primary objectives were to: 1) calculate the incidence of LARC use among postpartum Malawian women, and 2) assess if LARC knowledge and intent to use LARC were associated with LARC uptake. Methods This study was a prospective cohort study of 634 postpartum women who were recruited from the postpartum ward of Bwaila Hospital in Lilongwe, Malawi. Study participants completed a baseline survey in the postpartum ward. Follow-up telephone surveys about contraceptive use were conducted at 3, 6, and 12 months postpartum. Cox proportional hazards regression analysis was performed to evaluate if implant knowledge and intent to use implant were associated with implant uptake. Results One hundred thirty-seven implant and 10 IUC placements were reported over 12 months of follow-up; given the low rate of IUC uptake, further analysis was only done for implant uptake. The incidence rate for implant uptake was 35.6 per 100 person-years (95 % CI 30.0, 42.2). Correct implant knowledge (adjusted HR = 1.69; 95 % CI 1.06, 2.68) and intent to use implant (adjusted HR 1.95; 95 % CI 1.28, 2.98) were both associated with implant uptake. Conclusions More women reported implant use than IUC use in our study. Correct implant knowledge and intent to use implant were both associated with implant uptake, with a stronger association for intent. Interventions to increase LARC uptake should focus on improving LARC knowledge and removing barriers to LARC. Trial registration Clinical Trial Registration #: NCT0189302

Experimental warming differentially affects vegetative and reproductive phenology of tundra plants

Rapid climate warming is altering Arctic and alpine tundra ecosystem structure and function, including shifts in plant phenology. While the advancement of green up and flowering are well-documented, it remains unclear whether all phenophases, particularly those later in the season, will shift in unison or respond divergently to warming. Here, we present the largest synthesis to our knowledge of experimental warming effects on tundra plant phenology from the International Tundra Experiment. We examine the effect of warming on a suite of season-wide plant phenophases. Results challenge the expectation that all phenophases will advance in unison to warming. Instead, we find that experimental warming caused: (1) larger phenological shifts in reproductive versus vegetative phenophases and (2) advanced reproductive phenophases and green up but delayed leaf senescence which translated to a lengthening of the growing season by approximately 3%. Patterns were consistent across sites, plant species and over time. The advancement of reproductive seasons and lengthening of growing seasons may have significant consequences for trophic interactions and ecosystem function across the tundra